Sample records for nanoporous microparticles npmps

  1. Formulation, stability and pharmacokinetics of sugar-based salmon calcitonin-loaded nanoporous/nanoparticulate microparticles (NPMPs) for inhalation.

    PubMed

    Amaro, Maria Inês; Tewes, Frederic; Gobbo, Oliviero; Tajber, Lidia; Corrigan, Owen I; Ehrhardt, Carsten; Healy, Anne Marie

    2015-04-10

    A challenge exists to produce dry powder inhaler (DPI) formulations with appropriate formulation stability, biological activity and suitable physicochemical and aerosolisation characteristics that provide a viable alternative to parenteral formulations. The present study aimed to produce sugar-based nanoporous/nanoparticulate microparticles (NPMPs) loaded with a therapeutic peptide - salmon calcitonin (sCT). The physicochemical properties of the powders and their suitability for pulmonary delivery of sCT were determined. Production of powders composed of sCT loaded into raffinose or trehalose with or without hydroxypropyl-β-cyclodextrin was carried out using a laboratory scale spray dryer. Spray dried microparticles were spherical, porous and of small geometric size (≤2 μm). Aerodynamic assessment showed that the fine particle fraction (FPF) less than 5 μm ranged from 45 to 86%, depending on the formulation. The mass median aerodynamic diameter (MMAD) varied between 1.9 and 4.7 μm. Compared to unprocessed sCT, sCT:raffinose composite systems presented a bioactivity of approximately 100% and sCT:trehalose composite systems between 70-90% after spray drying. Storage stability studies demonstrated composite systems with raffinose to be more stable than those containing trehalose. These sugar-based salmon calcitonin-loaded NPMPs retain reasonable sCT bioactivity and have micromeritic and physicochemical properties which indicate their suitability for pulmonary delivery. Formulations presented a similar pharmacokinetic profile to sCT solution. Hence the advantage of a dry powder formulation is its non-invasive delivery route and ease of administration of the sCT. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Spray drying from organic solvents to prepare nanoporous/nanoparticulate microparticles of protein: excipient composites designed for oral inhalation.

    PubMed

    Ní Ógáin, Orla; Tajber, Lidia; Corrigan, Owen I; Healy, Anne Marie

    2012-09-01

    The aim of this study was to determine if spray-drying could successfully produce microparticles containing the model protein trypsin in a form suitable for inhalation. Trypsin was spray-dried with raffinose from a methanol : n-butyl acetate solvent system (MeOH : BA). The solvent system was then adjusted to include water, and trypsin was co-spray-dried with raffinose, trehalose or hydroxpropyl-β-cyclodextrin. The spray-dried products were characterised by SEM, XRD, DSC, TGA and FTIR. Protein biological activity and in-vitro deposition of trypsin : excipient nanoporous/nanoparticulate microparticles (NPMPs) was also assessed. The inclusion of water in a MeOH : BA solvent system allowed for the successful production of NPMPs of trypsin : excipient by spray-drying. Trypsin formulated as trypsin : excipient NPMPs retained biological activity on processing and showed no deterioration in activity or morphological characteristics when stored with desiccant at either 4 or 25°C. Hydroxpropyl-β-cyclodextrin showed advantages over the sugars in terms of producing powders with appropriate density and with greater physical stability under high-humidity conditions. Fine particle fractions of between 41 and 45% were determined for trypsin : excipient NPMPs. NPMPs of trypsin : excipient systems can be produced by spray-drying by adjustment of the solvent system to allow for adequate solubility of trypsin. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

  3. Optimisation of spray drying process conditions for sugar nanoporous microparticles (NPMPs) intended for inhalation.

    PubMed

    Amaro, Maria Inês; Tajber, Lidia; Corrigan, Owen I; Healy, Anne Marie

    2011-12-12

    The present study investigated the effect of operating parameters of a laboratory spray dryer on powder characteristics, in order to optimise the production of trehalose and raffinose powders, intended to be used as carriers of biomolecules for inhalation. The sugars were spray dried from 80:20 methanol:n-butyl acetate (v/v) solutions using a Büchi Mini Spray dryer B-290. A 2(4) factorial design of experiment (DOE) was undertaken. Process parameters studied were inlet temperature, gas flow rate, feed solution flow rate (pump setting) and feed concentration. Resulting powders where characterised in terms of yield, particle size (PS), residual solvent content (RSC) and outlet temperature. An additional outcome evaluated was the specific surface area (SSA) (by BET gas adsorption), and a relation between SSA and the in vitro deposition of the sugar NPMPs powders was also investigated. The DOE resulted in well fitted models. The most significant factors affecting the characteristics of the NPMPs prepared, at a 95% confidence interval, were gas flow: yield, PS and SSA; pump setting: yield; inlet temperature: RSC. Raffinose NPMPs presented better characteristics than trehalose NPMPs in terms of their use for inhalation, since particles with larger surface area resulting in higher fine particle fraction can be produced. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Particle engineering of materials for oral inhalation by dry powder inhalers. I-Particles of sugar excipients (trehalose and raffinose) for protein delivery.

    PubMed

    Ogáin, Orla Ní; Li, Jianhe; Tajber, Lidia; Corrigan, Owen I; Healy, Anne Marie

    2011-02-28

    The pulmonary route of delivery offers a potential alternative to parenteral administration of peptides and proteins. Protection of protein structure is essential in both processing and storage of the final formulation. Sugars, such as trehalose and raffinose, have been employed to act as protein stabilisers. Optimisation of the aerodynamic characteristics of microparticles in dry powder inhaler formulations is critical to ensure optimum deposition of the formulation into the respiratory tract. In the present study we examine the adaptation to hydrophilic materials, specifically the disaccharide, trehalose and the trisaccharide, raffinose, of a previously reported spray drying process for producing nanoporous microparticles (NPMPs). We also investigate the feasibility of incorporating a model protein, lysozyme, into these sugar-based NPMPs. While spray drying raffinose or trehalose from aqueous solution or ethanol:water solutions resulted in non-porous microspheres, spray drying from a methanol:n-butyl acetate mixed solvent system resulted in microparticles which appeared to consist of an agglomeration of individual nanoparticles, i.e. nanoporous/nanoparticulate microparticles. NPMPs of trehalose and raffinose were amorphous, with glass transition temperatures (Tgs) that were sufficiently high (124°C and ∼120°C for trehalose and raffinose, respectively) to suggest good physical stability at room temperature and good potential to act as protein carriers and/or stabilisers. NPMPs demonstrated improved aerosolisation properties compared to spray dried non-porous particles. The successful incorporation of lysozyme into these NPMPs at a sugar to protein weight ratio of 1:4 demonstrated the potential of these systems to act as carriers for peptide or protein drugs which could be delivered via the pulmonary route. Copyright © 2010 Elsevier B.V. All rights reserved.

  5. Capture, enrichment, and mass spectrometric detection of low-molecular-weight biomarkers with nanoporous silicon microparticles.

    PubMed

    Tan, Jie; Zhao, Wei-Jie; Yu, Jie-Kai; Ma, Sai; Sailor, Michael J; Wu, Jian-Min

    2012-11-01

    Mining the disease information contained in the low-molecular-weight range of a proteomic profile is becoming of increasing interest in cancer research. This work evaluates the ability of nanoporous silicon microparticles (NPSMPs) to capture, enrich, protect, and detect low-molecular-weight peptides (LMWPs) sieved from a pool of highly abundant plasma proteins. The average pore size and porosity of NPSMPs are controlled by the electrochemical preparation conditions, and the critical parameters for admission or exclusion of protein with a definite molecular weight are determined by reflectometric-interference Fourier transform spectroscopy (RIFTS). Sodium dodecyl sulfate polyacrylamide-gel electrophoresis (SDS-PAGE) and matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) analysis of the proteins captured by the NPSMPs show that the chemical nature of the NPSMPs surface and the solution pH also play vital roles in determining the affinity of NPSMPs for target analytes. It is found that carboxyl-terminated porous microparticles with a porosity of 26% (pore diameter around 9.0 nm) specifically fractionate, enrich and protect LMWPs sieved from either simulated samples or human serum samples. Moreover, NPSMPs containing captured peptides can be directly spotted onto a MALDI plate. When placed in a conventional MALDI matrix, laser irradiation of the particles results in the release of the target peptides confined in the nanopores, which are then ionized and detected in the MALDI experiment. As a proof-of-principle test case, mass spectra of NPSMPs prepared using serum from colorectal cancer patients and from control patients can be clearly distinguished by statistical analysis. The work demonstrates the utility of the method for discovery of biomarkers in the untapped LMWP fraction of human serum, which can be of significant value in the early diagnosis and management of diseases. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Removal of nano and microparticles by granular filter media coated with nanoporous aluminium oxide.

    PubMed

    Lau, B L T; Harrington, G W; Anderson, M A; Tejedor, I

    2004-01-01

    Conventional filtration was designed to achieve high levels of particle and pathogen removal. Previous studies have examined the possibility of modifying filtration media to improve their ability to remove microorganisms and viruses. Although these studies have evaluated filter media coatings for this purpose, none have evaluated nanoscale particle suspensions as coating materials. The overall goal of this paper is to describe the preliminary test results of nanoporous aluminium oxide coated media that can be used to enhance filtration of nano and microparticles. Filtration tests were carried out using columns packed with uncoated and coated forms of granular anthracite or granular activated carbon. A positive correlation between isoelectric pH of filter media and particle removal was observed. The modified filter media with a higher isoelectric pH facilitated better removal of bacteriophage MS2 and 3 microm latex microspheres, possibly due to increased favorable electrostatic interactions.

  7. Rational Design of Photonic Dust from Nanoporous Anodic Alumina Films: A Versatile Photonic Nanotool for Visual Sensing

    PubMed Central

    Chen, Yuting; Santos, Abel; Wang, Ye; Kumeria, Tushar; Ho, Daena; Li, Junsheng; Wang, Changhai; Losic, Dusan

    2015-01-01

    Herein, we present a systematic study on the development, optimisation and applicability of interferometrically coloured distributed Bragg reflectors based on nanoporous anodic alumina (NAA-DBRs) in the form of films and nanoporous microparticles as visual/colorimetric analytical tools. Firstly, we synthesise a complete palette of NAA-DBRs by galvanostatic pulse anodisation approach, in which the current density is altered in a periodic fashion in order to engineer the effective medium of the resulting photonic films in depth. NAA-DBR photonic films feature vivid colours that can be tuned across the UV-visible-NIR spectrum by structural engineering. Secondly, the effective medium of the resulting photonic films is assessed systematically by visual analysis and reflectometric interference spectroscopy (RIfS) in order to establish the most optimal nanoporous platforms to develop visual/colorimetric tools. Then, we demonstrate the applicability of NAA-DBR photonic films as a chemically selective sensing platform for visual detection of mercury(II) ions. Finally, we generate a new nanomaterial, so-called photonic dust, by breaking down NAA-DBRs films into nanoporous microparticles. The resulting microparticles (μP-NAA-DBRs) display vivid colours and are sensitive towards changes in their effective medium, opening new opportunities for developing advanced photonic nanotools for a broad range of applications. PMID:26245759

  8. Rational Design of Photonic Dust from Nanoporous Anodic Alumina Films: A Versatile Photonic Nanotool for Visual Sensing

    NASA Astrophysics Data System (ADS)

    Chen, Yuting; Santos, Abel; Wang, Ye; Kumeria, Tushar; Ho, Daena; Li, Junsheng; Wang, Changhai; Losic, Dusan

    2015-08-01

    Herein, we present a systematic study on the development, optimisation and applicability of interferometrically coloured distributed Bragg reflectors based on nanoporous anodic alumina (NAA-DBRs) in the form of films and nanoporous microparticles as visual/colorimetric analytical tools. Firstly, we synthesise a complete palette of NAA-DBRs by galvanostatic pulse anodisation approach, in which the current density is altered in a periodic fashion in order to engineer the effective medium of the resulting photonic films in depth. NAA-DBR photonic films feature vivid colours that can be tuned across the UV-visible-NIR spectrum by structural engineering. Secondly, the effective medium of the resulting photonic films is assessed systematically by visual analysis and reflectometric interference spectroscopy (RIfS) in order to establish the most optimal nanoporous platforms to develop visual/colorimetric tools. Then, we demonstrate the applicability of NAA-DBR photonic films as a chemically selective sensing platform for visual detection of mercury(II) ions. Finally, we generate a new nanomaterial, so-called photonic dust, by breaking down NAA-DBRs films into nanoporous microparticles. The resulting microparticles (μP-NAA-DBRs) display vivid colours and are sensitive towards changes in their effective medium, opening new opportunities for developing advanced photonic nanotools for a broad range of applications.

  9. Synthesis of Hierarchical Nanoporous Microstructures via the Kirkendall Effect in Chemical Reduction Process

    NASA Astrophysics Data System (ADS)

    Gao, Ling; Pang, Chao; He, Dafang; Shen, Liming; Gupta, Arunava; Bao, Ningzhong

    2015-11-01

    A series of novel hierarchical nanoporous microstructures have been synthesized through one-step chemical reduction of micron size Cu2O and Co3O4 particles. By controlling the reduction time, non-porous Cu2O microcubes sequentially transform to nanoporous Cu/Cu2O/Cu dented cubic composites and hollow eightling-like Cu microparticles. The mechanism involved in the complex structural evolution is explained based on oxygen diffusion and Kirkendall effect. The nanoporous Cu/Cu2O/Cu dented cubic composites exhibit superior electrochemical performance as compared to solid Cu2O microcubes. The reduction of nonporous Co3O4 also exhibits a uniform sequential reduction process from nonporous Co3O4 to porous Co3O4/CoO composites, porous CoO, porous CoO/Co composites, and porous foam-like Co particles. Nanoscale channels originate from the particle surface and eventually develop inside the entire product, resulting in porous foam-like Co microparticles. The Kirkendall effect is believed to facilitate the formation of porous structures in both processes.

  10. Strategy for the hemocompatibility testing of microparticles.

    PubMed

    Braune, S; Basu, S; Kratz, K; Johansson, J Bäckemo; Reinthaler, M; Lendlein, A; Jung, F

    2016-01-01

    Polymer-based microparticles are applied as non-thrombogenic or thrombogenic materials in a wide variety of intra- or extra-corporeal medical devices. As demanded by the regulatory agencies, the hemocompatibility of these blood contacting biomaterials has to be evaluated in vitro to ensure that the particle systems appropriately fulfill the envisioned function without causing undesired events such as thrombosis or inflammation. Currently described in vitro assays for hemocompatibility testing of particles comprise tests with different single cell types (e.g. erythrocytes or leukocytes), varying concentrations/dilutions of the used blood cells or whole blood, which are not standardized.Here, we report about an in vitro dynamic test system for studying the hemocompatibility of polymeric microparticles utilizing fresh human whole blood from apparently healthy subjects, collected and processed under standardized conditions. Spherical poly(ether imide) microparticles with an average diameter of 140±30 μm were utilized as model systems. Reported as candidate materials for the removal of uremic toxins, these microparticles are anticipated to facilitate optimal flow conditions in a dialyzer with minimal backflow and blood cell damage. Pristine (PEI) and potassium hydroxide (PEI-KOH) functionalized microparticles exhibited similarly nanoporous surfaces (PEI: ØExternal pore = 90±60 nm; PEI-KOH ØExternal pore = 150±130 nm) but varying water wettabilities (PEI: θadv = 112±10° PEI-KOH θadv = 60±2°). The nanoporosity of the microparticle surfaces allows the exchange of toxic solutes from blood towards the interconnective pores in the particle core, while an immigration of the substantially larger blood cells is inhibited.Sterilized PEI microparticles were incorporated -air-free -in a syringe-based test system and exposed to whole blood for 60 minutes under gentle agitation. Thereafter, thrombi formation on the particles surfaces were analyzed

  11. Single Molecule Sensing by Nanopores and Nanopore Devices

    PubMed Central

    Gu, Li-Qun; Shim, Ji Wook

    2010-01-01

    Molecular-scale pore structures, called nanopores, can be assembled by protein ion channels through genetic engineering or be artificially fabricated on solid substrates using fashion nanotechnology. When target molecules interact with the functionalized lumen of a nanopore, they characteristically block the ion pathway. The resulting conductance changes allow for identification of single molecules and quantification of target species in the mixture. In this review, we first overview nanopore-based sensory techniques that have been created for the detection of myriad biomedical targets, from metal ions, drug compounds, and cellular second messengers to proteins and DNA. Then we introduce our recent discoveries in nanopore single molecule detection: (1) using the protein nanopore to study folding/unfolding of the G-quadruplex aptamer; (2) creating a portable and durable biochip that is integrated with a single-protein pore sensor (this chip is compared with recently developed protein pore sensors based on stabilized bilayers on glass nanopore membranes and droplet interface bilayer); and (3) creating a glass nanopore-terminated probe for single-molecule DNA detection, chiral enantiomer discrimination, and identification of the bioterrorist agent ricin with an aptamer-encoded nanopore. PMID:20174694

  12. Influence of Nanopore Shapes on Thermal Conductivity of Two-Dimensional Nanoporous Material.

    PubMed

    Huang, Cong-Liang; Huang, Zun; Lin, Zi-Zhen; Feng, Yan-Hui; Zhang, Xin-Xin; Wang, Ge

    2016-12-01

    The influence of nanopore shapes on the electronic thermal conductivity (ETC) was studied in this paper. It turns out that with same porosity, the ETC will be quite different for different nanopore shapes, caused by the different channel width for different nanopore shapes. With same channel width, the influence of different nanopore shapes can be approximately omitted if the nanopore is small enough (smaller than 0.5 times EMFP in this paper). The ETC anisotropy was discovered for triangle nanopores at a large porosity with a large nanopore size, while there is a similar ETC for small pore size. It confirmed that the structure difference for small pore size may not be seen by electrons in their moving.

  13. Improved Analysis of Nanopore Sequence Data and Scanning Nanopore Techniques

    NASA Astrophysics Data System (ADS)

    Szalay, Tamas

    The field of nanopore research has been driven by the need to inexpensively and rapidly sequence DNA. In order to help realize this goal, this thesis describes the PoreSeq algorithm that identifies and corrects errors in real-world nanopore sequencing data and improves the accuracy of de novo genome assembly with increasing coverage depth. The approach relies on modeling the possible sources of uncertainty that occur as DNA advances through the nanopore and then using this model to find the sequence that best explains multiple reads of the same region of DNA. PoreSeq increases nanopore sequencing read accuracy of M13 bacteriophage DNA from 85% to 99% at 100X coverage. We also use the algorithm to assemble E. coli with 30X coverage and the lambda genome at a range of coverages from 3X to 50X. Additionally, we classify sequence variants at an order of magnitude lower coverage than is possible with existing methods. This thesis also reports preliminary progress towards controlling the motion of DNA using two nanopores instead of one. The speed at which the DNA travels through the nanopore needs to be carefully controlled to facilitate the detection of individual bases. A second nanopore in close proximity to the first could be used to slow or stop the motion of the DNA in order to enable a more accurate readout. The fabrication process for a new pyramidal nanopore geometry was developed in order to facilitate the positioning of the nanopores. This thesis demonstrates that two of them can be placed close enough to interact with a single molecule of DNA, which is a prerequisite for being able to use the driving force of the pores to exert fine control over the motion of the DNA. Another strategy for reading the DNA is to trap it completely with one pore and to move the second nanopore instead. To that end, this thesis also shows that a single strand of immobilized DNA can be captured in a scanning nanopore and examined for a full hour, with data from many scans at many

  14. Single-molecule nanopore enzymology

    PubMed Central

    Wloka, Carsten; Maglia, Giovanni

    2017-01-01

    Biological nanopores are a class of membrane proteins that open nanoscale water-conduits in biological membranes. When they are reconstituted in artificial membranes and a bias voltage is applied across the membrane, the ionic current passing through individual nanopores can be used to monitor chemical reactions, to recognize individual molecules and, of most interest, to sequence DNA. More recently, proteins and enzymes have started being analysed with nanopores. Monitoring enzymatic reactions with nanopores, i.e. nanopore enzymology, has the unique advantage that it allows long-timescale observations of native proteins at the single-molecule level. Here we describe the approaches and challenges in nanopore enzymology. PMID:28630164

  15. Microparticle analysis system and method

    NASA Technical Reports Server (NTRS)

    Morrison, Dennis R. (Inventor)

    2007-01-01

    A device for analyzing microparticles is provided which includes a chamber with an inlet and an outlet for respectively introducing and dispensing a flowing fluid comprising microparticles, a light source for providing light through the chamber and a photometer for measuring the intensity of light transmitted through individual microparticles. The device further includes an imaging system for acquiring images of the fluid. In some cases, the device may be configured to identify and determine a quantity of the microparticles within the fluid. Consequently, a method for identifying and tracking microparticles in motion is contemplated herein. The method involves flowing a fluid comprising microparticles in laminar motion through a chamber, transmitting light through the fluid, measuring the intensities of the light transmitted through the microparticles, imaging the fluid a plurality of times and comparing at least some of the intensities of light between different images of the fluid.

  16. Oxygen delivery using engineered microparticles

    PubMed Central

    Seekell, Raymond P.; Lock, Andrew T.; Peng, Yifeng; Cole, Alexis R.; Perry, Dorothy A.; Kheir, John N.; Polizzotti, Brian D.

    2016-01-01

    A continuous supply of oxygen to tissues is vital to life and interruptions in its delivery are poorly tolerated. The treatment of low-blood oxygen tensions requires restoration of functional airways and lungs. Unfortunately, severe oxygen deprivation carries a high mortality rate and can make otherwise-survivable illnesses unsurvivable. Thus, an effective and rapid treatment for hypoxemia would be revolutionary. The i.v. injection of oxygen bubbles has recently emerged as a potential strategy to rapidly raise arterial oxygen tensions. In this report, we describe the fabrication of a polymer-based intravascular oxygen delivery agent. Polymer hollow microparticles (PHMs) are thin-walled, hollow polymer microcapsules with tunable nanoporous shells. We show that PHMs are easily charged with oxygen gas and that they release their oxygen payload only when exposed to desaturated blood. We demonstrate that oxygen release from PHMs is diffusion-controlled, that they deliver approximately five times more oxygen gas than human red blood cells (per gram), and that they are safe and effective when injected in vivo. Finally, we show that PHMs can be stored at room temperature under dry ambient conditions for at least 2 mo without any effect on particle size distribution or gas carrying capacity. PMID:27791101

  17. Nanoporous thermosetting polymers.

    PubMed

    Raman, Vijay I; Palmese, Giuseppe R

    2005-02-15

    Potential applications of nanoporous thermosetting polymers include polyelectrolytes in fuel cells, separation membranes, adsorption media, and sensors. Design of nanoporous polymers for such applications entails controlling permeability by tailoring pore size, structure, and interface chemistry. Nanoporous thermosetting polymers are often synthesized via free radical mechanisms using solvents that phase separate during polymerization. In this work, a novel technique for the synthesis of nanoporous thermosets is presented that is based on the reactive encapsulation of an inert solvent using step-growth cross-linking polymerization without micro/macroscopic phase separation. The criteria for selecting such a monomer-polymer-solvent system are discussed based on FTIR analysis, observed micro/macroscopic phase separation, and thermodynamics of swelling. Investigation of resulting network pore structures by scanning electron microscopy (SEM) and small-angle X-ray scattering following extraction and supercritical drying using carbon dioxide showed that nanoporous polymeric materials with pore sizes ranging from 1 to 50 nm can be synthesized by varying the solvent content. The differences in the porous morphology of these materials compared to more common free radically polymerized analogues that exhibit phase separation were evident from SEM imaging. Furthermore, it was demonstrated that the chemical activity of the nanoporous materials obtained by our method could be tailored by grafting appropriate functional groups at the pore interface.

  18. Plasma-derived microparticles in polycythaemia vera.

    PubMed

    Ahadon, M; Abdul Aziz, S; Wong, C L; Leong, C F

    2018-04-01

    Microparticles are membrane bound vesicles, measuring less than 1.0 um, which are released during cellular activation or during apoptosis. Studies have shown that these circulating microparticles play a role in coagulation, cell signaling and cellular interactions. Increased levels of circulating microparticles have been observed in a number of conditions where there is vascular dysfunction, thrombosis and inflammation. The objective of this study was to determine the various plasma-derived microparticles in patients with polycythaemia vera (PV) in Universiti Kebangsaan Malaysia Medical Centre and to compare them with normal control. A total of 15 patients with PV and 15 healthy volunteers were included in this cross-sectional descriptive study. Plasma samples from both patients and healthy volunteers were prepared and further processed for isolation of microparticles. Flow cytometry analyses were then carried out in all samples to determine the cellular origin of the microparticles. Full blood count parameters for both groups were also collected. Data collected were analyzed using SPSS version 12.0. Patients with PV had a significantly higher percentage of platelet derived microparticles compared to healthy controls (P <0.05). The control group had a higher level of endothelial derived microparticles but the differences were not statistically significant (P > 0.05). The median percentage of positive events for platelet derived microparticles was higher in patients with PV compared to normal healthy controls.

  19. Microfluidic multiplexing of solid-state nanopores

    NASA Astrophysics Data System (ADS)

    Jain, Tarun; Rasera, Benjamin C.; Guerrero, Ricardo Jose S.; Lim, Jong-Min; Karnik, Rohit

    2017-12-01

    Although solid-state nanopores enable electronic analysis of many clinically and biologically relevant molecular structures, there are few existing device architectures that enable high-throughput measurement of solid-state nanopores. Herein, we report a method for microfluidic integration of multiple solid-state nanopores at a high density of one nanopore per (35 µm2). By configuring microfluidic devices with microfluidic valves, the nanopores can be rinsed from a single fluid input while retaining compatibility for multichannel electrical measurements. The microfluidic valves serve the dual purpose of fluidic switching and electric switching, enabling serial multiplexing of the eight nanopores with a single pair of electrodes. Furthermore, the device architecture exhibits low noise and is compatible with electroporation-based in situ nanopore fabrication, providing a scalable platform for automated electronic measurement of a large number of integrated solid-state nanopores.

  20. DNA translocation through graphene nanopores.

    PubMed

    Merchant, Christopher A; Healy, Ken; Wanunu, Meni; Ray, Vishva; Peterman, Neil; Bartel, John; Fischbein, Michael D; Venta, Kimberly; Luo, Zhengtang; Johnson, A T Charlie; Drndić, Marija

    2010-08-11

    We report on DNA translocations through nanopores created in graphene membranes. Devices consist of 1-5 nm thick graphene membranes with electron-beam sculpted nanopores from 5 to 10 nm in diameter. Due to the thin nature of the graphene membranes, we observe larger blocked currents than for traditional solid-state nanopores. However, ionic current noise levels are several orders of magnitude larger than those for silicon nitride nanopores. These fluctuations are reduced with the atomic-layer deposition of 5 nm of titanium dioxide over the device. Unlike traditional solid-state nanopore materials that are insulating, graphene is an excellent electrical conductor. Use of graphene as a membrane material opens the door to a new class of nanopore devices in which electronic sensing and control are performed directly at the pore.

  1. Nanoporous polymer electrolyte

    DOEpatents

    Elliott, Brian [Wheat Ridge, CO; Nguyen, Vinh [Wheat Ridge, CO

    2012-04-24

    A nanoporous polymer electrolyte and methods for making the polymer electrolyte are disclosed. The polymer electrolyte comprises a crosslinked self-assembly of a polymerizable salt surfactant, wherein the crosslinked self-assembly includes nanopores and wherein the crosslinked self-assembly has a conductivity of at least 1.0.times.10.sup.-6 S/cm at 25.degree. C. The method of making a polymer electrolyte comprises providing a polymerizable salt surfactant. The method further comprises crosslinking the polymerizable salt surfactant to form a nanoporous polymer electrolyte.

  2. Cell-derived microparticles and the lung.

    PubMed

    Nieri, Dario; Neri, Tommaso; Petrini, Silvia; Vagaggini, Barbara; Paggiaro, Pierluigi; Celi, Alessandro

    2016-09-01

    Cell-derived microparticles are small (0.1-1 μm) vesicles shed by most eukaryotic cells upon activation or during apoptosis. Microparticles carry on their surface, and enclose within their cytoplasm, molecules derived from the parental cell, including proteins, DNA, RNA, microRNA and phospholipids. Microparticles are now considered functional units that represent a disseminated storage pool of bioactive effectors and participate both in the maintenance of homeostasis and in the pathogenesis of diseases. The mechanisms involved in microparticle generation include intracellular calcium mobilisation, cytoskeleton rearrangement, kinase phosphorylation and activation of the nuclear factor-κB. The role of microparticles in blood coagulation and inflammation, including airway inflammation, is well established in in vitro and animal models. The role of microparticles in human pulmonary diseases, both as pathogenic determinants and biomarkers, is being actively investigated. Microparticles of endothelial origin, suggestive of apoptosis, have been demonstrated in the peripheral blood of patients with emphysema, lending support to the hypothesis that endothelial dysfunction and apoptosis are involved in the pathogenesis of the disease and represent a link with cardiovascular comorbidities. Microparticles also have potential roles in patients with asthma, diffuse parenchymal lung disease, thromboembolism, lung cancer and pulmonary arterial hypertension. Copyright ©ERS 2016.

  3. Nanofluidic Device with Embedded Nanopore

    NASA Astrophysics Data System (ADS)

    Zhang, Yuning; Reisner, Walter

    2014-03-01

    Nanofluidic based devices are robust methods for biomolecular sensing and single DNA manipulation. Nanopore-based DNA sensing has attractive features that make it a leading candidate as a single-molecule DNA sequencing technology. Nanochannel based extension of DNA, combined with enzymatic or denaturation-based barcoding schemes, is already a powerful approach for genome analysis. We believe that there is revolutionary potential in devices that combine nanochannels with nanpore detectors. In particular, due to the fast translocation of a DNA molecule through a standard nanopore configuration, there is an unfavorable trade-off between signal and sequence resolution. With a combined nanochannel-nanopore device, based on embedding a nanopore inside a nanochannel, we can in principle gain independent control over both DNA translocation speed and sensing signal, solving the key draw-back of the standard nanopore configuration. We demonstrate that we can detect - using fluorescent microscopy - successful translocation of DNA from the nanochannel out through the nanopore, a possible method to 'select' a given barcode for further analysis. We also show that in equilibrium DNA will not escape through an embedded sub-persistence length nanopore until a certain voltage bias is added.

  4. Novel injectable, self-gelling hydrogel-microparticle composites for bone regeneration consisting of gellan gum and calcium and magnesium carbonate microparticles.

    PubMed

    Douglas, Timothy E L; Łapa, Agata; Reczyńska, Katarzyna; Krok-Borkowicz, Małgorzata; Pietryga, Krzysztof; Samal, Sangram Keshari; Declercq, Heidi A; Schaubroeck, David; Boone, Marijn; Van der Voort, Pascal; De Schamphelaere, Karel; Stevens, Christian V; Bliznuk, Vitaliy; Balcaen, Lieve; Parakhonskiy, Bogdan V; Vanhaecke, Frank; Cnudde, Veerle; Pamuła, Elżbieta; Skirtach, Andre G

    2016-11-21

    The suitability of hydrogel biomaterials for bone regeneration can be improved by incorporation of an inorganic phase in particle form, thus maintaining hydrogel injectability. In this study, carbonate microparticles containing different amounts of calcium (Ca) and magnesium (Mg) were added to solutions of the anionic polysaccharide gellan gum (GG) to crosslink GG by release of Ca 2+ and Mg 2+ from microparticles and thereby induce formation of hydrogel-microparticle composites. It was hypothesized that increasing Mg content of microparticles would promote GG hydrogel formation. The effect of Mg incorporation on cytocompatibility and cell growth was also studied. Microparticles were formed by mixing Ca 2+ and Mg 2+ and [Formula: see text] ions in varying concentrations. Microparticles were characterized physiochemically and subsequently mixed with GG solution to form hydrogel-microparticle composites. The elemental Ca:Mg ratio in the mineral formed was similar to the Ca:Mg ratio of the ions added. In the absence of Mg, vaterite was formed. At low Mg content, magnesian calcite was formed. Increasing the Mg content further caused formation of amorphous mineral. Microparticles of vaterite and magnesium calcite did not induce GG hydrogel formation, but addition of Mg-richer amorphous microparticles induced gelation within 20 min. Microparticles were dispersed homogeneously in hydrogels. MG-63 osteoblast-like cells were cultured in eluate from hydrogel-microparticle composites and on the composites themselves. All composites were cytocompatible. Cell growth was highest on composites containing particles with an equimolar Ca:Mg ratio. In summary, carbonate microparticles containing a sufficient amount of Mg induced GG hydrogel formation, resulting in injectable, cytocompatible hydrogel-microparticle composites.

  5. Atomic layer deposition of nanoporous biomaterials.

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Narayan, R. J.; Adiga, S. P.; Pellin, M. J.

    2010-03-01

    Due to its chemical stability, uniform pore size, and high pore density, nanoporous alumina is being investigated for use in biosensing, drug delivery, hemodialysis, and other medical applications. In recent work, we have examined the use of atomic layer deposition for coating the surfaces of nanoporous alumina membranes. Zinc oxide coatings were deposited on nanoporous alumina membranes using atomic layer deposition. The zinc oxide-coated nanoporous alumina membranes demonstrated antimicrobial activity against Escherichia coli and Staphylococcus aureus bacteria. These results suggest that atomic layer deposition is an attractive technique for modifying the surfaces of nanoporous alumina membranes and other nanostructured biomaterials.more » Nanoporous alumina, also known as anodic aluminum oxide (AAO), is a nanomaterial that exhibits several unusual properties, including high pore densities, straight pores, small pore sizes, and uniform pore sizes. In 1953, Keller et al. showed that anodizing aluminum in acid electrolytes results in a thick layer of nearly cylindrical pores, which are arranged in a close-packed hexagonal cell structure. More recently, Matsuda & Fukuda demonstrated preparation of highly ordered platinum and gold nanohole arrays using a replication process. In this study, a negative structure of nanoporous alumina was initially fabricated and a positive structure of a nanoporous metal was subsequently fabricated. Over the past fifteen years, nanoporous alumina membranes have been used as templates for growth of a variety of nanostructured materials, including nanotubes, nanowires, nanorods, and nanoporous membranes.« less

  6. Method for determining surface properties of microparticles

    DOEpatents

    Eisenthal, Kenneth B.

    2000-01-01

    Second harmonic generation (SHG), sum frequency generation (SFG) and difference frequency generation (DFG) can be used for surface analysis or characterization of microparticles having a non-metallic surface feature. The microparticles can be centrosymmetric or such that non-metallic molecules of interest are centrosymmetrically distributed inside and outside the microparticles but not at the surface of the microparticles where the asymmetry aligns the molecules. The signal is quadratic in incident laser intensity or proportional to the product of two incident laser intensities for SFG, it is sharply peaked at the second harmonic wavelength, quadratic in the density of molecules adsorbed onto the microparticle surface, and linear in microparticles density. In medical or pharmacological applications, molecules of interest may be of drugs or toxins, for example.

  7. Microfluidic production of polymeric functional microparticles

    NASA Astrophysics Data System (ADS)

    Jiang, Kunqiang

    This dissertation focuses on applying droplet-based microfluidics to fabricate new classes of polymeric microparticles with customized properties for various applications. The integration of microfluidic techniques with microparticle engineering allows for unprecedented control over particle size, shape, and functional properties. Specifically, three types of microparticles are discussed here: (1) Magnetic and fluorescent chitosan hydrogel microparticles and their in-situ assembly into higher-order microstructures; (2) Polydimethylsiloxane (PDMS) microbeads with phosphorescent properties for oxygen sensing; (3) Macroporous microparticles as biological immunosensors. First, we describe a microfluidic approach to generate monodisperse chitosan hydrogel microparticles that can be further connected in-situ into higher-order microstructures. Microparticles of the biopolymer chitosan are created continuously by contacting an aqueous solution of chitosan at a microfluidic T-junction with a stream of hexadecane containing a nonionic detergent, followed by downstream crosslinking of the generated droplets by a ternary flow of glutaraldehyde. Functional properties of the microparticles can be easily varied by introducing payloads such as magnetic nanoparticles and/or fluorescent dyes into the chitosan solution. We then use these prepared microparticles as "building blocks" and assemble them into high ordered microstructures, i.e. microchains with controlled geometry and flexibility. Next, we describe a new approach to produce monodisperse microbeads of PDMS using microfluidics. Using a flow-focusing configuration, a PDMS precursor solution is dispersed into microdroplets within an aqueous continuous phase. These droplets are collected and thermally cured off-chip into soft, solid microbeads. In addition, our technique allows for direct integration of payloads, such as an oxygen-sensitive porphyrin dye, into the PDMS microbeads. We then show that the resulting dye

  8. Controlled Electrospray Generation of Nonspherical Alginate Microparticles.

    PubMed

    Jeyhani, Morteza; Mak, Sze Yi; Sammut, Stephen; Shum, Ho Cheung; Hwang, Dae Kun; Tsai, Scott S H

    2017-12-11

    Electrospraying is a technique used to generate microparticles in a high throughput manner. For biomedical applications, a biocompatible electrosprayed material is often desirable. Using polymers, such as alginate hydrogels, makes it possible to create biocompatible and biodegradable microparticles that can be used for cell encapsulation, to be employed as drug carriers, and for use in 3D cell culturing. Evidence in the literature suggests that the morphology of the biocompatible microparticles is relevant in controlling the dynamics of the microparticles in drug delivery and 3D cell culturing applications. Yet, most electrospray-based techniques only form spherical microparticles, and there is currently no widely adopted technique for producing nonspherical microparticles at a high throughput. Here, we demonstrate the generation of nonspherical biocompatible alginate microparticles by electrospraying, and control the shape of the microparticles by varying experimental parameters such as chemical concentration and the distance between the electrospray tip and the particle-solidification bath. Importantly, we show that these changes to the experimental setup enable the synthesis of different shaped particles, and the systematic change in parameters, such as chemical concentration, result in monotonic changes to the particle aspect ratio. We expect that these results will find utility in many biomedical applications that require biocompatible microparticles of specific shapes. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Noise Properties of Rectifying Nanopores

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Powell, M R; Sa, N; Davenport, M

    2011-02-18

    Ion currents through three types of rectifying nanoporous structures are studied and compared for the first time: conically shaped polymer nanopores, glass nanopipettes, and silicon nitride nanopores. Time signals of ion currents are analyzed by power spectrum. We focus on the low-frequency range where the power spectrum magnitude scales with frequency, f, as 1/f. Glass nanopipettes and polymer nanopores exhibit non-equilibrium 1/f noise, thus the normalized power spectrum depends on the voltage polarity and magnitude. In contrast, 1/f noise in rectifying silicon nitride nanopores is of equilibrium character. Various mechanisms underlying the voltage-dependent 1/f noise are explored and discussed, includingmore » intrinsic pore wall dynamics, and formation of vortices and non-linear flow patterns in the pore. Experimental data are supported by modeling of ion currents based on the coupled Poisson-Nernst-Planck and Navier Stokes equations. We conclude that the voltage-dependent 1/f noise observed in polymer and glass asymmetric nanopores might result from high and asymmetric electric fields inducing secondary effects in the pore such as enhanced water dissociation.« less

  10. Noise Properties of Rectifying Nanopore

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Vlassiouk, Ivan V

    2011-01-01

    Ion currents through three types of rectifying nanoporous structures are studied and compared: conically shaped polymer nanopores, glass nanopipettes, and silicon nitride nanopores. Time signals of ion currents are analyzed by the power spectrum. We focus on the low-frequency range where the power spectrum magnitude scales with frequency, f, as 1/f. Glass nanopipettes and polymer nanopores exhibit nonequilibrium 1/f noise; thus, the normalized power spectrum depends on the voltage polarity and magnitude. In contrast, 1/f noise in rectifying silicon nitride nanopores is of equilibrium character. Various mechanisms underlying the voltage-dependent 1/f noise are explored and discussed, including intrinsic pore wallmore » dynamics and formation of vortices and nonlinear flow patterns in the pore. Experimental data are supported by modeling of ion currents based on the coupled Poisson-Nernst-Planck and Navier-Stokes equations. We conclude that the voltage-dependent 1/f noise observed in polymer and glass asymmetric nanopores might result from high and asymmetric electric fields, inducing secondary effects in the pore, such as enhanced water dissociation.« less

  11. Expanding the functionality and applications of nanopore sensors

    NASA Astrophysics Data System (ADS)

    Venta, Kimberly E.

    Nanopore sensors have developed into powerful tools for single-molecule studies since their inception two decades ago. Nanopore sensors function as nanoscale Coulter counters, by monitoring ionic current modulations as particles pass through a nanopore. While nanopore sensors can be used to study any nanoscale particle, their most notable application is as a low cost, fast alternative to current DNA sequencing technologies. In recent years, signifcant progress has been made toward the goal of nanopore-based DNA sequencing, which requires an ambitious combination of a low-noise and high-bandwidth nanopore measurement system and spatial resolution. In this dissertation, nanopore sensors in thin membranes are developed to improve dimensional resolution, and these membranes are used in parallel with a high-bandwidth amplfier. Using this nanopore sensor system, the signals of three DNA homopolymers are differentiated for the first time in solid-state nanopores. The nanopore noise is also reduced through the addition of a layer of SU8, a spin-on polymer, to the supporting chip structure. By increasing the temporal and spatial resolution of nanopore sensors, studies of shorter molecules are now possible. Nanopore sensors are beginning to be used for the study and characterization of nanoparticles. Nanoparticles have found many uses from biomedical imaging to next-generation solar cells. However, further insights into the formation and characterization of nanoparticles would aid in developing improved synthesis methods leading to more effective and customizable nanoparticles. This dissertation presents two methods of employing nanopore sensors to benet nanoparticle characterization and fabrication. Nanopores were used to study the formation of individual nanoparticles and serve as nanoparticle growth templates that could be exploited to create custom nanoparticle arrays. Additionally, nanopore sensors were used to characterize the surface charge density of anisotropic

  12. Threading DNA through nanopores for biosensing applications

    NASA Astrophysics Data System (ADS)

    Fyta, Maria

    2015-07-01

    This review outlines the recent achievements in the field of nanopore research. Nanopores are typically used in single-molecule experiments and are believed to have a high potential to realize an ultra-fast and very cheap genome sequencer. Here, the various types of nanopore materials, ranging from biological to 2D nanopores are discussed together with their advantages and disadvantages. These nanopores can utilize different protocols to read out the DNA nucleobases. Although, the first nanopore devices have reached the market, many still have issues which do not allow a full realization of a nanopore sequencer able to sequence the human genome in about a day. Ways to control the DNA, its dynamics and speed as the biomolecule translocates the nanopore in order to increase the signal-to-noise ratio in the reading-out process are examined in this review. Finally, the advantages, as well as the drawbacks in distinguishing the DNA nucleotides, i.e., the genetic information, are presented in view of their importance in the field of nanopore sequencing.

  13. Microparticle Flow Sensor

    NASA Technical Reports Server (NTRS)

    Morrison, Dennis R.

    2005-01-01

    The microparticle flow sensor (MFS) is a system for identifying and counting microscopic particles entrained in a flowing liquid. The MFS includes a transparent, optoelectronically instrumented laminar-flow chamber (see figure) and a computer for processing instrument-readout data. The MFS could be used to count microparticles (including micro-organisms) in diverse applications -- for example, production of microcapsules, treatment of wastewater, pumping of industrial chemicals, and identification of ownership of liquid products.

  14. Nanoporous frameworks exhibiting multiple stimuli responsiveness

    NASA Astrophysics Data System (ADS)

    Kundu, Pintu K.; Olsen, Gregory L.; Kiss, Vladimir; Klajn, Rafal

    2014-04-01

    Nanoporous frameworks are polymeric materials built from rigid molecules, which give rise to their nanoporous structures with applications in gas sorption and storage, catalysis and others. Conceptually new applications could emerge, should these beneficial properties be manipulated by external stimuli in a reversible manner. One approach to render nanoporous frameworks responsive to external signals would be to immobilize molecular switches within their nanopores. Although the majority of molecular switches require conformational freedom to isomerize, and switching in the solid state is prohibited, the nanopores may provide enough room for the switches to efficiently isomerize. Here we describe two families of nanoporous materials incorporating the spiropyran molecular switch. These materials exhibit a variety of interesting properties, including reversible photochromism and acidochromism under solvent-free conditions, light-controlled capture and release of metal ions, as well reversible chromism induced by solvation/desolvation.

  15. Microparticles with hierarchical porosity

    DOEpatents

    Petsev, Dimiter N; Atanassov, Plamen; Pylypenko, Svitlana; Carroll, Nick; Olson, Tim

    2012-12-18

    The present disclosure provides oxide microparticles with engineered hierarchical porosity and methods of manufacturing the same. Also described are structures that are formed by templating, impregnating, and/or precipitating the oxide microparticles and method for forming the same. Suitable applications include catalysts, electrocatalysts, electrocatalysts support materials, capacitors, drug delivery systems, sensors and chromatography.

  16. Intracellular origin and ultrastructure of platelet-derived microparticles.

    PubMed

    Ponomareva, A A; Nevzorova, T A; Mordakhanova, E R; Andrianova, I A; Rauova, L; Litvinov, R I; Weisel, J W

    2017-08-01

    Essentials Platelet microparticles play a major role in pathologies, including hemostasis and thrombosis. Platelet microparticles have been analyzed and classified based on their ultrastructure. The structure and intracellular origin of microparticles depend on the cell-activating stimulus. Thrombin-treated platelets fall apart and form microparticles that contain cellular organelles. Background Platelet-derived microparticles comprise the major population of circulating blood microparticles that play an important role in hemostasis and thrombosis. Despite numerous studies on the (patho)physiological roles of platelet-derived microparticles, mechanisms of their formation and structural details remain largely unknown. Objectives Here we studied the formation, ultrastructure and composition of platelet-derived microparticles from isolated human platelets, either quiescent or stimulated with one of the following activators: arachidonic acid, ADP, collagen, thrombin or calcium ionophore A23187. Methods Using flow cytometry, transmission and scanning electron microscopy, we analyzed the intracellular origin, structural diversity and size distributions of the subcellular particles released from platelets. Results The structure, dimensions and intracellular origin of microparticles depend on the cell-activating stimulus. The main structural groups include a vesicle surrounded by one thin membrane or multivesicular structures. Thrombin, unlike other stimuli, induced formation of microparticles not only from the platelet plasma membrane and cytoplasm but also from intracellular structures. A fraction of these vesicular particles having an intracellular origin contained organelles, such as mitochondria, glycogen granules and vacuoles. The size of platelet-derived microparticles depended on the nature of the cell-activating stimulus. Conclusion The results obtained provide a structural basis for the qualitative differences of various platelet activators, for specific

  17. Nanopore-CMOS Interfaces for DNA Sequencing

    PubMed Central

    Magierowski, Sebastian; Huang, Yiyun; Wang, Chengjie; Ghafar-Zadeh, Ebrahim

    2016-01-01

    DNA sequencers based on nanopore sensors present an opportunity for a significant break from the template-based incumbents of the last forty years. Key advantages ushered by nanopore technology include a simplified chemistry and the ability to interface to CMOS technology. The latter opportunity offers substantial promise for improvement in sequencing speed, size and cost. This paper reviews existing and emerging means of interfacing nanopores to CMOS technology with an emphasis on massively-arrayed structures. It presents this in the context of incumbent DNA sequencing techniques, reviews and quantifies nanopore characteristics and models and presents CMOS circuit methods for the amplification of low-current nanopore signals in such interfaces. PMID:27509529

  18. Nanopore-CMOS Interfaces for DNA Sequencing.

    PubMed

    Magierowski, Sebastian; Huang, Yiyun; Wang, Chengjie; Ghafar-Zadeh, Ebrahim

    2016-08-06

    DNA sequencers based on nanopore sensors present an opportunity for a significant break from the template-based incumbents of the last forty years. Key advantages ushered by nanopore technology include a simplified chemistry and the ability to interface to CMOS technology. The latter opportunity offers substantial promise for improvement in sequencing speed, size and cost. This paper reviews existing and emerging means of interfacing nanopores to CMOS technology with an emphasis on massively-arrayed structures. It presents this in the context of incumbent DNA sequencing techniques, reviews and quantifies nanopore characteristics and models and presents CMOS circuit methods for the amplification of low-current nanopore signals in such interfaces.

  19. Transport of Proteins through Nanopores

    NASA Astrophysics Data System (ADS)

    Luan, Binquan

    In biological cells, a malfunctioned protein (such as misfolded or damaged) is degraded by a protease in which an unfoldase actively drags the protein into a nanopore-like structure and then a peptidase cuts the linearized protein into small fragments (i.e. a recycling process). Mimicking this biological process, many experimental studies have focused on the transport of proteins through a biological protein pore or a synthetic solid-state nanopore. Potentially, the nanopore-based sensors can provide a platform for interrogating proteins that might be disease-related or be targeted by a new drug molecule. The single-profile of a protein chain inside an extremely small nanopore might even permit the sequencing of the protein. Here, through all-atom molecular dynamics simulations, I will show various types of protein transport through a nanopore and reveal the nanoscale mechanics/energetics that plays an important role governing the protein transport.

  20. A nanoporous gold membrane for sensing applications

    PubMed Central

    Oo, Swe Zin; Silva, Gloria; Carpignano, Francesca; Noual, Adnane; Pechstedt, Katrin; Mateos, Luis; Grant-Jacob, James A.; Brocklesby, Bill; Horak, Peter; Charlton, Martin; Boden, Stuart A.; Melvin, Tracy

    2016-01-01

    Design and fabrication of three-dimensionally structured, gold membranes containing hexagonally close-packed microcavities with nanopores in the base, are described. Our aim is to create a nanoporous structure with localized enhancement of the fluorescence or Raman scattering at, and in the nanopore when excited with light of approximately 600 nm, with a view to provide sensitive detection of biomolecules. A range of geometries of the nanopore integrated into hexagonally close-packed assemblies of gold micro-cavities was first evaluated theoretically. The optimal size and shape of the nanopore in a single microcavity were then considered to provide the highest localized plasmon enhancement (of fluorescence or Raman scattering) at the very center of the nanopore for a bioanalyte traversing through. The optimized design was established to be a 1200 nm diameter cavity of 600 nm depth with a 50 nm square nanopore with rounded corners in the base. A gold 3D-structured membrane containing these sized microcavities with the integrated nanopore was successfully fabricated and ‘proof of concept’ Raman scattering experiments are described. PMID:26973809

  1. Building membrane nanopores

    NASA Astrophysics Data System (ADS)

    Howorka, Stefan

    2017-07-01

    Membrane nanopores--hollow nanoscale barrels that puncture biological or synthetic membranes--have become powerful tools in chemical- and biosensing, and have achieved notable success in portable DNA sequencing. The pores can be self-assembled from a variety of materials, including proteins, peptides, synthetic organic compounds and, more recently, DNA. But which building material is best for which application, and what is the relationship between pore structure and function? In this Review, I critically compare the characteristics of the different building materials, and explore the influence of the building material on pore structure, dynamics and function. I also discuss the future challenges of developing nanopore technology, and consider what the next-generation of nanopore structures could be and where further practical applications might emerge.

  2. Microparticles prepared from sulfenamide-based polymers

    PubMed Central

    D’Mello, Sheetal R.; Yoo, Jun; Bowden, Ned B.; Salem, Aliasger K.

    2015-01-01

    Polysulfenamides (PSN), with a SN linkage (RSNR2) along the polymer backbone, are a new class of biodegradable and biocompatible polymers. These polymers were unknown prior to 2012 when their synthesis and medicinally relevant properties were reported. The aim of this study was to develop microparticles as a controlled drug delivery system using polysulfenamide as the matrix material. The microparticles were prepared by a water-in-oil-in-water double emulsion solvent evaporation method. For producing drug-loaded particles, FITC-dextran was used as a model hydrophilic compound. At the optimal formulation conditions, the external morphology of the PSN microparticles was examined by scanning electron microscopy to show the formation of smooth-surfaced spherical particles with low polydispersity. The microparticles had a net negative surface charge (−23 mV) as analyzed by the zetasizer. The drug encapsulation efficiency of the particles and the drug loading were found to be dependent on the drug molecular weight, amount of FITC-dextran used in fabricating FITC-dextran loaded microparticles, concentration of PSN and surfactant, and volume of the internal and external water phases. FITC-dextran was found to be distributed throughout the PSN microparticles and was released in an initial burst followed by more continuous release over time. Confocal laser scanning microscopy was used to qualitatively observe the cellular uptake of PSN microparticles and indicated localization of the particles in both the cytoplasm and the nucleus. PMID:23862723

  3. In situ heavy ion irradiation studies of nanopore shrinkage and enhanced radiation tolerance of nanoporous Au

    DOE PAGES

    Li, Jin; Fan, Cuncai; Ding, Jie; ...

    2017-01-03

    High energy particle radiations induce severe microstructural damage in metallic materials. Nanoporous materials with a giant surface-to-volume ratio may alleviate radiation damage in irradiated metallic materials as free surface are defect sinks. We show, by using in situ Kr ion irradiation in a transmission electron microscope at room temperature, that nanoporous Au indeed has significantly improved radiation tolerance comparing with coarse-grained, fully dense Au. In situ studies show that nanopores can absorb and eliminate a large number of radiation-induced defect clusters. Meanwhile, nanopores shrink (self-heal) during radiation, and their shrinkage rate is pore size dependent. Furthermore, the in situ studiesmore » show dose-rate-dependent diffusivity of defect clusters. Our study sheds light on the design of radiation-tolerant nanoporous metallic materials for advanced nuclear reactor applications.« less

  4. Leukocyte- and endothelial-derived microparticles: a circulating source for fibrinolysis

    PubMed Central

    Lacroix, Romaric; Plawinski, Laurent; Robert, Stéphane; Doeuvre, Loïc; Sabatier, Florence; Martinez de Lizarrondo, Sara; Mezzapesa, Anna; Anfosso, Francine; Leroyer, Aurelie S.; Poullin, Pascale; Jourde, Noémie; Njock, Makon-Sébastien; Boulanger, Chantal M.; Anglés-Cano, Eduardo; Dignat-George, Françoise

    2012-01-01

    Background We recently assigned a new fibrinolytic function to cell-derived microparticles in vitro. In this study we explored the relevance of this novel property of microparticles to the in vivo situation. Design and Methods Circulating microparticles were isolated from the plasma of patients with thrombotic thrombocytopenic purpura or cardiovascular disease and from healthy subjects. Microparticles were also obtained from purified human blood cell subpopulations. The plasminogen activators on microparticles were identified by flow cytometry and enzyme-linked immunosorbent assays; their capacity to generate plasmin was quantified with a chromogenic assay and their fibrinolytic activity was determined by zymography. Results Circulating microparticles isolated from patients generate a range of plasmin activity at their surface. This property was related to a variable content of urokinase-type plasminogen activator and/or tissue plasminogen activator. Using distinct microparticle subpopulations, we demonstrated that plasmin is generated on endothelial and leukocyte microparticles, but not on microparticles of platelet or erythrocyte origin. Leukocyte-derived microparticles bear urokinase-type plasminogen activator and its receptor whereas endothelial microparticles carry tissue plasminogen activator and tissue plasminogen activator/inhibitor complexes. Conclusions Endothelial and leukocyte microparticles, bearing respectively tissue plasminogen activator or urokinase-type plasminogen activator, support a part of the fibrinolytic activity in the circulation which is modulated in pathological settings. Awareness of this blood-borne fibrinolytic activity conveyed by microparticles provides a more comprehensive view of the role of microparticles in the hemostatic equilibrium. PMID:22733025

  5. Detection and quantification of microparticles from different cellular lineages using flow cytometry. Evaluation of the impact of secreted phospholipase A2 on microparticle assessment.

    PubMed

    Rousseau, Matthieu; Belleannee, Clemence; Duchez, Anne-Claire; Cloutier, Nathalie; Levesque, Tania; Jacques, Frederic; Perron, Jean; Nigrovic, Peter A; Dieude, Melanie; Hebert, Marie-Josee; Gelb, Michael H; Boilard, Eric

    2015-01-01

    Microparticles, also called microvesicles, are submicron extracellular vesicles produced by plasma membrane budding and shedding recognized as key actors in numerous physio(patho)logical processes. Since they can be released by virtually any cell lineages and are retrieved in biological fluids, microparticles appear as potent biomarkers. However, the small dimensions of microparticles and soluble factors present in body fluids can considerably impede their quantification. Here, flow cytometry with improved methodology for microparticle resolution was used to detect microparticles of human and mouse species generated from platelets, red blood cells, endothelial cells, apoptotic thymocytes and cells from the male reproductive tract. A family of soluble proteins, the secreted phospholipases A2 (sPLA2), comprises enzymes concomitantly expressed with microparticles in biological fluids and that catalyze the hydrolysis of membrane phospholipids. As sPLA2 can hydrolyze phosphatidylserine, a phospholipid frequently used to assess microparticles, and might even clear microparticles, we further considered the impact of relevant sPLA2 enzymes, sPLA2 group IIA, V and X, on microparticle quantification. We observed that if enriched in fluids, certain sPLA2 enzymes impair the quantification of microparticles depending on the species studied, the source of microparticles and the means of detection employed (surface phosphatidylserine or protein antigen detection). This study provides analytical considerations for appropriate interpretation of microparticle cytofluorometric measurements in biological samples containing sPLA2 enzymes.

  6. Graphene nanopore devices for DNA sensing.

    PubMed

    Merchant, Chris A; Drndić, Marija

    2012-01-01

    We describe here a method for detecting the translocation of individual DNA molecules through nanopores created in graphene membranes. The devices consist of 1-5-nm thick graphene membranes with electron-beam sculpted nanopores from 5 to 10 nm in diameter. Due to the thin nature of the graphene membranes, and the reduced electrical resistance, we observe larger blocked currents than for traditional solid-state nanopores. We also show how ionic current noise levels can be reduced with the atomic-layer deposition of a few nanometers of titanium dioxide over the graphene surface. Unlike traditional solid-state nanopore materials that are insulating, graphene is an excellent electrical conductor, and its use opens the door to a new future class of nanopore devices in which electronic sensing and control is performed directly at the pore.

  7. Ion transport in a pH-regulated nanopore.

    PubMed

    Yeh, Li-Hsien; Zhang, Mingkan; Qian, Shizhi

    2013-08-06

    Fundamental understanding of ion transport phenomena in nanopores is crucial for designing the next-generation nanofluidic devices. Due to surface reactions of dissociable functional groups on the nanopore wall, the surface charge density highly depends upon the proton concentration on the nanopore wall, which in turn affects the electrokinetic transport of ions, fluid, and particles within the nanopore. Electrokinetic ion transport in a pH-regulated nanopore, taking into account both multiple ionic species and charge regulation on the nanopore wall, is theoretically investigated for the first time. The model is verified by the experimental data of nanopore conductance available in the literature. The results demonstrate that the spatial distribution of the surface charge density at the nanopore wall and the resulting ion transport phenomena, such as ion concentration polarization (ICP), ion selectivity, and conductance, are significantly affected by the background solution properties, such as the pH and salt concentration.

  8. Effects of Inhalable Microparticles of Seonpyejeongcheon-Tang in an Asthma Mouse Model: - Effects of Microparticles of SJT.

    PubMed

    Yang, Won-Kyung; Lee, Chul-Hwa; Kim, Min-Hee; Kim, Seung-Hyeong; Choi, Hae-Yoon; Yeo, Yoon; Park, Yang-Chun

    2016-12-01

    Allergic asthma generally presents with symptoms of wheezing, coughing, breathlessness, and airway inflammation. Seonpyejeongcheon-tang (SJT) consists of 12 herbs. It originated from Jeongcheon-tang (JT), also known as Ding-chuan-tang, composed of 7 herbs, in She-sheng-zhong-miao-fang. This study aimed to evaluate the effects of local delivery of SJT via inhalable microparticles in an asthma mouse model. Microparticles containing SJT were produced by spray-drying with leucine as an excipient. SJT microparticles were evaluated with respect to their aerodynamic properties, in vitro cytotoxicity, in vivo toxicity, and therapeutic effects on ovalbumin (OVA)-induced asthma in comparison with orally-administered SJT. SJT microparticles provided desirable aerodynamic properties (fine particle fraction of 48.9% ± 6.4% and mass median aerodynamic diameter of 3.7 ± 0.3 μm). SJT microparticles did not show any cytotoxicity against RAW 264.7 macrophages at concentrations of 0.01 - 3 mg/mL. Inhaled SJT microparticles decreased the levels of IL-4, IL-5, IL-13, IL-17A, eotaxin and OVA-IgE in bronchoalveolar lavage fluid (BALF) in mice with OVA-induced asthma. These effects were verified by histological evaluation of the levels of infiltration of inflammatory cells and collagen, destructions of alveoli and bronchioles, and hyperplasia of goblet cells in lung tissues. The effects of SJT microparticles in the asthma model were equivalent to those of orally-administered SJT extract. This study suggests that SJT is a promising agent for inhalation therapy for patients with asthma.

  9. Marathon running increases circulating endothelial- and thrombocyte-derived microparticles.

    PubMed

    Schwarz, Viktoria; Düsing, Philip; Liman, Thomas; Werner, Christian; Herm, Juliane; Bachelier, Katrin; Krüll, Matthias; Brechtel, Lars; Jungehulsing, Gerhard J; Haverkamp, Wilhelm; Böhm, Michael; Endres, Matthias; Haeusler, Karl Georg; Laufs, Ulrich

    2018-02-01

    Background Acute vascular effects of high intensity physical activity are incompletely characterized. Circulating microparticles are cellular markers for vascular activation and damage. Methods Microparticles were analysed in 99 marathon runners (49 ± 6 years, 22% female) of the prospective Berlin Beat of Running study. Blood samples were taken within three days before, immediately after and within two days after the marathon run. Endothelial-derived microparticles were labelled with CD144, CD31 and CD62E, platelet-derived microparticles with CD62P and CD42b, leukocyte-derived microparticles with CD45 and monocyte-derived microparticles with CD14. Results Marathon running induced leukocytosis (5.9 ± 0.1 to 14.8 ± 0.3 10 9 /l, p < 0.0001) and increased platelet counts (239 ± 4.6 to 281 ± 5.9 10 9 /l, p < 0.0001) immediately after the marathon. Blood monocytes increased and lymphocytes decreased after the run ( p < 0.0001). Endothelial-derived microparticles were acutely increased ( p = 0.008) due to a 23% increase of apoptotic endothelial-derived microparticles ( p = 0.007) and returned to baseline within two days after the marathon. Thrombocyte-derived microparticles acutely increased by 38% accompanied by an increase in activated and apoptotic thrombocyte-derived microparticles ( p ≤ 0.0001) each. Both monocyte- and leukocyte-derived microparticles were decreased immediately after marathon run ( p < 0.0001) and remained below baseline until day 2. Troponin T increased from 12 to 32 ng/l ( p < 0.0001) immediately after the run and returned to baseline after two days. Conclusion Circulating apoptotic endothelial- and thrombocyte-derived microparticles increased after marathon running consistent with an acute pro-thrombotic and pro-inflammatory state. Exercise-induced vascular damage reflected by microparticles could indicate potential mechanisms of post-exertional cardiovascular complications. Further

  10. Injectable nanosilica-chitosan microparticles for bone regeneration applications.

    PubMed

    Gaihre, Bipin; Lecka-Czernik, Beata; Jayasuriya, Ambalangodage C

    2018-01-01

    This study was aimed at assessing the effects of silica nanopowder incorporation into chitosan-tripolyphosphate microparticles with the ultimate goal of improving their osteogenic properties. The microparticles were prepared by simple coacervation technique and silica nanopowder was added at 0% (C), 2.5% (S1), 5% (S2) and 10% (S3) (w/w) to chitosan. We observed that this simple incorporation of silica nanopowder improved the growth and proliferation of osteoblasts along the surface of the microparticles. In addition, the composite microparticles also showed the increased expression of alkaline phosphatase and osteoblast specific genes. We observed a significant increase ( p < 0.05) in the expression of alkaline phosphatase by the cells growing on all sample groups compared to the control (C) groups at day 14. The morphological characterization of these microparticles through scanning electron microscopy showed that these microparticles were well suited to be used as the injectable scaffolds with perfectly spherical shape and size. The incorporation of silica nanopowder altered the nano-roughness of the microparticles as observed through atomic force microscopy scans with roughness values going down from C to S3. The results in this study, taken together, show the potential of chitosan-tripolyphosphate-silica nanopowder microparticles for improved bone regeneration applications.

  11. Polymer-modified opal nanopores.

    PubMed

    Schepelina, Olga; Zharov, Ilya

    2006-12-05

    The surface of nanopores in opal films, assembled from 205 nm silica spheres, was modified with poly(acrylamide) brushes using surface-initiated atom transfer radical polymerization. The colloidal crystal lattice remained unperturbed by the polymerization. The polymer brush thickness was controlled by polymerization time and was monitored by measuring the flux of redox species across the opal film using cyclic voltammetry. The nanopore size and polymer brush thickness were calculated on the basis of the limiting current change. Polymer brush thickness increased over the course of 26 h of polymerization in a logarithmic manner from 1.3 to 8.5 nm, leading to nanopores as small as 7.5 nm.

  12. WS2 nanopores for molecule analysis

    NASA Astrophysics Data System (ADS)

    Danda, Gopinath; Masih Das, Paul; Chou, Yung-Chien; Mlack, Jerome; Naylor, Carl; Perea-Lopez, Nestor; Lin, Zhong; Fulton, Laura Beth; Terrones, Mauricio; Johnson, A. T. Charlie; Drndic, Marija

    Atomically thin 2D materials like graphene and transition metal dichalcogenides (TMDs) are interesting as membranes in solid state nanopore sensors for DNA analysis as they may facilitate single base resolution sequencing. These materials also exhibit unique optical and electronic properties which may be exploited to enhance the functionality of nanopore sensors. Here, we report WS2 nanopores, fabricated using a focused TEM beam. We also report their controlled laser-induced expansion in ionic solution. This study demonstrates the possibility of dynamic control of nanopore characteristics optically. NIH Grant R21HG007856, NSF EFRI-1542707.

  13. Optofluidic devices with integrated solid-state nanopores

    PubMed Central

    Hawkins, Aaron R.; Schmidt, Holger

    2016-01-01

    This review (with 90 refs.) covers the state of the art in optofluidic devices with integrated solid-state nanopores for use in detection and sensing. Following an introduction into principles of optofluidics and solid-state nanopore technology, we discuss features of solid-state nanopore based assays using optofluidics. This includes the incorporation of solid-state nanopores into optofluidic platforms based on liquid-core anti-resonant reflecting optical waveguides (ARROWs), methods for their fabrication, aspects of single particle detection and particle manipulation. We then describe the new functionalities provided by solid-state nanopores integrated into optofluidic chips, in particular acting as smart gates for correlated electro-optical detection and discrimination of nanoparticles. This enables the identification of viruses and λ-DNA, particle trajectory simulations, enhancing sensitivity by tuning the shape of nanopores. The review concludes with a summary and an outlook. PMID:27046940

  14. Controlled formation of closed-edge nanopores in graphene

    NASA Astrophysics Data System (ADS)

    He, Kuang; Robertson, Alex W.; Gong, Chuncheng; Allen, Christopher S.; Xu, Qiang; Zandbergen, Henny; Grossman, Jeffrey C.; Kirkland, Angus I.; Warner, Jamie H.

    2015-07-01

    Dangling bonds at the edge of a nanopore in monolayer graphene make it susceptible to back-filling at low temperatures from atmospheric hydrocarbons, leading to potential instability for nanopore applications, such as DNA sequencing. We show that closed edge nanopores in bilayer graphene are robust to back-filling under atmospheric conditions for days. A controlled method for closed edge nanopore formation starting from monolayer graphene is reported using an in situ heating holder and electron beam irradiation within an aberration-corrected transmission electron microscopy. Tailoring of closed-edge nanopore sizes is demonstrated from 1.4-7.4 nm. These results should provide mechanisms for improving the stability of nanopores in graphene for a wide range of applications involving mass transport.Dangling bonds at the edge of a nanopore in monolayer graphene make it susceptible to back-filling at low temperatures from atmospheric hydrocarbons, leading to potential instability for nanopore applications, such as DNA sequencing. We show that closed edge nanopores in bilayer graphene are robust to back-filling under atmospheric conditions for days. A controlled method for closed edge nanopore formation starting from monolayer graphene is reported using an in situ heating holder and electron beam irradiation within an aberration-corrected transmission electron microscopy. Tailoring of closed-edge nanopore sizes is demonstrated from 1.4-7.4 nm. These results should provide mechanisms for improving the stability of nanopores in graphene for a wide range of applications involving mass transport. Electronic supplementary information (ESI) available: Low magnification images, image processing techniques employed, modelling and simulation of closed edge nanoribbon, comprehensive AC-TEM dataset, and supporting analysis. See DOI: 10.1039/c5nr02277k

  15. The Influence of Nanopore Dimensions on the Electrochemical Properties of Nanopore Arrays Studied by Impedance Spectroscopy

    PubMed Central

    Kant, Krishna; Priest, Craig; Shapter, Joe G.; Losic, Dusan

    2014-01-01

    The understanding of the electrochemical properties of nanopores is the key factor for better understanding their performance and applications for nanopore-based sensing devices. In this study, the influence of pore dimensions of nanoporous alumina (NPA) membranes prepared by an anodization process and their electrochemical properties as a sensing platform using impedance spectroscopy was explored. NPA with four different pore diameters (25 nm, 45 nm and 65 nm) and lengths (5 μm to 20 μm) was used and their electrochemical properties were explored using different concentration of electrolyte solution (NaCl) ranging from 1 to 100 μM. Our results show that the impedance and resistance of nanopores are influenced by the concentration and ion species of electrolytes, while the capacitance is independent of them. It was found that nanopore diameters also have a significant influence on impedance due to changes in the thickness of the double layer inside the pores. PMID:25393785

  16. Circulating Microparticles Alter Formation, Structure, and Properties of Fibrin Clots.

    PubMed

    Zubairova, Laily D; Nabiullina, Roza M; Nagaswami, Chandrasekaran; Zuev, Yuriy F; Mustafin, Ilshat G; Litvinov, Rustem I; Weisel, John W

    2015-12-04

    Despite the importance of circulating microparticles in haemostasis and thrombosis, there is limited evidence for potential causative effects of naturally produced cell-derived microparticles on fibrin clot formation and its properties. We studied the significance of blood microparticles for fibrin formation, structure, and susceptibility to fibrinolysis by removing them from platelet-free plasma using filtration. Clots made in platelet-free and microparticle-depleted plasma samples from the same healthy donors were analyzed in parallel. Microparticles accelerate fibrin polymerisation and support formation of more compact clots that resist internal and external fibrinolysis. These variations correlate with faster thrombin generation, suggesting thrombin-mediated kinetic effects of microparticles on fibrin formation, structure, and properties. In addition, clots formed in the presence of microparticles, unlike clots from the microparticle-depleted plasma, contain 0.1-0.5-μm size granular and CD61-positive material on fibres, suggesting that platelet-derived microparticles attach to fibrin. Therefore, the blood of healthy individuals contains functional microparticles at the levels that have a procoagulant potential. They affect the structure and stability of fibrin clots indirectly through acceleration of thrombin generation and through direct physical incorporation into the fibrin network. Both mechanisms underlie a potential role of microparticles in haemostasis and thrombosis as modulators of fibrin formation, structure, and resistance to fibrinolysis.

  17. Ca:Mg:Zn:CO3 and Ca:Mg:CO3-tri- and bi-elemental carbonate microparticles for novel injectable self-gelling hydrogel-microparticle composites for tissue regeneration.

    PubMed

    Douglas, Timothy E L; Sobczyk, Katarzyna; Łapa, Agata; Włodarczyk, Katarzyna; Brackman, Gilles; Vidiasheva, Irina; Reczyńska, Katarzyna; Pietryga, Krzysztof; Schaubroeck, David; Bliznuk, Vitaliy; Voort, Pascal Van Der; Declercq, Heidi A; Bulcke, Jan Van den; Samal, Sangram Keshari; Khalenkow, Dmitry; Parakhonskiy, Bogdan V; Van Acker, Joris; Coenye, Tom; Lewandowska-Szumieł, Małgorzata; Pamuła, Elżbieta; Skirtach, Andre G

    2017-03-24

    Injectable composites for tissue regeneration can be developed by dispersion of inorganic microparticles and cells in a hydrogel phase. In this study, multifunctional carbonate microparticles containing different amounts of calcium, magnesium and zinc were mixed with solutions of gellan gum (GG), an anionic polysaccharide, to form injectable hydrogel-microparticle composites, containing Zn, Ca and Mg. Zn and Ca were incorporated into microparticle preparations to a greater extent than Mg. Microparticle groups were heterogeneous and contained microparticles of differing shape and elemental composition. Zn-rich microparticles were 'star shaped' and appeared to consist of small crystallites, while Zn-poor, Ca- and Mg-rich microparticles were irregular in shape and appeared to contain lager crystallites. Zn-free microparticle groups exhibited the best cytocompatibility and, unexpectedly, Zn-free composites showed the highest antibacterial activity towards methicilin-resistant Staphylococcus aureus. Composites containing Zn-free microparticles were cytocompatible and therefore appear most suitable for applications as an injectable biomaterial. This study proves the principle of creating bi- and tri-elemental microparticles to induce the gelation of GG to create injectable hydrogel-microparticle composites.

  18. Ultra-Thin Solid-State Nanopores: Fabrication and Applications

    NASA Astrophysics Data System (ADS)

    Kuan, Aaron Tzeyang

    Solid-state nanopores are a nanofluidic platform with unique advantages for single-molecule analysis and filtration applications. However, significant improvements in device performance and scalable fabrication methods are needed to make nanopore devices competitive with existing technologies. This dissertation investigates the potential advantages of ultra-thin nanopores in which the thickness of the membrane is significantly smaller than the nanopore diameter. Novel, scalable fabrication methods were first developed and then utilized to examine device performance for water filtration and single molecule sensing applications. Fabrication of nanometer-thin pores in silicon nitride membranes was achieved using a feedback-controlled ion beam method in which ion sputtering is arrested upon detection of the first few ions that drill through the membrane. Performing fabrication at liquid nitrogen temperatures prevents surface atom rearrangements that have previously complicated similar processes. A novel cross-sectional imaging method was also developed to allow careful examination of the full nanopore geometry. Atomically-thin graphene nanopores were fabricated via an electrical pulse method in which sub-microsecond electrical pulses applied across a graphene membrane in electrolyte solution are used to create a defect in the membrane and controllably enlarge it into a nanopore. This method dramatically increases the accuracy and reliability of graphene nanopore production, allowing consistent production of single nanopores down to subnanometer sizes. In filtration applications in which nanopores are used to selectively restrict the passage of dissolved contaminants, ultra-thin nanopores minimize the flow resistance, increasing throughput and energy-efficiency. The ability of graphene nanopores to separate different ions was characterized via ionic conductance and reversal potential measurements. Graphene nanopores were observed to conduct cations preferentially over

  19. Orodispersible films and tablets with prednisolone microparticles.

    PubMed

    Brniak, Witold; Maślak, Ewelina; Jachowicz, Renata

    2015-07-30

    Orodispersible tablets (ODTs) and orodispersible films (ODFs) are solid oral dosage forms disintegrating or dissolving rapidly when placed in the mouth. One of the main issues related to their preparation is an efficient taste masking of a bitter drug substance. Therefore, the aim of this study was to prepare and evaluate the microparticles intended to mask a bitter taste of the prednisolone and use them in further preparation of two orodispersible dosage forms. Microparticles based on the Eudragit E PO or E 100 as a taste-masking agent were prepared with spray-drying technique. Tablets containing microparticles, co-processed ODT excipient Pharmaburst, and lubricant were directly compressed with single-punch tablet press. Orodispersible films were prepared by casting polymeric solutions of hydroxypropyl methylcellulose containing uniformly dispersed microparticles. Physicochemical properties of microparticles were evaluated, as well as mechanical properties analysis, disintegration time measurements and dissolution tests were performed for prepared dosage forms. Both formulations showed good mechanical resistance while maintaining excellent disintegration properties. The dissolution studies showed good masking properties of microparticles with Eudragit E 100. The amount of prednisolone released during the first minute in phosphate buffer 6.8 was around 0.1%. After incorporation into the orodispersible forms, the amount of released prednisolone increased significantly. It was probably the effect of faster microparticles wetting in orodispersible forms and their partial destruction by compression force during tableting process. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Heterogeneity in Neutrophil Microparticles Reveals Distinct Proteome and Functional Properties*

    PubMed Central

    Dalli, Jesmond; Montero-Melendez, Trinidad; Norling, Lucy V; Yin, Xiaoke; Hinds, Charles; Haskard, Dorian; Mayr, Manuel; Perretti, Mauro

    2013-01-01

    Altered plasma neutrophil microparticle levels have recently been implicated in a number of vascular and inflammatory diseases, yet our understanding of their actions is very limited. Herein, we investigate the proteome of neutrophil microparticles in order to shed light on their biological actions. Stimulation of human neutrophils, either in suspension or adherent to an endothelial monolayer, led to the production of microparticles containing >400 distinct proteins with only 223 being shared by the two subsets. For instance, postadherent microparticles were enriched in alpha-2 macroglobulin and ceruloplasmin, whereas microparticles produced by neutrophils in suspension were abundant in heat shock 70 kDa protein 1. Annexin A1 and lactotransferrin were expressed in both microparticle subsets. We next determined relative abundance of these proteins in three types of human microparticle samples: healthy volunteer plasma, plasma of septic patients and skin blister exudates finding that these proteins were differentially expressed on neutrophil microparticles from these samples reflecting in part the expression profiles we found in vitro. Functional assessment of the neutrophil microparticles subsets demonstrated that in response to direct stimulation neutrophil microparticles produced reactive oxygen species and leukotriene B4 as well as locomoted toward a chemotactic gradient. Finally, we investigated the actions of the two neutrophil microparticles subsets described herein on target cell responses. Microarray analysis with human primary endothelial cells incubated with either microparticle subset revealed a discrete modulation of endothelial cell gene expression profile. These findings demonstrate that neutrophil microparticles are heterogenous and can deliver packaged information propagating the activation status of the parent cell, potentially exerting novel and fundamental roles both under homeostatic and disease conditions. PMID:23660474

  1. Circulating Microparticles Alter Formation, Structure, and Properties of Fibrin Clots

    PubMed Central

    Zubairova, Laily D.; Nabiullina, Roza M.; Nagaswami, Chandrasekaran; Zuev, Yuriy F.; Mustafin, Ilshat G.; Litvinov, Rustem I.; Weisel, John W.

    2015-01-01

    Despite the importance of circulating microparticles in haemostasis and thrombosis, there is limited evidence for potential causative effects of naturally produced cell-derived microparticles on fibrin clot formation and its properties. We studied the significance of blood microparticles for fibrin formation, structure, and susceptibility to fibrinolysis by removing them from platelet-free plasma using filtration. Clots made in platelet-free and microparticle-depleted plasma samples from the same healthy donors were analyzed in parallel. Microparticles accelerate fibrin polymerisation and support formation of more compact clots that resist internal and external fibrinolysis. These variations correlate with faster thrombin generation, suggesting thrombin-mediated kinetic effects of microparticles on fibrin formation, structure, and properties. In addition, clots formed in the presence of microparticles, unlike clots from the microparticle-depleted plasma, contain 0.1–0.5-μm size granular and CD61-positive material on fibres, suggesting that platelet-derived microparticles attach to fibrin. Therefore, the blood of healthy individuals contains functional microparticles at the levels that have a procoagulant potential. They affect the structure and stability of fibrin clots indirectly through acceleration of thrombin generation and through direct physical incorporation into the fibrin network. Both mechanisms underlie a potential role of microparticles in haemostasis and thrombosis as modulators of fibrin formation, structure, and resistance to fibrinolysis. PMID:26635081

  2. Spray-dried chitosan/acid/NaCl microparticles enhance saltiness perception.

    PubMed

    Yi, Cheng; Tsai, Min-Lang; Liu, Tristan

    2017-09-15

    The composition, physicochemical properties and salinity of spray-dried chitosan/acid/NaCl microparticles were tested to ensure a low-sodium and high-salinity salty agent. The spray-dried chitosan/acid/NaCl microparticles were hollow and had a favourable hygroscopicity, and increased NaCl content and decreased organic acid content. Their size of the microparticles was 15.4-32.0μm and increased with NaCl concentration. The microparticles of acetic and lactic acid groups had a NaCl crystal size of 1-2 and 1-4μm, respectively. The NaCl crystals of acetic, lactic and citric acid group microparticles were distributed on the microparticle matrices, mostly on the microparticle surface and mainly on the inner walls of the microparticles walls, respectively. The acetic and lactic acid group microparticles were relatively smaller than general salt, with NaCl crystals distributed on the particle surfaces. Consequently, they were perceived as saltier than general salt and could potentially be regarded as a low-sodium salt for surface-salted foods. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Recent Advances in Nanoporous Membranes for Water Purification

    PubMed Central

    Wang, Zhuqing; Colombi Ciacchi, Lucio

    2018-01-01

    Nanoporous materials exhibit wide applications in the fields of electrocatalysis, nanodevice fabrication, energy, and environmental science, as well as analytical science. In this review, we present a summary of recent studies on nanoporous membranes for water purification application. The types and fabrication strategies of various nanoporous membranes are first introduced, and then the fabricated nanoporous membranes for removing various water pollutants, such as salt, metallic ions, anions, nanoparticles, organic chemicals, and biological substrates, are demonstrated and discussed. This work will be valuable for readers to understand the design and fabrication of various nanoporous membranes, and their potential purification mechanisms towards different water pollutants. In addition, it will be helpful for developing new nanoporous materials for quick, economic, and high-performance water purification. PMID:29370128

  4. Nanopores formed by DNA origami: a review.

    PubMed

    Bell, Nicholas A W; Keyser, Ulrich F

    2014-10-01

    Nanopores have emerged over the past two decades to become an important technique in single molecule experimental physics and biomolecule sensing. Recently DNA nanotechnology, in particular DNA origami, has been used for the formation of nanopores in insulating materials. DNA origami is a very attractive technique for the formation of nanopores since it enables the construction of 3D shapes with precise control over geometry and surface functionality. DNA origami has been applied to nanopore research by forming hybrid architectures with solid state nanopores and by direct insertion into lipid bilayers. This review discusses recent experimental work in this area and provides an outlook for future avenues and challenges. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  5. Increased circulating leukocyte-derived microparticles in ischemic cerebrovascular disease.

    PubMed

    He, Zhangping; Tang, Yanyan; Qin, Chao

    2017-06-01

    Circulating leukocyte-derived microparticles act as proinflammatory mediators that reflect vascular inflammation. In this study, we examined the hypothesis that the quantity of leukocyte-derived microparticles is increased in patients with ischemic cerebrovascular diseases, and investigated utility of various phenotypes of leukocyte-derived microparticles as specific biomarkers of vascular inflammation injury. Additionally we focused on identifying leukocyte-derived microparticles that may be correlated with stroke severity in acute ischemic stroke patients. The plasma concentration of leukocyte-derived microparticles obtained by a series of centrifugations of 76 consecutive patients with ischemic cerebrovascular diseases and 70 age-, sex-, and race-matched healthy controls were determined by flow cytometry. Significantly elevated numbers of leukocyte (CD45+), monocyte (CD14+), lymphocyte (CD4+), granulocyte (CD15+) derived microparticles were found in the plasma samples of patients ischemic cerebrovascular diseases, compared to healthy controls (p<0.05). Furthermore, the plasma levels of CD14+ microparticles were significantly correlated with stroke severity (r=0.355, p=0.019), cerebral vascular stenosis severity (r=0.255, p=0.025) and stroke subtype (r=0.242, p=0.036). No association with stroke was observed for other leukocyte-derived phenotypes. These results demonstrate that circulating leukocyte-derived microparticles amounts are increased in patients with ischemic cerebrovascular diseases, compared with healthy controls. As proinflammatory mediators, leukocyte-derived microparticles may contribute to vascular inflammatory and the inflammatory process in acute ischemic stroke. Levels of CD14+ microparticles may be a promising biomarker of ischemic severity and outcome of stroke in the clinic. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Solid-State Nanopore.

    PubMed

    Yuan, Zhishan; Wang, Chengyong; Yi, Xin; Ni, Zhonghua; Chen, Yunfei; Li, Tie

    2018-02-20

    Solid-state nanopore has captured the attention of many researchers due to its characteristic of nanoscale. Now, different fabrication methods have been reported, which can be summarized into two broad categories: "top-down" etching technology and "bottom-up" shrinkage technology. Ion track etching method, mask etching method chemical solution etching method, and high-energy particle etching and shrinkage method are exhibited in this report. Besides, we also discussed applications of solid-state nanopore fabrication technology in DNA sequencing, protein detection, and energy conversion.

  7. Solid-State Nanopore

    NASA Astrophysics Data System (ADS)

    Yuan, Zhishan; Wang, Chengyong; Yi, Xin; Ni, Zhonghua; Chen, Yunfei; Li, Tie

    2018-02-01

    Solid-state nanopore has captured the attention of many researchers due to its characteristic of nanoscale. Now, different fabrication methods have been reported, which can be summarized into two broad categories: "top-down" etching technology and "bottom-up" shrinkage technology. Ion track etching method, mask etching method chemical solution etching method, and high-energy particle etching and shrinkage method are exhibited in this report. Besides, we also discussed applications of solid-state nanopore fabrication technology in DNA sequencing, protein detection, and energy conversion.

  8. Fabricatable nanopore sensors with an atomic thickness

    NASA Astrophysics Data System (ADS)

    Luan, Binquan; Bai, Jingwei; Stolovitzky, Gustavo

    2013-10-01

    When analyzing biological molecules (such as DNA and proteins) transported through a nanopore sensor, the pore length limits both the sensitivity and the spatial resolution. Atomically thin as a graphene nanopore is, it is difficult to make graphene pores and the scalable-fabrication of those pores has not yet been possible. We theoretically studied a type of atomically thin nanopores that are formed by intersection of two perpendicular nano-slits. Based on theoretical analyses, we demonstrate that slit nanopores behave similarly to graphene pores and can be manufactured at a wafer scale.

  9. Multitarget sensing of glucose and cholesterol based on Janus hydrogel microparticles.

    PubMed

    Sun, Xiao-Ting; Zhang, Ying; Zheng, Dong-Hua; Yue, Shuai; Yang, Chun-Guang; Xu, Zhang-Run

    2017-06-15

    A visualized sensing method for glucose and cholesterol was developed based on the hemispheres of the same Janus hydrogel microparticles. Single-phase and Janus hydrogel microparticles were both generated using a centrifugal microfluidic chip. For glucose sensing, concanavalin A and fluorescein labeled dextran used for competitive binding assay were encapsulated in alginate microparticles, and the fluorescence of the microparticles was positively correlated with glucose concentration. For cholesterol sensing, the microparticles embedded with γ-Fe 2 O 3 nanoparticles were used as catalyst for the oxidation of 3,3',5,5'-Tetramethylbenzidine by H 2 O 2 , an enzymatic hydrolysis product of cholesterol. And the color transition was more sensitive in the microparticles than in solutions, indicating the microparticles are more applicable for visualized determination. Furthermore, Janus microparticles were employed for multitarget sensing in the two hemespheres, and glucose and cholesterol were detected within the same microparticles without obvious interference. Besides, the particles could be manipulated by an external magnetic field. The glucose and cholesterol levels were measured in human serum utilizing the microparticles, which confirmed the potential application of the microparticles in real sample detection. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Cell-derived microparticles in haemostasis and vascular medicine.

    PubMed

    Burnier, Laurent; Fontana, Pierre; Kwak, Brenda R; Angelillo-Scherrer, Anne

    2009-03-01

    Considerable interest for cell-derived microparticles has emerged, pointing out their essential role in haemostatic response and their potential as disease markers, but also their implication in a wide range of physiological and pathological processes. They derive from different cell types including platelets - the main source of microparticles - but also from red blood cells, leukocytes and endothelial cells, and they circulate in blood. Despite difficulties encountered in analyzing them and disparities of results obtained with a wide range of methods, microparticle generation processes are now better understood. However, a generally admitted definition of microparticles is currently lacking. For all these reasons we decided to review the literature regarding microparticles in their widest definition, including ectosomes and exosomes, and to focus mainly on their role in haemostasis and vascular medicine.

  11. Thermal conductivity model for nanoporous thin films

    NASA Astrophysics Data System (ADS)

    Huang, Congliang; Zhao, Xinpeng; Regner, Keith; Yang, Ronggui

    2018-03-01

    Nanoporous thin films have attracted great interest because of their extremely low thermal conductivity and potential applications in thin thermal insulators and thermoelectrics. Although there are some numerical and experimental studies about the thermal conductivity of nanoporous thin films, a simplified model is still needed to provide a straightforward prediction. In this paper, by including the phonon scattering lifetimes due to film thickness boundary scattering, nanopore scattering and the frequency-dependent intrinsic phonon-phonon scattering, a fitting-parameter-free model based on the kinetic theory of phonon transport is developed to predict both the in-plane and the cross-plane thermal conductivities of nanoporous thin films. With input parameters such as the lattice constants, thermal conductivity, and the group velocity of acoustic phonons of bulk silicon, our model shows a good agreement with available experimental and numerical results of nanoporous silicon thin films. It illustrates that the size effect of film thickness boundary scattering not only depends on the film thickness but also on the size of nanopores, and a larger nanopore leads to a stronger size effect of the film thickness. Our model also reveals that there are different optimal structures for getting the lowest in-plane and cross-plane thermal conductivities.

  12. Single Nanopore Investigations with Ion Conductance Microscopy

    PubMed Central

    Chen, Chiao-Chen; Zhou, Yi; Baker, Lane A.

    2011-01-01

    A three-electrode scanning ion conductance microscope (SICM) was used to investigate the local current-voltage properties of a single nanopore. In this experimental configuration, the response measured is a function of changes in the resistances involved in the pathways of ion migration. Single nanopore membranes utilized in this study were prepared with an epoxy painting procedure to isolate a single nanopore from a track-etch multi-pore membrane. Current-voltage responses measured with the SICM probe in the vicinity of a single nanopore were investigated in detail and agreed well with equivalent circuit models proposed in this study. With this modified SICM, the current-voltage responses characterized for the case of a single cylindrical pore and a single conical pore exhibit distinct conductance properties that originate from the geometry of nanopores. PMID:21923184

  13. Electrospray of multifunctional microparticles for image-guided drug delivery

    NASA Astrophysics Data System (ADS)

    Zhang, Leilei; Yan, Yan; Mena, Joshua; Sun, Jingjing; Letson, Alan; Roberts, Cynthia; Zhou, Chuanqing; Chai, Xinyu; Ren, Qiushi; Xu, Ronald

    2012-03-01

    Anti-VEGF therapies have been widely explored for the management of posterior ocular disease, like neovascular age-related macular degeneration (AMD). Loading anti-VEGF therapies in biodegradable microparticles may enable sustained drug release and improved therapeutic outcome. However, existing microfabrication processes such as double emulsification produce drug-loaded microparticles with low encapsulation rate and poor antibody bioactivity. To overcome these limitations, we fabricate multifunctional microparticles by both single needle and coaxial needle electrospray. The experimental setup for the process includes flat-end syringe needles (both single needle and coaxial needle), high voltage power supplies, and syringe pumps. Microparticles are formed by an electrical field between the needles and the ground electrode. Droplet size and morphology are controlled by multiple process parameters and material properties, such as flow rate and applied voltage. The droplets are collected and freezing dried to obtain multifunctional microparticles. Fluorescent beads encapsulated poly(DL-lactide-co-glycolide) acid (PLGA) microparticles are injected into rabbits eyes through intravitreal injection to test the biodegradable time of microparticles.

  14. Anti-Neutrophil Cytoplasmic Antibodies Stimulate Release of Neutrophil Microparticles

    PubMed Central

    Eleftheriou, Despina; Hussain, Abdullah A.K.; Price-Kuehne, Fiona E.; Savage, Caroline O.; Jayne, David; Little, Mark A.; Salama, Alan D.; Klein, Nigel J.; Brogan, Paul A.

    2012-01-01

    The mechanisms by which anti-neutrophil cytoplasmic antibodies (ANCAs) may contribute to the pathogenesis of ANCA-associated vasculitis are not well understood. In this study, both polyclonal ANCAs isolated from patients and chimeric proteinase 3–ANCA induced the release of neutrophil microparticles from primed neutrophils. These microparticles expressed a variety of markers, including the ANCA autoantigens proteinase 3 and myeloperoxidase. They bound endothelial cells via a CD18-mediated mechanism and induced an increase in endothelial intercellular adhesion molecule-1 expression, production of endothelial reactive oxygen species, and release of endothelial IL-6 and IL-8. Removal of the neutrophil microparticles by filtration or inhibition of reactive oxygen species production with antioxidants abolished microparticle-mediated endothelial activation. In addition, these microparticles promoted the generation of thrombin. In vivo, we detected more neutrophil microparticles in the plasma of children with ANCA-associated vasculitis compared with that in healthy controls or those with inactive vasculitis. Taken together, these results support a role for neutrophil microparticles in the pathogenesis of ANCA-associated vasculitis, potentially providing a target for future therapeutics. PMID:22052057

  15. Preparation and characterization of safe microparticles based on xylan.

    PubMed

    Cartaxo da Costa Urtiga, Silvana; Aquino Azevedo de Lucena Gabi, Camilla; Rodrigues de Araújo Eleamen, Giovanna; Santos Souza, Bartolomeu; Pessôa, Hilzeth de Luna Freire; Marcelino, Henrique Rodrigues; Afonso de Moura Mendonça, Elisângela; Egito, Eryvaldo Sócrates Tabosa do; Oliveira, Elquio Eleamen

    2017-10-01

    This work describes the preparation and evaluation of safe xylan-based microparticles prepared by cross-linking polymerization using sodium trimetaphosphate. The resulting microparticles were evaluated for morphology, particle size, polymer-cross-link agent interaction, and in vitro toxicity. The microparticles showed narrow monodisperse size distributions with their mean sizes being between 3.5 and 12.5 µm in dried state. FT-IR analyzes confirmed the interaction between sodium trimetaphosphate and xylan during the cross-linking process with formation of phosphate ester bonds. Additionally, the X-ray diffraction patterns and FT-IR analyzes suggested that little or no cross-linking agent remained inside the microparticles. Furthermore, the in-vitro studies using Artemia salina and human erythrocytes revealed that the microparticles are not toxic. Therefore, the overall results suggest that these xylan microparticles can be used as a platform for new drug delivery system.

  16. Nanopore sequencing in microgravity

    PubMed Central

    McIntyre, Alexa B R; Rizzardi, Lindsay; Yu, Angela M; Alexander, Noah; Rosen, Gail L; Botkin, Douglas J; Stahl, Sarah E; John, Kristen K; Castro-Wallace, Sarah L; McGrath, Ken; Burton, Aaron S; Feinberg, Andrew P; Mason, Christopher E

    2016-01-01

    Rapid DNA sequencing and analysis has been a long-sought goal in remote research and point-of-care medicine. In microgravity, DNA sequencing can facilitate novel astrobiological research and close monitoring of crew health, but spaceflight places stringent restrictions on the mass and volume of instruments, crew operation time, and instrument functionality. The recent emergence of portable, nanopore-based tools with streamlined sample preparation protocols finally enables DNA sequencing on missions in microgravity. As a first step toward sequencing in space and aboard the International Space Station (ISS), we tested the Oxford Nanopore Technologies MinION during a parabolic flight to understand the effects of variable gravity on the instrument and data. In a successful proof-of-principle experiment, we found that the instrument generated DNA reads over the course of the flight, including the first ever sequenced in microgravity, and additional reads measured after the flight concluded its parabolas. Here we detail modifications to the sample-loading procedures to facilitate nanopore sequencing aboard the ISS and in other microgravity environments. We also evaluate existing analysis methods and outline two new approaches, the first based on a wave-fingerprint method and the second on entropy signal mapping. Computationally light analysis methods offer the potential for in situ species identification, but are limited by the error profiles (stays, skips, and mismatches) of older nanopore data. Higher accuracies attainable with modified sample processing methods and the latest version of flow cells will further enable the use of nanopore sequencers for diagnostics and research in space. PMID:28725742

  17. Highly active thermally stable nanoporous gold catalyst

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Biener, Juergen; Wittstock, Arne; Biener, Monika M.

    In one embodiment, a system includes a nanoporous gold structure and a plurality of oxide particles deposited on the nanoporous gold structure; the oxide particles are characterized by a crystalline phase. In another embodiment, a method includes depositing oxide nanoparticles on a nanoporous gold support to form an active structure and functionalizing the deposited oxide nanoparticles.

  18. Adiabatic burst evaporation from bicontinuous nanoporous membranes

    PubMed Central

    Ichilmann, Sachar; Rücker, Kerstin; Haase, Markus; Enke, Dirk

    2015-01-01

    Evaporation of volatile liquids from nanoporous media with bicontinuous morphology and pore diameters of a few 10 nm is an ubiquitous process. For example, such drying processes occur during syntheses of nanoporous materials by sol–gel chemistry or by spinodal decomposition in the presence of solvents as well as during solution impregnation of nanoporous hosts with functional guests. It is commonly assumed that drying is endothermic and driven by non-equilibrium partial pressures of the evaporating species in the gas phase. We show that nearly half of the liquid evaporates in an adiabatic mode involving burst-like liquid-to-gas conversions. During single adiabatic burst evaporation events liquid volumes of up to 107 μm3 are converted to gas. The adiabatic liquid-to-gas conversions occur if air invasion fronts get unstable because of the built-up of high capillary pressures. Adiabatic evaporation bursts propagate avalanche-like through the nanopore systems until the air invasion fronts have reached new stable configurations. Adiabatic cavitation bursts thus compete with Haines jumps involving air invasion front relaxation by local liquid flow without enhanced mass transport out of the nanoporous medium and prevail if the mean pore diameter is in the range of a few 10 nm. The results reported here may help optimize membrane preparation via solvent-based approaches, solution-loading of nanopore systems with guest materials as well as routine use of nanoporous membranes with bicontinuous morphology and may contribute to better understanding of adsorption/desorption processes in nanoporous media. PMID:25926406

  19. Signal and Noise in FET-Nanopore Devices.

    PubMed

    Parkin, William M; Drndić, Marija

    2018-02-23

    The combination of a nanopore with a local field-effect transistor (FET-nanopore), like a nanoribbon, nanotube, or nanowire, in order to sense single molecules translocating through the pore is promising for DNA sequencing at megahertz bandwidths. Previously, it was experimentally determined that the detection mechanism was due to local potential fluctuations that arise when an analyte enters a nanopore and constricts ion flow through it, rather than the theoretically proposed mechanism of direct charge coupling between the DNA and nanowire. However, there has been little discussion on the experimentally observed detection mechanism and its relation to the operation of real devices. We model the intrinsic signal and noise in such an FET-nanopore device and compare the results to the ionic current signal. The physical dimensions of DNA molecules limit the change in gate voltage on the FET to below 40 mV. We discuss the low-frequency flicker noise (<10 kHz), medium-frequency thermal noise (<100 kHz), and high-frequency capacitive noise (>100 kHz) in FET-nanopore devices. At bandwidths dominated by thermal noise, the signal-to-noise ratio in FET-nanopore devices is lower than in the ionic current signal. At high frequencies, where noise due to parasitic capacitances in the amplifier and chip is the dominant source of noise in ionic current measurements, high-transconductance FET-nanopore devices can outperform ionic current measurements.

  20. Fabrication of Protein Microparticles and Microcapsules with Biomolecular Tools

    NASA Astrophysics Data System (ADS)

    Cheung, Kwan Yee; Lai, Kwok Kei; Mak, Wing Cheung

    2018-05-01

    Microparticles have attracted much attention for medical, analytical and biological applications. Calcium carbonate (CaCO3) templating method with the advantages of having narrow size distribution, controlled morphology and good biocompatibility that has been widely used for the synthesis of various protein-based microparticles. Despite CaCO3 template is biocompatible, most of the conventional methods to create stable protein microparticles are mainly driven by chemical crosslink reagents which may induce potential harmful effect and remains undesirable especially for biomedical or clinical applications. In this article, we demonstrate the fabrication of protein microparticles and microcapsules with an innovative method using biomolecular tools such as enzymes and affinity molecules to trigger the assembling of protein molecules within a porous CaCO3 template followed by a template removal step. We demonstrated the enzyme-assisted fabrication of collagen microparticles triggered by transglutaminase, as well as the affinity-assisted fabrication of BSA-biotin avidin microcapsules triggered by biotin-avidin affinity interaction, respectively. Based on the different protein assemble mechanisms, the collagen microparticles appeared as a solid-structured particles, while the BSA-biotin avidin microcapsules appeared as hollow-structured morphology. The fabrication procedures are simple and robust that allows producing protein microparticles or microcapsules under mild conditions at physiological pH and temperature. In addition, the microparticle morphologies, protein compositions and the assemble mechanisms were studied. Our technology provides a facile approach to design and fabricate protein microparticles and microcapsules that are useful in the area of biomaterials, pharmaceuticals and analytical chemistry.

  1. Swellable microparticles as carriers for sustained pulmonary drug delivery.

    PubMed

    El-Sherbiny, Ibrahim M; McGill, Shayna; Smyth, Hugh D C

    2010-05-01

    In this investigation, novel biodegradable physically crosslinked hydrogel microparticles were developed and evaluated in vitro as potential carriers for sustained pulmonary drug delivery. To facilitate sustained release in the lungs, aerosols must first navigate past efficient aerodynamic filtering to penetrate to the deep lung (requires small particle size) where they must then avoid rapid macrophage clearance (enhanced by large particle size). The strategy suggested in this study to solve this problem is to deliver drug-loaded hydrogel microparticles with aerodynamic characteristics allowing them to be respirable when dry but attain large swollen sizes once deposited on moist lung surfaces to reduce macrophage uptake rates. The microparticles are based on PEG graft copolymerized onto chitosan in combination with Pluronic(R) F-108 and were prepared via cryomilling. The synthesized polymers used in preparation of the microparticles were characterized using FTIR, EA, 2D-XRD, and differential scanning calorimetry (DSC). The microparticles size, morphology, moisture content, and biodegradation rates were investigated. Swelling studies and in vitro drug release profiles were determined. An aerosolization study was conducted and macrophage uptake rates were evaluated against controls. The microparticles showed a respirable fraction of approximately 15% when prepared as dry powders. Enzymatic degradation of microparticles started within the first hour and about 7-41% weights were remaining after 240 h. Microparticles showed sustained release up to 10 and 20 days in the presence and absence of lysozyme, respectively. Preliminary macrophage interaction studies indicate that the developed hydrogel microparticles significantly delayed phagocytosis and may have the potential for sustained drug delivery to the lung.

  2. Cyclosporine Induces Endothelial Cell Release of Complement-Activating Microparticles

    PubMed Central

    Renner, Brandon; Klawitter, Jelena; Goldberg, Ryan; McCullough, James W.; Ferreira, Viviana P.; Cooper, James E.; Christians, Uwe

    2013-01-01

    Defective control of the alternative pathway of complement is an important risk factor for several renal diseases, including atypical hemolytic uremic syndrome. Infections, drugs, pregnancy, and hemodynamic insults can trigger episodes of atypical hemolytic uremic syndrome in susceptible patients. Although the mechanisms linking these clinical events with disease flares are unknown, recent work has revealed that each of these clinical conditions causes cells to release microparticles. We hypothesized that microparticles released from injured endothelial cells promote intrarenal complement activation. Calcineurin inhibitors cause vascular and renal injury and can trigger hemolytic uremic syndrome. Here, we show that endothelial cells exposed to cyclosporine in vitro and in vivo release microparticles that activate the alternative pathway of complement. Cyclosporine-induced microparticles caused injury to bystander endothelial cells and are associated with complement-mediated injury of the kidneys and vasculature in cyclosporine-treated mice. Cyclosporine-induced microparticles did not bind factor H, an alternative pathway regulatory protein present in plasma, explaining their complement-activating phenotype. Finally, we found that in renal transplant patients, the number of endothelial microparticles in plasma increases 2 weeks after starting tacrolimus, and treatment with tacrolimus associated with increased C3 deposition on endothelial microparticles in the plasma of some patients. These results suggest that injury-associated release of endothelial microparticles is an important mechanism by which systemic insults trigger intravascular complement activation and complement-dependent renal diseases. PMID:24092930

  3. Preparation of donut-shaped starch microparticles by aqueous-alcoholic treatment.

    PubMed

    Farrag, Yousof; Sabando, Constanza; Rodríguez-Llamazares, Saddys; Bouza, Rebeca; Rojas, Claudio; Barral, Luís

    2018-04-25

    A simple method for producing donut-shaped starch microparticles by adding ethanol to a heated aqueous slurry of corn starch is presented. The obtained microparticles were analysed by SEM, XRD and DSC. The average size of microparticles was 14.1 ± 0.3 μm with holes of an average size of 4.6 ± 0.2 μm. The crystalline arrangement of the microparticles was of a V-type single helix. The change in crystallinity from A-type of the starch granules to a more open structure, where water molecules could penetrate easier within the microparticles, substantially increased their solubility and swelling power. The microparticles exhibited a higher gelatinization temperature and a lower gelatinization enthalpy than did the starch granules. The donut-shaped microparticles were stable for more than 18 months and can be used as a carrier of an active compound or as a filler in bioplastics. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Chitosan microparticles for sustaining the topical delivery of minoxidil sulphate.

    PubMed

    Gelfuso, Guilherme Martins; Gratieri, Taís; Simão, Patrícia Sper; de Freitas, Luís Alexandre Pedro; Lopez, Renata Fonseca Vianna

    2011-01-01

    Given the hypothesis that microparticles can penetrate the skin barrier along the transfollicular route, this work aimed to obtain and characterise chitosan microparticles loaded with minoxidil sulphate (MXS) and to study their ability to sustain the release of the drug, attempting a further application utilising them in a targeted delivery system for the topical treatment of alopecia. Chitosan microparticles, containing different proportions of MXS/polymer, were prepared by spray drying and were characterised by yield, encapsulation efficiency, size and morphology. Microparticles selected for further studies showed high encapsulation efficiency (∼82%), a mean diameter of 3.0 µm and a spherical morphology without porosities. When suspended in an ethanol/water solution, chitosan microparticles underwent instantaneous swelling, increasing their mean diameter by 90%. Release studies revealed that the chitosan microparticles were able to sustain about three times the release rate of MXS. This feature, combined with suitable size, confers to these microparticles the potential to target and improve topical therapy of alopecia with minoxidil.

  5. DNA Origami-Graphene Hybrid Nanopore for DNA Detection.

    PubMed

    Barati Farimani, Amir; Dibaeinia, Payam; Aluru, Narayana R

    2017-01-11

    DNA origami nanostructures can be used to functionalize solid-state nanopores for single molecule studies. In this study, we characterized a nanopore in a DNA origami-graphene heterostructure for DNA detection. The DNA origami nanopore is functionalized with a specific nucleotide type at the edge of the pore. Using extensive molecular dynamics (MD) simulations, we computed and analyzed the ionic conductivity of nanopores in heterostructures carpeted with one or two layers of DNA origami on graphene. We demonstrate that a nanopore in DNA origami-graphene gives rise to distinguishable dwell times for the four DNA base types, whereas for a nanopore in bare graphene, the dwell time is almost the same for all types of bases. The specific interactions (hydrogen bonds) between DNA origami and the translocating DNA strand yield different residence times and ionic currents. We also conclude that the speed of DNA translocation decreases due to the friction between the dangling bases at the pore mouth and the sequencing DNA strands.

  6. Circulating Mesenchymal Stem Cells Microparticles in Patients with Cerebrovascular Disease

    PubMed Central

    Cho, Yeon Hee; Kang, Ho Young; Hyung, Na Kyum; Kim, Donghee; Lee, Ji Hyun; Nam, Ji Yoon; Bang, Oh Young

    2012-01-01

    Preclinical and clinical studies have shown that the application of CD105+ mesenchymal stem cells (MSCs) is feasible and may lead to recovery after stroke. In addition, circulating microparticles are reportedly functional in various disease conditions. We tested the levels of circulating CD105+ microparticles in patients with acute ischemic stroke. The expression of CD105 (a surface marker of MSCs) and CXCR4 (a CXC chemokine receptor for MSC homing) on circulating microparticles was evaluated by flow cytometry of samples from 111 patients and 50 healthy subjects. The percentage of apoptotic CD105 microparticles was determined based on annexin V (AV) expression. The relationship between serum levels of CD105+/AV− microparticles, stromal cells derived factor-1α (SDF-1α), and the extensiveness of cerebral infarcts was also evaluated. CD105+/AV− microparticles were higher in stroke patients than control subjects. Correlation analysis showed that the levels of CD105+/AV− microparticles increased as the baseline stroke severity increased. Multivariate testing showed that the initial severity of stroke was independently associated with circulating CD105+/AV− microparticles (OR, 1.103 for 1 point increase in the NIHSS score on admission; 95% CI, 1.032–1.178) after adjusting for other variables. The levels of CD105+/CXCR4+/AV− microparticles were also increased in patients with severe disability (r = 0.192, p = 0.046 for NIHSS score on admission), but were decreased with time after stroke onset (r = −0.204, p = 0.036). Risk factor profiles were not associated with the levels of circulating microparticles or SDF-1α. In conclusion, our data showed that stroke triggers the mobilization of MSC-derived microparticles, especially in patients with extensive ischemic stroke. PMID:22615882

  7. Applications of Nanoporous Materials in Agriculture

    USDA-ARS?s Scientific Manuscript database

    Nanoporous materials possess organized pore distributions and increased surface areas. Advances in the systematic design of nanoporous materials enable incorporation of functionality for better sensitivity in detection methods, increased capacity of sorbents, and improved selectivity and yield in ca...

  8. pH-Sensitive Microparticles with Matrix-Dispersed Active Agent

    NASA Technical Reports Server (NTRS)

    Calle, Luz M. (Inventor); Jolley, Scott T. (Inventor); Buhrow, Jerry W. (Inventor); Li, Wenyan (Inventor)

    2014-01-01

    Methods to produce pH-sensitive microparticles that have an active agent dispersed in a polymer matrix have certain advantages over microcapsules with an active agent encapsulated in an interior compartment/core inside of a polymer wall. The current invention relates to pH-sensitive microparticles that have a corrosion-detecting or corrosion-inhibiting active agent or active agents dispersed within a polymer matrix of the microparticles. The pH-sensitive microparticles can be used in various coating compositions on metal objects for corrosion detecting and/or inhibiting.

  9. Fabrication and characterization of carboxymethyl cellulose novel microparticles for bone tissue engineering.

    PubMed

    Gaihre, Bipin; Jayasuriya, Ambalangodage C

    2016-12-01

    In this study we developed carboxymethyl cellulose (CMC) microparticles through ionic crosslinking with the aqueous ion complex of zirconium (Zr) and further complexing with chitosan (CS) and determined the physio-chemical and biological properties of these novel microparticles. In order to assess the role of Zr, microparticles were prepared in 5% and 10% (w/v) zirconium tetrachloride solution. Scanning electron microscopy (SEM) with energy dispersive X-ray spectrometer (EDS) results showed that Zr was uniformly distributed on the surface of the microparticles as a result of which uniform groovy surface was obtained. We found that Zr enhances the surface roughness of the microparticles and stability studies showed that it also increases the stability of microparticles in phosphate buffered saline. The crosslinking of anionic CMC with cationic Zr and CS was confirmed by Fourier transform infrared spectroscopy (FTIR) results. The response of murine pre-osteoblasts (OB-6) when cultured with microparticles was investigated. Live/dead cell assay showed that microparticles did not induce any cytotoxic effects as cells were attaching and proliferating on the well plate as well as along the surface of microparticles. In addition, SEM images showed that microparticles support the attachment of cells and they appeared to be directly interacting with the surface of microparticle. Within 10days of culture most of the top surface of microparticles was covered with a layer of cells indicating that they were proliferating well throughout the surface of microparticles. We observed that Zr enhances the cell attachment and proliferation as more cells were present on microparticles with 10% Zr. These promising results show the potential applications of CMC-Zr microparticles in bone tissue engineering. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Integrating Sub-3 nm Plasmonic Gaps into Solid-State Nanopores.

    PubMed

    Shi, Xin; Verschueren, Daniel; Pud, Sergii; Dekker, Cees

    2018-05-01

    Plasmonic nanopores combine the advantages of nanopore sensing and surface plasmon resonances by introducing confined electromagnetic fields to a solid-state nanopore. Ultrasmall nanogaps between metallic nanoantennas can generate the extremely enhanced localized electromagnetic fields necessary for single-molecule optical sensing and manipulation. Challenges in fabrication, however, hamper the integration of such nanogaps into nanopores. Here, a top-down approach for integrating a plasmonic antenna with an ultrasmall nanogap into a solid-state nanopore is reported. Employing a two-step e-beam lithography process, the reproducible fabrication of nanogaps down to a sub-1 nm scale is demonstrated. Subsequently, nanopores are drilled through the 20 nm SiN membrane at the center of the nanogap using focused-electron-beam sculpting with a transmission electron microscope, at the expense of a slight gap expansion for the smallest gaps. Using this approach, sub-3 nm nanogaps can be readily fabricated on solid-state nanopores. The functionality of these plasmonic nanopores for single-molecule detection is shown by performing DNA translocations. These integrated devices can generate intense electromagnetic fields at the entrance of the nanopore and can be expected to find applications in nanopore-based single-molecule trapping and optical sensing. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Single Nanoparticle Translocation Through Chemically Modified Solid Nanopore

    NASA Astrophysics Data System (ADS)

    Tan, Shengwei; Wang, Lei; Liu, Hang; Wu, Hongwen; Liu, Quanjun

    2016-02-01

    The nanopore sensor as a high-throughput and low-cost technology can detect single nanoparticle in solution. In the present study, the silicon nitride nanopores were fabricated by focused Ga ion beam (FIB), and the surface was functionalized with 3-aminopropyltriethoxysilane to change its surface charge density. The positively charged nanopore surface attracted negatively charged nanoparticles when they were in the vicinity of the nanopore. And, nanoparticle translocation speed was slowed down to obtain a clear and deterministic signal. Compared with previous studied small nanoparticles, the electrophoretic translocation of negatively charged polystyrene (PS) nanoparticles (diameter ~100 nm) was investigated in solution using the Coulter counter principle in which the time-dependent nanopore current was recorded as the nanoparticles were driven across the nanopore. A linear dependence was found between current drop and biased voltage. An exponentially decaying function ( t d ~ e -v/v0 ) was found between the duration time and biased voltage. The interaction between the amine-functionalized nanopore wall and PS microspheres was discussed while translating PS microspheres. We explored also translocations of PS microspheres through amine-functionalized solid-state nanopores by varying the solution pH (5.4, 7.0, and 10.0) with 0.02 M potassium chloride (KCl). Surface functionalization showed to provide a useful step to fine-tune the surface property, which can selectively transport molecules or particles. This approach is likely to be applied to gene sequencing.

  12. Delivery of chemotherapeutic drugs in tumour cell-derived microparticles.

    PubMed

    Tang, Ke; Zhang, Yi; Zhang, Huafeng; Xu, Pingwei; Liu, Jing; Ma, Jingwei; Lv, Meng; Li, Dapeng; Katirai, Foad; Shen, Guan-Xin; Zhang, Guimei; Feng, Zuo-Hua; Ye, Duyun; Huang, Bo

    2012-01-01

    Cellular microparticles are vesicular plasma membrane fragments with a diameter of 100-1,000 nanometres that are shed by cells in response to various physiological and artificial stimuli. Here we demonstrate that tumour cell-derived microparticles can be used as vectors to deliver chemotherapeutic drugs. We show that tumour cells incubated with chemotherapeutic drugs package these drugs into microparticles, which can be collected and used to effectively kill tumour cells in murine tumour models without typical side effects. We describe several mechanisms involved in this process, including uptake of drug-containing microparticles by tumour cells, synthesis of additional drug-packaging microparticles by these cells that contribute to the cytotoxic effect and the inhibition of drug efflux from tumour cells. This study highlights a novel drug delivery strategy with potential clinical application.

  13. Reaching the Ionic Current Detection Limit in Silicon-Based Nanopores

    NASA Astrophysics Data System (ADS)

    Puster, Matthew; Rodriguez-Manzo, Julio Alejandro; Nicolai, Adrien; Meunier, Vincent; Drndic, Marija

    2015-03-01

    Solid-state nanopores act as single-molecule sensors whereby passage of an individual molecule in aqueous electrolyte through a nanopore is registered as a change in ionic conductance (ΔG). Future nanopore applications such as DNA sequencing at high bandwidth require high ΔG for optimal signal-to-noise ratio. Reducing the nanopore diameter and thickness increase ΔG. Molecule size limits the diameter, thus efforts concentrate on minimizing the thickness by thinning oxide/nitride films or using 2D materials. Weighted by electrolyte conductivity the highest ΔG reported to date for DNA translocations were obtained with nanopores made in oxide/nitride films. We present a controlled electron irradiation technique to thin such films to the limit of their stability, producing nanopores tailored to molecule size in amorphous Si with thicknesses less than 2 nm. We compare ΔG values with results found in the literature for DNA translocation through these nanopores, where access resistance becomes comparable to the resistance through the nanopore itself.

  14. CIRCULATING MICROPARTICLES IN PATIENTS WITH ANTIPHOSPHOLIPID ANTIBODIES: CHARACTERIZATION AND ASSOCIATIONS

    PubMed Central

    Chaturvedi, Shruti; Cockrell, Erin; Espinola, Ricardo; Hsi, Linda; Fulton, Stacey; Khan, Mohammad; Li, Liang; Fonseca, Fabio; Kundu, Suman; McCrae, Keith R.

    2014-01-01

    The antiphospholipid syndrome is characterized by venous or arterial thrombosis and/or recurrent fetal loss in the presence of circulating antiphospholipid antibodies. These antibodies cause activation of endothelial and other cell types leading to the release of microparticles with procoagulant and pro-inflammatory properties. The aims of this study were to characterize the levels of endothelial cell, monocyte, platelet derived, and tissue factor-bearing microparticles in patients with antiphospholipid antibodies, to determine the association of circulating microparticles with anticardiolipin and anti-β2-glycoprotein antibodies, and to define the cellular origin of microparticles that express tissue factor. Microparticle content within citrated blood from 47 patients with antiphospholipid antibodies and 144 healthy controls was analyzed within 2 hours of venipuncture. Levels of Annexin-V, CD105 and CD144 (endothelial derived), CD41 (platelet derived) and tissue factor positive microparticles were significantly higher in patients than controls. Though levels of CD14 (monocyte-derived) microparticles in patient plasma were not significantly increased, increased levels of CD14 and tissue factor positive microparticles were observed in patients. Levels of microparticles that stained for CD105 and CD144 showed a positive correlation with IgG (R = 0.60, p=0.006) and IgM anti-beta2-glycoprotein I antibodies (R=0.58, p=0.006). The elevation of endothelial and platelet derived microparticles in patients with APS and their correlation with anti-β2-glycoprotein I antibodies suggests a chronic state of vascular cell activation in these individuals and an important role for β2-glycoprotein I in development of the pro-thrombotic state associated with antiphospholipid antibodies. PMID:25467081

  15. Characterization of nitric oxide-releasing microparticles for the mucosal delivery.

    PubMed

    Yoo, Jin-Wook; Lee, Jae-Suk; Lee, Chi H

    2010-03-15

    For the treatment of female sexual arousal disorder (FSAD), we developed microparticles made of PLGA containing nitric oxide (NO) donor (DETA NONOate) to efficiently deliver NO to vaginal mucosa. The NO-releasing microparticles were prepared by various emulsion methods. SEM and DSC studies were performed to examine the microparticles. The release studies were conducted under various conditions to optimize the loading dose in the microparticles. NO diffusivity through vaginal epithelial cells was evaluated and pharmacological activity of NO-releasing microparticles was examined by assessment of intracellular cGMP level in vaginal cells. Through the modified double emulsion solvent evaporation method (w/o/w(a)), the acid labile DETA NONOate was stabilized during the fabrication process and homogenous morphology and high entrapment efficiency were achieved. DETA NONOate was protected under the acidic conditions of the vagina and NO was released from the microparticles in a controlled manner. A significant amount of NO produced from DETA NONOate penetrated through the vaginal epithelial cells. The intracellular cGMP level increased with the treatment of NO-releasing microparticles in vaginal cells. These findings suggest that NO-releasing microparticles could improve the vaginal blood perfusion and open up the possibilities of novel treatment of FSAD. (c) 2009 Wiley Periodicals, Inc.

  16. Preparation and evaluation of posaconazole-loaded enteric microparticles in rats.

    PubMed

    Yang, Min; Dong, Zhonghua; Zhang, Yongchun; Zhang, Fang; Wang, Yongjie; Zhao, Zhongxi

    2017-04-01

    Posaconazole (POS) is an antifungal compound which has a low oral bioavailability. The aim of this study was to prepare POS enteric microparticles to enhance its oral bioavailability. POS enteric microparticles were prepared with hypromellose acetate succinate (HPMCAS) via the spray drying method. The solvent mixtures of acetone and ethanol used in the preparation of the microparticles were optimized to produce the ideal POS enteric microparticles. Multivariate data analysis using a principal component analysis (PCA) was used to find the relationship among the HPMCAS molecular characteristics, particle properties and drug release kinetics from the spray dried microparticles. The optimal spray solvent mixtures were critical to produce the POS microparticles with the defined polymer entanglement index, drug surface enrichment, particle size and drug loading. The HPMCAS molecular characteristics affected the microscopic connectivity and diffusivity of polymer matrix and eventually influenced the drug release behavior, and enhanced the bioavailability of POS. These studies suggested that the selection of suitable solvent mixtures of acetone and ethanol used in the spray drying of the microparticles was quite important to produce the entangled polymer structures with preferred polymer molecular properties of polymer coiling, overlap concentration and entanglement index. Additional studies on particle size and surface drug enrichment eventually produced HPMCAS-based enteric microparticles to enhance the oral bioavailability of POS.

  17. Improving the performance of transglutaminase-crosslinked microparticles for enteric delivery.

    PubMed

    Tello, Fernando; Prata, Ana S; Rodrigues, Rodney A F; Sartoratto, Adilson; Grosso, Carlos R F

    2016-10-01

    Various agents for cross-linking have been investigated for stabilizing and controlling the barrier properties of microparticles for enteric applications. Transglutaminase, in addition to being commercially available for human consumption, presents inferior cross-linking action compared to glutaraldehyde. In this study, the intensity of this enzymatic cross-linking was investigated in microparticles obtained by complex coacervation between gelatin and gum Arabic. The effectiveness of cross-linking in these microparticles was evaluated based on swelling, release of a model substance (parika oleoresin: colored and hydrophobic) and gastrointestinal assays. The cross-linked microparticles remained intact under gastric conditions, whereas the uncross-linked microparticles have been dissolved. However, all of the microparticles have been dissolved under intestinal conditions. The amount of oily core that was released decreased as the amount of transglutaminase increased. For the most efficient microparticles (50U/g of protein), the performance was improved by increasing the pH of cross-linking from 4.0 to 6.0, resulting in a release of 17.1% rather than 32.3% of the core material. These results were considerably closer to the 10.3% of core material released by glutaraldehyde-cross-linked microparticles (1mM/g of protein). Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Dynamic release and clearance of circulating microparticles during cardiac stress.

    PubMed

    Augustine, Daniel; Ayers, Lisa V; Lima, Eduardo; Newton, Laura; Lewandowski, Adam J; Davis, Esther F; Ferry, Berne; Leeson, Paul

    2014-01-03

    Microparticles are cell-derived membrane vesicles, relevant to a range of biological responses and known to be elevated in cardiovascular disease. To investigate microparticle release during cardiac stress and how this response differs in those with vascular disease. We measured a comprehensive panel of circulating cell-derived microparticles by a standardized flow cytometric protocol in 119 patients referred for stress echocardiography. Procoagulant, platelet, erythrocyte, and endothelial but not leukocyte, granulocyte, or monocyte-derived microparticles were elevated immediately after a standardized dobutamine stress echocardiogram and decreased after 1 hour. Twenty-five patients developed stress-induced wall motion abnormalities suggestive of myocardial ischemia. They had similar baseline microparticle levels to those who did not develop ischemia, but, interestingly, their microparticle levels did not change during stress. Furthermore, no stress-induced increase was observed in those without inducible ischemia but with a history of vascular disease. Fourteen patients subsequently underwent coronary angiography. A microparticle rise during stress echocardiography had occurred only in those with normal coronary arteries. Procoagulant, platelet, erythrocyte, and endothelial microparticles are released during cardiac stress and then clear from the circulation during the next hour. This stress-induced rise seems to be a normal physiological response that is diminished in those with vascular disease.

  19. Immunogenicity and Protection of Oral Influenza Vaccines Formulated into Microparticles

    PubMed Central

    SHASTRI, PRATHAP NAGARAJA; KIM, MIN-CHUL; QUAN, FU-SHI; D’SOUZA, MARTIN J.; KANG, SANG-MOO

    2017-01-01

    Influenza is a deadly disease affecting humans and animals. It is recommended that every individual should be vaccinated annually against influenza. Considering the frequency of administration of this vaccine, we have explored the oral route of vaccination with a microparticulate formulation. Microparticles containing inactivated influenza A/PR/34/8 H1N1 virus with Eudragit S and trehalose as a matrix were prepared using the Buchi spray dryer. Particle size distribution of microparticles was measured and the bioactivity of vaccine in a microparticle form was analyzed using a hemagglutination activity test. Furthermore, the efficacy of microparticle vaccines was evaluated in vivo in Balb/c mice. Analysis of serum samples showed that microparticles resulted in enhanced antigen-specific immunoglobulin G (IgG), IgG1, and IgG2a antibodies. Upon challenge with homologous and heterologous influenza viruses, microparticle vaccines showed significantly increased levels of protection. Use of microparticles to deliver vaccines could be a promising tool for the development of an oral influenza vaccine. PMID:22711602

  20. Circulating microparticles from obstructive sleep apnea syndrome patients induce endothelin-mediated angiogenesis.

    PubMed

    Tual-Chalot, Simon; Gagnadoux, Frédéric; Trzepizur, Wojciech; Priou, Pascaline; Andriantsitohaina, Ramaroson; Martinez, M Carmen

    2014-02-01

    Microparticles are deemed true biomarkers and vectors of biological information between cells. Depending on their origin, the composition of microparticles varies and the subsequent message transported by them, such as proteins, mRNA, or miRNA, can differ. In obstructive sleep apnea syndrome (OSAS), circulating microparticles are associated with endothelial dysfunction by reducing endothelial-derived nitric oxide production. Here, we have analyzed the potential role of circulating microparticles from OSAS patients on the regulation of angiogenesis and the involved pathway. VEGF content carried by circulating microparticles from OSAS patients was increased when compared with microparticles from non-OSAS patients. Circulating microparticles from OSAS patients induced an increase of angiogenesis that was abolished in the presence of the antagonist of endothelin-1 receptor type B. In addition, endothelin-1 secretion was increased in human endothelial cells treated by OSAS microparticles. We highlight that circulating microparticles from OSAS patients can modify the secretome of endothelial cells leading to angiogenesis. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Controlled Lateral Positioning of Microparticles Inside Droplets Using Acoustophoresis.

    PubMed

    Fornell, Anna; Nilsson, Johan; Jonsson, Linus; Periyannan Rajeswari, Prem Kumar; Joensson, Haakan N; Tenje, Maria

    2015-10-20

    In this paper, we utilize bulk acoustic waves to control the position of microparticles inside droplets in two-phase microfluidic systems and demonstrate a method to enrich the microparticles. In droplet microfluidics, different unit operations are combined and integrated on-chip to miniaturize complex biochemical assays. We present a droplet unit operation capable of controlling the position of microparticles during a trident shaped droplet split. An acoustic standing wave field is generated in the microchannel, and the acoustic forces direct the encapsulated microparticles to the center of the droplets. The method is generic, requires no labeling of the microparticles, and is operated in a noncontact fashion. It was possible to achieve 2+-fold enrichment of polystyrene beads (5 μm in diameter) in the center daughter droplet with an average recovery of 89% of the beads. Red blood cells were also successfully manipulated inside droplets. These results show the possibility to use acoustophoresis in two-phase systems to enrich microparticles and open up the possibility for new droplet-based assays that are not performed today.

  2. Nanoporous hard data: optical encoding of information within nanoporous anodic alumina photonic crystals

    NASA Astrophysics Data System (ADS)

    Santos, Abel; Law, Cheryl Suwen; Pereira, Taj; Losic, Dusan

    2016-04-01

    Herein, we present a method for storing binary data within the spectral signature of nanoporous anodic alumina photonic crystals. A rationally designed multi-sinusoidal anodisation approach makes it possible to engineer the photonic stop band of nanoporous anodic alumina with precision. As a result, the transmission spectrum of these photonic nanostructures can be engineered to feature well-resolved and selectively positioned characteristic peaks across the UV-visible spectrum. Using this property, we implement an 8-bit binary code and assess the versatility and capability of this system by a series of experiments aiming to encode different information within the nanoporous anodic alumina photonic crystals. The obtained results reveal that the proposed nanosized platform is robust, chemically stable, versatile and has a set of unique properties for data storage, opening new opportunities for developing advanced nanophotonic tools for a wide range of applications, including sensing, photonic tagging, self-reporting drug releasing systems and secure encoding of information.Herein, we present a method for storing binary data within the spectral signature of nanoporous anodic alumina photonic crystals. A rationally designed multi-sinusoidal anodisation approach makes it possible to engineer the photonic stop band of nanoporous anodic alumina with precision. As a result, the transmission spectrum of these photonic nanostructures can be engineered to feature well-resolved and selectively positioned characteristic peaks across the UV-visible spectrum. Using this property, we implement an 8-bit binary code and assess the versatility and capability of this system by a series of experiments aiming to encode different information within the nanoporous anodic alumina photonic crystals. The obtained results reveal that the proposed nanosized platform is robust, chemically stable, versatile and has a set of unique properties for data storage, opening new opportunities for

  3. Reconfigurable engineered motile semiconductor microparticles.

    PubMed

    Ohiri, Ugonna; Shields, C Wyatt; Han, Koohee; Tyler, Talmage; Velev, Orlin D; Jokerst, Nan

    2018-05-03

    Locally energized particles form the basis for emerging classes of active matter. The design of active particles has led to their controlled locomotion and assembly. The next generation of particles should demonstrate robust control over their active assembly, disassembly, and reconfiguration. Here we introduce a class of semiconductor microparticles that can be comprehensively designed (in size, shape, electric polarizability, and patterned coatings) using standard microfabrication tools. These custom silicon particles draw energy from external electric fields to actively propel, while interacting hydrodynamically, and sequentially assemble and disassemble on demand. We show that a number of electrokinetic effects, such as dielectrophoresis, induced charge electrophoresis, and diode propulsion, can selectively power the microparticle motions and interactions. The ability to achieve on-demand locomotion, tractable fluid flows, synchronized motility, and reversible assembly using engineered silicon microparticles may enable advanced applications that include remotely powered microsensors, artificial muscles, reconfigurable neural networks and computational systems.

  4. Tailored nanoporous coatings fabricated on conformable polymer substrates.

    PubMed

    Poxson, David J; Mont, Frank W; Cho, Jaehee; Schubert, E Fred; Siegel, Richard W

    2012-11-01

    Nanoporous coatings have become the subject of intense investigation, in part because they have been shown to have unique and tailorable physical properties that can depart greatly from their dense or macroscopic counterparts. Nanoporous coatings are frequently fabricated utilizing oblique-angle or glancing-angle physical vapor-phase deposition techniques. However, a significant limitation for such coatings exists; they are almost always deposited on smooth and rigid planar substrates, such as silicon and glass. This limitation greatly constrains the applicability, tailorability, functionality and even the economic viability, of such nanoporous coatings. Here, we report our findings on nanoporous/polymer composite systems (NPCS) fabricated by utilizing oblique-angle electron-beam methodology. These unique composite systems exhibit several favorable characteristics, namely, (i) fine-tuned control over coating nanoporosity and thickness, (ii) excellent adhesion between the nanoporous coating and polymer substrate, (iii) the ability to withstand significant and repeated bending, and (iv) the ability to be molded conformably on two and three-dimensional surfaces while closely retaining the composite system's designed nanoporous film structure and, hence, properties.

  5. Protease-functionalized mucus penetrating microparticles: In-vivo evidence for their potential.

    PubMed

    Mahmood, Arshad; Laffleur, Flavia; Leonaviciute, Gintare; Bernkop-Schnürch, Andreas

    2017-10-30

    The focus of the current study was to explore whether immobilization of proteases to microparticles could result in their enhanced penetration into mucus. The proteases papain (PAP) and bromelain (BROM) were covalently attached to a polyacrylate (PAA; Carbopol 971P) via amide bond formation based on carbodiimide reaction. Microparticles containing these conjugates were generated via ionic gelation with calcium chloride and were characterized regarding size, surface charge, enzymatic activity and fluorescein diacetate (FDA) loading efficiency. Furthermore, mucus penetration potential of these microparticles was evaluated in-vitro on freshly collected porcine intestinal mucus, on intact intestinal mucosa and in-vivo in Sprague-Dawley rats. Results showed mean diameter of microparticles ranging between 2-3μm and surface charge between -8 to -18mV. The addition of PAA-microparticles to porcine intestinal mucus led to a 1.39-fold increase in dynamic viscosity whereas a 3.10- and 2.12-fold decrease was observed in case of PAA-PAP and PAA-BROM microparticles, respectively. Mucus penetration studies showed a 4.27- and 2.21- fold higher permeation of FDA loaded PAA-PAP and PAA-BROM microparticles as compared to PAA microparticles, respectively. Extent of mucus diffusion determined via silicon tube assay illustrated 3.96- fold higher penetration for PAA-PAP microparticles and 1.99- fold for PAA-BROM microparticles. An in-vitro analysis on porcine intestinal mucosa described up to 16- and 7.35-fold higher degree of retention and furthermore, during in-vivo evaluation in Sprague-Dawley rats a 3.35- and 2.07-fold higher penetration behavior was observed in small intestine for PAA-PAP and PAA-BROM microparticles as compared to PAA microparticles, respectively. According to these results, evidence for microparticles decorated with proteases in order to overcome the mucus barrier and to reach the absorption lining has been provided that offers wide ranging applications in mucosal

  6. Injectable chitosan microparticles incorporating bone morphogenetic protein-7 for bone tissue regeneration

    PubMed Central

    Mantripragada, Venkata P.; Jayasuriya, Ambalangodage C.

    2014-01-01

    This study investigates the influence of the controlled release of bone morphogenetic protein 7 (BMP-7) from cross-linked chitosan microparticles on pre-osteoblasts (OB-6) in vitro. BMP-7 was incorporated into microparticles by encapsulation during the particle preparation and coating after particle preparation. Chitosan microparticles had an average diameter of 700 μm containing ~100 ng of BMP-7. The release study profile indicates that nearly 98% of the BMP-7 coated on the microparticles was released in a period of 18 days while only 36% of the BMP-7 encapsulated in the microparticles was released in the same time period. Cell attachment study indicated that the BMP-7 coated microparticles have many cells adhered on the microparticles in comparison with microparticles without growth factors on day 10. DNA assay indicated a statistical significant increase (p<0.05) in the amount of DNA obtained from BMP-7 encapsulated and coated microparticles in comparison with microparticles without any growth factors. A real time RT-PCR experiment was performed to determine the expression of a few osteoblast specific genes - Dlx5, runx2, osterix, osteopontin, osteocalcin, and bone sialoprotein. The results thus suggest that chitosan microparticles obtained by coacervation method are biocompatible and helps in improving the encapsulation efficiency of BMP-7. Also BMP-7 incorporated in the microparticles is being released in a controlled fashion to support attachment, proliferation and differentiation of pre-osteoblasts, thus acting as a good scaffold for bone tissue regeneration. PMID:24497318

  7. Preparation and Characterization of Doripenem-Loaded Microparticles for Pulmonary Delivery.

    PubMed

    Yildiz-Peköz, Ayca; Akbal, Ozlem; Tekarslan, S Hande; Sagirli, A Olcay; Mulazimoglu, Lütfiye; Morina, Deniz; Cevher, Erdal

    2018-06-07

    Pneumonia is a bacterial lower respiratory tract infection that has a high morbidity rate. The gram-negative pathogen Pseudomonas aeruginosa is a significant cause of nosocomial infections and ventilator-associated pneumonias and is mainly treated by carbapenems. Doripenem is a carbapenem drug, which has a broad-spectrum antibacterial activity. The aim of this study was to develop doripenem-loaded chitosan microparticles for pulmonary administration to provide more efficient treatment for pneumonia. Ionotropic gelation and the spray-drying method were used to obtain doripenem-loaded chitosan microparticles with different lactose, trehalose, and L-leucine concentrations. Physicochemical characteristics, in vitro drug release properties, and aerodynamics properties were investigated and in vitro antimicrobial susceptibility tests of the formulations were performed. Assessment of aerodynamic properties of the powders, including Mass Median Aerodynamic Diameter, size distribution, and fine particle fraction (FPF), were performed using a Next Generation Impactor. Cytotoxicity of the fabricated microparticles was assessed using the Calu-3 cell airway epithelial cell line. Optimum microparticles were produced using a combination of ionotropic gelation and spray-drying methods. Spray-dried microparticle production yield was relatively high (74.03% ± 3.88% to 98.23% ± 1.70%). Lactose, trehalose, and L-leucine were added to the formulation to prevent aggregation produced by the ionotropic gelation spray-drying method. Each formulation's encapsulation efficiency was above 78.98% ± 2.37%. The doripenem-loaded microparticle mean diameter ranged from 3.8 ± 0.110 to 6.9 ± 0.090 μm. Microparticles with 20% (w/w) L-leucine had the highest FPF ratio indicating the best aerosolization properties of the formulations. The efficacy of the formulations as an antibacterial agent was increased by forming doripenem-loaded microparticles compared to blank

  8. Polyelectrolyte layer-by-layer deposition in cylindrical nanopores.

    PubMed

    Lazzara, Thomas D; Lau, K H Aaron; Abou-Kandil, Ahmed I; Caminade, Anne-Marie; Majoral, Jean-Pierre; Knoll, Wolfgang

    2010-07-27

    Layer-by-layer (LbL) deposition of polyelectrolytes within nanopores in terms of the pore size and the ionic strength was experimentally studied. Anodic aluminum oxide (AAO) membranes, which have aligned, cylindrical, nonintersecting pores, were used as a model nanoporous system. Furthermore, the AAO membranes were also employed as planar optical waveguides to enable in situ monitoring of the LbL process within the nanopores by optical waveguide spectroscopy (OWS). Structurally well-defined N,N-disubstituted hydrazine phosphorus-containing dendrimers of the fourth generation, with peripherally charged groups and diameters of approximately 7 nm, were used as the model polyelectrolytes. The pore diameter of the AAO was varied between 30-116 nm and the ionic strength was varied over 3 orders of magnitude. The dependence of the deposited layer thickness on ionic strength within the nanopores is found to be significantly stronger than LbL deposition on a planar surface. Furthermore, deposition within the nanopores can become inhibited even if the pore diameter is much larger than the diameter of the G4-polyelectrolyte, or if the screening length is insignificant relative to the dendrimer diameter at high ionic strengths. Our results will aid in the template preparation of polyelectrolyte multilayer nanotubes, and our experimental approach may be useful for investigating theories regarding the partitioning of nano-objects within nanopores where electrostatic interactions are dominant. Furthermore, we show that the enhanced ionic strength dependence of polyelectrolyte transport within the nanopores can be used to selectively deposit a LbL multilayer atop a nanoporous substrate.

  9. Nanopore-based fourth-generation DNA sequencing technology.

    PubMed

    Feng, Yanxiao; Zhang, Yuechuan; Ying, Cuifeng; Wang, Deqiang; Du, Chunlei

    2015-02-01

    Nanopore-based sequencers, as the fourth-generation DNA sequencing technology, have the potential to quickly and reliably sequence the entire human genome for less than $1000, and possibly for even less than $100. The single-molecule techniques used by this technology allow us to further study the interaction between DNA and protein, as well as between protein and protein. Nanopore analysis opens a new door to molecular biology investigation at the single-molecule scale. In this article, we have reviewed academic achievements in nanopore technology from the past as well as the latest advances, including both biological and solid-state nanopores, and discussed their recent and potential applications. Copyright © 2015 The Authors. Production and hosting by Elsevier Ltd.. All rights reserved.

  10. Platelet and not erythrocyte microparticles are procoagulant in transfused thalassaemia major patients.

    PubMed

    Agouti, Imane; Cointe, Sylvie; Robert, Stéphane; Judicone, Coralie; Loundou, Anderson; Driss, Fathi; Brisson, Alain; Steschenko, Dominique; Rose, Christian; Pondarré, Corinne; Bernit, Emmanuelle; Badens, Catherine; Dignat-George, Françoise; Lacroix, Romaric; Thuret, Isabelle

    2015-11-01

    The level of circulating platelet-, erythrocyte-, leucocyte- and endothelial-derived microparticles detected by high-sensitivity flow cytometry was investigated in 37 β-thalassaemia major patients receiving a regular transfusion regimen. The phospholipid procoagulant potential of the circulating microparticles and the microparticle-dependent tissue factor activity were evaluated. A high level of circulating erythrocyte- and platelet-microparticles was found. In contrast, the number of endothelial microparticles was within the normal range. Platelet microparticles were significantly higher in splenectomized than in non-splenectomized patients, independent of platelet count (P < 0·001). Multivariate analysis indicated that phospholipid-dependent procoagulant activity was influenced by both splenectomy (P = 0·001) and platelet microparticle level (P < 0·001). Erythrocyte microparticles were not related to splenectomy, appear to be devoid of proper procoagulant activity and no relationship between their production and haemolysis, dyserythropoiesis or oxidative stress markers could be established. Intra-microparticle labelling with anti-HbF antibodies showed that they originate only partially (median of 28%) from thalassaemic erythropoiesis. In conclusion, when β-thalassaemia major patients are intensively transfused, the procoagulant activity associated with thalassaemic erythrocyte microparticles is probably diluted by transfusions. In contrast, platelet microparticles, being both more elevated and more procoagulant, especially after splenectomy, may contribute to the residual thrombotic risk reported in splenectomized multi-transfused β-thalassaemia major patients. © 2015 John Wiley & Sons Ltd.

  11. Method to fabricate functionalized conical nanopores

    DOEpatents

    Small, Leo J.; Spoerke, Erik David; Wheeler, David R.

    2016-07-12

    A pressure-based chemical etch method is used to shape polymer nanopores into cones. By varying the pressure, the pore tip diameter can be controlled, while the pore base diameter is largely unaffected. The method provides an easy, low-cost approach for conically etching high density nanopores.

  12. Antifungal Effect of a Dental Tissue Conditioner Containing Nystatin-Loaded Alginate Microparticles.

    PubMed

    Kim, Hyun-Jin; Son, Jun Sik; Kwon, Tae-Yub

    2018-02-01

    In this in vitro study, nystatin-alginate microparticles were successfully fabricated to control the release of nystatin from a commercial dental tissue conditioner. These nystatin-alginate microparticles were spherical and had a slightly rough surface. The microparticles incorporated into the tissue conditioner were distributed homogeneously throughout the tissue conditioner matrix. The incorporation of the microparticles did not deteriorate the mechanical properties of the original material. The agar diffusion test results showed that the tissue conditioner containing the microparticles had a good antifungal effect against Candida albicans. The nystatin-alginate microparticles efficiently controlled the release of nystatin from the tissue conditioner matrix over the experimental period of 14 days. Moreover, the nystatin-alginate microparticles incorporated in the tissue conditioner showed effective antifungal function even at lower concentrations of nystatin. The current study suggests that the tissue conditioner containing the nystatin-alginate microparticle carrier system has potential as an effective antifungal material.

  13. Controlling Ionic Transport for Device Design in Synthetic Nanopores

    NASA Astrophysics Data System (ADS)

    Kalman, Eric Boyd

    Polymer nanopores present a number of behaviors not seen in microscale systems, such as ion current rectification, ionic selectivity, size exclusion and potential dependent ion concentrations in and near the pore. The existence of these effects stems from the small size of nanopores with respect to the characteristic length scales of surface interactions at the interface between the nanopore surface and the solution within it. The large surface-to-volume ratio due to the nanoscale geometry of a nanopore, as well as similarity in scale between geometry and interaction demands the solution interact with the nanopore walls. As surfaces in solution almost always carry residual charge, these surface forces are primarily the electrostatic interactions between the charge groups on the pore surface and the ions in solution. These interactions may be used by the experimentalist to control ionic transport through synthetic nanopores, and use them as a template for the construction of devices. In this research, we present our work on creating a number of ionic analogs to seminal electronic devices, specifically diodes, and transistors, by controlling ionic transport through the electrostatic interactions between a single synthetic nanopore and ions. Control is achieved by "doping" the effective charge carrier concentration in specific regions of the nanopore through manipulation of the pore's surface charge. This manipulation occurs through two mechanisms: chemical modification of the surface charge and electrostatic manipulation of the local internal nanopore potential using a gate electrode. Additionally, the innate selectivity of the charged nanopores walls allows for the separation of charges in solution. This well-known effect, which spawns measureable quantities, the streaming potential and current, has been used to create nanoscale water desalination membranes. We attempt to create a device using membranes with large nanopore densities for the desalination of water

  14. Nanoporous hard data: optical encoding of information within nanoporous anodic alumina photonic crystals.

    PubMed

    Santos, Abel; Law, Cheryl Suwen; Pereira, Taj; Losic, Dusan

    2016-04-21

    Herein, we present a method for storing binary data within the spectral signature of nanoporous anodic alumina photonic crystals. A rationally designed multi-sinusoidal anodisation approach makes it possible to engineer the photonic stop band of nanoporous anodic alumina with precision. As a result, the transmission spectrum of these photonic nanostructures can be engineered to feature well-resolved and selectively positioned characteristic peaks across the UV-visible spectrum. Using this property, we implement an 8-bit binary code and assess the versatility and capability of this system by a series of experiments aiming to encode different information within the nanoporous anodic alumina photonic crystals. The obtained results reveal that the proposed nanosized platform is robust, chemically stable, versatile and has a set of unique properties for data storage, opening new opportunities for developing advanced nanophotonic tools for a wide range of applications, including sensing, photonic tagging, self-reporting drug releasing systems and secure encoding of information.

  15. Endothelial- and Platelet-Derived Microparticles Are Generated During Liver Resection in Humans.

    PubMed

    Banz, Yara; Item, Gian-Marco; Vogt, Andreas; Rieben, Robert; Candinas, Daniel; Beldi, Guido

    2016-01-01

    Cell-derived plasma microparticles (<1.5 μm) originating from various cell types have the potential to regulate thrombogenesis and inflammatory responses. The aim of this study was to test the hypothesis that microparticles generated during hepatic surgery co-regulate postoperative procoagulant and proinflammatory events. In 30 patients undergoing liver resection, plasma microparticles were isolated, quantitated, and characterized as endothelial (CD31+, CD41-), platelet (CD41+), or leukocyte (CD11b+) origin by flow cytometry and their procoagulant and proinflammatory activity was measured by immunoassays. During liver resection, the total numbers of microparticles increased with significantly more Annexin V-positive, endothelial and platelet-derived microparticles following extended hepatectomy compared to standard and minor liver resections. After liver resection, microparticle tissue factor and procoagulant activity increased along with overall coagulation as assessed by thrombelastography. Levels of leukocyte-derived microparticles specifically increased in patients with systemic inflammation as assessed by C-reactive protein but are independent of the extent of liver resection. Endothelial and platelet-derived microparticles are specifically elevated during liver resection, accompanied by increased procoagulant activity. Leukocyte-derived microparticles are a potential marker for systemic inflammation. Plasma microparticles may represent a specific response to surgical stress and may be an important mediator of postoperative coagulation and inflammation.

  16. Particulate matter induces prothrombotic microparticle shedding by human mononuclear and endothelial cells.

    PubMed

    Neri, Tommaso; Pergoli, Laura; Petrini, Silvia; Gravendonk, Lotte; Balia, Cristina; Scalise, Valentina; Amoruso, Angela; Pedrinelli, Roberto; Paggiaro, Pierluigi; Bollati, Valentina; Celi, Alessandro

    2016-04-01

    Particulate airborne pollution is associated with increased cardiopulmonary morbidity. Microparticles are extracellular vesicles shed by cells upon activation or apoptosis involved in physiological processes such as coagulation and inflammation, including airway inflammation. We investigated the hypothesis that particulate matter causes the shedding of microparticles by human mononuclear and endothelial cells. Cells, isolated from the blood and the umbilical cords of normal donors, were cultured in the presence of particulate from a standard reference. Microparticles were assessed in the supernatant as phosphatidylserine concentration. Microparticle-associated tissue factor was assessed by an one-stage clotting assay. Nanosight technology was used to evaluate microparticle size distribution. Particulate matter induces a dose- and time- dependent, rapid (1h) increase in microparticle generation in both cells. These microparticles express functional tissue factor. Particulate matter increases intracellular calcium concentration and phospholipase C inhibition reduces microparticle generation. Nanosight analysis confirmed that upon exposure to particulate matter both cells express particles with a size range consistent with the definition of microparticles (50-1000 nm). Exposure of mononuclear and endothelial cells to particulate matter upregulates the generation of microparticles at least partially mediated by calcium mobilization. This observation might provide a further link between airborne pollution and cardiopulmonary morbidity. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Assessment of formulated amodiaquine microparticles in Leishmania donovani infected rats.

    PubMed

    Nettey, Henry; Allotey-Babington, Grace Lovia; Somuah, Isaac; Banga, N'guessan Benoit; Afrane, Barima; Amponsah, Seth Kwabena; Annor, Henrietta; Darko, Henry; Hanson, Kwame; Aidoo, Anoa; Broni, Marisa Nyarkoa; Sasu, Clement; Nyarko, Alexander

    2017-02-01

    The aim of this study was to formulate, characterise and evaluate the activity of amodiaquine microparticles against Leishmania donovani. Microparticles were formulated by encapsulating the drug in bovine serum albumin using the spray-dryer method. The microparticles were evaluated for size, zeta potential, drug content, encapsulation efficiency and in vitro release profile. The size range of the microparticles formulated was between 1.9 and 10 μm with an average zeta potential of -25.5 mV. Of the expected 20% drug loading, an average of 18.27% was obtained giving an encapsulation efficiency of 91.35%. Pharmacokinetic profile of amodiaquine improved with microencapsulation of the drug with C max , AUC 0→48 and t 1//2 all significantly higher than amodiaquine solution. Amodiaquine microparticles showed an overall higher bioavailability and hence were more effective in eliminating intra-tissue parasites than the drug solution. It would therefore be expected that the formulated microparticles will be more effective in treating visceral leishmaniasis.

  18. In vitro release kinetics of Tolmetin from tabletted Eudragit microparticles.

    PubMed

    Pignatello, R; Consoli, P; Puglisi, G

    2000-01-01

    In a previous paper the preparation has been described, by three different techniques, of microparticles made of Eudragit RS 100 and RL 100 containing a NSAI agent, Tolmetin. Freely flowing microparticles failed to affect significantly the in vitro drug release, which displayed a similar dissolution profile after micro-encapsulation to the free drug powder. Microparticles were then converted into tablets and the effect of compression on drug delivery, as well as that of the presence of co-additives, was studied in the present work. Furthermore, microparticles were also prepared by adding MgO to the polymer matrix, to reduce the sensitivity of the drug to pH changes during its dissolution. Similarly, magnesium stearate was also used for microparticle formation as a droplet stabilizer, in order to reduce particle size and hinder rapid drug release. A mathematical evaluation, by using two semi-empirical equations, was applied to evaluate the influence of dissolution and diffusion phenomena upon drug release from microparticle tablets.

  19. Agents for Change: Nonphysician Medical Providers and Health Care Quality

    PubMed Central

    Boucher, Nathan A; McMillen, Marvin A; Gould, James S

    2015-01-01

    Quality medical care is a clinical and public health imperative, but defining quality and achieving improved, measureable outcomes are extremely complex challenges. Adherence to best practice invariably improves outcomes. Nonphysician medical providers (NPMPs), such as physician assistants and advanced practice nurses (eg, nurse practitioners, advanced practice registered nurses, certified registered nurse anesthetists, and certified nurse midwives), may be the first caregivers to encounter the patient and can act as agents for change for an organization’s quality-improvement mandate. NPMPs are well positioned to both initiate and ensure optimal adherence to best practices and care processes from the moment of initial contact because they have robust clinical training and are integral to trainee/staff education and the timely delivery of care. The health care quality aspects that the practicing NPMP can affect are objective, appreciative, and perceptive. As bedside practitioners and participants in the administrative and team process, NPMPs can fine-tune care delivery, avoiding the problem areas defined by the Institute of Medicine: misuse, overuse, and underuse of care. This commentary explores how NPMPs can affect quality by 1) supporting best practices through the promotion of guidelines and protocols, and 2) playing active, if not leadership, roles in patient engagement and organizational quality-improvement efforts. PMID:25663213

  20. Milled non-mulberry silk fibroin microparticles as biomaterial for biomedical applications.

    PubMed

    Bhardwaj, Nandana; Rajkhowa, Rangam; Wang, Xungai; Devi, Dipali

    2015-11-01

    Silk fibroin has been widely employed in various forms as biomaterials for biomedical applications due to its superb biocompatibility and tunable degradation and mechanical properties. Herein, silk fibroin microparticles of non-mulberry silkworm species (Antheraea assamensis, Antheraea mylitta and Philosamia ricini) were fabricated via a top-down approach using a combination of wet-milling and spray drying techniques. Microparticles of mulberry silkworm (Bombyx mori) were also utilized for comparative studies. The fabricated microparticles were physico-chemically characterized for size, stability, morphology, chemical composition and thermal properties. The silk fibroin microparticles of all species were porous (∼5μm in size) and showed nearly spherical morphology with rough surface as revealed from dynamic light scattering and microscopic studies. Non-mulberry silk microparticles maintained the typical silk-II structure with β-sheet secondary conformation with higher thermal stability. Additionally, non-mulberry silk fibroin microparticles supported enhanced cell adhesion, spreading and viability of mouse fibroblasts than mulberry silk fibroin microparticles (p<0.001) as evidenced from fluorescence microscopy and cytotoxicity studies. Furthermore, in vitro drug release from the microparticles showed a significantly sustained release over 3 weeks. Taken together, this study demonstrates promising attributes of non-mulberry silk fibroin microparticles as a potential drug delivery vehicle/micro carrier for diverse biomedical applications. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Cryopreservation alters the membrane and cytoskeletal protein profile of platelet microparticles.

    PubMed

    Raynel, Sarah; Padula, Matthew P; Marks, Denese C; Johnson, Lacey

    2015-10-01

    Cryopreservation of platelets (PLTs) in dimethyl sulfoxide (DMSO) and storage at -80 °C extends the PLT shelf life to at least 2 years, allowing greater accessibility in military and rural environments. While cryopreserved PLTs have been extensively characterized, the microparticles formed as a result of cryopreservation are yet to be fully described. Apheresis PLTs were cryopreserved at -80 °C with 5% DMSO and sampled before freezing and after thawing. Microparticle number, size, surface receptor phenotype, and function were assessed by microscopy, flow cytometry, dynamic light scattering, and thrombin-generating capacity. Proteomic changes were examined using two-dimensional gel electrophoresis and Western blotting. PLT cryopreservation resulted in a 15-fold increase in the number of microparticles compared to fresh PLTs. The surface receptor phenotype of these microparticles differed to microparticles from fresh PLTs, with more microparticles expressing glycoprotein (GP)IV, GPIIb, and the GPIb-V-IX complex. Cryopreservation drastically altered the abundance of many cytoskeletal proteins in the PLT microparticles, including actin, filamin, gelsolin, and tropomyosin. Despite these changes, PLT microparticles were functional and contributed to phosphatidylserine- and tissue factor- induced thrombin generation. This study demonstrates that PLT microparticles formed by cryopreservation are phenotypically distinct from those present before freezing. These differences may be associated with the procoagulant properties of cryopreserved PLTs. © 2015 AABB.

  2. 3-D simulation of nanopore structure for DNA sequencing.

    PubMed

    Park, Jun-Mo; Pak, Y Eugene; Chun, Honggu; Lee, Jong-Ho

    2012-07-01

    In this paper, we propose a method for simulating nanopore structure by using conventional 3-D simulation tool to mimic the I-V behavior of the nanopore structure. In the simulation, we use lightly doped silicon for ionic solution where some parameters like electron affinity and dielectric constant are fitted to consider the ionic solution. By using this method, we can simulate the I-V behavior of nanopore structure depending on the location and the size of the sphere shaped silicon oxide which is considered to be an indicator of a DNA base. In addition, we simulate an Ionic Field Effect Transistor (IFET) which has basically the nanopore structure, and show that the simulated curves follow sufficiently the I-V behavior of the measurement data. Therefore, we think it is reasonable to apply parameter modeling mentioned above to simulate nanopore structure. The key idea is to modify electron affinity of silicon which is used to mimic the KCl solution to avoid band bending and depletion inside the nanopore. We could efficiently utilize conventional 3-D simulation tool to simulate the I-V behavior of nanopore structures.

  3. Characterization of Nanoporous Materials with Atom Probe Tomography.

    PubMed

    Pfeiffer, Björn; Erichsen, Torben; Epler, Eike; Volkert, Cynthia A; Trompenaars, Piet; Nowak, Carsten

    2015-06-01

    A method to characterize open-cell nanoporous materials with atom probe tomography (APT) has been developed. For this, open-cell nanoporous gold with pore diameters of around 50 nm was used as a model system, and filled by electron beam-induced deposition (EBID) to obtain a compact material. Two different EBID precursors were successfully tested-dicobalt octacarbonyl [Co2(CO)8] and diiron nonacarbonyl [Fe2(CO)9]. Penetration and filling depth are sufficient for focused ion beam-based APT sample preparation. With this approach, stable APT analysis of the nanoporous material can be performed. Reconstruction reveals the composition of the deposited precursor and the nanoporous material, as well as chemical information of the interfaces between them. Thus, it is shown that, using an appropriate EBID process, local chemical information in three dimensions with sub-nanometer resolution can be obtained from nanoporous materials using APT.

  4. Microparticles variability in fresh frozen plasma: preparation protocol and storage time effects.

    PubMed

    Kriebardis, Anastasios G; Antonelou, Marianna H; Georgatzakou, Hara T; Tzounakas, Vassilis L; Stamoulis, Konstantinos E; Papassideri, Issidora S

    2016-05-01

    Extracellular vesicles or microparticles exhibiting procoagulant and thrombogenic activity may contribute to the haemostatic potential of fresh frozen plasma. Fresh frozen plasma was prepared from platelet-rich plasma at 20 °C (Group-1 donors) or directly from whole blood at 4 °C (Group-2 donors). Each unit was aseptically divided into three parts, stored frozen for specific periods of time, and analysed by flow cytometry for procoagulant activity immediately after thaw or following post-thaw storage for 24 h at 4 °C. Donors' haematologic, biochemical and life-style profiles as well as circulating microparticles were analysed in parallel. Circulating microparticles exhibited a considerable interdonor but not intergroup variation. Fresh frozen plasma units were enriched in microparticles compared to plasma in vivo. Duration of storage significantly affected platelet- and red cell-derived microparticles. Fresh frozen plasma prepared directly from whole blood contained more residual platelets and more platelet-derived microparticles compared to fresh frozen plasma prepared from platelet-rich plasma. Consequently, there was a statistically significant difference in total, platelet- and red cell-derived microparticles between the two preparation protocols over storage time in the freezer. Preservation of the thawed units for 24 h at 4 °C did not significantly alter microparticle accumulation. Microparticle accumulation and anti-oxidant capacity of fresh frozen plasma was positively or negatively correlated, respectively, with the level of circulating microparticles in individual donors. The preparation protocol and the duration of storage in the freezer, independently and in combination, influenced the accumulation of microparticles in fresh frozen plasma units. In contrast, storage of thawed units for 24 h at 4 °C had no significant effect on the concentration of microparticles.

  5. Biological Nanopores: Confined Spaces for Electrochemical Single-Molecule Analysis.

    PubMed

    Cao, Chan; Long, Yi-Tao

    2018-02-20

    Nanopore sensing is developing into a powerful single-molecule approach to investigate the features of biomolecules that are not accessible by studying ensemble systems. When a target molecule is transported through a nanopore, the ions occupying the pore are excluded, resulting in an electrical signal from the intermittent ionic blockade event. By statistical analysis of the amplitudes, duration, frequencies, and shapes of the blockade events, many properties of the target molecule can be obtained in real time at the single-molecule level, including its size, conformation, structure, charge, geometry, and interactions with other molecules. With the development of the use of α-hemolysin to characterize individual polynucleotides, nanopore technology has attracted a wide range of research interest in the fields of biology, physics, chemistry, and nanoscience. As a powerful single-molecule analytical method, nanopore technology has been applied for the detection of various biomolecules, including oligonucleotides, peptides, oligosaccharides, organic molecules, and disease-related proteins. In this Account, we highlight recent developments of biological nanopores in DNA-based sensing and in studying the conformational structures of DNA and RNA. Furthermore, we introduce the application of biological nanopores to investigate the conformations of peptides affected by charge, length, and dipole moment and to study disease-related proteins' structures and aggregation transitions influenced by an inhibitor, a promoter, or an applied voltage. To improve the sensing ability of biological nanopores and further extend their application to a wider range of molecular sensing, we focus on exploring novel biological nanopores, such as aerolysin and Stable Protein 1. Aerolysin exhibits an especially high sensitivity for the detection of single oligonucleotides both in current separation and duration. Finally, to facilitate the use of nanopore measurements and statistical analysis

  6. Solid lipid microparticles containing loratadine prepared using a Micromixer.

    PubMed

    Milak, Spomenka; Medlicott, Natalie; Tucker, Ian G

    2006-12-01

    Solid lipid microparticles were investigated as a taste-masking approach for a lipophilic weak base in a suspension. The idea was that the drug concentration in the aqueous phase of a suspension might be reduced by its partitioning into the solid lipid particles. Loratadine, as a model drug, was used to prepare Precirol ATO 5 microparticles by a Micromixer. The effects of three process variables: drug loading, PVA concentration and water/lipid ratio on the microparticle size, encapsulation efficiency, surface appearance, in-vitro release and drug partitioning in a suspension were studied. Loratadine release was slow in simulated saliva and very fast at the pH of stomach. In suspension of loratadine lipid microparticles, drug was released into the aqueous phase to the same concentration as in a drug suspension. Therefore, the usefulness of these microparticles for taste-masking in liquids is limited. However, they might be useful for taste-masking in solid dosage forms.

  7. Aqueous Two Phase System Assisted Self-Assembled PLGA Microparticles

    NASA Astrophysics Data System (ADS)

    Yeredla, Nitish; Kojima, Taisuke; Yang, Yi; Takayama, Shuichi; Kanapathipillai, Mathumai

    2016-06-01

    Here, we produce poly(lactide-co-glycolide) (PLGA) based microparticles with varying morphologies, and temperature responsive properties utilizing a Pluronic F127/dextran aqueous two-phase system (ATPS) assisted self-assembly. The PLGA polymer, when emulsified in Pluronic F127/dextran ATPS, forms unique microparticle structures due to ATPS guided-self assembly. Depending on the PLGA concentration, the particles either formed a core-shell or a composite microparticle structure. The microparticles facilitate the simultaneous incorporation of both hydrophobic and hydrophilic molecules, due to their amphiphilic macromolecule composition. Further, due to the lower critical solution temperature (LCST) properties of Pluronic F127, the particles exhibit temperature responsiveness. The ATPS based microparticle formation demonstrated in this study, serves as a novel platform for PLGA/polymer based tunable micro/nano particle and polymersome development. The unique properties may be useful in applications such as theranostics, synthesis of complex structure particles, bioreaction/mineralization at the two-phase interface, and bioseparations.

  8. Methotrexate loaded gellan gum microparticles for drug delivery.

    PubMed

    Dhanka, Mukesh; Shetty, Chaitra; Srivastava, Rohit

    2018-04-15

    Recently, polysaccharides based microparticles have been found to offer an attractive potential as a carrier in drug delivery field. In this study, bare gellan gum microparticles (GG MPs) and methotrexate (MTX) loaded gellan gum microparticles (MTX-GG MPs) prepared by using simple water-in-oil (W/O) emulsion solvent diffusion method. The developed microparticles (MPs) were found discretely distributed in a spherical shape. MTX has been encapsulated in microparticles with 84.8 ± 1.68% encapsulation efficiency (%EE) and 6.45 ± 0.07% loading capacity (%LC). The Fourier Transform Infrared Spectroscopy (FTIR) characterization of the MPs clearly indicated the physical encapsulation of MTX into polymeric matrix of MPs. Thermogravimetric analysis (TGA) characterization showed slightly higher thermal stability of MTX-GG MPs in comparison to the GG MPs. In vitro release study of MTX-GG MPs showed 84% drug release within 24 h. The hemolysis study of GG MPs and MTX-GG MPs on human red blood cells (RBCs) showed <1.0% hemolysis. The cell viability studies on L929 showed GG MPs, and MTX-GG MPs are biocompatible. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Titanium Dioxide Nanofibers and Microparticles Containing Nickel Nanoparticles.

    PubMed

    Sheikh, Faheem A; Macossay, Javier; Kanjwal, Muzafar A; Abdal-Hay, Abdalla; Tantry, Mudasir A; Kim, Hern

    2012-10-12

    The present study reports on the introduction of various nanocatalysts containing nickel (Ni) nanoparticles (NPs) embedded within TiO 2 nanofibers and TiO 2 microparticles. Typically, a sol-gel consisting of titanium isopropoxide and Ni NPs was prepared to produce TiO 2 nanofibers by the electrospinning process. Similarly, TiO 2 microparticles containing Ni were prepared using a sol-gel syntheses process. The resultant structures were studied by SEM analyses, which confirmed well-obtained nanofibers and microparticles. Further, the XRD results demonstrated the crystalline feature of both TiO 2 and Ni in the obtained composites. Internal morphology of prepared nanofibers and microparticles containing Ni NPs was characterized by TEM, which demonstrated characteristic structures with good dispersion of Ni NPs. In addition, the prepared structures were studied as a model for hydrogen production applications. The catalytic activity of the prepared materials was studied by in situ hydrolysis of NaBH 4 , which indicated that the nanofibers containing Ni NPs can lead to produce higher amounts of hydrogen when compared to other microparticles, also reported in this paper. Overall, these results confirm the potential use of these materials in hydrogen production systems.

  10. Titanium Dioxide Nanofibers and Microparticles Containing Nickel Nanoparticles

    PubMed Central

    Sheikh, Faheem A.; Macossay, Javier; Kanjwal, Muzafar A.; Abdal-hay, Abdalla; Tantry, Mudasir A.; Kim, Hern

    2013-01-01

    The present study reports on the introduction of various nanocatalysts containing nickel (Ni) nanoparticles (NPs) embedded within TiO2 nanofibers and TiO2 microparticles. Typically, a sol-gel consisting of titanium isopropoxide and Ni NPs was prepared to produce TiO2 nanofibers by the electrospinning process. Similarly, TiO2 microparticles containing Ni were prepared using a sol-gel syntheses process. The resultant structures were studied by SEM analyses, which confirmed well-obtained nanofibers and microparticles. Further, the XRD results demonstrated the crystalline feature of both TiO2 and Ni in the obtained composites. Internal morphology of prepared nanofibers and microparticles containing Ni NPs was characterized by TEM, which demonstrated characteristic structures with good dispersion of Ni NPs. In addition, the prepared structures were studied as a model for hydrogen production applications. The catalytic activity of the prepared materials was studied by in situ hydrolysis of NaBH4, which indicated that the nanofibers containing Ni NPs can lead to produce higher amounts of hydrogen when compared to other microparticles, also reported in this paper. Overall, these results confirm the potential use of these materials in hydrogen production systems. PMID:24436780

  11. Nanopore thin film enabled optical platform for drug loading and release.

    PubMed

    Song, Chao; Che, Xiangchen; Que, Long

    2017-08-07

    In this paper, a drug loading and release device fabricated using nanopore thin film and layer-by-layer (LbL) nanoassembly is reported. The nanopore thin film is a layer of anodic aluminum oxide (AAO), consisting of honeycomb-shape nanopores. Using the LbL nanoassembly process, the drug, using gentamicin sulfate (GS) as the model, can be loaded into the nanopores and the stacked layers on the nanopore thin film surface. The drug release from the device is achieved by immersing it into flowing DI water. Both the loading and release processes can be monitored optically. The effect of the nanopore size/volume on drug loading and release has also been evaluated. Further, the neuron cells have been cultured and can grow normally on the nanopore thin film, verifying its bio-compatibility. The successful fabrication of nanopore thin film device on silicon membrane render it as a potential implantable controlled drug release device.

  12. Improved circulating microparticle analysis in acid-citrate dextrose (ACD) anticoagulant tube.

    PubMed

    György, Bence; Pálóczi, Krisztina; Kovács, Alexandra; Barabás, Eszter; Bekő, Gabriella; Várnai, Katalin; Pállinger, Éva; Szabó-Taylor, Katalin; Szabó, Tamás G; Kiss, Attila A; Falus, András; Buzás, Edit I

    2014-02-01

    Recently extracellular vesicles (exosomes, microparticles also referred to as microvesicles and apoptotic bodies) have attracted substantial interest as potential biomarkers and therapeutic vehicles. However, analysis of microparticles in biological fluids is confounded by many factors such as the activation of cells in the blood collection tube that leads to in vitro vesiculation. In this study we aimed at identifying an anticoagulant that prevents in vitro vesiculation in blood plasma samples. We compared the levels of platelet microparticles and non-platelet-derived microparticles in platelet-free plasma samples of healthy donors. Platelet-free plasma samples were isolated using different anticoagulant tubes, and were analyzed by flow cytometry and Zymuphen assay. The extent of in vitro vesiculation was compared in citrate and acid-citrate-dextrose (ACD) tubes. Agitation and storage of blood samples at 37 °C for 1 hour induced a strong release of both platelet microparticles and non-platelet-derived microparticles. Strikingly, in vitro vesiculation related to blood sample handling and storage was prevented in samples in ACD tubes. Importantly, microparticle levels elevated in vivo remained detectable in ACD tubes. We propose the general use of the ACD tube instead of other conventional anticoagulant tubes for the assessment of plasma microparticles since it gives a more realistic picture of the in vivo levels of circulating microparticles and does not interfere with downstream protein or RNA analyses. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Graphene Nanopores for Protein Sequencing.

    PubMed

    Wilson, James; Sloman, Leila; He, Zhiren; Aksimentiev, Aleksei

    2016-07-19

    An inexpensive, reliable method for protein sequencing is essential to unraveling the biological mechanisms governing cellular behavior and disease. Current protein sequencing methods suffer from limitations associated with the size of proteins that can be sequenced, the time, and the cost of the sequencing procedures. Here, we report the results of all-atom molecular dynamics simulations that investigated the feasibility of using graphene nanopores for protein sequencing. We focus our study on the biologically significant phenylalanine-glycine repeat peptides (FG-nups)-parts of the nuclear pore transport machinery. Surprisingly, we found FG-nups to behave similarly to single stranded DNA: the peptides adhere to graphene and exhibit step-wise translocation when subject to a transmembrane bias or a hydrostatic pressure gradient. Reducing the peptide's charge density or increasing the peptide's hydrophobicity was found to decrease the translocation speed. Yet, unidirectional and stepwise translocation driven by a transmembrane bias was observed even when the ratio of charged to hydrophobic amino acids was as low as 1:8. The nanopore transport of the peptides was found to produce stepwise modulations of the nanopore ionic current correlated with the type of amino acids present in the nanopore, suggesting that protein sequencing by measuring ionic current blockades may be possible.

  14. A Protein Nanopore-Based Approach for Bacteria Sensing

    NASA Astrophysics Data System (ADS)

    Apetrei, Aurelia; Ciuca, Andrei; Lee, Jong-kook; Seo, Chang Ho; Park, Yoonkyung; Luchian, Tudor

    2016-11-01

    We present herein a first proof of concept demonstrating the potential of a protein nanopore-based technique for real-time detection of selected Gram-negative bacteria ( Pseudomonas aeruginosa or Escherichia coli) at a concentration of 1.2 × 108 cfu/mL. The anionic charge on the bacterial outer membrane promotes the electrophoretically driven migration of bacteria towards a single α-hemolysin nanopore isolated in a lipid bilayer, clamped at a negative electric potential, and followed by capture at the nanopore's mouth, which we found to be described according to the classical Kramers' theory. By using a specific antimicrobial peptide as a putative molecular biorecognition element for the bacteria used herein, we suggest that the detection system can combine the natural sensitivity of the nanopore-based sensing techniques with selective biological recognition, in aqueous samples, and highlight the feasibility of the nanopore-based platform to provide portable, sensitive analysis and monitoring of bacterial pathogens.

  15. Nanopore Electrochemistry: A Nexus for Molecular Control of Electron Transfer Reactions

    PubMed Central

    2018-01-01

    Pore-based structures occur widely in living organisms. Ion channels embedded in cell membranes, for example, provide pathways, where electron and proton transfer are coupled to the exchange of vital molecules. Learning from mother nature, a recent surge in activity has focused on artificial nanopore architectures to effect electrochemical transformations not accessible in larger structures. Here, we highlight these exciting advances. Starting with a brief overview of nanopore electrodes, including the early history and development of nanopore sensing based on nanopore-confined electrochemistry, we address the core concepts and special characteristics of nanopores in electron transfer. We describe nanopore-based electrochemical sensing and processing, discuss performance limits and challenges, and conclude with an outlook for next-generation nanopore electrode sensing platforms and the opportunities they present. PMID:29392173

  16. Circulating microparticles and endogenous estrogen in newly menopausal women

    PubMed Central

    Jayachandran, M.; Litwiller, R. D.; Owen, W. G.; Miller, V. M.

    2011-01-01

    Background Estrogen modulates antithrombotic characteristics of the vascular endothelium and the interaction of blood elements with the vascular surface. A marker of these modulatory activities is formation of cell-specific microparticles. This study examined the relationship between blood-borne microparticles and endogenous estrogen at menopause. Methods Platelet activation and plasma microparticles were characterized from women being screened (n = 146) for the Kronos Early Estrogen Prevention Study. Women were grouped according to serum estrogen (< 20 pg/ml; low estrogen, n = 21 or > 40 pg/ml; high estrogen, n = 11). Results Age, body mass index, blood pressure and blood chemistries were the same in both groups. No woman was hypertensive, diabetic or a current smoker. Platelet counts, basal and activated expression of P-selectin on platelet membranes were the same, but activated expression of glycoprotein IIb/IIIa was greater in the high-estrogen group. Numbers of endothelium-, platelet-, monocyte- and granulocyte-derived microparticles were greater in the low-estrogen group. Of the total numbers of microparticles, those positive for phosphatidylserine and tissue factor were also greater in the low-estrogen group. Conclusion These results suggest that, with declines in endogenous estrogen at menopause, numbers of procoagulant microparticles increase and thus may provide a means to explore mechanisms for cardiovascular risk development in newly menopausal women. PMID:19051075

  17. Microparticles variability in fresh frozen plasma: preparation protocol and storage time effects

    PubMed Central

    Kriebardis, Anastasios G.; Antonelou, Marianna H.; Georgatzakou, Hara T.; Tzounakas, Vassilis L.; Stamoulis, Konstantinos E.; Papassideri, Issidora S.

    2016-01-01

    Background Extracellular vesicles or microparticles exhibiting procoagulant and thrombogenic activity may contribute to the haemostatic potential of fresh frozen plasma. Materials and methods Fresh frozen plasma was prepared from platelet-rich plasma at 20 °C (Group-1 donors) or directly from whole blood at 4 °C (Group-2 donors). Each unit was aseptically divided into three parts, stored frozen for specific periods of time, and analysed by flow cytometry for procoagulant activity immediately after thaw or following post-thaw storage for 24 h at 4 °C. Donors’ haematologic, biochemical and life-style profiles as well as circulating microparticles were analysed in parallel. Results Circulating microparticles exhibited a considerable interdonor but not intergroup variation. Fresh frozen plasma units were enriched in microparticles compared to plasma in vivo. Duration of storage significantly affected platelet- and red cell-derived microparticles. Fresh frozen plasma prepared directly from whole blood contained more residual platelets and more platelet-derived microparticles compared to fresh frozen plasma prepared from platelet-rich plasma. Consequently, there was a statistically significant difference in total, platelet- and red cell-derived microparticles between the two preparation protocols over storage time in the freezer. Preservation of the thawed units for 24 h at 4 °C did not significantly alter microparticle accumulation. Microparticle accumulation and anti-oxidant capacity of fresh frozen plasma was positively or negatively correlated, respectively, with the level of circulating microparticles in individual donors. Discussion The preparation protocol and the duration of storage in the freezer, independently and in combination, influenced the accumulation of microparticles in fresh frozen plasma units. In contrast, storage of thawed units for 24 h at 4 °C had no significant effect on the concentration of microparticles. PMID:27136430

  18. Nanopore Kinetic Proofreading of DNA Sequences

    NASA Astrophysics Data System (ADS)

    Ling, Xinsheng Sean

    The concept of DNA sequencing using the time dependence of the nanopore ionic current was proposed in 1996 by Kasianowicz, Brandin, Branton, and Deamer (KBBD). The KBBD concept has generated tremendous amount interests in recent decade. In this talk, I will review the current understanding of the DNA ``translocation'' dynamics and how it can be described by Schrodinger's 1915 paper on first-passage-time distribution function. Schrodinger's distribution function can be used to give a rigorous criterion for achieving nanopore DNA sequencing which turns out to be identical to that of gel electrophoresis used by Sanger in the first-generation Sanger method. A nanopore DNA sequencing technology also requires discrimination of bases with high accuracies. I will describe a solid-state nanopore sandwich structure that can function as a proofreading device capable of discriminating between correct and incorrect hybridization probes with an accuracy rivaling that of high-fidelity DNA polymerases. The latest results from Nanjing will be presented. This work is supported by China 1000-Talent Program at Southeast University, Nanjing, China.

  19. Nanopore fabrication and characterization by helium ion microscopy

    NASA Astrophysics Data System (ADS)

    Emmrich, D.; Beyer, A.; Nadzeyka, A.; Bauerdick, S.; Meyer, J. C.; Kotakoski, J.; Gölzhäuser, A.

    2016-04-01

    The Helium Ion Microscope (HIM) has the capability to image small features with a resolution down to 0.35 nm due to its highly focused gas field ionization source and its small beam-sample interaction volume. In this work, the focused helium ion beam of a HIM is utilized to create nanopores with diameters down to 1.3 nm. It will be demonstrated that nanopores can be milled into silicon nitride, carbon nanomembranes, and graphene with well-defined aspect ratio. To image and characterize the produced nanopores, helium ion microscopy and high resolution scanning transmission electron microscopy were used. The analysis of the nanopores' growth behavior allows inferring on the profile of the helium ion beam.

  20. Synthesis and applications of nanoporous perovskite metal oxides

    PubMed Central

    Huang, Xiubing; Zhao, Guixia

    2018-01-01

    Perovskite-type metal oxides have been widely investigated and applied in various fields in the past several decades due to their extraordinary variability of compositions and structures with targeted physical and chemical properties (e.g., redox behaviour, oxygen mobility, electronic and ionic conductivity). Recently, nanoporous perovskite metal oxides have attracted extensive attention because of their special morphology and properties, as well as superior performance. This minireview aims at summarizing and reviewing the different synthesis methods of nanoporous perovskite metal oxides and their various applications comprehensively. The correlations between the nanoporous structures and the specific performance of perovskite oxides are summarized and highlighted. The future research directions of nanoporous perovskite metal oxides are also prospected. PMID:29862001

  1. Streaming current magnetic fields in a charged nanopore.

    PubMed

    Mansouri, Abraham; Taheri, Peyman; Kostiuk, Larry W

    2016-11-11

    Magnetic fields induced by currents created in pressure driven flows inside a solid-state charged nanopore were modeled by numerically solving a system of steady state continuum partial differential equations, i.e., Poisson, Nernst-Planck, Ampere and Navier-Stokes equations (PNPANS). This analysis was based on non-dimensional transport governing equations that were scaled using Debye length as the characteristic length scale, and applied to a finite length cylindrical nano-channel. The comparison of numerical and analytical studies shows an excellent agreement and verified the magnetic fields density both inside and outside the nanopore. The radially non-uniform currents resulted in highly non-uniform magnetic fields within the nanopore that decay as 1/r outside the nanopore. It is worth noting that for either streaming currents or streaming potential cases, the maximum magnetic field occurred inside the pore in the vicinity of nanopore wall, as opposed to a cylindrical conductor that carries a steady electric current where the maximum magnetic fields occur at the perimeter of conductor. Based on these results, it is suggested and envisaged that non-invasive external magnetic fields readouts generated by streaming/ionic currents may be viewed as secondary electronic signatures of biomolecules to complement and enhance current DNA nanopore sequencing techniques.

  2. Streaming current magnetic fields in a charged nanopore

    NASA Astrophysics Data System (ADS)

    Mansouri, Abraham; Taheri, Peyman; Kostiuk, Larry W.

    2016-11-01

    Magnetic fields induced by currents created in pressure driven flows inside a solid-state charged nanopore were modeled by numerically solving a system of steady state continuum partial differential equations, i.e., Poisson, Nernst-Planck, Ampere and Navier-Stokes equations (PNPANS). This analysis was based on non-dimensional transport governing equations that were scaled using Debye length as the characteristic length scale, and applied to a finite length cylindrical nano-channel. The comparison of numerical and analytical studies shows an excellent agreement and verified the magnetic fields density both inside and outside the nanopore. The radially non-uniform currents resulted in highly non-uniform magnetic fields within the nanopore that decay as 1/r outside the nanopore. It is worth noting that for either streaming currents or streaming potential cases, the maximum magnetic field occurred inside the pore in the vicinity of nanopore wall, as opposed to a cylindrical conductor that carries a steady electric current where the maximum magnetic fields occur at the perimeter of conductor. Based on these results, it is suggested and envisaged that non-invasive external magnetic fields readouts generated by streaming/ionic currents may be viewed as secondary electronic signatures of biomolecules to complement and enhance current DNA nanopore sequencing techniques.

  3. Streaming current magnetic fields in a charged nanopore

    PubMed Central

    Mansouri, Abraham; Taheri, Peyman; Kostiuk, Larry W.

    2016-01-01

    Magnetic fields induced by currents created in pressure driven flows inside a solid-state charged nanopore were modeled by numerically solving a system of steady state continuum partial differential equations, i.e., Poisson, Nernst-Planck, Ampere and Navier-Stokes equations (PNPANS). This analysis was based on non-dimensional transport governing equations that were scaled using Debye length as the characteristic length scale, and applied to a finite length cylindrical nano-channel. The comparison of numerical and analytical studies shows an excellent agreement and verified the magnetic fields density both inside and outside the nanopore. The radially non-uniform currents resulted in highly non-uniform magnetic fields within the nanopore that decay as 1/r outside the nanopore. It is worth noting that for either streaming currents or streaming potential cases, the maximum magnetic field occurred inside the pore in the vicinity of nanopore wall, as opposed to a cylindrical conductor that carries a steady electric current where the maximum magnetic fields occur at the perimeter of conductor. Based on these results, it is suggested and envisaged that non-invasive external magnetic fields readouts generated by streaming/ionic currents may be viewed as secondary electronic signatures of biomolecules to complement and enhance current DNA nanopore sequencing techniques. PMID:27833119

  4. Encapsulation of antigen-loaded silica nanoparticles into microparticles for intradermal powder injection.

    PubMed

    Deng, Yibin; Mathaes, Roman; Winter, Gerhard; Engert, Julia

    2014-10-15

    Epidermal powder immunisation (EPI) is being investigated as a promising needle-free delivery methods for vaccination. The objective of this work was to prepare a nanoparticles-in-microparticles (nano-in-micro) system, integrating the advantages of nanoparticles and microparticles into one vaccine delivery system for epidermal powder immunisation. Cationic mesoporous silica nanoparticles (MSNP-NH2) were prepared and loaded with ovalbumin as a model antigen. Loading was driven by electrostatic interactions. Ovalbumin-loaded silica nanoparticles were subsequently formulated into sugar-based microparticles by spray-freeze-drying. The obtained microparticles meet the size requirement for EPI. Confocal microscopy was used to demonstrate that the nanoparticles are homogeneously distributed in the microparticles. Furthermore, the silica nanoparticles in the dry microparticles can be re-dispersed in aqueous solution showing no aggregation. The recovered ovalbumin shows integrity compared to native ovalbumin. The present nano-in-micro system allows (1) nanoparticles to be immobilized and finely distributed in microparticles, (2) microparticle formation and (3) re-dispersion of nanoparticles without subsequent aggregation. The nanoparticles inside microparticles can (1) adsorb proteins to cationic shell/surface voids in spray-dried products without detriment to ovalbumin stability, (2) deliver antigens in nano-sized modes to allow recognition by the immune system. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Assessing consumption of bioactive micro-particles by filter-feeding Asian carp

    USGS Publications Warehouse

    Jensen, Nathan R.; Amberg, Jon J.; Luoma, James A.; Walleser, Liza R.; Gaikowski, Mark P.

    2012-01-01

    Silver carp Hypophthalmichthys molitrix (SVC) and bighead carp H. nobilis (BHC) have impacted waters in the US since their escape. Current chemical controls for aquatic nuisance species are non-selective. Development of a bioactive micro-particle that exploits filter-feeding habits of SVC or BHC could result in a new control tool. It is not fully understood if SVC or BHC will consume bioactive micro-particles. Two discrete trials were performed to: 1) evaluate if SVC and BHC consume the candidate micro-particle formulation; 2) determine what size they consume; 3) establish methods to evaluate consumption of filter-feeders for future experiments. Both SVC and BHC were exposed to small (50-100 μm) and large (150-200 μm) micro-particles in two 24-h trials. Particles in water were counted electronically and manually (microscopy). Particles on gill rakers were counted manually and intestinal tracts inspected for the presence of micro-particles. In Trial 1, both manual and electronic count data confirmed reductions of both size particles; SVC appeared to remove more small particles than large; more BHC consumed particles; SVC had fewer overall particles in their gill rakers than BHC. In Trial 2, electronic counts confirmed reductions of both size particles; both SVC and BHC consumed particles, yet more SVC consumed micro-particles compared to BHC. Of the fish that ate micro-particles, SVC consumed more than BHC. It is recommended to use multiple metrics to assess consumption of candidate micro-particles by filter-feeders when attempting to distinguish differential particle consumption. This study has implications for developing micro-particles for species-specific delivery of bioactive controls to help fisheries, provides some methods for further experiments with bioactive micro-particles, and may also have applications in aquaculture.

  6. Increased serum concentration of immune cell derived microparticles in polymyositis/dermatomyositis.

    PubMed

    Baka, Zsuzsanna; Senolt, Ladislav; Vencovsky, Jiri; Mann, Herman; Simon, Piroska Sebestyén; Kittel, Agnes; Buzás, Edit; Nagy, György

    2010-02-16

    Microparticles are recently recognized players of intercellular communication. They are involved in signal transduction, cell activation and apoptosis. Their importance is also suggested in autoimmune diseases such as rheumatoid arthritis and systemic sclerosis. We investigated the role of microparticles in polymyositis/dermatomyositis, a group of rare autoimmune diseases, characterized by specific skin lesions and muscle weakness. The plasma concentration of monocyte and lymphocyte derived microparticles of 20 patients with polymyositis/dermatomyositis and 20 healthy controls were determined by flow cytometry. The structure of microparticles was visualized by electron microscopy. Significantly elevated numbers of monocyte (CD14 positive), T-lymphocyte (CD3 positive) and B-lymphocyte (CD19 positive) derived microparticles were found in the plasma samples of polymyositis/dermatomyositis patients, compared to healthy controls (p=0.001, 0.01 and 0.006, respectively). Furthermore, the plasma levels of monocyte and B-lymphocyte derived microparticles correlated with the manual muscle strength test (r=0.497, p=0.027; r=0.508, p=0.023; respectively). Patients with anti-Jo-1 antibody and lung involvement had significantly higher numbers of T- and B-lymphocyte and monocyte derived MPs (p=0.006, 0.012 and 0.007, respectively, for anti-Jo-1; p=0.013, 0.016 and 0.025, respectively, for lung involvement). After ultracentrifugation, CK activity could be detected only in traces in the resuspended pellet containing microparticles of healthy and diseased individuals. The electron microscopy revealed slightly different microparticles in the samples of patients with polymyositis/dermatomyositis. These results suggest that immune cell derived microparticles may contribute to the inflammatory process in polymyositis/dermatomyositis, however, CK-positive, possibly muscle derived microparticles do not seem to be present in the blood of patients with polymyositis

  7. Cell-derived microparticles and complement activation in preeclampsia versus normal pregnancy.

    PubMed

    Biró, E; Lok, C A R; Hack, C E; van der Post, J A M; Schaap, M C L; Sturk, A; Nieuwland, R

    2007-01-01

    Inflammation plays a major role in the vascular dysfunction seen in preeclampsia, and several studies suggest involvement of the complement system. To investigate whether complement activation on the surface of microparticles is increased in plasma of preeclamptic patients versus healthy pregnant controls. Microparticles from plasma of preeclamptic (n=10), healthy pregnant (n=10) and healthy nonpregnant (n=10) women were analyzed by flow cytometry for bound complement components (C1q, C4, C3) and complement activator molecules (C-reactive protein [CRP], serum amyloid P component [SAP], immunoglobulin [Ig]M, IgG). Fluid phase complement activation products and activator molecules were also determined. Levels of microparticles with bound complement components showed no increase in complement activation on the microparticle surface in preeclamptic women, in line with levels of fluid phase complement activation products. In healthy nonpregnant and pregnant women, bound CRP was associated with classical pathway activation on the microparticle surface, and in healthy pregnant women IgM and IgG molecules also contributed. In preeclamptic women, microparticles with bound SAP and those with IgG seemed to contribute to C1q binding without a clear association to further classical pathway activation. Furthermore, significantly increased levels of microparticles with bound CRP were present in preeclamptic compared with healthy pregnant women (median 178x10(6)/L versus 47x10(6)/L, P<0.01), but without concomitant increases in complement activation. We found no evidence of increased complement activation on the microparticle surface in preeclamptic women. Microparticles with bound CRP were significantly increased, but in contrast to healthy pregnant and nonpregnant women, this was not associated with increased classical pathway activation on the surface of the microparticles.

  8. Liposomes self-assembled from electrosprayed composite microparticles

    NASA Astrophysics Data System (ADS)

    Yu, Deng-Guang; Yang, Jun-He; Wang, Xia; Tian, Feng

    2012-03-01

    Composite microparticles, consisting of polyvinylpyrrolidone (PVP), naproxen (NAP) and lecithin (PC), have been successfully prepared using an electrospraying process and exploited as templates to manipulate molecular self-assembly for the synthesis of liposomes in situ. Field emission scanning electron microscope (FESEM) and transmission electron microscope (TEM) observations demonstrate that the microparticles have an average diameter of 960 ± 140 nm and a homogeneous structure. X-ray diffraction (XRD) patterns, differential scanning calorimetry (DSC) and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) results verify that the building blocks NAP and PC are scattered in the polymer matrix in a molecular way owing to the very fast drying of the electrospraying process and the favorable secondary interactions among the components. FESEM, scanning probe microscope (SPM) and TEM observations demonstrate that the liposomes can be achieved through molecular self-assembly in situ when the microparticles contact water thanks to ‘like prefers like’ and by means of the confinement effect of the microparticles. The liposomes have an encapsulation rate of 91.3%, and 80.7% of the drug in the liposomes can be freed into the dissolution medium in a sustained way and by a diffusion mechanism over a period of 24 h. The developed strategy not only provides a new, facile, and effective method to assemble and organize molecules of multiple components into liposomes with electrosprayed microparticles as templates, but also opens a new avenue for nanofabrication in a step-by-step and controllable way.

  9. Microparticles Mediate Hepatic Ischemia-Reperfusion Injury and Are the Targets of Diannexin (ASP8597)

    PubMed Central

    Wong, Heng Jian; Croft, Kevin; Mori, Trevor; Farrell, Geoffrey C.

    2014-01-01

    Background & Aims Ischemia–reperfusion injury (IRI) can cause hepatic failure after liver surgery or transplantation. IRI causes oxidative stress, which injures sinusoidal endothelial cells (SECs), leading to recruitment and activation of Kupffer cells, platelets and microcirculatory impairment. We investigated whether injured SECs and other cell types release microparticles during post-ischemic reperfusion, and whether such microparticles have pro-inflammatory, platelet-activating and pro-injurious effects that could contribute to IRI pathogenesis. Methods C57BL6 mice underwent 60 min of partial hepatic ischemia followed by 15 min–24 hrs of reperfusion. We collected blood and liver samples, isolated circulating microparticles, and determined protein and lipid content. To establish mechanism for microparticle production, we subjected murine primary hepatocytes to hypoxia-reoxygenation. Because microparticles express everted phosphatidylserine residues that are the target of annexin V, we analyzed the effects of an annexin V-homodimer (Diannexin or ASP8597) on post-ischemia microparticle production and function. Results Microparticles were detected in the circulation 15–30 min after post-ischemic reperfusion, and contained markers of SECs, platelets, natural killer T cells, and CD8+ cells; 4 hrs later, they contained markers of macrophages. Microparticles contained F2-isoprostanes, indicating oxidative damage to membrane lipids. Injection of mice with TNF-α increased microparticle formation, whereas Diannexin substantially reduced microparticle release and prevented IRI. Hypoxia-re-oxygenation generated microparticles from primary hepatocytes by processes that involved oxidative stress. Exposing cultured hepatocytes to preparations of microparticles isolated from the circulation during IRI caused injury involving mitochondrial membrane permeability transition. Microparticles also activated platelets and induced neutrophil migration in vitro. The inflammatory

  10. Phagocytosis of microparticles by alveolar macrophages during acute lung injury requires MerTK.

    PubMed

    Mohning, Michael P; Thomas, Stacey M; Barthel, Lea; Mould, Kara J; McCubbrey, Alexandria L; Frasch, S Courtney; Bratton, Donna L; Henson, Peter M; Janssen, William J

    2018-01-01

    Microparticles are a newly recognized class of mediators in the pathophysiology of lung inflammation and injury, but little is known about the factors that regulate their accumulation and clearance. The primary objective of our study was to determine whether alveolar macrophages engulf microparticles and to elucidate the mechanisms by which this occurs. Alveolar microparticles were quantified in bronchoalveolar fluid of mice with lung injury induced by LPS and hydrochloric acid. Microparticle numbers were greatest at the peak of inflammation and declined as inflammation resolved. Isolated, fluorescently labeled particles were placed in culture with macrophages to evaluate ingestion in the presence of endocytosis inhibitors. Ingestion was blocked with cytochalasin D and wortmannin, consistent with a phagocytic process. In separate experiments, mice were treated intratracheally with labeled microparticles, and their uptake was assessed though microscopy and flow cytometry. Resident alveolar macrophages, not recruited macrophages, were the primary cell-ingesting microparticles in the alveolus during lung injury. In vitro, microparticles promoted inflammatory signaling in LPS primed epithelial cells, signifying the importance of microparticle clearance in resolving lung injury. Microparticles were found to have phosphatidylserine exposed on their surfaces. Accordingly, we measured expression of phosphatidylserine receptors on macrophages and found high expression of MerTK and Axl in the resident macrophage population. Endocytosis of microparticles was markedly reduced in MerTK-deficient macrophages in vitro and in vivo. In conclusion, microparticles are released during acute lung injury and peak in number at the height of inflammation. Resident alveolar macrophages efficiently clear these microparticles through MerTK-mediated phagocytosis.

  11. Galvanic zinc-copper microparticles inhibit melanogenesis via multiple pigmentary pathways.

    PubMed

    Won, Yen-Kim; Lin, Connie B; Seiberg, Miri; Chen, Nannan; Hu, Yaping; Rossetti, Dianne; Saliou, Claude; Loy, Chong-Jin

    2014-01-01

    The endogenous electrical field of human skin plays an important role in many skin functions. However, the biological effects and mechanism of action of externally applied electrical stimulation on skin remain unclear. Recent study showed that galvanic zinc-copper microparticles produce electrical stimulation and reduce inflammatory and immune responses in intact skin, suggesting the important role of electrical stimulation in non-wounded skin. The objective of this study is to investigate the biological effect of galvanic zinc-copper microparticles on skin pigmentation. Our findings showed that galvanic zinc-copper microparticles inhibited melanogenesis in a human melanoma cell line (MNT-1), human keratinocytes and melanoma cells co-cultures, and in pigmented epidermal equivalents. Treatment of galvanic zinc-copper microparticles inhibited melanogenesis by reducing the promoter transactivation of tyrosinase and tyrosinase-related protein-1 in human melanoma cells. In a co-culture Transwell system of keratinocytes and melanoma cells, galvanic zinc-copper microparticles reduced melanin production via downregulation of endothelin-1 secretion from keratinocytes and reduced tyrosinase gene expression in melanoma cells. In addition, exposure of pigmented epidermal equivalents to galvanic zinc-copper microparticles resulted in reduced melanin deposition. In conclusion, our data demonstrated for the first time that galvanic zinc-copper microparticles reduced melanogenesis in melanoma cells and melanin deposition in pigmented epidermal equivalents by affecting multiple pigmentary pathways.

  12. In vivo biocompatibility of the PLGA microparticles in parotid gland

    PubMed Central

    Cantín, Mario; Miranda, Patricio; Suazo Galdames, Iván; Zavando, Daniela; Arenas, Patricia; Velásquez, Luis; Vilos, Cristian

    2013-01-01

    Poly(lactic-co-glycolic acid) (PLGA) microparticles are used in various disorders for the controlled or sustained release of drugs, with the management of salivary gland pathologies possible using this technology. There is no record of the response to such microparticles in the glandular parenchyma. The purpose of this study was to assess the morphological changes in the parotid gland when injected with a single dose of PLGA microparticles. We used 12 adult female Sprague Dawley rats (Rattus norvegicus) that were injected into their right parotid gland with sterile vehicle solution (G1, n=4), 0.5 mg PLGA microparticles (G2, n=4), and 0.75 mg PLGA microparticles (G3, n=4); the microparticles were dissolved in a sterile vehicle solution. The intercalar and striated ducts lumen, the thickness of the acini and the histology aspect in terms of the parenchyma organization, cell morphology of acini and duct system, the presence of polymeric residues, and inflammatory response were determined at 14 days post-injection. The administration of the compound in a single dose modified some of the morphometric parameters of parenchyma (intercalar duct lumen and thickness of the glandular acini) but did not induce tissue inflammatory response, despite the visible presence of polymer waste. This suggests that PLGA microparticles are biocompatible with the parotid tissue, making it possible to use intraglandular controlled drug administration. PMID:24228103

  13. PREFACE New developments in nanopore research—from fundamentals to applications New developments in nanopore research—from fundamentals to applications

    NASA Astrophysics Data System (ADS)

    Albrecht, Tim; Edel, Joshua B.; Winterhalter, Mathias

    2010-11-01

    Biological and solid-state nanopores are an exciting field of research, which has seen a rapid development over the last 10 to 20 years. Activities in this area range from theoretical and experimental work on the underlying fundamental (bio)physics to applications in single-molecule biosensing. And while the prospect of DNA sequencing continues to be a major driving force, other applications with potentially similar impact begin to emerge, for example the detection of small molecules, proteins, protein/protein and protein/DNA complexes, and RNA to name just a few. It has also become apparent that both classes of nanopore devices have intrinsic advantages and disadvantages; hybrid structures combining the better of the two worlds would be a logical consequence and are beginning to appear in the literature. Many other highly innovative ideas and concepts continue to emerge and the number of nanopore-related publications has increased drastically over recent years. We found that more than 100 research groups worldwide are active in this area; several commercial settings are in the process of translating fundamental research into real-life applications. We therefore felt that now is the right time to showcase these new developments in a special issue: to inspire researchers active in the field, to liberate inherent synergies, and not least, to demonstrate to the outside world the current state-of-the-art and future opportunities. The title 'New developments in nanopore research—from fundamentals to applications' in some way reflects these ambitions and, even though not everyone invited was able to contribute, we were able to assemble 34 high-quality research papers from all over the world. We would like to acknowledge and thank all the contributors for their submissions, which made this special issue possible in the first place. Moreover, we would like to thank the staff at IOP Publishing for helping us with the administrative aspects and for coordinating the

  14. Preparation and in vitro evaluation of pyridostigmine bromide microparticles.

    PubMed

    Hegazy, Nahed; Demirel, Müzeyyen; Yazan, Yasemin

    2002-08-21

    Pyridostigmine bromide (PB) is an anticholinesterase agent whose aqueous solubility is high and which has a short elimination half-life. Its dosage rate in the treatment of myastenia gravis is frequent due to the short half-life and it exhibits side effects. Microparticles designed to deliver a pharmaceutical active ingredient efficiently at the minimum dose and also to enhance stability, reduce side effects and modify drug release were prepared in this study using an acrylic polymer (Eudragit) as the vehicle by the spray-drying technique. The drug was either dissolved or dispersed in the polymeric solution and following the preparation of microparticles using different ratios of ingredients, characterization studies including the determination of shape, particle size distribution, amount loaded, release and stability of PB were performed. The results obtained were compared to those of pure PB. Drug release from microparticles could be modified and was found to depend on the shapes of the microparticles. In vitro evaluation results indicate that the frequent dosage and side effects of pure PB may be reduced with the formulation of microparticles.

  15. Voltage-Rectified Current and Fluid Flow in Conical Nanopores.

    PubMed

    Lan, Wen-Jie; Edwards, Martin A; Luo, Long; Perera, Rukshan T; Wu, Xiaojian; Martin, Charles R; White, Henry S

    2016-11-15

    Ion current rectification (ICR) refers to the asymmetric potential-dependent rate of the passage of solution ions through a nanopore, giving rise to electrical current-voltage characteristics that mimic those of a solid-state electrical diode. Since the discovery of ICR in quartz nanopipettes two decades ago, synthetic nanopores and nanochannels of various geometries, fabricated in membranes and on wafers, have been extensively investigated to understand fundamental aspects of ion transport in highly confined geometries. It is now generally accepted that ICR requires an asymmetric electrical double layer within the nanopore, producing an accumulation or depletion of charge-carrying ions at opposite voltage polarities. Our research groups have recently explored how the voltage-dependent ion distributions and ICR within nanopores can induce novel nanoscale flow phenomena that have applications in understanding ionics in porous materials used in energy storage devices, chemical sensing, and low-cost electrical pumping of fluids. In this Account, we review our most recent investigations on this topic, based on experiments using conical nanopores (10-300 nm tip opening) fabricated in thin glass, mica, and polymer membranes. Measurable fluid flow in nanopores can be induced either using external pressure forces, electrically via electroosmotic forces, or by a combination of these two forces. We demonstrate that pressure-driven flow can greatly alter the electrical properties of nanopores and, vice versa, that the nonlinear electrical properties of conical nanopores can impart novel and useful flow phenomena. Electroosmotic flow (EOF), which depends on the magnitude of the ion fluxes within the double layer of the nanopore, is strongly coupled to the accumulation/depletion of ions. Thus, the same underlying cause of ICR also leads to EOF rectification, i.e., unequal flows occurring for the same voltage but opposite polarities. EOF rectification can be used to electrically

  16. Rectification of nanopores in aprotic solvents - transport properties of nanopores with surface dipoles

    NASA Astrophysics Data System (ADS)

    Plett, Timothy; Shi, Wenqing; Zeng, Yuhan; Mann, William; Vlassiouk, Ivan; Baker, Lane A.; Siwy, Zuzanna S.

    2015-11-01

    Nanopores have become a model system to understand transport properties at the nanoscale. We report experiments and modeling of ionic current in aprotic solvents with different dipole moments through conically shaped nanopores in a polycarbonate film and through glass nanopipettes. We focus on solutions of the salt LiClO4, which is of great importance in modeling lithium based batteries. Results presented suggest ion current rectification observed results from two effects: (i) adsorption of Li+ ions to the pore walls, and (ii) a finite dipole moment rendered by adsorbed solvent molecules. Properties of surfaces in various solvents were probed by means of scanning ion conductance microscopy, which confirmed existence of an effectively positive surface potential in aprotic solvents with high dipole moments.Nanopores have become a model system to understand transport properties at the nanoscale. We report experiments and modeling of ionic current in aprotic solvents with different dipole moments through conically shaped nanopores in a polycarbonate film and through glass nanopipettes. We focus on solutions of the salt LiClO4, which is of great importance in modeling lithium based batteries. Results presented suggest ion current rectification observed results from two effects: (i) adsorption of Li+ ions to the pore walls, and (ii) a finite dipole moment rendered by adsorbed solvent molecules. Properties of surfaces in various solvents were probed by means of scanning ion conductance microscopy, which confirmed existence of an effectively positive surface potential in aprotic solvents with high dipole moments. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06340j

  17. DNA origami nanopores: developments, challenges and perspectives

    NASA Astrophysics Data System (ADS)

    Hernández-Ainsa, Silvia; Keyser, Ulrich F.

    2014-11-01

    DNA nanotechnology has enabled the construction of DNA origami nanopores; synthetic nanopores that present improved capabilities for the area of single molecule detection. Their extraordinary versatility makes them a new and powerful tool in nanobiotechnology for a wide range of important applications beyond molecular sensing. In this review, we briefly present the recent developments in this emerging field of research. We discuss the current challenges and possible solutions that would enhance the sensing capabilities of DNA origami nanopores. Finally, we anticipate novel avenues for future research and highlight a range of exciting ideas and applications that could be explored in the near future.

  18. Bilayer mucoadhesive microparticles for the delivery of metoprolol succinate: Formulation and evaluation.

    PubMed

    Kumar, Krishan; Dhawan, Neha; Sharma, Harshita; Patwal, Pramod S; Vaidya, Shubha; Vaidya, Bhuvaneshwar

    2015-01-01

    Metoprolol succinate is a very potent drug for the treatment of hypertension but suffers from poor bioavailability due to its erratic absorption in lower GI tract. Therefore, in the present study, it was hypothesized that by formulating mucoadhesive particles, the residence time in the GIT and release of drug may be prolonged that will enhance the bioavailability of metoprolol succinate. Metoprolol succinate loaded chitosan microparticles were prepared by ionic gelation method. The optimized microparticles were coated with sodium alginate to form a layer over chitosan microparticles to increase the mucoadhesive strength and to release the drug in controlled manner. Coated and uncoated microparticles were evaluated for particle size, zeta potential, morphology, entrapment efficiency, drug loading and in vitro drug release. The coated microparticles showed comparatively less drug release in the 0.1 N HCl while sustained release in PBS (pH 6.8) as compared to uncoated microparticles. The in vivo study on albino rats demonstrated an increase in bioavailability of the coated microparticles as compared to marketed formulation. From the study it can be concluded that alginate coated chitosan microparticles could be a useful carrier for the oral delivery of metoprolol succinate.

  19. Inhalable microparticles containing large payload of anti-tuberculosis drugs.

    PubMed

    Muttil, Pavan; Kaur, Jatinder; Kumar, Kaushlendra; Yadav, Awadh Bihari; Sharma, Rolee; Misra, Amit

    2007-10-01

    Microparticles containing large payloads of two anti-tuberculosis (TB) drugs were prepared and evaluated for suitability as a dry powder inhalation targeting alveolar macrophages. A solution containing one part each of isoniazid and rifabutin, plus two parts poly(lactic acid) (L-PLA) was spray-dried. Drug content and in vitro release were assayed by HPLC, and DSC was used to elucidate release behaviour. Particle size was measured by laser scattering and aerosol characteristics by cascade impaction using a Lovelace impactor. Microparticles were administered to mice using an in-house inhalation apparatus or by intra-tracheal instillation. Drugs in solution were administered orally and by intra-cardiac injection. Flow cytometry and HPLC were used to investigate the specificity and magnitude of targeting macrophages. Microparticles having drug content approximately 50% (w/w), particle size approximately 5 microm and satisfactory aerosol characteristics (median mass aerodynamic diameter, MMAD=3.57 microm; geometric standard deviation, GSD=1.41 microm; fine particle fraction, FPF(<4.6 microm)=78.91+/-8.4%) were obtained in yields of >60%. About 70% of the payload was released in vitro in 10 days. Microparticles targeted macrophages and not epithelial cells on inhalation. Drug concentrations in macrophages were approximately 20 times higher when microparticles were inhaled rather than drug solutions administered. Microparticles were thus deemed suitable for enhanced targeted drug delivery to lung macrophages.

  20. Bone regeneration using injectable BMP-7 loaded chitosan microparticles in rat femoral defect.

    PubMed

    Mantripragada, Venkata P; Jayasuriya, Ambalangodage C

    2016-06-01

    Injectable chitosan microparticles were prepared using a simple coacervation method under physiologically friendly conditions by eliminating oil or toxic chemical, and employing low temperature and pressure for growth factor stability. Amount of 200 ng of bone morphogenetic protein-7 (BMP-7) was incorporated in the chitosan microparticles by two methods: encapsulating and coating techniques. These microparticles were tested in vivo to determine the biological response in a rat femoral bone defect at 6 and 12 weeks. Four groups (n=10) were tested which include two groups for BMP-7 incorporated microparticles (by two techniques), microparticles without BMP-7, and defect itself (negative control). Healthy bone formation was observed around the microparticles, which were only confined to the defect site and did not disperse. Histology indicated minor inflammatory response around the microparticles at 6 weeks, which reduced by 12 weeks. Micro-CT analysis of bone surface density and porosity was found to be significantly more (p<0.05) for microparticles containing groups, in comparison with controls, which suggests that the new bone formed in the presence of microparticles is more interconnected and porous. Collagen fibrils analysis conducted using multiphoton microscopy showed significant improvement in the formation of bundled collagen area (%) in microparticles containing groups in comparison with controls, indicating higher cross-linking between the fibrils. Microparticles were biocompatible and did not degrade in the 12 week implant period. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Aluminum silicide microparticles transformed from aluminum thin films by hypoeutectic interdiffusion

    PubMed Central

    2014-01-01

    Aluminum silicide microparticles with oxidized rough surfaces were formed on Si substrates through a spontaneous granulation process of Al films. This microparticle formation was caused by interdiffusion of Al and Si atoms at hypoeutectic temperatures of Al-Si systems, which was driven by compressive stress stored in Al films. The size, density, and the composition of the microparticles could be controlled by adjusting the annealing temperature, time, and the film thickness. High-density microparticles of a size around 10 μm and with an atomic ratio of Si/Al of approximately 0.8 were obtained when a 90-nm-thick Al film on Si substrate was annealed for 9 h at 550°C. The microparticle formation resulted in a rapid increase of the sheet resistance, which is a consequence of substantial consumption of Al film. This simple route to size- and composition-controllable microparticle formation may lay a foundation stone for the thermoelectric study on Al-Si alloy-based heterogeneous systems. PMID:24994964

  2. Aluminum silicide microparticles transformed from aluminum thin films by hypoeutectic interdiffusion.

    PubMed

    Noh, Jin-Seo

    2014-01-01

    Aluminum silicide microparticles with oxidized rough surfaces were formed on Si substrates through a spontaneous granulation process of Al films. This microparticle formation was caused by interdiffusion of Al and Si atoms at hypoeutectic temperatures of Al-Si systems, which was driven by compressive stress stored in Al films. The size, density, and the composition of the microparticles could be controlled by adjusting the annealing temperature, time, and the film thickness. High-density microparticles of a size around 10 μm and with an atomic ratio of Si/Al of approximately 0.8 were obtained when a 90-nm-thick Al film on Si substrate was annealed for 9 h at 550°C. The microparticle formation resulted in a rapid increase of the sheet resistance, which is a consequence of substantial consumption of Al film. This simple route to size- and composition-controllable microparticle formation may lay a foundation stone for the thermoelectric study on Al-Si alloy-based heterogeneous systems.

  3. Numerical Simulations of the Digital Microfluidic Manipulation of Single Microparticles.

    PubMed

    Lan, Chuanjin; Pal, Souvik; Li, Zhen; Ma, Yanbao

    2015-09-08

    Single-cell analysis techniques have been developed as a valuable bioanalytical tool for elucidating cellular heterogeneity at genomic, proteomic, and cellular levels. Cell manipulation is an indispensable process for single-cell analysis. Digital microfluidics (DMF) is an important platform for conducting cell manipulation and single-cell analysis in a high-throughput fashion. However, the manipulation of single cells in DMF has not been quantitatively studied so far. In this article, we investigate the interaction of a single microparticle with a liquid droplet on a flat substrate using numerical simulations. The droplet is driven by capillary force generated from the wettability gradient of the substrate. Considering the Brownian motion of microparticles, we utilize many-body dissipative particle dynamics (MDPD), an off-lattice mesoscopic simulation technique, in this numerical study. The manipulation processes (including pickup, transport, and drop-off) of a single microparticle with a liquid droplet are simulated. Parametric studies are conducted to investigate the effects on the manipulation processes from the droplet size, wettability gradient, wetting properties of the microparticle, and particle-substrate friction coefficients. The numerical results show that the pickup, transport, and drop-off processes can be precisely controlled by these parameters. On the basis of the numerical results, a trap-free delivery of a hydrophobic microparticle to a destination on the substrate is demonstrated in the numerical simulations. The numerical results not only provide a fundamental understanding of interactions among the microparticle, the droplet, and the substrate but also demonstrate a new technique for the trap-free immobilization of single hydrophobic microparticles in the DMF design. Finally, our numerical method also provides a powerful design and optimization tool for the manipulation of microparticles in DMF systems.

  4. Effect of pH on ion current through conical nanopores

    NASA Astrophysics Data System (ADS)

    Chander, M.; Kumar, R.; Kumar, S.; Kumar, N.

    2018-05-01

    Here, we examined ionic current behavior of conical nanopores at different pH and a fixed ion concentration of potassium halide (KCl). Conical shaped nanopores have been developed by chemical etching technique in polyethylene terephthalate (PET) membrane/foil of thickness 12 micron. For this we employed a self-assembled electrochemical cell having two chambers and the foil was fitted in the centre of cell. The nanopores were produced in the foil using etching and stopping solutions. The experimental results show that ionic current rectification (ICR) occurs through synthesized conical nanopores. Further, ion current increases significantly with increase of voltage from the base side of nanopores to the tip side at fixed pH of electrolyte.

  5. Superdiffusive gas recovery from nanopores

    NASA Astrophysics Data System (ADS)

    Wu, Haiyi; He, Yadong; Qiao, Rui

    2016-11-01

    Understanding the recovery of gas from reservoirs featuring pervasive nanopores is essential for effective shale gas extraction. Classical theories cannot accurately predict such gas recovery and many experimental observations are not well understood. Here we report molecular simulations of the recovery of gas from single nanopores, explicitly taking into account molecular gas-wall interactions. We show that, in very narrow pores, the strong gas-wall interactions are essential in determining the gas recovery behavior both quantitatively and qualitatively. These interactions cause the total diffusion coefficients of the gas molecules in nanopores to be smaller than those predicted by kinetic theories, hence slowing down the rate of gas recovery. These interactions also lead to significant adsorption of gas molecules on the pore walls. Because of the desorption of these gas molecules during gas recovery, the gas recovery from the nanopore does not exhibit the usual diffusive scaling law (i.e., the accumulative recovery scales as R ˜t1 /2 ) but follows a superdiffusive scaling law R ˜tn (n >0.5 ), which is similar to that observed in some field experiments. For the system studied here, the superdiffusive gas recovery scaling law can be captured well by continuum models in which the gas adsorption and desorption from pore walls are taken into account using the Langmuir model.

  6. Potential roles of cell-derived microparticles in ischemic brain disease.

    PubMed

    Horstman, Lawrence L; Jy, Wenche; Bidot, Carlos J; Nordberg, Mary L; Minagar, Alireza; Alexander, J Steven; Kelley, Roger E; Ahn, Yeon S

    2009-10-01

    The objective of this study is to review the role of cell-derived microparticles in ischemic cerebrovascular diseases. An extensive PubMed search of literature pertaining to this study was performed in April 2009 using specific keyword search terms related to cell-derived microparticles and ischemic stroke. Some references are not cited here as it is not possible to be all inclusive or due to space limitation. Cell-derived microparticles are small membranous vesicles released from the plasma membranes of platelets, leukocytes, red cells and endothelial cells in response to diverse biochemical agents or mechanical stresses. They are the main carriers of circulating tissue factor, the principal initiator of intravascular thrombosis, and are implicated in a variety of thrombotic and inflammatory disorders. This review outlines evidence suggesting that cell-derived microparticles are involved predominantly with microvascular, as opposed to macrovascular, thrombosis. More specifically, cell-derived microparticles may substantially contribute to ischemic brain disease in several settings, as well as to neuroinflammatory conditions. If further work confirms this hypothesis, novel therapeutic strategies for minimizing cell-derived microparticles-mediated ischemia are available or can be developed, as discussed.

  7. Microparticles: Facile and High-Throughput Synthesis of Functional Microparticles with Quick Response Codes (Small 24/2016).

    PubMed

    Ramirez, Lisa Marie S; He, Muhan; Mailloux, Shay; George, Justin; Wang, Jun

    2016-06-01

    Microparticles carrying quick response (QR) barcodes are fabricated by J. Wang and co-workers on page 3259, using a massive coding of dissociated elements (MiCODE) technology. Each microparticle can bear a special custom-designed QR code that enables encryption or tagging with unlimited multiplexity, and the QR code can be easily read by cellphone applications. The utility of MiCODE particles in multiplexed DNA detection and microtagging for anti-counterfeiting is explored. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Increased levels of circulating platelet derived microparticles in Crohn's disease patients.

    PubMed

    Tziatzios, Georgios; Polymeros, Dimitrios; Spathis, Aris; Triantafyllou, Maria; Gkolfakis, Paraskevas; Karakitsos, Petros; Dimitriadis, George; Triantafyllou, Konstantinos

    2016-10-01

    Platelet activation is a consistent feature in inflammatory bowel disease. However, the role of circulating platelet derived microparticles (PDMPs) and the effects of disease activity and treatment on their levels has not been clarified yet in this disorder. Using flow cytometry, we measured platelet derived microparticles and platelet derived microparticles expressing Annexin V in platelet rich plasma from 47 Crohn's disease and 43 ulcerative colitis patients and 24 healthy controls. Crohn's disease patients have greater PDMPs (0.31% ± 0.07% versus 0.14% ± 0.04%, p = 0.02) and PDMPs expressing Annexin V (27% ± 2.6% versus 14.6% ± 2.7%, p = 0.002) levels in comparison with healthy controls; however, both microparticles levels are not related with disease activity. Crohn's disease patients on 5-ASA therapy show lower levels of PDMPs in comparison with those on no 5-ASA (0.30% ± 0.07% versus 0.32% ± 0.09%, p = 0.048). Ulcerative colitis patients have similar PDMPs and PDMPs expressing Annexin V levels, compared to healthy controls (p = 0.06 and p = 0.2, respectively) and there is no correlation of both microparticles expression with disease activity. 5-ASA has no effect on both microparticles levels in ulcerative colitis patients. Anti-TNF-α treatment has no effect on study's microparticles expression in Crohn's and ulcerative colitis patients. Circulating levels of platelet derived microparticles are increased only in Crohn's patients, but they do not correlate with disease activity. 5-ASA treatment is associated with lower levels of PDMPs only in Crohn's, while anti-TNF-α treatment does not influence expression of microparticles in inflammatory bowel disease patients.

  9. Gassmann Theory Applies to Nanoporous Media

    NASA Astrophysics Data System (ADS)

    Gor, Gennady Y.; Gurevich, Boris

    2018-01-01

    Recent progress in extraction of unconventional hydrocarbon resources has ignited the interest in the studies of nanoporous media. Since many thermodynamic and mechanical properties of nanoscale solids and fluids differ from the analogous bulk materials, it is not obvious whether wave propagation in nanoporous media can be described using the same framework as in macroporous media. Here we test the validity of Gassmann equation using two published sets of ultrasonic measurements for a model nanoporous medium, Vycor glass, saturated with two different fluids, argon, and n-hexane. Predictions of the Gassmann theory depend on the bulk and shear moduli of the dry samples, which are known from ultrasonic measurements and the bulk moduli of the solid and fluid constituents. The solid bulk modulus can be estimated from adsorption-induced deformation or from elastic effective medium theory. The fluid modulus can be calculated according to the Tait-Murnaghan equation at the solvation pressure in the pore. Substitution of these parameters into the Gassmann equation provides predictions consistent with measured data. Our findings set up a theoretical framework for investigation of fluid-saturated nanoporous media using ultrasonic elastic wave propagation.

  10. Nanopore fabricated in pyramidal HfO2 film by dielectric breakdown method

    NASA Astrophysics Data System (ADS)

    Wang, Yifan; Chen, Qi; Deng, Tao; Liu, Zewen

    2017-10-01

    The dielectric breakdown method provides an innovative solution to fabricate solid-state nanopores on insulating films. A nanopore generation event via this method is considered to be caused by random charged traps (i.e., structural defects) and high electric fields in the membrane. Thus, the position and number of nanopores on planar films prepared by the dielectric breakdown method is hard to control. In this paper, we propose to fabricate nanopores on pyramidal HfO2 films (10-nm and 15-nm-thick) to improve the ability to control the location and number during the fabrication process. Since the electric field intensity gets enhanced at the corners of the pyramid-shaped film, the probability of nanopore occurrence at vertex and edge areas increases. This priority of appearance provides us chance to control the location and number of nanopores by monitoring a sudden irreversible discrete increase in current. The experimental results showed that the probability of nanopore occurrence decreases in an order from the vertex area, the edge area to the side face area. The sizes of nanopores ranging from 30 nm to 10 nm were obtained. Nanopores fabricated on the pyramid-shaped HfO2 film also showed an obvious ion current rectification characteristic, which might improve the nanopore performance as a biomolecule sequencing platform.

  11. Probing the size of proteins with glass nanopores

    NASA Astrophysics Data System (ADS)

    Steinbock, L. J.; Krishnan, S.; Bulushev, R. D.; Borgeaud, S.; Blokesch, M.; Feletti, L.; Radenovic, A.

    2014-11-01

    Single molecule studies using nanopores have gained attention due to the ability to sense single molecules in aqueous solution without the need to label them. In this study, short DNA molecules and proteins were detected with glass nanopores, whose sensitivity was enhanced by electron reshaping which decreased the nanopore diameter and created geometries with a reduced sensing length. Further, proteins having molecular weights (MW) ranging from 12 kDa to 480 kDa were detected, which showed that their corresponding current peak amplitude changes according to their MW. In the case of the 12 kDa ComEA protein, its DNA-binding properties to an 800 bp long DNA molecule was investigated. Moreover, the influence of the pH on the charge of the protein was demonstrated by showing a change in the translocation direction. This work emphasizes the wide spectrum of detectable molecules using nanopores from glass nanocapillaries, which stand out because of their inexpensive, lithography-free, and rapid manufacturing process.Single molecule studies using nanopores have gained attention due to the ability to sense single molecules in aqueous solution without the need to label them. In this study, short DNA molecules and proteins were detected with glass nanopores, whose sensitivity was enhanced by electron reshaping which decreased the nanopore diameter and created geometries with a reduced sensing length. Further, proteins having molecular weights (MW) ranging from 12 kDa to 480 kDa were detected, which showed that their corresponding current peak amplitude changes according to their MW. In the case of the 12 kDa ComEA protein, its DNA-binding properties to an 800 bp long DNA molecule was investigated. Moreover, the influence of the pH on the charge of the protein was demonstrated by showing a change in the translocation direction. This work emphasizes the wide spectrum of detectable molecules using nanopores from glass nanocapillaries, which stand out because of their

  12. Formation of inhalable rifampicin-poly(L-lactide) microparticles by supercritical anti-solvent process.

    PubMed

    Patomchaiviwat, Vipaluk; Paeratakul, Ornlaksana; Kulvanich, Poj

    2008-01-01

    Formation of inhalable microparticles containing rifampicin and poly(L-lactide) (L-PLA) by using supercritical anti-solvent process (SAS) was investigated. The solutions of drug and polymer in methylene chloride were sprayed into supercritical carbon dioxide. The effect of polymer content and operating conditions, temperature, pressure, carbon dioxide molar fraction, and concentration of solution, on product characteristics were studied. The prepared microparticles were characterized with respect to their morphology, particle size and size distribution, drug content, drug loading efficiency, and drug release characteristic. Discrete, spherical microparticles were obtained at high polymer:drug ratios of 7:3, 8:2, and 9:1. The shape of L-PLA microparticles became more irregular and agglomerated with decreasing polymer content. Microparticles with polymer content higher than 60% exhibited volumetric mean diameter less than 5 microm, but percent drug loading efficiency was relatively low. Drug-loaded microparticles containing 70% and 80% L-PLA showed a sustainable drug release property without initial burst release. Operating temperature level influenced on mean size and size distribution of microparticles. The operating pressure and carbon dioxide molar fraction in the range investigated were unlikely to have an effect on microparticle formation. An increasing concentration of feed solution provided larger size microparticles. Rifampicin-loaded L-PLA microparticles could be produced by SAS in a size range suitable for dry powder inhaler formulation.

  13. Recent patents of nanopore DNA sequencing technology: progress and challenges.

    PubMed

    Zhou, Jianfeng; Xu, Bingqian

    2010-11-01

    DNA sequencing techniques witnessed fast development in the last decades, primarily driven by the Human Genome Project. Among the proposed new techniques, Nanopore was considered as a suitable candidate for the single DNA sequencing with ultrahigh speed and very low cost. Several fabrication and modification techniques have been developed to produce robust and well-defined nanopore devices. Many efforts have also been done to apply nanopore to analyze the properties of DNA molecules. By comparing with traditional sequencing techniques, nanopore has demonstrated its distinctive superiorities in main practical issues, such as sample preparation, sequencing speed, cost-effective and read-length. Although challenges still remain, recent researches in improving the capabilities of nanopore have shed a light to achieve its ultimate goal: Sequence individual DNA strand at single nucleotide level. This patent review briefly highlights recent developments and technological achievements for DNA analysis and sequencing at single molecule level, focusing on nanopore based methods.

  14. Impedance nanopore biosensor: influence of pore dimensions on biosensing performance.

    PubMed

    Kant, Krishna; Yu, Jingxian; Priest, Craig; Shapter, Joe G; Losic, Dusan

    2014-03-07

    Knowledge about electrochemical and electrical properties of nanopore structures and the influence of pore dimensions on these properties is important for the development of nanopore biosensing devices. The aim of this study was to explore the influence of nanopore dimensions (diameter and length) on biosensing performance using non-faradic electrochemical impedance spectroscopy (EIS). Nanoporous alumina membranes (NPAMs) prepared by self-ordered electrochemical anodization of aluminium were used as model nanopore sensing platforms. NPAMs with different pore diameters (25-65 nm) and lengths (4-18 μm) were prepared and the internal pore surface chemistry was modified by covalently attaching streptavidin and biotin. The performance of this antibody nanopore biosensing platform was evaluated using various concentrations of biotin as a model analyte. EIS measurements of pore resistivity and conductivity were carried out for pores with different diameters and lengths. The results showed that smaller pore dimensions of 25 nm and pore lengths up to 10 μm provide better biosensing performance.

  15. Nanoporous Ag prepared from the melt-spun Cu-Ag alloys

    NASA Astrophysics Data System (ADS)

    Li, Guijing; Song, Xiaoping; Sun, Zhanbo; Yang, Shengchun; Ding, Bingjun; Yang, Sen; Yang, Zhimao; Wang, Fei

    2011-07-01

    Nanoporous Ag ribbons with different morphology and porosity were achieved by the electrochemical corrosion of the melt-spun Cu-Ag alloys. The Cu-rich phase in the alloys was removed, resulting in the formation of the nanopores distributed across the whole ribbon. It is found that the structures, morphology and porosity of the nanoporous Ag ribbons were dependent on the microstructures of the parent alloys. The most of ligaments presented a rod-like shape due to the formation of pseudoeutectic microstructure in the melt-spun Cu 55Ag 45 and Cu 70Ag 30 alloys. For nanoporous Ag prepared from Cu 85Ag 15 alloys, the ligaments were camber-like because of the appearance of the divorced microstructures. Especially, a novel bamboo-grove-like structure could be observed at the cross-section of the nanoporous Ag ribbons. The experiment reveals that nanoporous Ag ribbons exhibited excellent enhancement of surface-enhanced Raman scattering (SERS) effect, but a slight difference existed due to the discrepancy of their morphology.

  16. The role of nanopore shape in surface-induced crystallization

    NASA Astrophysics Data System (ADS)

    Diao, Ying; Harada, Takuya; Myerson, Allan S.; Alan Hatton, T.; Trout, Bernhardt L.

    2011-11-01

    Crystallization of a molecular liquid from solution often initiates at solid-liquid interfaces, and nucleation rates are generally believed to be enhanced by surface roughness. Here we show that, on a rough surface, the shape of surface nanopores can also alter nucleation kinetics. Using lithographic methods, we patterned polymer films with nanopores of various shapes and found that spherical nanopores 15-120 nm in diameter hindered nucleation of aspirin crystals, whereas angular nanopores of the same size promoted it. We also show that favourable surface-solute interactions are required for angular nanopores to promote nucleation, and propose that pore shape affects nucleation kinetics through the alteration of the orientational order of the crystallizing molecule near the angles of the pores. Our findings have clear technological implications, for instance in the control of pharmaceutical polymorphism and in the design of ‘seed’ particles for the regulation of crystallization of fine chemicals.

  17. Formation and photopatterning of nanoporous titania thin films

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Park, Oun-Ho; Cheng, Joy Y.; Kim, Hyun Suk

    2007-06-04

    Photopatternable nanoporous titania thin films were generated from mixtures of an organic diblock copolymer, poly(styrene-b-ethylene oxide) (PS-b-PEO), and an oligomeric titanate (OT) prepared from a chelated titanium isopropoxide. The PS-b-PEO templates well-defined microdomains in thin films of the mixtures, which upon thermal treatment at 450 deg. C, become nanopores in titania. Average pore size and porosity are controlled by the molecular weight and loading level of the PS-b-PEO, respectively. Patterns of nanoporous titania were created by selectively exposing UV light on the mixture films. The UV irradiation destroys the chelating bond and induces the cross-linking reaction of the OT. Subsequentmore » wet development followed by thermal treatment gives patterned nanoporous films of anatase phase titania.« less

  18. Study of polymer molecules and conformations with a nanopore

    DOEpatents

    Golovchenko, Jene A.; Li, Jiali; Stein, Derek; Gershow, Marc H.

    2013-03-12

    The invention features methods for evaluating the conformation of a polymer, for example, for determining the conformational distribution of a plurality of polymers and to detect binding or denaturation events. The methods employ a nanopore which the polymer, e.g., a nucleic acid, traverses. As the polymer traverses the nanopore, measurements of transport properties of the nanopore yield data on the conformation of the polymer.

  19. Study of polymer molecules and conformations with a nanopore

    DOEpatents

    Golovchenko, Jene A.; Li, Jiali; Stein, Derek; Gershow, Marc H.

    2010-12-07

    The invention features methods for evaluating the conformation of a polymer, for example, for determining the conformational distribution of a plurality of polymers and to detect binding or denaturation events. The methods employ a nanopore which the polymer, e.g., a nucleic acid, traverses. As the polymer traverses the nanopore, measurements of transport properties of the nanopore yield data on the conformation of the polymer.

  20. Study of polymer molecules and conformations with a nanopore

    DOEpatents

    Golovchenko, Jene A; Li, Jiali; Stein, Derek; Gershow, Marc H

    2015-03-03

    The invention features methods for evaluating the conformation of a polymer, for example, for determining the conformational distribution of a plurality of polymers and to detect binding or denaturation events. The methods employ a nanopore which the polymer, e.g., a nucleic acid, traverses. As the polymer traverses the nanopore, measurements of transport properties of the nanopore yield data on the conformation of the polymer.

  1. IGF-1 Release Kinetics from Chitosan Microparticles Fabricated Using Environmentally Benign Conditions

    PubMed Central

    Mantripragada, Venkata P.; Jayasuriya, Ambalangodage C.

    2014-01-01

    The main objective of this study is to maximize growth factor encapsulation efficiency into microparticles. The novelty of this study is to maximize the encapsulated growth factors into microparticles by minimizing the use of organic solvents and using relatively low temperatures. The microparticles were fabricated using chitosan biopolymer as a base polymer and cross-linked with tripolyphosphate (TPP). Insulin like-growth factor-1 (IGF-1) was encapsulated into microparticles to study release kinetics and bioactivity. In order to authenticate the harms of using organic solvents like hexane and acetone during microparticle preparation, IGF-1 encapsulated microparticles prepared by the emulsification and coacervation methods were compared. The microparticles fabricated by emulsification method have shown a significant decrease (p<0.05) in IGF-1 encapsulation efficiency, and cumulative release during the two-week period. The biocompatibility of chitosan microparticles and the bioactivity of the released IGF-1 were determined in vitro by live/dead viability assay. The mineralization data observed with Von Kossa assay, was supported by mRNA expression levels of osterix and runx2, which are transcription factors necessary for osteoblasts differentiation. Real time RT-PCR data showed an increased expression of runx 2 and a decreased expression of osterix over time, indicating differentiating osteoblasts. Chitosan microparticles prepared in optimum environmental conditions are a promising controlled delivery system for cells to attach, proliferate, differentiate and mineralize, thereby acting as a suitable bone repairing material. PMID:25063148

  2. Facile and High-Throughput Synthesis of Functional Microparticles with Quick Response Codes.

    PubMed

    Ramirez, Lisa Marie S; He, Muhan; Mailloux, Shay; George, Justin; Wang, Jun

    2016-06-01

    Encoded microparticles are high demand in multiplexed assays and labeling. However, the current methods for the synthesis and coding of microparticles either lack robustness and reliability, or possess limited coding capacity. Here, a massive coding of dissociated elements (MiCODE) technology based on innovation of a chemically reactive off-stoichimetry thiol-allyl photocurable polymer and standard lithography to produce a large number of quick response (QR) code microparticles is introduced. The coding process is performed by photobleaching the QR code patterns on microparticles when fluorophores are incorporated into the prepolymer formulation. The fabricated encoded microparticles can be released from a substrate without changing their features. Excess thiol functionality on the microparticle surface allows for grafting of amine groups and further DNA probes. A multiplexed assay is demonstrated using the DNA-grafted QR code microparticles. The MiCODE technology is further characterized by showing the incorporation of BODIPY-maleimide (BDP-M) and Nile Red fluorophores for coding and the use of microcontact printing for immobilizing DNA probes on microparticle surfaces. This versatile technology leverages mature lithography facilities for fabrication and thus is amenable to scale-up in the future, with potential applications in bioassays and in labeling consumer products. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Embedded CMOS basecalling for nanopore DNA sequencing.

    PubMed

    Chengjie Wang; Junli Zheng; Magierowski, Sebastian; Ghafar-Zadeh, Ebrahim

    2016-08-01

    DNA sequencing based on nanopore sensors is now entering the marketplace. The ability to interface this technology to established CMOS microelectronics promises significant improvements in functionality and miniaturization. Among the key functions to benefit from this interface will be basecalling, the conversion of raw electronic molecular signatures to nucleotide sequence predictions. This paper presents the design and performance potential of custom CMOS base-callers embedded alongside nanopore sensors. A basecalliing architecture implemented in 32-nm technology is discussed with the ability to process the equivalent of 20 human genomes per day in real-time at a power density of 5 W/cm2 assuming a 3-mer nanopore sensor.

  4. Modulation of Molecular Flux Using a Graphene Nanopore Capacitor.

    PubMed

    Shankla, Manish; Aksimentiev, Aleksei

    2017-04-20

    Modulation of ionic current flowing through nanoscale pores is one of the fundamental biological processes. Inspired by nature, nanopores in synthetic solid-state membranes are being developed to enable rapid analysis of biological macromolecules and to serve as elements of nanofludic circuits. Here, we theoretically investigate ion and water transport through a graphene-insulator-graphene membrane containing a single, electrolyte-filled nanopore. By means of all-atom molecular dynamics simulations, we show that the charge state of such a graphene nanopore capacitor can regulate both the selectivity and the magnitude of the nanopore ionic current. At a fixed transmembrane bias, the ionic current can be switched from being carried by an equal mixture of cations and anions to being carried almost exclusively by either cationic or anionic species, depending on the sign of the charge assigned to both plates of the capacitor. Assigning the plates of the capacitor opposite sign charges can either increase the nanopore current or reduce it substantially, depending on the polarity of the bias driving the transmembrane current. Facilitated by the changes of the nanopore surface charge, such ionic current modulations are found to occur despite the physical dimensions of the nanopore being an order of magnitude larger than the screening length of the electrolyte. The ionic current rectification is accompanied by a pronounced electro-osmotic effect that can transport neutral molecules such as proteins and drugs across the solid-state membrane and thereby serve as an interface between electronic and chemical signals.

  5. Colour-barcoded magnetic microparticles for multiplexed bioassays.

    PubMed

    Lee, Howon; Kim, Junhoi; Kim, Hyoki; Kim, Jiyun; Kwon, Sunghoon

    2010-09-01

    Encoded particles have a demonstrated value for multiplexed high-throughput bioassays such as drug discovery and clinical diagnostics. In diverse samples, the ability to use a large number of distinct identification codes on assay particles is important to increase throughput. Proper handling schemes are also needed to readout these codes on free-floating probe microparticles. Here we create vivid, free-floating structural coloured particles with multi-axis rotational control using a colour-tunable magnetic material and a new printing method. Our colour-barcoded magnetic microparticles offer a coding capacity easily into the billions with distinct magnetic handling capabilities including active positioning for code readouts and active stirring for improved reaction kinetics in microscale environments. A DNA hybridization assay is done using the colour-barcoded magnetic microparticles to demonstrate multiplexing capabilities.

  6. Thermoporometry characterization of silica microparticles and nanowires.

    PubMed

    Wu, Jiaxin; Zheng, Han; Cheng, He; Zhou, L; Leong, K C; Rajagopalan, R; Too, H P; Choi, W K

    2014-03-04

    We present the results of a systematic study on the porosity of silica microparticles and nanowires prepared by glancing angle deposition-metal-assisted chemical etching (GLAD-MACE) and interference lithography-metal-assisted chemical etching (IL-MACE) techniques using the thermoporometry (TPM) method. Good agreement was obtained between our TPM results and published data provided by the suppliers of silica microparticles. TPM characterization of the GLAD-MACE and IL-MACE nanowires was carried out on the basis of parameters obtained from TPM experiments on microparticles. Our nanowires showed a similar trend but lower values of the pore volume and surface area than nanowires prepared by MACE with AgNO3 solution. We attribute the enhanced bioanalysis performance of the GLAD-MACE nanowires based devices to the increased pore volume and total surface area of the nanowires.

  7. Anti-reflective nanoporous silicon for efficient hydrogen production

    DOEpatents

    Oh, Jihun; Branz, Howard M

    2014-05-20

    Exemplary embodiments are disclosed of anti-reflective nanoporous silicon for efficient hydrogen production by photoelectrolysis of water. A nanoporous black Si is disclosed as an efficient photocathode for H.sub.2 production from water splitting half-reaction.

  8. Balancing size exclusion and adsorption of polymers in nanopores

    NASA Astrophysics Data System (ADS)

    Kim, Won; Ryu, Chang Y.

    2006-03-01

    The liquid chromatography at critical condition (LCCC) presents the condition, at which the size exclusion and adsorption of polymer chains are balanced upon interactions with nanoporous substrates. In this study, we investigate how the polymer interactions with nanopores are affected by the solvent quality and nanopore size. Specifically, we measure the retention times of monodisperse polystyrenes in C18-bonded nanoporous silica column as a function of molecular weight, when a mixed solvent of methylene chloride and acetonitrile are used as elutent. C18-bonded silica particles with 70, 100, and 250 A pore size are used as a stationary phase to study how the transition from SEC-like to IC-like retention behavior depends on the condition of temperature and solvent composition. To locate the LCCC at various nanopore sizes, the temperature and solvent composition have been varied from 0 to 60 C and from 51 to 62 v/v% of methylene chloride, respectively.

  9. Integrated nanopore sensing platform with sub-microsecond temporal resolution

    PubMed Central

    Rosenstein, Jacob K; Wanunu, Meni; Merchant, Christopher A; Drndic, Marija; Shepard, Kenneth L

    2012-01-01

    Nanopore sensors have attracted considerable interest for high-throughput sensing of individual nucleic acids and proteins without the need for chemical labels or complex optics. A prevailing problem in nanopore applications is that the transport kinetics of single biomolecules are often faster than the measurement time resolution. Methods to slow down biomolecular transport can be troublesome and are at odds with the natural goal of high-throughput sensing. Here we introduce a low-noise measurement platform that integrates a complementary metal-oxide semiconductor (CMOS) preamplifier with solid-state nanopores in thin silicon nitride membranes. With this platform we achieved a signal-to-noise ratio exceeding five at a bandwidth of 1 MHz, which to our knowledge is the highest bandwidth nanopore recording to date. We demonstrate transient signals as brief as 1 μs from short DNA molecules as well as current signatures during molecular passage events that shed light on submolecular DNA configurations in small nanopores. PMID:22426489

  10. Four-dimensional (4D) tracking of high-temperature microparticles

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang, Zhehui, E-mail: zwang@lanl.gov; Liu, Q.; Waganaar, W.

    High-speed tracking of hot and molten microparticles in motion provides rich information about burning plasmas in magnetic fusion. An exploding-wire apparatus is used to produce moving high-temperature metallic microparticles and to develop four-dimensional (4D) or time-resolved 3D particle tracking techniques. The pinhole camera model and algorithms developed for computer vision are used for scene calibration and 4D reconstructions. 3D positions and velocities are then derived for different microparticles. Velocity resolution approaches 0.1 m/s by using the local constant velocity approximation.

  11. Four-dimensional (4D) tracking of high-temperature microparticles

    NASA Astrophysics Data System (ADS)

    Wang, Zhehui; Liu, Q.; Waganaar, W.; Fontanese, J.; James, D.; Munsat, T.

    2016-11-01

    High-speed tracking of hot and molten microparticles in motion provides rich information about burning plasmas in magnetic fusion. An exploding-wire apparatus is used to produce moving high-temperature metallic microparticles and to develop four-dimensional (4D) or time-resolved 3D particle tracking techniques. The pinhole camera model and algorithms developed for computer vision are used for scene calibration and 4D reconstructions. 3D positions and velocities are then derived for different microparticles. Velocity resolution approaches 0.1 m/s by using the local constant velocity approximation.

  12. Four-dimensional (4D) tracking of high-temperature microparticles

    DOE PAGES

    Wang, Zhehui; Liu, Qiuguang; Waganaar, Bill; ...

    2016-07-08

    High-speed tracking of hot and molten microparticles in motion provides rich information about burning plasmas in magnetic fusion. An exploding-wire apparatus is used to produce moving high-temperature metallic microparticles and to develop four-dimensional (4D) or time-resolved 3D particle tracking techniques. The pinhole camera model and algorithms developed for computer vision are used for scene calibration and 4D reconstructions. 3D positions and velocities are then derived for different microparticles. As a result, velocity resolution approaches 0.1 m/s by using the local constant velocity approximation.

  13. Four-dimensional (4D) tracking of high-temperature microparticles.

    PubMed

    Wang, Zhehui; Liu, Q; Waganaar, W; Fontanese, J; James, D; Munsat, T

    2016-11-01

    High-speed tracking of hot and molten microparticles in motion provides rich information about burning plasmas in magnetic fusion. An exploding-wire apparatus is used to produce moving high-temperature metallic microparticles and to develop four-dimensional (4D) or time-resolved 3D particle tracking techniques. The pinhole camera model and algorithms developed for computer vision are used for scene calibration and 4D reconstructions. 3D positions and velocities are then derived for different microparticles. Velocity resolution approaches 0.1 m/s by using the local constant velocity approximation.

  14. Single Protein Structural Analysis with a Solid-state Nanopore Sensor

    NASA Astrophysics Data System (ADS)

    Li, Jiali; Golovchenko, Jene; McNabb, David

    2005-03-01

    We report on the use of solid-state nanopore sensors to detect single polypeptides. These solid-state nanopores are fabricated in thin membranes of silicon nitride by ion beam sculpting...[1]. When an electrically biased nanopore is exposed to denatured proteins in ionic solution, discrete transient electronic signals: current blockages are observed. We demonstrate examples of such transient electronic signals for Bovine Serum Albumin (BSA) and human placental laminin M proteins in Guanidine hydrochloride solution, which suggest that these polypeptides are individually translocating through the nanopore during the detecting process. The amplitude of the current blockages is proportional to the bias voltage. No transient current blockages are observed when proteins are not present in the solution. To probe protein-folding state, pH and temperature dependence experiments are performed. The results demonstrate a solid-state nanopore sensor can be used to detect and analyze single polypeptide chains. Similarities and differences with signals obtained from double stranded DNA in a solid-state nanopore and single stranded DNA in a biological nanopore are discussed. [.1] Li, J., D. Stein, C. McMullan, D. Branton, M.J. Aziz, and J.A. Golovchenko, Ion-beam sculpting at nanometre length scales. Nature, 2001. 412(12 July): p. 166-169.

  15. Nanoporous Pirani sensor based on anodic aluminum oxide

    NASA Astrophysics Data System (ADS)

    Jeon, Gwang-Jae; Kim, Woo Young; Shim, Hyun Bin; Lee, Hee Chul

    2016-09-01

    A nanoporous Pirani sensor based on anodic aluminum oxide (AAO) is proposed, and the quantitative relationship between the performance of the sensor and the porosity of the AAO membrane is characterized with a theoretical model. The proposed Pirani sensor is composed of a metallic resistor on a suspended nanoporous membrane, which simultaneously serves as the sensing area and the supporting structure. The AAO membrane has numerous vertically-tufted nanopores, resulting in a lower measurable pressure limit due to both the increased effective sensing area and the decreased effective thermal loss through the supporting structure. Additionally, the suspended AAO membrane structure, with its outer periphery anchored to the substrate, known as a closed-type design, is demonstrated using nanopores of AAO as an etch hole without a bulk micromachining process used on the substrate. In a CMOS-compatible process, a 200 μm × 200 μm nanoporous Pirani sensor with porosity of 25% was capable of measuring the pressure from 0.1 mTorr to 760 Torr. With adjustment of the porosity of the AAO, the measurable range could be extended toward lower pressures of more than one decade compared to a non-porous membrane with an identical footprint.

  16. Cell-derived microparticles in the pathogenesis of cardiovascular disease: friend or foe?

    PubMed

    Tushuizen, Maarten E; Diamant, Michaela; Sturk, Augueste; Nieuwland, Rienk

    2011-01-01

    Microparticles are ascribed important roles in coagulation, inflammation, and endothelial function. These processes are mandatory to safeguard the integrity of the organism, and their derangements contribute to the development of atherosclerosis and cardiovascular disease. More recently, the presumed solely harmful role of microparticles has been challenged because microparticles may also be involved in the maintenance and preservation of cellular homeostasis and in promoting defense mechanisms. Here, we summarize recent studies revealing these 2 faces of microparticles in cardiovascular disease.

  17. The Utility of Nanopore Technology for Protein and Peptide Sensing.

    PubMed

    Robertson, Joseph W F; Reiner, Joseph E

    2018-06-28

    Resistive-pulse nanopore sensing enables label-free single-molecule analysis of a wide range of analytes. An increasing number of studies have demonstrated the feasibility and usefulness of nanopore sensing for protein and peptide characterization. Nanopores offer the potential to study a variety of protein-related phenomena that includes unfolding kinetics, differences in unfolding pathways, protein structure stability and free energy profiles of DNA-protein and RNA-protein binding. In addition to providing a tool for fundamental protein characterization, nanopores have also been used as highly selective protein detectors in various solution mixtures and conditions. This review highlights these and other developments in the area of nanopore-based protein and peptide detection. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  18. Nanopores and nucleic acids: prospects for ultrarapid sequencing

    NASA Technical Reports Server (NTRS)

    Deamer, D. W.; Akeson, M.

    2000-01-01

    DNA and RNA molecules can be detected as they are driven through a nanopore by an applied electric field at rates ranging from several hundred microseconds to a few milliseconds per molecule. The nanopore can rapidly discriminate between pyrimidine and purine segments along a single-stranded nucleic acid molecule. Nanopore detection and characterization of single molecules represents a new method for directly reading information encoded in linear polymers. If single-nucleotide resolution can be achieved, it is possible that nucleic acid sequences can be determined at rates exceeding a thousand bases per second.

  19. Detection of microparticles from human red blood cells by multiparametric flow cytometry

    PubMed Central

    Grisendi, Giulia; Finetti, Elena; Manganaro, Daniele; Cordova, Nicoletta; Montagnani, Giuliano; Spano, Carlotta; Prapa, Malvina; Guarneri, Valentina; Otsuru, Satoru; Horwitz, Edwin M.; Mari, Giorgio; Dominici, Massimo

    2015-01-01

    Background During storage, red blood cells (RBC) undergo chemical and biochemical changes referred to as “storage lesions”. These events determine the loss of RBC integrity, resulting in lysis and release of microparticles. There is growing evidence of the clinical importance of microparticles and their role in blood transfusion-related side effects and pathogen transmission. Flow cytometry is currently one of the most common techniques used to quantify and characterise microparticles. Here we propose multiparametric staining to monitor and quantify the dynamic release of microparticles by stored human RBC. Material and methods RBC units (n=10) were stored under blood bank conditions for up to 42 days. Samples were tested at different time points to detect microparticles and determine the haemolysis rate (HR%). Microparticles were identified by flow cytometry combining carboxyfluorescein diacetate succinimidyl ester (CFSE) dye, annexin V and anti-glycophorin A antibody. Results We demonstrated that CFSE can be successfully used to label closed vesicles with an intact membrane. The combination of CFSE and glycophorin A antibody was effective for monitoring and quantifying the dynamic release of microparticles from RBC during storage. Double staining with CFSE/glycophorin A was a more precise approach, increasing vesicle detection up to 4.7-fold vs the use of glycophorin A/annexin V alone. Moreover, at all the time points tested, we found a robust correlation (R=0.625; p=0.0001) between HR% and number of microparticles detected. Discussion Multiparametric staining, based on a combination of CFSE, glycophorin A antibody and annexin V, was able to detect, characterise and monitor the release of microparticles from RBC units during storage, providing a sensitive approach to labelling and identifying microparticles for transfusion medicine and, more broadly, for cell-based therapies. PMID:25369588

  20. Mucoadhesive microparticles for local treatment of gastrointestinal diseases.

    PubMed

    Preisig, Daniel; Roth, Roger; Tognola, Sandy; Varum, Felipe J O; Bravo, Roberto; Cetinkaya, Yalcin; Huwyler, Jörg; Puchkov, Maxim

    2016-08-01

    Mucoadhesive microparticles formulated in a capsule and delivered to the gastrointestinal tract might be useful for local drug delivery. However, swelling and agglomeration of hydrophilic polymers in the gastrointestinal milieu can have a negative influence on particle retention of mucoadhesive microparticles. In this work, we investigated the impact of dry-coating with nano-sized hydrophilic fumed silica on dispersibility and particle retention of mucoadhesive microparticles. As a model for local treatment of gastrointestinal diseases, antibiotic therapy of Clostridium difficile infections with metronidazole was selected. For particle preparation, we used a two-step fluidized-bed method based on drug loading of porous microcarriers and subsequent outer coating with the mucoadhesive polymer chitosan. The prepared microparticles were analysed for drug content, and further characterized by thermal analysis, X-ray diffraction, and scanning electron microscopy. The optimal molecular weight and content of chitosan were selected by measuring particle retention on porcine colonic mucosa under dynamic flow conditions. Mucoadhesive microparticles coated with 5% (weight of chitosan coating/total weight of particles) of low molecular weight chitosan showed good in vitro particle retention, and were used for the investigation of dispersibility enhancement. By increasing the amount of silica, the dissolution rate measured in the USPIV apparatus was increased, which was an indirect indication for improved dispersibility due to increased surface area. Importantly, mucoadhesion was not impaired up to a silica concentration of 5% (w/w). In summary, mucoadhesive microparticles with sustained-release characteristics over several hours were manufactured at pilot scale, and dry-coating with silica nanoparticles has shown to improve the dispersibility, which is essential for better particle distribution along the intestinal mucosa in humans. Therefore, this advanced drug delivery

  1. Endocytosis of Red Blood Cell Microparticles by Pulmonary Endothelial Cells is Mediated By Rab5.

    PubMed

    Kim, Young; Abplanalp, William A; Jung, Andrew D; Schuster, Rebecca M; Lentsch, Alex B; Gulbins, Erich; Caldwell, Charles C; Pritts, Timothy A

    2018-03-01

    Microparticles are submicron vesicles shed from aging erythrocytes as a characteristic feature of the red blood cell (RBC) storage lesion. Exposure of pulmonary endothelial cells to RBC-derived microparticles promotes an inflammatory response, but the mechanisms underlying microparticle-induced endothelial cell activation are poorly understood. In the present study, cultured murine lung endothelial cells (MLECs) were treated with microparticles isolated from aged murine packed RBCs or vehicle. Microparticle-treated cells demonstrated increased expression of the adhesion molecules ICAM and E-selectin, as well as the cytokine, IL-6. To identify mechanisms that mediate these effects of microparticles on MLECs, cells were treated with microparticles covalently bound to carboxyfluorescein succinimidyl ester (CFSE) and cellular uptake of microparticles was quantified via flow cytometry. Compared with controls, there was a greater proportion of CFSE-positive MLECs from 15 min up to 24 h, suggesting endocytosis of the microparticles by endothelial cells. Colocalization of microparticles with lysosomes was observed via immunofluorescence, indicating endocytosis and endolysosomal trafficking. This process was inhibited by endocytosis inhibitors. SiRNA knockdown of Rab5 signaling protein in endothelial cells resulted in impaired microparticle uptake as compared with nonsense siRNA-treated cells, as well as an attenuation of the inflammatory response to microparticle treatment. Taken together, these data suggest that endocytosis of RBC-derived microparticles by lung endothelial cells results in endothelial cell activation. This response seems to be mediated, in part, by the Rab5 signaling protein.

  2. Spray Dried Chitosan Microparticles for Intravesical Delivery of Celecoxib: Preparation and Characterization.

    PubMed

    Lopedota, Angela; Cutrignelli, Annalisa; Laquintana, Valentino; Denora, Nunzio; Iacobazzi, Rosa Maria; Perrone, Mara; Fanizza, Elisabetta; Mastrodonato, Maria; Mentino, Donatella; Lopalco, Antonio; Depalo, Nicoletta; Franco, Massimo

    2016-09-01

    Chitosan microparticles containing celecoxib (CB), were developed as chemoprevention of bladder cancer. Furthermore two inclusion complexes of CB with methyl-β-cyclodextrin (C1 and C2) were prepared to improve the solubility of the drug. C1 and C2 were obtained by freeze-drying and characterized in the solid state and in solution. Microparticles loaded with CB or C1 or C2 were prepared by spray drying and fully characterized. The yield and encapsulation efficiencies of microparticles depended by both the viscosity and the presence of the inclusion complex in the feed medium nebulised. Generally, the microparticles exhibited a spherical shape with mean diameter of approximately 2 μm which was compatible with local intravesical administration using a catheter. The CB release studies from the microparticles allowed us to identify both immediate release systems (microparticles including the complexes) and prolonged release systems (microparticles including CB alone). The latter exhibited good adhesion to the bladder mucosa, as highlighted by a mucoadhesion study. Histological studies revealed a desquamation of the superficial cells when the bladder mucosa was treated with microparticles loaded with CB, while the morphology of the urothelium did not change when it was treated with microparticles loaded with the inclusion complex. A new CB intravesical formulation than can easily be administered with a catheter and is able to release the drug at the target site for several hours was realized. This new delivery system could be a good alternative to classic oral CB administration.

  3. Optimized preparation of in situ forming microparticles for the parenteral delivery of vinpocetine.

    PubMed

    Li, Jizhong; Chen, Fei; Hu, Chanjuan; He, Ling; Yan, Keshu; Zhou, Liying; Pan, Weisan

    2008-06-01

    A spherical symmetric design-response surface methodology was applied to optimize the preparation of vinpocetine-loaded poly(D,L-lactide-co-glycolide) PLGA in situ forming microparticles (ISM system). The influence of the ratio of PLGA to vinpocetine (w/w), the concentration of Tween 80 (w/v) and the volume of propylene glycol on the burst release, medium particle diameter and size distribution was evaluated. Scan electron microscopy of the optimized in situ microparticles exhibited spherical shape, and vinpocetine-loading mainly inside the microparticles. The data showed that the release of vinpocetine from in situ microparticles in vitro and in vivo lasted about 40 d. In vivo pharmacokinetic characteristics of the optimized in situ microparticles was assessed after they were intramuscularly injected into rats. HPLC method was used to determine the plasma concentration of vinpocetine. The absolute bioavailability of vinpocetine in the microparticles was 27.6% in rats, which suggested that PLGA in situ microparticles were a valuable system for the delivery of vinpocetine.

  4. Novel hierarchical microparticles super-assembled from nanoparticles with the induction of casein micelles

    NASA Astrophysics Data System (ADS)

    Xiong, Xiaopeng; Duan, Jiangjiang; Wang, Yong; Yu, Zhaoju

    2013-08-01

    We have demonstrated a solution-based synthesis of novel waxberry-like hierarchical ZnO microparticles in the presence casein micelles under mild conditions. The microstructures of the sub-micrometer-sized hierarchical microparticles were characterized, and the synthesis conditions were optimized. The formation mechanism of the hierarchical microparticle was analyzed through control experiments. The hierarchical ZnO microparticles are found to be super-assemblies of 30-70 nm ZnO nanoparticles, which are thought to be based on casein micelle induction followed by Ostwald ripening. In the same manner, copper-based hierarchical microparticles with a similar morphology have also been successfully synthesized. By controlling the synthetic time or temperature, solid or hollow microparticles can be fabricated. The narrowly distributed ZnO microparticles have a high specific surface area, exhibiting great potential application in fields such as photocatalytic and energy conversion. Our findings may meanwhile open a new bottom-up strategy in order to construct structurally sophisticated nanomaterials.

  5. Novel cryomilled physically cross-linked biodegradable hydrogel microparticles as carriers for inhalation therapy.

    PubMed

    El-Sherbiny, I M; Smyth, H D C

    2010-01-01

    In this study, novel biodegradable physically cross-linked hydrogel microparticles were developed and evaluated in-vitro as potential carriers for inhalation therapy. These hydrogel microparticles were prepared to be respirable (desired aerodynamic size) when dry and also designed to avoid the macrophage uptake (attain large swollen size once deposited in lung). The swellable microparticles, prepared using cryomilling, were based on Pluronic® F-108 in combination with PEG grafted onto both chitosan (Cs) and its N-phthaloyl derivative (NPHCs). Polymers synthesized in the study were characterized using EA, FTIR, 2D-XRD and DSC. Morphology, particle size, density, biodegradation and moisture content of the microparticles were quantified. Swelling characteristics for both drug-free and drug-loaded microparticles showed excellent size increases (between 700-1300%) and the release profiles indicated sustained release could be achieved for up to 20 days. The respirable microparticles showed drug loading efficiency up to 92%. The enzymatic degradation of developed microparticles started within the first hour and only ∼10% weights were remaining after 10 days. In conclusion, these respirable microparticles demonstrated promising in-vitro performance for potential sustained release vectors in pulmonary drug delivery.

  6. New Poly(3-hydroxybutyrate) Microparticles with Paclitaxel Sustained Release for Intraperitoneal Administration.

    PubMed

    Bonartsev, Anton P; Zernov, Anton L; Yakovlev, Sergey G; Zharkova, Irina I; Myshkina, Vera L; Mahina, Tatiana K; Bonartseva, Garina A; Andronova, Natalia V; Smirnova, Galina B; Borisova, Juliya A; Kalishjan, Mikhail S; Shaitan, Konstantin V; Treshalina, Helena M

    2017-01-01

    Poly(hydroxyalkanoates) (PHA) have recently attracted increasing attention due to their biodegradability and high biocompatibility, which makes them suitable for the development of new prolong drug formulations. This study was conducted to develop new prolong paclitaxel (PTX) formulation based on poly(3- hydroxybutyrate) (PHB) microparticles. PHB microparticles loaded with antitumor cytostatic drug PTX were obtained by spray-drying method using Nano Spray Dryer B-90. The PTX release kinetics in vitro from PHB microparticles and their cytotoxity on murine hepatoma cell line MH-22a were studied. Microparticles antitumor activity in vivo was studied using intraperitoneally (i.p.) transplanted tumor models: murine Lewis lung carcinoma and xenografts of human breast cancer RMG1. Uniform PTX release from PHB-microparticles during 2 months was observed. PTX-loaded PHB microparticles have demonstrated a significant antitumor activity versus pure drug both in vitro in murine hepatoma cells and in vivo when administered i.p. to mice with murine Lewis lung carcinoma and xenografts of human breast cancer RMG1. The developed technique of PTX sustained delivery from PHB-microparticles has therapeutic potential as prolong anticancer drug formulation. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Ion Current Rectification, Limiting and Overlimiting Conductances in Nanopores

    PubMed Central

    van Oeffelen, Liesbeth; Van Roy, Willem; Idrissi, Hosni; Charlier, Daniel; Lagae, Liesbet; Borghs, Gustaaf

    2015-01-01

    Previous reports on Poisson-Nernst-Planck (PNP) simulations of solid-state nanopores have focused on steady state behaviour under simplified boundary conditions. These are Neumann boundary conditions for the voltage at the pore walls, and in some cases also Donnan equilibrium boundary conditions for concentrations and voltages at both entrances of the nanopore. In this paper, we report time-dependent and steady state PNP simulations under less restrictive boundary conditions, including Neumann boundary conditions applied throughout the membrane relatively far away from the nanopore. We simulated ion currents through cylindrical and conical nanopores with several surface charge configurations, studying the spatial and temporal dependence of the currents contributed by each ion species. This revealed that, due to slow co-diffusion of oppositely charged ions, steady state is generally not reached in simulations or in practice. Furthermore, it is shown that ion concentration polarization is responsible for the observed limiting conductances and ion current rectification in nanopores with asymmetric surface charges or shapes. Hence, after more than a decade of collective research attempting to understand the nature of ion current rectification in solid-state nanopores, a relatively intuitive model is retrieved. Moreover, we measured and simulated current-voltage characteristics of rectifying silicon nitride nanopores presenting overlimiting conductances. The similarity between measurement and simulation shows that overlimiting conductances can result from the increased conductance of the electric double-layer at the membrane surface at the depletion side due to voltage-induced polarization charges. The MATLAB source code of the simulation software is available via the website http://micr.vub.ac.be. PMID:25978328

  8. Endothelial cell-derived microparticles induce plasmacytoid dendritic cell maturation: potential implications in inflammatory diseases

    PubMed Central

    Angelot, Fanny; Seillès, Estelle; Biichlé, Sabeha; Berda, Yael; Gaugler, Béatrice; Plumas, Joel; Chaperot, Laurence; Dignat-George, Françoise; Tiberghien, Pierre; Saas, Philippe; Garnache-Ottou, Francine

    2009-01-01

    Background Increased circulating endothelial microparticles, resulting from vascular endothelium dysfunction, and plasmacytoid dendritic cell activation are both encountered in common inflammatory disorders. The aim of our study was to determine whether interactions between endothelial microparticles and plasmacytoid dendritic cells could contribute to such pathologies. Design and Methods Microparticles generated from endothelial cell lines, platelets or activated T cells were incubated with human plasmacytoid dendritic cells sorted from healthy donor blood or with monocyte-derived dendritic cells. Dendritic cell maturation was evaluated by flow cytometry, cytokine secretion as well as naive T-cell activation and polarization. Labeled microparticles were also used to study cellular interactions. Results Endothelial microparticles induced plasmacytoid dendritic cell maturation. In contrast, conventional dendritic cells were resistant to endothelial microparticle-induced maturation. In addition to upregulation of co-stimulatory molecules, endothelial microparticle-matured plasmacytoid dendritic cells secreted inflammatory cytokines (interleukins 6 and 8, but no interferon-α) and also induced allogeneic naive CD4+ T cells to proliferate and to produce type 1 cytokines such as interferon-γ and tumor necrosis factor-α. Endothelial microparticle endocytosis by plasmacytoid dendritic cells appeared to be required for plasmacytoid dendritic cell maturation. Importantly, the ability of endothelial microparticles to induce plasmacytoid dendritic cells to mature was specific as microparticles derived from activated T cells or platelets (the major source of circulating microparticules in healthy subjects) did not induce such plasmacytoid dendritic cell maturation. Conclusions Our data show that endothelial microparticles specifically induce plasmacytoid dendritic cell maturation and production of inflammatory cytokines. This novel activation pathway may be implicated in

  9. Endothelial cell-derived microparticles induce plasmacytoid dendritic cell maturation: potential implications in inflammatory diseases.

    PubMed

    Angelot, Fanny; Seillès, Estelle; Biichlé, Sabeha; Berda, Yael; Gaugler, Béatrice; Plumas, Joel; Chaperot, Laurence; Dignat-George, Françoise; Tiberghien, Pierre; Saas, Philippe; Garnache-Ottou, Francine

    2009-11-01

    Increased circulating endothelial microparticles, resulting from vascular endothelium dysfunction, and plasmacytoid dendritic cell activation are both encountered in common inflammatory disorders. The aim of our study was to determine whether interactions between endothelial microparticles and plasmacytoid dendritic cells could contribute to such pathologies. Microparticles generated from endothelial cell lines, platelets or activated T cells were incubated with human plasmacytoid dendritic cells sorted from healthy donor blood or with monocyte-derived dendritic cells. Dendritic cell maturation was evaluated by flow cytometry, cytokine secretion as well as naive T-cell activation and polarization. Labeled microparticles were also used to study cellular interactions. Endothelial microparticles induced plasmacytoid dendritic cell maturation. In contrast, conventional dendritic cells were resistant to endothelial microparticle-induced maturation. In addition to upregulation of co-stimulatory molecules, endothelial microparticle-matured plasmacytoid dendritic cells secreted inflammatory cytokines (interleukins 6 and 8, but no interferon-alpha) and also induced allogeneic naive CD4(+) T cells to proliferate and to produce type 1 cytokines such as interferon-gamma and tumor necrosis factor-alpha. Endothelial microparticle endocytosis by plasmacytoid dendritic cells appeared to be required for plasmacytoid dendritic cell maturation. Importantly, the ability of endothelial microparticles to induce plasmacytoid dendritic cells to mature was specific as microparticles derived from activated T cells or platelets (the major source of circulating microparticules in healthy subjects) did not induce such plasmacytoid dendritic cell maturation. Our data show that endothelial microparticles specifically induce plasmacytoid dendritic cell maturation and production of inflammatory cytokines. This novel activation pathway may be implicated in various inflammatory disorders and

  10. Nanoporous Polymers Based on Liquid Crystals

    PubMed Central

    Mulder, Dirk Jan; Sijbesma, Rint; Schenning, Albert

    2018-01-01

    In the present review, we discuss recent advances in the field of nanoporous networks based on polymerisable liquid crystals. The field has matured in the last decade, yielding polymers having 1D, 2D, and 3D channels with pore sizes on the nanometer scale. Next to the current progress, some of the future challenges are presented, with the integration of nanoporous membranes in functional devices considered as the biggest challenge. PMID:29324669

  11. Effect of strenuous physical exercise on circulating cell-derived microparticles.

    PubMed

    Chaar, Vicky; Romana, Marc; Tripette, Julien; Broquere, Cédric; Huisse, Marie-Geneviève; Hue, Olivier; Hardy-Dessources, Marie-Dominique; Connes, Philippe

    2011-01-01

    Strenuous exercise is associated with an inflammatory response involving the activation of several types of blood cells. In order to document the specific activation of these cell types, we studied the effect of three maximal exercise tests conducted to exhaustion on the quantitative and qualitative pattern of circulating cell-derived microparticles and inflammatory molecules in healthy subjects. This study mainly indicated that the plasma concentration of microparticles from platelets and polymorphonuclear neutrophils (PMN) was increased immediately after the strenuous exercise. In addition, the increase in plasma concentration of microparticles from PMN and platelets was still observed after 2 hours of recovery. A similar pattern was observed for the IL-6 plasma level. In contrast, no change was observed for either soluble selectins or plasma concentration of microparticles from red blood cells, monocytes and endothelial cells. In agreement, sVCAM-1 and sICAM-1 levels were not changed by the exercise. We conclude that a strenuous exercise is accompanied by platelet- and PMN-derived microparticle production that probably reflects the activation of these two cell types.

  12. Nanopore formation in neuroblastoma cells following ultrashort electric pulse exposure

    NASA Astrophysics Data System (ADS)

    Roth, Caleb C.; Payne, Jason A.; Wilmink, Gerald J.; Ibey, Bennett L.

    2011-03-01

    Ultrashort or nanosecond electrical pulses (USEP) cause repairable damage to the plasma membranes of cells through formation of nanopores. These nanopores are able to pass small ions such as sodium, calcium, and potassium, but remain impermeable to larger molecules like trypan blue and propidium iodide. What remains uncertain is whether generation of nanopores by ultrashort electrical pulses can inhibit action potentials in excitable cells. In this paper, we explored the sensitivity of excitable cells to USEP using Calcium Green AM 1 ester fluorescence to measure calcium uptake indicative of nanopore formation in the plasma membrane. We determined the threshold for nanopore formation in neuroblastoma cells for three pulse parameters (amplitude, pulse width, and pulse number). Measurement of such thresholds will guide future studies to determine if USEP can inhibit action potentials without causing irreversible membrane damage.

  13. Ion selection of charge-modified large nanopores in a graphene sheet

    NASA Astrophysics Data System (ADS)

    Zhao, Shijun; Xue, Jianming; Kang, Wei

    2013-09-01

    Water desalination becomes an increasingly important approach for clean water supply to meet the rapidly growing demand of population boost, industrialization, and urbanization. The main challenge in current desalination technologies lies in the reduction of energy consumption and economic costs. Here, we propose to use charged nanopores drilled in a graphene sheet as ion exchange membranes to promote the efficiency and capacity of desalination systems. Using molecular dynamics simulations, we investigate the selective ion transport behavior of electric-field-driven KCl electrolyte solution through charge modified graphene nanopores. Our results reveal that the presence of negative charges at the edge of graphene nanopore can remarkably impede the passage of Cl- while enhance the transport of K+, which is an indication of ion selectivity for electrolytes. We further demonstrate that this selectivity is dependent on the pore size and total charge number assigned at the nanopore edge. By adjusting the nanopore diameter and electric charge on the graphene nanopore, a nearly complete rejection of Cl- can be realized. The electrical resistance of nanoporous graphene, which is a key parameter to evaluate the performance of ion exchange membranes, is found two orders of magnitude lower than commercially used membranes. Our results thus suggest that graphene nanopores are promising candidates to be used in electrodialysis technology for water desalinations with a high permselectivity.

  14. Combined AC electroosmosis and dielectrophoresis for controlled rotation of microparticles

    PubMed Central

    Walid Rezanoor, Md.; Dutta, Prashanta

    2016-01-01

    Electrorotation is widely used for characterization of biological cells and materials using a rotating electric field. Generally, multiphase AC electric fields and quadrupolar electrode configuration are needed to create a rotating electric field for electrorotation. In this study, we demonstrate a simple method to rotate dielectrophoretically trapped microparticles using a stationary AC electric field. Coplanar interdigitated electrodes are used to create a linearly polarized nonuniform AC electric field. This nonuniform electric field is employed for dielectrophoretic trapping of microparticles as well as for generating electroosmotic flow in the vicinity of the electrodes resulting in rotation of microparticles in a microfluidic device. The rotation of barium titanate microparticles is observed in 2-propanol and methanol solvent at a frequency below 1 kHz. A particle rotation rate as high as 240 revolutions per minute is observed. It is demonstrated that precise manipulation (both rotation rate and equilibrium position) of the particles is possible by controlling the frequency of the applied electric field. At low frequency range, the equilibrium positions of the microparticles are observed between the electrode edge and electrode center. This method of particle manipulation is different from electrorotation as it uses induced AC electroosmosis instead of electric torque as in the case of electrorotation. Moreover, it has been shown that a microparticle can be rotated along its own axis without any translational motion. PMID:27014394

  15. Combined AC electroosmosis and dielectrophoresis for controlled rotation of microparticles.

    PubMed

    Walid Rezanoor, Md; Dutta, Prashanta

    2016-03-01

    Electrorotation is widely used for characterization of biological cells and materials using a rotating electric field. Generally, multiphase AC electric fields and quadrupolar electrode configuration are needed to create a rotating electric field for electrorotation. In this study, we demonstrate a simple method to rotate dielectrophoretically trapped microparticles using a stationary AC electric field. Coplanar interdigitated electrodes are used to create a linearly polarized nonuniform AC electric field. This nonuniform electric field is employed for dielectrophoretic trapping of microparticles as well as for generating electroosmotic flow in the vicinity of the electrodes resulting in rotation of microparticles in a microfluidic device. The rotation of barium titanate microparticles is observed in 2-propanol and methanol solvent at a frequency below 1 kHz. A particle rotation rate as high as 240 revolutions per minute is observed. It is demonstrated that precise manipulation (both rotation rate and equilibrium position) of the particles is possible by controlling the frequency of the applied electric field. At low frequency range, the equilibrium positions of the microparticles are observed between the electrode edge and electrode center. This method of particle manipulation is different from electrorotation as it uses induced AC electroosmosis instead of electric torque as in the case of electrorotation. Moreover, it has been shown that a microparticle can be rotated along its own axis without any translational motion.

  16. Amorphous Calcium Carbonate Based-Microparticles for Peptide Pulmonary Delivery.

    PubMed

    Tewes, Frederic; Gobbo, Oliviero L; Ehrhardt, Carsten; Healy, Anne Marie

    2016-01-20

    Amorphous calcium carbonate (ACC) is known to interact with proteins, for example, in biogenic ACC, to form stable amorphous phases. The control of amorphous/crystalline and inorganic/organic ratios in inhalable calcium carbonate microparticles may enable particle properties to be adapted to suit the requirements of dry powders for pulmonary delivery by oral inhalation. For example, an amorphous phase can immobilize and stabilize polypeptides in their native structure and amorphous and crystalline phases have different mechanical properties. Therefore, inhalable composite microparticles made of inorganic (i.e., calcium carbonate and calcium formate) and organic (i.e., hyaluronan (HA)) amorphous and crystalline phases were investigated for peptide and protein pulmonary aerosol delivery. The crystalline/amorphous ratio and polymorphic form of the inorganic component was altered by changing the microparticle drying rate and by changing the ammonium carbonate and HA initial concentration. The bioactivity of the model peptide, salmon calcitonin (sCT), coprocessed with alpha-1-antitrypsin (AAT), a model protein with peptidase inhibitor activity, was maintained during processing and the microparticles had excellent aerodynamic properties, making them suitable for pulmonary aerosol delivery. The bioavailability of sCT after aerosol delivery as sCT and AAT-loaded composite microparticles to rats was 4-times higher than that of sCT solution.

  17. Isolation and phenotypic characteristics of microparticles in acute respiratory distress syndrome

    PubMed Central

    Li, Hongxia; Meng, Xiangyu; Gao, Yue; Cai, Shaohua

    2015-01-01

    Objective: To investigate the alterations of microparticles in acute respiratory distress syndrome (ARDS) in rats. Methods: 18 Wistar male rats were randomly divided into three groups: no intervention, sham (saline control) group and ARDS group (LPS induced). Blood was collected from abdominal aorta and microparticles were extracted through multiple rounds of centrifugation. Particles were analyzed by flow cytometry and transmission electron microscope. Results: The circulating concentration of total microparticles of rats with ARDS induced by lipopolysaccharide (LPS) did not change compared with other two groups. However, ARDS rats expressed higher concentration of leukocyte- and endothelium- derived microparticles in the three groups. Conclusion: Our results indicate that leukocyte and endothelial cell-derived particles may play an important role in ARDS. Thus it is important not only to monitor total microparticle levels but also the phenotypes, which may contribute to the prevention and early treatment of ARDS. PMID:25973049

  18. Nanowire-nanopore transistor sensor for DNA detection during translocation

    NASA Astrophysics Data System (ADS)

    Xie, Ping; Xiong, Qihua; Fang, Ying; Qing, Quan; Lieber, Charles

    2011-03-01

    Nanopore sequencing, as a promising low cost, high throughput sequencing technique, has been proposed more than a decade ago. Due to the incompatibility between small ionic current signal and fast translocation speed and the technical difficulties on large scale integration of nanopore for direct ionic current sequencing, alternative methods rely on integrated DNA sensors have been proposed, such as using capacitive coupling or tunnelling current etc. But none of them have been experimentally demonstrated yet. Here we show that for the first time an amplified sensor signal has been experimentally recorded from a nanowire-nanopore field effect transistor sensor during DNA translocation. Independent multi-channel recording was also demonstrated for the first time. Our results suggest that the signal is from highly localized potential change caused by DNA translocation in none-balanced buffer condition. Given this method may produce larger signal for smaller nanopores, we hope our experiment can be a starting point for a new generation of nanopore sequencing devices with larger signal, higher bandwidth and large-scale multiplexing capability and finally realize the ultimate goal of low cost high throughput sequencing.

  19. Nanoporous carbon actuator and methods of use thereof

    DOEpatents

    Biener, Juergen [San Leandro, CA; Baumann, Theodore F [Discovery Bay, CA; Shao, Lihua [Karlsruhe, DE; Weissmueller, Joerg [Stutensee, DE

    2012-07-31

    An electrochemically driveable actuator according to one embodiment includes a nanoporous carbon aerogel composition capable of exhibiting charge-induced reversible strain when wetted by an electrolyte and a voltage is applied thereto. An electrochemically driven actuator according to another embodiment includes a nanoporous carbon aerogel composition wetted by an electrolyte; and a mechanism for causing charge-induced reversible strain of the composition. A method for electrochemically actuating an object according to one embodiment includes causing charge-induced reversible strain of a nanoporous carbon aerogel composition wetted with an electrolyte to actuate the object by the strain.

  20. Silicon deposition in nanopores using a liquid precursor.

    PubMed

    Masuda, Takashi; Tatsuda, Narihito; Yano, Kazuhisa; Shimoda, Tatsuya

    2016-11-22

    Techniques for depositing silicon into nanosized spaces are vital for the further scaling down of next-generation devices in the semiconductor industry. In this study, we filled silicon into 3.5-nm-diameter nanopores with an aspect ratio of 70 by exploiting thermodynamic behaviour based on the van der Waals energy of vaporized cyclopentasilane (CPS). We originally synthesized CPS as a liquid precursor for semiconducting silicon. Here we used CPS as a gas source in thermal chemical vapour deposition under atmospheric pressure because vaporized CPS can fill nanopores spontaneously. Our estimation of the free energy of CPS based on Lifshitz van der Waals theory clarified the filling mechanism, where CPS vapour in the nanopores readily undergoes capillary condensation because of its large molar volume compared to those of other vapours such as water, toluene, silane, and disilane. Consequently, a liquid-specific feature was observed during the deposition process; specifically, condensed CPS penetrated into the nanopores spontaneously via capillary force. The CPS that filled the nanopores was then transformed into solid silicon by thermal decomposition at 400 °C. The developed method is expected to be used as a nanoscale silicon filling technology, which is critical for the fabrication of future quantum scale silicon devices.

  1. Silicon deposition in nanopores using a liquid precursor

    NASA Astrophysics Data System (ADS)

    Masuda, Takashi; Tatsuda, Narihito; Yano, Kazuhisa; Shimoda, Tatsuya

    2016-11-01

    Techniques for depositing silicon into nanosized spaces are vital for the further scaling down of next-generation devices in the semiconductor industry. In this study, we filled silicon into 3.5-nm-diameter nanopores with an aspect ratio of 70 by exploiting thermodynamic behaviour based on the van der Waals energy of vaporized cyclopentasilane (CPS). We originally synthesized CPS as a liquid precursor for semiconducting silicon. Here we used CPS as a gas source in thermal chemical vapour deposition under atmospheric pressure because vaporized CPS can fill nanopores spontaneously. Our estimation of the free energy of CPS based on Lifshitz van der Waals theory clarified the filling mechanism, where CPS vapour in the nanopores readily undergoes capillary condensation because of its large molar volume compared to those of other vapours such as water, toluene, silane, and disilane. Consequently, a liquid-specific feature was observed during the deposition process; specifically, condensed CPS penetrated into the nanopores spontaneously via capillary force. The CPS that filled the nanopores was then transformed into solid silicon by thermal decomposition at 400 °C. The developed method is expected to be used as a nanoscale silicon filling technology, which is critical for the fabrication of future quantum scale silicon devices.

  2. Preparation and Characterization of Rivastigmine Transdermal Patch Based on Chitosan Microparticles.

    PubMed

    Sadeghi, Mohsen; Ganji, Fariba; Taghizadeh, Seyyed Mojtaba; Daraei, Bahram

    2016-01-01

    Here we report a novel approach for preparation of a 6-day transdermal drug delivery system (TDDS) as treatment for mild to moderate Alzheimer's disease. The spray drying method was used to prepare microparticles containing the anti-Alzheimer drug, Rivastigmine, in combination with the natural polymer, chitosan, for transdermal drug delivery applications. The content of the drug was determined by High Performance Liquid Chromatography (HPLC) method which was validated as per FDA guidelines. The morphology and size range of the microparticles were determined; and the effect of drug concentration in the solution injected into the spray dryer on the particles characterizations was studied. The stability of Rivastigmine at high temperature was confirmed using FTIR analysis as well as a validate HPLC assay. The obtained results show that the drug was stable at high temperatures with 7 to 42% loading in the microparticles, and the higher drug concentrations of the solution injected into the spray dryer resulted in increase of the drug loading, surface drug and microparticles distortion. The TDDS containing the microparticles was also prepared with microparticle to dry adhesive ratios of 5, 10 and 15% using acrylic adhesive. Based on adhesion properties of the patches, gained from the probe tack and the peel adhesion 180° tests, and the 15% patch by having more drug content per unit area of the patch, and still having similar adhesion properties was compared to the microparticles-free patch of 5.1% Rivastigmine salt (equivalent to the drug content of the 15% patch) from the permeation point of view by using Franz cell diffusion over 6 days. The drug permeation rate from the microparticle-free patch was slower than the 15% microparticles patch, which is the result of crystallization of Rivastigmine salt in the acrylic adhesive. The 6-day-prepared TDDS can be considered as an alternative for one-week application of 6 Exelon patches.

  3. Theoretical and experimental studies on ionic currents in nanopore-based biosensors.

    PubMed

    Liu, Lei; Li, Chu; Ma, Jian; Wu, Yingdong; Ni, Zhonghua; Chen, Yunfei

    2014-12-01

    Novel generation of analytical technology based on nanopores has provided possibilities to fabricate nanofluidic devices for low-cost DNA sequencing or rapid biosensing. In this paper, a simplified model was suggested to describe DNA molecule's translocation through a nanopore, and the internal potential, ion concentration, ionic flowing speed and ionic current in nanopores with different sizes were theoretically calculated and discussed on the basis of Poisson-Boltzmann equation, Navier-Stokes equation and Nernst-Planck equation by considering several important parameters, such as the applied voltage, the thickness and the electric potential distributions in nanopores. In this way, the basic ionic currents, the modulated ionic currents and the current drops induced by translocation were obtained, and the size effects of the nanopores were carefully compared and discussed based on the calculated results and experimental data, which indicated that nanopores with a size of 10 nm or so are more advantageous to achieve high quality ionic current signals in DNA sensing.

  4. Procoagulant effects of lung cancer chemotherapy: impact on microparticles and cell-free DNA.

    PubMed

    Lysov, Zakhar; Dwivedi, Dhruva J; Gould, Travis J; Liaw, Patricia C

    2017-01-01

    Lung cancer is the second leading type of cancer, with venous thromboembolism being the second leading cause of death. Studies have shown increased levels of microparticles and cell-free DNA (CFDNA) in cancer patients, which can activate coagulation through extrinsic and intrinsic pathways, respectively. However, the impact of lung cancer chemotherapy on microparticle and/or CFDNA generation is not completely understood. The aim of the study was to study the effects of platinum-based chemotherapeutic agents on generation of procoagulant microparticles and CFDNA in vitro and in vivo. Microparticles were isolated from chemotherapy-treated monocytes, human umbilical vein endothelial cells, or cancer cells. Tissue factor (TF) and phosphatidylserine levels were characterized and thrombin/factor Xa generation assays were used to determine microparticle procoagulant activity. CFDNA levels were isolated from cell supernatants and plasma. A murine xenograft model of human lung carcinoma was used to study the procoagulant effects of TF microparticles and CFDNA in vivo. In vitro, platinum-based chemotherapy induced TF/phosphatidylserine microparticle shedding from A549 and A427 lung cancers cells, which enhanced thrombin generation in plasma in a FVII-dependent manner. CFDNA levels were increased in supernatants of chemotherapy-treated neutrophils and plasma of chemotherapy-treated mice. TF microparticles were elevated in plasma of chemotherapy-treated tumour-bearing mice. Plasma CFDNA levels are increased in chemotherapy-treated tumour-free mice and correlate with increased thrombin generation. In tumour-bearing mice, chemotherapy increases plasma levels of CFDNA and TF/phosphatidylserine microparticles. Platinum-based chemotherapy induces the shedding of TF/phosphatidylserine microparticles from tumour cells and the release of CFDNA from host neutrophils.

  5. Computational modeling and analysis of thermoelectric properties of nanoporous silicon

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, H.; Yu, Y.; Li, G., E-mail: gli@clemson.edu

    2014-03-28

    In this paper, thermoelectric properties of nanoporous silicon are modeled and studied by using a computational approach. The computational approach combines a quantum non-equilibrium Green's function (NEGF) coupled with the Poisson equation for electrical transport analysis, a phonon Boltzmann transport equation (BTE) for phonon thermal transport analysis and the Wiedemann-Franz law for calculating the electronic thermal conductivity. By solving the NEGF/Poisson equations self-consistently using a finite difference method, the electrical conductivity σ and Seebeck coefficient S of the material are numerically computed. The BTE is solved by using a finite volume method to obtain the phonon thermal conductivity k{sub p}more » and the Wiedemann-Franz law is used to obtain the electronic thermal conductivity k{sub e}. The figure of merit of nanoporous silicon is calculated by ZT=S{sup 2}σT/(k{sub p}+k{sub e}). The effects of doping density, porosity, temperature, and nanopore size on thermoelectric properties of nanoporous silicon are investigated. It is confirmed that nanoporous silicon has significantly higher thermoelectric energy conversion efficiency than its nonporous counterpart. Specifically, this study shows that, with a n-type doping density of 10{sup 20} cm{sup –3}, a porosity of 36% and nanopore size of 3 nm × 3 nm, the figure of merit ZT can reach 0.32 at 600 K. The results also show that the degradation of electrical conductivity of nanoporous Si due to the inclusion of nanopores is compensated by the large reduction in the phonon thermal conductivity and increase of absolute value of the Seebeck coefficient, resulting in a significantly improved ZT.« less

  6. Preparation and evaluation of microparticles from thiolated polymers via air jet milling.

    PubMed

    Hoyer, Herbert; Schlocker, Wolfgang; Krum, Kafedjiiski; Bernkop-Schnürch, Andreas

    2008-06-01

    Microparticles were formulated by incorporation of the model protein horseradish peroxidase in (thiolated) chitosan and (thiolated) poly(acrylic acid) via co-precipitation. Dried protein/polymer complexes were ground with an air jet mill and resulting particles were evaluated regarding size distribution, shape, zeta potential, drug load, protein activity, release pattern, swelling behaviour and cytotoxicity. The mean particle size distribution was 0.5-12 microm. Non-porous microparticles with a smooth surface were prepared. Microparticles from (thiolated) chitosan had a positive charge whereas microparticles from (thiolated) poly(acrylic acid) were negatively charged. The maximum protein load for microparticles based on chitosan, chitosan-glutathione (Ch-GSH), poly(acrylic acid) (PAA) and for poly(acrylic acid)-glutathione (PAA-GSH) was 7+/-1%, 11+/-2%, 4+/-0.2% and 7+/-2%, respectively. The release profile of all microparticles followed a first order release kinetic. Chitosan (0.5mg), Ch-GSH, PAA and PAA-GSH particles showed a 31.4-, 13.8-, 54.2- and a 42.2-fold increase in weight, respectively. No significant cytotoxicity could be found. Thiolated microparticles prepared by jet milling technique were shown to be stable and to have controlled drug release characteristics. After further optimizations the preparation method described here might be a useful tool for the production of protein loaded drug delivery systems.

  7. Nanopores: A journey towards DNA sequencing

    PubMed Central

    Wanunu, Meni

    2013-01-01

    Much more than ever, nucleic acids are recognized as key building blocks in many of life's processes, and the science of studying these molecular wonders at the single-molecule level is thriving. A new method of doing so has been introduced in the mid 1990's. This method is exceedingly simple: a nanoscale pore that spans across an impermeable thin membrane is placed between two chambers that contain an electrolyte, and voltage is applied across the membrane using two electrodes. These conditions lead to a steady stream of ion flow across the pore. Nucleic acid molecules in solution can be driven through the pore, and structural features of the biomolecules are observed as measurable changes in the trans-membrane ion current. In essence, a nanopore is a high-throughput ion microscope and a single-molecule force apparatus. Nanopores are taking center stage as a tool that promises to read a DNA sequence, and this promise has resulted in overwhelming academic, industrial, and national interest. Regardless of the fate of future nanopore applications, in the process of this 16-year-long exploration, many studies have validated the indispensability of nanopores in the toolkit of single-molecule biophysics. This review surveys past and current studies related to nucleic acid biophysics, and will hopefully provoke a discussion of immediate and future prospects for the field. PMID:22658507

  8. Controlled electrosprayed formation of non-spherical microparticles

    NASA Astrophysics Data System (ADS)

    Jeyhani, Morteza; Mak, Sze Yi; Sammut, Stephen; Shum, Ho Cheung; Hwang, Dae Kun; Tsai, Scott S. H.

    2017-11-01

    Fabrication of biocompatible microparticles, such as alginate particles, with the possibility of controlling the particles' morphology in a high-throughput manner, is essential for pharmaceutical and cosmetic industries. Even though the shape of alginate particles has been shown to be an important parameter in controlling drug delivery, there are very limited manufacturing methods to produce non-spherical alginate microparticles in a high-throughput fashion. Here, we present a system that generates non-spherical biocompatible alginate microparticles with a tunable size and shape, and at high-throughput, using an electrospray technique. Alginate solution, which is a highly biocompatible material, is flown through a needle using a constant flow rate syringe pump. The alginate phase is connected to a high-voltage power supply to charge it positively. There is a metallic ring underneath the needle that is charged negatively. The applied voltage creates an electric field that forces the dispensing droplets to pass through the metallic ring toward the collection bath. During this migration, droplets break up to smaller droplets to dissipate their energy. When the droplets reach the calcium chloride bath, polymerization happens and solidifies the droplets. We study the effects of changing the distance from the needle to the bath, and the concentration of calcium chloride in the bath, to control the size and the shape of the resulting microparticles.

  9. Formation of self-organized nanoporous anodic oxide from metallic gallium.

    PubMed

    Pandey, Bipin; Thapa, Prem S; Higgins, Daniel A; Ito, Takashi

    2012-09-25

    This paper reports the formation of self-organized nanoporous gallium oxide by anodization of solid gallium metal. Because of its low melting point (ca. 30 °C), metallic gallium can be shaped into flexible structures, permitting the fabrication of nanoporous anodic oxide monoliths within confined spaces like the inside of a microchannel. Here, solid gallium films prepared on planar substrates were employed to investigate the effects of anodization voltage (1, 5, 10, 15 V) and H(2)SO(4) concentration (1, 2, 4, 6 M) on anodic oxide morphology. Self-organized nanopores aligned perpendicular to the film surface were obtained upon anodization of gallium films in ice-cooled 4 and 6 M aqueous H(2)SO(4) at 10 and 15 V. Nanopore formation could be recognized by an increase in anodic current after a current decrease reflecting barrier oxide formation. The average pore diameter was in the range of 18-40 nm with a narrow diameter distribution (relative standard deviation ca. 10-20%), and was larger at lower H(2)SO(4) concentration and higher applied voltage. The maximum thickness of nanoporous anodic oxide was ca. 2 μm. In addition, anodic formation of self-organized nanopores was demonstrated for a solid gallium monolith incorporated at the end of a glass capillary. Nanoporous anodic oxide monoliths formed from a fusible metal will lead to future development of unique devices for chemical sensing and catalysis.

  10. Pharmacokinetics of intramuscular microparticle depot of valdecoxib in an experimental model.

    PubMed

    Agnihotri, Sagar M; Vavia, Pradeep R

    2009-09-01

    We did a prospective study to investigate pharmacokinetics of a single intramuscularly (i.m.) administered Valdecoxib (VC) polymeric microparticles in New Zealand white rabbits. Poly[lac(glc-leu)] microparticles encapsulating a potent cyclooxygenase-2- selective inhibitor, VC, were prepared by emulsion and solvent evaporation technique and administered i.m. to rabbits for pharmacokinetic study. A single i.m. dose of drug-loaded poly[lac(glc-leu)] microparticles resulted in sustained therapeutic drug levels in the plasma for 49 days. The relative bioavailability was increased severalfold as compared with unencapsulated drug. Injectable poly[lac(glc-leu)] microparticles hold promise for increasing drug bioavailability and reducing dosing frequency for better management of rheumatoid arthritis.

  11. Development of a 3D origami multiplex electrochemical immunodevice using a nanoporous silver-paper electrode and metal ion functionalized nanoporous gold-chitosan.

    PubMed

    Li, Weiping; Li, Long; Li, Meng; Yu, Jinghua; Ge, Shenguang; Yan, Mei; Song, Xianrang

    2013-10-25

    A simple and sensitive 3D microfluidic origami multiplex electrochemical immunodevice was developed for the first time using a novel nanoporous silver modified paper working electrode as a sensor platform and different metal ion functionalized nanoporous gold-chitosan as a tracer.

  12. Stimuli sensitive polymethacrylic acid microparticles (PMAA)--oral insulin delivery.

    PubMed

    Victor, Sunita Prem; Sharma, Chandra P

    2002-10-01

    This study investigated polymethacrylic acid (PMAA) microparticles for controlled release of Insulin in oral administration. The microparticles were characterised by scanning electron microscopy (SEM) for morphological studies. The swelling behaviour and drug release profile in various pH media were studied. The % swelling of gels was found to be inversely related to the amount of crosslinker added. Inclusion complex of betaCD and Insulin was studied using polyacrylamide gel electrophoresis (PAGE). Optimum complexation was obtained in the ratio 100 mg betaCD: 200 IU Insulin. The release pattern of Insulin from Insulin-betaCD complex encapsulated PMAA microparticles showed release of Insulin for more than seven hours.

  13. Microfabrication of curcumin-loaded microparticles using coaxial electrohydrodynamic atomization

    NASA Astrophysics Data System (ADS)

    Yuan, Shuai; Si, Ting; Liu, Zhongfa; Xu, Ronald X.

    2014-03-01

    Encapsulation of curcumin in PLGA microparticles is performed by a coaxial electrohydrodynamic atomization device. To optimize the process, the effects of different control parameters on morphology and size distribution of resultant microparticles are studied systemically. Four main flow modes are identified as the applied electric field intensity increases. The stable cone-jet configuration is found to be available for fabricating monodisperse microparticles with core-shell structures. The results are compared with those observed in traditional emulsion. The drug-loading efficiency is also checked. The present system is advantageous for the enhancement of particle size distribution and drug-loading efficiency in various applications such as drug delivery, biomedicine and image-guided therapy.

  14. Passive heat stress reduces circulating endothelial and platelet microparticles.

    PubMed

    Bain, Anthony R; Ainslie, Philip N; Bammert, Tyler D; Hijmans, Jamie G; Sekhon, Mypinder; Hoiland, Ryan L; Flück, Daniela; Donnelly, Joseph; DeSouza, Christopher A

    2017-06-01

    What is the central question of this study? Does passive heat stress of +2°C oesophageal temperature change concentrations of circulating arterial endothelial- and platelet-derived microparticles in healthy adults? What is the main finding and its importance? Concentrations of circulating endothelial- and platelet-derived microparticles were markedly decreased in heat stress. Reductions in circulating microparticles might indicate favourable vascular changes associated with non-pathological hyperthermia. Interest in circulating endothelial- and platelet-derived microparticles (EMPs and PMPs, respectively) has increased because of their potential pathogenic role in vascular disease and as biomarkers for vascular health. Hyperthermia is commonly associated with a pro-inflammatory stress but might also provide vascular protection when the temperature elevation is non-pathological. Circulating microparticles might contribute to the cellular adjustments and resultant vascular impacts of hyperthermia. Here, we determined whether circulating concentrations of arterial EMPs and PMPs are altered by passive heat stress (+2°C oesophageal temperature). Ten healthy young men (age 23 ± 3 years) completed the study. Hyperthermia was achieved by circulating ∼49°C water through a water-perfused suit that covered the entire body except the hands, feet and head. Arterial (radial) blood samples were obtained immediately before heating (normothermia) and in hyperthermia. The mean ± SD oesophageal temperature in normothermia was 37.2 ± 0.1°C and in hyperthermia 39.1 ± 0.1°C. Concentrations of circulating EMPs and PMPs were markedly decreased in hyperthermia. Activation-derived EMPs were reduced by ∼30% (mean ± SD; from 61 ± 8 to 43 ± 7 microparticles μl -1 ; P < 0.05) and apoptosis-derived EMPs by ∼45% (from 46 ± 7 to 23 ± 3 microparticles μl -1 ; P < 0.05). Likewise, circulating PMPs were reduced by ∼75% in response to hyperthermia

  15. An experimental study of microneedle-assisted microparticle delivery.

    PubMed

    Zhang, Dongwei; Das, Diganta B; Rielly, Chris D

    2013-10-01

    A set of well-defined experiments has been carried out to explore whether microneedles (MNs) can enhance the penetration depths of microparticles moving at high velocity such as those expected in gene guns for delivery of gene-loaded microparticles into target tissues. These experiments are based on applying solid MNs that are used to reduce the effect of mechanical barrier function of the target so as to allow delivery of microparticles at less imposed pressure as compared with most typical gene guns. Further, a low-cost material, namely, biomedical-grade stainless steel microparticle with size ranging between 1 and 20 μm, has been used in this study. The microparticles are compressed and bound in the form of a cylindrical pellet and mounted on a ground slide, which are then accelerated together by compressed air through a barrel. When the ground slide reaches the end of the barrel, the pellet is separated from the ground slide and is broken down into particle form by a mesh that is placed at the end of the barrel. Subsequently, these particles penetrate into the target. This paper investigates the implications of velocity of the pellet along with various other important factors that affect the particle delivery into the target. Our results suggest that the particle passage increases with an increase in pressure, mesh pore size, and decreases with increase in polyvinylpyrrolidone concentration. Most importantly, it is shown that MNs increase the penetration depths of the particles. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

  16. Sputter-Coated Microparticle Additives for Tailored Optical Properties

    DTIC Science & Technology

    2016-09-01

    hour at best). The microspheres coated in this work will be incorporated into a polymer matrix for composite and large-area coating applications...demonstrated, they will be incorporated into a polymer matrix for further testing. 15. SUBJECT TERMS fluidized bed, thin film, microparticles, coating...films of metals, ceramics , and multilayered materials.1 This is a practical method for the batch production of microparticles with tailored optical

  17. Molecular-based design and emerging applications of nanoporous carbon spheres

    NASA Astrophysics Data System (ADS)

    Liu, Jian; Wickramaratne, Nilantha P.; Qiao, Shi Zhang; Jaroniec, Mietek

    2015-08-01

    Over the past decade, considerable progress has been made in the synthesis and applications of nanoporous carbon spheres ranging in size from nanometres to micrometres. This Review presents the primary techniques for preparing nanoporous carbon spheres and the seminal research that has inspired their development, presented potential applications and uncovered future challenges. First we provide an overview of the synthesis techniques, including the Stöber method and those based on templating, self-assembly, emulsion and hydrothermal carbonization, with special emphasis on the design and functionalization of nanoporous carbon spheres at the molecular level. Next, we cover the key applications of these spheres, including adsorption, catalysis, separation, energy storage and biomedicine -- all of which might benefit from the regular geometry, good liquidity, tunable porosity and controllable particle-size distribution offered by nanoporous carbon spheres. Finally, we present the current challenges and opportunities in the development and commercial applications of nanoporous carbon spheres.

  18. Molecular-based design and emerging applications of nanoporous carbon spheres.

    PubMed

    Liu, Jian; Wickramaratne, Nilantha P; Qiao, Shi Zhang; Jaroniec, Mietek

    2015-08-01

    Over the past decade, considerable progress has been made in the synthesis and applications of nanoporous carbon spheres ranging in size from nanometres to micrometres. This Review presents the primary techniques for preparing nanoporous carbon spheres and the seminal research that has inspired their development, presented potential applications and uncovered future challenges. First we provide an overview of the synthesis techniques, including the Stöber method and those based on templating, self-assembly, emulsion and hydrothermal carbonization, with special emphasis on the design and functionalization of nanoporous carbon spheres at the molecular level. Next, we cover the key applications of these spheres, including adsorption, catalysis, separation, energy storage and biomedicine — all of which might benefit from the regular geometry, good liquidity, tunable porosity and controllable particle-size distribution offered by nanoporous carbon spheres. Finally, we present the current challenges and opportunities in the development and commercial applications of nanoporous carbon spheres.

  19. Differential procoagulant activity of microparticles derived from monocytes, granulocytes, platelets and endothelial cells: impact of active tissue factor.

    PubMed

    Shustova, Olga N; Antonova, Olga A; Golubeva, Nina V; Khaspekova, Svetlana G; Yakushkin, Vladimir V; Aksuk, Svetlana A; Alchinova, Irina B; Karganov, Mikhail Y; Mazurov, Alexey V

    2017-07-01

    : Microparticles released by activated/apoptotic cells exhibit coagulation activity as they express phosphatidylserine and some of them - tissue factor. We compared procoagulant properties of microparticles from monocytes, granulocytes, platelets and endothelial cells and assessed the impact of tissue factor in observed differences. Microparticles were sedimented (20 000g, 30 min) from the supernatants of activated monocytes, monocytic THP-1 cells, granulocytes, platelets and endothelial cells. Coagulation activity of microparticles was examined using plasma recalcification assay. The size of microparticles was evaluated by dynamic light scattering. Tissue factor activity was measured by its ability to activate factor X. All microparticles significantly accelerated plasma coagulation with the shortest lag times for microparticles derived from monocytes, intermediate - for microparticles from THP-1 cells and endothelial cells, and the longest - for microparticles from granulocytes and platelets. Average diameters of microparticles ranged within 400-600 nm. The largest microparticles were produced by endothelial cells and granulocytes, smaller - by monocytes, and the smallest - by THP-1 cells and platelets. The highest tissue factor activity was detected in microparticles from monocytes, lower activity - in microparticles from endothelial cells and THP-1 cells, and no activity - in microparticles from platelets and granulocytes. Anti-tissue factor antibodies extended coagulation lag times for microparticles from monocytes, endothelial cells and THP-1 cells and equalized them with those for microparticles from platelets and granulocytes. Higher coagulation activity of microparticles from monocytes, THP-1 cells and endothelial cells in comparison with microparticles from platelets and granulocytes is determined mainly by the presence of active tissue factor.

  20. In vitro assessment of biopolymer-modified porous silicon microparticles for wound healing applications.

    PubMed

    Mori, Michela; Almeida, Patrick V; Cola, Michela; Anselmi, Giulia; Mäkilä, Ermei; Correia, Alexandra; Salonen, Jarno; Hirvonen, Jouni; Caramella, Carla; Santos, Hélder A

    2014-11-01

    The wound healing stands as very complex and dynamic process, aiming the re-establishment of the damaged tissue's integrity and functionality. Thus, there is an emerging need for developing biopolymer-based composites capable of actively promoting cellular proliferation and reconstituting the extracellular matrix. The aims of the present work were to prepare and characterize biopolymer-functionalized porous silicon (PSi) microparticles, resulting in the development of drug delivery microsystems for future applications in wound healing. Thermally hydrocarbonized PSi (THCPSi) microparticles were coated with both chitosan and a mixture of chondroitin sulfate/hyaluronic acid, and subsequently loaded with two antibacterial model drugs, vancomycin and resveratrol. The biopolymer coating, drug loading degree and drug release behavior of the modified PSi microparticles were evaluated in vitro. The results showed that both the biopolymer coating and drug loading of the THCPSi microparticles were successfully achieved. In addition, a sustained release was observed for both the drugs tested. The viability and proliferation profiles of a fibroblast cell line exposed to the modified THCPSi microparticles and the subsequent reactive oxygen species (ROS) production were also evaluated. The cytotoxicity and proliferation results demonstrated less toxicity for the biopolymer-coated THCPSi microparticles at different concentrations and time points comparatively to the uncoated counterparts. The ROS production by the fibroblasts exposed to both uncoated and biopolymer-coated PSi microparticles showed that the modified PSi microparticles did not induce significant ROS production at the concentrations tested. Overall, the biopolymer-based PSi microparticles developed in this study are promising platforms for wound healing applications. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Thalassemic erythrocytes release microparticles loaded with hemichromes by redox activation of p72Syk kinase.

    PubMed

    Ferru, Emanuela; Pantaleo, Antonella; Carta, Franco; Mannu, Franca; Khadjavi, Amina; Gallo, Valentina; Ronzoni, Luisa; Graziadei, Giovanna; Cappellini, Maria Domenica; Turrini, Francesco

    2014-03-01

    High counts of circulating microparticles, originated from the membrane of abnormal erythrocytes, have been associated with increased thrombotic risk in hemolytic disorders. Our studies indicate that in thalassemia intermedia patients the number of circulating microparticles correlates with the capability of the thalassemic erythrocytes to release microparticles. The microparticles are characteristically loaded with hemichromes formed by denatured α-chains. This finding was substantiated by the positive correlation observed in thalassemia intermedia patients between the amount of hemichromes measured in erythrocytes, their capability to release microparticles and the levels of plasma hemichromes. We observed that hemichromes, following their binding to the cytoplasmic domain of band 3, induce the formation of disulfide band 3 dimers that are subsequently phosphorylated by p72Syk kinase. Phosphorylation of oxidized band 3 appears to be relevant for the formation of large hemichromes/band 3 clusters that, in turn, induce local membrane instability and the release of microparticles. Proteomic analysis of microparticles released from thalassemia intermedia erythrocytes indicated that, besides hemichromes and clustered band 3, the microparticles contain a characteristic set of proteins that includes catalase, heat shock protein 70, peroxiredoxin 2 and carbonic anhydrase. High amounts of immunoglobulins and C3 have also been found to be associated with microparticles, accounting for their intense phagocytosis. The effect of p72Syk kinase inhibitors on the release of microparticles from thalassemia intermedia erythrocytes may indicate new perspectives for controlling the release of circulating microparticles in hemolytic anemias.

  2. Effect of short-chain fatty acids on the formation of amylose microparticles by amylosucrase.

    PubMed

    Lim, Min-Cheol; Park, Kyu-Hwan; Choi, Jong-Hyun; Lee, Da-Hee; Letona, Carlos Andres Morales; Baik, Moo-Yeol; Park, Cheon-Seok; Kim, Young-Rok

    2016-10-20

    Amylose microparticles can be produced by self-assembly of amylose molecules through an amylosucrase-mediated synthesis. Here we investigated the role of short-chain fatty acids in the formation of amylose microparticles and the fate of these fatty acids at the end of the reaction. The rate of self-assembly and production yields of amylose microparticles were significantly enhanced in the presence of fatty acids. The effect was dependent on the length of the fatty acid carbon tail; butanoic acid (C4) was the most effective, followed by hexanoic acid (C6) and octanoic acid (C8). The amylose microparticles were investigated by carrying out SEM, XRD, Raman, NMR, FT-IR and DSC analysis. The size, morphology and crystal structure of the resulting amylose microparticles were comparable with those of amylose microparticles produced without fatty acids. The results indicated the carboxyl group of the fatty acid to be responsible for promoting the self-assembly of amylose chains to form microparticles. The fatty acids were eventually removed from the microstructure through the tight association of amylose double helices to form the amylose microparticles. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Rectification of nanopores in aprotic solvents--transport properties of nanopores with surface dipoles.

    PubMed

    Plett, Timothy; Shi, Wenqing; Zeng, Yuhan; Mann, William; Vlassiouk, Ivan; Baker, Lane A; Siwy, Zuzanna S

    2015-12-07

    Nanopores have become a model system to understand transport properties at the nanoscale. We report experiments and modeling of ionic current in aprotic solvents with different dipole moments through conically shaped nanopores in a polycarbonate film and through glass nanopipettes. We focus on solutions of the salt LiClO4, which is of great importance in modeling lithium based batteries. Results presented suggest ion current rectification observed results from two effects: (i) adsorption of Li(+) ions to the pore walls, and (ii) a finite dipole moment rendered by adsorbed solvent molecules. Properties of surfaces in various solvents were probed by means of scanning ion conductance microscopy, which confirmed existence of an effectively positive surface potential in aprotic solvents with high dipole moments.

  4. Coordinative nanoporous polymers synthesized with hydrogen-bonded columnar liquid crystals.

    PubMed

    Ishihara, Shinsuke; Furuki, Yusuke; Hill, Jonathan P; Ariga, Katsuhiko; Takeoka, Shinji

    2012-10-01

    In this paper, we report the development of nanoporous polymer which demonstrates the coordination property toward zinc porphyrin. A hydrogen-bonded columnar liquid crystalline precursor composed of a triphenylene template and three equivalent of the surrounding dendric amphiphile bearing a pyridyl head group and a polymerizable aliphatic chain, was covalently fixed by photopolymerization, and then the subsequent selective removal of the template successively resulted in a nanoporous polymer in which the pore wall is modified with pyridyl groups. The nanoporous polymer reflected the conformation of template, and displayed considerable coordination ability of the pyridyl groups towards zinc porphyrin. The coordinative nanoporous polymer is promising as a nano-scaled scaffold for the organization of dyes into functional supramolecular architectures.

  5. Engineering the internal surfaces of three-dimensional nanoporous catalysts by surfactant-modified dealloying.

    PubMed

    Wang, Zhili; Liu, Pan; Han, Jiuhui; Cheng, Chun; Ning, Shoucong; Hirata, Akihiko; Fujita, Takeshi; Chen, Mingwei

    2017-10-20

    Tuning surface structures by bottom-up synthesis has been demonstrated as an effective strategy to improve the catalytic performances of nanoparticle catalysts. Nevertheless, the surface modification of three-dimensional nanoporous metals, fabricated by a top-down dealloying approach, has not been achieved despite great efforts devoted to improving the catalytic performance of three-dimensional nanoporous catalysts. Here we report a surfactant-modified dealloying method to tailor the surface structure of nanoporous gold for amplified electrocatalysis toward methanol oxidation and oxygen reduction reactions. With the assistance of surfactants, {111} or {100} faceted internal surfaces of nanoporous gold can be realized in a controllable manner by optimizing dealloying conditions. The surface modified nanoporous gold exhibits significantly enhanced electrocatalytic activities in comparison with conventional nanoporous gold. This study paves the way to develop high-performance three-dimensional nanoporous catalysts with a tunable surface structure by top-down dealloying for efficient chemical and electrochemical reactions.

  6. Electrochemical annealing of nanoporous gold by application of cyclic potential sweeps

    PubMed Central

    Sharma, Abeera; Bhattarai, Jay K.; Alla, Allan J.; Demchenko, Alexei V.; Stine, Keith J.

    2015-01-01

    An electrochemical method for annealing the pore sizes of nanoporous gold is reported. The pore sizes of nanoporous gold can be increased by electrochemical cycling with the upper potential limit being just at the onset of gold oxide formation. This study has been performed in electrolyte solutions including potassium chloride, sodium nitrate and sodium perchlorate. Scanning electron microscopy images have been used for ligament and pore size analysis. We examine the modifications of nanoporous gold due to annealing using electrochemical impedance spectroscopy, and cyclic voltammetry and offer a comparison of the surface coverage using the gold oxide stripping method as well as the method in which electrochemically accessible surface area is determined by using a diffusing redox probe. The effect of additives adsorbed on the nanoporous gold surface when subjected to annealing in different electrolytes as well as the subsequent structural changes in nanoporous gold are also reported. The effect of the annealing process on the application of nanoporous gold as a substrate for glucose electro-oxidation is briefly examined. PMID:25649027

  7. Nonfaradaic nanoporous electrochemistry for conductometry at high electrolyte concentration.

    PubMed

    Bae, Je Hyun; Kang, Chung Mu; Choi, Hyoungseon; Kim, Beom Jin; Jang, Woohyuk; Lim, Sung Yul; Kim, Hee Chan; Chung, Taek Dong

    2015-02-17

    Nanoporous electrified surfaces create a unique nonfaradaic electrochemical behavior that is sensitively influenced by pore size, morphology, ionic strength, and electric field modulation. Here, we report the contributions of ion concentration and applied ac frequency to the electrode impedance through an electrical double layer overlap and ion transport along the nanopores. Nanoporous Pt with uniform pore size and geometry (L2-ePt) responded more sensitively to conductivity changes in aqueous solutions than Pt black with poor uniformity despite similar real surface areas and enabled the previously difficult quantitative conductometry measurements at high electrolyte concentrations. The nanopores of L2-ePt were more effective in reducing the electrode impedance and exhibited superior linear responses to not only flat Pt but also Pt black, leading to successful conductometric detection in ion chromatography without ion suppressors and at high ionic strengths.

  8. Control of Alginate Core Size in Alginate-Poly (Lactic-Co-Glycolic) Acid Microparticles

    NASA Astrophysics Data System (ADS)

    Lio, Daniel; Yeo, David; Xu, Chenjie

    2016-01-01

    Core-shell alginate-poly (lactic-co-glycolic) acid (PLGA) microparticles are potential candidates to improve hydrophilic drug loading while facilitating controlled release. This report studies the influence of the alginate core size on the drug release profile of alginate-PLGA microparticles and its size. Microparticles are synthesized through double-emulsion fabrication via a concurrent ionotropic gelation and solvent extraction. The size of alginate core ranges from approximately 10, 50, to 100 μm when the emulsification method at the first step is homogenization, vortexing, or magnetic stirring, respectively. The second step emulsification for all three conditions is performed with magnetic stirring. Interestingly, although the alginate core has different sizes, alginate-PLGA microparticle diameter does not change. However, drug release profiles are dramatically different for microparticles comprising different-sized alginate cores. Specifically, taking calcein as a model drug, microparticles containing the smallest alginate core (10 μm) show the slowest release over a period of 26 days with burst release less than 1 %.

  9. Catalytic nanoporous membranes

    DOEpatents

    Pellin, Michael J [Naperville, IL; Hryn, John N [Naperville, IL; Elam, Jeffrey W [Elmhurst, IL

    2009-12-01

    A nanoporous catalytic membrane which displays several unique features including pores which can go through the entire thickness of the membrane. The membrane has a higher catalytic and product selectivity than conventional catalysts. Anodic aluminum oxide (AAO) membranes serve as the catalyst substrate. This substrate is then subjected to Atomic Layer Deposition (ALD), which allows the controlled narrowing of the pores from 40 nm to 10 nm in the substrate by deposition of a preparatory material. Subsequent deposition of a catalytic layer on the inner surfaces of the pores reduces pore sizes to less than 10 nm and allows for a higher degree of reaction selectivity. The small pore sizes allow control over which molecules enter the pores, and the flow-through feature can allow for partial oxidation of reactant species as opposed to complete oxidation. A nanoporous separation membrane, produced by ALD is also provided for use in gaseous and liquid separations. The membrane has a high flow rate of material with 100% selectivity.

  10. Optimized nanoporous materials.

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Braun, Paul V.; Langham, Mary Elizabeth; Jacobs, Benjamin W.

    2009-09-01

    Nanoporous materials have maximum practical surface areas for electrical charge storage; every point in an electrode is within a few atoms of an interface at which charge can be stored. Metal-electrolyte interfaces make best use of surface area in porous materials. However, ion transport through long, narrow pores is slow. We seek to understand and optimize the tradeoff between capacity and transport. Modeling and measurements of nanoporous gold electrodes has allowed us to determine design principles, including the fact that these materials can deplete salt from the electrolyte, increasing resistance. We have developed fabrication techniques to demonstrate architectures inspired bymore » these principles that may overcome identified obstacles. A key concept is that electrodes should be as close together as possible; this is likely to involve an interpenetrating pore structure. However, this may prove extremely challenging to fabricate at the finest scales; a hierarchically porous structure can be a worthy compromise.« less

  11. Protein encapsulation via porous CaCO3 microparticles templating.

    PubMed

    Volodkin, Dmitry V; Larionova, Natalia I; Sukhorukov, Gleb B

    2004-01-01

    Porous microparticles of calcium carbonate with an average diameter of 4.75 microm were prepared and used for protein encapsulation in polymer-filled microcapsules by means of electrostatic layer-by-layer assembly (ELbL). Loading of macromolecules in porous CaCO3 particles is affected by their molecular weight due to diffusion-limited permeation inside the particles and also by the affinity to the carbonate surface. Adsorption of various proteins and dextran was examined as a function of pH and was found to be dependent both on the charge of the microparticles and macromolecules. The electrostatic effect was shown to govern this interaction. This paper discusses the factors which can influence the adsorption capacity of proteins. A new way of protein encapsulation in polyelectrolyte microcapsules is proposed exploiting the porous, biocompatible, and decomposable microparticles from CaCO3. It consists of protein adsorption in the pores of the microparticles followed by ELbL of oppositely charged polyelectrolytes and further core dissolution. This resulted in formation of polyelectrolyte-filled capsules with protein incorporated in interpenetrating polyelectrolyte network. The properties of CaCO3 microparticles and capsules prepared were characterized by scanning electron microscopy, microelectrophoresis, and confocal laser scanning microscopy. Lactalbumin was encapsulated by means of the proposed technique yielding a content of 0.6 pg protein per microcapsule. Horseradish peroxidase saves 37% of activity after encapsulation. However, the thermostability of the enzyme was improved by encapsulation. The results demonstrate that porous CaCO3 microparticles can be applied as microtemplates for encapsulation of proteins into polyelectrolyte capsules at neutral pH as an optimal medium for a variety of bioactive material, which can also be encapsulated by the proposed method. Microcapsules filled with encapsulated material may find applications in the field of

  12. Simultaneous Size Control of Microcapsule and Its Nanopores Using Polymer Concentration

    NASA Astrophysics Data System (ADS)

    Cha, Jemyung; Jeong, Eun Ho; Takahiro, Arakawa; Kim, Kyung Chun; Shoji, Shuich; Go, Jeung Sang

    2010-03-01

    Polymeric microcapsules with nanopores are produced using the droplet-based self-assembly of a block copolymer in the microfluidic channel. Differently from the conventional wise, the sizes of the microcapsule and its nanopores are controlled by changing the concentration of the block copolymer dissolved in an organic solvent. The increase in the polymer concentration shows the increase in the size of the microcapsule and the decrease of the size and number of the nanopores. Also, to obtain the optimal morphology of the nanopores in the microcapsule, the removal process of a surfactant is newly developed by using a microporous metal mesh.

  13. Solid-state nanopores of controlled geometry fabricated in a transmission electron microscope

    NASA Astrophysics Data System (ADS)

    Qian, Hui; Egerton, Ray F.

    2017-11-01

    Energy-filtered transmission electron microscopy and electron tomography were applied to in situ studies of the formation, shape, and diameter of nanopores formed in a silicon nitride membrane in a transmission electron microscope. The nanopore geometry was observed in three dimensions by electron tomography. Drilling conditions, such as probe current, beam convergence angle, and probe position, affect the formation rate and the geometry of the pores. With a beam convergence semi-angle of α = 22 mrad, a conical shaped nanopore is formed but at α = 45 mrad, double-cone (hourglass-shaped) nanopores were produced. Nanopores with an effective diameter between 10 nm and 1.8 nm were fabricated by controlling the drilling time.

  14. Selective Separation of Metal Ions via Monolayer Nanoporous Graphene with Carboxyl Groups.

    PubMed

    Li, Zhan; Liu, Yanqi; Zhao, Yang; Zhang, Xin; Qian, Lijuan; Tian, Longlong; Bai, Jing; Qi, Wei; Yao, Huijun; Gao, Bin; Liu, Jie; Wu, Wangsuo; Qiu, Hongdeng

    2016-10-18

    Graphene-coated plastic substrates, such as polyethylene terephthalate (PET), are regularly used in flexible electronic devices. Here we demonstrate a new application of the graphene-coated nanoporous PET membrane for the selective separation of metal ions in an ion exchange manner. Irradiation with swift heavy ions is used to perforate graphene and PET substrate. This process could create graphene nanopores with carboxyl groups, thus forming conical holes in the PET after chemical etching to support graphene nanopores. Therefore, a monolayer nanoporous graphene membrane with a PET substrate is constructed successfully to investigate its ionic selective separation. We find that the permeation ratio of ions strongly depends on the temperature and H + concentration in the driving solution. An electric field can increase the permeation ratio of ions through the graphene nanopores, but it inhibits the ion selective separation. Moreover, the structure of the graphene nanopore with carboxyl groups is resolved at the density functional theory level. The results show the asymmetric structure of the nanopore with carboxyl groups, and the analysis indicates that the ionic permeation can be attributed to the ion exchange between metal ions and protons on the two sides of graphene nanopores. These results would be beneficial to the design of membrane separation materials made from graphene with efficient online and offline bulk separation.

  15. Large apparent electric size of solid-state nanopores due to spatially extended surface conduction.

    PubMed

    Lee, Choongyeop; Joly, Laurent; Siria, Alessandro; Biance, Anne-Laure; Fulcrand, Rémy; Bocquet, Lydéric

    2012-08-08

    Ion transport through nanopores drilled in thin membranes is central to numerous applications, including biosensing and ion selective membranes. This paper reports experiments, numerical calculations, and theoretical predictions demonstrating an unexpectedly large ionic conduction in solid-state nanopores, taking its origin in anomalous entrance effects. In contrast to naive expectations based on analogies with electric circuits, the surface conductance inside the nanopore is shown to perturb the three-dimensional electric current streamlines far outside the nanopore in order to meet charge conservation at the pore entrance. This unexpected contribution to the ionic conductance can be interpreted in terms of an apparent electric size of the solid-state nanopore, which is much larger than its geometric counterpart whenever the number of charges carried by the nanopore surface exceeds its bulk counterpart. This apparent electric size, which can reach hundreds of nanometers, can have a major impact on the electrical detection of translocation events through nanopores, as well as for ionic transport in biological nanopores.

  16. Confining metal-halide perovskites in nanoporous thin films

    PubMed Central

    Demchyshyn, Stepan; Roemer, Janina Melanie; Groiß, Heiko; Heilbrunner, Herwig; Ulbricht, Christoph; Apaydin, Dogukan; Böhm, Anton; Rütt, Uta; Bertram, Florian; Hesser, Günter; Scharber, Markus Clark; Sariciftci, Niyazi Serdar; Nickel, Bert; Bauer, Siegfried; Głowacki, Eric Daniel; Kaltenbrunner, Martin

    2017-01-01

    Controlling the size and shape of semiconducting nanocrystals advances nanoelectronics and photonics. Quantum-confined, inexpensive, solution-derived metal halide perovskites offer narrowband, color-pure emitters as integral parts of next-generation displays and optoelectronic devices. We use nanoporous silicon and alumina thin films as templates for the growth of perovskite nanocrystallites directly within device-relevant architectures without the use of colloidal stabilization. We find significantly blue-shifted photoluminescence emission by reducing the pore size; normally infrared-emitting materials become visibly red, and green-emitting materials become cyan and blue. Confining perovskite nanocrystals within porous oxide thin films drastically increases photoluminescence stability because the templates auspiciously serve as encapsulation. We quantify the template-induced size of the perovskite crystals in nanoporous silicon with microfocus high-energy x-ray depth profiling in transmission geometry, verifying the growth of perovskite nanocrystals throughout the entire thickness of the nanoporous films. Low-voltage electroluminescent diodes with narrow, blue-shifted emission fabricated from nanocrystalline perovskites grown in embedded nanoporous alumina thin films substantiate our general concept for next-generation photonic devices. PMID:28798959

  17. Nanoporous PbSe-SiO2 Thermoelectric Composites.

    PubMed

    Wu, Chao-Feng; Wei, Tian-Ran; Sun, Fu-Hua; Li, Jing-Feng

    2017-11-01

    Nanoporous architecture has long been predicted theoretically for its proficiency in suppressing thermal conduction, but less concerned as a practical approach for better thermoelectric materials hitherto probably due to its technical challenges. This article demonstrates a study on nanoporous PbSe-SiO 2 composites fabricated by a facile method of mechanical alloying assisted by subsequent wet-milling and then spark plasma sintering. Owing to the formation of random nanopores and additional interface scattering, the lattice thermal conductivity is limited to a value as low as 0.56 W m -1 K -1 at above 600 K, almost the same low level achieved by introducing nanoscale precipitates. Besides, the room-temperature electrical transport is found to be dominated by the grain-boundary potential barrier scattering, whose effect fades away with increasing temperatures. Consequently, a maximum ZT of 1.15 at 823 K is achieved in the PbSe + 0.7 vol% SiO 2 composition with >20% increase in average ZT , indicating the great potential of nanoporous structuring toward high thermoelectric conversion efficiency.

  18. Lipid-coated mannitol core microparticles for sustained release of protein.

    PubMed

    Wang, Bifeng; Friess, Wolfgang

    2018-07-01

    Parenteral sustained release systems for proteins which provide therapeutic levels over a longer period avoiding frequent administration, which preserve protein stability during manufacturing, storage and application and which are biodegradable and highly biocompatible in the body are intensively sought after. The aim of this study was to generate and study mannitol core microparticles loaded with a monoclonal antibody IgG1 and coated with lipid either hard fat or glyceryl stearate at different coating levels. The protein was stabilized with 22.5 mg/mL sucrose, 0.1% PS 80, 10 mM methionine in 10 mM His buffer pH 7.2 during the spray loading process. 30 g protein-loaded mannitol carrier microparticles were coated with 5 g, 10 g, 20 g and 30 g of lipid, respectively. Placing more lipid onto the protein-loaded microparticles reduced both burst and release rate, and the particles maintained their geometric form during the release test. The IgG1 release from microparticles covered with a hard fat layer extended up to 6 weeks. The IgG1 was released in its monomeric form and maintained its secondary structure as shown by FTIR. Incomplete release of IgG1 from glyceryl stearate-coated microparticles was observed, which may be due to the small pore sizes of the glyceryl stearate layer or a detrimental surfactant character of glyceryl stearate to protein. Hence, these hard fat-coated mannitol core microparticles have high potential for protein delivery. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Optical Trap Loading of Dielectric Microparticles In Air.

    PubMed

    Park, Haesung; LeBrun, Thomas W

    2017-02-05

    We demonstrate a method to trap a selected dielectric microparticle in air using radiation pressure from a single-beam gradient optical trap. Randomly scattered dielectric microparticles adhered to a glass substrate are momentarily detached using ultrasonic vibrations generated by a piezoelectric transducer (PZT). Then, the optical beam focused on a selected particle lifts it up to the optical trap while the vibrationally excited microparticles fall back to the substrate. A particle may be trapped at the nominal focus of the trapping beam or at a position above the focus (referred to here as the levitation position) where gravity provides the restoring force. After the measurement, the trapped particle can be placed at a desired position on the substrate in a controlled manner. In this protocol, an experimental procedure for selective optical trap loading in air is outlined. First, the experimental setup is briefly introduced. Second, the design and fabrication of a PZT holder and a sample enclosure are illustrated in detail. The optical trap loading of a selected microparticle is then demonstrated with step-by-step instructions including sample preparation, launching into the trap, and use of electrostatic force to excite particle motion in the trap and measure charge. Finally, we present recorded particle trajectories of Brownian and ballistic motions of a trapped microparticle in air. These trajectories can be used to measure stiffness or to verify optical alignment through time domain and frequency domain analysis. Selective trap loading enables optical tweezers to track a particle and its changes over repeated trap loadings in a reversible manner, thereby enabling studies of particle-surface interaction.

  20. High-Mobility Group Box 1 From Hypoxic Trophoblasts Promotes Endothelial Microparticle Production and Thrombophilia in Preeclampsia.

    PubMed

    Hu, Yae; Yan, Ruhong; Zhang, Ce; Zhou, Zhichao; Liu, Meng; Wang, Can; Zhang, Hong; Dong, Liang; Zhou, Tiantian; Wu, Yi; Dong, Ningzheng; Wu, Qingyu

    2018-04-12

    Thrombophilia is a major complication in preeclampsia, a disease associated with placental hypoxia and trophoblast inflammation. Preeclampsia women are known to have increased circulating microparticles that are procoagulant, but the underlying mechanisms remain unclear. In this study, we sought to understand the mechanism connecting placental hypoxia, circulating microparticles, and thrombophilia. We analyzed protein markers on plasma microparticles from preeclampsia women and found that the increased circulating microparticles were mostly from endothelial cells. In proteomic studies, we identified HMGB1 (high-mobility group box 1), a proinflammatory protein, as a key factor from hypoxic trophoblasts in stimulating microparticle production in human umbilical vein endothelial cells. Immunodepletion or inhibition of HMGB1 in the conditioned medium from hypoxic human trophoblasts abolished the endothelial microparticle-stimulating activity. Conversely, recombinant HMGB1 stimulated microparticle production in cultured human umbilical vein endothelial cells. The microparticles from recombinant HMGB1-stimulated human umbilical vein endothelial cells promoted blood coagulation and neutrophil activation in vitro. Injection of recombinant HMGB1 in pregnant mice increased plasma endothelial microparticles and promoted blood coagulation. In preeclampsia women, elevated placental HMGB1 expression was detected and high levels of plasma HMGB1 correlated with increased plasma endothelial microparticles. Our results indicate that placental hypoxia-induced HMGB1 expression and release from trophoblasts are important mechanism underlying increased circulating endothelial microparticles and thrombophilia in preeclampsia. © 2018 American Heart Association, Inc.

  1. Microparticles Produced by the Hydrogel Template Method for Sustained Drug Delivery

    PubMed Central

    Lu, Ying; Sturek, Michael; Park, Kinam

    2014-01-01

    Polymeric microparticles have been used widely for sustained drug delivery. Current methods of microparticle production can be improved by making homogeneous particles in size and shape, increasing the drug loading, and controlling the initial burst release. In the current study, the hydrogel template method was used to produce homogeneous poly(lactide-co-glycolide) (PLGA) microparticles and to examine formulation and process-related parameters. Poly(vinyl alcohol) (PVA) was used to make hydrogel templates. The parameters examined include PVA molecular weight, type of PLGA (as characterized by lactide content, inherent viscosity), polymer concentration, drug concentration and composition of solvent system. Three model compounds studied were risperidone, methylprednisolone acetate and paclitaxel. The ability of the hydrogel template method to produce microparticles with good conformity to template was dependent on molecular weight of PVA and viscosity of the PLGA solution. Drug loading and encapsulation efficiency were found to be influenced by PLGA lactide content, polymer concentration and composition of the solvent system. The drug loading and encapsulation efficiency were 28.7% and 82% for risperidone, 31.5% and 90% for methylprednisolone acetate, and 32.2 % and 92 % for paclitaxel, respectively. For all three drugs, release was sustained for weeks, and the in vitro release profile of risperidone was comparable to that of microparticles prepared using the conventional emulsion method. The hydrogel template method provides a new approach of manipulating microparticles. PMID:24333903

  2. Thiol functionalized polymethacrylic acid-based hydrogel microparticles for oral insulin delivery.

    PubMed

    Sajeesh, S; Vauthier, C; Gueutin, C; Ponchel, G; Sharma, Chandra P

    2010-08-01

    In the present study thiol functionalized polymethacrylic acid-polyethylene glycol-chitosan (PCP)-based hydrogel microparticles were utilized to develop an oral insulin delivery system. Thiol modification was achieved by grafting cysteine to the activated surface carboxyl groups of PCP hydrogels (Cys-PCP). Swelling and insulin loading/release experiments were conducted on these particles. The ability of these particles to inhibit protease enzymes was evaluated under in vitro experimental conditions. Insulin transport experiments were performed on Caco-2 cell monolayers and excised intestinal tissue with an Ussing chamber set-up. Finally, the efficacy of insulin-loaded particles in reducing the blood glucose level in streptozotocin-induced diabetic rats was investigated. Thiolated hydrogel microparticles showed less swelling and had a lower insulin encapsulation efficiency as compared with unmodified PCP particles. PCP and Cys-PCP microparticles were able to inhibit protease enzymes under in vitro conditions. Thiolation was an effective strategy to improve insulin absorption across Caco-2 cell monolayers, however, the effect was reduced in the experiments using excised rat intestinal tissue. Nevertheless, functionalized microparticles were more effective in eliciting a pharmacological response in diabetic animal, as compared with unmodified PCP microparticles. From these studies thiolation of hydrogel microparticles seems to be a promising approach to improve oral delivery of proteins/peptides. Copyright 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  3. RBC Storage Effect on Coagulation, Microparticles and Microchimerism in Critically Ill Patients

    DTIC Science & Technology

    2015-03-01

    Award Number: W81XWH-11-2-0028 TITLE: “RBC Storage Effect on Coagulation, Microparticles and Microchimerism in Critically Ill Patients...27 DEC 2010 - 26 DEC 2015 – 4. TITLE AND SUBTITLE "“RBC Storage Effect on Coagulation, Microparticles and 5a. CONTRACT NUMBER Microchimerism in...15. SUBJECT TERMS RBC storage age; microchimerism; critically ill patients; coagulation; microparticles 16. SECURITY CLASSIFICATION OF: U 17

  4. Design and evaluation of acrylate polymeric carriers for fabrication of pH-sensitive microparticles.

    PubMed

    Arya, Amit; Majumdar, Dipak K; Pathak, Dharam Pal; Sharma, Anil K; Ray, Alok R

    2017-02-01

    Colon-targeted microparticles loaded with a model anti-inflammatory drug were fabricated using especially designed acrylic acid-butyl methacrylate copolymers. Microparticles were prepared by oil-in-oil solvent evaporation method using Span 80 as emulsifier. Microparticles were found to be spherical in shape, hemocompatible and anionic with zeta potential of -27.4 and -29.0 mV. Entrapment of drug in the microparticles was confirmed by Fourier transform infrared (FTIR) spectroscopy. However, X-ray diffraction (XRD) and differential scanning calorimetry (DSC) revealed amorphous nature of microparticles due to the dilution effect of amorphous polymer. The microparticles released less than 5% drug at pH 1.2, while more than 90% of the drug load was released at pH 7.4. This suggested the colon targeting nature of the formulations. In experimentally developed colitis in Wistar rats, the microparticle formulation showed significant reduction (p < .05) in the disease activity score (disease symptoms), the colon-to-body weight ratio (tissue edema) and the myeloperoxidase, tumor necrosis factor (TNF)-α and interleukin (IL)-1β activities.

  5. Single cigar-shaped nanopores functionalized with amphoteric amino acid chains: experimental and theoretical characterization.

    PubMed

    Ali, Mubarak; Ramirez, Patricio; Nguyen, Hung Quoc; Nasir, Saima; Cervera, Javier; Mafe, Salvador; Ensinger, Wolfgang

    2012-04-24

    We present an experimental and theoretical characterization of single cigar-shaped nanopores with pH-responsive carboxylic acid and lysine chains functionalized on the pore surface. The nanopore characterization includes (i) optical images of the nanostructure obtained by FESEM; (ii) different chemical procedures for the nanopore preparation (etching time and functionalizations; pH and electrolyte concentration of the external solution) allowing externally tunable nanopore responses monitored by the current-voltage (I-V) curves; and (iii) transport simulations obtained with a multilayer nanopore model. We show that a single, approximately symmetric nanopore can be operated as a reconfigurable diode showing different rectifying behaviors by applying chemical and electrical signals. The remarkable characteristics of the new nanopore are the sharp response observed in the I-V curves, the improved tunability (with respect to previous designs of symmetric nanopores) which is achieved because of the direct external access to the nanostructure mouths, and the broad range of rectifying properties. The results concern both fundamental concepts useful for the understanding of transport processes in biological systems (ion channels) and applications relevant for tunable nanopore technology (information processing and drug controlled release).

  6. Thermal Conductivity in Nanoporous Gold Films during Electron-Phonon Nonequilibrium

    DOE PAGES

    Hopkins, Patrick E.; Norris, Pamela M.; Phinney, Leslie M.; ...

    2008-01-01

    The reduction of nanodevices has given recent attention to nanoporous materials due to their structure and geometry. However, the thermophysical properties of these materials are relatively unknown. In this article, an expression for thermal conductivity of nanoporous structures is derived based on the assumption that the finite size of the ligaments leads to electron-ligament wall scattering. This expression is then used to analyze the thermal conductivity of nanoporous structures in the event of electron-phonon nonequilibrium.

  7. Hierarchical nanoporous metals as a path toward the ultimate three-dimensional functionality.

    PubMed

    Fujita, Takeshi

    2017-01-01

    Nanoporous metals prepared via dealloying or selective leaching of solid solution alloys and compounds represent an emerging class of materials. They possess a three-dimensional (3D) structure of randomly interpenetrating ligaments/nanopores with sizes between 5 nm and several tens of micrometers, which can be tuned by varying their preparation conditions (such as dealloying time and temperature) or additional thermal coarsening. As compared to other nanostructured materials, nanoporous metals have many advantages, including their bicontinuous structure, tunable pore sizes, bulk form, good electrical conductivity, and high structural stability. Therefore, nanoporous metals represent ideal 3D materials with versatile functionality, which can be utilized in various fields. In this review, we describe the recent applications of nanoporous metals in molecular detection, catalysis, 3D graphene synthesis, hierarchical pore formation, and additive manufacturing (3D printing) together with our own achievements in these areas. Finally, we discuss possible ways of realizing the ultimate 3D functionality beyond the scope of nanoporous metals.

  8. Hierarchical nanoporous metals as a path toward the ultimate three-dimensional functionality

    PubMed Central

    Fujita, Takeshi

    2017-01-01

    Abstract Nanoporous metals prepared via dealloying or selective leaching of solid solution alloys and compounds represent an emerging class of materials. They possess a three-dimensional (3D) structure of randomly interpenetrating ligaments/nanopores with sizes between 5 nm and several tens of micrometers, which can be tuned by varying their preparation conditions (such as dealloying time and temperature) or additional thermal coarsening. As compared to other nanostructured materials, nanoporous metals have many advantages, including their bicontinuous structure, tunable pore sizes, bulk form, good electrical conductivity, and high structural stability. Therefore, nanoporous metals represent ideal 3D materials with versatile functionality, which can be utilized in various fields. In this review, we describe the recent applications of nanoporous metals in molecular detection, catalysis, 3D graphene synthesis, hierarchical pore formation, and additive manufacturing (3D printing) together with our own achievements in these areas. Finally, we discuss possible ways of realizing the ultimate 3D functionality beyond the scope of nanoporous metals. PMID:29057026

  9. Hierarchical nanoporous metals as a path toward the ultimate three-dimensional functionality

    NASA Astrophysics Data System (ADS)

    Fujita, Takeshi

    2017-12-01

    Nanoporous metals prepared via dealloying or selective leaching of solid solution alloys and compounds represent an emerging class of materials. They possess a three-dimensional (3D) structure of randomly interpenetrating ligaments/nanopores with sizes between 5 nm and several tens of micrometers, which can be tuned by varying their preparation conditions (such as dealloying time and temperature) or additional thermal coarsening. As compared to other nanostructured materials, nanoporous metals have many advantages, including their bicontinuous structure, tunable pore sizes, bulk form, good electrical conductivity, and high structural stability. Therefore, nanoporous metals represent ideal 3D materials with versatile functionality, which can be utilized in various fields. In this review, we describe the recent applications of nanoporous metals in molecular detection, catalysis, 3D graphene synthesis, hierarchical pore formation, and additive manufacturing (3D printing) together with our own achievements in these areas. Finally, we discuss possible ways of realizing the ultimate 3D functionality beyond the scope of nanoporous metals.

  10. Metformin reduces total microparticles and microparticles-expressing tissue factor in women with polycystic ovary syndrome.

    PubMed

    Carvalho, Laura M L; Ferreira, Cláudia N; Candido, Ana L; Reis, Fernando M; Sóter, Mirelle O; Sales, Mariana F; Silva, Ieda F O; Nunes, Fernanda F C; Gomes, Karina Braga

    2017-10-01

    The objective of this study was to evaluate the levels of total microparticles (MPs) and microparticles-expressing tissue factor (TFMPs) in women with polycystic ovarian syndrome (PCOS) who use metformin comparing to those who do not take metformin. We quantified total MPs and TFMPs in the plasma of 50 patients with PCOS-13 of these women used metformin (850 mg 2×/day during at least 6 months) and the other 37 did not. For this purpose, the microparticles (MPs) were purified by differential centrifugation of the plasma and, subsequently, by flow cytometry, using annexin-V and CD142 as markers. Total MPs levels were lower in treated patients (59.58 ± 28.43 MPs/µL) when compared to untreated group (97.32 ± 59.42; p = 0.033). Plasma levels of TFMPs were also significantly lower in the group of patients who used metformin (1.10 ± 0.94 MPs/µL) when compared to untreated patients (2.20 ± 1.42 MPs/µL) (p = 0.003). Considering that metformin reduced the levels of total MPs and TFMPs, our results suggest that this mechanism could be involved in the antithrombotic metformin effect, corroborating with the indication of this drug in the PCOS treatment.

  11. Single molecule transistor based nanopore for the detection of nicotine

    NASA Astrophysics Data System (ADS)

    Ray, S. J.

    2014-12-01

    A nanopore based detection methodology was proposed and investigated for the detection of Nicotine. This technique uses a Single Molecular Transistor working as a nanopore operational in the Coulomb Blockade regime. When the Nicotine molecule is pulled through the nanopore area surrounded by the Source(S), Drain (D), and Gate electrodes, the charge stability diagram can detect the presence of the molecule and is unique for a specific molecular structure. Due to the weak coupling between the different electrodes which is set by the nanopore size, the molecular energy states stay almost unaffected by the electrostatic environment that can be realised from the charge stability diagram. Identification of different orientation and position of the Nicotine molecule within the nanopore area can be made from specific regions of overlap between different charge states on the stability diagram that could be used as an electronic fingerprint for detection. This method could be advantageous and useful to detect the presence of Nicotine in smoke which is usually performed using chemical chromatography techniques.

  12. Single molecule transistor based nanopore for the detection of nicotine

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ray, S. J., E-mail: ray.sjr@gmail.com

    A nanopore based detection methodology was proposed and investigated for the detection of Nicotine. This technique uses a Single Molecular Transistor working as a nanopore operational in the Coulomb Blockade regime. When the Nicotine molecule is pulled through the nanopore area surrounded by the Source(S), Drain (D), and Gate electrodes, the charge stability diagram can detect the presence of the molecule and is unique for a specific molecular structure. Due to the weak coupling between the different electrodes which is set by the nanopore size, the molecular energy states stay almost unaffected by the electrostatic environment that can be realisedmore » from the charge stability diagram. Identification of different orientation and position of the Nicotine molecule within the nanopore area can be made from specific regions of overlap between different charge states on the stability diagram that could be used as an electronic fingerprint for detection. This method could be advantageous and useful to detect the presence of Nicotine in smoke which is usually performed using chemical chromatography techniques.« less

  13. Monitoring structural features, biocompatibility and biological efficacy of gamma-irradiated methotrexate-loaded spray-dried microparticles.

    PubMed

    de Oliveira, Alice R; Mesquita, Philippe C; Machado, Paula R L; Farias, Kleber J S; de Almeida, Yêda M B; Fernandes-Pedrosa, Matheus F; Cornélio, Alianda M; do Egito, Eryvaldo Sócrates T; da Silva-Júnior, Arnóbio A

    2017-11-01

    In this study, biodegradable and biocompatible gamma irradiated poly-(dl-lactide-co-glycolide) (PLGA) spray-dried microparticles were prepared aiming to improve the efficacy of methotrexate (MTX). The experimental design included three formulations of microparticles containing distinct drug amount (9%, 18%, and 27% w/w) and three distinct gamma irradiation dose (15kGy, 25kGy, and 30kGy). The physicochemical and drug release properties of the microparticles supported their biocompatibility and biological efficacy studies in different cell lines. The irradiation induced slight changes in the spherical shape of the microparticles and the formation of free radicals was dependent on the drug loading. However, the amorphous character, particle size, drug loading, and drug release rate of the microparticles were preserved. The drug release data from all microparticles formulation were evaluated by using four drug kinetic models and by comparison of their similarity factor (f 2 ). The gamma irradiation did not induce changes in the biocompatibility of PLGA microparticles and in the biological activity of the MTX-loaded microparticles. Finally, the spray-dried MTX-loaded PLGA microparticles enhanced the efficacy of the drug in the human cervical cancer cells (SiHa cell line). This study demonstrated the feasibility of the gamma irradiated spray dried PLGA microparticles for prolonged release of MTX, supporting a promising antitumor-drug delivery system for parenteral (subcutaneous) or pulmonary use. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Stretching and Controlled Motion of Single-Stranded DNA in Locally-Heated Solid-State Nanopores

    PubMed Central

    Belkin, Maxim; Maffeo, Christopher; Wells, David B.

    2013-01-01

    Practical applications of solid-state nanopores for DNA detection and sequencing require the electrophoretic motion of DNA through the nanopores to be precisely controlled. Controlling the motion of single-stranded DNA presents a particular challenge, in part because of the multitude of conformations that a DNA strand can adopt in a nanopore. Through continuum, coarse-grained and atomistic modeling, we demonstrate that local heating of the nanopore volume can be used to alter the electrophoretic mobility and conformation of single-stranded DNA. In the nanopore systems considered, the temperature near the nanopore is modulated via a nanometer-size heater element that can be radiatively switched on and off. The local enhancement of temperature produces considerable stretching of the DNA fragment confined within the nanopore. Such stretching is reversible, so that the conformation of DNA can be toggled between compact (local heating is off) and extended (local heating is on) states. The effective thermophoretic force acting on single-stranded DNA in the vicinity of the nanopore is found to be sufficiently large (4–8 pN) to affect such changes in the DNA conformation. The local heating of the nanopore volume is observed to promote single-file translocation of DNA strands at transmembrane biases as low as 10 mV, which opens new avenues for using solid-state nanopores for detection and sequencing of DNA. PMID:23876013

  15. Theory for polymer analysis using nanopore-based single-molecule mass spectrometry

    PubMed Central

    Reiner, Joseph E.; Kasianowicz, John J.; Nablo, Brian J.; Robertson, Joseph W. F.

    2010-01-01

    Nanometer-scale pores have demonstrated potential for the electrical detection, quantification, and characterization of molecules for biomedical applications and the chemical analysis of polymers. Despite extensive research in the nanopore sensing field, there is a paucity of theoretical models that incorporate the interactions between chemicals (i.e., solute, solvent, analyte, and nanopore). Here, we develop a model that simultaneously describes both the current blockade depth and residence times caused by individual poly(ethylene glycol) (PEG) molecules in a single α-hemolysin ion channel. Modeling polymer-cation binding leads to a description of two significant effects: a reduction in the mobile cation concentration inside the pore and an increase in the affinity between the polymer and the pore. The model was used to estimate the free energy of formation for K+-PEG inside the nanopore (≈-49.7 meV) and the free energy of PEG partitioning into the nanopore (≈0.76 meV per ethylene glycol monomer). The results suggest that rational, physical models for the analysis of analyte-nanopore interactions will develop the full potential of nanopore-based sensing for chemical and biological applications. PMID:20566890

  16. Fabrication of starch-based microparticles by an emulsification-crosslinking method

    USDA-ARS?s Scientific Manuscript database

    Starch-based microparticles (MPs) fabricated by a water-in-water (w/w) emulsification-crosslinking method could be used as a controlled-release delivery vehicle for food bioactives. Due to the processing route without the use of toxic organic solvents, it is expected that these microparticles can be...

  17. Cavitational Iron Microparticles Generation By Plasma Procedures For Medical Applications

    NASA Astrophysics Data System (ADS)

    Bica, Ioan; Bunoiu, Madalin; Chirigiu, Liviu; Spunei, Marius; Juganaru, Iulius

    2012-12-01

    The paper presents the experimental installation for the production, in argon plasma, of cavitational iron microparticles (pore microspheres, microtubes and octopus-shaped microparticles). Experimental results are presented and discussed and it is shown that absorbant particles with a minimum iron content are obtained by the plasma procedures

  18. Slow DNA Transport through Nanopores in Hafnium Oxide Membranes

    PubMed Central

    Bell, David C.; Cohen-Karni, Tzahi; Rosenstein, Jacob K.; Wanunu, Meni

    2016-01-01

    We present a study of double- and single-stranded DNA transport through nanopores fabricated in ultrathin (2–7 nm thick) free-standing hafnium oxide (HfO2) membranes. The high chemical stability of ultrathin HfO2 enables long-lived experiments with <2 nm diameter pores that last several hours, in which we observe >50 000 DNA translocations with no detectable pore expansion. Mean DNA velocities are slower than velocities through comparable silicon nitride pores, providing evidence that HfO2 nanopores have favorable physicochemical interactions with nucleic acids that can be leveraged to slow down DNA in a nanopore. PMID:24083444

  19. Nanoporous Ni with High Surface Area for Potential Hydrogen Storage Application.

    PubMed

    Zhou, Xiaocao; Zhao, Haibo; Fu, Zhibing; Qu, Jing; Zhong, Minglong; Yang, Xi; Yi, Yong; Wang, Chaoyang

    2018-06-01

    Nanoporous metals with considerable specific surface areas and hierarchical pore structures exhibit promising applications in the field of hydrogen storage, electrocatalysis, and fuel cells. In this manuscript, a facile method is demonstrated for fabricating nanoporous Ni with a high surface area by using SiO₂ aerogel as a template, i.e., electroless plating of Ni into an SiO₂ aerogel template followed by removal of the template at moderate conditions. The effects of the prepared conditions, including the electroless plating time, temperature of the structure, and the magnetism of nanoporous Ni are investigated in detail. The resultant optimum nanoporous Ni with a special 3D flower-like structure exhibited a high specific surface area of about 120.5 m²/g. The special nanoporous Ni exhibited a promising prospect in the field of hydrogen storage, with a hydrogen capacity of 0.45 wt % on 4.5 MPa at room temperature.

  20. Nanostructural Engineering of Nanoporous Anodic Alumina for Biosensing Applications

    PubMed Central

    Ferré-Borrull, Josep; Pallarès, Josep; Macías, Gerard; Marsal, Lluis F.

    2014-01-01

    Modifying the diameter of the pores in nanoporous anodic alumina opens new possibilities in the application of this material. In this work, we review the different nanoengineering methods by classifying them into two kinds: in situ and ex situ. Ex situ methods imply the interruption of the anodization process and the addition of intermediate steps, while in situ methods aim at realizing the in-depth pore modulation by continuous changes in the anodization conditions. Ex situ methods permit a greater versatility in the pore geometry, while in situ methods are simpler and adequate for repeated cycles. As an example of ex situ methods, we analyze the effect of changing drastically one of the anodization parameters (anodization voltage, electrolyte composition or concentration). We also introduce in situ methods to obtain distributed Bragg reflectors or rugate filters in nanoporous anodic alumina with cyclic anodization voltage or current. This nanopore engineering permits us to propose new applications in the field of biosensing: using the unique reflectance or photoluminescence properties of the material to obtain photonic barcodes, applying a gold-coated double-layer nanoporous alumina to design a self-referencing protein sensor or giving a proof-of-concept of the refractive index sensing capabilities of nanoporous rugate filters. PMID:28788127

  1. Investigation of Carrageenan Aerogel Microparticles as a Potential Drug Carrier.

    PubMed

    Obaidat, Rana M; Alnaief, Mohammad; Mashaqbeh, Hadeia

    2018-05-07

    Carrageenan is an anionic polysaccharide offering many advantages to be used in drug delivery applications. These include availability, thermo-stability, low toxicity, and encapsulating properties. Combination of these properties with aerogel properties like large surface area and porosity make them an ideal candidate for drug adsorption and delivery applications. Emulsion-gelation technique was used to prepare carrageenan gel microparticles with supercritical CO 2 for drying and loading purposes. Ibuprofen has been selected as a model drug for drug loading inside. The prepared microparticles were characterized using particle size analysis, X-ray diffraction, differential scanning calorimetry, Fourier transform infrared spectroscopy, density measurements, surface area, and porosity measurements. Finally, dissolution was applied to the loaded preparations to test in vitro drug release. Ibuprofen was successfully loaded in the amorphous form inside the prepared microparticles with a significant enhancement in the drug release profile. In conclusion, prepared carrageenan aerogel microparticles showed an excellent potential for use as a drug carrier.

  2. Thermoelectric studies of nanoporous thin films with adjusted pore-edge charges

    NASA Astrophysics Data System (ADS)

    Hao, Qing; Zhao, Hongbo; Xu, Dongchao

    2017-03-01

    In recent years, nanoporous thin films have been widely studied for thermoelectric applications. High thermoelectric performance is reported for nanoporous Si films, which is attributed to the dramatically reduced lattice thermal conductivity and bulk-like electrical properties. Porous materials can also be used in gas sensing applications by engineering the surface-trapped charges on pore edges. In this work, an analytical model is developed to explore the relationship between the thermoelectric properties and pore-edge charges in a periodic two-dimensional nanoporous material. The presented model can be widely used to analyze the measured electrical properties of general nanoporous thin films and two-dimensional materials.

  3. An overview on the characterization and mechanical behavior of nanoporous Gold

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hodge, A M; Hayes, J R; Caro, J A

    2005-09-13

    In this paper we present what we believe are the most pressing issues in understanding the mechanical behavior of nanoporous foams. We have postulated that a gold foam presents the best candidate for a systematic study of nanoporous foams since it can be synthesized with a wide range of ligaments sizes and densities. We have also conducted preliminary tests that demonstrate (a) Au foams have a fracture behavior dictated by the ligament size, and (b) nanoporous Au is a high yield strength material. Thus, we have demonstrated the potential in developing nanoporous foams as a new class of high yieldmore » strength/low density materials.« less

  4. Chitosan-Based Nano-Embedded Microparticles: Impact of Nanogel Composition on Physicochemical Properties

    PubMed Central

    Islam, Paromita; Water, Jorrit J.; Bohr, Adam; Rantanen, Jukka

    2016-01-01

    Chitosan-based nanogels have been widely applied as drug delivery vehicles. Spray-drying of said nanogels allows for the preparation of dry powder nano-embedded microparticles. In this work, chitosan-based nanogels composed of chitosan, alginate, and/or sodium tri-penta phosphate were investigated, particularly with respect to the impact of composition on the resulting physicochemical properties. Different compositions were obtained as nanogels with sizes ranging from 203 to 561 nm. The addition of alginate and exclusion of sodium tri-penta phosphate led to an increase in nanogel size. The nanogels were subsequently spray-dried to form nano-embedded microparticles with trehalose or mannitol as matrix excipient. The microparticles of different composition were mostly spherical with a smooth surface and a mass median aerodynamic diameter of 6–10 µm. Superior redispersibility was observed for microparticles containing amorphous trehalose. This study demonstrates the potential of nano-embedded microparticles for stabilization and delivery of nanogel-based delivery systems. PMID:28025505

  5. Chitosan-Based Nano-Embedded Microparticles: Impact of Nanogel Composition on Physicochemical Properties.

    PubMed

    Islam, Paromita; Water, Jorrit J; Bohr, Adam; Rantanen, Jukka

    2016-12-22

    Chitosan-based nanogels have been widely applied as drug delivery vehicles. Spray-drying of said nanogels allows for the preparation of dry powder nano-embedded microparticles. In this work, chitosan-based nanogels composed of chitosan, alginate, and/or sodium tri-penta phosphate were investigated, particularly with respect to the impact of composition on the resulting physicochemical properties. Different compositions were obtained as nanogels with sizes ranging from 203 to 561 nm. The addition of alginate and exclusion of sodium tri-penta phosphate led to an increase in nanogel size. The nanogels were subsequently spray-dried to form nano-embedded microparticles with trehalose or mannitol as matrix excipient. The microparticles of different composition were mostly spherical with a smooth surface and a mass median aerodynamic diameter of 6-10 µm. Superior redispersibility was observed for microparticles containing amorphous trehalose. This study demonstrates the potential of nano-embedded microparticles for stabilization and delivery of nanogel-based delivery systems.

  6. Production of microparticles of molinate degrading biocatalysts using the spray drying technique.

    PubMed

    Lopes, Ana R; Sousa, Vera M; Estevinho, Berta N; Leite, José P; Moreira, Nuno F F; Gales, Luís; Rocha, Fernando; Nunes, Olga C

    2016-10-01

    Previous studies demonstrated the capability of mixed culture DC1 to mineralize the thiocarbamate herbicide molinate through the activity of molinate hydrolase (MolA). Because liquid suspensions are not compatible with long-term storage and are not easy to handle when bioremediation strategies are envisaged, in this study spray drying was evaluated as a cost-effective method to store and transport these molinate biocatalysts. Microparticles of mixed culture DC1 (DC1) and of cell free crude extracts containing MolA (MA) were obtained without any carrier polymer, and with calcium alginate (CA) or modified chitosan (MCt) as immobilizing agents. All the DC1 microparticles showed high molinate degrading activity upon storage for 6 months, or after 9 additions of ∼0.4 mM molinate over 1 month. The DC1-MCt microparticles were those with the highest survival rate and lowest heterogeneity. For MA microparticles, only MA-MCt degraded molinate. However, its Vmax was only 1.4% of that of the fresh cell free extract (non spray dried). The feasibility of using the DC1-MCt and MA-MCt microparticles in bioaugmentation processes was assessed in river water microcosms, using mass (g):volume (L) ratios of 1:13 and 1:0.25, respectively. Both type of microparticles removed ∼65-75% of the initial 1.5 mg L(-1) molinate, after 7 days of incubation. However, only DC1-MCt microparticles were able to degrade this environmental concentration of molinate without disturbing the native bacterial community. These results suggest that spray drying can be successfully used to produce DC1-MCt microparticles to remediate molinate polluted sites through a bioaugmentation strategy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Cutting-edge analysis of extracellular microparticles using ImageStream(X) imaging flow cytometry.

    PubMed

    Headland, Sarah E; Jones, Hefin R; D'Sa, Adelina S V; Perretti, Mauro; Norling, Lucy V

    2014-06-10

    Interest in extracellular vesicle biology has exploded in the past decade, since these microstructures seem endowed with multiple roles, from blood coagulation to inter-cellular communication in pathophysiology. In order for microparticle research to evolve as a preclinical and clinical tool, accurate quantification of microparticle levels is a fundamental requirement, but their size and the complexity of sample fluids present major technical challenges. Flow cytometry is commonly used, but suffers from low sensitivity and accuracy. Use of Amnis ImageStream(X) Mk II imaging flow cytometer afforded accurate analysis of calibration beads ranging from 1 μm to 20 nm; and microparticles, which could be observed and quantified in whole blood, platelet-rich and platelet-free plasma and in leukocyte supernatants. Another advantage was the minimal sample preparation and volume required. Use of this high throughput analyzer allowed simultaneous phenotypic definition of the parent cells and offspring microparticles along with real time microparticle generation kinetics. With the current paucity of reliable techniques for the analysis of microparticles, we propose that the ImageStream(X) could be used effectively to advance this scientific field.

  8. SEM-induced shrinkage and site-selective modification of single-crystal silicon nanopores

    NASA Astrophysics Data System (ADS)

    Chen, Qi; Wang, Yifan; Deng, Tao; Liu, Zewen

    2017-07-01

    Solid-state nanopores with feature sizes around 5 nm play a critical role in bio-sensing fields, especially in single molecule detection and sequencing of DNA, RNA and proteins. In this paper we present a systematic study on shrinkage and site-selective modification of single-crystal silicon nanopores with a conventional scanning electron microscope (SEM). Square nanopores with measurable sizes as small as 8 nm × 8 nm and rectangle nanopores with feature sizes (the smaller one between length and width) down to 5 nm have been obtained, using the SEM-induced shrinkage technique. The analysis of energy dispersive x-ray spectroscopy and the recovery of the pore size and morphology reveal that the grown material along with the edge of the nanopore is the result of deposition of hydrocarbon compounds, without structural damage during the shrinking process. A simplified model for pore shrinkage has been developed based on observation of the cross-sectional morphology of the shrunk nanopore. The main factors impacting on the task of controllably shrinking the nanopores, such as the accelerating voltage, spot size, scanned area of e-beam, and the initial pore size have been discussed. It is found that single-crystal silicon nanopores shrink linearly with time under localized irradiation by SEM e-beam in all cases, and the pore shrinkage rate is inversely proportional to the initial equivalent diameter of the pore under the same e-beam conditions.

  9. Fabrication of highly oriented nanoporous fibers via airflow bubble-spinning

    NASA Astrophysics Data System (ADS)

    Liu, Fujuan; Li, Shaokai; Fang, Yue; Zheng, Fangfang; Li, Junhua; He, Jihuan

    2017-11-01

    Highly oriented Poly(lactic acid) (PLA) nanofibers with nanoporous structures has been successfully fabricated via airflow bubble-spinning without electrostatic hazard. In this work, the volatile solvent was necessary for preparing the nanoporous fiber, which was attributed to the competition between phase separation and solvent evaporation. The interconnected porous structures were affected by the processing variables of solution concentration, airflow temperature, collecting distance and relative humidity (RH). Besides, the rheological properties of solutions were studied and the highly oriented PLA nanofibers with nanoporous structure were also completely characterized using scanning electron microscope (SEM). This study provided a novel technique that successfully gets rid of the potential safety hazards caused by unexpected static to prepare highly oriented nanoporous fibers, which would demonstrate an impressive prospect for the fields of adsorption and filtration.

  10. Nanoporous cerium oxide thin film for glucose biosensor.

    PubMed

    Saha, Shibu; Arya, Sunil K; Singh, S P; Sreenivas, K; Malhotra, B D; Gupta, Vinay

    2009-03-15

    Nanoporous cerium oxide (CeO(2)) thin film deposited onto platinum (Pt) coated glass plate using pulsed laser deposition (PLD) has been utilized for immobilization of glucose oxidase (GOx). Atomic force microscopy studies reveal the formation of nanoporous surface morphology of CeO(2) thin film. Response studies carried out using differential pulsed voltammetry (DPV) and optical measurements show that the GOx/CeO(2)/Pt bio-electrode shows linearity in the range of 25-300 mg/dl of glucose concentration. The low value of Michaelis-Menten constant (1.01 mM) indicates enhanced enzyme affinity of GOx to glucose. The observed results show promising application of the nanoporous CeO(2) thin film for glucose sensing application without any surface functionalization or mediator.

  11. Preparation, In Vitro Characterization, and In Vivo Pharmacokinetic Evaluation of Respirable Porous Microparticles Containing Rifampicin

    PubMed Central

    Kundawala, Aliasgar; Patel, Vishnu; Patel, Harsha; Choudhary, Dhaglaram

    2014-01-01

    Abstract This study aimed to prepare and evaluate rifampicin microparticles for the lung delivery of rifampicin as respirable powder. The microparticles were prepared using chitosan by the spray-drying method and evaluated for aerodynamic properties and pulmonary drug absorption. To control the drug release, tripoly-phosphate in different concentrations 0.6, 0.9, 1.2, and 1.5 was employed to get a sustained drug release profile. The microparticles were evaluated for drug loading, % entrapment efficiency, tapped density, morphological characteristics, and in vitro drug release studies. Aerosol properties were determined using the Andersen cascade impactor. Porous microparticles with particle sizes (d0.5) less than 10 μm were obtained. The entrapment of rifampicin in microparticles was up to 72%. In vitro drug release suggested that the crosslinked microparticles showed sustained release for more than 12 hrs. The drug release rate was found to be decreased as the TPP concentration was increased. The microparticles showed a fine particle fraction in the range of 55–63% with mass median aerodynamic diameter (MMAD) values below 3 μm. The in vivo pulmonary absorption of the chitosan microparticles suggested a sustained drug release profile up to 72 hrs with an elimination rate of 0.010 per hr. The studies revealed that the spray-dried porous microparticles have suitable properties to be used as respirable powder in rifampicin delivery to the lungs. PMID:25853075

  12. Development of Aerosol Phospholipid Microparticles for the Treatment of Pulmonary Hypertension.

    PubMed

    Brousseau, Sarah; Wang, Zimeng; Gupta, Sweta K; Meenach, Samantha A

    2017-11-01

    Pulmonary arterial hypertension (PAH) is an incurable cardiovascular disease characterized by high blood pressure in the arteries leading from the heart to the lungs. Over two million people in the USA are diagnosed with PAH annually and the typical survival rate is only 3 years after diagnosis. Current treatments are insufficient because of limited bioavailability, toxicity, and costs associated with approved therapeutics. Aerosol delivery of drugs is an attractive approach to treat respiratory diseases because it increases localized drug concentration while reducing systemic side effects. In this study, we developed phospholipid-based aerosol microparticles via spray drying consisting of the drug tacrolimus and the excipients dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylglycerol. The phospholipid-based spray-dried aerosol microparticles were shown to be smooth and spherical in size, ranging from 1 to 3 μm in diameter. The microparticles exhibited thermal stability and were amorphous after spray drying. Water content in the microparticles was under 10%, which will allow successful aerosol dispersion and long-term storage stability. In vitro aerosol dispersion showed that the microparticles could successfully deposit in the deep lung, as they exhibited favorable aerodynamic diameters and high fine particle fractions. In vitro dose-response analysis showed that TAC is nontoxic in the low concentrations that would be delivered to the lungs. Overall, this work shows that tacrolimus-loaded phospholipid-based microparticles can be successfully created with optimal physicochemical and toxicological characteristics.

  13. Mucoadhesive Microparticles in a Rapidly Dissolving Tablet for Sustained Drug Delivery to the Eye

    PubMed Central

    Choy, Young Bin; Patel, Samirkumar R.; Park, Jung-Hwan; McCarey, Bernard E.; Edelhauser, Henry F.

    2011-01-01

    Purpose. To test the hypothesis that mucoadhesive microparticles formulated in a rapidly dissolving tablet can achieve sustained drug delivery to the eye. Methods. Mucoadhesive microparticles, smaller than 5 μm were fabricated with poly(lactic-co-glycolic acid) and poly(ethylene glycol) as a core material and mucoadhesion promoter, respectively, and encapsulated pilocarpine as a model drug. These microparticles were embedded in a poly(vinyl alcohol) matrix to form a dry tablet designed to reduce rapid clearance of the microparticles on initial application to the eye. Results. This in vitro drug release study exhibited that for all formulations, approximately 90% of pilocarpine was released during the first 10 minutes, and the remaining 10% was released slowly for 3 hours. In vivo mucoadhesion test on the rabbit eye indicated that mucoadhesive microparticles adhered significantly better to the preocular surface than other formulations. To assess the pharmacodynamics, the most prolonged pilocarpine-induced pupil constriction was observed in rabbit eyes in vivo using a tablet with mucoadhesive microparticles; it lasted up to 330 minutes. Conclusions. The authors conclude that mucoadhesive microparticles formulated into a dry dosage form is a promising system for sustained drug delivery to the eye. PMID:21245405

  14. Nano-encapsulations liberated from barley protein microparticles for oral delivery of bioactive compounds.

    PubMed

    Wang, Ruoxi; Tian, Zhigang; Chen, Lingyun

    2011-03-15

    Novel microparticles (3-5 μm) were created by pre-emulsifying barley proteins with a homogenizer followed a microfluidizer system. These microparticles exhibited a high oil carrying capacity (encapsulation efficiency, 93-97%; loading efficiency, 46-49%). Microparticle degradation and bioactive compound release behaviours were studied in the simulated gastro-intestinal (GI) tract. The data revealed that nano-encapsulations (20-30 nm) were formed as a result of enzymatic degradation of barley protein microparticle bulk matrix in the simulated gastric tract. These nano-encapsulations delivered β-carotene to a simulated human intestinal tract intact, where they were degraded by pancreatic enzymes and steadily released the β-carotene. These uniquely structured microparticles may provide a new strategy for the nutraceutical and pharmaceutical industries to develop targeted delivery systems for lipophilic bioactive compounds. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Galectin-3 binding protein links circulating microparticles with electron dense glomerular deposits in lupus nephritis.

    PubMed

    Nielsen, C T; Østergaard, O; Rekvig, O P; Sturfelt, G; Jacobsen, S; Heegaard, N H H

    2015-10-01

    A high level of galectin-3-binding protein (G3BP) appears to distinguish circulating cell-derived microparticles in systemic lupus erythematosus (SLE). The aim of this study is to characterize the population of G3BP-positive microparticles from SLE patients compared to healthy controls, explore putative clinical correlates, and examine if G3BP is present in immune complex deposits in kidney biopsies from patients with lupus nephritis. Numbers of annexin V-binding and G3BP-exposing plasma microparticles from 56 SLE patients and 36 healthy controls were determined by flow cytometry. Quantitation of microparticle-associated G3BP, C1q and immunoglobulins was obtained by liquid chromatography tandem mass spectrometry (LC-MS/MS). Correlations between microparticle-G3BP data and clinical parameters were analyzed. Co-localization of G3BP with in vivo-bound IgG was examined in kidney biopsies from one non-SLE control and from patients with class IV (n = 2) and class V (n = 1) lupus nephritis using co-localization immune electron microscopy. Microparticle-G3BP, microparticle-C1q and microparticle-immunoglobulins were significantly (P < 0.01) increased in SLE patients by LC-MS/MS. Three G3BP-exposing microparticle populations could be discerned by flow cytometry, including two subpopulations that were significantly increased in SLE samples (P = 0.01 and P = 0.0002, respectively). No associations of G3BP-positive microparticles with clinical manifestations or disease activity were found. Immune electron microscopy showed co-localization of G3BP with in vivo-bound IgG in glomerular electron dense immune complex deposits in all lupus nephritis biopsies. Both circulating microparticle-G3BP numbers as well as G3BP expression are increased in SLE patients corroborating G3BP being a feature of SLE microparticles. By demonstrating G3BP co-localized with deposited immune complexes in lupus nephritis, the study supports cell-derived microparticles as a major

  16. Formation mechanism of human serum albumin monolayers on positively charged polymer microparticles.

    PubMed

    Nattich-Rak, Małgorzata; Sadowska, Marta; Adamczyk, Zbigniew; Cieśla, Michał; Kąkol, Małgorzata

    2017-11-01

    Human serum albumin (HSA) adsorption on positively and negatively charged polystyrene microparticles was studied at various pHs and NaCl concentrations. Thorough electrophoretic mobility measurements were carried out that enabled to monitor in situ the progress of protein adsorption. The maximum coverage of irreversibly adsorbed HSA on microparticles was determined by different concentration depletion methods, one of them involving AFM imaging of residual molecules. An anomalous adsorption of HSA on the positive microparticles was observed at pH 3.5 where the maximum coverage attained 1.0mgm -2 for NaCl concentrations of 0.05M despite that the molecules were on average positively charged. For comparison, the maximum coverage of HSA on negatively charged microparticles was equal to 1.3mgm -2 at this pH and NaCl concentration. At pH 7.4 the maximum coverage on positive microparticles was equal to 2.1mgm -2 for 0.05M NaCl concentration. On the other hand, for negative microparticles, negligible adsorption of HSA was observed at pH 7.4 and 9.7. These experimental data were adequately interpreted in terms of the random sequential adsorption approach exploiting the bead model of the HSA molecule. Different orientations of adsorbed molecules, inert alia, the edge-on orientation prevailing for positively charged microparticles at pH 7.4, were confirmed. This was explained in terms of a heterogeneous charge distribution over the HSA molecule prevailing for a wide range of pHs. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Incorporation of essential oil in alginate microparticles by multiple emulsion/ionic gelation process.

    PubMed

    Hosseini, Seyede Marzieh; Hosseini, Hedayat; Mohammadifar, Mohammad Amin; Mortazavian, Amir Mohammad; Mohammadi, Abdorreza; Khosravi-Darani, Kianoosh; Shojaee-Aliabadi, Saeedeh; Dehghan, Solmaz; Khaksar, Ramin

    2013-11-01

    In this study, an o/w/o multiple emulsion/ionic gelation method was developed for production of alginate microparticles loaded with Satureja hortensis essential oil (SEO). It was found that the essential oil concentration has significant influence on encapsulation efficiency (EE), loading capacity (LC) and size of microparticles. The values of EE, LC and particle mean diameter were about 52-66%, 20-26%, and 47-117 μm, respectively, when the initial SEO content was 1-3% (v/v) .The essential oil-loaded microparticles were porous, as displayed by scanning electron micrograph. The presence of SEO in alginate microparticles was confirmed by Fourier transform-infrared (FT-IR) spectroscopy and differential scanning calorimetry (DSC) analyses. SEO-loaded microparticles showed good antioxidant (with DPPH radical scavenging activity of 40.7-73.5%) and antibacterial properties; this effect was greatly improved when the concentration of SEO was 3% (v/v). S. aureus was found to be the most sensitive bacterium to SEO and showed a highest inhibition zone of 304.37 mm(2) in the microparticles incorporated with 3% (v/v) SEO. In vitro release studies showed an initial burst release and followed by a slow release. In addition, the release of SEO from the microparticles followed Fickian diffusion with acceptable release. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Patterning and manipulating microparticles into a three-dimensional matrix using standing surface acoustic waves

    NASA Astrophysics Data System (ADS)

    Nguyen, T. D.; Tran, V. T.; Fu, Y. Q.; Du, H.

    2018-05-01

    A method based on standing surface acoustic waves (SSAWs) is proposed to pattern and manipulate microparticles into a three-dimensional (3D) matrix inside a microchamber. An optical prism is used to observe the 3D alignment and patterning of the microparticles in the vertical and horizontal planes simultaneously. The acoustic radiation force effectively patterns the microparticles into lines of 3D space or crystal-lattice-like matrix patterns. A microparticle can be positioned precisely at a specified vertical location by balancing the forces of acoustic radiation, drag, buoyancy, and gravity acting on the microparticle. Experiments and finite-element numerical simulations both show that the acoustic radiation force increases gradually from the bottom of the chamber to the top, and microparticles can be moved up or down simply by adjusting the applied SSAW power. Our method has great potential for acoustofluidic applications, building the large-scale structures associated with biological objects and artificial neuron networks.

  19. Hydrophobicity of silver surfaces with microparticle geometry

    NASA Astrophysics Data System (ADS)

    Macko, Ján; Oriňaková, Renáta; Oriňak, Andrej; Kovaľ, Karol; Kupková, Miriam; Erdélyi, Branislav; Kostecká, Zuzana; Smith, Roger M.

    2016-11-01

    The effect of the duration of the current deposition cycle and the number of current pulses on the geometry of silver microstructured surfaces and on the free surface energy, polarizability, hydrophobicity and thus adhesion force of the silver surfaces has been investigated. The changes in surface hydrophobicity were entirely dependent on the size and density of the microparticles on the surface. The results showed that formation of the silver microparticles was related to number of current pulses, while the duration of one current pulse played only a minor effect on the final surface microparticle geometry and thus on the surface tension and hydrophobicity. The conventional geometry of the silver particles has been transformed to the fractal dimension D. The surface hydrophobicity depended predominantly on the length of the dendrites not on their width. The highest silver surface hydrophobicity was observed on a surface prepared by 30 current pulses with a pulse duration of 1 s, the lowest one when deposition was performed by 10 current pulses with a duration of 0.1 s. The partial surface tension coefficients γDS and polarizability kS of the silver surfaces were calculated. Both parameters can be applied in future applications in living cells adhesion prediction and spectral method selection. Silver films with microparticle geometry showed a lower variability in final surface hydrophobicity when compared to nanostructured surfaces. The comparisons could be used to modify surfaces and to modulate human cells and bacterial adhesion on body implants, surgery instruments and clean surfaces.

  20. Gate modulation of proton transport in a nanopore.

    PubMed

    Mei, Lanju; Yeh, Li-Hsien; Qian, Shizhi

    2016-03-14

    Proton transport in confined spaces plays a crucial role in many biological processes as well as in modern technological applications, such as fuel cells. To achieve active control of proton conductance, we investigate for the first time the gate modulation of proton transport in a pH-regulated nanopore by a multi-ion model. The model takes into account surface protonation/deprotonation reactions, surface curvature, electroosmotic flow, Stern layer, and electric double layer overlap. The proposed model is validated by good agreement with the existing experimental data on nanopore conductance with and without a gate voltage. The results show that the modulation of proton transport in a nanopore depends on the concentration of the background salt and solution pH. Without background salt, the gated nanopore exhibits an interesting ambipolar conductance behavior when pH is close to the isoelectric point of the dielectric pore material, and the net ionic and proton conductance can be actively regulated with a gate voltage as low as 1 V. The higher the background salt concentration, the lower is the performance of the gate control on the proton transport.

  1. Nanoporous membranes with electrochemically switchable, chemically stabilized ionic selectivity

    NASA Astrophysics Data System (ADS)

    Small, Leo J.; Wheeler, David R.; Spoerke, Erik D.

    2015-10-01

    Nanopore size, shape, and surface charge all play important roles in regulating ionic transport through nanoporous membranes. The ability to control these parameters in situ provides a means to create ion transport systems tunable in real time. Here, we present a new strategy to address this challenge, utilizing three unique electrochemically switchable chemistries to manipulate the terminal functional group and control the resulting surface charge throughout ensembles of gold plated nanopores in ion-tracked polycarbonate membranes 3 cm2 in area. We demonstrate the diazonium mediated surface functionalization with (1) nitrophenyl chemistry, (2) quinone chemistry, and (3) previously unreported trimethyl lock chemistry. Unlike other works, these chemistries are chemically stabilized, eliminating the need for a continuously applied gate voltage to maintain a given state and retain ionic selectivity. The effect of surface functionalization and nanopore geometry on selective ion transport through these functionalized membranes is characterized in aqueous solutions of sodium chloride at pH = 5.7. The nitrophenyl surface allows for ionic selectivity to be irreversibly switched in situ from cation-selective to anion-selective upon reduction to an aminophenyl surface. The quinone-terminated surface enables reversible changes between no ionic selectivity and a slight cationic selectivity. Alternatively, the trimethyl lock allows ionic selectivity to be reversibly switched by up to a factor of 8, approaching ideal selectivity, as a carboxylic acid group is electrochemically revealed or hidden. By varying the pore shape from cylindrical to conical, it is demonstrated that a controllable directionality can be imparted to the ionic selectivity. Combining control of nanopore geometry with stable, switchable chemistries facilitates superior control of molecular transport across the membrane, enabling tunable ion transport systems.Nanopore size, shape, and surface charge all play

  2. Assessing the biodegradability of microparticles disposed down the drain.

    PubMed

    McDonough, Kathleen; Itrich, Nina; Casteel, Kenneth; Menzies, Jennifer; Williams, Tom; Krivos, Kady; Price, Jason

    2017-05-01

    Microparticles made from naturally occurring materials or biodegradable plastics such as poly(3-hydroxy butyrate)-co-(3-hydroxy valerate), PHBV, are being evaluated as alternatives to microplastics in personal care product applications but limited data is available on their ultimate biodegradability (mineralization) in down the drain environmental compartments. An OECD 301B Ready Biodegradation Test was used to quantify ultimate biodegradability of microparticles made of PHBV foam, jojoba wax, beeswax, rice bran wax, stearyl stearate, blueberry seeds and walnut shells. PHBV polymer was ready biodegradable reaching 65.4 ± 4.1% evolved CO 2 in 5 d and 90.5 ± 3.1% evolved CO 2 in 80 d. PHBV foam microparticles (125-500 μm) were mineralized extensively with >66% CO 2 evolution in 28 d and >82% CO 2 evolution in 80 d. PHBV foam microparticles were mineralized at a similar rate and extent as microparticles made of jojoba wax, beeswax, rice bran wax, and stearyl stearate which reached 84.8  ± 4.8, 84.9  ± 2.2, 82.7  ± 4.7, and 86.4 ± 3.2% CO 2 evolution respectively in 80 d. Blueberry seeds and walnut shells mineralized more slowly only reaching 39.3  ± 6.9 and 5.1 ± 2.8% CO 2 evolution in 80 d respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Formation of monodisperse mesoporous silica microparticles via spray-drying.

    PubMed

    Waldron, Kathryn; Wu, Winston Duo; Wu, Zhangxiong; Liu, Wenjie; Selomulya, Cordelia; Zhao, Dongyuan; Chen, Xiao Dong

    2014-03-15

    In this work, a protocol to synthesize monodisperse mesoporous silica microparticles via a unique microfluidic jet spray-drying route is reported for the first time. The microparticles demonstrated highly ordered hexagonal mesostructures with surface areas ranging from ~900 up to 1500 m(2)/g and pore volumes from ~0.6 to 0.8 cm(3)/g. The particle size could be easily controlled from ~50 to 100 μm from the same diameter nozzle via changing the initial solute content, or changing the drying temperature. The ratio of the surfactant (CTAB) and silica (TEOS), and the amount of water in the precursor were found to affect the degree of ordering of mesopores by promoting either the self-assembly of the surfactant-silica micelles or the condensation of the silica as two competing processes in evaporation induced self-assembly. The drying rate and the curvature of particles also affected the self-assembly of the mesostructure. The particle mesostructure is not influenced by the inlet drying temperature in the range of 92-160 °C, with even a relatively low temperature of 92 °C producing highly ordered mesoporous microparticles. The spray-drying derived mesoporous silica microparticles, while of larger sizes and more rapidly synthesized, showed a comparable performance with the conventional mesoporous silica MCM-41 in controlled release of a dye, Rhodamine B, indicating that these spray dried microparticles could be used for the immobilisation and controlled release of small molecules. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Protein conducting nanopores

    NASA Astrophysics Data System (ADS)

    Harsman, Anke; Krüger, Vivien; Bartsch, Philipp; Honigmann, Alf; Schmidt, Oliver; Rao, Sanjana; Meisinger, Christof; Wagner, Richard

    2010-11-01

    About 50% of the cellular proteins have to be transported into or across cellular membranes. This transport is an essential step in the protein biosynthesis. In eukaryotic cells secretory proteins are transported into the endoplasmic reticulum before they are transported in vesicles to the plasma membrane. Almost all proteins of the endosymbiotic organelles chloroplasts and mitochondria are synthesized on cytosolic ribosomes and posttranslationally imported. Genetic, biochemical and biophysical approaches led to rather detailed knowledge on the composition of the translocon-complexes which catalyze the membrane transport of the preproteins. Comprehensive concepts on the targeting and membrane transport of polypeptides emerged, however little detail on the molecular nature and mechanisms of the protein translocation channels comprising nanopores has been achieved. In this paper we will highlight recent developments of the diverse protein translocation systems and focus particularly on the common biophysical properties and functions of the protein conducting nanopores. We also provide a first analysis of the interaction between the genuine protein conducting nanopore Tom40SC as well as a mutant Tom40SC (\\mathrm {S}_{54} \\to E ) containing an additional negative charge at the channel vestibule and one of its native substrates, CoxIV, a mitochondrial targeting peptide. The polypeptide induced a voltage-dependent increase in the frequency of channel closure of Tom40SC corresponding to a voltage-dependent association rate, which was even more pronounced for the Tom40SC S54E mutant. The corresponding dwelltime reflecting association/transport of the peptide could be determined with \\bar {t}_{\\mathrm {off}} \\cong 1.1 ms for the wildtype, whereas the mutant Tom40SC S54E displayed a biphasic dwelltime distribution (\\bar {t}_{\\mathrm {off}}^1 \\cong 0.4 ms \\bar {t}_{\\mathrm {off}}^2 \\cong 4.6 ms).

  5. Na⁺ and K⁺ ion selectivity by size-controlled biomimetic graphene nanopores.

    PubMed

    Kang, Yu; Zhang, Zhisen; Shi, Hui; Zhang, Junqiao; Liang, Lijun; Wang, Qi; Ågren, Hans; Tu, Yaoquan

    2014-09-21

    Because biological ionic channels play a key role in cellular transport phenomena, they have attracted extensive research interest for the design of biomimetic nanopores with high permeability and selectivity in a variety of technical applications. Inspired by the structure of K(+) channel proteins, we designed a series of oxygen doped graphene nanopores of different sizes by molecular dynamics simulations to discriminate between K(+) and Na(+) channel transport. The results from free energy calculations indicate that the ion selectivity of such biomimetic graphene nanopores can be simply controlled by the size of the nanopore; compared to K(+), the smaller radius of Na(+) leads to a significantly higher free energy barrier in the nanopore of a certain size. Our results suggest that graphene nanopores with a distance of about 3.9 Å between two neighboring oxygen atoms could constitute a promising candidate to obtain excellent ion selectivity for Na(+) and K(+) ions.

  6. Optical characterization of nanoporous AAO sensor substrate

    NASA Astrophysics Data System (ADS)

    Kassu, Aschalew; Farley, Carlton W.; Sharma, Anup

    2014-05-01

    Nanoporous anodic aluminum oxide (AAO) has been investigated as an ideal and cost-effective chemical and biosensing platform. In this paper, we report the optical properties of periodic 100 micron thick nanoporous anodic alumina membranes with uniform and high density cylindrical pores penetrating the entire thickness of the substrate, ranging in size from 18 nm to 150 nm in diameter and pore periods from 44 nm to 243 nm. The surface geometry of the top and bottom surface of each membrane is studied using atomic force microscopy. The optical properties including transmittance, reflectance, and absorbance spectra on both sides of each substrate are studied and found to be symmetrical. It is observed that, as the pore size increases, the peak resonance intensity in transmittance decreases and in absorbance increases. The effects of the pore sizes on the optical properties of the bare nanoporous membranes and the benefit of using arrays of nanohole arrays with varying hole size and periodicity as a chemical sensing platform is also discussed. To characterize the optical sensing technique, transmittance and reflectance measurements of various concentrations of a standard chemical adsorbed on the bare nanoporous substrates are investigated. The preliminary results presented here show variation in transmittance and reflectance spectra with the concentration of the chemical used or the amount of the material adsorbed on the surface of the substrate.

  7. Method for making nanoporous hydrophobic coatings

    DOEpatents

    Fan, Hongyou; Sun, Zaicheng

    2013-04-23

    A simple coating method is used to form nanoporous hydrophobic films that can be used as optical coatings. The method uses evaporation-induced self-assembly of materials. The coating method starts with a homogeneous solution comprising a hydrophobic polymer and a surfactant polymer in a selective solvent. The solution is coated onto a substrate. The surfactant polymer forms micelles with the hydrophobic polymer residing in the particle core when the coating is dried. The surfactant polymer can be dissolved and selectively removed from the separated phases by washing with a polar solvent to form the nanoporous hydrophobic film.

  8. Detecting the Length of Double-stranded DNA with Solid State Nanopores

    NASA Astrophysics Data System (ADS)

    Li, Jiali; Gershow, Marc; Stein, Derek; Qun, Cai; Brandin, Eric; Wang, Hui; Huang, Albert; Branton, Dan; Golovchenko, Jene

    2003-03-01

    We report on the use of nanometer scale diameter, solid-state nanopores as single molecule detectors of double stranded DNA molecules. These solid-state nanopores are fabricated in thin membranes of silicon nitride, by ion beam sculpting 1. They produce discrete electronic signals: current blockages, when an electrically biased nanopore is exposed to DNA molecules in aqueous salt solutions. We demonstrate examples of such electronic signals for 3k base pairs (bp) and 10k bp double stranded DNA molecules, which suggest that these molecules are individually translocating through the nanopore during the detection process. The translocating time for the 10k bp double stranded DNA is about 3 times longer than the 3k bp, demonstrating that a solid-state nanopore device can be used to detect the lengths of double stranded DNA molecules. Similarities and differences with signals obtained from single stranded DNA in a biological nanopores are discussed 2. 1. Li, J., Stein, D., McMullan, C., Branton, D. Aziz, M. J. and Golovchenko, J. Ion Beam Sculpting at nanometer length scales. Nature 412, 166-169 (2001). 2. Meller, A., L. Nivon, E. Brandin, Golovchenko, J. & Branton, D. Proc. Natl. Acad. Sci. USA 97, 1079-1084 (2000).

  9. Fabrication of nanoporous thin-film working electrodes and their biosensing applications.

    PubMed

    Li, Tingjie; Jia, Falong; Fan, Yaxi; Ding, Zhifeng; Yang, Jun

    2013-04-15

    Electrochemical detection for point-of-care diagnostics is of great interest due to its high sensitivity, fast analysis time and ability to operate on a small scale. Herein, we report the fabrication of a nanoporous thin-film electrode and its application in the configuration of a simple and robust enzymatic biosensor. The nanoporous thin-film was formed in a planar gold electrode through an alloying/dealloying process. The nanoporous electrode has an electroactive surface area up to 40 times higher than that of a flat gold electrode of the same size. The nanoporous electrode was used as a substrate to build an enzymatic electrochemical biosensor for the detection of glucose in standard samples and control serum samples. The example glucose biosensor has a linear response up to 30 mM, with a high sensitivity of 0.50 μA mM⁻¹ mm⁻², and excellent anti-interference ability against lactate, uric acid and ascorbic acid. Abundant catalyst and enzyme were stably entrapped in the nanoporous structure, leading to high stability and reproducibility of the biosensor. Development of such nanoporous structure enables the miniaturization of high-performance electrochemical biosensors for point-of-care diagnostics or environmental field testing. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Nanopore extended field-effect transistor for selective single-molecule biosensing.

    PubMed

    Ren, Ren; Zhang, Yanjun; Nadappuram, Binoy Paulose; Akpinar, Bernice; Klenerman, David; Ivanov, Aleksandar P; Edel, Joshua B; Korchev, Yuri

    2017-09-19

    There has been a significant drive to deliver nanotechnological solutions to biosensing, yet there remains an unmet need in the development of biosensors that are affordable, integrated, fast, capable of multiplexed detection, and offer high selectivity for trace analyte detection in biological fluids. Herein, some of these challenges are addressed by designing a new class of nanoscale sensors dubbed nanopore extended field-effect transistor (nexFET) that combine the advantages of nanopore single-molecule sensing, field-effect transistors, and recognition chemistry. We report on a polypyrrole functionalized nexFET, with controllable gate voltage that can be used to switch on/off, and slow down single-molecule DNA transport through a nanopore. This strategy enables higher molecular throughput, enhanced signal-to-noise, and even heightened selectivity via functionalization with an embedded receptor. This is shown for selective sensing of an anti-insulin antibody in the presence of its IgG isotype.Efficient detection of single molecules is vital to many biosensing technologies, which require analytical platforms with high selectivity and sensitivity. Ren et al. combine a nanopore sensor and a field-effect transistor, whereby gate voltage mediates DNA and protein transport through the nanopore.

  11. Highly sensitive detection using microring resonator and nanopores

    NASA Astrophysics Data System (ADS)

    Bougot-Robin, K.; Hoste, J. W.; Le Thomas, N.; Bienstman, P.; Edel, J. B.

    2016-04-01

    One of the most significant challenges facing physical and biological scientists is the accurate detection and identification of single molecules in free-solution environments. The ability to perform such sensitive and selective measurements opens new avenues for a large number of applications in biological, medical and chemical analysis, where small sample volumes and low analyte concentrations are the norm. Access to information at the single or few molecules scale is rendered possible by a fine combination of recent advances in technologies. We propose a novel detection method that combines highly sensitive label-free resonant sensing obtained with high-Q microcavities and position control in nanoscale pores (nanopores). In addition to be label-free and highly sensitive, our technique is immobilization free and does not rely on surface biochemistry to bind probes on a chip. This is a significant advantage, both in term of biology uncertainties and fewer biological preparation steps. Through combination of high-Q photonic structures with translocation through nanopore at the end of a pipette, or through a solid-state membrane, we believe significant advances can be achieved in the field of biosensing. Silicon microrings are highly advantageous in term of sensitivity, multiplexing, and microfabrication and are chosen for this study. In term of nanopores, we both consider nanopore at the end of a nanopipette, with the pore being approach from the pipette with nanoprecise mechanical control. Alternatively, solid state nanopores can be fabricated through a membrane, supporting the ring. Both configuration are discussed in this paper, in term of implementation and sensitivity.

  12. Self-ordered, controlled structure nanoporous membranes using constant current anodization.

    PubMed

    Lee, Kwan; Tang, Yun; Ouyang, Min

    2008-12-01

    We report a constant current (CC) based anodization technique to fabricate and control structure of mechanically stable anodic aluminum oxide (AAO) membranes with a long-range ordered hexagonal nanopore pattern. For the first time we show that interpore distance (Dint) of a self-ordered nanopore feature can be continuously tuned over a broad range with CC anodization and is uniquely defined by the conductivity of sulfuric acid as electrolyte. We further demonstrate that this technique can offer new degrees of freedom for engineering planar nanopore structures by fine tailoring the CC based anodization process. Our results not only facilitate further understanding of self-ordering mechanism of alumina membranes but also provide a fast, simple (without requirement of prepatterning or preoxide layer), and flexible methodology for controlling complex nanoporous structures, thus offering promising practical applications in nanotechnology.

  13. Characterization of Chlorhexidine-Loaded Calcium-Hydroxide Microparticles as a Potential Dental Pulp-Capping Material.

    PubMed

    Priyadarshini, Balasankar M; Selvan, Subramanian T; Narayanan, Karthikeyan; Fawzy, Amr S

    2017-06-22

    This study explores the delivery of novel calcium hydroxide [Ca(OH)₂] microparticles loaded with chlorhexidine (CHX) for potential dental therapeutic and preventive applications. Herein, we introduce a new approach for drug-delivery to deep dentin-surfaces in the form of drug-loaded microparticles. Unloaded Ca(OH)₂ [Ca(OH)₂/Blank] and CHX-loaded/Ca(OH)₂ microparticles were fabricated by aqueous chemical-precipitation technique. The synthesized-microparticles were characterized in vitro for determination of surface-morphology, crystalline-features and thermal-properties examined by energy-dispersive X-ray scanning and transmission electron-microscopy (EDX-SEM/TEM), Fourier-transform infrared-spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA) and differential scanning-calorimetry (DSC). Time-related pH changes, initial antibacterial/biofilm-abilities and cytotoxicity of CHX-loaded/Ca(OH)₂ microparticles were evaluated. Microparticles were delivered to dentin-surfaces with subsequent SEM examination of treated dentin-substrates. The in vitro and ex vivo CHX-release profiles were characterized. Ca(OH)₂/Blank were hexagonal-shaped with highest z -average diameter whereas CHX-inclusion evidenced micro-metric spheres with distinguishable surface "rounded deposits" and a negative-shift in diameter. CHX:Ca(OH)₂/50 mg exhibited maximum encapsulation-efficiency with good antibacterial and cytocompatible properties. SEM examination revealed an intact layer of microparticles on exposed dentin-surfaces with retention of spherical shape and smooth texture. Microparticles loaded on dentin-surfaces showed prolonged release of CHX indicating substantial retention on dentin-substrates. This study validated the inherent-applicability of this novel drug-delivery approach to dentin-surfaces using micro-metric CHX-loaded/Ca(OH)₂ microparticles.

  14. Characterization of Chlorhexidine-Loaded Calcium-Hydroxide Microparticles as a Potential Dental Pulp-Capping Material

    PubMed Central

    Priyadarshini, Balasankar M.; Selvan, Subramanian T.; Narayanan, Karthikeyan; Fawzy, Amr S.

    2017-01-01

    This study explores the delivery of novel calcium hydroxide [Ca(OH)2] microparticles loaded with chlorhexidine (CHX) for potential dental therapeutic and preventive applications. Herein, we introduce a new approach for drug-delivery to deep dentin-surfaces in the form of drug-loaded microparticles. Unloaded Ca(OH)2 [Ca(OH)2/Blank] and CHX-loaded/Ca(OH)2 microparticles were fabricated by aqueous chemical-precipitation technique. The synthesized-microparticles were characterized in vitro for determination of surface-morphology, crystalline-features and thermal-properties examined by energy-dispersive X-ray scanning and transmission electron-microscopy (EDX-SEM/TEM), Fourier-transform infrared-spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA) and differential scanning-calorimetry (DSC). Time-related pH changes, initial antibacterial/biofilm-abilities and cytotoxicity of CHX-loaded/Ca(OH)2 microparticles were evaluated. Microparticles were delivered to dentin-surfaces with subsequent SEM examination of treated dentin-substrates. The in vitro and ex vivo CHX-release profiles were characterized. Ca(OH)2/Blank were hexagonal-shaped with highest z-average diameter whereas CHX-inclusion evidenced micro-metric spheres with distinguishable surface “rounded deposits” and a negative-shift in diameter. CHX:Ca(OH)2/50 mg exhibited maximum encapsulation-efficiency with good antibacterial and cytocompatible properties. SEM examination revealed an intact layer of microparticles on exposed dentin-surfaces with retention of spherical shape and smooth texture. Microparticles loaded on dentin-surfaces showed prolonged release of CHX indicating substantial retention on dentin-substrates. This study validated the inherent-applicability of this novel drug-delivery approach to dentin-surfaces using micro-metric CHX-loaded/Ca(OH)2 microparticles. PMID:28952538

  15. Biomimetic novel nanoporous niobium oxide coating for orthopaedic applications

    NASA Astrophysics Data System (ADS)

    Pauline, S. Anne; Rajendran, N.

    2014-01-01

    Niobium oxide was synthesized by sol-gel methodology and a crystalline, nanoporous and adherent coating of Nb2O5 was deposited on 316L SS using the spin coating technique and heat treatment. The synthesis conditions were optimized to obtain a nanoporous morphology. The coating was characterized using attenuated total reflectance-Infrared spectroscopy (ATR-IR), X-ray diffraction analysis (XRD), scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDX), atomic force microscopy (AFM) and transmission electron microscopy (TEM) and the formation of crystalline Nb2O5 coating with nanoporous morphology was confirmed. Mechanical studies confirmed that the coating has excellent adherence to the substrate and the hardness value of the coating was excellent. Contact angle analysis showed increased hydrophilicity for the coated substrate. In vitro bioactivity test confirmed that the Nb2O5 coating with nanoporous morphology facilitated the growth of hydroxyapatite (HAp). This was further confirmed by the solution analysis test where increased uptake of calcium and phosphorous ions from simulated body fluid (SBF) was observed. Electrochemical evaluation of the coating confirmed that the crystalline coating is insulative and protective in nature and offered excellent corrosion protection to 316L SS. Thus, this study confirmed that the nanoporous crystalline Nb2O5 coating conferred bioactivity and enhanced corrosion resistance on 316L SS.

  16. Effect of Graphene with Nanopores on Metal Clusters

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhou, Hu; Chen, Xianlang; Wang, Lei

    Porous graphene, which is a novel type of defective graphene, shows excellent potential as a support material for metal clusters. In this work, the stability and electronic structures of metal clusters (Pd, Ir, Rh) supported on pristine graphene and graphene with different sizes of nanopore were investigated by first-principle density functional theory (DFT) calculations. Thereafter, CO adsorption and oxidation reaction on the Pd-graphene system were chosen to evaluate its catalytic performance. Graphene with nanopore can strongly stabilize the metal clusters and cause a substantial downshift of the d-band center of the metal clusters, thus decreasing CO adsorption. All binding energies,more » d-band centers, and adsorption energies show a linear change with the size of the nanopore: a bigger size of nanopore corresponds to a stronger metal clusters bond to the graphene, lower downshift of the d-band center, and weaker CO adsorption. By using a suitable size nanopore, supported Pd clusters on the graphene will have similar CO and O2 adsorption ability, thus leading to superior CO tolerance. The DFT calculated reaction energy barriers show that graphene with nanopore is a superior catalyst for CO oxidation reaction. These properties can play an important role in instructing graphene-supported metal catalyst preparation to prevent the diffusion or agglomeration of metal clusters and enhance catalytic performance. This work was supported by National Basic Research Program of China (973Program) (2013CB733501), the National Natural Science Foundation of China (NSFC-21176221, 21136001, 21101137, 21306169, and 91334013). D. Mei acknowledges the support from the US Department of Energy, Office of Science, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences & Biosciences. Pacific Northwest National Laboratory (PNNL) is a multiprogram national laboratory operated for DOE by Battelle. Computing time was granted by the grand challenge of computational

  17. Miconazole Nitrate-loaded Microparticles For Buccal Use: Immediate Drug Release and Antifungal Effect.

    PubMed

    Cartagena, Andres Felipe; Lyra, Amanda Martinez; Kapuchczinski, Aline Cristina; Urban, Amanda Migliorini; Esmerino, Luis Antonio; Klein, Traudi; Nadal, Jessica Mendes; Farago, Paulo Vitor; Campanha, Nara Hellen

    2017-01-01

    Miconazole nitrate has been widely employed in treatment of oral mycoses, however your immediate bio-availability and location in the affected area is critical. The aim of this study was to prepare and evaluate Eudragit® L100 and Gantrez MS-955 microparticles containing miconazole nitrate for oral delivery. Microparticles were prepared by spray-drying method to achieve high encapsulation efficiency and increase the drug solubility. The microparticles were formed containing 10% and 20% of drug on polymer Eudragit® L100 (E10 and E20), Gantrez MS-955 (G10 and G20) or their combination (EG10 and EG20). The influence of formulation factors (polymer:drug ratio, type of polymer) on yield percent, encapsulation efficiency, particle size, Fourier-transformed infrared spectroscopy (FTIR), X-ray diffraction, differential scanning calorimetry, in vitro drug release and antifungal activity were investigated. Acceptable yield, micrometer-sized and drug-loading efficiencies higher than 89% were obtained. No change in FTIR assignments was recorded after the microencapsulation procedure. X-ray and differential scanning calorimetry studies revealed amorphous/non-crystalline formulations. Miconazole nitrate-microparticles provided a remarkable increase of dissolution rate of the drug. Miconazole nitrate and G10, G20 and EG20 microparticles fitted to biexponential kinetic model, and E10, E20 and EG10 microparticles, monoexponential kinetic model. The antifungal activity test demonstrated that miconazole nitrate-microparticles possessed the same anti-Candida albicans activity as the pure drug. These results indicate that miconazole nitrate-microparticles are feasible carriers for increased release of miconazole at oral environment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Circulating erythrocyte-derived microparticles are associated with coagulation activation in sickle cell disease

    PubMed Central

    van Beers, Eduard J.; Schaap, Marianne C.L.; Berckmans, René J.; Nieuwland, Rienk; Sturk, Augueste; van Doormaal, Frederiek F.; Meijers, Joost C.M.; Biemond, Bart J.

    2009-01-01

    Background Sickle cell disease is characterized by a hypercoagulable state as a result of multiple factors, including chronic hemolysis and circulating cell-derived microparticles. There is still no consensus on the cellular origin of such microparticles and the exact mechanism by which they may enhance coagulation activation in sickle cell disease. Design and Methods In the present study, we analyzed the origin of circulating microparticles and their procoagulant phenotype during painful crises and steady state in 25 consecutive patients with sickle cell disease. Results The majority of microparticles originated from platelets (GPIIIa,CD61) and erythrocytes (glycophorin A,CD235), and their numbers did not differ significantly between crisis and steady state. Erythrocyte-derived microparticles strongly correlated with plasma levels of markers of hemolysis, i.e. hemoglobin (r=−0.58, p<0.001) and lactate dehydrogenase (r=0.59, p<0.001), von Willebrand factor as a marker of platelet/endothelial activation (r=0.44, p<0.001), and D-dimer and prothrombin fragment F1+2 (r=0.52, p<0.001 and r=0.59, p<0.001, respectively) as markers of fibrinolysis and coagulation activation. Thrombin generation depended on the total number of microparticles (r=0.63, p<0.001). Anti-human factor XI inhibited thrombin generation by about 50% (p<0.001), whereas anti-human factor VII was ineffective (p>0.05). The extent of factor XI inhibition was associated with erythrocyte-derived microparticles (r=0.50, p=0.023). Conclusions We conclude that the procoagulant state in sickle cell disease is partially explained by the factor XI-dependent procoagulant properties of circulating erythrocyte-derived microparticles. PMID:19815831

  19. Prospects of pharmaceuticals and biopharmaceuticals loaded microparticles prepared by double emulsion technique for controlled delivery

    PubMed Central

    Giri, Tapan Kumar; Choudhary, Chhatrapal; Ajazuddin; Alexander, Amit; Badwaik, Hemant; Tripathi, Dulal Krishna

    2012-01-01

    Several methods and techniques are potentially useful for the preparation of microparticles in the field of controlled drug delivery. The type and the size of the microparticles, the entrapment, release characteristics and stability of drug in microparticles in the formulations are dependent on the method used. One of the most common methods of preparing microparticles is the single emulsion technique. Poorly soluble, lipophilic drugs are successfully retained within the microparticles prepared by this method. However, the encapsulation of highly water soluble compounds including protein and peptides presents formidable challenges to the researchers. The successful encapsulation of such compounds requires high drug loading in the microparticles, prevention of protein and peptide degradation by the encapsulation method involved and predictable release, both rate and extent, of the drug compound from the microparticles. The above mentioned problems can be overcome by using the double emulsion technique, alternatively called as multiple emulsion technique. Aiming to achieve this various techniques have been examined to prepare stable formulations utilizing w/o/w, s/o/w, w/o/o, and s/o/o type double emulsion methods. This article reviews the current state of the art in double emulsion based technologies for the preparation of microparticles including the investigation of various classes of substances that are pharmaceutically and biopharmaceutically active. PMID:23960828

  20. Phagocytosis of PLGA Microparticles in Rat Peritoneal Exudate Cells: A Time-Dependent Study

    NASA Astrophysics Data System (ADS)

    Gomes, Anderson De Jesus; Nain Lunardi, Claure; Henrique Caetano, Flávio; Orive Lunardi, Laurelúcia; da Hora Machado, Antonio Eduardo

    2006-07-01

    With the purpose of enhancing the efficacy of microparticle-encapsulated therapeutic agents, in this study we evaluated the phagocytic ability of rat peritoneal exudate cells and the preferential location of poly(D,L-lactide-co-glycolic acid) (PLGA) microparticles inside these cells. The microparticles used were produced by a solvent evaporation method and were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Size distribution analysis using DLS and SEM showed that the particles were spherical, with diameters falling between 0.5 and 1.5 [mu]m. Results from cell adhesion by SEM assay, indicated that the PLGA microparticles are not toxic to cells and do not cause any distinct damage to them as confirmed by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. Among the large variety of cell populations found in the peritoneal exudates (neutrophils, eosinophils, monocytes, and macrophages), TEM showed that only the latter phagocytosed PLGA microparticles, in a time-dependent manner. The results obtained indicate that the microparticles studied show merits as possible carriers of drugs for intracellular delivery.

  1. Single-Molecule Sensing with Nanopore Confinement: From Chemical Reactions to Biological Interactions.

    PubMed

    Lin, Yao; Ying, Yi-Lun; Gao, Rui; Long, Yi-Tao

    2018-03-25

    The nanopore can generate an electrochemical confinement for single-molecule sensing that help understand the fundamental chemical principle in nanoscale dimensions. By observing the generated ionic current, individual bond-making and bond-breaking steps, single biomolecule dynamic conformational changes and electron transfer processes that occur within pore can be monitored with high temporal and current resolution. These single-molecule studies in nanopore confinement are revealing information about the fundamental chemical and biological processes that cannot be extracted from ensemble measurements. In this Concept article, we introduce and discuss the electrochemical confinement effects on single-molecule covalent reactions, conformational dynamics of individual molecules and host-guest interactions in protein nanopores. Then, we extend the concept of nanopore confinement effects to confine electrochemical redox reactions in solid-state nanopores for developing new sensing mechanisms. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Decellularized extracellular matrix microparticles as a vehicle for cellular delivery in a model of anastomosis healing.

    PubMed

    Hoganson, David M; Owens, Gwen E; Meppelink, Amanda M; Bassett, Erik K; Bowley, Chris M; Hinkel, Cameron J; Finkelstein, Eric B; Goldman, Scott M; Vacanti, Joseph P

    2016-07-01

    Extracellular matrix (ECM) materials from animal and human sources have become important materials for soft tissue repair. Microparticles of ECM materials have increased surface area and exposed binding sites compared to sheet materials. Decellularized porcine peritoneum was mechanically dissociated into 200 µm microparticles, seeded with fibroblasts and cultured in a low gravity rotating bioreactor. The cells avidly attached and maintained excellent viability on the microparticles. When the seeded microparticles were placed in a collagen gel, the cells quickly migrated off the microparticles and through the gel. Cells from seeded microparticles migrated to and across an in vitro anastomosis model, increasing the tensile strength of the model. Cell seeded microparticles of ECM material have potential for paracrine and cellular delivery therapies when delivered in a gel carrier. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1728-1735, 2016. © 2016 Wiley Periodicals, Inc.

  3. Rotating of low-refractive-index microparticles with a quasi-perfect optical vortex.

    PubMed

    Liang, Yansheng; Lei, Ming; Yan, Shaohui; Li, Manman; Cai, Yanan; Wang, Zhaojun; Yu, Xianghua; Yao, Baoli

    2018-01-01

    Low-refractive-index microparticles, such as hollow microspheres, have shown great significance in some applications, such as biomedical sensing and targeted drug delivery. However, optical trapping and manipulation of low-refractive-index microparticles are challenging, owing to the repelling force exerted by typical optical traps. In this paper, we demonstrated optical trapping and rotating of large-sized low-refractive-index microparticles by using quasi-perfect optical vortex (quasi-POV) beams, which were generated by Fourier transform of high-order quasi-Bessel beams. Numerical simulation was carried out to characterize the focusing property of the quasi-POV beams. The dynamics of low-refractive-index microparticles in the quasi-POV with various topological charges was investigated in detail. To improve the trapping and rotating performances of the vortex, a point trap was introduced at the center of the ring. Experimental results showed that the quasi-POV was preferable for manipulation of large-sized low-refractive-index microparticles, with its control of the particles' rotating velocity dependent only on the topological charge due to the unchanged orbital radius.

  4. Mucoadhesive microparticles with a nanostructured surface for enhanced bioavailability of glaucoma drug.

    PubMed

    Park, Chun Gwon; Kim, Young Kook; Kim, Mi Jeung; Park, Min; Kim, Myung Hun; Lee, Seung Ho; Choi, Sung Yoon; Lee, Won Seok; Chung, You Jung; Jung, Young Eun; Park, Ki Ho; Choy, Young Bin

    2015-12-28

    Topical drug administration to the eye is limited by low drug bioavailability due to its rapid clearance from the preocular surface. Thus, multiple daily administrations are often needed, but patient compliance is low, hence a high chance of unsatisfactory treatment of ocular diseases. To resolve this, we propose mucoadhesive microparticles with a nanostructured surface as potential carriers for delivery of brimonidine, an ocular drug for glaucoma treatment. For sustained drug delivery, the microparticles were composed mainly of a diffusion-wall material, poly(lactic-co-glycolic acid) and a mucoadhesive polymer, polyethylene glycol, was used as an additive. Due to their nanostructured surface, the microparticles with a mucoadhesive material exhibited a 13-fold increase in specific surface area and could thus adhere better to the mucous layer on the eye, as compared with the conventional spherical microparticles. When loaded with brimonidine, the mucoadhesive microparticles with a nanostructured surface increased both drug bioavailability and its activity period by a factor of more than 2 over Alphagan P, a marketed eye drop of brimonidine. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Elastic properties of protein functionalized nanoporous polymer films

    DOE PAGES

    Charles T. Black; Wang, Haoyu; Akcora, Pinar

    2015-12-16

    Retaining the conformational structure and bioactivity of immobilized proteins is important for biosensor designs and drug delivery systems. Confined environments often lead to changes in conformation and functions of proteins. In this study, lysozyme is chemically tethered into nanopores of polystyrene thin films, and submicron pores in poly(methyl methacrylate) films are functionalized with streptavidin. Nanoindentation experiments show that stiffness of streptavidin increases with decreasing submicron pore sizes. Lysozymes in polystyrene nanopores are found to behave stiffer than the submicron pore sizes and still retain their specific bioactivity relative to the proteins on flat surfaces. Lastly, our results show that proteinmore » functionalized ordered nanoporous polystyrene/poly(methyl methacrylate) films present heterogeneous elasticity and can be used to study interactions between free proteins and designed surfaces.« less

  6. Methotrexate loaded alginate microparticles and effect of Ca2+ post-crosslinking: An in vitro physicochemical and biological evaluation.

    PubMed

    Dhanka, Mukesh; Shetty, Chaitra; Srivastava, Rohit

    2018-04-15

    Methotrexate (MTX) loaded alginate microparticles were produced by simple water-in-oil (W/O) emulsion solvent diffusion method with homogenization and then subsequently cross-linked by Ca 2+ . The mean sizes of developed microparticles (bare non-crosslinked, crosslinked, drug-loaded non-crosslinked, and drug-loaded cross-linked) were found to be <11μm. The morphology of bare non-crosslinked and crosslinked microparticles were observed to be spherical with smooth surface morphology. However, MTX loaded non-crosslinked and crosslinked microparticles were found to have an irregular shape with rough surface morphology. The encapsulation efficiency (% EE) and loading capacity (% LC) of MTX loaded non-crosslinked microparticles were estimated to be 92.19±1.85 and 9.35±0.22, respectively. However, in case of cross-linked microparticles, the % EE and % LC values slightly decreased, i.e., 83.26±1.69% and 8.44±0.21%, respectively. Crosslinked microparticles were found to release MTX at a slower rate as compared to non-crosslinked microparticles. The physicochemical characterizations of microparticles by Fourier Transform Infrared Spectroscopy and High-Resolution X-Ray Diffraction have shown that drug encapsulated in the microparticles without chemical interactions has lost its crystalline nature. The biocompatibility and hemocompatibility studies of the microparticles have demonstrated that microparticles are biocompatible and were non-hemolytic at low concentrations. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Roughness-controlled self-assembly of mannitol/LB agar microparticles by polymorphic transformation for pulmonary drug delivery.

    PubMed

    Zhang, Fengying; Ngoc, Nguyen Thi Quynh; Tay, Bao Hui; Mendyk, Aleksander; Shao, Yu-Hsuan; Lau, Raymond

    2015-01-05

    Novel roughness-controlled mannitol/LB Agar microparticles were synthesized by polymorphic transformation and self-assembly method using hexane as the polymorphic transformation reagent and spray-dried mannitol/LB Agar microparticles as the starting material. As-prepared microparticles were characterized by Fourier transform infrared spectra (FTIR), X-ray diffraction spectra (XRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), thermal gravimetric analysis (TGA), and Andersen Cascade Impactor (ACI). The XRD and DSC results indicate that after immersing spray-dried mannitol/LB Agar microparticles in hexane, β-mannitol was completely transformed to α-mannitol in 1 h, and all the δ-mannitol was transformed to α form after 14 days. SEM shows that during the transformation the nanobelts on the spray-dried mannitol/LB Agar microparticles become more dispersed and the contour of the individual nanobelts becomes more noticeable. Afterward, the nanobelts self-assemble to nanorods and result in rod-covered mannitol/LB Agar microparticles. FTIR indicates new hydrogen bonds were formed among mannitol, LB Agar, and hexane. SEM images coupled with image analysis software reveal that different surface morphology of the microparticles have different drug adhesion mechanisms. Comparison of ACI results and image analysis of SEM images shows that an increase in the particle surface roughness can increase the fine particle fractions (FPFs) using the rod-covered mannitol microparticles as drug carriers. Transformed microparticles show higher FPFs than commercially available lactose carriers. An FPF of 28.6 ± 2.4% was achieved by microparticles transformed from spray-dried microparticles using 2% mannitol(w/v)/LB Agar as feed solution. It is comparable to the highest FPF reported in the literature using lactose and spray-dried mannitol as carriers.

  8. Preparation, Characterization and Properties of Alginate/Poly(γ-glutamic acid) Composite Microparticles

    PubMed Central

    Tong, Zongrui; Chen, Yu; Liu, Yang; Tong, Li; Chu, Jiamian; Xiao, Kecen; Zhou, Zhiyu; Dong, Wenbo; Chu, Xingwu

    2017-01-01

    Alginate (Alg) is a renewable polymer with excellent hemostatic properties and biocapability and is widely used for hemostatic wound dressing. However, the swelling properties of alginate-based wound dressings need to be promoted to meet the requirements of wider application. Poly(γ-glutamic acid) (PGA) is a natural polymer with high hydrophility. In the current study, novel Alg/PGA composite microparticles with double network structure were prepared by the emulsification/internal gelation method. It was found from the structure characterization that a double network structure was formed in the composite microparticles due to the ion chelation interaction between Ca2+ and the carboxylate groups of Alg and PGA and the electrostatic interaction between the secondary amine group of PGA and the carboxylate groups of Alg and PGA. The swelling behavior of the composite microparticles was significantly improved due to the high hydrophility of PGA. Influences of the preparing conditions on the swelling behavior of the composites were investigated. The porous microparticles could be formed while compositing of PGA. Thermal stability was studied by thermogravimetric analysis method. Moreover, in vitro cytocompatibility test of microparticles exhibited good biocompatibility with L929 cells. All results indicated that such Alg/PGA composite microparticles are a promising candidate in the field of wound dressing for hemostasis or rapid removal of exudates. PMID:28398222

  9. Preparation, Characterization and Properties of Alginate/Poly(γ-glutamic acid) Composite Microparticles.

    PubMed

    Tong, Zongrui; Chen, Yu; Liu, Yang; Tong, Li; Chu, Jiamian; Xiao, Kecen; Zhou, Zhiyu; Dong, Wenbo; Chu, Xingwu

    2017-04-11

    Alginate (Alg) is a renewable polymer with excellent hemostatic properties and biocapability and is widely used for hemostatic wound dressing. However, the swelling properties of alginate-based wound dressings need to be promoted to meet the requirements of wider application. Poly( γ -glutamic acid) (PGA) is a natural polymer with high hydrophility. In the current study, novel Alg/PGA composite microparticles with double network structure were prepared by the emulsification/internal gelation method. It was found from the structure characterization that a double network structure was formed in the composite microparticles due to the ion chelation interaction between Ca 2+ and the carboxylate groups of Alg and PGA and the electrostatic interaction between the secondary amine group of PGA and the carboxylate groups of Alg and PGA. The swelling behavior of the composite microparticles was significantly improved due to the high hydrophility of PGA. Influences of the preparing conditions on the swelling behavior of the composites were investigated. The porous microparticles could be formed while compositing of PGA. Thermal stability was studied by thermogravimetric analysis method. Moreover, in vitro cytocompatibility test of microparticles exhibited good biocompatibility with L929 cells. All results indicated that such Alg/PGA composite microparticles are a promising candidate in the field of wound dressing for hemostasis or rapid removal of exudates.

  10. Microparticles Engineered to Highly Express Peroxisome Proliferator-Activated Receptor-γ Decreased Inflammatory Mediator Production and Increased Adhesion of Recipient Monocytes

    PubMed Central

    Sahler, Julie; Woeller, Collynn F.; Phipps, Richard P.

    2014-01-01

    Circulating blood microparticles are submicron vesicles released primarily by megakaryocytes and platelets that act as transcellular communicators. Inflammatory conditions exhibit elevated blood microparticle numbers compared to healthy conditions. Direct functional consequences of microparticle composition, especially internal composition, on recipient cells are poorly understood. Our objective was to evaluate if microparticle composition could impact the function of recipient cells, particularly during inflammatory provocation. We therefore engineered the composition of megakaryocyte culture-derived microparticles to generate distinct microparticle populations that were given to human monocytes to assay for influences recipient cell function. Herein, we tested the responses of monocytes exposed to either control microparticles or microparticles that contain the anti-inflammatory transcription factor, peroxisome proliferator-activated receptor-γ (PPARγ). In order to normalize relative microparticle abundance from two microparticle populations, we implemented a novel approach that utilizes a Nanodrop Spectrophotometer to assay for microparticle density rather than concentration. We found that when given to peripheral blood mononuclear cells, microparticles were preferentially internalized by CD11b+ cells, and furthermore, microparticle composition had a profound functional impact on recipient monocytes. Specifically, microparticles containing PPARγ reduced activated monocyte production of the proinflammatory cytokines interleukin-8 and monocyte chemotactic protein-1 compared to activated monocytes exposed to control microparticles. Additionally, treatment with PPARγ microparticles greatly increased monocyte cell adherence. This change in morphology occurred simultaneously with increased production of the key extracellular matrix protein, fibronectin and increased expression of the fibronectin-binding integrin, ITGA5. PPARγ microparticles also changed monocyte

  11. Microparticles engineered to highly express peroxisome proliferator-activated receptor-γ decreased inflammatory mediator production and increased adhesion of recipient monocytes.

    PubMed

    Sahler, Julie; Woeller, Collynn F; Phipps, Richard P

    2014-01-01

    Circulating blood microparticles are submicron vesicles released primarily by megakaryocytes and platelets that act as transcellular communicators. Inflammatory conditions exhibit elevated blood microparticle numbers compared to healthy conditions. Direct functional consequences of microparticle composition, especially internal composition, on recipient cells are poorly understood. Our objective was to evaluate if microparticle composition could impact the function of recipient cells, particularly during inflammatory provocation. We therefore engineered the composition of megakaryocyte culture-derived microparticles to generate distinct microparticle populations that were given to human monocytes to assay for influences recipient cell function. Herein, we tested the responses of monocytes exposed to either control microparticles or microparticles that contain the anti-inflammatory transcription factor, peroxisome proliferator-activated receptor-γ (PPARγ). In order to normalize relative microparticle abundance from two microparticle populations, we implemented a novel approach that utilizes a Nanodrop Spectrophotometer to assay for microparticle density rather than concentration. We found that when given to peripheral blood mononuclear cells, microparticles were preferentially internalized by CD11b+ cells, and furthermore, microparticle composition had a profound functional impact on recipient monocytes. Specifically, microparticles containing PPARγ reduced activated monocyte production of the proinflammatory cytokines interleukin-8 and monocyte chemotactic protein-1 compared to activated monocytes exposed to control microparticles. Additionally, treatment with PPARγ microparticles greatly increased monocyte cell adherence. This change in morphology occurred simultaneously with increased production of the key extracellular matrix protein, fibronectin and increased expression of the fibronectin-binding integrin, ITGA5. PPARγ microparticles also changed monocyte

  12. Proteomic Analysis of Serum Opsonins Impacting Biodistribution and Cellular Association of Porous Silicon Microparticles

    PubMed Central

    Serda, Rita E.; Blanco, Elvin; Mack, Aaron; Stafford, Susan J.; Amra, Sarah; Li, Qingpo; van de Ven, Anne L.; Tanaka, Takemi; Torchilin, Vladimir P.; Wiktorowicz, John E.; Ferrari, Mauro

    2014-01-01

    Mass transport of drug delivery vehicles is guided by particle properties, such as shape, composition and surface chemistry, as well as biomolecules and serum proteins that adsorb to the particle surface. In an attempt to identify serum proteins influencing cellular associations and biodistribution of intravascularly injected particles, we used two dimensional gel electrophoresis and mass spectrometry to identify proteins eluted from the surface of cationic and anionic silicon microparticles. Cationic microparticles displayed a 25-fold greater abundance of Ig light chain variable region, fibrinogen, and complement component 1 compared to their anionic counterparts. The anionic-surface favored equal accumulation of microparticles in the liver and spleen, while cationic-surfaces favored preferential accumulation in the spleen. Immunohistochemistry supported macrophage internalization of both anionic and cationic silicon microparticles in the liver, as well as evidence of association of cationic microparticles with hepatic endothelial cells. Furthermore, scanning electron micrographs supported cellular competition for cationic microparticles by endothelial cells and macrophages. Despite high macrophage content in the lungs and tumor, microparticle uptake by these cells was minimal, supporting differences in the repertoire of surface receptors expressed by tissue-specific macrophages. In summary, particle surface chemistry drives selective binding of serum components impacting cellular interactions and biodistribution. PMID:21303614

  13. Plasma levels of endothelial and B-cell-derived microparticles are restored by fingolimod treatment in multiple sclerosis patients.

    PubMed

    Zinger, Anna; Latham, Sharissa L; Combes, Valery; Byrne, Scott; Barnett, Michael H; Hawke, Simon; Grau, Georges E

    2016-12-01

    No molecular marker can monitor disease progression and treatment efficacy in multiple sclerosis (MS). Circulating microparticles represent a potential snapshot of disease activity at the blood brain barrier. To profile plasma microparticles by flow cytometry in MS and determine how fingolimod could impact endothelial microparticles production. In non-treated MS patients compared to healthy and fingolimod-treated patients, endothelial microparticles were higher, while B-cell-microparticle numbers were lower. Fingolimod dramatically reduced tumour necrosis factor (TNF)-induced endothelial microparticle release in vitro. Fingolimod restored dysregulated endothelial and B-cell-microparticle numbers, which could serve as a biomarker in MS. © The Author(s), 2016.

  14. Redox-responsive solid lipid microparticles composed of octadecyl acrylate and allyl disulfide.

    PubMed

    Kim, Tae Hoon; Kim, Jin-Chul

    2018-04-01

    Redox-responsive solid lipid microparticles were prepared by an emulsification photo-polymerization method. Octadecyl acrylate (ODA) and a cross-linker (i.e. allyl disulfide (ADS) and octadiene (ODE)) were dissolved in dichloromethane, it was emulsified in poly(vinyl alcohol) solution, and the resulting O/W emulsion was irradiated with UV light. On the scanning electron microscope micrographs, the microparticles were sphere-like and they were not markedly different from the oil droplets in size. Using the atomic compositions analyzed by energy dispersive X-ray spectroscopy, the ODA to cross-linker molar ratio of ODA/ADS microparticles and ODA/ODE ones were calculated to be 1:0.13 and 1:0.15, respectively. In the FT-IR spectra of the microparticles, the signal of the vinyl group was hardly detected, implying that the monomer and the cross-linkers participated in the photo-polymerization. In differential scanning calorimetry study, ODA/ADS microparticles and ODA/ODE ones exhibited their endothermic peaks around 42.9 and 41.3 °C, respectively, possibly due to the melting of polymeric ODA. Dithiothreitol (DTT, a reducing agent) concentration had little effect on the release degree of dye loaded in ODA/ODE microparticles. Whereas, DTT concentration had a significant effect on the release degree of dye loaded in ODA/ADS microparticles. The release degree at 26 °C was weakly affected by DTT concentration. When the temperature was 37 °C, DTT concentration had a strong effect on the release degree. The disulfide cross-linker (i.e. ADS) can be broken to thiol compounds by the reducing agent, resulting in an increase in the release degree.

  15. Heparin Microparticle Effects on Presentation and Bioactivity of Bone Morphogenetic Protein-2

    PubMed Central

    Hettiaratchi, Marian H.; Miller, Tobias; Temenoff, Johnna S.; Guldberg, Robert E.; McDevitt, Todd C.

    2014-01-01

    Biomaterials capable of providing localized and sustained presentation of bioactive proteins are critical for effective therapeutic growth factor delivery. However, current biomaterial delivery vehicles commonly suffer from limitations that can result in low retention of growth factors at the site of interest or adversely affect growth factor bioactivity. Heparin, a highly sulfated glycosaminoglycan, is an attractive growth factor delivery vehicle due to its ability to reversibly bind positively charged proteins, provide sustained delivery, and maintain protein bioactivity. This study describes the fabrication and characterization of heparin methacrylamide (HMAm) microparticles for recombinant growth factor delivery. HMAm microparticles were shown to efficiently bind several heparin-binding growth factors (e.g. bone morphogenetic protein-2 (BMP-2), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (FGF-2)), including a wide range of BMP-2 concentrations that exceeds the maximum binding capacity of other common growth factor delivery vehicles, such as gelatin. BMP-2 bioactivity was assessed on the basis of alkaline phosphatase (ALP) activity induced in skeletal myoblasts (C2C12). Microparticles loaded with BMP-2 stimulated comparable C2C12 ALP activity to soluble BMP-2 treatment, indicating that BMP-2-loaded microparticles retain bioactivity and potently elicit a functional cell response. In summary, our results suggest that heparin microparticles stably retain large amounts of bioactive BMP-2 for prolonged periods of time, and that presentation of BMP-2 via heparin microparticles can elicit cell responses comparable to soluble BMP-2 treatment. Consequently, heparin microparticles present an effective method of delivering and spatially retaining growth factors that could be used in a variety of systems to enable directed induction of cell fates and tissue regeneration. PMID:24881028

  16. PEGylated Biodegradable Polyesters for PGSS Microparticles Formulation: Processability, Physical and Release Properties.

    PubMed

    Perinelli, D R; Cespi, M; Bonacucina, G; Naylor, A; Whitaker, M; Lam, J K W; Howdle, S M; Casettari, L; Palmieri, G F

    2016-01-01

    Particles from Gas Saturated Solution (PGSS) is an emergent method that employs supercritical carbon dioxide (scCO2) to produce microparticles. It is suitable for encapsulating biologically active compounds including therapeutic peptides and proteins. Poly(lactide acid) (PLA) and/or poly(lactic-coglycolic acid) (PLGA) are the most commonly used materials in PGSS, due to their good processability in scCO2. Previous studies demonstrated that the properties of the microparticles can be modulated by adding polyethylene glycol (PEG) or tri-block PEGylated copolymers. In the present work, the effect of the addition of biodegradable PEGylated di-block copolymers on the physical properties and drug release performance of microparticles prepared by PGSS technique was evaluated. mPEG5kDa-P(L)LA and mPEG5kDa-P(L)LGA with similar molecular weights were synthesized and their behaviour, when exposed to supercritical CO2, was investigated. Different microparticle formulations, composed of a high (81%) or low (9%) percentage of the synthesized copolymers were prepared and compared in terms of particle size distribution, morphology, yield and protein release. Drug release studies were performed using bovine serum albumin (BSA) as a model protein. PEGylated copolymers showed good processability in PGSS without significant changes to the physical properties of the microparticles. However, the addition of PEG exerted a modulating effect on the microparticle drug dissolution behaviour, increasing the rate of BSA release as a function of its content in the formulation. This study demonstrated the feasibility of producing microparticles by using PEGylated di-block copolymers through a PGSS technique at mild operating conditions (low operating pressure and temperature).

  17. Characterization of microparticles prepared by emulsion method from pectin and protein

    USDA-ARS?s Scientific Manuscript database

    In this study, pectin was extracted from apple peel and formulated into microparticles in combination with zein, an edible food protein. The physical, chemical, and structural properties of the resultant pectin structures were evaluated. The resultant microparticles were also examined in vitro for c...

  18. Robust Label-free, Quantitative Profiling of Circulating Plasma Microparticle (MP) Associated Proteins*

    PubMed Central

    Braga-Lagache, Sophie; Buchs, Natasha; Iacovache, Mircea-Ioan; Zuber, Benoît; Jackson, Christopher Benjamin

    2016-01-01

    Cells of the vascular system release spherical vesicles, called microparticles, in the size range of 0.1–1 μm induced by a variety of stress factors resulting in variable concentrations between health and disease. Furthermore, microparticles have intercellular communication/signaling properties and interfere with inflammation and coagulation pathways. Today's most used analytical technology for microparticle characterization, flow cytometry, is lacking sensitivity and specificity, which might have led to the publication of contradicting results in the past. We propose the use of nano-liquid chromatography two-stage mass spectrometry as a nonbiased tool for quantitative MP proteome analysis. For this, we developed an improved microparticle isolation protocol and quantified the microparticle protein composition of twelve healthy volunteers with a label-free, data-dependent and independent proteomics approach on a quadrupole orbitrap instrument. Using aliquots of 250 μl platelet-free plasma from one individual donor, we achieved excellent reproducibility with an interassay coefficient of variation of 2.7 ± 1.7% (mean ± 1 standard deviation) on individual peptide intensities across 27 acquisitions performed over a period of 3.5 months. We show that the microparticle proteome between twelve healthy volunteers were remarkably similar, and that it is clearly distinguishable from whole cell and platelet lysates. We propose the use of the proteome profile shown in this work as a quality criterion for microparticle purity in proteomics studies. Furthermore, one freeze thaw cycle damaged the microparticle integrity, articulated by a loss of cytoplasm proteins, encompassing a specific set of proteins involved in regulating dynamic structures of the cytoskeleton, and thrombin activation leading to MP clotting. On the other hand, plasma membrane protein composition was unaffected. Finally, we show that multiplexed data-independent acquisition can be used for relative

  19. Lithography-based fabrication of nanopore arrays in freestanding SiN and graphene membranes

    NASA Astrophysics Data System (ADS)

    Verschueren, Daniel V.; Yang, Wayne; Dekker, Cees

    2018-04-01

    We report a simple and scalable technique for the fabrication of nanopore arrays on freestanding SiN and graphene membranes based on electron-beam lithography and reactive ion etching. By controlling the dose of the single-shot electron-beam exposure, circular nanopores of any size down to 16 nm in diameter can be fabricated in both materials at high accuracy and precision. We demonstrate the sensing capabilities of these nanopores by translocating dsDNA through pores fabricated using this method, and find signal-to-noise characteristics on par with transmission-electron-microscope-drilled nanopores. This versatile lithography-based approach allows for the high-throughput manufacturing of nanopores and can in principle be used on any substrate, in particular membranes made out of transferable two-dimensional materials.

  20. Selective microrobot control using a thermally responsive microclamper for microparticle manipulation

    NASA Astrophysics Data System (ADS)

    Go, Gwangjun; Choi, Hyunchul; Jeong, Semi; Ko, Seong Young; Park, Jong-Oh; Park, Sukho

    2016-03-01

    Microparticle manipulation using a microrobot in an enclosed environment, such as a lab-on-a-chip, has been actively studied because an electromagnetic actuated microrobot can have accurate motility and wireless controllability. In most studies on electromagnetic actuated microrobots, only a single microrobot has been used to manipulate cells or microparticles. However, the use of a single microrobot can pose several limitations when performing multiple roles in microparticle manipulation. To overcome the limitations associated with using a single microrobot, we propose a new method for the control of multiple microrobots. Multiple microrobots can be controlled independently by an electromagnetic actuation system and multiple microclampers combined with microheaters. To select a specific microrobot among multiple microrobots, we propose a microclamper composed of a clamper structure using thermally responsive hydrogel and a microheater for controlling the microclamper. A fundamental test of the proposed microparticle manipulation system is performed by selecting a specific microrobot among multiple microrobots. Through the independent locomotion of multiple microrobots with U- and V-shaped tips, heterogeneous microparticle manipulation is demonstrated in the creation of a two-dimensional structure. In the future, our proposed multiple-microrobot system can be applied to tasks that are difficult to perform using a single microrobot, such as cell manipulation, cargo delivery, tissue assembly, and cloning.

  1. Water desalination with a single-layer MoS2 nanopore

    NASA Astrophysics Data System (ADS)

    Heiranian, Mohammad; Farimani, Amir Barati; Aluru, Narayana R.

    2015-10-01

    Efficient desalination of water continues to be a problem facing the society. Advances in nanotechnology have led to the development of a variety of nanoporous membranes for water purification. Here we show, by performing molecular dynamics simulations, that a nanopore in a single-layer molybdenum disulfide can effectively reject ions and allow transport of water at a high rate. More than 88% of ions are rejected by membranes having pore areas ranging from 20 to 60 Å2. Water flux is found to be two to five orders of magnitude greater than that of other known nanoporous membranes. Pore chemistry is shown to play a significant role in modulating the water flux. Pores with only molybdenum atoms on their edges lead to higher fluxes, which are ~70% greater than that of graphene nanopores. These observations are explained by permeation coefficients, energy barriers, water density and velocity distributions in the pores.

  2. Water desalination with a single-layer MoS2 nanopore.

    PubMed

    Heiranian, Mohammad; Farimani, Amir Barati; Aluru, Narayana R

    2015-10-14

    Efficient desalination of water continues to be a problem facing the society. Advances in nanotechnology have led to the development of a variety of nanoporous membranes for water purification. Here we show, by performing molecular dynamics simulations, that a nanopore in a single-layer molybdenum disulfide can effectively reject ions and allow transport of water at a high rate. More than 88% of ions are rejected by membranes having pore areas ranging from 20 to 60 Å(2). Water flux is found to be two to five orders of magnitude greater than that of other known nanoporous membranes. Pore chemistry is shown to play a significant role in modulating the water flux. Pores with only molybdenum atoms on their edges lead to higher fluxes, which are ∼ 70% greater than that of graphene nanopores. These observations are explained by permeation coefficients, energy barriers, water density and velocity distributions in the pores.

  3. Nanoporous carbon tunable resistor/transistor and methods of production thereof

    DOEpatents

    Biener, Juergen; Baumann, Theodore F; Dasgupta, Subho; Hahn, Horst

    2014-04-22

    In one embodiment, a tunable resistor/transistor includes a porous material that is electrically coupled between a source electrode and a drain electrode, wherein the porous material acts as an active channel, an electrolyte solution saturating the active channel, the electrolyte solution being adapted for altering an electrical resistance of the active channel based on an applied electrochemical potential, wherein the active channel comprises nanoporous carbon arranged in a three-dimensional structure. In another embodiment, a method for forming the tunable resistor/transistor includes forming a source electrode, forming a drain electrode, and forming a monolithic nanoporous carbon material that acts as an active channel and selectively couples the source electrode to the drain electrode electrically. In any embodiment, the electrolyte solution saturating the nanoporous carbon active channel is adapted for altering an electrical resistance of the nanoporous carbon active channel based on an applied electrochemical potential.

  4. Dynamics of rigid microparticles at the interface of co-flowing immiscible liquids in a microchannel.

    PubMed

    Jayaprakash, K S; Banerjee, U; Sen, A K

    2017-05-01

    We report the dynamical migration behavior of rigid polystyrene microparticles at an interface of co-flowing streams of primary CP 1 (aqueous) and secondary CP 2 (oils) immiscible phases at low Reynolds numbers (Re) in a microchannel. The microparticles initially suspended in the CP 1 either continue to flow in the bulk CP 1 or migrate across the interface into CP 2 , when the stream width of the CP 1 approaches the diameter of the microparticles. Experiments were performed with different secondary phases and it is found that the migration criterion depends on the sign of the spreading parameter S and the presence of surfactant at the interface. To substantiate the migration criterion, experiments were also carried out by suspending the microparticles in CP 2 (oil phase). Our study reveals that in case of aqueous-silicone oil combination, the microparticles get attached to the interface since S<0 and the three phase contact angle, θ>90°. For complete detachment of microparticles from the interface into the secondary phase, additional energy ΔG is needed. We discuss the role of interfacial perturbation, which causes detachment of microparticles from the interface. In case of mineral and olive oils, the surfactants present at the interface prevents attachment of the microparticles to the interface due to the repulsive disjoining pressure. Finally, using a aqueous-silicone oil system, we demonstrate size based sorting of microparticles of size 25μm and 15μm respectively from that of 15μm and 10μm and study the variation of separation efficiency η with the ratio of the width of the aqueous stream to the diameter of the microparticles ρ. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Sustained-releasing hollow microparticles with dual-anticancer drugs elicit greater shrinkage of tumor spheroids.

    PubMed

    Baek, Jong-Suep; Choo, Chee Chong; Tan, Nguan Soon; Loo, Say Chye Joachim

    2017-10-06

    Polymeric particulate delivery systems are vastly explored for the delivery of chemotherapeutic agents. However, the preparation of polymeric particulate systems with the capability of providing sustained release of two or more drugs is still a challenge. Herein, poly (D, L-lactic-co-glycolic acid, 50:50) hollow microparticles co-loaded with doxorubicin and paclitaxel were developed through double-emulsion solvent evaporation technique. Hollow microparticles were formed through the addition of an osmolyte into the fabrication process. The benefits of hollow over solid microparticles were found to be higher encapsulation efficiency and a more rapid drug release rate. Further modification of the hollow microparticles was accomplished through the introduction of methyl-β-cyclodextrin. With this, a higher encapsulation efficiency of both drugs and an enhanced cumulative release were achieved. Spheroid study further demonstrated that the controlled release of the drugs from the methyl-β-cyclodextrin -loaded hollow microparticles exhibited enhanced tumor regressions of MCF-7 tumor spheroids. Such hollow dual-drug-loaded hollow microparticles with sustained releasing capabilities may have a potential for future applications in cancer therapy.

  6. Effects of anti-TNF-α agents on circulating endothelial-derived and platelet-derived microparticles in psoriasis.

    PubMed

    Pelletier, Fabien; Garnache-Ottou, Francine; Biichlé, Sabeha; Vivot, Aurore; Humbert, Philippe; Saas, Philippe; Seillès, Estelle; Aubin, François

    2014-12-01

    Psoriasis involves TNF-α secretion leading to release of microparticles into the bloodstream. We investigated the effect of TNF blockers on microparticles levels before and after treatment in patients (twenty treated by anti-TNF-α agents and 6 by methotrexate) with severe psoriasis. Plasmatic microparticles were labelled using fluorescent monoclonal antibodies and were analysed using cytometry. Three months later, 70% of patients treated with anti-TNF-α agents achieved a reduction in PASI score of at least 75%. The clinical improvement in patients treated with anti-TNF-α agents was associated with a significant reduction of the mean number of platelet microparticles (2837/μl vs 1849/μl, P = 0.02) and of endothelial microparticles (64/μl vs 22/μl, P = 0.001). Microparticles are significantly decreased in psoriatic patients successfully treated by anti-TNF-α. Microparticles levels as circulating endothelial cells represent signs of endothelial dysfunction and are elevated in psoriasis. Then, TNF blockade may be effective to reduce cardiovascular risk through the reduction of circulating microparticles. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Boosting infrared energy transfer in 3D nanoporous gold antennas.

    PubMed

    Garoli, D; Calandrini, E; Bozzola, A; Ortolani, M; Cattarin, S; Barison, S; Toma, A; De Angelis, F

    2017-01-05

    The applications of plasmonics to energy transfer from free-space radiation to molecules are currently limited to the visible region of the electromagnetic spectrum due to the intrinsic optical properties of bulk noble metals that support strong electromagnetic field confinement only close to their plasma frequency in the visible/ultraviolet range. In this work, we show that nanoporous gold can be exploited as a plasmonic material for the mid-infrared region to obtain strong electromagnetic field confinement, co-localized with target molecules into the nanopores and resonant with their vibrational frequency. The effective optical response of the nanoporous metal enables the penetration of optical fields deep into the nanopores, where molecules can be loaded thus achieving a more efficient light-matter coupling if compared to bulk gold. In order to realize plasmonic resonators made of nanoporous gold, we develop a nanofabrication method based on polymeric templates for metal deposition and we obtain antenna arrays resonating at mid-infrared wavelengths selected by design. We then coat the antennas with a thin (3 nm) silica layer acting as the target dielectric layer for optical energy transfer. We study the strength of the light-matter coupling at the vibrational absorption frequency of silica at 1240 cm -1 through the analysis of the experimental Fano lineshape that is benchmarked against identical structures made of bulk gold. The boost in the optical energy transfer from free-space mid-infrared radiation to molecular vibrations in nanoporous 3D nanoantenna arrays can open new application routes for plasmon-enhanced physical-chemical reactions.

  8. Investigation of thermal conduction in symmetric and asymmetric nanoporous structures

    NASA Astrophysics Data System (ADS)

    Yu, Ziqi; Ferrer-Argemi, Laia; Lee, Jaeho

    2017-12-01

    Nanoporous structures with a critical dimension comparable to or smaller than the phonon mean free path have demonstrated significant thermal conductivity reductions that are attractive for thermoelectric applications, but the presence of various geometric parameters complicates the understanding of governing mechanisms. Here, we use a ray tracing technique to investigate phonon boundary scattering phenomena in Si nanoporous structures of varying pore shapes, pore alignments, and pore size distributions, and identify mechanisms that are primarily responsible for thermal conductivity reductions. Our simulation results show that the neck size, or the smallest distance between nearest pores, is the key parameter in understanding nanoporous structures of varying pore shapes and the same porosities. When the neck size and the porosity are both identical, asymmetric pore shapes provide a lower thermal conductivity compared with symmetric pore shapes, due to localized heat fluxes. Asymmetric nanoporous structures show possibilities of realizing thermal rectification even with fully diffuse surface boundaries, in which optimal arrangements of triangular pores show a rectification ratio up to 13 when the injection angles are optimally controlled. For symmetric nanoporous structures, hexagonal-lattice pores achieve larger thermal conductivity reductions than square-lattice pores due to the limited line of sight for phonons. We also show that nanoporous structures of alternating pore size distributions from large to small pores yield a lower thermal conductivity compared with those of uniform pore size distributions in the given porosity. These findings advance the understanding of phonon boundary scattering phenomena in complex geometries and enable optimal designs of artificial nanostructures for thermoelectric energy harvesting and solid-state cooling systems.

  9. Real-time dynamics of high-velocity micro-particle impact

    NASA Astrophysics Data System (ADS)

    Veysset, David; Hsieh, Alex; Kooi, Steve; Maznev, Alex A.; Tang, Shengchang; Olsen, Bradley D.; Nelson, Keith A.

    High-velocity micro-particle impact is important for many areas of science and technology, from space exploration to the development of novel drug delivery platforms. We present real-time observations of supersonic micro-particle impacts using multi-frame imaging. In an all optical laser-induced projectile impact test, a monolayer of micro-particles is placed on a transparent substrate coated with a laser absorbing polymer layer. Ablation of a laser-irradiated polymer region accelerates the micro-particles into free space with speeds up to 1.0 km/s. The particles are monitored during the impact on the target with an ultrahigh-speed multi-frame camera that can record up to 16 images with time resolution as short as 3 ns. In particular, we investigated the high-velocity impact deformation response of poly(urethane urea) (PUU) elastomers to further the fundamental understanding of the molecular influence on dynamical behaviors of PUUs. We show the dynamic-stiffening response of the PUUs and demonstrate the significance of segmental dynamics in the response. We also present movies capturing individual particle impact and penetration in gels, and discuss the observed dynamics. The results will provide an impetus for modeling high-velocity microscale impact responses and high strain rate deformation in polymers, gels, and other materials.

  10. Calpastatin Controls Polymicrobial Sepsis by Limiting Procoagulant Microparticle Release

    PubMed Central

    Gerotziafas, Grigoris; Byrnes, Colleen; Hu, Xuzhen; Perez, Joelle; Lévi, Charlène; Placier, Sandrine; Letavernier, Emmanuel; Leelahavanichkul, Asada; Haymann, Jean-philippe; Elalamy, Ismail; Miller, Jeffrey L.; Star, Robert A.; Yuen, Peter S. T.; Baud, Laurent

    2012-01-01

    Rationale: Sepsis, a leading cause of death worldwide, involves widespread activation of inflammation, massive activation of coagulation, and lymphocyte apoptosis. Calpains, calcium-activated cysteine proteases, have been shown to increase inflammatory reactions and lymphocyte apoptosis. Moreover, calpain plays an essential role in microparticle release. Objectives: We investigated the contribution of calpain in eliciting tissue damage during sepsis. Methods: To test our hypothesis, we induced polymicrobial sepsis by cecal ligation and puncture in wild-type (WT) mice and transgenic mice expressing high levels of calpastatin, a calpain-specific inhibitor. Measurements and Main Results: In WT mice, calpain activity increased transiently peaking at 6 hours after cecal ligation and puncture surgery. Calpastatin overexpression improved survival, organ dysfunction (including lung, kidney, and liver damage), and lymphocyte apoptosis. It decreased the sepsis-induced systemic proinflammatory response and disseminated intravascular coagulation, by reducing the number of procoagulant circulating microparticles and therefore delaying thrombin generation. The deleterious effect of microparticles in this model was confirmed by transferring microparticles from septic WT to septic transgenic mice, worsening their survival and coagulopathy. Conclusions: These results demonstrate an important role of the calpain/calpastatin system in coagulation/inflammation pathways during sepsis, because calpain inhibition is associated with less severe disseminated intravascular coagulation and better overall outcomes in sepsis. PMID:22268136

  11. Evaluation of Plasma Platelet Microparticles in Thrombotic Thrombocytopenic Purpura.

    PubMed

    Tahmasbi, Leila; Karimi, Mehran; Kafiabadi, Sedigheh Amini; Nikougoftar, Mahin; Haghpanah, Sezaneh; Ranjbaran, Reza; Moghadam, Mohamad

    2017-01-01

    Platelet microparticles (PMPs) have a procoagulant activity about 50-100 times greater than active platelets due to high expression of negatively charged phospholipids on their surfaces. In this study, we evaluated microparticle immunophenotyping and also plasma PMPs level in patients with Thrombotic Thrombocytopenic Purpura (TTP) in Southern Iran. We had two study groups: 15 TTP patients and 15 healthy control group and PMPs from platelet concentrate (PC) at the 5 th day of storage. Microparticles were prepared in two steps, by low and high centrifugation followed by size confirmation via 'Dynamic Light Scattering (DLS)' Zetasizer. Immunophenotyping of PMPs was done via flow cytometry, using a FACS Calibur flow cytometer (BD, USA). PMPs counts were obtained using Partec-cyflow and Polysciences Microbeads (1 micron in diameter). Results were analyzed using FlowJo 7.6 (Treestar, USA) and Partec FlowMax software. Our results showed that the majority of microparticles in TTP patients and normal individuals were PMPs and also demonstrated that the plasma PMPs level in TTP patients was higher than the normal control group ( P -value<0.001). It seems that elevated PMPs level in TTP patients could be related to thrombotic events. Nevertheless, more studies are needed to confirm these results. © 2017 by the Association of Clinical Scientists, Inc.

  12. Molecular Sensing by Nanoporous Crystalline Polymers

    PubMed Central

    Pilla, Pierluigi; Cusano, Andrea; Cutolo, Antonello; Giordano, Michele; Mensitieri, Giuseppe; Rizzo, Paola; Sanguigno, Luigi; Venditto, Vincenzo; Guerra, Gaetano

    2009-01-01

    Chemical sensors are generally based on the integration of suitable sensitive layers and transducing mechanisms. Although inorganic porous materials can be effective, there is significant interest in the use of polymeric materials because of their easy fabrication process, lower costs and mechanical flexibility. However, porous polymeric absorbents are generally amorphous and hence present poor molecular selectivity and undesired changes of mechanical properties as a consequence of large analyte uptake. In this contribution the structure, properties and some possible applications of sensing polymeric films based on nanoporous crystalline phases, which exhibit all identical nanopores, will be reviewed. The main advantages of crystalline nanoporous polymeric materials with respect to their amorphous counterparts are, besides a higher selectivity, the ability to maintain their physical state as well as geometry, even after large guest uptake (up to 10–15 wt%), and the possibility to control guest diffusivity by controlling the orientation of the host polymeric crystalline phase. The final section of the review also describes the ability of suitable polymeric films to act as chirality sensors, i.e., to sense and memorize the presence of non-racemic volatile organic compounds. PMID:22303150

  13. Nanopore analysis of polymers in solution.

    NASA Astrophysics Data System (ADS)

    Deamer, David

    2002-03-01

    Nanopores represent a novel approach for investigating macromolecules in solution. Polymers that have been analyzed by this technique include polyethylene glycol (PEG), certain proteins and nucleic acids. The a-hemolysin pore inserted into lipid bilayers provides continuous non-gated ion current through a pore diameter of approximately 1.5 - 2 nm. Nucleic acid molecules can be driven through the pore by imposing a voltage across the supporting membrane. Single stranded, but not double stranded nucleic acids pass through in strict linear sequence from one end of the molecule to the other. While in the pore, the molecule reduces ionic current, and properties of the ionic current blockade such as duration, mean amplitude and modulations of amplitude provide information about structure and composition of the nucleic acid. For a given molecular species, the duration of the blockade is a function of chain length, and the rate of blockades is linearly related to concentration. More recent studies have shown that the a-hemolysin nanopore can discriminate between synthetic DNA molecules differing by a single base pair or even a single nucleotide. These results indicate that a nanopore may have the resolution required for nucleic acid sequencing applications.

  14. Liver Cell-Derived Microparticles Activate Hedgehog Signaling and Alter Gene Expression in Hepatic Endothelial Cells

    PubMed Central

    Witek, Rafal P.; Yang, Liu; Liu, Renshui; Jung, Youngmi; Omenetti, Alessia; Syn, Wing-Kin; Choi, Steve S.; Cheong, Yeiwon; Fearing, Caitlin M.; Agboola, Kolade M.; Chen, Wei; Diehl, Anna Mae

    2013-01-01

    Background & Aims Angiogenesis contributes to vascular remodeling during cirrhosis. In cirrhotic livers, cholangiocytes and myofibroblastic hepatic stellate cells (MF-HSC) produce Hedgehog (Hh) ligands. During embryogenesis Hh ligands are released from ligand-producing cells in microparticles and activate Hh signaling in endothelial cells. We studied whether adult liver cell-derived microparticles contain Hh ligands that alter hepatic sinusoidal endothelial cells (SEC). Methods MF-HSCs and cholangiocytes were exposed to platelet-derived growth factor (PDGF) to induce Hh ligands; microparticles were isolated from medium, analyzed by transmission electron microscopy (TEM) and immunoblots, and applied to Hh-reporter containing cells. Microparticles were also obtained from serum and bile of rats after bile duct ligation (BDL) or sham surgery and applied to normal primary liver SEC with or without cyclopamine, a Hh signaling inhibitor. Effects on SEC gene expression were evaluated by QRT-PCR and immunoblotting. Finally, Hh target gene expression and SEC activation markers were compared in primary SEC and in liver sections from healthy and BDL rats. Results PDGF-treated MF-HSC and cholangiocytes released exosome-enriched microparticles containing biologically active Hh ligands. BDL also increased release of Hh-containing exosome-enriched microparticles into plasma and bile. TEM and immunoblots revealed similarities among microparticles from all sources; all microparticles induced similar Hh-dependent changes in SEC gene expression. SEC from healthy livers did not express Hh target genes or activation markers, but both were up-regulated in SEC after BDL. Conclusions Hh-containing exosome-enriched microparticles released from liver cells alter hepatic SEC gene expression, suggesting a novel mechanism for cirrhotic vasculopathy. PMID:19013163

  15. Liver cell-derived microparticles activate hedgehog signaling and alter gene expression in hepatic endothelial cells.

    PubMed

    Witek, Rafal P; Yang, Liu; Liu, Renshui; Jung, Youngmi; Omenetti, Alessia; Syn, Wing-Kin; Choi, Steve S; Cheong, Yeiwon; Fearing, Caitlin M; Agboola, Kolade M; Chen, Wei; Diehl, Anna Mae

    2009-01-01

    Angiogenesis contributes to vascular remodeling during cirrhosis. In cirrhotic livers, cholangiocytes, and myofibroblastic hepatic stellate cells (MF-HSC) produce Hedgehog (Hh) ligands. During embryogenesis Hh ligands are released from ligand-producing cells in microparticles and activate Hh signaling in endothelial cells. We studied whether adult liver cell-derived microparticles contain Hh ligands that alter hepatic sinusoidal endothelial cells (SEC). MF-HSC and cholangiocytes were exposed to platelet-derived growth factor to induce Hh ligands; microparticles were isolated from medium, analyzed by transmission electron microscopy and immunoblots, and applied to Hh-reporter-containing cells. Microparticles were obtained from serum and bile of rats after bile duct ligation (BDL) or sham surgery and applied to normal primary liver SEC with or without cyclopamine, an Hh signaling inhibitor. Effects on SEC gene expression were evaluated by quantitative reverse-transcription polymerase chain reaction and immunoblotting. Hh target gene expression and SEC activation markers were compared in primary SEC and in liver sections from healthy and BDL rats. Platelet-derived growth factor-treated MF-HSC and cholangiocytes released exosome-enriched microparticles containing biologically-active Hh ligands. BDL increased release of Hh-containing exosome-enriched microparticles into plasma and bile. Transmission electron microscopy and immunoblots revealed similarities among microparticles from all sources; all microparticles induced similar Hh-dependent changes in SEC gene expression. SEC from healthy livers did not express Hh target genes or activation markers, but both were up-regulated in SEC after BDL. Hh-containing exosome-enriched microparticles released from liver cells alter hepatic SEC gene expression, suggesting a novel mechanism for cirrhotic vasculopathy.

  16. Porous microwells for geometry-selective, large-scale microparticle arrays

    NASA Astrophysics Data System (ADS)

    Kim, Jae Jung; Bong, Ki Wan; Reátegui, Eduardo; Irimia, Daniel; Doyle, Patrick S.

    2017-01-01

    Large-scale microparticle arrays (LSMAs) are key for material science and bioengineering applications. However, previous approaches suffer from trade-offs between scalability, precision, specificity and versatility. Here, we present a porous microwell-based approach to create large-scale microparticle arrays with complex motifs. Microparticles are guided to and pushed into microwells by fluid flow through small open pores at the bottom of the porous well arrays. A scaling theory allows for the rational design of LSMAs to sort and array particles on the basis of their size, shape, or modulus. Sequential particle assembly allows for proximal and nested particle arrangements, as well as particle recollection and pattern transfer. We demonstrate the capabilities of the approach by means of three applications: high-throughput single-cell arrays; microenvironment fabrication for neutrophil chemotaxis; and complex, covert tags by the transfer of an upconversion nanocrystal-laden LSMA.

  17. Ion transport by gating voltage to nanopores produced via metal-assisted chemical etching method

    NASA Astrophysics Data System (ADS)

    Van Toan, Nguyen; Inomata, Naoki; Toda, Masaya; Ono, Takahito

    2018-05-01

    In this work, we report a simple and low-cost way to create nanopores that can be employed for various applications in nanofluidics. Nano sized Ag particles in the range from 1 to 20 nm are formed on a silicon substrate with a de-wetting method. Then the silicon nanopores with an approximate 15 nm average diameter and 200 μm height are successfully produced by the metal-assisted chemical etching method. In addition, electrically driven ion transport in the nanopores is demonstrated for nanofluidic applications. Ion transport through the nanopores is observed and could be controlled by an application of a gating voltage to the nanopores.

  18. Ion transport by gating voltage to nanopores produced via metal-assisted chemical etching method.

    PubMed

    Van Toan, Nguyen; Inomata, Naoki; Toda, Masaya; Ono, Takahito

    2018-05-11

    In this work, we report a simple and low-cost way to create nanopores that can be employed for various applications in nanofluidics. Nano sized Ag particles in the range from 1 to 20 nm are formed on a silicon substrate with a de-wetting method. Then the silicon nanopores with an approximate 15 nm average diameter and 200 μm height are successfully produced by the metal-assisted chemical etching method. In addition, electrically driven ion transport in the nanopores is demonstrated for nanofluidic applications. Ion transport through the nanopores is observed and could be controlled by an application of a gating voltage to the nanopores.

  19. Nanoporous Gold: Fabrication, Characterization, and Applications

    PubMed Central

    Seker, Erkin; Reed, Michael L.; Begley, Matthew R.

    2009-01-01

    Nanoporous gold (np-Au) has intriguing material properties that offer potential benefits for many applications due to its high specific surface area, well-characterized thiol-gold surface chemistry, high electrical conductivity, and reduced stiffness. The research on np-Au has taken place on various fronts, including advanced microfabrication and characterization techniques to probe unusual nanoscale properties and applications spanning from fuel cells to electrochemical sensors. Here, we provide a review of the recent advances in np-Au research, with special emphasis on microfabrication and characterization techniques. We conclude the paper with a brief outline of challenges to overcome in the study of nanoporous metals.

  20. Characterization of Microparticle Separation Utilizing Electrokinesis within an Electrodeless Dielectrophoresis Chip

    PubMed Central

    Chiou, Chi-Han; Pan, Jia-Cheng; Chien, Liang-Ju; Lin, Yu-Ying; Lin, Jr-Lung

    2013-01-01

    This study demonstrated the feasibility of utilizing electrokinesis in an electrodeless dielectrophoresis chip to separate and concentrate microparticles such as biosamples. Numerical simulations and experimental observations were facilitated to investigate the phenomena of electrokinetics, i.e., electroosmosis, dielectrophoresis, and electrothermosis. Moreover, the proposed operating mode can be used to simultaneously convey microparticles through a microfluidic device by using electroosmotic flow, eliminating the need for an additional micropump. These results not only revealed that the directions of fluids could be controlled with a forward/backward electroosmotic flow but also categorized the optimum separating parameters for various microparticle sizes (0.5, 1.0 and 2.0 μm). Separation of microparticles can be achieved by tuning driving frequencies at a specific electric potential (90 Vpp·cm−1). Certainly, the device can be designed as a single automated device that carries out multiple functions such as transportation, separation, and detection for the realization of the envisioned Lab-on-a-Chip idea. PMID:23447009

  1. Light-scattering flow cytometry for identification and characterization of blood microparticles

    NASA Astrophysics Data System (ADS)

    Konokhova, Anastasiya I.; Yurkin, Maxim A.; Moskalensky, Alexander E.; Chernyshev, Andrei V.; Tsvetovskaya, Galina A.; Chikova, Elena D.; Maltsev, Valeri P.

    2012-05-01

    We describe a novel approach to study blood microparticles using the scanning flow cytometer, which measures light scattering patterns (LSPs) of individual particles. Starting from platelet-rich plasma, we separated spherical microparticles from non-spherical plasma constituents, such as platelets and cell debris, based on similarity of their LSP to that of sphere. This provides a label-free method for identification (detection) of microparticles, including those larger than 1 μm. Next, we rigorously characterized each measured particle, determining its size and refractive index including errors of these estimates. Finally, we employed a deconvolution algorithm to determine size and refractive index distributions of the whole population of microparticles, accounting for largely different reliability of individual measurements. Developed methods were tested on a blood sample of a healthy donor, resulting in good agreement with literature data. The only limitation of this approach is size detection limit, which is currently about 0.5 μm due to used laser wavelength of 0.66 μm.

  2. Controlling filamentous fungi morphology with microparticles to enhanced β-mannanase production.

    PubMed

    Yatmaz, Ercan; Karahalil, Ercan; Germec, Mustafa; Ilgin, Merve; Turhan, İrfan

    2016-09-01

    β-mannanase was produced mainly by Aspergillus species and can degrade the β-1,4-mannose linkages of galactomannans. This study was undertaken to enhance mannanase production using talcum and aluminum oxide as the microparticles, which control cell morphology of recombinant Aspergillus sojae in glucose and carob extract medium. Both microparticles improved fungal growth in glucose and carob pod extract medium. Aluminum oxide (1 g/L) was the best agent for glucose medium which resulted in 514.0 U/ml. However, the highest mannanase activity was found as 568.7 U/ml with 5 g/L of talcum in carob extract medium. Increase in microparticle concentration resulted in decreasing the pellet size diameter. Furthermore, more than 10 g/L of talcum addition changed the filamentous fungi growth type from pellet to pellet/mycelium mixture. Results showed that right type and concentration of microparticle in fermentation media improved the mannanase activity and production rate by controlling the growth morphology.

  3. Ion transport in sub-5-nm graphene nanopores.

    PubMed

    Suk, Myung E; Aluru, N R

    2014-02-28

    Graphene nanopore is a promising device for single molecule sensing, including DNA bases, as its single atom thickness provides high spatial resolution. To attain high sensitivity, the size of the molecule should be comparable to the pore diameter. However, when the pore diameter approaches the size of the molecule, ion properties and dynamics may deviate from the bulk values and continuum analysis may not be accurate. In this paper, we investigate the static and dynamic properties of ions with and without an external voltage drop in sub-5-nm graphene nanopores using molecular dynamics simulations. Ion concentration in graphene nanopores sharply drops from the bulk concentration when the pore radius is smaller than 0.9 nm. Ion mobility in the pore is also smaller than bulk ion mobility due to the layered liquid structure in the pore-axial direction. Our results show that a continuum analysis can be appropriate when the pore radius is larger than 0.9 nm if pore conductivity is properly defined. Since many applications of graphene nanopores, such as DNA and protein sensing, involve ion transport, the results presented here will be useful not only in understanding the behavior of ion transport but also in designing bio-molecular sensors.

  4. Leakage conduction behavior in electron-beam-cured nanoporous silicate films

    NASA Astrophysics Data System (ADS)

    Liu, Po-Tsun; Tsai, T. M.; Chang, T. C.

    2005-05-01

    This letter explores the application of electron-beam curing on nanoporous silicate films. The electrical conduction mechanism for the nanoporous silicate film cured by electron-beam radiation has been studied with metal-insulator-semiconductor capacitors. Electrical analyses over a varying temperature range from room temperature to 150°C provide evidence for space-charge-limited conduction in the electron-beam-cured thin film, while Schottky-emission-type leaky behavior is seen in the counterpart typically cured by a thermal furnace. A physical model consistent with electrical analyses is also proposed to deduce the origin of conduction behavior in the nanoporous silicate thin film.

  5. Solvothermal synthesis of nanoporous polymer chalk for painting superhydrophobic surfaces.

    PubMed

    Zhang, Yong-Lai; Wang, Jian-Nan; He, Yan; He, Yinyan; Xu, Bin-Bin; Wei, Shu; Xiao, Feng-Shou

    2011-10-18

    Reported here is a facile synthesis of nanoporous polymer chalk for painting superhydrophobic surfaces. Taking this nanoporous polymer as a media, superhydrophobicity is rapidly imparted onto three typical kinds of substrates, including paper, transparent polydimethylsiloxane (PDMS), and finger skin. Quantitative characterization showed that the adhesion between the water droplet and polymer-coated substrates decreased significantly compared to that on the original surface, further indicating the effective wetting mode transformation. The nanoporous polymer coating would open a new door for facile, rapid, safe, and larger scale fabrication of superhydrophobic surfaces on general substrates. © 2011 American Chemical Society

  6. Computational modeling of ion transport through nanopores.

    PubMed

    Modi, Niraj; Winterhalter, Mathias; Kleinekathöfer, Ulrich

    2012-10-21

    Nanoscale pores are ubiquitous in biological systems while artificial nanopores are being fabricated for an increasing number of applications. Biological pores are responsible for the transport of various ions and substrates between the different compartments of biological systems separated by membranes while artificial pores are aimed at emulating such transport properties. As an experimental method, electrophysiology has proven to be an important nano-analytical tool for the study of substrate transport through nanopores utilizing ion current measurements as a probe for the detection. Independent of the pore type, i.e., biological or synthetic, and objective of the study, i.e., to model cellular processes of ion transport or electrophysiological experiments, it has become increasingly important to understand the dynamics of ions in nanoscale confinements. To this end, numerical simulations have established themselves as an indispensable tool to decipher ion transport processes through biological as well as artificial nanopores. This article provides an overview of different theoretical and computational methods to study ion transport in general and to calculate ion conductance in particular. Potential new improvements in the existing methods and their applications are highlighted wherever applicable. Moreover, representative examples are given describing the ion transport through biological and synthetic nanopores as well as the high selectivity of ion channels. Special emphasis is placed on the usage of molecular dynamics simulations which already have demonstrated their potential to unravel ion transport properties at an atomic level.

  7. Pharmacological activity and protein phosphorylation caused by nitric oxide-releasing microparticles.

    PubMed

    Yoo, Jin-Wook; Choe, Eun-Sang; Ahn, Sung-Min; Lee, Chi H

    2010-01-01

    Nitric oxide (NO)-releasing microparticles were developed as a potential treatment option against various blood flow irregulations including sexual dysfunction, atherosclerosis and metal stent-induced restenosis. Polymeric microparticles containing diethylenetriamine diazeniumdiolate (DETA NONOate), a NO donor, were prepared using modified double-emulsion solvent evaporation method to maximize the loading efficacy and stability of DETA NONOate. The pharmacological effects of the NO-releasing microparticles were evaluated by examining the changes in the vaginal blood flow in rats. The effects of NO on the phosphorylation of protein kinase C (PKC) and mitogen activated protein (MAP) kinases in excised vaginal mucosa, such as extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK) and p38, were examined using immunoblotting technique to determine whether NO activates PKC, which subsequently plays an integral role in the formation of PKC-MAP kinase modules. The viability of vagina cells (VK2E6E7) upon exposure to NO-releasing microparticles was examined for cytotoxicity assessment. In contrast to rapid and short-term effects of non-formulated DETA NONOate, microparticles containing DETA NONOate exerted beneficial effects on the blood flow (148+/-13%) for an extended period of time, inducing a significant change at 5 min after its application and the maximum blood flow of 172+/-23% at 120 min. The enhanced vaginal blood flow was maintained for up to 210 min and gradually returned to the baseline afterward. The results of Western immunoblotting study displayed differential expression of MAP kinases (ERK1/2 and JNK) upon NO treatment, clearly demonstrating that PKC is involved in the blood flow regulation process. There were no significant changes in cell viability in vaginal cells upon exposure to NO-releasing microparticles as compared with the control. The results of this work supported that NO-releasing microparticles could improve the

  8. Red blood cell-derived microparticles: An overview.

    PubMed

    Westerman, Maxwell; Porter, John B

    2016-07-01

    The red blood cell (RBC) is historically the original parent cell of microparticles (MPs). In this overview, we describe the discovery and the early history of red cell-derived microparticles (RMPs) and present an overview of the evolution of RMP. We report the formation, characteristics, effects of RMP and factors which may affect RMP evaluation. The review examines RMP derived from both normal and pathologic RBC. The pathologic RBC studies include sickle cell anemia (SCA), sickle cell trait (STr), thalassemia intermedia (TI), hereditary spherocytosis (HS), hereditary elliptocytosis (HE), hereditary stomatocytosis (HSt) and glucose-6-phosphate dehydrogenase deficiency (G6PD). Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Method of fabricating a scalable nanoporous membrane filter

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tringe, Joseph W; Balhorn, Rodney L; Zaidi, Saleem

    A method of fabricating a nanoporous membrane filter having a uniform array of nanopores etch-formed in a thin film structure (e.g. (100)-oriented single crystal silicon) having a predetermined thickness, by (a) using interferometric lithography to create an etch pattern comprising a plurality array of unit patterns having a predetermined width/diameter, (b) using the etch pattern to etch frustum-shaped cavities or pits in the thin film structure such that the dimension of the frustum floors of the cavities are substantially equal to a desired pore size based on the predetermined thickness of the thin film structure and the predetermined width/diameter ofmore » the unit patterns, and (c) removing the frustum floors at a boundary plane of the thin film structure to expose, open, and thereby create the nanopores substantially having the desired pore size.« less

  10. Nanoporous Au: An experimental study on the porosity of dealloyed AuAg leafs

    NASA Astrophysics Data System (ADS)

    Grillo, R.; Torrisi, V.; Ruffino, F.

    2016-12-01

    We present a study on the fraction of porosity for dealloyed nanoporous Au leafs. Nanoporous Au is attracting great scientific interest due to its peculiar plasmonic properties and the high exposed surface (∼10 m2/g). As examples, it was used in prototypes of chemical and biological devices. However, the maximization of the devices sensitivity is subjected to the maximization of the exposed surface by the nanoporous Au, i. e. maximization of the porosity fraction. So, we report on the analyses of the porosity fraction in nanoporous Au leafs as a function of the fabrication process parameters. We dealloyed 60 μm-thick Au23Ag77 at.% leafs and we show that: a) for dealloying time till to 6 h, only a 450 nm-thick surface layer of the leafs assumes a nanoporous structure with a porosity fraction of 32%. For a dealloying time of 20 h the leafs result fragmented in small black pieces with a porosity fraction increased to 60%. b) After 600 °C-30 minutes annealing of the previous samples, the nanopores disappear due to the Au/residual Ag inter-diffusion. c) After a second dealloying process on the previously annealed samples, the surface nanoporous structure is, again, obtained with the porosity fraction increased to 50%.

  11. Biomimetic glass nanopores employing aptamer gates responsive to a small molecule†

    PubMed Central

    Abelow, Alexis E.; Schepelina, Olga; White, Ryan J.; Vallée-Bélisle, Alexis

    2011-01-01

    We report the preparation of 20 and 65 nm radii glass nanopores whose surface is modified with DNA aptamers controlling the molecular transport through the nanopores in response to small molecule binding. PMID:20865192

  12. Characterization of Noble Gas Ion Beam Fabricated Single Molecule Nanopore Detectors

    NASA Astrophysics Data System (ADS)

    Rollings, Ryan; Ledden, Bradley; Shultz, John; Fologea, Daniel; Li, Jiali; Chervinsky, John; Golovchenko, Jene

    2006-03-01

    Nanopores fabricated with low energy noble gas ion beams in a silicon nitride membrane can be employed as the fundamental element of single biomolecule detection and characterization devices [1,2]. With the help of X-ray Photoelectron Spectroscopy (XPS) and Rutherford Backscattering (RBS), we demonstrate that the electrical noise properties, and hence ultimate sensitivity of nanopore single molecule detectors depends on ion beam species and nanopore annealing conditions. .1. Li, J., D. Stein, C. McMullan, D. Branton, M.J. Aziz, and J.A. Golovchenko, Ion-beam sculpting at nanometre length scales. Nature, 2001. 412(12 July): p. 166-169. 2. Li, J., M. Gershow, D. Stein, E. Brandin, and J.A. Golovchenko, DNA Molecules and Configurations in a Solid-state Nanopore Microscope. Nature Materials, 2003. 2: p. 611-615.

  13. Utilization of microparticles in next-generation assays for microflow cytometers.

    PubMed

    Kim, Jason S; Ligler, Frances S

    2010-11-01

    Micron-sized particles have primarily been used in microfabricated flow cytometers for calibration purposes and proof-of-concept experiments. With increasing frequency, microparticles are serving as a platform for assays measured in these small analytical devices. Light scattering has been used to measure the agglomeration of antibody-coated particles in the presence of an antigen. Impedance detection is another technology being integrated into microflow cytometers for microparticle-based assays. Fluorescence is the most popular detection method in flow cytometry, enabling highly sensitive multiplexed assays. Finally, magnetic particles have also been used to measure antigen levels using a magnetophoretic micro-device. We review the progress of microparticle-based assays in microflow cytometry in terms of the advantages and limitations of each approach.

  14. Pirfenidone inhibits p38-mediated generation of procoagulant microparticles by human alveolar epithelial cells.

    PubMed

    Neri, Tommaso; Lombardi, Stefania; Faìta, Francesca; Petrini, Silvia; Balìa, Cristina; Scalise, Valentina; Pedrinelli, Roberto; Paggiaro, Pierluigi; Celi, Alessandro

    2016-08-01

    Pirfenidone is a drug recently approved for idiopathic pulmonary fibrosis but its mechanisms of action are partially unknown. We have previously demonstrated that the airways of patients with idiopathic pulmonary fibrosis contain procoagulant microparticles that activate coagulation factor X to its active form, Xa, a proteinase that signals fibroblast growth and differentiation, thus potentially contributing to the pathogenesis of the disease. We also reported that in vitro exposure of human alveolar cells to H2O2 causes microparticle generation. Since p38 activation is involved in microparticle generation in some cell models and p38 inhibition is one of the mechanisms of action of pirfenidone, we investigated the hypothesis that H2O2-induced generation of microparticles by alveolar cells is dependent on p38 phosphorylation and is inhibited by pirfenidone. H2O2 stimulation of alveolar cells caused p38 phosphorylation that was inhibited by pirfenidone. The drug also inhibited H2O2 induced microparticle generation as assessed by two independent methods (solid phase thrombin generation and flow cytometry). The shedding of microparticle-bound tissue factor activity was also inhibited by pirfenidone. Inhibition of p38-mediated generation of procoagulant microparticle is a previously unrecognized mechanism of action of the antifibrotic drug, pirfenidone. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Electrochemistry at Edge of Single Graphene Layer in a Nanopore

    PubMed Central

    Banerjee, Shouvik; Shim, Jiwook; Rivera, Jose; Jin, Xiaozhong; Estrada, David; Solovyeva, Vita; You, Xiuque; Pak, James; Pop, Eric; Aluru, Narayana; Bashir, Rashid

    2013-01-01

    We study the electrochemistry of single layer graphene edges using a nanopore-based structure consisting of stacked graphene and Al2O3 dielectric layers. Nanopores, with diameters ranging from 5 to 20 nm, are formed by an electron beam sculpting process on the stacked layers. This leads to unique edge structure which, along with the atomically thin nature of the embedded graphene electrode, demonstrates electrochemical current densities as high as 1.2 × 104 A/cm2. The graphene edge embedded structure offers a unique capability to study the electrochemical exchange at an individual graphene edge, isolated from the basal plane electrochemical activity. We also report ionic current modulation in the nanopore by biasing the embedded graphene terminal with respect to the electrodes in the fluid. The high electrochemical specific current density for a graphene nanopore-based device can have many applications in sensitive chemical and biological sensing, and energy storage devices. PMID:23249127

  16. Water desalination with a single-layer MoS2 nanopore

    PubMed Central

    Heiranian, Mohammad; Farimani, Amir Barati; Aluru, Narayana R.

    2015-01-01

    Efficient desalination of water continues to be a problem facing the society. Advances in nanotechnology have led to the development of a variety of nanoporous membranes for water purification. Here we show, by performing molecular dynamics simulations, that a nanopore in a single-layer molybdenum disulfide can effectively reject ions and allow transport of water at a high rate. More than 88% of ions are rejected by membranes having pore areas ranging from 20 to 60 Å2. Water flux is found to be two to five orders of magnitude greater than that of other known nanoporous membranes. Pore chemistry is shown to play a significant role in modulating the water flux. Pores with only molybdenum atoms on their edges lead to higher fluxes, which are ∼70% greater than that of graphene nanopores. These observations are explained by permeation coefficients, energy barriers, water density and velocity distributions in the pores. PMID:26465062

  17. Electrochemical Generation of a Hydrogen Bubble at a Recessed Platinum Nanopore Electrode.

    PubMed

    Chen, Qianjin; Luo, Long; White, Henry S

    2015-04-21

    We report the electrochemical generation of a single hydrogen bubble within the cavity of a recessed Pt nanopore electrode. The recessed Pt electrode is a conical pore in glass that contains a micrometer-scale Pt disk (1-10 μm radius) at the nanopore base and a nanometer-scale orifice (10-100 nm radius) that restricts diffusion of electroactive molecules and dissolved gas between the nanopore cavity and bulk solution. The formation of a H2 bubble at the Pt disk electrode in voltammetric experiments results from the reduction of H(+) in a 0.25 M H2SO4 solution; the liquid-to-gas phase transformation is indicated in the voltammetric response by a precipitous decrease in the cathodic current due to rapid bubble nucleation and growth within the nanopore cavity. Finite element simulations of the concentration distribution of dissolved H2 within the nanopore cavity, as a function of the H(+) reduction current, indicate that H2 bubble nucleation at the recessed Pt electrode surface occurs at a critical supersaturation concentration of ∼0.22 M, in agreement with the value previously obtained at (nonrecessed) Pt disk electrodes (∼0.25 M). Because the nanopore orifice limits the diffusion of H2 out of the nanopore cavity, an anodic peak corresponding to the oxidation of gaseous and dissolved H2 trapped in the recessed cavity is readily observed on the reverse voltammetric scan. Integration of the charge associated with the H2 oxidation peak is found to approach that of the H(+) reduction peak at high scan rates, confirming the assignment of the anodic peak to H2 oxidation. Preliminary results for the electrochemical generation of O2 bubbles from water oxidation at a recessed nanopore electrode are consistent with the electrogeneration of H2 bubbles.

  18. Structure-dependent water transport across nanopores of carbon nanotubes: toward selective gating upon temperature regulation.

    PubMed

    Zhao, Kuiwen; Wu, Huiying

    2015-04-28

    Determining water structure in nanopores and its influence on water transport behaviour is of great importance for understanding and regulating the transport across nanopores. Here we report an ultrafast-slow flow transition phenomenon for water transport across nanopores of carbon nanotubes owing to the change in water structure in nanopores induced by temperature. By performing extensive molecular dynamics simulations, we show the dependence of water transport behaviours on water structures. Our results indicate that owing to the change in water structure in nanopores, water flux across nanopores with certain pore sizes decreases sharply (nearly 3 orders of magnitude) with the decreasing temperature. This phenomenon is very sensitive to the pore size. The threshold temperatures for the occurrence of the ultrafast-slow flow transition for water transport are also determined for various pore sizes. These findings suggest a novel protocol for selective gating of water and proton conduction across nanopores and temperature-controlled drug release.

  19. Silicon microfluidic flow focusing devices for the production of size-controlled PLGA based drug loaded microparticles.

    PubMed

    Keohane, Kieran; Brennan, Des; Galvin, Paul; Griffin, Brendan T

    2014-06-05

    The increasing realisation of the impact of size and surface properties on the bio-distribution of drug loaded colloidal particles has driven the application of micro fabrication technologies for the precise engineering of drug loaded microparticles. This paper demonstrates an alternative approach for producing size controlled drug loaded PLGA based microparticles using silicon Microfluidic Flow Focusing Devices (MFFDs). Based on the precise geometry and dimensions of the flow focusing channel, microparticle size was successfully optimised by modifying the polymer type, disperse phase (Qd) flow rate, and continuous phase (Qc) flow rate. The microparticles produced ranged in sizes from 5 to 50 μm and were highly monodisperse (coefficient of variation <5%). A comparison of Ciclosporin (CsA) loaded PLGA microparticles produced by MFFDs vs conventional production techniques was also performed. MFFDs produced microparticles with a narrower size distribution profile, relative to the conventional approaches. In-vitro release kinetics of CsA was found to be influenced by the production technique, with the MFFD approach demonstrating the slowest rate of release over 7 days (4.99 ± 0.26%). Finally, MFFDs were utilised to produce pegylated microparticles using the block co-polymer, PEG-PLGA. In contrast to the smooth microparticles produced using PLGA, PEG-PLGA microparticles displayed a highly porous surface morphology and rapid CsA release, with 85 ± 6.68% CsA released after 24h. The findings from this study demonstrate the utility of silicon MFFDs for the precise control of size and surface morphology of PLGA based microparticles with potential drug delivery applications. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Phospholipid Binding Protein C Inhibitor (PCI) Is Present on Microparticles Generated In Vitro and In Vivo

    PubMed Central

    Einfinger, Katrin; Badrnya, Sigrun; Furtmüller, Margareta; Handschuh, Daniela; Lindner, Herbert; Geiger, Margarethe

    2015-01-01

    Protein C inhibitor is a secreted, non-specific serine protease inhibitor with broad protease reactivity. It binds glycosaminoglycans and anionic phospholipids, which can modulate its activity. Anionic phospholipids, such as phosphatidylserine are normally localized to the inner leaflet of the plasma membrane, but are exposed on activated and apoptotic cells and on plasma membrane-derived microparticles. In this report we show by flow cytometry that microparticles derived from cultured cells and activated platelets incorporated protein C inhibitor during membrane blebbing. Moreover, protein C inhibitor is present in/on microparticles circulating in normal human plasma as judged from Western blots, ELISAs, flow cytometry, and mass spectrometry. These plasma microparticles are mainly derived from megakaryocytes. They seem to be saturated with protein C inhibitor, since they do not bind added fluorescence-labeled protein C inhibitor. Heparin partially removed microparticle-bound protein C inhibitor, supporting our assumption that protein C inhibitor is bound via phospholipids. To assess the biological role of microparticle-bound protein C inhibitor we performed protease inhibition assays and co-precipitated putative binding partners on microparticles with anti-protein C inhibitor IgG. As judged from amidolytic assays microparticle-bound protein C inhibitor did not inhibit activated protein C or thrombin, nor did microparticles modulate the activity of exogenous protein C inhibitor. Among the proteins co-precipitating with protein C inhibitor, complement factors, especially complement factor 3, were most striking. Taken together, our data do not support a major role of microparticle-associated protein C inhibitor in coagulation, but rather suggest an interaction with proteins of the complement system present on these phospholipid vesicles. PMID:26580551

  1. Protein sequencing via nanopore based devices: a nanofluidics perspective

    NASA Astrophysics Data System (ADS)

    Chinappi, Mauro; Cecconi, Fabio

    2018-05-01

    Proteins perform a huge number of central functions in living organisms, thus all the new techniques allowing their precise, fast and accurate characterization at single-molecule level certainly represent a burst in proteomics with important biomedical impact. In this review, we describe the recent progresses in the developing of nanopore based devices for protein sequencing. We start with a critical analysis of the main technical requirements for nanopore protein sequencing, summarizing some ideas and methodologies that have recently appeared in the literature. In the last sections, we focus on the physical modelling of the transport phenomena occurring in nanopore based devices. The multiscale nature of the problem is discussed and, in this respect, some of the main possible computational approaches are illustrated.

  2. Optimizing Prednisolone Loading into Distiller's Dried Grain Kafirin Microparticles, and In vitro Release for Oral Delivery.

    PubMed

    Lau, Esther T L; Johnson, Stuart K; Williams, Barbara A; Mikkelsen, Deirdre; McCourt, Elizabeth; Stanley, Roger A; Mereddy, Ram; Halley, Peter J; Steadman, Kathryn J

    2017-05-19

    Kafirin microparticles have potential as colon-targeted delivery systems because of their ability to protect encapsulated material from digestive processes of the upper gastrointestinal tract (GIT). The aim was to optimize prednisolone loading into kafirin microparticles, and investigate their potential as an oral delivery system. Response surface methodology (RSM) was used to predict the optimal formulation of prednisolone loaded microparticles. Prednisolone release from the microparticles was measured in simulated conditions of the GIT. The RSM models were inadequate for predicting the relationship between starting quantities of kafirin and prednisolone, and prednisolone loading into microparticles. Compared to prednisolone released in the simulated gastric and small intestinal conditions, no additional drug release was observed in simulated colonic conditions. Hence, more insight into factors affecting drug loading into kafirin microparticles is required to improve the robustness of the RSM model. This present method of formulating prednisolone-loaded kafirin microparticles is unlikely to offer clinical benefits over commercially available dosage forms. Nevertheless, the overall amount of prednisolone released from the kafirin microparticles in conditions simulating the human GIT demonstrates their ability to prevent the release of entrapped core material. Further work developing the formulation methods may result in a delivery system that targets the lower GIT.

  3. Catalytic nanoporous membranes

    DOEpatents

    Pellin, Michael J; Hryn, John N; Elam, Jeffrey W

    2013-08-27

    A nanoporous catalytic membrane which displays several unique features Including pores which can go through the entire thickness of the membrane. The membrane has a higher catalytic and product selectivity than conventional catalysts. Anodic aluminum oxide (AAO) membranes serve as the catalyst substrate. This substrate is then subjected to Atomic Layer Deposition (ALD), which allows the controlled narrowing of the pores from 40 nm to 10 nm in the substrate by deposition of a preparatory material. Subsequent deposition of a catalytic layer on the inner surfaces of the pores reduces pore sizes to less than 10 nm and allows for a higher degree of reaction selectivity. The small pore sizes allow control over which molecules enter the pores, and the flow-through feature can allow for partial oxidation of reactant species as opposed to complete oxidation. A nanoporous separation membrane, produced by ALD is also provided for use in gaseous and liquid separations. The membrane has a high flow rate of material with 100% selectivity. Also provided is a method for producing a catalytic membrane having flow-through pores and discreet catalytic clusters adhering to the inside surfaces of the pores.

  4. Nanochannel Device with Embedded Nanopore: a New Approach for Single-Molecule DNA Analysis and Manipulation

    NASA Astrophysics Data System (ADS)

    Zhang, Yuning; Reisner, Walter

    2013-03-01

    Nanopore and nanochannel based devices are robust methods for biomolecular sensing and single DNA manipulation. Nanopore-based DNA sensing has attractive features that make it a leading candidate as a single-molecule DNA sequencing technology. Nanochannel based extension of DNA, combined with enzymatic or denaturation-based barcoding schemes, is already a powerful approach for genome analysis. We believe that there is revolutionary potential in devices that combine nanochannels with embedded pore detectors. In particular, due to the fast translocation of a DNA molecule through a standard nanopore configuration, there is an unfavorable trade-off between signal and sequence resolution. With a combined nanochannel-nanopore device, based on embedding a pore inside a nanochannel, we can in principle gain independent control over both DNA translocation speed and sensing signal, solving the key draw-back of the standard nanopore configuration. We demonstrate that we can optically detect successful translocation of DNA from the nanochannel out through the nanopore, a possible method to 'select' a given barcode for further analysis. In particular, we show that in equilibrium DNA will not escape through an embedded sub-persistence length nanopore, suggesting that the pore could be used as a nanoscale window through which to interrogate a nanochannel extended DNA molecule. Furthermore, electrical measurements through the nanopore are performed, indicating that DNA sensing is feasible using the nanochannel-nanopore device.

  5. Properties of iopamidol-incorporated poly(vinyl alcohol) microparticle as an X-ray imaging flow tracer.

    PubMed

    Ahn, Sungsook; Jung, Sung Yong; Lee, Jin Pyung; Lee, Sang Joon

    2011-02-10

    We have recently reported on poly(vinyl alcohol) microparticles containing X-ray contrast agent, iopamidol, designed as a flow tracer working in synchrotron X-ray imaging ( Biosens. Bioelectron. 2010 , 25 , 1571 ). Although iopamidol is physically encapsulated in the microparticles, it displays a great contrast enhancement and stable feasibility in in vitro human blood pool. Nonetheless, a direct relation between the absolute amount of incorporated iopamidol and the enhancement in imaging efficiency was not observed. In this study, physical properties of the designed microparticle are systematically investigated experimentally with theoretical interpretation to correlate an enhancement in X-ray imaging efficiency. The compositional ratio of X-ray contrast agent in polymeric microparticle is controlled as 1/1 and 10/1 [contrast agent/polymer microparticle (w/w)] with changed degree of cross-linkings. Flory-Huggins interaction parameter (χ), retractive force (τ) and degree of swelling of the designed polymeric microparticles are investigated. In addition, the hydrodynamic size (D(H)) and ζ-potential are evaluated in terms of environment responsiveness. The physical properties of the designed flow tracer microparticles under a given condition are observed to be strongly related with the X-ray absorption efficiency, which are also supported by the Beer-Lambert-Bouguer law. The designed microparticles are almost nontoxic with a reasonable concentration and time period, enough to be utilized as a flow tracer in various biomedical applications. This study would contribute to the basic understanding on the physical property connected with the imaging efficiency of contrast agents.

  6. A study on arrangement characteristics of microparticles in sedimentation on flat and round substrates

    NASA Astrophysics Data System (ADS)

    Yeo, Eunju; Son, Minhee; Kim, Kwanoh; Kim, Jeong Hwan; Yoo, Yeong-Eun; Choi, Doo-Sun; Kim, Jungchul; Yoon, Seok Ho; Yoon, Jae Sung

    2017-12-01

    Recent advances of microfabrication techniques have enabled diverse structures and devices on the microscale. This fabrication method using microparticles is one of the most promising technologies because it can provide a cost effective process for large areas. So, many researchers are studying modulation and manipulation of the microparticles in solution to obtain a proper arrangement. However, the microparticles are in sedimentation status during the process in many cases, which makes it difficult to control their arrangement. In this study, droplets containing microparticles were placed on a substrate with minimal force and we investigated the arrangement of these microparticles after evaporation of the liquid. Experiments have been performed with upward and downward substrates to change the direction of gravity. The geometry of substrates was also changed, which were flat or round. The results show that the arrangement depends on the size of particles and gravity and geometry of the substrate. The arrangement also depends on the movement of the contact line of the droplets, which may recede or be pinned during evaporation. This study is expected to provide a method of the fabrication process for microparticles which may not be easily manipulated due to sedimentation.

  7. Study on the Characteristics of Gas Molecular Mean Free Path in Nanopores by Molecular Dynamics Simulations

    PubMed Central

    Liu, Qixin; Cai, Zhiyong

    2014-01-01

    This paper presents studies on the characteristics of gas molecular mean free path in nanopores by molecular dynamics simulation. Our study results indicate that the mean free path of all molecules in nanopores depend on both the radius of the nanopore and the gas-solid interaction strength. Besides mean free path of all molecules in the nanopore, this paper highlights the gas molecular mean free path at different positions of the nanopore and the anisotropy of the gas molecular mean free path at nanopores. The molecular mean free path varies with the molecule’s distance from the center of the nanopore. The least value of the mean free path occurs at the wall surface of the nanopore. The present paper found that the gas molecular mean free path is anisotropic when gas is confined in nanopores. The radial gas molecular mean free path is much smaller than the mean free path including all molecular collisions occuring in three directions. Our study results also indicate that when gas is confined in nanopores the gas molecule number density does not affect the gas molecular mean free path in the same way as it does for the gas in unbounded space. These study results may bring new insights into understanding the gas flow’s characteristic at nanoscale. PMID:25046745

  8. Selectively Sized Graphene-Based Nanopores for in Situ Single Molecule Sensing

    PubMed Central

    2015-01-01

    The use of nanopore biosensors is set to be extremely important in developing precise single molecule detectors and providing highly sensitive advanced analysis of biological molecules. The precise tailoring of nanopore size is a significant step toward achieving this, as it would allow for a nanopore to be tuned to a corresponding analyte. The work presented here details a methodology for selectively opening nanopores in real-time. The tunable nanopores on a quartz nanopipette platform are fabricated using the electroetching of a graphene-based membrane constructed from individual graphene nanoflakes (ø ∼30 nm). The device design allows for in situ opening of the graphene membrane, from fully closed to fully opened (ø ∼25 nm), a feature that has yet to be reported in the literature. The translocation of DNA is studied as the pore size is varied, allowing for subfeatures of DNA to be detected with slower DNA translocations at smaller pore sizes, and the ability to observe trends as the pore is opened. This approach opens the door to creating a device that can be target to detect specific analytes. PMID:26204996

  9. Single-molecule Protein Unfolding in Solid State Nanopores

    PubMed Central

    Talaga, David S.; Li, Jiali

    2009-01-01

    We use single silicon nitride nanopores to study folded, partially folded and unfolded single proteins by measuring their excluded volumes. The DNA-calibrated translocation signals of β-lactoglobulin and histidine-containing phosphocarrier protein match quantitatively with that predicted by a simple sum of the partial volumes of the amino acids in the polypeptide segment inside the pore when translocation stalls due to the primary charge sequence. Our analysis suggests that the majority of the protein molecules were linear or looped during translocation and that the electrical forces present under physiologically relevant potentials can unfold proteins. Our results show that the nanopore translocation signals are sensitive enough to distinguish the folding state of a protein and distinguish between proteins based on the excluded volume of a local segment of the polypeptide chain that transiently stalls in the nanopore due to the primary sequence of charges. PMID:19530678

  10. Advances in nanopore sensing promises to transform healthcare.

    PubMed

    Haque, Farzin; Wang, Shaoying; Wu, Taoxiang; Guo, Peixuan

    2017-08-01

    International Conference on Nanopore Technology (Shenzhen), 30 March-1 April 2017, Shenzhen, China The International Conference on Nanopore Technology (Shenzhen) was held from 30 March to 1 April 2017 in Shenzhen, China. The goal of the meeting was threefold: leverage the unique properties of nanopore technology to promote transformative advances in medicine, encourage cross-disciplinary collaborations in the research community within China and abroad; and discuss critical challenges that need to be addressed to rapidly advance the field. The meeting was chaired by Peixuan Guo, Endowed chair professor and Director of The Center for RNA Nanobiotechnology & Nanomedicine at The Ohio State University, USA and co-chaired by Xian-En Zhang, distinguished professor of the Institute of Biophysics, Chinese Academy of Sciences, China. The conference was attended by more than 300 academic researchers, hospital administrators, government leaders and scientists from many disciplines across the country from both academic institutions and industry.

  11. On the origin of microparticles: From “platelet dust” to mediators of intercellular communication

    PubMed Central

    Hargett, Leslie A.; Bauer, Natalie N.

    2013-01-01

    Microparticles are submicron vesicles shed from a variety of cells. Peter Wolf first identified microparticles in the midst of ongoing blood coagulation research in 1967 as a product of platelets. He termed them platelet dust. Although initially thought to be useless cellular trash, decades of research focused on the tiny vesicles have defined their roles as participators in coagulation, cellular signaling, vascular injury, and homeostasis. The purpose of this review is to highlight the science leading up to the discovery of microparticles, feature discoveries made by key contributors to the field of microparticle research, and discuss their positive and negative impact on the pulmonary circulation. PMID:24015332

  12. Buckling Causes Nonlinear Dynamics of Filamentous Viruses Driven through Nanopores.

    PubMed

    McMullen, Angus; de Haan, Hendrick W; Tang, Jay X; Stein, Derek

    2018-02-16

    Measurements and Langevin dynamics simulations of filamentous viruses driven through solid-state nanopores reveal a superlinear rise in the translocation velocity with driving force. The mobility also scales with the length of the virus in a nontrivial way that depends on the force. These dynamics are consequences of the buckling of the leading portion of a virus as it emerges from the nanopore and is put under compressive stress by the viscous forces it encounters. The leading tip of a buckled virus stalls and this reduces the total viscous drag force. We present a scaling theory that connects the solid mechanics to the nonlinear dynamics of polyelectrolytes translocating nanopores.

  13. Top-down solid-phase fabrication of nanoporous cadmium oxide architectures.

    PubMed

    Yu, Haidong; Wang, Deshen; Han, Ming-Yong

    2007-02-28

    In this article, we have demonstrated one-step solid-phase transformation from high-quality cadmium carbonate microcrystals into highly nanoporous cadmium oxide. The high crystal quality of cadmium carbonate is critical for the successful fabrication of porous nanoarchitectures with predetermined morphology and well-controlled internal structure. This novel strategy has a good potential to prepare nanoporous materials at a large scale by using perfect monolithic carbonate crystals, and it is also useful to synthesize different nanoporous materials on metal-oxide-coated substrates. Meanwhile, this simple thermal transformation of cadmium carbonate into porous structures has further been extended to convert calcium carbonate into such porous structures.

  14. Buckling Causes Nonlinear Dynamics of Filamentous Viruses Driven through Nanopores

    NASA Astrophysics Data System (ADS)

    McMullen, Angus; de Haan, Hendrick W.; Tang, Jay X.; Stein, Derek

    2018-02-01

    Measurements and Langevin dynamics simulations of filamentous viruses driven through solid-state nanopores reveal a superlinear rise in the translocation velocity with driving force. The mobility also scales with the length of the virus in a nontrivial way that depends on the force. These dynamics are consequences of the buckling of the leading portion of a virus as it emerges from the nanopore and is put under compressive stress by the viscous forces it encounters. The leading tip of a buckled virus stalls and this reduces the total viscous drag force. We present a scaling theory that connects the solid mechanics to the nonlinear dynamics of polyelectrolytes translocating nanopores.

  15. Engineering of highly ordered TiO2 nanopore arrays by anodization

    NASA Astrophysics Data System (ADS)

    Wang, Huijie; Huang, Zhennan; Zhang, Li; Ding, Jie; Ma, Zhaoxia; Liu, Yong; Kou, Shengzhong; Yang, Hangsheng

    2016-07-01

    Finite element analysis was used to simulate the current density distributions in the TiO2 barrier layer formed at the initial stage of Ti anodization. The morphology modification of the barrier layer was found to induce current density distribution change. By starting the anodization with proper TiO2 barrier layer morphology, the current density distribution can be adjusted to favor the formation of either nanotube arrays or nanopore arrays of anodic TiO2. We also found that the addition of sodium acetate into the electrolyte suppressed both the field-assisted chemical dissolution of TiO2 and the TiF62- hydrolysis induced TiO2 deposition during anodization, and thus further favored the nanopore formation. Accordingly, highly ordered anodic TiO2 nanopore arrays, similar to anodic aluminum oxide nanopore arrays, were successfully prepared.

  16. Alumina plate containing photosystem I reaction center complex oriented inside plate-penetrating silica nanopores.

    PubMed

    Kamidaki, Chihiro; Kondo, Toru; Noji, Tomoyasu; Itoh, Tetsuji; Yamaguchi, Akira; Itoh, Shigeru

    2013-08-22

    The photosynthetic photosystem I reaction center complex (PSI-RC), which has a molecular diameter of 21 nm with 100 pigments, was incorporated into silica nanopores with a 100-nm diameter that penetrates an alumina plate of 60-μm thickness to make up an inorganic-biological hybrid photocell. PSI-RCs, purified from a thermophilic cyanobacterium, were stable inside the nanopores and rapidly photoreduced a mediator dye methyl viologen. The reduced dye was more stable inside nanopores suggesting the decrease of dissolved oxygen. The analysis by a cryogenic electron spin paramagnetic resonance indicated the oriented arrangement of RCs inside the 100-nm nanopores, with their surface parallel to the silica wall and perpendicular to the plane of the alumina plate. PSI RC complex in the semicrystalline orientation inside silica nanopores can be a new type of light energy conversion unit to supply strong reducing power selectively to other molecules inside or outside nanopores.

  17. Spray-dried nanofibrillar cellulose microparticles for sustained drug release.

    PubMed

    Kolakovic, Ruzica; Laaksonen, Timo; Peltonen, Leena; Laukkanen, Antti; Hirvonen, Jouni

    2012-07-01

    Nanofibrillar cellulose (also referred to as cellulose nanofibers, nanocellulose, microfibrillated or nanofibrillated cellulose) has gained a lot of attention in recent years in different research areas including biomedical applications. In this study we have evaluated the applicability of nanofibrillar cellulose (NFC) as a material for the formation of matrix systems for sustained drug delivery. For that purpose, drug loaded NFC microparticles were produced by a spray drying method. The microparticles were characterized in terms of size and morphology, total drug loading, and physical state of the encapsulated drug. Drug release from the microparticles was assessed by dissolution tests, and suitable mathematical models were used to explain the drug releasing kinetics. The particles had spherical shapes with diameters of around 5 μm; the encapsulated drug was mainly in amorphous form. The controlled drug release was achieved. The drug releasing curves were fitted to a mathematical model describing the drug releasing kinetics from a spherical matrix. Different drugs had different release kinetics, which was a consequence of several factors, including different solubilities of the drugs in the chosen medium and different affinities of the drugs to the NFC. It can be concluded that NFC microparticles can sustain drug release by forming a tight fiber network and thus limit drug diffusion from the system. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Preparation of porous yttrium oxide microparticles by gelation of ammonium alginate in aqueous solution containing yttrium ions.

    PubMed

    Kawashita, Masakazu; Matsui, Naoko; Li, Zhixia; Miyazaki, Toshiki

    2010-06-01

    Porous Y2O3 microparticles 500 microm in size were obtained, when 1 wt%-ammonium alginate aqueous solution was dropped into 0.5 M-YCl3 aqueous solution by a Pasteur pipette and the resultant gel microparticles were heat-treated at 1100 degrees C. Small pores less than 1 microm were formed in the microparticles by the heat treatment. The bulk density of the heat-treated microparticle was as low as 0.66 g cm(-3). The chemical durability of the heat-treated microparticles in simulated body fluid at pH = 6 and 7 was high enough for clinical application of in situ radiotherapy. Although the size of the microparticles should be decreased to around 25 microm using atomizing device such as spray gun for clinical application, we found that the porous Y2O3 microparticles with high chemical durability and low density can be obtained by utilizing gelation of ammonium alginate in YCl3 aqueous solution in this study.

  19. Properties of gelatin-based films incorporated with chitosan-coated microparticles charged with rutin.

    PubMed

    Dammak, Ilyes; Bittante, Ana Mônica Quinta Barbosa; Lourenço, Rodrigo Vinicius; do Amaral Sobral, Paulo José

    2017-08-01

    The aim of this study was development an active film based on gelatin incorporated with antioxidant, rutin carried into microparticles. The complexation between oppositely charged lecithin and chitosan was applied to prepare the chitosan-coated microparticles. The generated microparticles had an average size of 520±4nm and a span of 0.3 were formulated by a rotor-stator homogenize at the homogenization speed 10,000rpm. Composite films were prepared by incorporating chitosan-coated microparticles, at various concentrations (0.05, 0.1, 0.5, or 1% (based on the weight of the gelatin powder)) in the gelatin-based films. For the prepared films, the results showed that obtained physicochemical, water vapor barrier, and mechanical were compared with native gelatin film with a slight decrease for chitosan concentration higher than 0.5%. The microstructure studies done by scanning electron microscopes, revealed different micropores embedded with oil resulting from the incorporation of the microparticles into the gelatin matrix. Moreover, the calorimetric results were comparable to those of gelatin control film with T g value 45°C and increased crystallinity percentage with increasing incorporation of microparticles. This original concept of composite biodegradable films may thus be a good alternative to incorporate liposoluble active compounds to design an active packaging with good properties. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Paclitaxel-loaded polymeric microparticles: Quantitative relationships between in vitro drug release rate and in vivo pharmacodynamics

    PubMed Central

    Tsai, Max; Lu, Ze; Wientjes, M. Guillaume; Au, Jessie L.-S.

    2013-01-01

    Intraperitoneal therapy (IP) has demonstrated survival advantages in patients with peritoneal cancers, but has not become a widely practiced standard-of-care in part due to local toxicity and sub-optimal drug delivery. Paclitaxel-loaded, polymeric microparticles were developed to overcome these limitations. The present study evaluated the effects of microparticle properties on paclitaxel release (extent and rate) and in vivo pharmacodynamics. In vitro paclitaxel release from microparticles with varying physical characteristics (i.e., particle size, copolymer viscosity and composition) was evaluated. A method was developed to simulate the dosing rate and cumulative dose released in the peritoneal cavity based on the in vitro release data. The relationship between the simulated drug delivery and treatment outcomes of seven microparticle compositions was studied in mice bearing IP human pancreatic tumors, and compared to that of the intravenous Cremophor micellar paclitaxel solution used off-label in previous IP studies. Paclitaxel release from polymeric microparticles in vitro was multi-phasic; release was greater and more rapid from microparticles with lower polymer viscosities and smaller diameters (e.g., viscosity of 0.17 vs. 0.67 dl/g and diameter of 5–6 vs. 50–60 μm). The simulated drug release in the peritoneal cavity linearly correlated with treatment efficacy in mice (r2>0.8, p<0.001). The smaller microparticles, which distribute more evenly in the peritoneal cavity compared to the large microparticles, showed greater dose efficiency. For single treatment, the microparticles demonstrated up to 2-times longer survival extension and 4-times higher dose efficiency, relative to the paclitaxel/Cremophor micellar solution. Upon repeated dosing, the paclitaxel/Cremophor micellar solution showed cumulative toxicity whereas the microparticle that yielded 2-times longer survival did not display cumulative toxicity. The efficacy of IP therapy depended on both

  1. Engineering fungal morphology for enhanced production of hydrolytic enzymes by Aspergillus oryzae SBS50 using microparticles.

    PubMed

    Singh, Bijender

    2018-06-01

    Effect of microparticles and silver nanoparticles was studied on the production of hydrolytic enzymes by a potent phytase-producing mould, Aspergillus oryzae SBS50. Addition of microparticles, viz. talc powder and aluminum oxide enhanced phytase production from 2894 to 3903 and 2847 to 4204 U/L, cellulase from 2529 to 4931 and 2455 to 3444 U/L, xylanase from 9067 to 9642 and 9994 to 14,783 U/L, amylase from 5880 to 11,000 and 6130 to 13,145 U/L, respectively. Fungal morphology was also engineered by the use of microparticles. Fungal pellet size was significantly reduced (~ 90%) by the addition of microparticles. Fermentation time was reduced from 4 to 3 days after the addition of microparticles, thus increasing the productivity of the enzymes significantly. These results confirmed the importance of microparticles in engineering fungal morphology for enhanced production of hydrolytic enzymes.

  2. Fundamental Bounds for Sequence Reconstruction from Nanopore Sequencers.

    PubMed

    Magner, Abram; Duda, Jarosław; Szpankowski, Wojciech; Grama, Ananth

    2016-06-01

    Nanopore sequencers are emerging as promising new platforms for high-throughput sequencing. As with other technologies, sequencer errors pose a major challenge for their effective use. In this paper, we present a novel information theoretic analysis of the impact of insertion-deletion (indel) errors in nanopore sequencers. In particular, we consider the following problems: (i) for given indel error characteristics and rate, what is the probability of accurate reconstruction as a function of sequence length; (ii) using replicated extrusion (the process of passing a DNA strand through the nanopore), what is the number of replicas needed to accurately reconstruct the true sequence with high probability? Our results provide a number of important insights: (i) the probability of accurate reconstruction of a sequence from a single sample in the presence of indel errors tends quickly (i.e., exponentially) to zero as the length of the sequence increases; and (ii) replicated extrusion is an effective technique for accurate reconstruction. We show that for typical distributions of indel errors, the required number of replicas is a slow function (polylogarithmic) of sequence length - implying that through replicated extrusion, we can sequence large reads using nanopore sequencers. Moreover, we show that in certain cases, the required number of replicas can be related to information-theoretic parameters of the indel error distributions.

  3. Probe DNA-Cisplatin Interaction with Solid-State Nanopores

    NASA Astrophysics Data System (ADS)

    Zhou, Zhi; Hu, Ying; Li, Wei; Xu, Zhi; Wang, Pengye; Bai, Xuedong; Shan, Xinyan; Lu, Xinghua; Nanopore Collaboration

    2014-03-01

    Understanding the mechanism of DNA-cisplatin interaction is essential for clinical application and novel drug design. As an emerging single-molecule technology, solid-state nanopore has been employed in biomolecule detection and probing DNA-molecule interactions. Herein, we reported a real-time monitoring of DNA-cisplatin interaction by employing solid-state SiN nanopores. The DNA-cisplatin interacting process is clearly classified into three stages by measuring the capture rate of DNA-cisplatin adducts. In the first stage, the negative charged DNA molecules were partially discharged due to the bonding of positive charged cisplatin and forming of mono-adducts. In the second stage, forming of DNA-cisplatin di-adducts with the adjacent bases results in DNA bending and softening. The capture rate increases since the softened bi-adducts experience a lower barrier to thread into the nanopores. In the third stage, complex structures, such as micro-loop, are formed and the DNA-cisplatin adducts are aggregated. The capture rate decreases to zero as the aggregated adduct grows to the size of the pore. The characteristic time of this stage was found to be linear with the diameter of the nanopore and this dynamic process can be described with a second-order reaction model. We are grateful to Laboratory of Microfabrication, Dr. Y. Yao, and Prof. R.C. Yu (Institute of Physics, Chinese Academy of Sciences) for technical assistance.

  4. Development and Evaluation of Chitosan Microparticles Based Dry Powder Inhalation Formulations of Rifampicin and Rifabutin.

    PubMed

    Pai, Rohan V; Jain, Rajesh R; Bannalikar, Anilkumar S; Menon, Mala D

    2016-04-01

    The lung is the primary entry site and target for Mycobacterium tuberculosis; more than 80% of the cases reported worldwide are of pulmonary tuberculosis. Hence, direct delivery of anti-tubercular drugs to the lung would be beneficial in reducing both, the dose required, as well as the duration of therapy for pulmonary tuberculosis. In the present study, microsphere-based dry powder inhalation systems of the anti-tubercular drugs, rifampicin and rifabutin, were developed and evaluated, with a view to achieve localized and targeted delivery of these drugs to the lung. The drug-loaded chitosan microparticles were prepared by an ionic gelation method, followed by spray-drying to obtain respirable particles. The microparticles were evaluated for particle size and drug release. The drug-loaded microparticles were then adsorbed onto an inhalable lactose carrier and characterized for in vitro lung deposition on an Andersen Cascade Impactor (ACI) followed by in vitro uptake study in U937 human macrophage cell lines. In vivo toxicity of the developed formulations was evaluated using Sprague Dawley rats. Both rifampicin and rifabutin-loaded microparticles had MMAD close to 5 μm and FPF values of 21.46% and 29.97%, respectively. In vitro release study in simulated lung fluid pH 7.4 showed sustained release for 12 hours for rifampicin microparticles and up to 96 hours for rifabutin microparticles, the release being dependent on both swelling of the polymer and solubility of the drugs in the dissolution medium. In vitro uptake studies in U937 human macrophage cell line suggested that microparticles were internalized within the macrophages. In vivo acute toxicity study of the microparticles in Sprague Dawley rats revealed no significant evidence for local adverse effects. Thus, spray-dried microparticles of the anti-tubercular drugs, rifampicin and rifabutin, could prove to be an improved, targeted, and efficient system for treatment of tuberculosis.

  5. Microparticle Shedding from Neural Progenitor Cells and Vascular Compartment Cells Is Increased in Ischemic Stroke.

    PubMed

    Chiva-Blanch, Gemma; Suades, Rosa; Crespo, Javier; Peña, Esther; Padró, Teresa; Jiménez-Xarrié, Elena; Martí-Fàbregas, Joan; Badimon, Lina

    2016-01-01

    Ischemic stroke has shown to induce platelet and endothelial microparticle shedding, but whether stroke induces microparticle shedding from additional blood and vascular compartment cells is unclear. Neural precursor cells have been shown to replace dying neurons at sites of brain injury; however, if neural precursor cell activation is associated to microparticle shedding, and whether this activation is maintained at long term and associates to stroke type and severity remains unknown. We analyzed neural precursor cells and blood and vascular compartment cells microparticle shedding after an acute ischemic stroke. Forty-four patients were included in the study within the first 48h after the onset of stroke. The cerebral lesion size was evaluated at 3-7 days of the stroke. Circulating microparticles from neural precursor cells and blood and vascular compartment cells (platelets, endothelial cells, erythrocytes, leukocytes, lymphocytes, monocytes and smooth muscle cells) were analyzed by flow cytometry at the onset of stroke and at 7 and 90 days. Forty-four age-matched high cardiovascular risk subjects without documented vascular disease were used as controls. Compared to high cardiovascular risk controls, patients showed higher number of neural precursor cell- and all blood and vascular compartment cell-derived microparticles at the onset of stroke, and after 7 and 90 days. At 90 days, neural precursor cell-derived microparticles decreased and smooth muscle cell-derived microparticles increased compared to levels at the onset of stroke, but only in those patients with the highest stroke-induced cerebral lesions. Stroke increases blood and vascular compartment cell and neural precursor cell microparticle shedding, an effect that is chronically maintained up to 90 days after the ischemic event. These results show that stroke induces a generalized blood and vascular cell activation and the initiation of neuronal cell repair process after stroke. Larger cerebral lesions

  6. A Microparticle/Hydrogel Combination Drug-Delivery System for Sustained Release of Retinoids

    PubMed Central

    Gao, Song-Qi; Maeda, Tadao; Okano, Kiichiro; Palczewski, Krzysztof

    2012-01-01

    Purpose. To design and develop a drug-delivery system containing a combination of poly(d,l-lactide-co-glycolide) (PLGA) microparticles and alginate hydrogel for sustained release of retinoids to treat retinal blinding diseases that result from an inadequate supply of retinol and generation of 11-cis-retinal. Methods. To study drug release in vivo, either the drug-loaded microparticle–hydrogel combination was injected subcutaneously or drug-loaded microparticles were injected intravitreally into Lrat−/− mice. Orally administered 9-cis-retinoids were used for comparison and drug concentrations in plasma were determined by HPLC. Electroretinography (ERG) and both chemical and histologic analyses were used to evaluate drug effects on visual function and morphology. Results. Lrat−/− mice demonstrated sustained drug release from the microparticle/hydrogel combination that lasted 4 weeks after subcutaneous injection. Drug concentrations in plasma of the control group treated with the same oral dose rose to higher levels for 6−7 hours but then dropped markedly by 24 hours. Significantly increased ERG responses and a markedly improved retinal pigmented epithelium (RPE)–rod outer segment (ROS) interface were observed after subcutaneous injection of the drug-loaded delivery combination. Intravitreal injection of just 2% of the systemic dose of drug-loaded microparticles provided comparable therapeutic efficacy. Conclusions. Sustained release of therapeutic levels of 9-cis-retinoids was achieved in Lrat−/− mice by subcutaneous injection in a microparticle/hydrogel drug-delivery system. Both subcutaneous and intravitreal injections of drug-loaded microparticles into Lrat−/− mice improved visual function and retinal structure. PMID:22918645

  7. Circulating cell-derived microparticles in patients with minimally symptomatic obstructive sleep apnoea.

    PubMed

    Ayers, L; Ferry, B; Craig, S; Nicoll, D; Stradling, J R; Kohler, M

    2009-03-01

    Moderate-severe obstructive sleep apnoea (OSA) has been associated with several pro-atherogenic mechanisms and increased cardiovascular risk, but it is not known if minimally symptomatic OSA has similar effects. Circulating cell-derived microparticles have been shown to have pro-inflammatory, pro-coagulant and endothelial function-impairing effects, as well as to predict subclinical atherosclerosis and cardiovascular risk. In 57 patients with minimally symptomatic OSA, and 15 closely matched control subjects without OSA, AnnexinV-positive, platelet-, leukocyte- and endothelial cell-derived microparticles were measured by flow cytometry. In patients with OSA, median (interquartile range) levels of AnnexinV-positive microparticles were significantly elevated compared with control subjects: 2,586 (1,566-3,964) microL(-1) versus 1,206 (474-2,501) microL(-1), respectively. Levels of platelet-derived and leukocyte-derived microparticles were also significantly higher in patients with OSA (2,267 (1,102-3,592) microL(-1) and 20 (14-31) microL(-1), respectively) compared with control subjects (925 (328-2,068) microL(-1) and 15 (5-23) microL(-1), respectively). Endothelial cell-derived microparticle levels were similar in patients with OSA compared with control subjects (13 (8-25) microL(-1) versus 11 (6-17) microL(-1)). In patients with minimally symptomatic obstructive sleep apnoea, levels of AnnexinV-positive, platelet- and leukocyte-derived microparticles are elevated when compared with closely matched control subjects without obstructive sleep apnoea. These findings suggest that these patients may be at increased cardiovascular risk, despite being minimally symptomatic.

  8. Bioresponsive Materials for Drug Delivery Based on Carboxymethyl Chitosan/Poly(γ-Glutamic Acid) Composite Microparticles

    PubMed Central

    Yan, Xiaoting; Tong, Zongrui; Chen, Yu; Mo, Yanghe; Feng, Huaiyu; Li, Peng; Qu, Xiaosai; Jin, Shaohua

    2017-01-01

    Carboxymethyl chitosan (CMCS) microparticles are a potential candidate for hemostatic wound dressing. However, its low swelling property limits its hemostatic performance. Poly(γ-glutamic acid) (PGA) is a natural polymer with excellent hydrophilicity. In the current study, a novel CMCS/PGA composite microparticles with a dual-network structure was prepared by the emulsification/internal gelation method. The structure and thermal stability of the composite were determined by Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), scanning electron microscope (SEM), X-ray photoelectron spectroscopy (XPS), and thermogravimetric analysis (TGA). The effects of preparation conditions on the swelling behavior of the composite were investigated. The results indicate that the swelling property of CMCS/PGA composite microparticles is pH sensitive. Levofloxacin (LFX) was immobilized in the composite microparticles as a model drug to evaluate the drug delivery performance of the composite. The release kinetics of LFX from the composite microparticles with different structures was determined. The results suggest that the CMCS/PGA composite microparticles are an excellent candidate carrier for drug delivery. PMID:28452963

  9. Noise in solid-state nanopores

    PubMed Central

    Smeets, R. M. M.; Keyser, U. F.; Dekker, N. H.; Dekker, C.

    2008-01-01

    We study ionic current fluctuations in solid-state nanopores over a wide frequency range and present a complete description of the noise characteristics. At low frequencies (f ≲ 100 Hz) we observe 1/f-type of noise. We analyze this low-frequency noise at different salt concentrations and find that the noise power remarkably scales linearly with the inverse number of charge carriers, in agreement with Hooge's relation. We find a Hooge parameter α = (1.1 ± 0.1) × 10−4. In the high-frequency regime (f ≳ 1 kHz), we can model the increase in current power spectral density with frequency through a calculation of the Johnson noise. Finally, we use these results to compute the signal-to-noise ratio for DNA translocation for different salt concentrations and nanopore diameters, yielding the parameters for optimal detection efficiency. PMID:18184817

  10. Noise in solid-state nanopores.

    PubMed

    Smeets, R M M; Keyser, U F; Dekker, N H; Dekker, C

    2008-01-15

    We study ionic current fluctuations in solid-state nanopores over a wide frequency range and present a complete description of the noise characteristics. At low frequencies (f approximately < 100 Hz) we observe 1/f-type of noise. We analyze this low-frequency noise at different salt concentrations and find that the noise power remarkably scales linearly with the inverse number of charge carriers, in agreement with Hooge's relation. We find a Hooge parameter alpha = (1.1 +/- 0.1) x 10(-4). In the high-frequency regime (f approximately > 1 kHz), we can model the increase in current power spectral density with frequency through a calculation of the Johnson noise. Finally, we use these results to compute the signal-to-noise ratio for DNA translocation for different salt concentrations and nanopore diameters, yielding the parameters for optimal detection efficiency.

  11. Capture, Unfolding, and Detection of Individual tRNA Molecules Using a Nanopore Device

    PubMed Central

    Smith, Andrew M.; Abu-Shumays, Robin; Akeson, Mark; Bernick, David L.

    2015-01-01

    Transfer RNAs (tRNA) are the most common RNA molecules in cells and have critical roles as both translators of the genetic code and regulators of protein synthesis. As such, numerous methods have focused on studying tRNA abundance and regulation, with the most widely used methods being RNA-seq and microarrays. Though revolutionary to transcriptomics, these assays are limited by an inability to encode tRNA modifications in the requisite cDNA. These modifications are abundant in tRNA and critical to their function. Here, we describe proof-of-concept experiments where individual tRNA molecules are examined as linear strands using a biological nanopore. This method utilizes an enzymatically ligated synthetic DNA adapter to concentrate tRNA at the lipid bilayer of the nanopore device and efficiently denature individual tRNA molecules, as they are pulled through the α-hemolysin (α-HL) nanopore. Additionally, the DNA adapter provides a loading site for ϕ29 DNA polymerase (ϕ29 DNAP), which acts as a brake on the translocating tRNA. This increases the dwell time of adapted tRNA in the nanopore, allowing us to identify the region of the nanopore signal that is produced by the translocating tRNA itself. Using adapter-modified Escherichia coli tRNAfMet and tRNALys, we show that the nanopore signal during controlled translocation is dependent on the identity of the tRNA. This confirms that adapter-modified tRNA can translocate end-to-end through nanopores and provide the foundation for future work in direct sequencing of individual transfer RNA with a nanopore-based device. PMID:26157798

  12. Measurement of DNA translocation dynamics in a solid-state nanopore at 100-ns temporal resolution

    PubMed Central

    Shekar, Siddharth; Niedzwiecki, David J.; Chien, Chen-Chi; Ong, Peijie; Fleischer, Daniel A.; Lin, Jianxun; Rosenstein, Jacob K.; Drndic, Marija; Shepard, Kenneth L.

    2017-01-01

    Despite the potential for nanopores to be a platform for high-bandwidth study of single-molecule systems, ionic current measurements through nanopores have been limited in their temporal resolution by noise arising from poorly optimized measurement electronics and large parasitic capacitances in the nanopore membranes. Here, we present a complementary metal-oxide-semiconductor (CMOS) nanopore (CNP) amplifier capable of low noise recordings at an unprecedented 10 MHz bandwidth. When integrated with state-of-the-art solid-state nanopores in silicon nitride membranes, we achieve an SNR of greater than 10 for ssDNA translocations at a measurement bandwidth of 5 MHz, which represents the fastest ion current recordings through nanopores reported to date. We observe transient features in ssDNA translocation events that are as short as 200 ns, which are hidden even at bandwidths as high as 1 MHz. These features offer further insights into the translocation kinetics of molecules entering and exiting the pore. This platform highlights the advantages of high-bandwidth translocation measurements made possible by integrating nanopores and custom-designed electronics. PMID:27332998

  13. Basic evaluation of typical nanoporous silica nanoparticles in being drug carrier: Structure, wettability and hemolysis.

    PubMed

    Li, Jing; Guo, Yingyu

    2017-04-01

    Herein, the present work devoted to study the basic capacity of nanoporous silica nanoparticles in being drug carrier that covered structure, wettability and hemolysis so as to provide crucial evaluation. Typical nanoporous silica nanoparticles that consist of nanoporous silica nanoparticles (NSN), amino modified nanoporous silica nanoparticles (amino-NSN), carboxyl modified nanoporous silica nanoparticles (carboxyl-NSN) and hierachical nanoporous silica nanoparticles (hierachical-NSN) were studied. The results showed that their wettability and hemolysis were closely related to structure and surface modification. Basically, wettability became stronger as the amount of OH on the surface of NSN was higher. Both large nanopores and surface modification can reduce the wettability of NSN. Furthermore, NSN series were safe to be used when they circulated into the blood in low concentration, while if high concentration can not be avoided during administration, high porosity or amino modification of NSN were safer to be considered. It is believed that the basic evaluation of NSN can make contribution in providing scientific instruction for designing drug loaded NSN systems. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Fabrication of 10nm diameter carbon nanopores

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Radenovic, Aleksandra; Trepagnier, Eliane; Csencsits, Roseann

    2008-09-25

    The addition of carbon to samples, during imaging, presents a barrier to accurate TEM analysis, the controlled deposition of hydrocarbons by a focused electron beam can be a useful technique for local nanometer-scale sculpting of material. Here we use hydrocarbon deposition to form nanopores from larger focused ion beam (FIB) holes in silicon nitride membranes. Using this method, we close 100-200nm diameter holes to diameters of 10nm and below, with deposition rates of 0.6nm per minute. I-V characteristics of electrolytic flow through these nanopores agree quantitatively with a one dimensional model at all examined salt concentrations.

  15. Nanopore arrays in a silicon membrane for parallel single-molecule detection: DNA translocation

    NASA Astrophysics Data System (ADS)

    Zhang, Miao; Schmidt, Torsten; Jemt, Anders; Sahlén, Pelin; Sychugov, Ilya; Lundeberg, Joakim; Linnros, Jan

    2015-08-01

    Optical nanopore sensing offers great potential in single-molecule detection, genotyping, or DNA sequencing for high-throughput applications. However, one of the bottle-necks for fluorophore-based biomolecule sensing is the lack of an optically optimized membrane with a large array of nanopores, which has large pore-to-pore distance, small variation in pore size and low background photoluminescence (PL). Here, we demonstrate parallel detection of single-fluorophore-labeled DNA strands (450 bps) translocating through an array of silicon nanopores that fulfills the above-mentioned requirements for optical sensing. The nanopore array was fabricated using electron beam lithography and anisotropic etching followed by electrochemical etching resulting in pore diameters down to ∼7 nm. The DNA translocation measurements were performed in a conventional wide-field microscope tailored for effective background PL control. The individual nanopore diameter was found to have a substantial effect on the translocation velocity, where smaller openings slow the translocation enough for the event to be clearly detectable in the fluorescence. Our results demonstrate that a uniform silicon nanopore array combined with wide-field optical detection is a promising alternative with which to realize massively-parallel single-molecule detection.

  16. Tailoring the hydrophobicity of graphene for its use as nanopores for DNA translocation

    NASA Astrophysics Data System (ADS)

    Schneider, Grégory F.; Xu, Qiang; Hage, Susanne; Luik, Stephanie; Spoor, Johannes N. H.; Malladi, Sairam; Zandbergen, Henny; Dekker, Cees

    2013-10-01

    Graphene nanopores are potential successors to biological and silicon-based nanopores. For sensing applications, it is however crucial to understand and block the strong nonspecific hydrophobic interactions between DNA and graphene. Here we demonstrate a novel scheme to prevent DNA-graphene interactions, based on a tailored self-assembled monolayer. For bare graphene, we encounter a paradox: whereas contaminated graphene nanopores facilitated DNA translocation well, clean crystalline graphene pores very quickly exhibit clogging of the pore. We attribute this to strong interactions between DNA nucleotides and graphene, yielding sticking and irreversible pore closure. We develop a general strategy to noncovalently tailor the hydrophobic surface of graphene by designing a dedicated self-assembled monolayer of pyrene ethylene glycol, which renders the surface hydrophilic. We demonstrate that this prevents DNA to adsorb on graphene and show that single-stranded DNA can now be detected in graphene nanopores with excellent nanopore durability and reproducibility.

  17. Lipid-induced toxicity stimulates hepatocytes to release angiogenic microparticles that require Vanin-1 for uptake by endothelial cells

    PubMed Central

    Povero, Davide; Eguchi, Akiko; Niesman, Ingrid R.; Andronikou, Nektaria; de Mollerat du Jeu, Xavier; Mulya, Anny; Berk, Michael; Lazic, Milos; Thapaliya, Samjana; Parola, Maurizio; Patel, Hemal H.; Feldstein, Ariel E.

    2014-01-01

    Angiogenesis is a key pathological feature of experimental and human steatohepatitis, a common chronic liver disease that is associated with obesity. We demonstrated that hepatocytes generated a type of membrane-bound vesicle, microparticles, in response to conditions that mimicked the lipid accumulation that occurs in the liver in some forms of steatohepatitis and that these microparticles promoted angiogenesis. When applied to an endothelial cell line, medium conditioned by murine hepatocytes or a human hepatocyte cell line exposed to saturated free fatty acids induced migration and tube formation, two processes required for angiogenesis. Medium from hepatocytes in which caspase 3 was inhibited or medium in which the microparticles were removed by ultracentrifugation lacked proangiogenic activity. Isolated hepatocyte-derived microparticles induced migration and tube formation of an endothelial cell line in vitro and angiogenesis in mice, processes that depended on internalization of microparticles. Microparticle internalization required the interaction of the ectoenzyme Vanin-1 (VNN1), an abundant surface protein on the microparticles, with lipid raft domains of endothelial cells. Large quantities of hepatocyte-derived microparticles were detected in the blood of mice with diet-induced steatohepatitis, and microparticle quantity correlated with disease severity. Genetic ablation of caspase 3 or RNA interference directed against VNN1 protected mice from steatohepatitis-induced pathological angiogenesis in the liver and resulted in a loss of the proangiogenic effects of microparticles. Our data identify hepatocyte-derived microparticles as critical signals that contribute to angiogenesis and liver damage in steatohepatitis and suggest a therapeutic target for this condition. PMID:24106341

  18. Chemopreventive efficacy of curcumin-loaded PLGA microparticles in a transgenic mouse model of HER-2-positive breast cancer.

    PubMed

    Grill, Alex E; Shahani, Komal; Koniar, Brenda; Panyam, Jayanth

    2018-04-01

    Curcumin has shown promising inhibitory activity against HER-2-positive tumor cells in vitro but suffers from poor oral bioavailability in vivo. Our lab has previously developed a polymeric microparticle formulation for sustained delivery of curcumin for chemoprevention. The goal of this study was to examine the anticancer efficacy of curcumin-loaded polymeric microparticles in a transgenic mouse model of HER-2 cancer, Balb-neuT. Microparticles were injected monthly, and mice were examined for tumor appearance and growth. Initiating curcumin microparticle treatment at 2 or 4 weeks of age delayed tumor appearance by 2-3 weeks compared to that in control mice that received empty microparticles. At 12 weeks, abnormal (lobular hyperplasia, carcinoma in situ, and invasive carcinoma) mammary tissue area was significantly decreased in curcumin microparticle-treated mice, as was CD-31 staining. Curcumin treatment decreased mammary VEGF levels significantly, which likely contributed to slower tumor formation. When compared to saline controls, however, blank microparticles accelerated tumorigenesis and curcumin treatment abrogated this effect, suggesting that PLGA microparticles enhance tumorigenesis in this model. PLGA microparticle administration was shown to be associated with higher plasma lactic acid levels and increased activation of NF-κΒ. The unexpected side effects of PLGA microparticles may be related to the high dose of the microparticles that was needed to achieve sustained curcumin levels in vivo. Approaches that can decrease the overall dose of curcumin (for example, by increasing its potency or reducing its clearance rate) may allow the development of sustained release curcumin dosage forms as a practical approach to cancer chemoprevention.

  19. Multichannel detection of ionic currents through two nanopores fabricated on integrated Si3N4 membranes.

    PubMed

    Yanagi, Itaru; Akahori, Rena; Aoki, Mayu; Harada, Kunio; Takeda, Ken-Ichi

    2016-08-16

    Integration of solid-state nanopores and multichannel detection of signals from each nanopore are effective measures for realizing high-throughput nanopore sensors. In the present study, we demonstrated fabrication of Si3N4 membrane arrays and the simultaneous measurement of ionic currents through two nanopores formed in two adjacent membranes. Membranes with thicknesses as low as 6.4 nm and small nanopores with diameters of less than 2 nm could be fabricated using the poly-Si sacrificial-layer process and multilevel pulse-voltage injection. Using the fabricated nanopore membranes, we successfully achieved simultaneous detection of clear ionic-current blockades when single-stranded short homopolymers (poly(dA)60) passed through two nanopores. In addition, we investigated the signal crosstalk and leakage current among separated chambers. When two nanopores were isolated on the front surface of the membrane, there was no signal crosstalk or leakage current between the chambers. However, when two nanopores were isolated on the backside of the Si substrate, signal crosstalk and leakage current were observed owing to high-capacitance coupling between the chambers and electrolysis of water on the surface of the Si substrate. The signal crosstalk and leakage current could be suppressed by oxidizing the exposed Si surface in the membrane chip. Finally, the observed ionic-current blockade when poly(dA)60 passed through the nanopore in the oxidized chip was approximately half of that observed in the non-oxidized chip.

  20. Increased CD39 Nucleotidase Activity on Microparticles from Patients with Idiopathic Pulmonary Arterial Hypertension

    PubMed Central

    Visovatti, Scott H.; Hyman, Matthew C.; Bouis, Diane; Neubig, Richard; McLaughlin, Vallerie V.; Pinsky, David J.

    2012-01-01

    Background Idiopathic pulmonary arterial hypertension (IPAH) is a devastating disease characterized by increased pulmonary vascular resistance, smooth muscle and endothelial cell proliferation, perivascular inflammatory infiltrates, and in situ thrombosis. Circulating intravascular ATP, ADP, AMP and adenosine activate purinergic cell signaling pathways and appear to induce many of the same pathologic processes that underlie IPAH. Extracellular dephosphorylation of ATP to ADP and AMP occurs primarily via CD39 (ENTPD1), an ectonucleotidase found on the surface of leukocytes, platelets, and endothelial cells [1]. Microparticles are micron-sized phospholipid vesicles formed from the membranes of platelets and endothelial cells. Objectives: Studies here examine whether CD39 is an important microparticle surface nucleotidase, and whether patients with IPAH have altered microparticle-bound CD39 activity that may contribute to the pathophysiology of the disease. Methodology/ Principal Findings Kinetic parameters, inhibitor blocking experiments, and immunogold labeling with electron microscopy support the role of CD39 as a major nucleotidase on the surface of microparticles. Comparison of microparticle surface CD39 expression and nucleotidase activity in 10 patients with advanced IPAH and 10 healthy controls using flow cytometry and thin layer chromatograph demonstrate the following: 1) circulating platelet (CD39+CD31+CD42b+) and endothelial (CD39+CD31+CD42b−) microparticle subpopulations in patients with IPAH show increased CD39 expression; 2) microparticle ATPase and ADPase activity in patients with IPAH is increased. Conclusions/ Significance We demonstrate for the first time increased CD39 expression and function on circulating microparticles in patients with IPAH. Further research is needed to elucidate whether these findings identify an important trigger for the development of the disease, or reflect a physiologic response to IPAH. PMID:22792409

  1. Oral delivery of microparticles containing plasmid DNA encoding hepatitis-B surface antigen.

    PubMed

    Bhowmik, Tuhin; D'Souza, Bernadette; Uddin, Mohammad N; D'Souza, Martin J

    2012-05-01

    The role of albumin-based chitosan microparticles on enhancing immune response of plasmid DNA (pDNA) to hepatitis-B surface antigen (HBsAg) vaccine after oral administration was investigated in mice. The pDNA encoding HBsAg was entrapped in albumin microparticles using a one-step spray drying technique optimized in our laboratory. The encapsulated particles were also characterized in vitro for their shape, size, encapsulation efficiency, content, and stability. Albumin microparticles could protect the DNA from nuclease degradation as confirmed in our agarose gel study. Further immune modulating effect was studied in our formulation by measuring IgG antibodies in serum as well as IgA antibodies in fecal extracts. The mice were immunized with a prime dose of 100 μg of pDNA in microparticle formulations with and without interleukins biweekly until week 7 followed by a booster dose of equivalent strength on week 33 to compare the response with the subcutaneous group. The oral immunization with the pDNA to HBsAg microparticles gave significantly higher titer level of both sIgA and IgG at week 9 and 34, respectively, in oral vaccine with interleukins group when compared with the subcutaneous group. Thus, we observed an augmentation of both humoral and cellular immune responses for prolonged periods after immunization.

  2. Detection of microparticles in dynamic processes

    NASA Astrophysics Data System (ADS)

    Ten, K. A.; Pruuel, E. R.; Kashkarov, A. O.; Rubtsov, I. A.; Shechtman, L. I.; Zhulanov, V. V.; Tolochko, B. P.; Rykovanov, G. N.; Muzyrya, A. K.; Smirnov, E. B.; Stolbikov, M. Yu; Prosvirnin, K. M.

    2016-11-01

    When a metal plate is subjected to a strong shock impact, its free surface emits a flow of particles of different sizes (shock-wave “dusting”). Traditionally, the process of dusting is investigated by the methods of pulsed x-ray or piezoelectric sensor or via an optical technique. The particle size ranges from a few microns to hundreds of microns. The flow is assumed to include also finer particles, which cannot be detected with the existing methods yet. On the accelerator complex VEPP-3-VEPP-4 at the BINP there are two experiment stations for research on fast processes, including explosion ones. The stations enable measurement of both passed radiation (absorption) and small-angle x-ray scattering on synchrotron radiation (SR). Radiation is detected with a precision high-speed detector DIMEX. The detector has an internal memory of 32 frames, which enables recording of the dynamics of the process (shooting of movies) with intervals of 250 ns to 2 μs. Flows of nano- and microparticles from free surfaces of various materials (copper and tin) have been examined. Microparticle flows were emitted from grooves of 50-200 μs in size and joints (gaps) between metal parts. With the soft x-ray spectrum of SR one can explore the dynamics of a single microjet of micron size. The dynamics of density distribution along micro jets were determined. Under a shock wave (∼ 60 GPa) acting on tin disks, flows of microparticles from a smooth surface were recorded.

  3. Highly cross-linked nanoporous polymers

    DOEpatents

    Steckle, Jr., Warren P.; Apen, Paul G.; Mitchell, Michael A.

    1998-01-01

    Condensation polymerization followed by a supercritical extraction step can be used to obtain highly cross-linked nanoporous polymers with high surface area, controlled pore sizes and rigid structural integrity. The invention polymers are useful for applications requiring separation membranes.

  4. Highly cross-linked nanoporous polymers

    DOEpatents

    Steckle, Jr., Warren P.; Apen, Paul G.; Mitchell, Michael A.

    1997-01-01

    Condensation polymerization followed by a supercritical extraction step can be used to obtain highly cross-linked nanoporous polymers with high surface area, controlled pore sizes and rigid structural integrity. The invention polymers are useful for applications requiring separation membranes.

  5. Brittle-to-ductile transition of lithiated silicon electrodes: Crazing to stable nanopore growth.

    PubMed

    Wang, Haoran; Wang, Xueju; Xia, Shuman; Chew, Huck Beng

    2015-09-14

    Using first principle calculations, we uncover the underlying mechanisms explaining the brittle-to-ductile transition of LixSi electrodes in lithium ion batteries with increasing Li content. We show that plasticity initiates at x = ∼ 0.5 with the formation of a craze-like network of nanopores separated by Si-Si bonds, while subsequent failure is still brittle-like with the breaking of Si-Si bonds. Transition to ductile behavior occurs at x ⩾ 1 due to the increased density of highly stretchable Li-Li bonds, which delays nanopore formation and stabilizes nanopore growth. Collapse of the nanopores during unloading of the LixSi alloys leads to significant strain recovery.

  6. Effect of Formulation and Process Parameters on Chitosan Microparticles Prepared by an Emulsion Crosslinking Technique.

    PubMed

    Rodriguez, Lidia B; Avalos, Abraham; Chiaia, Nicholas; Nadarajah, Arunan

    2017-05-01

    There are many studies about the synthesis of chitosan microparticles; however, most of them have very low production rate, have wide size distribution, are difficult to reproduce, and use harsh crosslinking agents. Uniform microparticles are necessary to obtain repeatable drug release behavior. The main focus of this investigation was to study the effect of the process and formulation parameters during the preparation of chitosan microparticles in order to produce particles with narrow size distribution. The technique evaluated during this study was emulsion crosslinking technique. Chitosan is a biocompatible and biodegradable material but lacks good mechanical properties; for that reason, chitosan was ionically crosslinked with sodium tripolyphosphate (TPP) at three different ratios (32, 64, and 100%). The model drug used was acetylsalicylic acid (ASA). During the preparation of the microparticles, chitosan was first mixed with ASA and then dispersed in oil containing an emulsifier. The evaporation of the solvents hardened the hydrophilic droplets forming microparticles with spherical shape. The process and formulation parameters were varied, and the microparticles were characterized by their morphology, particle size, drug loading efficiency, and drug release behavior. The higher drug loading efficiency was achieved by using 32% mass ratio of TPP to chitosan. The average microparticle size was 18.7 μm. The optimum formulation conditions to prepare uniform spherical microparticles were determined and represented by a region in a triangular phase diagram. The drug release analyses were evaluated in phosphate buffer solution at pH 7.4 and were mainly completed at 24 h.

  7. Detection of circulating microparticles by flow cytometry: influence of centrifugation, filtration of buffer, and freezing

    PubMed Central

    Dey-Hazra, Emily; Hertel, Barbara; Kirsch, Torsten; Woywodt, Alexander; Lovric, Svjetlana; Haller, Hermann; Haubitz, Marion; Erdbruegger, Uta

    2010-01-01

    The clinical importance of microparticles resulting from vesiculation of platelets and other blood cells is increasingly recognized, although no standardized method exists for their measurement. Only a few studies have examined the analytical and preanalytical steps and variables affecting microparticle detection. We focused our analysis on microparticle detection by flow cytometry. The goal of our study was to analyze the effects of different centrifugation protocols looking at different durations of high and low centrifugation speeds. We also analyzed the effect of filtration of buffer and long-term freezing on microparticle quantification, as well as the role of Annexin V in the detection of microparticles. Absolute and platelet-derived microparticles were 10- to 15-fold higher using initial lower centrifugation speeds at 1500 × g compared with protocols using centrifugation speeds at 5000 × g (P < 0.01). A clear separation between true events and background noise was only achieved using higher centrifugation speeds. Filtration of buffer with a 0.2 μm filter reduced a significant amount of background noise. Storing samples for microparticle detection at −80°C decreased microparticle levels at days 28, 42, and 56 (P < 0.05 for all comparisons with fresh samples). We believe that staining with Annexin V is necessary to distinguish true events from cell debris or precipitates. Buffers should be filtered and fresh samples should be analyzed, or storage periods will have to be standardized. Higher centrifugation speeds should be used to minimize contamination by smaller size platelets. PMID:21191433

  8. Regulatory T Cell-Enriching Microparticles for Promoting Vascularized Composite Allotransplant Survival

    DTIC Science & Technology

    2016-10-01

    AWARD NUMBER: W81XWH-15-1-0244 TITLE: Regulatory T Cell-Enriching Microparticles for Promoting Vascularized Composite Allotransplant Survival...2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Regulatory T Cell-Enriching Microparticles for Promoting Vascularized Composite Allotransplant Survival...observed effects these particles have on allograft survival. Key Words CTA Composite Tissue Allotransplantation VCA Vascularized Composite

  9. Circulating levels of cell-derived microparticles are reduced by mild hypobaric hypoxia: data from a randomised controlled trial.

    PubMed

    Ayers, Lisa; Stoewhas, Anne-Christin; Ferry, Berne; Latshang, Tsogyal D; Lo Cascio, Christian M; Sadler, Ross; Stadelmann, Katrin; Tesler, Noemi; Huber, Reto; Achermann, Peter; Bloch, Konrad E; Kohler, Malcolm

    2014-05-01

    Hypoxia is known to induce the release of microparticles in vitro. However, few publications have addressed the role of hypoxia in vivo on circulating levels of microparticles. This randomised, controlled, crossover trial aimed to determine the effect of mild hypoxia on in vivo levels of circulating microparticles in healthy individuals. Blood was obtained from 51 healthy male volunteers (mean age of 26.9 years) at baseline altitude (490 m) and after 24 and 48 h at moderate altitude (2,590 m). The order of altitude exposure was randomised. Flow cytometry was used to assess platelet-poor plasma for levels of circulating microparticles derived from platelets, endothelial cells, leucocytes, granulocytes, monocytes, red blood cells and procoagulant microparticles. Mean (standard deviation) oxygen saturation was significantly lower on the first and second day after arrival at 2,590 m, 91.0 (2.0) and 92.0 (2.0) %, respectively, compared to 490 m, 96 (1.0) %, p < 0.001 for both comparisons. A significant decrease in the levels of procoagulant microparticles (annexin V+ -221/μl 95 % CI -370.8/-119.0, lactadherin+ -202/μl 95 % CI -372.2/-93.1), platelet-derived microparticles (-114/μl 95 % CI -189.9/-51.0) and red blood cell-derived microparticles (-81.4 μl 95 % CI -109.9/-57.7) after 48 h at moderate altitude was found. Microparticles derived from endothelial cells, granulocytes, monocytes and leucocytes were not significantly altered by exposure to moderate altitude. In healthy male individuals, mild hypobaric hypoxia, induced by a short-term stay at moderate altitude, is associated with lower levels of procoagulant microparticles, platelet-derived microparticles and red blood cell-derived microparticles, suggesting a reduction in thrombotic potential.

  10. Asymmetric nanopore membranes: Single molecule detection and unique transport properties

    NASA Astrophysics Data System (ADS)

    Bishop, Gregory William

    Biological systems rely on the transport properties of transmembrane channels. Such pores can display selective transport by allowing the passage of certain ions or molecules while rejecting others. Recent advances in nanoscale fabrication have allowed the production of synthetic analogs of such channels. Synthetic nanopores (pores with a limiting dimension of 1--100 nm) can be produced in a variety of materials by several different methods. In the Martin group, we have been exploring the track-etch method to produce asymmetric nanopores in thin films of polymeric or crystalline materials. Asymmetric nanopores are of particular interest due to their ability to serve as ion-current rectifiers. This means that when a membrane that contains such a pore or collection of pores is used to separate identical portions of electrolyte solution, the magnitude of the ionic current will depend not only on the magnitude of the applied potential (as expected) but also the polarity. Ion-current rectification is characterized by an asymmetric current--potential response. Here, the interesting transport properties of asymmetric nanopores (ion-current rectification and the related phenomenon of electroosmotic flow rectification) are explored. The effects of pore shape and pore density on these phenomena are investigated. Membranes that contain a single nanopore can serve as platforms for the single-molecule sensing technique known as resistive pulse sensing. The resistive-pulse sensing method is based on the Coulter principle. Thus, the selectivity of the technique is based largely upon size, making the analysis of mixtures by this method difficult in many cases. Here, the surface of a single nanopore membrane is modified with a molecular recognition agent in an attempt to obtain a more selective resistive-pulse sensor for a specific analyte.

  11. Nanoporous biomaterials for uremic toxin adsorption in artificial kidney systems: A review.

    PubMed

    Cheah, Wee-Keat; Ishikawa, Kunio; Othman, Radzali; Yeoh, Fei-Yee

    2017-07-01

    Hemodialysis, one of the earliest artificial kidney systems, removes uremic toxins via diffusion through a semipermeable porous membrane into the dialysate fluid. Miniaturization of the present hemodialysis system into a portable and wearable device to maintain continuous removal of uremic toxins would require that the amount of dialysate used within a closed-system is greatly reduced. Diffused uremic toxins within a closed-system dialysate need to be removed to maintain the optimum concentration gradient for continuous uremic toxin removal by the dialyzer. In this dialysate regenerative system, adsorption of uremic toxins by nanoporous biomaterials is essential. Throughout the years of artificial kidney development, activated carbon has been identified as a potential adsorbent for uremic toxins. Adsorption of uremic toxins necessitates nanoporous biomaterials, especially activated carbon. Nanoporous biomaterials are also utilized in hemoperfusion for uremic toxin removal. Further miniaturization of artificial kidney system and improvements on uremic toxin adsorption capacity would require high performance nanoporous biomaterials which possess not only higher surface area, controlled pore size, but also designed architecture or structure and surface functional groups. This article reviews on various nanoporous biomaterials used in current artificial kidney systems and several emerging nanoporous biomaterials. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1232-1240, 2017. © 2016 Wiley Periodicals, Inc.

  12. Boron Nitride Nanoporous Membranes with High Surface Charge by Atomic Layer Deposition.

    PubMed

    Weber, Matthieu; Koonkaew, Boonprakrong; Balme, Sebastien; Utke, Ivo; Picaud, Fabien; Iatsunskyi, Igor; Coy, Emerson; Miele, Philippe; Bechelany, Mikhael

    2017-05-17

    In this work, we report the design and the fine-tuning of boron nitride single nanopore and nanoporous membranes by atomic layer deposition (ALD). First, we developed an ALD process based on the use of BBr 3 and NH 3 as precursors in order to synthesize BN thin films. The deposited films were characterized in terms of thickness, composition, and microstructure. Next, we used the newly developed process to grow BN films on anodic aluminum oxide nanoporous templates, demonstrating the conformality benefit of BN prepared by ALD, and its scalability for the manufacturing of membranes. For the first time, the ALD process was then used to tune the diameter of fabricated single transmembrane nanopores by adjusting the BN thickness and to enable studies of the fundamental aspects of ionic transport on a single nanopore. At pH = 7, we estimated a surface charge density of 0.16 C·m -2 without slip and 0.07 C·m -2 considering a reasonable slip length of 3 nm. Molecular dynamics simulations performed with experimental conditions confirmed the conductivities and the sign of surface charges measured. The high ion transport results obtained and the ability to fine-tune nanoporous membranes by such a scalable method pave the way toward applications such as ionic separation, energy harvesting, and ultrafiltration devices.

  13. Modeling electrochemical deposition inside nanotubes to obtain metal-semiconductor multiscale nanocables or conical nanopores.

    PubMed

    Lebedev, Konstantin; Mafé, Salvador; Stroeve, Pieter

    2005-08-04

    Nanocables with a radial metal-semiconductor heterostructure have recently been prepared by electrochemical deposition inside metal nanotubes. First, a bare nanoporous polycarbonate track-etched membrane is coated uniformly with a metal film by electroless deposition. The film forms a working electrode for further deposition of a semiconductor layer that grows radially inside the nanopore when the deposition rate is slow. We propose a new physical model for the nanocable synthesis and study the effects of the deposited species concentration, potential-dependent reaction rate, and nanopore dimensions on the electrochemical deposition. The problem involves both axial diffusion through the nanopore and radial transport to the nanopore surface, with a surface reaction rate that depends on the axial position and the time. This is so because the radial potential drop across the deposited semiconductor layer changes with the layer thickness through the nanopore. Since axially uniform nanocables are needed for most applications, we consider the relative role of reaction and axial diffusion rates on the deposition process. However, in those cases where partial, empty-core deposition should be desirable (e.g., for producing conical nanopores to be used in single nanoparticle detection), we give conditions where asymmetric geometries can be experimentally realized.

  14. A nanoporous alumina microelectrode array for functional cell-chip coupling.

    PubMed

    Wesche, Manuel; Hüske, Martin; Yakushenko, Alexey; Brüggemann, Dorothea; Mayer, Dirk; Offenhäusser, Andreas; Wolfrum, Bernhard

    2012-12-14

    The design of electrode interfaces has a strong impact on cell-based bioelectronic applications. We present a new type of microelectrode array chip featuring a nanoporous alumina interface. The chip is fabricated in a combination of top-down and bottom-up processes using state-of-the-art clean room technology and self-assembled generation of nanopores by aluminum anodization. The electrode characteristics are investigated in phosphate buffered saline as well as under cell culture conditions. We show that the modified microelectrodes exhibit decreased impedance compared to planar microelectrodes, which is caused by a nanostructuring effect of the underlying gold during anodization. The stability and biocompatibility of the device are demonstrated by measuring action potentials from cardiomyocyte-like cells growing on top of the chip. Cross sections of the cell-surface interface reveal that the cell membrane seals the nanoporous alumina layer without bending into the sub-50 nm apertures. The nanoporous microelectrode array device may be used as a platform for combining extracellular recording of cell activity with stimulating topographical cues.

  15. Near-Infrared Imaging Method for the In Vivo Assessment of the Biodistribution of Nanoporous Silicon Particles

    PubMed Central

    Tasciotti, Ennio; Godin, Biana; Martinez, Jonathan O.; Chiappini, Ciro; Bhavane, Rohan; Liu, Xuewu; Ferrari, Mauro

    2011-01-01

    In the development of new nanoparticle-based technologies for therapeutic and diagnostic purposes, understanding the fate of nanoparticles in the body is crucial. We recently developed a multistage vector delivery system comprising biodegradable and biocompatible nanoporous silicon particles (first-stage microparticles [S1MPs]) able to host, protect, and deliver second-stage therapeutic and diagnostic nanoparticles (S2NPs) on intravenous injection. This delivery system aims at sequentially overcoming the biologic barriers en route to the target delivery site by separating and assigning tasks to the coordinated logic-embedded vectors constituting it. In this work, by conjugating a near-infrared dye on the surface of the S1MP without compromising the porous structure and potential loading of S2NPs, we were able to monitor the in vivo distribution of S1MPs in healthy mice using an optical imaging system. It was observed that particles predominantly accumulated in the liver and spleen at the end of 24 hours. Further quantification of S1MPs in the major organs of the animals by elemental analysis of silicon using inductively coupled plasma-atomic electron spectroscopy verified the accuracy of in vivo near-infrared imaging as a tool for evaluation of nanovector biodistribution. PMID:21303615

  16. Highly cross-linked nanoporous polymers

    DOEpatents

    Steckle, W.P. Jr.; Apen, P.G.; Mitchell, M.A.

    1998-01-20

    Condensation polymerization followed by a supercritical extraction step can be used to obtain highly cross-linked nanoporous polymers with high surface area, controlled pore sizes and rigid structural integrity. The invention polymers are useful for applications requiring separation membranes. 1 fig.

  17. Thermal evaporation and condensation synthesis of metallic Zn layered polyhedral microparticles

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Khan, Waheed S.; Cao, Chuanbao, E-mail: cbcao@bit.edu.cn; Usman, Zahid

    2011-12-15

    Highlights: Black-Right-Pointing-Pointer Zn polyhedral microparticles prepared by thermal evaporation and condensation route. Black-Right-Pointing-Pointer Vapour-solid process based growth model governs the formation of Zn microparticles. Black-Right-Pointing-Pointer A strong PL emission band is observed at 369 nm in UV region. Black-Right-Pointing-Pointer Radiative recombination of electrons in the s, p conduction band and the holes in the d bands causes this emission. -- Abstract: Metallic zinc layered polyhedral microparticles have been fabricated by thermal evaporation and condensation technique using zinc as precursor at 750 Degree-Sign C for 120 min and NH{sub 3} as a carrier gas. The zinc polyhedral microparticles with oblate sphericalmore » shape are observed to be 2-9 {mu}m in diameter along major axes and 1-7 {mu}m in thickness along minor axes. The structural, compositional and morphological characterizations were performed by X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDS), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and selected area electron diffraction (SAED). A vapour-solid (VS) mechanism based growth model has been proposed for the formation of Zn microparticles. Room temperature photoluminescence (PL) emission spectrum of the product exhibited a strong emission band at 369 nm attributed to the radiative recombination of electrons in the s, p conduction band near Fermi surface and the holes in the d bands generated by the optical excitation.« less

  18. Identification of Essential Sensitive Regions of the Aerolysin Nanopore for Single Oligonucleotide Analysis.

    PubMed

    Wang, Ya-Qian; Li, Meng-Yin; Qiu, Hu; Cao, Chan; Wang, Ming-Bo; Wu, Xue-Yuan; Huang, Jin; Ying, Yi-Lun; Long, Yi-Tao

    2018-06-11

    The aerolysin nanopore channel is one of the confined spaces for single molecule analysis which displays high spatial and temporal resolution for the discrimination of single nucleotides, identification of DNA base modification, and analyzing the structural transition of DNAs. However, to overcome the challenge of achieving the ultimate goal of the widespread real analytical application, it is urgent to probe the sensing regions of the aerolysin to further improve the sensitivity. In this paper, we explore the sensing regions of the aerolysin nanopore by a series of well-designed mutant nanopore experiments combined with molecular dynamics simulations-based electrostatic analysis. The positively charged lumen-exposed Lys-238, identified as one of the key sensing sites due to the presence of a deep valley in the electrostatic potentials, was replaced by different charged and sized amino acids. The results show that the translocation time of oligonucleotides through the nanopore can be readily modulated by the choice of the target amino acid at the 238 site. In particular, a 7-fold slower translocation at a voltage bias of +120 mV is observed with respect to the wild-type aerolysin, which provides a high resolution for methylated cytosine discrimination. We further determine that both the electrostatic properties and geometrical structure of the aerolysin nanopore are crucial to its sensing ability. These insights open ways for rationally designing the sensing mechanism of the aerolysin nanopore, thus providing a novel paradigm for nanopore sensing.

  19. Use of prebiotic carbohydrate as wall material on lime essential oil microparticles.

    PubMed

    Campelo, Pedro Henrique; Figueiredo, Jayne de Abreu; Domingues, Rosana Zacarias; Fernandes, Regiane Victória de Barros; Botrel, Diego Alvarenga; Borges, Soraia Vilela

    2017-09-01

    The aim of this work was to study the use of different prebiotic biopolymers in lime essential oil microencapsulation. Whey protein isolate, inulin and oligofructose biopolymers were used. The addition of prebiotic biopolymers reduced emulsion viscosity, although it produced larger droplet sizes (0.31-0.32 µm). Moisture values (2.94-3.13 g/100 g dry solids) and water activity (0.152-0.185) were satisfactory, being within the appropriate range for powdered food quality. Total oil content, limonene retention values and antioxidant activity of the microparticles containing essential oil decreased in the presence of the carbohydrates. The addition of prebiotic biopolymers reduced the microparticle thermal stability. X-ray diffraction confirmed the amorphous characteristic of the microparticles and the interaction of the essential oil with the wall material. The presence of prebiotic biopolymers can be a good alternative for lime essential oil microparticles, mainly using fibre that has a functional food appeal and can improve consumer health.

  20. Hierarchical assembly of viral nanotemplates with encoded microparticles via nucleic acid hybridization.

    PubMed

    Tan, Wui Siew; Lewis, Christina L; Horelik, Nicholas E; Pregibon, Daniel C; Doyle, Patrick S; Yi, Hyunmin

    2008-11-04

    We demonstrate hierarchical assembly of tobacco mosaic virus (TMV)-based nanotemplates with hydrogel-based encoded microparticles via nucleic acid hybridization. TMV nanotemplates possess a highly defined structure and a genetically engineered high density thiol functionality. The encoded microparticles are produced in a high throughput microfluidic device via stop-flow lithography (SFL) and consist of spatially discrete regions containing encoded identity information, an internal control, and capture DNAs. For the hybridization-based assembly, partially disassembled TMVs were programmed with linker DNAs that contain sequences complementary to both the virus 5' end and a selected capture DNA. Fluorescence microscopy, atomic force microscopy (AFM), and confocal microscopy results clearly indicate facile assembly of TMV nanotemplates onto microparticles with high spatial and sequence selectivity. We anticipate that our hybridization-based assembly strategy could be employed to create multifunctional viral-synthetic hybrid materials in a rapid and high-throughput manner. Additionally, we believe that these viral-synthetic hybrid microparticles may find broad applications in high capacity, multiplexed target sensing.

  1. A novel input-parasitic compensation technique for a nanopore-based CMOS DNA detection sensor

    NASA Astrophysics Data System (ADS)

    Kim, Jungsuk

    2016-12-01

    This paper presents a novel input-parasitic compensation (IPC) technique for a nanopore-based complementary metal-oxide-semiconductor (CMOS) DNA detection sensor. A resistive-feedback transimpedance amplifier is typically adopted as the headstage of a DNA detection sensor to amplify the minute ionic currents generated from a nanopore and convert them to a readable voltage range for digitization. But, parasitic capacitances arising from the headstage input and the nanopore often cause headstage saturation during nanopore sensing, thereby resulting in significant DNA data loss. To compensate for the unwanted saturation, in this work, we propose an area-efficient and automated IPC technique, customized for a low-noise DNA detection sensor, fabricated using a 0.35- μm CMOS process; we demonstrated this prototype in a benchtop test using an α-hemolysin ( α-HL) protein nanopore.

  2. Integration of solid-state nanopores in a 0.5 μm cmos foundry process

    PubMed Central

    Uddin, A; Yemenicioglu, S; Chen, C-H; Corigliano, E; Milaninia, K; Theogarajan, L

    2013-01-01

    High-bandwidth and low-noise nanopore sensor and detection electronics are crucial in achieving single-DNA base resolution. A potential way to accomplish this goal is to integrate solid-state nanopores within a CMOS platform, in close proximity to the biasing electrodes and custom-designed amplifier electronics. Here we report the integration of solid-state nanopore devices in a commercial complementary metal-oxide semiconductor (CMOS) potentiostat chip implemented in On-Semiconductor’s 0.5 μm technology. Nanopore membranes incorporating electrodes are fabricated by post-CMOS micromachining utilizing the N+ polysilicon/SiO2/N+ polysilicon capacitor structure available in the aforementioned process. Nanopores are created in the CMOS process by drilling in a transmission electron microscope and shrinking by atomic layer deposition. We also describe a batch fabrication method to process a large of number of electrode-embedded nanopores with sub-10 nm diameter across CMOS-compatible wafers by electron beam lithography and atomic layer deposition. The CMOS-compatibility of our fabrication process is verified by testing the electrical functionality of on-chip circuitry. We observe high current leakage with the CMOS nanopore devices due to the ionic diffusion through the SiO2 membrane. To prevent this leakage, we coat the membrane with Al2O3 which acts as an efficient diffusion barrier against alkali ions. The resulting nanopore devices also exhibit higher robustness and lower 1/f noise as compared to SiO2 and SiNx. Furthermore, we propose a theoretical model for our low-capacitance CMOS nanopore devices, showing good agreement with the experimental value. In addition, experiments and theoretical models of translocation studies are presented using 48.5 kbp λ-DNA in order to prove the functionality of on-chip pores coated with Al2O3. PMID:23519330

  3. In vitro extracellular recording and stimulation performance of nanoporous gold-modified multi-electrode arrays.

    PubMed

    Kim, Yong Hee; Kim, Gook Hwa; Kim, Ah Young; Han, Young Hwan; Chung, Myung-Ae; Jung, Sang-Don

    2015-12-01

    Nanoporous gold (Au) structures can reduce the impedance and enhance the charge injection capability of multi-electrode arrays (MEAs) used for interfacing neuronal networks. Even though there are various nanoporous Au preparation techniques, fabrication of MEA based on low-cost electro-codeposition of Ag:Au has not been performed. In this work, we have modified a Au MEA via the electro-codeposition of Ag:Au alloy, followed by the chemical etching of Ag, and report on the in vitro extracellular recording and stimulation performance of the nanoporous Au-modified MEA. Ag:Au alloy was electro-codeposited on a bilayer lift-off resist sputter-deposition passivated Au MEA followed by chemical etching of Ag to form a porous Au structure. The porous Au structure was analyzed by scanning electron microscopy and tunneling electron microscopy and found to have an interconnected nanoporous Au structure. The impedance value of the nanoporous Au-modified MEA is 15.4 ± 0.55 kΩ at 1 kHz, accompanied by the base noise V rms of 2.4 ± 0.3 μV. The charge injection limit of the nanoporous Au-modified electrode estimated from voltage transient measurement is approximately 1 mC cm(-2), which is comparable to roughened platinum and carbon nanotube electrodes. The charge injection capability of the nanoporous Au-modified MEA was confirmed by observing stimulus-induced spikes at above 0.2 V. The nanoporous Au-modified MEA showed mechanical durability upon ultrasonic treatment for up to an hour. Electro-codeposition of Ag:Au alloy combined with chemical etching Ag is a low-cost process for fabricating nanoporous Au-modified MEA suitable for establishing the stimulus-response relationship of cultured neuronal networks.

  4. In vitro extracellular recording and stimulation performance of nanoporous gold-modified multi-electrode arrays

    NASA Astrophysics Data System (ADS)

    Kim, Yong Hee; Kim, Gook Hwa; Kim, Ah Young; Han, Young Hwan; Chung, Myung-Ae; Jung, Sang-Don

    2015-12-01

    Objective. Nanoporous gold (Au) structures can reduce the impedance and enhance the charge injection capability of multi-electrode arrays (MEAs) used for interfacing neuronal networks. Even though there are various nanoporous Au preparation techniques, fabrication of MEA based on low-cost electro-codeposition of Ag:Au has not been performed. In this work, we have modified a Au MEA via the electro-codeposition of Ag:Au alloy, followed by the chemical etching of Ag, and report on the in vitro extracellular recording and stimulation performance of the nanoporous Au-modified MEA. Approach. Ag:Au alloy was electro-codeposited on a bilayer lift-off resist sputter-deposition passivated Au MEA followed by chemical etching of Ag to form a porous Au structure. Main results. The porous Au structure was analyzed by scanning electron microscopy and tunneling electron microscopy and found to have an interconnected nanoporous Au structure. The impedance value of the nanoporous Au-modified MEA is 15.4 ± 0.55 kΩ at 1 kHz, accompanied by the base noise V rms of 2.4 ± 0.3 μV. The charge injection limit of the nanoporous Au-modified electrode estimated from voltage transient measurement is approximately 1 mC cm-2, which is comparable to roughened platinum and carbon nanotube electrodes. The charge injection capability of the nanoporous Au-modified MEA was confirmed by observing stimulus-induced spikes at above 0.2 V. The nanoporous Au-modified MEA showed mechanical durability upon ultrasonic treatment for up to an hour. Significance. Electro-codeposition of Ag:Au alloy combined with chemical etching Ag is a low-cost process for fabricating nanoporous Au-modified MEA suitable for establishing the stimulus-response relationship of cultured neuronal networks.

  5. Single nanopore transport of synthetic and biological polyelectrolytes in three-dimensional hybrid microfluidic/nanofluidic devices

    DOE PAGES

    King, Travis L.; Gatimu, Enid N.; Bohn, Paul W.

    2009-01-02

    This paper presents a study of electrokinetic transport in single nanopores integrated into vertically-stacked three-dimensional hybrid microfluidic/nanofluidic structures. In these devices single nanopores, created by focused ion beam (FIB) milling in thin polymer films, provide fluidic connection between two vertically separated, perpendicular microfluidic channels. Experiments address both systems in which the nanoporous membrane is composed of the same (homojunction) or different (heterojunction) polymer as the microfluidic channels. These devices are then used to study the electrokinetic transport properties of synthetic (i.e., polystyrene sulfonate and polyallylamine) and biological (i.e.,DNA) polyelectrolytes across these nanopores. Single nanopore transport of polyelectrolytes across these nanoporesmore » using both electrical current measurements and confocal microscopy. Both optical and electrical measurements indicate that electroosmotic transport is predominant over electrophoresis in single nanopores with d > 180 nm, consistent with results obtained under similar conditions for nanocapillary array membranes.« less

  6. Carbon nanotube-based coatings to induce flow enhancement in hydrophilic nanopores

    NASA Astrophysics Data System (ADS)

    Wagemann, Enrique; Walther, J. H.; Zambrano, Harvey A.

    2016-11-01

    With the emergence of the field of nanofluidics, the transport of water in hydrophilic nanopores has attracted intensive research due to its many promising applications. Experiments and simulations have found that flow resistance in hydrophilic nanochannels is much higher than those in macrochannels. Indeed, this might be attributed to significant fluid adsorption on the channel walls and to the effect of the increased surface to volume ratio inherent to the nanoconfinement. Therefore, it is desirable to explore strategies for drag reduction in nanopores. Recently, studies have found that carbon nanotubes (CNTs) feature ultrafast water flow rates which result in flow enhancements of 1 to 5 orders of magnitude compared to Hagen-Poiseuille predictions. In the present study, CNT-based coatings are considered to induce water flow enhancement in silica nanopores with different radius. We conduct atomistic simulations of pressurized water flow inside tubular silica nanopores with and without inner coaxial carbon nanotubes. In particular, we compute water density and velocity profiles, flow enhancement and slip lengths to understand the drag reduction capabilities of single- and multi-walled carbon nanotubes implemented as coating material in silica nanopores. We wish to thank partial funding from CRHIAM and FONDECYT project 11130559, computational support from DTU and NLHPC (Chile).

  7. Photochemistry of nanoporous carbons: Perspectives in energy conversion and environmental remediation.

    PubMed

    Gomis-Berenguer, Alicia; Velasco, Leticia F; Velo-Gala, Inmaculada; Ania, Conchi O

    2017-03-15

    The interest in the use of nanoporous carbon materials in applications related to energy conversion and storage, either as catalysts or additives, has grown over recent decades in various disciplines. Since the early studies reporting the benefits of the use of nanoporous carbons as inert supports of semiconductors and as electron acceptors that enhance the splitting of the photogenerated excitons, many researchers have investigated the key role of carbon matrices coupled to all types of photoactive materials. More recently, our group has demonstrated the ability of semiconductor-free nanoporous carbons to convert the absorbed photons into chemical reactions (i.e. oxidation of pollutants, water splitting, reduction of surface groups) opening new opportunities beyond conventional applications in light energy conversion. The aim of this paper is to review the recent progress on the application of nanoporous carbons in photochemistry using varied illumination conditions (UV, simulated solar light) and covering their role as additives to semiconductors as well as their use as photocatalysts in various fields, describing the photochemical quantum yield of nanoporous carbons for different reactions, and discussing the mechanisms postulated for the carbon/light interactions in confined pore spaces. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Comparative studies on the properties of glycyrrhetinic acid-loaded PLGA microparticles prepared by emulsion and template methods.

    PubMed

    Wang, Hong; Zhang, Guangxing; Sui, Hong; Liu, Yanhua; Park, Kinam; Wang, Wenping

    2015-12-30

    The O/W emulsion method has been widely used for the production of poly (lactide-co-glycolide) (PLGA) microparticles. Recently, a template method has been used to make homogeneous microparticles with predefined size and shape, and shown to be useful in encapsulating different types of active compounds. However, differences between the template method and emulsion method have not been examined. In the current study, PLGA microparticles were prepared by the two methods using glycyrrhetinic acid (GA) as a model drug. The properties of obtained microparticles were characterized and compared on drug distribution, in vitro release, and degradation. An encapsulation efficiency of over 70% and a mean particle size of about 40μm were found for both methods. DSC thermograms and XRPD diffractograms indicated that GA was highly dispersed or in the amorphous state in the matrix of microparticles. The emulsion method produced microparticles of a broad size distribution with a core-shell type structure and many drug-rich domains inside each microparticle. Its drug release and matrix degradation was slow before Day 50 and then accelerated. In contrast, the template method formed microparticles with narrow size distribution and drug distribution without apparent drug-rich domains. The template microparticles with a loading efficiency of 85% exhibited a zero-order release profile for 3 months after the initial burst release of 26.7%, and a steady surface erosion process as well. The same microparticles made by two different methods showed two distinguished drug release profiles. The two different methods can be supplementary with each other in optimization of drug formulation for achieving predetermined drug release patterns. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. The Young's Modulus, Fracture Stress, and Fracture Strain of Gellan Hydrogels Filled with Whey Protein Microparticles.

    PubMed

    Lam, Cherry Wing Yu; Ikeda, Shinya

    2017-05-01

    Texture modifying abilities of whey protein microparticles are expected to be dependent on pH during heat-induced aggregation of whey protein in the microparticulation process. Therefore, whey protein microparticles were prepared at either pH 5.5 or 6.8 and their effects on small and large deformation properties of gellan gels containing whey protein microparticles as fillers were investigated. The majority of whey protein microparticles had diameters around 2 μm. Atomic force microscopy images showed that whey protein microparticles prepared at pH 6.8 partially collapsed and flatted by air-drying, while those prepared at pH 5.5 did not. The Young's modulus of filled gels adjusted to pH 5.5 decreased by the addition of whey protein microparticles, while those of filled gels adjusted to pH 6.8 increased with increasing volume fraction of filler particles. These results suggest that filler particles were weakly bonded to gel matrices at pH 5.5 but strongly at pH 6.8. Whey protein microparticles prepared at pH 5.5 showed more enhanced increases in the Young's modulus than those prepared at pH 6.8 at volume fractions between 0.2 and 0.4, indicating that microparticles prepared at pH 5.5 were mechanically stronger. The fracture stress of filled gels showed trends somewhat similar to those of the Young's modulus, while their fracture strains decreased by the addition of whey protein microparticles in all examined conditions, indicating that the primary effect of these filler particles was to enhance the brittleness of filled gels. © 2017 Institute of Food Technologists®.

  10. Effects of transplanted circulating endothelial progenitor cells and platelet microparticles in atherosclerosis development.

    PubMed

    Georgescu, Adriana; Alexandru, Nicoleta; Andrei, Eugen; Dragan, Emanuel; Cochior, Daniel; Dias, Sérgio

    2016-08-01

    Atherosclerosis is an inflammatory disease, in which risk factors such as hyperlipidemia and hypertension affect the arterial endothelium, resulting in dysfunction, cell damage or both. The number of circulating endothelial progenitor cells and microparticles provides invaluable outcome prediction for atherosclerosis disease. However, evidence for the therapeutic potential of endothelial progenitor cells and microparticles in atherosclerosis development is limited. Our study was designed to investigate the possible protective role of a cell therapy-based approach, using endothelial progenitor cells and the dual behaviour of circulating platelet microparticles, on atherosclerosis development in hypertensive-hypercholesterolemic hamster model. Consequently, control hamsters received four intravenous inoculations of: (1) 1×10(5) endothelial progenitor cells of healthy origins in one dose per month, during four months of diet-induced atherosclerosis, and after hypertensive-hypercholesterolemic diet for further four months; (2) in a second set of experiments, 1×10(5) endothelial progenitor cells of healthy origins or/and 1×10(5) platelet microparticles of atherosclerotic origins were inoculated every other month during hypertensive-hypercholesterolemic diet. Endothelial progenitor cell treatment had the following effects: (1) re-established plasmatic parameters: cholesterol and triglyceride concentrations, blood pressure, heart rate, cytokine and chemokine profiles, platelet microparticle pro-thrombotic activity and endothelial progenitor cell paracrine activity reflected by cytokine/chemokine detection; (2) reduced lipid, macrophage and microparticle accumulation in liver; (3) reduced atherosclerosis development, revealed by decreased lipid, macrophage and microparticle content of arterial wall; (4) induced the recruitment and incorporation of endothelial progenitor cells into liver and arterial wall; (5) improved arterial dysfunction by increasing contraction and

  11. Enhancing microparticle internalization by nonphagocytic cells through the use of noncovalently conjugated polyethyleneimine

    PubMed Central

    Patiño, Tania; Nogués, Carme; Ibáñez, Elena; Barrios, Leonardo

    2012-01-01

    Development of micro- and nanotechnology for the study of living cells, especially in the field of drug delivery, has gained interest in recent years. Although several studies have reported successful results in the internalization of micro- and nanoparticles in phagocytic cells, when nonphagocytic cells are used, the low internalization efficiency represents a limitation that needs to be overcome. It has been reported that covalent surface modification of micro- and nanoparticles increases their internalization rate. However, this surface modification represents an obstacle for their use as drug-delivery carriers. For this reason, the aim of the present study was to increase the capability for microparticle internalization of HeLa cells through the use of noncovalently bound transfection reagents: polyethyleneimine (PEI) Lipofectamine™ 2000 and FuGENE 6®. Both confocal microscopy and flow cytometry techniques allowed us to precisely quantify the efficiency of microparticle internalization by HeLa cells, yielding similar results. In addition, intracellular location of microparticles was analyzed through transmission electron microscopy and confocal microscopy procedures. Our results showed that free PEI at a concentration of 0.05 mM significantly increased microparticle uptake by cells, with a low cytotoxic effect. As determined by transmission electron and confocal microscopy analyses, microparticles were engulfed by plasma-membrane projections during internalization, and 24 hours later they were trapped in a lysosomal compartment. These results show the potential use of noncovalently conjugated PEI in microparticle internalization assays. PMID:23152683

  12. Microparticles from stored red blood cells promote a hypercoagulable state in a murine model of transfusion.

    PubMed

    Kim, Young; Xia, Brent T; Jung, Andrew D; Chang, Alex L; Abplanalp, William A; Caldwell, Charles C; Goodman, Michael D; Pritts, Timothy A

    2018-02-01

    Red blood cell-derived microparticles are biologically active, submicron vesicles shed by erythrocytes during storage. Recent clinical studies have linked the duration of red blood cell storage with thromboembolic events in critically ill transfusion recipients. In the present study, we hypothesized that microparticles from aged packed red blood cell units promote a hypercoagulable state in a murine model of transfusion. Microparticles were isolated from aged, murine packed red blood cell units via serial centrifugation. Healthy male C57BL/6 mice were transfused with microparticles or an equivalent volume of vehicle, and whole blood was harvested for analysis via rotational thromboelastometry. Serum was harvested from a separate set of mice after microparticles or saline injection, and analyzed for fibrinogen levels. Red blood cell-derived microparticles were analyzed for their ability to convert prothrombin to thrombin. Finally, mice were transfused with either red blood cell microparticles or saline vehicle, and a tail bleeding time assay was performed after an equilibration period of 2, 6, 12, or 24 hours. Mice injected with red blood cell-derived microparticles demonstrated an accelerated clot formation time (109.3 ± 26.9 vs 141.6 ± 28.2 sec) and increased α angle (68.8 ± 5.0 degrees vs 62.8 ± 4.7 degrees) compared with control (each P < .05). Clotting time and maximum clot firmness were not significantly different between the 2 groups. Red blood cell-derived microparticles exhibited a hundredfold greater conversion of prothrombin substrate to its active thrombin form (66.60 ± 0.03 vs 0.70 ± 0.01 peak OD; P<.0001). Additionally, serum fibrinogen levels were lower in microparticles-injected mice compared with saline vehicle, suggesting thrombin-mediated conversion to insoluble fibrin (14.0 vs 16.5 µg/mL, P<.05). In the tail bleeding time model, there was a more rapid cessation of bleeding at 2 hours posttransfusion (90

  13. Nanochannel Device with Embedded Nanopore: a New Approach for Single-Molecule DNA Analysis and Manipulation

    NASA Astrophysics Data System (ADS)

    Zhang, Yuning; Reisner, Walter

    2012-02-01

    Nanopore and nanochannel based devices are robust methods for biomolecular sensing and single DNA manipulation. Nanopore-based DNA sensing has attractive features that make it a leading candidate as a single-molecule DNA sequencing technology. Nanochannel based extension of DNA, combined with enzymatic or denaturation-based barcoding schemes, is already a powerful approach for genome analysis. We believe that there is revolutionary potential in devices that combine nanochannels with nanpore detectors. In particular, due to the fast translocation of a DNA molecule through a standard nanopore configuration, there is an unfavorable trade-off between signal and sequence resolution. With a combined nanochannel-nanopore device, based on embedding a nanopore inside a nanochannel, we can in principle gain independent control over both DNA translocation speed and sensing signal, solving the key draw-back of the standard nanopore configuration. We will discuss our recent progress on device fabrication and characterization. In particular, we demonstrate that we can detect - using fluorescent microscopy - successful translocation of DNA from the nanochannel out through the nanopore, a possible method to 'select' a given barcode for further analysis. In particular, we show that in equilibrium DNA will not escape through an embedded sub-persistence length nanopore, suggesting that the embedded pore could be used as a nanoscale window through which to interrogate a nanochannel extended DNA molecule.

  14. Nanopore sensing of individual transcription factors bound to DNA

    PubMed Central

    Squires, Allison; Atas, Evrim; Meller, Amit

    2015-01-01

    Transcription factor (TF)-DNA interactions are the primary control point in regulation of gene expression. Characterization of these interactions is essential for understanding genetic regulation of biological systems and developing novel therapies to treat cellular malfunctions. Solid-state nanopores are a highly versatile class of single-molecule sensors that can provide rich information about local properties of long charged biopolymers using the current blockage patterns generated during analyte translocation, and provide a novel platform for characterization of TF-DNA interactions. The DNA-binding domain of the TF Early Growth Response Protein 1 (EGR1), a prototypical zinc finger protein known as zif268, is used as a model system for this study. zif268 adopts two distinct bound conformations corresponding to specific and nonspecific binding, according to the local DNA sequence. Here we implement a solid-state nanopore platform for direct, label- and tether-free single-molecule detection of zif268 bound to DNA. We demonstrate detection of single zif268 TFs bound to DNA according to current blockage sublevels and duration of translocation through the nanopore. We further show that the nanopore can detect and discriminate both specific and nonspecific binding conformations of zif268 on DNA via the distinct current blockage patterns corresponding to each of these two known binding modes. PMID:26109509

  15. Nanopore sensing of individual transcription factors bound to DNA

    NASA Astrophysics Data System (ADS)

    Squires, Allison; Atas, Evrim; Meller, Amit

    2015-06-01

    Transcription factor (TF)-DNA interactions are the primary control point in regulation of gene expression. Characterization of these interactions is essential for understanding genetic regulation of biological systems and developing novel therapies to treat cellular malfunctions. Solid-state nanopores are a highly versatile class of single-molecule sensors that can provide rich information about local properties of long charged biopolymers using the current blockage patterns generated during analyte translocation, and provide a novel platform for characterization of TF-DNA interactions. The DNA-binding domain of the TF Early Growth Response Protein 1 (EGR1), a prototypical zinc finger protein known as zif268, is used as a model system for this study. zif268 adopts two distinct bound conformations corresponding to specific and nonspecific binding, according to the local DNA sequence. Here we implement a solid-state nanopore platform for direct, label- and tether-free single-molecule detection of zif268 bound to DNA. We demonstrate detection of single zif268 TFs bound to DNA according to current blockage sublevels and duration of translocation through the nanopore. We further show that the nanopore can detect and discriminate both specific and nonspecific binding conformations of zif268 on DNA via the distinct current blockage patterns corresponding to each of these two known binding modes.

  16. Warming up human body by nanoporous metallized polyethylene textile.

    PubMed

    Cai, Lili; Song, Alex Y; Wu, Peilin; Hsu, Po-Chun; Peng, Yucan; Chen, Jun; Liu, Chong; Catrysse, Peter B; Liu, Yayuan; Yang, Ankun; Zhou, Chenxing; Zhou, Chenyu; Fan, Shanhui; Cui, Yi

    2017-09-19

    Space heating accounts for the largest energy end-use of buildings that imposes significant burden on the society. The energy wasted for heating the empty space of the entire building can be saved by passively heating the immediate environment around the human body. Here, we demonstrate a nanophotonic structure textile with tailored infrared (IR) property for passive personal heating using nanoporous metallized polyethylene. By constructing an IR-reflective layer on an IR-transparent layer with embedded nanopores, the nanoporous metallized polyethylene textile achieves a minimal IR emissivity (10.1%) on the outer surface that effectively suppresses heat radiation loss without sacrificing wearing comfort. This enables 7.1 °C decrease of the set-point compared to normal textile, greatly outperforming other radiative heating textiles by more than 3 °C. This large set-point expansion can save more than 35% of building heating energy in a cost-effective way, and ultimately contribute to the relief of global energy and climate issues.Energy wasted for heating the empty space of the entire building can be saved by passively heating the immediate environment around the human body. Here, the authors show a nanophotonic structure textile with tailored infrared property for passive personal heating using nanoporous metallized polyethylene.

  17. Neurokinin 1 Receptor Mediates Membrane Blebbing and Sheer Stress-Induced Microparticle Formation in HEK293 Cells

    PubMed Central

    Chen, Panpan; Douglas, Steven D.; Meshki, John; Tuluc, Florin

    2012-01-01

    Cell-derived microparticles participate in intercellular communication similar to the classical messenger systems of small and macro-molecules that bind to specialized membrane receptors. Microparticles have been implicated in the regulation of a variety of complex physiopathologic processes, such as thrombosis, the control of innate and adaptive immunity, and cancer. The neurokinin 1 receptor (NK1R) is a Gq-coupled receptor present on the membrane of a variety of tissues, including neurons in the central and peripheral nervous system, immune cells, endocrine and exocrine glands, and smooth muscle. The endogenous agonist of NK1R is the undecapeptide substance P (SP). We have previously described intracellular signaling mechanisms that regulate NK1R-mediated rapid cell shape changes in HEK293 cells and U373MG cells. In the present study, we show that the activation of NK1R in HEK293 cells, but not in U373MG cells, leads to formation of sheer-stress induced microparticles that stain positive with the membrane-selective fluorescent dye FM 2–10. SP-induced microparticle formation is independent of elevated intracellular calcium concentrations and activation of NK1R present on HEK293-derived microparticles triggers detectable calcium increase in SP-induced microparticles. The ROCK inhibitor Y27632 and the dynamin inhibitor dynasore inhibited membrane blebbing and microparticle formation in HEK293 cells, strongly suggesting that microparticle formation in this cell type is dependent on membrane blebbing. PMID:23024816

  18. Neurokinin 1 receptor mediates membrane blebbing and sheer stress-induced microparticle formation in HEK293 cells.

    PubMed

    Chen, Panpan; Douglas, Steven D; Meshki, John; Tuluc, Florin

    2012-01-01

    Cell-derived microparticles participate in intercellular communication similar to the classical messenger systems of small and macro-molecules that bind to specialized membrane receptors. Microparticles have been implicated in the regulation of a variety of complex physiopathologic processes, such as thrombosis, the control of innate and adaptive immunity, and cancer. The neurokinin 1 receptor (NK1R) is a Gq-coupled receptor present on the membrane of a variety of tissues, including neurons in the central and peripheral nervous system, immune cells, endocrine and exocrine glands, and smooth muscle. The endogenous agonist of NK1R is the undecapeptide substance P (SP). We have previously described intracellular signaling mechanisms that regulate NK1R-mediated rapid cell shape changes in HEK293 cells and U373MG cells. In the present study, we show that the activation of NK1R in HEK293 cells, but not in U373MG cells, leads to formation of sheer-stress induced microparticles that stain positive with the membrane-selective fluorescent dye FM 2-10. SP-induced microparticle formation is independent of elevated intracellular calcium concentrations and activation of NK1R present on HEK293-derived microparticles triggers detectable calcium increase in SP-induced microparticles. The ROCK inhibitor Y27632 and the dynamin inhibitor dynasore inhibited membrane blebbing and microparticle formation in HEK293 cells, strongly suggesting that microparticle formation in this cell type is dependent on membrane blebbing.

  19. Incorporation of iodine in polymeric microparticles and emulsions

    NASA Astrophysics Data System (ADS)

    Kolontaeva, Olga A.; Khokhlova, Anastasia R.; Markina, Natalia E.; Markin, Alexey V.; Burmistrova, Natalia A.

    2016-04-01

    Application of different methods for formation of microcontainers containing iodine is proposed in this paper. Two types of microcontainers: microemulsions and microparticles have been investigated, conditions and methods for obtaining microcontainers were optimized. Microparticles were formed by layer-by-layer method with cores of calcium carbonate (CaCO3) as templates. Incorporation of complexes of iodine with polymers (chitosan, starch, polyvinyl alcohol) into core, shell and hollow capsules was investigated and loadings of microparticles with iodine were estimated. It was found that the complex of iodine with chitosan adsorbed at CaCO3 core is the most stable under physiological conditions and its value of loading can be 450 μg of I2 per 1 g of CaCO3. Moreover, chitosan was chosen as a ligand because of its biocompatibility and biodegradability as well as very low toxicity while its complex with iodine is very stable. A small amount of microparticles containing a iodine-chitosan complex can be used for prolonged release of iodine in the human body since iodine daily intake for adults is around 100 μg. "Oil-in-water" emulsions were prepared by ultrasonication of iodinated oils (sunflower and linseed) with sodium laurilsulfate (SLS) as surfactant solution. At optimal conditions, the homogenous emulsions remained stable for weeks, with total content of iodine in such emulsion being up to 1% (w/w). The oil:SLS ratio was equal to 1:10 (w/w), optimal duration and power of ultrasound exposure were 1.5 min and 7 W, correspondingly. Favorable application of iodized linseed oil for emulsion preparation with suitable oil microdroplets size was proved.

  20. Imaging efficiency of an X-ray contrast agent-incorporated polymeric microparticle.

    PubMed

    Ahn, Sungsook; Jung, Sung Yong; Lee, Jin Pyung; Lee, Sang Joon

    2011-01-01

    Biocompatible polymeric encapsulants have been widely used as a delivery vehicle for a variety of drugs and imaging agents. In this study, X-ray contrast agent (iopamidol) is encapsulated into a polymeric microparticle (polyvinyl alcohol) as a particulate flow tracer in synchrotron X-ray imaging system. The physical properties of the designed microparticles are investigated and correlated with enhancement in the imaging efficiency by experimental observation and theoretical interpretation. The X-ray absorption ability of the designed microparticle is assessed by Beer-Lambert-Bouguer law. Particle size, either in dried state or in solvent, primarily dominates the X-ray absorption ability under the given condition, thus affecting imaging efficiency of the designed X-ray contrast flow tracers. Copyright © 2011 John Wiley & Sons, Ltd.

  1. Fabrication of complete titania nanoporous structures via electrochemical anodization of Ti

    PubMed Central

    2011-01-01

    We present a novel method to fabricate complete and highly oriented anodic titanium oxide (ATO) nano-porous structures with uniform and parallel nanochannels. ATO nano-porous structures are fabricated by anodizing a Ti-foil in two different organic viscous electrolytes at room temperature using a two-step anodizing method. TiO2 nanotubes covered with a few nanometer thin nano-porous layer is produced when the first and the second anodization are carried out in the same electrolyte. However, a complete titania nano-porous (TNP) structures are obtained when the second anodization is conducted in a viscous electrolyte when compared to the first one. TNP structure was attributed to the suppression of F-rich layer dissolution between the cell boundaries in the viscous electrolyte. The structural morphologies were examined by field emission scanning electron microscope. The average pore diameter is approximately 70 nm, while the average inter-pore distance is approximately 130 nm. These TNP structures are useful to fabricate other nanostructure materials and nanodevices. PMID:21711844

  2. Interconnected V2O5 nanoporous network for high-performance supercapacitors.

    PubMed

    Saravanakumar, B; Purushothaman, Kamatchi K; Muralidharan, G

    2012-09-26

    Vanadium pentoxide (V(2)O(5)) has attracted attention for supercapcitor applications because of its extensive multifunctional properties. In the present study, V(2)O(5) nanoporous network was synthesized via simple capping-agent-assisted precipitation technique and it is further annealed at different temperatures. The effect of annealing temperature on the morphology, electrochemical and structural properties, and stability upon oxidation-reduction cycling has been analyzed for supercapacitor application. We achieved highest specific capacitance of 316 F g(-1) for interconnected V(2)O(5) nanoporous network. This interconnected nanoporous network creates facile nanochannels for ion diffusion and facilitates the easy accessibility of ions. Moreover, after six hundred consecutive cycling processes the specific capacitance has changed only by 24%. A simple cost-effective preparation technique of V(2)O(5) nanoporous network with excellent capacitive behavior, energy density, and stability encourages its possible commercial exploitation for the development of high-performance supercapacitors.

  3. Rapid ultrasensitive single particle surface-enhanced Raman spectroscopy using metallic nanopores.

    PubMed

    Cecchini, Michael P; Wiener, Aeneas; Turek, Vladimir A; Chon, Hyangh; Lee, Sangyeop; Ivanov, Aleksandar P; McComb, David W; Choo, Jaebum; Albrecht, Tim; Maier, Stefan A; Edel, Joshua B

    2013-10-09

    Nanopore sensors embedded within thin dielectric membranes have been gaining significant interest due to their single molecule sensitivity and compatibility of detecting a large range of analytes, from DNA and proteins, to small molecules and particles. Building on this concept we utilize a metallic Au solid-state membrane to translocate and rapidly detect single Au nanoparticles (NPs) functionalized with 589 dye molecules using surface-enhanced resonance Raman spectroscopy (SERRS). We show that, due to the plasmonic coupling between the Au metallic nanopore surface and the NP, signal intensities are enhanced when probing analyte molecules bound to the NP surface. Although not single molecule, this nanopore sensing scheme benefits from the ability of SERRS to provide rich vibrational information on the analyte, improving on current nanopore-based electrical and optical detection techniques. We show that the full vibrational spectrum of the analyte can be detected with ultrahigh spectral sensitivity and a rapid temporal resolution of 880 μs.

  4. Nanopore sensing at ultra-low concentrations using single-molecule dielectrophoretic trapping

    NASA Astrophysics Data System (ADS)

    Freedman, Kevin J.; Otto, Lauren M.; Ivanov, Aleksandar P.; Barik, Avijit; Oh, Sang-Hyun; Edel, Joshua B.

    2016-01-01

    Single-molecule techniques are being developed with the exciting prospect of revolutionizing the healthcare industry by generating vast amounts of genetic and proteomic data. One exceptionally promising route is in the use of nanopore sensors. However, a well-known complexity is that detection and capture is predominantly diffusion limited. This problem is compounded when taking into account the capture volume of a nanopore, typically 108-1010 times smaller than the sample volume. To rectify this disproportionate ratio, we demonstrate a simple, yet powerful, method based on coupling single-molecule dielectrophoretic trapping to nanopore sensing. We show that DNA can be captured from a controllable, but typically much larger, volume and concentrated at the tip of a metallic nanopore. This enables the detection of single molecules at concentrations as low as 5 fM, which is approximately a 103 reduction in the limit of detection compared with existing methods, while still maintaining efficient throughput.

  5. Nanopore sensing at ultra-low concentrations using single-molecule dielectrophoretic trapping

    PubMed Central

    Freedman, Kevin J.; Otto, Lauren M.; Ivanov, Aleksandar P.; Barik, Avijit; Oh, Sang-Hyun; Edel, Joshua B.

    2016-01-01

    Single-molecule techniques are being developed with the exciting prospect of revolutionizing the healthcare industry by generating vast amounts of genetic and proteomic data. One exceptionally promising route is in the use of nanopore sensors. However, a well-known complexity is that detection and capture is predominantly diffusion limited. This problem is compounded when taking into account the capture volume of a nanopore, typically 108–1010 times smaller than the sample volume. To rectify this disproportionate ratio, we demonstrate a simple, yet powerful, method based on coupling single-molecule dielectrophoretic trapping to nanopore sensing. We show that DNA can be captured from a controllable, but typically much larger, volume and concentrated at the tip of a metallic nanopore. This enables the detection of single molecules at concentrations as low as 5 fM, which is approximately a 103 reduction in the limit of detection compared with existing methods, while still maintaining efficient throughput. PMID:26732171

  6. A Comparison of Aerosolization and Homogenization Techniques for Production of Alginate Microparticles for Delivery of Corticosteroids to the Colon.

    PubMed

    Samak, Yassmin O; El Massik, Magda; Coombes, Allan G A

    2017-01-01

    Alginate microparticles incorporating hydrocortisone hemisuccinate were produced by aerosolization and homogenization methods to investigate their potential for colonic drug delivery. Microparticle stabilization was achieved by CaCl 2 crosslinking solution (0.5 M and 1 M), and drug loading was accomplished by diffusion into blank microparticles or by direct encapsulation. Homogenization method produced smaller microparticles (45-50 μm), compared to aerosolization (65-90 μm). High drug loadings (40% wt/wt) were obtained for diffusion-loaded aerosolized microparticles. Aerosolized microparticles suppressed drug release in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) prior to drug release in simulated colonic fluid (SCF) to a higher extent than homogenized microparticles. Microparticles prepared using aerosolization or homogenization (1 M CaCl 2 , diffusion loaded) released 5% and 17% of drug content after 2 h in SGF and 4 h in SIF, respectively, and 75% after 12 h in SCF. Thus, aerosolization and homogenization techniques show potential for producing alginate microparticles for colonic drug delivery in the treatment of inflammatory bowel disease. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  7. Nanoporous structures on ZnO thin films

    NASA Astrophysics Data System (ADS)

    Gür, Emre; Kılıç, Bayram; Coşkun, C.; Tüzemen, S.; Bayrakçeken, Fatma

    2010-01-01

    Porous structures were formed on ZnO thin films which were grown by an electrochemical deposition (ECD) method. The growth processes were carried out in a solution of dimethylsulfoxide (DMSO) zinc perchlorate, Zn(ClO 4) 2, at 120 ∘C on indium tin oxide (ITO) substrates. Optical and structural characterizations of electrochemically grown ZnO thin films have shown that the films possess high (0002) c-axis orientation, high nucleation, high intensity and low FWHM of UV emission at the band edge region and a sharp UV absorption edge. Nanoporous structures were formed via self-assembled monolayers (SAMs) of hexanethiol (C 6SH) and dodecanethiol (C 12SH). Scanning electron microscope (SEM) measurements showed that while a nanoporous structure (pore radius 20 nm) is formed on the ZnO thin films by hexanathiol solution, a macroporous structure (pore radius 360 nm) is formed by dodecanethiol solution. No significant variation is observed in X-ray diffraction (XRD) measurements on the ZnO thin films after pore formation. However, photoluminescence (PL) measurements showed that green emission is observed as the dominant emission for the macroporous structures, while no variation is observed for the thin film nanoporous ZnO sample.

  8. Pre-breakdown cavitation nanopores in the dielectric fluid in the inhomogeneous, pulsed electric fields

    NASA Astrophysics Data System (ADS)

    Pekker, Mikhail; Shneider, Mikhail N.

    2015-10-01

    This paper discusses the nanopores emerging and developing in a liquid dielectric under the action of the ponderomotive electrostrictive forces in a nonuniform electric field. It is shown that the gradient of the electric field in the vicinity of the rupture (cavitation nanopore) substantially increases and determines whether the rupture grows or collapses. The cavitation rupture in the liquid (nanopore) tends to stretch along the lines of the original field. The mechanism of the breakdown associated with the generation of secondary ruptures in the vicinity of the poles of the nanopore is proposed. The estimations of the extension time for nanopore in water and oil (polar and nonpolar liquids, respectively) are presented. A new mechanism of nano- and subnanosecond breakdown in the insulating (transformer) oil that can be realized in the vicinity of water microdroplets in nanosecond high-voltage devices is considered.

  9. One-step synthesis of zero-dimensional hollow nanoporous gold nanoparticles with enhanced methanol electrooxidation performance.

    PubMed

    Pedireddy, Srikanth; Lee, Hiang Kwee; Tjiu, Weng Weei; Phang, In Yee; Tan, Hui Ru; Chua, Shu Quan; Troadec, Cedric; Ling, Xing Yi

    2014-09-17

    Nanoporous gold with networks of interconnected ligaments and highly porous structure holds stimulating technological implications in fuel cell catalysis. Current syntheses of nanoporous gold mainly revolve around de-alloying approaches that are generally limited by stringent and harsh multistep protocols. Here we develop a one-step solution phase synthesis of zero-dimensional hollow nanoporous gold nanoparticles with tunable particle size (150-1,000 nm) and ligament thickness (21-54 nm). With faster mass diffusivity, excellent specific electroactive surface area and large density of highly active surface sites, our zero-dimensional nanoporous gold nanoparticles exhibit ~1.4 times enhanced catalytic activity and improved tolerance towards carbonaceous species, demonstrating their superiority over conventional nanoporous gold sheets. Detailed mechanistic study also reveals the crucial heteroepitaxial growth of gold on the surface of silver chloride templates, implying that our synthetic protocol is generic and may be extended to the synthesis of other nanoporous metals via different templates.

  10. One-step synthesis of zero-dimensional hollow nanoporous gold nanoparticles with enhanced methanol electrooxidation performance

    NASA Astrophysics Data System (ADS)

    Pedireddy, Srikanth; Lee, Hiang Kwee; Tjiu, Weng Weei; Phang, In Yee; Tan, Hui Ru; Chua, Shu Quan; Troadec, Cedric; Ling, Xing Yi

    2014-09-01

    Nanoporous gold with networks of interconnected ligaments and highly porous structure holds stimulating technological implications in fuel cell catalysis. Current syntheses of nanoporous gold mainly revolve around de-alloying approaches that are generally limited by stringent and harsh multistep protocols. Here we develop a one-step solution phase synthesis of zero-dimensional hollow nanoporous gold nanoparticles with tunable particle size (150-1,000 nm) and ligament thickness (21-54 nm). With faster mass diffusivity, excellent specific electroactive surface area and large density of highly active surface sites, our zero-dimensional nanoporous gold nanoparticles exhibit ~1.4 times enhanced catalytic activity and improved tolerance towards carbonaceous species, demonstrating their superiority over conventional nanoporous gold sheets. Detailed mechanistic study also reveals the crucial heteroepitaxial growth of gold on the surface of silver chloride templates, implying that our synthetic protocol is generic and may be extended to the synthesis of other nanoporous metals via different templates.

  11. Biomimetic Molecular Signaling using DNA Walkers on Microparticles.

    PubMed

    Damase, Tulsi Ram; Spencer, Adam; Samuel, Bamidele; Allen, Peter B

    2017-06-22

    We report the release of catalytic DNA walkers from hydrogel microparticles and the detection of those walkers by substrate-coated microparticles. This might be considered a synthetic biology analog of molecular signal release and reception. One type of particles was coated with components of a DNA one-step strand displacement (OSD) reaction to release the walker. A second type of particle was coated with substrate (or "track") for the molecular walker. We distinguish these particle types using fluorescence barcoding: we synthesized and distinguished multiple particle types with multicolor fluorescence microscopy and automated image analysis software. This represents a step toward amplified, multiplex, and microscopically localized detection based on DNA nanotechnology.

  12. Immunogenicity and protection in small-animal models with controlled-release tetanus toxoid microparticles as a single-dose vaccine.

    PubMed Central

    Singh, M; Li, X M; Wang, H; McGee, J P; Zamb, T; Koff, W; Wang, C Y; O'Hagan, D T

    1997-01-01

    Tetanus toxoid (TT) was encapsulated in microparticles prepared from polylactide-co-glycolide polymers by a solvent-evaporation technique. Combinations of small- and large-sized microparticles with controlled-release characteristics were used to immunize Sprague-Dawley rats, and the antibody responses were monitored for 1 year. For comparison, control groups of rats were immunized at 0, 1, and 2 months with TT adsorbed to alum. The antibody responses generated by the TT entrapped in microparticles were comparable to those generated by TT adsorbed to alum in control groups from 32 weeks onwards. Microparticles with a single entrapped antigen (TT) induced better antibody responses than microparticles with two antigens (TT and diphtheria toxoid) entrapped simultaneously. A combination vaccine consisting of TT adsorbed to alum and also entrapped in microparticles gave the best antibody responses. In an inhibition assay designed to determine the relative levels of binding of antisera to the antigens, the sera from the microparticle- and the alum-immunized animals showed comparable levels of binding. In addition, in a passive-challenge study with mice, TT adsorbed to alum and TT entrapped in microparticles provided equal levels of protection against a lethal challenge with tetanus toxin. An intradermal-challenge study was also performed with rabbits, which showed similar levels of protection in sera from alum- and microparticle-immunized animals at 4, 12, and 32 weeks after immunization. PMID:9125552

  13. Electrospray Charging of Minerals: Surface Chemistry and Applications to High-Velocity Microparticle Impacts

    NASA Astrophysics Data System (ADS)

    Daly, T.; Call, S.; Austin, D. E.

    2010-12-01

    Electrospray is a soft ionization technique commonly used to charge large biomolecules; it has, however, also been applied to inorganic compounds. We are extending this technique to mineral microparticles. Electrospray-charged mineral microparticles are interesting in the context of surface science because surface chemistry dictates where and how charge carriers can bond to mineral surfaces. In addition, using electrospray to charge mineral particles allows these particles to be electrostatically accelerated as projectiles in high- and hyper-velocity impacts. Since current techniques for producing high- and hyper-velocity microparticle impacts are largely limited to metal or metal-coated projectiles, using minerals as projectiles is a significant innovation. Electrospray involves three steps: creation of charged droplets containing solute/particles, evaporation and bifurcation of droplets, and desolvation of the solute/particles. An acidified solution is slowly pumped through a needle in a strong DC field, which causes the solution to break into tiny, charged droplets laden with protons. Solvent evaporates from the electrosprayed droplets as they move through the electric field toward a grounded plate, causing the charge on the droplet to increase relative to its mass. When the electrosprayed droplet’s charge becomes such that the droplet is no longer stable, it bifurcates, and each of the resulting droplets carries some of the original droplet’s charge. Evaporation and bifurcation continues until the solute particle is completely desolvated. The result is a protonated solute molecule or particle. We built an instrument that electrosprays particles into vacuum and measures them using an image charge detector. Mineral microparticles were prepared by grinding natural mineral samples to ~2 µm diameter. These microparticles are then added to a 4:1 methanol:water solution to create a 0.005% w/v suspension. The suspension is electrosprayed into vacuum, where the

  14. Fluorescent microparticles for sensing cell microenvironment oxygen levels within 3D scaffolds

    PubMed Central

    Acosta, Miguel A.; Ymele-Leki, Patrick; Kostov, Yordan V.; Leach, Jennie B.

    2010-01-01

    We present the development and characterization of fluorescent oxygen-sensing microparticles designed for measuring oxygen concentration in microenvironments existing within standard cell culture and transparent three-dimensional (3D) cell scaffolds. The microparticle synthesis employs poly(dimethylsiloxane) to encapsulate silica gel particles bound with an oxygen-sensitive luminophore as well as a reference or normalization fluorophore that is insensitive to oxygen. We developed a rapid, automated and non-invasive sensor analysis method based on fluorescence microscopy to measure oxygen concentration in a hydrogel scaffold. We demonstrate that the microparticles are non-cytotoxic and that their response is comparable to that of a traditional dissolved oxygen meter. Microparticle size (5–40 μm) was selected for microscale-mapping of oxygen concentration to allow measurements local to individual cells. Two methods of calibration were evaluated and revealed that the sensor system enables characterization of a range of hypoxic to hyperoxic conditions relevant to cell and tissue biology (i.e., pO2 10–160 mm Hg). The calibration analysis also revealed that the microparticles have a high fraction of quenched luminophore (0.90 ± 0.02), indicating that the reported approach provides significant advantages for sensor performance. This study thus reports a versatile oxygen-sensing technology that enables future correlations of local oxygen concentration with individual cell response in cultured engineered tissues. PMID:19285719

  15. Fluorescent microparticles for sensing cell microenvironment oxygen levels within 3D scaffolds.

    PubMed

    Acosta, Miguel A; Ymele-Leki, Patrick; Kostov, Yordan V; Leach, Jennie B

    2009-06-01

    We present the development and characterization of fluorescent oxygen-sensing microparticles designed for measuring oxygen concentration in microenvironments existing within standard cell culture and transparent three-dimensional (3D) cell scaffolds. The microparticle synthesis employs poly(dimethylsiloxane) to encapsulate silica gel particles bound with an oxygen-sensitive luminophore as well as a reference or normalization fluorophore that is insensitive to oxygen. We developed a rapid, automated and non-invasive sensor analysis method based on fluorescence microscopy to measure oxygen concentration in a hydrogel scaffold. We demonstrate that the microparticles are non-cytotoxic and that their response is comparable to that of a traditional dissolved oxygen meter. Microparticle size (5-40 microm) was selected for microscale-mapping of oxygen concentration to allow measurements local to individual cells. Two methods of calibration were evaluated and revealed that the sensor system enables characterization of a range of hypoxic to hyperoxic conditions relevant to cell and tissue biology (i.e., pO(2) 10-160 mmHg). The calibration analysis also revealed that the microparticles have a high fraction of quenched luminophore (0.90+/-0.02), indicating that the reported approach provides significant advantages for sensor performance. This study thus reports a versatile oxygen-sensing technology that enables future correlations of local oxygen concentration with individual cell response in cultured engineered tissues.

  16. Asymmetric Nanopore Electrode-Based Amplification for Electron Transfer Imaging in Live Cells.

    PubMed

    Ying, Yi-Lun; Hu, Yong-Xu; Gao, Rui; Yu, Ru-Jia; Gu, Zhen; Lee, Luke P; Long, Yi-Tao

    2018-04-25

    Capturing real-time electron transfer, enzyme activity, molecular dynamics, and biochemical messengers in living cells is essential for understanding the signaling pathways and cellular communications. However, there is no generalizable method for characterizing a broad range of redox-active species in a single living cell at the resolution of cellular compartments. Although nanoelectrodes have been applied in the intracellular detection of redox-active species, the fabrication of nanoelectrodes to maximize the signal-to-noise ratio of the probe remains challenging because of the stringent requirements of 3D fabrication. Here, we report an asymmetric nanopore electrode-based amplification mechanism for the real-time monitoring of NADH in a living cell. We used a two-step 3D fabrication process to develop a modified asymmetric nanopore electrode with a diameter down to 90 nm, which allowed for the detection of redox metabolism in living cells. Taking advantage of the asymmetric geometry, the above 90% potential drop at the two terminals of the nanopore electrode converts the faradaic current response into an easily distinguishable bubble-induced transient ionic current pattern. Therefore, the current signal was amplified by at least 3 orders of magnitude, which was dynamically linked to the presence of trace redox-active species. Compared to traditional wire electrodes, this wireless asymmetric nanopore electrode exhibits a high signal-to-noise ratio by increasing the current resolution from nanoamperes to picoamperes. The asymmetric nanopore electrode achieves the highly sensitive and selective probing of NADH concentrations as low as 1 pM. Moreover, it enables the real-time nanopore monitoring of the respiration chain (i.e., NADH) in a living cell and the evaluation of the effects of anticancer drugs in an MCF-7 cell. We believe that this integrated wireless asymmetric nanopore electrode provides promising building blocks for the future imaging of electron

  17. Synthesis and characterization of hyaluronic acid coated manganese dioxide microparticles that act as ROS scavengers.

    PubMed

    Bizeau, Joëlle; Tapeinos, Christos; Marella, Claudio; Larrañaga, Aitor; Pandit, Abhay

    2017-11-01

    Atherosclerosis is a chronic inflammatory disease of the arterial wall that leads to cardiovascular diseases which are the major cause of deaths worldwide. There is currently no treatment that can stop or reverse the disease. However, the use of microparticles with anti-inflammatory properties could represent a promising treatment. Herein, spherical microparticles with a core-shell structure and an average diameter of 1μm were synthesized. The microparticles were comprised of a MnCO 3 and MnO 2 core and a 4-arm PEG-amine cross-linked shell of hyaluronic acid. The HA-Mn-SM microparticles were loaded with D-α-tocopherol (vitamin-E) (TOC), to fabricate a targeted biocompatible delivery platform for the treatment of atherosclerotic inflamed cells. Loading and release studies of TOC demonstrated a lactic acid concentration dependant controlled release profile of the HA-Mn-SM mimicking the atherosclerotic environment where lactic acid is over-produced. The microparticles exhibited a high scavenging ability towards H 2 O 2 in addition to the controlled generation of O 2 . The optimal results were obtained for 250μg/mL microparticles which in the presence of 1000μM H 2 O 2 resulted in the scavenging of almost all the H 2 O 2 . Our results demonstrate that 50μg/mL of microparticles scavenged continuously produced H 2 O 2 up to a concentration of 1000μM, a characteristic that demonstrates the sustained therapeutic effect of the HA-Mn-SM microparticles in an environment that mimics that of inflamed tissues. Our results indicate the potential use of HA-Mn-SM as a novel platform for the treatment of atherosclerosis. In vitro studies confirmed that the microparticles are not cytotoxic at concentrations up to 250μg/mL and for 72h. These preliminary results indicate the potential use of HA-Mn-SM as a novel drug delivery system for atherosclerotic tissues. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Microparticle Shedding from Neural Progenitor Cells and Vascular Compartment Cells Is Increased in Ischemic Stroke

    PubMed Central

    Chiva-Blanch, Gemma; Suades, Rosa; Crespo, Javier; Peña, Esther; Padró, Teresa; Jiménez-Xarrié, Elena; Martí-Fàbregas, Joan; Badimon, Lina

    2016-01-01

    Purpose Ischemic stroke has shown to induce platelet and endothelial microparticle shedding, but whether stroke induces microparticle shedding from additional blood and vascular compartment cells is unclear. Neural precursor cells have been shown to replace dying neurons at sites of brain injury; however, if neural precursor cell activation is associated to microparticle shedding, and whether this activation is maintained at long term and associates to stroke type and severity remains unknown. We analyzed neural precursor cells and blood and vascular compartment cells microparticle shedding after an acute ischemic stroke. Methods Forty-four patients were included in the study within the first 48h after the onset of stroke. The cerebral lesion size was evaluated at 3–7 days of the stroke. Circulating microparticles from neural precursor cells and blood and vascular compartment cells (platelets, endothelial cells, erythrocytes, leukocytes, lymphocytes, monocytes and smooth muscle cells) were analyzed by flow cytometry at the onset of stroke and at 7 and 90 days. Forty-four age-matched high cardiovascular risk subjects without documented vascular disease were used as controls. Results Compared to high cardiovascular risk controls, patients showed higher number of neural precursor cell- and all blood and vascular compartment cell-derived microparticles at the onset of stroke, and after 7 and 90 days. At 90 days, neural precursor cell-derived microparticles decreased and smooth muscle cell-derived microparticles increased compared to levels at the onset of stroke, but only in those patients with the highest stroke-induced cerebral lesions. Conclusions Stroke increases blood and vascular compartment cell and neural precursor cell microparticle shedding, an effect that is chronically maintained up to 90 days after the ischemic event. These results show that stroke induces a generalized blood and vascular cell activation and the initiation of neuronal cell repair process

  19. Ion-sculpting of nanopores in amorphous metals, semiconductors, and insulators

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    George, H. Bola; Madi, Charbel S.; Aziz, Michael J.

    2010-06-28

    We report the closure of nanopores to single-digit nanometer dimensions by ion sculpting in a range of amorphous materials including insulators (SiO{sub 2} and SiN), semiconductors (a-Si), and metallic glasses (Pd{sub 80}Si{sub 20})--the building blocks of a single-digit nanometer electronic device. Ion irradiation of nanopores in crystalline materials (Pt and Ag) does not cause nanopore closure. Ion irradiation of c-Si pores below 100 deg. C and above 600 deg. C, straddling the amorphous-crystalline dynamic transition temperature, yields closure at the lower temperature but no mass transport at the higher temperature. Ion beam nanosculpting appears to be restricted to materials thatmore » either are or become amorphous during ion irradiation.« less

  20. Detecting a single molecule using a micropore-nanopore hybrid chip

    PubMed Central

    2013-01-01

    Nanopore-based DNA sequencing and biomolecule sensing have attracted more and more attention. In this work, novel sensing devices were built on the basis of the chips containing nanopore arrays in polycarbonate (PC) membranes and micropores in Si3N4 films. Using the integrated chips, the transmembrane ionic current induced by biomolecule's translocation was recorded and analyzed, which suggested that the detected current did not change linearly as commonly expected with increasing biomolecule concentration. On the other hand, detailed translocation information (such as translocation gesture) was also extracted from the discrete current blockages in basic current curves. These results indicated that the nanofluidic device based on the chips integrated by micropores and nanopores possessed comparative potentials in biomolecule sensing. PMID:24261484

  1. Detecting a single molecule using a micropore-nanopore hybrid chip.

    PubMed

    Liu, Lei; Zhu, Lizhong; Ni, Zhonghua; Chen, Yunfei

    2013-11-21

    Nanopore-based DNA sequencing and biomolecule sensing have attracted more and more attention. In this work, novel sensing devices were built on the basis of the chips containing nanopore arrays in polycarbonate (PC) membranes and micropores in Si3N4 films. Using the integrated chips, the transmembrane ionic current induced by biomolecule's translocation was recorded and analyzed, which suggested that the detected current did not change linearly as commonly expected with increasing biomolecule concentration. On the other hand, detailed translocation information (such as translocation gesture) was also extracted from the discrete current blockages in basic current curves. These results indicated that the nanofluidic device based on the chips integrated by micropores and nanopores possessed comparative potentials in biomolecule sensing.

  2. Towards the Ultimate Membranes: Two-dimensional Nanoporous Materials and Films.

    PubMed

    Agrawal, Kumar Varoon

    2018-05-30

    The energy-efficient separation of molecules has been a popular topic in chemistry and chemical engineering as a consequence of the large energy-footprint of separation processes in the chemical industry. The Laboratory of Advanced Separations (LAS) at EPFL, led by Prof. Kumar Varoon Agrawal, is focused to develop next-generation, high-performance membranes that can improve the energy efficiency of hydrogen purification, carbon capture, hydrocarbon and water purification. For this, LAS is seeking to develop the ultimate nanoporous membranes, those with a thickness of 1 nm and possessing an array of size-selective nanopores. In this article, the research activities at LAS, especially in the bottom-up and top-down synthesis of chemically and thermally stable, nanoporous two-dimensional materials and membranes are discussed.

  3. Enhanced Azo-Dyes Degradation Performance of Fe-Si-B-P Nanoporous Architecture

    PubMed Central

    Weng, Nan; Wang, Feng; Qin, Fengxiang; Tang, Wanying; Dan, Zhenhua

    2017-01-01

    Nanoporous structures were fabricated from Fe76Si9B10P5 amorphous alloy annealed at 773 K by dealloying in 0.05 M H2SO4 solution, as a result of preferential dissolution of α-Fe grains in form of the micro-coupling cells between α-Fe and cathodic residual phases. Nanoporous Fe-Si-B-P powders exhibit much better degradation performance to methyl orange and direct blue azo dyes compared with gas-atomized Fe76Si9B10P5 amorphous powders and commercial Fe powders. The degradation reaction rate constants of nanoporous powders are almost one order higher than those of the amorphous counterpart powders and Fe powders, accompanying with lower activation energies of 19.5 and 26.8 kJ mol−1 for the degradation reactions of methyl orange and direct blue azo dyes, respectively. The large surface area of the nanoporous structure, and the existence of metalloids as well as residual amorphous phase with high catalytic activity are responsible for the enhanced azo-dyes degradation performance of the nanoporous Fe-Si-B-P powders. PMID:28846622

  4. Association between cell-derived microparticles and adverse events in patients with nonpulsatile left ventricular assist devices

    PubMed Central

    Nascimbene, Angelo; Hernandez, Ruben; George, Joggy K.; Parker, Anita; Bergeron, Angela L.; Pradhan, Subhashree; Vijayan, K. Vinod; Civitello, Andrew; Simpson, Leo; Nawrot, Maria; Lee, Vei-Vei; Mallidi, Hari R.; Delgado, Reynolds M.; Dong, Jing Fei; Frazier, O.H.

    2014-01-01

    BACKGROUND Continuous-flow left ventricular assist devices (LVADs) expose blood cells to high shear stress, potentially resulting in the production of microparticles that express phosphatidylserine (PS+) and promote coagulation and inflammation. In this prospective study, we attempted to determine whether PS+ microparticle levels correlate with clinical outcomes in LVAD-supported patients. METHODS We enrolled 20 patients undergoing implantation of the HeartMate II LVAD and 10 healthy controls who provided reference values for the microparticle assays. Plasma was collected before LVAD implantation, at discharge, at 3-month follow-up, and when an adverse clinical event occurred. We quantified PS+ microparticles in the plasma using flow cytometry. RESULTS During the study period, 8 patients developed adverse clinical events: ventricular tachycardia storm (n=1), non–ST-elevation myocardial infarction (n=2), arterial thrombosis (n=2), gastrointestinal bleeding (n=2), and stroke (n=3). Levels of PS+ microparticles were higher in patients at baseline than in healthy controls (2.11%±1.26 vs 0.69±0.46, P=0.007). After LVAD implantation, patient PS+ microparticle levels increased to 2.39%±1.22 at discharge and then leveled to 1.97%±1.25 at 3-month follow-up. Importantly, patients who developed an adverse event had significantly higher levels of PS+ microparticles than did patients with no events (3.82%±1.17 vs 1.57%±0.59, P<0.001), even though the 2 patient groups did not markedly differ in other clinical and hematologic parameters. CONCLUSIONS Our results suggest that an elevation of PS+ microparticle levels may be associated with adverse clinical events. Thus, measuring PS+ microparticle levels in LVAD-supported patients may help identify patients at increased risk for adverse events. PMID:24656391

  5. Association between cell-derived microparticles and adverse events in patients with nonpulsatile left ventricular assist devices.

    PubMed

    Nascimbene, Angelo; Hernandez, Ruben; George, Joggy K; Parker, Anita; Bergeron, Angela L; Pradhan, Subhashree; Vijayan, K Vinod; Civitello, Andrew; Simpson, Leo; Nawrot, Maria; Lee, Vei-Vei; Mallidi, Hari R; Delgado, Reynolds M; Dong, Jing Fei; Frazier, O H

    2014-05-01

    Continuous-flow left ventricular assist devices (LVADs) expose blood cells to high shear stress, potentially resulting in the production of microparticles that express phosphatidylserine (PS+) and promote coagulation and inflammation. In this prospective study, we attempted to determine whether PS+ microparticle levels correlate with clinical outcomes in LVAD-supported patients. We enrolled 20 patients undergoing implantation of the HeartMate II LVAD (Thoratec Corp, Pleasanton, CA) and 10 healthy controls who provided reference values for the microparticle assays. Plasma was collected before LVAD implantation, at discharge, at the 3-month follow-up, and when an adverse clinical event occurred. We quantified PS+ microparticles in the plasma using flow cytometry. During the study period, 8 patients developed adverse clinical events: ventricular tachycardia storm in 1, non-ST-elevation myocardial infarction in 2, arterial thrombosis in 2, gastrointestinal bleeding in 2, and stroke in 3. Levels of PS+ microparticles were higher in patients at baseline than in healthy controls (2.11% ± 1.26% vs 0.69% ± 0.46%, p = 0.007). After LVAD implantation, patient PS+ microparticle levels increased to 2.39% ± 1.22% at discharge and then leveled to 1.97% ± 1.25% at the 3-month follow-up. Importantly, levels of PS+ microparticles were significantly higher in patients who developed an adverse event than in patients with no events (3.82% ± 1.17% vs 1.57% ± 0.59%, p < 0.001), even though the 2 patient groups did not markedly differ in other clinical and hematologic parameters. Our results suggest that an elevation of PS+ microparticle levels may be associated with adverse clinical events. Thus, measuring PS+ microparticle levels in LVAD-supported patients may help identify patients at increased risk for adverse events. Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  6. Nanopore arrays in a silicon membrane for parallel single-molecule detection: fabrication

    NASA Astrophysics Data System (ADS)

    Schmidt, Torsten; Zhang, Miao; Sychugov, Ilya; Roxhed, Niclas; Linnros, Jan

    2015-08-01

    Solid state nanopores enable translocation and detection of single bio-molecules such as DNA in buffer solutions. Here, sub-10 nm nanopore arrays in silicon membranes were fabricated by using electron-beam lithography to define etch pits and by using a subsequent electrochemical etching step. This approach effectively decouples positioning of the pores and the control of their size, where the pore size essentially results from the anodizing current and time in the etching cell. Nanopores with diameters as small as 7 nm, fully penetrating 300 nm thick membranes, were obtained. The presented fabrication scheme to form large arrays of nanopores is attractive for parallel bio-molecule sensing and DNA sequencing using optical techniques. In particular the signal-to-noise ratio is improved compared to other alternatives such as nitride membranes suffering from a high-luminescence background.

  7. Nanopore arrays in a silicon membrane for parallel single-molecule detection: fabrication.

    PubMed

    Schmidt, Torsten; Zhang, Miao; Sychugov, Ilya; Roxhed, Niclas; Linnros, Jan

    2015-08-07

    Solid state nanopores enable translocation and detection of single bio-molecules such as DNA in buffer solutions. Here, sub-10 nm nanopore arrays in silicon membranes were fabricated by using electron-beam lithography to define etch pits and by using a subsequent electrochemical etching step. This approach effectively decouples positioning of the pores and the control of their size, where the pore size essentially results from the anodizing current and time in the etching cell. Nanopores with diameters as small as 7 nm, fully penetrating 300 nm thick membranes, were obtained. The presented fabrication scheme to form large arrays of nanopores is attractive for parallel bio-molecule sensing and DNA sequencing using optical techniques. In particular the signal-to-noise ratio is improved compared to other alternatives such as nitride membranes suffering from a high-luminescence background.

  8. Enhanced Biological Functions of Human Mesenchymal Stem-Cell Aggregates Incorporating E-Cadherin-Modified PLGA Microparticles.

    PubMed

    Zhang, Yan; Mao, Hongli; Gao, Chao; Li, Suhua; Shuai, Qizhi; Xu, Jianbin; Xu, Ke; Cao, Lei; Lang, Ren; Gu, Zhongwei; Akaike, Toshihiro; Yang, Jun

    2016-08-01

    Mesenchymal stem cells (MSCs) have emerged as a promising source of multipotent cells for various cell-based therapies due to their unique properties, and formation of 3D MSC aggregates has been explored as a potential strategy to enhance therapeutic efficacy. In this study, poly(lactic-co-glycolic acid) (PLGA) microparticles modified with human E-cadherin fusion protein (hE-cad-PLGA microparticles) have been fabricated and integrated with human MSCs to form 3D cell aggregates. The results show that, compared with the plain PLGA, the hE-cad-PLGA microparticles distribute within the aggregates more evenly and further result in a more significant improvement of cellular proliferation and secretion of a series of bioactive factors due to the synergistic effects from the bioactive E-cadherin fragments and the PLGA microparticles. Meanwhile, the hE-cad-PLGA microparticles incorporated in the aggregates upregulate the phosphorylation of epidermal growth factor receptors and activate the AKT and ERK1/2 signaling pathways in the MSCs. Additionally, the E-cadherin/β-catenin cellular membrane complex in the MSCs is markedly stimulated by the hE-cad-PLGA microparticles. Therefore, engineering 3D cell aggregates with hE-cad-PLGA microparticles can be a promising method for ex vivo multipotent stem-cell expansion with enhanced biological functions and may offer a novel route to expand multipotent stem-cell-based clinical applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Chitosan-modified porous silicon microparticles for enhanced permeability of insulin across intestinal cell monolayers.

    PubMed

    Shrestha, Neha; Shahbazi, Mohammad-Ali; Araújo, Francisca; Zhang, Hongbo; Mäkilä, Ermei M; Kauppila, Jussi; Sarmento, Bruno; Salonen, Jarno J; Hirvonen, Jouni T; Santos, Hélder A

    2014-08-01

    Porous silicon (PSi) based particulate systems are emerging as an important drug delivery system due to its advantageous properties such as biocompatibility, biodegradability and ability to tailor the particles' physicochemical properties. Here, annealed thermally hydrocarbonized PSi (AnnTHCPSi) and undecylenic acid modified AnnTHCPSi (AnnUnTHCPSi) microparticles were developed as a PSi-based platform for oral delivery of insulin. Chitosan (CS) was used to modify the AnnUnTHCPSi microparticles to enhance the intestinal permeation of insulin. Surface modification with CS led to significant increase in the interaction of PSi microparticles with Caco-2/HT-29 cell co-culture monolayers. Compared to pure insulin, the CS-conjugated microparticles significantly improved the permeation of insulin across the Caco-2/HT-29 cell monolayers, with ca. 20-fold increase in the amount of insulin permeated and ca. 7-fold increase in the apparent permeability (P(app)) value. Moreover, among all the investigated particles, the CS-conjugated microparticles also showed the highest amount of insulin associated with the mucus layer and the intestinal Caco-2 cells and mucus secreting HT-29 cells. Our results demonstrate that CS-conjugated AnnUnTHCPSi microparticles can efficiently enhance the insulin absorption across intestinal cells, and thus, they are promising microsystems for the oral delivery of proteins and peptides across the intestinal cell membrane. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Starch, inulin and maltodextrin as encapsulating agents affect the quality and stability of jussara pulp microparticles.

    PubMed

    Lacerda, Ellen Cristina Quirino; Calado, Verônica Maria de Araújo; Monteiro, Mariana; Finotelli, Priscilla Vanessa; Torres, Alexandre Guedes; Perrone, Daniel

    2016-10-20

    The influence of encapsulating carbohydrates (EC) with varying properties on the technological and functional properties of jussara pulp microparticles produced by spray drying were evaluated using experimental design. Microparticles produced with sodium octenyl succinate (OSA) starch at 0.5 core to EC ratio and with mixtures of inulin and maltodextrin at 1.0 and 2.0 core to EC ratio showed darker color, and higher anthocyanins contents and antioxidant activity. Seven microparticles showing high water solubility and desirable surface morphology. Hygroscopicity (10.7% and 11.5%) and wettability (41s and 43s) were improved when OSA starch and mixtures of inulin and maltodextrin were used. The anthocyanins contents and color of the microparticles did not change when exposed to light at 50°C for 38days. Finally, microparticles produced at 1.0 core to EC ratio with 2/3 OSA starch, 1/6 inulin and 1/6 maltodextrin were selected. These microparticles may be applied as colorant in numerous foods, whilst adding prebiotic fiber and anthocyanins. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Formulation of olfactory-targeted microparticles with tamarind seed polysaccharide to improve nose-to-brain transport of drugs.

    PubMed

    Yarragudi, Sasi B; Richter, Robert; Lee, Helen; Walker, Greg F; Clarkson, Andrew N; Kumar, Haribalan; Rizwan, Shakila B

    2017-05-01

    Targeted delivery and retention of drug formulations in the olfactory mucosa, the target site for nose-to-brain drug absorption is a major challenge due to the geometrical complexity of the nose and nasal clearance. Recent modelling data indicates that 10μm-sized microparticles show maximum deposition in the olfactory mucosa. In the present study we tested the hypothesis that 10μm-sized mucoadhesive microparticles would preferentially deposit on, and increase retention of drug on, the olfactory mucosa in a novel 3D-printed human nasal-replica cast under simulated breathing. The naturally occurring mucoadhesive polymer, tamarind seed polysaccharide (TSP) was used to formulate the microparticles using a spray drying technique. Physicochemical properties of microparticles such as size, morphology and mucoadhesiveness was investigated using a combination of laser diffraction, electron microscopy and texture-analysis. Furthermore, FITC-dextrans (5-40kDa) were incorporated in TSP-microparticles as model drugs. Size-dependent permeability of the FITC-dextrans was observed ex vivo using porcine nasal mucosa. Using the human nasal-replica cast, greater deposition of 10μm TSP-microparticles in the olfactory region was observed compared to TSP-microparticles 2μm in size. Collectively, these findings support our hypothesis that 10μm-sized mucoadhesive microparticles can achieve selective deposition and retention of drug in the olfactory mucosa. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Quasi-static motion of microparticles at the depinning contact line of an evaporating droplet on PDMS surface

    NASA Astrophysics Data System (ADS)

    Yu, Ying-Song; Xia, Xue-Lian; Zheng, Xu; Huang, Xianfu; Zhou, Jin-Zhi

    2017-09-01

    In this paper, evaporation of sessile water droplets containing fluorescent polystyrene (PS) microparticles on polydimethylsiloxane (PDMS) surfaces with different curing ratios was studied experimentally using laser confocal microscopy. At the beginning, there were some microparticles located at the contact line and some microparticles moved towards the line. Due to contact angle hysteresis, at first both the contact line and the microparticles were pinned. With the depinning contact line, the microparticles moved together spontaneously. Using the software ImageJ, the location of contact lines at different time were acquired and the circle centers and radii of the contact lines were obtained via the least square method. Then the average distance of two neighbor contact lines at a certain time interval was obtained to characterize the motion of the contact line. Fitting the distance-time curve at the depinning contact line stage with polynomials and differentiating the polynomials with time, we obtained the velocity and acceleration of both the contact line and the microparticles located at the line. The velocity and the maximum acceleration were, respectively, of the orders of 1 μm/s and 20-200 nm/s2, indicating that the motion of the microparticles located at the depinning contact line was quasi-static. Finally, we presented a theoretical model to describe the quasi-static process, which may help in understanding both self-pinning and depinning of microparticles.

  13. Precise fabrication of a 5 nm graphene nanopore with a helium ion microscope for biomolecule detection

    NASA Astrophysics Data System (ADS)

    Deng, Yunsheng; Huang, Qimeng; Zhao, Yue; Zhou, Daming; Ying, Cuifeng; Wang, Deqiang

    2017-01-01

    We report a scalable method to fabricate high-quality graphene nanopores for biomolecule detection using a helium ion microscope (HIM). HIM milling shows promising capabilities for precisely controlling the size and shape, and may allow for the potential production of nanopores at wafer scale. Nanopores could be fabricated at different sizes ranging from 5 to 30 nm in diameter in few minutes. Compared with the current solid-state nanopore fabrication techniques, e.g. transmission electron microscopy, HIM is fast. Furthermore, we investigated the exposure-time dependence of graphene nanopore formation: the rate of pore expansion did not follow a simple linear relationship with exposure time, but a fast expansion rate at short exposure time and a slow rate at long exposure time. In addition, we performed biomolecule detection with our patterned graphene nanopore. The ionic current signals induced by 20-base single-stranded DNA homopolymers could be used as a basis for homopolymer differentiation. However, the charge interaction of homopolymer chains with graphene nanopores, and the conformations of homopolymer chains need to be further considered to improve the accuracy of discrimination.

  14. Nanoporous metallic surface: Facile fabrication and enhancement of boiling heat transfer

    NASA Astrophysics Data System (ADS)

    Tang, Yong; Tang, Biao; Qing, Jianbo; Li, Qing; Lu, Longsheng

    2012-09-01

    The paper reports a flexible and low-cost approach, hot-dip galvanizing and dealloying, for the fabrication of enhanced nanoporous metallic surfaces. A Cu-Zn alloy layer mainly composed of γ-Cu5Zn8 and β'-CuZn was formed during the hot-dipping process. The multiple oxidation peaks recorded in the anodic liner sweep voltammetry measurements indicate different dezincification preferences of the alloy phases. A nanoporous copper surface with approximately 50-200 nm in pore size was obtained after a free corrosion process. The nanoporous structure improves the surface wettability and shows dramatic reduction of wall superheat compared to that of the plain surface in the pool-boiling experiments.

  15. Nanopore with Transverse Nanoelectrodes for Electrical Characterization and Sequencing of DNA

    PubMed Central

    Gierhart, Brian C.; Howitt, David G.; Chen, Shiahn J.; Zhu, Zhineng; Kotecki, David E.; Smith, Rosemary L.; Collins, Scott D.

    2009-01-01

    A DNA sequencing device which integrates transverse conducting electrodes for the measurement of electrode currents during DNA translocation through a nanopore has been nanofabricated and characterized. A focused electron beam (FEB) milling technique, capable of creating features on the order of 1 nm in diameter, was used to create the nanopore. The device was characterized electrically using gold nanoparticles as an artificial analyte with both DC and AC measurement methods. Single nanoparticle/electrode interaction events were recorded. A low-noise, high-speed transimpedance current amplifier for the detection of nano to picoampere currents at microsecond time scales was designed, fabricated and tested for future integration with the nanopore device. PMID:19584949

  16. Nanopore with Transverse Nanoelectrodes for Electrical Characterization and Sequencing of DNA.

    PubMed

    Gierhart, Brian C; Howitt, David G; Chen, Shiahn J; Zhu, Zhineng; Kotecki, David E; Smith, Rosemary L; Collins, Scott D

    2008-06-16

    A DNA sequencing device which integrates transverse conducting electrodes for the measurement of electrode currents during DNA translocation through a nanopore has been nanofabricated and characterized. A focused electron beam (FEB) milling technique, capable of creating features on the order of 1 nm in diameter, was used to create the nanopore. The device was characterized electrically using gold nanoparticles as an artificial analyte with both DC and AC measurement methods. Single nanoparticle/electrode interaction events were recorded. A low-noise, high-speed transimpedance current amplifier for the detection of nano to picoampere currents at microsecond time scales was designed, fabricated and tested for future integration with the nanopore device.

  17. Localization Transport in Granular and Nanoporous Carbon Systems.

    NASA Astrophysics Data System (ADS)

    Fung, Alex Weng Pui

    Porous carbon materials have long since been used in industry to make capacitors and adsorption agents because of their high specific surface area. Although their adsorption properties have been extensively studied, we have not seen the same vigor in the investigation of their physical properties, which are important not only for providing complementary characterization methods, but also for understanding the physics which underlies the manufacturing process and motivates intelligent design of these materials. The study of the new physics in these novel nanoporous materials also straddles the scientific forefronts of nanodimensional and disordered systems. In this thesis, we study the structural and electrical properties of two nanoporous carbons, namely activated carbon fibers and carbon aerogels. Specifically, we perform Raman scattering, x-ray diffraction, magnetic susceptibility, electrical transport and magnetotransport experiments. Results from other experiments reported in the literature or communicated to us by our collaborators, such as porosity and surface area measurements by adsorption methods, electron spin resonance, transmission electron microscopy, mechanical properties measurements and so on, are also frequently used in this thesis for additional characterization information. By correlating all the relevant results, we obtain the structure -property relationships in these nanoporous materials. This study shows that the transport properties of these porous materials can be used on one hand for sensitive characterization of complex materials, and on the other hand, for observing interesting and unusual physical phenomena. For example, as-prepared nanoporous carbon systems, exhibit in their low-temperature electrical conductivity a universal temperature dependence which is characteristic of a granular metallic system, despite their morphological differences. By studying further the magnetoresistance in these carbon materials, it is found that the

  18. Gamma-oryzanol-loaded calcium pectinate microparticles reinforced with chitosan: optimization and release characteristics.

    PubMed

    Lee, Ji-Soo; Kim, Jong Soo; Lee, Hyeon Gyu

    2009-05-01

    Response surface methodology was used to optimize microparticle preparation conditions, including the ratio of pectin:gamma-oryzanol (OZ) (X(1)), agitation speed (X(2)), and the concentration of emulsifier (X(3)), for maximal entrapment efficiency (EE) of OZ-loaded Ca pectinate microparticles. The optimized values of X(1), X(2), and X(3) were found to be 2.72:5.28, 1143.5 rpm, and 2.61%, respectively. Experimental results obtained for the optimum formulation agreed favorably with the predicted results, indicating the usefulness of predicting models for EE. In order to evaluate the effect of chitosan-coating and blending on the release pattern of the entrapped OZ from microparticles, chitosan-coated and blended Ca pectinate microparticles were prepared. Release studies revealed that the chitosan treatments, especially the chitosan-coating, were effective in suppressing the release in both simulated gastric fluid (SGF) and intestinal fluid (SIF).

  19. Enhancing the Microparticle Deposition Stability and Homogeneity on Planer for Synthesis of Self-Assembly Monolayer.

    PubMed

    Shih, An-Ci; Han, Chi-Jui; Kuo, Tsung-Cheng; Cheng, Yun-Chien

    2018-03-14

    The deposition stability and homogeneity of microparticles improved with mask, lengthened nozzle and flow rate adjustment. The microparticles can be used to encapsulate monomers, before the monomers in the microparticles can be deposited onto a substrate for nanoscale self-assembly. For the uniformity of the synthesized nanofilm, the homogeneity of the deposited microparticles becomes an important issue. Based on the ANSYS simulation results, the effects of secondary flow were minimized with a lengthened nozzle. The ANSYS simulation was also used to investigate the ring-vortex generation and why the ring vortex can be eliminated by adding a mask with an aperture between the nozzle and deposition substrate. The experimental results also showed that particle deposition with a lengthened nozzle was more stable, while adding the mask stabilized deposition and diminished the ring-vortex contamination. The effects of flow rate and pressure were also investigated. Hence, the deposition stability and homogeneity of microparticles was improved.

  20. Capreomycin oleate microparticles for intramuscular administration: Preparation, in vitro release and preliminary in vivo evaluation.

    PubMed

    Cambronero-Rojas, Adrián; Torres-Vergara, Pablo; Godoy, Ricardo; von Plessing, Carlos; Sepúlveda, Jacqueline; Gómez-Gaete, Carolina

    2015-07-10

    Capreomycin sulfate (CS) is a second-line drug used for the treatment of multidrug-resistant tuberculosis (MDR-TB). The adverse effects profile and uncomfortable administration scheme of CS has led to the development of formulations based on liposomes and polymeric microparticles. However, as CS is a water-soluble peptide that does not encapsulate properly into hydrophobic particulate matrices, it was necessary to reduce its aqueous solubility by forming the pharmacologically active capreomycin oleate (CO) ion pair. The aim of this research was to develop a new formulation of CO for intramuscular injection, based on biodegradable microparticles that encapsulate CO in order to provide a controlled release of the drug with reduced local and systemic adverse effects. The CO-loaded microparticles prepared by spray drying or solvent emulsion-evaporation were characterized in their morphology, encapsulation efficiency, in vitro/in vivo kinetics and tissue tolerance. Through scanning electron microscopy it was confirmed that the microparticles were monodisperse and spherical, with an optimal size for intramuscular administration. The interaction between CO and the components of the microparticle matrix was confirmed on both formulations by X-ray powder diffraction and differential scanning calorimetry analyses. The encapsulation efficiencies for the spray-dried and emulsion-evaporation microparticles were 92% and 56%, respectively. The in vitro kinetics performed on both formulations demonstrated a controlled and continuous release of CO from the microparticles, which was successfully reproduced on an in vivo rodent model. The results of the histological analysis demonstrated that none of the formulations produced significant tissue damage on the site of injection. Therefore, the results suggest that injectable CO microparticles obtained by spray drying and solvent emulsion-evaporation could represent an interesting therapeutic alternative for the treatment of MDR