Duplexed sandwich immunoassays on a fiber-optic microarray.

PubMed

Rissin, David M; Walt, David R

2006-03-30

In this paper, we describe a duplexed imaging optical fiber array-based immunoassay for immunoglobulin A (IgA) and lactoferrin. To fabricate the individually addressable array, microspheres were functionalized with highly specific monoclonal antibodies. The microspheres were loaded in microwells etched into the distal face of an imaging optical fiber bundle. Two microsphere-based sandwich immunoassays were developed to simultaneously detect IgA and lactoferrin, two innate immune system proteins found in human saliva. Individual microspheres could be interrogated for the simultaneous measurement of both proteins. The working concentration range for IgA detection was between 700 pM and 100 nM, while the working concentration range for lactoferrin was between 385 pM and 10 nM. The cross-reactivity between detection antibodies and their non-specific targets was relatively low in comparison to the signal generated by the specific binding with their targets. These results suggest that the degree of multiplexing on this fiber-optic array platform can be increased beyond a duplex.

Fiber-optic microsphere-based arrays for multiplexed biological warfare agent detection.

PubMed

Song, Linan; Ahn, Soohyoun; Walt, David R

2006-02-15

We report a multiplexed high-density DNA array capable of rapid, sensitive, and reliable identification of potential biological warfare agents. An optical fiber bundle containing 6000 individual 3.1-mum-diameter fibers was chemically etched to yield microwells and used as the substrate for the array. Eighteen different 50-mer single-stranded DNA probes were covalently attached to 3.1-mum microspheres. Probe sequences were designed for Bacillus anthracis, Yersinia pestis, Francisella tularensis, Brucella melitensis, Clostridium botulinum, Vaccinia virus, and one biological warfare agent (BWA) simulant, Bacillus thuringiensis kurstaki. The microspheres were distributed into the microwells to form a randomized multiplexed high-density DNA array. A detection limit of 10 fM in a 50-microL sample volume was achieved within 30 min of hybridization for B. anthracis, Y. pestis, Vaccinia virus, and B. thuringiensis kurstaki. We used both specific responses of probes upon hybridization to complementary targets as well as response patterns of the multiplexed array to identify BWAs with high accuracy. We demonstrated the application of this multiplexed high-density DNA array for parallel identification of target BWAs in spiked sewage samples after PCR amplification. The array's miniaturized feature size, fabrication flexibility, reusability, and high reproducibility may enable this array platform to be integrated into a highly sensitive, specific, and reliable portable instrument for in situ BWA detection.

Suspension arrays based on nanoparticle-encoded microspheres for high-throughput multiplexed detection

PubMed Central

Leng, Yuankui

2017-01-01

Spectrometrically or optically encoded microsphere based suspension array technology (SAT) is applicable to the high-throughput, simultaneous detection of multiple analytes within a small, single sample volume. Thanks to the rapid development of nanotechnology, tremendous progress has been made in the multiplexed detecting capability, sensitivity, and photostability of suspension arrays. In this review, we first focus on the current stock of nanoparticle-based barcodes as well as the manufacturing technologies required for their production. We then move on to discuss all existing barcode-based bioanalysis patterns, including the various labels used in suspension arrays, label-free platforms, signal amplification methods, and fluorescence resonance energy transfer (FRET)-based platforms. We then introduce automatic platforms for suspension arrays that use superparamagnetic nanoparticle-based microspheres. Finally, we summarize the current challenges and their proposed solutions, which are centered on improving encoding capacities, alternative probe possibilities, nonspecificity suppression, directional immobilization, and “point of care” platforms. Throughout this review, we aim to provide a comprehensive guide for the design of suspension arrays, with the goal of improving their performance in areas such as multiplexing capacity, throughput, sensitivity, and cost effectiveness. We hope that our summary on the state-of-the-art development of these arrays, our commentary on future challenges, and some proposed avenues for further advances will help drive the development of suspension array technology and its related fields. PMID:26021602

Validation of large-scale, monochromatic UV disinfection systems for drinking water using dyed microspheres.

PubMed

Blatchley, E R; Shen, C; Scheible, O K; Robinson, J P; Ragheb, K; Bergstrom, D E; Rokjer, D

2008-02-01

Dyed microspheres have been developed as a new method for validation of ultraviolet (UV) reactor systems. When properly applied, dyed microspheres allow measurement of the UV dose distribution delivered by a photochemical reactor for a given operating condition. Prior to this research, dyed microspheres had only been applied to a bench-scale UV reactor. The goal of this research was to extend the application of dyed microspheres to large-scale reactors. Dyed microsphere tests were conducted on two prototype large-scale UV reactors at the UV Validation and Research Center of New York (UV Center) in Johnstown, NY. All microsphere tests were conducted under conditions that had been used previously in biodosimetry experiments involving two challenge bacteriophage: MS2 and Qbeta. Numerical simulations based on computational fluid dynamics and irradiance field modeling were also performed for the same set of operating conditions used in the microspheres assays. Microsphere tests on the first reactor illustrated difficulties in sample collection and discrimination of microspheres against ambient particles. Changes in sample collection and work-up were implemented in tests conducted on the second reactor that allowed for improvements in microsphere capture and discrimination against the background. Under these conditions, estimates of the UV dose distribution from the microspheres assay were consistent with numerical simulations and the results of biodosimetry, using both challenge organisms. The combined application of dyed microspheres, biodosimetry, and numerical simulation offers the potential to provide a more in-depth description of reactor performance than any of these methods individually, or in combination. This approach also has the potential to substantially reduce uncertainties in reactor validation, thereby leading to better understanding of reactor performance, improvements in reactor design, and decreases in reactor capital and operating costs.

Evaluation of a magnetic microsphere antibody detection assay for the investigation of exposure to Cryptosporidium parvum and Cryptosporidium hominis

EPA Science Inventory

Anti-Cryptosporidium IgA and IgG are useful markers of exposure to Cryptosporidium in human populations, but detection in saliva may be difficult. To evaluate a magnetic microsphere assay for detection of anti-Cryptosporidium IgA and IgG in saliva, recombinant sporozoite gp15 (1...

Single-analyte to multianalyte fluorescence sensors

NASA Astrophysics Data System (ADS)

Lavigne, John J.; Metzger, Axel; Niikura, Kenichi; Cabell, Larry A.; Savoy, Steven M.; Yoo, J. S.; McDevitt, John T.; Neikirk, Dean P.; Shear, Jason B.; Anslyn, Eric V.

1999-05-01

The rational design of small molecules for the selective complexation of analytes has reached a level of sophistication such that there exists a high degree of prediction. An effective strategy for transforming these hosts into sensors involves covalently attaching a fluorophore to the receptor which displays some fluorescence modulation when analyte is bound. Competition methods, such as those used with antibodies, are also amenable to these synthetic receptors, yet there are few examples. In our laboratories, the use of common dyes in competition assays with small molecules has proven very effective. For example, an assay for citrate in beverages and an assay for the secondary messenger IP3 in cells have been developed. Another approach we have explored focuses on multi-analyte sensor arrays with attempt to mimic the mammalian sense of taste. Our system utilizes polymer resin beads with the desired sensors covalently attached. These functionalized microspheres are then immobilized into micromachined wells on a silicon chip thereby creating our taste buds. Exposure of the resin to analyte causes a change in the transmittance of the bead. This change can be fluorescent or colorimetric. Optical interrogation of the microspheres, by illuminating from one side of the wafer and collecting the signal on the other, results in an image. These data streams are collected using a CCD camera which creates red, green and blue (RGB) patterns that are distinct and reproducible for their environments. Analysis of this data can identify and quantify the analytes present.

Microsphere integrated microfluidic disk: synergy of two techniques for rapid and ultrasensitive dengue detection.

PubMed

Hosseini, Samira; Aeinehvand, Mohammad M; Uddin, Shah M; Benzina, Abderazak; Rothan, Hussin A; Yusof, Rohana; Koole, Leo H; Madou, Marc J; Djordjevic, Ivan; Ibrahim, Fatimah

2015-11-09

The application of microfluidic devices in diagnostic systems is well-established in contemporary research. Large specific surface area of microspheres, on the other hand, has secured an important position for their use in bioanalytical assays. Herein, we report a combination of microspheres and microfluidic disk in a unique hybrid platform for highly sensitive and selective detection of dengue virus. Surface engineered polymethacrylate microspheres with carefully designed functional groups facilitate biorecognition in a multitude manner. In order to maximize the utility of the microspheres' specific surface area in biomolecular interaction, the microfluidic disk was equipped with a micromixing system. The mixing mechanism (microballoon mixing) enhances the number of molecular encounters between spheres and target analyte by accessing the entire sample volume more effectively, which subsequently results in signal amplification. Significant reduction of incubation time along with considerable lower detection limits were the prime motivations for the integration of microspheres inside the microfluidic disk. Lengthy incubations of routine analytical assays were reduced from 2 hours to 5 minutes while developed system successfully detected a few units of dengue virus. Obtained results make this hybrid microsphere-microfluidic approach to dengue detection a promising avenue for early detection of this fatal illness.

Molecular identification of common Salmonella serovars using multiplex DNA sensor-based suspension array.

PubMed

Aydin, Muhsin; Carter-Conger, Jacqueline; Gao, Ning; Gilmore, David F; Ricke, Steven C; Ahn, Soohyoun

2018-04-01

Salmonella is one of major foodborne pathogens and the leading cause of foodborne illness-related hospitalizations and deaths. It is critical to develop a sensitive and rapid detection assay that can identify Salmonella to ensure food safety. In this study, a DNA sensor-based suspension array system of high multiplexing ability was developed to identify eight Salmonella serovars commonly associated with foodborne outbreaks to the serotype level. Each DNA sensor was prepared by activating pre-encoded microspheres with oligonucleotide probes that are targeting virulence genes and serovar-specific regions. The mixture of 12 different types of DNA sensors were loaded into a 96-well microplate and used as a 12-plex DNA sensor array platform. DNA isolated from Salmonella was amplified by multiplex polymerase chain reaction (mPCR), and the presence of Salmonella was determined by reading fluorescent signals from hybridization between probes on DNA sensors and fluorescently labeled target DNA using the Bio-Plex® system. The developed multiplex array was able to detect synthetic DNA at the concentration as low as 100 fM and various Salmonella serovars as low as 100 CFU/mL within 1 h post-PCR. Sensitivity of this assay was further improved to 1 CFU/mL with 6-h enrichment. The array system also correctly and specifically identified serotype of tested Salmonella strains without any cross-reactivity with other common foodborne pathogens. Our results indicate the developed DNA sensor suspension array can be a rapid and reliable high-throughput method for simultaneous detection and molecular identification of common Salmonella serotypes.

An Electrochemical Genosensing Assay Based on Magnetic Beads and Gold Nanoparticle-Loaded Latex Microspheres for Vibrio cholerae Detection.

PubMed

Low, Kim-Fatt; Rijiravanich, Patsamon; Singh, Kirnpal Kaur Banga; Surareungchai, Werasak; Yean, Chan Yean

2015-04-01

An ultrasensitive electrochemical genosensing assay was developed for the sequence-specific detection of Vibrio cholerae DNA using magnetic beads as the biorecognition surface and gold nanoparticle-loaded latex microspheres (latex-AuNPs) as a signal-amplified hybridization tag. This biorecognition surface was prepared by immobilizing specific biotinylated capturing probes onto the streptavidin-coupled magnetic beads. Fabricating a hybridization tag capable of amplifying the electrochemical signal involved loading multiple AuNPs onto polyelectrolyte multilayer film-coated poly(styrene-co-acrylic acid) latex microspheres as carrier particles. The detection targets, single-stranded 224-bp asymmetric PCR amplicons of the V. cholerae lolB gene, were sandwich-hybridized to magnetic bead-functionalized capturing probes and fluorescein-labeled detection probes and tagged with latex-AuNPs. The subsequent electrochemical stripping analysis of chemically dissolved AuNPs loaded onto the latex microspheres allowed for the quantification of the target amplicons. The high-loading capacity of the AuNPs on the latex microspheres for sandwich-type dual-hybridization genosensing provided eminent signal amplification. The genosensing variables were optimized, and the assay specificity was demonstrated. The clinical applicability of the assay was evaluated using spiked stool specimens. The current signal responded linearly to the different V. cholerae concentrations spiked into stool specimens with a detection limit of 2 colony-forming units (CFU)/ml. The proposed latex-AuNP-based magnetogenosensing platform is promising, exhibits an effective amplification performance, and offers new opportunities for the ultrasensitive detection of other microbial pathogens.

High resolution photolithography using arrays of polystyrene and SiO2 micro- and nano-sized spherical lenses

NASA Astrophysics Data System (ADS)

Dvoretckaia, L. N.; Mozharov, A. M.; Mukhin, I. S.

2017-11-01

Photolithography mask made of close-packed array of micro- and nano-sized spherical lenses allows to obtain the ordered structures and provides highest “optical resolution/cost” ratio between all existing photolithography and laser direct writing methods. In this letter, we present results of modeling the propagation of a plane wave falling on the array of quartz (SiO2) microspherical lenses and focusing in the image reverse photoresist layer. We present here experimental results on fabrication of ordered arrays of submicron wells and columns and substrate preparation for growth of monocrystalline nanowires on metal surface using photolithography with mask of SiO2 microspheres. Such ordered nano-sized arrays of wells and columns can be used in fabrication of further growth of monocrystalline nanowires, quantum dots and production of plasmon structures.

Monolayer Colloidal Crystals by Modified Air-Water Interface Self-Assembly Approach

PubMed Central

Ye, Xin; Huang, Jin; Zeng, Yong; Sun, Lai-Xi; Geng, Feng; Liu, Hong-Jie; Wang, Feng-Rui; Jiang, Xiao-Dong; Wu, Wei-Dong; Zheng, Wan-Guo

2017-01-01

Hexagonally ordered arrays of polystyrene (PS) microspheres were prepared by a modified air-water self-assembly method. A detailed analysis of the air-water interface self-assembly process was conducted. Several parameters affect the quality of the monolayer colloidal crystals, i.e., the colloidal microsphere concentration on the latex, the surfactant concentration, the polystyrene microsphere diameter, the microsphere polydispersity, and the degree of sphericity of polystyrene microspheres. An abrupt change in surface tension was used to improve the quality of the monolayer colloidal crystal. Three typical microstructures, i.e., a cone, a pillar, and a binary structure were prepared by reactive-ion etching using a high-quality colloidal crystal mask. This study provides insight into the production of microsphere templates with flexible structures for large-area patterned materials. PMID:28946664

Multiplexed SNP genotyping using the Qbead™ system: a quantum dot-encoded microsphere-based assay

PubMed Central

Xu, Hongxia; Sha, Michael Y.; Wong, Edith Y.; Uphoff, Janet; Xu, Yanzhang; Treadway, Joseph A.; Truong, Anh; O’Brien, Eamonn; Asquith, Steven; Stubbins, Michael; Spurr, Nigel K.; Lai, Eric H.; Mahoney, Walt

2003-01-01

We have developed a new method using the Qbead™ system for high-throughput genotyping of single nucleotide polymorphisms (SNPs). The Qbead system employs fluorescent Qdot™ semiconductor nanocrystals, also known as quantum dots, to encode microspheres that subsequently can be used as a platform for multiplexed assays. By combining mixtures of quantum dots with distinct emission wavelengths and intensities, unique spectral ‘barcodes’ are created that enable the high levels of multiplexing required for complex genetic analyses. Here, we applied the Qbead system to SNP genotyping by encoding microspheres conjugated to allele-specific oligonucleotides. After hybridization of oligonucleotides to amplicons produced by multiplexed PCR of genomic DNA, individual microspheres are analyzed by flow cytometry and each SNP is distinguished by its unique spectral barcode. Using 10 model SNPs, we validated the Qbead system as an accurate and reliable technique for multiplexed SNP genotyping. By modifying the types of probes conjugated to microspheres, the Qbead system can easily be adapted to other assay chemistries for SNP genotyping as well as to other applications such as analysis of gene expression and protein–protein interactions. With its capability for high-throughput automation, the Qbead system has the potential to be a robust and cost-effective platform for a number of applications. PMID:12682378

Nanoporous Monolithic Microsphere Arrays Have Anti-Adhesive Properties Independent of Humidity

PubMed Central

Eichler-Volf, Anna; Xue, Longjian; Kovalev, Alexander; Gorb, Elena V.; Gorb, Stanislav N.; Steinhart, Martin

2016-01-01

Bioinspired artificial surfaces with tailored adhesive properties have attracted significant interest. While fibrillar adhesive pads mimicking gecko feet are optimized for strong reversible adhesion, monolithic microsphere arrays mimicking the slippery zone of the pitchers of carnivorous plants of the genus Nepenthes show anti-adhesive properties even against tacky counterpart surfaces. In contrast to the influence of topography, the influence of relative humidity (RH) on adhesion has been widely neglected. Some previous works deal with the influence of RH on the adhesive performance of fibrillar adhesive pads. Commonly, humidity-induced softening of the fibrils enhances adhesion. However, little is known on the influence of RH on solid anti-adhesive surfaces. We prepared polymeric nanoporous monolithic microsphere arrays (NMMAs) with microsphere diameters of a few 10 µm to test their anti-adhesive properties at RHs of 2% and 90%. Despite the presence of continuous nanopore systems through which the inner nanopore walls were accessible to humid air, the topography-induced anti-adhesive properties of NMMAs on tacky counterpart surfaces were retained even at RH = 90%. This RH-independent robustness of the anti-adhesive properties of NMMAs significantly contrasts the adhesion enhancement by humidity-induced softening on nanoporous fibrillar adhesive pads made of the same material. PMID:28773497

Solution-based analysis of multiple analytes by a sensor array: toward the development of an electronic tongue

NASA Astrophysics Data System (ADS)

Savoy, Steven M.; Lavigne, John J.; Yoo, J. S.; Wright, John; Rodriguez, Marc; Goodey, Adrian; McDoniel, Bridget; McDevitt, John T.; Anslyn, Eric V.; Shear, Jason B.; Ellington, Andrew D.; Neikirk, Dean P.

1998-12-01

A micromachined sensor array has been developed for the rapid characterization of multi-component mixtures in aqueous media. The sensor functions in a manner analogous to that of the mammalian tongue, using an array composed of individually immobilized polystyrene-polyethylene glycol composite microspheres selectively arranged in micromachined etch cavities localized o n silicon wafers. Sensing occurs via colorimetric or fluorometric changes to indicator molecules that are covalently bound to amine termination sites on the polymeric microspheres. The hybrid micromachined structure has been interfaced directly to a charged-coupled-device that is used for the simultaneous acquisition of the optical data from the individually addressable `taste bud' elements. With the miniature sensor array, acquisition of data streams composed of red, green, and blue color patterns distinctive for the analytes in the solution are rapidly acquired. The unique combination of carefully chosen reporter molecules with water permeable microspheres allows for the simultaneous detection and quantification of a variety of analytes. The fabrication of the sensor structures and the initial colorimetric and fluorescent responses for pH, Ca+2, Ce+3, and sugar are reported. Interface to microfluidic components should also be possible, producing a complete sampling/sensing system.

Screening unlabeled DNA targets with randomly ordered fiber-optic gene arrays.

PubMed

Steemers, F J; Ferguson, J A; Walt, D R

2000-01-01

We have developed a randomly ordered fiber-optic gene array for rapid, parallel detection of unlabeled DNA targets with surface immobilized molecular beacons (MB) that undergo a conformational change accompanied by a fluorescence change in the presence of a complementary DNA target. Microarrays are prepared by randomly distributing MB-functionalized 3-microm diameter microspheres in an array of wells etched in a 500-microm diameter optical imaging fiber. Using several MBs, each designed to recognize a different target, we demonstrate the selective detection of genomic cystic fibrosis related targets. Positional registration and fluorescence response monitoring of the microspheres was performed using an optical encoding scheme and an imaging fluorescence microscope system.

Digital barcodes of suspension array using laser induced breakdown spectroscopy

PubMed Central

He, Qinghua; Liu, Yixi; He, Yonghong; Zhu, Liang; Zhang, Yilong; Shen, Zhiyuan

2016-01-01

We show a coding method of suspension array based on the laser induced breakdown spectroscopy (LIBS), which promotes the barcodes from analog to digital. As the foundation of digital optical barcodes, nanocrystals encoded microspheres are prepared with self-assembly encapsulation method. We confirm that digital multiplexing of LIBS-based coding method becomes feasible since the microsphere can be coded with direct read-out data of wavelengths, and the method can avoid fluorescence signal crosstalk between barcodes and analyte tags, which lead to overall advantages in accuracy and stability to current fluorescent multicolor coding method. This demonstration increases the capability of multiplexed detection and accurate filtrating, expanding more extensive applications of suspension array in life science. PMID:27808270

Efficient delivery of recombinant human bone morphogenetic protein (rhBMP-2) with dextran sulfate-chitosan microspheres.

PubMed

Xia, Yuan-Jun; Xia, Hong; Chen, Ling; Ying, Qing-Shui; Yu, Xiang; Li, Li-Hua; Wang, Jian-Hua; Zhang, Ying

2018-04-01

Bone morphogenetic protein-2 (BMP-2) serves an important role in the development of bone and cartilage. However, administration of BMP-2 protein alone by intravenous delivery is not very effective. Sustained delivery of stabilized BMP-2 by carriers has been proven necessary to improve the osteogenesis effect of BMP-2. The present study constructed a novel drug delivery system using dextran sulfate (DS)-chitosan (CS) microspheres and investigated the efficiency of the delivery system on recombinant human bone morphogenetic protein (rhBMP-2). The microsphere morphology, optimal ratio of DS/CS/rhBMP-2, and drug loading rate and entrapment efficiency of rhBMP-2 CS nanoparticles were determined. L929 cells were used to evaluate the cytotoxicity and effect of DS/CS/rhBMP-2 microspheres on cell proliferation. Differentiation study was conducted using bone marrow mesenchymal stem cells (BMSCs-C57) cells treated with DS/CS/rhBMP-2 microspheres or the control microspheres. The DS/CS/rhBMP-2 microspheres delivery system was successfully established. Subsequent complexation of rhBMP-2-bound DS with polycations afforded well defined microspheres with a diameter of ~250 nm. High protein entrapment efficiency (85.6%) and loading ratio (47.245) µg/mg were achieved. Release of rhBMP-2 from resultant microspheres persisted for over 20 days as determined by ELISA assay. The bioactivity of rhBMP-2 encapsulated in the CS/DS microsphere was observed to be well preserved as evidenced by the alkaline phosphatase activity assay and calcium nodule formation of BMSCs-C57 incubated with rhBMP-2-loaded microspheres. The results demonstrated that microspheres based on CS-DS polyion complexes were a highly efficient vehicle for delivery of rhBMP-2 protein. The present study may provide novel orientation for bone tissue engineering for repairing and regenerating bone defects.

Conversion of a Capture ELISA to a Luminex xMAP Assay using a Multiplex Antibody Screening Method

PubMed Central

Baker, Harold N.; Murphy, Robin; Lopez, Erica; Garcia, Carlos

2012-01-01

The enzyme-linked immunosorbent assay (ELISA) has long been the primary tool for detection of analytes of interest in biological samples for both life science research and clinical diagnostics. However, ELISA has limitations. It is typically performed in a 96-well microplate, and the wells are coated with capture antibody, requiring a relatively large amount of sample to capture an antigen of interest . The large surface area of the wells and the hydrophobic binding of capture antibody can also lead to non-specific binding and increased background. Additionally, most ELISAs rely upon enzyme-mediated amplification of signal in order to achieve reasonable sensitivity. Such amplification is not always linear and can thus skew results. In the past 15 years, a new technology has emerged that offers the benefits of the ELISA, but also enables higher throughput, increased flexibility, reduced sample volume, and lower cost, with a similar workflow 1, 2. Luminex xMAP Technology is a microsphere (bead) array platform enabling both monoplex and multiplex assays that can be applied to both protein and nucleic acid applications 3-5. The beads have the capture antibody covalently immobilized on a smaller surface area, requiring less capture antibody and smaller sample volumes, compared to ELISA, and non-specific binding is significantly reduced. Smaller sample volumes are important when working with limiting samples such as cerebrospinal fluid, synovial fluid, etc. 6. Multiplexing the assay further reduces sample volume requirements, enabling multiple results from a single sample. Recent improvements by Luminex include: the new MAGPIX system, a smaller, less expensive, easier-to-use analyzer; Low-Concentration Magnetic MagPlex Microspheres which eliminate the need for expensive filter plates and come in a working concentration better suited for assay development and low-throughput applications; and the xMAP Antibody Coupling (AbC) Kit, which includes a protocol, reagents, and consumables necessary for coupling beads to the capture antibody of interest. (See Materials section for a detailed list of kit contents.) In this experiment, we convert a pre-optimized ELISA assay for TNF-alpha cytokine to the xMAP platform and compare the performance of the two methods 7-11. TNF-alpha is a biomarker used in the measurement of inflammatory responses in patients with autoimmune disorders. We begin by coupling four candidate capture antibodies to four different microsphere sets or regions. When mixed together, these four sets allow for the simultaneous testing of all four candidates with four separate detection antibodies to determine the best antibody pair, saving reagents, sample and time. Two xMAP assays are then constructed with the two most optimal antibody pairs and their performance is compared to that of the original ELISA assay in regards to signal strength, dynamic range, and sensitivity. PMID:22806215

Hydrophilic/hydrophobic surface modification impact on colloid lithography: Schottky-like defects, dislocation, and ideal distribution

NASA Astrophysics Data System (ADS)

Burtsev, Vasilii; Marchuk, Valentina; Kugaevskiy, Artem; Guselnikova, Olga; Elashnikov, Roman; Miliutina, Elena; Postnikov, Pavel; Svorcik, Vaclav; Lyutakov, Oleksiy

2018-03-01

Nano-spheres lithography is actually considered as a powerful tool to manufacture various periodic structures with a wide potential in the field of nano- and micro-fabrication. However, during self-assembling of colloid microspheres, various defects and mismatches can appear. In this work the size and quality of single-domains of closed-packed polystyrene (PS), grown up on thin Au layers modified by hydrophilic or hydrophobic functional groups via diazonium chemistry was studied. The effects of the surface modification on the quality and single-domain size of polystyrene (PS) microspheres array were investigated and discussed. Modified surfaces were characterized using the AFM and wettability tests. PS colloidal suspension was deposited using the drop evaporation method. Resulted PS microspheres array was characterized using the SEM, AFM and confocal microscopy technique.

Microsphere integrated microfluidic disk: synergy of two techniques for rapid and ultrasensitive dengue detection

PubMed Central

Hosseini, Samira; Aeinehvand, Mohammad M.; Uddin, Shah M.; Benzina, Abderazak; Rothan, Hussin A.; Yusof, Rohana; Koole, Leo H.; Madou, Marc J.; Djordjevic, Ivan; Ibrahim, Fatimah

2015-01-01

The application of microfluidic devices in diagnostic systems is well-established in contemporary research. Large specific surface area of microspheres, on the other hand, has secured an important position for their use in bioanalytical assays. Herein, we report a combination of microspheres and microfluidic disk in a unique hybrid platform for highly sensitive and selective detection of dengue virus. Surface engineered polymethacrylate microspheres with carefully designed functional groups facilitate biorecognition in a multitude manner. In order to maximize the utility of the microspheres’ specific surface area in biomolecular interaction, the microfluidic disk was equipped with a micromixing system. The mixing mechanism (microballoon mixing) enhances the number of molecular encounters between spheres and target analyte by accessing the entire sample volume more effectively, which subsequently results in signal amplification. Significant reduction of incubation time along with considerable lower detection limits were the prime motivations for the integration of microspheres inside the microfluidic disk. Lengthy incubations of routine analytical assays were reduced from 2 hours to 5 minutes while developed system successfully detected a few units of dengue virus. Obtained results make this hybrid microsphere-microfluidic approach to dengue detection a promising avenue for early detection of this fatal illness. PMID:26548806

Integration of Microsphere Resonators with Bioassay Fluidics for Whispering Gallery Mode Imaging

PubMed Central

Kim, Daniel C.; Armendariz, Kevin P.

2013-01-01

Whispering gallery mode resonators are small, radially symmetric dielectrics that trap light through continuous total internal reflection. The resonant condition at which light is efficiently confined within the structure is linked with refractive index, which has led to the development of sensitive label-free sensing schemes based on whispering gallery mode resonators. One resonator design uses inexpensive high index glass microspheres that offer intrinsically superior optical characteristics, but have proven difficult to multiplex and integrate with the fluidics for sample delivery and fluid exchange necessary for assay development. Recently, we introduced a fluorescence imaging approach that enables large scale multiplexing with microsphere resonators, thus removing one obstacle for assay development. Here we report an approach for microsphere immobilization that overcomes limitations arising from their integration with fluidic delivery. The approach is an adaptation of a calcium-assisted glass bonding method originally developed for microfluidic glass chip fabrication. Microspheres bonded to glass using this technique are shown to be stable with respect to fluid flow and show no detectable loss in optical performance. Measured Q-factors, for example, remain unchanged following sphere bonding to the substrate. The stability of the immobilized resonators is further demonstrated by transferring lipid films onto the immobilized spheres using the Langmuir-Blodgett technique. Bilayers of DOPC doped with GM1 were transferred onto immobilized resonators to detect the binding of cholera toxin to GM1. Binding curves generated from shifts in the whispering gallery mode resonance result in a measured Kd of 1.5 × 10−11 with a limit of detection of 3.3 pM. These results are discussed in terms of future assay development using microsphere resonators. PMID:23615457

Utilizing hyaluronic acid as a versatile platform for fluorescence resonance energy transfer-based glucose sensing.

PubMed

Ge, Minghao; Bai, Pengli; Chen, Mingli; Tian, Jingjing; Hu, Jun; Zhi, Xu; Yin, Huancai; Yin, Jian

2018-03-01

Here, we utilized the ultrasonic emulsification technique to generate hyaluronic acid microspheres incorporating a fluorescence-based glucose biosensor. We synthesized a novel lanthanide ion luminophore based on Eu 3+ . Eu sulfosuccinimidyl dextran (Eu-dextran) and Alexa Fluor 647 sulfosuccinimidyl-ConA (Alexa Fluor 647-ConA) were encapsulated in hyaluronic acid hydrogel to generate microspheres. Glucose sensing was carried out using a fluorescence resonance energy transfer (FRET)-based assay principle. A proportional fluorescence intensity increase was found within a 0.5-10-mM glucose concentration range. The glucose-sensing strategy showed an excellent tolerance for potential interferents. Meanwhile, the fluorescent signal of hyaluronic acid microspheres was very stable after testing for 72 h in glucose solution. Overall, hyaluronic acid microspheres encapsulating sensing biomolecules offer a stable and biocompatible biosensor for a variety of applications including cell culture systems, tissue engineering, detection of blood glucose, etc. Graphical abstract We report an ingenious biosensor encapsulated in hyaluronic acid microspheres for monitoring of glucose. Glucose sensing is carried out using a fluorescence resonance energy transfer-based assay principle with a novel lanthanide ions luminophore. The glucose detection system has excellent biocompatibility and stability for monitoring of glucose.

Gold surface plasmon crystal structure based-on polystyrene template for biosensor application.

PubMed

Cheng, Min-Zhuo; Zhang, Jing; Bao, Dequan; Huang, Xiwei

2018-05-21

In this communication, we assembled ordered polystyrene (PS) microsphere array as a template with the drop-coating method, and the oxygen plasma was used to etch the template to adjust the spacing between the PS microspheres. Nano-triangular gold array and silver nano-pyramid array were obtained by ion beam sputtering to deposit precious metal gold and silver. We observed the surface morphology of Au and Au/Ag composite films by scanning electron microscope and characterized the films by X-ray diffraction and ultraviolet/visible light spectrophotometer. The results show that the etching time of oxygen plasma has an obvious effect in adjusting the spacing between PSs and has a significant effect on the morphology of Au structure. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Common path point diffraction interferometer using liquid crystal phase shifting

NASA Technical Reports Server (NTRS)

Mercer, Carolyn R. (Inventor)

1997-01-01

A common path point diffraction interferometer uses dyed, parallel nematic liquid crystals which surround an optically transparent microsphere. Coherent, collimated and polarized light is focused on the microsphere at a diameter larger than that of the microsphere. A portion of the focused light passes through the microsphere to form a spherical wavefront reference beam and the rest of the light is attenuated by the dyed liquid crystals to form an object beam. The two beams form an interferogram which is imaged by a lens onto an electronic array sensor and into a computer which determines the wavefront of the object beam. The computer phase shifts the interferogram by stepping up an AC voltage applied across the liquid crystals without affecting the reference beam.

Multiplex immunoassay for persistent organic pollutants in tilapia: Comparison of imaging- and flow cytometry-based platforms using spectrally encoded paramagnetic microspheres

USDA-ARS?s Scientific Manuscript database

Recent developments in spectrally encoded microspheres (SEMs)-based technologies provide high multiplexing possibilities. Most SEMs-based assays required a flow cytometer with sophisticated fluidics and optics. The new imaging superparamagnetic SEMs-based platform transports SEMs with considerably ...

Development of Internal Controls for the Luminex Instrument as Part of a Multiplex Seven-Analyte Viral Respiratory Antibody Profile

PubMed Central

Martins, Thomas B.

2002-01-01

The ability of the Luminex system to simultaneously quantitate multiple analytes from a single sample source has proven to be a feasible and cost-effective technology for assay development. In previous studies, my colleagues and I introduced two multiplex profiles consisting of 20 individual assays into the clinical laboratory. With the Luminex instrument’s ability to classify up to 100 distinct microspheres, however, we have only begun to realize the enormous potential of this technology. By utilizing additional microspheres, it is now possible to add true internal controls to each individual sample. During the development of a seven-analyte serologic viral respiratory antibody profile, internal controls for detecting sample addition and interfering rheumatoid factor (RF) were investigated. To determine if the correct sample was added, distinct microspheres were developed for measuring the presence of sufficient quantities of immunoglobulin G (IgG) or IgM in the diluted patient sample. In a multiplex assay of 82 samples, the IgM verification control correctly identified 23 out of 23 samples with low levels (<20 mg/dl) of this antibody isotype. An internal control microsphere for RF detected 30 out of 30 samples with significant levels (>10 IU/ml) of IgM RF. Additionally, RF-positive samples causing false-positive adenovirus and influenza A virus IgM results were correctly identified. By exploiting the Luminex instrument’s multiplexing capabilities, I have developed true internal controls to ensure correct sample addition and identify interfering RF as part of a respiratory viral serologic profile that includes influenza A and B viruses, adenovirus, parainfluenza viruses 1, 2, and 3, and respiratory syncytial virus. Since these controls are not assay specific, they can be incorporated into any serologic multiplex assay. PMID:11777827

Development of internal controls for the Luminex instrument as part of a multiplex seven-analyte viral respiratory antibody profile.

PubMed

Martins, Thomas B

2002-01-01

The ability of the Luminex system to simultaneously quantitate multiple analytes from a single sample source has proven to be a feasible and cost-effective technology for assay development. In previous studies, my colleagues and I introduced two multiplex profiles consisting of 20 individual assays into the clinical laboratory. With the Luminex instrument's ability to classify up to 100 distinct microspheres, however, we have only begun to realize the enormous potential of this technology. By utilizing additional microspheres, it is now possible to add true internal controls to each individual sample. During the development of a seven-analyte serologic viral respiratory antibody profile, internal controls for detecting sample addition and interfering rheumatoid factor (RF) were investigated. To determine if the correct sample was added, distinct microspheres were developed for measuring the presence of sufficient quantities of immunoglobulin G (IgG) or IgM in the diluted patient sample. In a multiplex assay of 82 samples, the IgM verification control correctly identified 23 out of 23 samples with low levels (<20 mg/dl) of this antibody isotype. An internal control microsphere for RF detected 30 out of 30 samples with significant levels (>10 IU/ml) of IgM RF. Additionally, RF-positive samples causing false-positive adenovirus and influenza A virus IgM results were correctly identified. By exploiting the Luminex instrument's multiplexing capabilities, I have developed true internal controls to ensure correct sample addition and identify interfering RF as part of a respiratory viral serologic profile that includes influenza A and B viruses, adenovirus, parainfluenza viruses 1, 2, and 3, and respiratory syncytial virus. Since these controls are not assay specific, they can be incorporated into any serologic multiplex assay.

Sputter coating of microspherical substrates by levitation

DOEpatents

Lowe, A.T.; Hosford, C.D.

Microspheres are substantially uniformly coated with metals or nonmetals by simltaneously levitating them and sputter coating them at total chamber pressures less than 1 torr. A collimated hole structure comprising a parallel array of upwardly projecting individual gas outlets is machined out to form a dimple. Glass microballoons,, which are particularly useful in laser fusion applications, can be substantially uniformly coated using the coating method and apparatus.

Evaporation-Induced Assembly of Quantum Dots into Nanorings

PubMed Central

Chen, Jixin; Liao, Wei-Ssu; Chen, Xin; Yang, Tinglu; Wark, Stacey E.; Son, Dong Hee; Batteas, James D.; Cremer, Paul S.

2011-01-01

Herein, we demonstrate the controlled formation of two-dimensional periodic arrays of ring-shaped nanostructures assembled from CdSe semiconductor quantum dots (QDs). The patterns were fabricated by using an evaporative templating method. This involves the introduction of an aqueous solution containing both quantum dots and polystyrene microspheres onto the surface of a planar hydrophilic glass substrate. The quantum dots became confined to the meniscus of the microspheres during evaporation, which drove ring assembly via capillary forces at the polystyrene sphere/glass substrate interface. The geometric parameters for nanoring formation could be controlled by tuning the size of the microspheres and the concentration of the QDs employed. This allowed hexagonal arrays of nanorings to be formed with thicknesses ranging from single dot necklaces to thick multilayer structures over surface areas of many square millimeters. Moreover, the diameter of the ring structures could be simultaneously controlled. A simple model was employed to explain the forces involved in the formation of nanoparticle nanorings. PMID:19206264

Detecting Biological Warfare Agents

PubMed Central

Song, Linan; Ahn, Soohyoun

2005-01-01

We developed a fiber-optic, microsphere-based, high-density array composed of 18 species-specific probe microsensors to identify biological warfare agents. We simultaneously identified multiple biological warfare agents in environmental samples by looking at specific probe responses after hybridization and response patterns of the multiplexed array. PMID:16318712

One-step growth of nanosheet-assembled BiOCl/BiOBr microspheres for highly efficient visible photocatalytic performance

NASA Astrophysics Data System (ADS)

Zhang, Jinfeng; Lv, Jiali; Dai, Kai; Liang, Changhao; Liu, Qi

2018-02-01

In this work, we have developed a simple synthetic approach of nanosheet-assembled BiOCl/BiOBr microspheres by an ethylene glycol (EG)-assisted hydrothermal method. The crystalline form, morphology, chemical composition, optical performance and surface area of BiOCl/BiOBr microspheres were identified using X-ray diffraction (XRD), transmission electron microscopy (TEM), high resolution TEM (HRTEM), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy spectra (EDX), UV-vis diffuse reflectance spectroscopy (DRS) analysis, high resolution X-ray photoelectron spectra (XPS) and N2 adsorption-desorption isotherms. BiOCl/BiOBr microspheres were nanosheet-assembled particles, which possessed visible light absorption under LED light irridation. Additionally, the methylene blue (MB) photodegradation performance of different BiOCl/BiOBr microspheres irradiated under 410 nm LED light arrays were investigated, the results exhibited that as-prepared BiOCl/BiOBr products showed higher catalytic effiency than pure BiOCl or BiOBr. By optimizing the composition ration of the BiOCl and BiOBr, up to 93% degradation rate can be obtained in the 40%BiOCl/BiOBr microspheres. Finally, the photocatalytic mechanism of BiOCl/BiOBr microspheres had been proposed.

Sputter coating of microspherical substrates by levitation

DOEpatents

Lowe, Arthur T.; Hosford, Charles D.

1981-01-01

Microspheres are substantially uniformly coated with metals or nonmetals by simultaneously levitating them and sputter coating them at total chamber pressures less than 1 torr. A collimated hole structure 12 comprising a parallel array of upwardly projecting individual gas outlets 16 is machined out to form a dimple 11. Glass microballoons, which are particularly useful in laser fusion applications, can be substantially uniformly coated using the coating method and apparatus.

Real-time analysis of endosomal lipid transport by live cell scintillation proximity assay

PubMed Central

Stockinger, Walter; Castoreno, Adam B.; Wang, Yan; Pagnon, Joanne C.; Nohturfft, Axel

2007-01-01

A scintillation proximity assay has been developed to study the endosomal trafficking of radiolabeled cholesterol in living cells. Mouse macrophages were cultured in the presence of tritiated cholesterol and scintillant microspheres. Microspheres were taken up by phagocytosis and stored in phagolysosomes. Absorption of tritium β particles by the scintillant produces light signals that can be measured in standard scintillation counters. Because of the short range of tritium β particles and for geometric reasons, scintillant microspheres detect only that fraction of tritiated cholesterol localized inside phagolysosomes or within a distance of ~600 nm. By incubating cultures in a temperature-controlled microplate reader, the kinetics of phagocytosis and cholesterol transport could be analyzed in near-real time. Scintillation signals were significantly increased in response to inhibitors of lysosomal cholesterol export. This method should prove a useful new tool for the study of endosomal trafficking of lipids and other molecules. PMID:15314094

Increasing sensitivity and angle-of-view of mid-wave infrared detectors by integration with dielectric microspheres

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

Allen, Kenneth W., E-mail: kenneth.allen@gtri.gatech.edu; Astratov, Vasily N., E-mail: astratov@uncc.edu; Air Force Research Laboratory, Sensors Directorate, Wright Patterson AFB, Ohio 45433

2016-06-13

We observed up to 100 times enhancement of sensitivity of mid-wave infrared photodetectors in the 2–5 μm range by using photonic jets produced by sapphire, polystyrene, and soda-lime glass microspheres with diameters in the 90–300 μm range. By finite-difference time-domain (FDTD) method for modeling, we gain insight into the role of the microspheres refractive index, size, and alignment with respect to the detector mesa. A combination of enhanced sensitivity with angle-of-view (AOV) up to 20° is demonstrated for individual photodetectors. It is proposed that integration with microspheres can be scaled up for large focal plane arrays, which should provide maximal light collectionmore » efficiencies with wide AOVs, a combination of properties highly attractive for imaging applications.« less

Preparation of chitosan/nano hydroxyapatite organic-inorganic hybrid microspheres for bone repair.

PubMed

Chen, Jingdi; Pan, Panpan; Zhang, Yujue; Zhong, Shengnan; Zhang, Qiqing

2015-10-01

In this work, we encapsulated icariin (ICA) into chitosan (CS)/nano hydroxyapatite (nHAP) composite microspheres to form organic-inorganic hybrid microspheres for drug delivery carrier. The composition and morphology of composite microspheres were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and differential scanning calorimetry- thermogravimetric analysis (DSC-TGA). Moreover, we further studied the performance of swelling properties, degradation properties and drug release behavior of the microspheres. ICA, the extract of traditional Chinese medicine-epimedium, was combined to study drug release properties of the microspheres. ICA loaded microspheres take on a sustained release behavior, which can be not only ascribed to electrostatic interaction between reactive negative hydroxyl (OH) of ICA and positive amine groups (NH₂) of CS, but also depended on the homogeneous dispersion of HAP nanoparticles inside CS organic matrix. In addition, the adhesion and morphology of osteoblasts were detected by inverted fluorescence microscopy. The biocompatibility of CS/nHAP/ICA microspheres was evaluated by the MTT cytotoxicity assay, Hoechst 33258 and PI fluorescence staining. These studies demonstrate that composite microspheres provide a suitable microenvironment for osteoblast attachment and proliferation. It can be speculated that the ICA loaded CS-based organic-inorganic hybrid microspheres might have potential applications in drug delivery systems. Copyright © 2015 Elsevier B.V. All rights reserved.

An ultra-sensitive monoclonal antibody-based fluorescent microsphere immunochromatographic test strip assay for detecting aflatoxin M1 in milk

USDA-ARS?s Scientific Manuscript database

A rapid lateral flow fluorescent microspheres immunochromatography test strip (FMs-ICTS) has been developed for the detection of aflatoxin M1 (AFM1) residues in milk. For this purpose, an ultra-sensitive anti-AFM1 monoclonal antibody (MAb) 1D3 was prepared and identified. The IC50 value of the MA...

Sustained release of nerve growth factor from biodegradable polymer microspheres.

PubMed

Camarata, P J; Suryanarayanan, R; Turner, D A; Parker, R G; Ebner, T J

1992-03-01

Although grafted adrenal medullary tissue to the striatum has been used both experimentally and clinically in parkinsonism, there is a definite need to augment long-term survival. Infusion of nerve growth factor (NGF) or implantation of NGF-rich tissue into the area of the graft prolongs survival and induces differentiation into neural-like cells. To provide for prolonged, site-specific delivery of this growth factor to the grafted tissue in a convenient manner, we fabricated biodegradable polymer microspheres of poly(L-lactide)co-glycolide (70:30) containing NGF. Biologically active NGF was released from the microspheres, as assayed by neurite outgrowth in a dorsal root ganglion tissue culture system. Anti-NGF could block this outgrowth. An enzyme-linked immunosorbent assay detected NGF still being released in vitro for longer than 5 weeks. In vivo immunohistochemical studies showed release over a 4.5-week period. This technique should prove useful for incorporating NGF and other growth factors into polymers and delivering proteins and other macromolecules intracerebrally over a prolonged time period. These growth factor-containing polymer microspheres can be used in work aimed at prolonging graft survival, treating experimental Alzheimer's disease, and augmenting peripheral nerve regeneration.

Sonochemical synthesis of fructose 1,6-bisphosphate dicalcium porous microspheres and their application in promotion of osteogenic differentiation.

PubMed

Qi, Chao; Zhou, Ding; Zhu, Ying-Jie; Sun, Tuan-Wei; Chen, Feng; Zhang, Chang-Qing

2017-08-01

Human bone mesenchymal stem cells (hBMSCs) have the ability to differentiate into bone and cartilage for clinical bone regeneration. Biomaterials with an innate ability to stimulate osteogenic differentiation of hBMSCs into bone and cartilage are considered attractive candidates for the applications in bone tissue engineering and regeneration. In this paper, we synthesized fructose 1,6-bisphosphate dicalcium (Ca 2 FBP) porous microspheres by the sonochemical method, and investigated the ability of Ca 2 FBP for the promotion of the osteogenic differentiation of hBMSCs. After the hBMSCs were co-cultured with the sterilized powder of Ca 2 FBP porous microspheres for different times, the cell proliferation assay, alkaline phosphatase activity assay, quantitative real-time polymerase chain reaction and western blotting were performed to investigate the bioactivity and osteogenic differentiation performance of the as-prepared product. Compared with hydroxyapatite nanorods, Ca 2 FBP porous microspheres show a superior bioactivity and osteoinductive potential, and can promote the cell differentiation of hBMSCs in vitro, thus, they are promising for applications in the tissue engineering field such as dental and bone defect repair. Copyright © 2017 Elsevier B.V. All rights reserved.

Detection of Neisseria meningitidis in cerebrospinal fluid using a multiplex PCR and the Luminex detection technology.

PubMed

Møller, Jens Kjølseth

2012-01-01

Rapid clinical and laboratory diagnoses are the foundation for a successful management of serious infections with Neisseria meningitidis. A species-specific multiplex polymerase chain reaction (PCR) coupled with fluidic microarrays using microbeads (the Luminex xMAP™ Technology) can detect pathogens most frequently found in the cerebrospinal fluid of patients. The Luminex suspension array system uniquely combines flow cytometry, microspheres, laser technology, digital signal processing, and traditional chemistry. In this method, the reaction is carried out in one vessel, in which distinctly color-coded bead sets, each conjugated with a different specific nucleic acid reactant, are hybridized with the PCR products, and a reporter molecule is used to quantify the interaction. The flow-based Luminex array reader identifies each reaction (bead set) after excitation by a red classification laser. Reporter signals from each reaction are simultaneously quantified by fluorescence generated by a green reporter laser. This nonculture, multiplex assay may prove to be an important tool for optimal laboratory diagnosis, not only of meningococcal meningitis, but also of meningitis caused by other bacterial or viral pathogens.

Antibody quantum dot conjugates developed via copper-free click chemistry for rapid analysis of biological samples using a microfluidic microsphere array system.

PubMed

Kotagiri, Nalinikanth; Li, Zhenyu; Xu, Xiaoxiao; Mondal, Suman; Nehorai, Arye; Achilefu, Samuel

2014-07-16

Antibody-based proteomics is an enabling technology that has significant implications for cancer biomarker discovery, diagnostic screening, prognostic and pharmacodynamic evaluation of disease state, and targeted therapeutics. Quantum dot based fluoro-immunoconjugates possess promising features toward realization of this goal such as high photostability, brightness, and multispectral tunability. However, current strategies to generate such conjugates are riddled with complications such as improper orientation of antigen binding sites of the antibody, aggregation, and stability issues. We report a facile yet effective strategy to conjugate anti-epidermal growth factor receptor (EGFR) antibody to quantum dots using copper-free click reaction, and compared them to similar constructs prepared using traditional strategies such as succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC) and biotin-streptavidin schemes. The Fc and Fab regions of the conjugates retain their binding potential, compared to those generated through the traditional schemes. We further applied the conjugates in testing a novel microsphere array device designed to carry out sensitive detection of cancer biomarkers through fluoroimmunoassays. Using purified EGFR, we determined the limit of detection of the microscopy centric system to be 12.5 ng/mL. The biological assay, in silico, was successfully tested and validated by using tumor cell lysates, as well as human serum from breast cancer patients, and the results were compared to normal serum. A pattern consistent with established clinical data was observed, which further validates the effectiveness of the developed conjugates and its successful implementation both in vitro as well as in silico fluoroimmunoassays. The results suggest the potential development of a high throughput in silico paradigm for predicting the class of patient cancer based on EGFR expression levels relative to normal reference levels in blood.

Molecular Diagnostic Tools for Detection and Differentiation of Phytoplasmas Based on Chaperonin-60 Reveal Differences in Host Plant Infection Patterns

PubMed Central

Dumonceaux, Tim J.; Green, Margaret; Hammond, Christine; Perez, Edel; Olivier, Chrystel

2014-01-01

Phytoplasmas (‘Candidatus Phytoplasma’ spp.) are insect-vectored bacteria that infect a wide variety of plants, including many agriculturally important species. The infections can cause devastating yield losses by inducing morphological changes that dramatically alter inflorescence development. Detection of phytoplasma infection typically utilizes sequences located within the 16S–23S rRNA-encoding locus, and these sequences are necessary for strain identification by currently accepted standards for phytoplasma classification. However, these methods can generate PCR products >1400 bp that are less divergent in sequence than protein-encoding genes, limiting strain resolution in certain cases. We describe a method for accessing the chaperonin-60 (cpn60) gene sequence from a diverse array of ‘Ca.Phytoplasma’ spp. Two degenerate primer sets were designed based on the known sequence diversity of cpn60 from ‘Ca.Phytoplasma’ spp. and used to amplify cpn60 gene fragments from various reference samples and infected plant tissues. Forty three cpn60 sequences were thereby determined. The cpn60 PCR-gel electrophoresis method was highly sensitive compared to 16S-23S-targeted PCR-gel electrophoresis. The topology of a phylogenetic tree generated using cpn60 sequences was congruent with that reported for 16S rRNA-encoding genes. The cpn60 sequences were used to design a hybridization array using oligonucleotide-coupled fluorescent microspheres, providing rapid diagnosis and typing of phytoplasma infections. The oligonucleotide-coupled fluorescent microsphere assay revealed samples that were infected simultaneously with two subtypes of phytoplasma. These tools were applied to show that two host plants, Brassica napus and Camelina sativa, displayed different phytoplasma infection patterns. PMID:25551224

Biomechanical characterization of a low density silicone elastomer filled with hollow microspheres for maxillofacial prostheses.

PubMed

Liu, Q; Shao, L Q; Xiang, H F; Zhen, D; Zhao, N; Yang, S G; Zhang, X L; Xu, J

2013-01-01

An ideal material for maxillofacial prostheses has not been found. We created a novel material: silicone elastomer filled with hollow microspheres and characterized its biomechanical properties. Expancel hollow microspheres were mixed with MDX4-4210 silicone elastomer using Q7-9180 silicone fluid as diluent. The volume fractions of microspheres were 0, 5, 15, and 30% v/v (volume ratio to the total volume of MDX4-4210 and microspheres). The microspheres dispersed well in the matrix. The physical properties and biocompatibility of the composites were examined. Shock absorption was the greatest by the 5% v/v composite, and decreased with increasing concentrations of microspheres. The density, thermal conductivity, Shore A hardness, tear and tensile strength decreased with increasing concentrations of microspheres, while elongation at break increased. Importantly, the tear strength of all composites was markedly lower than that of pure silicone elastomer. Cell viability assays indicated that the composite was of good biocompatibility. The composite with a volume fraction of 5% exhibited the optimal properties for use as a maxillofacial prosthesis, though its tear strength was markedly lower than that of silicone elastomer. In conclusion, we developed a novel light and soft material with good flexibility and biocompatibility, which holds a promising prospect for clinical application as maxillofacial prosthesis.

Chitosan microsphere scaffold tethered with RGD-conjugated poly(methacrylic acid) brushes as effective carriers for the endothelial cells.

PubMed

Yang, Zhenyi; Yuan, Shaojun; Liang, Bin; Liu, Yang; Choong, Cleo; Pehkonen, Simo O

2014-09-01

Endothelial cell-matrix interactions play a vital role in promoting vascularization of engineered tissues. The current study reports a facile and controllable method to develop a RGD peptide-functionalized chitosan microsphere scaffolds for rapid cell expansion of human umbilical vein endothelial cells (HUVECs). Functional poly(methacrylic acid) (PMAA) brushes are grafted from the chitosan microsphere surfaces via surface-initiated ATRP. Subsequent conjugation of RGD peptides on the pendent carboxyl groups of PMAA side chain is accomplished by carbodiimide chemistry to facilitate biocompatibility of the 3D CS scaffolding system. In vitro cell-loading assay of HUVECs exhibits a significant improvment of cell adhesion, spreading, and proliferation on the RGD peptide-immobilized CS microsphere surfaces. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Magnetically stimulated ciprofloxacin release from polymeric microspheres entrapping iron oxide nanoparticles

PubMed Central

Sirivisoot, Sirinrath; Harrison, Benjamin S

2015-01-01

To extend the external control capability of drug release, iron oxide nanoparticles (NPs) encapsulated into polymeric microspheres were used as magnetic media to stimulate drug release using an alternating magnetic field. Chemically synthesized iron oxide NPs, maghemite or hematite, and the antibiotic ciprofloxacin were encapsulated together within polycaprolactone microspheres. The polycaprolactone microspheres entrapping ciprofloxacin and magnetic NPs could be triggered for immediate drug release by magnetic stimulation at a maximum value of 40%. Moreover, the microspheres were cytocompatible with fibroblasts in vitro with a cell viability percentage of more than 100% relative to a nontreated control after 24 hours of culture. Macrophage cell cultures showed no signs of increased inflammatory responses after in vitro incubation for 56 hours. Treatment of Staphylococcus aureus with the magnetic microspheres under an alternating (isolating) magnetic field increased bacterial inhibition further after 2 days and 5 days in a broth inhibition assay. The findings of the present study indicate that iron oxide NPs, maghemite and hematite, can be used as media for stimulation by an external magnetic energy to activate immediate drug release. PMID:26185446

Self-Assembly of pH-Responsive Microspheres for Intestinal Delivery of Diverse Lipophilic Therapeutics.

PubMed

Zhou, Xing; Zhao, Yang; Chen, Siyu; Han, Songling; Xu, Xiaoqiu; Guo, Jiawei; Liu, Mengyu; Che, Ling; Li, Xiaohui; Zhang, Jianxiang

2016-08-08

Targeted delivery of therapeutics to the intestine is preferred for the management of many diseases due to its diverse advantages. Currently, there are still challenges in creating cost-effective and translational pH-responsive microspheres for intestinal delivery of various hydrophobic drugs. Herein we report a multiple noncovalent interactions-mediated assembly strategy in which carboxyl-bearing compounds (CBCs) are guest molecules, while poly(N-isopropylacrylamide) (PNIPAm) serves as a host polymer. Formation of microparticles and therapeutic packaging can be achieved simultaneously by this assembly approach, leading to well-shaped microspheres with extremely higher drug loading capacity as compared to microspheres based on two FDA-approved materials of poly(d,l-lactide-co-glycolide) (PLGA) and an enteric coating polymer EudragitS 100 (S100). Also, carboxyl-deficient hydrophobic drugs can be effectively entrapped. These assembled microspheres, with excellent reconstitution capability as well as desirable scalability, could selectively release drug molecules under intestinal conditions. By significantly enhancing drug dissolution/release in the intestine, these pH-responsive assemblies may notably improve the oral bioavailability of loaded therapeutics. Moreover, the assembled microspheres possessed superior therapeutic performance in rodent models of inflammation and tumor over the control microspheres derived from PLGA and S100. Therapy with newly developed microspheres did not cause undesirable side effects. Furthermore, in vivo evaluation in mice revealed the carrier material PNIPAm was safe for oral delivery at doses as high as 10 g/kg. Collectively, our findings demonstrated that this type of pH-responsive microsphere may function as superior and translational intestine-directed delivery systems for a diverse array of therapeutics.

Starch-entrapped biopolymer microspheres as a novel approach to vary blood glucose profiles.

PubMed

Venkatachalam, Mahesh; Kushnick, Michael R; Zhang, Genyi; Hamaker, Bruce R

2009-10-01

With emerging knowledge of the impact of the metabolic quality of glycemic carbohydrates on human health, there is a need for novel carbohydrate ingredients that can be custom-made to deliver controlled amounts of glucose to the body and to test hypotheses on the postprandial metabolic consequences of carbohydrates. The goal of the present study was to demonstrate the applicability and action of starch-entrapped biopolymer microspheres as customized, novel, slowly digestible carbohydrates to obtain desired glycemic responses. Starch-entrapped microspheres were developed; and starch digestion and glucose release, subsequent to their cooking (100 degrees C, 20 min) in water, were initially monitored by measuring the rapidly digestible, slowly digestible, and resistant starch fractions using the in vitro Englyst assay. Glycemic and insulinemic responses after consumption of glucose and two different slowly digestible starch microsphere diets were compared using a crossover study in 10 healthy individuals. The mechanism of starch digestion in the microspheres was elucidated from scanning electron microscopic images of the in vitro digested microspheres. Factors such as biopolymer type and concentration, microsphere size, and starch type were manipulated to obtain starch materials with defined amounts of slowly digestible starch based on in vitro studies. Scanning electron microscopy showed that cooked starch entrapped in the dense biopolymer matrix is digested layer by layer from the outside to the inside of the microsphere. Glycemic and insulinemic responses to microsphere test diets were moderate as compared to a glucose diet, but more important, they showed extended glucose release. Starch-entrapped microspheres provide a useful tool to study the postprandial metabolic consequences of slowly digestible carbohydrates.

Synthesis of adriamycin-coupled polyglutaraldehyde microspheres and evaluation of their cytostatic activity

NASA Technical Reports Server (NTRS)

Tokes, Z. A.; Rogers, K. E.; Rembaum, A.

1982-01-01

Adriamycin was coupled to polyglutaraldehyde microspheres having an average diameter of 4500 A. The coupled microspheres remained stable during incubation with cells. Full cytostatic activity was observed when the coupled adriamycin was tested with murine or human leukemia and murine sarcoma cell lines. A 10-fold increase in sensitivity was obtained with drug-resistant human leukemia cell lines. Repeated use of the coupled microspheres in the cytostatic assays did not decrease their activity, indicating that these complexes can be recycled. The results suggest that coupled adriamycin sufficiently perturbs the plasma membrane to lead to cytostatic activity. It is proposed that this mode of drug delivery provides multiple and repetitious sites for drug-cell interactions. In addition, the drug-polymer complexes may overcome those forms of resistance that are the result of decreased drug binding at the cell surface.

Fabrication of channeled scaffolds with ordered array of micro-pores through microsphere leaching and indirect Rapid Prototyping technique.

PubMed

Tan, J Y; Chua, C K; Leong, K F

2013-02-01

Advanced scaffold fabrication techniques such as Rapid Prototyping (RP) are generally recognized to be advantageous over conventional fabrication methods in terms architectural control and reproducibility. Yet, most RP techniques tend to suffer from resolution limitations which result in scaffolds with uncontrollable, random-size pores and low porosity, albeit having interconnected channels which is characteristically present in most RP scaffolds. With the increasing number of studies demonstrating the profound influences of scaffold pore architecture on cell behavior and overall tissue growth, a scaffold fabrication method with sufficient architectural control becomes imperative. The present study demonstrates the use of RP fabrication techniques to create scaffolds having interconnected channels as well as controllable micro-size pores. Adopted from the concepts of porogen leaching and indirect RP techniques, the proposed fabrication method uses monodisperse microspheres to create an ordered, hexagonal closed packed (HCP) array of micro-pores that surrounds the existing channels of the RP scaffold. The pore structure of the scaffold is shaped using a single sacrificial construct which comprises the microspheres and a dissolvable RP mold that were sintered together. As such, the size of pores as well as the channel configuration of the scaffold can be tailored based on the design of the RP mold and the size of microspheres used. The fabrication method developed in this work can be a promising alternative way of preparing scaffolds with customized pore structures that may be required for specific studies concerning cell-scaffold interactions.

A microflow cytometer on a chip

NASA Astrophysics Data System (ADS)

Golden, Joel P.; Kim, Jason; Anderson, George P.; Hashemi, Nastaran; Howell, Peter J.; Ligler, Frances S.

2010-02-01

A rapid, automated, multi-analyte Microflow Cytometer is being developed as a portable, field-deployable sensor for onsite diagnosis of biothreat agent exposure and environmental monitoring. The technology relies on a unique method for ensheathing a sample stream in continuous flow past an interrogation region where optical fibers provide excitation and collect emission. This approach efficiently focuses particles in the interrogation region of the fluidic channel, avoids clogging and provides for subsequent separation of the core and sheath fluids in order to capture the target for confirmatory assays and recycling of the sheath fluid. Fluorescently coded microspheres provide the capability for highly multiplexed assays. Optical analysis at four different wavelengths identified six sets of the coded microspheres recognizing Escherichia coli, Listeria, and Salmonella as well as cholera toxin, staphylococcal enterotoxin B (SEB), and ricin, and assay results were compared with those of a commercial Luminex analysis system.

Photonic nanojet super-resolution in immersed ordered assembly of dielectric microspheres

NASA Astrophysics Data System (ADS)

Geints, Y. E.; Zemlyanov, A. A.

2017-10-01

Specific spatially-localized optical field structure, which is often referred to as a photonic nanojet (PNJ), is formed in the near-field scattering area of non-absorbing dielectric micron-sized particle exposed to an optical radiation. By virtue of the finite-difference time-domain technique we numerically simulate the two-dimensional array of PNJs created by an ordered single-layer microassembly of glass microspheres immersed in a transparent polymer matrix. The behavior of the main PNJ parameters (length, diameter, and intensity) is analyzed subject to the immersion depth of the microparticles and cooperative interference effects of the neighboring microspheres. We show that depending on microassembly configuration, the PNJ quality can be significantly improved; in particular, the PNJ spatial resolution better than λ/5 can be achieved.

Functionalized antibiofilm thin coatings based on PLA-PVA microspheres loaded with usnic acid natural compounds fabricated by MAPLE

NASA Astrophysics Data System (ADS)

Grumezescu, Valentina; Socol, Gabriel; Grumezescu, Alexandru Mihai; Holban, Alina Maria; Ficai, Anton; Truşcǎ, Roxana; Bleotu, Coralia; Balaure, Paul Cǎtǎlin; Cristescu, Rodica; Chifiriuc, Mariana Carmen

2014-05-01

We report the fabrication of thin coatings of PLA-PVA microspheres loaded with usnic acid by matrix assisted pulsed laser evaporation (MAPLE) onto Ti substrate. The obtained coatings have been physico-chemically characterized by scanning electron microscopy (SEM) and infrared microscopy (IRM). In vitro biological assays have been performed in order to evaluate the influence of fabricated microsphere thin coatings on the Staphylococcus aureus biofilm development as well as their biocompatibility. SEM micrographs have revealed a uniform morphology of thin coatings, while IRM investigations have proved both the homogeneity and functional groups integrity of prepared thin coatings. The obtained microsphere-based thin coatings have proved to be efficient vehicles for usnic acid natural compound with antibiofilm activity, as demonstrated by the inhibitory activity on S. aureus mature biofilm development, opening new perspectives for the prevention and therapy associated to biofilm related infections.

Comparative assessment of in vitro release kinetics of calcitonin polypeptide from biodegradable microspheres.

PubMed

Prabhu, Sunil; Sullivan, Jennifer L; Betageri, Guru V

2002-01-01

The objective of our study was to compare the in vitro release kinetics of a sustained-release injectable microsphere formulation of the polypeptide drug, calcitonin (CT), to optimize the characteristics of drug release from poly-(lactide-co-glycolide) (PLGA) copolymer biodegradable microspheres. A modified solvent evaporation and double emulsion technique was used to prepare the microspheres. Release kinetic studies were carried out in silanized tubes and dialysis bags, whereby microspheres were suspended and incubated in phosphate buffered saline, sampled at fixed intervals, and analyzed for drug content using a modified Lowry protein assay procedure. An initial burst was observed whereby about 50% of the total dose of the drug was released from the microspheres within 24 hr and 75% within 3 days. This was followed by a period of slow release over a period of 3 weeks in which another 10-15% of drug was released. Drug release from the dialysis bags was more gradual, and 50% CT was released only after 4 days and 75% after 12 days of release. Scanning electron micrographs revealed spherical particles with channel-like structures and a porous surface after being suspended in an aqueous solution for 5 days. Differential scanning calorimetric studies revealed that CT was present as a mix of amorphous and crystalline forms within the microspheres. Overall, these studies demonstrated that sustained release of CT from PLGA microspheres over a 3-week period is feasible and that release of drug from dialysis bags was more predictable than from tubes.

A competitive aptamer chemiluminescence assay for ochratoxin A using a single silica photonic crystal microsphere.

PubMed

Shen, Peng; Li, Wei; Ding, Zhi; Deng, Yang; Liu, Yan; Zhu, Xuerui; Cai, Tingting; Li, Jianlin; Zheng, Tiesong

2018-08-01

We designed a competitive aptamer chemiluminescence assay for ochratoxin A (OTA) on the surface of a single silica photonic crystal microsphere (SPCM) in cereal samples. The structural color of SPCMs is used to recognize and trace the microspheres during process of detection. Anti-aptamer was immobilized on the surface of SPCM. OTA and anti-aptamer competed to bind to aptamer when OTA and its aptamer (labeled by biotin at 5'end) were added in the system. The chemiluminescence signal was developed by the horseradish peroxidase (HRP), luminol and H 2 O 2 . The molecules on the single SPCM can produce enough chemiluminescence signal intensity for quantitative detection for OTA. The linear detection range for OTA was from 1 pg/mL to 1 ng/mL and recovery rates were 89%-95%, 81%-92% and 94%-105% in rice, wheat and corn, respectively. The results showed that the developed method for OTA using a single SPCM has a great application potential in cereal samples. Copyright © 2018 Elsevier Inc. All rights reserved.

Optical super-resolution and periodical focusing effects by dielectric microspheres

NASA Astrophysics Data System (ADS)

Darafsheh, Arash

Optical microscopy is one of the oldest and most important imaging techniques; however, its far-field resolution is diffraction-limited. In this dissertation, we proposed and developed a novel method of optical microscopy with super-resolution by using high-index dielectric microspheres immersed in liquid and placed on the surface of the structures under study. We used barium titanate glass microspheres with diameters of D~2-220 mum and refractive indices n˜1.9-2.1 to discern minimal feature sizes ˜lambda/4 (down to ˜lambda/7) of various photonic and plasmonic nanostructures, where lambda is the illumination wavelength. We studied the magnification, field of view, and resolving power, in detail, as a function of sphere sizes. We studied optical coupling, transport, focusing, and polarization properties of linear arrays of dielectric spheres. We showed that in arrays of spheres with refractive index n=3, a special type of rays with transverse magnetic (TM) polarization incident on the spheres under the Brewster's angle form periodically focused modes with radial polarization and 2D period, where D is the diameter of the spheres. We showed that the formation of periodically focused modes in arrays of dielectric spheres gives a physical explanation for beam focusing and extraordinarily small attenuation of light in such chains. We showed that the light propagation in such arrays is strongly polarization-dependent, indicating that such arrays can be used as filters of beams with radial polarization. The effect of forming progressively smaller focused beams was experimentally observed in chains of sapphire spheres in agreement with the theory. We studied optical coupling,transport, focusing, and polarization properties of linear arrays of dielectric spheres. We showed that in arrays of spheres with refractive index n=a3, a special type of rays with transverse magnetic (TM) polarization incident on the spheres under the Brewster's angle form periodically focused modes with radial polarization and 2D period, where D is the diameter of the spheres. We showed that the formation of periodically focused modes in arrays of dielectric spheres gives a physical explanation for beam focusing and extraordinarily small attenuation of light in such chains. We showed that the light propagation in such arrays is strongly polarization-dependent, indicating that such arrays can be used as filters of beams with radial polarization. The effect of forming progressively smaller focused beams was experimentally observed in chains of sapphire spheres in agreement with the theory.

Approaching near real-time biosensing: microfluidic microsphere based biosensor for real-time analyte detection.

PubMed

Cohen, Noa; Sabhachandani, Pooja; Golberg, Alexander; Konry, Tania

2015-04-15

In this study we describe a simple lab-on-a-chip (LOC) biosensor approach utilizing well mixed microfluidic device and a microsphere-based assay capable of performing near real-time diagnostics of clinically relevant analytes such cytokines and antibodies. We were able to overcome the adsorption kinetics reaction rate-limiting mechanism, which is diffusion-controlled in standard immunoassays, by introducing the microsphere-based assay into well-mixed yet simple microfluidic device with turbulent flow profiles in the reaction regions. The integrated microsphere-based LOC device performs dynamic detection of the analyte in minimal amount of biological specimen by continuously sampling micro-liter volumes of sample per minute to detect dynamic changes in target analyte concentration. Furthermore we developed a mathematical model for the well-mixed reaction to describe the near real time detection mechanism observed in the developed LOC method. To demonstrate the specificity and sensitivity of the developed real time monitoring LOC approach, we applied the device for clinically relevant analytes: Tumor Necrosis Factor (TNF)-α cytokine and its clinically used inhibitor, anti-TNF-α antibody. Based on the reported results herein, the developed LOC device provides continuous sensitive and specific near real-time monitoring method for analytes such as cytokines and antibodies, reduces reagent volumes by nearly three orders of magnitude as well as eliminates the washing steps required by standard immunoassays. Copyright © 2014 Elsevier B.V. All rights reserved.

Automated processing integrated with a microflow cytometer for pathogen detection in clinical matrices

PubMed Central

Golden, J.P.; Verbarg, J.; Howell, P.B.; Shriver-Lake, L.C.; Ligler, F.S.

2012-01-01

A spinning magnetic trap (MagTrap) for automated sample processing was integrated with a microflow cytometer capable of simultaneously detecting multiple targets to provide an automated sample-to-answer diagnosis in 40 min. After target capture on fluorescently coded magnetic microspheres, the magnetic trap automatically concentrated the fluorescently coded microspheres, separated the captured target from the sample matrix, and exposed the bound target sequentially to biotinylated tracer molecules and streptavidin-labeled phycoerythrin. The concentrated microspheres were then hydrodynamically focused in a microflow cytometer capable of 4-color analysis (two wavelengths for microsphere identification, one for light scatter to discriminate single microspheres and one for phycoerythrin bound to the target). A three-fold decrease in sample preparation time and an improved detection limit, independent of target preconcentration, was demonstrated for detection of Escherichia coli 0157:H7 using the MagTrap as compared to manual processing. Simultaneous analysis of positive and negative controls, along with the assay reagents specific for the target, was used to obtain dose–response curves, demonstrating the potential for quantification of pathogen load in buffer and serum. PMID:22960010

Automated processing integrated with a microflow cytometer for pathogen detection in clinical matrices.

PubMed

Golden, J P; Verbarg, J; Howell, P B; Shriver-Lake, L C; Ligler, F S

2013-02-15

A spinning magnetic trap (MagTrap) for automated sample processing was integrated with a microflow cytometer capable of simultaneously detecting multiple targets to provide an automated sample-to-answer diagnosis in 40 min. After target capture on fluorescently coded magnetic microspheres, the magnetic trap automatically concentrated the fluorescently coded microspheres, separated the captured target from the sample matrix, and exposed the bound target sequentially to biotinylated tracer molecules and streptavidin-labeled phycoerythrin. The concentrated microspheres were then hydrodynamically focused in a microflow cytometer capable of 4-color analysis (two wavelengths for microsphere identification, one for light scatter to discriminate single microspheres and one for phycoerythrin bound to the target). A three-fold decrease in sample preparation time and an improved detection limit, independent of target preconcentration, was demonstrated for detection of Escherichia coli 0157:H7 using the MagTrap as compared to manual processing. Simultaneous analysis of positive and negative controls, along with the assay reagents specific for the target, was used to obtain dose-response curves, demonstrating the potential for quantification of pathogen load in buffer and serum. Published by Elsevier B.V.

Solvent extraction employing a static micromixer: a simple, robust and versatile technology for the microencapsulation of proteins.

PubMed

Freitas, S; Walz, A; Merkle, H P; Gander, B

2003-01-01

The potential of a static micromixer for the production of protein-loaded biodegradable polymeric microspheres by a modified solvent extraction process was examined. The mixer consists of an array of microchannels and features a simple set-up, consumes only very small space, lacks moving parts and offers simple control of the microsphere size. Scale-up from lab bench to industrial production is easily feasible through parallel installation of a sufficient number of micromixers ('number-up'). Poly(lactic-co-glycolic acid) microspheres loaded with a model protein, bovine serum albumin (BSA), were prepared. The influence of various process and formulation parameters on the characteristics of the microspheres was examined with special focus on particle size distribution. Microspheres with monomodal size distributions having mean diameters of 5-30 micro m were produced with excellent reproducibility. Particle size distributions were largely unaffected by polymer solution concentration, polymer type and nominal BSA load, but depended on the polymer solvent. Moreover, particle mean diameters could be varied in a considerable range by modulating the flow rates of the mixed fluids. BSA encapsulation efficiencies were mostly in the region of 75-85% and product yields ranged from 90-100%. Because of its simple set-up and its suitability for continuous production, static micromixing is suggested for the automated and aseptic production of protein-loaded microspheres.

End-specific strategies of attachment of long double stranded DNA onto gold-coated nanofiber arrays

NASA Astrophysics Data System (ADS)

Peckys, Diana B.; de Jonge, Niels; Simpson, Michael L.; McKnight, Timothy E.

2008-10-01

We report the effective and site-specific binding of long double stranded (ds)DNA to high aspect ratio carbon nanofiber arrays. The carbon nanofibers were first coated with a thin gold layer to provide anchorage for two controllable binding methods. One method was based on the direct binding of thiol end-labeled dsDNA. The second and enhanced method used amine end-labeled dsDNA bound with crosslinkers to a carboxyl-terminated self-assembled monolayer. The bound dsDNA was first visualized with a fluorescent, dsDNA-intercalating dye. The specific binding onto the carbon nanofiber was verified by a high resolution detection method using scanning electron microscopy in combination with the binding of neutravidin-coated fluorescent microspheres to the immobilized and biotinylated dsDNA. Functional activity of thiol end-labeled dsDNA on gold-coated nanofiber arrays was verified with a transcriptional assay, whereby Chinese hamster lung cells (V79) were impaled upon the DNA-modified nanofibers and scored for transgene expression of the tethered template. Thiol end-labeled dsDNA demonstrated significantly higher expression levels than nanofibers prepared with control dsDNA that lacked a gold-binding end-label. Employing these site-specific and robust techniques of immobilization of dsDNA onto nanodevices can be of advantage for the study of DNA/protein interactions and for gene delivery applications.

Fabrication of a multiplexed microfluidic system for scaled up production of cross-linked biocatalytic microspheres

NASA Astrophysics Data System (ADS)

Mbanjwa, Mesuli B.; Chen, Hao; Fourie, Louis; Ngwenya, Sibusiso; Land, Kevin

2014-06-01

Multiplexed or parallelised droplet microfluidic systems allow for increased throughput in the production of emulsions and microparticles, while maintaining a small footprint and utilising minimal ancillary equipment. The current paper demonstrates the design and fabrication of a multiplexed microfluidic system for producing biocatalytic microspheres. The microfluidic system consists of an array of 10 parallel microfluidic circuits, for simultaneous operation to demonstrate increased production throughput. The flow distribution was achieved using a principle of reservoirs supplying individual microfluidic circuits. The microfluidic devices were fabricated in poly (dimethylsiloxane) (PDMS) using soft lithography techniques. The consistency of the flow distribution was determined by measuring the size variations of the microspheres produced. The coefficient of variation of the particles was determined to be 9%, an indication of consistent particle formation and good flow distribution between the 10 microfluidic circuits.

Multiplexed flow cytometric sensing of blood electrolytes in physiological samples using fluorescent bulk optode microspheres.

PubMed

Xu, Chao; Wygladacz, Katarzyna; Retter, Robert; Bell, Michael; Bakker, Eric

2007-12-15

Polymeric bulk optode microsphere ion sensors in combination with suspension array technologies such as analytical flow cytometry may become a power tool for measuring electrolytes in physiological samples. In this work, the methodology for the direct measurement of common blood electrolytes in physiological samples using bulk optode microsphere sensors was explored. The simultaneous determination of Na(+), K(+), and Ca(2+) in diluted sheep blood plasma was demonstrated for the first time, using a random suspension array containing three types of mixed microsphere bulk optodes of similar size, fabricated from the same chromoionophore without additional labeling. Sodium ionophore X, potassium ionophore III, and grafted AU-1 in poly(butyl acrylate) were the ionophores used in the bulk optode microsphere ion sensors for Na(+), K(+), and Ca(2+), respectively, in combination with the cation-exchanger NaTFPB (sodium tetrakis-[3,5-bis(trifluoromethyl)phenyl]borate) and the same concentration of the chromoionophore ETH 5294 (9-(di-ethylamino)-5-octadecanoylimino-5H-benzo[a]phen-oxazine) in plasticized poly(vinyl chloride). Excellent reproducibility was achieved for the sensing of potassium ions. The effect of sample pH was relatively small at near-physiological pH and followed theoretical predictions, yet the sample temperature was found to influence the sensor response to a larger extent. Multiplexed ion sensing was achieved by taking advantage of the chemical tunability of the sensor response, adjusting the sensor compositions so that the three types of ion sensors responded with distinct levels of protonation of the chromoionophore. Consequently, three well-resolved peaks were simultaneously observed in the single-channel histogram during the multiplexed calibration as well as in the subsequent measurement of the three cations in 10-fold-diluted sheep plasma. The assigned peak positions corresponded very well to the physiological range of the measured ions.

Construct 3D porous hollow Co3O4 micro-sphere: A potential oxidizer of nano-energetic materials with superior reactivity

NASA Astrophysics Data System (ADS)

Wang, Jun; Zheng, Bo; Qiao, Zhiqiang; Chen, Jin; Zhang, Liyuan; Zhang, Long; Li, Zhaoqian; Zhang, Xingquan; Yang, Guangcheng

2018-06-01

High energy density and rapid reactivity are the future trend for nano-energetic materials. Energetic performance of nano-energetic materials depends on the interfacial diffusion and mass transfer during the reacted process. However, the development of desired structure to significantly enhance reactivity still remains challenging. Here we focused on the design and preparation of 3D porous hollow Co3O4 micro-spheres, in which gas-blowing agents (air) and maximize interfacial interactions were introduced to enhance mass transport and reduce the diffusion distance between the oxidizer and fuel (Aluminum). The 3D hierarchical Co3O4/Al based nano-energetic materials show a low-onset decomposition temperature (423 °C), and high heat output (3118 J g-1) resulting from porous and hollow nano-structure of Co3O4 micro-spheres. Furthermore, 3D hierarchical Co3O4/Al arrays were directly fabricated on the silicon substrate, which was fully compatible with silicon-based microelectromechanical systems to achieve functional nanoenergetics-on-a-chip. This approach provides a simple and efficient way to fabricate 3D ordered nano-energetic arrays with superior reactivity and the potential on the application in micro-energetic devices.

Effective cell trapping using PDMS microspheres in an acoustofluidic chip.

PubMed

Yin, Di; Xu, Gangwei; Wang, Mengyuan; Shen, Mingwu; Xu, Tiegang; Zhu, Xiaoyue; Shi, Xiangyang

2017-09-01

We present a facile particle-based cell manipulation method using acoustic radiation forces. In this work, we selected several representative particles including poly(lactic-co-glycolic acid) (PLGA) microspheres, silica-coated magnetic microbeads, polydimethylsiloxane (PDMS) microspheres and investigated the responses of these particle systems to ultrasonic standing waves (USWs) in a microfluidic chip. We show that depending on the nature (positive or negative acoustic contrast factors) of the particles, these particle systems display different alignment behaviors along the microfluidic channel under USWs. Specifically, PLGA microspheres and silica-coated magnetic microbeads are able to be aligned in the middle of the microfluidic channel, while PDMS microspheres are translocated to the side walls of the channel, which is beneficial for cell trapping and manipulation. Further results demonstrate that the functional PDMS microspheres with a negative acoustic contrast factor can be used to trap cells to the pressure antinodes in the acoustofluidic chip. Cell viability tests reveal that the ultrasonic manipulation does not exert any harmful effect to the cells. This acoustic-based particle and cell manipulation technique may hold a great promise for the development of rapid, noninvasive, continuous assays for detecting of cells and separation of biological samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Nanocomposite strategies for limiting medical and marine biofouling

NASA Astrophysics Data System (ADS)

Cooper, Scott Patrick

Microorganisms affect many aspects of human life. When microorganisms colonize a surface, the resulting microbial community is called a biofilm. Biofilms can negatively affect human health and productivity. Osteomyelitis is caused by biofilms of bacteria attached to the bone. These biofilms pose a threat to human life and lead to the loss of healthy tissue. Biofilms attached to marine vessels decrease the fuel economy of ships, resulting in a significant economic cost. There is a need to develop new materials which eradicate and prevent biofouling. Nanocomposites and mixed-phase organic/inorganic materials are presented in various embodiments as a means to limit biofouling. Antibiotic-filled microspheres are created to improve the treatment of osteomyelitis. These microspheres consist of bioactive glass and poly(n-vinylpyrrolidone) (PVP) or gelatin. Bioactive glasses have historically been shown to promote the regeneration of bone. Sol-gel chemistry is used to make the bioactive glass component, in this case a calcium silicate. The low temperature of the reaction allows organic molecules such as drugs and polymers to be blended with the glass. The catalyst used during the sol-gel reaction affects the structure and composition of the microspheres. Base catalysis leads to microspheres that exhibit behavior indicative of a nanocomposite structure. Acid catalysis produces microspheres that appear to exist as more as a mixed phase between silica and PVP. These structures directly affect the stability of the microspheres in simulated body fluid (SBF): base-catalyzed microspheres degrade within the first day in SBF, while acid-catalyzed microspheres are stable for at least one week. The morphology of acid-catalyzed microspheres is directly affected by the following compositional parameters: molecular weight of PVP, concentration of PVP, and concentration of calcium. Solid, hollow, and core/shell morphologies are produced by adjusting these parameters. These morphologies are likely caused by various rates of silicate hydrolysis, condensation, and hydrogen bonding to PVP. Viscosity of the sol plays little role in determining the diameter of the dried microspheres. An antibiotic, vancomycin, is successfully incorporated into these hybrid microspheres. Vancomycin is released for 5-7 days as measured by UV absorption. An in vitro assay against cultures of Staphylococcus aureus demonstrates that the drug remains effective for 4 days. Marine biofouling is addressed by imparting topography onto silica-reinforced poly(dimethylsiloxane) elastomeric (PDMSe) films. Swimming zoospores from the green alga Ulva are used as a model fouling organism. A bio-inspired topography deterred attachment of the zoospores by 70-80% over a 4-hr assay. Image analysis of the zoospores suggests that the topography may inhibit biofilm formation by disrupting the early-stage aggregation of spores on the surface. The attachment kinetics fit, with high correlation, equations used to describe that adsorption of bacteria to surfaces. This suggests the same physical phenomena drives the attachment of bacteria and swimming algal zoospores to solid surfaces.

Validation of an Immunodiagnostic Assay for Detection of 13 Streptococcus pneumoniae Serotype-Specific Polysaccharides in Human Urine

PubMed Central

Huijts, Susanne M.; Wu, Kangjian; Souza, Victor; Passador, Sherry; Tinder, Chunyan; Song, Esther; Elfassy, Arik; McNeil, Lisa; Menton, Ronald; French, Roger; Callahan, Janice; Webber, Chris; Gruber, William C.; Bonten, Marc J. M.; Jansen, Kathrin U.

2012-01-01

To improve the clinical diagnosis of pneumococcal infection in bacteremic and nonbacteremic community-acquired pneumonia (CAP), a Luminex technology-based multiplex urinary antigen detection (UAD) diagnostic assay was developed and validated. The UAD assay can simultaneously detect 13 different serotypes of Streptococcus pneumoniae by capturing serotype-specific S. pneumoniae polysaccharides (PnPSs) secreted in human urine. Assay specificity is achieved by capturing the polysaccharides with serotype-specific monoclonal antibodies (MAbs) on spectrally unique microspheres. Positivity for each serotype was based on positivity cutoff values calculated from a standard curve run on each assay plate together with positive- and negative-control urine samples. The assay is highly specific, since significant signals are detected only when each PnPS was paired with its homologous MAb-coated microspheres. Validation experiments demonstrated excellent accuracy and precision. The UAD assay and corresponding positivity cutoff values were clinically validated by assessing 776 urine specimens obtained from patients with X-ray-confirmed CAP. The UAD assay demonstrated 97% sensitivity and 100% specificity using samples obtained from patients with bacteremic, blood culture-positive CAP. Importantly, the UAD assay identified Streptococcus pneumoniae (13 serotypes) in a proportion of individuals with nonbacteremic CAP, a patient population for which the pneumococcal etiology of CAP was previously difficult to assess. Therefore, the UAD assay provides a specific, noninvasive, sensitive, and reproducible tool to support vaccine efficacy as well as epidemiological evaluation of pneumococcal disease, including CAP, in adults. PMID:22675155

Validation of an immunodiagnostic assay for detection of 13 Streptococcus pneumoniae serotype-specific polysaccharides in human urine.

PubMed

Pride, Michael W; Huijts, Susanne M; Wu, Kangjian; Souza, Victor; Passador, Sherry; Tinder, Chunyan; Song, Esther; Elfassy, Arik; McNeil, Lisa; Menton, Ronald; French, Roger; Callahan, Janice; Webber, Chris; Gruber, William C; Bonten, Marc J M; Jansen, Kathrin U

2012-08-01

To improve the clinical diagnosis of pneumococcal infection in bacteremic and nonbacteremic community-acquired pneumonia (CAP), a Luminex technology-based multiplex urinary antigen detection (UAD) diagnostic assay was developed and validated. The UAD assay can simultaneously detect 13 different serotypes of Streptococcus pneumoniae by capturing serotype-specific S. pneumoniae polysaccharides (PnPSs) secreted in human urine. Assay specificity is achieved by capturing the polysaccharides with serotype-specific monoclonal antibodies (MAbs) on spectrally unique microspheres. Positivity for each serotype was based on positivity cutoff values calculated from a standard curve run on each assay plate together with positive- and negative-control urine samples. The assay is highly specific, since significant signals are detected only when each PnPS was paired with its homologous MAb-coated microspheres. Validation experiments demonstrated excellent accuracy and precision. The UAD assay and corresponding positivity cutoff values were clinically validated by assessing 776 urine specimens obtained from patients with X-ray-confirmed CAP. The UAD assay demonstrated 97% sensitivity and 100% specificity using samples obtained from patients with bacteremic, blood culture-positive CAP. Importantly, the UAD assay identified Streptococcus pneumoniae (13 serotypes) in a proportion of individuals with nonbacteremic CAP, a patient population for which the pneumococcal etiology of CAP was previously difficult to assess. Therefore, the UAD assay provides a specific, noninvasive, sensitive, and reproducible tool to support vaccine efficacy as well as epidemiological evaluation of pneumococcal disease, including CAP, in adults.

Microspherical polyaniline/graphene nanocomposites for high performance supercapacitors

NASA Astrophysics Data System (ADS)

Cao, Hailiang; Zhou, Xufeng; Zhang, Yiming; Chen, Liang; Liu, Zhaoping

2013-12-01

Polyaniline/graphene nanocomposites with microspherical morphology and porous structure are prepared as electrode materials for supercapacitors. Using few-layer graphene obtained by liquid phase exfoliation of graphite as the raw material, porous graphene microspheres are produced by spray drying, and are then employed as the substrates for the growth of polyaniline nanowire arrays by in situ polymerization. In the composite, interconnected graphene sheets with few structural defects constitute a high-efficient conductive network to improve the electrical conductivity of polyaniline. Furthermore, the microspherical architecture prevents restacking of polyaniline/graphene composite nanosheets, thus facilitates fast diffusion of electrolytes. Consequently, the nanocomposite exhibits excellent electrochemical performance. A specific capacitance of 338 F g-1 is reached in 1 M H2SO4 at a scan rate of 20 mV s-1, and a high capacity retention rate of 87.4% after 10,000 cycles at a current density of 3 A g-1 can be achieved, which suggests that the polyaniline/graphene composite with such kind of 3D architecture is a promising electrode material for high-performance supercapacitors.

Quantum Dot-Based Luminescent Oxygen Channeling Assay for Potential Application in Homogeneous Bioassays.

PubMed

Zhuang, Si-Hui; Guo, Xin-Xin; Wu, Ying-Song; Chen, Zhen-Hua; Chen, Yao; Ren, Zhi-Qi; Liu, Tian-Cai

2016-01-01

The unique photoproperties of quantum dots are promising for potential application in bioassays. In the present study, quantum dots were applied to a luminescent oxygen channeling assay. The reaction system developed in this study was based on interaction of biotin with streptavidin. Carboxyl-modified polystyrene microspheres doped with quantum dots were biotinylated and used as acceptors. Photosensitizer-doped carboxyl-modified polystyrene microspheres were conjugated with streptavidin and used as donors. The results indicated that the singlet oxygen that was released from the donor beads diffused into the acceptor beads. The acceptor beads were then exited via thioxene, and were subsequently fluoresced. To avoid generating false positives, a high concentration (0.01 mg/mL) of quantum dots is required for application in homogeneous immunoassays. Compared to a conventional luminescent oxygen channeling assay, this quantum dots-based technique requires less time, and would be easier to automate and miniaturize because it requires no washing to remove excess labels.

Development and validation of a fluorescent microsphere immunoassay for soluble CD30 testing.

PubMed

Pavlov, Igor; Martins, Thomas B; Delgado, Julio C

2009-09-01

Testing for soluble CD30 (sCD30), an indicator of Th2 immune response, is a useful prognostic marker in solid organ transplantation, lymphoproliferative disorders, autoimmunity, and various parasitic diseases. In this study we report the development and validation of a fluorescent microsphere immunoassay for the detection of sCD30 in serum, plasma, and culture supernatants. The dynamic range of this assay is 1 to 400 ng/ml, and the rate of recovery of various concentrations of recombinant sCD30 ranges from 97 to 116% (average recovery, 105%). The test showed a high degree of precision in both intra-assay and interassay studies (coefficients of variation, as high as 7% and 8%, respectively), with a sensitivity of 1 ng/ml. The normal reference range calculated for a cohort of 151 healthy individuals was 1 to 29 ng/ml. The clinical usefulness of the sCD30 fluorescent microsphere immunoassay was demonstrated by showing that levels of sCD30 have a positive correlation with specimens containing high titers of anti-double-stranded DNA antibodies and high titers of immunoglobulin G against Leishmania species. Given the multiplexing potential of the sCD30 fluorescent microsphere immunoassay reported in this study, it is expected that testing of sCD30 concentrations along with those of other cytokines will become an important diagnostic tool for selected immunological and inflammatory diseases where Th2-type cytokine responses have been reported.

Development and Validation of a Fluorescent Microsphere Immunoassay for Soluble CD30 Testing▿

PubMed Central

Pavlov, Igor; Martins, Thomas B.; Delgado, Julio C.

2009-01-01

Testing for soluble CD30 (sCD30), an indicator of Th2 immune response, is a useful prognostic marker in solid organ transplantation, lymphoproliferative disorders, autoimmunity, and various parasitic diseases. In this study we report the development and validation of a fluorescent microsphere immunoassay for the detection of sCD30 in serum, plasma, and culture supernatants. The dynamic range of this assay is 1 to 400 ng/ml, and the rate of recovery of various concentrations of recombinant sCD30 ranges from 97 to 116% (average recovery, 105%). The test showed a high degree of precision in both intra-assay and interassay studies (coefficients of variation, as high as 7% and 8%, respectively), with a sensitivity of 1 ng/ml. The normal reference range calculated for a cohort of 151 healthy individuals was 1 to 29 ng/ml. The clinical usefulness of the sCD30 fluorescent microsphere immunoassay was demonstrated by showing that levels of sCD30 have a positive correlation with specimens containing high titers of anti-double-stranded DNA antibodies and high titers of immunoglobulin G against Leishmania species. Given the multiplexing potential of the sCD30 fluorescent microsphere immunoassay reported in this study, it is expected that testing of sCD30 concentrations along with those of other cytokines will become an important diagnostic tool for selected immunological and inflammatory diseases where Th2-type cytokine responses have been reported. PMID:19605595

Magnetic bead based immuno-detection of Listeria monocytogenes and Listeria ivanovii from infant formula and leafy green vegetables using the Bio-Plex suspension array system.

PubMed

Day, J B; Basavanna, U

2015-04-01

Listeriosis, a disease contracted via the consumption of foods contaminated with pathogenic Listeria species, can produce severe symptoms and high mortality in susceptible people and animals. The development of molecular methods and immuno-based techniques for detection of pathogenic Listeria in foods has been challenging due to the presence of assay inhibiting food components. In this study, we utilize a macrophage cell culture system for the isolation and enrichment of Listeria monocytogenes and Listeria ivanovii from infant formula and leafy green vegetables for subsequent identification using the Luminex xMAP technique. Macrophage monolayers were exposed to infant formula, lettuce and celery contaminated with L. monocytogenes or L. ivanovii. Magnetic microspheres conjugated to Listeria specific antibody were used to capture Listeria from infected macrophages and then analyzed using the Bio-Plex 200 analyzer. As few as 10 CFU/mL or g of L. monocytogenes was detected in all foods tested. The detection limit for L. ivanovii was 10 CFU/mL in infant formula and 100 CFU/g in leafy greens. Microsphere bound Listeria obtained from infected macrophage lysates could also be isolated on selective media for subsequent confirmatory identification. This method presumptively identifies L. monocytogenes and L. ivanovii from infant formula, lettuce and celery in less than 28 h with confirmatory identifications completed in less than 48 h. Published by Elsevier Ltd.

High-Precision Pinpointing of Luminescent Targets in Encoder-Assisted Scanning Microscopy Allowing High-Speed Quantitative Analysis.

PubMed

Zheng, Xianlin; Lu, Yiqing; Zhao, Jiangbo; Zhang, Yuhai; Ren, Wei; Liu, Deming; Lu, Jie; Piper, James A; Leif, Robert C; Liu, Xiaogang; Jin, Dayong

2016-01-19

Compared with routine microscopy imaging of a few analytes at a time, rapid scanning through the whole sample area of a microscope slide to locate every single target object offers many advantages in terms of simplicity, speed, throughput, and potential for robust quantitative analysis. Existing techniques that accommodate solid-phase samples incorporating individual micrometer-sized targets generally rely on digital microscopy and image analysis, with intrinsically low throughput and reliability. Here, we report an advanced on-the-fly stage scanning method to achieve high-precision target location across the whole slide. By integrating X- and Y-axis linear encoders to a motorized stage as the virtual "grids" that provide real-time positional references, we demonstrate an orthogonal scanning automated microscopy (OSAM) technique which can search a coverslip area of 50 × 24 mm(2) in just 5.3 min and locate individual 15 μm lanthanide luminescent microspheres with standard deviations of 1.38 and 1.75 μm in X and Y directions. Alongside implementation of an autofocus unit that compensates the tilt of a slide in the Z-axis in real time, we increase the luminescence detection efficiency by 35% with an improved coefficient of variation. We demonstrate the capability of advanced OSAM for robust quantification of luminescence intensities and lifetimes for a variety of micrometer-scale luminescent targets, specifically single down-shifting and upconversion microspheres, crystalline microplates, and color-barcoded microrods, as well as quantitative suspension array assays of biotinylated-DNA functionalized upconversion nanoparticles.

Arrays of hollow out-of-plane microneedles made by metal electrodeposition onto solvent cast conductive polymer structures

NASA Astrophysics Data System (ADS)

Mansoor, I.; Liu, Y.; Häfeli, U. O.; Stoeber, B.

2013-08-01

Transdermal drug delivery using microneedles is a technique to potentially replace hypodermic needles for injection of many vaccines and drugs. Fabrication of hollow metallic microneedles so far has been associated with time-consuming steps that restrict batch production of these devices. Here, we are presenting a novel method for making metallic microneedles with any desired height, spacing, and lumen size. In our process, we use solvent casting to coat a mold, which contains an array of pillars, with a conductive polymer composite layer. The conductive layer is then used as a seed layer in a metal electrodeposition process. To characterize the process, the conductivity of the polymer composite with respect to different filler concentrations was investigated. In addition, plasma etching of the polymer was characterized. The electroplating process was also studied further to control the thickness of the microneedle array plate. The strength of the microneedle devices was evaluated through a series of compression tests, while their performance for transdermal drug delivery was tested by injection of 2.28 µm fluorescent microspheres into animal skin. The fabricated metallic microneedles seem appropriate for subcutaneous delivery of drugs and microspheres.

Bioactive and biodegradable silica biomaterial for bone regeneration.

PubMed

Wang, Shunfeng; Wang, Xiaohong; Draenert, Florian G; Albert, Olga; Schröder, Heinz C; Mailänder, Volker; Mitov, Gergo; Müller, Werner E G

2014-10-01

Biosilica, a biocompatible, natural inorganic polymer that is formed by an enzymatic, silicatein-mediated reaction in siliceous sponges to build up their inorganic skeleton, has been shown to be morphogenetically active and to induce mineralization of human osteoblast-like cells (SaOS-2) in vitro. In the present study, we prepared beads (microspheres) by encapsulation of β-tricalcium phosphate [β-TCP], either alone (control) or supplemented with silica or silicatein, into the biodegradable copolymer poly(d,l-lactide-co-glycolide) [PLGA]. Under the conditions used, ≈5% β-TCP, ≈9% silica, and 0.32μg/mg of silicatein were entrapped into the PLGA microspheres (diameter≈800μm). Determination of the biocompatibility of the β-TCP microspheres, supplemented with silica or silicatein, revealed no toxicity in the MTT based cell viability assay using SaOS-2 cells. The adherence of SaOS-2 cells to the surface of silica-containing microspheres was higher than for microspheres, containing only β-TCP. In addition, the silica-containing β-TCP microspheres and even more pronounced, a 1:1 mixture of microspheres containing β-TCP and silica, and β-TCP and silicatein, were found to strongly enhance the mineral deposition by SaOS-2 cells. Using these microspheres, first animal experiments with silica/biosilica were performed in female, adult New Zealand White rabbits to study the effect of the inorganic polymer on bone regeneration in vivo. The microspheres were implanted into 5mm thick holes, drilled into the femur of the animals, applying a bilateral comparison study design (3 test groups with 4-8 animals each). The control implant on one of the two hind legs contained microspheres with only β-TCP, while the test implant on the corresponding leg consisted either of microspheres containing β-TCP and silica, or a 1:1 mixture of microspheres, supplemented with β-TCP and silica, and β-TCP and silicatein. The results revealed that tissue/bone sections of silica containing implants and implants, composed of a 1:1 mixture of silica-containing microspheres and silicatein-containing microspheres, show an enhanced regeneration of bone tissue around the microspheres, compared to the control implants containing only β-TCP. The formation of new bone induced by the microspheres is also evident from measurements of the stiffness/reduced Young's modulus of the regenerated bone tissue. The reduced Young's modulus of the regenerating bone tissue around the implants was markedly higher for the silica-containing microspheres (1.1MPa), and even more for the 1:1 mixture of the silica- and silicatein-containing microspheres (1.4MPa), compared to the β-TCP microsphere controls (0.4MPa). We propose that based on their morphogenetic activity on bone-forming cells in vitro and the results of the animal experiments presented here, silica/biosilica-based scaffolds are promising materials for bone repair/regeneration. Copyright © 2014 Elsevier Inc. All rights reserved.

Easy approach to assembling a biomimetic color film with tunable structural colors.

PubMed

Wang, Wentao; Tang, Bingtao; Ma, Wei; Zhang, Jian; Ju, Benzhi; Zhang, Shufen

2015-06-01

The self-assembly of silica microspheres into a close-packed array is a simple method of fabricating three-dimensional photonic crystal structural color films. However, the color is very dull because of the interferences of scattering and background light. In this study, we added a small quantity of surface-modified carbon black (CB) to the system of colloidal silica in n-propanol. The use of n-propanol as a dispersant is beneficial to the rapid development of photonic crystal films during the process of dip-coating. The doping of CB into silica microspheres can absorb background and scattering light, resulting in vivid structural colors.

Use of an automated fluorescent microsphere method to measure regional blood flow in the fetal lamb.

PubMed

Tan, W; Riggs, K W; Thies, R L; Rurak, D W

1997-08-01

We have developed a method for measuring regional blood flow by means of fluorescent microspheres in all organs and tissues of the fetal lamb, including brain, heart, lung, liver, gut, spleen, kidney, adrenal, brown fat, skin, muscle, bone, and placenta. Five different fluorescent-labeled microspheres were used: blue (B), yellow-green (Y), orange (O), red (R), and crimson (C). An automated, 96-well microplate fluorescent reader (bottom reading) was chosen for the assay because of the rapidity and high throughput that it offers. Tissue samples were digested by 4 M ethanolic KOH. The sedimentation method and dye extraction with Cellosolve acetate, as previously reported by others, were used for the sample processing. The bones were crushed and allowed to directly soak in Cellosolve acetate to extract the dye. The relationship between microsphere number and fluorescent intensity was linear over a broad range of microsphere numbers (80-20,000/mL). The coefficients of variation of within-run and between-run precision were 3.39 +/- 1.10% and 4.54 +/- 1.10%, respectively. Recovery of microspheres from tissues and blood averaged 94.3 +/- 2.5% and was not dependent on microsphere number. The spillover of the fluorescent signals into adjacent colors was 4.0 +/- 0.1% for O to Y, 8.1 +/- 0.4% for O to R, and 9.1 +/- 0.5% for R to C, and these values were constant over a wide range in concentrations of the microsphere pairs. No evidence was obtained for quenching of the emission of one fluorophore via photon absorption by another fluorophore. The measurements of regional blood flow obtained with fluorescent microspheres in three chronically instrumented fetal lambs at approximately 140 days gestation were similar to the flow estimates obtained using radioactive microspheres in four other fetal lambs at the same gestational age. The fluorescent method is thus a viable alternative to the radioactive technique for the measurement of regional blood flow to all fetal organs and tissues, particularly when an automated fluorescent microplate reader is employed to reduce analysis time.

Development of a Luminex based competitive immunoassay for 2,4,6-trinitrotoluene (TNT).

PubMed

Anderson, George P; Lamar, Jacqueline D; Charles, Paul T

2007-04-15

Previously, a displacement immunoassay for 2,4,6-trinitrotoluene (TNT) was demonstrated using the Luminex 100. The work presented utilized this same specialized flow cytometer to demonstrate a highly sensitive and rapid competitive immunoassay for TNT. This required a TNT analog to be attached to the microsphere surface. Various linkers were evaluated; bovine serum albumin provided over 3 times more binding sites in comparison to various shorter diamine linkers. For this assay TNB-coated microspheres were added to samples; then biotinylated anti-TNT antibody and the reporter molecule, Streptavidin-R-Phycoerythrin, were added. In the absence of TNT, a highly fluorescent complex was formed on the surface of the microsphere. The presence of TNT resulted in dose-dependent decreased fluorescence. Various anti-TNT antibodies were evaluated; Mab 30-1 gave the strongest response, yielding the lowest limit of detection (<1.0 ng/mL) and a dynamic range up to 1 microg/mL. Other factors such as reaction time, cross reactivity to other nitro-compounds, evaluation of acetone extracts of TNT contaminated soils, testing in environmental matrices such as fresh water and seawater were all completed. Finally, a multiplex assay for TNT and three protein toxins was successfully conducted using the competitive format.

Thermal preparation of lysozyme-imprinted microspheres by using ionic liquid as a stabilizer.

PubMed

Qian, Li-Wei; Hu, Xiao-Ling; Guan, Ping; Gao, Bo; Wang, Dan; Wang, Chao-Li; Li, Ji; Du, Chun-Bao; Song, Wen-Qi

2014-11-01

Thermal preparation of lysozyme-imprinted microspheres was firstly investigated by using biocompatible ionic liquid (IL) as a thermal stabilizer. The imprinted microspheres made with IL could obtain the good recognition ability to template protein, whereas the imprinted polymer synthesized in the absence of it had a similar adsorption capacity to the non-imprinted one. Furthermore, the preparation conditions of imprinted polymers (MIPs) including the content of IL, temperature of polymerization, and types of functional monomers and crosslinkers were systematically analyzed via circular dichroism spectrum and activity assay. The results illustrated that using hydroxyethyl acrylate as the functional monomer, ethylene glycol dimethacrylate as the crosslinker, 5 % IL as the stabilizer, and 75 °C as the reaction temperature could retain the structure of template protein as much as possible. The obtained MIPs showed excellent recognition ability to the template protein with the separation factor and selectivity factor value of 4.30 and 2.21, respectively. Consequently, it is an effective way to accurately imprint and separate template protein by cooperatively using circular dichroism spectroscopy and activity assay during the preparation of protein MIPs. The method of utilizing IL to stabilizing protein at high temperature would offer a good opportunity for various technologies to improve the development of macromolecules imprinting.

Development of a Microsphere-based Immunoassay for Serological Detection of African Horse Sickness Virus and Comparison with Other Diagnostic Techniques.

PubMed

Sánchez-Matamoros, A; Beck, C; Kukielka, D; Lecollinet, S; Blaise-Boisseau, S; Garnier, A; Rueda, P; Zientara, S; Sánchez-Vizcaíno, J M

2016-12-01

African horse sickness (AHS) is a viral disease that causes high morbidity and mortality rates in susceptible Equidae and therefore significant economic losses. More rapid, sensitive and specific assays are required by diagnostic laboratories to support effective surveillance programmes. A novel microsphere-based immunoassay (Luminex assay) in which beads are coated with recombinant AHS virus (AHSV) structural protein 7 (VP7) has been developed for serological detection of antibodies against VP7 of any AHSV serotype. The performance of this assay was compared with that of a commercial enzyme-linked immunosorbent assay (ELISA) and commercial lateral flow assay (LFA) on a large panel of serum samples from uninfected horses (n = 92), from a reference library of all AHSV serotypes (n = 9), on samples from horses experimentally infected with AHSV (n = 114), and on samples from West African horses suspected of having AHS (n = 85). The Luminex assay gave the same negative results as ELISA when used to test the samples from uninfected horses. Both assays detected antibodies to all nine AHSV serotypes. In contrast, the Luminex assay detected a higher rate of anti-VP7 positivity in the West African field samples than did ELISA or LFA. The Luminex assay detected anti-VP7 positivity in experimentally infected horses at 7 days post-infection, compared to 13 days for ELISA. This novel immunoassay provides a platform for developing multiplex assays, in which the presence of antibodies against multiple ASHV antigens can be detected simultaneously. This would be useful for serotyping or for differentiating infected from vaccinated animals. © 2015 Blackwell Verlag GmbH.

Super-Resolution Imaging by Arrays of High-Index Spheres Embedded in Transparent Matrices

DTIC Science & Technology

2014-06-25

microsphere-assisted imaging. Roles of surface excitations, plasmons, polaritons and Tamm-states, as well as the role of nanoscale gap separating the object...nanometric gap between the object and spheres and the role of surface polariton -plasmons in the metallic nanostructures. Our results, however, show that

Template-etching route to construct uniform rattle-type Fe3O4@SiO2 hollow microspheres as drug carrier.

PubMed

Cheng, Lin; Liu, Yuanyuan; Zou, Bingfang; Yu, Yong; Ruan, Weimin; Wang, Yongqiang

2017-06-01

Template-etching strategy was put forward to synthesize rattle-type magnetic silica (Fe 3 O 4 @SiO 2 ) hollow microspheres in a controlled way. During the experiment, monodisperse Fe 2 O 3 microspheres were fabricated as physical template to generate uniform Fe 2 O 3 @SiO 2 with controlled shell thicknesses through sol-gel method, and the subsequent Fe 2 O 3 template etching process created variable space between Fe 2 O 3 core and SiO 2 shell, and the final calcination process transformed rattle-type Fe 2 O 3 @SiO 2 hollow microspheres into corresponding Fe 3 O 4 @SiO 2 product in hydrogen/nitrogen atmosphere. Compared with traditional physical template, here template-etching synthesis of rattle-type hollow microspheres saved the insertion of middle shells and their removal, which simplified the synthesis process with controllable core size and shell thickness. The rattle-type Fe 3 O 4 @SiO 2 hollow microspheres as drug carrier show efficient doxorubicin (DOX) loading, and the release rate of DOX loaded the rattle-type Fe 3 O 4 @SiO 2 hollow microspheres exhibit a surprising shell-thickness-dependent and a pH responsive drug release features. Additionally, MTT assays in HeLa cells demonstrated that the Fe 3 O 4 @SiO 2 nanocarriers were non-toxic even at the concentration of 250µgmL -1 for 48h. Thus, our results revealed that the Fe 3 O 4 @SiO 2 -DOX could play an important role in the development of intracellular delivery nanodevices for cancer therapy. Copyright © 2017. Published by Elsevier B.V.

Holographic optical assembly and photopolymerized joining of planar microspheres

DOE PAGES

Shaw, L. A.; Chizari, S.; Panas, R. M.; ...

2016-07-27

The aim of this research is to demonstrate a holographically driven photopolymerization process for joining colloidal particles to create planar microstructures fixed to a substrate, which can be monitored with real-time measurement. Holographic optical tweezers (HOT) have been used to arrange arrays of microparticles prior to this work; here we introduce a new photopolymerization process for rapidly joining simultaneously handled microspheres in a plane. Additionally, we demonstrate a new process control technique for efficiently identifying when particles have been successfully joined by measuring a sufficient reduction in the particles’ Brownian motion. Furthermore, this technique and our demonstrated joining approach enablemore » HOT technology to take critical steps toward automated additive fabrication of microstructures.« less

Formation and oral administration of alginate microspheres loaded with pDNA coding for lymphocystis disease virus (LCDV) to Japanese flounder.

PubMed

Tian, Ji-Yuan; Sun, Xiu-Qin; Chen, Xi-Guang

2008-05-01

Oral delivery of plasmid DNA (pDNA) is a desirable approach for fish immunization in intensive culture. However, its effectiveness is limited because of possible degradation of pDNA in the fish's digestive system. In this report, alginate microspheres loaded with pDNA coding for fish lymphocystis disease virus (LCDV) and green fluorescent protein were prepared with a modified oil containing water (W/O) emulsification method. Yield, loading percent and encapsulation efficiency of alginate microspheres were 90.5%, 1.8% and 92.7%, respectively. The alginate microspheres had diameters of less than 10 microm, and their shape was spherical. As compared to sodium alginate, a remarkable increase of DNA-phosphodiester and DNA-phosphomonoester bonds was observed for alginate microspheres loaded with pDNA by Fourier transform infrared (FTIR) spectroscopic analysis. Agarose gel electrophoresis showed a little supercoiled pDNA was transformed to open circular and linear pDNA during encapsulation. The cumulative release of pDNA in alginate microspheres was or=0.3) for anti-LCDV antibody from week 3 to week 16 for fish orally vaccinated with alginate microspheres loaded with pDNA, in comparison with fish orally vaccinated with naked pDNA. Our results display that alginate microspheres obtained by W/O emulsification are promising carriers for oral delivery of pDNA. This encapsulation technique has the potential for DNA vaccine delivery applications due to its ease of operation, low cost and significant immune effect.

SU-D-201-02: Prediction of Delivered Dose Based On a Joint Histogram of CT and FDG PET Images

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

Park, M; Choi, Y; Cho, A

2015-06-15

Purpose: To investigate whether pre-treatment images can be used in predicting microsphere distribution in tumors. When intra-arterial radioembolization using Y90 microspheres was performed, the microspheres were often delivered non-uniformly within the tumor, which could lead to an inefficient therapy. Therefore, it is important to estimate the distribution of microspheres. Methods: Early arterial phase CT and FDG PET images were acquired for patients with primary liver cancer prior to radioembolization (RE) using Y90 microspheres. Tumor volume was delineated on CT images and fused with FDG PET images. From each voxel (3.9×3.9×3.3 mm3) in the tumor, the Hounsfield unit (HU) from themore » CT and SUV values from the FDG PET were harvested. We binned both HU and SUV into 11 bins and then calculated a normalized joint-histogram in an 11×11 array.Patients also underwent a post-treatment Y90 PET imaging. Radiation dose for the tumor was estimated using convolution of the Y90 distribution with a dose-point kernel. We also calculated a fraction of the tumor volume that received a radiation dose great than 100Gy. Results: Averaged over 40 patients, 55% of tumor volume received a dose greater than 100Gy (range : 1.1 – 100%). The width of the joint histogram was narrower for patients with a high dose. For patients with a low dose, the width was wider and a larger fraction of tumor volume had low HU. Conclusion: We have shown the pattern of joint histogram of the HU and SUV depends on delivered dose. The patterns can predict the efficacy of uniform intra-arterial delivery of Y90 microspheres.« less

Multiplexed chemiluminescent assays in ArrayPlates for high-throughput measurement of gene expression

NASA Astrophysics Data System (ADS)

Martel, Ralph R.; Rounseville, Matthew P.; Botros, Ihab W.; Seligmann, Bruce E.

2002-06-01

Multiplexed Molecular Profiling (MMP) assays for drug discovery are performed in ArrayPlates. ArrayPlates are 96- well microtiter plates that contain a 16-element array at the bottom of each well. Each element within an array measures one analyte in a sample. A CCD imager records the quantitative chemiluminescent readout of all 1,536 elements in a 96-well plate simultaneously. Since array elements are reagent modifiable by the end-user, ArrayPlates can be adapted to a broad range of nucleic acid- and protein-based assays. Such multiplexed assays are rapidly established, flexible, robust, automation-friendly and cost-effective. Nucleic acid assays in ArrayPlates can detect DNA and RNA, including SNPs and ESTs. A multiplexed mRNA assay to measure the expression of 16 genes is described. The assay combines a homogeneous nuclease protection assay with subsequent probe immobilization to the array by means of a sandwich hybridization followed with chemiluminescent detection. This assay was used to examine cells grown and treated in microplates and avoided cloning, transfection, RNA insolation, reverse transcription, amplification and fluorochrome labeling. Standard deviations for the measurement of 16 genes ranged from 3 percent to 13 percent in samples of 30,000 cells. Such ArrayPlates transcription assays are useful in drug discovery and development for target validation, screening, lead optimization, metabolism and toxicity profiling. Chemiluminescent detection provides ArrayPlates assays with high signal-to-noise readout and simplifies imager requirements. Imaging a 2D surface that contains arrays simplifies lens requirements relative to imaging columns of liquid in microtiter plate wells. The Omix imager for ArrayPlates is described.

The effects of biodegradable poly(lactic-co-glycolic acid)-based microspheres loaded with quercetin on stemness, viability and osteogenic differentiation potential of stem cell spheroids.

PubMed

Lee, H; Nguyen, T T; Kim, M; Jeong, J-H; Park, J-B

2018-05-31

Quercetin has been reported to exert many beneficial effects on the protection against various diseases, such as diabetes, cancer, and inflammation. The aim of this study is to evaluate the potential osteogenic differentiation ability of mesenchymal stem cells in the presence of quercetin. Quercetin-loaded poly(lactic-co-glycolic acid) microspheres were prepared using an electrospraying technique. Characterization of the microspheres was evaluated with a scanning electron microscope and release profile. Three-dimensional cell spheroids were fabricated using silicon elastomer-based concave microwells. Qualitative results of cellular viability were seen under a confocal microscope, and quantitative cellular viability was evaluated using the Cell Counting Kit-8 assay. The alkaline phosphatase activity and Alizarin Red S staining were performed. A quantitative real-time polymerase chain reaction and a western blot analysis were performed. Spheroids were well formed irrespective of quercetin concentration. Most of the cells in spheroids emitted green fluorescence, and the morphology was round without significant changes. The application of quercetin-loaded microspheres produced a significant increase in the alkaline phosphatase activity. The real-time polymerase chain reaction results showed a significant increase in Runx2, and western blot results showed higher expression of Runx2 protein expression. Biodegradable microspheres loaded with quercetin produced prolonged release profiles with increased mineralization. Microspheres loaded with quercetin can be used for the enhancement of osteoblastic differentiation in cell therapy. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Porous PLGA microspheres tailored for dual delivery of biomolecules via layer-by-layer assembly.

PubMed

Go, Dewi P; Palmer, Jason A; Mitchell, Geraldine M; Gras, Sally L; O'Connor, Andrea J

2015-05-01

Tissue engineering is a complex and dynamic process that requires varied biomolecular cues to promote optimal tissue growth. Consequently, the development of delivery systems capable of sequestering more than one biomolecule with controllable release profiles is a key step in the advancement of this field. This study develops multilayered polyelectrolyte films incorporating alpha-melanocyte stimulating hormone (α-MSH), an anti-inflammatory molecule, and basic fibroblast growth factor (bFGF). The layers were successfully formed on macroporous poly lactic-co-glycolic acid microspheres produced using a combined inkjet and thermally induced phase separation technique. Release profiles could be varied by altering layer properties including the number of layers and concentrations of layering molecules. α-MSH and bFGF were released in a sustained manner and the bioactivity of α-MSH was shown to be preserved using an activated macrophage cell assay in vitro. The system performance was also tested in vivo subcutaneously in rats. The multilayered microspheres reduced the inflammatory response induced by a carrageenan stimulus 6 weeks after implantation compared to the non-layered microspheres without the anti-inflammatory and growth factors, demonstrating the potential of such multilayered constructs for the controlled delivery of bioactive molecules. © 2014 Wiley Periodicals, Inc.

Fiber-optic microsensor array based on fluorescent bulk optode microspheres for the trace analysis of silver ions.

PubMed

Wygladacz, Katarzyna; Radu, Aleksandar; Xu, Chao; Qin, Yu; Bakker, Eric

2005-08-01

An optical microsensor array is described for the rapid analysis of silver ions at low parts per trillion levels. Because the ionophore o-xylylenebis(N,N-diisobutyldithiocarbamate) (Cu-I) was reevaluated and shown to exhibit excellent selectivity for silver ions, ion-selective electrode (ISE) membranes were optimized and found to exhibit the lowest reported detection limit so far (3 x 10(-10) M). A corresponding Ag+-selective fluorescent optical microsensor array for the rapid sensing of trace level Ag+ was then developed. It was fabricated using plasticized PVC-based micrometer-scale fluorescent microspheres that were produced via a sonic particle casting device. They contained 156 mmol/kg Cu-I, 10 mmol/kg 9-(diethylamino)-5-[4-(15-butyl-1,13-dioxo-2,14-dioxanodecyl) phenylimino]benzo[a]phenoxazine (chromoionophore VII, ETH 5418), 2.3 mmol/kg 1,1' '-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (internal reference dye), and 14 mmol/kg sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate and were deposited onto the etched distal end of a 3200-microm-diameter optical fiber bundle. The microarray was characterized by fluorescence spectroscopy in samples containing 10(-12)-10(-8) M AgNO3 at pH 7.4, with selectivity characteristics comparable to the corresponding ISEs. The response time of the microsensor array was found to be less than 15 min for 10(-9) M AgNO3, which is drastically shorter than earlier data on optode films (8 h) and corresponding ISEs (30 min). A detection limit of 4 x 10(-11) M for Ag+ was observed, lower than any previously reported optode or silver-selective ISE. The microsensor array was applied for measurement of free silver levels in buffered pond water samples.

Development of Yersinia pestis F1 antigen-loaded microspheres vaccine against plague

PubMed Central

Huang, Shih-shiung; Li, I-Hsun; Hong, Po-da; Yeh, Ming-kung

2014-01-01

Yersinia pestis F1 antigen-loaded poly(DL-lactide-co-glycolide)/polyethylene glycol (PEG) (PLGA/PEG) microspheres were produced using a water-in-oil-in-water emulsion/solvent extraction technique and assayed for their percent yield, entrapment efficiency, surface morphology, particle size, zeta potential, in vitro release properties, and in vivo animal protect efficacy. The Y. pestis F1 antigen-loaded microspheres (mean particle size 3.8 μm) exhibited a high loading capacity (4.5% w/w), yield (85.2%), and entrapment efficiency (38.1%), and presented a controlled in vitro release profile with a low initial burst (18.5%), then continued to release Y. pestis F1 antigen over 70 days. The distribution (%) of Y. pestis F1 on the microspheres surface, outer layer, and core was 3.1%, 28.9%, and 60.7%, respectively. A steady release rate was noticed to be 0.55 μg Y. pestis F1 antigen/mg microspheres/day of Y. pestis F1 antigen release maintained for 42 days. The cumulative release amount at the 1st, 28th, and 42nd days was 8.2, 26.7, and 31.0 μg Y. pestis F1 antigen/mg microspheres, respectively. The 100 times median lethal dose 50% (LD50) of Y. pestis Yokohama-R strain by intraperitoneal injection challenge in mice test, in which mice received one dose of 40 μg F1 antigen content of PLGA/PEG microspheres, F1 antigen in Al(OH)3, and in comparison with F1 antigen in Al(OH)3 vaccine in two doses, was evaluated after given by subcutaneous immunization of BALB/c mice. The study results show that the greatest survival was observed in the group of mice immunized with one dose of F1 antigen-loaded PLGA/PEG microspheres, and two doses of F1 antigen in Al(OH)3 vaccine (100%). In vivo vaccination studies also demonstrated that F1 vaccines microspheres had a protective ability; its steady-state IgG immune protection in mice plasma dramatic increased from 2 weeks (18,764±3,124) to 7 weeks (126,468±19,176) after vaccination. These findings strongly suggest that F1-antigen loaded microspheres vaccine offer a new therapeutic strategy in optimizing the vaccine incorporation and delivery properties of these potential vaccine targeting carriers. PMID:24550673

Developing a novel fiber optic fluorescence device for multiplexed high-throughput cytotoxic screening.

PubMed

Lee, Dennis; Barnes, Stephen

2010-01-01

The need for new pharmacological agents is unending. Yet the drug discovery process has changed substantially over the past decade and continues to evolve in response to new technologies. There is presently a high demand to reduce discovery time by improving specific lab disciplines and developing new technology platforms in the area of cell-based assay screening. Here we present the developmental concept and early stage testing of the Ab-Sniffer, a novel fiber optic fluorescence device for high-throughput cytotoxicity screening using an immobilized whole cell approach. The fused silica fibers are chemically functionalized with biotin to provide interaction with fluorescently labeled, streptavidin functionalized alginate-chitosan microspheres. The microspheres are also functionalized with Concanavalin A to facilitate binding to living cells. By using lymphoma cells and rituximab in an adaptation of a well-known cytotoxicity protocol we demonstrate the utility of the Ab-Sniffer for functional screening of potential drug compounds rather than indirect, non-functional screening via binding assay. The platform can be extended to any assay capable of being tied to a fluorescence response including multiple target cells in each well of a multi-well plate for high-throughput screening.

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

Cai, Chang-Yun; Yang, Hongta, E-mail: hyang@dragon.nchu.edu.tw; Lin, Kun-Yi Andrew

This article reports a scalable technology for fabricating polymer films with excellent water-repelling and anti-ultraviolet properties. A roll-to-roll compatible doctor blade coating technology is utilized to prepare silica colloidal crystal-polymer composites. The silica microspheres can then be selectively removed to create flexible self-standing macroporous polymer films with crystalline arrays of pores. The void sizes are controlled by tuning the duration of a reactive ion etching process prior to the removal of the templating silica microspheres. After surface modification, superhydrophobic surface can be achieved. This study further demonstrates that the as-prepared transparent porous films with 200 nm of pores exhibit diffraction ofmore » ultraviolet lights originated from the Bragg's diffractive of light from the three-dimensional highly ordered air cavities.« less

Fabrication of Nonperiodic Metasurfaces by Microlens Projection Lithography.

PubMed

Gonidec, Mathieu; Hamedi, Mahiar M; Nemiroski, Alex; Rubio, Luis M; Torres, Cesar; Whitesides, George M

2016-07-13

This paper describes a strategy that uses template-directed self-assembly of micrometer-scale microspheres to fabricate arrays of microlenses for projection photolithography of periodic, quasiperiodic, and aperiodic infrared metasurfaces. This method of "template-encoded microlens projection lithography" (TEMPL) enables rapid prototyping of planar, multiscale patterns of similarly shaped structures with critical dimensions down to ∼400 nm. Each of these structures is defined by local projection lithography with a single microsphere acting as a lens. This paper explores the use of TEMPL for the fabrication of a broad range of two-dimensional lattices with varying types of nonperiodic spatial distribution. The matching optical spectra of the fabricated and simulated metasurfaces confirm that TEMPL can produce structures that conform to expected optical behavior.

SpermCheck: a simplified screening assay for immunological infertility.

PubMed

McClure, R D; Tom, R A; Watkins, M; Murthy, S

1989-10-01

SpermCheck (Bio-Rad Laboratories, Hercules, CA), a new screening test for regional surface antibodies on motile sperm, uses monodispersed latex microspheres of uniform size as a vehicle to link rabbit antihuman immunoglobulins (IgA, IgG, IgM) and provides both negative and positive control sera, as well as sufficient buffer for sperm preparation in ambient CO2 atmosphere. When compared with reference data available for the immunobead test (IBT), the direct protocol (semen) for SpermCheck yielded 94.4% sensitivity with 100% specificity; the indirect protocol (serum) provided a sensitivity of 100% with 94.7% specificity. The microspheres of SpermCheck maintain a nearly uniform concentration per volume, with none to negligible clumping. The greater difference between the optical densities of latex and cytoplasm allows use of a light microscope for the rapid assessment of the percent of regional binding rather than the phase-contrast microscope required for the IBT. SpermCheck eliminates many difficulties encountered with the IBT, making SpermCheck a convenient screening assay for use in the physician's office.

Fabrication and investigation of the bionic curved visual microlens array films

NASA Astrophysics Data System (ADS)

Kuo, Wen-Kai; Lin, Syuan-You; Hsu, Sheng-Wei; Yu, Hsin Her

2017-04-01

The compound eyes of insects are smaller, lighter, and have a wider field of view and high sensitivity to moving targets. In recent years, these advantages have attracted many researchers to develop minimized optical devices. In this study, a high performance microlens was fabricated, mimicking the biological visual feature. Polystyrene (PS) microspheres were synthesized by dispersion polymerization first, and then a close-packed monolayer of PS microspheres was assembled by the Langmuir-Blodgett (LB) deposition method. Following this, a 2D polydimethylsiloxane (PDMS) concave mold was fabricated by a soft lithography technique. Different aperture sizes of poly(methyl methacrylate) (PMMA) curved microlens array replicated films were prepared using traditional Chinese medicine cupping tool with a temperature-controllable hot plate, which eliminated the need for inconvenient metal modeling. The optical performance of the curved microlens films were evaluated by a system of optical microscopy (OM) and a home-made image capture charge-coupled device (CCD). The field of view (FOV) and the light intensity distribution of the curved microlens array were also investigated. We found that a broader field of view corresponded to a smaller aperture size of the curved microlens films, as the convex heights of the films are identical. The resolution of the curved microlens films was not affected by their aperture sizes, but was determined by their interommatidial angle and the diameter of the microlens.

Contact microspherical nanoscopy: from fundamentals to biomedical applications

NASA Astrophysics Data System (ADS)

Astratov, V. N.; Maslov, A. V.; Brettin, A.; Blanchette, K. F.; Nesmelov, Y. E.; Limberopoulos, N. I.; Walker, D. E.; Urbas, A. M.

2017-02-01

The mechanisms of super-resolution imaging by contact microspherical or microcylindrical nanoscopy remain an enigmatic question since these lenses neither have an ability to amplify the near-fields like in the case of far-field superlens, nor they have a hyperbolic dispersion similar to hyperlenses. In this work, we present results along two lines. First, we performed numerical modeling of super-resolution properties of two-dimensional (2-D) circular lens in the limit of wavelength-scale diameters, λ <= D <= 2λ, and relatively high indices of refraction, n=2. Our preliminary results on imaging point dipoles indicate that the resolution is generally close to λ/4 however on resonance with whispering gallery modes it may be slightly higher. Second, experimentally, we used actin protein filaments for the resolution quantification in microspherical nanoscopy. The critical feature of our approach is based on using arrayed cladding layer with strong localized surface plasmon resonances. This layer is used for enhancing plasmonic near-field illumination of our objects. In combination with the magnification of virtual image, this technique resulted in the lateral resolution of actin protein filaments on the order of λ/7.

Physicochemical characterization of spray-dried PLGA/PEG microspheres, and preliminary assessment of biological response.

PubMed

Javiya, Curie; Jonnalagadda, Sriramakamal

2016-09-01

The use of spray-drying to prepare blended PLGA:PEG microspheres with lower immune detection. To study physical properties, polymer miscibility and alveolar macrophage response for blended PLGA:PEG microspheres prepared by a laboratory-scale spray-drying process. Microspheres were prepared by spray-drying 0-20% w/w ratios of PLGA 65:35 and PEG 3350 in dichloromethane. Particle size and morphology was studied using scanning electron microscopy. Polymer miscibility and residual solvent levels evaluated by thermal analysis (differential scanning calorimetry - DSC and thermogravimetric analysis - TGA). Immunogenicity was assessed in vitro by response of rat alveolar macrophages (NR8383) by the MTT-based cell viability assay and reactive oxygen species (ROS) detection. The spray dried particles were spherical, with a size range of about 2-3 µm and a yield of 16-60%. Highest yield was obtained at 1% PEG concentration. Thermal analysis showed a melting peak at 59 °C (enthalpy: 170.61 J/g) and a degradation-onset of 180 °C for PEG 3350. PLGA 65:35 was amorphous, with a Tg of 43 °C. Blended PLGA:PEG microspheres showed a delayed degradation-onset of 280 °C, and PEG enthalpy-loss corresponding to 15% miscibility of PEG in PLGA. NR8383 viability studies and ROS detection upon exposure to these cells suggested that blended PLGA:PEG microspheres containing 1 and 5% PEG are optimal in controling cell proliferation and activation. This research establishes the feasibility of using a spray-drying process to prepare spherical particles (2-3 µm) of molecularly-blended PLGA 65:35 and PEG 3350. A PEG concentration of 1-5% was optimal to maximize process yield, with minimal potential for immune detection.

Scaffolds for bone regeneration made of hydroxyapatite microspheres in a collagen matrix.

PubMed

Cholas, Rahmatullah; Kunjalukkal Padmanabhan, Sanosh; Gervaso, Francesca; Udayan, Gayatri; Monaco, Graziana; Sannino, Alessandro; Licciulli, Antonio

2016-06-01

Biomimetic scaffolds with a structural and chemical composition similar to native bone tissue may be promising for bone tissue regeneration. In the present work hydroxyapatite mesoporous microspheres (mHA) were incorporated into collagen scaffolds containing an ordered interconnected macroporosity. The mHA were obtained by spray drying of a nano hydroxyapatite slurry prepared by the precipitation technique. X-ray diffraction (XRD) analysis revealed that the microspheres were composed only of hydroxyapatite (HA) phase, and energy-dispersive x-ray spectroscopy (EDS) analysis revealed the Ca/P ratio to be 1.69 which is near the value for pure HA. The obtained microspheres had an average diameter of 6 μm, a specific surface area of 40 m(2)/g as measured by Brunauer-Emmett-Teller (BET) analysis, and Barrett-Joyner-Halenda (BJH) analysis showed a mesoporous structure with an average pore diameter of 16 nm. Collagen/HA-microsphere (Col/mHA) composite scaffolds were prepared by freeze-drying followed by dehydrothermal crosslinking. SEM observations of Col/mHA scaffolds revealed HA microspheres embedded within a porous collagen matrix with a pore size ranging from a few microns up to 200 μm, which was also confirmed by histological staining of sections of paraffin embedded scaffolds. The compressive modulus of the composite scaffold at low and high strain values was 1.7 and 2.8 times, respectively, that of pure collagen scaffolds. Cell proliferation measured by the MTT assay showed more than a 3-fold increase in cell number within the scaffolds after 15 days of culture for both pure collagen scaffolds and Col/mHA composite scaffolds. Attractive properties of this composite scaffold include the potential to load the microspheres for drug delivery and the controllability of the pore structure at various length scales. Copyright © 2016 Elsevier B.V. All rights reserved.

Immunomicrospheres - Reagents for cell labeling and separation

NASA Technical Reports Server (NTRS)

Rembaum, A.; Dreyer, W. J.

1980-01-01

Immunomicrospheres are specially designed microscopic particles that have antibodies or similar molecules chemically bound to their surfaces. The antibody-coated microspheres react in a highly specific way with target cells, viruses, or other antigenic agents. Immunomicrospheres may be synthesized so that they incorporate compounds that are highly radioactive, intensely fluorescent, magnetic, electron opaque, highly colored, or pharmacologically active. These various types of microspheres may be coated with pure, highly specific monoclonal antibodies obtained by the new hybridoma cell cloning techniques or with conventional antibody preparations. Some of the many present and potential applications for these new reagents are (1) new types of radioimmune or immunofluorescent assays, (2) improved fluorescence microscopy, (3) separation of cells on the basis of the fluorescent, electrophoretic, or magnetic properties of bound immunomicrospheres, (4) markers for use in several types of electron or standard light microscopy, and (5) delivery of lethal compouds to specific undesirable living cells. The combination of the various new types of synthetic microspheres and the newly available homogeneous antibodies offers new opportunities in research, diagnosis, and therapy.

Correlation of two bioadhesion assays: the everted sac technique and the CAHN microbalance.

PubMed

Santos, C A; Jacob, J S; Hertzog, B A; Freedman, B D; Press, D L; Harnpicharnchai, P; Mathiowitz, E

1999-08-27

This contribution correlates two in vitro methods utilized to determine bioadhesion. One method, the everted intestinal sac technique, is a passive test for bioadhesion involving several polymer microspheres and a section of everted intestinal tissue. The other method, the CAHN microbalance, employs a CAHN dynamic contact angle analyzer with modified software to record the tensile forces measured as a single polymer microsphere is pulled from intestinal tissue. This study demonstrates that CAHN and everted sac experiments yield similar results when used to quantify the bioadhesive nature of polymer microsphere systems. A polymer showing high adhesion in one method also demonstrates high bioadhesion in the other method; polymers that exhibit high fracture strength and tensile work measurements with the CAHN microbalance also yield high binding percentages with the everted sac method. The polymers tested and reported here are poly(caprolactone) and different copolymer ratios of poly(fumaric-co-sebacic anhydride). The results of this correlation demonstrate that each method alone is a valuable indicator of bioadhesion.

Fluorescence-based bioassays for the detection and evaluation of food materials.

PubMed

Nishi, Kentaro; Isobe, Shin-Ichiro; Zhu, Yun; Kiyama, Ryoiti

2015-10-13

We summarize here the recent progress in fluorescence-based bioassays for the detection and evaluation of food materials by focusing on fluorescent dyes used in bioassays and applications of these assays for food safety, quality and efficacy. Fluorescent dyes have been used in various bioassays, such as biosensing, cell assay, energy transfer-based assay, probing, protein/immunological assay and microarray/biochip assay. Among the arrays used in microarray/biochip assay, fluorescence-based microarrays/biochips, such as antibody/protein microarrays, bead/suspension arrays, capillary/sensor arrays, DNA microarrays/polymerase chain reaction (PCR)-based arrays, glycan/lectin arrays, immunoassay/enzyme-linked immunosorbent assay (ELISA)-based arrays, microfluidic chips and tissue arrays, have been developed and used for the assessment of allergy/poisoning/toxicity, contamination and efficacy/mechanism, and quality control/safety. DNA microarray assays have been used widely for food safety and quality as well as searches for active components. DNA microarray-based gene expression profiling may be useful for such purposes due to its advantages in the evaluation of pathway-based intracellular signaling in response to food materials.

Fluorescence-Based Bioassays for the Detection and Evaluation of Food Materials

PubMed Central

Nishi, Kentaro; Isobe, Shin-Ichiro; Zhu, Yun; Kiyama, Ryoiti

2015-01-01

We summarize here the recent progress in fluorescence-based bioassays for the detection and evaluation of food materials by focusing on fluorescent dyes used in bioassays and applications of these assays for food safety, quality and efficacy. Fluorescent dyes have been used in various bioassays, such as biosensing, cell assay, energy transfer-based assay, probing, protein/immunological assay and microarray/biochip assay. Among the arrays used in microarray/biochip assay, fluorescence-based microarrays/biochips, such as antibody/protein microarrays, bead/suspension arrays, capillary/sensor arrays, DNA microarrays/polymerase chain reaction (PCR)-based arrays, glycan/lectin arrays, immunoassay/enzyme-linked immunosorbent assay (ELISA)-based arrays, microfluidic chips and tissue arrays, have been developed and used for the assessment of allergy/poisoning/toxicity, contamination and efficacy/mechanism, and quality control/safety. DNA microarray assays have been used widely for food safety and quality as well as searches for active components. DNA microarray-based gene expression profiling may be useful for such purposes due to its advantages in the evaluation of pathway-based intracellular signaling in response to food materials. PMID:26473869

Testing implications of varying targets for Bordetella pertussis: comparison of the FilmArray Respiratory Panel and the Focus B. pertussis PCR assay

PubMed Central

Jerris, Robert C; Williams, Sally R; MacDonald, Heather J; Ingebrigtsen, Danielle R; Westblade, Lars F; Rogers, Beverly B

2015-01-01

Background The FilmArray Respiratory Panel (RP) detects multiple pathogens, including Bordetella pertussis. The multiplex PCR system is appropriate for a core laboratory or point of care due to ease of use. The purpose of this study is to compare the analytical sensitivity of the FilmArray RP, which targets the promoter region of the B. pertussis toxin gene, with the Focus real-time PCR assay, which targets the insertion sequence IS481. Methods Seventy-one specimens from patients aged 1 month to 18 years, which had tested positive for B. pertussis using the Focus assay, were analysed using the FilmArray RP. Results Forty-six specimens were positive for B. pertussis by both the Focus and the FilmArray RP assays. Twenty-five specimens were negative for B. pertussis using the FilmArray RP assay, but positive using the Focus assay. Conclusions The FilmArray RP assays will detect approximately 1/3 less cases of B. pertussis than the Focus assay. PMID:25742911

ROS-Responsive Microspheres for On Demand Antioxidant Therapy in a Model of Diabetic Peripheral Arterial Disease

PubMed Central

Poole, KM; Nelson, CE; Joshi, RV; Martin, JR; Gupta, MK; Haws, SC; Kavanaugh, TE; Skala, MC; Duvall, CL

2014-01-01

A new microparticle-based delivery system was synthesized from reactive oxygen species (ROS)-responsive poly(propylene sulfide) (PPS) and tested for “on demand” antioxidant therapy. PPS is hydrophobic but undergoes a phase change to become hydrophilic upon oxidation and thus provides a useful platform for ROS-demanded drug release. This platform was tested for delivery of the promising anti-inflammatory and antioxidant therapeutic molecule curcumin, which is currently limited in use in its free form due to poor pharmacokinetic properties. PPS microspheres efficiently encapsulated curcumin through oil-in-water emulsion and provided sustained, on demand release that was modulated in vitro by hydrogen peroxide concentration. The cytocompatible, curcumin-loaded microspheres preferentially targeted and scavenged intracellular ROS in activated macrophages, reduced in vitro cell death in the presence of cytotoxic levels of ROS, and decreased tissue-level ROS in vivo in the diabetic mouse hind limb ischemia model of peripheral arterial disease. Interestingly, due to the ROS scavenging behavior of PPS, the blank microparticles also showed inherent therapeutic properties that were synergistic with the effects of curcumin in these assays. Functionally, local delivery of curcumin-PPS microspheres accelerated recovery from hind limb ischemia in diabetic mice, as demonstrated using non-invasive imaging techniques. This work demonstrates the potential for PPS microspheres as a generalizable vehicle for ROS-demanded drug release and establishes the utility of this platform for improving local curcumin bioavailability for treatment of chronic inflammatory diseases. PMID:25522975

Ternary particles for effective vaccine delivery to the pulmonary system

NASA Astrophysics Data System (ADS)

Terry, Treniece La'shay

Progress in the fields of molecular biology and genomics has provided great insight into the pathogenesis of disease and the defense mechanisms of the immune system. This knowledge has lead to the classification of an array of abnormal genes, for which, treatment relies on cellular expression of proteins. The utility of DNA-based vaccines hold great promise for the treatment of genetically based and infectious diseases, which ranges from hemophilia, cystic fibrosis, and HIV. Synthetic delivery systems consisting of cationic polymers, such as polyethylenimine (PEI), are capable of condensing DNA into compact structures, maximizing cellular uptake of DNA and yielding high levels of protein expression. To date, short term expression is a major obstacle in the development of gene therapies and has halted their expansion in clinical applications. This study intends to develop a sustained release vaccine delivery system using PLA-PEG block copolymers encapsulating PEI:DNA polyplexes. To enhance the effectiveness of such DNA-based vaccines, resident antigen presenting cells, macrophages and dendritic cells, will be targeted within the alveoli regions of the lungs. Porous microspheres will be engineered with aerodynamic properties capable of achieving deep lung deposition. A fabrication technique using concentric nozzles will be developed to produce porous microspheres. It was observed that modifications in the dispersed to continuous phase ratios have the largest influence on particle size distributions, release rates and encapsulation efficiency which ranged form 80--95% with fourteen days of release. Amphiphilic block copolymers were also used to fabricate porous microspheres. The confirmation of PEG within the biodegradable polymer backbone was found to have a tremendous impact on the microsphere morphology and encapsulation efficiency which varied from 50--90%. Porous microspheres were capable of providing sustained gene expression when tested in vitro using the luciferase reporter gene plasmid DNA. Prolonged expression was obtained for 9 days. PLGA and PLA-PEG microspheres were administered in vivo by intra-tracheal instillation and produced an acute inflammatory response, as observed from the large presence of neutrophils. The response using PLA-PEG microspheres yielded a lower total cell count signifying the incorporation of PEG into the copolymer backbone enhances the biocompatibility of the delivery system.

Glucose response of near-infrared alginate-based microsphere sensors under dynamic reversible conditions.

PubMed

Chaudhary, Ayesha; Harma, Harri; Hanninen, Pekka; McShane, Michael J; Srivastava, Rohit

2011-08-01

Minimally invasive optical glucose biosensors with increased functional longevity form one of the most promising techniques for continuous glucose monitoring, because of their long-term stability, reversibility, repeatability, specificity, and high sensitivity. They are based on the principle of competitive binding and fluorescence resonance energy transfer. Moving to the near-infrared region of the spectrum has the potential to improve signal throughput for implanted sensors, but requires a change in dye chemistry that could alter response sensitivity, range, and toxicity profiles. The near-infrared dissolved-core alginate microsphere sensors were fabricated by emulsion followed by surface coating by layer-by-layer self-assembly. The particles were characterized for sensor stability, sensor response, and reversibility in deionized water and simulated interstitial fluid. The sensor response to step changes in bulk glucose concentrations was also evaluated under dynamic conditions using a microflow cell unit. Finally, in vitro cytotoxicity assays were performed with L929 mouse fibroblast cell lines to demonstrate preliminary biocompatibility of the sensors. The glucose sensitivity under controlled and dynamic conditions was observed to be 0.86%/mM glucose with an analytical response range of 0-30 mM glucose, covering both the physiological and pathophysiological range. The sensor demonstrated a repeatable, reversible, and reproducible response, with a maximum response time of 120 s. In vitro cytotoxicity assays revealed nearly 95% viability of cells, thereby suggesting that the alginate microsphere sensor system does not exhibit cytotoxicity. The incorporation of near-infrared dyes shows promise in improving sensor response because of their high sensitivity and improved tissue penetration of infrared light. The sensitivity for the sensors was approximately 1.5 times greater than that observed for visible dye sensors, and the new dye chemistry did not significantly alter the biocompatibility of the materials. These findings provide additional support for the potential application of alginate microspheres and similar systems such as "smart-tattoo" glucose sensors.

Evaluation of Fluorescence Microsphere Immunoassay for the Detection of Antibodies to Rift Valley Fever Nucleocapsid Protein and Glycoproteins

USDA-ARS?s Scientific Manuscript database

Rift Valley Fever virus (RVFV) is a zoonotic virus that infects ruminants including cattle, sheep, goats, camels and buffalo. Multiplexing diagnostic assays that can simultaneously detect antibodies against multiple RVFV antigens offer a high throughput test for disease surveillance and vaccine eva...

Validation of a Microsphere Immunoassay for Serological Leptospirosis Diagnosis in Human Serum by Comparison to the Current Gold Standard

PubMed Central

Wynwood, Sarah J.; Burns, Mary-Anne A.; Graham, Glenn C.; Weier, Steven L.; McKay, David B.; Craig, Scott B.

2015-01-01

A microsphere immunoassay (MIA) utilising Luminex xMap technology that is capable of determining leptospirosis IgG and IgM independently was developed. The MIA was validated using 200 human samples submitted for routine leptospirosis serology testing. The traditional microscopic agglutination (MAT) method (now 100 years old) suffers from a significant range of technical problems including a dependence on antisera which is difficult to source and produce, false positive reactions due to auto-agglutination and an inability to differentiate between IgG and IgM antibodies. A comparative validation method of the MIA against the MAT was performed and used to determine the ability of the MIA to detect leptospiral antibodies when compared with the MAT. The assay was able to determine samples in the reactive, equivocal and non-reactive ranges when compared to the MAT and was able to differentiate leptospiral IgG antibodies from leptospiral IgM antibodies. The MIA is more sensitive than the MAT and in true infections was able to detect low levels of antibody in the later stages of the acute phase as well as detect higher levels of IgM antibody earlier in the immune phase of the infection. The relatively low cost, high throughput platform and significantly reduced dependency on large volumes of rabbit antisera make this assay worthy of consideration for any microbiological assay that currently uses agglutination assays. PMID:25807009

Development of novel fluorescent particles applicable for phagocytosis assays with human macrophages.

PubMed

Sóñora, Cecilia; Arbildi, Paula; Miraballes-Martínez, Iris; Hernández, Ana

2018-01-01

Phagocytosis is a fundamental process for removal of pathogens and for clearance of apoptotic cells. The objective of this work was the preparation of fluorescent microspheres by a simple method and the evaluation of its applicability in phagocytosis assays by using different human derived cells, differentiated THP-1 cell line and blood monocytes, with flow cytometry measurements for functionality assays. Our results show that microparticles are efficiently internalised in a non-opsonised form and in dose-dependent manner by both cellular types. Concerning mechanism we determined that tTG-β3 integrin signaling could be involved in the uptake of these particles.

Diamond Lattice Colloidal Crystals from Binary DNA-grafted Microspheres

NASA Astrophysics Data System (ADS)

Crocker, John; Wang, Yifan; Jenkins, Ian; McGinley, James; Sinno, Talid

Future optical materials promise to do for photonics what semiconductors did for electronics, but the challenge has long been in creating the structure they require regular, three-dimensional array of transparent microspheres arranged like the atoms in a diamond crystal. Here we demonstrate a simple approach for spontaneously growing double-diamond (or B32) crystals from a binary suspension of sub-micron polymer microspheres with synthetic DNA grafted to their surfaces. While diamond symmetry crystals have previously been grown from much smaller nanoparticles, none of those methods appear workable for the larger particles needed for photonic applications, whose size must be comparable to the wavelength of visible light. Intriguingly, matched simulations fail to nucleate or grow B32 crystals from suspension; nor have they been predicted on the basis of theoretical arguments. We conjecture that the B32 crystals may form via transformation from a precursor with a different lattice structure in the bulk or on its surface. The feasibility of converting our self-assembled crystals into diamond-symmetry photonic templates will be discussed. This finding suggests that still other unexpected microstructures may be accessible using this approach. US National Science Foundation, CBET- 1403237.

Usnic acid-loaded biocompatible magnetic PLGA-PVA microsphere thin films fabricated by MAPLE with increased resistance to staphylococcal colonization.

PubMed

Grumezescu, V; Holban, A M; Grumezescu, A M; Socol, G; Ficai, A; Vasile, B S; Truscă, R; Bleotu, C; Lazar, V; Chifiriuc, C M; Mogosanu, G D

2014-09-01

Due to their persistence and resistance to the current therapeutic approaches, Staphylococcus aureus biofilm-associated infections represent a major cause of morbidity and mortality in the hospital environment. Since (+)-usnic acid (UA), a secondary lichen metabolite, possesses antimicrobial activity against Gram-positive cocci, including S. aureus, the aim of this study was to load magnetic polylactic-co-glycolic acid-polyvinyl alcohol (PLGA-PVA) microspheres with UA, then to obtain thin coatings using matrix-assisted pulsed laser evaporation and to quantitatively assess the capacity of the bio-nano-active modified surface to control biofilm formation by S. aureus, using a culture-based assay. The UA-loaded microspheres inhibited both the initial attachment of S. aureus to the coated surfaces, as well as the development of mature biofilms. In vitro bioevalution tests performed on the fabricated thin films revealed great biocompatibility, which may endorse them as competitive candidates for the development of improved non-toxic surfaces resistant to S. aureus colonization and as scaffolds for stem cell cultivation and tissue engineering.

Kefiran-alginate gel microspheres for oral delivery of ciprofloxacin.

PubMed

Blandón, Lina M; Islan, German A; Castro, Guillermo R; Noseda, Miguel D; Thomaz-Soccol, Vanete; Soccol, Carlos R

2016-09-01

Ciprofloxacin is a broad-spectrum antibiotic associated with gastric and intestinal side effects after extended oral administration. Alginate is a biopolymer commonly employed in gel synthesis by ionotropic gelation, but unstable in the presence of biological metal-chelating compounds and/or under dried conditions. Kefiran is a microbial biopolymer able to form gels with the advantage of displaying antimicrobial activity. In the present study, kefiran-alginate gel microspheres were developed to encapsulate ciprofloxacin for antimicrobial controlled release and enhanced bactericidal effect against common pathogens. Scanning electron microscopy (SEM) analysis of the hybrid gel microspheres showed a spherical structure with a smoother surface compared to alginate gel matrices. In vitro release of ciprofloxacin from kefiran-alginate microspheres was less than 3.0% and 5.0% at pH 1.2 (stomach), and 5.0% and 25.0% at pH 7.4 (intestine) in 3 and 21h, respectively. Fourier transform infrared spectroscopy (FTIR) of ciprofloxacin-kefiran showed the displacement of typical bands of ciprofloxacin and kefiran, suggesting a cooperative interaction by hydrogen bridges between both molecules. Additionally, the thermal analysis of ciprofloxacin-kefiran showed a protective effect of the biopolymer against ciprofloxacin degradation at high temperatures. Finally, antimicrobial assays of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhymurium, and Staphylococcus aureus demonstrated the synergic effect between ciprofloxacin and kefiran against the tested microorganisms. Copyright © 2016 Elsevier B.V. All rights reserved.

Magnetic focusing immunosensor for the detection of Salmonella typhimurium in foods

NASA Astrophysics Data System (ADS)

Pivarnik, Philip E.; Cao, He; Letcher, Stephen V.; Pierson, Arthur H.; Rand, Arthur G.

1999-01-01

From 1988 through 1992 Salmonellosis accounted for 27% of the total reported foodborne disease outbreaks and 57% of the outbreaks in which the pathogen was identified. The prevalence of Salmonellosis and the new requirements to monitor the organism as a marker in pathogen reduction programs will drive the need for rapid, on-site testing. A compact fiber optic fluorometer using a red diode laser as an excitation source and fiber probes for analyte detection has been constructed and used to measure Salmonella. The organisms were isolated with anti-Salmonella magnetic beads and were labeled with a secondary antibody conjugated to a red fluorescent dye. The response of the system was proportional to the concentration of Salmonella typhimurium from 3.2 X 105 colony forming units (CFU)/ml to 1.6 X 107 CFU/ml. The system was developed to utilize a fiber-optic magnetic focusing problem that attracted the magnetic microspheres to the surface of a sample chamber directly in front of the excitation and emission fibers. The signal obtained from a homogenous suspension of fluorescent magnetic microspheres was 9 to 10 picowatts. After focusing, the signal from the fluorescent labeled magnetic microspheres increased to 200 picowatts, approximately 20 times greater than the homogeneous suspension. The magnetic focusing assay detected 1.59 X 105 colony forming units/ml of Salmonella typhimurium cultured in growth media. The process of magnetic focusing in front of the fibers has the potential to reduce the background fluorescence from unbound secondary antibodies, eliminating several rinsing steps, resulting in a simple rapid assay.

PELA microspheres with encapsulated arginine-chitosan/pBMP-2 nanoparticles induce pBMP-2 controlled-release, transfected osteoblastic progenitor cells, and promoted osteogenic differentiation.

PubMed

Xu, Xiaolong; Qiu, Sujun; Zhang, Yuxian; Yin, Jie; Min, Shaoxiong

2017-03-01

Repair of the bone injury remains a challenge in clinical practices. Recent progress in tissue engineering and therapeutic gene delivery systems have led to promising new strategies for successful acceleration of bone repair process. The aim of this study was to create a controlled-release system to slowly release the arginine-chitosan/plasmid DNA nanoparticles encoding BMP-2 gene (Arg-CS/pBMP-2 NPs), efficiently transfect osteoblastic progenitor cells, secrete functional BMP-2 protein, and promote osteogenic differentiation. In this study, chitosan was conjugated with arginine to generate arginine-chitosan polymer (Arg-CS) for gene delivery. Mix the Arg-CS with pBMP-2 to condense pBMP-2 into nano-sized particles. In vitro transfection assays demonstrated that the transfection efficiency of Arg-CS/pBMP-2 nanoparticles and the expression level of BMP-2 was obviously exceed control groups. Further, PELA microspheres as the controlled-release carrier for the nanoparticles were used to encapsulate Arg-CS/pBMP-2 NPs. We demonstrated that the Arg-CS/pBMP-2 NPs could slowly release from the PELA microspheres at least for 42 d. During the co-culture with the PELA microspheres, the content of BMP-2 protein secreted by MC3T3-E1 reached the peak at 7 d. After 21d, the secretion of BMP-2 protein still maintain a higher level. The alkaline phosphatase activity, alizarin red staining, and osteogenesis-related gene expression by real-time quantitative PCR analysis all showed the PELA microspheres entrapping with Arg-CS/pBMP-2 NPs can obviously induce the osteogenic differentiation. The results indicated that the Arg-CS is a suitable gene vector which can promote the gene transfection. And the novel PELA microspheres-nanoparticle controlled-release system has potential clinical application in the future after further research.

Development of a Multiplexed Bead-Based Suspension Array for the Detection and Discrimination of Pospiviroid Plant Pathogens

PubMed Central

van Brunschot, Sharon L.; Bergervoet, Jan H. W.; Pagendam, Daniel E.; de Weerdt, Marjanne; Geering, Andrew D. W.; Drenth, André; van der Vlugt, René A. A.

2014-01-01

Efficient and reliable diagnostic tools for the routine indexing and certification of clean propagating material are essential for the management of pospiviroid diseases in horticultural crops. This study describes the development of a true multiplexed diagnostic method for the detection and identification of all nine currently recognized pospiviroid species in one assay using Luminex bead-based suspension array technology. In addition, a new data-driven, statistical method is presented for establishing thresholds for positivity for individual assays within multiplexed arrays. When applied to the multiplexed array data generated in this study, the new method was shown to have better control of false positives and false negative results than two other commonly used approaches for setting thresholds. The 11-plex Luminex MagPlex-TAG pospiviroid array described here has a unique hierarchical assay design, incorporating a near-universal assay in addition to nine species-specific assays, and a co-amplified plant internal control assay for quality assurance purposes. All assays of the multiplexed array were shown to be 100% specific, sensitive and reproducible. The multiplexed array described herein is robust, easy to use, displays unambiguous results and has strong potential for use in routine pospiviroid indexing to improve disease management strategies. PMID:24404188

High-throughput kinase assays with protein substrates using fluorescent polymer superquenching.

PubMed

Rininsland, Frauke; Stankewicz, Casey; Weatherford, Wendy; McBranch, Duncan

2005-05-31

High-throughput screening is used by the pharmaceutical industry for identifying lead compounds that interact with targets of pharmacological interest. Because of the key role that aberrant regulation of protein phosphorylation plays in diseases such as cancer, diabetes and hypertension, kinases have become one of the main drug targets. With the exception of antibody-based assays, methods to screen for specific kinase activity are generally restricted to the use of small synthetic peptides as substrates. However, the use of natural protein substrates has the advantage that potential inhibitors can be detected that affect enzyme activity by binding to a site other than the catalytic site. We have previously reported a non-radioactive and non-antibody-based fluorescence quench assay for detection of phosphorylation or dephosphorylation using synthetic peptide substrates. The aim of this work is to develop an assay for detection of phosphorylation of chemically unmodified proteins based on this polymer superquenching platform. Using a modified QTL Lightspeed assay, phosphorylation of native protein was quantified by the interaction of the phosphorylated proteins with metal-ion coordinating groups co-located with fluorescent polymer deposited onto microspheres. The binding of phospho-protein inhibits a dye-labeled "tracer" peptide from associating to the phosphate-binding sites present on the fluorescent microspheres. The resulting inhibition of quench generates a "turn on" assay, in which the signal correlates with the phosphorylation of the substrate. The assay was tested on three different proteins: Myelin Basic Protein (MBP), Histone H1 and Phosphorylated heat- and acid-stable protein (PHAS-1). Phosphorylation of the proteins was detected by Protein Kinase Calpha (PKCalpha) and by the Interleukin -1 Receptor-associated Kinase 4 (IRAK4). Enzyme inhibition yielded IC50 values that were comparable to those obtained using peptide substrates. Statistical parameters that are used in the high-throughput community to determine assay robustness (Z'-value) demonstrate the suitability of this format for high-throughput screening applications for detection of inhibitors of enzyme activity. The QTL Lightspeed protein detection system provides a simple mix and measure "turn on" assay for the detection of kinase activity using natural protein substrates. The platform is robust and allows for identification of inhibitors of kinase activity.

A microsphere assembly method with laser microwelding for fabrication of three-dimensional periodic structures

NASA Astrophysics Data System (ADS)

Takagi, Kenta; Omote, Masanori; Kawasaki, Akira

2010-03-01

The orderly build-up of monosized microspheres with sizes of hundreds of micrometres enabled us to develop three-dimensional (3D) photonic crystal devices for terahertz electromagnetic waves. We designed and manufactured an original 3D particle assembly system capable of fabricating arbitrary periodic structures from these spherical particles. This method employs a pick-and-place assembling approach with robotic manipulation and interparticle laser microwelding in order to incorporate a contrivance for highly accurate arraying: an operation that compensates the size deviation of raw monosized particles. Pre-examination of particles of various materials revealed that interparticle laser welding must be achieved with local melting by suppressing heat diffusion from the welding area. By optimizing the assembly conditions, we succeeded in fabricating an accurate periodic structure with a diamond lattice from 400 µm polyethylene composite particles. This structure demonstrated a photonic bandgap in the terahertz frequency range.

Fabrication and characterization of hexagonally patterned quasi-1D ZnO nanowire arrays

PubMed Central

2014-01-01

Quasi-one-dimensional (quasi-1D) ZnO nanowire arrays with hexagonal pattern have been successfully synthesized via the vapor transport process without any metal catalyst. By utilizing polystyrene microsphere self-assembled monolayer, sol–gel-derived ZnO thin films were used as the periodic nucleation sites for the growth of ZnO nanowires. High-quality quasi-1D ZnO nanowires were grown from nucleation sites, and the original hexagonal periodicity is well-preserved. According to the experimental results, the vapor transport solid condensation mechanism was proposed, in which the sol–gel-derived ZnO film acting as a seed layer for nucleation. This simple method provides a favorable way to form quasi-1D ZnO nanostructures applicable to diverse fields such as two-dimensional photonic crystal, nanolaser, sensor arrays, and other optoelectronic devices. PMID:24521308

Comparison of the FilmArray Respiratory Panel and Prodesse Real-Time PCR Assays for Detection of Respiratory Pathogens ▿ †

PubMed Central

Loeffelholz, M. J.; Pong, D. L.; Pyles, R. B.; Xiong, Y.; Miller, A. L.; Bufton, K. K.; Chonmaitree, T.

2011-01-01

We compared the diagnostic performance and overall respiratory pathogen detection rate of the premarket version of the FilmArray Respiratory Panel (RP) multiplex PCR assay (Idaho Technology, Inc., Salt Lake City, UT) with those of the Food and Drug Administration (FDA)-cleared Prodesse ProFlu+, ProFAST+, ProParaflu+, Pro hMPV+, and ProAdeno+ real-time PCR assays (Gen-Probe, San Diego, CA). The assays were performed on a panel of 192 nasopharyngeal-secretion specimens collected from 81 children under 1 year of age with upper respiratory tract symptoms. To resolve discordant results and confirm pathogens detected only by the larger FilmArray panel, we performed laboratory-developed real-time PCR assays. Among viruses detectable by both commercial assays (adenovirus, human metapneumovirus, influenza A virus, influenza B virus, parainfluenza viruses 1 to 3, and respiratory syncytial virus), the FilmArray and Prodesse assays showed good overall agreement (181/192 [94.3%]; kappa = 0.87; 95% CI, 0.79 to 0.94). FilmArray RP detected more parainfluenza viruses 1 and 3 than ProParaflu+ (18 versus 13) while ProAdeno+ detected more adenoviruses (11 versus 6), but these differences were not statistically significant. Additionally, FilmArray RP detected 138 pathogens (confirmed as true positives) not included in the Prodesse assays (rhinovirus [RV]/enterovirus [EV], 118; bocavirus, 8; coronavirus, 7; parainfluenza virus 4, 4; Mycoplasma pneumoniae, 1). FilmArray RP was cleared by the FDA following the completion of this study. The FDA-cleared version includes the following targets: adenovirus, coronaviruses HKU1 and NL63, human metapneumovirus (hMPV), influenza A virus (to type level only), influenza A H1 seasonal virus, influenza A H3 seasonal virus, influenza A virus H1-2009, influenza B virus, parainfluenza viruses 1 to 4, respiratory syncytial virus (RSV), and RV/EV (no differentiation). The larger panel in the FilmArray RP assay allowed the detection of additional respiratory pathogens compared to the Prodesse assays. In this population of young children with upper respiratory tract infection, RV/EV accounted for the majority of the additional pathogens detected by FilmArray RP. PMID:21998418

Macrophages influence a competition of contact guidance and chemotaxis for fibroblast alignment in a fibrin gel coculture assay.

PubMed

Bromberek, B A; Enever, P A J; Shreiber, D I; Caldwell, M D; Tranquillo, R T

2002-05-01

Rat dermal fibroblasts were dispersed initially in the outer shell of a fibrin gel sphere, while the inner core either was devoid of cells or contained peritoneal exudate cells (primarily macrophages), thereby mimicking the inflammatory phase of wound healing. The fibroblasts compacted floating fibrin microspheres over time. In the absence of macrophages, the initial distribution of fibroblasts (only in the shell) induced circumferential alignment of fibrin fibrils via compaction of the shell relative to the core. The aligned fibrils created a contact guidance field, which was manifested by strong circumferential alignment of the fibroblasts. However, in the presence of macrophages, the fibroblasts exhibited more radial alignment despite the simultaneous contact guidance field in the circumferential direction associated with compaction. This was attributed to a chemotactic gradient emanating from the core due to a putative factor(s) released by the macrophages. The presence of a radial chemotactic stimulus was supported by the finding of even greater radial alignment when fibrin microspheres were embedded in an agarose-fibrin gel that abolished compaction and consequently the contact guidance field. Our assay permits the simulation of tissue morphogenetic processes that involve cell guidance phenomena and tractional restructuring of the extracellular matrix.

Facile preparation of multifunctional uniform magnetic microspheres for T1-T2 dual modal magnetic resonance and optical imaging.

PubMed

Zhang, Li; Liang, Shuang; Liu, Ruiqing; Yuan, Tianmeng; Zhang, Shulai; Xu, Zushun; Xu, Haibo

2016-08-01

Molecular imaging is of significant importance for early detection and diagnosis of cancer. Herein, a novel core-shell magnetic microsphere for dual modal magnetic resonance imaging (MRI) and optical imaging was produced by one-pot emulsifier-free emulsion polymerization, which could provide high resolution rate of histologic structure information and realize high sensitive detection at the same time. The synthesized magnetic microspheres composed of cores containing oleic acid (OA) and sodium undecylenate (NaUA) modified Fe3O4 nanoparticles and styrene (St), Glycidyl methacrylate (GMA), and polymerizable lanthanide complexes (Gd(AA)3Phen and Eu(AA)3Phen) polymerized on the surface for outer shells. Fluorescence spectra show characteristic emission peaks from Eu(3+) at 590nm and 615nm and vivid red fluorescence luminescence can be observed by 2-photon confocal scanning laser microscopy (CLSM). In vitro cytotoxicity tests based on the MTT assay demonstrate good cytocompatibility, the composites have longitudinal relaxivity value (r1) of 8.39mM(-1)s(-1) and also have transverse relaxivity value (r2) of 71.18mM(-1)s(-1) at clinical 3.0 T MR scanner. In vitro and in vivo MRI studies exhibit high signal enhancement on both T1- and T2-weighted MR images. These fascinating multifunctional properties suggest that the polymer microspheres have large clinical potential as multi-modal MRI/optical probes. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Evaluation of Eudragit® Retard Polymers for the Microencapsulation of Alpha-Lipoic Acid.

PubMed

Pecora, Tiziana M G; Musumeci, Teresa; Musumeci, Lucrezia; Fresta, Massimo; Pignatello, Rosario

2016-01-01

Microencapsulation of natural antioxidants in polymeric systems represents a possible strategy for improving the oral bioavailability of compounds that are otherwise poorly soluble. α-lipoic acid (ALA) was microencapsulated with polymethacrylate polymers (blends at various ratios of Eudragit® RS100 and RL100 resins). Microspheres were produced by solvent displacement of an ethanol cosolution of ALA and polymers; the microsuspensions were then freeze-dried, using trehalose as a cryoprotector. Microspheres were characterized in the solid state for micromeritic properties and drug loading, as well as by infrared spectroscopy, powder X-ray diffractometry and differential scanning calorimetry. The antioxidant activity of free and encapsulated ALA was assessed by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. In vitro release studies, performed in simulated gastric (pH 1.2) and intestinal fluid (pH 6.8), showed that, depending on polymer composition and drug-to-polymer ratio, ALA release can be slowed down, compared to the dissolution pattern of the free drug. Solid-state characterization confirmed the chemical stability of ALA in the microspheres, suggesting that ALA did not develop strong interactions with the polymer and was present in an amorphous or a disordered-crystalline state within the polymer network. As indicated by the DPPH assay, the microencapsulation of ALA in Eudragit® Retard matrices did not alter its antioxidant activity. ALA was effectively encapsulated in Eudragit® Retard matrices, showing a chemical stability up to 6 months at room conditions and at 40°C. Moreover, since the drug maintained its antioxidant activity in vitro, the potential application of these microparticulate systems for oral administration would deserve further studies.

The osteogenic response of mesenchymal stem cells to an injectable PLGA bone regeneration system.

PubMed

Curran, Judith M; Fawcett, Sandra; Hamilton, Lloyd; Rhodes, Nicholas P; Rahman, Cheryl V; Alexander, Morgan; Shakesheff, Kevin; Hunt, John A

2013-12-01

The enrichment of substrates/surfaces with selected functional groups, methyl (-CH3), allyl amine (-NH2), allyl alcohol (-OH) and acrylic acid (-COOH), can be used to trigger mesenchymal stem (MSC) cell differentiation into specified lineages, minimising the need for exogenous biological supplementation. We present the successful translation of this research phenomenon to an injectable two phase injectable PLGA system, utilising plasma techniques, for the repair of bone defects. Modified microspheres were characterised using water contact angel (WCA), X-ray Photon Spectroscopy (XPS) and scanning electron microscopy (SEM). When cultured in contact with MSCs in vitro, the ability of the modified particles, within the 2 phase system, to induce differentiation was characterised using quantitative assays for cell viability and histological analysis for key markers of differentiation throughout the entirety of the three dimensional scaffold. Biological analysis proved that selected modified microspheres have the ability to induce MSC osteogenic (-NH2 modified scaffolds) and chondrogenic (-OH modified scaffolds) differentiation throughout the entirety of the formed scaffold. Therefore optimised plasma modification of microspheres is an effective tool for the production of injectable systems for the repair of bone and cartilage defects. Copyright © 2013 Elsevier Ltd. All rights reserved.

Protein microspheres for controlled drug delivery and related analysis of biopolymers

NASA Astrophysics Data System (ADS)

Kirk, James Forrest

Rheumatoid arthritis (RA) is a systemic disorder which manifests itself most notably in the synovial joints. In recent years, methotrexate (MTX), a foliate antagonist, has been used with some success for treatment of RA. MTX has a maximum cumulative dose beyond which it becomes dangerous to administer due primarily to liver toxicity. This unfortunate side effect has prompted research into means of delivering MTX to the synovial joint in hopes of making more efficient use of the drug. Both MTX and its sodium salt (Na-MTX) were loaded into microspheres (MS) composed of bovine serum albumin (BSA) stabilized by cross linking with dialdehydes or ferric ion. MS were prepared with two levels of drug loading at two different levels of cross linking. MTX loading densities as high as 46.8% w/w were achieved in the aldehyde cross linking system and as high as 46.3% w/w were achieved with ferric ion cross linking. Using Na-MTX, the values were 37.2% w/w and 31.7% w/w respectively. Both MTX and Na-MTX were elutable from the MS into phosphate buffered saline at 37sp°C. MTX elution from aldehyde cross linked microspheres was load dependent with ca. 60% eluted by 9 hours at low loading and ca. 60% eluted by 24 hours at high loading. In the ferric ion cross link system, the elution was independent of loading with 50% elution occurring between 20 and 48 hours. Na-MTX elution was independent of drug loading or cross link system with 50% elution occurring in less than two hours in all cases. Other investigations included the loading of mitoxantrone (NOV) and of enzyme. NOV was loaded onto BSA microspheres to a concentration of 19.3% w/w and was used successfully in the treatment of murine ovarian tumors. Acid phosphatase was successfully loaded onto and into BSA microspheres. This enzyme retained its initial activity up to four months on post-loaded spheres. The enzyme also remained active inside the microsphere as demonstrated by a substrate cleavage assay.

Development of a Smart Diagnostics Platform for Early-Stage Screening of Breast Cancer

DTIC Science & Technology

2007-04-01

Kawaguchi, H.; Fujimoto, K. A Novel Preparation of Nonsymmetrical Microspheres Using the Langmuir Blodgett Technique. Langmuir 2000, 16, 7882–7886. 64...performance liquid chromatography, gas chromatography, mass spectrometry, and enzyme-linked immunosorbent assay. All of these methods require...important criterion for selection of suitable signal transduction systems. A 10 manuscript describing the stability has been published in Langmuir in 2007

Enhanced target-specific signal detection using an Escherichia coli lysate in multiplex microbead immunoassays with E. coli-derived recombinant antigens.

PubMed

Crestani, Sandra; Leitolis, Amanda; Lima, Lucianna Freitas Oliveira; Krieger, Marco A; Foti, Leonardo

2016-08-01

Diverse techniques have been developed to analyze antibody-mediated responses to infections. However, the most common tests, i.e., enzyme-linked immunosorbent assays, require separate reactions for each antigen and consequently necessitate large sample volumes. Luminex technology allows the detection of multiple antibodies in a single experiment, but nonspecific binding can impair the results. Therefore, we examined the use of Escherichia coli lysates to reduce nonspecific binding and improve the results of liquid microarrays based on Luminex technology. Anti-bacteria antibodies were detected in human serum samples, as evidenced by high median fluorescence intensity (MFI) in assays performed with paramagnetic microspheres coupled with E. coli lysates. Moreover, the addition of an E. coli lysate as a blocker reduced the nonspecific binding of antigens produced by E. coli in a concentration-dependent manner. Tris-HCl reduced MFI values in negative samples, but did not affect MFI for positive samples. For microspheres coupled with different antigens, an E. coli lysate blocker significantly improved the fluorescence signals from positive samples. The addition of Tris-HCl and the E. coli lysate induced antigen-specific differences in MFI. This combination of the E. coli lysate blocker and Tris-HCl yielded a statistically significant improvement in MFI in the assays for Chagas disease and hepatitis C virus samples. However, for the Treponema pallidum p47 antigen improvement in MFI was only observed for the preparation with the E. coli blocker at a concentration of 3%. In conclusion, the addition of an E. coli lysate and Tris-HCl to the microarray assay reduced the nonspecific binding of human anti-bacteria antibodies and, therefore, increased the specific MFI. Copyright © 2016 Elsevier B.V. All rights reserved.

Bioinspired polyethylene terephthalate nanocone arrays with underwater superoleophobicity and anti-bioadhesion properties

NASA Astrophysics Data System (ADS)

Liu, Wendong; Liu, Xueyao; Fangteng, Jiaozi; Wang, Shuli; Fang, Liping; Shen, Huaizhong; Xiang, Siyuan; Sun, Hongchen; Yang, Bai

2014-10-01

This paper presents a facile method to fabricate bioinspired polyethylene terephthalate (PET) nanocone arrays via colloidal lithography. The aspect ratio (AR) of the nanocones can be finely modulated ranging from 1 to 6 by regulating the etching time. The samples with the AR value of 6 can present underwater superoleophobicity with the underwater oil contact angle (OCA) of 171.8°. The as-prepared PET nanocone arrays perform anti-bioadhesion behavior, which inhibits the formation of the actin cytoskeleton when it used as the substrate for cell culture. Moreover, the oil wettability is temperature controlled after modifying the PET nanocone arrays with PNIPAAm film, and the oil wettability of the functionalized nanocone arrays can be transformed from the superoleophobic state with OCA about 151° to the oleophilic state with OCA about 25° reversibly. Due to the high-throughput, parallel fabrication and cost-efficiency of this method, it will be favourable for researchers to introduce oleophobic properties to various substrate and device surfaces. Due to the superoleophobicity and simple functionalizing properties, the PET nanocone arrays are very promising surfaces for anti-adhesion, self-cleaning and have potential applications in material, medical, and biological fields.This paper presents a facile method to fabricate bioinspired polyethylene terephthalate (PET) nanocone arrays via colloidal lithography. The aspect ratio (AR) of the nanocones can be finely modulated ranging from 1 to 6 by regulating the etching time. The samples with the AR value of 6 can present underwater superoleophobicity with the underwater oil contact angle (OCA) of 171.8°. The as-prepared PET nanocone arrays perform anti-bioadhesion behavior, which inhibits the formation of the actin cytoskeleton when it used as the substrate for cell culture. Moreover, the oil wettability is temperature controlled after modifying the PET nanocone arrays with PNIPAAm film, and the oil wettability of the functionalized nanocone arrays can be transformed from the superoleophobic state with OCA about 151° to the oleophilic state with OCA about 25° reversibly. Due to the high-throughput, parallel fabrication and cost-efficiency of this method, it will be favourable for researchers to introduce oleophobic properties to various substrate and device surfaces. Due to the superoleophobicity and simple functionalizing properties, the PET nanocone arrays are very promising surfaces for anti-adhesion, self-cleaning and have potential applications in material, medical, and biological fields. Electronic supplementary information (ESI) available: The optical microscopy image of the self-assembled 2D PS microspheres over a large area, the diameter of the PS microsphere is 580 nm; The top-view SEM image of the PET nanocone arrays over a large area, the AR of the nanocone is 6; The SEM image of the PET nanocone arrays obtained after 30 min etching; The optical image of the water droplet on the PET nanocone arrays with an AR of 6; The schematic illustration of the nanocone arrays modification with PNIPAAm; High resolution XPS spectra of the PNIPAAm modified PET nanocone arrays. See DOI: 10.1039/c4nr04471a

xMAP Technology: Applications in Detection of Pathogens

PubMed Central

Reslova, Nikol; Michna, Veronika; Kasny, Martin; Mikel, Pavel; Kralik, Petr

2017-01-01

xMAP technology is applicable for high-throughput, multiplex and simultaneous detection of different analytes within a single complex sample. xMAP multiplex assays are currently available in various nucleic acid and immunoassay formats, enabling simultaneous detection and typing of pathogenic viruses, bacteria, parasites and fungi and also antigen or antibody interception. As an open architecture platform, the xMAP technology is beneficial to end users and therefore it is used in various pharmaceutical, clinical and research laboratories. The main aim of this review is to summarize the latest findings and applications in the field of pathogen detection using microsphere-based multiplex assays. PMID:28179899

Multiplexed screening assay for mRNA combining nuclease protection with luminescent array detection.

PubMed

Martel, Ralph R; Botros, Ihab W; Rounseville, Matthew P; Hinton, James P; Staples, Robin R; Morales, David A; Farmer, John B; Seligmann, Bruce E

2002-11-01

The principles and performance are described for the ArrayPlate mRNA assay, a multiplexed mRNA assay for high-throughput and high-content screening and drug development. THP-1 monocytes grown and subjected to compound treatments in 96-well plates were subjected to a multiplexed nuclease protection assay in situ. The nuclease protection assay destroyed all cell-derived mRNA, but left intact stoichiometric amounts of 16 target-specific oligonucleotide probes. Upon transfer of processed cell lysates to a microplate that contained a 16-element oligonucleotide array at the bottom of each well, the various probe species were separated by immobilization at predefined elements of the array. Quantitative detection of array-bound probes was by enzyme-mediated chemiluminescence. A high-resolution charge-coupled device imager was used for the simultaneous readout of all 1536 array elements in a 96-well plate. For the measurement of 16 genes in samples of 25000 cells, the average standard deviation from well to well within a plate was 8.6% of signal intensity and was 10.8% from plate to plate. Assay response was linear and reproducibility was constant for all detected genes in samples ranging from 1000 to 50000 cells. When THP-1 monocytes were differentiated with phorbol ester and subsequently activated with bacterial lipopolysaccharide that contained different concentrations of dexamethasone, dose-dependent effects of dexamethasone on the mRNA levels of several genes were observed.

Development of Technologies for Early Detection and Stratification of Breast Cancer

DTIC Science & Technology

2015-10-01

fatal disease progression, or in the cases of over-treatment, unnecessary physical and emotional trauma.4 ELISA, the most common immunoassay for...laboratory to discover new biomarkers that meet these requirements within serum so that a simple blood test can be implemented. We are also working to...microspheres and tested first on standard samples. Assay performance characteristics will be determined to ascertain that they will address

2D mesoscale colloidal crystal patterns on polymer substrates

NASA Astrophysics Data System (ADS)

Bredikhin, Vladimir; Bityurin, Nikita

2018-05-01

The development of nanosphere lithography relies on the ability of depositing 2D colloidal crystals comprising micro- and nano-size elements on substrates of different materials. One of the most difficult problems here is deposition of coatings on hydrophobic substrates, e.g. polymers, from aqueous colloidal solutions. We use UV photooxidation for substrate hydrophilization. We demonstrate a new method of producing a two-dimensional ordered array of polymer microparticles (polystyrene microspheres ∼1 μm in diameter) on a polymer substrate (PMMA). We show that implementation of the new deposition technique for directed self-assembly of microspheres on an UV irradiated surface provides an opportunity to obtain coatings on a hydrophilized PMMA surface of large area (∼5 cm2). UV irradiation of the surface through masks allows creating 2D patterns consisting of mesoscale elements formed by the deposited self-assembled microparticles owing to the fact that the colloidal particles are deposited only on the irradiated area leaving the non-irradiated sections intact.

Fabrication of a Porous Fiber Cladding Material Using Microsphere Templating for Improved Response Time with Fiber Optic Sensor Arrays

PubMed Central

Henning, Paul E.; Rigo, M. Veronica; Geissinger, Peter

2012-01-01

A highly porous optical-fiber cladding was developed for evanescent-wave fiber sensors, which contains sensor molecules, maintains guiding conditions in the optical fiber, and is suitable for sensing in aqueous environments. To make the cladding material (a poly(ethylene) glycol diacrylate (PEGDA) polymer) highly porous, a microsphere templating strategy was employed. The resulting pore network increases transport of the target analyte to the sensor molecules located in the cladding, which improves the sensor response time. This was demonstrated using fluorescein-based pH sensor molecules, which were covalently attached to the cladding material. Scanning electron microscopy was used to examine the structure of the templated polymer and the large network of interconnected pores. Fluorescence measurements showed a tenfold improvement in the response time for the templated polymer and a reliable pH response over a pH range of five to nine with an estimated accuracy of 0.08 pH units. PMID:22654644

Polymers mediate a one-pot route for functionalized quantum dot barcodes with a large encoding capacity.

PubMed

Zhang, Ding Sheng-Zi; Jiang, Yang; Wei, Dan; Wei, Xunbin; Xu, Hong; Gu, Hongchen

2018-06-21

With the increasing demands for high-throughput multiplexed bioassays, quantum dot (QD)-encoded microbeads as biocarriers for various bioreactions have attracted considerable attention. However, three key requirements for these biocarriers are still longstanding issues: a stable fluorescence intensity, a large encoding capacity and abundant surface functional groups. Here, a novel one-pot strategy is developed, generating functionalized QD-encoded microspheres with a strong fluorescence intensity and optical stability. With poly(styrene-co-maleic anhydride) (PSMA) molecules as mediators, the encapsulation of QDs and carboxylation of the bead surface are integrated together, greatly improving the preparation efficiency and guaranteeing their potential application in biodetection. Moreover, the mechanism for preparing QD-doped beads is further proposed, which helps to precisely manipulate the preparation process and accurately encode the beads. Through this approach, a single- and dual-color barcode library of QD-encoded microspheres has been successfully established, which demonstrates their great potential in suspension arrays.

Development of a Multiplexed Microsphere PCR for Culture-Free Detection and Gram-Typing of Bacteria in Human Blood Samples.

PubMed

Liang, Fang; Browne, Daniel J; Gray, Megan J; Gartlan, Kate H; Smith, David D; Barnard, Ross T; Hill, Geoffrey R; Corrie, Simon R; Markey, Kate A

2018-05-11

Bloodstream infection is a significant clinical problem, particularly in vulnerable patient groups such as those undergoing chemotherapy and bone marrow transplantation. Clinical diagnostics for suspected bloodstream infection remain centered around blood culture (highly variable timing, in the order of hours to days to become positive), and empiric use of broad-spectrum antibiotics is therefore employed for patients presenting with febrile neutropenia. Gram-typing provides the first opportunity to target therapy (e.g., combinations containing vancomycin or teicoplanin for Gram-positives; piperacillin-tazobactam or a carbapenem for Gram-negatives); however, current approaches require blood culture. In this study, we describe a multiplexed microsphere-PCR assay with flow cytometry readout, which can distinguish Gram-positive from Gram-negative bacterial DNA in a 3.5 h time period. The combination of a simple assay design (amplicon-dependent release of Gram-type specific Cy3-labeled oligonucleotides) and the Luminex-based readout (for quantifying each specific Cy3-labeled sequence) opens opportunities for further multiplexing. We demonstrate the feasibility of detecting common Gram-positive and Gram-negative organisms after spiking whole bacteria into healthy human blood prior to DNA extraction. Further development of DNA extraction methods is required to reach detection limits comparable to blood culture.

Epitaxially Grown Colloidal Crystals of Silica Microspheres on Patterned Substrate of Triangular Arrays

DTIC Science & Technology

2008-07-16

min after addition of binary mixture. Other images are taken (d) after supernatant removal, (e) after ammonia exposure, ( f ) after air-drying and dye...12] J.P. Hoogenboom , D. Derks, P. Vergeer, A. van Blaaderen, J. Chem. Phys. 117 (2002) 11320. [13] A. van Blaaderen, R. Ruel, P. Wiltzius, Nature...Axe, Y. Fujii, Phys. Rev. Lett. 62 (1989) 1524. [19] F . El Azhar, M. Baus, J.P. Ryekaert, E.J. Meijer, J. Chem. Phys. 112 (2000) 5121. [20] M.S

Oxygen sensing glucose biosensors based on alginate nano-micro systems

NASA Astrophysics Data System (ADS)

Chaudhari, Rashmi; Joshi, Abhijeet; Srivastava, Rohit

2014-04-01

Clinically glucose monitoring in diabetes management is done by point-measurement. However, an accurate, continuous glucose monitoring, and minimally invasive method is desirable. The research aims at developing fluorescence-mediated glucose detecting biosensors based on near-infrared radiation (NIR) oxygen sensitive dyes. Biosensors based on Glucose oxidase (GOx)-Rudpp loaded alginate microspheres (GRAM) and GOx-Platinum-octaethylporphyrin (PtOEP)-PLAalginate microsphere system (GPAM) were developed using air-driven atomization and characterized using optical microscopy, CLSM, fluorescence spectro-photometry etc. Biosensing studies were performed by exposing standard solutions of glucose. Uniform sized GRAM and GPAM with size 50+/-10μm were formed using atomization. CLSM imaging of biosensors suggests that Rudpp and PtOEP nanoparticles are uniformly distributed in alginate microspheres. The GRAM and GPAM showed a good regression constant of 0.974 and of 0.9648 over a range of 0-10 mM of glucose with a high sensitivity of 3.349%/mM (625 nm) and 2.38%/mM (645 nm) at 10 mM of glucose for GRAM and GPAM biosensor. GRAM and GPAM biosensors show great potential in development of an accurate and minimally invasive glucose biosensor. NIR dye based assays can aid sensitive, minimally-invasive and interference-free detection of glucose in diabetic patients.

In Vitro and In Vivo Biocompatibility Evaluation of Polyallylamine and Macromolecular Heparin Conjugates Modified Alginate Microbeads.

PubMed

Vaithilingam, Vijayaganapathy; Steinkjer, Bjørg; Ryan, Liv; Larsson, Rolf; Tuch, Bernard Edward; Oberholzer, Jose; Rokstad, Anne Mari

2017-09-15

Host reactivity to biocompatible immunoisolation devices is a major challenge for cellular therapies, and a human screening model would be of great value. We designed new types of surface modified barium alginate microspheres, and evaluated their inflammatory properties using human whole blood, and the intraperitoneal response after three weeks in Wistar rats. Microspheres were modified using proprietary polyallylamine (PAV) and coupled with macromolecular heparin conjugates (Corline Heparin Conjugate, CHC). The PAV-CHC strategy resulted in uniform and stable coatings with increased anti-clot activity and low cytotoxicity. In human whole blood, PAV coating at high dose (100 µg/ml) induced elevated complement, leukocyte CD11b and inflammatory mediators, and in Wistar rats increased fibrotic overgrowth. Coating of high dose PAV with CHC significantly reduced these responses. Low dose PAV (10 µg/ml) ± CHC and unmodified alginate microbeads showed low responses. That the human whole blood inflammatory reactions paralleled the host response shows a link between inflammatory potential and initial fibrotic response. CHC possessed anti-inflammatory activity, but failed to improve overall biocompatibility. We conclude that the human whole blood assay is an efficient first-phase screening model for inflammation, and a guiding tool in development of new generation microspheres for cell encapsulation therapy.

Peptide Nucleic Acid Array for Detection of Point Mutations in Hepatitis B Virus Associated with Antiviral Resistance ▿ †

PubMed Central

Jang, Hyunjung; Kim, Jihyun; Choi, Jae-jin; Son, Yeojin; Park, Heekyung

2010-01-01

The detection of antiviral-resistant hepatitis B virus (HBV) mutations is important for monitoring the response to treatment and for effective treatment decisions. We have developed an array using peptide nucleic acid (PNA) probes to detect point mutations in HBV associated with antiviral resistance. PNA probes were designed to detect mutations associated with resistance to lamivudine, adefovir, and entecavir. The PNA array assay was sensitive enough to detect 102 copies/ml. The PNA array assay was able to detect mutants present in more than 5% of the virus population when the total HBV DNA concentration was greater than 104 copies/ml. We analyzed a total of 68 clinical samples by this assay and validated its usefulness by comparing results to those of the sequencing method. The PNA array correctly identified viral mutants and has high concordance (98.3%) with direct sequencing in detecting antiviral-resistant mutations. Our results showed that the PNA array is a rapid, sensitive, and easily applicable assay for the detection of antiviral-resistant mutation in HBV. Thus, the PNA array is a useful and powerful diagnostic tool for the detection of point mutations or polymorphisms. PMID:20573874

Demonstration of four immunoassay formats using the array biosensor

NASA Technical Reports Server (NTRS)

Sapsford, Kim E.; Charles, Paul T.; Patterson, Charles H Jr; Ligler, Frances S.

2002-01-01

The ability of a fluorescence-based array biosensor to measure and quantify the binding of an antigen to an immobilized antibody has been demonstrated using the four different immunoassay formats: direct, competitive, displacement, and sandwich. A patterned array of antibodies specific for 2,4,6-trinitrotoluene (TNT) immobilized onto the surface of a planar waveguide and used to measure signals from different antigen concentrations simultaneously. For direct, competitive, and displacement assays, which are one-step assays, measurements were obtained in real time. Dose-response curves were calculated for all four assay formats, demonstrating the array biosensor's ability to quantify the amount of antigen present in solution.

Surface assembly of poly(I:C) on PEGylated microspheres to shield from adverse interactions with fibroblasts.

PubMed

Hafner, Annina M; Burschowsky, Daniel; Corthésy, Blaise; Textor, Marcus; Merkle, Hans P

2012-04-30

By expressing an array of pattern recognition receptors (PRRs), fibroblasts play an important role in stimulating and modulating the response of the innate immune system. The TLR3 ligand polyriboinosinic acid-polyribocytidylic acid, poly(I:C), a mimic of viral dsRNA, is a vaccine adjuvant candidate to activate professional antigen presenting cells (APCs). However, owing to its ligation with extracellular TLR3 on fibroblasts, subcutaneously administered poly(I:C) bears danger towards autoimmunity. It is thus in the interest of its clinical safety to deliver poly(I:C) in such a way that its activation of professional APCs is as efficacious as possible, whereas its interference with non-immune cells such as fibroblasts is controlled or even avoided. Complementary to our previous work with monocyte-derived dendritic cells (MoDCs), here we sought to control the delivery of poly(I:C) surface-assembled on microspheres to human foreskin fibroblasts (HFFs). Negatively charged polystyrene (PS) microspheres were equipped with a poly(ethylene glycol) (PEG) corona through electrostatically driven coatings with a series of polycationic poly(L-lysine)-graft-poly(ethylene glycol) copolymers, PLL-g-PEG, of varying grafting ratios g from 2.2 up to 22.7. Stable surface assembly of poly(I:C) was achieved by incubation of polymer-coated microspheres with aqueous poly(I:C) solutions. Notably, recognition of both surface-assembled and free poly(I:C) by extracellular TLR3 on HFFs halted their phagocytic activity. Ligation of surface-assembled poly(I:C) with extracellular TLR3 on HFFs could be controlled by tuning the grafting ratio g and thus the chain density of the PEG corona. When assembled on PLL-5.7-PEG-coated microspheres, poly(I:C) was blocked from triggering class I MHC molecule expression on HFFs. Secretion of interleukin (IL)-6 by HFFs after exposure to surface-assembled poly(I:C) was distinctly lower as compared to free poly(I:C). Overall, surface assembly of poly(I:C) may have potential to contribute to the clinical safety of this vaccine adjuvant candidate. Copyright © 2012 Elsevier B.V. All rights reserved.

Cellphone-based detection platform for rbST biomarker analysis in milk extracts using a microsphere fluorescence immunoassay.

PubMed

Ludwig, Susann K J; Zhu, Hongying; Phillips, Stephen; Shiledar, Ashutosh; Feng, Steve; Tseng, Derek; van Ginkel, Leendert A; Nielen, Michel W F; Ozcan, Aydogan

2014-11-01

Current contaminant and residue monitoring throughout the food chain is based on sampling, transport, administration, and analysis in specialized control laboratories. This is a highly inefficient and costly process since typically more than 99% of the samples are found to be compliant. On-site simplified prescreening may provide a scenario in which only samples that are suspect are transported and further processed. Such a prescreening can be performed using a small attachment on a cellphone. To this end, a cellphone-based imaging platform for a microsphere fluorescence immunoassay that detects the presence of anti-recombinant bovine somatotropin (rbST) antibodies in milk extracts was developed. RbST administration to cows increases their milk production, but is illegal in the EU and a public health concern in the USA. The cellphone monitors the presence of anti-rbST antibodies (rbST biomarker), which are endogenously produced upon administration of rbST and excreted in milk. The rbST biomarker present in milk extracts was captured by rbST covalently coupled to paramagnetic microspheres and labeled by quantum dot (QD)-coupled detection antibodies. The emitted fluorescence light from these captured QDs was then imaged using the cellphone camera. Additionally, a dark-field image was taken in which all microspheres present were visible. The fluorescence and dark-field microimages were analyzed using a custom-developed Android application running on the same cellphone. With this setup, the microsphere fluorescence immunoassay and cellphone-based detection were successfully applied to milk sample extracts from rbST-treated and untreated cows. An 80% true-positive rate and 95% true-negative rate were achieved using this setup. Next, the cellphone-based detection platform was benchmarked against a newly developed planar imaging array alternative and found to be equally performing versus the much more sophisticated alternative. Using cellphone-based on-site analysis in future residue monitoring can limit the number of samples for laboratory analysis already at an early stage. Therewith, the entire monitoring process can become much more efficient and economical.

High-speed particle tracking in microscopy using SPAD image sensors

NASA Astrophysics Data System (ADS)

Gyongy, Istvan; Davies, Amy; Miguelez Crespo, Allende; Green, Andrew; Dutton, Neale A. W.; Duncan, Rory R.; Rickman, Colin; Henderson, Robert K.; Dalgarno, Paul A.

2018-02-01

Single photon avalanche diodes (SPADs) are used in a wide range of applications, from fluorescence lifetime imaging microscopy (FLIM) to time-of-flight (ToF) 3D imaging. SPAD arrays are becoming increasingly established, combining the unique properties of SPADs with widefield camera configurations. Traditionally, the photosensitive area (fill factor) of SPAD arrays has been limited by the in-pixel digital electronics. However, recent designs have demonstrated that by replacing the complex digital pixel logic with simple binary pixels and external frame summation, the fill factor can be increased considerably. A significant advantage of such binary SPAD arrays is the high frame rates offered by the sensors (>100kFPS), which opens up new possibilities for capturing ultra-fast temporal dynamics in, for example, life science cellular imaging. In this work we consider the use of novel binary SPAD arrays in high-speed particle tracking in microscopy. We demonstrate the tracking of fluorescent microspheres undergoing Brownian motion, and in intra-cellular vesicle dynamics, at high frame rates. We thereby show how binary SPAD arrays can offer an important advance in live cell imaging in such fields as intercellular communication, cell trafficking and cell signaling.

Comparison of the Roche Cobas(®) 4800 HPV assay to Digene Hybrid Capture 2, Roche Linear Array and Roche Amplicor for Detection of High-Risk Human Papillomavirus Genotypes in Women undergoing treatment for cervical dysplasia.

PubMed

Phillips, Samuel; Garland, Suzanne M; Tan, Jeffery H; Quinn, Michael A; Tabrizi, Sepehr N

2015-01-01

The recently FDA (U.S. food and drug administration) approved Roche Cobas(®) 4800 (Cobas) human papillomavirus (HPV) has limited performance data compared to current HPV detection methods for test of cure in women undergoing treatment for high grade lesions. Evaluation of Cobas HPV assay using historical samples from women undergoing treatment for cervical dysplasia. A selection of 407 samples was tested on the Cobas assay and compared to previous results from Hybrid Capture 2, HPV Amplicor and Roche Linear Array. Overall, a correlation between high-risk HPV positivity and high grade histological diagnosis was 90.6% by the Cobas, 86.1% by Hybrid Capture 2, 92.9% by HPV Amplicor and 91.8% by Roche Linear Array. The Cobas HPV assay is comparative to both the HPV Amplicor and Roche Linear Array assays and better than Hybrid capture 2 assay in the detection of High-Risk HPV in women undergoing treatment for cervical dysplasia. Copyright © 2014 Elsevier B.V. All rights reserved.

In vitro evaluation of biodegradable microspheres with surface-bound ligands.

PubMed

Keegan, Mark E; Royce, Sara M; Fahmy, Tarek; Saltzman, W Mark

2006-02-21

Protein ligands were conjugated to the surface of biodegradable microspheres. These microsphere-ligand conjugates were then used in two in vitro model systems to evaluate the effect of conjugated ligands on microsphere behavior. Microsphere retention in agarose columns was increased by ligands on the microsphere surface specific for receptors on the agarose matrix. In another experiment, conjugating the lectin Ulex europaeus agglutinin 1 to the microsphere surface increased microsphere adhesion to Caco-2 monolayers compared to control microspheres. This increase in microsphere adhesion was negated by co-administration of l-fucose, indicating that the increase in adhesion is due to specific interaction of the ligand with carbohydrate receptors on the cell surface. These results demonstrate that the ligands conjugated to the microspheres maintain their receptor binding activity and are present on the microsphere surface at a density sufficient to target the microspheres to both monolayers and three-dimensional matrices bearing complementary receptors.

Optimization and qualification of an Fc Array assay for assessments of antibodies against HIV-1/SIV.

PubMed

Brown, Eric P; Weiner, Joshua A; Lin, Shu; Natarajan, Harini; Normandin, Erica; Barouch, Dan H; Alter, Galit; Sarzotti-Kelsoe, Marcella; Ackerman, Margaret E

2018-04-01

The Fc Array is a multiplexed assay that assesses the Fc domain characteristics of antigen-specific antibodies with the potential to evaluate up to 500 antigen specificities simultaneously. Antigen-specific antibodies are captured on antigen-conjugated beads and their functional capacity is probed via an array of Fc-binding proteins including antibody subclassing reagents, Fcγ receptors, complement proteins, and lectins. Here we present the results of the optimization and formal qualification of the Fc Array, performed in compliance with Good Clinical Laboratory Practice (GCLP) guidelines. Assay conditions were optimized for performance and reproducibility, and the final version of the assay was then evaluated for specificity, accuracy, precision, limits of detection and quantitation, linearity, range and robustness. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Getting the most from microfluidic platforms for biomedical applications (Conference Presentation)

NASA Astrophysics Data System (ADS)

Shen, Amy

2016-03-01

Microfluidics has emerged in recent years as a versatile method of manipulating fluids at small length-scales, and in particular, for generating and manipulating micron size droplets with controllable size and functionality. For example, many research groups developed microfluidics devices for cell encapsulation, and synthesizing functionalized polymer microspheres and inorganic nanoparticles with precise control over their shapes and sizes. In this talk, I will showcase 2 microfluidic platforms to highlight their versatility and potential biomedical applications. (1) Droplet microfluidic platforms (a) A droplet microfluidics method to fabricate alginate microspheres while simultaneously immobilizing anti-Mycobacterium tuberculosis complex IgY and anti-Escherichia coli IgG antibodies primarily on the porous alginate carriers for specific binding and binding affinity tests. The binding affinity of antibodies is directly measured by fluorescence intensity of stained target bacteria on the microspheres. We demonstrate that the functionalized alginate microspheres yield specificity comparable with an enzyme-linked immunosorbent assay. We can easily modify the size and shape of alginate microspheres, and increase the concentration of functionalized alginate microspheres to further enhance binding kinetics and enable multiplexing. (b) A novel droplet microfluidics method to image oxygen in single islets (pancreatic cells) for glucose sensing. Individual islets and a fluorescent oxygen-sensitive dye were encased within a thin alginate polymer microcapsule for insulin secretion monitoring. The sensing system operated similarly from 2-48 hours following encapsulation, and viability and function of the islets were not significantly affected by the encapsulation process. This approach should be applicable to other cell types and dyes sensitive to other biologically important molecules. (2) A microfluidic chamber to perform uniform electric field stimulation in circular shaped culturewares A 3D computer-aided designed (CAD) polymeric insert is designed and retrofitted to circular shaped culturewares in an integrated microfluidic electrical stimulation platform to generate uniform EF with higher cell yields. In particular, NIH/3T3 mouse embryonic fibroblast cells are used to validate the performance of the 3D designed Poly(methyl methacrylate) (PMMA) inserts in a circular-shaped 6-well plate. The CAD based inserts can be easily scaled up to further increase effective stimulation area percentages, and also be implemented in commercially available culturewares for a wide variety of EF-related research such as EF-cell interaction and tissue regeneration studies.

Antimicrobial action of minocycline microspheres versus 810-nm diode laser on human dental plaque microcosm biofilms.

PubMed

Song, Xiaoqing; Yaskell, Tina; Klepac-Ceraj, Vanja; Lynch, Michael C; Soukos, Nikolaos S

2014-02-01

The purpose of this study is to investigate the antimicrobial effects of minocycline hydrochloride microspheres versus infrared light at 810 nm from a diode laser on multispecies oral biofilms in vitro. These biofilms were grown from dental plaque inoculum (oral microcosms) and were obtained from six systemically healthy individuals with generalized chronic periodontitis. Multispecies biofilms were derived using supra- and subgingival plaque samples from mesio-buccal aspects of premolars and molars exhibiting probing depths in the 4- to 5-mm range and 1- to 2-mm attachment loss. Biofilms were developed anaerobically on blood agar surfaces in 96-well plates using a growth medium of prereduced, anaerobically sterilized brain-heart infusion with 2% horse serum. Minocycline HCl 1 mg microspheres were applied on biofilms on days 2 and 5 of their development. Biofilms were also exposed on days 2 and 5 of their growth to 810-nm light for 30 seconds using a power of 0.8 W in a continuous-wave mode. The susceptibility of microorganisms to minocycline or infrared light was evaluated by a colony-forming assay and DNA probe analysis at different time points. At all time points of survival assessment, minocycline was more effective (>2 log10 colony-forming unit reduction) than light treatment (P <0.002). Microbial analysis did not reveal susceptibility of certain dental plaque pathogens to light, and it was not possible after treatment with minocycline due to lack of bacterial growth. The cumulative action of minocycline microspheres on multispecies oral biofilms in vitro led to enhanced killing of microorganisms, whereas a single exposure of light at 810 nm exhibited minimal and non-selective antimicrobial effects.

Large-Scale Femtoliter Droplet Array for Single Cell Efflux Assay of Bacteria.

PubMed

Iino, Ryota; Sakakihara, Shouichi; Matsumoto, Yoshimi; Nishino, Kunihiko

2018-01-01

Large-scale femtoliter droplet array as a platform for single cell efflux assay of bacteria is described. Device microfabrication, femtoliter droplet array formation and concomitant enclosure of single bacterial cells, fluorescence-based detection of efflux activity at the single cell level, and collection of single cells from droplet and subsequent gene analysis are described in detail.

Nanoscale Surface Plasmonics Sensor With Nanofluidic Control

NASA Technical Reports Server (NTRS)

Wei, Jianjun; Singhal, Sameer; Waldeck, David H.; Kofke, Matthew

2013-01-01

Conventional quantitative protein assays of bodily fluids typically involve multiple steps to obtain desired measurements. Such methods are not well suited for fast and accurate assay measurements in austere environments such as spaceflight and in the aftermath of disasters. Consequently, there is a need for a protein assay technology capable of routinely monitoring proteins in austere environments. For example, there is an immediate need for a urine protein assay to assess astronaut renal health during spaceflight. The disclosed nanoscale surface plasmonics sensor provides a core detection method that can be integrated to a lab-on-chip device that satisfies the unmet need for such a protein assay technology. Assays based upon combinations of nanoholes, nanorings, and nanoslits with transmission surface plasmon resonance (SPR) are used for assays requiring extreme sensitivity, and are capable of detecting specific analytes at concentrations as low as picomole to femtomole level in well-controlled environments. The device operates in a transmission mode configuration in which light is directed at one planar surface of the array, which functions as an optical aperture. The incident light induces surface plasmon light transmission from the opposite surface of the array. The presence of a target analyte is detected by changes in the spectrum of light transmitted by the array when a target analyte induces a change in the refractive index of the fluid within the nanochannels. This occurs, for example, when a target analyte binds to a receptor fixed to the walls of the nanochannels in the array. Independent fluid handling capability for individual nanoarrays on a nanofluidic chip containing a plurality of nanochannel arrays allows each array to be used to sense a different target analyte and/or for paired arrays to analyze control and test samples simultaneously in parallel. The present invention incorporates transmission mode nanoplasmonics and nanofluidics into a single, microfluidically controlled device. The device comprises one or more arrays of aligned nanochannels that are in fluid communication with inflowing and outflowing fluid handling manifolds that control the flow of fluid through the arrays. The array acts as an aperture in a plasmonic sensor. Fluid, in the form of a liquid or a gas and comprising a sample for analysis, is moved from an inlet manifold through the nanochannel array, and out through an exit manifold. The fluid may also contain a reagent used to modify the interior surfaces of the nanochannels, and/or a reagent required for the detection of an analyte.

Droplet Array-Based 3D Coculture System for High-Throughput Tumor Angiogenesis Assay.

PubMed

Du, Xiaohui; Li, Wanming; Du, Guansheng; Cho, Hansang; Yu, Min; Fang, Qun; Lee, Luke P; Fang, Jin

2018-03-06

Angiogenesis is critical for tumor progression and metastasis, and it progresses through orchestral multicellular interactions. Thus, there is urgent demand for high-throughput tumor angiogenesis assays for concurrent examination of multiple factors. For investigating tumor angiogenesis, we developed a microfluidic droplet array-based cell-coculture system comprising a two-layer polydimethylsiloxane chip featuring 6 × 9 paired-well arrays and an automated droplet-manipulation device. In each droplet-pair unit, tumor cells were cultured in 3D in one droplet by mixing cell suspensions with Matrigel, and in the other droplet, human umbilical vein endothelial cells (HUVECs) were cultured in 2D. Droplets were fused by a newly developed fusion method, and tumor angiogenesis was assayed by coculturing tumor cells and HUVECs in the fused droplet units. The 3D-cultured tumor cells formed aggregates harboring a hypoxic center-as observed in vivo-and secreted more vascular endothelial growth factor (VEGF) and more strongly induced HUVEC tubule formation than did 2D-cultured tumor cells. Our single array supported 54 assays in parallel. The angiogenic potentials of distinct tumor cells and their differential responses to antiangiogenesis agent, Fingolimod, could be investigated without mutual interference in a single array. Our droplet-based assay is convenient to evaluate multicellular interaction in high throughput in the context of tumor sprouting angiogenesis, and we envision that the assay can be extensively implementable for studying other cell-cell interactions.

Polymeric microspheres

DOEpatents

Walt, David R.; Mandal, Tarun K.; Fleming, Michael S.

2004-04-13

The invention features core-shell microsphere compositions, hollow polymeric microspheres, and methods for making the microspheres. The microspheres are characterized as having a polymeric shell with consistent shell thickness.

Enhancing amplitude changes by mode localization in trio cantilevers with mass perturbation

NASA Astrophysics Data System (ADS)

Wang, Dong F.; Li, Xiaodong; Yang, Xu; Ikehara, Tsuyoshi; Maeda, Ryutaro

2015-09-01

A simplified three-cantilever array was designed and micro-fabricated for demonstrating the response enhancement in amplitude changes when applying small mass perturbations. Three micro-cantilevers, defined as side (outermost) cantilever, center cantilever and another side cantilever, are identical in geometry and are connected micro-mechanically with each other by two coupling overhangs. In the case of analytical characterizations, by applying a picogram order mass perturbation (10 pg) on one side cantilever, significant enhancements in amplitude changes were obtained at the 2nd resonance mode from both of the unloaded cantilevers. The amplitude change from the center cantilever is about 7000 times higher than that with no mass perturbation, while the change in amplitude from another side cantilever is about 4000 times higher. In the aspect of experimental characterizations, the enhancement in amplitude change at the 2nd resonance mode was verified by applying two polystyrene micro-spheres (about 8.8 pg) as a picogram order mass perturbation onto one side cantilever. Due to the operational difficulties in quantitatively manipulating polystyrene micro-spheres, the effects of mass variations on the enhancement in amplitude changes from unloaded cantilevers were further analytically characterized under a range of 0.01-100 pg for three resonance modes respectively. This work is the first comparative study using three identical spring-mass beams on both analytical characterizations by applying small mass perturbations and sensing verification by manipulating a picogram polystyrene micro-sphere.

A portable array biosensor for food safety

NASA Astrophysics Data System (ADS)

Golden, Joel P.; Ngundi, Miriam M.; Shriver-Lake, Lisa C.; Taitt, Chris R.; Ligler, Frances S.

2004-11-01

An array biosensor developed for simultaneous analysis of multiple samples has been utilized to develop assays for toxins and pathogens in a variety of foods. The biochemical component of the multi-analyte biosensor consists of a patterned array of biological recognition elements immobilized on the surface of a planar waveguide. A fluorescence assay is performed on the patterned surface, yielding an array of fluorescent spots, the locations of which are used to identify what analyte is present. Signal transduction is accomplished by means of a diode laser for fluorescence excitation, optical filters and a CCD camera for image capture. A laptop computer controls the miniaturized fluidics system and image capture. Results for four mycotoxin competition assays in buffer and food samples are presented.

Fiber-optic microarray for simultaneous detection of multiple harmful algal bloom species.

PubMed

Ahn, Soohyoun; Kulis, David M; Erdner, Deana L; Anderson, Donald M; Walt, David R

2006-09-01

Harmful algal blooms (HABs) are a serious threat to coastal resources, causing a variety of impacts on public health, regional economies, and ecosystems. Plankton analysis is a valuable component of many HAB monitoring and research programs, but the diversity of plankton poses a problem in discriminating toxic from nontoxic species using conventional detection methods. Here we describe a sensitive and specific sandwich hybridization assay that combines fiber-optic microarrays with oligonucleotide probes to detect and enumerate the HAB species Alexandrium fundyense, Alexandrium ostenfeldii, and Pseudo-nitzschia australis. Microarrays were prepared by loading oligonucleotide probe-coupled microspheres (diameter, 3 mum) onto the distal ends of chemically etched imaging fiber bundles. Hybridization of target rRNA from HAB cells to immobilized probes on the microspheres was visualized using Cy3-labeled secondary probes in a sandwich-type assay format. We applied these microarrays to the detection and enumeration of HAB cells in both cultured and field samples. Our study demonstrated a detection limit of approximately 5 cells for all three target organisms within 45 min, without a separate amplification step, in both sample types. We also developed a multiplexed microarray to detect the three HAB species simultaneously, which successfully detected the target organisms, alone and in combination, without cross-reactivity. Our study suggests that fiber-optic microarrays can be used for rapid and sensitive detection and potential enumeration of HAB species in the environment.

A High-Performance Multiplex Immunoassay for Serodiagnosis of Flavivirus-Associated Neurological Diseases in Horses

PubMed Central

Beck, Cécile; Desprès, Philippe; Paulous, Sylvie; Vanhomwegen, Jessica; Lowenski, Steeve; Nowotny, Norbert; Durand, Benoit; Garnier, Annabelle; Blaise-Boisseau, Sandra; Guitton, Edouard; Yamanaka, Takashi; Zientara, Stéphan; Lecollinet, Sylvie

2015-01-01

West Nile virus (WNV), Japanese encephalitis virus (JEV), and tick-borne encephalitis virus (TBEV) are flaviviruses responsible for severe neuroinvasive infections in humans and horses. The confirmation of flavivirus infections is mostly based on rapid serological tests such as enzyme-linked immunosorbent assays (ELISAs). These tests suffer from poor specificity, mainly due to antigenic cross-reactivity among flavivirus members. Robust diagnosis therefore needs to be validated through virus neutralisation tests (VNTs) which are time-consuming and require BSL3 facilities. The flavivirus envelope (E) glycoprotein ectodomain is composed of three domains (D) named DI, DII, and DIII, with EDIII containing virus-specific epitopes. In order to improve the serological differentiation of flavivirus infections, the recombinant soluble ectodomain of WNV E (WNV.sE) and EDIIIs (rEDIIIs) of WNV, JEV, and TBEV were synthesised using the Drosophila S2 expression system. Purified antigens were covalently bonded to fluorescent beads. The microspheres coupled to WNV.sE or rEDIIIs were assayed with about 300 equine immune sera from natural and experimental flavivirus infections and 172 nonimmune equine sera as negative controls. rEDIII-coupled microspheres captured specific antibodies against WNV, TBEV, or JEV in positive horse sera. This innovative multiplex immunoassay is a powerful alternative to ELISAs and VNTs for veterinary diagnosis of flavivirus-related diseases. PMID:26457301

A robotics platform for automated batch fabrication of high density, microfluidics-based DNA microarrays, with applications to single cell, multiplex assays of secreted proteins

NASA Astrophysics Data System (ADS)

Ahmad, Habib; Sutherland, Alex; Shin, Young Shik; Hwang, Kiwook; Qin, Lidong; Krom, Russell-John; Heath, James R.

2011-09-01

Microfluidics flow-patterning has been utilized for the construction of chip-scale miniaturized DNA and protein barcode arrays. Such arrays have been used for specific clinical and fundamental investigations in which many proteins are assayed from single cells or other small sample sizes. However, flow-patterned arrays are hand-prepared, and so are impractical for broad applications. We describe an integrated robotics/microfluidics platform for the automated preparation of such arrays, and we apply it to the batch fabrication of up to eighteen chips of flow-patterned DNA barcodes. The resulting substrates are comparable in quality with hand-made arrays and exhibit excellent substrate-to-substrate consistency. We demonstrate the utility and reproducibility of robotics-patterned barcodes by utilizing two flow-patterned chips for highly parallel assays of a panel of secreted proteins from single macrophage cells.

A robotics platform for automated batch fabrication of high density, microfluidics-based DNA microarrays, with applications to single cell, multiplex assays of secreted proteins

PubMed Central

Ahmad, Habib; Sutherland, Alex; Shin, Young Shik; Hwang, Kiwook; Qin, Lidong; Krom, Russell-John; Heath, James R.

2011-01-01

Microfluidics flow-patterning has been utilized for the construction of chip-scale miniaturized DNA and protein barcode arrays. Such arrays have been used for specific clinical and fundamental investigations in which many proteins are assayed from single cells or other small sample sizes. However, flow-patterned arrays are hand-prepared, and so are impractical for broad applications. We describe an integrated robotics/microfluidics platform for the automated preparation of such arrays, and we apply it to the batch fabrication of up to eighteen chips of flow-patterned DNA barcodes. The resulting substrates are comparable in quality with hand-made arrays and exhibit excellent substrate-to-substrate consistency. We demonstrate the utility and reproducibility of robotics-patterned barcodes by utilizing two flow-patterned chips for highly parallel assays of a panel of secreted proteins from single macrophage cells. PMID:21974603

A robotics platform for automated batch fabrication of high density, microfluidics-based DNA microarrays, with applications to single cell, multiplex assays of secreted proteins.

PubMed

Ahmad, Habib; Sutherland, Alex; Shin, Young Shik; Hwang, Kiwook; Qin, Lidong; Krom, Russell-John; Heath, James R

2011-09-01

Microfluidics flow-patterning has been utilized for the construction of chip-scale miniaturized DNA and protein barcode arrays. Such arrays have been used for specific clinical and fundamental investigations in which many proteins are assayed from single cells or other small sample sizes. However, flow-patterned arrays are hand-prepared, and so are impractical for broad applications. We describe an integrated robotics/microfluidics platform for the automated preparation of such arrays, and we apply it to the batch fabrication of up to eighteen chips of flow-patterned DNA barcodes. The resulting substrates are comparable in quality with hand-made arrays and exhibit excellent substrate-to-substrate consistency. We demonstrate the utility and reproducibility of robotics-patterned barcodes by utilizing two flow-patterned chips for highly parallel assays of a panel of secreted proteins from single macrophage cells. © 2011 American Institute of Physics

Recombinant blood group proteins for use in antibody screening and identification tests.

PubMed

Seltsam, Axel; Blasczyk, Rainer

2009-11-01

The present review elucidates the potentials of recombinant blood group proteins (BGPs) for red blood cell (RBC) antibody detection and identification in pretransfusion testing and the achievements in this field so far. Many BGPs have been eukaryotically and prokaryotically expressed in sufficient quantity and quality for RBC antibody testing. Recombinant BGPs can be incorporated in soluble protein reagents or solid-phase assays such as ELISA, color-coded microsphere and protein microarray chip-based techniques. Because novel recombinant protein-based assays use single antigens, a positive reaction of a serum with the recombinant protein directly indicates the presence and specificity of the target antibody. Inversely, conventional RBC-based assays use panels of human RBCs carrying a huge number of blood group antigens at the same time and require negative reactions of samples with antigen-negative cells for indirect determination of antibody specificity. Because of their capacity for single-step, direct RBC antibody determination, recombinant protein-based assays may greatly facilitate and accelerate the identification of common and rare RBC antibodies.

GeneChip{sup {trademark}} screening assay for cystic fibrosis mutations

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

Cronn, M.T.; Miyada, C.G.; Fucini, R.V.

1994-09-01

GeneChip{sup {trademark}} assays are based on high density, carefully designed arrays of short oligonucleotide probes (13-16 bases) built directly on derivatized silica substrates. DNA target sequence analysis is achieved by hybridizing fluorescently labeled amplification products to these arrays. Fluorescent hybridization signals located within the probe array are translated into target sequence information using the known probe sequence at each array feature. The mutation screening assay for cystic fibrosis includes sets of oligonucleotide probes designed to detect numerous different mutations that have been described in 14 exons and one intron of the CFTR gene. Each mutation site is addressed by amore » sub-array of at least 40 probe sequences, half designed to detect the wild type gene sequence and half designed to detect the reported mutant sequence. Hybridization with homozygous mutant, homozygous wild type or heterozygous targets results in distinctive hybridization patterns within a sub-array, permitting specific discrimination of each mutation. The GeneChip probe arrays are very small (approximately 1 cm{sup 2}). There miniature size coupled with their high information content make GeneChip probe arrays a useful and practical means for providing CF mutation analysis in a clinical setting.« less

Free-standing 3D graphene/polyaniline composite film electrodes for high-performance supercapacitors

NASA Astrophysics Data System (ADS)

Wang, Shiyong; Ma, Li; Gan, Mengyu; Fu, Shenna; Dai, Wenqin; Zhou, Tao; Sun, Xiaowu; Wang, Huihui; Wang, Huining

2015-12-01

The research paper describes polyaniline (PANI) nanowires array on flexible polystyrene microsphere/reduced graphene (PS/rGN) film is synthesized by dilute polymerization, and then the PS microspheres are removed to form free-standing three-dimensional (3D) rGN/PANI composite film. The chemical and structural properties of the 3D rGN/PANI film are characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS) and Brunauer-Emmett-Teller (BET), and the results confirm the 3D rGN/PANI film is synthesized successfully. When the film is used as a supercapacitor electrode, the maximum specific capacitance is as high as 740 F g-1 (or 581 F cm-3 for volumetric capacitance) at a current density of 0.5 A g-1 and the specific capacitance retains 87% of the initial after constant charge-discharge 1000 cycles at current density of 10 A g-1. It is believed that the free-standing 3D rGN/PANI film will have a great potential for application in supercapacitors.

Isotropic-resolution linear-array-based photoacoustic computed tomography through inverse Radon transform

NASA Astrophysics Data System (ADS)

Li, Guo; Xia, Jun; Li, Lei; Wang, Lidai; Wang, Lihong V.

2015-03-01

Linear transducer arrays are readily available for ultrasonic detection in photoacoustic computed tomography. They offer low cost, hand-held convenience, and conventional ultrasonic imaging. However, the elevational resolution of linear transducer arrays, which is usually determined by the weak focus of the cylindrical acoustic lens, is about one order of magnitude worse than the in-plane axial and lateral spatial resolutions. Therefore, conventional linear scanning along the elevational direction cannot provide high-quality three-dimensional photoacoustic images due to the anisotropic spatial resolutions. Here we propose an innovative method to achieve isotropic resolutions for three-dimensional photoacoustic images through combined linear and rotational scanning. In each scan step, we first elevationally scan the linear transducer array, and then rotate the linear transducer array along its center in small steps, and scan again until 180 degrees have been covered. To reconstruct isotropic three-dimensional images from the multiple-directional scanning dataset, we use the standard inverse Radon transform originating from X-ray CT. We acquired a three-dimensional microsphere phantom image through the inverse Radon transform method and compared it with a single-elevational-scan three-dimensional image. The comparison shows that our method improves the elevational resolution by up to one order of magnitude, approaching the in-plane lateral-direction resolution. In vivo rat images were also acquired.

Methods and devices for protein assays

DOEpatents

Chhabra, Swapnil [San Jose, CA; Cintron, Jose M [Indianapolis, IN; Shediac, Renee [Oakland, CA

2009-11-03

Methods and devices for protein assays based on Edman degradation in microfluidic channels are disclosed herein. As disclosed, the cleaved amino acid residues may be immobilized in an array format and identified by detectable labels, such as antibodies, which specifically bind given amino acid residues. Alternatively, the antibodies are immobilized in an array format and the cleaved amino acids are labeled identified by being bound by the antibodies in the array.

A reproducible accelerated in vitro release testing method for PLGA microspheres.

PubMed

Shen, Jie; Lee, Kyulim; Choi, Stephanie; Qu, Wen; Wang, Yan; Burgess, Diane J

2016-02-10

The objective of the present study was to develop a discriminatory and reproducible accelerated in vitro release method for long-acting PLGA microspheres with inner structure/porosity differences. Risperidone was chosen as a model drug. Qualitatively and quantitatively equivalent PLGA microspheres with different inner structure/porosity were obtained using different manufacturing processes. Physicochemical properties as well as degradation profiles of the prepared microspheres were investigated. Furthermore, in vitro release testing of the prepared risperidone microspheres was performed using the most common in vitro release methods (i.e., sample-and-separate and flow through) for this type of product. The obtained compositionally equivalent risperidone microspheres had similar drug loading but different inner structure/porosity. When microsphere particle size appeared similar, porous risperidone microspheres showed faster microsphere degradation and drug release compared with less porous microspheres. Both in vitro release methods investigated were able to differentiate risperidone microsphere formulations with differences in porosity under real-time (37 °C) and accelerated (45 °C) testing conditions. Notably, only the accelerated USP apparatus 4 method showed good reproducibility for highly porous risperidone microspheres. These results indicated that the accelerated USP apparatus 4 method is an appropriate fast quality control tool for long-acting PLGA microspheres (even with porous structures). Copyright © 2015 Elsevier B.V. All rights reserved.

Characterization of a Polyamine Microsphere and Its Adsorption for Protein

PubMed Central

Wang, Feng; Liu, Pei; Nie, Tingting; Wei, Huixian; Cui, Zhenggang

2013-01-01

A novel polyamine microsphere, prepared from the water-in-oil emulsion of polyethylenimine, was characterized. The investigation of scanning electron microscopy showed that the polyamine microsphere is a regular ball with a smooth surface. The diameter distribution of the microsphere is 0.37–4.29 μm. The isoelectric point of the microsphere is 10.6. The microsphere can adsorb proteins through the co-effect of electrostatic and hydrophobic interactions. Among the proteins tested, the highest value of adsorption of microsphere, 127.8 mg·g−1 microsphere, was obtained with lipase. In comparison with other proteins, the hydrophobic force is more important in promoting the adsorption of lipase. The microsphere can preferentially adsorb lipase from an even mixture of proteins. The optimum temperature and pH for the selective adsorption of lipase by the microsphere was 35 °C and pH 7.0. PMID:23344018

Serotype determination of Salmonella by xTAG assay.

PubMed

Zheng, Zhibei; Zheng, Wei; Wang, Haoqiu; Pan, Jincao; Pu, Xiaoying

2017-10-01

Currently, no protocols or commercial kits are available to determine the serotypes of Salmonella by using Luminex MAGPIX®. In this study, an xTAG assay for serotype determination of Salmonella suitable for Luminex MAGPIX® is described and 228 Salmonella isolates were serotype determined by this xTAG assay. The xTAG assay consists of two steps: 1) Multiplex PCR to amplify simultaneously O, H and Vi antigen genes of Salmonella, and 2) Magplex-TAG™ microsphere hybridization to identify accurately the specific PCR products of different antigens. Compared with the serotyping results of traditional serum agglutination test, the sensitivity and specificity of the xTAG assay were 95.1% and 100%, respectively. The agreement rate of these two assays was 95.2%. Compared with Luminex xMAP® Salmonella Serotyping Assay (SSA) kit, the advantages of this xTAG assay are: First, the magnetic beads make it applicable to both the Luminex®100/200™ and MAGPIX® systems. Second, only primers rather than both primers and probes are needed in the xTAG assay, and the process of coupling antigen-specific oligonucleotide probes to beads is circumvented, which make the xTAG assay convenient to be utilized by other laboratories. The xTAG assay may serve as a rapid alternative or complementary method for traditional Salmonella serotyping tests, especially for laboratories that utilize the MAGPIX® systems. Copyright © 2017 Elsevier B.V. All rights reserved.

A facile method for preparing porous, optically active, magnetic Fe3 O4 @poly(N-acryloyl-leucine) inverse core/shell composite microspheres.

PubMed

Liu, Dong; Deng, Jianping; Yang, Wantai

2014-01-01

The first synthesis of porous, optically active, magnetic Fe3 O4 @poly(N-acryloyl-leucine) inverse core/shell composite microspheres is reported, in which the core is constructed of chiral polymer and the shell is constructed of Fe3 O4 NPs. The microspheres integrate three significant concepts, "porosity", "chirality", and "magneticity", in one single microspheric entity. The microspheres consist of Fe3 O4 nanoparticles and porous optically active microspheres, and thus combine the advantages of both magnetic nanoparticles and porous optically active microspheres. The pore size and specific surface area of the microspheres are characterized by N2 adsorption, from which it is found that the composite microspheres possess a desirable porous structure. Circular dichroism and UV-vis absorption spectroscopy measurements demonstrate that the microspheres exhibit the expected optical activity. The microspheres also have high saturation magnetization of 14.7 emu g(-1) and rapid magnetic responsivity. After further optimization, these novel microspheres may potentially find applications in areas such as asymmetric catalysis, chiral adsorption, etc. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Genome-Wide Nucleic Acid/Protein Interaction in Breast Cancer

DTIC Science & Technology

2005-04-01

Chen W, Zhang J et al: Large-scale genotyping of complex DNA. Nat Biotechnol 2003, 21(10):1233-1237. 25. Bolstad BM, Irizarry RA, Astrand M, Speed TP...2124836802660188/sup8.xls 235 Analysis of RNA-protein interactions by flow cytometry Alexander S Brodsky’*, Angus PR Johnston 2, Matt Trau 2 & Pamela A Silver1...Natl Acad Sci USA (2001) 98(23):12954-12959. genotyping using the Qbead system: A quantum dot-encoded microsphere-based assay. Nucleic Acids Res (2003

Efficacy of the biomaterials 3wt%-nanostrontium-hydroxyapatite-enhanced calcium phosphate cement (nanoSr-CPC) and nanoSr-CPC-incorporated simvastatin-loaded poly(lactic-co-glycolic-acid) microspheres in osteogenesis improvement: An explorative multi-phase experimental in vitro/vivo study.

PubMed

Masaeli, Reza; Jafarzadeh Kashi, Tahereh Sadat; Dinarvand, Rassoul; Rakhshan, Vahid; Shahoon, Hossein; Hooshmand, Behzad; Mashhadi Abbas, Fatemeh; Raz, Majid; Rajabnejad, Alireza; Eslami, Hossein; Khoshroo, Kimia; Tahriri, Mohammadreza; Tayebi, Lobat

2016-12-01

The purpose of this multi-phase explorative in vivo animal/surgical and in vitro multi-test experimental study was to (1) create a 3wt%-nanostrontium hydroxyapatite-enhanced calcium phosphate cement (Sr-HA/CPC) for increasing bone formation and (2) creating a simvastatin-loaded poly(lactic-co-glycolic acid) (SIM-loaded PLGA) microspheres plus CPC composite (SIM-loaded PLGA+nanostrontium-CPC). The third goal was the extensive assessment of multiple in vitro and in vivo characteristics of the above experimental explorative products in vitro and in vivo (animal and surgical studies). Physical and chemical properties of the prepared Sr-HA/CPC were evaluated. MTT assay and alkaline phosphatase activities, and radiological and histological examinations of Sr-HA/CPC, CPC and negative control were compared. X-ray diffraction (XRD) indicated that crystallinity of the prepared cement increased by increasing the powder-to-liquid ratio. Incorporation of Sr-HA into CPC increased MTT assay (biocompatibility) and ALP activity (P<0.05). Histomorphometry showed greater bone formation after 4weeks, after implantation of Sr-HA/CPC in 10 rats compared to implantations of CPC or empty defects in the same rats (n=30, ANOVA P<0.05). METHODS AND RESULTS PERTAINING TO SIM-LOADED PLGA MICROSPHERES+NANOSTRONTIUM-CPC COMPOSITE: After SEM assessment, the produced composite of microspheres and enhanced CPC were implanted for 8weeks in 10 rabbits, along with positive and negative controls, enhanced CPC, and enhanced CPC plus SIM (n=50). In the control group, only a small amount of bone had been regenerated (localized at the boundary of the defect); whereas, other groups showed new bone formation within and around the materials. A significant difference was found in the osteogenesis induced by the groups sham control (16.96±1.01), bone materials (32.28±4.03), nanostrontium-CPC (24.84±2.6), nanostrontium-CPC-simvastatin (40.12±3.29), and SIM-loaded PLGA+nanostrontium-CPC (44.8±6.45) (ANOVA P<0.001). All the pairwise comparisons were significant (Tukey P<0.01), except that of nanostrontium-CPC-simvastatin and SIM-loaded PLGA+nanostrontium-CPC. This confirmed the efficacy of the SIM-loaded PLGA+nanostrontium-CPC composite, and its superiority over all materials except SIM-containing nanostrontium-CPC. Copyright © 2016 Elsevier B.V. All rights reserved.

Enhanced autonomic shutdown of Li-ion batteries by polydopamine coated polyethylene microspheres

DOE PAGES

Baginska, Marta; Blaiszik, Benjamin J.; Rajh, Tijana; ...

2014-07-17

Thermally triggered autonomic shutdown of a Lithium-ion (Li-ion) battery is demonstrated using polydopamine (PDA)-coated polyethylene microspheres applied onto a battery anode. The microspheres are dispersed in a buffered 10 mM dopamine salt solution and the pH is raised to initiate the polymerization and coat the microspheres. Coated microspheres are then mixed with an aqueous binder, applied onto a battery anode surface, dried, and incorporated into Li-ion coin cells. FTIR and Raman spectroscopy are used to verify the presence of the polydopamine on the surface of the microspheres. Scanning electron microscopy is used to examine microsphere surface morphology and resulting anodemore » coating quality. Charge and discharge capacity, as well as impedance, are measured for Li-ion coin cells as a function of microsphere content. Autonomous shutdown is achieved by applying 1.7 mg cm –2 of PDA-coated microspheres to the electrode. Furthermore, the PDA coating significantly reduces the mass of microspheres for effective shutdown compared to our prior work with uncoated microspheres.« less

Hydrogeological characterization of a bank filtration experiment site at the Rio Grande, El Paso, Texas, USA

NASA Astrophysics Data System (ADS)

Langford, R.; Schulze-Makuch, D.; Pillai, S.; Abdel-Fattah, A.; Widmer, K.

2003-04-01

An experiment site was constructed along an artificial channel of the Rio Grande in El Paso, Texas. The experiment was funded by the EPA and is designed to measure the effectiveness of bank filtration in an arid environment. Regionally, the experiment is important because of the hundreds of thousands of people drinking water from shallow wells drilled in close proximity to septic systems. A pumping well was drilled 17 meters from the stream bank and screened from 3.5 to 8 m depth. A cruciform array of observation wells with several multilevel completions allows detection of downstream and vertical movement of water as well as flow from the stream to the well. All of the wells were continuously cored during drilling. Analysis of the cores reveals that the site consists of two stacked channels filled with sand deposited from the meandering Rio Grande. A grid of ground-penetrating radar lines provided three-dimensional coverage between wells and showed bedding to 6.5 m depth. Constant head hydraulic conductivities show that the aquifer consists of two more permeable units separated by the less permeable upper fill of the lower channel complex, with vertical hydraulic conductivities of (1x10-6 to 2x10-6 m/s?). The intervals above and below this interval have the highest vertical conductivities (up to 3.5x10-5 m/s). A multiple pumping and tracer test was conducted using the cruciform array of the field site that consisted of a pumping well, 16 observation wells, and a stream sampling point. The average hydraulic conductivity of the geological media at the field site was about 2 x 10-3 m/s based on pumping test analysis. However, the type curve responses revealed significant heterogeneity of hydraulic conductivity throughout the field site. For the tracer test, bromide and microspheres were used as tracers. Microspheres were used to mimic the behavior of Giardia and Cryptosporidium. The tracers (bromide and microspheres of different sizes and colors) were injected in one observation wells screened into the riverbank, one observation wells screened into the geological medium at the field site, and into one piezometer pushed into the stream sediments within the stream. The bromide recovery in the pumping well and in the deeper observation wells showed an early and a late peak with a long tail indicating the possibility that the geological medium at the field site behaves like a double-porosity medium allowing the tracer to move relatively quickly through the higher conductivity units while being significantly retarded in the low hydraulic conductivity units. The analysis of the microspheres in the laboratory, which is not yet complete, will shed more light on the transport behavior of pathogens at the field site.

Ulex europaeus 1 lectin targets microspheres to mouse Peyer's patch M-cells in vivo.

PubMed

Foster, N; Clark, M A; Jepson, M A; Hirst, B H

1998-03-01

The interaction of latex microspheres with mouse Peyer's patch membranous M-cells was studied in a mouse gut loop model after the microspheres were coated with a variety of agents. Carboxylated microspheres (diameter 0.5 micron) were covalently coated with lectins Ulex europaeus 1, Concanavalin A, Euonymus europaeus and Bandeiraea simplicifolia 1 isolectin-B4, human immunoglobulin A or bovine serum albumin. Of the treatments examined, only Ulex europaeus (UEA1) resulted in significant selective binding of microspheres to M-cells. UEA1-coated microspheres bound to M-cells at a level 100-fold greater than BSA-coated microspheres, but binding to enterocytes was unaffected. Incubation of UEA1-coated microspheres with alpha-L-fucose reduced M-cell binding to a level comparable with BSA-coated microspheres. This indicated that targeting by UEA1 was via a carbohydrate receptor on the M-cell surface. Adherence of UEA1-coated microspheres to M-cells occurred within 10 min of inoculation into mouse gut loops and UEA1-coated microspheres were transported to 10 microns below the apical surface of M-cells within 60 min of inoculation. UEA1-coated microspheres also targeted mouse Peyer's patch M-cells after intragastric administration. These results demonstrated that altering the surface chemistry of carboxylated polystyrene microspheres increased M-cell targeting, suggesting a strategy to enhance delivery of vaccine antigens to the mucosal immune system.

A novel strategy for the preparation of porous microspheres and its application in peptide drug loading.

PubMed

Wei, Yi; Wang, Yuxia; Zhang, Huixia; Zhou, Weiqing; Ma, Guanghui

2016-09-15

A new strategy is developed to prepare porous microspheres with narrow size distribution for peptides controlled release, involving a fabrication of porous microspheres without any porogens followed by a pore closing process. Amphiphilic polymers with different hydrophobic segments (poly(monomethoxypolyethylene glycol-co-d,l-lactide) (mPEG-PLA), poly(monomethoxypolyethylene glycol-co-d,l-lactic-co-glycolic acid) (mPEG-PLGA)) are employed as microspheres matrix to prepare porous microspheres based on a double emulsion-premix membrane emulsification technique combined with a solvent evaporation method. Both microspheres possess narrow size distribution and porous surface, which are mainly caused by (a) hydrophilic polyethylene glycol (PEG) segments absorbing water molecules followed by a water evaporation process and (b) local explosion of microspheres due to fast evaporation of dichloromethane (MC). Importantly, mPEG-PLGA microspheres have a honeycomb like structure while mPEG-PLA microspheres have a solid structure internally, illustrating that the different hydrophobic segments could modulate the affinity between solvent and matrix polymer and influence the phase separation rate of microspheres matrix. Long term release patterns are demonstrated with pore-closed microspheres, which are prepared from mPEG-PLGA microspheres loading salmon calcitonin (SCT). These results suggest that it is potential to construct porous microspheres for drug sustained release using permanent geometric templates as new porogens. Copyright © 2016 Elsevier Inc. All rights reserved.

A study of factors affecting properties of AM/AMPS/NVP terpolymeric microspheres prepared by inverse suspension polymerization

NASA Astrophysics Data System (ADS)

Jiang, J. F.; Zhao, Q.; Lin, M. Q.; Wang, Y. F.; Dang, S. M.; Sun, F. F.

2015-12-01

Terpolymeric microspheres were synthesized by the inverse suspension polymerization of functional monomers including AMPS, NVP, and AM. The morphology and size of the obtained microspheres were measured by scanning electron microscopy (SEM) and optical microscopy. Furthermore, the swelling performances of the obtained microspheres were measured with alaser particle analyzer (LPA), and the thermal stability of the microspheres obtained was measured by differential thermal analysis (DSC-TG) and high temperature experiments involving microsphere/water dispersion. The results revealed that the extreme value of the microsphere size distribution decreased from 280 μm to 20 μm as the stirring rate increased from 175 rpm to 500 rpm. At temperatures below 25°C, the maximum achieved swelling ratio of the microspheres was 21, and the thermal stability of the terpolymer microspheres was significantly higher than that of the dipolymer microspheres. The terpolymer/water dispersions were kept at 120°C for 19d before any damage was observed.

Microradiographic microsphere manipulator

DOEpatents

Singleton, R.M.

A method and apparatus is disclosed for radiographic characterization of small hollow spherical members (microspheres), constructed of either optically transparent or opaque materials. The apparatus involves a microsphere manipulator which holds a batch of microspheres between two parallel thin plastic films for contact microradiographic characterization or projection microradiography thereof. One plastic film is translated relative to and parallel to the other to roll the microspheres through any desired angle to allow different views of the microspheres.

Microradiographic microsphere manipulator

DOEpatents

Singleton, Russell M.

1980-01-01

A method and apparatus for radiographic characterization of small hollow spherical members (microspheres), constructed of either optically transparent or opaque materials. The apparatus involves a microsphere manipulator which holds a batch of microspheres between two parallel thin plastic films for contact microradiographic characterization or projection microradiography thereof. One plastic film is translated to relative to and parallel to the other to roll the microspheres through any desired angle to allow different views of the microspheres.

Preparation of Tea Tree Oil/Poly(styrene-butyl methacrylate) Microspheres with Sustained Release and Anti-Bacterial Properties

PubMed Central

Lin, Guanquan; Chen, Huayao; Zhou, Hongjun; Zhou, Xinhua; Xu, Hua

2018-01-01

Using butyl methacrylate (BMA) and styrene (St) as monomers and divinylbenzene (DVB) as a crosslinking agent, P(St-BMA) microspheres were prepared by suspension polymerization. Tea tree oil (TTO) microspheres were prepared by adsorbing TTO on P(St-BMA) microspheres. The structure and surface morphology of P(St-BMA) microspheres and TTO microspheres were characterized by Fourier transformed infrared spectroscopy (FTIR), optical microscopy, and Thermogravimetric analysis (TGA). In doing so, the structural effect of P(St-BMA) microspheres on oil absorption and sustained release properties could be investigated. The results show that the surface of the P(St-BMA) microspheres in the process of TTO microsphere formation changed from initially concave to convex. The TTO microspheres significantly improved the stability of TTO, which was found to completely decompose as the temperature of the TTO increased from about 110 °C to 150 °C. The oil absorption behavior, which was up to 3.85 g/g, could be controlled by adjusting the monomer ratio and the amount of crosslinking agent. Based on Fickian diffusion, the sustained release behavior of TTO microspheres was consistent with the Korsmeyer-Pappas kinetic model. After 13 h of natural release, the anti-bacterial effect of the TTO microspheres was found to be significantly improved compared to TTO. PMID:29723967

Small-scale screening of anticancer drugs acting specifically on neural stem/progenitor cells derived from human-induced pluripotent stem cells using a time-course cytotoxicity test.

PubMed

Fukusumi, Hayato; Handa, Yukako; Shofuda, Tomoko; Kanemura, Yonehiro

2018-01-01

Since the development of human-induced pluripotent stem cells (hiPSCs), various types of hiPSC-derived cells have been established for regenerative medicine and drug development. Neural stem/progenitor cells (NSPCs) derived from hiPSCs (hiPSC-NSPCs) have shown benefits for regenerative therapy of the central nervous system. However, owing to their intrinsic proliferative potential, therapies using transplanted hiPSC-NSPCs carry an inherent risk of undesired growth in vivo . Therefore, it is important to find cytotoxic drugs that can specifically target overproliferative transplanted hiPSC-NSPCs without damaging the intrinsic in vivo stem-cell system. Here, we examined the chemosensitivity of hiPSC-NSPCs and human neural tissue-derived NSPCs (hN-NSPCs) to the general anticancer drugs cisplatin, etoposide, mercaptopurine, and methotrexate. A time-course analysis of neurospheres in a microsphere array identified cisplatin and etoposide as fast-acting drugs, and mercaptopurine and methotrexate as slow-acting drugs. Notably, the slow-acting drugs were eventually cytotoxic to hiPSC-NSPCs but not to hN-NSPCs, a phenomenon not evident in the conventional endpoint assay on day 2 of treatment. Our results indicate that slow-acting drugs can distinguish hiPSC-NSPCs from hN-NSPCs and may provide an effective backup safety measure in stem-cell transplant therapies.

Preparation and drug controlled release of porous octyl-dextran microspheres.

PubMed

Hou, Xin; Liu, Yanfei

2015-01-01

In this work, porous octyl-dextran microspheres with excellent properties were prepared by two steps. Firstly, dextran microspheres were synthesized by reversed-phase suspension polymerization. Secondly, octyl-dextran microspheres were prepared by the reaction between dextran microspheres and ethylhexyl glycidyl ether and freezing-drying method. Porous structure of microspheres was formed through the interaction between octyl groups and organic solvents. The structure, morphology, dry density, porosity and equilibrium water content of porous octyl-dextran microspheres were systematically investigated. The octyl content affected the properties of microspheres. The results showed that the dry density of microspheres decreased from 2.35 to 1.21 g/ml, porosity increased from 80.68 to 95.05% with the octyl content increasing from 0.49 to 2.28 mmol/g. Meanwhile, the equilibrium water content presented a peak value (90.18%) when the octyl content was 2.25 mmol/g. Octyl-dextran microspheres showed high capacity. Naturally drug carriers play an important role in drug-delivery systems for their biodegradability, wide raw materials sources and nontoxicity. Doxorubicin (DOX) was used as a drug model to examine the drug-loading capacity of porous octyl-dextran microspheres. The drug-loading efficiency increased with the increase in microspheres/drug ratio, while the encapsulation efficiency decreased. When microspheres/drug mass ratio was 4/1, the drug-loading efficiency and encapsulation efficiency were 10.20 and 51.00%, respectively. The release rate of DOX increased as drug content and porosity increased. In conclusion, porous octyl-dextran microspheres were synthesized successfully and have the potential to serve as an effective delivery system in drug controlled release.

A MULTIPLEXED ASSAY FOR DETERMINATION OF NEUROTOXICANT EFFECTS ON SPONTANEOUS NETWORK ACTIVITY AND CELL VIABILITY FROM MICROELECTRODE ARRAYS

EPA Science Inventory

AbstractTITLE: A MULTIPLEXED ASSAY FOR DETERMINATION OF NEUROTOXICANT EFFECTS ON SPONTANEOUS NETWORK ACTIVITY AND CELL VIABILITY FROM MICROELECTRODE ARRAYSABSTRACT BODY: Microelectrode array (MEA) recordings are increasingly being used as an in vitro method to detect and characte...

[Optimization of riboflavin sodium phosphate loading to calcium alginate floating microspheres by response surface methodology].

PubMed

Zhang, An-yang; Fan, Tian-yuan

2009-12-18

To investigate the preparation, optimization and in vitro properties of riboflavin sodium phosphate floating microspheres. The floating microspheres composed of riboflavin sodium phosphate and calcium alginate were prepared using ion gelatin-oven drying method. The properties of the microspheres were investigated, including the buoyancy, release, appearance and entrapment efficiency. The formulation was optimized by response surface methodology (RSM). The optimized microspheres were round. The entrapment efficiency was 57.49%. All the microspheres could float on the artificial gastric juice over 8 hours. The release of the drug from the microspheres complied with Fick's diffusion.

Sustained release of simvastatin from hollow carbonated hydroxyapatite microspheres prepared by aspartic acid and sodium dodecyl sulfate.

PubMed

Wang, Ke; Wang, Yinjing; Zhao, Xu; Li, Yi; Yang, Tao; Zhang, Xue; Wu, Xiaoguang

2017-06-01

Hollow carbonated hydroxyapatite (HCHAp) microspheres as simvastatin (SV) sustained-release vehicles were fabricated through a novel and simple one-step biomimetic strategy. Firstly, hollow CaCO 3 microspheres were precipitated through the reaction of CaCl 2 with Na 2 CO 3 in the presence of aspartic acid and sodium dodecyl sulfate. Then, the as-prepared hollow CaCO 3 microspheres were transformed into HCHAp microspheres with a controlled anion-exchange method. The HCHAp microspheres were 3-5μm with a shell thickness of 0.5-1μm and were constructed of short needle nanoparticles. The HCHAp microspheres were then loaded with SV, exhibiting excellent drug-loading capacity and sustained release properties. These results present a new material synthesis strategy for HCHAp microspheres and suggest that the as-prepared HCHAp microspheres are promising for applications in drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of mean diameter and polydispersity of PLG microspheres on drug release: experiment and theory.

PubMed

Berchane, N S; Carson, K H; Rice-Ficht, A C; Andrews, M J

2007-06-07

The need to tailor release rate profiles from polymeric microspheres is a significant problem. Microsphere size, which has a significant effect on drug release rate, can potentially be varied to design a controlled drug delivery system with desired release profile. In this work the effects of microspheres mean diameter, polydispersity, and polymer degradation on drug release rate from poly(lactide-co-glycolide) (PLG) microspheres are described. Piroxicam containing PLG microspheres were fabricated at 20% loading, and at three different impeller speeds. A portion of the microspheres was then sieved giving five different size distributions. In vitro release kinetics were determined for each preparation. Based on these experimental results, a suitable mathematical theory has been developed that incorporates the effect of microsphere size distribution and polymer degradation on drug release. We show from in vitro release experiments that microsphere size has a significant effect on drug release rate. The initial release rate decreased with an increase in microsphere size. In addition, the release profile changed from first order to concave-upward (sigmoidal) as the microsphere size was increased. The mathematical model gave a good fit to the experimental release data. For highly polydisperse populations (polydispersity parameter b<3), incorporating the microsphere size distribution into the mathematical model gave a better fit to the experimental results than using the representative mean diameter. The validated mathematical model can be used to predict small-molecule drug release from PLG microsphere populations.

In situ growth of copper nanocrystals from carbonaceous microspheres with electrochemical glucose sensing properties

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

Zhou, Xiaoliang; Yan, Zhengguang, E-mail: yanzg2004@gmail.com; Han, Xiaodong, E-mail: xdhan@bjut.edu.cn

2014-02-01

Graphical abstract: In situ growth of copper nanoparticles from hydrothermal copper-containing carbonaceous microspheres was induced by annealing or electron beam irradiation. Obtained micro-nano carbon/copper composite microspheres show electrochemical glucose sensing properties. - Highlights: • We synthesized carbonaceous microspheres containing non-nanoparicle copper species through a hydrothermal route. • By annealing or electron beam irradiation, copper nanoparticles would form from the carbonaceous microspheres in situ. • By controlling the annealing temperature, particle size of copper could be controlled in the range of 50–500 nm. • The annealed carbon/copper hierarchical composite microspheres were used to fabricate an electrochemical glucose sensor. - Abstract: Inmore » situ growth of copper nanocrystals from carbon/copper microspheres was observed in a well-controlled annealing or an electron beam irradiation process. Carbonaceous microspheres containing copper species with a smooth appearance were yielded by a hydrothermal synthesis using copper nitrate and ascorbic acid as reactants. When annealing the carbonaceous microspheres under inert atmosphere, copper nanoparticles were formed on carbon microspheres and the copper particle sizes can be increased to a range of 50–500 nm by altering the heating temperature. Similarly, in situ formation of copper nanocrystals from these carbonaceous microspheres was observed on the hydrothermal product carbonaceous microspheres with electron beam irradiation in a vacuum transmission electron microscopy chamber. The carbon/copper composite microspheres obtained through annealing were used to modify a glassy carbon electrode and tested as an electrochemical glucose sensor.« less

Development of optical micro resonance based sensor for detection and identification of microparticles and biological agents

NASA Astrophysics Data System (ADS)

Saetchnikov, Vladimir A.; Tcherniavskaia, Elina A.; Schweiger, Gustav

2009-05-01

A novel emerging technique for the label-free analysis of nanoparticles including biomolecules using optical micro cavity resonance of whispering-gallery-type modes is being developed. Schemes of such a method based on microsphere melted by laser on the tip of a standard single mode fiber optical cable with a laser and free microsphere matrix have been developed. Using a calibration principal of ultra high resolution spectroscopy based on such a scheme the method is being transformed to make further development for microbial application. The sensitivity of developed schemes has been tested to refractive index changes by monitoring the magnitude of the whispering gallery modes spectral shift. Water solutions of ethanol, glucose, vitamin C and biotin have been used. Some other schemes using similar principals: stand-alone, array and matrix microsphere resonators, liquid core optical ring resonators are also being under development. The influences of the gap in whispering-gallery modes on energy coupling, resonance quality and frequency have been investigated. An optimum gap for sensing applications has been defined at the half maximum energy coupling where both the Q factor and coupling efficiency are high and the resonance frequency is little affected by the gap variation. Developed schemes have been demonstrated to be a promising technology platform for sensitive, lab-on-chip type sensor which can be used for development of diagnostic tools for different biological molecules, e.g. proteins, oligonucleotides, oligosaccharides, lipids, small molecules, viral particles, cells as well as in different experimental contexts e.g. proteomics, genomics, drug discovery, and membrane studies.

Semiconductor light-emitting devices having concave microstructures providing improved light extraction efficiency and method for producing same

DOEpatents

Tansu, Nelson; Gilchrist, James F; Ee, Yik-Khoon; Kumnorkaew, Pisist

2013-11-19

A conventional semiconductor LED is modified to include a microlens layer over its light-emitting surface. The LED may have an active layer including at least one quantum well layer of InGaN and GaN. The microlens layer includes a plurality of concave microstructures that cause light rays emanating from the LED to diffuse outwardly, leading to an increase in the light extraction efficiency of the LED. The concave microstructures may be arranged in a substantially uniform array, such as a close-packed hexagonal array. The microlens layer is preferably constructed of curable material, such as polydimethylsiloxane (PDMS), and is formed by soft-lithography imprinting by contacting fluid material of the microlens layer with a template bearing a monolayer of homogeneous microsphere crystals, to cause concave impressions, and then curing the material to fix the concave microstructures in the microlens layer and provide relatively uniform surface roughness.

Autonomous colloidal crystallization in a galvanic microreactor

NASA Astrophysics Data System (ADS)

Punckt, Christian; Jan, Linda; Jiang, Peng; Frewen, Thomas A.; Saville, Dudley A.; Kevrekidis, Ioannis G.; Aksay, Ilhan A.

2012-10-01

We report on a technique that utilizes an array of galvanic microreactors to guide the assembly of two-dimensional colloidal crystals with spatial and orientational order. Our system is comprised of an array of copper and gold electrodes in a coplanar arrangement, immersed in a dilute hydrochloric acid solution in which colloidal micro-spheres of polystyrene and silica are suspended. Under optimized conditions, two-dimensional colloidal crystals form at the anodic copper with patterns and crystal orientation governed by the electrode geometry. After the aggregation process, the colloidal particles are cemented to the substrate by co-deposition of reaction products. As we vary the electrode geometry, the dissolution rate of the copper electrodes is altered. This way, we control the colloidal motion as well as the degree of reaction product formation. We show that particle motion is governed by a combination of electrokinetic effects acting directly on the colloidal particles and bulk electrolyte flow generated at the copper-gold interface.

Colloidal crystals with diamond symmetry at optical lengthscales

NASA Astrophysics Data System (ADS)

Wang, Yifan; Jenkins, Ian C.; McGinley, James T.; Sinno, Talid; Crocker, John C.

2017-02-01

Future optical materials promise to do for photonics what semiconductors did for electronics, but the challenge has long been in creating the structure they require--a regular, three-dimensional array of transparent microspheres arranged like the atoms in a diamond crystal. Here we demonstrate a simple approach for spontaneously growing double-diamond (or B32) crystals that contain a suitable diamond structure, using DNA to direct the self-assembly process. While diamond symmetry crystals have been grown from much smaller nanoparticles, none of those previous methods suffice for the larger particles needed for photonic applications, whose size must be comparable to the wavelength of visible light. Intriguingly, the crystals we observe do not readily form in previously validated simulations; nor have they been predicted theoretically. This finding suggests that other unexpected microstructures may be accessible using this approach and bodes well for future efforts to inexpensively mass-produce metamaterials for an array of photonic applications.

Preparation and release characteristics of polymer-coated and blended alginate microspheres.

PubMed

Lee, D W; Hwang, S J; Park, J B; Park, H J

2003-01-01

To prevent a rapid drug release from alginate microspheres in simulated intestinal media, alginate microspheres were coated or blended with polymers. Three polymers were selected and evaluated such as HPMC, Eudragit RS 30D and chitosan, as both coating materials and additive polymers for controlling the drug release. This study focused on the release characteristics of polymer-coated and blended alginate microspheres, varying the type of polymer and its concentration. The alginate microspheres were prepared by dropping the mixture of drug and sodium alginate into CaCl(2) solution using a spray-gun. Polymer-coated microspheres were prepared by adding alginate microspheres into polymer solution with mild stirring. Polymer-blended microspheres were prepared by dropping the mixture of drug, sodium alginate and additive polymer with plasticizer into CaCl(2) solution. In vitro release test was carried out to investigate the release profiles in 500 ml of phosphate buffered saline (PBS, pH 7.4). As the amount of polymer in sodium alginate or coating solution increase, the drug release generally decreased. HPMC-blended microspheres swelled but withstood the disintegration, showing an ideal linear release profiles. Chitosan-coated microspheres showed smooth and round surface and extended the release of drug. In comparison with chitosan-coated microspheres, HPMC-blended alginate microspheres can be easily made and used for controlled drug delivery systems due to convenient process and controlled drug release.

Temperature-feedback direct laser reshaping of silicon nanostructures

NASA Astrophysics Data System (ADS)

Aouassa, M.; Mitsai, E.; Syubaev, S.; Pavlov, D.; Zhizhchenko, A.; Jadli, I.; Hassayoun, L.; Zograf, G.; Makarov, S.; Kuchmizhak, A.

2017-12-01

Direct laser reshaping of nanostructures is a cost-effective and fast approach to create or tune various designs for nanophotonics. However, the narrow range of required laser parameters along with the lack of in-situ temperature control during the nanostructure reshaping process limits its reproducibility and performance. Here, we present an approach for direct laser nanostructure reshaping with simultaneous temperature control. We employ thermally sensitive Raman spectroscopy during local laser melting of silicon pillar arrays prepared by self-assembly microsphere lithography. Our approach allows establishing the reshaping threshold of an individual nanostructure, resulting in clean laser processing without overheating of the surrounding area.

Experimental study on microsphere assisted nanoscope in non-contact mode

NASA Astrophysics Data System (ADS)

Ling, Jinzhong; Li, Dancui; Liu, Xin; Wang, Xiaorui

2018-07-01

Microsphere assisted nanoscope was proposed in existing literatures to capture super-resolution images of the nano-structures beneath the microsphere attached on sample surface. In this paper, a microsphere assisted nanoscope working in non-contact mode is designed and demonstrated, in which the microsphere is controlled with a gap separated to sample surface. With a gap, the microsphere is moved in parallel to sample surface non-invasively, so as to observe all the areas of interest. Furthermore, the influence of gap size on image resolution is studied experimentally. Only when the microsphere is close enough to the sample surface, super-resolution image could be obtained. Generally, the resolution decreases when the gap increases as the contribution of evanescent wave disappears. To keep an appropriate gap size, a quantitative method is implemented to estimate the gap variation by observing Newton's rings around the microsphere, serving as a real-time feedback for tuning the gap size. With a constant gap, large-area image with high resolution can be obtained during microsphere scanning. Our study of non-contact mode makes the microsphere assisted nanoscope more practicable and easier to implement.

Preparation, characterization, and in vitro release of gentamicin from coralline hydroxyapatite-alginate composite microspheres.

PubMed

Sivakumar, M; Rao, K Panduranga

2003-05-01

In this work, composite microspheres were prepared from bioactive ceramics such as coralline hydroxyapatite [Ca(10)(PO(4))(6)(OH)(2)] granules, a biodegradable polymer, sodium alginate, and an antibiotic, gentamicin. Previously, we have shown a gentamicin release from coralline hydroxyapatite granules-chitosan composite microspheres. In the present investigation, we attempted to prepare composite microspheres containing coralline hydroxyapatite granules and sodium alginate by the dispersion polymerization technique with gentamicin incorporated by absorption method. The crystal structure of the composite microspheres was analyzed using X-ray powder diffractometer. Fourier transform infrared spectra clearly indicated the presence of per-acid of sodium alginate, phosphate, and hydroxyl groups in the composite microspheres. Scanning electron micrographs and optical micrographs showed that the composite microspheres were spherical in shape and porous in nature. The particle size of composite microspheres was analyzed, and the average size was found to be 15 microns. The thermal behavior of composite microspheres was studied using thermogravimetric analysis and differential scanning calorimetric analysis. The cumulative in vitro release profile of gentamicin from composite microspheres showed near zero order patterns. Copyright 2003 Wiley Periodicals, Inc.

Preparation, characterization and in vitro release of gentamicin from coralline hydroxyapatite-gelatin composite microspheres.

PubMed

Sivakumar, M; Panduranga Rao, K

2002-08-01

Composite microspheres have been prepared from bioactive ceramics such as coralline hydroxyapatite [CHA, Ca10(PO4)6(OH)2] granules, a biodegradable polymer, gelatin and an antibiotic, gentamicin. In our earlier work, we have shown a gentamicin release from CHA granules--chitosan composite microspheres. In the present investigation, an attempt was made to prepare the composite microspheres containing coralline hydroxyapatite and gelatin (CHA-G), which were prepared by the dispersion polymerization technique and the gentamicin was incorporated by the absorption method. The crystal structure of the composite microspheres was analyzed using X-ray powder diffractometer. The Fourier transformed infrared spectrum clearly indicated the presence of amide and hydroxyl groups in the composite microspheres. Scanning electron micrographs and optical micrographs show that the composite microspheres are spherical in shape and porous in nature. The particle size of composite microspheres was analyzed and the average size was found to be 16 microm. The thermal behavior of composite microspheres was studied using thermogravimetric analysis and differential scanning calorimetric analysis. The cumulative in vitro release profile of gentamicin from composite microspheres showed near zero order patterns.

Myocardial uptake and kinetic properties of technetium-99m-Q3 in dogs

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

Gerson, M.C.; Millard, R.W.; McGoron, A.J.

1994-10-01

We postulated that {sup 99m}Tc-Q3, a cationic imaging agent, produces myocardial activity related to myocardial blood flow during myocardial ischemia and pharmacologic coronary artery vasodilation, and shows little or no myocardial redistribution over 4 hr after intravenous injection. In six Group 1 dogs, the chest was opened, the left circumflex coronary artery was acutely ligated, and dipyridamole (0.32, 0.56 or 0.84 mg/kg) was infused into the right atrium, followed by 10 mCi of {sup 99m}Tc-Q3. Myocardial blood flow was measured by radiolabeled microspheres. The animals were euthanized and 357 myocardial samples were assayed in a well counter for {sup 99m}Tcmore » activity. One week later, radiolabeled microsphere activity was counted and myocardial blood flow calculated. In nine Group 2 dogs, a variable occluder was placed around the left circumflex coronary artery and an ischemic level of circumflex blood flow was maintained constant over 4 hr as measured by an ultrasonic flow meter. Dipyridamole (0.56 mg/kg) was then infused into the right atrium followed by 10mCi of {sup 99m}Tc-Q3. Gamma camera images were acquired at 5, 15, 30, 60, 120 and 240 min following k{sup 99m}Tc-Q3 injection. Microsphere blood flow and endocardial biopsies (n - 6 dogs) were performed at 30, 60, 120 and 240 min following {sup 99m}TcQ3 injection. 31 refs., 9 figs., 1 tab.« less

Evaluation of a combined drug-delivery system for proteins assembled with polymeric nanoparticles and porous microspheres; characterization and protein integrity studies.

PubMed

Alcalá-Alcalá, Sergio; Benítez-Cardoza, Claudia G; Lima-Muñoz, Enrique J; Piñón-Segundo, Elizabeth; Quintanar-Guerrero, David

2015-07-15

This work presents an evaluation of the adsorption/infiltration process in relation to the loading of a model protein, α-amylase, into an assembled biodegradable polymeric system, free of organic solvents and made up of poly(D,L-lactide-co-glycolide) acid (PLGA). Systems were assembled in a friendly aqueous medium by adsorbing and infiltrating polymeric nanoparticles into porous microspheres. These assembled systems are able to load therapeutic amounts of the drug through adsorption of the protein onto the large surface area characteristic of polymeric nanoparticles. The subsequent infiltration of nanoparticles adsorbed with the protein into porous microspheres enabled the controlled release of the protein as a function of the amount of infiltrated nanoparticles, since the surface area available on the porous structure is saturated at different levels, thus modifying the protein release rate. Findings were confirmed by both the BET technique (N2 isotherms) and in vitro release studies. During the adsorption process, the pH of the medium plays an important role by creating an environment that favors adsorption between the surfaces of the micro- and nano-structures and the protein. Finally, assays of α-amylase activity using 2-chloro-4-nitrophenyl-α-D-maltotrioside (CNP-G3) as the substrate and the circular dichroism technique confirmed that when this new approach was used no conformational changes were observed in the protein after release. Copyright © 2015 Elsevier B.V. All rights reserved.

Morphogenesis and crystallization of ZnS microspheres by a soft template-assisted hydrothermal route: synthesis, growth mechanism, and oxygen sensitivity.

PubMed

Yang, Liangbao; Han, Jun; Luo, Tao; Li, Minqiang; Huang, Jiarui; Meng, Fanli; Liu, Jinhuai

2009-01-05

Almost monodisperse ZnS microspheres have been synthesized on a large scale by a hydrothermal route, in which tungstosilicate acid (TSA) was used as a soft template. By controlling the reaction conditions, such as reaction temperature, pH value of the solutions, and the reaction medium, almost monodisperse microspheres can be synthesized. The structure of these microspheres is sensitive to the reaction conditions. The growth mechanism of these nearly monodisperse microspheres was examined. Oxygen sensing is realized from ZnS microspheres. The current through the ZnS microspheres under UV illumination increases as the oxygen concentration decreases.

Effect of medium-chain triglycerides on the release behavior of Endostar encapsulated PLGA microspheres.

PubMed

Meng, Boyu; Li, Ling; Hua, Su; Wang, Qingsong; Liu, Chunhui; Xu, Xiangyang; Yin, Xiaojin

2010-09-15

The incomplete release of Endostar from PLGA microspheres was observed in our previous study. In the present study, we focused on the effect of medium-chain triglycerides (MCT) on the in vitro/in vivo release behavior of Endostar encapsulated PLGA microspheres, which were prepared by a water-in-oil-in-water (W/O/W) double-emulsion method with or without MCT. The in vitro accumulated release of Endostar from microspheres co-encapsulated with 30% MCT was found to be 79.04% after a 30-day incubation period in PBS (pH 7.4) at 37 degrees C. However, the accumulated release of Endostar from MCT-free microspheres was found to be only 32.22%. Pouches containing Endostar encapsulated PLGA microspheres were implanted subcutaneously in rats. The effect of MCT on the in vivo release showed a similar trend to the in vitro release. After 30 days, only 9.87% of the total encapsulated Endostar was retained in microspheres co-encapsulated with 30% MCT, while 42.25% of Endostar was retained in MCT-free microspheres. The co-encapsulation of MCT provided the microspheres with a porous surface, which significantly improved the in vitro/in vivo release of Endostar from PLGA microspheres. In addition, in vitro experiments showed that MCT co-encapsulated PLGA microspheres had more inter-connected pores, faster degradation of PLGA, and faster swelling of microspheres, which helped to explain the mechanism of the effect of MCT on improving the release of Endostar from PLGA microspheres. Copyright 2010 Elsevier B.V. All rights reserved.

Preparation of Syndiotactic Poly(vinyl alcohol)/Poly(vinyl pivalate/vinyl acetate) Microspheres with Radiopacity Using Suspension Copolymerization and Saponification

NASA Astrophysics Data System (ADS)

Seok Lyoo, Won; Wook Cha, Jin; Young Kwak, Kun; Jae Lee, Young; Yong Jeon, Han; Sik Chung, Yong; Kyun Noh, Seok

2010-06-01

To prepare Poly(vinyl pivalate/vinyl acetate) [P(VPi/VAc)] microspheres with radiopacity, the suspension copolymerization approach in the presence of aqueous radiopaque nanoparticles was used. After, The P(VPi/VAc) microspheres with radiopacity were saponified in heterogeneous system, and then P(VPi/VAc) microspheres without aggregates were converted to s-PVA/P(VPi/VAc) microspheres of skin/core structure through the heterogeneous surface saponification. Radiopacity of microspheres was confirmed with Computed tomography (CT).

Mesoporous metal oxide microsphere electrode compositions and their methods of making

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

Parans Paranthaman, Mariappan; Bi, Zhonghe; Bridges, Craig A.

Compositions and methods of making are provided for treated mesoporous metal oxide microspheres electrodes. The compositions include microspheres with an average diameter between about 200 nanometers and about 10 micrometers and mesopores on the surface and interior of the microspheres. The methods of making include forming a mesoporous metal oxide microsphere composition and treating the mesoporous metal oxide microspheres by at least annealing in a reducing atmosphere, doping with an aliovalent element, and coating with a coating composition.

FORMULATION AND EVALUATION OF MICROSPHERES CONTAINING LOSARTAN POTASSIUM BY SPRAY-DRYING TECHNIQUE.

PubMed

Balwierz, Radoslaw; Jankowski, Andrzej; Jasinska, Agata; Marciniak, Dominik; Pluta, Janusz

2016-09-01

Despite numerous applications of microspheres, few works devoted to the preparation of microspheres containing cardiac medications have been published. This study presents the potential of receiving microspheres containing losartan potassium, based on a matrix containing Eudragit L30D55. The study focuses on the possibilities of controlled release of losartan potassium from microspheres in order to reduce the dosage frequency, and also provides information on the effect of the addition of excipients to the quality of the microspheres. Microspheres are monolithic, porous or smooth microparticles ranging from 1 to 500 microns in size. For the preparation of microspheres containing losartan potassium, the spray-drying method was used. The performed study confirmed that the spray-drying technology used to obtain microspheres meets the criteria of size and morphology of the microparticles. The assessment of the kinetics of losartan potassium release from the examined microspheres demonstrated that the release profile followed the first- and/or zero-order kinetics. The use of spray-drying techniques as well as Eudragit L30D55 polymer matrix to obtain the microspheres containing losartan potassium makes it possible to obtain a product with the required particle morphology and particle size ensuring the release of the active substance up to 12 h.

Using a Maxwell's demon to orient a microsphere in a laser trap and initiate thermodynamic assays of photonic nanofields

NASA Astrophysics Data System (ADS)

Beranek, Vaclav; Kuznetsov, Igor R.; Evans, Evan A.

2016-09-01

Seeking to control free rotations of a microsphere in a laser trap, we have created a "Maxwell's demon" that identifies and captures a preferred "up-or-down" polarity of the microsphere. Breaking rotational symmetry, we attach a single "Raleigh-size" nanoparticle to a micron-size sphere, which establishes a "nanodirector" defining microsphere orientations in a trap. With radius <10% of the NIR trapping wavelength (1.064 μm), a polystyrene nanoparticle appended to a 1.3 μm glass sphere adds negligibly to scattering of the trapping beam and imperceptibly to forces trapping a doublet probe. Yet, constrained to a large orbit ( 1.5 μm diameter), the weak Raleigh dipole force induced in the nanoparticle imparts significant pole-attracting torques to the probe. At the same time, Brownian-thermal excitations contribute torque fluctuations to the probe randomizing orientations. Thus, we have combined demon control and Boltzmann thermodynamics to examine the intense competition between photonic torques aligning the nanodirector to the optical axis and the entropy confinement opposing alignment when equilibrated over long times for an order of magnitude span in laser powers. To reveal orientation, we developed novel multistep pattern-processing software to expose and enhance weak-diffuse visible light scattered from the nanoparticle. Processing a continuous stream of doublet images offline at 700 fps, the final step is to super resolve the transverse XY origin of the scattering pattern relative to the synchronous probe center, albeit limited to "up" state segments because of intensity. Transforming the dense histograms ( 104-105) of radial positions to polar angle (θ) distributions, we plot the results on a natural log scale versus sin(θ) to quantify the photonic potentials aligning the nanodirector to the optical axis. Then guided by principles of canonical thermodynamics, we invoke self-consistent methodology to reveal photonic potentials in the "down" state.

Development and evaluation of a novel biodegradable sustained release microsphere formulation of paclitaxel intended to treat breast cancer

PubMed Central

Shiny, Jacob; Ramchander, Thadkapally; Goverdhan, Puchchakayala; Habibuddin, Mohammad; Aukunuru, Jithan Venkata

2013-01-01

Objective: The objective of this study was to develop a novel 1 month depot paclitaxel (PTX) microspheres that give a sustained and complete drug release. Materials and Methods: PTX loaded microspheres were prepared by o/w emulsion solvent evaporation technique using the blends of poly(lactic-co-glycolic acid) (PLGA) 75/25, polycaprolactone 14,000 and polycaprolactone 80,000. Fourier transform infrared spectroscopy was used to investigate drug excipient compatibility. Compatible blends were used to prepare F1-F6 microspheres, the process was characterised and the optimum formulation was selected based on the release. Optimised formulation was characterised for solid state of the drug using the differential scanning calorimetry (DSC) studies, surface morphology using the scanning electron microscopy (SEM), in vivo drug release, in vitro in vivo correlation (IVIVC) and anticancer activity. Anticancer activity of release medium was determined using the cell viability assay in Michigan Cancer Foundation (MCF-7) cell line. Results: Blend of PLGA with polycaprolactone (Mwt 14,000) at a ratio of 1:1 (F5) resulted in complete release of the drug in a time frame of 30 days. F5 was considered as the optimised formulation. Incomplete release of the drug resulted from other formulations. The surface of the optimised formulation was smooth and the drug changed its solid state upon fabrication. The formulation also resulted in 1-month drug release in vivo. The released drug from F5 demonstrated anticancer activity for 1-month. Cell viability was reduced drastically with the release medium from F5 formulation. A 100% IVIVC was obtained with F5 formulation suggesting the authenticity of in vitro release, in vivo release and the use of the formulation in breast cancer. Conclusions: From our study, it was concluded that with careful selection of different polymers and their combinations, PTX 1 month depot formulation with 100% drug release and that can be used in breast cancer was developed. PMID:24167783

Production of hollow aerogel microspheres

DOEpatents

Upadhye, Ravindra S.; Henning, Sten A.

1993-01-01

A method is described for making hollow aerogel microspheres of 800-1200 .mu. diameter and 100-300 .mu. wall thickness by forming hollow alcogel microspheres during the sol/gel process in a catalytic atmosphere and capturing them on a foam surface containing catalyst. Supercritical drying of the formed hollow alcogel microspheres yields hollow aerogel microspheres which are suitable for ICF targets.

5-Fluorouracil:carnauba wax microspheres for chemoembolization: an in vitro evaluation.

PubMed

Benita, S; Zouai, O; Benoit, J P

1986-09-01

5-Fluorouracil:carnauba wax microspheres were prepared using a meltable dispersion process with the aid of a surfactant as a wetting agent. It was noted that only hydrophilic surfactants were able to wet the 5-fluorouracil and substantially increased its content in the microspheres. No marked effect was observed in the particle size distribution of the solid microspheres as a function of the nature of the surfactant. Increasing the stirring rate in the preparation process decreased, first, the mean droplet size of the emulsified melted dispersion in the vehicle during the heating process, and, consequently, the mean particle size of the solidified microspheres during the cooling process. 5-Fluorouracil cumulative release from the microspheres followed first-order kinetics, as shown by nonlinear regression analysis. Although the kinetic results were not indicative of the true release mechanism from a single microsphere, it was believed that 5-fluorouracil release from the microspheres was probably governed by a dissolution process, rather than by a leaching process through the carnauba wax microspheres.

Synthesis and characterisation of multifunctional alginate microspheres via the in situ formation of ZnO quantum dots and the graft of 4-(1-pyrenyl) butyric acid to sodium alginate.

PubMed

Luo, Guilin; Wang, Jianxin; Wang, Yingying; Feng, Bo; Weng, Jie

2015-01-01

Growth factor-loaded fluorescent alginate microspheres, which can realise sustained growth factor release and fluorescence imaging, were synthesised by in situ formation of ZnO quantum dots (QDs) and covalent graft of 4-(1-pyrenyl) butyric acid (PBA). BSA was chosen as a growth factor model protein to study the release kinetic of growth factors from alginate microspheres. The microsphere size and fluorescent properties were also investigated. Investigations of cell culture were used for evaluating biocompatibility of BSA-loaded fluorescent microspheres and fluorescence imaging property of ZnO QDs and PBA-grafted sodium alginate from the microspheres. The results show that they have good fluorescent property either to microspheres or to cells and fluorescent microspheres have good biocompatibility and property in sustained release of growth factors. The obtained microspheres will be expected to realise the imaging of cells and materials and also the release of growth factor in tissue engineering or in cell culture.

Topological Transformation of Defects in Nematic Liquid Crystals

NASA Astrophysics Data System (ADS)

Pagel, Zachary; Atherton, Timothy; Guasto, Jeffrey; Cebe, Peggy

A topological transformation around silica microsphere inclusions in nematic liquid crystal cells (LCC) is experimentally studied. Silica microspheres are coated to induce homeotropic LC anchoring to the spheres. Parallel rub directions of the alignment polymer during LCC construction create a splay wall that traps the microspheres. Application of an out-of-plane electric field then permits a transformation of hedgehog defects, reversing the orientation of the defect around microspheres. The transformation controllably reverses the microsphere's direction of travel during AC electrophoresis due to defect-dependent velocity anisotropy. A similar transformation is studied on chains of microspheres with hedgehog defects, where the defect orientation is reversed on the entire chain. Polarized and confocal microscopies are used to study the defect structures. Results contribute to recent developments in microsphere electrokinetics in nematic LCs, as the transformation adds an additional degree of control in the electrophoretic motion of microspheres and chains of microspheres with dipolar defects. The author thanks NSF Grant DMR-1608126 for funding reseearch and Tufts University for funding travel.

Fabrication and characterization of novel microsphere-embedded optical devices for enhancing microscopy resolution

NASA Astrophysics Data System (ADS)

Darafsheh, Arash

2018-02-01

Microsphere-assisted imaging can be incorporated onto conventional light microscopes allowing wide-field and flourescence imaging with enhanced resolution. We demonstrated that imaging of specimens containing subdiffraction-limited features is achievable through high-index microspheres embedded in a transparent thin film placed over the specimen. We fabricated novel microsphere-embedded microscope slides composed of barium titanate glass microspheres (with diameter 10-100 μm and refractive index 1.9-2.2) embedded in a transparent polydimethylsiloxane (PDMS) elastomer layer with controllable thickness. We characterized the imaging performance of such microsphere-embedded devices in white-light microscopies, by measuring the imaging resolution, field-of-view, and magnification as a function of microsphere size. Our results inform on the design of novel optical devices, such as microsphere-embedded microscope slides for imaging applications.

Preparation of polymethacrylic acid-grafted HEMA/PVP microspheres and preliminary study on basic protein adsorption.

PubMed

Gao, Baojiao; Hu, Hongyan; Guo, Jianfeng; Li, Yanbin

2010-06-01

The crosslinked copolymeric microspheres (HEMA/NVP) of N-vinylpyrrolidone (NVP) and 2-hydroxyethyl methacrylate (HEMA) were prepared using inverse suspension polymerization method. Subsequently, the reaction of methacryloyl chloride with the hydroxyl groups on the surfaces of HEMA/NVP microspheres was performed, leading to the introduction of polymerisable double bonds onto the surfaces of microspheres HEMA/NVP. Afterward, methacrylic acid was allowed to be graft-polymerized on microspheres HEMA/NVP in the manner of "grafting from", resulting in the grafted microspheres PMAA-HEMA/NVP. The grafted microspheres PMAA-HEMA/NVP were fully characterized with several means. The graft-polymerization of MAA on microspheres HEMA/NVP was studied in detail, and the optimal reaction conditions were determined. Thereafter, the adsorption property of the grafted microspheres PMAA-HEMA/NVP for lysozyme as a basic protein model was preliminarily examined to explore the feasibility of removing deleterious basic protein such as density lipoprotein from blood. The experimental results indicate that the PMAA grafting degree on microspheres HEMA/NVP is limited because an enwinding polymer layer as a kinetic barrier on the surfaces of HEMA/NVP microspheres will be formed during the graft-polymerization, and block the graft-polymerization. In order to enhance PMAA grafting degree, reaction temperature, monomer concentration and the used amount of initiator should be effectively controlled. The experimental results also reveal that the grafted microspheres PMAA-HEMA/NVP possess very strong adsorption ability for lysozyme by right of strong electrostatic interaction. Copyright 2010 Elsevier B.V. All rights reserved.

Pluronic F127/chitosan blend microspheres for mucoadhesive drug delivery

NASA Astrophysics Data System (ADS)

Gu, W. Z.; Hu, X. F.

2017-01-01

Pluronic F127/chitosan blend microspheres were prepared via emulsification and cross-linking process using glutaraldehyde as a cross-linker. Compared with chitosan microspheres fabricated under the same experimental conditions, blend microspheres exhibited better physical stability and higher swelling capacity. Puerarin, a traditional Chinese medicine, was incorporated into microparticlesas the model drug. The in vitro release of puerarin from blend microspheres was reduced because of the improved compatibility of the drug with the matrices. According to the results from in vitro adhesion experiments, mucoadhesive behavior of blend microspheres on a mucosa-like surface was similar to that of chitosan microspheres, despite their good ability of anti-protein absorption in solution.

Comprehensive GMO detection using real-time PCR array: single-laboratory validation.

PubMed

Mano, Junichi; Harada, Mioko; Takabatake, Reona; Furui, Satoshi; Kitta, Kazumi; Nakamura, Kosuke; Akiyama, Hiroshi; Teshima, Reiko; Noritake, Hiromichi; Hatano, Shuko; Futo, Satoshi; Minegishi, Yasutaka; Iizuka, Tayoshi

2012-01-01

We have developed a real-time PCR array method to comprehensively detect genetically modified (GM) organisms. In the method, genomic DNA extracted from an agricultural product is analyzed using various qualitative real-time PCR assays on a 96-well PCR plate, targeting for individual GM events, recombinant DNA (r-DNA) segments, taxon-specific DNAs, and donor organisms of the respective r-DNAs. In this article, we report the single-laboratory validation of both DNA extraction methods and component PCR assays constituting the real-time PCR array. We selected some DNA extraction methods for specified plant matrixes, i.e., maize flour, soybean flour, and ground canola seeds, then evaluated the DNA quantity, DNA fragmentation, and PCR inhibition of the resultant DNA extracts. For the component PCR assays, we evaluated the specificity and LOD. All DNA extraction methods and component PCR assays satisfied the criteria set on the basis of previous reports.

Effect of a freeze-dried CMC/PLGA microsphere matrix of rhBMP-2 on bone healing.

PubMed

Schrier, J A; Fink, B F; Rodgers, J B; Vasconez, H C; DeLuca, P P

2001-10-07

The hypothesis of this research was that implants of poly(lactide-co-glycolide) (PLGA) microspheres loaded with bone morphogenetic protein-2 (rhBMP-2) and distributed in a freeze-dried carboxymethylcellulose (CMC) matrix would produce more new bone than would matrix implants of non-protein-loaded microspheres or matrix implants of only CMC. To test this hypothesis it was necessary to fashion microsphere-loaded CMC implants that were simple to insert, fit precisely into a defect, and would not elicit swelling. Microspheres were produced via a water-in-oil-in-water double-emulsion system and were loaded with rhBMP-2 by soaking them in a buffered solution of the protein at a concentration of 5.4 mg protein per gram of PLGA. Following recovery of the loaded microspheres by lyophilization, matrices for implantation were prepared by lyophilizing a suspension of the microspheres in 2% CMC in flat-bottom tissue culture plates. Similar matrices were made with 2% CMC and with 2% CMC containing blank microspheres. A full-thickness calvarial defect model in New Zealand white rabbits was used to assess bone growth. Implants fit the defect well, allowing for direct application. Six weeks postsurgery, defects were collected and processed for undecalcified histology. In vitro, 60% of the loaded rhBMP-2 released from devices or microspheres in 5 to 7 days, with the unembedded microspheres releasing faster than those embedded in CMC. In vivo, the rhBMP-2 microspheres greatly enhanced bone healing, whereas nonloaded PLGA microspheres in the CMC implants had little effect. The results showed that a lyophilized device of rhBMP-2/PLGA microspheres in CMC was an effective implantable protein-delivery system for use in bone repair.

A colorimetric indicator-displacement assay array for selective detection and identification of biological thiols.

PubMed

Qian, Sihua; Lin, Hengwei

2014-03-01

A simple, inexpensive yet highly selective colorimetric indicator-displacement assay array for the simultaneous detection and identification of three important biothiols at micromolar concentrations under physiological conditions and in real samples has been developed in this work. With use of an array composed of metal indicators and metal ions, clear differentiation among cysteine, homocysteine and glutathione was achieved. On the basis of the colour change of the array, quantification of each analyte was accomplished easily, and different biothiols were identified readily using standard chemometric approaches (hierarchical clustering analysis). Moreover, the colorimetric sensor array was not responsive to changes with 19 other natural amino acids, and it showed excellent reproducibility. Importantly, the sensor array developed was successfully applied to the determination and identification of the three biothiols in a real biological sample.

Histological Comparison of Kidney Tissue Following Radioembolization with Yttrium-90 Resin Microspheres and Embolization with Bland Microspheres

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

Silva, Suresh de, E-mail: suresh.desilva@unsw.edu.au; Mackie, Simon; Aslan, Peter

BackgroundIntra-arterial brachytherapy with yttrium-90 ({sup 90}Y) resin microspheres (radioembolization) is a procedure to selectively deliver high-dose radiation to tumors. The purpose of this research was to compare the radioembolic effect of {sup 90}Y-radioembolization versus the embolic effect of bland microspheres in the porcine kidney model.MethodsIn each of six pigs, ~25–33 % of the kidney volume was embolized with {sup 90}Y resin microspheres and an equivalent number of bland microspheres in the contralateral kidney. Kidney volume was estimated visually from contrast-enhanced fluoroscopy imaging. Morphologic and histologic analysis was performed 8–9 weeks after the procedure to assess the locations of the microspheres and extentmore » of tissue necrosis from {sup 90}Y-radioembolization and bland embolization. A semi-quantified evaluation of the non-acute peri-particle and perivascular tissue reaction was conducted. All guidelines for the care and use of animals were followed.ResultsKidneys embolized with {sup 90}Y-radioembolization decreased in mass by 30–70 % versus the contralateral kidney embolized with bland microspheres. These kidneys showed significant necrosis/fibrosis, avascularization, and glomerular atrophy in the immediate vicinity of the {sup 90}Y resin microspheres. By contrast, glomerular changes were not observed, even with clusters of bland microspheres in afferent arterioles. Evidence of a foreign body reaction was recorded in some kidneys with bland microspheres, and subcapsular scarring/infarction only with the highest load (4.96 × 10{sup 6}) of bland microspheres.ConclusionThis study showed that radioembolization with {sup 90}Y resin microspheres produces localized necrosis/fibrosis and loss of kidney mass in a porcine kidney model. This result supports the study of {sup 90}Y resin microspheres for the localized treatment of kidney tumors.« less

Microspheres for the oral delivery of insulin: preparation, evaluation and hypoglycaemic effect in streptozotocin-induced diabetic rats.

PubMed

Zhang, Huan; Wang, Weimei; Li, Haoran; Peng, Yi; Zhang, Zhiqing

2018-01-01

Insulin-loaded microspheres were prepared by alternating deposition film layers that were composed of insulin and poly(vinyl sulfate) potassium on the surface of poly(lactic acid) (PLA) microspheres. The preparation of the insulin-loaded microspheres was optimized by an orthogonal test design, and the relationship between drug loading (DL) and film layers was studied. The particle size, DL and encapsulation efficiency of the obtained insulin-loaded microspheres with 10 films were 5.25 ± 0.15 µm, 111.33 ± 1.15 mg/g and 33.7 ± 0.19%, respectively. Following this, the physical characteristics of the insulin-loaded microspheres were investigated. The results from scanning electron microscopy and a laser particle size analyzer (LPSA) indicated the spherical morphology, rough surface and increasing particle sizes of the insulin-loaded microspheres, which were compared to those of PLA microspheres. An in vitro release study showed that the insulin-loaded microspheres were stable in HCl solution (pH 1.0) and released insulin slowly in phosphate-buffered solution (pH 6.8). Finally, the drug efficacy of the prepared insulin-loaded microspheres via oral administration was evaluated in rats with diabetes induced by streptozotocin, and an obvious dose-dependent hypoglycemic effect was observed. This preliminary data could illustrate the prospect of using microspheres for the oral delivery of insulin.

Preparation and properties of BSA-loaded microspheres based on multi-(amino acid) copolymer for protein delivery

PubMed Central

Chen, Xingtao; Lv, Guoyu; Zhang, Jue; Tang, Songchao; Yan, Yonggang; Wu, Zhaoying; Su, Jiacan; Wei, Jie

2014-01-01

A multi-(amino acid) copolymer (MAC) based on ω-aminocaproic acid, γ-aminobutyric acid, L-alanine, L-lysine, L-glutamate, and hydroxyproline was synthetized, and MAC microspheres encapsulating bovine serum albumin (BSA) were prepared by a double-emulsion solvent extraction method. The experimental results show that various preparation parameters including surfactant ratio of Tween 80 to Span 80, surfactant concentration, benzyl alcohol in the external water phase, and polymer concentration had obvious effects on the particle size, morphology, and encapsulation efficiency of the BSA-loaded microspheres. The sizes of BSA-loaded microspheres ranged from 60.2 μm to 79.7 μm, showing different degrees of porous structure. The encapsulation efficiency of BSA-loaded microspheres also ranged from 38.8% to 50.8%. BSA release from microspheres showed the classic biphasic profile, which was governed by diffusion and polymer erosion. The initial burst release of BSA from microspheres at the first week followed by constant slow release for the next 7 weeks were observed. BSA-loaded microspheres could degrade gradually in phosphate buffered saline buffer with pH value maintained at around 7.1 during 8 weeks incubation, suggesting that microsphere degradation did not cause a dramatic pH drop in phosphate buffered saline buffer because no acidic degradation products were released from the microspheres. Therefore, the MAC microspheres might have great potential as carriers for protein delivery. PMID:24855351

Synthesis and catalytic performance of SiO2@Ni and hollow Ni microspheres

NASA Astrophysics Data System (ADS)

Liu, Xin; Liu, Yanhua; Shi, Xueting; Yu, Zhengyang; Feng, Libang

2016-11-01

Nickel (Ni) catalyst has been widely used in catalytic reducing reactions such as catalytic hydrogenation of organic compounds and catalytic reduction of organic dyes. However, the catalytic efficiency of pure Ni is low. In order to improve the catalytic performance, Ni nanoparticle-loaded microspheres can be developed. In this study, we have prepared Ni nanoparticle-loaded microspheres (SiO2@Ni) and hollow Ni microspheres using two-step method. SiO2@Ni microspheres with raspberry-like morphology and core-shell structure are synthesized successfully using SiO2 microsphere as a template and Ni2+ ions are adsorbed onto SiO2 surfaces via electrostatic interaction and then reduced and deposited on surfaces of SiO2 microspheres. Next, the SiO2 cores are removed by NaOH etching and the hollow Ni microspheres are prepared. The NaOH etching time does no have much influence on the crystal structure, shape, and surface morphology of SiO2@Ni; however, it can change the phase composition evidently. The hollow Ni microspheres are obtained when the NaOH etching time reaches 10 h and above. The as-synthesized SiO2@Ni microspheres exhibit much higher catalytic performance than the hollow Ni microspheres and pure Ni nanoparticles in the catalytic reduction of methylene blue. Meanwhile, the SiO2@Ni catalyst has high stability and hence it can be recycled for reuse.

Size effect of optical silica microsphere pressure sensors

NASA Astrophysics Data System (ADS)

Jiao, Xinbing; Hao, Ruirui; Pan, Qian; Zhao, Xinwei; Bai, Xue

2018-07-01

Two types of optical pressure sensors with silica microspheres are proposed. The size effect of optical silica microsphere pressure sensors is studied by using a single-wavelength laser beam and polarimeters. The silica microspheres with diameters of 1.0 μm, 1.5 μm and 2.0 μm are prepared on garnet substrates by a self-assembly method. The pressure and the optical properties of the silica microspheres are measured by a resistance strain sensor and Thorlabs Stokes polarimeters as a function of the external direct current (DC) voltage. The optical silica microsphere sensor in transmission mode is suitable for pressure measuring. The results show that the pressure increases, while the diameter of the silica microspheres decreases. The maximum internal pressure can reach up to 7.3 × 107 Pa when the diameter of the silica microspheres is 1.0 μm.

Identification of target proteins of mangiferin in mice with acute lung injury using functionalized magnetic microspheres based on click chemistry.

PubMed

Wang, Jiajia; Nie, Yan; Li, Yunjuan; Hou, Yuanyuan; Zhao, Wei; Deng, Jiagang; Wang, Peng George; Bai, Gang

2015-11-18

Prevention of the occurrence and development of inflammation is a vital therapeutic strategy for treating acute lung injury (ALI). Increasing evidence has shown that a wealth of ingredients from natural foods and plants have potential anti-inflammatory activity. In the present study, mangiferin, a natural C-glucosyl xanthone that is primarily obtained from the peels and kernels of mango fruits and the bark of the Mangifera indica L. tree, alleviated the inflammatory responses in lipopolysaccharide (LPS)-induced ALI mice. Mangiferin-modified magnetic microspheres (MMs) were developed on the basis of click chemistry to capture the target proteins of mangiferin. Mass spectrometry and molecular docking identified 70 kDa heat-shock protein 5 (Hspa5) and tyrosine 3-monooxygenase (Ywhae) as mangiferin-binding proteins. Furthermore, an enzyme-linked immunosorbent assay (ELISA) indicated that mangiferin exerted its anti-inflammatory effect by binding Hspa5 and Ywhae to suppress downstream mitogen-activated protein kinase (MAPK) signaling pathways. Thoroughly revealing the mechanism and function of mangiferin will contribute to the development and utilization of agricultural resources from M. indica L.

Fractionation of Magnetic Microspheres in a Microfluidic Spiral: Interplay between Magnetic and Hydrodynamic Forces

PubMed Central

Hayden, M. E.; Häfeli, U. O.

2017-01-01

Magnetic forces and curvature-induced hydrodynamic drag have both been studied and employed in continuous microfluidic particle separation and enrichment schemes. Here we combine the two. We investigate consequences of applying an outwardly directed magnetic force to a dilute suspension of magnetic microspheres circulating in a spiral microfluidic channel. This force is realized with an array of permanent magnets arranged to produce a magnetic field with octupolar symmetry about the spiral axis. At low flow rates particles cluster around an apparent streamline of the flow near the outer wall of the turn. At high flow rates this equilibrium is disrupted by the induced secondary (Dean) flow and a new equilibrium is established near the inner wall of the turn. A model incorporating key forces involved in establishing these equilibria is described, and is used to extract quantitative information about the magnitude of local Dean drag forces from experimental data. Steady-state fractionation of suspensions by particle size under the combined influence of magnetic and hydrodynamic forces is demonstrated. Extensions of this work could lead to new continuous microscale particle sorting and enrichment processes with improved fidelity and specificity. PMID:28107472

Fabrication of Poly(styrene-co-maleic anhydride)@Ag Spheres with High Surface Charge Intensity and their Self-Assembly into Photonic Crystal Films.

PubMed

Bi, Jiajie; Fan, Genrui; Wu, Suli; Su, Xin; Xia, Hongbo; Zhang, Shu-Fen

2017-10-01

Herein, we developed a method to prepare monodisperse poly(styrene-co-maleic anhydride)@Ag (PSMA@Ag) core-shell microspheres with high surface charge intensity by using an in situ reduction method. In this method, ethylenediamine tetraacetic acid tetrasodium salt (Na 4 EDTA) was used as a reducing agent to promote the growth of Ag, and at the same time endowed the PSMA@Ag spheres with a surface charge. The monodispersity of PSMA and PSMA@Ag and the ordered array of the photonic crystal films were characterized by using SEM. The formation of Ag nanoparticles was confirmed by using TEM, HR-TEM, and XRD characterizations. Due to the existence of surface charges, the obtained PSMA@Ag microspheres easily self-assembled to form photonic crystal structures. In addition, the surface-enhanced Raman scattering (SERS) activity of the PSMA@Ag photonic crystal films was evaluated by detecting the signal from Raman probe molecules, 4-aminothiophenol (4-ATP). The PSMA@Ag photonic crystal films exhibited a high SERS effect, a low detection limit of up to 10 -8 for 4-ATP, good uniformity, and reproducibility.

The 400 microsphere per piece "rule" does not apply to all blood flow studies.

PubMed

Polissar, N L; Stanford, D C; Glenny, R W

2000-01-01

Microsphere experiments are useful in measuring regional organ perfusion as well as heterogeneity of blood flow within organs and correlation of perfusion between organ pieces at different time points. A 400 microspheres/piece "rule" is often used in planning experiments or to determine whether experiments are valid. This rule is based on the statement that 400 microspheres must lodge in a region for 95% confidence that the observed flow in the region is within 10% of the true flow. The 400 microspheres precision rule, however, only applies to measurements of perfusion to a single region or organ piece. Examples, simulations, and an animal experiment were carried out to show that good precision for measurements of heterogeneity and correlation can be obtained from many experiments with <400 microspheres/piece. Furthermore, methods were developed and tested for correcting the observed heterogeneity and correlation to remove the Poisson "noise" due to discrete microsphere measurements. The animal experiment shows adjusted values of heterogeneity and correlation that are in close agreement for measurements made with many or few microspheres/piece. Simulations demonstrate that the adjusted values are accurate for a variety of experiments with far fewer than 400 microspheres/piece. Thus the 400 microspheres rule does not apply to many experiments. A "rule of thumb" is that experiments with a total of at least 15,000 microspheres, for all pieces combined, are very likely to yield accurate estimates of heterogeneity. Experiments with a total of at least 25,000 microspheres are very likely to yield accurate estimates of correlation coefficients.

Thermal oxidation synthesis hollow MoO{sub 3} microspheres and their applications in lithium storage and gas-sensing

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

Zhao, Xinyu; School of Petrochemical Engineering, Shenyang University of Technology, Liaoyang 111003; Cao, Minhua, E-mail: caomh@bit.edu.cn

2013-06-01

Graphical abstract: MoO{sub 3} hollow microspheres were synthesized via a facile and template-free solvothermal route and subsequent heat treatment in air. The MoO{sub 3} hollow microspheres exhibit an improved lithium storage and gas-sensing performance. Highlights: ► Hollow MoO{sub 3} microspheres were synthesized by thermal oxidation of hollow MoO{sub 2}. ► The MoO{sub 3} hollow microspheres have a relatively high specific surface area. ► The MoO{sub 3} hollow microspheres exhibit improved lithium storage performance. ► The MoO{sub 3} hollow microspheres show good responses to ammonia gas. - Abstract: In this paper, MoO{sub 3} hollow microspheres were synthesized via a facile andmore » template-free solvothermal route and subsequent heat treatment in air. The MoO{sub 3} hollow microspheres have a relatively high specific surface area, and with such a feature, the as-synthesized MoO{sub 3} hollow microspheres have potential applications in Li-ion battery and gas-sensor. When tested as a Li-storage anode material, the MoO{sub 3} hollow microspheres show a higher discharge capacity of 1377.1 mA h g{sup −1} in the first discharge and a high reversible capacity of 780 mA h g{sup −1} after 100 cycles at a rate of 1 C. Furthermore, as a gas sensing material, the MoO{sub 3} hollow microspheres exhibit an improved sensitivity and short response/recovery time to trace levels of ammonia gas.« less

Preparation of monodisperse PEG hydrogel composite microspheres via microfluidic chip with rounded channels

NASA Astrophysics Data System (ADS)

Yu, Bing; Cong, Hailin; Liu, Xuesong; Ren, Yumin; Wang, Jilei; Zhang, Lixin; Tang, Jianguo; Ma, Yurong; Akasaka, Takeshi

2013-09-01

An effective microfluidic method to fabricate monodisperse polyethylene glycol (PEG) hydrogel composite microspheres with tunable dimensions and properties is reported in this paper. A T-junction microfluidic chip equipped with rounded channels and online photopolymerization system is applied for the microsphere microfabrication. The shape and size of the microspheres are well controlled by the rounded channels and PEG prepolymer/silicon oil flow rate ratios. The obtained PEG/aspirin composite microspheres exhibit a sustained release of aspirin for a wide time range; the obtained PEG/Fe3O4 nanocomposite microspheres exhibit excellent magnetic properties; and the obtained binary PEG/dye composite microspheres show the ability to synchronously load two functional components in the same peanut-shaped or Janus hydrogel particles.

Fabrication of glass microspheres with conducting surfaces

DOEpatents

Elsholz, William E.

1984-01-01

A method for making hollow glass microspheres with conducting surfaces by adding a conducting vapor to a region of the glass fabrication furnace. As droplets or particles of glass forming material pass through multiple zones of different temperature in a glass fabrication furnace, and are transformed into hollow glass microspheres, the microspheres pass through a region of conducting vapor, forming a conducting coating on the surface of the microspheres.

Fabrication of glass microspheres with conducting surfaces

DOEpatents

Elsholz, W.E.

1982-09-30

A method for making hollow glass microspheres with conducting surfaces by adding a conducting vapor to a region of the glass fabrication furnace. As droplets or particles of glass forming material pass through multiple zones of different temperature in a glass fabrication furnace, and are transformed into hollow glass microspheres, the microspheres pass through a region of conducting vapor, forming a conducting coating on the surface of the microspheres.

Polarization Dependent Whispering Gallery Modes in Microspheres

NASA Technical Reports Server (NTRS)

Adamovsky, Grigory (Inventor); Wrbanek, Susan Y. (Inventor)

2016-01-01

A tunable resonant system is provided and includes a microsphere that receives an incident portion of a light beam generated via a light source, the light beam having a fundamental mode, a waveguide medium that transmits the light beam from the light source to the microsphere, and a polarizer disposed in a path of the waveguide between the light source and the microsphere. The incident portion of the light beam creates a fundamental resonance inside the microsphere. A change in a normalized frequency of the wavelength creates a secondary mode in the waveguide and the secondary mode creates a secondary resonance inside the microsphere.

Evaluation of an Extended-Release, Abuse-Deterrent, Microsphere-in-Capsule Analgesic for the Management of Patients with Chronic Pain With Dysphagia (CPD).

PubMed

Fleming, Alison B; Carlson, Douglas R; Varanasi, Ravi K; Grima, Michael; Mayock, Stephen P; Saim, Said; Kopecky, Ernest A

2016-03-01

Patients who have chronic pain with dysphagia (difficulty swallowing) (CPD) often have difficulty taking oral medication and, as such, alter their medications by crushing or chewing in an attempt to make it easier to swallow. Such manipulation of currently marketed, extended-release (ER) opioid analgesics can significantly alter the pharmacokinetic (PK) properties of the formulations, resulting in poor treatment outcome or serious adverse events. There is an unmet medical need for oral ER opioid formulations suitable for patients with CPD. The primary objectives of this study were to conduct in vitro studies to evaluate alternate means of administration of a new, extended-release (ER), abuse-deterrent, microsphere-in-capsule formulation of oxycodone for patients with CPD. Specifically, these studies investigated the in vitro equivalence of drug release rates from Oxycodone DETERx® ER intact capsules (control condition) and administration via alternate modes-opening the capsule and sprinkling the microspheres onto soft foods or administration through enteral tubes. Secondary objectives were to compare alternate modes of administration of Oxycodone DETERx® to a commercially available ER-morphine product. Soft food study: Oxycodone DETERx® microspheres were sprinkled onto and mixed with several soft foods (ie, applesauce, vanilla pudding, strawberry jam, yogurt, and vanilla ice cream); the effect of drug contact time (0, 30, and 60 minutes) on drug release was studied. Enteral tube study: Oxycodone DETERx® microspheres were administered through varying sizes of nasogastric (10 and 12 Fr.) tubes and a 16 Fr. gastrostomy tube using 5 different delivery vehicles (ie, water, liquid nutritional feeds [Jevity®, Ensure®], and milk [whole milk and 2% milk]). Drug release rate was characterized using a standard in vitro dissolution methodology; dissolution of intact Oxycodone DETERx® capsules served as the control for both the soft food and enteral tube studies. Oxycodone concentration was measured using a standardized high-performance liquid chromatography (HPLC) assay. Similarity factor (f2) analysis was used to compare similarity of the dissolution profiles of test and control conditions. The mean dissolution profile of Oxycodone DETERx® microspheres sprinkled onto and mixed with each of the soft foods were similar (f2 > 50) to that of the control. Study drug-food contact time did not impact dissolution profiles. The dissolution data obtained from Oxycodone DETERx® microspheres passed through enteral feeding tubes of varying sizes were similar (f2 > 50) to that of the control. Unlike a marketed morphine sulfate ER pellet formulation, Oxycodone DETERx® did not clog any of the studied enteral tubes. A new ER, abuse-deterrent, microsphere-in-capsule formulation of oxycodone can be administered by sprinkling onto soft food without affecting the drug release profile of the formulation. The formulation can also be administered directly via enteral tubes without affecting drug release and without clogging enteral tubes. Oxycodone DETERx® may offer physicians and patients with CPD an alternate treatment option, especially in those patients who have dysphagia or an aversion to swallowing monolithic tablet/capsule formulations and for whom analgesic patches or other opioid formulations are not a viable therapeutic option. © 2015 World Institute of Pain.

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

Chen, Limiao, E-mail: chenlimiao@csu.edu.cn; College of Chemistry and Chemical Engineering, Central South University, Changsha 410083; Wu, Min

The semiconductor nanostructures decorated with noble metals have attracted increasing attention due to their interesting physical and chemical properties. In this work, urchin-like monoclinic (m-) LaVO{sub 4} microspheres were prepared by a hydrothermal method and used as a template to fabricate Ag nanoparticle-decorated m-LaVO{sub 4} composites. The morphology and structure were characterized by transmission electron microscope, high-resolution transmission electron microscope, scanning electron microscope, and energy-dispersive X-ray. It was found that Ag nanoparticles with narrow size distribution were uniformly loaded on urchin-like m-LaVO{sub 4} microspheres, and the resulted composite microspheres showed distinct surface plasmon absorption band compared to pure m-LaVO{sub 4}more » microspheres. Photocatalytic activities of as-prepared samples were examined by studying the degradation of methyl orange solutions under visible-light irradiation (> 400 nm). Results clearly showed that urchin-like m-LaVO{sub 4}/Ag microspheres possess much higher photocatalytic activity than pure m-LaVO{sub 4} microspheres and P25. - Highlights: • m-LaVO{sub 4}/Ag composites microspheres were fabricated by a hydrothermal method. • m-LaVO{sub 4} microspheres show higher photocatalytic activity than m-LaVO{sub 4} microspheres. • m-LaVO{sub 4}/Ag microspheres exhibit a good stability.« less

Multiplexed and Microparticle-based Analyses: Quantitative Tools for the Large-Scale Analysis of Biological Systems

PubMed Central

Nolan, John P.; Mandy, Francis

2008-01-01

While the term flow cytometry refers to the measurement of cells, the approach of making sensitive multiparameter optical measurements in a flowing sample stream is a very general analytical approach. The past few years have seen an explosion in the application of flow cytometry technology for molecular analysis and measurements using micro-particles as solid supports. While microsphere-based molecular analyses using flow cytometry date back three decades, the need for highly parallel quantitative molecular measurements that has arisen from various genomic and proteomic advances has driven the development in particle encoding technology to enable highly multiplexed assays. Multiplexed particle-based immunoassays are now common place, and new assays to study genes, protein function, and molecular assembly. Numerous efforts are underway to extend the multiplexing capabilities of microparticle-based assays through new approaches to particle encoding and analyte reporting. The impact of these developments will be seen in the basic research and clinical laboratories, as well as in drug development. PMID:16604537

Development and optimization of enteric coated mucoadhesive microspheres of duloxetine hydrochloride using 3(2) full factorial design.

PubMed

Setia, Anupama; Kansal, Sahil; Goyal, Naveen

2013-07-01

Microspheres constitute an important part of oral drug delivery system by virtue of their small size and efficient carrier capacity. However, the success of these microspheres is limited due to their short residence time at the site of absorption. The objective of the present study was to formulate and systematically evaluate in vitro performance of enteric coated mucoadhesive microspheres of duloxetine hydrochloride (DLX), an acid labile drug. DLX microspheres were prepared by simple emulsification phase separation technique using chitosan as carrier and glutaraldehyde as a cross-linking agent. Microspheres prepared were coated with eudragit L-100 using an oil-in-oil solvent evaporation method. Eudragit L-100was used as enteric coating polymer with the aim to release the drug in small intestine The microspheres prepared were characterized by particle size, entrapment efficiency, swelling index (SI), mucoadhesion time, in vitro drug release and surface morphology. A 3(2) full factorial design was employed to study the effect of independent variables polymer-to-drug ratio (X1) and stirring speed (X2) on dependent variables, particle size, entrapment efficiency, SI, in vitro mucoadhesion and drug release up to 24 h (t24). Microspheres formed were discrete, spherical and free flowing. The microspheres exhibited good mucoadhesive property and also showed high percentage entrapment efficiency. The microspheres were able to sustain the drug release up to 24 h. Thus, the prepared enteric coated mucoadhesive microspheres may prove to be a potential controlled release formulation of DLX for oral administration.

Preparation and evaluation of 188 Re sulfide colloidal nanoparticles loaded biodegradable poly (L-lactic acid) microspheres for radioembolization therapy.

PubMed

Jamre, Mina; Shamsaei, Mojtaba; Erfani, Mostafa; Sadjadi, Sodeh; Ghannadi Maragheh, Mohammad

2018-04-12

Radioembolization with radioactive microspheres has been an effective method for the treatment of liver lesions. The aim of this study was to prepare carrier-free 188 Re loaded poly (L-lactic acid) (PLLA) microspheres through 188 Re sulfide colloidal nanoparticles ( 188 Re-SC nanoparticles). The formation of 188 Re-SC nanoparticles was confirmed by ultraviolet-visible spectrophotometry. The labeling yield of 188 Re-SC nanoparticles was verified using the RTLC method. Effects of synthesis parameters on morphology and size of prepared 188 Re-sulfide colloidal-PLLA microspheres ( 188 Re-SC-PLLA microspheres) were studied by scanning electron microscopy. In vitro stability of 188 Re-SC-PLLA microspheres was investigated in normal saline at room temperature and in human serum at 37°C. In vivo distribution studies and gamma camera imaging were performed in healthy BALB/c mice. The microspheres could be prepared with sizes between 13 and 48 μm (modal value 29 μm) and radiolabeling efficiency >99%. After incubation, the microspheres were found stable in vitro up to 72 hours. The biodistribution after intravenous injection in healthy BALB/c mice showed high accumulation in lung as a first capture pathway organ for microsphere followed by great retention over 48 hours for these microspheres. These data show that 188 Re-SC-PLLA microspheres are suitable candidate for clinical studies. Copyright © 2018 John Wiley & Sons, Ltd.

Exploring target-specific primer extension in combination with a bead-based suspension array for multiplexed detection and typing using Streptococcus suis as a model pathogen

PubMed Central

van der Wal, Fimme J.; Achterberg, René P.; van Solt-Smits, Conny; Bergervoet, Jan H. W.; de Weerdt, Marjanne; Wisselink, Henk J.

2017-01-01

We investigated the feasibility of an assay based on target-specific primer extension, combined with a suspension array, for the multiplexed detection and typing of a veterinary pathogen in animal samples, using Streptococcus suis as a model pathogen. A procedure was established for simultaneous detection of 6 S. suis targets in pig tonsil samples (i.e., 4 genes associated with serotype 1, 2, 7, or 9, the generic S. suis glutamate dehydrogenase gene [gdh], and the gene encoding the extracellular protein factor [epf]). The procedure was set up as a combination of protocols: DNA isolation from porcine tonsils, a multiplex PCR, a multiplex target-specific primer extension, and finally a suspension array as the readout. The resulting assay was compared with a panel of conventional PCR assays. The proposed multiplex assay can correctly identify the serotype of isolates and is capable of simultaneous detection of multiple targets in porcine tonsillar samples. The assay is not as sensitive as the current conventional PCR assays, but with the correct sampling strategy, the assay can be useful for screening pig herds to establish which S. suis serotypes are circulating in a pig population. PMID:28980519

Microspheres and their methods of preparation

DOEpatents

Bose, Anima B; Yang, Junbing

2015-03-24

Carbon microspheres are doped with boron to enhance the electrical and physical properties of the microspheres. The boron-doped carbon microspheres are formed by a CVD process in which a catalyst, carbon source and boron source are evaporated, heated and deposited onto an inert substrate.

Preparation and evaluation of sustained release loxoprofen loaded microspheres.

PubMed

Venkatesan, P; Manavalan, R; Valliappan, K

2011-06-01

The aim of present study was to formulate and evaluate the loxoprofen loaded Sustained release microspheres by emulsion solvent evaporation technique. Ethylcellulose, a biocompatible polymer is used as the retardant material. The effects of process conditions such as drug loading, polymer type and solvent type on the characteristics of microspheres were investigated. The prepared microspheres were characterized for their particle size and drug loading and drug release. The in-vitro release studies were carried out in phosphate buffer at pH 7.4. The prepared microspheres were white, free flowing and spherical in shape. The drug-loaded microspheres showed 71.2% of entrapment and the in-vitro release studies showed that Loxoprofen microspheres of 1:3 ratios showed better sustained effect over a period of 8 hours.

Preparation and evaluation of sustained release loxoprofen loaded microspheres

PubMed Central

Venkatesan, P.; Manavalan, R.; Valliappan, K.

2011-01-01

The aim of present study was to formulate and evaluate the loxoprofen loaded Sustained release microspheres by emulsion solvent evaporation technique. Ethylcellulose, a biocompatible polymer is used as the retardant material. The effects of process conditions such as drug loading, polymer type and solvent type on the characteristics of microspheres were investigated. The prepared microspheres were characterized for their particle size and drug loading and drug release. The in-vitro release studies were carried out in phosphate buffer at pH 7.4. The prepared microspheres were white, free flowing and spherical in shape. The drug-loaded microspheres showed 71.2% of entrapment and the in-vitro release studies showed that Loxoprofen microspheres of 1:3 ratios showed better sustained effect over a period of 8 hours PMID:24826017

Mesoporous metal oxide microsphere electrode compositions and their methods of making

DOEpatents

Paranthaman, Mariappan Parans; Liu, Hansan; Brown, Gilbert M.; Sun, Xiao-Guang; Bi, Zhonghe

2016-12-06

Compositions and methods of making are provided for mesoporous metal oxide microspheres electrodes. The mesoporous metal oxide microsphere compositions comprise (a) microspheres with an average diameter between 200 nanometers (nm) and 10 micrometers (.mu.m); (b) mesopores on the surface and interior of the microspheres, wherein the mesopores have an average diameter between 1 nm and 50 nm and the microspheres have a surface area between 50 m.sup.2/g and 500 m.sup.2/g. The methods of making comprise forming composite powders. The methods may also comprise refluxing the composite powders in a basic solution to form an etched powder, washing the etched powder with an acid to form a hydrated metal oxide, and heat-treating the hydrated metal oxide to form mesoporous metal oxide microspheres.

Mobilization of microspheres from a fractured soil during intermittent infiltration events

USGS Publications Warehouse

Mohanty, Sanjay; Bulicek, Mark; Metge, David W.; Harvey, Ronald W.; Ryan, Joseph N.; Boehm, Alexandria B.

2015-01-01

Pathogens or biocolloids mobilized in the vadose zone may consequently contaminate groundwater. We found that microspheres were mobilized from a fractured soil during intermittent rainfall and the mobilization was greater when the microsphere size was larger and when the soil had greater water permeability.The vadose zone filters pathogenic microbes from infiltrating water and consequently protects the groundwater from possible contamination. In some cases, however, the deposited microbes may be mobilized during rainfall and migrate into the groundwater. We examined the mobilization of microspheres, surrogates for microbes, in an intact core of a fractured soil by intermittent simulated rainfall. Fluorescent polystyrene microspheres of two sizes (0.5 and 1.8 mm) and Br− were first applied to the core to deposit the microspheres, and then the core was subjected to three intermittent infiltration events to mobilize the deposited microspheres. Collecting effluent samples through a 19-port sampler at the base of the core, we found that water flowed through only five ports, and the flow rates varied among the ports by a factor of 12. These results suggest that flow paths leading to the ports had different permeabilities, partly due to macropores. Although 40 to 69% of injected microspheres were retained in the core during their application, 12 to 30% of the retained microspheres were mobilized during three intermittent infiltration events. The extent of microsphere mobilization was greater in flow paths with greater permeability, which indicates that macropores could enhance colloid mobilization during intermittent infiltration events. In all ports, the 1.8-mm microspheres were mobilized to a greater extent than the 0.5-mm microspheres, suggesting that larger colloids are more likely to mobilize. These results are useful in assessing the potential of pathogen mobilization and colloid-facilitated transport of contaminants in the subsurface under natural infiltration events.

Polymer-coated albumin microspheres as carriers for intravascular tumour targeting of cisplatin.

PubMed

Verrijk, R; Smolders, I J; McVie, J G; Begg, A C

1991-01-01

We used a poly-lactide-co-glycolide polymer (PLAGA 50:50) to formulate cisplatin (cDDP) into microspheres designed for intravascular administration. Two systems were developed. PLAGA-coated albumin microspheres and microspheres consisting of PLAGA only. PLAGA-coated microspheres displayed a mean diameter of 31.8 +/- 0.9 microns and a payload of 7.5% cDDP (w/w). Solid PLAGA microspheres exhibited a mean diameter of 19.4 +/- 0.6 microns and a payload of 20% cDDP. Release characteristics and in vitro effects on L1210 leukemia and B16 melanoma cell lines were investigated. Both types of microsphere overcame the initial rapid release of cDDP (burst effect), and PLAGA-coated albumin microspheres also showed a lag phase of approximately 30 min before cDDP release began. PLAGA-coated albumin microspheres released most of their payload through diffusion, and the coating eventually cracked after 7 days' incubation in saline supplemented with 0.1% Tween at 37 degrees C, enabling the release of any cDDP remaining. Effects of platinum, pre-released from PLAGA-coated albumin microspheres on the in vitro growth of L1210 cells were comparable with those of standard formulations (dissolved) of cDDP. Material released from non-drug-loaded PLAGA microspheres had no effect on L1210 cell growth, suggesting the absence of cytotoxic compounds in the matrix. The colony-forming ability of B16 cells was also equally inhibited by standard cDDP and pre-released drug. These studies show that formulation of cDDP in PLAGA-based microspheres prevents the rapid burst effect of cDDP seen in previous preparations and offers an improved system of administration for hepatic artery infusion or adjuvant therapy, enabling better clinical handling and the promise of a higher ratio of tumour tissue to normal tissue.

High-resolution Antibody Array Analysis of Childhood Acute Leukemia Cells*

PubMed Central

Kanderova, Veronika; Kuzilkova, Daniela; Stuchly, Jan; Vaskova, Martina; Brdicka, Tomas; Fiser, Karel; Hrusak, Ondrej; Lund-Johansen, Fridtjof

2016-01-01

Acute leukemia is a disease pathologically manifested at both genomic and proteomic levels. Molecular genetic technologies are currently widely used in clinical research. In contrast, sensitive and high-throughput proteomic techniques for performing protein analyses in patient samples are still lacking. Here, we used a technology based on size exclusion chromatography followed by immunoprecipitation of target proteins with an antibody bead array (Size Exclusion Chromatography-Microsphere-based Affinity Proteomics, SEC-MAP) to detect hundreds of proteins from a single sample. In addition, we developed semi-automatic bioinformatics tools to adapt this technology for high-content proteomic screening of pediatric acute leukemia patients. To confirm the utility of SEC-MAP in leukemia immunophenotyping, we tested 31 leukemia diagnostic markers in parallel by SEC-MAP and flow cytometry. We identified 28 antibodies suitable for both techniques. Eighteen of them provided excellent quantitative correlation between SEC-MAP and flow cytometry (p < 0.05). Next, SEC-MAP was applied to examine 57 diagnostic samples from patients with acute leukemia. In this assay, we used 632 different antibodies and detected 501 targets. Of those, 47 targets were differentially expressed between at least two of the three acute leukemia subgroups. The CD markers correlated with immunophenotypic categories as expected. From non-CD markers, we found DBN1, PAX5, or PTK2 overexpressed in B-cell precursor acute lymphoblastic leukemias, LAT, SH2D1A, or STAT5A overexpressed in T-cell acute lymphoblastic leukemias, and HCK, GLUD1, or SYK overexpressed in acute myeloid leukemias. In addition, OPAL1 overexpression corresponded to ETV6-RUNX1 chromosomal translocation. In summary, we demonstrated that SEC-MAP technology is a powerful tool for detecting hundreds of proteins in clinical samples obtained from pediatric acute leukemia patients. It provides information about protein size and reveals differences in protein expression between particular leukemia subgroups. Forty-seven of SEC-MAP identified targets were validated by other conventional method in this study. PMID:26785729

Preparation and characterization of monodisperse large-porous silica microspheres as the matrix for protein separation.

PubMed

Xia, Hongjun; Wan, Guangping; Zhao, Junlong; Liu, Jiawei; Bai, Quan

2016-11-04

High performance liquid chromatography (HPLC) is a kind of efficient separation technology and has been used widely in many fields. Micro-sized porous silica microspheres as the most popular matrix have been used for fast separation and analysis in HPLC. In this paper, the monodisperse large-porous silica microspheres with controllable size and structure were successfully synthesized with polymer microspheres as the templates and characterized. First, the poly(glycidyl methacrylate-co-ethyleneglycol dimethacrylate) microspheres (P GMA-EDMA ) were functionalized with tetraethylenepentamine (TEPA) to generate amino groups which act as a catalyst in hydrolysis of tetraethyl orthosilicate (TEOS) to form Si-containing low molecular weight species. Then the low molecular weight species diffused into the functionalized P GMA-EDMA microspheres by induction force of the amino groups to form polymer/silica hybrid microspheres. Finally, the organic polymer templates were removed by calcination, and the large-porous silica microspheres were obtained. The compositions, morphology, size distribution, specific surface area and pore size distribution of the porous silica microspheres were characterized by infrared analyzer, scanning-electron microscopy, dynamic laser scattering, the mercury intrusion method and thermal gravimetric analysis, respectively. The results show that the agglomeration of the hybrid microspheres can be overcome when the templates were functionalized with TEPA as amination reagent, and the yield of 95.7% of the monodisperse large-porous silica microspheres can be achieved with high concentration of polymer templates. The resulting large-porous silica microspheres were modified with octadecyltrichlorosilane (ODS) and the chromatographic evaluation was performed by separating the proteins and the digest of BSA. The baseline separation of seven kinds of protein standards was achieved, and the column delivered a better performance when separating BSA digests comparing with the commercial one currently available. The high column efficiency and good reproducibility present that the large-porous silica microspheres obtained can be used as a matrix for peptide and protein separation. Copyright © 2016 Elsevier B.V. All rights reserved.

Albumin microspheres as an ocular delivery system for pilocarpine nitrate.

PubMed

Rathod, Sudha; Deshpande, S G

2008-01-01

Pilocarpine nitrate loaded egg albumin microspheres were prepared by thermal denaturation process in the size range of 1-12 mum. A series of batches were prepared to study factors, which may affect the size and entrapment efficiency of drug in microspheres and optimized the process. Drug loaded microspheres so obtained were evaluated for their size, entrapment efficiency, release rate and biological response. Electron photomicrographs were taken (8000X) to study the morphological characteristics of microspheres. The entrapment and encapsulation of pilocarpine after process optimization was found to be 82.63% and 62.5% respectively. In vitro dissolution rate studies revealed that the release of drug from the microspheres followed spherical matrix mechanism. Biological response of microspheric suspension was measured by reduction in intraocular pressure in albino rabbit eyes and compared with marketed eye drops. Various pharmacokinetic parameters viz. onset of action, duration of action, Tmax and AUC were studied. A measurable difference was found in the mean miotic response, duration and AUC of pilocarpine nitrate microspheric suspension.

Acrolein Microspheres Are Bonded To Large-Area Substrates

NASA Technical Reports Server (NTRS)

Rembaum, Alan; Yen, Richard C. K.

1988-01-01

Reactive cross-linked microspheres produced under influence of ionizing radiation in aqueous solutions of unsaturated aldehydes, such as acrolein, with sodium dodecyl sulfate. Diameters of spheres depend on concentrations of ingredients. If polystyrene, polymethylmethacrylate, or polypropylene object immersed in solution during irradiation, microspheres become attached to surface. Resulting modified surface has grainy coating with reactivity similar to free microspheres. Aldehyde-substituted-functional microspheres react under mild conditions with number of organic reagents and with most proteins. Microsphere-coated macrospheres or films used to immobilize high concentrations of proteins, enzymes, hormones, viruses, cells, and large number of organic compounds. Applications include separation techniques, clinical diagnostic tests, catalytic processes, and battery separators.

Drug-loaded poly (ε-caprolactone)/Fe3O4 composite microspheres for magnetic resonance imaging and controlled drug delivery

NASA Astrophysics Data System (ADS)

Wang, Guangshuo; Zhao, Dexing; Li, Nannan; Wang, Xuehan; Ma, Yingying

2018-06-01

In this study, poly (ε-caprolactone) (PCL) microspheres loading magnetic Fe3O4 nanoparticles and anti-cancer drug of doxorubicin hydrochloride (DOX) were successfully prepared by a modified solvent-evaporation method. The obtained magnetic composite microspheres exhibited dual features of magnetic resonance imaging and controlled drug delivery. The morphology, structure, thermal behavior and magnetic properties of the drug-loaded magnetic microspheres were investigated in detail by SEM, XRD, DSC and SQUID. The obtained composite microspheres showed superparamagnetic behavior and T2-weighted enhancement effect. The drug loading, encapsulation efficiency, releasing behavior and in vitro cytotoxicity of the drug-loaded composite microspheres were systematically investigated. It was found that the values of drug loading and encapsulation efficiency were 36.7% and 25.8%, respectively. The composite microspheres were sensitive to pH and released in a sustained way, and both the release curves under various pH conditions (4.0 and 7.4) were well satisfied with the biphase kinetics function. In addition, the magnetic response of the drug-loaded microspheres was studied and the results showed that the composite microspheres had a good magnetic stability and strong targeting ability.

Eudragit-coated dextran microspheres of 5-fluorouracil for site-specific delivery to colon.

PubMed

Rai, Gopal; Yadav, Awesh K; Jain, Narendra K; Agrawal, Govind P

2016-01-01

Objective of the present investigation was to prepare and evaluate the potential of enteric coated dextran microspheres for colon targeting of 5-fluorouracil (5-FU). Dextran microspheres were prepared by emulsification-crosslinking method and the formulation variables studied included different molecular weights of dextran, drug:polymer ratio, volume of crosslinking agent, stirring speed and time. Enteric coating (Eudragit S-100) of dextran microspheres was performed by oil-in-oil solvent evaporation method using different coat:core ratios (4:1 or 8:1). Uncoated and coated dextran microspheres were characterized by particle size, surface morphology, entrapment efficiency, DSC, in vitro drug release in the presence of dextranase and 2% rat cecal contents. The release study of 5-FU from coated dextran microspheres was pH dependent. No release was observed at acidic pH; however, the drug was released quickly where Eudragit starts solublizing there was continuous release of drug from the microspheres. Organ distribution study was suggested that coated dextran microspheres retard the release of drug in gastric and intestinal pH environment and released of drug from microspheres in colon due to the degradation of dextran by colonic enzymes.

Preparation and Characterization of Thermoresponsive Poly(N-isopropylacrylamide-co-acrylic acid)-Grafted Hollow Fe3O4/SiO2 Microspheres with Surface Holes for BSA Release

PubMed Central

Zhao, Jing; Zeng, Ming; Zheng, Kaiqiang; He, Xinhua; Xie, Minqiang; Fu, Xiaoyi

2017-01-01

Thermoresponsive P(NIPAM-AA)/Fe3O4/SiO2 microspheres with surface holes serving as carriers were prepared using p-Fe3O4/SiO2 microspheres with a thermoresponsive copolymer. The p-Fe3O4/SiO2 microspheres was obtained using a modified Pickering method and chemical etching. The surface pore size of p-Fe3O4/SiO2 microspheres was in the range of 18.3 nm~37.2 nm and the cavity size was approximately 60 nm, which are suitable for loading and transporting biological macromolecules. P(NIPAM-AA) was synthesized inside and outside of the p-Fe3O4/SiO2 microspheres via atom transfer radical polymerization of NIPAM, MBA and AA. The volume phase transition temperature (VPTT) of the specifically designed P(NIPAM-AA)/Fe3O4/SiO2 microspheres was 42.5 °C. The saturation magnetization of P(NIPAM-AA)/Fe3O4/SiO2 microspheres was 72.7 emu/g. The P(NIPAM-AA)/Fe3O4/SiO2 microspheres were used as carriers to study the loading and release behavior of BSA. This microsphere system shows potential for the loading of proteins as a drug delivery platform. PMID:28772770

Microsphere based improved sunscreen formulation of ethylhexyl methoxycinnamate.

PubMed

Gogna, Deepak; Jain, Sunil K; Yadav, Awesh K; Agrawal, G P

2007-04-01

Polymethylmethacrylate (PMMA) microspheres of ethylhexyl methoxycinnamate (EHM) were prepared by emulsion solvent evaporation method to improve its photostability and effectiveness as sunscreening agent. Process parameters like stirring speed and aqueous polyvinyl alcohol (PVA) concentration were analyzed in order to optimize the formulations. Shape and surface morphology of the microspheres were examined using scanning electron microscopy. Particle size of the microspheres was determined using laser diffraction particle size analyzer. The PMMA microspheres of EHM were incorporated in water-removable cream base. The in vitro drug release of EHM in pH 7.4 was performed using dialysis membrane. Thin layer chromatography was performed to determine photostability of EHM inside the microspheres. The formulations were evaluated for sun protection factor (SPF) and minimum erythema dose (MED) in albino rats. Cream base formulation containing microspheres prepared using EHM:PMMA in ratio of 1:3 (C(3)) showed slowest drug (EHM) release and those prepared with EHM: PMMA in ratio of 1:1 showed fastest release. The cream base formulations containing EHM loaded microspheres had shown better SPF (more than 16.0) as compared to formulation C(d) that contained 3% free EHM as sunscreen agent and showed SPF 4.66. These studies revealed that the incorporation of EHM loaded PMMA microspheres into cream base had greatly increased the efficacy of sunscreen formulation approximately four times. Further, photostability was also shown to be improved in PMMA microspheres.

POE/PLGA composite microspheres: formation and in vitro behavior of double walled microspheres.

PubMed

Yang, Yi-Yan; Shi, Meng; Goh, Suat-Hong; Moochhala, Shabbir M; Ng, Steve; Heller, Jorge

2003-03-07

The poly(ortho ester) (POE) and poly(D,L-lactide-co-glycolide) 50:50 (PLGA) composite microspheres were fabricated by a water-in-oil-in-water (w/o/w) double emulsion process. The morphology of the composite microspheres varied depending on POE content. When the POE content was 50, 60 or 70% in weight, the double walled microspheres with a dense core of POE and a porous shell of PLGA were formed. The formation of the double walled POE/PLGA microspheres was analysed. Their in vitro degradation behavior was characterized by scanning electron microscopy, gel permeation chromatography, Fourier-transform infrared microscopy and nuclear magnetic resonance spectroscopy (NMR). It was found that compared to the neat POE or PLGA microspheres, distinct degradation mechanism was achieved in the double walled POE/PLGA microspheres system. The degradation of the POE core was accelerated due to the acidic microenvironment produced by the hydrolysis of the outer PLGA layer. The formation of hollow microspheres became pronounced after the first week in vitro. 1H NMR spectra showed that the POE core was completely degraded after 4 weeks. On the other hand, the outer PLGA layer experienced slightly retarded degradation after the POE core disappeared. PLGA in the double walled microspheres kept more than 32% of its initial molecular weight over a period of 7 weeks.

Hydrothermal synthesis and photocatalytic performance of hierarchical Bi{sub 2}MoO{sub 6} microspheres using BiOI microspheres as self-sacrificing templates

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

Xu, Ming; Zhang, Wei-De, E-mail: zhangwd@scut.edu.cn

2015-07-15

Bi{sub 2}MoO{sub 6} hierarchical microspheres were successfully prepared through phase transformation from BiOI microspheres with the assistance of sodium citrate under hydrothermal condition. The possible formation mechanism for the conversion of BiOI to Bi{sub 2}MoO{sub 6} is discussed here. After being annealed at 300 °C for 2 h, the obtained Bi{sub 2}MoO{sub 6} microspheres exhibited remarkably enhanced photocatalytic activity towards the degradation of rhodamine B and phenol. The superior catalytic performance can be attributed to its larger surface area and higher crystallinity. In addition, Bi{sub 2}MoO{sub 6} microspheres are stable during the degradation reaction and can be used repeatedly. -more » Graphical abstract: Bi{sub 2}MoO{sub 6} hierarchical microspheres were successfully prepared through a facile partial anion exchange strategy using BiOI microspheres as self-sacrificing templates. The Bi{sub 2}MoO{sub 6} microspheres show high visible light photocatalytic activity. - Highlights: • Bi{sub 2}MoO{sub 6} microspheres were prepared via self-sacrificing template anion exchange. • Sodium citrate-assisted anion exchange for preparation of Bi{sub 2}MoO{sub 6} photocatalyst. • Bi{sub 2}MoO{sub 6} catalysts show high visible light photocatalytic activity.« less

Photocleavage-based affinity purification of biomarkers from serum: Application to multiplex allergy testing.

PubMed

Wan, Zhi; Ostendorff, Heather P; Liu, Ziying; Schneider, Lynda C; Rothschild, Kenneth J; Lim, Mark J

2018-01-01

Multiplex serological immunoassays, such as implemented on microarray or microsphere-based platforms, provide greater information content and higher throughput, while lowering the cost and blood volume required. These features are particularly attractive in pediatric food allergy testing to facilitate high throughput multi-allergen analysis from finger- or heel-stick collected blood. However, the miniaturization and microfluidics necessary for creating multiplex assays make them highly susceptible to the "matrix effect" caused by interference from non-target agents in serum and other biofluids. Such interference can result in lower sensitivity, specificity, reproducibility and quantitative accuracy. These problems have in large part prevented wide-spread implementation of multiplex immunoassays in clinical laboratories. We report the development of a novel method to eliminate the matrix effect by utilizing photocleavable capture antibodies to purify and concentrate blood-based biomarkers (a process termed PC-PURE) prior to detection in a multiplex immunoassay. To evaluate this approach, it was applied to blood-based allergy testing. Patient total IgE was purified and enriched using PC-PURE followed by multiplex microsphere-based detection of allergen-specific IgEs (termed the AllerBead assay). AllerBead was formatted to detect the eight most common pediatric food allergens: milk, soy, wheat, egg, peanuts, tree nuts, fin fish and shellfish, which account for >90% of all pediatric food allergies. 205 serum samples obtained from Boston Children's Hospital were evaluated. When PC-PURE was employed with AllerBead, excellent agreement was obtained with the standard, non-multiplex, ImmunoCAP® assay (average sensitivity above published negative predictive cutoffs = 96% and average Pearson r = 0.90; average specificity = 97%). In contrast, poor ImmunoCAP®-correlation was observed when PC-PURE was not utilized (average sensitivity above published negative predictive cutoffs = 59% and average Pearson r = 0.61; average specificity = 97%). This approach should be adaptable to improve a wide range of multiplex immunoassays such as in cancer, infectious disease and autoimmune disease.

Photocleavage-based affinity purification of biomarkers from serum: Application to multiplex allergy testing

PubMed Central

Wan, Zhi; Ostendorff, Heather P.; Liu, Ziying; Schneider, Lynda C.; Rothschild, Kenneth J.

2018-01-01

Multiplex serological immunoassays, such as implemented on microarray or microsphere-based platforms, provide greater information content and higher throughput, while lowering the cost and blood volume required. These features are particularly attractive in pediatric food allergy testing to facilitate high throughput multi-allergen analysis from finger- or heel-stick collected blood. However, the miniaturization and microfluidics necessary for creating multiplex assays make them highly susceptible to the “matrix effect” caused by interference from non-target agents in serum and other biofluids. Such interference can result in lower sensitivity, specificity, reproducibility and quantitative accuracy. These problems have in large part prevented wide-spread implementation of multiplex immunoassays in clinical laboratories. We report the development of a novel method to eliminate the matrix effect by utilizing photocleavable capture antibodies to purify and concentrate blood-based biomarkers (a process termed PC-PURE) prior to detection in a multiplex immunoassay. To evaluate this approach, it was applied to blood-based allergy testing. Patient total IgE was purified and enriched using PC-PURE followed by multiplex microsphere-based detection of allergen-specific IgEs (termed the AllerBead assay). AllerBead was formatted to detect the eight most common pediatric food allergens: milk, soy, wheat, egg, peanuts, tree nuts, fin fish and shellfish, which account for >90% of all pediatric food allergies. 205 serum samples obtained from Boston Children’s Hospital were evaluated. When PC-PURE was employed with AllerBead, excellent agreement was obtained with the standard, non-multiplex, ImmunoCAP® assay (average sensitivity above published negative predictive cutoffs = 96% and average Pearson r = 0.90; average specificity = 97%). In contrast, poor ImmunoCAP®-correlation was observed when PC-PURE was not utilized (average sensitivity above published negative predictive cutoffs = 59% and average Pearson r = 0.61; average specificity = 97%). This approach should be adaptable to improve a wide range of multiplex immunoassays such as in cancer, infectious disease and autoimmune disease. PMID:29389948

Soluble curcumin amalgamated chitosan microspheres augmented drug delivery and cytotoxicity in colon cancer cells: In vitro and in vivo study.

PubMed

Jyoti, Kiran; Bhatia, Richa Kaur; Martis, Elvis A F; Coutinho, Evans C; Jain, Upendra Kumar; Chandra, Ramesh; Madan, Jitender

2016-12-01

In present investigation, initially curcumin was complexed with 2-HP-β-CD (curcumin-2-HP-β-CD-complex) in 1:1 ratio and later amalgamated with chitosan microspheres (curcumin-2-HP-β-CD-CMs) for selective delivery in colon only through oral route of administration. Various analytical, spectral and in-silico docking techniques revealed that the curcumin was deeply inserted in the 2-HP-β-CD cavity with apparent stability constant of 3.35×10 -3 M. Furthermore, the mean particle size of 6.8±2.6μm and +39.2±4.1mV surface charge of curcumin-2-HP-β-CD-complex-CMs in addition to encapsulation efficiency of about 79.8±6.3% exhibited that the tailored microspheres were optimum for colon delivery of curcumin. This was also demonstrated in dissolution testing and standard cell proliferation assay in which curcumin-2-HP-β-CD-complex-CMs exhibited maximum release in simulated colonic fluid (SCF, pH ∼7.0-8.0, almond emulsion-β-glucosidase) with improved therapeutic index in HT-29 cells. Consistently, curcumin-2-HP-β-CD-complex-CMs successively enhanced the colonic bio-distribution of curcumin by ∼8.36 folds as compared to curcumin suspension in preclinical pharmacokinetic studies. In conclusion, curcumin-2-HP-β-CD-complex-CMs warrant further in vivo tumor regression study to establish its therapeutic efficacy in experimental colon cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

Hydrogel Microencapsulated Insulin-Secreting Cells Increase Keratinocyte Migration, Epidermal Thickness, Collagen Fiber Density, and Wound Closure in a Diabetic Mouse Model of Wound Healing.

PubMed

Aijaz, Ayesha; Faulknor, Renea; Berthiaume, François; Olabisi, Ronke M

2015-11-01

Wound healing is a hierarchical process of intracellular and intercellular signaling. Insulin is a potent chemoattractant and mitogen for cells involved in wound healing. Insulin's potential to promote keratinocyte growth and stimulate collagen synthesis in fibroblasts is well described. However, there currently lacks an appropriate delivery mechanism capable of consistently supplying a wound environment with insulin; current approaches require repeated applications of insulin, which increase the chances of infecting the wound. In this study, we present a novel cell-based therapy that delivers insulin to the wound area in a constant or glucose-dependent manner by encapsulating insulin-secreting cells in nonimmunogenic poly(ethylene glycol) diacrylate (PEGDA) hydrogel microspheres. We evaluated cell viability and insulin secretory characteristics of microencapsulated cells. Glucose stimulation studies verified free diffusion of glucose and insulin through the microspheres, while no statistical difference in insulin secretion was observed between cells in microspheres and cells in monolayers. Scratch assays demonstrated accelerated keratinocyte migration in vitro when treated with microencapsulated cells. In excisional wounds on the dorsa of diabetic mice, microencapsulated RIN-m cells accelerated wound closure by postoperative day 7; a statistically significant increase over AtT-20ins-treated and control groups. Histological results indicated significantly greater epidermal thickness in both microencapsulated RIN-m and AtT-20ins-treated wounds. The results suggest that microencapsulation enables insulin-secreting cells to persist long enough at the wound site for a therapeutic effect and thereby functions as an effective delivery vehicle to accelerate wound healing.

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

Shaw, L. A.; Chizari, S.; Panas, R. M.

The aim of this research is to demonstrate a holographically driven photopolymerization process for joining colloidal particles to create planar microstructures fixed to a substrate, which can be monitored with real-time measurement. Holographic optical tweezers (HOT) have been used to arrange arrays of microparticles prior to this work; here we introduce a new photopolymerization process for rapidly joining simultaneously handled microspheres in a plane. Additionally, we demonstrate a new process control technique for efficiently identifying when particles have been successfully joined by measuring a sufficient reduction in the particles’ Brownian motion. Furthermore, this technique and our demonstrated joining approach enablemore » HOT technology to take critical steps toward automated additive fabrication of microstructures.« less

Shape-coded silica nanotubes for multiplexed bioassay: rapid and reliable magnetic decoding protocols

PubMed Central

He, Bo; Kim, Sung Kyoung; Son, Sang Jun; Lee, Sang Bok

2010-01-01

Aims The recent development of 1D barcode arrays has proved their capabilities to be applicable to highly multiplexed bioassays. This article introduces two magnetic decoding protocols for suspension arrays of shape-coded silica nanotubes to process multiplexed assays rapidly and easily, which will benefit the minimization and automation of the arrays. Methods In the first protocol, the magnetic nanocrystals are incorporated into the inner voids of barcoded silica nanotubes in order to give the nanotubes magnetic properties. The second protocol is performed by trapping the barcoded silica nanotubes onto streptavidin-modified magnetic beads. Results The rapid and easy decoding process was demonstrated by applying the above two protocols to multiplexed assays, resulting in high selectivity. Furthermore, the magnetic bead-trapped barcode nanotubes provided a great opportunity to exclude the use of dye molecules in multiplexed assays by using barcode nanotubes as signals. Conclusion The rapid and easy manipulation of encoded carriers using magnetic properties could be used to develop promising suspension arrays for portable bioassays. PMID:20025466

The development of injectable gelatin/silk fibroin microspheres for the dual delivery of curcumin and piperine.

PubMed

Ratanavaraporn, Juthamas; Kanokpanont, Sorada; Damrongsakkul, Siriporn

2014-02-01

The objective of this study was to develop the microspheres from gelatin (G) and silk fibroin (SF) aimed to be applied for the controlled release of curcumin and piperine. The glutaraldehyde-crosslinked G/SF microspheres at various weight blending ratios (100/0, 70/30, 50/50, and 30/70) were successfully fabricated by water in oil emulsion technique. The microspheres prepared from all compositions were in a round shape with homogeneous size distribution both in the dried (194-217 μm) and swollen states (297-367 μm). When subjected in collagenase solution at physiological condition, the G microspheres gradually degraded within 14 days while the blended G/SF microspheres, particularly at 50/50 and 30/70, were not degraded. For the release application, the microspheres were loaded with curcumin and/or piperine. It was found that the microspheres composed of SF tended to entrap curcumin and piperine with the high entrapment and loading efficiencies, possibly due to their hydrophobic interactions. The G/SF microspheres, particularly at the ratios of 50/50 and 30/70, released curcumin and piperine in a sustained manner both for the single and dual release systems. The controlled dual release of curcumin and piperine from the G/SF microspheres would prolong their half-life, provide the optimal concentrations for therapeutic effects at a target site, and improve the bioavailability of curcumin. These novel injectable microspheres dually releasing curcumin and piperine would be introduced for the treatment of diseases without the need of operation.

Development and optimization of enteric coated mucoadhesive microspheres of duloxetine hydrochloride using 32 full factorial design

PubMed Central

Setia, Anupama; Kansal, Sahil; Goyal, Naveen

2013-01-01

Background: Microspheres constitute an important part of oral drug delivery system by virtue of their small size and efficient carrier capacity. However, the success of these microspheres is limited due to their short residence time at the site of absorption. Objective: The objective of the present study was to formulate and systematically evaluate in vitro performance of enteric coated mucoadhesive microspheres of duloxetine hydrochloride (DLX), an acid labile drug. Materials and Methods: DLX microspheres were prepared by simple emulsification phase separation technique using chitosan as carrier and glutaraldehyde as a cross-linking agent. Microspheres prepared were coated with eudragit L-100 using an oil-in-oil solvent evaporation method. Eudragit L-100was used as enteric coating polymer with the aim to release the drug in small intestine The microspheres prepared were characterized by particle size, entrapment efficiency, swelling index (SI), mucoadhesion time, in vitro drug release and surface morphology. A 32 full factorial design was employed to study the effect of independent variables polymer-to-drug ratio (X1) and stirring speed (X2) on dependent variables, particle size, entrapment efficiency, SI, in vitro mucoadhesion and drug release up to 24 h (t24). Results: Microspheres formed were discrete, spherical and free flowing. The microspheres exhibited good mucoadhesive property and also showed high percentage entrapment efficiency. The microspheres were able to sustain the drug release up to 24 h. Conclusion: Thus, the prepared enteric coated mucoadhesive microspheres may prove to be a potential controlled release formulation of DLX for oral administration. PMID:24167786

Optically Reconfigurable Chiral Microspheres of Self-Organized Helical Superstructures with Handedness Inversion.

PubMed

Wang, Ling; Chen, Dong; Gutierrez-Cuevas, Karla G; Bisoyi, Hari Krishna; Fan, Jing; Zola, Rafael S; Li, Guoqiang; Urbas, Augustine M; Bunning, Timothy J; Weitz, David A; Li, Quan

2017-01-01

Optically reconfigurable monodisperse chiral microspheres of self-organized helical superstructures with dynamic chirality were fabricated via a capillary-based microfluidic technique. Light-driven handedness-invertible transformations between different configurations of microspheres were vividly observed and optically tunable RGB photonic cross-communications among the microspheres were demonstrated.

Multiplex Microsphere Immunoassays for the Detection of IgM and IgG to Arboviral Diseases

PubMed Central

Basile, Alison J.; Horiuchi, Kalanthe; Panella, Amanda J.; Laven, Janeen; Kosoy, Olga; Lanciotti, Robert S.; Venkateswaran, Neeraja; Biggerstaff, Brad J.

2013-01-01

Serodiagnosis of arthropod-borne viruses (arboviruses) at the Division of Vector-Borne Diseases, CDC, employs a combination of individual enzyme-linked immunosorbent assays and microsphere immunoassays (MIAs) to test for IgM and IgG, followed by confirmatory plaque-reduction neutralization tests. Based upon the geographic origin of a sample, it may be tested concurrently for multiple arboviruses, which can be a cumbersome task. The advent of multiplexing represents an opportunity to streamline these types of assays; however, because serologic cross-reactivity of the arboviral antigens often confounds results, it is of interest to employ data analysis methods that address this issue. Here, we constructed 13-virus multiplexed IgM and IgG MIAs that included internal and external controls, based upon the Luminex platform. Results from samples tested using these methods were analyzed using 8 different statistical schemes to identify the best way to classify the data. Geographic batteries were also devised to serve as a more practical diagnostic format, and further samples were tested using the abbreviated multiplexes. Comparative error rates for the classification schemes identified a specific boosting method based on logistic regression “Logitboost” as the classification method of choice. When the data from all samples tested were combined into one set, error rates from the multiplex IgM and IgG MIAs were <5% for all geographic batteries. This work represents both the most comprehensive, validated multiplexing method for arboviruses to date, and also the most systematic attempt to determine the most useful classification method for use with these types of serologic tests. PMID:24086608

Preparation of novel porous starch microsphere foam for loading and release of poorly water soluble drug.

PubMed

Jiang, Tongying; Wu, Chao; Gao, Yikun; Zhu, Wenquan; Wan, Long; Wang, Zhanyou; Wang, Siling

2014-02-01

Organic porous material is a promising carrier for enhancing the dissolution of poorly water soluble drug. The aim of the present study was to enhance dissolution and oral bioavailability of lovastatin (LV) by preparing a porous starch microsphere foam (PSM) using a novel method, meanwhile, looking into the mechanism of improving dissolution of LV. PSM was prepared by the W/O emulsion-freeze thawing method. The porous structure of PSM was characterized by scanning electron microscopy (SEM) and nitrogen adsorption/desorption analysis. The adsorption role of nanopores on the drug dissolution and physical state of LV was systematically studied by instrumental analysis, and in vitro and in vivo drug dissolution studies. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate carrier cytotoxicity. The SEM images of PSM showed nanometer-sized pores. Physical state characterization indicated that porous structure effectively limited the degree of crystallinity of LV. The results of in vitro and in vivo tests testified that PSM accelerated the release of LV and enhanced its oral bioavailability in comparison with crude LV and commercial capsules. The loaded PSM powder indicated a good physical stability under storage for 12 months. MTT assay shows PSM has no toxicity for Caco-2 cell. The preparation was a promising method to produce small and uniform PSM with markedly enhanced dissolution rate and oral bioavailability due to the spatial confinement effect of porous structure. The present work demonstrates the significant potential for the use of PSM as a novel delivery system for poorly water soluble drugs.

EFFECTS OF THE GRAM STAIN ON MICROSPHERES FROM THERMAL POLYAMINO ACIDS1

PubMed Central

Fox, Sidney W.; Yuyama, Shuhei

1963-01-01

Fox, Sidney W. (The Florida State University, Tallahassee) and Shuhei Yuyama. Effects of the Gram stain on microspheres from thermal polyamino acids. J. Bacteriol. 85:279–283. 1963.—Microspheres produced from acid proteinoid accept the Gram stain. The stain is negative, but microspheres produced from mixtures containing a sufficient proportion of lysine proteinoid stain positive. Microspheres produced from mixtures containing the appropriate proportions contain individuals which stain positive and others which stain negative. Images PMID:13959050

Bioassay and biomolecular identification, sorting, and collection methods using magnetic microspheres

DOEpatents

Kraus, Jr., Robert H.; Zhou, Feng [Los Alamos, NM; Nolan, John P [Santa Fe, NM

2007-06-19

The present invention is directed to processes of separating, analyzing and/or collecting selected species within a target sample by use of magnetic microspheres including magnetic particles, the magnetic microspheres adapted for attachment to a receptor agent that can subsequently bind to selected species within the target sample. The magnetic microspheres can be sorted into a number of distinct populations, each population with a specific range of magnetic moments and different receptor agents can be attached to each distinct population of magnetic microsphere.

Three-dimensional assembly structure of anatase TiO2 hollow microspheres with enhanced photocatalytic performance

NASA Astrophysics Data System (ADS)

Tang, Yihao; Zhan, Shuai; Wang, Li; Zhang, Bin; Ding, Minghui

The pure anatase TiO2 hollow microspheres are synthesized by a one-step template-free hydrothermal route. By defining temperature and time limits, we produce TiO2 hollow microspheres with a fluoride-mediated self-transformation. The surface morphology of TiO2 hollow microspheres was studied by SEM. The hollow microspheres have diameters of about 800 nm and are remarkably uniform. The UV-light photocatalytic activity and the stability/multifunction of TiO2 hollow microspheres structure were evaluated by photocatalytic degradation of methylene blue and photocatalytic hydrogen evolution. The excellent photocatalytic activity is attributed to large specific surface area, more active sites, unique hollow structures, and improved light scattering.

Method of detecting luminescent target ions with modified magnetic microspheres

DOEpatents

Shkrob, Ilya A; Kaminski, Michael D

2014-05-13

This invention provides methods of using modified magnetic microspheres to extract target ions from a sample in order to detect their presence in a microfluidic environment. In one or more embodiments, the microspheres are modified with molecules on the surface that allow the target ions in the sample to form complexes with specific ligand molecules on the microsphere surface. In one or more embodiments, the microspheres are modified with molecules that sequester the target ions from the sample, but specific ligand molecules in solution subsequently re-extract the target ions from the microspheres into the solution, where the complexes form independent of the microsphere surface. Once the complexes form, they are exposed to an excitation wavelength light source suitable for exciting the target ion to emit a luminescent signal pattern. Detection of the luminescent signal pattern allows for determination of the presence of the target ions in the sample.

Synthesis of porous poly(styrene-co-acrylic acid) microspheres through one-step soap-free emulsion polymerization: whys and wherefores.

PubMed

Yan, Rui; Zhang, Yaoyao; Wang, Xiaohui; Xu, Jianxiong; Wang, Da; Zhang, Wangqing

2012-02-15

Synthesis of porous poly(styrene-co-acrylic acid) (PS-co-PAA) microspheres through one-step soap-free emulsion polymerization is reported. Various porous PS-co-PAA microspheres with the particle size ranging from 150 to 240 nm and with the pore size ranging from 4 to 25 nm are fabricated. The porous structure of the microspheres is confirmed by the transmission electron microscopy measurement and Brunauer-Emmett-Teller (BET) analysis. The reason for synthesis of the porous PS-co-PAA microspheres is discussed, and the phase separation between the encapsulated hydrophilic poly(acrylic acid) segment and the hydrophobic polystyrene domain within the PS-co-PAA microspheres is ascribed to the pore formation. The present synthesis of the porous PS-co-PAA microspheres is anticipated to be a new and convenient way to fabricate porous polymeric particles. Copyright © 2011 Elsevier Inc. All rights reserved.

Enhanced gastric retention and drug release via development of novel floating microspheres based on Eudragit E100 and polycaprolactone: synthesis and in vitro evaluation

PubMed Central

Farooq, Umar; Khan, Samiullah; Nawaz, Shahid; Ranjha, Nazar Mohammad; Haider, Malik Salman; Khan, Muhammad Muzamil; Dar, Eshwa; Nawaz, Ahmad

2017-01-01

Abstract Eudragit E 100 and polycaprolactone (PCL) floating microspheres for enhanced gastric retention and drug release were successfully prepared by oil in water solvent evaporation method. Metronidazole benzoate, an anti-protozoal drug, was used as a model drug. Polyvinyl alcohol was used as an emulsifier. The prepared microspheres were observed for % recovery, % degree of hydration, % water uptake, % drug loading, % buoyancy and % drug release. The physico-chemical properties of the microspheres were studied by calculating encapsulation efficiency of microspheres and drug release kinetics. Drug release characteristics of microspheres were studied in simulated gastric fluid and simulated intestinal fluid i.e., at pH 1.2 and 7.4 respectively. Fourier transform infrared spectroscopy was used to reveal the chemical interaction between drug and polymers. Scanning electron microscopy was conducted to study the morphology of the synthesized microspheres. PMID:29491813

Monodisperse, polymeric microspheres produced by irradiation of slowly thawing frozen drops

NASA Technical Reports Server (NTRS)

Rhim, Won-Kyu (Inventor); Hyson, Michael T. (Inventor); Chung, Sang-Kun (Inventor); Colvin, Michael S. (Inventor); Chang, Manchium (Inventor)

1991-01-01

Monodisperse, polymeric microspheres are formed by injecting uniformly shaped droplets of radiation polymerizable monomers, preferably a biocompatible monomer, having covalent binding sites such as hydroxyethylmethacrylate, into a zone, impressing a like charge on the droplet so that they mutually repel each other, spheroidizing the droplets within the zone and collecting the droplets in a pool of cryogenic liquid. As the droplets enter the liquid, they freeze into solid, glassy microspheres, which vaporizes a portion of the cryogenic liquid to form a layer. The like-charged microspheres, suspended within the layer, move to the edge of the vessel holding the pool, are discharged, fall and are collected. The collected microspheres are irradiated while frozen in the cryogenic liquid to form latent free radicals. The frozen microspheres are then slowly thawed to activate the free radicals which polymerize the monomer to form evenly-sized, evenly-shaped, monodisperse polymeric microspheres.

Mesoporous metal oxide microsphere electrode compositions and their methods of making

DOEpatents

Parans Paranthaman, Mariappan; Bi, Zhonghe; Bridges, Craig A; Brown, Gilbert M

2014-12-16

Compositions and methods of making are provided for treated mesoporous metal oxide microspheres electrodes. The compositions comprise (a) microspheres with an average diameter between 200 nanometers (nm) and 10 micrometers (.mu.m); (b) mesopores on the surface and interior of the microspheres, wherein the mesopores have an average diameter between 1 nm and 50 nm and the microspheres have a surface area between 50 m.sup.2/g and 500 m.sup.2/g, and wherein the composition has an electrical conductivity of at least 1.times.10.sup.-7 S/cm at 25.degree. C. and 60 MPa. The methods of making comprise forming a mesoporous metal oxide microsphere composition and treating the mesoporous metal oxide microspheres by at least one method selected from the group consisting of: (i) annealing in a reducing atmosphere, (ii) doping with an aliovalent element, and (iii) coating with a coating composition.

Method for the production of fabricated hollow microspheroids

DOEpatents

Wickramanayake, Shan; Luebke, David R.

2015-06-09

The method relates to the fabrication of a polymer microspheres comprised of an asymmetric layer surrounding a hollow interior. The fabricated hollow microsphere is generated from a nascent hollow microsphere comprised of an inner core of core fluid surrounded by a dope layer of polymer dope, where the thickness of the dope layer is at least 10% and less than 50% of the diameter of the inner core. The nascent hollow microsphere is exposed to a gaseous environment, generating a vitrified hollow microsphere, which is subsequently immersed in a coagulation bath. Solvent exchange produces a fabricated hollow microsphere comprised of a densified outer skin surrounding a macroporous inner layer, which surrounds a hollow interior. In an embodiment, the polymer is a polyimide or a polyamide-imide, and the non-solvent in the core fluid and the coagulation bath is water. The fabricated hollow microspheres are particularly suited as solvent supports for gas separation processes.

Mixed uranium dicarbide and uranium dioxide microspheres and process of making same

DOEpatents

Stinton, David P.

1983-01-01

Nuclear fuel microspheres are made by sintering microspheres containing uranium dioxide and uncombined carbon in a 1 mole percent carbon monoxide/99 mole percent argon atmosphere at 1550.degree. C. and then sintering the microspheres in a 3 mole percent carbon monoxide/97 mole percent argon atmosphere at the same temperature.

The Pharmacokinetics and Pharmacodynamics of Lidocaine-Loaded Biodegradable Poly(lactic-co-glycolic acid) Microspheres

PubMed Central

Liu, Jianming; Lv, Xin

2014-01-01

The purpose of this study was to develop novel lidocaine microspheres. Microspheres were prepared by the oil-in-water (o/w) emulsion technique using poly(d,l-lactide-co-glycolide acid) (PLGA) for the controlled delivery of lidocaine. The average diameter of lidocaine PLGA microspheres was 2.34 ± 0.3 μm. The poly disperse index was 0.21 ± 0.03, and the zeta potential was +0.34 ± 0.02 mV. The encapsulation efficiency and drug loading of the prepared microspheres were 90.5% ± 4.3% and 11.2% ± 1.4%. In vitro release indicated that the lidocaine microspheres had a well-sustained release efficacy, and in vivo studies showed that the area under the curve of lidocaine in microspheres was 2.02–2.06-fold that of lidocaine injection (p < 0.05). The pharmacodynamics results showed that lidocaine microspheres showed a significant release effect in rats, that the process to achieve efficacy was calm and lasting and that the analgesic effect had a significant dose-dependency. PMID:25268618

Insulin delivery through nasal route using thiolated microspheres.

PubMed

Nema, Tarang; Jain, Ashish; Jain, Aviral; Shilpi, Satish; Gulbake, Arvind; Hurkat, Pooja; Jain, Sanjay K

2013-01-01

The aim of the present study was to investigate the potential of developed thiolated microspheres for insulin delivery through nasal route. In the present study, cysteine was immobilized on carbopol using EDAC. A total of 269.93 µmol free thiol groups per gram polymer were determined. The prepared nonthiolated and thiolated microspheres were studied for particle shape, size, drug content, swellability, mucoadhesion and in vitro insulin release. The thiolated microspheres exhibited higher mucoadhesion due to formation of covalent bonds via disulfide bridges with the mucus gel layer. Drug permeation through goat nasal mucosa of nonthiolated and thiolated microspheres were found as 52.62 ± 2.4% and 78.85 ± 3.1% in 6 h, respectively. Thiolated microspheres bearing insulin showed better reduction in blood glucose level (BGL) in comparison to nonthiolated microspheres as 31.23 ± 2.12% and 75.25 ± 0.93% blood glucose of initial BGL were observed at 6 h after nasal delivery of thiolated and nonthiolated microspheres in streptozotocin-induced diabetic rabbits.

Preparation and Analysis of Co-precipitated, Biodegradable Poly-(Lactide-co-Glycolide) and Polyethylene Glycol Microspheres Prepared by Spray Drying

NASA Astrophysics Data System (ADS)

Javiya, Curie

Biodegradable poly-(d,l-lactide-co-glycolide) (PLGA) based microspheres are commonly used for numerous clinical applications. PEG is a widely used polymer due to its hydrophilic, biocompatible, and nontoxic nature. In this study, different blends of PLGA/PEG microspheres were prepared using a spray drying technique. The microspheres were spherical with maximum yield found to be 60.3% and average particle size in the range of 2.4 to 3.1 microm. Under the spray drying processing conditions, the polymers showed full miscibility slightly below 15% w/w and partial miscibility up to 20% w/w of PEG in the blended microspheres. At higher temperatures, PLGA and PEG were miscible in all proportions used for the blended microspheres. Blending 10% w/w PEG in PLGA membranes showed significant reduction in attachment of macrophages compared to PLGA membranes. The in-vitro response of macrophage towards the miscible blends of PLGA/PEG microspheres was further characterized. Results showed some reduction in macrophage viability and activation, however, significant effects with PLGA/PEG microspheres were not observed.

Fabrication and characterization of Tm3+-Ho3+ co-doped tellurite glass microsphere lasers operating at ∼2.1 μm

NASA Astrophysics Data System (ADS)

Yang, Zhengsheng; Wu, Yuehao; Yang, Kun; Xu, Peipeng; Zhang, Wei; Dai, Shixun; Xu, Tiefeng

2017-10-01

We used a Tm3+-Ho3+ co-doped tellurite glass as the laser medium to build active microsphere laser resonators. A droplet method is implemented and hundreds of high quality microspheres can be fabricated simultaneously. Typical Quality factors (Q-factors) of microspheres fabricated in this work reach 106. Silica fiber tapers are used as the coupling mechanism and a commercial 808 nm laser diode is used as the pump source. Laser lines at ∼2.1 μm can be observed in the emission spectrum of these active microsphere resonators. Pump thresholds for generating single mode laser lines in a 59.52 μm diameter microsphere is measured to be 0.887 mW and as the pump power is increased to 1.413 mW, multi-mode laser lines can be generated. We also demonstrate microsphere lasers fabricated in this work can be thermally tuned with a temperature sensitivity of 32 pm/°C, implying these microspheres can be used as highly compact temperature sensors in various mid-infrared applications.

X-ray tests of a microchannel plate detector and amorphous silicon pixel array readout for neutron radiography

NASA Astrophysics Data System (ADS)

Ambrosi, R. M.; Street, R.; Feller, B.; Fraser, G. W.; Watterson, J. I. W.; Lanza, R. C.; Dowson, J.; Ross, D.; Martindale, A.; Abbey, A. F.; Vernon, D.

2007-03-01

High-performance large area imaging detectors for fast neutrons in the 5-14 MeV energy range do not exist at present. The aim of this project is to combine microchannel plates or MCPs (or similar electron multiplication structures) traditionally used in image intensifiers and X-ray detectors with amorphous silicon (a-Si) pixel arrays to produce a composite converter and intensifier position sensitive imaging system. This detector will provide an order of magnitude improvement in image resolution when compared with current millimetre resolution limits obtained using phosphor or scintillator-based hydrogen rich converters. In this study we present the results of the initial experimental evaluation of the prototype system. This study was carried out using a medical X-ray source for the proof of concept tests, the next phase will involve neutron imaging tests. The hybrid detector described in this study is a unique development and paves the way for large area position sensitive detectors consisting of MCP or microsphere plate detectors and a-Si or polysilicon pixel arrays. Applications include neutron and X-ray imaging for terrestrial applications. The technology could be extended to space instrumentation for X-ray astronomy.

A Comparative Study of Production of Glass Microspheres by using Thermal Process

NASA Astrophysics Data System (ADS)

Lee, May Yan; Tan, Jully; Heng, Jerry YY; Cheeseman, Christopher

2017-06-01

Microspheres are spherical particles that can be distinguished into two categories; solid or hollow. Microspheres typical ranges from 1 to 200 μm in diameter. Microsphere are made from glass, ceramic, carbon or plastic depending on applications. Solid glass microsphere is manufactured by direct burning of glass powders while hollow glass microspheres is produced by adding blowing agent to glass powder. This paper presented the production of glass microspheres by using the vertical thermal flame (VTF) process. Pre-treated soda lime glass powder with particle sized range from 90 to 125μm was used in this work. The results showed that glass microspheres produced by two passes through the flame have a more spherical shape as compared with the single pass. Under the Scanning Electron Microscope (SEM), it is observed that there is a morphology changed from uneven surface of glass powders to smooth spherical surface particles. Qualitative analysis for density of the pre-burned and burned particles was performed. Burned particles floats in water while pre-burned particles sank indicated the change of density of the particles. Further improvements of the VTF process in terms of the VTF set-up are required to increase the transformation of glass powders to glass microspheres.

Intracellular degradation of microspheres based on cross-linked dextran hydrogels or amphiphilic block copolymers: A comparative Raman microscopy study

PubMed Central

van Manen, Henk-Jan; van Apeldoorn, Aart A; Verrijk, Ruud; van Blitterswijk, Clemens A; Otto, Cees

2007-01-01

Micro- and nanospheres composed of biodegradable polymers show promise as versatile devices for the controlled delivery of biopharmaceuticals. Whereas important properties such as drug release profiles, biocompatibility, and (bio)degradability have been determined for many types of biodegradable particles, information about particle degradation inside phagocytic cells is usually lacking. Here, we report the use of confocal Raman microscopy to obtain chemical information about cross-linked dextran hydrogel microspheres and amphiphilic poly(ethylene glycol)-terephthalate/poly(butylene terephthalate) (PEGT/PBT) microspheres inside RAW 264.7 macrophage phagosomes. Using quantitative Raman microspectroscopy, we show that the dextran concentration inside phagocytosed dextran microspheres decreases with cell incubation time. In contrast to dextran microspheres, we did not observe PEGT/PBT microsphere degradation after 1 week of internalization by macrophages, confirming previous studies showing that dextran microsphere degradation proceeds faster than PEGT/PBT degradation. Raman microscopy further showed the conversion of macrophages to lipid-laden foam cells upon prolonged incubation with both types of microspheres, suggesting that a cellular inflammatory response is induced by these biomaterials in cell culture. Our results exemplify the power of Raman microscopy to characterize microsphere degradation in cells and offer exciting prospects for this technique as a noninvasive, label-free optical tool in biomaterials histology and tissue engineering. PMID:17722552

Albumin-coated monodisperse magnetic poly(glycidyl methacrylate) microspheres with immobilized antibodies: application to the capture of epithelial cancer cells.

PubMed

Horák, Daniel; Svobodová, Zuzana; Autebert, Julien; Coudert, Benoit; Plichta, Zdeněk; Královec, Karel; Bílková, Zuzana; Viovy, Jean-Louis

2013-01-01

Monodisperse (4 μm) macroporous crosslinked poly(glycidyl methacrylate) (PGMA) microspheres for use in microfluidic immunomagnetic cell sorting, with a specific application to the capture of circulating tumor cells (CTCs), were prepared by multistep swelling polymerization in the presence of cyclohexyl acetate porogen and hydrolyzed and ammonolyzed. Iron oxide was then precipitated in the microspheres to render them magnetic. Repeated precipitation made possible to raise the iron oxide content to more than 30 wt %. To minimize nonspecific adsorption of the microspheres in a microchannel and of cells on the microspheres, they were coated with albumin crosslinked with glutaraldehyde. Antibodies of epithelial cell adhesion molecule (anti-EpCAM) were then immobilized on the albumin-coated magnetic microspheres using the carbodiimide method. Capture of breast cancer MCF7 cells as a model of CTCs by the microspheres with immobilized anti-EpCAM IgG was performed in a batch experiment. Finally, MCF7 cells were captured by the anti-EpCAM-immobilized albumin-coated magnetic microspheres in an Ephesia chip. A very good rejection of lymphocytes was achieved. Thus, albumin-coated monodisperse magnetic PGMA microspheres with immobilized anti-EpCAM seem to be promising for capture of CTCs in a microfluidic device. Copyright © 2012 Wiley Periodicals, Inc.

Super-Resolution Imaging of a Dielectric Microsphere Is Governed by the Waist of Its Photonic Nanojet.

PubMed

Yang, Hui; Trouillon, Raphaël; Huszka, Gergely; Gijs, Martin A M

2016-08-10

Dielectric microspheres with appropriate refractive index can image objects with super-resolution, that is, with a precision well beyond the classical diffraction limit. A microsphere is also known to generate upon illumination a photonic nanojet, which is a scattered beam of light with a high-intensity main lobe and very narrow waist. Here, we report a systematic study of the imaging of water-immersed nanostructures by barium titanate glass microspheres of different size. A numerical study of the light propagation through a microsphere points out the light focusing capability of microspheres of different size and the waist of their photonic nanojet. The former correlates to the magnification factor of the virtual images obtained from linear test nanostructures, the biggest magnification being obtained with microspheres of ∼6-7 μm in size. Analyzing the light intensity distribution of microscopy images allows determining analytically the point spread function of the optical system and thereby quantifies its resolution. We find that the super-resolution imaging of a microsphere is dependent on the waist of its photonic nanojet, the best resolution being obtained with a 6 μm Ø microsphere, which generates the nanojet with the minimum waist. This comparison allows elucidating the super-resolution imaging mechanism.

Enteric-coated epichlorohydrin crosslinked dextran microspheres for site-specific delivery to colon.

PubMed

Rai, Gopal; Yadav, Awesh K; Jain, Narendra K; Agrawal, Govind P

2015-01-01

Enteric-coated epichlorohydrin crosslinked dextran microspheres containing 5-Fluorouracil (5-FU) for colon drug delivery was prepared by emulsification-crosslinking method. The formulation variables studied includes different molecular weights of dextran, volume of crosslinking agent, stirring speed, time and temperature. Dextran microspheres showed mean entrapment efficiencies ranging between 77 and 87% and mean particle size ranging between 10 and 25 µm. About 90% of drug was released from uncoated dextran microspheres within 8 h, suggesting the fast release and indicated the drug loaded in uncoated microspheres, released before they reached colon. Enteric coating (Eudragit-S-100 and Eudragit-L-100) of dextran microspheres was performed by oil-in-oil solvent evaporation method. The release study of 5-FU from coated dextran microspheres was complete retardation in simulated gastric fluid (pH 1.2) and once the coating layer of enteric polymer was dissolved at higher pH (7.4 and 6.8), a controlled release of the drug from the microspheres was observed. Further, the release of drug was found to be higher in the presence of dextranase and rat caecal contents, indicating the susceptibility of dextran microspheres to colonic enzymes. Organ distribution and pharmacokinetic study in albino rats was performed to establish the targeting potential of optimized formulation in the colon.

Riems influenza a typing array (RITA): An RT-qPCR-based low density array for subtyping avian and mammalian influenza a viruses.

PubMed

Hoffmann, Bernd; Hoffmann, Donata; Henritzi, Dinah; Beer, Martin; Harder, Timm C

2016-06-03

Rapid and sensitive diagnostic approaches are of the utmost importance for the detection of humans and animals infected by specific influenza virus subtype(s). Cascade-like diagnostics starting with the use of pan-influenza assays and subsequent subtyping devices are normally used. Here, we demonstrated a novel low density array combining 32 TaqMan(®) real-time RT-PCR systems in parallel for the specific detection of the haemagglutinin (HA) and neuraminidase (NA) subtypes of avian and porcine hosts. The sensitivity of the newly developed system was compared with that of the pan-influenza assay, and the specificity of all RT-qPCRs was examined using a broad panel of 404 different influenza A virus isolates representing 45 different subtypes. Furthermore, we analysed the performance of the RT-qPCR assays with diagnostic samples obtained from wild birds and swine. Due to the open format of the array, adaptations to detect newly emerging influenza A virus strains can easily be integrated. The RITA array represents a competitive, fast and sensitive subtyping tool that requires neither new machinery nor additional training of staff in a lab where RT-qPCR is already established.

Preparation of magnetic polylactic acid microspheres and investigation of its releasing property for loading curcumin

NASA Astrophysics Data System (ADS)

Li, Fengxia; Li, Xiaoli; Li, Bin

2011-11-01

In order to obtain a targeting drug carrier system, magnetic polylactic acid (PLA) microspheres loading curcumin were synthesized by the classical oil-in-water emulsion solvent-evaporation method. In the Fourier transform infrared spectra of microspheres, the present functional groups of PLA were all kept invariably. The morphology and size distribution of magnetic microspheres were observed with scanning electron microscopy and dynamic light scattering, respectively. The results showed that the microspheres were regularly spherical and the surface was smooth with a diameter of 0.55-0.75 μm. Magnetic Fe 3O 4 was loaded in PLA microspheres and the content of magnetic particles was 12 wt% through thermogravimetric analysis. The magnetic property of prepared microspheres was measured by vibrating sample magnetometer. The results showed that the magnetic microspheres exhibited typical superparamagnetic behavior and the saturated magnetization was 14.38 emu/g. Through analysis of differential scanning calorimetry, the curcumin was in an amorphous state in the magnetic microspheres. The drug loading, encapsulation efficiency and releasing properties of curcumin in vitro were also investigated by ultraviolet-visible spectrum analysis. The results showed that the drug loading and encapsulation efficiency were 8.0% and 24.2%, respectively. And curcumin was obviously slowly released because the cumulative release percentage of magnetic microspheres in the phosphate buffer (pH=7.4) solution was only 49.01% in 72 h, and the basic release of curcumin finished in 120 h.

Novel PLA modification of organic microcontainers based on ring opening polymerization: synthesis, characterization, biocompatibility and drug loading/release properties.

PubMed

Efthimiadou, E K; Tziveleka, L-A; Bilalis, P; Kordas, G

2012-05-30

In the current study, poly lactic acid (PLA) modified hollow crosslinked poly(hydroxyethyl methacrylate) (PHEMA) microspheres have been prepared, in order to obtain a stimulus-responsive, biocompatible carrier with sustained drug release properties. The synthetical process consisted of the preparation of poly(methacrylic acid)@poly(hydroxyethyl methacrylate-co-N,N'-methylene bis(acrylamide)) microspheres by a two stage distillation-precipitation polymerization technique using 2,2'-azobisisobutyronitrile as initiator. Following core removal, a PLA coating of the microspheres was formed, after ring opening polymerization of DL-lactide, attributing the initiator's role to the active hydroxyl groups of PHEMA. The anticancer drug daunorubicin (DNR) was selected for the study of loading and release behavior of the coated microspheres. The loading capacity of the PLA modified microspheres was found to be four times higher than that of the parent ones (16% compared to 4%). This coated microspherical carrier exhibited a moderate pH responsive drug release behavior due to the pH dependent water uptake of PHEMA, and PLA hydrolysis. The in vitro cytotoxicity of both the parent and the DNR-loaded or empty modified hollow microspheres has been also examined on MCF-7 breast cancer cells. The results showed that although the empty microspheres were moderately cytotoxic, the DNR-loaded microspheres had more potent anti-tumor effect than the free drug. Therefore, the prepared coated microspheres are interesting drug delivery systems. Copyright © 2012 Elsevier B.V. All rights reserved.

Simple Synthesis of Molybdenum Disulfide/Reduced Graphene Oxide Composite Hollow Microspheres as Supercapacitor Electrode Material.

PubMed

Xiao, Wei; Zhou, Wenjie; Feng, Tong; Zhang, Yanhua; Liu, Hongdong; Tian, Liangliang

2016-09-20

MoS₂/RGO composite hollow microspheres were hydrothermally synthesized by using SiO₂/GO microspheres as a template, which were obtained via the sonication-assisted interfacial self-assembly of tiny GO sheets on positively charged SiO₂ microspheres. The structure, morphology, phase, and chemical composition of MoS₂/RGO hollow microspheres were systematically investigated by a series of techniques such as FE-SEM, TEM, XRD, TGA, BET, and Raman characterizations, meanwhile, their electrochemical properties were carefully evaluated by CV, GCD, and EIS measurements. It was found that MoS₂/RGO hollow microspheres possessed unique porous hollow architecture with high-level hierarchy and large specific surface area up to 63.7 m²·g -1 . When used as supercapacitor electrode material, MoS₂/RGO hollow microspheres delivered a maximum specific capacitance of 218.1 F·g -1 at the current density of 1 A·g -1 , which was much higher than that of contrastive bare MoS₂ microspheres developed in the present work and most of other reported MoS₂-based materials. The enhancement of supercapacitive behaviors of MoS₂/RGO hollow microspheres was likely due to the improved conductivity together with their distinct structure and morphology, which not only promoted the charge transport but also facilitated the electrolyte diffusion. Moreover, MoS₂/RGO hollow microsphere electrode displayed satisfactory long-term stability with 91.8% retention of the initial capacitance after 1000 charge/discharge cycles at the current density of 3 A·g -1 , showing excellent application potential.

In situ fabrication of hollow hydroxyapatite microspheres by phosphate solution immersion

NASA Astrophysics Data System (ADS)

Wang, Yingchun; Yao, Aihua; Huang, Wenhai; Wang, Deping; zhou, Jun

2011-07-01

Hollow hydroxyapatite (HAP) microspheres with pores on their surfaces were prepared by converting Li 2O-CaO-B 2O 3 (LCB) glass microspheres in phosphate solution. The structure, phase composition, surface morphology, and porosity of the hollow HAP microspheres were characterized by SEM, SEM-EDS, XRD, FTIR, ICP-AES, and N 2 adsorption-desorption techniques. The formation and conversion mechanism of the hollow HAP microspheres during immersion process were discussed. The as-prepared microspheres consisted of calcium deficient carbonated hydroxyapatite, which is biomimetic. FTIR spectra indicated that the resulting apatite were B-type CO 3HAP, in which carbonate ions occupied the phosphate sites. After 600 °C heating treatment, hollow microspheres were completely composed of calcium deficient hydroxyapatite crystals including CO32-. The pore size distribution of the as-prepared hollow HAP microspheres were mainly the mesopores in the range of 2-40 nm with the pore volume 0.5614 cm 3/g, and the mean pore size 10.5 nm, respectively. The results confirmed that LCB glass were transformed to hydroxyapatite without changing the external shape and dimension of the original glass object and the resulting microspheres possessed good hollow structures. Once immersed in phosphate solution, Ca-P-OH hydrates were in situ formed on the surface of the glass and precipitated in the position occupied by Ca 2+, while the pores were formed in the position occupied by Li + and B 3+. These hollow HAP microspheres with such structures may be used as promising drug delivery devices.

The development of non-toxic ionic-crosslinked chitosan-based microspheres as carriers for the controlled release of silk sericin.

PubMed

Aramwit, Pornanong; Ekasit, Sanong; Yamdech, Rungnapha

2015-10-01

Silk sericin is recently shown to possess various biological activities for biomedical applications. While various sericin carriers were developed for drug delivery system, very few researches considered sericin as a bioactive molecule itself. In this study, sericin incorporated in the chitosan-based microspheres was introduced as a bioactive molecule and bioactive carrier at the same time. The chitosan/sericin (CH/SS) microspheres at different composition (80/20, 70/30, 60/40, and 50/50) were successfully fabricated using anhydroustri-polyphosphate (TPP) as a polyanionic crosslinker. The microspheres with an average size of 1-4 μm and narrow size distribution were obtained. From FT-IR spectra, the presence of both chitosan and sericin in the microspheres confirmed the occurrence of ionic interaction that crosslink them within the microspheres. We also found that the CH/SS microspheres prepared at 50/50 could encapsulate sericin at the highest percentage (37.28%) and release sericin in the most sustained behavior, possibly due to the strong ionic interaction of the positively charged chitosan and the negatively charged sericin. On the other hand, the composition of CH/SS had no effect on the degradation rate of microspheres. All microspheres continuously degraded and remained around 20% after 14 days of enzymatic degradation. This explained that the ionic crosslinkings between chitosan and sericin could be demolished by the enzyme and hydrolysis. Furthermore, we have verified that all CH/SS microspheres at any concentrations showed non-toxicity to L929 mouse fibroblast cells. Therefore, we suggested that the non-toxic ionic-crosslinked CH/SS microspheres could be incorporated in wound dressing material to achieve the sustained release of sericin for accelerated wound healing.

Intestinal absorption of PLAGA microspheres in the rat.

PubMed Central

Damgé, C; Aprahamian, M; Marchais, H; Benoit, J P; Pinget, M

1996-01-01

Rhodamine B-labelled poly (DL-lactide-co-glycolide) (PLAGA) microspheres of 2 different sizes, 1-5 microns and 5-10 microns, were administered as a single dose (1.44 x 10(9) and 1.83 x 10(8) particles, respectively) into the ileal lumen of adult rats. The content of rhodamine in the mesenteric vein and ileal lumen was analysed periodically from 10 min to 48 h as well as the distribution of microspheres in the intestinal mucosa and various other tissues. The concentration of rhodamine decreased progressively in the intestinal lumen and was negligible after 24 h. The number of microspheres in the mesenteric vein increased rapidly and reached a maximum after 4 h whatever the size of the particles. It then decreased progressively, but more rapidly with microspheres > 5 microns than with microspheres < 5 microns. The absorption efficiency was low for the former batch (about 0.11% of the administered dose) and higher for the latter (about 12.7%). The intraileal administration of free rhodamine B was followed by intense labelling of the epithelial cells and basement membranes in mesenteric lymph nodes, spleen, kidney and liver. PLAGA microspheres mainly crossed the intestinal mucosa at the site of Peyer's patches where microspheres of < 5 microns appeared after 3 h. Microspheres > 5 microns were retained in the ileal lumen. A few small microspheres were occasionally observed in the epithelial cells. Only the smallest particles were recovered in the liver, lymph nodes and spleen while basement membranes were always labelled. It is concluded that PLAGA microspheres could be useful for the oral delivery of antigens if their size is between 1 and 5 microns. Images Fig. 1 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:8982822

Intestinal absorption of PLAGA microspheres in the rat.

PubMed

Damgé, C; Aprahamian, M; Marchais, H; Benoit, J P; Pinget, M

1996-12-01

Rhodamine B-labelled poly (DL-lactide-co-glycolide) (PLAGA) microspheres of 2 different sizes, 1-5 microns and 5-10 microns, were administered as a single dose (1.44 x 10(9) and 1.83 x 10(8) particles, respectively) into the ileal lumen of adult rats. The content of rhodamine in the mesenteric vein and ileal lumen was analysed periodically from 10 min to 48 h as well as the distribution of microspheres in the intestinal mucosa and various other tissues. The concentration of rhodamine decreased progressively in the intestinal lumen and was negligible after 24 h. The number of microspheres in the mesenteric vein increased rapidly and reached a maximum after 4 h whatever the size of the particles. It then decreased progressively, but more rapidly with microspheres > 5 microns than with microspheres < 5 microns. The absorption efficiency was low for the former batch (about 0.11% of the administered dose) and higher for the latter (about 12.7%). The intraileal administration of free rhodamine B was followed by intense labelling of the epithelial cells and basement membranes in mesenteric lymph nodes, spleen, kidney and liver. PLAGA microspheres mainly crossed the intestinal mucosa at the site of Peyer's patches where microspheres of < 5 microns appeared after 3 h. Microspheres > 5 microns were retained in the ileal lumen. A few small microspheres were occasionally observed in the epithelial cells. Only the smallest particles were recovered in the liver, lymph nodes and spleen while basement membranes were always labelled. It is concluded that PLAGA microspheres could be useful for the oral delivery of antigens if their size is between 1 and 5 microns.

Dynamic in vivo imaging of dual-triggered microspheres for sustained release applications: synthesis, characterization and cytotoxicity study.

PubMed

Efthimiadou, Eleni K; Tapeinos, Christos; Chatzipavlidis, Alexandros; Boukos, Nikos; Fragogeorgi, Eirini; Palamaris, Lazaros; Loudos, George; Kordas, George

2014-01-30

This paper deals with the synthesis, characterization and property evaluation of drug-loaded magnetic microspheres with pH-responsive cross-linked polymer shell. The synthetic procedure consists of 3 steps, of which the first two comprise the synthesis of a poly methyl methacrylate (PMMA) template and the synthesis of a shell by using acrylic acid (AA) and methyl methacrylate (MMA) as monomers, and divinyl benzene (DVB) as cross-linker. The third step of the procedure refers to the formation of magnetic nanoparticles on the microsphere's surface. AA that attaches pH-sensitivity in the microspheres and magnetic nanoparticles in the inner and the outer surface of the microspheres, enhance the efficacy of this intelligent drug delivery system (DDS), which constitutes a promising approach toward cancer therapy. A number of experimental techniques were used to characterize the resulting microspheres. In order to investigate the in vitro controlled release behavior of the synthesized microspheres, we studied the Dox release percentage under different pH conditions and under external magnetic field. Hyperthermia caused by an alternating magnetic field (AFM) is used in order to study the doxorubicin (Dox) release behavior from microspheres with pH functionality. The in vivo fate of these hybrid-microspheres was tracked by labeling them with the γ-emitting radioisotope (99m)Tc after being intravenously injected in normal mice. According to our results, microsphere present a pH depending and a magnetic heating, release behavior. As expected, labeled microspheres were mainly found in the mononuclear phagocyte system (MPS). The highlights of the current research are: (i) to illustrate the advantages of controlled release by combining hyperthermia and pH-sensitivity and (ii) to provide noninvasive, in vivo information on the spatiotemporal biodistribution of these microsphere by dynamic γ-imaging. Copyright © 2013 Elsevier B.V. All rights reserved.

Development of in vitro-in vivo correlation of parenteral naltrexone loaded polymeric microspheres.

PubMed

Andhariya, Janki V; Shen, Jie; Choi, Stephanie; Wang, Yan; Zou, Yuan; Burgess, Diane J

2017-06-10

Establishment of in vitro-in vivo correlations (IVIVCs) for parenteral polymeric microspheres has been very challenging, due to their complex multiphase release characteristics (which is affected by the nature of the drug) as well as the lack of compendial in vitro release testing methods. Previously, a Level A correlation has been established and validated for polymeric microspheres containing risperidone (a practically water insoluble small molecule drug). The objectives of the present study were: 1) to investigate whether a Level A IVIVC can be established for polymeric microspheres containing another small molecule drug with different solubility profiles compared to risperidone; and 2) to determine whether release characteristic differences (bi-phasic vs tri-phasic) between microspheres can affect the development and predictability of IVIVCs. Naltrexone was chosen as the model drug. Three compositionally equivalent formulations of naltrexone microspheres with different release characteristics were prepared using different manufacturing processes. The critical physicochemical properties (such as drug loading, particle size, porosity, and morphology) as well as the in vitro release characteristics of the prepared naltrexone microspheres and the reference-listed drug (Vivitrol®) were determined. The pharmacokinetics of the naltrexone microspheres were investigated using a rabbit model. The obtained pharmacokinetic profiles were deconvoluted using the Loo-Riegelman method, and compared with the in vitro release profiles of the naltrexone microspheres obtained using USP apparatus 4. Level A IVIVCs were established and validated for predictability. The results demonstrated that the developed USP 4 method was capable of detecting manufacturing process related performance changes, and most importantly, predicting the in vivo performance of naltrexone microspheres in the investigated animal model. A critical difference between naltrexone and risperidone loaded microspheres is their respective bi-phasic and tri-phasic release profiles with varying burst release and lag phase. These variations in release profiles affect the development of IVIVCs. Nevertheless, IVIVCs have been established and validated for polymeric microspheres with different release characteristics. Copyright © 2017. Published by Elsevier B.V.

Optimization of sustained release aceclofenac microspheres using response surface methodology.

PubMed

Deshmukh, Rameshwar K; Naik, Jitendra B

2015-03-01

Polymeric microspheres containing aceclofenac were prepared by single emulsion (oil-in-water) solvent evaporation method using response surface methodology (RSM). Microspheres were prepared by changing formulation variables such as the amount of Eudragit® RS100 and the amount of polyvinyl alcohol (PVA) by statistical experimental design in order to enhance the encapsulation efficiency (E.E.) of the microspheres. The resultant microspheres were evaluated for their size, morphology, E.E., and in vitro drug release. The amount of Eudragit® RS100 and the amount of PVA were found to be significant factors respectively for determining the E.E. of the microspheres. A linear mathematical model equation fitted to the data was used to predict the E.E. in the optimal region. Optimized formulation of microspheres was prepared using optimal process variables setting in order to evaluate the optimization capability of the models generated according to IV-optimal design. The microspheres showed high E.E. (74.14±0.015% to 85.34±0.011%) and suitably sustained drug release (minimum; 40% to 60%; maximum) over a period of 12h. The optimized microspheres formulation showed E.E. of 84.87±0.005 with small error value (1.39). The low magnitudes of error and the significant value of R(2) in the present investigation prove the high prognostic ability of the design. The absence of interactions between drug and polymers was confirmed by Fourier transform infrared (FTIR) spectroscopy. Differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRPD) revealed the dispersion of drug within microspheres formulation. The microspheres were found to be discrete, spherical with smooth surface. The results demonstrate that these microspheres could be promising delivery system to sustain the drug release and improve the E.E. thus prolong drug action and achieve the highest healing effect with minimal gastrointestinal side effects. Copyright © 2014 Elsevier B.V. All rights reserved.

In vitro biocompatibility and electrical stability of thick-film platinum/gold alloy electrodes printed on alumina

NASA Astrophysics Data System (ADS)

Carnicer-Lombarte, Alejandro; Lancashire, Henry T.; Vanhoestenberghe, Anne

2017-06-01

Objective. High-density electrode arrays are a powerful tool in both clinical neuroscience and basic research. However, current manufacturing techniques require the use of specialised techniques and equipment, which are available to few labs. We have developed a high-density electrode array with customisable design, manufactured using simple printing techniques and with commercially available materials. Approach. Electrode arrays were manufactured by thick-film printing a platinum-gold alloy (Pt/Au) and an insulating dielectric on 96% alumina ceramic plates. Arrays were conditioned in serum and serum-free conditions, with and without 1 kHz, 200 µA, charge balanced stimulation for up to 21 d. Array biocompatibility was assessed using an extract assay and a PC-12 cell contact assay. Electrode impedance, charge storage capacity and charge injection capacity were before and after array conditioning. Main results. The manufactured Pt/Au electrodes have a highly porous surface and exhibit electrical properties comparable to arrays manufactured using alternative techniques. Materials used in array manufacture were found to be non-toxic to L929 fibroblasts by extract assay, and neuronal-like PC-12 cells adhered and extended neurites on the array surfaces. Arrays remained functional after long-term delivery of electrical pulses while exposed to protein-rich environments. Charge storage capacities and charge injection capacities increased following stimulation accounted for by an increase in surface index (real surface area) observed by vertical scanning interferometry. Further, we observed accumulation of proteins at the electrode sites following conditioning in the presence of serum. Significance. This study demonstrates the in vitro biocompatibility of commercially available thick-film printing materials. The printing technique is both simple and versatile, with layouts readily modified to produce customized electrode arrays. Thick-film electrode arrays are an attractive tool that may be implemented for general tissue engineering and neuroscience research.

Control of silk microsphere formation using polyethylene glycol (PEG).

PubMed

Wu, Jianbing; Zheng, Zhaozhu; Li, Gang; Kaplan, David L; Wang, Xiaoqin

2016-07-15

A one step, rapid method to prepare silk microspheres was developed, with particle size controlled by the addition of polyethylene glycol (PEG). PEG molecular weight (4.0K-20.0KDa) and concentration (20-50wt%), as well as silk concentration (5-20wt%), were key factors that determined particle sizes varying in a range of 1-100μm. Addition of methanol to the PEG-silk combinations increased the content of crystalline β-sheet in the silk microspheres. To track the distribution and degradation of silk microspheres in vivo, 3-mercaptopropionic acid (MPA)-coated CdTe quantum dots (QDs) were physically entrapped in the silk microspheres. QDs tightly bound to the β-sheet domains of silk via hydrophobic interactions, with over 96% of the loaded QDs remaining in the silk microspheres after exhaustive extraction. The fluorescence of QDs-incorporated silk microspheres less stable in cell culture medium than in phosphate buffer solution (PBS) and water. After subcutaneous injection in mice, microspheres prepared from 20% silk (approx. 30μm diameter particles) still fluoresced at 24h, while those prepared from 8% silk (approx. 4μm diameter particles) and free QDs were not detectable, reflecting the QDs quenching and particle size effect on microsphere clearance in vivo. The larger microspheres were more resistant to cell internalization and degradation. Since PEG is an FDA-approved polymer, and silk is FDA approved for some medical devices, the methods developed in the present study will be useful in a variety of biomedical applications where simple, rapid and scalable preparation of silk microspheres is required. The work is of significance to the biomaterial and controlled release society because it provides a new option for fabricating silk microspheres in one simple step of mixing silk and polyethylene glycol (PEG), with the size and properties of microspheres controllable by PEG molecular weight as well as PEG and silk concentrations. Although fabrication of silk microspheres have been reported previously using spray-drying, liposome-templating, polyvinyl alcohol (PVA) emulsification, etc., applications were hindered due to harsh conditions (temperature, solvents, etc.) and complicated procedures used as well as low yield and less controllable particle size (usually <10μm). Since PEG is an FDA-approved polymer, and silk is FDA approved for some medical devices, the methods developed in the present study will be useful in a variety of biomedical applications where simple, rapid and scalable preparation of silk microspheres is required. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Transport and attenuation of carboxylate-modified latex microspheres in fractured rock laboratory and field tracer tests

USGS Publications Warehouse

Becker, M.W.; Reimus, P.W.; Vilks, P.

1999-01-01

Understanding colloid transport in ground water is essential to assessing the migration of colloid-size contaminants, the facilitation of dissolved contaminant transport by colloids, in situ bioremediation, and the health risks of pathogen contamination in drinking water wells. Much has been learned through laboratory and field-scale colloid tracer tests, but progress has been hampered by a lack of consistent tracer testing methodology at different scales and fluid velocities. This paper presents laboratory and field tracer tests in fractured rock that use the same type of colloid tracer over an almost three orders-of-magnitude range in scale and fluid velocity. Fluorescently-dyed carboxylate-modified latex (CML) microspheres (0.19 to 0.98 ??m diameter) were used as tracers in (1) a naturally fractured tuff sample, (2) a large block of naturally fractured granite, (3) a fractured granite field site, and (4) another fractured granite/schist field site. In all cases, the mean transport time of the microspheres was shorter than the solutes, regardless of detection limit. In all but the smallest scale test, only a fraction of the injected microsphere mass was recovered, with the smaller microspheres being recovered to a greater extent than the larger microspheres. Using existing theory, we hypothesize that the observed microsphere early arrival was due to volume exclusion and attenuation was due to aggregation and/or settling during transport. In most tests, microspheres were detected using flow cytometry, which proved to be an excellent method of analysis. CML microspheres appear to be useful tracers for fractured rock in forced gradient and short-term natural gradient tests, but longer residence times may result in small microsphere recoveries.Understanding colloid transport in ground water is essential to assessing the migration of colloid-size contaminants, the facilitation of dissolved contaminant transport by colloids, in situ bioremediation, and the health risks of pathogen contamination in drinking water wells. Much has been learned through laboratory and field-scale colloid tracer tests, but progress has been hampered by a lack of consistent tracer testing methodology at different scales and fluid velocities. This paper presents laboratory and field tracer tests in fractured rock that use the same type of colloid tracer over an almost three orders-of-magnitude range in scale and fluid velocity. Fluorescently-dyed carboxylate-modified latex (CML) microspheres (0.19 to 0.98 ??m diameter) were used as tracers in (1) a naturally fractured tuff sample, (2) a large block of naturally fractured granite, (3) a fractured granite field site, and (4) another fractured granite/schist field site. In all cases, the mean transport time of the microspheres was shorter than the solutes, regardless of detection limit. In all but the smallest scale test, only a fraction of the injected microsphere mass was recovered, with the smaller microspheres being recovered to a greater extent than the larger microspheres. Using existing theory, we hypothesize that the observed microsphere early arrival was due to volume exclusion and attenuation was due to aggregation and/or settling during transport. In most tests, microspheres were detected using flow cytometry, which proved to be an excellent method of analysis. CML microspheres appear to be useful tracers for fractured rock in forced gradient and short-term natural gradient tests, but longer residence times may result in small microsphere recoveries.

Hollow porous-wall glass microspheres for hydrogen storage

DOEpatents

Heung, Leung K.; Schumacher, Ray F.; Wicks, George G.

2010-02-23

A porous wall hollow glass microsphere is provided having a diameter range of between 1 to 200 microns, a density of between 1.0 to 2.0 gm/cc, a porous-wall structure having wall openings defining an average pore size of between 10 to 1000 angstroms, and which contains therein a hydrogen storage material. The porous-wall structure facilitates the introduction of a hydrogen storage material into the interior of the porous wall hollow glass microsphere. In this manner, the resulting hollow glass microsphere can provide a membrane for the selective transport of hydrogen through the porous walls of the microsphere, the small pore size preventing gaseous or liquid contaminants from entering the interior of the hollow glass microsphere.

Conjugation of (E)-5-[2-(Methoxycarbonyl)ethenyl]cytidine to hydrophilic microspheres: development of a mobile microscale UV light actinometer.

PubMed

Fang, Shiyue; Guan, Yousheng; Blatchley, Ernest R; Shen, Chengyue; Bergstrom, Donald E

2008-03-01

( E)-5-[2-(Methoxycarbonyl)ethenyl]cytidine was biotinylated through a diisopropylsilylacetal linkage and attached to the surface of hydrophilic streptavidin-coated microspheres through the high-affinity noncovalent interaction between biotin and streptavidin. The functionalized microspheres form a stable suspension in water. Upon UV irradiation, the nonfluorescent ( E)-5-[2-(methoxycarbonyl)ethenyl]cytidine on the microspheres undergoes photocyclization to produce highly fluorescent 3-beta-D-ribofuranosyl-2,7-dioxopyrido[2,3-d]pyrimidine. The fluorescence intensity of the microspheres can be correlated to the particle-specific UV doses applied at different suspension concentrations. The microspheres allow one to measure the UV dose (fluence) distribution in high-throughput water disinfection systems.

Active Q switching of a fiber laser with a microsphere resonator

NASA Astrophysics Data System (ADS)

Kieu, Khanh; Mansuripur, Masud

2006-12-01

We propose and demonstrate an active Q-switched fiber laser using a high-Q microsphere resonator as the Q-switching element. The laser cavity consists of an Er-doped fiber as the gain medium, a glass microsphere reflector (coupled through a fiber taper) at one end of the cavity, and a fiber Bragg grating reflector at the other end. The reflectivity of the microsphere is modulated by changing the gap between the microsphere and the fiber taper. Active Q switching is realized by oscillating the microsphere in and out of contact with the taper. Using this novel technique, we have obtained giant pulses (maximum peak power ˜102W, duration ˜160ns) at a low pump-power threshold (˜3mW).

Assessing the efficacy of vesicle fusion with planar membrane arrays using a mitochondrial porin as reporter

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

Pszon-Bartosz, Kamila; Hansen, Jesper S.; Technical University of Denmark, Department of Micro- and Nanotechnology, DK-2800 Kongens Lyngby

2011-03-04

Research highlights: {yields} We have established a vesicle fusion efficacy assay based on the major non-specific porin of Fusobacterium nucleatum (FomA). {yields} Maximal fusion obtained was almost 150,000 porin insertions during 20 min. {yields} Incorporation can be either first order or exponential kinetics which has implications for establishing protein delivery to biomimetic membranes. -- Abstract: Reconstitution of functionally active membrane protein into artificially made lipid bilayers is a challenge that must be overcome to create a membrane-based biomimetic sensor and separation device. In this study we address the efficacy of proteoliposome fusion with planar membrane arrays. We establish a proteinmore » incorporation efficacy assay using the major non-specific porin of Fusobacterium nucleatum (FomA) as reporter. We use electrical conductance measurements and fluorescence microscopy to characterize proteoliposome fusion with an array of planar membranes. We show that protein reconstitution in biomimetic membrane arrays may be quantified using the developed FomA assay. Specifically, we show that FomA vesicles are inherently fusigenic. Optimal FomA incorporation is obtained with a proteoliposome lipid-to-protein molar ratio (LPR) = 50 more than 10{sup 5} FomA proteins could be incorporated in a bilayer array with a total membrane area of 2 mm{sup 2} within 20 min. This novel assay for quantifying protein delivery into lipid bilayers may be a useful tool in developing biomimetic membrane applications.« less

Data transformation methods for multiplexed assays

DOEpatents

Tammero, Lance F. Bentley; Dzenitis, John M; Hindson, Benjamin J

2013-07-23

Methods to improve the performance of an array assay are described. A correlation between fluorescence intensity-related parameters and negative control values of the assay is determined. The parameters are then adjusted as a function of the correlation. As a result, sensitivity of the assay is improved without changes in its specificity.

Effect of pH on polyethylene glycol (PEG)-induced silk microsphere formation for drug delivery.

PubMed

Wu, Jianbing; Xie, Xusheng; Zheng, Zhaozhu; Li, Gang; Wang, Xiaoqin; Wang, Yansong

2017-11-01

The effects of changing solution pH in the range of 3.6-10.0 during a one-step silk microsphere preparation process, by mixing silk and polyethylene glycol (PEG), was assessed. The microspheres prepared at low pH (3.6) showed a more homogeneous size (1-3μm) and less porous texture than those prepared at neutral pH. High pH (10.0) inhibited microsphere formation, yielding small and inhomogeneous microspheres. Compared to neutral pH, low pH also increased the content of silk crystalline β-sheet structure from approx. 30% to above 40%. As a result, the microspheres produced at low pH were more thermally stable as well as resistant to chemical (8M urea) and enzymatic (protease XIV) degradation when compared to microspheres prepared at neutral pH. Doxorubicin hydrochloride (DOX) and curcumin (CUR) were successfully loaded in silk microspheres via control of solution pH. The loading efficiency of DOX was approx. 95% at pH7.0 and approx. 60% for CUR at pH3.6, attributed to charge-charge interactions and hydrophobic interactions between the silk and drug molecules, respectively. When PBS, pH7.4, was used as a medium for release studies, the pH3.6 microspheres released both drugs more slowly than the pH7.0 microspheres, likely due to the high content of crystalline β-sheet structure that enhanced drug-silk interactions as well as restricted drug molecule diffusion. Copyright © 2017. Published by Elsevier B.V.

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

Cheng, J.P., E-mail: chengjp@zju.edu.cn; Chen, X.; Ma, R.

Flower-like Co{sub 3}O{sub 4} hierarchical microspheres composed of self-assembled porous nanoplates have been prepared by a two-step method without employing templates. The first step involves the synthesis of flower-like Co(OH){sub 2} microspheres by a solution route at low temperatures. The second step includes the calcination of the as-prepared Co(OH){sub 2} microspheres at 200 deg. C for 1 h, causing their decomposition to form porous Co{sub 3}O{sub 4} microspheres without destruction of their original morphology. The samples were characterized by scanning electron microscope, transmission electron microscope, X-ray diffractormeter and Fourier transform infrared spectroscope. Some experimental factors including solution temperature and surfactantmore » on the morphologies of the final products have been investigated. The magnetic properties of Co{sub 3}O{sub 4} microspheres were also investigated. - Graphical Abstract: Flower-like Co{sub 3}O{sub 4} microspheres are composed of self-assembled nanoplates and these nanoplates appear to be closely packed in the microspheres. These nanoplates consist of a large number of nanocrystallites less than 5 nm in size with a porous structure, in which the connection between nanocrystallites is random. Research Highlights: {yields} Flower-like Co{sub 3}O{sub 4} hierarchical microspheres composed of self-assembled porous nanoplates have been prepared by a two-step method without employing templates. {yields} Layered Co(OH){sub 2} microspheres were prepared with an appropriate approach under low temperatures for 1 h reaction. {yields} Calcination caused Co(OH){sub 2} decomposition to form porous Co{sub 3}O{sub 4} microspheres without destruction of their original morphology.« less

Differential Regulation of Angiogenesis using Degradable VEGF-Binding Microspheres

PubMed Central

Belair, David G.; Miller, Michael J.; Wang, Shoujian; Darjatmokon, Soesiawati R.; Binder, Bernard Y.K.; Sheibani, Nader; Murphy, William L.

2016-01-01

Vascular endothelial growth factor (VEGF) spatial and temporal activity must be tightly controlled during angiogenesis to form perfusable vasculature in a healing wound. The native extracellular matrix (ECM) regulates growth factor activity locally via sequestering, and researchers have used ECM-mimicking approaches to regulate the activity of VEGF in cell culture and in vivo. However, the impact of dynamic, affinity-mediated growth factor sequestering has not been explored in detail with biomaterials. Here, we sought to modulate VEGF activity dynamically over time using poly(ethylene glycol) microspheres containing VEGF-binding peptides (VBPs) and exhibiting varying degradation rates. The degradation rate of VBP microspheres conferred a differential ability to up- or down-regulate VEGF activity in culture with primary human endothelial cells. VBP microspheres with fast-degrading crosslinks reduced VEGF activity and signaling, while VBP microspheres with no inherent degradability sequestered and promoted VEGF activity in culture with endothelial cells. VBP microspheres with degradable crosslinks significantly reduced neovascularization in vivo, but neither non-degradable VBP microspheres nor bolus delivery of soluble VBP reduced neovascularization. The covalent incorporation of VBP to degradable microspheres was required to reduce neovascularization in a mouse model of choroidal neovascularization in vivo, which demonstrates a potential clinical application of degradable VBP microspheres to reduce pathological angiogenesis. The results herein highlight the ability to modulate the activity of a sequestered growth factor by changing the crosslinker identity within PEG hydrogel microspheres. The insights gained here may instruct the design and translation of affinity-based growth factor sequestering biomaterials for regenerative medicine applications. PMID:27061268

Formulation and evaluation of microsphere based oro dispersible tablets of itopride hcl

PubMed Central

2012-01-01

Background The purpose of the present work is to mask the intensely bitter taste of Itopride HCl and to formulate an Oro dispersible tablet (ODT) of the taste-masked drug by incorporation of microspheres in the tablets for use in specific populations viz. pediatrics, geriatrics and patients experiencing difficulty in swallowing. Methods With this objective in mind, microspheres loaded with Itopride HCl were prepared by solvent evaporation method using acetone as solvent for pH-sensitive polymer, Eudragit EPO and light liquid paraffin as the encapsulating medium. The prepared microspheres were characterized with regard to yield, drug content, flow properties, particle size and size distribution, surface features, in vitro drug release and taste. The ODTs so prepared from these microspheres were evaluated for hardness, thickness, weight variation, friability, disintegration time, drug content, wetting time, water absorption ratio, moisture uptake, in vitro dispersion, in vitro disintegration, in vitro drug release and stability. Results The average size of microspheres was found to be satisfactory in terms of the size and size distribution. Microspheres prepared were of a regular spherical shape. Comparison of the dissolution profiles of microspheres in different pH media showed that microspheres having drug: polymer ratio of 1:2 produced a retarding effect in simulated salivary fluid (pH 6.8) and were further used for formulation into ODTs after addition of suitable amounts of excipients such as superdisintegrant, diluent, sweetener and flavor of directly compressible grade. Conclusions Effective taste-masking was achieved for Itopride HCl by way of preparation of microspheres and ODTs of acceptable characteristics. PMID:23351176

Formulation and evaluation of microsphere based oro dispersible tablets of itopride hcl.

PubMed

Shah, Sanjay; Madan, Sarika; Agrawal, Ss

2012-09-03

The purpose of the present work is to mask the intensely bitter taste of Itopride HCl and to formulate an Oro dispersible tablet (ODT) of the taste-masked drug by incorporation of microspheres in the tablets for use in specific populations viz. pediatrics, geriatrics and patients experiencing difficulty in swallowing. With this objective in mind, microspheres loaded with Itopride HCl were prepared by solvent evaporation method using acetone as solvent for pH-sensitive polymer, Eudragit EPO and light liquid paraffin as the encapsulating medium. The prepared microspheres were characterized with regard to yield, drug content, flow properties, particle size and size distribution, surface features, in vitro drug release and taste. The ODTs so prepared from these microspheres were evaluated for hardness, thickness, weight variation, friability, disintegration time, drug content, wetting time, water absorption ratio, moisture uptake, in vitro dispersion, in vitro disintegration, in vitro drug release and stability. The average size of microspheres was found to be satisfactory in terms of the size and size distribution. Microspheres prepared were of a regular spherical shape. Comparison of the dissolution profiles of microspheres in different pH media showed that microspheres having drug: polymer ratio of 1:2 produced a retarding effect in simulated salivary fluid (pH 6.8) and were further used for formulation into ODTs after addition of suitable amounts of excipients such as superdisintegrant, diluent, sweetener and flavor of directly compressible grade. Effective taste-masking was achieved for Itopride HCl by way of preparation of microspheres and ODTs of acceptable characteristics.

Demonstration of sub-femtomole sensitivity for small molecules with microsphere ring resonator sensors

NASA Astrophysics Data System (ADS)

White, Ian M.; Oveys, Hesam; Fan, Xudong

2006-02-01

Optical microsphere resonators can function as highly sensitive bio/chemical sensors due to the large Q-factor, which leads to high light-matter interaction. The whispering gallery modes (WGM) arise at the surface of the microsphere, creating a highly enhanced optical field that interacts with matter on or near the microsphere surface. As a result, the spectral position of the WGM is extremely sensitive to refractive index changes near the surface, such as when bio/chemical molecules bind to the sphere. We show the potential feasibility of a microsphere ring resonator as a sensor for small molecules by demonstrating detection of sub-femtomole changes in SiO II molecules at the surface of the microsphere. In this experiment, the silica molecules act as an excellent model for small molecule analytes because of their 60 Dalton molecular weight, and because we know nearly the exact quantity of molecules at the surface, which enables a sensitivity characterization. We measure the spectral shifts in the WGMs when low concentrations of hydrofluoric acid (HF) are added to a solution that is being probed by the microsphere. As the HF molecules break apart the SiO II molecules at the sphere surface, the WGMs shift due to the sub-nano-scale decrease in the size of the microsphere. These calculations show that the sensitivity of this microsphere resonator is on the order of 500 attomoles. Our results will lead to the utilization of optical microspheres for detection of trace quantities of small molecules for such applications as drug discovery, environmental monitoring, and enzyme detection using peptide cleavage.

Low-temperature and highly enhanced NO2 sensing performance of Au-functionalized WO3 microspheres with a hierarchical nanostructure

NASA Astrophysics Data System (ADS)

Shen, Yanbai; Bi, Hongshan; Li, Tingting; Zhong, Xiangxi; Chen, Xiangxiang; Fan, Anfeng; Wei, Dezhou

2018-03-01

Hierarchically nanostructured WO3 microspheres that had two types of Au functionalization modes (i.e., Au-loaded mode and Au-doped mode) were characterized in terms of their microstructure and NO2 sensing performance. Pure, Au-loaded, and Au-doped WO3 microspheres were synthesized using a hydrothermal method, followed by a dipping method for Au-loaded WO3 microspheres. Microstructure characterization indicated that uniform microspheres with 3-6 μm in diameter were assembled from numerous well-defined individual WO3 nanorods with a single crystal hexagonal structure. The morphology and size of the WO3 microspheres were not affected by the functionalization of the Au nanoparticles, and the W, O, and Au elements were well-distributed in the WO3 microspheres. The NO2 sensing properties indicated that the Au nanoparticles not only improved the sensor response and reproducibility but also decreased the operating temperature at which the sensor response reached a maximum. Gas sensors based on pure, Au-loaded, and Au-doped WO3 microspheres exhibited a linear relationship between the sensor response and NO2 concentration. The sensing performance was significantly enhanced in the following order: pure, Au-loaded, and Au-doped WO3 microspheres. This result is due to the modulation of the depletion layer via oxygen adsorption as well as chemical and electronic sensitization of Au nanoparticles.

Nitrogen-doped hierarchical porous carbon microsphere through KOH activation for supercapacitors.

PubMed

Jiang, Jingui; Chen, Hao; Wang, Zhao; Bao, Luke; Qiang, Yiwei; Guan, Shiyou; Chen, Jianding

2015-08-15

A porous carbon microsphere with moderate specific surface area and superior specific capacitance for supercapacitors is fabricated from polyphosphazene microsphere as the single heteroatoms source by the carbonization and subsequent KOH activation under N2 atmosphere. With KOH activation, X-ray photoelectron spectroscopy analysis confirms that the phosphorus of polyphosphazene microsphere totally vanishes, and the doping content of nitrogen and its population of various functionalities on porous carbon microsphere surface are tuned. Compared with non-porous carbon microsphere, the texture property of the resultant porous carbon microsphere subjected to KOH activation has been remarkably developed with the specific surface area growing from 315 to 1341 m(2) g(-1)and the pore volume turning from 0.17 to 0.69 cm(3) g(-1). Prepared with the KOH/non-porous carbon microsphere weight ratio at 1.0, the porous carbon microsphere with moderate specific surface area of 568 m(2) g(-1), exhibits intriguing electrochemical behavior in 1 M H2SO4 aqueous electrolyte, with superior specific capacitance (278 F g(-1) at 0.1 A g(-1)), good rate capability (147 F g(-1) remained at 10 A g(-1)) and robust cycling durability (No capacitance loss after 5000 cycles). The promising electrochemical performance could be ascribed to the synergy of nitrogen heteroatom functionalities and the porous morphology. Copyright © 2015 Elsevier Inc. All rights reserved.

Preparation and Application of Hollow Silica/magnetic Nanocomposite Particle

NASA Astrophysics Data System (ADS)

Wang, Cheng-Chien; Lin, Jing-Mo; Lin, Chun-Rong; Wang, Sheng-Chang

The hollow silica/cobalt ferrite (CoFe2O4) magnetic microsphere with amino-groups were successfully prepared via several steps, including preparing the chelating copolymer microparticles as template by soap-free emulsion polymerization, manufacturing the hollow cobalt ferrite magnetic microsphere by in-situ chemical co-precipitation following calcinations, and surface modifying of the hollow magnetic microsphere by 3-aminopropyltrime- thoxysilane via the sol-gel method. The average diameter of polymer microspheres was ca. 200 nm from transmission electron microscope (TEM) measurement. The structure of the hollow magnetic microsphere was characterized by using TEM and scanning electron microscope (SEM). The spinel-type lattice of CoFe2O4 shell layer was identified by using XRD measurement. The diameter of CoFe2O4 crystalline grains ranged from 54.1 nm to 8.5 nm which was estimated by Scherrer's equation. Additionally, the hollow silica/cobalt ferrite microsphere possesses superparamagnetic property after VSM measurement. The result of BET measurement reveals the hollow magnetic microsphere which has large surface areas (123.4m2/g). After glutaraldehyde modified, the maximum value of BSA immobilization capacity of the hollow magnetic microsphere was 33.8 mg/g at pH 5.0 buffer solution. For microwave absorption, when the hollow magnetic microsphere was compounded within epoxy resin, the maximum reflection loss of epoxy resins could reach -35dB at 5.4 GHz with 1.9 mm thickness.

Carbidopa/levodopa-loaded biodegradable microspheres: in vivo evaluation on experimental Parkinsonism in rats.

PubMed

Arica, Betül; Kaş, H Süheyla; Moghdam, Amir; Akalan, Nejat; Hincal, A Atilla

2005-02-16

The purpose of this study was to prepare and characterize injectable carbidopa (CD)/levodopa (LD)-loaded Poly(L-lactides) (L-PLA), Poly(D,L-lactides) (D,L-PLA) and Poly(D,L-lactide-co-glycolide) (PLAGA) microspheres for the intracerebral treatment of Parkinson's disease. The microspheres were prepared by solvent evaporation method. The polymers' (L-PLA, D,L-PLA and PLAGA) concentrations were 10% (w/w) in the organic phase; the emulsifiers [sodium carboxymethylcellulose (NaCMC):sodium oleate (SO) and Polyvinyl alcohol (PVA):SO mixture (4:1 w/v)] concentrations were 0.75% in the aqueous phase. Microspheres were analyzed for morphological characteristics, size distribution, drug loading and in vitro release. The release profile of CD/LD from microspheres was characterized in the range of 12-35% within the first hour of the in vitro release experiment. The efficiency of CD- and LD-encapsulated microspheres to striatal transplantation and the altering of apomorphine-induced rotational behavior in the 6-hydroxydopamine (6-OHDA) unilaterally lesioned rat model were also tested. 6-OHDA/CD-LD-loaded microsphere groups exhibited lower rotation scores than 6-OHDA/Blank microsphere groups as early as 1 week postlesion. These benefits continued throughout the entire experimental period and they were statistically significant during the 1, 2 and 8 weeks (p<0.05). CD/LD-loaded microspheres were specifically prepared to apply as an injectable dosage forms for brain implantation.

Dual Drug Loaded Biodegradable Nanofibrous Microsphere for Improving Anti-Colon Cancer Activity

PubMed Central

Fan, Rangrang; Li, Xiaoling; Deng, Jiaojiao; Gao, Xiang; Zhou, Liangxue; Zheng, Yu; Tong, Aiping; Zhang, Xiaoning; You, Chao; Guo, Gang

2016-01-01

One of the approaches being explored to increase antitumor activity of chemotherapeutics is to inject drug-loaded microspheres locally to specific anatomic sites, providing for a slow, long term release of a chemotherapeutic while minimizing systemic exposure. However, the used clinically drug carriers available at present have limitations, such as their low stability, renal clearance and residual surfactant. Here, we report docetaxel (DOC) and curcumin (CUR) loaded nanofibrous microspheres (DOC + CUR/nanofibrous microspheres), self-assembled from biodegradable PLA-PEO-PPO-PEO-PLA polymers as an injectable drug carrier without adding surfactant during the emulsification process. The obtained nanofibrous microspheres are composed entirely of nanofibers and have an open hole on the shell without the assistance of a template. It was shown that these DOC + CUR/nanofibrous microspheres could release curcumin and docetaxel slowly in vitro. The slow, sustained release of curcumin and docetaxel in vivo may help maintain local concentrations of active drug. The mechanism by which DOC + CUR/nanofibrous microspheres inhibit colorectal peritoneal carcinomatosis might involve increased induction of apoptosis in tumor cells and inhibition of tumor angiogenesis. In vitro and in vivo evaluations demonstrated efficacious synergistic antitumor effects against CT26 of curcumin and docetaxel combined nanofibrous microspheres. In conclusion, the dual drug loaded nanofibrous microspheres were considered potentially useful for treating abdominal metastases of colorectal cancer. PMID:27324595

Influence of polymeric microspheres on the myocardial oxygen partial pressure in the beating heart of pigs.

PubMed

Hiebl, B; Mrowietz, C; Lee, S; Braune, S; Knaut, M; Lendlein, A; Franke, R P; Jung, F

2011-07-01

Injection of labeled microspheres is an established method in animal models to analyze the capillary organ blood flow at different time points. However, the microspheres can lead to stenoses of the capillary lumen, which might affect tissue oxygen supply. Our study aimed to investigate the influence of repeated injections of microspheres into the left coronary artery on the tissue oxygen partial pressure (pO(2)) in the downstream supplied myocardium of Göttingen minipigs. Tests (n=6 pigs each) were performed with two differently sized microspheres (ø=10 ± 0.1 μm (M10) or ø=15 ± 0.15 μm (M15)) from polystyrene. The pO(2) was measured in the midmyocardium of the left and right ventricle for 6 min continuously after each of five injections (1 × 10(6) microspheres each). There was a time laps of 12 min between each injection. In addition, the influence of the carrier solution was analyzed solely in the identical time frame. pO(2) decreased significantly in the myocardial area supplied by the ramus interventricularis paraconalis after injection of M15 microspheres. In contrast, the application of the M10 microspheres did not change the myocardial pO(2). This finding suggests to use microspheres with diameters not exceeding 10 μm for the coronary blood flow assessment. Copyright © 2011 Elsevier Inc. All rights reserved.

Dual Drug Loaded Biodegradable Nanofibrous Microsphere for Improving Anti-Colon Cancer Activity

NASA Astrophysics Data System (ADS)

Fan, Rangrang; Li, Xiaoling; Deng, Jiaojiao; Gao, Xiang; Zhou, Liangxue; Zheng, Yu; Tong, Aiping; Zhang, Xiaoning; You, Chao; Guo, Gang

2016-06-01

One of the approaches being explored to increase antitumor activity of chemotherapeutics is to inject drug-loaded microspheres locally to specific anatomic sites, providing for a slow, long term release of a chemotherapeutic while minimizing systemic exposure. However, the used clinically drug carriers available at present have limitations, such as their low stability, renal clearance and residual surfactant. Here, we report docetaxel (DOC) and curcumin (CUR) loaded nanofibrous microspheres (DOC + CUR/nanofibrous microspheres), self-assembled from biodegradable PLA-PEO-PPO-PEO-PLA polymers as an injectable drug carrier without adding surfactant during the emulsification process. The obtained nanofibrous microspheres are composed entirely of nanofibers and have an open hole on the shell without the assistance of a template. It was shown that these DOC + CUR/nanofibrous microspheres could release curcumin and docetaxel slowly in vitro. The slow, sustained release of curcumin and docetaxel in vivo may help maintain local concentrations of active drug. The mechanism by which DOC + CUR/nanofibrous microspheres inhibit colorectal peritoneal carcinomatosis might involve increased induction of apoptosis in tumor cells and inhibition of tumor angiogenesis. In vitro and in vivo evaluations demonstrated efficacious synergistic antitumor effects against CT26 of curcumin and docetaxel combined nanofibrous microspheres. In conclusion, the dual drug loaded nanofibrous microspheres were considered potentially useful for treating abdominal metastases of colorectal cancer.

SPHRINT - Printing Drug Delivery Microspheres from Polymeric Melts.

PubMed

Shpigel, Tal; Uziel, Almog; Lewitus, Dan Y

2018-06-01

This paper describes a simple, straightforward, and rapid method for producing microspheres from molten polymers by merely printing them in an inkjet-like manner onto a superoleophobic surface (microsphere printing, hence SPHRINT). Similar to 3D printing, a polymer melt is deposited onto a surface; however, in contrast to 2D or 3D printing, the surface is not wetted (i.e. exhibiting high contact angles with liquids, above 150°, due to its low surface energy), resulting in the formation of discrete spherical microspheres. In this study, microspheres were printed using polycaprolactone and poly(lactic-co-glycolic acid) loaded with a model active pharmaceutical ingredient-ibuprofen (IBU). The formation of microspheres was captured by high-speed imaging and was found to involve several physical phenomena characterized by non-dimensional numbers, including the thinning and breakup of highly viscous, weakly elastic filaments, which are first to be described in pure polymer melts. The resulting IBU-loaded microspheres had higher sphericity, reproducible sizes and shapes, and superior drug encapsulation efficiencies with a distinctly high process yield (>95%) as compared to the conservative solvent-based methods used presently. Furthermore, the microspheres showed sustained release profiles. Copyright © 2018 Elsevier B.V. All rights reserved.

Hollow Polycaprolactone Microspheres with/without a Single Surface Hole by Co-Electrospraying

PubMed Central

2017-01-01

We describe the co-electrospraying of hollow microspheres from a polycaprolactone (PCL) shell solution and various core solutions including water, cyclohexane, poly(ethylene oxide) (PEO), and polyethylene glycol (PEG), using different collectors. The morphologies of the resultant microspheres were characterized by scanning electron microscopy (SEM), confocal microscopy, and nano-X-ray computed tomography (nano-XCT). The core/shell solution miscibility played an important role in the co-electrospraying process and the formation of microsphere structures. Spherical particles were more likely to be produced from miscible combinations of core/shell solutions than from immiscible ones. Hollow PCL microspheres with a single hole in their surfaces were produced when an ethanol bath was used as the collector. The mechanism by which the core/shell structure is transformed into single-hole hollow microspheres is proposed to be primarily based on the evaporation through the shell and extraction by ethanol of the core solution and is described in detail. Additionally, we present a 3D macroscopic tubular structure composed of hollow PCL microspheres, directly assembled on a copper wire collector during co-electrospraying. SEM and nano-XCT confirm that microspheres in the 3D bulk structure remain hollow. PMID:28901145

Evaluation of BSA protein release from hollow hydroxyapatite microspheres into PEG hydrogel

PubMed Central

Fu, Hailuo; Rahaman, Mohamed N.; Brown, Roger F.; Day, Delbert E.

2013-01-01

Implants that simultaneously function as an osteoconductive matrix and as a device for local drug or growth factor delivery could provide an attractive system for bone regeneration. In our previous work, we prepared hollow hydroxyapatite (abbreviated HA) microspheres with a high surface area, mesoporous shell wall and studied the release of a model protein, bovine serum albumin (BSA), from the microspheres into phosphate-buffered saline (PBS). The present work is an extension of our previous work to study the release of BSA from similar HA microspheres into a biocompatible hydrogel, poly(ethylene glycol) (PEG). BSA-loaded HA microspheres were placed in a PEG solution which was rapidly gelled using ultraviolet radiation. The BSA release rate into the PEG hydrogel, measured using a spectrophotometric method, was slower than into PBS, and it was dependent on the initial BSA loading and on the microstructure of the microsphere shell wall. A total of 35–40% of the BSA initially loaded into the microspheres was released into PEG over ~14 days. The results indicate that these hollow HA microspheres have promising potential as an osteoconductive device for local drug or growth factor delivery in bone regeneration and in the treatment of bone diseases. PMID:23498254

Development and gamma-scintigraphy study of Hibiscus rosasinensis polysaccharide-based microspheres for nasal drug delivery.

PubMed

Sharma, Nitin; Tyagi, Shanu; Gupta, Satish Kumar; Kulkarni, Giriraj Thirupathirao; Bhatnagar, Aseem; Kumar, Neeraj

2016-11-01

This work describes the application of natural plant polysaccharide as pharmaceutical mucoadhesive excipients in delivery systems to reduce the clearance rate through nasal cavity. Novel natural polysaccharide (Hibiscus rosasinensis)-based mucoadhesive microspheres were prepared by using emulsion crosslinking method for the delivery of rizatriptan benzoate (RB) through nasal route. Mucoadhesive microspheres were characterized for different parameters and nasal clearance of technetium-99m ((99m)Tc)-radiolabeled microspheres was determined by using gamma-scintigraphy. Their Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) studies showed that the drug was stable during preparation of microspheres. Aerodynamic diameter of microspheres was in the range 13.23 ± 1.83-33.57 ± 3.69 µm. Change in drug and polysaccharide ratio influenced the mucoadhesion, encapsulation efficiency and in-vitro release property. Scintigraphs taken at regular interval indicate that control solution was cleared rapidly from nasal cavity, whereas microspheres showed slower clearance (p < 0.005) with half-life of 160 min. Natural polysaccharide-based microspheres achieved extended residence by minimizing effect of mucociliary clearance with opportunity of sustained delivery for longer duration.

Synthesis and effect of modification on methacylate - acrylate microspheres for Trametes versicolor laccase enzyme immobilization

NASA Astrophysics Data System (ADS)

Mazlan, Siti Zulaikha; Hanifah, Sharina Abu

2014-09-01

Immobilization of laccase on the modified copolymer methacrylate-acrylate microspheres was studied. A poly (glycidyl methacrylate-co-n-butyl acrylate) microsphere consists of epoxy groups were synthesized using suspension photocuring technique. The epoxy group in poly (GMA-nBA) microspheres were converted into amino groups with aldehyde group. Laccase immobilization is based on having the amino groups on the enzyme surface and aldehyde group on the microspheres via covalent binding. Fourier transform infrared spectroscopy (FT-IR) analysis proved the successful surface modification on microspheres. The FTIR spectrum shows the characteristic peaks at 1646 cm-1 assigned to the conformation of the polymerization that took place between monomer GMA and nBA respectively. In addition, after modification, FTIR peaks that assigned to the epoxy ring (844 cm-1 and 904 cm-1) were decreased. The results obtained from FTIR method signify good agreement with the epoxy content method. Hence, the activity of the laccase-immobilized microspheres increased upon increasing the epoxy content. Furthermore, poly (GMA-nBA) exhibited uniform microspheres with below 2 μm surface. Immobilized enzyme showed a broader pH profile and higher temperature compared native enzyme.

Performance evaluation of bipolar and tripolar excitations during nozzle-jetting-based alginate microsphere fabrication

NASA Astrophysics Data System (ADS)

Herran, C. Leigh; Huang, Yong; Chai, Wenxuan

2012-08-01

Microspheres, small spherical (polymeric) particles with or without second phase materials embedded or encapsulated, are important for many biomedical applications such as drug delivery and organ printing. Scale-up fabrication with the ability to precisely control the microsphere size and morphology has always been of great manufacturing interest. The objective of this work is to experimentally study the performance differences of bipolar and tripolar excitation waveforms in using drop-on-demand (DOD)-based single nozzle jetting for alginate microsphere fabrication. The fabrication performance has been evaluated based on the formability of alginate microspheres as a function of materials properties (sodium alginate and calcium chloride concentrations) and operating conditions. The operating conditions for each excitation include voltage rise/fall times, dwell times and excitation voltage amplitudes. Overall, the bipolar excitation is more robust in making spherical, monodispersed alginate microspheres as good microspheres for its wide working range of material properties and operating conditions, especially during the fabrication of highly viscous materials such as the 2% sodium alginate solution. For both bipolar and tripolar excitations, the sodium alginate concentration and the voltage dwell times should be carefully selected to achieve good microsphere formability.

MO-A-BRD-00: Current Trends in Y90-Microsphere Therapy: Delivery and Dosimetry

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

NONE

2015-06-15

Yttrium-90 (Y90) microsphere therapy, a form of radiation therapy, is an increasingly popular option for care of patients with liver metastases or unresectable hepatocellular carcinoma. The therapy directly delivers Y90 microspheres via the hepatic artery to disease sites. Following delivery, a vast majority of microspheres preferentially lodge in the capillary vessels due to their embolic size and targeted trans-arterial delivery – depositing up to 90% of its energy in the first 5 mm of tissue. There have been a number of advances in tomographic imaging within both interventional radiology and nuclear medicine that has advanced therapy planning techniques. Quantitative imagingmore » of Y90 microsphere distribution post-therapy has also seen innovations that have led to improvements in tumor dosimetry and characterization of tumor response. A review of current trends and recent innovation in Y90 microsphere therapies will be presented. Learning Objectives: To present the imaging requirements for Y90 microsphere therapy planning To explain the standard dosimetry models used in Y90 microsphere therapy planning To report on advances in imaging for therapy planning and posttherapy assessment of tumor dosimetry and response.« less

Effect of palmitic acid on the characteristics and release profiles of rotigotine-loaded microspheres.

PubMed

Wang, Aiping; Liang, Rongcai; Liu, Wanhui; Sha, Chunjie; Li, Youxin; Sun, Kaoxiang

2016-01-01

The initial burst release is a major obstacle to the development of microsphere-formulated drug products. To investigate the influence of palmitic acid on the characteristics and release profiles of rotigotine-loaded poly(d,l-lactide-co-glycolide) microspheres. Rotigotine-loaded microspheres (RMS) were prepared using the oil-in-water emulsion solvent evaporation technique. The in vitro characteristics of the RMS were evaluated with scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and a particle size analyzer. The in vitro drug release and in vivo pharmacokinetics of the RMS were investigated. The SEM results showed that the addition of palmitic acid changed the surface morphology of the microspheres from smooth to dimpled and then to non-smooth as the palmitic acid content increased. DSC revealed the existence of molecularly dispersed forms of palmitic acid in the microspheres. The in vitro and in vivo release profiles indicated that the addition of 5% and 8% palmitic acid significantly decreased the burst release of rotigotine from the microspheres, and the late-stage release was delayed as the palmitic acid content increased across the investigated range (5-15%). The addition of palmitic acid to the microspheres significantly affects the release profile of rotigotine from RMS.

Preparation and Characterization of Silica Aerogel Microspheres

PubMed Central

Chen, Qifeng; Wang, Hui; Sun, Luyi

2017-01-01

Silica aerogel microspheres based on alkali silica sol were synthesized using the emulsion method. The experimental results revealed that the silica aerogel microspheres (4–20 µm in diameter) were mesoporous solids with an average pore diameter ranging from 6 to 35 nm. The tapping densities and specific surface areas of the aerogel microspheres are in the range of 0.112–0.287 g/cm3 and 207.5–660.6 m2/g, respectively. The diameter of the silica aerogel microspheres could be tailored by varying the processing conditions including agitation rate, water/oil ratio, mass ratio of Span 80: Tween 80, and emulsifier concentration. The effects of these parameters on the morphology and textural properties of the synthesized silica aerogel microspheres were systematically investigated. Such silica aerogel microspheres can be used to prepare large-scale silica aerogels at an ambient pressure for applications in separation and high efficiency catalysis, which requires features of high porosity and easy fill and recovery. PMID:28772795

Effects of formulation variables and characterization of guaifenesin wax microspheres for controlled release.

PubMed

Mani, Narasimhan; Park, M O; Jun, H W

2005-01-01

Sustained-release wax microspheres of guaifenesin, a highly water-soluble drug, were prepared by the hydrophobic congealable disperse method using a salting-out procedure. The effects of formulation variables on the loading efficiency, particle properties, and in-vitro drug release from the microspheres were determined. The type of dispersant, the amount of wetting agent, and initial stirring time used affected the loading efficiency, while the volume of external phase and emulsification speed affected the particle size of the microspheres to a greater extent. The crystal properties of the drug in the wax matrix and the morphology of the microspheres were studied by differential scanning calorimetry (DSC), powder x-ray diffraction (XRD), and scanning electron microscopy (SEM). The DSC thermograms of the microspheres showed that the drug lost its crystallinity during the microencapsulation process, which was further confirmed by the XRD data. The electron micrographs of the drug-loaded microspheres showed well-formed spherical particles with a rough exterior.

CO2 Biofixation of Actinobacillus succinogenes Through Novel Amine-Functionalized Polystyrene Microsphere Materials.

PubMed

Zhu, Wenhao; Li, Qiang; Dai, Ning

2017-02-01

CO 2 -derived succinate production was enhanced by Actinobacillus succinogenes through polystyrene (PSt) microsphere materials for CO 2 adsorption in bioreactor, and the adhesion forces between A. succinogenes bacteria and PSt materials were characterized. Synthesized uniformly sized and highly cross-linked PSt microspheres had high specific surface areas. After modification with amine functional groups, the novel amine-functionalized PSt microspheres exhibited a high adsorption capacity of 25.3 mg CO 2 /g materials. After addition with the functionalized microspheres into the culture broth, CO 2 supply to the cells increased. Succinate production by A. succinogenes can be enhanced from 29.6 to 48.1 g L -1 . Moreover, the characterization of interaction forces between A. succinogenes cells and the microspheres indicated that the maximal adhesive force was about 250 pN. The amine-functionalized PSt microspheres can adsorb a large amount of CO 2 and be employed for A. succinogenes anaerobic cultivation in bioreactor for high-efficiency production of CO 2 -derived succinate.

Preparation of cellulose based microspheres by combining spray coagulating with spray drying.

PubMed

Wang, Qiao; Fu, Aiping; Li, Hongliang; Liu, Jingquan; Guo, Peizhi; Zhao, Xiu Song; Xia, Lin Hua

2014-10-13

Porous microspheres of regenerated cellulose with size in range of 1-2 μm and composite microspheres of chitosan coated cellulose with size of 1-3 μm were obtained through a two-step spray-assisted approach. The spray coagulating process must combine with a spray drying step to guarantee the formation of stable microspheres of cellulose. This approach exhibits the following two main virtues. First, the preparation was performed using aqueous solution of cellulose as precursor in the absence of organic solvent and surfactant; Second, neither crosslinking agent nor separated crosslinking process was required for formation of stable microspheres. Moreover, the spray drying step also provided us with the chance to encapsulate guests into the resultant cellulose microspheres. The potential application of the cellulose microspheres acting as drug delivery vector has been studied in two PBS (phosphate-buffered saline) solution with pH values at 4.0 and 7.4 to mimic the environments of stomach and intestine, respectively. Copyright © 2014 Elsevier Ltd. All rights reserved.

Polyamine/salt-assembled microspheres coated with hyaluronic acid for targeting and pH sensing.

PubMed

Zhang, Pan; Yang, Hui; Wang, Guojun; Tong, Weijun; Gao, Changyou

2016-06-01

The poly(allylamine hydrochloride)/trisodium citrate aggregates were fabricated and further covalently crosslinked via the coupling reaction of carboxylic sites on trisodium citrate with the amine groups on polyamine, onto which poly-L-lysine and hyaluronic acid were sequentially assembled, forming stable microspheres. The pH sensitive dye and pH insensitive dye were further labeled to enable the microspheres with pH sensing property. Moreover, these microspheres could be specifically targeted to HeLa tumor cells, since hyaluronic acid can specifically recognize and bind to CD44, a receptor overexpressed on many tumor cells. Quantitative pH measurement by confocal laser scanning microscopy demonstrated that the microspheres were internalized into HeLa cells, and accumulated in acidic compartments. By contrast, only a few microspheres were adhered on the NIH 3T3 cells surface. The microspheres with combined pH sensing property and targeting ability can enhance the insight understanding of the targeted drug vehicles trafficking after cellular internalization. Copyright © 2016 Elsevier B.V. All rights reserved.

Nanofibrous hollow microspheres self-assembled from star-shaped polymers as injectable cell carriers for knee repair.

PubMed

Liu, Xiaohua; Jin, Xiaobing; Ma, Peter X

2011-05-01

To repair complexly shaped tissue defects, an injectable cell carrier is desirable to achieve an accurate fit and to minimize surgical intervention. However, the injectable carriers available at present have limitations, and are not used clinically for cartilage regeneration. Here, we report nanofibrous hollow microspheres self-assembled from star-shaped biodegradable polymers as an injectable cell carrier. The nanofibrous hollow microspheres, integrating the extracellular-matrix-mimicking architecture with a highly porous injectable form, were shown to efficiently accommodate cells and enhance cartilage regeneration, compared with control microspheres. The nanofibrous hollow microspheres also supported a significantly larger amount of, and higher-quality, cartilage regeneration than the chondrocytes-alone group in an ectopic implantation model. In a critical-size rabbit osteochondral defect-repair model, the nanofibrous hollow microspheres/chondrocytes group achieved substantially better cartilage repair than the chondrocytes-alone group that simulates the clinically available autologous chondrocyte implantation procedure. These results indicate that the nanofibrous hollow microspheres are an excellent injectable cell carrier for cartilage regeneration.

Preparation and Characterization of Silica Aerogel Microspheres.

PubMed

Chen, Qifeng; Wang, Hui; Sun, Luyi

2017-04-20

Silica aerogel microspheres based on alkali silica sol were synthesized using the emulsion method. The experimental results revealed that the silica aerogel microspheres (4-20 µm in diameter) were mesoporous solids with an average pore diameter ranging from 6 to 35 nm. The tapping densities and specific surface areas of the aerogel microspheres are in the range of 0.112-0.287 g/cm³ and 207.5-660.6 m²/g, respectively. The diameter of the silica aerogel microspheres could be tailored by varying the processing conditions including agitation rate, water/oil ratio, mass ratio of Span 80: Tween 80, and emulsifier concentration. The effects of these parameters on the morphology and textural properties of the synthesized silica aerogel microspheres were systematically investigated. Such silica aerogel microspheres can be used to prepare large-scale silica aerogels at an ambient pressure for applications in separation and high efficiency catalysis, which requires features of high porosity and easy fill and recovery.

Evaluation of the Thermosensitive Release Properties of Microspheres Containing an Agrochemical Compound.

PubMed

Terada, Takatoshi; Ohtsubo, Toshiro; Iwao, Yasunori; Noguchi, Shuji; Itai, Shigeru

2017-01-01

The purpose of this study was to develop a deeper understanding of the key physicochemical parameters involved in the release profiles of microsphere-encapsulated agrochemicals at different temperatures. Microspheres consisting of different polyurethanes (PUs) were prepared using our previously reported solventless microencapsulation technique. Notably, these microspheres exhibited considerable differences in their thermodynamic characteristics, including their glass transition temperature (T g ), extrapolated onset temperature (T o ) and extrapolated end temperature (T e ). At test temperatures below the T o of the PU, only 5-10% of the agrochemical was rapidly released from the microspheres within 1 d, and none was released thereafter. However, at test temperatures above the T o of the PU, the rate of agrochemical release gradually increased with increasing temperatures, and the rate of release from the microspheres was dependent on the composition of the PU. Taken together, these results show that the release profiles of the microspheres were dependent on their thermodynamic characteristics and changes in their PU composition.

Preparation and Characterization of Fluorescent SiO2 Microspheres

NASA Astrophysics Data System (ADS)

Xu, Cui; Zhang, Hao; Guan, Ruifang

2018-01-01

Fluorescent compound without typical fluorophores was synthesized with citric acid (CA) and aminopropyltriethoxysilane (APTS) firstly, and then it was grafted to the surface of the prepared SiO2 microspheres by chemical reaction. The fluorescent SiO2 microspheres with good fluorescent properties were obtained by optimizing the reaction conditions. And the morphology and structure of the fluorescent SiO2 microspheres have been characterized by scanning electron microscopy (SEM) and fourier transform infrared (FTIR) spectroscopy. The results showed that the preparation of fluorescent SiO2 microspheres have good monodispersity and narrow particle size distribution. Moreover, the fluorescent SiO2 microspheres can be applied to detect Fe3+ in aqueous solution, prepare fluorescent SiO2 rubber, and have potential to be applied in the fluorescent labeling and fingerprint appearing technique fields.

Thermal response of chalcogenide microsphere resonators

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

Ahmad, H; Aryanfar, I; Lim, K S

2012-05-31

A chalcogenide microsphere resonator (CMR) used for temperature sensing is proposed and demonstrated. The CMR is fabricated using a simple technique of heating chalcogenide glass and allowing the molten glass to form a microsphere on the waist of a tapered silica fibre. The thermal responses of the CMR is investigated and compared to that of a single-mode-fibre (SMF) based microsphere resonator. It is observed that the CMR sensitivity to ambient temperature changes is 8 times higher than that of the SMF-based microsphere resonator. Heating the chalcogenide microsphere with a laser beam periodically turned on and off shows periodic shifts inmore » the transmission spectrum of the resonator. By injecting an intensity-modulated cw signal through the resonator a thermal relaxation time of 55 ms is estimated.« less

Experimental evaluation of the magnetic properties of commercially available magnetic microspheres.

PubMed

Connolly, Joan; St Pierre, Timothy G; Dobson, Jon

2005-01-01

The magnetic properties of 5 commercially available magnetic microsphere samples are tested and compared with those stated by their manufacturers. A suspension of magnetic, iron oxide nanoparticles is studied for comparison. Two of the microsphere samples have magnetic properties which do not support the manufacturer's claims of superparamagnetism. The remaining 3 microsphere samples as well as the nanoparticle suspension are superparamagnetic or ferromagnetic as claimed by the manufacturers. Field cooled and zero field cooled magnetisations indicate that the non-superparamagnetic microsphere samples contain blocked magnetic particles at room temperature. This observation is supported by the open hysteresis loops of the room temperature, field dependent magnetisation measurement. There is a significant paramagnetic component in the superparamagnetic microspheres. This is also present to a lesser extent in a nanoparticle suspension.

PREPARATION OF FLOWER-LIKE Co3O4/Fe3O4 MAGNETIC MICROSPHERES FOR PHOTODEGRADATION OF RhB UNDER UV LIGHT

NASA Astrophysics Data System (ADS)

Zhang, Baoliang; Zhang, Hepeng; Zhou, Lunwei; Ali, Nisar; Geng, Wangchang; Zhang, Qiuyu

2013-07-01

Flower-like Co3O4/Fe3O4 magnetic microspheres were prepared by coprecipitation of Fe2+ and Fe3+ in presence of flower-like Co3O4 microspheres as template. The preparation process included three steps: preparation of flower-like Co3O4 microspheres by hydrothermal method; immersion of Fe2+ and Fe3+ ions; coprecipitation in the presence of OH-. Rhodamine B (RhB) was chosen as model pollutants to investigate the photodegradation capacities of Co3O4/Fe3O4 magnetic microspheres. The results showed that the microspheres exhibited excellent degradation property and can be recycled to use again. After four times use the degradation efficiency was still above 90%.

Biomimetic composite microspheres of collagen/chitosan/nano-hydroxyapatite: In-situ synthesis and characterization.

PubMed

Teng, Shu-Hua; Liang, Mian-Hui; Wang, Peng; Luo, Yong

2016-01-01

The collagen/chitosan/hydroxyapatite (COL/CS/HA) composite microspheres with a good spherical form and a high dispersity were successfully obtained using an in-situ synthesis method. The FT-IR and XRD results revealed that the inorganic phase in the microspheres was crystalline HA containing carbonate ions. The morphology of the composite microspheres was dependent on the HA content, and a more desirable morphology was achieved when 20 wt.% HA was contained. The composite microspheres exhibited a narrow particle distribution, most of which ranged from 5 to 10 μm. In addition, the needle-like HA nano-particles were uniformly distributed in the composite microspheres, and their crystallinity and crystal size decreased with the HA content. Copyright © 2015 Elsevier B.V. All rights reserved.

Synthesis, characterization and evaluation of uniformly sized core-shell imprinted microspheres for the separation trans-resveratrol from giant knotweed

NASA Astrophysics Data System (ADS)

Zhang, Zhaohui; Liu, Li; Li, Hui; Yao, Shouzhuo

2009-09-01

A novel core-shell molecularly imprinting microspheres (MIMs) with trans-resveratrol as the template molecule; acrylamide (AA) as functional monomer and ethylene glycol dimethacrylate (EGDMA) as cross-linker, was prepared based on SiO 2 microspheres with surface imprinting technique. These core-shell trans-resveratrol imprinted microspheres were characterized by infrared spectra (IR), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and high performance liquid chromatography (HPLC). The results showed that these core-shell imprinted microspheres, which take on perfect spherical shape with average shell thickness of 150 nm, exhibit especially selective recognition for trans-resveratrol. These imprinted microspheres were applied as solid-phase extraction materials for selective extraction of trans-resveratrol from giant knotweed extracting solution successfully.

Coupling system to a microsphere cavity

NASA Technical Reports Server (NTRS)

Iltchenko, Vladimir (Inventor); Maleki, Lute (Inventor); Yao, Steve (Inventor); Wu, Chi (Inventor)

2002-01-01

A system of coupling optical energy in a waveguide mode, into a resonator that operates in a whispering gallery mode. A first part of the operation uses a fiber in its waveguide mode to couple information into a resonator e.g. a microsphere. The fiber is cleaved at an angle .PHI. which causes total internal reflection within the fiber. The energy in the fiber then forms an evanescent field and a microsphere is placed in the area of the evanescent field. If the microsphere resonance is resonant with energy in the fiber, then the information in the fiber is effectively transferred to the microsphere.

Effective medium model for a granular monolayer on an elastic substrate

NASA Astrophysics Data System (ADS)

Maznev, Alexei

Effective medium models have been shown to work well in describing experimental observations of the interaction of surface Rayleigh waves with contact vibrations of a monolayer of microspheres . However, these models contain intrinsic conceptual problems: for example, the local displacement of the substrate at the contact point is equated to the effective medium average value of the surface displacement. I will present a rigorous derivation of the effective medium model for a random arrangement of mass-spring oscillators on an elastic half-space using elastodynamic surface Green's function formalism. We will see that the model equating the local surface displacement to the effective medium displacement is indeed valid if the spring constant of the oscillators is modified to include the stiffness of the contact calculated in the quasistatic approximation. In the case of contact vibrations of microspheres, this means using the spring constant calculated using the Hertzian contact model. Thus the results obtained in the prior work were correct despite the apparent inconsistencies in the model. The presented analysis will provide a solid foundation for effective medium models used to describe dynamics of microparticle arrays adhered to a solid substrate. This work was supported by the U. S. Army Research Office through the Institute for Soldier Nanotechnologies under Grant W911NF-13-D-0001.

High-throughput microsphiltration to assess red blood cell deformability and screen for malaria transmission-blocking drugs.

PubMed

Duez, Julien; Carucci, Mario; Garcia-Barbazan, Irene; Corral, Matias; Perez, Oscar; Presa, Jesus Luis; Henry, Benoit; Roussel, Camille; Ndour, Papa Alioune; Rosa, Noemi Bahamontes; Sanz, Laura; Gamo, Francisco-Javier; Buffet, Pierre

2018-06-01

The mechanical retention of rigid erythrocytes in the spleen is central in major hematological diseases such as hereditary spherocytosis, sickle-cell disease and malaria. Here, we describe the use of microsphiltration (microsphere filtration) to assess erythrocyte deformability in hundreds to thousands of samples in parallel, by filtering them through microsphere layers in 384-well plates adapted for the discovery of compounds that stiffen Plasmodium falciparum gametocytes, with the aim of interrupting malaria transmission. Compound-exposed gametocytes are loaded into microsphiltration plates, filtered and then transferred to imaging plates for analysis. High-content imaging detects viable gametocytes upstream and downstream from filters and quantifies spleen-like retention. This screening assay takes 3-4 d. Unlike currently available methods used to assess red blood cell (RBC) deformability, microsphiltration enables high-throughput pharmacological screening (tens of thousands of compounds tested in a matter of months) and involves a cell mechanical challenge that induces a physiologically relevant dumbbell-shape deformation. It therefore directly assesses the ability of RBCs to cross inter-endothelial splenic slits in vivo. This protocol has potential applications in quality control for transfusion and in determination of phenotypic markers of erythrocytes in hematological diseases.

Multimodality Imaging of Ethiodized Oil–loaded Radiopaque Microspheres during Transarterial Embolization of Rabbits with VX2 Liver Tumors

PubMed Central

Tacher, Vania; Duran, Rafael; Lin, MingDe; Sohn, Jae Ho; Sharma, Karun V.; Wang, Zhijun; Chapiro, Julius; Gacchina Johnson, Carmen; Bhagat, Nikhil; Dreher, Matthew R.; Schäfer, Dirk; Woods, David L.; Lewis, Andrew L.; Tang, Yiqing; Grass, Michael; Wood, Bradford J.

2016-01-01

Purpose To assess the visibility of radiopaque microspheres during transarterial embolization (TAE) in the VX2 rabbit liver tumor model by using multimodality imaging, including single-snapshot radiography, cone-beam computed tomography (CT), multidetector CT, and micro-CT. Materials and Methods The study was approved by the institutional animal care and use committee. Fifteen VX2-tumor-bearing rabbits were assigned to three groups depending on the type of embolic agent injected: 70–150-μm radiopaque microspheres in saline (radiopaque microsphere group), 70–150-μm radiopaque microspheres in contrast material (radiopaque microsphere plus contrast material group), and 70–150-μm radiolucent microspheres in contrast material (nonradiopaque microsphere plus contrast material group). Rabbits were imaged with single-snapshot radiography, cone-beam CT, and multidetector CT. Three to 5 weeks after sacrifice, excised livers were imaged with micro-CT and histologic analysis was performed. The visibility of the embolic agent was assessed with all modalities before and after embolization by using a qualitative three-point scale score reading study and a quantitative assessment of the signal-to-noise ratio (SNR) change in various regions of interest, including the tumor and its feeding arteries. The Kruskal-Wallis test was used to compare the rabbit characteristics across groups, and the Wilcoxon signed rank test was used to compare SNR measurements before and after embolization. Results Radiopaque microspheres were qualitatively visualized within tumor feeding arteries and targeted tissue with all imaging modalities (P < .05), and their presence was confirmed with histologic examination. SNRs of radiopaque microsphere deposition increased after TAE on multidetector CT, cone-beam CT, and micro-CT images (P < .05). Similar results were obtained when contrast material was added to radiopaque microspheres, except for additional image attenuation due to tumor enhancement. For the group with nonradiopaque microspheres and contrast material, retained tumoral contrast remained qualitatively visible with all modalities except for micro-CT, which demonstrated soluble contrast material washout over time. Conclusion Radiopaque microspheres were visible with all imaging modalities and helped increase conspicuity of the tumor as well as its feeding arteries after TAE in a rabbit VX2 liver tumor model. © RSNA, 2015 PMID:26678453

An optimized library for reference-based deconvolution of whole-blood biospecimens assayed using the Illumina HumanMethylationEPIC BeadArray.

PubMed

Salas, Lucas A; Koestler, Devin C; Butler, Rondi A; Hansen, Helen M; Wiencke, John K; Kelsey, Karl T; Christensen, Brock C

2018-05-29

Genome-wide methylation arrays are powerful tools for assessing cell composition of complex mixtures. We compare three approaches to select reference libraries for deconvoluting neutrophil, monocyte, B-lymphocyte, natural killer, and CD4+ and CD8+ T-cell fractions based on blood-derived DNA methylation signatures assayed using the Illumina HumanMethylationEPIC array. The IDOL algorithm identifies a library of 450 CpGs, resulting in an average R 2  = 99.2 across cell types when applied to EPIC methylation data collected on artificial mixtures constructed from the above cell types. Of the 450 CpGs, 69% are unique to EPIC. This library has the potential to reduce unintended technical differences across array platforms.

Covalent Immobilization of Microtubules on Glass Surfaces for Molecular Motor Force Measurements and Other Single-Molecule Assays

PubMed Central

Nicholas, Matthew P.; Rao, Lu; Gennerich, Arne

2014-01-01

Rigid attachment of microtubules (MTs) to glass cover slip surfaces is a prerequisite for a variety of microscopy experiments in which MTs are used as substrates for MT-associated proteins, such as the molecular motors kinesin and cytoplasmic dynein. We present an MT-surface coupling protocol in which aminosilanized glass is formylated using the cross-linker glutaraldehyde, fluorescence-labeled MTs are covalently attached, and the surface is passivated with highly pure beta-casein. The technique presented here yields rigid MT immobilization while simultaneously blocking the remaining glass surface against nonspecific binding by polystyrene optical trapping microspheres. This surface chemistry is straightforward and relatively cheap and uses a minimum of specialized equipment or hazardous reagents. These methods provide a foundation for a variety of optical tweezers experiments with MT-associated molecular motors and may also be useful in other assays requiring surface-immobilized proteins. PMID:24633798

Universal fieldable assay with unassisted visual detection

NASA Technical Reports Server (NTRS)

Chelyapov, Nicolas (Inventor)

2012-01-01

A universal detection system based on allosteric aptamers, signal amplification cascade, and eye-detectable phrase transition. A broadly applicable homogeneous detection system is provided. It utilizes components of the blood coagulation cascade in the presence of polystyrene microspheres (MS) as a signal amplifier. Russell's viper venom factor X activator (RVV-X) triggers the cascade, which results in an eye-visible phase transition--precipitation of MS bound to clotted fibrin. An allosteric RNA aptamer, RNA132, with affinity for RVV-X and human vascular endothelial growth factor (VEGF.sub.165) was created. RNA132 inhibits enzymatic activity of RVV-X. The effector molecule, VEGF.sub.165, reverses the inhibitory activity of RNA132 on RVV-X and restores its enzymatic activity, thus triggering the cascade and enabling the phase transition. Similar results were obtained for another allosteric aptamer modulated by a protein tyrosine phosphatase. The assay is instrumentation-free for both processing and readout.

Preparation, characterization, and in vitro testing of poly(lactide-co-glycolide) and dextran magnetic microspheres for in vivo applications

NASA Astrophysics Data System (ADS)

Leamy, Patrick J.

Many research groups are investigating degradable magnetic particles for magnetic resonance imaging (MRI) contrast agents and as carriers for magnetic drug guidance. These particles are composite materials with a degradable polymer matrix and iron oxide nanoparticles for magnetic properties. The degradable polymer matrix acts to provide colloidal stability and, for drug delivery applications, provides a reservoir for the storage and release of drugs. Natural polymers, like albumin and dextran, which degrade by the action of enzymes; have been used for the polymer matrix. Iron oxide nanoparticles are used for magnetic properties since they can be digested in vivo and have low toxicities. Polylactic acid (PLA) and its copolymers with polyglycolic acid (PLGA) are versatile polymers that degrade by simple hydrolysis without the aid of enzymes. Microspheres are easily formed using the solvent extraction/evaporation method and a wide range of drugs can be encapsulated in them. Magnetic PLGA microspheres suitable for applications were synthesized for the first time in this dissertation. This was accomplished by coating iron oxide nanoparticles with oleic acid to make them dispersible in the organic solvents used in the extraction/evaporation microsphere preparation method. In addition to the magnetic PLGA microspheres, a novel all-aqueous method for preparing crosslinked dextran magnetic microspheres was developed in this dissertation. This method uses free radical polymerization for crosslinking and does not require the use of flammable and harmful solvents. For efficient MRI contrast and magnetic drug guidance, maximized iron oxide content of microspheres is desirable. The two different microsphere preparation methods were optimized for iron oxide content. The effect of iron oxide content on microsphere size and morphology was studied. In addition, an in vitro circulation model was used to evaluate the ability of magnetic microspheres to be guided at physiologic blood flow velocities. The MRI contrast effect was studied as a function of microsphere concentration.

[Preparation of citrulline microspheres by spray drying technique for colonic targeting].

PubMed

Bahri, S; Zerrouk, N; Lassoued, M-A; Tsapis, N; Chaumeil, J-C; Sfar, S

2014-03-01

Citrulline is an amino acid that becomes essential in situations of intestinal insufficiency such as short bowel syndrome. It is therefore interesting to provide the patients with dosage forms for routing citrulline to the colon. The aim of this work is to formulate microspheres of citrulline for colonic targeting by the technique of spray drying. Eudragit(®) FS 30D was selected as polymer to encapsulate citrulline using the spray drying technique. Citrulline and Eudragit(®) FS 30D were dissolved in water and ethanol, respectively. The aqueous and the ethanolic solutions were then mixed in 1:2 (v/v) ratio. Microspheres were obtained by nebulizing the citrulline-Eudragit(®) FS 30D solution using a Mini spray dryer equipped with a 0.7mm nozzle. The microspheres have been formulated using citrulline and Eudragit(®) FS 30D. The size distribution of microspheres was determined by light diffraction. The morphology of the microspheres was studied by electron microscopy. Manufacturing yields, encapsulation rate and dissolution profiles were also studied. The microspheres obtained had a spherical shape with a smooth surface and a homogeneous size except for the microspheres containing the highest concentration of polymer (90 %). The formulation showed that the size and morphology of the microspheres are influenced by the polymer concentration. Manufacturing yields were about 51 % but encapsulation rate were always very high (above 90 %). The in vitro dissolution study showed that the use of the Eudragit(®) FS 30D under these conditions is not appropriate to change the dissolution profile of the citrulline. This technique has led to the formulation of microspheres with good physical properties in terms of morphology and size. The compression of the microspheres should help to control citrulline release for colonic targeting. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Enhancement of Poly(orthoester) Microspheres for DNA Vaccine Delivery by Blending with Poly(ethylenimine)

PubMed Central

Nguyen, David N.; Raghavan, Shyam S.; Tashima, Lauren M.; Lin, Elizabeth C.; Fredette, Stephen J.; Langer, Robert S.; Wang, Chun

2008-01-01

Poly(ortho ester) (POE) microspheres have been previously shown to possess certain advantages for the in vivo delivery of DNA vaccines. In particular, timing of DNA release from POE microspheres in response to acidic phagosomal pH was shown to be an important factor in determining immunogenicity, which was hypothesized to be linked to the natural progression of antigen presenting cell uptake, transfection, maturation, and antigen presentation. Here we report in vitro characterization of the enhanced the efficacy of POE microspheres by blending poly(ethylenimine) (PEI), a well-characterized cationic transfection agent, into the POE matrix. Blending of a tiny amount of PEI (approximately 0.04 wt%) with POE caused large alterations in POE microsphere properties. PEI provided greater control over the rate of pH-triggered DNA release by doubling the total release time of plasmid DNA and enhanced gene transfection efficiency of the microspheres up to 50-fold without any significant cytotoxicity. Confocal microscopy with labeled PEI and DNA plasmids revealed that PEI caused a surface-localizing distribution of DNA and PEI within the POE microsphere as well as focal co-localization of PEI with DNA. We provide evidence that upon degradation, the microspheres of POE-PEI blends released electrostatic complexes of DNA and PEI, which are responsible for the enhanced gene transfection. Furthermore, blending PEI into the POE microsphere induced 50% to 60% greater phenotypic maturation and activation of bone marrow-derived dendritic cells in vitro, judged by up-regulation of co-stimulatory markers on the cell surface. Physically blending PEI with POE is a simple approach for modulating the properties of biodegradable microspheres in terms of gene transfection efficiency and DNA release kinetics. Combined with the ability to induce maturation of antigen-presenting cells, POE-PEI blended microspheres may be excellent carriers for DNA vaccines. PMID:18400294

Double walled POE/PLGA microspheres: encapsulation of water-soluble and water-insoluble proteins and their release properties.

PubMed

Shi, Meng; Yang, Yi-Yan; Chaw, Cheng-Shu; Goh, Suat-Hong; Moochhala, Shabbir M; Ng, Steve; Heller, Jorge

2003-04-29

The poly(orthoester) (POE)-poly(D,L-lactide-co-glycolide) (50:50) (PLGA) double-walled microspheres with 50% POE in weight were loaded with hydrophilic bovine serum albumin (BSA) and hydrophobic cyclosporin A (CyA). Most of the BSA and CyA was entrapped within the shell and core, respectively, because of the difference in their hydrophilicity. The morphologies and release mechanisms of proteins-loaded double-walled POE/PLGA microspheres were investigated. Scanning electron microscope studies revealed that the CyA-BSA-loaded double-walled POE/PLGA microspheres yielded a more porous surface and PLGA shell than those without BSA. The neat POE and PLGA yielded slow and incomplete CyA and BSA release. In contrast, nearly complete BSA and more than 95% CyA were released in a sustained manner from the double-walled POE/PLGA microspheres. Both the BSA- and CyA-BSA-loaded POE/PLGA microspheres yielded a sustained BSA release over 5 days. The CyA release pattern of the CyA-loaded double-walled POE/PLGA microspheres was biphasic, characterized by a slow release over 15 days followed by a sustained release over 27 days. However, the CyA-BSA-loaded double-walled POE/PLGA microspheres provided a more constant and faster CyA release due to their more porous shell. In the CyA-BSA-loaded double-walled POE/PLGA microspheres system, the PLGA layer acted as a carrier for BSA and mild reservoir for CyA. During the first 5 days, most BSA was released from the shell but only 14% CyA was left from the microspheres. Subsequently, more than 80% CyA were released in the next 25 days. The distinct structure of double-walled POE/PLGA microspheres would make an interesting device for controlled delivery of therapeutic agents.

Development of a cell transducible RhoA inhibitor TAT-C3 transferase and its encapsulation in biocompatible microspheres to promote survival and enhance regeneration of severed neurons.

PubMed

Tan, Elaine Y M; Law, Janice W S; Wang, Chi-Hwa; Lee, Alan Y W

2007-12-01

Neurons in post-traumatized mammalian central nervous system show only limited degree of regeneration, which can be attributed to the presence of neurite outgrowth inhibitors in damaged myelin and glial scar, and to the apoptosis of severed central neurons and glial cells during secondary Wallerian degeneration. RhoA GTPase has been implicated as the common denominator in these counter-regeneration events, which shows significant and persistent up-regulation for weeks in injured spinal cord and cerebral infarct after stroke. While the exoenzyme C3 transferase is a potent RhoA inhibitor, its extremely low efficiency of cell entry and degradation in vivo has restricted the therapeutic value. This study aims to circumvent these problems by developing a membrane-permeating form of C3 transferase and a biopolymer-based microsphere depot system for sustainable controlled release of the protein. A membrane-permeating form of C3 transferase was developed by fusing a Tat (trans-activating transcription factor) transduction domain of human immunodeficiency virus to its amino terminal using standard molecular cloning techniques. After confirming efficient cell entry into epithelial and neuroblastoma cells, the resulting recombinant protein TAT-C3 was encapsulated in biocompatible polymer poly(D,L -lactide-co-glycolide) in the form of microspheres by a water-in-oil-in-water (W/O/W) emulsion method. By blending capped and uncapped form of the polymer at different ratios, TAT-C3 protein release profile was modified to suit the expression pattern of endogenous RhoA during CNS injuries. Bioactivity of TAT-C3 released from microspheres was assessed by RhoA ribosylation assay. In contrast to wild-type C3 transferase, the modified TAT-C3 protein was found to efficiently enter NIH3T3 and N1E-115 neuroblastoma cells as early as 6 hours of incubation. The fusion of TAT sequence to C3 transferase imposed no appreciable effects on its biological activity in promoting neurite outgrowth through RhoA inhibition. Characterization of TAT-C3 encapsulation in various blends of capped/uncapped PLGA polymer revealed the 30:70 formulation to be optimal in attaining a mild initial burst release of 25%, followed by a subsequent average daily release of 2.3% of encapsulated protein over one month, matching the change in RhoA level in severed brain and spinal cord. Importantly, TAT-C3 released from the microspheres remained active up to the first three weeks of incubation. Enhanced cell entry of TAT-C3 circumvents the need to administer high dose of the protein to site of injury. The encapsulation of TAT-C3 in different blends of capped/uncapped PLGA microspheres allows adjustment of protein release profile to suit the pattern of RhoA expression in injured CNS.

Controlled Release of Chitosan and Sericin from the Microspheres-Embedded Wound Dressing for the Prolonged Anti-microbial and Wound Healing Efficacy.

PubMed

Aramwit, Pornanong; Yamdech, Rungnapha; Ampawong, Sumate

2016-05-01

One approach in wound dressing development is to incorporate active molecules or drugs in the dressing. In order to reduce the frequency of dressing changes as well as to prolong wound healing efficacy, wound dressings that can sustain the release of the active molecules should be developed. In our previous work, we developed chitosan/sericin (CH/SS) microspheres that released sericin in a controlled rate. However, the difficulty of applying the microspheres that easily diffuse and quickly degrade onto the wound was its limitations. In this study, we aimed to develop wound dressing materials which are easier to apply and to provide extended release of sericin. Different amounts of CH/SS microspheres were embedded into various compositions of polyvinyl alcohol/gelatin (PVA/G) scaffolds and fabricated using freeze-drying and glutaraldehyde crosslinking techniques. The obtained CH/SS microspheres-embedded scaffolds with appropriate design and formulation were introduced as a wound dressing material. Sericin was released from the microspheres and the scaffolds in a sustained manner. Furthermore, an optimized formation of the microspheres-embedded scaffolds (2PVA2G+2CHSS) was shown to possess an effective antimicrobial activity against both gram-positive and gram-negative bacteria. These microspheres-embedded scaffolds were not toxic to L929 mouse fibroblast cells, and they did not irritate the tissue when applied to the wound. Finally, probably by the sustained release of sericin, these microspheres-embedded scaffolds could promote wound healing as well as or slightly better than a clinically used wound dressing (Allevyn®) in a mouse model. The antimicrobial CH/SS microspheres-embedded PVA/G scaffolds with sustained release of sericin would appear to be a promising candidate for wound dressing application.

γ-Fe2O3 and Fe3O4 magnetic hierarchically nanostructured hollow microspheres: preparation, formation mechanism, magnetic property, and application in water treatment.

PubMed

Xu, Jing-San; Zhu, Ying-Jie

2012-11-01

In this paper, we report the preparation of γ-Fe(2)O(3) and Fe(3)O(4) magnetic hierarchically nanostructured hollow microspheres by a solvothermal combined with precursor thermal conversion method. These γ-Fe(2)O(3) and Fe(3)O(4) magnetic hierarchically nanostructured hollow microspheres were constructed by three-dimensional self-assembly of nanosheets, forming porous nanostructures. The effects of experimental parameters including molar ratio of reactants and reaction temperature on the precursors were studied. The time-dependent experiments indicated that the Ostwald ripening was responsible for the formation of the hierarchically nanostructured hollow microspheres of the precursors. γ-Fe(2)O(3) and Fe(3)O(4) magnetic hierarchically nanostructured hollow microspheres were obtained by the thermal transformation of the precursor hollow microspheres. Both γ-Fe(2)O(3) and Fe(3)O(4) hierarchically nanostructured hollow microspheres exhibited a superparamagnetic property at room temperature and had the saturation magnetization of 44.2 and 55.4 emu/g, respectively, in the applied magnetic field of 20 KOe. Several kinds of organic pollutants including salicylic acid (SA), methylene blue (MB), and basic fuchsin (BF) were chosen as the model water pollutants to evaluate the removal abilities of γ-Fe(2)O(3) and Fe(3)O(4) magnetic hierarchically nanostructured hollow microspheres. It was found that γ-Fe(2)O(3) hierarchically nanostructured hollow microspheres showed a better adsorption ability over SA than MB and BF. However, Fe(3)O(4) hierarchically nanostructured hollow microspheres had the best performance for adsorbing MB. Copyright © 2012 Elsevier Inc. All rights reserved.

Diameter of fluorescent microspheres determines their distribution throughout the cortical watershed area in mice.

PubMed

Tsukada, Naoki; Katsumata, Masahiro; Oki, Koichi; Minami, Kazushi; Abe, Takato; Takahashi, Shinichi; Itoh, Yoshiaki; Suzuki, Norihiro

2018-01-15

A hemodynamic mechanism has long been assumed to play an important role in watershed infarction. In recent years, however, clinical evidence has indicated that an embolic mechanism is involved. The mechanism by which emboli are trapped preferentially in watershed areas remains unclear. In the present study, we developed a mouse embolus model using fluorescent microspheres with different diameters and evaluated the role of the microspheres' diameters in the generation of a watershed-patterned distribution. We injected fluorescent microspheres of four different diameters (i.e., 13, 24, 40, and 69 μm) into the internal carotid artery of C57BL/6 mice either (1) without ligation of the common carotid artery (normal perfusion pressure model: NPPM) or (2) with ligation of the common carotid artery (low perfusion pressure model: LPPM). Left common carotid artery ligation induced reductions in local cerebral blood flow in both the periphery and the core area of the left middle cerebral artery. A greater reduction in the border-zone area between the left anterior cerebral artery and the middle cerebral artery was also noted. After 24 h, the brains were removed and the distribution of the microspheres in the brain was evaluated using a fluorescence microscope. The 24-μm microspheres were distributed in the watershed area more frequently than the other microsphere sizes (P < .05, ANOVA followed by Tukey's test). Meanwhile, the distribution rates were similar between the NPPM and LPPM models for all microsphere sizes. This study suggested that the distribution pattern of the microspheres was only affected by the microspheres' diameters. Copyright © 2017 Elsevier B.V. All rights reserved.

SPIO-labeled Yttrium Microspheres for MR Imaging Quantification of Transcatheter Intrahepatic Delivery in a Rodent Model

PubMed Central

Li, Weiguo; Zhang, Zhuoli; Gordon, Andrew C.; Chen, Jeane; Nicolai, Jodi; Lewandowski, Robert J.; Omary, Reed A.

2016-01-01

Purpose To investigate the qualitative and quantitative impacts of labeling yttrium microspheres with increasing amounts of superparamagnetic iron oxide (SPIO) material for magnetic resonance (MR) imaging in phantom and rodent models. Materials and Methods Animal model studies were approved by the institutional Animal Care and Use Committee. The r2* relaxivity for each of four microsphere SPIO compositions was determined from 32 phantoms constructed with agarose gel and in eight concentrations from each of the four compositions. Intrahepatic transcatheter infusion procedures were performed in rats by using each of the four compositions before MR imaging to visualize distributions within the liver. For quantitative studies, doses of 5, 10, 15, or 20 mg 2% SPIO-labeled yttrium microspheres were infused into 24 rats (six rats per group). MR imaging R2* measurements were used to quantify the dose delivered to each liver. Pearson correlation, analysis of variance, and intraclass correlation analyses were performed to compare MR imaging measurements in phantoms and animal models. Results Increased r2* relaxivity was observed with incremental increases of SPIO microsphere content. R2* measurements of the 2% SPIO–labeled yttrium microsphere concentration were well correlated with known phantom concentrations (R2 = 1.00, P < .001) over a broader linear range than observed for the other three compositions. Microspheres were heterogeneously distributed within each liver; increasing microsphere SPIO content produced marked signal voids. R2*-based measurements of 2% SPIO–labeled yttrium microsphere delivery were well correlated with infused dose (intraclass correlation coefficient, 0.98; P < .001). Conclusion MR imaging R2* measurements of yttrium microspheres labeled with 2% SPIO can quantitatively depict in vivo intrahepatic biodistribution in a rat model. © RSNA, 2015 Online supplemental material is available for this article. PMID:26313619

Biodegradable and biocompatible poly(DL-lactide-co-glycolide) microspheres as an adjuvant for staphylococcal enterotoxin B toxoid which enhances the level of toxin-neutralizing antibodies.

PubMed Central

Eldridge, J H; Staas, J K; Meulbroek, J A; Tice, T R; Gilley, R M

1991-01-01

Microspheres composed of biocompatible, biodegradable poly(DL-lactide-co-glycolide) (DL-PLG) and staphylococcal enterotoxin B (SEB) toxoid were evaluated as a vaccine delivery system when subcutaneously injected into mice. As measured by circulating immunoglobulin G (IgG) antitoxin titers, the delivery of SEB toxoid via DL-PLG microspheres, 1 to 10 microns in diameter, induced an immune response which was approximately 500 times that seen with nonencapsulated toxoid. The kinetics, magnitude, and duration of the antitoxin response induced with microencapsulated toxoid were similar to those obtained when an equal toxoid dose was administered as an emulsion with complete Freund adjuvant. However, the microspheres did not induce the inflammation and granulomata formation seen with complete Freund adjuvant. The adjuvant activity of the microspheres was not dependent on the superantigenicity of SEB toxin and was equally effective at potentiating circulating IgG antitrinitrophenyl levels in response to microencapsulated trinitrophenyl-keyhole limpet hemocyanin. Empty DL-PLG microspheres were not mitogenic, and SEB toxoid injected as a mixture with empty DL-PLG microspheres was no more effective as an immunogen than toxoid alone. Antigen-containing microspheres 1 to 10 microns in diameter exhibited stronger adjuvant activity than those greater than 10 microns, which correlated with the delivery of the 1- to 10-microns, but not the greater than 10-microns, microspheres into the draining lymph nodes within macrophages. The antibody response induced through immunization with microencapsulated SEB toxoid was protective against the weight loss and splenic V beta 8+ T-cell expansion induced by intravenous toxin administration. These results show that DL-PLG microsphere vaccine delivery systems, which are composed of pharmaceutically acceptable components, possess a strong adjuvant activity for their encapsulated antigens. PMID:1879922

Synthesis of novel quaternary silica hybrid bioactive microspheres.

PubMed

Angelopoulou, A; Efthimiadou, E Κ; Kordas, G

2018-01-01

To survey the preparation of novel hybrid microspheres of quaternary silicate glassy composition (SiO 2 P 2 O 5 CaONa 2 O) and the prospect of using them as an osteogenic system with enhanced bioactive properties for the development of hydroxyapatite. In line with our previous synthetic procedure a two-step process was followed, wherein polystyrene (PS) microspheres were prepared by the emulsifier free-emulsion polymerization method and constituted the core for the sol-gel coating of the silicate inorganic shell. The development of the hybrid microspheres was based on silane and phosphate precursors and was assesses at different ratio of ethanol/water (of 9/1, 4/1, and 2/1, in mL) and at varied ammonia concentration of 4.8-1.0 mL. The hybrid microspheres had an average size ranged between 350 and 550 nm according to SEM, depending on the ethanol/water solution rate and ammonia content. The final microspheres probably exhibited a porous-like structure through the formation of diffused voids along with the low carbon content of the EDX analysis, which could be regulated by the catalyst content. The hybrid microspheres exhibited effective in vitro bioactivity assessed in simulated body fluids (SBF). Quaternary hybrid silica microspheres were effectively synthesized. The bioassay evaluation of the final microspheres revealed the rapid in vitro formation of a bone-like apatite layer. The results verify the bioactivity of the microspheres and promote further research of their suitability on regenerative treatment of bone abnormalities. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 112-120, 2018. © 2016 Wiley Periodicals, Inc.

Tabletted microspheres containing Cynara scolymus (var. Spinoso sardo) extract for the preparation of controlled release nutraceutical matrices.

PubMed

Gavini, E; Alamanni, M C; Cossu, M; Giunchedi, P

2005-08-01

Controlled release dosage forms based on tabletted microspheres containing fresh artichoke Cynara scolymus extract were performed for the oral administration of a nutritional supplement. Microspheres were prepared using a spray-drying technique; lactose or hypromellose have been chosen as excipients. Microspheres were characterized in terms of encapsulated extract content, size and morphology. Qualitative and quantitative composition of the extract before and after the spray process was determined. Compressed matrices (tablets) were prepared by direct compression of the spray-dried microspheres. In vitro release tests of microparticles and tablets prepared were carried out in both acidic and neutral media. Spray-drying is a good method to prepare microspheres containing the artichoke extract. The microspheres encapsulate an amount of extract close to the theoretical value. Particle size analyses indicate that the microparticles have dvs of approximately 6-7 microm. Electronic microscopy observations reveal that particles based on lactose have spherical shape and particles containing hypromellose are almost collapsed. The hydroalcoholic extract is stable to the microsphere production process: its polyphenolic composition (qualitative and quantitative) did not change after spraying. In vitro release studies show that microparticles characterized by a quick polyphenolic release both in acidic and neutral media due to the high water solubility of the carrier lactose. On the contrary, microspheres based hypromellose release only 20% of the loaded extract at pH 1.2 in 2 h and the total amount of polyphenols is released only after about further 6 h at pH 6.8. Matrices prepared tabletting lactose microspheres and hypromellose microparticles in the weight ratio 1:1 show a slow release rate, that lasts approximately 24 h. This one-a-day sustained release formulation containing Cynara scolymus extract could be proposed as a nutraceutical controlled release dosage form for oral administration.

Chitosan microspheres as candidate plasmid vaccine carrier for oral immunisation of Japanese flounder (Paralichthys olivaceus).

PubMed

Tian, Jiyuan; Yu, Juan; Sun, Xiuqin

2008-12-15

Oral DNA-based immunotherapy is a new treatment option for fish immunisation in intensive culture. However, because of the existence of the nucleases and severe gastrointestinal conditions, DNA-based vaccines can be hydrolyzed or denatured. In our laboratory, a plasmid DNA (pDNA) containing major capsid protein (MCP) gene of lymphocystis disease virus (LCDV) was prepared, and then pDNA was encapsulated in chitosan microspheres through an emulsion-based methodology. The yield, loading percent and encapsulation efficiency of microspheres were 93.6%, 0.3% and 94.5%, respectively. Scanning electron microscopy (SEM) showed that pDNA-loaded microspheres yielded a spherical shape with smooth surfaces. The disproportion of super-coiled to open circle and linear pDNA suggested that high transfection efficiencies of pDNA in microspheres were retained. The cumulative release of pDNA showed that chitosan microspheres were resistant to degradation in simulated gastrointestinal tract environment. The release profile at PBS buffer (pH 7.4) displayed that pDNA-loaded chitosan microspheres had a release up to 42 days after intestinal imbibition. RT-PCR showed that RNA containing information of MCP gene existed in various tissues 10-90 days post-vaccination. SDS-PAGE and immunofluorescent images indicated that pDNA expressed MCP in tissues of fish 10-90 days after oral administration. In addition, indirect ELISA displayed that the immune responses of sera were positive (O.D.> or =0.3) from week 1 to week 16 for fish vaccinated with microspheres, in comparison with fish vaccinated with naked pDNA. Data obtained suggested that chitosan microspheres were promising carriers for oral pDNA vaccine. Because this encapsulation technique was easy to operate and immunisation efficacy of microspheres loaded with pDNA was significant, it had potential to be used in drug delivery applications.

Affinity capture of aflatoxin B1 and B2 by aptamer-functionalized magnetic agarose microspheres prior to their determination by HPLC.

PubMed

Liu, Hongmei; Lu, Anxiang; Fu, Hailong; Li, Bingru; Yang, Meihua; Wang, Jihua; Luan, Yunxia

2018-06-12

A novel adsorbent is described for magnetic solid-phase extraction (MSPE) of the aflatoxins AFB 1 and AFB 2 (AFBs). Magnetic agarose microspheres (MAMs) were functionalized with an aptamer to bind the AFBs which then were quantified by HPLC and on-line post-column photochemical derivatization with fluorescence detection. Streptavidin-conjugated MAMs were synthesized first by a highly reproducible strategy. They possess strong magnetism and high surface area. The MAMs were characterized by transmission electron microscopy, scanning electron microscopy, optical microscopy, laser diffraction particle size analyzer, Fourier transform infrared spectrometry, vibrating sample magnetometry and laser scanning confocal microscopy. Then, the AFB-aptamers were immobilized on MAMs through biotin-streptavidin interaction. Finally, the MSPE is performed by suspending the aptamer-modified MAMs in the sample. They are then collected by an external magnetic field and the AFBs are eluted with methanol/buffer (20:80). Several parameters affecting the coupling, capturing and eluting efficiency were optimized. Under the optimized conditions, the method is fast, has good linearity, high selectivity, and sensitivity. The LODs are 25 pg·mL -1 for AFB 1 and 10 pg·mL -1 for AFB 2 . The binding capacity is 350 ± 8 ng·g -1 for AFB 1 and 384 ± 8 ng·g -1 for AFB 2 , and the precision of the assay is <8%. The method was successfully applied to the analysis of AFBs in spiked maize samples. Graphical abstract Schematic of novel aptamer functionalized magnetic agarose microspheres (Apt-MAM) as magnetic adsorbents for simultaneous and specific affinity capture of aflatoxins B 1 and B 2 (AFBs).

Intravitreal Injection of Proinsulin-Loaded Microspheres Delays Photoreceptor Cell Death and Vision Loss in the rd10 Mouse Model of Retinitis Pigmentosa.

PubMed

Isiegas, Carolina; Marinich-Madzarevich, Jorge A; Marchena, Miguel; Ruiz, José M; Cano, María J; de la Villa, Pedro; Hernández-Sánchez, Catalina; de la Rosa, Enrique J; de Pablo, Flora

2016-07-01

The induction of proinsulin expression by transgenesis or intramuscular gene therapy has been shown previously to retard retinal degeneration in mouse and rat models of retinitis pigmentosa (RP), a group of inherited conditions that result in visual impairment. We investigated whether intraocular treatment with biodegradable poly (lactic-co-glycolic) acid microspheres (PLGA-MS) loaded with proinsulin has cellular and functional neuroprotective effects in the retina. Experiments were performed using the Pde6brd10 mouse model of RP. Methionylated human recombinant proinsulin (hPI) was formulated in PLGA-MS, which were administered by intravitreal injection on postnatal days (P) 14 to 15. Retinal neuroprotection was assessed at P25 by electroretinography, and by evaluating outer nuclear layer (ONL) cellular preservation. The attenuation of photoreceptor cell death by hPI was determined by TUNEL assay in cultured P22 retinas, as well as Akt phosphorylation by immunoblotting. We successfully formulated hPI PLGA-MS to deliver the active molecule for several weeks in vitro. The amplitude of b-cone and mixed b-waves in electroretinographic recording was significantly higher in eyes injected with hPI-PLGA-MS compared to control eyes. Treatment with hPI-PLGA-MS attenuated photoreceptor cell loss, as revealed by comparing ONL thickness and the number of cell rows in this layer in treated versus untreated retinas. Finally, hPI prevented photoreceptor cell death and increased AktThr308 phosphorylation in organotypic cultured retinas. Retinal degeneration in the rd10 mouse was slowed by a single intravitreal injection of hPI-PLGA-MS. Human recombinant proinsulin elicited a rapid and effective neuroprotective effect when administered in biodegradable microspheres, which may constitute a future potentially feasible delivery method for proinsulin-based treatment of RP.

Magnetically responsive polycaprolactone nanoparticles for progesterone screening in biological and environmental samples using gas chromatography.

PubMed

Es'haghi, Zarrin; Nezhadali, Azizollah; Khatibi, Aram-Dokht

2016-08-01

A new Fe3O4/poly(є-caprolactone) (PCL) magnetite nanocomposite was fabricated and used as a sorbent for magnetically mediated PCL microspheres solid-phase extraction (MM-PCL-SPE) followed by gas chromatography-flame ionization detection (GC-FID) for monitoring of progesterone (PGN) hormone in biological and environmental matrices, namely blood serum, tap water, urine, and hospital wastewater. The nanomagnetite core of the sorbent was synthesized by a co-precipitation method. Magnetic nanoparticles (MNPs) were then microencapsulated with PCL microspheres using emulsion polymerization. The nanocomposite was characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). The magnetite sorbent can be effectively dispersed in aqueous solution and attracted to an external magnetic field. The MM-PCL-SPE process for PGN assay involved (a) dispersion of the sorbent in the donor phase aqueous solution with sonication, (b) exposure to a magnetic field to collect sorbent that had adsorbed the analyte, and (c) solvent desorption of extracted PGN for GC-FID analysis. The work demonstrates the usefulness of MM-PCL-SPE in the rapid and sensitive monitoring of trace amounts of PGN in real samples. The limit of detection (LOD) and limit of quantification (LOQ) were 1.00 and 3.30 ng/mL, respectively. The relative recoveries in real samples were adequate. Linearity was observed over a wide range of 2.2-10,000.0 ng/mL in aqueous media and urine and 0.01-70.0 μg/mL in blood serum. Graphical Abstract In this research new Fe3O4/poly(є-caprolactone) (PCL) magnetite microspheres were developed as an efficient sorbent for solid-phase extraction of progesterone hormone in biological and environmental matrices.

Real-time monitoring of glucose-6-phosphate dehydrogenase activity using liquid droplet arrays and its application to human plasma samples.

PubMed

Jung, Se-Hui; Ji, Su-Hyun; Han, Eun-Taek; Park, Won Sun; Hong, Seok-Ho; Kim, Young-Myeong; Ha, Kwon-Soo

2016-05-15

Glucose-6-phosphate dehydrogenase (G6PD) regulates nicotinamide adenine dinucleotide phosphate (NADPH) levels and is related to the pathogenesis of various diseases, including G6PD deficiency, type 2 diabetes, aldosterone-induced endothelial dysfunction, and cancer. Therefore, a highly sensitive array-based assay for determining quantitative G6PD activity is required. Here, we developed an on-chip G6PD activity assay using liquid droplet fluorescence arrays. Quantitative G6PD activity was determined by calculating reduced resorufin concentrations in liquid droplets. The limit of detection (LOD) of this assay was 0.162 mU/ml (2.89 pM), which is much more sensitive than previous assays. We used our activity assay to determine kinetic parameters, including Michaelis-Menten constants (Km) and maximum rates of enzymatic reaction (Vmax) for NADP(+) and G6P, and half-maximal inhibitory concentrations (IC50). We successfully applied this new assay to determine G6PD activity in human plasma from normal healthy individuals (n=30) and patients with inflammation (n=30). The inflammatory group showed much higher G6PD activities than did the normal group (p<0.001), with a high area under the curve value of 0.939. Therefore, this new activity assay has the potential to be used for diagnosis of G6PD-associated diseases and utilizing kinetic studies. Copyright © 2016 Elsevier B.V. All rights reserved.

Magnetic susceptibility characterisation of superparamagnetic microspheres

NASA Astrophysics Data System (ADS)

Grob, David Tim; Wise, Naomi; Oduwole, Olayinka; Sheard, Steve

2018-04-01

The separation of magnetic materials in microsystems using magnetophoresis has increased in popularity. The wide variety and availability of magnetic beads has fuelled this drive. It is important to know the magnetic characteristics of the microspheres in order to accurately use them in separation processes integrated on a lab-on-a-chip device. To investigate the magnetic susceptibility of magnetic microspheres, the magnetic responsiveness of three types of Dynabeads microspheres were tested using two different approaches. The magnetophoretic mobility of individual microspheres is studied using a particle tracking system and the magnetization of each type of Dynabeads microsphere is measured using SQUID relaxometry. The magnetic beads' susceptibility is obtained at four different applied magnetic fields in the range of 38-70 mT for both the mobility and SQUID measurements. The susceptibility values in both approaches show a consistent magnetic field dependence.

Controlled release of anticancer drug methotrexate from biodegradable gelatin microspheres.

PubMed

Narayani, R; Rao, K P

1994-01-01

Biodegradable hydrophilic gelatin microspheres containing the anticancer drug methotrexate (MTX) of different mean particle sizes (1-5, 5-10, and 15-20 microns) were prepared by polymer dispersion technique and crosslinked with glutaraldehyde. The microspheres were uniform, smooth, solid and in the form of free-flowing powder. About 80 per cent of MTX was incorporated in gelatin microspheres of different sizes. The in vitro release of MTX was investigated in two different media, namely simulated gastric and intestinal fluids. The release profiles indicated that gelatin microspheres released MTX in a zero-order fashion for 4-6 days in simulated gastric fluid and for 5-8 days in simulated intestinal fluid. The rate of release of MTX decreased with increase in the particle size of the microspheres. MTX release was faster in gastric fluid when compared to intestinal fluid.

Hierarchical Mn₂O₃ Microspheres In-Situ Coated with Carbon for Supercapacitors with Highly Enhanced Performances.

PubMed

Gong, Feilong; Lu, Shuang; Peng, Lifang; Zhou, Jing; Kong, Jinming; Jia, Dianzeng; Li, Feng

2017-11-23

Porous Mn₂O₃ microspheres have been synthesized and in-situ coated with amorphous carbon to form hierarchical C@Mn₂O₃ microspheres by first producing MnCO₃ microspheres in solvothermal reactions, and then annealing at 500 °C. The self-assembly growth of MnCO₃ microspheres can generate hollow structures inside each of the particles, which can act as micro-reservoirs to store biomass-glycerol for generating amorphous carbon onto the surfaces of Mn₂O₃ nanorods consisting of microspheres. The C@Mn₂O₃ microspheres, prepared at 500 °C, exhibit highly enhanced pseudocapacitive performances when compared to the particles after annealed at 400 °C and 600 °C. Specifically, the C@Mn₂O₃ microspheres prepared at 500 °C show high specific capacitances of 383.87 F g -1 at current density of 0.5 A g -1 , and excellent cycling stability of 90.47% of its initial value after cycling for 5000 times. The asymmetric supercapacitors assembled with C@Mn₂O₃ microspheres after annealed at 500 °C and activated carbon (AC) show an energy density of up to 77.8 Wh kg -1 at power density of 500.00 W kg -1 , and a maximum power density of 20.14 kW kg -1 at energy density of 46.8 Wh kg -1 . We can attribute the enhanced electrochemical performances of the materials to their three-dimensional (3D) hierarchical structure in-situ coated with carbon.

Mucoadhesive microspheres for gastroretentive delivery of acyclovir: in vitro and in vivo evaluation.

PubMed

Dhaliwal, Sumeet; Jain, Subheet; Singh, Hardevinder P; Tiwary, A K

2008-06-01

The aim of the present investigation was to evaluate the potential use of mucoadhesive microspheres for gastroretentive delivery of acyclovir. Chitosan, thiolated chitosan, Carbopol 71G and Methocel K15M were used as mucoadhesive polymers. Microsphere formulations were prepared using emulsion-chemical crosslinking technique and evaluated in vitro, ex-vivo and in-vivo. Gelatin capsules containing drug powder showed complete dissolution (90.5 +/- 3.6%) in 1 h. The release of drug was prolonged to 12 h (78.8 +/- 3.9) when incorporated into mucoadhesive microspheres. The poor bioavailability of acyclovir is attributed to short retention of its dosage form at the absorption sites (in upper gastrointestinal tract to duodenum and jejunum). The results of mucoadhesion study showed better retention of thiolated chitosan microspheres (8.0 +/- 0.8 h) in duodenal and jejunum regions of intestine. The results of qualitative and quantitative GI distribution study also showed significant higher retention of mucoadhesive microspheres in upper GI tract. Pharmacokinetic study revealed that administration of mucoadhesive microspheres could maintain measurable plasma concentration of acyclovir through 24 h, as compared to 5 h after its administration in solution form. Thiolated chitosan microsphere showed superiority over the other formulations as observed with nearly 4.0-fold higher AUC(0-24) value (1,090 +/- 51 ng h/ml) in comparison to drug solution (281 +/- 28 ng h/ml). Overall, the result indicated prolonged delivery with significant improvement in oral bioavailability of acyclovir from mucoadhesive microspheres due to enhanced retention in the upper GI tract.

Hydrophilic microspheres from water-in-oil emulsions by the water diffusion technique.

PubMed

Trotta, Michele; Chirio, Daniela; Cavalli, Roberta; Peira, Elena

2004-08-01

In this study, we developed and evaluated a novel method to produce insulin-loaded hydrophilic microspheres allowing high encapsulation efficiency and the preservation of peptide stability during particle processing. The preparation method used the diffusion of water by an excess of solvent starting from a water-in-solvent emulsion. The water dispersed phase containing albumin or lactose, or albumin-lactose in different weight ratios, and insulin was emulsified in water-saturated triacetin with and without emulsifiers, producing a water-in-triacetin emulsion. An excess of triacetin was added to the emulsion so that water could be extracted into the continuous phase, allowing the insulin-loaded microsphere precipitation. Insulin stability within the microspheres after processing was evaluated by reverse-phase and size-exclusion high-performance liquid chromatography. The water diffusion extraction process provided spherical microparticles of albumin or albumin-lactose. The mean diameter of the microspheres prepared with or without emulsifiers ranged from 2 to 10 microm, and the encapsulation efficiency of insulin was between 60% and 75%, respectively. The analysis of microsphere content after processing showed that insulin did not undergo any chemical modification within microspheres. The use of lactose alone led to the formation of highly viscous droplets that coalesced during the purification step. The water extraction procedures successfully produced insulin-loaded hydrophilic microspheres allowing the preservation of peptide stability. The type of excipient and the size of the disperse phase of the primary w/o emulsion were crucial determinants of microsphere characteristics.

Comparison of 68Ga- and fluorescence-labeled microspheres for measurement of relative pulmonary perfusion in anesthetized pigs.

PubMed

Braune, Anja; Scharffenberg, Martin; Naumann, Anne; Bluth, Thomas; de Abreu, Marcelo Gama; Kotzerke, Jörg

2018-06-01

We compared 68 Gallium ( 68 Ga)- and fluorescence-labeled microspheres for measurement of pulmonary perfusion distribution in anesthetized pigs without lung injury. In two mechanically ventilated pigs, the distribution of pulmonary perfusion was marked in vivo with 68 Ga- and fluorescence-labeled microspheres in supine and prone position. After each injection, the distribution of 68 Ga-labeled microspheres was measured in vivo with positron emission tomography/ computed tomography (PET/CT) in the position in which microspheres were injected and vice versa. The distribution of fluorescence-labeled microspheres was measured ex vivo . Perfusion distributions were compared between methods and postures within four lung regions and along the ventro-dorsal gradient. After each injection of 68 Ga-labeled microspheres, changes in ventro-dorsal perfusion gradients induced by repositioning were compared for volume- and mass-normalized PET/CT measurements. Regional and gradient analyses of in vivo and ex vivo measurements, respectively, consistently revealed higher pulmonary perfusion in dorsal than ventral regions in supine positioned animals. Both methods showed more pronounced perfusion gradients in supine compared to prone position. Changes in animal position were associated with alterations in the ventro-dorsal perfusion gradient when volume-, but not mass-normalization was conducted for PET/CT data. Ex vivo fluorescence- and in vivo 68 Ga-labeled microspheres measurements revealed similar perfusion distributions. Mass-normalized perfusion measurements by 68 Ga-labeled microspheres and PET/CT were not affected by positioning artifacts. Schattauer GmbH.

Potential differentiation ability of gingiva originated human mesenchymal stem cell in the presence of tacrolimus

PubMed Central

Ha, Dong-Ho; Pathak, Shiva; Yong, Chul Soon; Kim, Jong Oh; Jeong, Jee-Heon; Park, Jun-Beom

2016-01-01

The aim of the present study is to evaluate the potential differentiation ability of gingiva originated human mesenchymal stem cell in the presence of tacrolimus. Tacrolimus-loaded poly(lactic-co-glycolic acid) microspheres were prepared using electrospraying technique. In vitro release study of tacrolimus-loaded poly(lactic-co-glycolic acid) microspheres was performed in phosphate-buffered saline (pH 7.4). Gingiva-derived stem cells were isolated and incubated with tacrolimus or tacrolimus-loaded microspheres. Release study of the microspheres revealed prolonged release profiles of tacrolimus without any significant initial burst release. The microsphere itself did not affect the morphology of the mesenchymal stem cells, and cell morphology was retained after incubation with microspheres loaded with tacrolimus at 1 μg/mL to 10 μg/mL. Cultures grown in the presence of microspheres loaded with tacrolimus at 1 μg/mL showed the highest mineralization. Alkaline phosphatase activity increased with an increase in incubation time. The highest expression of pSmad1/5 was achieved in the group receiving tacrolimus 0.1 μg/mL every third day, and the highest expression of osteocalcin was achieved in the group receiving 1 μg/mL every third day. Biodegradable poly(lactic-co-glycolic acid)-based microspheres loaded with tacrolimus promoted mineralization. Microspheres loaded with tacrolimus may be applied for increased osteoblastic differentiation. PMID:27721434

A Novel Polymer-Synthesized Ceramic Composite Based System for Bone Repair: Osteoblast Growth on Scaffolds with Varied Calcium Phosphate Content

DTIC Science & Technology

2005-01-01

demongtrated the synthesis of degradable scaffolds from PLAGA /calcium phosphate composite microspheres in which an amorphous calcium phosphate is...EXPERIMENTAL DETAILS Scaffold Preparation Scaffolds were prepared as described in detail previously [3]. Briefly, PLAGA /calcium phosphate composite...culture polystyrene (TCPS) 2- pure PLAGA microspheres 64 3- composite microsphere matrices with a low polymer/ceramic ratio 4- composite microsphere

DNA hydrogel microspheres and their potential applications for protein delivery and live cell monitoring

PubMed Central

Kim, Taeyoung; Park, Seongmin; Baek, Solhee; Lee, Jong Bum; Park, Nokyoung

2016-01-01

Microfluidic devices have been extensively developed as methods for microscale materials fabrication. It has also been adopted for polymeric microsphere fabrication and in situ drug encapsulation. Here, we employed multi-inlet microfluidic channels for DNA hydrogel microsphere formation and in situ protein encapsulation. The release of encapsulated proteins from DNA hydrogels showed different profiles accordingly with the size of microspheres. PMID:27279936

Production of Monodisperse Cerium Oxide Microspheres with Diameters near 100 µm by Internal-Gelation Sol-Gel Methods

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

Katalenich, Jeffrey A.; Kitchen, Brian B.; Pierson, Bruce

Cerium dioxide microspheres with uniform diameters between 65 – 211 µm were fabricated using internal gelation sol-gel methods. Although uniform microspheres are produced for nuclear fuel applications with diameters above 300 µm, sol-gel microspheres with diameters of 50 - 200 µm have historically been made by emulsion techniques and had poor size uniformity [1, 2]. An internal gelation, sol-gel apparatus was designed and constructed to accommodate the production of small, uniform microspheres whereby cerium-containing solutions were dispersed into flowing silicone oil and heated in a gelation column to initiate solidification [3, 4]. Problems with premature feed gelation and microsphere coalescencemore » were overcome by equipment modifications unique among known internal gelation setups. Microspheres were fabricated and sized in batches as a function of dispersing needle diameter and silicone oil flow rate in the two-fluid nozzle in order to determine the range of sizes possible and corresponding degree of monodispersity. Initial experiments with poor size uniformity were linked to microsphere coalescence in the gelation column prior to solidification as well as excessive flow rates for the cerium feed solution. Average diameter standard deviations as low as 2.23% were observed after optimization of flow rates and minimization of coalescence reactions.« less

Measurement of thermal diffusivity of depleted uranium metal microspheres

NASA Astrophysics Data System (ADS)

Humrickhouse-Helmreich, Carissa J.; Corbin, Rob; McDeavitt, Sean M.

2014-03-01

The high void space of nuclear fuels composed of homogeneous uranium metal microspheres may allow them to achieve ultra-high burnup by accommodating fuel swelling and reducing fuel/cladding interactions; however, the relatively low thermal conductivity of microsphere nuclear fuels may limit their application. To support the development of microsphere nuclear fuels, an apparatus was designed in a glovebox and used to measure the apparent thermal diffusivity of a packed bed of depleted uranium (DU) microspheres with argon fill in the void spaces. The developed Crucible Heater Test Assembly (CHTA) recorded radial temperature changes due to an initial heat pulse from a central thin-diameter cartridge heater. Using thermocouple positions and time-temperature data, the apparent thermal diffusivity was calculated. The thermal conductivity of the DU microspheres was calculated based on the thermal diffusivity from the CHTA, known material densities and specific heat capacities, and an assumed 70% packing density based on prior measurements. Results indicate that DU metal microspheres have very low thermal conductivity, relative to solid uranium metal, and rapidly form an oxidation layer even in a low oxygen environment. At 500 °C, the thermal conductivity of the DU metal microsphere bed was 0.431 ± 0.0560 W/m-K compared to the literature value of approximately 32 W/m-K for solid uranium metal.

Production of monodisperse cerium oxide microspheres with diameters near 100 µm by internal-gelation sol–gel methods

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

Katalenich, Jeffrey A.; Kitchen, Brian B.; Pierson, Bruce D.

Cerium dioxide microspheres with uniform diameters between 65 – 211 µm were fabricated using internal gelation sol-gel methods. Although uniform microspheres are produced for nuclear fuel applications with diameters above 300 µm, sol-gel microspheres with diameters of 50 - 200 µm have historically been made by emulsion techniques and had poor size uniformity [1, 2]. An internal gelation, sol-gel apparatus was designed and constructed to accommodate the production of small, uniform microspheres whereby cerium-containing solutions were dispersed into flowing silicone oil and heated in a gelation column to initiate solidification [3, 4]. Problems with premature feed gelation and microsphere coalescencemore » were overcome by equipment modifications unique among known internal gelation setups. Microspheres were fabricated and sized in batches as a function of dispersing needle diameter and silicone oil flow rate in the two-fluid nozzle in order to determine the range of sizes possible and corresponding degree of monodispersity. Initial experiments with poor size uniformity were linked to microsphere coalescence in the gelation column prior to solidification as well as excessive flow rates for the cerium feed solution. Average diameter standard deviations as low as 2.23% were observed after optimization of flow rates and minimization of coalescence reactions.« less

Poly(methacrylic acid)-grafted chitosan microspheres via surface-initiated ATRP for enhanced removal of Cd(II) ions from aqueous solution.

PubMed

Huang, Liqiang; Yuan, Shaojun; Lv, Li; Tan, Guangqun; Liang, Bin; Pehkonen, S O

2013-09-01

Cross-linked chitosan (CCS) microspheres tethered with pH-sensitive poly(methacrylic acid) (PMAA) brushes were developed for the efficient removal of Cd(II) ions from aqueous solutions. Functional PMAA brushes containing dense and active carboxyl groups (COOH) were grafted onto the CCS microsphere surface via surface-initiated atom transfer radical polymerization (ATRP). Batch adsorption results showed that solution pH values had a major impact on cadmium adsorption by the PMAA-grafted CCS microspheres with the optimal removal observed above pH 5. The CCS-g-PMAA microsphere was found to achieve the adsorption equilibrium of Cd(II) within 1 h, much faster than about 7 h on the CCS microsphere. At pH 5 and with an initial concentration 0.089-2.49 mmol dm(-3), the maximum adsorption capacity of Cd(II), derived from the Langmuir fitting on the PMAA-grafted microspheres was around 1.3 mmol g(-1). Desorption and adsorption cycle experimental results revealed that the PMAA-grafted CCS microspheres loaded with Cd(II) can be effectively regenerated in a dilute HNO3 solution, and the adsorption capacity remained almost unchanged upon five cycle reuse. Copyright © 2013 Elsevier Inc. All rights reserved.

Recent advances in testing of microsphere drug delivery systems.

PubMed

Andhariya, Janki V; Burgess, Diane J

2016-01-01

This review discusses advances in the field of microsphere testing. In vitro release-testing methods such as sample and separate, dialysis membrane sacs and USP apparatus IV have been used for microspheres. Based on comparisons of these methods, USP apparatus IV is currently the method of choice. Accelerated in vitro release tests have been developed to shorten the testing time for quality control purposes. In vitro-in vivo correlations using real-time and accelerated release data have been developed, to minimize the need to conduct in vivo performance evaluation. Storage stability studies have been conducted to investigate the influence of various environmental factors on microsphere quality throughout the product shelf life. New tests such as the floating test and the in vitro wash-off test have been developed along with advancement in characterization techniques for other physico-chemical parameters such as particle size, drug content, and thermal properties. Although significant developments have been made in microsphere release testing, there is still a lack of guidance in this area. Microsphere storage stability studies should be extended to include microspheres containing large molecules. An agreement needs to be reached on the use of particle sizing techniques to avoid inconsistent data. An approach needs to be developed to determine total moisture content of microspheres.

Magnetic poly(glycidyl methacrylate) microspheres for protein capture.

PubMed

Koubková, Jana; Müller, Petr; Hlídková, Helena; Plichta, Zdeněk; Proks, Vladimír; Vojtěšek, Bořivoj; Horák, Daniel

2014-09-25

The efficient isolation and concentration of protein antigens from complex biological samples is a critical step in several analytical methods, such as mass spectrometry, flow cytometry and immunochemistry. These techniques take advantage of magnetic microspheres as immunosorbents. The focus of this study was on the development of new superparamagnetic polymer microspheres for the specific isolation of the tumor suppressor protein p53. Monodisperse macroporous poly(glycidyl methacrylate) (PGMA) microspheres measuring approximately 5 μm and containing carboxyl groups were prepared by multistep swelling polymerization of glycidyl methacrylate (GMA), 2-[(methoxycarbonyl)methoxy]ethyl methacrylate (MCMEMA) and ethylene dimethylacrylate (EDMA) as a crosslinker in the presence of cyclohexyl acetate as a porogen. To render the microspheres magnetic, iron oxide was precipitated within their pores; the Fe content in the particles received ∼18 wt%. Nonspecific interactions between the magnetic particles and biological media were minimized by coating the microspheres with poly(ethylene glycol) (PEG) terminated by carboxyl groups. The carboxyl groups of the magnetic PGMA microspheres were conjugated with primary amino groups of mouse monoclonal DO-1 antibody using conventional carbodiimide chemistry. The efficiency of protein p53 capture and the degree of nonspecific adsorption on neat and PEG-coated magnetic microspheres were determined by western blot analysis. Copyright © 2014 Elsevier B.V. All rights reserved.

High-speed observation of ZnO microspherical crystals produced by laser ablation (Conference Presentation)

NASA Astrophysics Data System (ADS)

Nakamura, Daisuke; Tasaki, Ryohei; Fujiwara, Yuki; Nagasaki, Fumiaki; Higashihata, Mitsuhiro; Ikenoue, Hiroshi; Okada, Tatsuo

2017-03-01

ZnO nano/microstructures have attracted much attention as building blocks for optoelectronic devices because of their high crystalline quality and unique structures. We have succeeded in synthesizing ZnO microspherical crystals by a simple atmospheric laser ablation method, and demonstrated ultraviolet whispering-gallery-mode lasing from the spheres. In the microsphere synthesis process, molten droplets formed into spherical shapes by surface tension, and crystalized during ejection from the ablation spot. In this study, we observed the generation of ZnO microspheres by high-speed camera. Now we are trying to control and manipulate the microspheres using a vortex beam.

Feasibility of human hair follicle-derived mesenchymal stem cells/CultiSpher(®)-G constructs in regenerative medicine.

PubMed

Li, Pengdong; Liu, Feilin; Wu, Chunling; Jiang, Wenyue; Zhao, Guifang; Liu, Li; Bai, Tingting; Wang, Li; Jiang, Yixu; Guo, Lili; Qi, Xiaojuan; Kou, Junna; Fan, Ruirui; Hao, Deshun; Lan, Shaowei; Li, Yulin; Liu, Jin Yu

2015-10-01

The use of human mesenchymal stem cells (hMSCs) in cell therapies has increased the demand for strategies that allow efficient cell scale-up. Preliminary data on the three-dimensional (3D) spinner culture describing the potential use of microcarriers for hMSCs culture scale-up have been reported. We exploited a rich source of autologous stem cells (human hair follicle) and demonstrated the robust in vitro long-term expansion of human hair follicle-derived mesenchymal stem cells (hHF-MSCs) by using CultiSpher(®)-G microcarriers. We analyzed the feasibility of 3D culture by using hHF-MSCs/CultiSpher(®)-G microcarrier constructs for its potential applicability in regenerative medicine by comparatively analyzing the performance of hHF-MSCs adhered to the CultiSpher(®)-G microspheres in 3D spinner culture and those grown on the gelatin-coated plastic dishes (2D culture), using various assays. We showed that the hHF-MSCs seeded at various densities quickly adhered to and proliferated well on the microspheres, thus generating at least hundreds of millions of hHF-MSCs on 1 g of CultiSpher(®)-G within 12 days. This resulted in a cumulative cell expansion of greater than 26-fold. Notably, the maximum and average proliferation rates in 3D culture were significantly greater than that of the 2D culture. However, the hHF-MSCs from both the cultures retained surface marker and nestin expression, proliferation capacity and differentiation potentials toward adipocytes, osteoblasts and smooth muscle cells and showed no significant differences as evidenced by Edu incorporation, cell cycle, colony formation, apoptosis, biochemical quantification and qPCR assays.

Screening study on microsphere used in profile control under the environment of microbial oil recovery

NASA Astrophysics Data System (ADS)

Zhang, Tiantian; Xie, Gang; Gao, Shanshan; Wang, Zhiqiang; Wei, Junjie; Shi, Lei; Zheng, Ya; Gu, Yi; Lei, Xiaoyang; Wang, Ai

2017-12-01

The performance of four microspheres samples (MS-1, MS-2, MS-3, and MS-4) were evaluated and optimized by indoor experiments. Firstly, the basic physical and chemical properties of the four kinds of microspheres were evaluated by analyzing the solid contents and the solubility in the water. Results showed that the content of the precipitated solids in MS-1 was the lowest in the four kinds of microsphere samples. The contents of the other three microspheres were similar in the value of solid content. Besides, the three microspheres of the solubility in the simulated formation water were excellent. Secondly, the expansion properties of three kinds of microspheres (MS-2, MS-3, and MS-4) were investigated. Results revealed that the expansion performance of MS-3 was greatly affected by microbial metabolism. However, the other two samples had excellent expansion performance under the condition of microbial flooding. Finally, the sealing performance of MS-2 and MS-4 was evaluated by physical simulation Block test. Results showed that compared with MS-2, MS-4 was more suitable for Block B.

Controlling Release Kinetics of PLG Microspheres Using a Manufacturing Technique

NASA Astrophysics Data System (ADS)

Berchane, Nader

2005-11-01

Controlled drug delivery offers numerous advantages compared with conventional free dosage forms, in particular: improved efficacy and patient compliance. Emulsification is a widely used technique to entrap drugs in biodegradable microspheres for controlled drug delivery. The size of the formed microspheres has a significant influence on drug release kinetics. Despite the advantages of controlled drug delivery, previous attempts to achieve predetermined release rates have seen limited success. This study develops a tool to tailor desired release kinetics by combining microsphere batches of specified mean diameter and size distribution. A fluid mechanics based correlation that predicts the average size of Poly(Lactide-co-Glycolide) [PLG] microspheres from the manufacturing technique, is constructed and validated by comparison with experimental results. The microspheres produced are accurately represented by the Rosin-Rammler mathematical distribution function. A mathematical model is formulated that incorporates the microsphere distribution function to predict the release kinetics from mono-dispersed and poly-dispersed populations. Through this mathematical model, different release kinetics can be achieved by combining different sized populations in different ratios. The resulting design tool should prove useful for the pharmaceutical industry to achieve designer release kinetics.

Preparation and characterization of oxybenzone-loaded gelatin microspheres for enhancement of sunscreening efficacy.

PubMed

Patel, M; Jain, Sunil K; Yadav, Awesh K; Gogna, D; Agrawal, G P

2006-01-01

The objective of our present study was to prepare and evaluate gelatin microspheres of oxybenzone to enhance its sunscreening efficacy. The gelatin microspheres of oxybenzone were prepared by emulsion method. Process parameters were analyzed to optimize the formulation. The in vitro drug release study was performed in pH 7.4 using cellulose acetate membrane. Microspheres prepared using oxybenzone:gelatin ratio of 1:6 showed slowest drug release and those prepared with oxybenzone:gelatin ratio of 1:2 showed fastest drug release. The gelatin microspheres of oxybenzone were incorporated in aloe vera gel. Sun exposure method using sodium nitroprusside solution was used for in vitro sunscreen efficacy testing. The formulation C5 containing oxybenzone-bearing gelatin microspheres in aloe vera gel showed best sunscreen efficacy. The formulations were evaluated for skin irritation test in human volunteers, sun protection factor, and minimum erythema dose in albino rats. These studies revealed that the incorporation of sunscreening agent-loaded microspheres into aloe vera gel greatly increased the efficacy of sunscreen formulation more than four times.

Suspension Plasma Spray Fabrication of Nanocrystalline Titania Hollow Microspheres for Photocatalytic Applications

NASA Astrophysics Data System (ADS)

Ren, Kun; Liu, Yi; He, Xiaoyan; Li, Hua

2015-10-01

Hollow inorganic microspheres with controlled internal pores in close-cell configuration are usually constructed by submicron-sized particles. Fast and efficient large-scale production of the microspheres with tunable sizes yet remains challenging. Here, we report a suspension plasma spray route for making hollow microspheres from nano titania particles. The processing permits most nano particles to retain their physiochemical properties in the as-sprayed microspheres. The microspheres have controllable interior cavities and mesoporous shell of 1-3 μm in thickness. Spray parameters and organic content in the starting suspension play the key role in regulating the efficiency of accomplishing the hollow sphere structure. For the ease of collecting the spheres for recycling use, ferriferous oxide particles were used as additives to make Fe3O4-TiO2 hollow magnetic microspheres. The spheres can be easily recycled through external magnetic field collection after each time use. Photocatalytic anti-bacterial activities of the hollow spheres were assessed by examining their capability of degrading methylene blue and sterilizing Escherichia coli bacteria. Excellent photocatalytic performances were revealed for the hollow spheres, giving insight into their potential versatile applications.

Improvement of Oral Bioavailability of Lopinavir Without Co-administration of Ritonavir Using Microspheres of Thiolated Xyloglucan.

PubMed

Madgulkar, Ashwini R; Bhalekar, Mangesh R; Kadam, Ashwini A

2018-01-01

Lopinavir is a BCS Class IV drug exhibiting poor bioavailability due to P-gp efflux and limited permeation. The aim of this research was to formulate and characterize microspheres of lopinavir using thiolated xyloglucan (TH-MPs) as carrier to improve its oral bioavailability without co-administration of ritonavir. Thiomeric microspheres were prepared by ionotropic gelation between alginic acid and calcium ions. Interaction studies were performed using Fourier transform infrared spectroscopy (FT-IR). The thiomeric microspheres were characterized for its entrapment efficiency, T 80 , surface morphology, and mucoadhesion employing in vitro wash off test. The microspheres were optimized by 3 2 factorial design. The optimized thiomeric microsphere formulation revealed 93.12% entrapment efficiency, time for 80% drug release (T 80 ) of 358.1 min, and 88% mucoadhesion after 1 h. The permeation of lopinavir from microspheres was enhanced 3.15 times as determined by ex vivo study using everted chick intestine and increased relative bioavailability over 3.22-fold over combination of lopinavir and ritonavir as determined by in vivo study in rat model.

Metronidazole loaded pectin microspheres for colon targeting.

PubMed

Vaidya, Ankur; Jain, Aviral; Khare, Piush; Agrawal, Ram K; Jain, Sanjay K

2009-11-01

A multiparticulate system having pH-sensitive property and specific enzyme biodegradability for colon-targeted delivery of metronidazole was developed. Pectin microspheres were prepared using emulsion-dehydration technique. These microspheres were coated with Eudragit(R) S-100 using oil-in-oil solvent evaporation method. The SEM was used to characterize the surface of these microspheres and a distinct coating over microspheres could be seen. The in vitro drug release studies exhibited no drug release at gastric pH, however continuous release of drug was observed from the formulation at colonic pH. Further, the release of drug from formulation was found to be higher in the presence of rat caecal contents, indicating the effect of colonic enzymes on the pectin microspheres. The in vivo studies were also performed by assessing the drug concentration in various parts of the GIT at different time intervals which exhibited the potentiality of formulation for colon targeting. Hence, it can be concluded that Eudragit coated pectin microspheres can be used for the colon specific delivery of drug. (c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association

MO-A-BRD-02: Physics Perspective

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

Kappadath, S.

2015-06-15

Yttrium-90 (Y90) microsphere therapy, a form of radiation therapy, is an increasingly popular option for care of patients with liver metastases or unresectable hepatocellular carcinoma. The therapy directly delivers Y90 microspheres via the hepatic artery to disease sites. Following delivery, a vast majority of microspheres preferentially lodge in the capillary vessels due to their embolic size and targeted trans-arterial delivery – depositing up to 90% of its energy in the first 5 mm of tissue. There have been a number of advances in tomographic imaging within both interventional radiology and nuclear medicine that has advanced therapy planning techniques. Quantitative imagingmore » of Y90 microsphere distribution post-therapy has also seen innovations that have led to improvements in tumor dosimetry and characterization of tumor response. A review of current trends and recent innovation in Y90 microsphere therapies will be presented. Learning Objectives: To present the imaging requirements for Y90 microsphere therapy planning To explain the standard dosimetry models used in Y90 microsphere therapy planning To report on advances in imaging for therapy planning and posttherapy assessment of tumor dosimetry and response.« less

MO-A-BRD-01: Clinical Perspective

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

Mahvash, A.

2015-06-15

Yttrium-90 (Y90) microsphere therapy, a form of radiation therapy, is an increasingly popular option for care of patients with liver metastases or unresectable hepatocellular carcinoma. The therapy directly delivers Y90 microspheres via the hepatic artery to disease sites. Following delivery, a vast majority of microspheres preferentially lodge in the capillary vessels due to their embolic size and targeted trans-arterial delivery – depositing up to 90% of its energy in the first 5 mm of tissue. There have been a number of advances in tomographic imaging within both interventional radiology and nuclear medicine that has advanced therapy planning techniques. Quantitative imagingmore » of Y90 microsphere distribution post-therapy has also seen innovations that have led to improvements in tumor dosimetry and characterization of tumor response. A review of current trends and recent innovation in Y90 microsphere therapies will be presented. Learning Objectives: To present the imaging requirements for Y90 microsphere therapy planning To explain the standard dosimetry models used in Y90 microsphere therapy planning To report on advances in imaging for therapy planning and posttherapy assessment of tumor dosimetry and response.« less

Observation of defect-assisted enhanced visible whispering gallery modes in ytterbium-doped ZnO microsphere

NASA Astrophysics Data System (ADS)

Khanum, Rizwana; Moirangthem, Rakesh S.; Das, Nayan Mani

2017-06-01

Smooth surfaced and crystalline undoped and ytterbium doped zinc oxide (ZnO) microspheres having an approximate size of 3-5 μm were synthesized by hydrothermal process. Out of these microspheres, a single microparticle was chosen and engaged as a whispering gallery wave microresonator. The defect induced luminescence from an individual ZnO microsphere was investigated with micro-photoluminescence measurement in the spectral range of 565 to 740 nm under the excitation of a green laser having a centered wavelength at 532 nm. The defects-related emissions from a single ZnO microsphere show optical resonance peaks so-called "whispering gallery modes" (WGMs) which are confirmed with the theoretical calculation. Further, ZnO microspheres were chemically doped with the different molar percentages of Ytterbium (Yb), and enhancement in their emission properties was investigated. Our experimental results show that ZnO microspheres with 0.5 mol. % doping of Yb gives the strongest optical emission and has highest Q-factor which can be employed in the development of WGM based optical biosensor or laser.

Biodegradable microsphere-mediated cell perforation in microfluidic channel using femtosecond laser

NASA Astrophysics Data System (ADS)

Ishii, Atsuhiro; Ariyasu, Kazumasa; Mitsuhashi, Tatsuki; Heinemann, Dag; Heisterkamp, Alexander; Terakawa, Mitsuhiro

2016-05-01

The use of small particles has expanded the capability of ultrashort pulsed laser optoinjection technology toward simultaneous treatment of multiple cells. The microfluidic platform is one of the attractive systems that has obtained synergy with laser-based technology for cell manipulation, including optoinjection. We have demonstrated the delivery of molecules into suspended-flowing cells in a microfluidic channel by using biodegradable polymer microspheres and a near-infrared femtosecond laser pulse. The use of polylactic-co-glycolic acid microspheres realized not only a higher optoinjection ratio compared to that with polylactic acid microspheres but also avoids optical damage to the microfluidic chip, which is attributable to its higher optical intensity enhancement at the localized spot under a microsphere. Interestingly, optoinjection ratios to nucleus showed a difference for adhered cells and suspended cells. The use of biodegradable polymer microspheres provides high throughput optoinjection; i.e., multiple cells can be treated in a short time, which is promising for various applications in cell analysis, drug delivery, and ex vivo gene transfection to bone marrow cells and stem cells without concerns about residual microspheres.

Preparation and evaluation of enrofloxacin microspheres and tissue distribution in rats

PubMed Central

Yang, Fan; Kang, Jijun; Yang, Fang; Zhao, Zhensheng; Kong, Tao

2015-01-01

New enrofloxacin microspheres were formulated, and their physical properties, lung-targeting ability, and tissue distribution in rats were examined. The microspheres had a regular and round shape. The mean diameter was 10.06 µm, and the diameter of 89.93% of all microspheres ranged from 7.0 µm to 30.0 µm. Tissue distribution of the microspheres was evaluated along with a conventional enrofloxacin preparation after a single intravenous injection (7.5 mg of enrofloxacin/kg bw). The results showed that the elimination half-life (t1/2β) of enrofloxacin from lung was prolonged from 7.94 h for the conventional enrofloxacin to 13.28 h for the microspheres. Area under the lung concentration versus time curve from 0 h to ∞ (AUC0-∞) was increased from 11.66 h·µg/g to 508.00 h·µg/g. The peak concentration (Cmax) in lung was increased from 5.95 µg/g to 93.36 µg/g. Three lung-targeting parameters were further assessed and showed that the microspheres had remarkable lung-targeting capabilities. PMID:25643802

Preparation and evaluation of enrofloxacin microspheres and tissue distribution in rats.

PubMed

Yang, Fan; Kang, Jijun; Yang, Fang; Zhao, Zhensheng; Kong, Tao; Zeng, Zhenling

2015-01-01

New enrofloxacin microspheres were formulated, and their physical properties, lung-targeting ability, and tissue distribution in rats were examined. The microspheres had a regular and round shape. The mean diameter was 10.06 µm, and the diameter of 89.93% of all microspheres ranged from 7.0 µm to 30.0 µm. Tissue distribution of the microspheres was evaluated along with a conventional enrofloxacin preparation after a single intravenous injection (7.5 mg of enrofloxacin/kg bw). The results showed that the elimination half-life (t1/2β) of enrofloxacin from lung was prolonged from 7.94 h for the conventional enrofloxacin to 13.28 h for the microspheres. Area under the lung concentration versus time curve from 0 h to ∞ (AUC00∞) was increased from 11.66 h·µg/g to 508.00 h·µg/g. The peak concentration (Cmax) in lung was increased from 5.95 µg/g to 93.36 µg/g. Three lung-targeting parameters were further assessed and showed that the microspheres had remarkable lung-targeting capabilities.

Method and apparatus for controlled size distribution of gel microspheres formed from aqueous dispersions

DOEpatents

Ryon, Allen D.; Haas, Paul A.; Vavruska, John S.

1984-01-01

The present invention is directed to a method and apparatus for making a population of dense, closely size-controlled microspheres by sol-gel procedures wherein said microspheres are characterized by a significant percentage of said population being within a predetermined, relatively narrow size range. Microsphere populations thus provided are useful in vibratory-packed processes for nuclear fuels to be irradiated in LWR- and FBR-type nuclear reactors.

Microsphere morphology tuning and photo-luminescence properties of monoclinic Y2WO6

NASA Astrophysics Data System (ADS)

Gao, Hong; Bai, Yulong; Zhang, Junying; Tang, Zilong

2015-04-01

Effects of the solution pH value and reaction time on the precursor morphology and photoluminescence properties are investigated for hydrothermally prepared monoclinic Y2WO6 phosphors. In the near-neutral environment, sodium dodecyl benzene sulfonate (SDBS) surfactant forms small microspheres micelles as template to synthesize microspherical precursor. H+ ions concentration affects the arrangement of negative ionic surfactant SDBS. As a result, jujube-liked and popcorn-like loose microspheres formed at low pH value. When the pH value is 5.2 and the hydrothermal reaction time reaches 24 h, respectively, the strongest luminescent intensity can be obtained. Under this condition, the precursor presented regular microsphere with diameter of 4.0 μm. After high-temperature heat treatment, the obtained phosphor particles still exhibit microsphere-like shape. Therefore, we provide an effective method to tune the morphology of Y2WO6 phosphors and study the relationship between morphology and luminescent performance.

Self-assembled dye-doped polymer microspheres as whispering gallery mode lasers

NASA Astrophysics Data System (ADS)

Chen, Xiaogang; Sun, Hongyi; Yang, Hongqin; Wu, Xiang; Xie, Shusen

2016-10-01

Microlasers based on high-Q whispering-gallery-mode (WGM) resonances are promising low-threshold laser sources for bio-sensing and imaging applications. In this talk, we demonstrate a cost effective approach to obtain size-controllable polymer microspheres, which can be served as good WGM microcavities. By injecting SU-8 solution into low-refractiveindex UV polymer, self-assembled spherical droplet with smooth surface can be created inside the elastic medium and then solidified by UV exposure. The size of the microspheres can be tuned from several to hundreds of microns. WGM Lasing has been achieved by optically pumping the dye-doped microspheres with ns lasers. Experimental results show that the microsphere lasers have high quality factors and low lasing thresholds. The self-assembled dye-doped polymer microspheres would provide an excellent platform for the micro-laser sources in on-chip biosensing and imaging systems.

Development of poly-l-lysine-coated calcium-alginate microspheres encapsulating fluorescein-labeled dextrans

NASA Astrophysics Data System (ADS)

Charron, Luc; Harmer, Andrea; Lilge, Lothar

2005-09-01

A technique to produce fluorescent cell phantom standards based on calcium alginate microspheres with encapsulated fluorescein-labeled dextrans is presented. An electrostatic ionotropic gelation method is used to create the microspheres which are then exposed to an encapsulation method using poly-l-lysine to trap the dextrans inside. Both procedures were examined in detail to find the optimal parameters producing cell phantoms meeting our requirements. Size distributions favoring 10-20 microns microspheres were obtained by varying the high voltage and needle size parameters. Typical size distributions of the samples were centered at 150 μm diameter. Neither the molecular weight nor the charge of the dextrans had a significant effect on their retention in the microspheres, though anionic dextrans were chosen to help in future capillary electrophoresis work. Increasing the exposure time of the microspheres to the poly-l-lysine solution decreased the leakage rates of fluorescein-labeled dextrans.

Integrated Cryogenic Experiment (ICE) microsphere investigation

NASA Technical Reports Server (NTRS)

Spradley, I.; Read, D.

1989-01-01

The main objective is to determine the performance of microsphere insulation in a 0-g environment and compare its performance to reference insulations such as multilayer insulation. The Lockheed Helium Extended-Life Dewar (HELD) is used to provide superfluid-helium cold sink for the experiment. The use of HELD allows the low-g dynamic properties of Passive Orbital Disconnect Struts (PODS) to be characterized and provides a flight demonstration of the PODS system. The thermal performance of microspheres in 1 and 0 g was predicted, a flight experiment was designed to determine microsphere thermal performance, and the interface was also designed between the experimental package and the shuttle through HELD and the Hitchhiker-M carrier. A single test cell was designed and fabricated. The cell was filled with uncoated glass microspheres and tested with a liquid-nitrogen cold sink. The data were found to agree with predictions of microsphere performance in 1 g.

Multicolor quantum dot-encoded microspheres for the fluoroimmunoassays of chicken newcastle disease and goat pox virus.

PubMed

Yuan, Pingfan; Ma, Qiang; Meng, Rizeng; Wang, Chao; Dou, Wenchao; Wang, Guannan; Su, Xingguang

2009-05-01

Semiconductor nanocrystals (or quantum dots, QDs) have the potential to overcome some of the limitations encountered by traditional fluorophores in fluorescence labeling applications. The unique spectroscopic properties of QDs make them hold immense promise as versatile labels for biological applications. In this work, we employ the layer-by-layer (LbL) method for the construction of bio-functional multicolor QD-encoded microspheres. Polystyrene microspheres with diameter of 3 microm were used as templates for the deposition of different sized CdTe QDs/polyelectrolyte multilayers. Two different antigens, Chicken newcastle disease (CND) antigen and goat pox virus (GPV) antigen, were conjugated to two kinds of biofunctional multicolor microspheres with different optical encoding. The multicolor microspheres can capture corresponding antibodies labeled with QDs, QDs-CND antibody and QDs-GPV antibody in the fluoroimmunoassays. The microspheres can be distinguished from each other based on their optical encoding.

Metal containing polymeric functional microspheres

NASA Technical Reports Server (NTRS)

Yen, Shiao-Ping S. (Inventor); Rembaum, Alan (Inventor); Molday, Robert S. (Inventor)

1979-01-01

Polymeric functional microspheres containing metal or metal compounds are formed by addition polymerization of a covalently bondable olefinic monomer such as hydroxyethylmethacrylate in the presence of finely divided metal or metal oxide particles, such as iron, gold, platinum or magnetite, which are embedded in the resulting microspheres. The microspheres can be covalently bonded to chemotherapeutic agents, antibodies, or other proteins providing a means for labeling or separating labeled cells. Labeled cells or microspheres can be concentrated at a specific body location such as in the vicinity of a malignant tumor by applying a magnetic field to the location and then introducing the magnetically attractable microspheres or cells into the circulatory system of the subject. Labeled cells can be separated from a cell mixture by applying a predetermined magnetic field to a tube in which the mixture is flowing. After collection of the labeled cells, the magnetic field is discontinued and the labeled sub-cell population recovered.

Synthesis of V2O5 microspheres by spray pyrolysis as cathode material for supercapacitors

NASA Astrophysics Data System (ADS)

Yin, Zhendong; Xu, Jie; Ge, Yali; Jiang, Qiaoya; Zhang, Yaling; Yang, Yawei; Sun, Yuping; Hou, Siyu; Shang, Yuanyuan; Zhang, Yingjiu

2018-03-01

Vanadium oxide (V2O5) microspheres have attracted considerable attention in the energy field due to their unique properties such as high stability and electrochemical activity. Here, massive V2O5 microspheres with smooth surface, hollow cavity and uniform particle sizes (0.4–1.5 μm), were synthesized by a facile spray pyrolysis process. Post-treatment at predefined temperatures effectively turned the microsphere shell into stacked nanorods with widths of 100 nm and lengths of 500 nm when processed at 500 °C for 3 h under nitrogen atmosphere, with enhanced crystallinity. When applied as cathode materials for supercapacitors, the post-treated V2O5 microspheres at 500 °C exhibited improved specific capacitance and longer discharge time. This is an effective method to manufacture massive V2O5 microspheres with tailored structure and potential applications in high-performance energy storage materials.

Ultraflexible nanostructures and implications for future nanorobots

NASA Astrophysics Data System (ADS)

Cohn, Robert W.; Panchapakesan, Balaji

2016-05-01

Several high aspect ratio nanostructures have been made by capillary force directed self-assembly including polymeric nanofiber air-bridges, trampoline-like membranes, microsphere-beaded nanofibers, and intermetallic nanoneedles. Arrays of polymer air-bridges form in seconds by simply hand brushing a bead of polymeric liquid over an array of micropillars. The domination of capillary force that is thinning unstable capillary bridges leads to uniform arrays of nanofiber air-bridges. Similarly, arrays of vertically oriented Ag2Ga nanoneedles have been formed by dipping silvercoated arrays of pyramidal silicon into melted gallium. Force-displacement measurements of these structures are presented. These nanostructures, especially when compressively or torsionally buckled, have extremely low stiffnesses, motion due to thermal fluctuations that is relatively easily detected, and the ability to move great distances for very small changes in applied force. Nanofibers with bead-on-a-string structure, where the beads are micron diameter and loaded with magnetic iron oxide (maghemite), are shown to be simply viewable under optical microscopes, have micronewton/ m stiffness, and have ultralow torsional stiffnesses enabling the bead to be rotated numerous revolutions without breaking. Combination of these high aspect ratio structures with stretched elastomers offer interesting possibilities for robotic actuation and locomotion. Polydimethylsiloxane loaded with nanomaterials, e.g. nanotubes, graphene or MoS2, can be efficiently heated with directed light. Heating produces considerable force through the thermoelastic effect, and this force can be used for continuous translation or to trigger reversible elastic buckling of the nanostructures. The remote stimulation of motion with light provides a possible mechanism for producing cooperative behavior between swarms of semiautonomous nanorobots.

Method for introduction of gases into microspheres

DOEpatents

Hendricks, Charles D.; Koo, Jackson C.; Rosencwaig, Allan

1981-01-01

A method for producing small hollow glass spheres filled with a gas by introduction of the gas during formation of the hollow glass spheres. Hollow glass microspheres having a diameter up to about 500.mu. with both thin walls (0.5 to 4.mu.) and thick walls (5 to 20.mu.) that contain various fill gases, such as Ar, Kr, Xe, Br, DT, H.sub.2, D.sub.2, He, N.sub.2, Ne, CO.sub.2, etc. in the interior thereof, can be produced by the diffusion of the fill gas or gases into the microsphere during the formation thereof from a liquid droplet of glass-forming solution. This is accomplished by filling at least a portion of the multiple-zone drop-furnace used in producing hollow microspheres with the gas or gases of interest, and then taking advantage of the high rate of gaseous diffusion of the fill gas through the wall of the gel membrane before it transforms into a glass microsphere as it is processed in the multiple-zone furnace. Almost any gas can be introduced into the inner cavity of a glass microsphere by this method during the formation of the microsphere provided that the gas is diffused into the gel membrane or microsphere prior to its transformation into glass. The process of this invention provides a significant savings of time and related expense of filling glass microspheres with various gases. For example, the time for filling a glass microballoon with 1 atmosphere of DT is reduced from about two hours to a few seconds.

PCL-PDMS-PCL Copolymer-Based Microspheres Mediate Cardiovascular Differentiation from Embryonic Stem Cells.

PubMed

Song, Liqing; Ahmed, Mohammad Faisel; Li, Yan; Bejoy, Julie; Zeng, Changchun; Li, Yan

2017-10-01

Poly-ɛ-caprolactone (PCL) based microspheres have received much attention as drug or growth factor delivery carriers and tissue engineering scaffolds due to their biocompatibility, biodegradability, and tunable biophysical properties. In addition, PCL and polydimethylsiloxane (PDMS) can be fabricated into thermoresponsive shape memory polymers for various biomedical applications (e.g., smart sutures and vascular stents). However, the influence of biophysical properties of PCL-PDMS based microspheres on stem cell lineage commitment has not been well understood. In this study, PDMS was used as soft segments of varying length to tailor the elastic modulus of PCL-based copolymers. It was found that lower elastic modulus (<10 kPa) of the tri-block copolymer PCL-PDMS-PCL promoted vascular differentiation of embryonic stem cells, but the range of 60-100 MPa PCL-PDMS-PCL had little influence on cardiovascular differentiation. Then different sizes (30-140 μm) of PCL-PDMS-PCL microspheres were fabricated and incorporated with embryoid bodies (EBs). Differential expression of KDR, CD31, and VE-cadherin was observed for the EBs containing microspheres of different sizes. Higher expression of KDR was observed for the condition with small size of microspheres (32 μm), while higher CD31 and VE-cadherin expression was observed for the group of medium size of microspheres (94 μm). Little difference in cardiac marker α-actinin was observed for different microspheres. This study indicates that the biophysical properties of PCL-PDMS-PCL microspheres impact vascular lineage commitment and have implications for drug delivery and tissue engineering.

Development and evaluation of intestinal targeted mucoadhesive microspheres of Bacillus coagulans.

PubMed

Alli, Sk Md Athar; Ali, Sk Md Ajhar; Samanta, Amalesh

2011-11-01

Intestinal targeted mucoadhesive microsphere of probiotics may provide numerous associated health benefits. To develop mucoadhesive microspheres that will deliver viable probiotic cells into gut protectively against harsh environmental conditions of stomach for extended period. Core mucoadhesive microspheres of Bacillus coagulans were prepared using hypromellose, following coacervation and phase separation technique and were then coated with hypromellose phthalate to achieve their site-specific release. Microspheres were evaluated for percent yield, entrapment efficiency, surface morphology, particle size and size distribution, flow property, swelling property, mucoadhesion property by the in vitro wash-off and the ex vivo mucoadhesive strength tests, in vitro release profile and release kinetic, in vivo probiotic activity, and stability. The values for kinetic constant and regression coefficient of model-dependent approaches and the difference factor, the similarity factor, and the Rescigno index of model-independent approaches were determined for accessing and comparing in vitro performance. Microsphere formulation batches have percent yield value between 56.26% and 69.13% and entrapment efficiency value between 66.95% and 77.89%. Microspheres were coarser with spherical shape having mean particle size from 28.03 to 48.31 μm. In vitro B. coagulans release profile follows zero-order kinetics and depends on the grade of hypromellose and the B. coagulans-to-hypromellose ratio. Experimental microspheres rendered adequate stability to B. coagulans at room temperature. Microspheres had delivered B. coagulans in simulated intestinal condition following zero-order kinetics, protectively in simulated gastric condition, exhibiting appreciable mucoadhesion in intestinal condition, which could be useful to achieve site-specific delivery for extended period.

Hierarchical Mn2O3 Microspheres In-Situ Coated with Carbon for Supercapacitors with Highly Enhanced Performances

PubMed Central

Gong, Feilong; Lu, Shuang; Peng, Lifang; Zhou, Jing; Kong, Jinming; Jia, Dianzeng; Li, Feng

2017-01-01

Porous Mn2O3 microspheres have been synthesized and in-situ coated with amorphous carbon to form hierarchical C@Mn2O3 microspheres by first producing MnCO3 microspheres in solvothermal reactions, and then annealing at 500 °C. The self-assembly growth of MnCO3 microspheres can generate hollow structures inside each of the particles, which can act as micro-reservoirs to store biomass-glycerol for generating amorphous carbon onto the surfaces of Mn2O3 nanorods consisting of microspheres. The C@Mn2O3 microspheres, prepared at 500 °C, exhibit highly enhanced pseudocapacitive performances when compared to the particles after annealed at 400 °C and 600 °C. Specifically, the C@Mn2O3 microspheres prepared at 500 °C show high specific capacitances of 383.87 F g−1 at current density of 0.5 A g−1, and excellent cycling stability of 90.47% of its initial value after cycling for 5000 times. The asymmetric supercapacitors assembled with C@Mn2O3 microspheres after annealed at 500 °C and activated carbon (AC) show an energy density of up to 77.8 Wh kg−1 at power density of 500.00 W kg−1, and a maximum power density of 20.14 kW kg−1 at energy density of 46.8 Wh kg−1. We can attribute the enhanced electrochemical performances of the materials to their three-dimensional (3D) hierarchical structure in-situ coated with carbon. PMID:29168756

PEGylation controls attachment and engulfment of monodisperse magnetic poly(2-hydroxyethyl methacrylate) microspheres by murine J774.2 macrophages

NASA Astrophysics Data System (ADS)

Horák, Daniel; Hlidková, Helena; Klyuchivska, Olga; Grytsyna, Iryna; Stoika, Rostyslav

2017-12-01

The first objective of this work was to prepare biocompatible magnetic polymer microspheres with reactive functional groups that could withstand nonspecific protein adsorption from biological media. Carboxyl group-containing magnetic poly(2-hydroxyethyl methacrylate) (mgt.PHEMA) microspheres ∼4 μm in size were prepared by multistage swelling polymerization, precipitation of iron oxide inside their pores, and coating with an α-methoxy-ω-amino poly(ethylene glycol) (CH3O-PEG750-NH2 or CH3O-PEG5,000-NH2)/α-amino-ω-t-Boc-amino poly(ethylene glycol) (H2N-PEG5,000-NH-t-Boc) mixture. The mgt.PHEMA@PEG microspheres contained ∼10 μmol COOH per g. Biocompatibility of the particles was evaluated by their treatment with human embryonic kidney cells of the HEK293 line. The microspheres did not interfere with the growth of these cells, suggesting that the particles can be considered non-toxic. A second goal of this study was to address on the interaction of the developed microspheres with macrophages that commonly eliminate foreign microbodies appearing in organisms. Murine J774.2 macrophages (J774.2) were cultured in the presence of the neat and PEGylated microspheres for 2 h. Mgt.PHEMA@PEG5,000 microspheres significantly adhered to the surface of J774.2 macrophages but were minimally engulfed. Due to these properties, the mgt.PHEMA@PEG microspheres might be useful for application in drug delivery systems and monitoring of the efficiency of phagocytosis.

Hydrophilic porous magnetic poly(GMA-MBAA-NVP) composite microspheres containing oxirane groups: An efficient carrier for immobilizing penicillin G acylase

NASA Astrophysics Data System (ADS)

Xue, Ping; Su, Weiguang; Gu, Yaohua; Liu, Haifeng; Wang, Julan

2015-03-01

Magnetic hydrophilic polymeric microspheres containing oxirane groups were prepared by inverse suspension polymerization of glycidyl methacrylate (GMA), N, N‧-methylene bisacrylamide (MBAA) and N-vinyl pyrrolidone (NVP) in the existence of formamide, which were denoted as magnetic poly(GMA-MBAA-NVP) microspheres. The magnetic poly(GMA-MBAA-NVP) microspheres were characterized by scanning electron microscopy (SEM), FT-IR spectroscopy, X-ray diffraction (XRD), vibrating sample magnetometer (VSM) and so on. The results showed that poly(GMA-MBAA-NVP) microspheres possessed well spherical shape, narrow size distribution, abundant porous structure, reactive oxirane groups and superparamagnetic properties. Formamide used in the present work served as a modifier, a dispersant and a porogen to form final porous polymer microspheres. The penicillin G acylase (PGA) was covalently immobilized onto the magnetic microspheres through the reaction between the amino groups of enzyme and the oxirane groups on the microspheres for producing 6-aminopenicillanic acid (6-APA). The effects of GMA/NVP ratio and crosslink density on the activity of immobilized PGA were investigated. The highest apparent activity, enzyme loading and coupling yield of immobilized PGA were 821 IU/g, 65.3 mg/g and 42.3% respectively when the mass ratio of GMA/NVP was 1:1 and crosslink density was 60%. Compared with the free PGA, immobilized PGA showed a wider range of pH value and reaction temperature. The relative activity and reaction rate of immobilized PGA remained almost constant after 20 recycles. The magnetic poly(GMA-MBAA-NVP) microspheres would be very promising carriers for immobilizing enzymes in industrial application.

An Accelerated Release Method of Risperidone Loaded PLGA Microspheres with Good IVIVC.

PubMed

Hu, Xiaoqin; Zhang, Jianwei; Tang, Xuemei; Li, Mingyuan; Ma, Siyu; Liu, Cheng; Gao, Yue; Zhang, Yue; Liu, Yan; Yu, Fanglin; Yang, Yang; Guo, Jia; Li, Zhiping; Mei, Xingguo

2018-01-01

A long release period lasting several days or several weeks is always needed and thereby it is tedious and time consuming to screen formulations of such microspheres with so long release period and evaluate their release profiles in vitro with conventional long-term or "real-time" release method. So, an accelerated release testing of such system is necessary for formulation design as well as quality control purpose. The purpose of this study is to obtain an accelerated release method of risperidone loaded poly(lactic-co-glycolic acid) (PLGA) microspheres with good in vitro/in vivo correlation (IVIVC). Two formulations of risperidone loaded PLGA microspheres used for evaluating IVIVC were prepared by O/W method. The accelerated release condition was optimized by investigating the effect of pH, osmotic pressure, temperature and ethanol concentration on the release of risperidone from microspheres and the in vitro accelerated release profiles of risperidone from PLGA microspheres were obtained under this optimized accelerated release condition. The plasma concentration of risperidone were also detected after subcutaneous injection of risperidone loaded microspheres to rats. The in vivo cumulative absorption profiles were then calculated using Wagner-Nelson model, Loo- Riegelman model and numerical convolution model, respectively. The correlation between in vitro accelerated release and in vivo cumulative absorption were finally evaluated with Least Square Method. It was shown that temperature and ethanol concentration significantly affected the release of risperidone from the microspheres while pH and osmotic pressure of release media slightly affected the release behavior of risperidone. The in vitro release of risperidone from microspheres were finally undergone in PBS (pH7.0, 300mosm) with 20% (V/V) ethanol at 45°C. The sustained and complete release of risperidone was observed in both formulations under the accelerated release condition although these two release profiles were dissimilar. The correlation coefficients (R2) of IVIVC were all above 0.95 and the slopes were all between 0.9564 and 1.1868 in spite of fitted model and microsphere formulation. An in vitro accelerated release method of risperidone microspheres with good IVIVC was established in this paper and this accelerated release method was supposed to have great potential in both in vivo performance prediction and quality control for risperidone loaded PLGA microspheres. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Design of polymeric immunomicrospheres for cell labelling and cell separation

NASA Technical Reports Server (NTRS)

Rembaum, A.; Margel, S.

1978-01-01

Synthesis of several classes of hydrophylic microspheres applied to cell labeling and cell separation is described. Five classes of cross-linked microspheres with functional groups such as carboxyl, hydroxyl, amide and/or pyridine groups were synthesized. These functional groups were used to bind covalently antibodies and other proteins to the surface of the microspheres. To optimize the derivatisation technique, polyglutaraldehyde immunomicrospheres were prepared and utilized. Specific populations of human and murine lymphocytes were labelled with microspheres synthesized by the emulsion of the ionizing radiation technique. The labelling of the cells by means of microspheres containing an iron core produced successful separation of B from T lymphocytes by means of a magnetic field.

Properties of rigid polyurethane foams filled with glass microspheres

NASA Astrophysics Data System (ADS)

Yakushin, V.; Bel'kova, L.; Sevastyanova, I.

2012-11-01

The effect of hollow glass microspheres with a density of 125 kg/m3 on the properties of low-density (54-90 kg/m3) rigid polyurethane foams is investigated. The thermal expansion coefficient of the foams and their properties in tension and compression in relation to the content of the microspheres (0.5-5 wt.%) are determined. An increase in the characteristics of the material in compression in the foam rise direction with increasing content of filler is revealed. The limiting content of the microspheres above which the mechanical characteristics of the filled foams begin to decrease is found. The distribution of the microspheres in elements of the cellular structure of the polyurethane foams is examined.

Method for selecting hollow microspheres for use in laser fusion targets

DOEpatents

Farnum, Eugene H.; Fries, R. Jay; Havenhill, Jerry W.; Smith, Maurice Lee; Stoltz, Daniel L.

1976-01-01

Hollow microspheres having thin and very uniform wall thickness are useful as containers for the deuterium and tritium gas mixture used as a fuel in laser fusion targets. Hollow microspheres are commercially available; however, in commercial lots only a very small number meet the rigid requirements for use in laser fusion targets. Those meeting these requirements may be separated from the unsuitable ones by subjecting the commercial lot to size and density separations and then by subjecting those hollow microspheres thus separated to an external pressurization at which those which are aspherical or which have nonuniform walls are broken and separating the sound hollow microspheres from the broken ones.

Ketoprofen spray-dried microspheres based on Eudragit RS and RL: study of the manufacturing parameters.

PubMed

Rassu, Giovanna; Gavini, Elisabetta; Spada, Gianpiera; Giunchedi, Paolo; Marceddu, Salvatore

2008-11-01

The preparation of ketoprofen spray-dried microspheres can be affected by the long drug recrystallization time. Polymer type and drug-polymer ratio as well as manufacturing parameters affect the preparation. The purpose of this work was to evaluate the possibility to obtain ketoprofen spray-dried microspheres using the Eudragit RS and RL; the influence of the spray-drying parameters on morphology, dimension, and physical stability of microspheres was studied. Ketoprofen microspheres based on Eudragit blend can be prepared by spray-drying and the nebulization parameters do not influence significantly particle properties; nevertheless, they can be affected by drying and storage methods. No effect of the container material is found.

Opportunities for bead-based multiplex assays in veterinary diagnostic laboratories

USDA-ARS?s Scientific Manuscript database

Bead based multiplex assays (BBMA) also referred to as Luminex, MultiAnalyte Profiling or cytometric bead array (CBA) assays, are applicable for high throughput, simultaneous detection of multiple analytes in solution (from several, up to 50-500 analytes within a single, small sample volume). Curren...

Microsphere Insulation Panels

NASA Technical Reports Server (NTRS)

Mohling, R.; Allen, M.; Baumgartner, R.

2006-01-01

Microsphere insulation panels (MIPs) have been developed as lightweight, longlasting replacements for the foam and vacuum-jacketed systems heretofore used for thermally insulating cryogenic vessels and transfer ducts. The microsphere core material of a typical MIP consists of hollow glass bubbles, which have a combination of advantageous mechanical, chemical, and thermal-insulation properties heretofore available only separately in different materials. In particular, a core filling of glass microspheres has high crush strength and low density, is noncombustible, and performs well in soft vacuum.

Fabrication of photonic band gap materials

DOEpatents

Constant, Kristen; Subramania, Ganapathi S.; Biswas, Rana; Ho, Kai-Ming

2002-01-15

A method for forming a periodic dielectric structure exhibiting photonic band gap effects includes forming a slurry of a nano-crystalline ceramic dielectric or semiconductor material and monodisperse polymer microspheres, depositing a film of the slurry on a substrate, drying the film, and calcining the film to remove the polymer microspheres therefrom. The film may be cold-pressed after drying and prior to calcining. The ceramic dielectric or semiconductor material may be titania, and the polymer microspheres may be polystyrene microspheres.

Polyacrolein microspheres

NASA Technical Reports Server (NTRS)

Rembaum, Alan (Inventor)

1983-01-01

Microspheres of acrolein homopolymers and co-polymer with hydrophillic comonomers such as methacrylic acid and/or hydroxyethylmethacrylate are prepared by cobalt gamma irradiation of dilute aqueous solutions of the monomers in presence of suspending agents, especially alkyl sulfates such as sodium dodecyl sulfate. Amine or hydroxyl modification is achieved by forming adducts with diamines or alkanol amines. Carboxyl modification is effected by oxidation with peroxides. Pharmaceuticals or other aldehyde reactive materials can be coupled to the microspheres. The microspheres directly form antibody adducts without agglomeration.

Polyacrolein microspheres

NASA Technical Reports Server (NTRS)

Rembaum, Alan (Inventor)

1986-01-01

Microspheres of acrolein homopolymers and copolymer with hydrophillic comonomers such as methacrylic acid and/or hydroxyethylmethacrylate are prepared by cobalt gamma irradiation of dilute aqueous solutions of the monomers in presence of suspending agents, especially alkyl sulfates such as sodium dodecyl sulfate. Amine or hydroxyl modification is achieved by forming adducts with diamines or alkanol amines. Carboxyl modification is effected by oxidation with peroxides. Pharmaceuticals or other aldehyde reactive materials can be coupled to the microspheres. The microspheres directly form antibody adducts without agglomeration.

Polyacrolein microspheres

NASA Technical Reports Server (NTRS)

Rembaum, Alan (Inventor)

1987-01-01

Microspheres of acrolein homopolymers and copolymer with hydrophillic comonomers such as methacrylic acid and/or hydroxyethylmethacrylate are prepared by cobalt gamma irradiation of dilute aqueous solutions of the monomers in presence of suspending agents, especially alkyl sulfates such as sodium dodecyl sulfate. Amine or hydroxyl modification is achieved by forming adducts with diamines or alkanol amines. Carboxyl modification is effected by oxidation with peroxides. Pharmaceuticals or other aldehyde reactive materials can be coupled to the microspheres. The microspheres directly form antibody adducts without agglomeration.

Microsphere coated substrate containing reactive aldehyde groups

NASA Technical Reports Server (NTRS)

Yen, Richard C. K. (Inventor); Rembaum, Alan (Inventor)

1984-01-01

A synthetic organic resin is coated with a continuous layer of contiguous, tangential, individual microspheres having a uniform diameter preferably between 100 Angstroms and 2000 Angstroms. The microspheres are an addition polymerized polymer of an unsaturated aldehyde containing 4 to 20 carbon atoms and are covalently bonded to the substrate by means of high energy radiation grafting. The microspheres contain reactive aldehyde groups and can form conjugates with proteins such as enzymes or other aldehyde reactive materials.

Preclinical and clinical in vitro in vivo correlation of an hGH dextran microsphere formulation.

PubMed

Vlugt-Wensink, K D F; de Vrueh, R; Gresnigt, M G; Hoogerbrugge, C M; van Buul-Offers, S C; de Leede, L G J; Sterkman, L G W; Crommelin, D J A; Hennink, W E; Verrijk, R

2007-12-01

To investigate the in vitro in vivo correlation of a sustained release formulation for human growth hormone (hGH) based on hydroxyethyl methacrylated dextran (dex-HEMA) microspheres in Pit-1 deficient Snell dwarf mice and in healthy human volunteers. A hGH-loaded microsphere formulation was developed and tested in Snell dwarf mice (pharmacodynamic study) and in healthy human volunteers (pharmacokinetic study). Single subcutaneous administration of the microspheres in mice resulted in a good correlation between hGH released in vitro and in vivo effects for the hGH-loaded microsphere formulation similar to daily injected hGH indicating a retained bioactivity. Testing the microspheres in healthy volunteers showed an increase (over 7-8 days) in hGH serum concentrations (peak concentrations: 1-2.5 ng/ml). A good in vitro in vivo correlation was obtained between the measured and calculated (from in vitro release data) hGH serum concentrations. Moreover, an increased serum concentration of biomarkers (insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3) was found again indicating that bioactive hGH was released from the microspheres. Good in vitro in vivo correlations were obtained for hGH-loaded dex-HEMA microspheres, which is an important advantage in predicting the effect of the controlled drug delivery product in a clinical situations.

Preclinical and Clinical In Vitro In Vivo Correlation of an hGH Dextran Microsphere Formulation

PubMed Central

de Vrueh, R.; Gresnigt, M. G.; Hoogerbrugge, C. M.; van Buul-Offers, S. C.; de Leede, L. G. J.; Sterkman, L. G. W.; Crommelin, D. J. A.; Hennink, W. E.; Verrijk, R.

2007-01-01

Purpose To investigate the in vitro in vivo correlation of a sustained release formulation for human growth hormone (hGH) based on hydroxyethyl methacrylated dextran (dex-HEMA) microspheres in Pit-1 deficient Snell dwarf mice and in healthy human volunteers. Materials and Methods A hGH-loaded microsphere formulation was developed and tested in Snell dwarf mice (pharmacodynamic study) and in healthy human volunteers (pharmacokinetic study). Results Single subcutaneous administration of the microspheres in mice resulted in a good correlation between hGH released in vitro and in vivo effects for the hGH-loaded microsphere formulation similar to daily injected hGH indicating a retained bioactivity. Testing the microspheres in healthy volunteers showed an increase (over 7–8 days) in hGH serum concentrations (peak concentrations: 1–2.5 ng/ml). A good in vitro in vivo correlation was obtained between the measured and calculated (from in vitro release data) hGH serum concentrations. Moreover, an increased serum concentration of biomarkers (insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3) was found again indicating that bioactive hGH was released from the microspheres. Conclusions Good in vitro in vivo correlations were obtained for hGH-loaded dex-HEMA microspheres, which is an important advantage in predicting the effect of the controlled drug delivery product in a clinical situations. PMID:17929148

Novel control methods for insect pests: development of a microencapsulation procedure for proteinaceous bioactives intended for oral delivery.

PubMed

Richards, Elaine H; Wontner-Smith, Tim; Bradish, Hannah; Dani, M Paulina; Cotterill, Jane V

2015-09-01

The objective was to develop an environmentally favourable microcapsule suitable for delivery of proteinaceous bioactive agents ('bioinsecticides') to pest insects. Utilising feeding bioassays, we determined that microspheres made of alginate can be produced in a variety of sizes and are palatable and non-toxic to larvae of the lepidopteran pest Lacanobia oleracea. Dehydrated microspheres were also readily ingested by larvae. Using a novel feeding bioassay and alginate microspheres containing a fluorescent marker material (coumarin 7 encapsulated in styrene maleic anhydride beads), we determined that the microspheres successfully deliver the marker to the insect gut. Moreover, the alginate microspheres rapidly break down in the alkaline conditions of the insect gut and release their contents, the beads passing through the gut in 2-3 h. Using bovine serum albumin as a test protein and western blotting, it was determined that alginate can successfully encapsulate protein, and that the microspheres can be stored in a CaCl2 solution for up to 24 days without extensive leakage. Importantly, it was also determined that alginate and the microsphere-making procedure developed do not inactivate rVPr1 (an insect immunosuppressive protein and potential bioinsecticide). An alginate-based microsphere has potential to deliver the proteinaceous bioactive rVPr1 to pest insects. © 2014 Crown copyright. Pest Management Science © 2014 Society of Chemical Industry.

Highlighting the Importance of Surface Grafting in Combination with a Layer-by-Layer Approach for Fabricating Advanced 3D Poly(l-lactide) Microsphere Scaffolds

PubMed Central

2016-01-01

A combined surface treatment (i.e., surface grafting and a layer-by-layer (LbL) approach) is presented to create advanced biomaterials, i.e., 3D poly(l-lactide) (PLLA) microsphere scaffolds, at room temperature. The grafted surface plays a crucial role in assembling polyelectrolyte multilayers (PEMs) onto the surface of the microspheres, thus improving the physicochemical properties of the 3D microsphere scaffolds. The grafted surface of the PLLA microspheres demonstrates much better PEM adsorption, improved surface coverage at low pH, and smoother surfaces at high pH compared with those of nongrafted surfaces of PLLA microspheres during the assembly of PEMs. They induce more swelling than nongrafted surfaces after the assembly of the PEMs and exhibit blue emission after functionalization of the microsphere surface with a fluorescent dye molecule. The 3D scaffolds functionalized with and without nanosheets not only exhibit good mechanical performance similar to the compressive modulus of cancellous bone but also exhibit the porosity required for cancellous bone regeneration. The magnetic nanoparticle-functionalized 3D scaffolds result in an electrical conductivity in the high range of semiconducting materials (i.e., 1–250 S cm–1). Thus, these 3D microsphere scaffolds fabricated by surface grafting and the LbL approach are promising candidates for bone tissue engineering. PMID:29503506

Polymer blends used to develop felodipine-loaded hollow microspheres for improved oral bioavailability.

PubMed

Pi, Chao; Feng, Ting; Liang, Jing; Liu, Hao; Huang, Dongmei; Zhan, Chenglin; Yuan, Jiyuan; Lee, Robert J; Zhao, Ling; Wei, Yumeng

2018-06-01

Felodipine (FD) has been widely used in anti-hypertensive treatment. However, it has extremely low aqueous solubility and poor bioavailability. To address these problems, FD hollow microspheres as multiple-unit dosage forms were synthesized by a solvent diffusion evaporation method. Particle size of the hollow microspheres, types of ethylcellulose (EC), amounts of EC, polyvinyl pyrrolidone (PVP) and FD were investigated based on an orthogonal experiment of three factors and three levels. In addition, the release kinetics in vitro and pharmacokinetics in beagle dogs of the optimized FD hollow microspheres was investigated and compared with Plendil (commercial FD sustained-release tablets) as a single-unit dosage form. Results showed that the optimal formulation was composed of EC 10 cp :PVP:FD (0.9:0.16:0.36, w/w). The FD hollow microspheres were globular with a hollow structure and have high drug loading (17.69±0.44%) and floating rate (93.82±4.05%) in simulated human gastric fluid after 24h. Pharmacokinetic data showed that FD hollow microspheres exhibited sustained-release behavior and significantly improved relative bioavailability of FD compared with the control. Pharmacodynamic study showed that the FD hollow microspheres could effectively lower blood pressure. Therefore, these findings demonstrated that the hollow microspheres were an effective sustained-release delivery system for FD. Copyright © 2018 Elsevier B.V. All rights reserved.

High-Q Microsphere Cavity for Laser Stabilization and Optoelectronic Microwave Oscillator

NASA Technical Reports Server (NTRS)

Ilchenko, Vladimir S.; Yao, X. Steve; Maleki, Lute

2000-01-01

With submillimeter size and optical Q up to approximately 10 (exp 10), microspheres with whispering-gallery (WG) modes are attractive new component for fiber-optics/photonics applications and a potential core in ultra-compact high-spectral-purity optical and microwave oscillators. In addition to earlier demonstrated optical locking of diode laser to WG mode in a microsphere, we report on microsphere application in the microwave optoelectronic oscillator, OEO. In OEO, a steady-state microwave modulation of optical carrier is obtained in a closed loop including electro-optical modulator, fiber-optic delay, detector and microwave amplifier. OEO demonstrates exceptionally low phase noise (-140 dBc/Hz at l0kHz from approximately 10GHz carrier) with a fiber length approximately 2km. Current technology allows to put all parts of the OEO, except the fiber, on the same chip. Microspheres, with their demonstrated Q equivalent to a kilometer fiber storage, can replace fiber delays in a truly integrated device. We have obtained microwave oscillation in microsphere-based OEO at 5 to 18 GHz, with 1310nm and 1550nm optical carrier, in two configurations: 1) with external DFB pump laser, and 2) with a ring laser including microsphere and a fiber optic amplifier. Also reported is a simple and efficient fiber coupler for microspheres facilitating their integration with existing fiber optics devices.

A novel sustained-release formulation of recombinant human growth hormone and its pharmacokinetic, pharmacodynamic and safety profiles.

PubMed

Wei, Yi; Wang, Yuxia; Kang, Aijun; Wang, Wei; Ho, Sa V; Gao, Junfeng; Ma, Guanghui; Su, Zhiguo

2012-07-02

An effective and safe formulation of sustained-release rhGH for two months using poly(monomethoxypolyethylene glycol-co-D,L-lactide) (mPEG-PLA, PELA) microspheres was developed to reduce the frequency of medication. The rhGH-loaded PELA microspheres with a narrow size distribution were successfully prepared by a double emulsion method combined with a premix membrane emulsification technique without any exogenous stabilizing excipients. The narrow size distribution of the microspheres would guarantee repeatable productivity and release behavior. Moreover, the amphiphilic PELA improved the bioactivity retention of protein drugs since it prevented protein contact with the oil/water interface and the hydrophobic network, and modulated diffusion of acidic degradation products from the carrier system. These PELA microspheres were compared in vivo with commercial rhGH solution, conventional poly(D,L-lactic acid) (PLA) and poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres. Administration of rhGH-PELA could extend the duration of rhGH release (for up to 56 days) and increase area under the curve (AUC) compared to rhGH solution, PLA or PLGA microspheres in Sprague-Dawley (SD) rats. In addition, rhGH-PELA microspheres induced a greater response in total insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) than other rhGH formulations. With a hypophysectomized SD rat model, the pharmacological efficacy of rhGH-PELA microspheres was shown to be better than that from daily administration of rhGH solutions over 6 days based on body weight gain and width of the tibial growth plate. Histological examination of the injection sites indicated a significantly milder inflammatory response than that observed after injection of PLA and PLGA microspheres. Neither anti-rhGH antibodies nor the toxic effects on heart, liver and kidney were detectable after administration of rhGH-PELA microspheres in SD rats. These results suggest that rhGH-PELA microspheres have the potential to be clinically effective and safe when administered only once every two months, a dose regimen for better patient acceptance and compliance.

Biocompatibility, Inflammatory Response, and Recannalization Characteristics of Nonradioactive Resin Microspheres: Histological Findings

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

Bilbao, Jose I., E-mail: Jibilbao@unav.e; Martino, Alba de; Luis, Esther de

2009-07-15

Intra-arterial radiotherapy with yttrium-90 microspheres (radioembolization) is a therapeutic procedure exclusively applied to the liver that allows the direct delivery of high-dose radiation to liver tumors, by means of endovascular catheters, selectively placed within the tumor vasculature. The aim of the study was to describe the distribution of spheres within the precapillaries, inflammatory response, and recannalization characteristics after embolization with nonradioactive resin microspheres in the kidney and liver. We performed a partial embolization of the liver and kidney vessels in nine white pigs. The left renal and left hepatic arteries were catheterized and filled with nonradioactive resin microspheres. Embolization wasmore » defined as the initiation of near-stasis of blood flow, rather than total occlusion of the vessels. The hepatic circulation was not isolated so that the effects of reflux of microspheres into stomach could be observed. Animals were sacrificed at 48 h, 4 weeks, and 8 weeks, and tissue samples from the kidney, liver, lung, and stomach evaluated. Microscopic evaluation revealed clusters of 10-30 microspheres (15-30 {mu}m in diameter) in the small vessels of the kidney (the arciform arteries, vasa recti, and glomerular afferent vessels) and liver. Aggregates were associated with focal ischemia and mild vascular wall damage. Occlusion of the small vessels was associated with a mild perivascular inflammatory reaction. After filling of the left hepatic artery with microspheres, there was some evidence of arteriovenous shunting into the lungs, and one case of cholecystitis and one case of marked gastritis and ulceration at the site of arterial occlusion due to the presence of clusters of microspheres. Beyond 48 h, microspheres were progressively integrated into the vascular wall by phagocytosis and the lumen recannalized. Eight-week evaluation found that the perivascular inflammatory reaction was mild. Liver cell damage, bile duct injury, and portal space fibrosis were not observed. In conclusion, resin microspheres (15-30 {mu}m diameter) trigger virtually no inflammatory response in target tissues (liver and kidney). Clusters rather than individual microspheres were associated with a mild to moderate perivascular inflammatory reaction. There was no evidence of either a prolonged inflammatory reaction or fibrosis in the liver parenchyma following recannalization.« less

384 hanging drop arrays give excellent Z-factors and allow versatile formation of co-culture spheroids.

PubMed

Hsiao, Amy Y; Tung, Yi-Chung; Qu, Xianggui; Patel, Lalit R; Pienta, Kenneth J; Takayama, Shuichi

2012-05-01

We previously reported the development of a simple, user-friendly, and versatile 384 hanging drop array plate for 3D spheroid culture and the importance of utilizing 3D cellular models in anti-cancer drug sensitivity testing. The 384 hanging drop array plate allows for high-throughput capabilities and offers significant improvements over existing 3D spheroid culture methods. To allow for practical 3D cell-based high-throughput screening and enable broader use of the plate, we characterize the robustness of the 384 hanging drop array plate in terms of assay performance and demonstrate the versatility of the plate. We find that the 384 hanging drop array plate performance is robust in fluorescence- and colorimetric-based assays through Z-factor calculations. Finally, we demonstrate different plate capabilities and applications, including: spheroid transfer and retrieval for Janus spheroid formation, sequential addition of cells for concentric layer patterning of different cell types, and culture of a wide variety of cell types. Copyright © 2011 Wiley Periodicals, Inc.

384 Hanging Drop Arrays Give Excellent Z-factors and Allow Versatile Formation of Co-culture Spheroids

PubMed Central

Hsiao, Amy Y.; Tung, Yi-Chung; Qu, Xianggui; Patel, Lalit R.; Pienta, Kenneth J.; Takayama, Shuichi

2012-01-01

We previously reported the development of a simple, user-friendly, and versatile 384 hanging drop array plate for 3D spheroid culture and the importance of utilizing 3D cellular models in anti-cancer drug sensitivity testing. The 384 hanging drop array plate allows for high-throughput capabilities and offers significant improvements over existing 3D spheroid culture methods. To allow for practical 3D cell-based high-throughput screening and enable broader use of the plate, we characterize the robustness of the 384 hanging drop array plate in terms of assay performance and demonstrate the versatility of the plate. We find that the 384 hanging drop array plate performance is robust in fluorescence- and colorimetric-based assays through z-factor calculations. Finally, we demonstrate different plate capabilities and applications, including: spheroid transfer and retrieval for Janus spheroid formation, sequential addition of cells for concentric layer patterning of different cell types, and culture of a wide variety of cell types. PMID:22161651

Making Polymeric Microspheres

NASA Technical Reports Server (NTRS)

Rhim, Won-Kyu; Hyson, Michael T.; Chung, Sang-Kun; Colvin, Michael S.; Chang, Manchium

1989-01-01

Combination of advanced techniques yields uniform particles for biomedical applications. Process combines ink-jet and irradiation/freeze-polymerization techniques to make polymeric microspheres of uniform size in diameters from 100 to 400 micrometer. Microspheres used in chromatography, cell sorting, cell labeling, and manufacture of pharmaceutical materials.

Apparatus for washing particulate material. [Removal of silicone oil from microspheres by trichloroethylene

DOEpatents

Rivera, A.L.; Fowler, V.L.; Justice, G.V.

1983-12-29

Transport of nuclear fuel microspheres through a wash liquid is facilitated by feeding a slurry containing the microspheres into the wash liquid via a column having a vibrating tubular screen located under its lower end.

Development and in-use evaluation of a novel Luminex MicroPlex microsphere-based (TRIOL) assay for simultaneous identification of Mycobacterium tuberculosis and detection of first-line and second-line anti-tuberculous drug resistance in China.

PubMed

Yin, Feifei; Chan, Jasper Fuk-Woo; Zhu, Qixuan; Fu, Ruijia; Chen, Jonathan Hon-Kwan; Choi, Garnet Kwan-Yue; Tee, Kah-Meng; Li, Lihua; Qian, Shiuyun; Yam, Wing-Cheong; Lu, Gang; Yuen, Kwok-Yung

2017-04-01

Rapid and accurate diagnostic assays with simultaneous microbial identification and drug resistance detection are essential for optimising treatment and control of tuberculosis. We developed a novel multiplex (TRIOL, Tuberculosis-Rifampicin-Isoniazid-Ofloxacin-Luminex) assay using the Luminex xMAP system that simultaneously identifies Mycobacterium tuberculosis and detects resistance to first-line and second-line anti-tuberculous drugs, and compared its performance with that by PCR sequencing, using phenotypic drug susceptibility testing as the gold standard. Identification of M. tuberculosis by the TRIOL assay was highly sensitive (100%) and specific (100%). The overall drug-specific specificities were excellent (100%). The overall sensitivity of the TRIOL assay was lower than that of the PCR-sequencing assays (72.4% vs 82.8%) because of a lower sensitivity of detecting rifampicin resistance (71.4% vs 92.9%). The sensitivity of detecting isoniazid and ofloxacin resistance was as good as the PCR-sequencing assays. Importantly, the TRIOL assay did not miss any mutations that were included in the assay. All of the resistant isolates that were missed had uncommon mutations or unknown resistance mechanisms that were not included in the assay. The TRIOL assay has higher throughput, lower cost and is less labour intensive than the PCR-sequencing assays. The TRIOL assay is advantageous in having the capability to detect resistance to multiple drugs and an open-architecture system that allows addition of more specific primers to detect uncommon mutations. Inclusion of additional primers for the identification of non-tuberculous mycobacteria, spoligotyping and improvement of rifampicin resistance detection would enhance the use of the TRIOL assay in future clinical and epidemiological studies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Comparison of FilmArray and Quantitative Real-Time Reverse Transcriptase PCR for Detection of Zaire Ebolavirus from Contrived and Clinical Specimens

PubMed Central

Southern, Timothy R.; Racsa, Lori D.; Albariño, César G.; Fey, Paul D.; Hinrichs, Steven H.; Murphy, Caitlin N.; Herrera, Vicki L.; Sambol, Anthony R.; Hill, Charles E.; Ryan, Emily L.; Kraft, Colleen S.; Campbell, Shelley; Sealy, Tara K.; Schuh, Amy; Ritchie, James C.; Lyon, G. Marshall; Mehta, Aneesh K.; Varkey, Jay B.; Ribner, Bruce S.; Brantly, Kent P.; Ströher, Ute; Iwen, Peter C.

2015-01-01

Rapid, reliable, and easy-to-use diagnostic assays for detection of Zaire ebolavirus (ZEBOV) are urgently needed. The goal of this study was to examine the agreement among emergency use authorization (EUA) tests for the detection of ZEBOV nucleic acids, including the BioFire FilmArray BioThreat (BT) panel, the FilmArray BT-E panel, and the NP2 and VP40 quantitative real-time reverse transcriptase (qRT) PCR assays from the Centers for Disease Control and Prevention (CDC). Specimens used in this study included whole blood spiked with inactivated ZEBOV at known titers and whole-blood, plasma, and urine clinical specimens collected from persons diagnosed with Ebola virus disease (EVD). The agreement for FilmArray and qRT-PCR results using contrived whole-blood specimens was 100% (6/6 specimens) for each ZEBOV dilution from 4 × 107 to 4 × 102 50% tissue culture infective dose (TCID50)/ml, as well as the no-virus negative-control sample. The limit of detection for FilmArray and qRT-PCR assays with inactivated ZEBOV, based on duplicate positive results, was determined to be 4 × 102 TCID50/ml. Rates of agreement between FilmArray and qRT-PCR results for clinical specimens from patients with EVD were 85% (23/27 specimens) for whole-blood specimens, 90% (18/20 specimens) for whole-blood specimens tested by FilmArray testing and matched plasma specimens tested by qRT-PCR testing, and 85% (11/13 specimens) for urine specimens. Among 60 specimens, eight discordant results were noted, with ZEBOV nucleic acids being detected only by FilmArray testing in four specimens and only by qRT-PCR testing in the remaining four specimens. These findings demonstrate that the rapid and easy-to-use FilmArray panels are effective tests for evaluating patients with EVD. PMID:26157148

A 5-fluorouracil-loaded floating gastroretentive hollow microsphere: development, pharmacokinetic in rabbits, and biodistribution in tumor-bearing mice

PubMed Central

Huang, Yu; Wei, Yumeng; Yang, Hongru; Pi, Chao; Liu, Hao; Ye, Yun; Zhao, Ling

2016-01-01

5-Fluorouracil (5-FU) was loaded in hollow microspheres to improve its oral bioavailability. 5-FU hollow microspheres were developed by a solvent diffusion–evaporation method. The effect of Span 80 concentration, ether/ethanol volume ratio, and polyvinyl pyrrolidone/ethyl cellulose weight ratio on physicochemical characteristics, floating, and in vitro release behaviors of 5-FU hollow microspheres was investigated and optimized. The formulation and technology composed of Span 80 (1.5%, w/v), ether/ethanol (1.0:10.0, v/v), and polyvinyl pyrrolidone/ethyl cellulose (1.0:10.0, w/w) were employed to develop three batch samples, which showed an excellent reproducibility. The microspheres were spherical with a hollow structure with high drug loading amount (28.4%±0.5%) and production yield (74.2%±0.6%); they exhibited excellent floating and sustained release characteristics in simulated gastric and intestinal fluid. Pharmacokinetic studies demonstrated that 5-FU hollow microspheres significantly enhanced oral bioavailability (area under curve, [AUC](0−t): 12.53±1.65 mg/L*h vs 7.80±0.83 and 5.82±0.83 mg/L*h) with longer elimination half-life (t1/2) (15.43±2.12 hours vs 2.25±0.22 and 1.43±0.18 hours) and mean residence time (7.65±0.97 hours vs 3.61±0.41 and 2.34±0.35 hours), in comparison with its solid microspheres and powder. In vivo distribution results from tumor-bearing nude mice demonstrated that the animals administered with 5-FU hollow microspheres had much higher drug content in tumor, plasma, and stomach at 1 and 8 hours except for 0.5 hours sample collection time point in comparison with those administered with 5-FU solid microspheres and its powder. These results suggested that the hollow microspheres would be a promising controlled drug delivery system for an oral chemotherapy agent like 5-FU. PMID:27042001

A 5-fluorouracil-loaded floating gastroretentive hollow microsphere: development, pharmacokinetic in rabbits, and biodistribution in tumor-bearing mice.

PubMed

Huang, Yu; Wei, Yumeng; Yang, Hongru; Pi, Chao; Liu, Hao; Ye, Yun; Zhao, Ling

2016-01-01

5-Fluorouracil (5-FU) was loaded in hollow microspheres to improve its oral bioavailability. 5-FU hollow microspheres were developed by a solvent diffusion-evaporation method. The effect of Span 80 concentration, ether/ethanol volume ratio, and polyvinyl pyrrolidone/ethyl cellulose weight ratio on physicochemical characteristics, floating, and in vitro release behaviors of 5-FU hollow microspheres was investigated and optimized. The formulation and technology composed of Span 80 (1.5%, w/v), ether/ethanol (1.0:10.0, v/v), and polyvinyl pyrrolidone/ethyl cellulose (1.0:10.0, w/w) were employed to develop three batch samples, which showed an excellent reproducibility. The microspheres were spherical with a hollow structure with high drug loading amount (28.4%±0.5%) and production yield (74.2%±0.6%); they exhibited excellent floating and sustained release characteristics in simulated gastric and intestinal fluid. Pharmacokinetic studies demonstrated that 5-FU hollow microspheres significantly enhanced oral bioavailability (area under curve, [AUC](0-t): 12.53±1.65 mg/L(*)h vs 7.80±0.83 and 5.82±0.83 mg/L(*)h) with longer elimination half-life (t1/2) (15.43±2.12 hours vs 2.25±0.22 and 1.43±0.18 hours) and mean residence time (7.65±0.97 hours vs 3.61±0.41 and 2.34±0.35 hours), in comparison with its solid microspheres and powder. In vivo distribution results from tumor-bearing nude mice demonstrated that the animals administered with 5-FU hollow microspheres had much higher drug content in tumor, plasma, and stomach at 1 and 8 hours except for 0.5 hours sample collection time point in comparison with those administered with 5-FU solid microspheres and its powder. These results suggested that the hollow microspheres would be a promising controlled drug delivery system for an oral chemotherapy agent like 5-FU.

Prolonged cytotoxic effect of colchicine released from biodegradable microspheres.

PubMed

Muvaffak, Asli; Gurhan, Ismet; Hasirci, Nesrin

2004-11-15

One the main problems of cancer chemotherapy is the unwanted damage to normal cells caused by the high toxicities of anticancer drugs. Any system of controlled drug delivery that would reduce the total amount of drug required, and thus reduce the side effects, would potentially help to improve chemotherapy. In this respect, biodegradable gelatin microspheres were prepared by water/oil emulsion polymerization and by crosslinking with glutaraldehyde (GTA) as the drug-carrier system. Microspheres were loaded with colchicine, a model antimitotic drug, which was frequently used as an antimitotic agent in cancer research involving cell cultures. Microsphere sizes, swelling and degradation properties, drug-release kinetics, and cytotoxities were studied. Swelling characteristics of microspheres changed upon changing GTA concentration. A decrease in swelling values was recorded as GTA crosslink density was increased. In vitro drug release in PBS (0.01M, pH 7.4) showed rapid colchicine release up to approximately 83% (at t = 92 h) for microspheres with low GTA (0.05% v/v), whereas a slower release profile (only approximately 39%) was obtained for microspheres with high GTA (0.50% v/v) content, for the same period. Cytotoxicity tests with MCF-7, HeLa and H-82 cancer cell lines showed that free colchicine was very toxic, showing an approximately 100% lethal effect in both HeLa and H-82 cell lines and more than 50% decrease in viability in MCF-7 cells in 4 days. Indeed, entrapped colchicine indicated similar initial high toxic effect on cell viability in MCF-7 cell line and this effect became more dominant as colchicine continued to be released from microspheres in the same period. In conclusion, the control of the release rate of colchicine from gelatin microspheres was achieved under in vitro conditions by gelatin through the alteration of crosslinking conditions. Indeed, the results suggested the potential application of gelatin microspheres crosslinked with GTA as a sustained drug-delivery system for anticancer drugs for local chemotherapy administrations. (c) 2004 Wiley Periodicals, Inc.

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

Yao, Aihua, E-mail: aihyao@126.com; Ai, Fanrong; Liu, Xin

Hollow hydroxyapatite microspheres, consisting of a hollow core and a porous shell, were prepared by converting Li{sub 2}O-CaO-B{sub 2}O{sub 3} glass microspheres in dilute phosphate solution at 37 {sup o}C. The results confirmed that Li{sub 2}O-CaO-B{sub 2}O{sub 3} glass was transformed to hydroxyapatite without changing the external shape and dimension of the original glass object. Scanning electron microscopy images showed the shell wall of the microsphere was built from hydroxyapatite particles, and these particles spontaneously align with one another to form a porous sphere with an interior cavity. Increase in phosphate concentration resulted in an increase in the reaction rate,more » which in turn had an effect on shell wall structure of the hollow hydroxyapatite microsphere. For the Li{sub 2}O-CaO-B{sub 2}O{sub 3} glass microspheres reacted in low-concentration K{sub 2}HPO{sub 4} solution, lower reaction rate and a multilayered microstructure were observed. On the other hand, the glass microspheres reacted in higher phosphate solution converted more rapidly and produced a single hydroxyapatite layer. Furthermore, the mechanism of forming hydroxyapatite hollow microsphere was described.« less

[Preparation of large-pore silica microspheres using templating method and their applications to protein separation with high performance liquid chromatography].

PubMed

Niu, Mengna; Ma, Hongyan; Hu, Fei; Wang, Shige; Liu, Lu; Chang, Haizhou; Huang, Mingxian

2017-06-08

Large-pore silica microspheres were synthesized by utilizing weak cation exchange polymer beads as templates, N -trimethoxysilylpropyl- N,N,N -trimethylammonium chloride (TMSPTMA) as a structure-directing agent, tetraethoxysilane (TEOS) as a silica precursor, and triethanolamine as a weak base catalyst. The hydrolysis and condensation of the silica precursors occurred inside the templating polymer beads yielded polymer/silica composite microspheres. After the organic polymer templates were removed in the calcination step, large-pore silica microspheres were produced. The effects of different reaction conditions on the morphology, structure and dispersibility of the formed silica microspheres were investigated. It has been shown that when the volume ratio of TMSPTMA, TEOS and triethanolamine was 1:2:2, silica microspheres with pore size range of 50-150 nm and particle size around 2 μm were obtained. The as-prepared silica microspheres were then bonded with chlorodimethyloctadecylsilane (C18), packed into a 50 mm×4.6 mm column, and evaluated for the separations of some common standard proteins and soybean isolation proteins. The results showed that the large-pore silica spheres from this work have potentials for protein separation in HPLC.

Demonstration of Microsphere Insulation in Cryogenic Vessels

NASA Astrophysics Data System (ADS)

Baumgartner, R. G.; Myers, E. A.; Fesmire, J. E.; Morris, D. L.; Sokalski, E. R.

2006-04-01

While microspheres have been recognized as a legitimate insulation material for decades, actual use in full-scale cryogenic storage tanks has not been demonstrated until now. The performance and life-cycle-cost advantages previously predicted have now been proven. Most bulk cryogenic storage tanks are insulated with either multilayer insulation (MLI) or perlite. Microsphere insulation, consisting of hollow glass bubbles, combines in a single material the desirable properties that other insulations only have individually. The material has high crush strength, low density, is noncombustible, and performs well in soft vacuum. These properties were proven during recent field testing of two 22,700-L (6,000-gallon) liquid nitrogen tanks, one insulated with microsphere insulation and the other with perlite. Normal evaporation rates (NER) for both tanks were monitored with precision test equipment and insulation levels within the tanks were observed through view ports as an indication of insulation compaction. Specific industrial applications were evaluated based on the test results and beneficial properties of microsphere insulation. Over-the-road trailers previously insulated with perlite will benefit not only from the reduced heat leak, but also the reduced mass of microsphere insulation. Economic assessments for microsphere-insulated cryogenic vessels including life-cycle cost are also presented.

A new rat model of portal hypertension induced by intraportal injection of microspheres

PubMed Central

Li, Xiang-Nong; Benjamin, IS; Alexander, B

1998-01-01

AIM: To produce a new rat model of portal hypertension by intraportal injection of microspheres. METHODS: Measured aliquots of single or different-sized microspheres (15, 40, 80μm) were injected into the portal vein to block intrahepatic portal radicals. The resultant changes in arterial,portal,hepatic venous and splenic pulp pressures were monitored. The liver and lungs were excised for histological examination. RESULTS: Portal venous pressure was elevated from basal value of 0.89-1.02 kPa to a steady-state of 1.98-3.19 kPa following the sequential injections of single- or different-sized microspheres, with a markedly lowered mean arterial pressure. However, a small-dose injection of 80 μm microspheres (1.8 × 105) produced a steady-state portal venous pressure of 2.53 × 0.17 kPa, and all rats showed normal arterial pressures. In addition, numerous microspheres were found in the lungs in all experimental groups. CONCLUSION: Portal hypertension can be reproduced in rats by intraportal injection of microspheres at a small dose of 80 μm (1.8 × 105). Intrahepatic portal-systemic shunts probably exist in the normal rat liver. PMID:11819236

In vitro and in vivo dissolution behavior of a dysprosium lithium borate glass designed for the radiation synovectomy treatment of rheumatoid arthritis.

PubMed

Conzone, Samuel D; Brown, Roger F; Day, Delbert E; Ehrhardt, Gary J

2002-05-01

Dysprosium lithium borate (DyLB) glass microspheres were investigated for use in the radiation synovectomy treatment of rheumatoid arthritis. In vitro testing focused on weight loss and cation dissolution from glass microspheres immersed in simulated synovial fluid (SSF) at 37 degrees C for up to 64 days. In vivo testing was performed by injecting glass microspheres into the stifle joints of Sprague-Dawley rats and monitoring the biodegradability of the microspheres and the tissue response within the joints. The DyLB microspheres reacted nonuniformly in SSF with the majority of lithium and boron being dissolved, whereas nearly all of the dysprosium (>99.7%) remained in the reacted microspheres. Because the DyLB glasses released negligible amounts of dysprosium while reacting with SSF, they are considered safe for radiation synovectomy from the standpoint of unwanted radiation release from the joint capsule. Furthermore, the DyLB microspheres fragmented, degraded, and reacted with body fluids while in the joints of rats without histologic evidence of joint damage. Copyright 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 260--268, 2002; DOI 10.1002/jbm.10047

Coating gigaporous polystyrene microspheres with cross-linked poly(vinyl alcohol) hydrogel as a rapid protein chromatography matrix.

PubMed

Qu, Jian-Bo; Huan, Guan-Sheng; Chen, Yan-Li; Zhou, Wei-Qing; Liu, Jian-Guo; Huang, Fang

2014-08-13

Gigaporous polystyrene (PS) microspheres were hydrophilized by in situ polymerization to give a stable cross-linked poly(vinyl alcohol) (PVA) hydrogel coating, which can shield proteins from the hydrophobic PS surface underneath. The amination of microspheres (PS-NH2) was first carried out through acetylization, oximation and reduction, and then 4,4'-azobis (4-cyanovaleric acid) (ACV), a polymerization initiator, was covalently immobilized on PS-NH2 through amide bond formation, and the cross-linked poly(vinyl acetate) (PVAc) was prepared by radical polymerization at the surfaces of ACV-immobilized PS microspheres (PS-ACV). Finally, the cross-linked PVA hydrogel coated gigaporous PS microspheres (PS-PVA) was easily achieved through alcoholysis of PVAc. Results suggested that the PS microspheres were effectively coated with cross-linked PVA hydrogel, where the gigaporrous structure remained under optimal conditions. After hydrophilic modification (PS-PVA), the protein-resistant ability of microspheres was greatly improved. The hydroxyl-rich PS-PVA surface can be easily derivatized by classical chemical methods. Performance advantages of the PS-PVA column in flow experiment include good permeability, low backpressure, and mechanical stability. These results indicated that PS-PVA should be promising in rapid protein chromatography.

Novel polystyrene microspheres functionalized by imidazolium and the electrocatalytic activity towards H2O2 of its Prussian blue composite

NASA Astrophysics Data System (ADS)

Mao, Hui; Song, Jinling; Zhang, Qian; Liu, Daliang; Gong, Naiqi; Li, Ying; Wu, Qiong; Verpoort, Francis; Song, Xi-Ming

2013-05-01

Copolymerization of styrene (St) and 1-vinyl-3-ethylimidazolium bromide (VEIB), novel poly(St-co-VEIB) microspheres were generated. Owing to the presence of imidazolium groups, such microspheres having an average diameter of 125 nm, behave electropositively when dispersed in aqueous solution. Furthermore, due to the presence of imidazolium groups, having a capacity of ion-exchange and weak reducibility on the surface of the PS microspheres, [Fe(CN)6]3- was absorbed on the surface of poly(St-co-VEIB) microspheres, and simultaneously, Fe3+ was reduced to Fe2+. Thus, in situ growth of Prussian blue (PB) nanoparticles could occur on the surface of poly(St-co-VEIB) microspheres without the addition of any other reducing agent. This methodology, utilizing the ion-exchange and weak reducibility properties of the imidazolium groups on the surface of micro-/nanostructures is a novel general method for assembling hierarchical nanostructured materials. Finally, the electrochemical property of the strawberry-like PS/PB composite microspheres was also investigated by applying a glassy carbon electrode. A good repeatability of the cyclic voltammetry responses, having a good linearity and sensitivity, for the electrocatalytic reduction of H2O2 was obtained.

Improvement for identification of heterophile antibody interference and AFP hook effect in immunoassays with multiplex suspension bead array system.

PubMed

Wang, Yajie; Yu, Jinsheng; Ren, Yuan; Liu, Li; Li, Haowen; Guo, Anchen; Shi, Congning; Fang, Fang; Juehne, Twyla; Yao, Jianer; Yang, Enhuan; Zhou, Xuelei; Kang, Xixiong

2013-11-15

A variety of immunoassays including multiplex suspension bead array have been developed for tumor marker detections; however, these assays could be compromised in their sensitivity and specificity by well-known heterophile antibody interference and hook effect. Using Luminex® multiplex suspension bead arrays, we modified protocols with two newly-developed solutions that can identify heterophile antibody interference and AFP hook effect. Effectiveness of the two solutions was assessed in serum samples from patients. Concentrations of 9 tumor markers in heterophile antibody positive samples assayed with Solution A, containing murine monoclonal antibodies and mouse serum, were significantly reduced when compared with those false high signals assayed without Solution A (all p<0.01). With incorporation of Solution H (fluorescent beads linked with AFP antigen), a new strategy for identification of AFP hook effect was established, and with this strategy AFP hook effect was identified effectively in serum samples with very high levels of AFP. Two proprietary solutions improve the identification of heterophile antibody interference and AFP hook effect. With these solutions, multiplex suspension bead arrays provide more reliable testing results in tumor marker detection where complex clinical serum samples are used. © 2013.

Beat frequency ultrasonic microsphere contrast agent detection system

NASA Technical Reports Server (NTRS)

Pretlow, Robert A., III (Inventor); Yost, William T. (Inventor); Cantrell, John H., Jr. (Inventor)

1995-01-01

A system for and method of detecting and measuring concentrations of an ultrasonically-reflective microsphere contrast agent involving detecting non-linear sum and difference beat frequencies produced by the microspheres when two impinging signals with non-identical frequencies are combined by mixing. These beat frequencies can be used for a variety of applications such as detecting the presence of and measuring the flow rates of biological fluids and industrial liquids, including determining the concentration level of microspheres in the myocardium.

Beat frequency ultrasonic microsphere contrast agent detection system

NASA Technical Reports Server (NTRS)

Pretlow, III, Robert A. (Inventor); Yost, William T. (Inventor); Cantrell, Jr., John H. (Inventor)

1997-01-01

A system for and method of detecting and measuring concentrations of an ultrasonically-reflective microsphere contrast agent involving detecting non-linear sum and difference beat frequencies produced by the microspheres when two impinging signals with non-identical frequencies are combined by mixing. These beat frequencies can be used for a variety of applications such as detecting the presence of and measuring the flow rates of biological fluids and industrial liquids, including determining the concentration level of microspheres in the myocardium.

Development of a fluorescent immnunochromatographic assay for the procalcitonin detection of clinical patients in China.

PubMed

Wang, Haiying; Wang, Hong; Chen, Shaopei; Dzakah, Emmanuel E; Kang, Keren; Wang, Jihua; Wang, Jufang

2015-04-15

Procalcitonin (PCT) has been recognized as a biomarker in severe inflammation, infection and sepsis. PCT detection in serum requires sensitive and specific antibodies. In this study, we generated monoclonal antibodies (mAbs) and developed fluorescent immunochromatographic assay for PCT detection. Human recombinant PCT was used as immunogen. mAbs against PCT were developed and applied to fluorescent immunochromatographic assay for PCT detection in clinical samples. Out of 35 hybridoma cell lines secreting antibodies against the recombinant PCT, five sensitive and specific cell lines were selected and designated as F6, G2, C2, D2 and E5. All these antibodies have no cross reaction with calcitonin or calcitonin gene-related peptides (CGRP). After screening for pairing, mAb F6 was labeled with fluorescent microspheres and C2 was coated on a nitrocellulose membrane for immunochromatographic test. All 35 clinical samples were detected by the mAb F6-C2 test strips and the bioMérieux PCT assay. The test strips showed high specificity and sensitivity for PCT. Good correlation was observed between our immunochromatographic test strips and the bioMérieux PCT assay (R(2):0.986). These newly developed anti-PCT mAbs and fluorescent immunochromatographic assay can serve as important diagnostic tools for a fast, reliable and point-of-care testing for easy determination of PCT in serum and diagnosis of bacterial infection, inflammation or sepsis. Copyright © 2015 Elsevier B.V. All rights reserved.

Production of monodisperse cerium oxide microspheres with diameters near 100 μm by internal-gelation sol–gel methods

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

Katalenich, Jeffrey A.; Kitchen, Brian B.; Pierson, Bruce D.

Internal gelation sol-gel methods have used a variety of sphere forming methods in the past to produce metal oxide microspheres, but typically with poor control over the size uniformity at diameters near 100 µm. This work describes efforts to make and measure internal gelation, sol-gel microspheres with very uniform diameters in the 100 – 200 µm size range using a two-fluid nozzle. A custom apparatus was used to form aqueous droplets of sol-gel feed solutions in silicone oil and heat them to cause gelation of the spheres. Gelled spheres were washed, dried, and sintered prior to mounting on glass slidesmore » for optical imaging and analysis. Microsphere diameters and shape factors were determined as a function of silicone oil flow rate in a two-fluid nozzle and the size of a needle dispensing the aqueous sol-gel solution. Nine batches of microspheres were analyzed and had diameters ranging from 65.5 ± 2.4 µm for the smallest needle and fastest silicone oil flow rate to 211 ± 4.7 µm for the largest needle and slowest silicone oil flow rate. Standard deviations for measured diameters were less than 8% for all samples and most were less than 4%. Microspheres had excellent circularity with measured shape factors of 0.9 – 1. However, processing of optical images was complicated by shadow effects in the photoresist layer on glass slides and by overlapping microspheres. Based on calculated flow parameters, microspheres were produced in a simple dripping mode in the two-fluid nozzle. Using flow rates consistent with a simple dripping mode in a two-fluid nozzle configuration allows for very uniform oxide microspheres to be produced using the internal-gelation sol-gel method.« less

Analytical advantages of copolymeric microspheres for fluorimetric sensing - tuneable sensitivity sensors and titration agents.

PubMed

Stelmach, Emilia; Maksymiuk, Krzysztof; Michalska, Agata

2017-01-15

Analytical benefits related to application of copolymeric microspheres containing different number of carboxylic acid mers have been studied on example of acrylate copolymers. These structures can be used as a reagent in heterogeneous pH titration, benefiting from different number of reactive groups - i.e. different concentration of a titrant - within the series of copolymers. Thus introducing the same amount of different microspheres from a series to the sample, different amount of the titrant is introduced. Copolymeric microspheres also can be used as optical sensors - in this respect the increasing number of reactive groups in the series is useful to improve the analytical performance of microprobes - sensitivity of determination or/and response range. The increase in ion-permeability of the spheres with increasing number of reactive mers is advantageous. It is shown that for pH sensitive microspheres containing higher number of carboxyl groups the higher sensitivity for alkaline pH samples is observed for an indicator present in the beads. The significant increase of optical responses is related to enhanced ion transport within the microspheres. For zinc or potassium ions model sensors tested it was shown that by choice of pH conditions and type of microspheres from the series, the optical responses can be tuned - to enhance sensitivity for analyte concentration change as well as to change the response pattern from sigmoidal (higher sensitivity, narrow range) to linear (broader response range). For classical optode systems (e.g. microspheres containing an optical transducer - pH sensitive dye and optically silent ionophore - receptor) copolymeric microspheres containing carboxylic acid mers in their structure allow application of the sensor in alkaline pH range, which is usually inaccessible for applied optical transducer. Copyright © 2016 Elsevier B.V. All rights reserved.

Self-templated Synthesis of Nickel Silicate Hydroxide/Reduced Graphene Oxide Composite Hollow Microspheres as Highly Stable Supercapacitor Electrode Material

NASA Astrophysics Data System (ADS)

Zhang, Yanhua; Zhou, Wenjie; Yu, Hong; Feng, Tong; Pu, Yong; Liu, Hongdong; Xiao, Wei; Tian, Liangliang

2017-05-01

Nickel silicate hydroxide/reduced graphene oxide (Ni3Si2O5(OH)4/RGO) composite hollow microspheres were one-pot hydrothermally synthesized by employing graphene oxide (GO)-wrapped SiO2 microspheres as the template and silicon source, which were prepared through sonication-assisted interfacial self-assembly of tiny GO sheets on positively charged SiO2 substrate microspheres. The composition, morphology, structure, and phase of Ni3Si2O5(OH)4/RGO microspheres as well as their electrochemical properties were carefully studied. It was found that Ni3Si2O5(OH)4/RGO microspheres featured distinct hierarchical porous morphology with hollow architecture and a large specific surface area as high as 67.6 m2 g-1. When utilized as a supercapacitor electrode material, Ni3Si2O5(OH)4/RGO hollow microspheres released a maximum specific capacitance of 178.9 F g-1 at the current density of 1 A g-1, which was much higher than that of the contrastive bare Ni3Si2O5(OH)4 hollow microspheres and bare RGO material developed in this work, displaying enhanced supercapacitive behavior. Impressively, the Ni3Si2O5(OH)4/RGO microsphere electrode exhibited outstanding rate capability and long-term cycling stability and durability with 97.6% retention of the initial capacitance after continuous charging/discharging for up to 5000 cycles at the current density of 6 A g-1, which is superior or comparable to that of most of other reported nickel-based electrode materials, hence showing promising application potential in the energy storage area.

Production of Monodisperse Cerium Oxide Microspheres with Diameters near 100 µm by Internal Gelation Sol-Gel Methods

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

Katalenich, Jeffrey A.; Kitchen, Brian B.; Pierson, Bruce

2018-05-01

Internal gelation sol-gel methods have used a variety of sphere forming methods in the past to produce metal oxide microspheres, but typically with poor control over the size uniformity at diameters near 100 µm. This work describes efforts to make and measure internal gelation, sol-gel microspheres with very uniform diameters in the 100 – 200 µm size range using a two-fluid nozzle. A custom apparatus was used to form aqueous droplets of sol-gel feed solutions in silicone oil and heat them to cause gelation of the spheres. Gelled spheres were washed, dried, and sintered prior to mounting on glass slidesmore » for optical imaging and analysis. Microsphere diameters and shape factors were determined as a function of silicone oil flow rate in a two-fluid nozzle and the size of a needle dispensing the aqueous sol-gel solution. Nine batches of microspheres were analyzed and had diameters ranging from 65.5 ± 2.4 µm for the smallest needle and fastest silicone oil flow rate to 211 ± 4.7 µm for the largest needle and slowest silicone oil flow rate. Standard deviations for measured diameters were less than 8% for all samples and most were less than 4%. Microspheres had excellent circularity with measured shape factors of 0.9 – 1. However, processing of optical images was complicated by shadow effects in the photoresist layer on glass slides and by overlapping microspheres. Based on calculated flow parameters, microspheres were produced in a simple dripping mode in the two-fluid nozzle. Using flow rates consistent with a simple dripping mode in a two-fluid nozzle configuration allows for very uniform oxide microspheres to be produced using the internal-gelation sol-gel method.« less

Uniform Cu{sub 2}Cl(OH){sub 3} hierarchical microspheres: A novel adsorbent for methylene blue adsorptive removal from aqueous solution

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

Wei, Wei; Gao, Pin; Xie, Jimin, E-mail: xiejm391@sohu.com

2013-08-15

Using the solution phase method without any surfactants or templates, the hierarchical of Cu{sub 2}Cl(OH){sub 3} microspheres were synthesized by freeze drying. The size and surface area of the microspheres are ca. 1–2 µm and 76.61 m{sup 2} g{sup −1}, respectively. A possible formation mechanism is presented based on the experimental results. Methylene blue was chosen to investigate the adsorption capacity of the as-prepared adsorbent. The effects of various experimental parameters, such as pH, initial dye concentration, and contact time were investigated. The results showed that the dye removal increased with the increasing in the initial concentration of the dyemore » and also increased in the amount of microspheres used and initial pH. Adsorption data fitted well with the Freundlich adsorption isotherm. The thermodynamic analysis presented the exothermic, spontaneous and more ordered arrangement process. The microspheres could be employed effective for removal of dyes from aqueous solution. - Graphical abstract: The single-crystalline hierarchical Cu{sub 2}Cl(OH){sub 3} spheres can be prepared for the first time by using a template-free process through freeze-drying. Meanwhile, the hierarchical spheres exhibited high adsorption capacity to methylene blue. Display Omitted - Highlights: • Cu{sub 2}Cl(OH){sub 3} microspheres were successfully synthesized through a freeze drying process. • A possible formation mechanism of hierarchical microspheres was presented. • The Cu{sub 2}Cl(OH){sub 3} microspheres have high methylene blue adsorption capacity. • Methylene blue adsorption is a spontaneous and exothermic process. • The adsorption mechanism of microspheres onto dye was proposed in detail.« less

Synthesis and characterization of poly(lactic acid-co-glycolic acid) complex microspheres as drug carriers.

PubMed

Wang, Fang; Liu, Xiuxiu; Yuan, Jian; Yang, Siqian; Li, Yueqin; Gao, Qinwei

2016-10-01

Poly(lactic-co-glycolic) acid (PLGA) is synthesized via melt polycondensation directly from lactic acid and glycolic acid with a feed molar ratio of 75/25. Bovine serum albumin, which is used as model protein, is entrapped into the poly(lactic-co-glycolic acid) microspheres with particle size of 260.9 ± 20.0 nm by the double emulsification method. Then it is the first report of producing more carboxyl groups by poly(lactic-co-glycolic acid) surface hydrolysis. The purpose is developing poly(lactic-co-glycolic acid) microspheres surface, which is modified with chitosan by chemical reaction between carboxyl groups and amine groups. The particle size and the positive zeta potential of the poly(lactic-co-glycolic acid)/chitosan microspheres are 388.2 ± 35.6 nm and 10.4 ± 2.9 mV, respectively. The drug loading ratio and encapsulation efficacy of poly(lactic-co-glycolic acid)/chitosan microspheres are 36.3% and 57.5%, which are higher than PLGA microspheres. Furthermore, the drug burst release of poly(lactic-co-glycolic acid)/chitosan microspheres at 10 h is decreased to 21.72% while the corresponding value of the poly(lactic-co-glycolic acid) microsphere is 64.56%. These results reveal that surface hydrolysis modification of poly(lactic-co-glycolic acid) is an efficient method to improve the negative potential and chemical reaction properties of the polymer. And furthermore, this study shows that chitosan-modified poly(lactic-co-glycolic acid) microspheres is a promising system for the controlled release of pharmaceutical proteins. © The Author(s) 2016.

Self-templated Synthesis of Nickel Silicate Hydroxide/Reduced Graphene Oxide Composite Hollow Microspheres as Highly Stable Supercapacitor Electrode Material.

PubMed

Zhang, Yanhua; Zhou, Wenjie; Yu, Hong; Feng, Tong; Pu, Yong; Liu, Hongdong; Xiao, Wei; Tian, Liangliang

2017-12-01

Nickel silicate hydroxide/reduced graphene oxide (Ni 3 Si 2 O 5 (OH) 4 /RGO) composite hollow microspheres were one-pot hydrothermally synthesized by employing graphene oxide (GO)-wrapped SiO 2 microspheres as the template and silicon source, which were prepared through sonication-assisted interfacial self-assembly of tiny GO sheets on positively charged SiO 2 substrate microspheres. The composition, morphology, structure, and phase of Ni 3 Si 2 O 5 (OH) 4 /RGO microspheres as well as their electrochemical properties were carefully studied. It was found that Ni 3 Si 2 O 5 (OH) 4 /RGO microspheres featured distinct hierarchical porous morphology with hollow architecture and a large specific surface area as high as 67.6 m 2  g -1 . When utilized as a supercapacitor electrode material, Ni 3 Si 2 O 5 (OH) 4 /RGO hollow microspheres released a maximum specific capacitance of 178.9 F g -1 at the current density of 1 A g -1 , which was much higher than that of the contrastive bare Ni 3 Si 2 O 5 (OH) 4 hollow microspheres and bare RGO material developed in this work, displaying enhanced supercapacitive behavior. Impressively, the Ni 3 Si 2 O 5 (OH) 4 /RGO microsphere electrode exhibited outstanding rate capability and long-term cycling stability and durability with 97.6% retention of the initial capacitance after continuous charging/discharging for up to 5000 cycles at the current density of 6 A g -1 , which is superior or comparable to that of most of other reported nickel-based electrode materials, hence showing promising application potential in the energy storage area.

Epitope presentation is an important determinant of the utility of antigens identified from protein arrays in the development of autoantibody diagnostic assays.

PubMed

Murphy, Mairead A; O'Connell, David J; O'Kane, Sara L; O'Brien, John K; O'Toole, Sharon; Martin, Cara; Sheils, Orla; O'Leary, John J; Cahill, Dolores J

2012-08-03

Autoantibodies represent an attractive biomarker for diagnostic assays principally due to the stability of immunoglobulin in patient serum facilitating measurement with conventional assays. Immune responses to tumorigenesis may facilitate detection of ovarian cancer in the early stages of the disease with identification of a panel of tumour specific autoantibodies. Despite the reporting of many tumour associated autoantibodies using arrays of tumour antigens, this has not led to the advance in diagnostic capability as rapidly as was initially expected. Here we examine the potential diagnostic utility of candidate autoantibody biomarkers identified via screening of serum samples on a high content human protein array from a unique cohort of early stage and late stage ovarian cancer patients. We analyse the performance of autoantibodies to the tumour suppressor protein p53 and the novel autoantigens alpha adducin and endosulfine alpha identified in our array screen. Each antigen has different performance characteristics using conventional ELISA format and Western blot immunoassay. The high attrition rate of promising autoantigens identified by array screening can in part be explained by the presentation of the epitope of the antigen in the subsequent method of validation and this study provides directions on maximising the potential of candidate biomarkers. This article is part of a Special Issue entitled: Translational Proteomics. Copyright © 2012 Elsevier B.V. All rights reserved.

Organic aerogel microspheres

DOEpatents

Mayer, S.T.; Kong, F.M.; Pekala, R.W.; Kaschmitter, J.L.

1999-06-01

Organic aerogel microspheres are disclosed which can be used in capacitors, batteries, thermal insulation, adsorption/filtration media, and chromatographic packings, having diameters ranging from about 1 micron to about 3 mm. The microspheres can be pyrolyzed to form carbon aerogel microspheres. This method involves stirring the aqueous organic phase in mineral oil at elevated temperature until the dispersed organic phase polymerizes and forms nonstick gel spheres. The size of the microspheres depends on the collision rate of the liquid droplets and the reaction rate of the monomers from which the aqueous solution is formed. The collision rate is governed by the volume ratio of the aqueous solution to the mineral oil and the shear rate, while the reaction rate is governed by the chemical formulation and the curing temperature.

Organic aerogel microspheres

DOEpatents

Mayer, Steven T.; Kong, Fung-Ming; Pekala, Richard W.; Kaschmitter, James L.

1999-01-01

Organic aerogel microspheres which can be used in capacitors, batteries, thermal insulation, adsorption/filtration media, and chromatographic packings, having diameters ranging from about 1 micron to about 3 mm. The microspheres can be pyrolyzed to form carbon aerogel microspheres. This method involves stirring the aqueous organic phase in mineral oil at elevated temperature until the dispersed organic phase polymerizes and forms nonsticky gel spheres. The size of the microspheres depends on the collision rate of the liquid droplets and the reaction rate of the monomers from which the aqueous solution is formed. The collision rate is governed by the volume ratio of the aqueous solution to the mineral oil and the shear rate, while the reaction rate is governed by the chemical formulation and the curing temperature.

Organic aerogel microspheres and fabrication method therefor

DOEpatents

Mayer, S.T.; Kong, F.M.; Pekala, R.W.; Kaschmitter, J.L.

1996-04-16

Organic aerogel microspheres which can be used in capacitors, batteries, thermal insulation, adsorption/filtration media, and chromatographic packings, having diameters ranging from about 1 micron to about 3 mm. The microspheres can be pyrolyzed to form carbon aerogel microspheres. This method involves stirring the aqueous organic phase in mineral oil at elevated temperature until the dispersed organic phase polymerizes and forms nonsticky gel spheres. The size of the microspheres depends on the collision rate of the liquid droplets and the reaction rate of the monomers from which the aqueous solution is formed. The collision rate is governed by the volume ratio of the aqueous solution to the mineral oil and the shear rate, while the reaction rate is governed by the chemical formulation and the curing temperature.

Organic aerogel microspheres and fabrication method therefor

DOEpatents

Mayer, Steven T.; Kong, Fung-Ming; Pekala, Richard W.; Kaschmitter, James L.

1996-01-01

Organic aerogel microspheres which can be used in capacitors, batteries, thermal insulation, adsorption/filtration media, and chromatographic packings, having diameters ranging from about 1 micron to about 3 mm. The microspheres can be pyrolyzed to form carbon aerogel microspheres. This method involves stirring the aqueous organic phase in mineral oil at elevated temperature until the dispersed organic phase polymerizes and forms nonsticky gel spheres. The size of the microspheres depends on the collision rate of the liquid droplets and the reaction rate of the monomers from which the aqueous solution is formed. The collision rate is governed by the volume ratio of the aqueous solution to the mineral oil and the shear rate, while the reaction rate is governed by the chemical formulation and the curing temperature.

Polystyrene-based Hollow Microsphere Synthesized by γ-ray Irradiation-assisted Polymerization and Self-Assembly and Its Application in Detection of Ionizing Radiation

NASA Astrophysics Data System (ADS)

Fan, Wenhui; Li, Qing; Hu, Liang; Yan, Siqi; Wen, Wanxin; Chai, Zhifang; Liu, Hanzhou

2017-01-01

To simply and multitudinously synthesize hollow microspheres in a pure system is important for relevant research and application. Here, a simple and novel one-pot synthetic strategy to prepare polystyrene (PS) hollow microspheres via irradiation-assisted free-radical polymerizing and self-assembly (IFPS) approach under γ-ray irradiation with no additives introduced into the system is presented. And PS/2,5-Diphenyloxazole (PPO) fluorescent microspheres have been prepared successfully by IFPS reaction, which can be used as scintillators for the detection of ionizing radiation. A linear relationship between emitted luminescence and dose-activity in water is obtained, which suggests that composite microspheres could be used as liquid scintillation in specific environment.

High diagnostic accuracy of histone H4-IgG autoantibodies in systemic lupus erythematosus.

PubMed

Vordenbäumen, Stefan; Böhmer, Paloma; Brinks, Ralph; Fischer-Betz, Rebecca; Richter, Jutta; Bleck, Ellen; Rengers, Petra; Göhler, Heike; Zucht, Hans-Dieter; Budde, Petra; Schulz-Knappe, Peter; Schneider, Matthias

2018-03-01

Diagnosis of SLE relies on the detection of autoantibodies. We aimed to assess the diagnostic potential of histone H4 and H2A variant antibodies in SLE. IgG-autoantibodies to histones H4 (HIST1H4A), H2A type 2-A (HIST2H2AA3) and H2A type 2-C (HIST2H2AC) were measured along with a standard antibody (SA) set including SSA, SSB, Sm, U1-RNP and RPLP2 in a multiplex magnetic microsphere-based assay in 153 SLE patients [85% female, 41 (13.5) years] and 81 healthy controls [77% female, 43.3 (12.4) years]. Receiver operating characteristic analysis was performed to assess diagnostic performance of individual markers. Logistic regression analysis was performed on a random split of samples to determine the additional value of histone antibodies in comparison with SA by likelihood ratio test and determination of diagnostic accuracy in the remaining validation samples. Microsphere-based assay showed good interclass correlation (mean 0.85, range 0.73-0.99) and diagnostic performance in receiver operating characteristic analysis (area under the curve (AUC) range 84.8-93.2) compared with routine assay for SA parameters. HIST1H4A-IgG was the marker with the best individual diagnostic performance for SLE vs healthy (AUC 0.97, sensitivity 95% at 90% specificity). HIST1H4A-IgG was an independent significant predictor for the diagnosis of SLE in multivariate modelling (P < 0.0001), and significantly improved prediction of SLE over SA parameters alone (residual deviance 45.9 vs 97.1, P = 4.3 × 10-11). Diagnostic accuracy in the training and validation samples was 89 and 86% for SA, and 95 and 89% with the addition of HIST1H4A-IgG. HIST1H4A-IgG antibodies improve diagnostic accuracy for SLE vs healthy. © The Author(s) 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. [br]For Permissions, please email: journals.permissions@oup.com

Detection of palytoxin-like compounds by a flow cytometry-based immunoassay supported by functional and analytical methods.

PubMed

Fraga, María; Vilariño, Natalia; Louzao, M Carmen; Fernández, Diego A; Poli, Mark; Botana, Luis M

2016-01-15

Palytoxin (PLTX) is a complex marine toxin produced by zoanthids (i.e. Palythoa), dinoflagellates (Ostreopsis) and cyanobacteria (Trichodesmium). PLTX outbreaks are usually associated with Indo-Pacific waters, however their recent repeated occurrence in Mediterranean-European Atlantic coasts demonstrate their current worldwide distribution. Human sickness and fatalities have been associated with toxic algal blooms and ingestion of seafood contaminated with PLTX-like molecules. These toxins represent a serious threat to human health. There is an immediate need to develop easy-to-use, rapid detection methods due to the lack of validated protocols for their detection and quantification. We have developed an immuno-detection method for PLTX-like molecules based on the use of microspheres coupled to flow-cytometry detection (Luminex 200™). The assay consisted of the competition between free PLTX-like compounds in solution and PLTX immobilized on the surface of microspheres for binding to a specific monoclonal anti-PLTX antibody. This method displays an IC50 of 1.83 ± 0.21 nM and a dynamic range of 0.47-6.54 nM for PLTX. An easy-to-perform extraction protocol, based on a mixture of methanol and acetate buffer, was applied to spiked mussel samples providing a recovery rate of 104 ± 8% and a range of detection from 374 ± 81 to 4430 ± 150 μg kg(-1) when assayed with this method. Extracts of Ostreopsis cf. siamensis and Palythoa tuberculosa were tested and yielded positive results for PLTX-like molecules. However, the data obtained for the coral sample suggested that this antibody did not detect 42-OH-PLTX efficiently. The same samples were further analyzed using a neuroblastoma cytotoxicity assay and UPLC-IT-TOF spectrometry, which also pointed to the presence of PLTX-like compounds. Therefore, this single detection method for PLTX provides a semi-quantitative tool useful for the screening of PLTX-like molecules in different matrixes. Copyright © 2015 Elsevier B.V. All rights reserved.

21 CFR 870.1360 - Trace microsphere.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Trace microsphere. 870.1360 Section 870.1360 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Diagnostic Devices § 870.1360 Trace microsphere. (a...

21 CFR 870.1360 - Trace microsphere.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Trace microsphere. 870.1360 Section 870.1360 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Diagnostic Devices § 870.1360 Trace microsphere. (a...

Nano-functionalization of protein microspheres

NASA Astrophysics Data System (ADS)

Yoon, Sungkwon; Nichols, William T.

2014-08-01

Protein microspheres are promising building blocks for the assembly of complex functional materials. Here we demonstrate a set of three techniques that add functionality to the surface of protein microspheres. In the first technique, a positive surface charge on the protein spheres is deposited by electrostatic adsorption. Negatively charged silica and gold nanoparticle colloids can then electrostatically bind reversibly to the microsphere surface. In the second technique, nanoparticles are covalently anchored to the protein shell using a simple one-pot process. The strong covalent bond between sulfur groups in cysteine in the protein shell irreversibly binds to the gold nanoparticles. In the third technique, surface morphology of the protein microsphere is tuned through hydrodynamic instability at the water-oil interface. This is accomplished through the degree of solubility of the oil phase in water. Taken together these three techniques form a platform to create nano-functionalized protein microspheres, which can then be used as building blocks for the assembly of more complex macroscopic materials.

Magnetic alginate microspheres: system for the position controlled delivery of nerve growth factor.

PubMed

Ciofani, Gianni; Raffa, Vittoria; Menciassi, Arianna; Cuschieri, Alfred; Micera, Silvestro

2009-04-01

The use of polymeric carriers containing dispersed magnetic nanocrystalline particles for targeted delivery of drugs in clinical practice has attracted the interest of the scientific community. In this paper a system comprised of alginate microparticles with a core of magnetite and carrying nerve growth factor (NGF) is described. The magnetic properties of these microspheres, typical of superparamagnetic materials, allow precise and controlled delivery to the intended tissue environment. Experiments carried out on PC12 cells with magnetic alginate microspheres loaded with NGF have confirmed the induction of cell differentiation which is strongly dependent on the distance from the microsphere cluster. In addition, finite element modelling (FEM) of the release profile from the microspheres in culture, indicated the possibility of creating defined and predictable NGF gradients from the loaded microspheres. These observations on the carriage and release of growth factors by the proposed microparticles open new therapeutic options for both neuronal regeneration and of the development of effective neuronal interfaces.

Use of Microsphere Technology for Targeted Delivery of Rifampin to Mycobacterium tuberculosis-Infected Macrophages

PubMed Central

Barrow, Esther L. W.; Winchester, Gary A.; Staas, Jay K.; Quenelle, Debra C.; Barrow, William W.

1998-01-01

Microsphere technology was used to develop formulations of rifampin for targeted delivery to host macrophages. These formulations were prepared by using biocompatible polymeric excipients of lactide and glycolide copolymers. Release characteristics were examined in vitro and also in two monocytic cell lines, the murine J774 and the human Mono Mac 6 cell lines. Bioassay assessment of cell culture supernatants from monocyte cell lines showed release of bioactive rifampin during a 7-day experimental period. Treatment of Mycobacterium tuberculosis H37Rv-infected monocyte cell lines with rifampin-loaded microspheres resulted in a significant decrease in numbers of CFU at 7 days following initial infection, even though only 8% of the microsphere-loaded rifampin was released. The levels of rifampin released from microsphere formulations within monocytes were more effective at reducing M. tuberculosis intracellular growth than equivalent doses of rifampin given as a free drug. These results demonstrate that rifampin-loaded microspheres can be formulated for effective sustained and targeted delivery to host macrophages. PMID:9756777

Microspheres

NASA Technical Reports Server (NTRS)

1990-01-01

Vital information on a person's physical condition can be obtained by identifying and counting the population of T-cells and B-cells, lymphocytes of the same shape and size that help the immune system protect the body from the invasion of disease. The late Dr. Alan Rembaum developed a method for identifying the cells. The method involved tagging the T-cells and B-cells with microspheres of different fluorescent color. Microspheres, which have fluorescent dye embedded in them, are chemically treated so that they can link with antibodies. With the help of a complex antibody/antigen reaction, the microspheres bind themselves to specific 'targets,' in this case the T-cells or B-cells. Each group of cells can then be analyzed by a photoelectronic instrument at different wavelengths emitted by the fluorescent dyes. Same concept was applied to the separation of cancer cells from normal cells. Microspheres were also used to conduct many other research projects. Under a patent license Magsphere, Inc. is producing a wide spectrum of microspheres on a large scale and selling them worldwide for various applications.

Gelatin microspheres containing calcitonin gene-related peptide or substance P repair bone defects in osteoporotic rabbits.

PubMed

Chen, Jianghao; Liu, Wei; Zhao, Jinxiu; Sun, Cong; Chen, Jie; Hu, Kaijin; Zhang, Linlin; Ding, Yuxiang

2017-03-01

To investigate the therapeutic effect of gelatin microspheres containing different concentrations of calcitonin gene-related peptide (CGRP) or substance P on repairing bone defects in a rabbit osteoporosis model. Gelatin microspheres containing different concentrations of CGRP or substance P promoted osteogenesis after 3 months in a rabbit osteoporotic bone defective model. From micro-computed tomography imaging results, 10 nM CGRP was optimal for increasing the trabecular number and decreasing the trabecular bone separation degree; similar effects were observed with the microspheres containing 1 µM substance P. Histological analysis showed that the gelatin microspheres containing CGRP or substance P, regardless of the concentration, effectively promoted osteogenesis, and the highest effect was achieved in the groups containing 1 µM CGRP or 1 µM substance P. Gelatin microspheres containing CGRP or substance P effectively promoted osteogenesis in a rabbit osteoporotic bone defect model dose-dependently, though their effects in repairing human alveolar ridge defects still need further investigation.

Preparation of "Cauliflower-Like" ZnO Micron-Sized Particles.

PubMed

Gordon, Tamar; Grinblat, Judith; Margel, Shlomo

2013-11-14

Porous polydivinyl benzene (PDVB) microspheres of narrow size distribution were formed by a single-step swelling process of template uniform polystyrene microspheres with divinyl benzene (DVB), followed by polymerization of the DVB within the swollen template microspheres. The PDVB porous particles were then formed by dissolution of the template polystyrene polymer. Unique "cauliflower-like" ZnO microparticles were prepared by the entrapping of the ZnO precursor ZnCl₂ in the PDVB porous microspheres under vacuum, followed by calcination of the obtained ZnCl₂-PDVB microspheres in an air atmosphere. The morphology, crystallinity and fluorescence properties of those ZnO microparticles were characterized. This "cauliflower-like" shape ZnO particles is in contrast to a previous study demonstrated the preparation of spherical shaped porous ZnO and C-ZnO microparticles by a similar method, using zinc acetate (ZnAc) as a precursor. Two diverted synthesis mechanisms for those two different ZnO microparticles structures are proposed, based on studies of the distribution of each of the ZnO precursors within the PDVB microspheres.

TiO2 Hollow Spheres: One-Pot Synthesis and Enhanced Photocatalysis

NASA Astrophysics Data System (ADS)

Jia, Changchao; Cao, Yongqiang; Yang, Ping

2013-04-01

Hollow TiO2 microspheres were successfully fabricated by metal salts with low solubility in ethanol acting as intelligent templates using a simple one-pot solvothermal method. Hollow spheres with large diameter were obtained using CuSO4ṡ5H2O as templates while small ones were obtained using Sr(NO3)2 as templates. It is found that titanium precursor plays an important role for the morphology of samples. Solid TiO2 microspheres were prepared by using titanium tetrabutoxide (TBT). In contrast, bowl-like hollow microspheres were obtained by using titanium tetrachloride (TiCl4). Furthermore, the amount of H2O can stimulate the hydrolysis rate of TiCl4 to form solid spheres. Compared with solid microspheres, hollow TiO2 microspheres depending on their interior cavity structure exhibited enhanced photocatalysis efficiency for the UV-light photodegradation of methyl orange. Quantificationally, the apparent photocatalytic degradation pseudo-first-rate constant of the hollow microspheres is 1.25 times of that of the solid ones.

[Optimization of calcium alginate floating microspheres loading aspirin by artificial neural networks and response surface methodology].

PubMed

Zhang, An-yang; Fan, Tian-yuan

2010-04-18

To investigate the preparation and optimization of calcium alginate floating microspheres loading aspirin. A model was used to predict the in vitro release of aspirin and optimize the formulation by artificial neural networks (ANNs) and response surface methodology (RSM). The amounts of the material in the formulation were used as inputs, while the release and floating rate of the microspheres were used as outputs. The performances of ANNs and RSM were compared. ANNs were more accurate in prediction. There was no significant difference between ANNs and RSM in optimization. Approximately 90% of the optimized microspheres could float on the artificial gastric juice over 4 hours. 42.12% of aspirin was released in 60 min, 60.97% in 120 min and 78.56% in 240 min. The release of the drug from the microspheres complied with Higuchi equation. The aspirin floating microspheres with satisfying in vitro release were prepared successfully by the methods of ANNs and RSM.

Processing and size range separation of pristine and magnetic poly(l-lactic acid) based microspheres for biomedical applications.

PubMed

Correia, D M; Sencadas, V; Ribeiro, C; Martins, P M; Martins, P; Gama, F M; Botelho, G; Lanceros-Méndez, S

2016-08-15

Biodegradable poly(l-lactic acid) (PLLA) and PLLA/CoFe2O4 magnetic microspheres with average sizes ranging between 0.16-3.9μm and 0.8-2.2μm, respectively, were obtained by an oil-in-water emulsion method using poly(vinyl alcohol) (PVA) solution as the emulsifier agent. The separation of the microspheres in different size ranges was then performed by centrifugation and the colloidal stability assessed at different pH values. Neat PLLA spheres are more stable in alkaline environments when compared to magnetic microspheres, both types being stable for pHs higher than 4, resulting in a colloidal suspension. On the other hand, in acidic environments the microspheres tend to form aggregates. The neat PLLA microspheres show a degree of crystallinity of 40% whereas the composite ones are nearly amorphous (17%). Finally, the biocompatibility was assessed by cell viability studies with MC3T3-E1 pre-osteoblast cells. Copyright © 2016 Elsevier Inc. All rights reserved.

Micro-light-pipe array with an excitation attenuation filter for lensless digital enzyme-linked immunosorbent assay

NASA Astrophysics Data System (ADS)

Takehara, Hironari; Nagasaki, Mizuki; Sasagawa, Kiyotaka; Takehara, Hiroaki; Noda, Toshihiko; Tokuda, Takashi; Ohta, Jun

2016-03-01

Digital enzyme-linked immunosorbent assay (ELISA) is used for detecting various biomarkers with hypersensitivity. We have been developing compact systems by replacing the fluorescence microscope with a CMOS image sensor. Here, we propose a micro-light-pipe array structure made of metal filled with dye-doped resin, which can be used as a fabrication substrate of the micro-reaction-chamber array of digital ELISA. The possibility that this structure enhances the coupling efficiency for fluorescence was simulated using a simple model. To realize the structure, we fabricated a 30-µm-thick micropipe array by copper electroplating around a thick photoresist pattern. The typical diameter of each fabricated micropipe was 10 µm. The pipes were filled with yellow-dye-doped epoxy resin. The transmittance ratio of fluorescence and excitation light could be controlled by adjusting the doping concentration. We confirmed that an angled excitation light incidence suppressed the leakage of excitation light.

Mapping protein-protein interactions using yeast two-hybrid assays.

PubMed

Mehla, Jitender; Caufield, J Harry; Uetz, Peter

2015-05-01

Yeast two-hybrid (Y2H) screens are an efficient system for mapping protein-protein interactions and whole interactomes. The screens can be performed using random libraries or collections of defined open reading frames (ORFs) called ORFeomes. This protocol describes both library and array-based Y2H screening, with an emphasis on array-based assays. Array-based Y2H is commonly used to test a number of "prey" proteins for interactions with a single "bait" (target) protein or pool of proteins. The advantage of this approach is the direct identification of interacting protein pairs without further downstream experiments: The identity of the preys is known and does not require further confirmation. In contrast, constructing and screening a random prey library requires identification of individual prey clones and systematic retesting. Retesting is typically performed in an array format. © 2015 Cold Spring Harbor Laboratory Press.

Applications of LaBr3(Ce) Gamma-ray Spectrometer Arrays for Nuclear Spectroscopy and Radionuclide Assay

NASA Astrophysics Data System (ADS)

Regan, PH; Shearman, R.; Daniel, T.; Lorusso, G.; Collins, SM; Judge, SM; Bell; Pearce, AK; Gurgi, LA; Rudigier, M.; Podolyák, Zs; Mărginean, N.; Mărginean, R.; Kisyov, S.

2016-10-01

An overview of the use of discrete energy gamma-ray detectors based on cerium- doped LaBr3 scintillators for use in nuclear spectroscopy is presented. This review includes recent applications of such detectors in mixed, 'hybrid' gamma-ray coincidence detection arrays such ROSPHERE at IFIN-HH, Bucharest; EXILL+FATIMA at ILL Grenoble, France; GAMMASPHERE+FATIMA at Argonne National Laboratory, USA; FATIMA + EURICA, at RIKEN, Japan; and the National Nuclear Array (NANA) at the UK's National Physical Laboratory. This conference paper highlights the capabilities and limitations of using these sub-nanosecond 'fast-timing', medium-resolution gamma-ray detectors for both nuclear structure research and radionuclide standardisation. Potential future application of such coincidence scintillator arrays in measurements of civilian nuclear fuel waste evaluation and assay is demonstrated using coincidence spectroscopy of a mixed 134,7Cs source.

Foam, a promising vehicle to deliver nanoparticles for vadose zone remediation.

PubMed

Shen, Xin; Zhao, Lin; Ding, Yuanzhao; Liu, Bo; Zeng, Hui; Zhong, Lirong; Li, Xiqing

2011-02-28

Foam delivery of remedial amendments for in situ immobilization of deep vadose zone contaminants can overcome the intrinsic problems associated with solution-based delivery, such as preferential flow and contaminant mobilization. In this work, the feasibility of using foam to deliver nanoparticles in unsaturated porous media was investigated. Carboxyl-modified polystyrene latex microspheres were used as surrogates for nanoparticles of remediation purposes. Foams generated from the solutions of six commonly available surfactants all had excellent abilities to carry the microspheres. The presence of the microspheres did not reduce the stabilities of the foams. When microsphere-laden foam was injected through the unsaturated columns, the fractions of microspheres exiting the column were much higher than that when the microsphere water suspensions were injected through the columns. The enhanced microsphere transport implies that foam delivery could significantly increase the radius of influence of injected nanoparticles of remediation purposes. Reduced tension at air-water interfaces by the surfactant and increased driving forces imparted on the microspheres at the interfaces by the flowing foam bubbles may have both contributed to the enhanced transport. Preliminary tests also demonstrated that foam can carry significant fractions of zero valent iron nanoparticles at concentrations relevant to field remediation conditions (up to 5.3 g L(-1)). As such, this study demonstrates that surfactant foam is potentially a promising vehicle to deliver nanoparticles for vadose zone remediation. Copyright © 2010 Elsevier B.V. All rights reserved.

Budesonide-Loaded Guar Gum Microspheres for Colon Delivery: Preparation, Characterization and in Vitro/in Vivo Evaluation

PubMed Central

Liu, Ye; Zhou, Hong

2015-01-01

A novel budesonide (BUD) colon delivery release system was developed by using a natural polysaccharide, guar gum. The rigidity of the microspheres was induced by a chemical cross-linking method utilizing glutaraldehyde as the cross-linker. The mean particle size of the microspheres prepared was found to be 15.21 ± 1.32 µm. The drug loading and entrapment efficiency of the formulation were 17.78% ± 2.31% and 81.6% ± 5.42%, respectively. The microspheres were spherical in shape with a smooth surface, and the size was uniform. The in vitro release profiles indicated that the release of BUD from the microspheres exhibited a sustained release behavior. The model that fitted best for BUD released from the microspheres was the Higuchi kinetic model with a correlation coefficient r = 0.9993. A similar phenomenon was also observed in a pharmacokinetic study. The prolongation of the half-life (t1/2), enhanced residence time (mean residence time, MRT) and decreased total clearance (CL) indicated that BUD microspheres could prolong the acting time of BUD in vivo. In addition, BUD guar gum microspheres are thought to have the potential to maintain BUD concentration within target ranges for a long time, decreasing the side effects caused by concentration fluctuation, ensuring the efficiency of treatment and improving patient compliance by reducing dosing frequency. None of the severe signs, like the appearance of epithelial necrosis and the sloughing of epithelial cells, were detected. PMID:25629228

Nanomechanics of biocompatible hollow thin-shell polymer microspheres.

PubMed

Glynos, Emmanouil; Koutsos, Vasileios; McDicken, W Norman; Moran, Carmel M; Pye, Stephen D; Ross, James A; Sboros, Vassilis

2009-07-07

The nanomechanical properties of biocompatible thin-shell hollow polymer microspheres with approximately constant ratio of shell thickness to microsphere diameter were measured by nanocompression tests in aqueous conditions. These microspheres encapsulate an inert gas and are used as ultrasound contrast agents by releasing free microbubbles in the presence of an ultrasound field as a result of free gas leakage from the shell. The tests were performed using an atomic force microscope (AFM) employing the force-distance curve technique. An optical microscope, on which the AFM was mounted, was used to guide the positioning of tipless cantilevers on top of individual microspheres. We performed a systematic study using several cantilevers with spring constants varying from 0.08 to 2.3 N/m on a population of microspheres with diameters from about 2 to 6 microm. The use of several cantilevers with various spring constants allowed a systematic study of the mechanical properties of the microsphere thin shell at different regimes of force and deformation. Using thin-shell mechanics theory for small deformations, the Young's modulus of the thin wall material was estimated and was shown to exhibit a strong size effect: it increased as the shell became thinner. The Young's modulus of thicker microsphere shells converged to the expected value for the macroscopic bulk material. For high applied forces, the force-deformation profiles showed a reversible and/or irreversible nonlinear behavior including "steps" and "jumps" which were attributed to mechanical instabilities such as buckling events.

Fabrication of Polymer Microspheres for Optical Resonator and Laser Applications.

PubMed

Yamamoto, Yohei; Okada, Daichi; Kushida, Soh; Ngara, Zakarias Seba; Oki, Osamu

2017-06-02

This paper describes three methods of preparing fluorescent microspheres comprising π-conjugated or non-conjugated polymers: vapor diffusion, interface precipitation, and mini-emulsion. In all methods, well-defined, micrometer-sized spheres are obtained from a self-assembling process in solution. The vapor diffusion method can result in spheres with the highest sphericity and surface smoothness, yet the types of the polymers able to form these spheres are limited. On the other hand, in the mini-emulsion method, microspheres can be made from various types of polymers, even from highly crystalline polymers with coplanar, π-conjugated backbones. The photoluminescent (PL) properties from single isolated microspheres are unusual: the PL is confined inside the spheres, propagates at the circumference of the spheres via the total internal reflection at the polymer/air interface, and self-interferes to show sharp and periodic resonant PL lines. These resonating modes are so-called "whispering gallery modes" (WGMs). This work demonstrates how to measure WGM PL from single isolated spheres using the micro-photoluminescence (µ-PL) technique. In this technique, a focused laser beam irradiates a single microsphere, and the luminescence is detected by a spectrometer. A micromanipulation technique is then used to connect the microspheres one by one and to demonstrate the intersphere PL propagation and color conversion from coupled microspheres upon excitation at the perimeter of one sphere and detection of PL from the other microsphere. These techniques, µ-PL and micromanipulation, are useful for experiments on micro-optic application using polymer materials.

pH-Sensitive Self-Assembled Microspheres Composed of Poly(Ethyleneimine) and Cinnamic Acid.

PubMed

Park, Danbi; Lee, Seung-Jun; Kim, Jin-Chul

2018-01-01

Microspheres which were sensitive to pH change were developed by utilizing cinnamic acid (CA) as a physical cross-linker for poly(ethyleneimine) (PEI). At pH 7.0, the microspheres were efficiently formed at the PEI/CA ratio of 1:3.4, 1:5.1, and 1:7.1 (w/w), which corresponded to the protonated amino group/deprotonated carboxyl group ratio of 5:5, 4:6, and 3:7. The mean diameter of wet microspheres was 3.2 ± 0.3 to 8.8 ± 0.5 μm and that of dry ones was 1.7 ± 0.2 to 2.7 ± 0.2 μm. The microspheres were disappeared upon the alkalification, possibly because the electrostatic interaction between PEI and CA was slackened down and the hydrophobic interaction among CA molecules was weakened. At pH 5.0 and 7.0, the microsphere released its content in a sustained manner and the release degree in 24 h was less than 40%. Whereas, at pH 8.0 and 9.0, the microsphere exhibited a burst release and the release degree in 24 h was greater than 80%. In the alkali condition, not only the electrostatic interaction between PEI and CA but also the hydrophobic interaction among CA molecules became weaker, leading to the disintegration of the microsphere and resulting in a burst and intensive release.

Naltrexone-loaded poly[La-(Glc-Leu)] polymeric microspheres for the treatment of alcohol dependence: in vitro characterization and in vivo biocompatibility assessment.

PubMed

Pagar, Kunal P; Vavia, Pradeep R

2014-06-01

The poly[La-(Glc-Leu)] copolymer was applied in the present investigation as polymeric carrier to fabricate naltrexone (NTX)-loaded poly[La-(Glc-Leu)] microspheres in the single emulsion solvent evaporation technique for the long-term treatment of alcohol dependence. Newly synthesized poly[La-(Glc-Leu)] copolymer exhibited diminished crystallanity, good biocompatibility and favorable biodegradability to be explored for drug delivery application. Scanning Electron Microscopy study revealed smooth and spherical-shaped NTX-loaded polymeric microspheres with a mean size of 10-90 µm. Influence of various decisive formulation variables such as amount of polymer, stabilizer concentration, homogenization speed, homogenization time, drug loading and organic-to-aqueous phase ratio on particle size, and entrapment efficiency was studied. Differential scanning calorimeter and X-ray diffractometry study confirmed the drug entrapment within polymer matrix into the microsphere environment. In vitro drug release showed the sustained drug release of formulation for the period of 28 d giving biphasic release pattern. Histological examination of NTX-loaded poly[La-(Glc-Leu)] microspheres injected intramuscularly into the thigh muscle of Wistar rats showed minimal inflammatory reaction, demonstrating that NTX-loaded microspheres were biocompatible. Insignificant increase in the serum creatine phosphokinase level (p < 0.05) as compared with the normal value revealed good muscle compatibility of the poly[La-(Glc-Leu)] microsphere system. Biocompatible nature and sustained drug-release action of poly[La-(Glc-Leu)] microspheres may have potential application in depot therapy.

Micro particle launcher/cleaner based on optical trapping technology.

PubMed

Liu, Zhihai; Liang, Peibo; Zhang, Yu; Zhang, Yaxun; Zhao, Enming; Yang, Jun; Yuan, Libo

2015-04-06

Efficient and controllable launching function of an optical tweezers is a challenging task. We present and demonstrate a novel single fiber optical tweezers which can trap and launch (clean) a target polystyrene (PS) microsphere (diameter~10μm) with independent control by using two wavelengths beams: 980nm and 1480nm. We employ 980nm laser beam to trap the target PS microsphere by molding the fiber tip into a special tapered-shape; and we employ 1480nm laser beam to launch the trapped PS microsphere with a certain velocity by using the thermophoresis force generated from the thermal effect due to the high absorption of the 1480nm laser beams in water. When the launching force is smaller than the trapping force, the PS microsphere will be trapped near the fiber tip, and the launching force will blow away other PS microspheres in the workspace realizing the cleaning function; When the launching force is larger than the trapping force, the trapped PS microsphere will be launched away from the fiber tip with a certain velocity and towards a certain direction, realizing the launching function. The launching velocity, acceleration and the distance can be measured by detecting the interference signals generated from the PS microsphere surface and the fiber tip end-face. This PS microsphere launching and cleaning functions expanded new features of single fiber optical tweezers, providing for the possibility of more practical applications in the micro manipulation research fields.

Kinetics of piroxicam release from low-methylated pectin/zein hydrogel microspheres

USDA-ARS?s Scientific Manuscript database

The kinetics of a model drug (piroxicam) release from pectin/zein hydrogel microspheres was studied under conditions simulating the gastrointestinal tract. It is established that the rate-limiting step in the release mechanism is drug diffusion out of the microspheres rather than its dissolution. ...

Pectin/zein microspheres as a sustained drug delivery system

USDA-ARS?s Scientific Manuscript database

A series of microspheres were prepared from pectins and corn proteins from various sources in the presence of the divalent ions calcium or zinc. The results showed that the yield of microsphere and the efficiency of drug incorporation were dependent on the type and ratio of biopolymers, the size of ...

Porous-wall hollow glass microspheres as carriers for biomolecules

DOEpatents

Li, Shuyi; Dynan, William S; Wicks, George; Serkiz, Steven

2013-09-17

The present invention includes compositions of porous-wall hollow glass microspheres and one or more biomolecules, wherein the one or more biomolecules are positioned within a void location within the hollow glass microsphere, and the use of such compositions for the diagnostic and/or therapeutic delivery of biomolecules.

Porous wall hollow glass microspheres as a medium or substrate for storage and formation of novel materials

DOEpatents

Wicks, George G; Serkiz, Steven M.; Zidan, Ragaiy; Heung, Leung K.

2014-06-24

Porous wall hollow glass microspheres are provided as a template for formation of nanostructures such as carbon nanotubes, In addition, the carbon nanotubes in combination with the porous wall hollow glass microsphere provides an additional reaction template with respect to carbon nanotubes.