Mixing in microfluidic devices and enhancement methods

PubMed Central

Ward, Kevin; Fan, Z Hugh

2015-01-01

Mixing in microfluidic devices presents a challenge due to laminar flows in microchannels, which result from low Reynolds numbers determined by the channel’s hydraulic diameter, flow velocity, and solution’s kinetic viscosity. To address this challenge, novel methods of mixing enhancement within microfluidic devices have been explored for a variety of applications. Passive mixing methods have been created, including those using ridges or slanted wells within the microchannels, as well as their variations with improved performance by varying geometry and patterns, by changing the properties of channel surfaces, and by optimization via simulations. In addition, active mixing methods including microstirrers, acoustic mixers, and flow pulsation have been investigated and integrated into microfluidic devices to enhance mixing in a more controllable manner. In general, passive mixers are easy to integrate, but difficult to control externally by users after fabrication. Active mixers usually take efforts to integrate within a device and they require external components (e.g. power sources) to operate. However, they can be controlled by users to a certain degree for tuned mixing. In this article, we provide a general overview of a number of passive and active mixers, discuss their advantages and disadvantages, and make suggestions on choosing a mixing method for a specific need as well as advocate possible integration of key elements of passive and active mixers to harness the advantages of both types. PMID:26549938

Mixing in microfluidic devices and enhancement methods.

PubMed

Ward, Kevin; Fan, Z Hugh

2015-09-01

Mixing in microfluidic devices presents a challenge due to laminar flows in microchannels, which result from low Reynolds numbers determined by the channel's hydraulic diameter, flow velocity, and solution's kinetic viscosity. To address this challenge, novel methods of mixing enhancement within microfluidic devices have been explored for a variety of applications. Passive mixing methods have been created, including those using ridges or slanted wells within the microchannels, as well as their variations with improved performance by varying geometry and patterns, by changing the properties of channel surfaces, and by optimization via simulations. In addition, active mixing methods including microstirrers, acoustic mixers, and flow pulsation have been investigated and integrated into microfluidic devices to enhance mixing in a more controllable manner. In general, passive mixers are easy to integrate, but difficult to control externally by users after fabrication. Active mixers usually take efforts to integrate within a device and they require external components (e.g. power sources) to operate. However, they can be controlled by users to a certain degree for tuned mixing. In this article, we provide a general overview of a number of passive and active mixers, discuss their advantages and disadvantages, and make suggestions on choosing a mixing method for a specific need as well as advocate possible integration of key elements of passive and active mixers to harness the advantages of both types.

Simulation analysis of rectifying microfluidic mixing with field-effect-tunable electrothermal induced flow.

PubMed

Liu, Weiyu; Ren, Yukun; Tao, Ye; Yao, Bobin; Li, You

2018-03-01

We report herein field-effect control on in-phase electrothermal streaming from a theoretical point of view, a phenomenon termed "alternating-current electrothermal-flow field effect transistor" (ACET-FFET), in the context of a new technology for handing analytes in microfluidics. Field-effect control through a gate terminal endows ACET-FFET the ability to generate arbitrary symmetry breaking in the transverse vortex flow pattern, which makes it attractive for mixing microfluidic samples. A computational model is developed to study the feasibility of this new microfluidic device design for micromixing. The influence of various parameters on developing an efficient mixer is investigated, and an integrated layout of discrete electrode array is suggested for achieving high-throughput mixing. Our physical demonstration with field-effect electrothermal flow control using a simple electrode structure proves invaluable for designing active micromixers for modern micro total analytical system. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Implementation of an optimized microfluidic mixer in alumina employing femtosecond laser ablation

NASA Astrophysics Data System (ADS)

Juodėnas, M.; Tamulevičius, T.; Ulčinas, O.; Tamulevičius, S.

2018-01-01

Manipulation of liquids at the lowest levels of volume and dimension is at the forefront of materials science, chemistry and medicine, offering important time and resource saving applications. However, manipulation by mixing is troublesome at the microliter and lower scales. One approach to overcome this problem is to use passive mixers, which exploit structural obstacles within microfluidic channels or the geometry of channels themselves to enforce and enhance fluid mixing. Some applications require the manipulation and mixing of aggressive substances, which makes conventional microfluidic materials, along with their fabrication methods, inappropriate. In this work, implementation of an optimized full scale three port microfluidic mixer is presented in a slide of a material that is very hard to process but possesses extreme chemical and physical resistance—alumina. The viability of the selected femtosecond laser fabrication method as an alternative to conventional lithography methods, which are unable to process this material, is demonstrated. For the validation and optimization of the microfluidic mixer, a finite element method (FEM) based numerical modeling of the influence of the mixer geometry on its mixing performance is completed. Experimental investigation of the laminar flow geometry demonstrated very good agreement with the numerical simulation results. Such a laser ablation microfabricated passive mixer structure is intended for use in a capillary force assisted nanoparticle assembly setup (CAPA).

Microfluidic mixing triggered by an external LED illumination.

PubMed

Venancio-Marques, Anna; Barbaud, Fanny; Baigl, Damien

2013-02-27

The mixing of confined liquids is a central yet challenging operation in miniaturized devices. Microfluidic mixing is usually achieved with passive mixers that are robust but poorly flexible, or active mixers that offer dynamic control but mainly rely on electrical or mechanical transducers, which increase the fragility, cost, and complexity of the device. Here, we describe the first remote and reversible control of microfluidic mixing triggered by a light illumination simply provided by an external LED illumination device. The approach is based on the light-induced generation of water microdroplets acting as reversible stirrers of two continuous oil phase flows containing samples to be mixed. We demonstrate many cycles of reversible photoinduced transitions between a nonmixing behavior and full homogenization of the two oil phases. The method is cheap, portable, and adaptable to many device configurations, thus constituting an essential brick for the generation of future all-optofluidic chip.

Microfluidic mixing using orbiting magnetic microbeads

NASA Astrophysics Data System (ADS)

Ballard, Matthew; Owen, Drew; Mao, Wenbin; Hesketh, Peter; Alexeev, Alexander

2013-11-01

Using three-dimensional simulations and experiments, we examine mixing in a microfluidic channel that incorporates a hybrid passive-active micromixer. The passive part of the mixer consists of a series of angled parallel ridges lining the top microchannel wall. The active component of the mixer is made up of microbeads rotating around small pillars on the bottom of the microchannel. In our simulations, we use a binary fluid lattice Boltzmann model to simulate the system and characterize the microfluidic mixing in the system. We consider the passive and active micromixers separately and evaluate their combined effect on the mixing of binary fluids. We compare our simulations with the experimental results obtained in a microchannel with magnetically actuated microbeads. Our findings guide the design of an efficient micromixer to be used in sampling in complex fluids. Financial support from NSF (CBET-1159726) is gratefully acknowledged.

Evaluation of peristaltic micromixers for highly integrated microfluidic systems

PubMed Central

Kim, Duckjong; Rho, Hoon Suk; Jambovane, Sachin; Shin, Soojeong; Hong, Jong Wook

2016-01-01

Microfluidic devices based on the multilayer soft lithography allow accurate manipulation of liquids, handling reagents at the sub-nanoliter level, and performing multiple reactions in parallel processors by adapting micromixers. Here, we have experimentally evaluated and compared several designs of micromixers and operating conditions to find design guidelines for the micromixers. We tested circular, triangular, and rectangular mixing loops and measured mixing performance according to the position and the width of the valves that drive nanoliters of fluids in the micrometer scale mixing loop. We found that the rectangular mixer is best for the applications of highly integrated microfluidic platforms in terms of the mixing performance and the space utilization. This study provides an improved understanding of the flow behaviors inside micromixers and design guidelines for micromixers that are critical to build higher order fluidic systems for the complicated parallel bio/chemical processes on a chip. PMID:27036809

Integrated microfluidic systems for cell lysis, mixing/pumping and DNA amplification

NASA Astrophysics Data System (ADS)

Lee, Chia-Yen; Lee, Gwo-Bin; Lin, Jr-Lung; Huang, Fu-Chun; Liao, Chia-Sheng

2005-06-01

The present paper reports a fully automated microfluidic system for the DNA amplification process by integrating an electroosmotic pump, an active micromixer and an on-chip temperature control system. In this DNA amplification process, the cell lysis is initially performed in a micro cell lysis reactor. Extracted DNA samples, primers and reagents are then driven electroosmotically into a mixing region where they are mixed by the active micromixer. The homogeneous mixture is then thermally cycled in a micro-PCR (polymerase chain reaction) chamber to perform DNA amplification. Experimental results show that the proposed device can successfully automate the sample pretreatment operation for DNA amplification, thereby delivering significant time and effort savings. The new microfluidic system, which facilitates cell lysis, sample driving/mixing and DNA amplification, could provide a significant contribution to ongoing efforts to miniaturize bio-analysis systems by utilizing a simple fabrication process and cheap materials.

Evaluation of peristaltic micromixers for highly integrated microfluidic systems

NASA Astrophysics Data System (ADS)

Kim, Duckjong; Rho, Hoon Suk; Jambovane, Sachin; Shin, Soojeong; Hong, Jong Wook

2016-03-01

Microfluidic devices based on the multilayer soft lithography allow accurate manipulation of liquids, handling reagents at the sub-nanoliter level, and performing multiple reactions in parallel processors by adapting micromixers. Here, we have experimentally evaluated and compared several designs of micromixers and operating conditions to find design guidelines for the micromixers. We tested circular, triangular, and rectangular mixing loops and measured mixing performance according to the position and the width of the valves that drive nanoliters of fluids in the micrometer scale mixing loop. We found that the rectangular mixer is best for the applications of highly integrated microfluidic platforms in terms of the mixing performance and the space utilization. This study provides an improved understanding of the flow behaviors inside micromixers and design guidelines for micromixers that are critical to build higher order fluidic systems for the complicated parallel bio/chemical processes on a chip.

An investigation of paper based microfluidic devices for size based separation and extraction applications.

PubMed

Zhong, Z W; Wu, R G; Wang, Z P; Tan, H L

2015-09-01

Conventional microfluidic devices are typically complex and expensive. The devices require the use of pneumatic control systems or highly precise pumps to control the flow in the devices. This work investigates an alternative method using paper based microfluidic devices to replace conventional microfluidic devices. Size based separation and extraction experiments conducted were able to separate free dye from a mixed protein and dye solution. Experimental results showed that pure fluorescein isothiocyanate could be separated from a solution of mixed fluorescein isothiocyanate and fluorescein isothiocyanate labeled bovine serum albumin. The analysis readings obtained from a spectrophotometer clearly show that the extracted tartrazine sample did not contain any amount of Blue-BSA, because its absorbance value was 0.000 measured at a wavelength of 590nm, which correlated to Blue-BSA. These demonstrate that paper based microfluidic devices, which are inexpensive and easy to implement, can potentially replace their conventional counterparts by the use of simple geometry designs and the capillary action. These findings will potentially help in future developments of paper based microfluidic devices. Copyright © 2015 Elsevier B.V. All rights reserved.

Microfluidic mixing through oscillatory transverse perturbations

NASA Astrophysics Data System (ADS)

Wu, J. W.; Xia, H. M.; Zhang, Y. Y.; Zhu, P.

2018-05-01

Fluid mixing in miniaturized fluidic devices is a challenging task. In this work, the mixing enhancement through oscillatory transverse perturbations coupling with divergent circular chambers is studied. To simplify the design, an autonomous microfluidic oscillator is used to produce the oscillatory flow. It is then applied to four side-channels that intersect with a central channel of constant flow. The mixing performance is tested at high fluid viscosities of up to 16 cP. Results show that the oscillatory flow can cause strong transverse perturbations which effectively enhance the mixing. The influence of a fluidic capacitor in the central channel is also examined, which at low viscosities can intensify the perturbations and further improve the mixing.

Study on Manipulations of Fluids in Micro-scale and Their Applications in Physical, Bio/chemistry

NASA Astrophysics Data System (ADS)

Zhou, Bingpu

Microfluidics is a highly interdisciplinary research field which manipulates, controls and analyzes fluids in micro-scale for physical and bio/chemical applications. In this thesis, several aspects of fluid manipulations in micro-scale were studied, discussed and employed for demonstrations of practical utilizations. To begin with, mixing in continuous flow microfluidic was raised and investigated. A simple method for mixing actuation based on magnetism was proposed and realized via integration of magnetically functionalized micropillar arrays inside the microfluidic channel.With such technique, microfluidic mixing could be swiftly switched on and off via simple application or retraction of the magnetic field. Thereafter, in Chapter 3 we mainly focused on how to establish stable while tunable concentration gradients inside microfluidic network using a simple design. The proposed scheme could also be modified with on-chip pneumatic actuated valve to realize pulsatile/temporal concentration gradients simultaneously in ten microfluidic branches. We further applied such methodology to obtain roughness gradients onPolydimethylsiloxane (PDMS) surface via combinations of the microfluidic network andphoto-polymerizations. The obtained materials were utilized in parallel cell culture to figure out the relationship between substrate morphologies and the cell behaviors. In the second part of this work, we emphasized on manipulations on microdroplets insidethe microfluidic channel and explored related applications in bio/chemical aspects. Firstly, microdroplet-based microfluidic universal logic gates were successfully demonstrated vialiquid-electronic hybrid divider. For application based on such novel scheme of control lable droplet generation, on-demand chemical reaction within paired microdroplets was presented using IF logic gate. Followed by this, another important operation of microdroplet - splitting -was investigated. Addition lateral continuous flow was applied at the bifurcation as a mediumto controllably divide microdroplets with highly tunable splitting ratios. Related physical mechanism was proposed and such approach was adopted further for rapid synthesis of multi-scale microspheres.

Integrated light-sheet imaging and flow-based enquiry (iLIFE) system for 3D in-vivo imaging of multicellular organism

NASA Astrophysics Data System (ADS)

Rasmi, Chelur K.; Padmanabhan, Sreedevi; Shirlekar, Kalyanee; Rajan, Kanhirodan; Manjithaya, Ravi; Singh, Varsha; Mondal, Partha Pratim

2017-12-01

We propose and demonstrate a light-sheet-based 3D interrogation system on a microfluidic platform for screening biological specimens during flow. To achieve this, a diffraction-limited light-sheet (with a large field-of-view) is employed to optically section the specimens flowing through the microfluidic channel. This necessitates optimization of the parameters for the illumination sub-system (illumination intensity, light-sheet width, and thickness), microfluidic specimen platform (channel-width and flow-rate), and detection sub-system (camera exposure time and frame rate). Once optimized, these parameters facilitate cross-sectional imaging and 3D reconstruction of biological specimens. The proposed integrated light-sheet imaging and flow-based enquiry (iLIFE) imaging technique enables single-shot sectional imaging of a range of specimens of varying dimensions, ranging from a single cell (HeLa cell) to a multicellular organism (C. elegans). 3D reconstruction of the entire C. elegans is achieved in real-time and with an exposure time of few hundred micro-seconds. A maximum likelihood technique is developed and optimized for the iLIFE imaging system. We observed an intracellular resolution for mitochondria-labeled HeLa cells, which demonstrates the dynamic resolution of the iLIFE system. The proposed technique is a step towards achieving flow-based 3D imaging. We expect potential applications in diverse fields such as structural biology and biophysics.

A multi-functional bubble-based microfluidic system

PubMed Central

Khoshmanesh, Khashayar; Almansouri, Abdullah; Albloushi, Hamad; Yi, Pyshar; Soffe, Rebecca; Kalantar-zadeh, Kourosh

2015-01-01

Recently, the bubble-based systems have offered a new paradigm in microfluidics. Gas bubbles are highly flexible, controllable and barely mix with liquids, and thus can be used for the creation of reconfigurable microfluidic systems. In this work, a hydrodynamically actuated bubble-based microfluidic system is introduced. This system enables the precise movement of air bubbles via axillary feeder channels to alter the geometry of the main channel and consequently the flow characteristics of the system. Mixing of neighbouring streams is demonstrated by oscillating the bubble at desired displacements and frequencies. Flow control is achieved by pushing the bubble to partially or fully close the main channel. Patterning of suspended particles is also demonstrated by creating a large bubble along the sidewalls. Rigorous analytical and numerical calculations are presented to describe the operation of the system. The examples presented in this paper highlight the versatility of the developed bubble-based actuator for a variety of applications; thus providing a vision that can be expanded for future highly reconfigurable microfluidics. PMID:25906043

Microfluidic Injector Models Based on Artificial Neural Networks

DTIC Science & Technology

2005-06-15

medicine, and chemistry [1], [2]. They generally perform chemical analysis involving sample preparation, mixing , reaction, injection, separation analysis...algorithms have been validated against many ex- periments found in the literature demonstrating microfluidic mixing , joule heating, injection, and...385 [7] K. Seiler, Z. H. Fan, K. Fluri, and D. J. Harrison, “ Electroosmotic pump- ing and valveless control of fluid flow within a manifold of

A dynamic bead-based microarray for parallel DNA detection

NASA Astrophysics Data System (ADS)

Sochol, R. D.; Casavant, B. P.; Dueck, M. E.; Lee, L. P.; Lin, L.

2011-05-01

A microfluidic system has been designed and constructed by means of micromachining processes to integrate both microfluidic mixing of mobile microbeads and hydrodynamic microbead arraying capabilities on a single chip to simultaneously detect multiple bio-molecules. The prototype system has four parallel reaction chambers, which include microchannels of 18 × 50 µm2 cross-sectional area and a microfluidic mixing section of 22 cm length. Parallel detection of multiple DNA oligonucleotide sequences was achieved via molecular beacon probes immobilized on polystyrene microbeads of 16 µm diameter. Experimental results show quantitative detection of three distinct DNA oligonucleotide sequences from the Hepatitis C viral (HCV) genome with single base-pair mismatch specificity. Our dynamic bead-based microarray offers an effective microfluidic platform to increase parallelization of reactions and improve microbead handling for various biological applications, including bio-molecule detection, medical diagnostics and drug screening.

AC electrothermal mixing for high conductive biofluids by arc-electrodes

NASA Astrophysics Data System (ADS)

Meng, Jiyu; Li, Shanshan; Li, Junwei; Yu, Chengzhuang; Wei, Chunyang; Dai, Shijie

2018-06-01

As a platform to mix the bioagents (i.e. serum, urine), we take advantage of the alternating current electrothermal (ACET) effect which is quite suitable for rapid pumping/mixing of high conductive biomicrofluids. Here we demonstrate the concept of a high-efficient mixing microfluidic chip as a basic unit to provide rapid mixing for lab-on-a-chip applications. As an active mixer, two streams are introduced into a ring-shape microchamber by a passive flow rate regulator, and then the microfluids in the chamber are actuated by a nonuniform electric field with a phase shift of 180°. It shows perfect mixing performance by arranging four arc-electrodes around the ring-shape microchamber subsequently. Taking the Joule heating and conductivity/permittivity changes into consideration, a temperature dependent fully coupled numerical model is presented. Then, the effects of applied voltages on mixing performance and temperature rise are provided to get an optimized design for ACET mixer. Moreover, the arrangement of the electrode array is analyzed to show the effects of electrode patterns on the swirls and mixing efficiencies. Since all the electrodes here are located along a ring-shape central microchamber, the ring-shape micromixer is quite suitable to function as a compact element modular for integrated microfluidic chips.

Combined Microfluidic-Eectric Diffused Mixing of Living Cells in Continuous Flow

NASA Astrophysics Data System (ADS)

Ming-Wen Wang,

2010-02-01

The mixing process is a crucially important stage in the operation of biological and chemical microfluidic devices. If the mixing is inadequate, reactants do not fully interact with each other, and the device may not operate properly. This paper describes a simplified microfluidic mixer (different from a chaotic mixer) which can uniformly mix a buffer solution with living cells by applying an AC electric charge. Diffusion of the living cells into the buffer solution occurs rapidly following the interface of the flow stream with the electric charge; no further agitating step is needed. To accomplish this, an asymmetric pair of electrodes was integrated at the inlets of the buffer solution and the cells fluid. When the buffer solution and the cells fluid were introduced into one flow path, they remained limited to that flow stream. When the electrodes were charged, however, the cells in a short distance were efficiently moved into the solution flow, and the original fluids were mixed. The mixing efficiency depends on the polarizability of the cells, and this in turn is governed by the dielectric properties of the cells, the medium, and the solvent. This micro device, capable of efficiently mixing living cells with a buffer solution, may potentially allow biological mixing to be done outside of hospitals, in facilities without biological analyzing instruments.

Performance analysis of a microfluidic mixer based on high gradient magnetic separation principles

NASA Astrophysics Data System (ADS)

Liu, Mengyu; Han, Xiaotao; Cao, Quanliang; Li, Liang

2017-09-01

To achieve a rapid mixing between a water-based ferrofluid and DI water in a microfluidic environment, a magnetically actuated mixing system based on high gradient magnetic separation principles is proposed in this work. The microfluidic system consists of a T-shaped mirochannel and an array of integrated soft-magnetic elements at the sidewall of the channel. With the aid of an external magnetic bias field, these elements are magnetized to produce a magnetic volume force acting on the fluids containing magnetic nanoparticles, and then to induce additional flows for improving the mixing performance. The mixing process is numerically investigated through analyzing the concentration distribution of magnetic nanoparticles using a coupled particle-fluid transport model, and mixing performances under different parametrical conditions are investigated in detail. Numerical results show that a high mixing efficiency around 97.5% can be achieved within 2 s under an inlet flow rate of 1 mm s-1 and a relatively low magnetic bias field of 50 mT. Meanwhile, it has been found that there is an optimum number of magnetic elements used for obtaining the best mixing performance. These results show the potential of the proposed mixing method in lab-on-a-chip system and could be helpful in designing and optimizing system performance.

Modelling and simulation of passive Lab-on-a-Chip (LoC) based micromixer for clinical application

NASA Astrophysics Data System (ADS)

Saikat, Chakraborty; Sharath, M.; Srujana, M.; Narayan, K.; Pattnaik, Prasant Kumar

2016-03-01

In biomedical application, micromixer is an important component because of many processes requires rapid and efficient mixing. At micro scale, the flow is Laminar due to small channel size which enables controlled rapid mixing. The reduction in analysis time along with high throughput can be achieved with the help of rapid mixing. In LoC application, micromixer is used for mixing of fluids especially for the devices which requires efficient mixing. Micromixer of this type of microfluidic devices with a rapid mixing is useful in application such as DNA/RNA synthesis, drug delivery system & biological agent detection. In this work, we design and simulate a microfluidic based passive rapid micromixer for lab-on-a-chip application.

Numerical Simulation of Mixing Performances of a Passive Micromixer with Internal Ribs

NASA Astrophysics Data System (ADS)

Guo, L.; Zhang, S. S.; Han, K. J.

2010-03-01

Effective mixing of microfluids is the basic requirement for biochemical analysis. Unfortunately, the macroscale mixing methods such as stirring and creation of turbulent flow are not applicable to the mixing of microfluids. To tackle such problems, we proposed a new, passive micromixer with internal ribs, which improves the mixing performances by changing the internal structure and shape of microchannels, and increasing the interfacial surface areas as far as possible. In this paper, the impact of geometric parameters on the mixing performance, and the pressure loss of the proposed micromixer were simulated using the software package FLUENT. The simulation shows that the mixing index M of each crosssection increases initially and then decreases with the increase of inlet velocity V. It also shows that at Point V = 0.01 m/s, the fluid mixing changes from convective mass transfer to molecular diffusion mass transfer. With the increase of W1, the mixing index M of each crosssection decreases gradually, whereas it increases accordingly with the growth of P/W. The larger the number of internal ribs is, the better the mixing performance of the micromixer will be. On the other hand, the mixing index M of the proposed micromixer decreases with the increase of H/W. At H/W> = 0.6, the variation of H/W imposes little influence on the micromixer's mixing performance. At Q = 28.8 mLh-1, an improved mixing efficiency and lowered pressure loss will be achieved, thus meeting the requirement of microfluidic chip.

3D nanomolding and fluid mixing in micromixers with micro-patterned microchannel walls

NASA Astrophysics Data System (ADS)

Farshchian, Bahador; Amirsadeghi, Alborz; Choi, Junseo; Park, Daniel S.; Kim, Namwon; Park, Sunggook

2017-03-01

Microfluidic devices where the microchannel walls were decorated with micro and nanostructures were fabricated using 3D nanomolding. Using 3D molded microfluidic devices with microchannel walls decorated with microscale gratings, the fluid mixing behavior was investigated through experiments and numerical simulation. The use of microscale gratings in the micromixer was predicated by the fact that large obstacles in a microchannel enhances the mixing performance. Slanted ratchet gratings on the channel walls resulted in a helical flow along the microchannel, thus increasing the interfacial area between fluids and cutting down the diffusion length. Increasing the number of walls decorated with continuous ratchet gratings intensified the strength of the helical flow, enhancing mixing further. When ratchet gratings on the surface of the top cover plate were aligned in a direction to break the continuity of gratings from the other three walls, a stack of two helical flows was formed one above each other. This work concludes that the 3D nanomolding process can be a cost-effective tool for scaling-up the fabrication of microfluidic mixers with improved mixing efficiencies.[Figure not available: see fulltext.

Development of a microfluidic device for simultaneous mixing and pumping

NASA Astrophysics Data System (ADS)

Kim, Byoung Jae; Yoon, Sang Youl; Lee, Kyung Heon; Sung, Hyung Jin

2009-01-01

We conducted experimental and numerical studies aimed at developing a microfluidic device capable of simultaneous mixing while pumping. The proposed multifunctional device makes use of alternating current electroosmotic flow and adopts an array of planar asymmetric microelectrodes with a diagonal or herringbone shape. The pumping performance was assessed in terms of the fluid velocity at the center of the microchannel, obtained by micro PIV. To assess the mixing, flow visualizations were carried out over the electrodes to verify the lateral flows. The mixing degree was quantified in terms of a mixing efficiency obtained by three-dimensional numerical simulations. The results showed that simultaneous mixing and pumping was achieved in the channels with diagonal or herringbone electrode configurations. A herringbone electrode configuration showed better pumping compared with a reference, as well as enhanced mixing.

Microfluidic size separation of cells and particles using a swinging bucket centrifuge.

PubMed

Yeo, Joo Chuan; Wang, Zhiping; Lim, Chwee Teck

2015-09-01

Biomolecular separation is crucial for downstream analysis. Separation technique mainly relies on centrifugal sedimentation. However, minuscule sample volume separation and extraction is difficult with conventional centrifuge. Furthermore, conventional centrifuge requires density gradient centrifugation which is laborious and time-consuming. To overcome this challenge, we present a novel size-selective bioparticles separation microfluidic chip on a swinging bucket minifuge. Size separation is achieved using passive pressure driven centrifugal fluid flows coupled with centrifugal force acting on the particles within the microfluidic chip. By adopting centrifugal microfluidics on a swinging bucket rotor, we achieved over 95% efficiency in separating mixed 20 μm and 2 μm colloidal dispersions from its liquid medium. Furthermore, by manipulating the hydrodynamic resistance, we performed size separation of mixed microbeads, achieving size efficiency of up to 90%. To further validate our device utility, we loaded spiked whole blood with MCF-7 cells into our microfluidic device and subjected it to centrifugal force for a mere duration of 10 s, thereby achieving a separation efficiency of over 75%. Overall, our centrifugal microfluidic device enables extremely rapid and label-free enrichment of different sized cells and particles with high efficiency.

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.

Automated Microfluidic Platform for Serial Polymerase Chain Reaction and High-Resolution Melting Analysis.

PubMed

Cao, Weidong; Bean, Brian; Corey, Scott; Coursey, Johnathan S; Hasson, Kenton C; Inoue, Hiroshi; Isano, Taisuke; Kanderian, Sami; Lane, Ben; Liang, Hongye; Murphy, Brian; Owen, Greg; Shinoda, Nobuhiko; Zeng, Shulin; Knight, Ivor T

2016-06-01

We report the development of an automated genetic analyzer for human sample testing based on microfluidic rapid polymerase chain reaction (PCR) with high-resolution melting analysis (HRMA). The integrated DNA microfluidic cartridge was used on a platform designed with a robotic pipettor system that works by sequentially picking up different test solutions from a 384-well plate, mixing them in the tips, and delivering mixed fluids to the DNA cartridge. A novel image feedback flow control system based on a Canon 5D Mark II digital camera was developed for controlling fluid movement through a complex microfluidic branching network without the use of valves. The same camera was used for measuring the high-resolution melt curve of DNA amplicons that were generated in the microfluidic chip. Owing to fast heating and cooling as well as sensitive temperature measurement in the microfluidic channels, the time frame for PCR and HRMA was dramatically reduced from hours to minutes. Preliminary testing results demonstrated that rapid serial PCR and HRMA are possible while still achieving high data quality that is suitable for human sample testing. © 2015 Society for Laboratory Automation and Screening.

In situ formation of leak-free polyethylene glycol (PEG) membranes in microfluidic fuel cells.

PubMed

Ho, W F; Lim, K M; Yang, K-L

2016-11-29

Membraneless microfluidic fuel cells operated under two co-laminar flows often face serious fuel cross-over problems, especially when flow rates are close to zero. In this study, we show that polyethylene glycol (PEG) monomers can be cross-linked inside microfluidic channels to form leak-free PEG membranes, which prevent mixing of two incompatible electrolyte solutions while allowing diffusion of certain molecules (e.g. glucose) and ions. By using PEG monomers of different molecular weights and cross-linking conditions, we are able to tailor selectivity of the membrane to allow passage of glucose while blocking larger molecules such as trypan blue. As a proof of principle, a microfluidic fuel cell with a PEG membrane and two incompatible electrolytes (acid and base) is demonstrated. Thanks to the leak-free nature of the PEG membrane, these two electrolytes do not mix together even at very slow flow rates. This microfluidic fuel cell is able to generate a voltage up to ∼450 mV from 10 mM of glucose with a flow rate of 20 μL min -1 . This microfluidic fuel cell is potentially useful as a miniature power source for many applications.

Microfluidic size separation of cells and particles using a swinging bucket centrifuge

PubMed Central

Yeo, Joo Chuan; Wang, Zhiping; Lim, Chwee Teck

2015-01-01

Biomolecular separation is crucial for downstream analysis. Separation technique mainly relies on centrifugal sedimentation. However, minuscule sample volume separation and extraction is difficult with conventional centrifuge. Furthermore, conventional centrifuge requires density gradient centrifugation which is laborious and time-consuming. To overcome this challenge, we present a novel size-selective bioparticles separation microfluidic chip on a swinging bucket minifuge. Size separation is achieved using passive pressure driven centrifugal fluid flows coupled with centrifugal force acting on the particles within the microfluidic chip. By adopting centrifugal microfluidics on a swinging bucket rotor, we achieved over 95% efficiency in separating mixed 20 μm and 2 μm colloidal dispersions from its liquid medium. Furthermore, by manipulating the hydrodynamic resistance, we performed size separation of mixed microbeads, achieving size efficiency of up to 90%. To further validate our device utility, we loaded spiked whole blood with MCF-7 cells into our microfluidic device and subjected it to centrifugal force for a mere duration of 10 s, thereby achieving a separation efficiency of over 75%. Overall, our centrifugal microfluidic device enables extremely rapid and label-free enrichment of different sized cells and particles with high efficiency. PMID:26487900

Predicting the behavior of microfluidic circuits made from discrete elements

PubMed Central

Bhargava, Krisna C.; Thompson, Bryant; Iqbal, Danish; Malmstadt, Noah

2015-01-01

Microfluidic devices can be used to execute a variety of continuous flow analytical and synthetic chemistry protocols with a great degree of precision. The growing availability of additive manufacturing has enabled the design of microfluidic devices with new functionality and complexity. However, these devices are prone to larger manufacturing variation than is typical of those made with micromachining or soft lithography. In this report, we demonstrate a design-for-manufacturing workflow that addresses performance variation at the microfluidic element and circuit level, in context of mass-manufacturing and additive manufacturing. Our approach relies on discrete microfluidic elements that are characterized by their terminal hydraulic resistance and associated tolerance. Network analysis is employed to construct simple analytical design rules for model microfluidic circuits. Monte Carlo analysis is employed at both the individual element and circuit level to establish expected performance metrics for several specific circuit configurations. A protocol based on osmometry is used to experimentally probe mixing behavior in circuits in order to validate these approaches. The overall workflow is applied to two application circuits with immediate use at on the bench-top: series and parallel mixing circuits that are modularly programmable, virtually predictable, highly precise, and operable by hand. PMID:26516059

Inertial focusing and passive micro-mixing techniques for rare cells capturing microfluidic platform

NASA Astrophysics Data System (ADS)

Phadke, Manisha; Shaner, Sebastian; Shah, Shreyas; Rodriguez, Ygnacio; Wibowo, Denni; Whulanza, Yudan; Teriete, Peter; Allen, Jeff; Kassegne, Sam

2018-02-01

Isolation and capture of rare cells continues to be a daunting task that is still looking for an innovative and efficient method. While a variety of approaches have been suggested over the past several years, immunocapturing in a microfluidic platform carries a substantial promise as shown by recent published works. In this paper, we introduced a combination of inertial focusing and passive micro-mixing through 3D chevron-type features in a microchannel to induce chaotic mixing within antibody-coated microchannels and, ultimately, promote rare cell capture. The device introduced in this work contains curved microchannels that consist of a series of staggered chevron grooves. The curved channels enable inertial focusing while the chevron grooves allow for chaotic mixing. The microfluidics platform microfabricated through soft lithography has a polydimethylsiloxane (PDMS) foundation and was thinly coated with an alginate hydrogel derivatized with streptavidin. We submitted that our qualitative and quantitative results demonstrated the potentials in advancements in rare cell isolation through this integration of two techniques.

Active mixing of complex fluids at the microscale

DOE PAGES

Ober, Thomas J.; Foresti, Daniele; Lewis, Jennifer A.

2015-09-22

Mixing of complex fluids at low Reynolds number is fundamental for a broad range of applications, including materials assembly, microfluidics, and biomedical devices. Of these materials, yield stress fluids (and gels) pose the most significant challenges, especially when they must be mixed in low volumes over short timescales. New scaling relationships between mixer dimensions and operating conditions are derived and experimentally verified to create a framework for designing active microfluidic mixers that can efficiently homogenize a wide range of complex fluids. As a result, active mixing printheads are then designed and implemented for multimaterial 3D printing of viscoelastic inks withmore » programmable control of local composition.« less

Active mixing of complex fluids at the microscale

PubMed Central

Ober, Thomas J.; Foresti, Daniele; Lewis, Jennifer A.

2015-01-01

Mixing of complex fluids at low Reynolds number is fundamental for a broad range of applications, including materials assembly, microfluidics, and biomedical devices. Of these materials, yield stress fluids (and gels) pose the most significant challenges, especially when they must be mixed in low volumes over short timescales. New scaling relationships between mixer dimensions and operating conditions are derived and experimentally verified to create a framework for designing active microfluidic mixers that can efficiently homogenize a wide range of complex fluids. Active mixing printheads are then designed and implemented for multimaterial 3D printing of viscoelastic inks with programmable control of local composition. PMID:26396254

Analysis of Electrically Induced Swirling Flow of Isotonic Saline in a Mixing Microchannel

NASA Astrophysics Data System (ADS)

Hirahara, Shuzo; Tsuruta, Tomoyuki; Matsumoto, Yoshinori; Minamitani, Haruyuki

We have designed a prototype microfluidic device to mix suspended particles with isotonic saline by use of electrically induced swirling flow in the microchannel. However, the principles underlying microfluidic rotation induced by AC electrodes are not well understood, and the characteristics of the rotation velocity are unpredictable. Furthermore, these properties have not been studied using a highly conductive liquid like isotonic saline, which is an important fluid in the medical and biological fields. The lack of such studies causes uncertainty in the design required for high-performance microfluidic devices. We have examined the electrical rotational properties of the microfluid at an isotonic concentration of saline using computer simulation, and here we show that buoyant flow, which has previously been largely ignored, has a significant effect in channels of 100-μm depth or deeper, and that AC electroosmotic flow is not induced at isotonic saline concentrations.

A microfluidic sub-critical water extraction instrument

NASA Astrophysics Data System (ADS)

Sherrit, Stewart; Noell, Aaron C.; Fisher, Anita; Lee, Mike C.; Takano, Nobuyuki; Bao, Xiaoqi; Kutzer, Thomas C.; Grunthaner, Frank

2017-11-01

This article discusses a microfluidic subcritical water extraction (SCWE) chip for autonomous extraction of amino acids from astrobiologically interesting samples. The microfluidic instrument is composed of three major components. These include a mixing chamber where the soil sample is mixed and agitated with the solvent (water), a subcritical water extraction chamber where the sample is sealed with a freeze valve at the chip inlet after a vapor bubble is injected into the inlet channels to ensure the pressure in the chip is in equilibrium with the vapor pressure and the slurry is then heated to ≤200 °C in the SCWE chamber, and a filter or settling chamber where the slurry is pumped to after extraction. The extraction yield of the microfluidic SCWE chip process ranged from 50% compared to acid hydrolysis and 80%-100% compared to a benchtop microwave SCWE for low biomass samples.

Sample flow switching techniques on microfluidic chips.

PubMed

Pan, Yu-Jen; Lin, Jin-Jie; Luo, Win-Jet; Yang, Ruey-Jen

2006-02-15

This paper presents an experimental investigation into electrokinetically focused flow injection for bio-analytical applications. A novel microfluidic device for microfluidic sample handling is presented. The microfluidic chip is fabricated on glass substrates using conventional photolithographic and chemical etching processes and is bonded using a high-temperature fusion method. The proposed valve-less device is capable not only of directing a single sample flow to a specified output port, but also of driving multiple samples to separate outlet channels or even to a single outlet to facilitate sample mixing. The experimental results confirm that the sample flow can be electrokinetically pre-focused into a narrow stream and guided to the desired outlet port by means of a simple control voltage model. The microchip presented within this paper has considerable potential for use in a variety of applications, including high-throughput chemical analysis, cell fusion, fraction collection, sample mixing, and many other applications within the micro-total-analysis systems field.

Mass spectrometry-based monitoring of millisecond protein–ligand binding dynamics using an automated microfluidic platform

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

Cong, Yongzheng; Katipamula, Shanta; Trader, Cameron D.

2016-01-01

Characterizing protein-ligand binding dynamics is crucial for understanding protein function and developing new therapeutic agents. We have developed a novel microfluidic platform that features rapid mixing of protein and ligand solutions, variable incubation times, and on-chip electrospray ionization to perform label-free, solution-based monitoring of protein-ligand binding dynamics. This platform offers many advantages including automated processing, rapid mixing, and low sample consumption.

Photoresponsive Passive Micromixers Based on Spiropyran Size-Tunable Hydrogels.

PubMed

Ter Schiphorst, Jeroen; Melpignano, Giuseppe G; Amirabadi, Hossein Eslami; Houben, Menno H J M; Bakker, Sterre; den Toonder, Jaap M J; Schenning, Albertus P H J

2018-01-01

Microfluidic devices allow the manipulation of fluids down to the micrometer scale and are receiving a lot of attention for applications where low volumes and high throughputs are required. In these micro channels, laminar flow usually dominates, which requires long residence times of the fluids, limiting the flow speed and throughput. Here a switchable passive mixer has been developed to control mixing and to easily clean microchannels. The mixer is based on a photoresponsive spiropyran based hydrogel of which the dimensions can be tuned by changing the intensity of the light. The size-tunable gels have been used to fabricate a passive slanted groove mixer that can be switched off by light allowing to change mixing of microfluidics to non-mixed flows. These findings open new possibilities for multi-purpose microfluidic devices where mixers and valves can be tuned by light. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

On demand nanoliter-scale microfluidic droplet generation, injection, and mixing using a passive microfluidic device

PubMed Central

Tangen, Uwe; Sharma, Abhishek

2015-01-01

We here present and characterize a programmable nanoliter scale droplet-on-demand device that can be used separately or readily integrated into low cost single layer rapid prototyping microfluidic systems for a wide range of user applications. The passive microfluidic device allows external (off-the-shelf) electronically controlled pinch valves to program the delivery of nanoliter scale aqueous droplets from up to 9 different inputs to a central outlet channel. The inputs can be either continuous aqueous fluid streams or microliter scale aqueous plugs embedded in a carrier fluid, in which case the number of effective input solutions that can be employed in an experiment is no longer strongly constrained (100 s–1000 s). Both nanoliter droplet sequencing output and nanoliter-scale droplet mixing are reported with this device. Optimization of the geometry and pressure relationships in the device was achieved in several hardware iterations with the support of open source microfluidic simulation software and equivalent circuit models. The requisite modular control of pressure relationships within the device is accomplished using hydrodynamic barriers and matched resistance channels with three different channel heights, custom parallel reversible microfluidic I/O connections, low dead-volume pinch valves, and a simply adjustable array of external screw valves. Programmable sequences of droplet mixes or chains of droplets can be achieved with the device at low Hz frequencies, limited by device elasticity, and could be further enhanced by valve integration. The chip has already found use in the characterization of droplet bunching during export and the synthesis of a DNA library. PMID:25759752

On demand nanoliter-scale microfluidic droplet generation, injection, and mixing using a passive microfluidic device.

PubMed

Tangen, Uwe; Sharma, Abhishek; Wagler, Patrick; McCaskill, John S

2015-01-01

We here present and characterize a programmable nanoliter scale droplet-on-demand device that can be used separately or readily integrated into low cost single layer rapid prototyping microfluidic systems for a wide range of user applications. The passive microfluidic device allows external (off-the-shelf) electronically controlled pinch valves to program the delivery of nanoliter scale aqueous droplets from up to 9 different inputs to a central outlet channel. The inputs can be either continuous aqueous fluid streams or microliter scale aqueous plugs embedded in a carrier fluid, in which case the number of effective input solutions that can be employed in an experiment is no longer strongly constrained (100 s-1000 s). Both nanoliter droplet sequencing output and nanoliter-scale droplet mixing are reported with this device. Optimization of the geometry and pressure relationships in the device was achieved in several hardware iterations with the support of open source microfluidic simulation software and equivalent circuit models. The requisite modular control of pressure relationships within the device is accomplished using hydrodynamic barriers and matched resistance channels with three different channel heights, custom parallel reversible microfluidic I/O connections, low dead-volume pinch valves, and a simply adjustable array of external screw valves. Programmable sequences of droplet mixes or chains of droplets can be achieved with the device at low Hz frequencies, limited by device elasticity, and could be further enhanced by valve integration. The chip has already found use in the characterization of droplet bunching during export and the synthesis of a DNA library.

Fundamentals of microfluidics for high school students with no prior knowledge of fluid mechanics.

PubMed

Tandon, Vishal; Peck, Walter

2013-01-01

Three microfluidics-based laboratory exercises were developed and implemented in a high school science classroom setting. The first exercise demonstrated ways in which flows are characterized, including viscosity, turbulence, shear stress, reversibility, compressibility, and hydrodynamic resistance. Students characterized flows in poly(dimethylsiloxane) microfluidic devices in the other two exercises, where they observed the mixing characteristics of laminar flows, and conservation of volumetric flow rate for incompressible flows. In surveys, the students self-reported increased knowledge of microfluidics, and an improved attitude toward science and nanotechnology.

Direct 3D-printing of cell-laden constructs in microfluidic architectures.

PubMed

Liu, Justin; Hwang, Henry H; Wang, Pengrui; Whang, Grace; Chen, Shaochen

2016-04-21

Microfluidic platforms have greatly benefited the biological and medical fields, however standard practices require a high cost of entry in terms of time and energy. The utilization of three-dimensional (3D) printing technologies has greatly enhanced the ability to iterate and build functional devices with unique functions. However, their inability to fabricate within microfluidic devices greatly increases the cost of producing several different devices to examine different scientific questions. In this work, a variable height micromixer (VHM) is fabricated using projection 3D-printing combined with soft lithography. Theoretical and flow experiments demonstrate that altering the local z-heights of VHM improved mixing at lower flow rates than simple geometries. Mixing of two fluids occurs as low as 320 μL min(-1) in VHM whereas the planar zigzag region requires a flow rate of 2.4 mL min(-1) before full mixing occurred. Following device printing, to further demonstrate the ability of this projection-based method, complex, user-defined cell-laden scaffolds are directly printed inside the VHM. The utilization of this unique ability to produce 3D tissue models within a microfluidic system could offer a unique platform for medical diagnostics and disease modeling.

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

Quantifying internal friction in unfolded and intrinsically disordered proteins with single-molecule spectroscopy

PubMed Central

Soranno, Andrea; Buchli, Brigitte; Nettels, Daniel; Cheng, Ryan R.; Müller-Späth, Sonja; Pfeil, Shawn H.; Hoffmann, Armin; Lipman, Everett A.; Makarov, Dmitrii E.; Schuler, Benjamin

2012-01-01

Internal friction, which reflects the “roughness” of the energy landscape, plays an important role for proteins by modulating the dynamics of their folding and other conformational changes. However, the experimental quantification of internal friction and its contribution to folding dynamics has remained challenging. Here we use the combination of single-molecule Förster resonance energy transfer, nanosecond fluorescence correlation spectroscopy, and microfluidic mixing to determine the reconfiguration times of unfolded proteins and investigate the mechanisms of internal friction contributing to their dynamics. Using concepts from polymer dynamics, we determine internal friction with three complementary, largely independent, and consistent approaches as an additive contribution to the reconfiguration time of the unfolded state. We find that the magnitude of internal friction correlates with the compactness of the unfolded protein: its contribution dominates the reconfiguration time of approximately 100 ns of the compact unfolded state of a small cold shock protein under native conditions, but decreases for more expanded chains, and approaches zero both at high denaturant concentrations and in intrinsically disordered proteins that are expanded due to intramolecular charge repulsion. Our results suggest that internal friction in the unfolded state will be particularly relevant for the kinetics of proteins that fold in the microsecond range or faster. The low internal friction in expanded intrinsically disordered proteins may have implications for the dynamics of their interactions with cellular binding partners. PMID:22492978

Quantifying internal friction in unfolded and intrinsically disordered proteins with single-molecule spectroscopy.

PubMed

Soranno, Andrea; Buchli, Brigitte; Nettels, Daniel; Cheng, Ryan R; Müller-Späth, Sonja; Pfeil, Shawn H; Hoffmann, Armin; Lipman, Everett A; Makarov, Dmitrii E; Schuler, Benjamin

2012-10-30

Internal friction, which reflects the "roughness" of the energy landscape, plays an important role for proteins by modulating the dynamics of their folding and other conformational changes. However, the experimental quantification of internal friction and its contribution to folding dynamics has remained challenging. Here we use the combination of single-molecule Förster resonance energy transfer, nanosecond fluorescence correlation spectroscopy, and microfluidic mixing to determine the reconfiguration times of unfolded proteins and investigate the mechanisms of internal friction contributing to their dynamics. Using concepts from polymer dynamics, we determine internal friction with three complementary, largely independent, and consistent approaches as an additive contribution to the reconfiguration time of the unfolded state. We find that the magnitude of internal friction correlates with the compactness of the unfolded protein: its contribution dominates the reconfiguration time of approximately 100 ns of the compact unfolded state of a small cold shock protein under native conditions, but decreases for more expanded chains, and approaches zero both at high denaturant concentrations and in intrinsically disordered proteins that are expanded due to intramolecular charge repulsion. Our results suggest that internal friction in the unfolded state will be particularly relevant for the kinetics of proteins that fold in the microsecond range or faster. The low internal friction in expanded intrinsically disordered proteins may have implications for the dynamics of their interactions with cellular binding partners.

Continuous synthesis of drug-loaded nanoparticles using microchannel emulsification and numerical modeling: effect of passive mixing

PubMed Central

Ortiz de Solorzano, Isabel; Uson, Laura; Larrea, Ane; Miana, Mario; Sebastian, Victor; Arruebo, Manuel

2016-01-01

By using interdigital microfluidic reactors, monodisperse poly(d,l lactic-co-glycolic acid) nanoparticles (NPs) can be produced in a continuous manner and at a large scale (~10 g/h). An optimized synthesis protocol was obtained by selecting the appropriated passive mixer and fluid flow conditions to produce monodisperse NPs. A reduced NP polydispersity was obtained when using the microfluidic platform compared with the one obtained with NPs produced in a conventional discontinuous batch reactor. Cyclosporin, an immunosuppressant drug, was used as a model to validate the efficiency of the microfluidic platform to produce drug-loaded monodisperse poly(d,l lactic-co-glycolic acid) NPs. The influence of the mixer geometries and temperatures were analyzed, and the experimental results were corroborated by using computational fluid dynamic three-dimensional simulations. Flow patterns, mixing times, and mixing efficiencies were calculated, and the model supported with experimental results. The progress of mixing in the interdigital mixer was quantified by using the volume fractions of the organic and aqueous phases used during the emulsification–evaporation process. The developed model and methods were applied to determine the required time for achieving a complete mixing in each microreactor at different fluid flow conditions, temperatures, and mixing rates. PMID:27524896

3D nanomolding and fluid mixing in micromixers with micro-patterned microchannel walls.

PubMed

Farshchian, Bahador; Amirsadeghi, Alborz; Choi, Junseo; Park, Daniel S; Kim, Namwon; Park, Sunggook

2017-01-01

Microfluidic devices where the microchannel walls were decorated with micro and nanostructures were fabricated using 3D nanomolding. Using 3D molded microfluidic devices with microchannel walls decorated with microscale gratings, the fluid mixing behavior was investigated through experiments and numerical simulation. The use of microscale gratings in the micromixer was predicated by the fact that large obstacles in a microchannel enhances the mixing performance. Slanted ratchet gratings on the channel walls resulted in a helical flow along the microchannel, thus increasing the interfacial area between fluids and cutting down the diffusion length. Increasing the number of walls decorated with continuous ratchet gratings intensified the strength of the helical flow, enhancing mixing further. When ratchet gratings on the surface of the top cover plate were aligned in a direction to break the continuity of gratings from the other three walls, a stack of two helical flows was formed one above each other. This work concludes that the 3D nanomolding process can be a cost-effective tool for scaling-up the fabrication of microfluidic mixers with improved mixing efficiencies.Graphical abstractIn this paper we show that a micromixer with patterned walls can be fabricated using 3D nanomolding and solvent-assisted bonding to manipulate the flow patterns to improve mixing.

Continuous synthesis of drug-loaded nanoparticles using microchannel emulsification and numerical modeling: effect of passive mixing.

PubMed

Ortiz de Solorzano, Isabel; Uson, Laura; Larrea, Ane; Miana, Mario; Sebastian, Victor; Arruebo, Manuel

2016-01-01

By using interdigital microfluidic reactors, monodisperse poly(d,l lactic-co-glycolic acid) nanoparticles (NPs) can be produced in a continuous manner and at a large scale (~10 g/h). An optimized synthesis protocol was obtained by selecting the appropriated passive mixer and fluid flow conditions to produce monodisperse NPs. A reduced NP polydispersity was obtained when using the microfluidic platform compared with the one obtained with NPs produced in a conventional discontinuous batch reactor. Cyclosporin, an immunosuppressant drug, was used as a model to validate the efficiency of the microfluidic platform to produce drug-loaded monodisperse poly(d,l lactic-co-glycolic acid) NPs. The influence of the mixer geometries and temperatures were analyzed, and the experimental results were corroborated by using computational fluid dynamic three-dimensional simulations. Flow patterns, mixing times, and mixing efficiencies were calculated, and the model supported with experimental results. The progress of mixing in the interdigital mixer was quantified by using the volume fractions of the organic and aqueous phases used during the emulsification-evaporation process. The developed model and methods were applied to determine the required time for achieving a complete mixing in each microreactor at different fluid flow conditions, temperatures, and mixing rates.

Droplet-based microfluidics platform for measurement of rapid erythrocyte water transport

PubMed Central

Jin, Byung-Ju; Esteva-Font, Cristina; Verkman, A.S.

2015-01-01

Cell membrane water permeability is an important determinant of epithelial fluid secretion, tissue swelling, angiogenesis, tumor spread and other biological processes. Cellular water channels, the aquaporins, are important drug targets. Water permeability is generally measured from the kinetics of cell volume change in response to an osmotic gradient. Here, we developed a microfluidics platform in which cells expressing a cytoplasmic, volume-sensing fluorescent dye are rapidly subjected to an osmotic gradient by solution mixing inside a ~ 0.1 nL droplet surrounded by oil. Solution mixing time was < 10 ms. Osmotic water permeability was deduced from a single, time-integrated fluorescence image of an observation area in which time after mixing is determined by spatial position. Water permeability was accurately measured in aquaporin-expressing erythrocytes with half-times for osmotic equilibration down to < 50 ms. Compared with conventional water permeability measurements using costly stopped-flow instrumentation, the microfluidics platform here utilizes sub-microliter blood sample volume, does not suffer from mixing artifact, and replaces challenging kinetic measurements by a single image capture using a standard laboratory fluorescence microscope. PMID:26159099

A Microfluidic System with Surface Patterning for Investigating Cavitation Bubble(s)-Cell Interaction and the Resultant Bioeffects at the Single-cell Level.

PubMed

Li, Fenfang; Yuan, Fang; Sankin, Georgy; Yang, Chen; Zhong, Pei

2017-01-10

In this manuscript, we first describe the fabrication protocol of a microfluidic chip, with gold dots and fibronectin-coated regions on the same glass substrate, that precisely controls the generation of tandem bubbles and individual cells patterned nearby with well-defined locations and shapes. We then demonstrate the generation of tandem bubbles by using two pulsed lasers illuminating a pair of gold dots with a few-microsecond time delay. We visualize the bubble-bubble interaction and jet formation by high-speed imaging and characterize the resultant flow field using particle image velocimetry (PIV). Finally, we present some applications of this technique for single cell analysis, including cell membrane poration with macromolecule uptake, localized membrane deformation determined by the displacements of attached integrin-binding beads, and intracellular calcium response from ratiometric imaging. Our results show that a fast and directional jetting flow is produced by the tandem bubble interaction, which can impose a highly localized shear stress on the surface of a cell grown in close proximity. Furthermore, different bioeffects can be induced by altering the strength of the jetting flow by adjusting the standoff distance from the cell to the tandem bubbles.

A novel micromixer based on the alternating current-flow field effect transistor.

PubMed

Wu, Yupan; Ren, Yukun; Tao, Ye; Hou, Likai; Hu, Qingming; Jiang, Hongyuan

2016-12-20

Induced-charge electroosmosis (ICEO) phenomena have been attracting considerable attention as a means for pumping and mixing in microfluidic systems with the advantage of simple structures and low-energy consumption. We propose the first effort to exploit a fixed-potential ICEO flow around a floating electrode for microfluidic mixing. In analogy with the field effect transistor (FET) in microelectronics, the floating electrode act as a "gate" electrode for generating asymmetric ICEO flow and thus the device is called an AC-flow FET (AC-FFET). We take advantage of a tandem electrode configuration containing two biased center metal strips arranged in sequence at the bottom of the channel to generate asymmetric vortexes. The current device is manufactured on low-cost glass substrates via an easy and reliable process. Mixing experiments were conducted in the proposed device and the comparison between simulation and experimental results was also carried out, which indicates that the micromixer permits an efficient mixing effect. The mixing performance can be further enhanced by the application of a suitable phase difference between the driving electrode and the gate electrode or a square wave signal. Finally, we performed a critical analysis of the proposed micromixer in comparison with different mixer designs using a comparative mixing index (CMI). The novel methods put forward here offer a simple solution to mixing issues in microfluidic systems.

A "twisted" microfluidic mixer suitable for a wide range of flow rate applications.

PubMed

Sivashankar, Shilpa; Agambayev, Sumeyra; Mashraei, Yousof; Li, Er Qiang; Thoroddsen, Sigurdur T; Salama, Khaled Nabil

2016-05-01

This paper proposes a new "twisted" 3D microfluidic mixer fabricated by a laser writing/microfabrication technique. Effective and efficient mixing using the twisted micromixers can be obtained by combining two general chaotic mixing mechanisms: splitting/recombining and chaotic advection. The lamination of mixer units provides the splitting and recombination mechanism when the quadrant of circles is arranged in a two-layered serial arrangement of mixing units. The overall 3D path of the microchannel introduces the advection. An experimental investigation using chemical solutions revealed that these novel 3D passive microfluidic mixers were stable and could be operated at a wide range of flow rates. This micromixer finds application in the manipulation of tiny volumes of liquids that are crucial in diagnostics. The mixing performance was evaluated by dye visualization, and using a pH test that determined the chemical reaction of the solutions. A comparison of the tornado-mixer with this twisted micromixer was made to evaluate the efficiency of mixing. The efficiency of mixing was calculated within the channel by acquiring intensities using ImageJ software. Results suggested that efficient mixing can be obtained when more than 3 units were consecutively placed. The geometry of the device, which has a length of 30 mm, enables the device to be integrated with micro total analysis systems and other lab-on-chip devices.

A “twisted” microfluidic mixer suitable for a wide range of flow rate applications

PubMed Central

Sivashankar, Shilpa; Agambayev, Sumeyra; Mashraei, Yousof; Li, Er Qiang; Thoroddsen, Sigurdur T.; Salama, Khaled Nabil

2016-01-01

This paper proposes a new “twisted” 3D microfluidic mixer fabricated by a laser writing/microfabrication technique. Effective and efficient mixing using the twisted micromixers can be obtained by combining two general chaotic mixing mechanisms: splitting/recombining and chaotic advection. The lamination of mixer units provides the splitting and recombination mechanism when the quadrant of circles is arranged in a two-layered serial arrangement of mixing units. The overall 3D path of the microchannel introduces the advection. An experimental investigation using chemical solutions revealed that these novel 3D passive microfluidic mixers were stable and could be operated at a wide range of flow rates. This micromixer finds application in the manipulation of tiny volumes of liquids that are crucial in diagnostics. The mixing performance was evaluated by dye visualization, and using a pH test that determined the chemical reaction of the solutions. A comparison of the tornado-mixer with this twisted micromixer was made to evaluate the efficiency of mixing. The efficiency of mixing was calculated within the channel by acquiring intensities using ImageJ software. Results suggested that efficient mixing can be obtained when more than 3 units were consecutively placed. The geometry of the device, which has a length of 30 mm, enables the device to be integrated with micro total analysis systems and other lab-on-chip devices. PMID:27453767

A “dry and wet hybrid” lithography technique for multilevel replication templates: Applications to microfluidic neuron culture and two-phase global mixing

PubMed Central

Paul, Debjani; Saias, Laure; Pedinotti, Jean-Cedric; Chabert, Max; Magnifico, Sebastien; Pallandre, Antoine; De Lambert, Bertrand; Houdayer, Claude; Brugg, Bernard; Peyrin, Jean-Michel; Viovy, Jean-Louis

2011-01-01

A broad range of microfluidic applications, ranging from cell culture to protein crystallization, requires multilevel devices with different heights and feature sizes (from micrometers to millimeters). While state-of-the-art direct-writing techniques have been developed for creating complex three-dimensional shapes, replication molding from a multilevel template is still the preferred method for fast prototyping of microfluidic devices in the laboratory. Here, we report on a “dry and wet hybrid” technique to fabricate multilevel replication molds by combining SU-8 lithography with a dry film resist (Ordyl). We show that the two lithography protocols are chemically compatible with each other. Finally, we demonstrate the hybrid technique in two different microfluidic applications: (1) a neuron culture device with compartmentalization of different elements of a neuron and (2) a two-phase (gas-liquid) global micromixer for fast mixing of a small amount of a viscous liquid into a larger volume of a less viscous liquid. PMID:21559239

Universal microfluidic automaton for autonomous sample processing: application to the Mars Organic Analyzer.

PubMed

Kim, Jungkyu; Jensen, Erik C; Stockton, Amanda M; Mathies, Richard A

2013-08-20

A fully integrated multilayer microfluidic chemical analyzer for automated sample processing and labeling, as well as analysis using capillary zone electrophoresis is developed and characterized. Using lifting gate microfluidic control valve technology, a microfluidic automaton consisting of a two-dimensional microvalve cellular array is fabricated with soft lithography in a format that enables facile integration with a microfluidic capillary electrophoresis device. The programmable sample processor performs precise mixing, metering, and routing operations that can be combined to achieve automation of complex and diverse assay protocols. Sample labeling protocols for amino acid, aldehyde/ketone and carboxylic acid analysis are performed automatically followed by automated transfer and analysis by the integrated microfluidic capillary electrophoresis chip. Equivalent performance to off-chip sample processing is demonstrated for each compound class; the automated analysis resulted in a limit of detection of ~16 nM for amino acids. Our microfluidic automaton provides a fully automated, portable microfluidic analysis system capable of autonomous analysis of diverse compound classes in challenging environments.

Microfluidic distillation chip for methanol concentration detection.

PubMed

Wang, Yao-Nan; Liu, Chan-Chiung; Yang, Ruey-Jen; Ju, Wei-Jhong; Fu, Lung-Ming

2016-03-17

An integrated microfluidic distillation system is proposed for separating a mixed ethanol-methanol-water solution into its constituent components. The microfluidic chip is fabricated using a CO2 laser system and comprises a serpentine channel, a boiling zone, a heating zone, and a cooled collection chamber filled with de-ionized (DI) water. In the proposed device, the ethanol-methanol-water solution is injected into the microfluidic chip and driven through the serpentine channel and into the collection chamber by means of a nitrogen carrier gas. Following the distillation process, the ethanol-methanol vapor flows into the collection chamber and condenses into the DI water. The resulting solution is removed from the collection tank and reacted with a mixed indicator. Finally, the methanol concentration is inversely derived from the absorbance measurements obtained using a spectrophotometer. The experimental results show the proposed microfluidic system achieves an average methanol distillation efficiency of 97%. The practicality of the proposed device is demonstrated by detecting the methanol concentrations of two commercial fruit wines. It is shown that the measured concentration values deviate by no more than 3% from those obtained using a conventional bench top system. Copyright © 2016 Elsevier B.V. All rights reserved.

Fluid mixing in droplet-based microfluidics with T junction and convergent-divergent sinusoidal microchannels.

PubMed

Yang, Li; Li, Shanshan; Liu, Jixiao; Cheng, Jingmeng

2018-02-01

To explore and utilize the advantages of droplet-based microfluidics, hydrodynamics, and mixing process within droplets traveling though the T junction channel and convergent-divergent sinusoidal microchannels are studied by numerical simulations and experiments, respectively. In the T junction channel, the mixing efficiency is significantly influenced by the twirling effect, which controls the initial distributions of the mixture during the droplet formation stage. Therefore, the internal recirculating flow can create a convection mechanism, thus improving mixing. The twirling effect is noticeably influenced by the velocity of the continuous phase; in the sinusoidal channel, the Dean vortices and droplet deformation are induced by centrifugal force and alternative velocity gradient, thus enhancing the mixing efficiency. The best mixing occurred when the droplet size is comparable with the channel width. Finally, we propose a unique optimized structure, which includes a T junction inlet joined to a sinusoidal channel. In this structure, the mixing of fluids in the droplets follows two routes: One is the twirling effect and symmetric recirculation flow in the straight channel. The other is the asymmetric recirculation and droplet deformation in the winding and variable cross-section. Among the three structures, the optimized structure has the best mixing efficiency at the shortest mixing time (0.25 ms). The combination of the twirling effect, variable cross-section effect, and Dean vortices greatly intensifies the chaotic flow. This study provides the insight of the mixing process and may benefit the design and operations of droplet-based microfluidics. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Magnetically Actuated Cilia for Microfluidic Manipulation

NASA Astrophysics Data System (ADS)

Hanasoge, Srinivas; Owen, Drew; Ballard, Matt; Hesketh, Peter J.; Alexeev, Alexander; Woodruff School of Mechanical Engineering Collaboration; Petit InstituteBioengineering; Biosciences Collaboration

2015-11-01

We demonstrate magnetic micro-cilia based microfluidic mixing and capture techniques. For this, we use a simple and easy to fabricate high aspect ratio cilia, which are actuated magnetically. These micro-features are fabricated by evaporating NiFe alloy at room temperature, on to patterned photoresist. The evaporated alloy curls upwards when the seed layer is removed to release the cilia, thus making a free standing `C' shaped magnetic microstructure. This is actuated using an external electromagnet or a rotating magnet. The artificial cilia can be actuated upto 20Hz. We demonstrate the active mixing these cilia can produce in the microchannel. Also, we demonstrate the capture of target species in a sample using these fast oscillating cilia. The surface of the cilia is functionalized by streptavidin which binds to biotin labelled fluorescent microspheres and mimic the capture of bacteria. We show very high capture efficiencies by using these methods. These simple to fabricate micro cilia can easily be incorporated into many microfluidic systems which require high mixing and capture efficiencies.

Continuous nanoparticle production by microfluidic-based emulsion, mixing and crystallization

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

Su, Y.-F.; Kim, H.; Kovenklioglu, S.

2007-09-15

BaSO{sub 4} and 2,2'-dipyridylamine (DPA) nanoparticles were synthesized as reactive crystallization and anti-solvent recrystallization examples, respectively, of using the microfluidic-based emulsion and mixing approach as a new avenue of continuously producing inorganic and organic nanoparticles. BaSO{sub 4} nanoparticles in the size range of 15-100 nm were reactively precipitated within the confinement of an aqueous droplet which was coalesced from two separate aqueous droplets containing BaCl{sub 2} and (NH{sub 4}){sub 2}SO{sub 4} using a three T-junction micromixer configuration constructed with commercially available simple tubing and fitting supplies. Also, DPA nanoparticles of about 200 nm were crystallized by combining DPA+ethanol and watermore » droplets using the same micromixer configuration. - Graphical abstract: BaSO{sub 4} and 2,2'-dipyridylamine (DPA) nanoparticles were synthesized as reactive crystallization and anti-solvent recrystallization examples, respectively, of using the microfluidic-based emulsion and mixing approach as a new avenue of continuously producing inorganic and organic nanoparticles.« less

Chemistry in Microfluidic Channels

ERIC Educational Resources Information Center

Chia, Matthew C.; Sweeney, Christina M.; Odom, Teri W.

2011-01-01

General chemistry introduces principles such as acid-base chemistry, mixing, and precipitation that are usually demonstrated in bulk solutions. In this laboratory experiment, we describe how chemical reactions can be performed in a microfluidic channel to show advanced concepts such as laminar fluid flow and controlled precipitation. Three sets of…

Multichannel Mars Organic Analyzer (McMOA): Microfluidic Networks for the Automated In Situ Microchip Electrophoretic Analysis of Organic Biomarkers on Mars

NASA Astrophysics Data System (ADS)

Chiesl, T. N.; Benhabib, M.; Stockton, A. M.; Mathies, R. A.

2010-04-01

We present the Multichannel Mars Organic Analyzer (McMOA) for the analysis of Amino Acids, PAHs, and Oxidized Carbon. Microfluidic architecures integrating automated metering, mixing, on chip reactions, and serial dilutions are also discussed.

Continuous microfluidic assembly of biodegradable poly(beta-amino ester)/DNA nanoparticles for enhanced gene delivery.

PubMed

Wilson, David R; Mosenia, Arman; Suprenant, Mark P; Upadhya, Rahul; Routkevitch, Denis; Meyer, Randall A; Quinones-Hinojosa, Alfredo; Green, Jordan J

2017-06-01

Translation of biomaterial-based nanoparticle formulations to the clinic faces significant challenges including efficacy, safety, consistency and scale-up of manufacturing, and stability during long-term storage. Continuous microfluidic fabrication of polymeric nanoparticles has the potential to alleviate the challenges associated with manufacture, while offering a scalable solution for clinical level production. Poly(beta-amino esters) (PBAE)s are a class of biodegradable cationic polymers that self-assemble with anionic plasmid DNA to form polyplex nanoparticles that have been shown to be effective for transfecting cancer cells specifically in vitro and in vivo. Here, we demonstrate the use of a microfluidic device for the continuous and scalable production of PBAE/DNA nanoparticles followed by lyophilization and long term storage that results in improved in vitro efficacy in multiple cancer cell lines compared to nanoparticles produced by bulk mixing as well as in comparison to widely used commercially available transfection reagents polyethylenimine and Lipofectamine® 2000. We further characterized the nanoparticles using nanoparticle tracking analysis (NTA) to show that microfluidic mixing resulted in fewer DNA-free polymeric nanoparticles compared to those produced by bulk mixing. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1813-1825, 2017. © 2017 Wiley Periodicals, Inc.

Microsecond Molecular Dynamics Simulations of Lipid Mixing

PubMed Central

2015-01-01

Molecular dynamics (MD) simulations of membranes are often hindered by the slow lateral diffusion of lipids and the limited time scale of MD. In order to study the dynamics of mixing and characterize the lateral distribution of lipids in converged mixtures, we report microsecond-long all-atom MD simulations performed on the special-purpose machine Anton. Two types of mixed bilayers, POPE:POPG (3:1) and POPC:cholesterol (2:1), as well as a pure POPC bilayer, were each simulated for up to 2 μs. These simulations show that POPE:POPG and POPC:cholesterol are each fully miscible at the simulated conditions, with the final states of the mixed bilayers similar to a random mixture. By simulating three POPE:POPG bilayers at different NaCl concentrations (0, 0.15, and 1 M), we also examined the effect of salt concentration on lipid mixing. While an increase in NaCl concentration is shown to affect the area per lipid, tail order, and lipid lateral diffusion, the final states of mixing remain unaltered, which is explained by the largely uniform increase in Na+ ions around POPE and POPG. Direct measurement of water permeation reveals that the POPE:POPG bilayer with 1 M NaCl has reduced water permeability compared with those at zero or low salt concentration. Our calculations provide a benchmark to estimate the convergence time scale of all-atom MD simulations of lipid mixing. Additionally, equilibrated structures of POPE:POPG and POPC:cholesterol, which are frequently used to mimic bacterial and mammalian membranes, respectively, can be used as starting points of simulations involving these membranes. PMID:25237736

The golden-mean surface pattern to enhance flow mixing in micro-channel.

PubMed

Wang, J F; Liu, Y; Xu, Y S

2009-04-01

Mixing of analytes and reagents in microfluidic devices is often crucial to the effective functioning of lab-on-a-chip. It is possible to affect the mixing in microfluidics by intelligently controlling the thermodynamic and chemical properties of the substrate surface. Numerous studies have shown that the phase behavior of mixtures is significantly affected by surface properties of microfluidics. For example, the phase separation between the fluids can be affected by heterogeneous patterns on the substrate. The patterned substrate can offer an effective means to control fluid behavior and in turn to enhance mixing. The golden mean is a ratio that is present in the growth patterns of many biological systems--the spiral formed by a shell or the curve of a fern, for example. The golden mean or golden section was derived by the ancient Greeks. Like "pi" the golden mean ratio is an irrational number 1.618, or (square root{5} + 1) / 2. It was found that the golden mean was an optimum ratio in natural convection heat transfer problem (Liu and Phan-Thien, Numer Heat Transf 37:613-630, 2000). In this study, we numerically studied the effect of optimum surface pattern on mixing in a micro channel and found that the flow oscillation and chaotic mixing were enhanced apparently when the ratio of hydrophobic and hydrophilic boundary follows the golden mean.

A microfluidic device for studying cell signaling with multiple inputs and adjustable amplitudes and frequencies

NASA Astrophysics Data System (ADS)

Ningsih, Zubaidah; Chon, James W. M.; Clayton, Andrew H. A.

2013-12-01

Cell function is largely controlled by an intricate web of macromolecular interactions called signaling networks. It is known that the type and the intensity (concentration) of stimulus affect cell behavior. However, the temporal aspect of the stimulus is not yet fully understood. Moreover, the process of distinguishing between two stimuli by a cell is still not clear. A microfluidic device enables the delivery of a precise and exact stimulus to the cell due to the laminar flow established inside its micro-channel. The slow stream delivers a constant stimulus which is adjustable according to the experiment set up. Moreover, with controllable inputs, microfluidic facilitates the stimuli delivery according to a certain pattern with adjustable amplitude, frequency and phase. Several designs of PDMS microfluidic device has been produced in this project via photolithography and soft lithography processes. To characterize the microfluidic performance, two experiments has been conducted. First, by comparing the fluorescence intensity and the lifetime of fluorescein in the present of KI, mixing extent between two inputs was observed using Frequency Lifetime Imaging Microscopy (FLIM). Furthermore, the input-output relationship of fluorescein concentration delivered was also drawn to characterize the amplitude, frequency and phase of the inputs. Second experiment involved the cell culturing inside microfluidic. Using NG108-15 cells, proliferation and differentiation were observed based on the cell number and cell physiological changes. Our results demonstrate that hurdle design gives 86% mixing of fluorescein and buffer. Relationship between inputoutput fluorescein concentrations delivered has also been demonstrated and cells were successfully cultured inside the microfluidic.

Integrated microfluidic chip for rapid DNA digestion and time-resolved capillary electrophoresis analysis

PubMed Central

Lin, Che-Hsin; Wang, Yao-Nan; Fu, Lung-Ming

2012-01-01

An integrated microfluidic chip is proposed for rapid DNA digestion and time-resolved capillary electrophoresis (CE) analysis. The chip comprises two gel-filled chambers for DNA enrichment and purification, respectively, a T-form micromixer for DNA/restriction enzyme mixing, a serpentine channel for DNA digestion reaction, and a CE channel for on-line capillary electrophoresis analysis. The DNA and restriction enzyme are mixed electroomostically using a pinched-switching DC field. The experimental and numerical results show that a mixing performance of 97% is achieved within a distance of 1 mm from the T-junction when a driving voltage of 90 V/cm and a switching frequency of 4 Hz are applied. Successive mixing digestion and capillary electrophoresis operation clearly present the changes on digesting φx-174 DNA in different CE runs. The time-resolved electropherograms show that the proposed device enables a φx-174 DNA sample comprising 11 fragments to be concentrated and analyzed within 24 min. Overall, the results presented in this study show that the proposed microfluidic chip provides a rapid and effective tool for DNA digestion and CE analysis applications. PMID:22662085

Investigating fast enzyme-DNA kinetics using multidimensional fluorescence imaging and microfluidics

NASA Astrophysics Data System (ADS)

Robinson, Tom; Manning, Hugh B.; Dunsby, Christopher; Neil, Mark A. A.; Baldwin, Geoff S.; de Mello, Andrew J.; French, Paul M. W.

2010-02-01

We have developed a rapid microfluidic mixing device to image fast kinetics. To verify the performance of the device it was simulated using computational fluid dynamics (CFD) and the results were directly compared to experimental fluorescence lifetime imaging (FLIM) measurements. The theoretical and measured mixing times of the device were found to be in agreement over a range of flow rates. This mixing device is being developed with the aim of analysing fast enzyme kinetics in the sub-millisecond time domain, which cannot be achieved with conventional macro-stopped flow devices. Here we have studied the binding of a DNA repair enzyme, uracil DNA glycosylase (UDG), to a fluorescently labelled DNA substrate. Bulk phase fluorescence measurements have been used to measure changes on binding: it was found that the fluorescence lifetime increased along with an increase in the polarisation anisotropy and rotational correlation time. Analysis of the same reaction in the microfluidic mixer by CFD enabled us to predict the mixing time of the device to be 46 μs, more than 20 times faster than current stopped-flow techniques. We also demonstrate that it is possible to image UDG-DNA interactions within the micromixer using the signal changes observed from the multidimensional spectrofluorometer.

Reactions in Droplets in Microfluidic Channels

PubMed Central

Song, Helen; Chen, Delai L.; Ismagilov, Rustem F.

2006-01-01

Fundamental and applied research in chemistry and biology benefits from opportunities provided by droplet-based microfluidic systems. These systems enable the miniaturization of reactions by compartmentalizing reactions in droplets of femoliter to microliter volumes. Compartmentalization in droplets provides rapid mixing of reagents, control of the timing of reactions on timescales from milliseconds to months, control of interfacial properties, and the ability to synthesize and transport solid reagents and products. Droplet-based microfluidics can help to enhance and accelerate chemical and biochemical screening, protein crystallization, enzymatic kinetics, and assays. Moreover, the control provided by droplets in microfluidic devices can lead to new scientific methods and insights. PMID:17086584

Smart swelling biopolymer microparticles by a microfluidic approach: synthesis, in situ encapsulation and controlled release.

PubMed

Fang, Aiping; Cathala, Bernard

2011-01-01

This paper reports a microfluidic synthesis of biopolymer microparticles aiming at smart swelling. Monodisperse aqueous emulsion droplets comprising biopolymer and its cross-linking agent were formed in mineral oil and solidified in the winding microfluidic channels by in situ chaotic mixing, which resulted in internal chemical gelation for hydrogels. The achievement of pectin microparticles from in situ mixing pectin with its cross-linking agent, calcium ions, successfully demonstrates the reliability of this microfluidic synthesis approach. In order to achieve hydrogels with smart swelling, the following parameters and their impacts on the swelling behaviour, stability and morphology of microparticles were investigated: (1) the type of biopolymers (alginate or mixture of alginate and carboxymethylcellulose, A-CMC); (2) rapid mixing; (3) concentration and type of cross-linking agent. Superabsorbent microparticles were obtained from A-CMC mixture by using ferric chloride as an additional external cross-linking agent. The in situ encapsulation of a model protein, bovine serum albumin (BSA), was also carried out. As a potential protein drug-delivery system, the BSA release behaviours of the biopolymer particles were studied in simulated gastric and intestinal fluids. Compared with alginate and A-CMC microparticles cross-linked with calcium ions, A-CMC microparticles cross-linked with both calcium and ferric ions demonstrate a significantly delayed release. The controllable release profile, the facile encapsulation as well as their biocompatibility, biodegradability, mucoadhesiveness render this microfluidic approach promising in achieving biopolymer microparticles as protein drug carrier for site-specific release. Copyright © 2010 Elsevier B.V. All rights reserved.

Inertio-elastic mixing in a straight microchannel with side wells

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

Hong, Sun Ok; Cooper-White, Justin J.; School of Chemical Engineering, University of Queensland, St Lucia, 4072 QLD

Mixing remains a challenging task in microfluidic channels because of their inherently small length scale. In this work, we propose an efficient microfluidic mixer based on the chaotic vortex dynamics of a viscoelastic flow in a straight channel with side wells. When the inertia and elasticity of a dilute polymer solution are balanced (i.e., the Reynolds number Re and Weissenberg number Wi are both on the order of 10{sup 1}), chaotic vortices appear in the side wells (inertio-elastic flow instability), enhancing the mixing of adjacent fluid streams. However, there is no chaotic vortex motion in Newtonian flows for any flowmore » rate. Efficient mixing by such an inertio-elastic instability is found to be relevant for a wide range of Re values.« less

Passive Microfluidic device for Sub Millisecond Mixing

PubMed Central

McMahon, Jay; Mohamed, Hisham; Barnard, David; Shaikh, Tanvir R.; Mannella, Carmen A.; Wagenknecht, Terence; Lu, Toh-Ming

2009-01-01

We report the investigation of a novel microfluidic mixing device to achieve submillisecond mixing. The micromixer combines two fluid streams of several microliters per second into a mixing compartment integrated with two T- type premixers and 4 butterfly-shaped in-channel mixing elements. We have employed three dimensional fluidic simulations to evaluate the mixing efficiency, and have constructed physical devices utilizing conventional microfabrication techniques. The simulation indicated thorough mixing at flow rate as low as 6 µL/s. The corresponding mean residence time is 0.44 ms for 90% of the particles simulated, or 0.49 ms for 95% of the particles simulated, respectively. The mixing efficiency of the physical device was also evaluated using fluorescein dye solutions and FluoSphere-red nanoparticles suspensions. The constructed micromixers achieved thorough mixing at the same flow rate of 6 µL/s, with the mixing indices of 96% ± 1%, and 98% ± 1% for the dye and the nanoparticle, respectively. The experimental results are consistent with the simulation data. The device demonstrated promising capabilities for time resolved studies for macromolecular dynamics of biological macromolecules. PMID:20161619

Coaxial microreactor for particle synthesis

DOEpatents

Bartsch, Michael; Kanouff, Michael P; Ferko, Scott M; Crocker, Robert W; Wally, Karl

2013-10-22

A coaxial fluid flow microreactor system disposed on a microfluidic chip utilizing laminar flow for synthesizing particles from solution. Flow geometries produced by the mixing system make use of hydrodynamic focusing to confine a core flow to a small axially-symmetric, centrally positioned and spatially well-defined portion of a flow channel cross-section to provide highly uniform diffusional mixing between a reactant core and sheath flow streams. The microreactor is fabricated in such a way that a substantially planar two-dimensional arrangement of microfluidic channels will produce a three-dimensional core/sheath flow geometry. The microreactor system can comprise one or more coaxial mixing stages that can be arranged singly, in series, in parallel or nested concentrically in parallel.

Surface acoustic wave microfluidics

PubMed Central

Ding, Xiaoyun; Li, Peng; Lin, Sz-Chin Steven; Stratton, Zackary S.; Nama, Nitesh; Guo, Feng; Slotcavage, Daniel; Mao, Xiaole; Shi, Jinjie; Costanzo, Francesco; Huang, Tony Jun

2014-01-01

The recent introduction of surface acoustic wave (SAW) technology onto lab-on-a-chip platforms has opened a new frontier in microfluidics. The advantages provided by such SAW microfluidics are numerous: simple fabrication, high biocompatibility, fast fluid actuation, versatility, compact and inexpensive devices and accessories, contact-free particle manipulation, and compatibility with other microfluidic components. We believe that these advantages enable SAW microfluidics to play a significant role in a variety of applications in biology, chemistry, engineering, and medicine. In this review article, we discuss the theory underpinning SAWs and their interactions with particles and the contacting fluids in which they are suspended. We then review the SAW-enabled microfluidic devices demonstrated to date, starting with devices that accomplish fluid mixing and transport through the use of travelling SAW; we follow that by reviewing the more recent innovations achieved with standing SAW that enable such actions as particle/cell focusing, sorting, and patterning. Finally, we look forward and appraise where the discipline of SAW microfluidics could go next. PMID:23900527

Microsecond time-scale kinetics of transient biochemical reactions

PubMed Central

Mitić, Sandra; Strampraad, Marc J. F.; de Vries, Simon

2017-01-01

To afford mechanistic studies in enzyme kinetics and protein folding in the microsecond time domain we have developed a continuous-flow microsecond time-scale mixing instrument with an unprecedented dead-time of 3.8 ± 0.3 μs. The instrument employs a micro-mixer with a mixing time of 2.7 μs integrated with a 30 mm long flow-cell of 109 μm optical path length constructed from two parallel sheets of silver foil; it produces ultraviolet-visible spectra that are linear in absorbance up to 3.5 with a spectral resolution of 0.4 nm. Each spectrum corresponds to a different reaction time determined by the distance from the mixer outlet, and by the fluid flow rate. The reaction progress is monitored in steps of 0.35 μs for a total duration of ~600 μs. As a proof of principle the instrument was used to study spontaneous protein refolding of pH-denatured cytochrome c. Three folding intermediates were determined: after a novel, extremely rapid initial phase with τ = 4.7 μs, presumably reflecting histidine re-binding to the iron, refolding proceeds with time constants of 83 μs and 345 μs to a coordinatively saturated low-spin iron form in quasi steady state. The time-resolution specifications of our spectrometer for the first time open up the general possibility for comparison of real data and molecular dynamics calculations of biomacromolecules on overlapping time scales. PMID:28973014

A compact model for electroosmotic flows in microfluidic devices

NASA Astrophysics Data System (ADS)

Qiao, R.; Aluru, N. R.

2002-09-01

A compact model to compute flow rate and pressure in microfluidic devices is presented. The microfluidic flow can be driven by either an applied electric field or a combined electric field and pressure gradient. A step change in the ζ-potential on a channel wall is treated by a pressure source in the compact model. The pressure source is obtained from the pressure Poisson equation and conservation of mass principle. In the proposed compact model, the complex fluidic network is simplified by an electrical circuit. The compact model can predict the flow rate, pressure distribution and other basic characteristics in microfluidic channels quickly with good accuracy when compared to detailed numerical simulation. Using the compact model, fluidic mixing and dispersion control are studied in a complex microfluidic network.

Experimental and theoretical characterization of an AC electroosmotic micromixer.

PubMed

Sasaki, Naoki; Kitamori, Takehiko; Kim, Haeng-Boo

2010-01-01

We have reported on a novel microfluidic mixer based on AC electroosmosis. To elucidate the mixer characteristics, we performed detailed measurements of mixing under various experimental conditions including applied voltage, frequency and solution viscosity. The results are discussed through comparison with results obtained from a theoretical model of AC electroosmosis. As predicted from the theoretical model, we found that a larger voltage (approximately 20 V(p-p)) led to more rapid mixing, while the dependence of the mixing on frequency (1-5 kHz) was insignificant under the present experimental conditions. Furthermore, the dependence of the mixing on viscosity was successfully explained by the theoretical model, and the applicability of the mixer in viscous solution (2.83 mPa s) was confirmed experimentally. By using these results, it is possible to estimate the mixing performance under given conditions. These estimations can provide guidelines for using the mixer in microfluidic chemical analysis.

[Synthesis of hollow titania microspheres by using microfluidic droplet-template].

PubMed

Ma, Jingyun; Jiang, Lei; Qin, Jianhu

2011-09-01

Droplet-based microfluidics is of great interest due to its particular characteristics compared with the conventional methods, such as reduced reagent consumption, rapid mixing, high-throughput, shape controlled, etc. A novel method using microfluidic droplet as soft template for the synthesis of hollow titania microspheres was developed. A typical polydimethylsiloxane (PDMS) microfluidic device containing "flow-focusing" geometry was used to generate water/oil (W/O) droplet. The mechanism for the hollow structure formation was based on the interfacial hydrolysis reaction between the continuous phase containing titanium butoxide precursor and the dispersed containing water. The continuous phase mixed with butanol was added in the downstream of the channel after the hydrolysis reaction. This step was used for drawing the water out of the microgels for further hydrolysis. The microgels obtained through a glass pipe integrated were washed, dried under vacuum and calcined after aging for a certain time. The fluorescence and scanning electron microscope (SEM) image of the microspheres indicated the hollow structure and the thickness of the shell. In addition, these microspheres with thin shell (about 2 microm) were apt to rupture and collapse. Droplet-based microfluidic offered a gentle and size-controllable manner to moderate this problem. Moreover, it has potential applications in photocatalysis combined with some modification realized on the chip simultaneously.

Optical chromatographic sample separation of hydrodynamically focused mixtures

PubMed Central

Terray, A.; Hebert, C. G.; Hart, S. J.

2014-01-01

Optical chromatography relies on the balance between the opposing optical and fluid drag forces acting on a particle. A typical configuration involves a loosely focused laser directly counter to the flow of particle-laden fluid passing through a microfluidic device. This equilibrium depends on the intrinsic properties of the particle, including size, shape, and refractive index. As such, uniquely fine separations are possible using this technique. Here, we demonstrate how matching the diameter of a microfluidic flow channel to that of the focusing laser in concert with a unique microfluidic platform can be used as a method to fractionate closely related particles in a mixed sample. This microfluidic network allows for a monodisperse sample of both polystyrene and poly(methyl methacrylate) spheres to be injected, hydrodynamically focused, and completely separated. To test the limit of separation, a mixed polystyrene sample containing two particles varying in diameter by less than 0.5 μm was run in the system. The analysis of the resulting separation sets the framework for continued work to perform ultra-fine separations. PMID:25553179

Passive Mixing Capabilities of Micro- and Nanofibres When Used in Microfluidic Systems.

PubMed

Matlock-Colangelo, Lauren; Colangelo, Nicholas W; Fenzl, Christoph; Frey, Margaret W; Baeumner, Antje J

2016-08-05

Nanofibres are increasingly being used in the field of bioanalytics due to their large surface-area-to-volume ratios and easy-to-functionalize surfaces. To date, nanofibres have been studied as effective filters, concentrators, and immobilization matrices within microfluidic devices. In addition, they are frequently used as optical and electrochemical transduction materials. In this work, we demonstrate that electrospun nanofibre mats cause appreciable passive mixing and therefore provide dual functionality when incorporated within microfluidic systems. Specifically, electrospun nanofibre mats were integrated into Y-shaped poly(methyl methacrylate) microchannels and the degree of mixing was quantified using fluorescence microscopy and ImageJ analysis. The degree of mixing afforded in relationship to fibre diameter, mat height, and mat length was studied. We observed that the most mixing was caused by small diameter PVA nanofibres (450-550 nm in diameter), producing up to 71% mixing at the microchannel outlet, compared to up to 51% with polystyrene microfibres (0.8-2.7 μm in diameter) and 29% mixing in control channels containing no fibres. The mixing afforded by the PVA nanofibres is caused by significant inhomogeneity in pore size and distribution leading to percolation. As expected, within all the studies, fluid mixing increased with fibre mat height, which corresponds to the vertical space of the microchannel occupied by the fibre mats. Doubling the height of the fibre mat led to an average increase in mixing of 14% for the PVA nanofibres and 8% for the PS microfibres. Overall, mixing was independent of the length of the fibre mat used (3-10 mm), suggesting that most mixing occurs as fluid enters and exits the fibre mat. The mixing effects observed within the fibre mats were comparable to or better than many passive mixers reported in literature. Since the nanofibre mats can be further functionalized to couple analyte concentration, immobilization, and detection with enhanced fluid mixing, they are a promising nanomaterial providing dual-functionality within lab-on-a-chip devices.

Passive Mixing Capabilities of Micro- and Nanofibres When Used in Microfluidic Systems

PubMed Central

Matlock-Colangelo, Lauren; Colangelo, Nicholas W.; Fenzl, Christoph; Frey, Margaret W.; Baeumner, Antje J.

2016-01-01

Nanofibres are increasingly being used in the field of bioanalytics due to their large surface-area-to-volume ratios and easy-to-functionalize surfaces. To date, nanofibres have been studied as effective filters, concentrators, and immobilization matrices within microfluidic devices. In addition, they are frequently used as optical and electrochemical transduction materials. In this work, we demonstrate that electrospun nanofibre mats cause appreciable passive mixing and therefore provide dual functionality when incorporated within microfluidic systems. Specifically, electrospun nanofibre mats were integrated into Y-shaped poly(methyl methacrylate) microchannels and the degree of mixing was quantified using fluorescence microscopy and ImageJ analysis. The degree of mixing afforded in relationship to fibre diameter, mat height, and mat length was studied. We observed that the most mixing was caused by small diameter PVA nanofibres (450–550 nm in diameter), producing up to 71% mixing at the microchannel outlet, compared to up to 51% with polystyrene microfibres (0.8–2.7 μm in diameter) and 29% mixing in control channels containing no fibres. The mixing afforded by the PVA nanofibres is caused by significant inhomogeneity in pore size and distribution leading to percolation. As expected, within all the studies, fluid mixing increased with fibre mat height, which corresponds to the vertical space of the microchannel occupied by the fibre mats. Doubling the height of the fibre mat led to an average increase in mixing of 14% for the PVA nanofibres and 8% for the PS microfibres. Overall, mixing was independent of the length of the fibre mat used (3–10 mm), suggesting that most mixing occurs as fluid enters and exits the fibre mat. The mixing effects observed within the fibre mats were comparable to or better than many passive mixers reported in literature. Since the nanofibre mats can be further functionalized to couple analyte concentration, immobilization, and detection with enhanced fluid mixing, they are a promising nanomaterial providing dual-functionality within lab-on-a-chip devices. PMID:27527184

Mithramycin encapsulated in polymeric micelles by microfluidic technology as novel therapeutic protocol for beta-thalassemia

PubMed Central

Capretto, Lorenzo; Mazzitelli, Stefania; Brognara, Eleonora; Lampronti, Ilaria; Carugo, Dario; Hill, Martyn; Zhang, Xunli; Gambari, Roberto; Nastruzzi, Claudio

2012-01-01

This report shows that the DNA-binding drug, mithramycin, can be efficiently encapsulated in polymeric micelles (PM-MTH), based on Pluronic® block copolymers, by a new microfluidic approach. The effect of different production parameters has been investigated for their effect on PM-MTH characteristics. The compared analysis of PM-MTH produced by microfluidic and conventional bulk mixing procedures revealed that microfluidics provides a useful platform for the production of PM-MTH with improved controllability, reproducibility, smaller size, and polydispersity. Finally, an investigation of the effects of PM-MTH, produced by microfluidic and conventional bulk mixing procedures, on the erythroid differentiation of both human erythroleukemia and human erythroid precursor cells is reported. It is demonstrated that PM-MTH exhibited a slightly lower toxicity and more pronounced differentiative activity when compared to the free drug. In addition, PM-MTH were able to upregulate preferentially γ-globin messenger ribonucleic acid production and to increase fetal hemoglobin (HbF) accumulation, the percentage of HbF-containing cells, and their HbF content without stimulating α-globin gene expression, which is responsible for the clinical symptoms of β-thalassemia. These results represent an important first step toward a potential clinical application, since an increase in HbF could alleviate the symptoms underlying β-thalassemia and sickle cell anemia. In conclusion, this report suggests that PM-MTH produced by microfluidic approach warrants further evaluation as a potential therapeutic protocol for β-thalassemia. PMID:22287841

Symmetry-breaking bifurcations and enhanced mixing in microfluidic cross-slots

NASA Astrophysics Data System (ADS)

Poole, Rob; Haward, Simon; Oliveira, Paulo; Alves, Manuel

2014-11-01

We investigate, both experimentally and numerically, a new subcritical bifurcation phenomenon for a Newtonian fluid flowing through three-dimensional cross-slot geometries. At low Reynolds numbers the flow remains steady and symmetric. For the case of square inlets and outlets, at a critical Reynolds number of approximately 40 (based on average velocity) a pitchfork bifurcation is observed beyond which the unstable symmetrical solution is replaced by a pair of steady asymmetric solutions. Sensitivity of this critical Reynolds number to the initial conditions of the simulation, resulting in a small degree of hysteresis, suggests a subcritical instability. At higher flowrates the flow becomes unsteady. The effects of channel aspect ratio are investigated on the critical conditions and excellent agreement is found between three-dimensional finite volume simulations and flow visualisation experiments in microfluidic channels. Finally we suggest this new flow bifurcation could be an effective method of enhancing mixing in microfluidic channels as significant increases in mixing quality are observed beyond the bifurcation. This enhancement occurs at flowrates more than a factor of two smaller than those observed in the well-known T-channel micromixer.

Rapid detection of hemagglutination using restrictive microfluidic channels equipped with waveguide-mode sensors

NASA Astrophysics Data System (ADS)

Ashiba, Hiroki; Fujimaki, Makoto; Awazu, Koichi; Fu, Mengying; Ohki, Yoshimichi; Tanaka, Torahiko; Makishima, Makoto

2016-02-01

Hemagglutination is utilized for various immunological assays, including blood typing and virus detection. Herein, we describe a method of rapid hemagglutination detection based on a microfluidic channel installed on an optical waveguide-mode sensor. Human blood samples mixed with hemagglutinating antibodies associated with different blood groups were injected into the microfluidic channel, and reflectance spectra of the samples were measured after stopping the flow. The agglutinated and nonagglutinated samples were distinguishable by the alterations in their reflectance spectra with time; the microfluidic channels worked as spatial restraints for agglutinated red blood cells. The demonstrated system allowed rapid hemagglutination detection within 1 min. The suitable height of the channels was also discussed.

A picoliter-volume mixer for microfluidic analytical systems.

PubMed

He, B; Burke, B J; Zhang, X; Zhang, R; Regnier, F E

2001-05-01

Mixing confluent liquid streams is an important, but difficult operation in microfluidic systems. This paper reports the construction and characterization of a 100-pL mixer for liquids transported by electroosmotic flow. Mixing was achieved in a microfabricated device with multiple intersecting channels of varying lengths and a bimodal width distribution. All channels running parallel to the direction of flow were 5 microm in width whereas larger 27-microm-width channels ran back and forth through the parallel channel network at a 45 degrees angle. The channel network composing the mixer was approximately 10 microm deep. It was observed that little mixing of the confluent solvent streams occurred in the 100-microm-wide, 300-microm-long mixer inlet channel where mixing would be achieved almost exclusively by diffusion. In contrast, after passage through the channel network in the approximately 200-microm-length static mixer bed, mixing was complete as determined by confocal microscopy and CCD detection. Theoretical simulations were also performed in an attempt to describe the extent of mixing in microfabricated systems.

Parametric study on mixing process in an in-plane spiral micromixer utilizing chaotic advection.

PubMed

Vatankhah, Parham; Shamloo, Amir

2018-08-31

Recent advances in the field of microfabrication have made the application of high-throughput microfluidics feasible. Mixing which is an essential part of any miniaturized standalone system remains the key challenge. This paper proposes a geometrically simple micromixer for efficient mixing for high-throughput microfluidic devices. The proposed micromixer utilizes a curved microchannel (spiral microchannel) to induce chaotic advection and enhance the mixing process. It is shown that the spiral microchannel is more efficient in comparison to a straight microchannel, mixing wise. The pressure drop in the spiral microchannel is only slightly higher than that in the straight microchannel. It is found that the mixing process in the spiral microchannel enhances with increasing the inlet velocity, unlike what happens in the straight microchannel. It is also realized that the initial radius of the spiral microchannel plays a prominent role in enhancing the mixing process. Studying different cross sections, it is gathered that the square cross section yields a higher mixing quality. Copyright © 2018 Elsevier B.V. All rights reserved.

A Microfluidic System with Surface Patterning for Investigating Cavitation Bubble(s)-Cell Interaction and the Resultant Bioeffects at the Single-Cell Level

PubMed Central

Li, Fenfang; Yuan, Fang; Sankin, Georgy; Yang, Chen; Zhong, Pei

2017-01-01

In this manuscript, we first describe the fabrication protocol of a microfluidic chip, with gold dots and fibronectin-coated regions on the same glass substrate that precisely controls the generation of tandem bubbles and individual cells patterned nearby with well-defined locations and shapes. We then demonstrate the generation of tandem bubbles by using two pulsed lasers illuminating a pair of gold dots with a few-microsecond time delay. We visualize the bubble-bubble interaction and jet formation by high-speed imaging and characterize the resultant flow field using particle image velocimetry (PIV). Finally, we present some applications of this technique for single cell analysis, including cell membrane poration with macromolecule uptake, localized membrane deformation determined by the displacements of attached integrin-binding beads, and intracellular calcium response from ratiometric imaging. Our results show that a fast and directional jetting flow is produced by the tandem bubble interaction, which can impose a highly-localized shear stress on the surface of a cell grown in close proximity. Furthermore, different bioeffects can be induced by altering the strength of the jetting flow by adjusting the standoff distance from the cell to the tandem bubbles. PMID:28117807

A microfluidic tubing method and its application for controlled synthesis of polymeric nanoparticles.

PubMed

Wang, Jidong; Chen, Wenwen; Sun, Jiashu; Liu, Chao; Yin, Qifang; Zhang, Lu; Xianyu, Yunlei; Shi, Xinghua; Hu, Guoqing; Jiang, Xingyu

2014-05-21

This report describes a straightforward but robust tubing method for connecting polydimethylsiloxane (PDMS) microfluidic devices to external equipment. The interconnection is irreversible and can sustain a pressure of up to 4.5 MPa that is characterized experimentally and theoretically. To demonstrate applications of this high-pressure tubing technique, we fabricate a semicircular microfluidic channel to implement a high-throughput, size-controlled synthesis of poly(lactic-co-glycolic acid) (PLGA) nanoparticles ranging from 55 to 135 nm in diameter. This microfluidic device allows for a total flow rate of 410 mL h(-1), resulting in enhanced convective mixing which can be utilized to precipitate small size nanoparticles with a good dispersion. We expect that this tubing technique would be widely used in microfluidic chips for nanoparticle synthesis, cell manipulation, and potentially nanofluidic applications.

Nature-inspired polymer actuators for micro-fluidic mixing.

NASA Astrophysics Data System (ADS)

den Toonder, Jaap M. J.; Bos, Femke; de Goede, Judith; Anderson, Patrick

2007-11-01

One particular micro-fluidics manipulation mechanism ``designed'' by nature is that due to a covering of beating cilia over the external surface of micro-organisms (e.g. Paramecium). A cilium can be viewed as a small hair or flexible rod (in protozoa: typical length 10 microns and diameter 0.1 microns) which is attached to the surface. We have developed polymer micro-actuators, made with standard micro-technology processing, which respond to an applied electrical or magnetic field by changing their shape. The shape and size of the polymer actuators mimics that of cilia occurring in nature. Flow visualization experiments show that the cilia can generate substantial fluid velocities, in the order of 1 mm/s. In addition, using specially designed geometrical configurations of the cilia, very efficient mixing is obtained. Since the artificial cilia can be actively controlled using electrical signals, they have exciting applications in micro-fluidic devices.

There can be turbulence in microfluidics at low Reynolds number.

PubMed

Wang, G R; Yang, Fang; Zhao, Wei

2014-04-21

Turbulence is commonly viewed as a type of macroflow, where the Reynolds number (Re) has to be sufficiently high. In microfluidics, when Re is below or on the order of 1 and fast mixing is required, so far only chaotic flow has been reported to enhance mixing based on previous publications since turbulence is believed not to be possible to generate in such a low Re microflow. There is even a lack of velocimeter that can measure turbulence in microchannels. In this work, we report a direct observation of the existence of turbulence in microfluidics with Re on the order of 1 in a pressure driven flow under electrokinetic forcing using a novel velocimeter having ultrahigh spatiotemporal resolution. The work could provide a new method to control flow and transport phenomena in lab-on-a-chip and a new perspective on turbulence.

A microfluidic galvanic cell on a single layer of paper

NASA Astrophysics Data System (ADS)

Purohit, Krutarth H.; Emrani, Saina; Rodriguez, Sandra; Liaw, Shi-Shen; Pham, Linda; Galvan, Vicente; Domalaon, Kryls; Gomez, Frank A.; Haan, John L.

2016-06-01

Paper microfluidics is used to produce single layer galvanic and hybrid cells to produce energy that could power paper-based analytical sensors. When two aqueous streams are absorbed onto paper to establish co-laminar flow, the streams stay in contact with each other with limited mixing. The interface at which mixing occurs acts as a charge-transfer region, eliminating the need for a salt bridge. We designed a Cusbnd Zn galvanic cell that powers an LED when two are placed in series. We also used more powerful redox couples (formate and silver, formate and permanganate) to produce higher power density (18 and 3.1 mW mg-1 Pd). These power densities are greater than previously reported paper microfluidic fuel cells using formate or methanol. The single layer design is much more simplified than previous reports of multi-layer galvanic cells on paper.

Multiphase flows with digital and traditional microfluidics

NASA Astrophysics Data System (ADS)

Nilsson, Michael A.

Multi-phase fluid systems are an important concept in fluid mechanics, seen every day in how fluids interact with solids, gases, and other fluids in many industrial, medical, agricultural, and other regimes. In this thesis, the development of a two-dimensional digital microfluidic device is presented, followed by the development of a two-phase microfluidic diagnostic tool designed to simulate sandstone geometries in oil reservoirs. In both instances, it is possible to take advantage of the physics involved in multiphase flows to affect positive outcomes in both. In order to make an effective droplet-based digital microfluidic device, one must be able to precisely control a number of key processes including droplet positioning, motion, coalescence, mixing, and sorting. For planar or open microfluidic devices, many of these processes have yet to be demonstrated. A suitable platform for an open system is a superhydrophobic surface, as suface characteristics are critical. Great efforts have been spent over the last decade developing hydrophobic surfaces exhibiting very large contact angles with water, and which allow for high droplet mobility. We demonstrate that sanding Teflon can produce superhydrophobic surfaces with advancing contact angles of up to 151° and contact angle hysteresis of less than 4°. We use these surfaces to characterize droplet coalescence, mixing, motion, deflection, positioning, and sorting. This research culminates with the presentation of two digital microfluidic devices: a droplet reactor/analyzer and a droplet sorter. As global energy usage increases, maximizing oil recovery from known reserves becomes a crucial multiphase challenge in order to meet the rising demand. This thesis presents the development of a microfluidic sandstone platform capable of quickly and inexpensively testing the performance of fluids with different rheological properties on the recovery of oil. Specifically, these microfluidic devices are utilized to examine how shear-thinning, shear-thickening, and viscoelastic fluids affect oil recovery. This work begins by looking at oil displacement from a microfluidic sandstone device, then investigates small-scale oil recovery from a single pore, and finally investigates oil displacement from larger scale, more complex microfluidic sandstone devices of varying permeability. The results demonstrate that with careful fluid design, it is possible to outperform current commercial additives using the patent-pending fluid we developed. Furthermore, the resulting microfluidic sandstone devices can reduce the time and cost of developing and testing of current and new enhanced oil recovery fluids.

A compact disk-like centrifugal microfluidic system for high-throughput nanoliter-scale protein crystallization screening.

PubMed

Li, Gang; Chen, Qiang; Li, Junjun; Hu, Xiaojian; Zhao, Jianlong

2010-06-01

A centrifuge-based microfluidic system has been developed that enables automated high-throughput and low-volume protein crystallizations. In this system, protein solution was automatically and accurately metered and dispensed into nanoliter-sized multiple reaction chambers, and it was mixed with various types of precipitants using a combination of capillary effect and centrifugal force. It has the advantages of simple fabrication, easy operation, and extremely low waste. To demonstrate the feasibility of this system, we constructed a chip containing 24 units and used it to perform lysozyme and cyan fluorescent protein (CyPet) crystallization trials. The results demonstrate that high-quality crystals can be grown and harvested from such a nanoliter-volume microfluidic system. Compared to other microfluidic technologies for protein crystallization, this microfluidic system allows zero waste, simple structure and convenient operation, which suggests that our microfluidic disk can be applied not only to protein crystallization, but also to the miniaturization of various biochemical reactions requiring precise nanoscale control.

Microfluidic integrated acoustic waving for manipulation of cells and molecules.

PubMed

Barani, Alireza; Paktinat, Hossein; Janmaleki, Mohsen; Mohammadi, Aminollah; Mosaddegh, Peiman; Fadaei-Tehrani, Alireza; Sanati-Nezhad, Amir

2016-11-15

Acoustophoresis with its simple and low-cost fabrication, rapid and localized fluid actuation, compatibility with microfluidic components, and biocompatibility for cellular studies, has been extensively integrated into microfluidics to provide on-chip microdevices for a variety of applications in biology, bioengineering and chemistry. Among different applications, noninvasive manipulation of cells and biomolecules are significantly important, which are addressed by acoustic-based microfluidics. Here in this paper, we briefly explain the principles and different configurations of acoustic wave and acoustic streaming for the manipulation of cells and molecules and overview its applications for single cell isolation, cell focusing and sorting, cell washing and patterning, cell-cell fusion and communication, and tissue engineering. We further discuss the application of acoustic-based microfluidic systems for the mixing and transport of liquids, manipulation of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) molecules, followed by explanation on the present challenges of acoustic-based microfluidics for the handling of cells and molecules, and highlighting the future directions. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Characterization of three-dimensional cancer cell migration in mixed collagen-Matrigel scaffolds using microfluidics and image analysis.

PubMed

Anguiano, María; Castilla, Carlos; Maška, Martin; Ederra, Cristina; Peláez, Rafael; Morales, Xabier; Muñoz-Arrieta, Gorka; Mujika, Maite; Kozubek, Michal; Muñoz-Barrutia, Arrate; Rouzaut, Ana; Arana, Sergio; Garcia-Aznar, José Manuel; Ortiz-de-Solorzano, Carlos

2017-01-01

Microfluidic devices are becoming mainstream tools to recapitulate in vitro the behavior of cells and tissues. In this study, we use microfluidic devices filled with hydrogels of mixed collagen-Matrigel composition to study the migration of lung cancer cells under different cancer invasion microenvironments. We present the design of the microfluidic device, characterize the hydrogels morphologically and mechanically and use quantitative image analysis to measure the migration of H1299 lung adenocarcinoma cancer cells in different experimental conditions. Our results show the plasticity of lung cancer cell migration, which turns from mesenchymal in collagen only matrices, to lobopodial in collagen-Matrigel matrices that approximate the interface between a disrupted basement membrane and the underlying connective tissue. Our quantification of migration speed confirms a biphasic role of Matrigel. At low concentration, Matrigel facilitates migration, most probably by providing a supportive and growth factor retaining environment. At high concentration, Matrigel slows down migration, possibly due excessive attachment. Finally, we show that antibody-based integrin blockade promotes a change in migration phenotype from mesenchymal or lobopodial to amoeboid and analyze the effect of this change in migration dynamics, in regards to the structure of the matrix. In summary, we describe and characterize a robust microfluidic platform and a set of software tools that can be used to study lung cancer cell migration under different microenvironments and experimental conditions. This platform could be used in future studies, thus benefitting from the advantages introduced by microfluidic devices: precise control of the environment, excellent optical properties, parallelization for high throughput studies and efficient use of therapeutic drugs.

A sample-to-result system for blood coagulation tests on a microfluidic disk analyzer

PubMed Central

Lin, Chia-Hui; Liu, Cheng-Yuan; Shih, Chih-Hsin; Lu, Chien-Hsing

2014-01-01

In this report, we describe in detail a microfluidic analyzer, which is able to conduct blood coagulation tests using whole blood samples. Sample preparation steps, such as whole blood aliquoting and metering, plasma separation, decanting, and mixing with reagents were performed in sequence through microfluidic functions integrated on a disk. Both prothrombin time (PT) and activated partial thromboplastin time (aPTT) were carried out on the same platform and the test results can be reported in 5 min. Fifty clinical samples were tested for both PT and aPTT utilizing the microfluidic disk analyzer and the instrument used in hospitals. The test results showed good correlation and agreement between the two instruments. PMID:25332733

Efficient gas-liquid contact using microfluidic membrane devices with staggered herringbone mixers.

PubMed

Femmer, Tim; Eggersdorfer, Max L; Kuehne, Alexander J C; Wessling, Matthias

2015-08-07

We describe a novel membrane based gas-liquid-contacting device with increased mass transport and reduced pressure loss by combining a membrane with a staggered herringbone static mixer. Herringbone structures are imposed on the microfluidic channel geometry via soft lithography, acting as mixers which introduce secondary flows at the membrane interface. Such flows include Dean vortices and Taylor flows generating effective mixing while improving mass transport and preventing concentration polarization in microfluidic channels. Furthermore, our static herringbone mixer membranes effectively reduce pressure losses leading to devices with enhanced transfer properties for microfluidic gas-liquid contact. We investigate the red blood cell distribution to tailor our devices towards miniaturised extracorporeal membrane oxygenation and improved comfort of patients with lung insufficiencies.

Recent Advancements towards Full-System Microfluidics

PubMed Central

Miled, Amine

2017-01-01

Microfluidics is quickly becoming a key technology in an expanding range of fields, such as medical sciences, biosensing, bioactuation, chemical synthesis, and more. This is helping its transformation from a promising R&D tool to commercially viable technology. Fuelling this expansion is the intensified focus on automation and enhanced functionality through integration of complex electrical control, mechanical properties, in situ sensing and flow control. Here we highlight recent contributions to the Sensors Special Issue series called “Microfluidics-Based Microsystem Integration Research” under the following categories: (i) Device fabrication to support complex functionality; (ii) New methods for flow control and mixing; (iii) Towards routine analysis and point of care applications; (iv) In situ characterization; and (v) Plug and play microfluidics. PMID:28757587

A microfluidic direct formate fuel cell on paper.

PubMed

Copenhaver, Thomas S; Purohit, Krutarth H; Domalaon, Kryls; Pham, Linda; Burgess, Brianna J; Manorothkul, Natalie; Galvan, Vicente; Sotez, Samantha; Gomez, Frank A; Haan, John L

2015-08-01

We describe the first direct formate fuel cell on a paper microfluidic platform. In traditional membrane-less microfluidic fuel cells (MFCs), external pumping consumes power produced by the fuel cell in order to maintain co-laminar flow of the anode stream and oxidant stream to prevent mixing. However, in paper microfluidics, capillary action drives flow while minimizing stream mixing. In this work, we demonstrate a paper MFC that uses formate and hydrogen peroxide as the anode fuel and cathode oxidant, respectively. Using these materials we achieve a maximum power density of nearly 2.5 mW/mg Pd. In a series configuration, our MFC achieves an open circuit voltage just over 1 V, and in a parallel configuration, short circuit of 20 mA absolute current. We also demonstrate that the MFC does not require continuous flow of fuel and oxidant to produce power. We found that we can pre-saturate the materials on the paper, stop the electrolyte flow, and still produce approximately 0.5 V for 15 min. This type of paper MFC has potential applications in point-of-care diagnostic devices and other electrochemical sensors. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Impedance feedback control of microfluidic valves for reliable post processing combinatorial droplet injection.

PubMed

Axt, Brant; Hsieh, Yi-Fan; Nalayanda, Divya; Wang, Tza-Huei

2017-09-01

Droplet microfluidics has found use in many biological assay applications as a means of high-throughput sample processing. One of the challenges of the technology, however, is the ability to control and merge droplets on-demand as they flow through the microdevices. It is in the interest of developing lab-on-chip devices to be able to combinatorically program additive mixing steps for more complex multistep and multiplex assays. Existing technologies to merge droplets are either passive in nature or require highly predictable droplet movement for feedforward control, making them vulnerable to errors during high throughput operation. In this paper, we describe and demonstrate a microfluidic valve-based device for the purpose of combinatorial droplet injection at any stage in a multistep assay. Microfluidic valves are used to robustly control fluid flow, droplet generation, and droplet mixing in the device on-demand, while on-chip impedance measurements taken in real time are used as feedback to accurately time the droplet injections. The presented system is contrasted to attempts without feedback, and is shown to be 100% reliable over long durations. Additionally, content detection and discretionary injections are explored and successfully executed.

Photo-actuation of liquids for light-driven microfluidics: state of the art and perspectives.

PubMed

Baigl, Damien

2012-10-07

Using light to control liquid motion is a new paradigm for the actuation of microfluidic systems. We review here the different principles and strategies to induce or control liquid motion using light, which includes the use of radiation pressure, optical tweezers, light-induced wettability gradients, the thermocapillary effect, photosensitive surfactants, the chromocapillary effect, optoelectrowetting, photocontrolled electroosmotic flows and optical dielectrophoresis. We analyze the performance of these approaches to control using light many kinds of microfluidic operations involving discrete pL- to μL-sized droplets (generation, driving, mixing, reaction, sorting) or fluid flows in microchannels (valve operation, injection, pumping, flow rate control). We show that a complete toolbox is now available to control microfluidic systems by light. We finally discuss the perspectives of digital optofluidics as well as microfluidics based on all optical fluidic chips and optically reconfigurable devices.

3D printed microfluidic mixer for point-of-care diagnosis of anemia.

PubMed

Plevniak, Kimberly; Campbell, Matthew; Mei He

2016-08-01

3D printing has been an emerging fabrication tool in prototyping and manufacturing. We demonstrated a 3D microfluidic simulation guided computer design and 3D printer prototyping for quick turnaround development of microfluidic 3D mixers, which allows fast self-mixing of reagents with blood through capillary force. Combined with smartphone, the point-of-care diagnosis of anemia from finger-prick blood has been successfully implemented and showed consistent results with clinical measurements. Capable of 3D fabrication flexibility and smartphone compatibility, this work presents a novel diagnostic strategy for advancing personalized medicine and mobile healthcare.

Science Issues Associated with the Use of a Microfluidic Chip Designed Specifically for Protein Crystallization

NASA Technical Reports Server (NTRS)

Holmes, Anna M.; Monaco, Lisa; Barnes, Cindy; Spearing, Scott; Jenkins, Andy; Johnson, Todd; Mayer, Derek; Cole, Helen

2003-01-01

The Iterative Biological Crystallization team in partnership with Caliper Technologies has produced a prototype microfluidic chip for batch crystallization that has been designed and tested. The chip is designed for the mixing and dispensing of up to five solutions with possible variation of the recipe being delivered to two growth wells. Developments that have led to the successful on-chip crystallization of a few model proteins have required investigative insight into many different areas, including fluid mixing dynamics, surface treatments, quantification and fidelity of reagent delivery. This presentation will encompass the ongoing studies and data accumulated toward these efforts.

Biosensing enhancement of dengue virus using microballoon mixers on centrifugal microfluidic platforms.

PubMed

Aeinehvand, Mohammad Mahdi; Ibrahim, Fatimah; Harun, Sulaiman Wadi; Djordjevic, Ivan; Hosseini, Samira; Rothan, Hussin A; Yusof, Rohana; Madou, Marc J

2015-05-15

Dengue is the current leading cause of death among children in several Latin American and Asian countries. Due to poverty in areas where the disease is prevalent and the high cost of conventional diagnostic systems, low cost devices are needed to reduce the burden caused by dengue infection. Centrifugal microfluidic platforms are an alternative solution to reduce costs and increase the availability of a rapid diagnostic system. The rate of chemical reactions in such devices often depends on the efficiency of the mixing techniques employed in their microfluidic networks. This paper introduces a micromixer that operates by the expansion and contraction of a microballoon to produce a consistent periodical 3D reciprocating flow. We established that microballoons reduced mixing time of 12 μl liquids from 170 min, for diffusional mixing, to less than 23 s. We have also tested the effect of the microballoon mixers on the detection of the dengue virus. The results indicate that employing a microballoon mixer enhances the detection sensitivity of the dengue virus by nearly one order of magnitude compared to the conventional ELISA method. Copyright © 2014 Elsevier B.V. All rights reserved.

Rapid, automated, parallel quantitative immunoassays using highly integrated microfluidics and AlphaLISA

PubMed Central

Tak For Yu, Zeta; Guan, Huijiao; Ki Cheung, Mei; McHugh, Walker M.; Cornell, Timothy T.; Shanley, Thomas P.; Kurabayashi, Katsuo; Fu, Jianping

2015-01-01

Immunoassays represent one of the most popular analytical methods for detection and quantification of biomolecules. However, conventional immunoassays such as ELISA and flow cytometry, even though providing high sensitivity and specificity and multiplexing capability, can be labor-intensive and prone to human error, making them unsuitable for standardized clinical diagnoses. Using a commercialized no-wash, homogeneous immunoassay technology (‘AlphaLISA’) in conjunction with integrated microfluidics, herein we developed a microfluidic immunoassay chip capable of rapid, automated, parallel immunoassays of microliter quantities of samples. Operation of the microfluidic immunoassay chip entailed rapid mixing and conjugation of AlphaLISA components with target analytes before quantitative imaging for analyte detections in up to eight samples simultaneously. Aspects such as fluid handling and operation, surface passivation, imaging uniformity, and detection sensitivity of the microfluidic immunoassay chip using AlphaLISA were investigated. The microfluidic immunoassay chip could detect one target analyte simultaneously for up to eight samples in 45 min with a limit of detection down to 10 pg mL−1. The microfluidic immunoassay chip was further utilized for functional immunophenotyping to examine cytokine secretion from human immune cells stimulated ex vivo. Together, the microfluidic immunoassay chip provides a promising high-throughput, high-content platform for rapid, automated, parallel quantitative immunosensing applications. PMID:26074253

Fluid control structures in microfluidic devices

DOEpatents

Mathies, Richard A.; Grover, William H.; Skelley, Alison; Lagally, Eric; Liu, Chung N.

2008-11-04

Methods and apparatus for implementing microfluidic analysis devices are provided. A monolithic elastomer membrane associated with an integrated pneumatic manifold allows the placement and actuation of a variety of fluid control structures, such as structures for pumping, isolating, mixing, routing, merging, splitting, preparing, and storing volumes of fluid. The fluid control structures can be used to implement a variety of sample introduction, preparation, processing, and storage techniques.

Fluid control structures in microfluidic devices

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

Mathies, Richard A.; Grover, William H.; Skelley, Alison

2017-05-09

Methods and apparatus for implementing microfluidic analysis devices are provided. A monolithic elastomer membrane associated with an integrated pneumatic manifold allows the placement and actuation of a variety of fluid control structures, such as structures for pumping, isolating, mixing, routing, merging, splitting, preparing, and storing volumes of fluid. The fluid control structures can be used to implement a variety of sample introduction, preparation, processing, and storage techniques.

Fluid control structures in microfluidic devices

NASA Technical Reports Server (NTRS)

Skelley, Alison (Inventor); Mathies, Richard A. (Inventor); Lagally, Eric (Inventor); Grover, William H. (Inventor); Liu, Chung N. (Inventor)

2008-01-01

Methods and apparatus for implementing microfluidic analysis devices are provided. A monolithic elastomer membrane associated with an integrated pneumatic manifold allows the placement and actuation of a variety of fluid control structures, such as structures for pumping, isolating, mixing, routing, merging, splitting, preparing, and storing volumes of fluid. The fluid control structures can be used to implement a variety of sample introduction, preparation, processing, and storage techniques.

Rapid three-dimensional microfluidic mixer for high viscosity solutions to unravel earlier folding kinetics of G-quadruplex under molecular crowding conditions.

PubMed

Liu, Chao; Li, Ying; Li, Yiwei; Chen, Peng; Feng, Xiaojun; Du, Wei; Liu, Bi-Feng

2016-01-01

Rapid mixing of highly viscous solutions is a great challenge, which helps to analyze the reaction kinetics in viscous liquid phase, particularly to discover the folding kinetics of macromolecules under molecular crowding conditions mimicking the conditions inside cells. Here, we demonstrated a novel microfluidic mixer based on Dean flows with three-dimensional (3D) microchannel configuration for fast mixing of high-viscosity fluids. The main structure contained three consecutive subunits, each consisting of a "U"-type channel followed by a chamber with different width and height. Thus, the two solutions injected from the two inlets would undergo a mixing in the first "U"-type channel due to the Dean flow effect, and simultaneous vortices expansions in both horizontal and vertical directions in the following chamber. Numerical simulations and experimental characterizations confirmed that the micromixer could achieve a mixing time of 122.4μs for solutions with viscosities about 33.6 times that of pure water. It was the fastest micromixer for high viscosity solutions compared with previous reports. With this highly efficient 3D microfluidic mixer, we further characterized the early folding kinetics of human telomere G-quadruplex under molecular crowding conditions, and unravelled a new folding process within 550μs. Copyright © 2015 Elsevier B.V. All rights reserved.

Collective oscillations and coupled modes in confined microfluidic droplet arrays

NASA Astrophysics Data System (ADS)

Schiller, Ulf D.; Fleury, Jean-Baptiste; Seemann, Ralf; Gompper, Gerhard

Microfluidic droplets have a wide range of applications ranging from analytic assays in cellular biology to controlled mixing in chemical engineering. Ensembles of microfluidic droplets are interesting model systems for non-equilibrium many-body phenomena. When flowing in a microchannel, trains of droplets can form microfluidic crystals whose dynamics are governed by long-range hydrodynamic interactions and boundary effects. In this contribution, excitation mechanisms for collective waves in dense and confined microfluidic droplet arrays are investigated by experiments and computer simulations. We demonstrate that distinct modes can be excited by creating specific `defect' patterns in flowing droplet trains. While longitudinal modes exhibit a short-lived cascade of pairs of laterally displacing droplets, transversely excited modes form propagating waves that behave like microfluidic phonons. We show that the confinement induces a coupling between longitudinal and transverse modes. We also investigate the life time of the collective oscillations and discuss possible mechanisms for the onset of instabilities. Our results demonstrate that microfluidic phonons can exhibit effects beyond the linear theory, which can be studied particularly well in dense and confined systems. This work was supported by Deutsche Forschungsgemeinschaft under Grant No. SE 1118/4.

Rapid fabrication of microfluidic chips based on the simplest LED lithography

NASA Astrophysics Data System (ADS)

Li, Yue; Wu, Ping; Luo, Zhaofeng; Ren, Yuxuan; Liao, Meixiang; Feng, Lili; Li, Yuting; He, Liqun

2015-05-01

Microfluidic chips are generally fabricated by a soft lithography method employing commercial lithography equipment. These heavy machines require a critical room environment and high lamp power, and the cost remains too high for most normal laboratories. Here we present a novel microfluidics fabrication method utilizing a portable ultraviolet (UV) LED as an alternative UV source for photolithography. With this approach, we can repeat several common microchannels as do these conventional commercial exposure machines, and both the verticality of the channel sidewall and lithography resolution are proved to be acceptable. Further microfluidics applications such as mixing, blood typing and microdroplet generation are implemented to validate the practicability of the chips. This simple but innovative method decreases the cost and requirement of chip fabrication dramatically and may be more popular with ordinary laboratories.

Microfluidic "Pouch" Chips for Immunoassays and Nucleic Acid Amplification Tests.

PubMed

Mauk, Michael G; Liu, Changchun; Qiu, Xianbo; Chen, Dafeng; Song, Jinzhao; Bau, Haim H

2017-01-01

Microfluidic cassettes ("chips") for processing and analysis of clinical specimens and other sample types facilitate point-of-care (POC) immunoassays and nucleic acid based amplification tests. These single-use test chips can be self-contained and made amenable to autonomous operation-reducing or eliminating supporting instrumentation-by incorporating laminated, pliable "pouch" and membrane structures for fluid storage, pumping, mixing, and flow control. Materials and methods for integrating flexible pouch compartments and diaphragm valves into hard plastic (e.g., acrylic and polycarbonate) microfluidic "chips" for reagent storage, fluid actuation, and flow control are described. We review several versions of these pouch chips for immunoassay and nucleic acid amplification tests, and describe related fabrication techniques. These protocols thus offer a "toolbox" of methods for storage, pumping, and flow control functions in microfluidic devices.

Ultrafast hydrogen exchange reveals specific structural events during the initial stages of folding of cytochrome c.

PubMed

Fazelinia, Hossein; Xu, Ming; Cheng, Hong; Roder, Heinrich

2014-01-15

Many proteins undergo a sharp decrease in chain dimensions during early stages of folding, prior to the rate-limiting step in folding. However, it remains unclear whether compact states are the result of specific folding events or a general hydrophobic collapse of the poly peptide chain driven by the change in solvent conditions. To address this fundamental question, we extended the temporal resolution of NMR-detected H/D exchange labeling experiments into the microsecond regime by adopting a microfluidics approach. By observing the competition between H/D exchange and folding as a function of labeling pH, coupled with direct measurement of exchange rates in the unfolded state, we were able to monitor hydrogen-bond formation for over 50 individual backbone NH groups within the initial 140 microseconds of folding of horse cytochrome c. Clusters of solvent-shielded amide protons were observed in two α-helical segments in the C-terminal half of the protein, while the N-terminal helix remained largely unstructured, suggesting that proximity in the primary structure is a major factor in promoting helix formation and association at early stages of folding, while the entropically more costly long-range contacts between the N- and C-terminal helices are established only during later stages. Our findings clearly indicate that the initial chain condensation in cytochrome c is driven by specific interactions among a subset of α-helical segments rather than a general hydrophobic collapse.

Characterization of three-dimensional cancer cell migration in mixed collagen-Matrigel scaffolds using microfluidics and image analysis

PubMed Central

Maška, Martin; Ederra, Cristina; Peláez, Rafael; Morales, Xabier; Muñoz-Arrieta, Gorka; Mujika, Maite; Kozubek, Michal; Muñoz-Barrutia, Arrate; Rouzaut, Ana; Arana, Sergio; Garcia-Aznar, José Manuel; Ortiz-de-Solorzano, Carlos

2017-01-01

Microfluidic devices are becoming mainstream tools to recapitulate in vitro the behavior of cells and tissues. In this study, we use microfluidic devices filled with hydrogels of mixed collagen-Matrigel composition to study the migration of lung cancer cells under different cancer invasion microenvironments. We present the design of the microfluidic device, characterize the hydrogels morphologically and mechanically and use quantitative image analysis to measure the migration of H1299 lung adenocarcinoma cancer cells in different experimental conditions. Our results show the plasticity of lung cancer cell migration, which turns from mesenchymal in collagen only matrices, to lobopodial in collagen-Matrigel matrices that approximate the interface between a disrupted basement membrane and the underlying connective tissue. Our quantification of migration speed confirms a biphasic role of Matrigel. At low concentration, Matrigel facilitates migration, most probably by providing a supportive and growth factor retaining environment. At high concentration, Matrigel slows down migration, possibly due excessive attachment. Finally, we show that antibody-based integrin blockade promotes a change in migration phenotype from mesenchymal or lobopodial to amoeboid and analyze the effect of this change in migration dynamics, in regards to the structure of the matrix. In summary, we describe and characterize a robust microfluidic platform and a set of software tools that can be used to study lung cancer cell migration under different microenvironments and experimental conditions. This platform could be used in future studies, thus benefitting from the advantages introduced by microfluidic devices: precise control of the environment, excellent optical properties, parallelization for high throughput studies and efficient use of therapeutic drugs. PMID:28166248

Fast and accurate enzyme activity measurements using a chip-based microfluidic calorimeter.

PubMed

van Schie, Morten M C H; Ebrahimi, Kourosh Honarmand; Hagen, Wilfred R; Hagedoorn, Peter-Leon

2018-03-01

Recent developments in microfluidic and nanofluidic technologies have resulted in development of new chip-based microfluidic calorimeters with potential use in different fields. One application would be the accurate high-throughput measurement of enzyme activity. Calorimetry is a generic way to measure activity of enzymes, but unlike conventional calorimeters, chip-based calorimeters can be easily automated and implemented in high-throughput screening platforms. However, application of chip-based microfluidic calorimeters to measure enzyme activity has been limited due to problems associated with miniaturization such as incomplete mixing and a decrease in volumetric heat generated. To address these problems we introduced a calibration method and devised a convenient protocol for using a chip-based microfluidic calorimeter. Using the new calibration method, the progress curve of alkaline phosphatase, which has product inhibition for phosphate, measured by the calorimeter was the same as that recorded by UV-visible spectroscopy. Our results may enable use of current chip-based microfluidic calorimeters in a simple manner as a tool for high-throughput screening of enzyme activity with potential applications in drug discovery and enzyme engineering. Copyright © 2017. Published by Elsevier Inc.

Experimental test of scaling of mixing by chaotic advection in droplets moving through microfluidic channels

PubMed Central

Song, Helen; Bringer, Michelle R.; Tice, Joshua D.; Gerdts, Cory J.; Ismagilov, Rustem F.

2006-01-01

This letter describes an experimental test of a simple argument that predicts the scaling of chaotic mixing in a droplet moving through a winding microfluidic channel. Previously, scaling arguments for chaotic mixing have been described for a flow that reduces striation length by stretching, folding, and reorienting the fluid in a manner similar to that of the baker’s transformation. The experimentally observed flow patterns within droplets (or plugs) resembled the baker’s transformation. Therefore, the ideas described in the literature could be applied to mixing in droplets to obtain the scaling argument for the dependence of the mixing time, t~(aw/U)log(Pe), where w [m] is the cross-sectional dimension of the microchannel, a is the dimensionless length of the plug measured relative to w, U [m s−1] is the flow velocity, Pe is the Péclet number (Pe=wU/D), and D [m2s−1] is the diffusion coefficient of the reagent being mixed. Experiments were performed to confirm the scaling argument by varying the parameters w, U, and D. Under favorable conditions, submillisecond mixing has been demonstrated in this system. PMID:17940580

Oxidation and adduct formation of xenobiotics in a microfluidic electrochemical cell with boron doped diamond electrodes and an integrated passive gradient rotation mixer.

PubMed

van den Brink, Floris T G; Wigger, Tina; Ma, Liwei; Odijk, Mathieu; Olthuis, Wouter; Karst, Uwe; van den Berg, Albert

2016-10-05

Reactive xenobiotic metabolites and their adduct formation with biomolecules such as proteins are important to study as they can be detrimental to human health. Here, we present a microfluidic electrochemical cell with integrated micromixer to study phase I and phase II metabolism as well as protein adduct formation of xenobiotics in a purely instrumental approach. The newly developed microfluidic device enables both the generation of reactive metabolites through electrochemical oxidation and subsequent adduct formation with biomolecules in a chemical microreactor. This allows us to study the detoxification of reactive species with glutathione and to predict potential toxicity of xenobiotics as a result of protein modification. Efficient mixing in microfluidic systems is a slow process due to the typically laminar flow conditions in shallow channels. Therefore, a passive gradient rotation micromixer has been designed that is capable of mixing liquids efficiently in a 790 pL volume within tens of milliseconds. The mixing principle relies on turning the concentration gradient that is initially established by bringing together two streams of liquid, to take advantage of the short diffusion distances in the shallow microchannels of thin-layer flow cells. The mixer is located immediately downstream of the working electrode of an electrochemical cell with integrated boron doped diamond electrodes. In conjunction with mass spectrometry, the two microreactors integrated in a single device provide a powerful tool to study the metabolism and toxicity of xenobiotics, which was demonstrated by the investigation of the model compound 1-hydroxypyrene.

A microfluidics-based technique for automated and rapid labeling of cells for flow cytometry

NASA Astrophysics Data System (ADS)

Patibandla, Phani K.; Estrada, Rosendo; Kannan, Manasaa; Sethu, Palaniappan

2014-03-01

Flow cytometry is a powerful technique capable of simultaneous multi-parametric analysis of heterogeneous cell populations for research and clinical applications. In recent years, the flow cytometer has been miniaturized and made portable for application in clinical- and resource-limited settings. The sample preparation procedure, i.e. labeling of cells with antibodies conjugated to fluorescent labels, is a time consuming (˜45 min) and labor-intensive procedure. Microfluidics provides enabling technologies to accomplish rapid and automated sample preparation. Using an integrated microfluidic device consisting of a labeling and washing module, we demonstrate a new protocol that can eliminate sample handling and accomplish sample and reagent metering, high-efficiency mixing, labeling and washing in rapid automated fashion. The labeling module consists of a long microfluidic channel with an integrated chaotic mixer. Samples and reagents are precisely metered into this device to accomplish rapid and high-efficiency mixing. The mixed sample and reagents are collected in a holding syringe and held for up to 8 min following which the mixture is introduced into an inertial washing module to obtain ‘analysis-ready’ samples. The washing module consists of a high aspect ratio channel capable of focusing cells to equilibrium positions close to the channel walls. By introducing the cells and labeling reagents in a narrow stream at the center of the channel flanked on both sides by a wash buffer, the elution of cells into the wash buffer away from the free unbound antibodies is accomplished. After initial calibration experiments to determine appropriate ‘holding time’ to allow antibody binding, both modules were used in conjunction to label MOLT-3 cells (T lymphoblast cell line) with three different antibodies simultaneously. Results confirm no significant difference in mean fluorescence intensity values for all three antibodies labels (p < 0.01) between the conventional procedure (45 min) and our microfluidic approach (12 min).

Synthesis and Manipulation of Semiconductor Nanocrystals inMicrofluidic Reactors

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

Chan, Emory Ming-Yue

2006-01-01

Microfluidic reactors are investigated as a mechanism tocontrol the growth of semiconductor nanocrystals and characterize thestructural evolution of colloidal quantum dots. Due to their shortdiffusion lengths, low thermal masses, and predictable fluid dynamics,microfluidic devices can be used to quickly and reproducibly alterreaction conditions such as concentration, temperature, and reactiontime, while allowing for rapid reagent mixing and productcharacterization. These features are particularly useful for colloidalnanocrystal reactions, which scale poorly and are difficult to controland characterize in bulk fluids. To demonstrate the capabilities ofnanoparticle microreactors, a size series of spherical CdSe nanocrystalswas synthesized at high temperature in a continuous-flow, microfabricatedglass reactor. Nanocrystalmore » diameters are reproducibly controlled bysystematically altering reaction parameters such as the temperature,concentration, and reaction time. Microreactors with finer control overtemperature and reagent mixing were designed to synthesize nanoparticlesof different shapes, such as rods, tetrapods, and hollow shells. The twomajor challenges observed with continuous flow reactors are thedeposition of particles on channel walls and the broad distribution ofresidence times that result from laminar flow. To alleviate theseproblems, I designed and fabricated liquid-liquid segmented flowmicroreactors in which the reaction precursors are encapsulated inflowing droplets suspended in an immiscible carrier fluid. The synthesisof CdSe nanocrystals in such microreactors exhibited reduced depositionand residence time distributions while enabling the rapid screening aseries of samples isolated in nL droplets. Microfluidic reactors werealso designed to modify the composition of existing nanocrystals andcharacterize the kinetics of such reactions. The millisecond kinetics ofthe CdSe-to-Ag 2Se nanocrystal cation exchange reaction are measured insitu with micro-X-ray Absorption Spectroscopy in silicon microreactorsspecifically designed for rapid mixing and time-resolved X-rayspectroscopy. These results demonstrate that microreactors are valuablefor controlling and characterizing a wide range of reactions in nLvolumes even when nanoscale particles, high temperatures, causticreagents, and rapid time scales are involved. These experiments providethe foundation for future microfluidic investigations into the mechanismsof nanocrystal growth, crystal phase evolution, and heterostructureassembly.« less

Controlling Mass Transport in Microfluidic Devices

PubMed Central

Kuo, Jason S.; Chiu, Daniel T.

2017-01-01

Microfluidic platforms offer exquisite capabilities in controlling mass transport for biological studies. In this review, we focus on recent developments in manipulating chemical concentrations at the microscale. Some techniques prevent or accelerate mixing, whereas others shape the concentration gradients of chemical and biological molecules. We also highlight several in vitro biological studies in the areas of organ engineering, cancer, and blood coagulation that have benefited from accurate control of mass transfer. PMID:21456968

Fast and sensitive trace analysis of malachite green using a surface-enhanced Raman microfluidic sensor.

PubMed

Lee, Sangyeop; Choi, Junghyun; Chen, Lingxin; Park, Byungchoon; Kyong, Jin Burm; Seong, Gi Hun; Choo, Jaebum; Lee, Yeonjung; Shin, Kyung-Hoon; Lee, Eun Kyu; Joo, Sang-Woo; Lee, Kyeong-Hee

2007-05-08

A rapid and highly sensitive trace analysis technique for determining malachite green (MG) in a polydimethylsiloxane (PDMS) microfluidic sensor was investigated using surface-enhanced Raman spectroscopy (SERS). A zigzag-shaped PDMS microfluidic channel was fabricated for efficient mixing between MG analytes and aggregated silver colloids. Under the optimal condition of flow velocity, MG molecules were effectively adsorbed onto silver nanoparticles while flowing along the upper and lower zigzag-shaped PDMS channel. A quantitative analysis of MG was performed based on the measured peak height at 1615 cm(-1) in its SERS spectrum. The limit of detection, using the SERS microfluidic sensor, was found to be below the 1-2 ppb level and this low detection limit is comparable to the result of the LC-Mass detection method. In the present study, we introduce a new conceptual detection technology, using a SERS microfluidic sensor, for the highly sensitive trace analysis of MG in water.

Macromolecular Crystallization in Microfluidics for the International Space Station

NASA Technical Reports Server (NTRS)

Monaco, Lisa A.; Spearing, Scott

2003-01-01

At NASA's Marshall Space Flight Center, the Iterative Biological Crystallization (IBC) project has begun development on scientific hardware for macromolecular crystallization on the International Space Station (ISS). Currently ISS crystallization research is limited to solution recipes that were prepared on the ground prior to launch. The proposed hardware will conduct solution mixing and dispensing on board the ISS, be fully automated, and have imaging functions via remote commanding from the ground. Utilizing microfluidic technology, IBC will allow for on orbit iterations. The microfluidics LabChip(R) devices that have been developed, along with Caliper Technologies, will greatly benefit researchers by allowing for precise fluid handling of nano/pico liter sized volumes. IBC will maximize the amount of science return by utilizing the microfluidic approach and be a valuable tool to structural biologists investigating medically relevant projects.

3D-printed microfluidic automation.

PubMed

Au, Anthony K; Bhattacharjee, Nirveek; Horowitz, Lisa F; Chang, Tim C; Folch, Albert

2015-04-21

Microfluidic automation - the automated routing, dispensing, mixing, and/or separation of fluids through microchannels - generally remains a slowly-spreading technology because device fabrication requires sophisticated facilities and the technology's use demands expert operators. Integrating microfluidic automation in devices has involved specialized multi-layering and bonding approaches. Stereolithography is an assembly-free, 3D-printing technique that is emerging as an efficient alternative for rapid prototyping of biomedical devices. Here we describe fluidic valves and pumps that can be stereolithographically printed in optically-clear, biocompatible plastic and integrated within microfluidic devices at low cost. User-friendly fluid automation devices can be printed and used by non-engineers as replacement for costly robotic pipettors or tedious manual pipetting. Engineers can manipulate the designs as digital modules into new devices of expanded functionality. Printing these devices only requires the digital file and electronic access to a printer.

Rapid Microfluidic Mixers Utilizing Dispersion Effect and Interactively Time-Pulsed Injection

NASA Astrophysics Data System (ADS)

Leong, Jik-Chang; Tsai, Chien-Hsiung; Chang, Chin-Lung; Lin, Chiu-Feng; Fu, Lung-Ming

2007-08-01

In this paper, we present a novel active microfluidic mixer utilizing a dispersion effect in an expansion chamber and applying interactively time-pulsed driving voltages to the respective inlet fluid flows to induce electroosmotic flow velocity variations for developing a rapid mixing effect in a microchannel. Without using any additional equipment to induce flow perturbations, only a single high-voltage power source is required for simultaneously driving and mixing sample fluids, which results in a simple and low-cost system for mixing. The effects of the applied main electrical field, interactive frequency, and expansion ratio on the mixing performance are thoroughly examined experimentally and numerically. The mixing ratio can be as high as 95% within a mixing length of 3000 μm downstream from the secondary T-form when a driving electric field strength of 250 V/cm, a periodic switching frequency of 5 Hz, and the expansion ratio M=1:10 are applied. In addition, the optimization of the driving electric field, switching frequency, expansion ratio, expansion entry length, and expansion chamber length for achieving a maximum mixing ratio is also discussed in this study. The novel method proposed in this study can be used for solving the mixing problem in the field of micro-total-analysis systems in a simple manner.

Ultrafast microfluidic mixer for tracking the early folding kinetics of human telomere G-quadruplex.

PubMed

Li, Ying; Liu, Chao; Feng, Xiaojun; Xu, Youzhi; Liu, Bi-Feng

2014-05-06

The folding of G-quadruplex is hypothesized to undergo a complex process, from the formation of a hairpin structure to a triplex intermediate and to the final G-quadruplex. Currently, no experimental evidence has been found for the hairpin formation, because it folds in the time regime of 10-100 μs, entailing the development of microfluidic mixers with a mixing time of less than 10 μs. In this paper, we reported an ultrarapid micromixer with a mixing time of 5.5 μs, which represents the fastest turbulent micromixer to our best knowledge. Evaluations of the micromixer were conducted to confirm its mixing efficiency for small molecules and macromolecules. This new micromixer enabled us to interrogate the hairpin formation in the early folding process of human telomere G-quadruplex. The experimental kinetic evidence for the formation of hairpin was obtained for the first time.

An acoustofluidic micromixer based on oscillating sidewall sharp-edges.

PubMed

Huang, Po-Hsun; Xie, Yuliang; Ahmed, Daniel; Rufo, Joseph; Nama, Nitesh; Chen, Yuchao; Chan, Chung Yu; Huang, Tony Jun

2013-10-07

Rapid and homogeneous mixing inside a microfluidic channel is demonstrated via the acoustic streaming phenomenon induced by the oscillation of sidewall sharp-edges. By optimizing the design of the sharp-edges, excellent mixing performance and fast mixing speed can be achieved in a simple device, making our sharp-edge-based acoustic micromixer a promising candidate for a wide variety of applications.

Studying enzymatic bioreactions in a millisecond microfluidic flow mixer

PubMed Central

Buchegger, Wolfgang; Haller, Anna; van den Driesche, Sander; Kraft, Martin; Lendl, Bernhard; Vellekoop, Michael

2012-01-01

In this study, the pre-steady state development of enzymatic bioreactions using a microfluidic mixer is presented. To follow such reactions fast mixing of reagents (enzyme and substrate) is crucial. By using a highly efficient passive micromixer based on multilaminar flow, mixing times in the low millisecond range are reached. Four lamination layers in a shallow channel reduce the diffusion lengths to a few micrometers only, enabling very fast mixing. This was proven by confocal fluorescence measurements in the channel’s cross sectional area. Adjusting the overall flow rate in the 200 μm wide and 900 μm long mixing and observation channel makes it possible to investigate enzyme reactions over several seconds. Further, the device enables changing the enzyme/substrate ratio from 1:1 up to 3:1, while still providing high mixing efficiency, as shown for the enzymatic hydrolysis using β-galactosidase. This way, the early kinetics of the enzyme reaction at multiple enzyme/substrate concentrations can be collected in a very short time (minutes). The fast and easy handling of the mixing device makes it a very powerful and convenient instrument for millisecond temporal analysis of bioreactions. PMID:22662071

Inertial instabilities in a mixing-separating microfluidic device

NASA Astrophysics Data System (ADS)

Domingues, Allysson; Poole, Robert; Dennis, David

2017-11-01

Combining and separating fluids has many industrial and biomedical applications. This numerical and experimental study explores inertial instabilities in a so-called mixing-separating cell micro-geometry which could potentiality be used to enhance mixing. Our microfluidic mixing-separating cell consists of two straight square parallel channels with flow from opposite directions with a central gap that allows the streams to interact, mix or remain separate (often referred to as the `H' geometry). A stagnation point is generated at the centre of symmetry due to the two opposed inlets and outlets. Under creeping flow conditions (Reynolds number [ Re 0 ]) the flow is steady, two-dimensional and produces a sharp symmetric boundary between fluids stream entering the geometry from opposite directions. For Re > 30 , an inertial instability appears which leads to the generation of a central vortex and the breaking of symmetry, although the flow remains steady. As Re increases the central vortex divides into two vortices. Our experimental and numerical investigations both show the same phenomena. The results suggest that the effect observed can be exploited to enhance mixing in biomedical or other applications. Work supported by CNPq Grant 203195/2014-0.

Design and fabrication of a multilayered polymer microfluidic chip with nanofluidic interconnects via adhesive contact printing.

PubMed

Flachsbart, Bruce R; Wong, Kachuen; Iannacone, Jamie M; Abante, Edward N; Vlach, Robert L; Rauchfuss, Peter A; Bohn, Paul W; Sweedler, Jonathan V; Shannon, Mark A

2006-05-01

The design and fabrication of a multilayered polymer micro-nanofluidic chip is described that consists of poly(methylmethacrylate) (PMMA) layers that contain microfluidic channels separated in the vertical direction by polycarbonate (PC) membranes that incorporate an array of nanometre diameter cylindrical pores. The materials are optically transparent to allow inspection of the fluids within the channels in the near UV and visible spectrum. The design architecture enables nanofluidic interconnections to be placed in the vertical direction between microfluidic channels. Such an architecture allows microchannel separations within the chip, as well as allowing unique operations that utilize nanocapillary interconnects: the separation of analytes based on molecular size, channel isolation, enhanced mixing, and sample concentration. Device fabrication is made possible by a transfer process of labile membranes and the development of a contact printing method for a thermally curable epoxy based adhesive. This adhesive is shown to have bond strengths that prevent leakage and delamination and channel rupture tests exceed 6 atm (0.6 MPa) under applied pressure. Channels 100 microm in width and 20 microm in depth are contact printed without the adhesive entering the microchannel. The chip is characterized in terms of resistivity measurements along the microfluidic channels, electroosmotic flow (EOF) measurements at different pH values and laser-induced-fluorescence (LIF) detection of green-fluorescent protein (GFP) plugs injected across the nanocapillary membrane and into a microfluidic channel. The results indicate that the mixed polymer micro-nanofluidic multilayer chip has electrical characteristics needed for use in microanalytical systems.

High-sensitivity microfluidic calorimeters for biological and chemical applications.

PubMed

Lee, Wonhee; Fon, Warren; Axelrod, Blake W; Roukes, Michael L

2009-09-08

High-sensitivity microfluidic calorimeters raise the prospect of achieving high-throughput biochemical measurements with minimal sample consumption. However, it has been challenging to realize microchip-based calorimeters possessing both high sensitivity and precise sample-manipulation capabilities. Here, we report chip-based microfluidic calorimeters capable of characterizing the heat of reaction of 3.5-nL samples with 4.2-nW resolution. Our approach, based on a combination of hard- and soft-polymer microfluidics, provides both exceptional thermal response and the physical strength necessary to construct high-sensitivity calorimeters that can be scaled to automated, highly multiplexed array architectures. Polydimethylsiloxane microfluidic valves and pumps are interfaced to parylene channels and reaction chambers to automate the injection of analyte at 1 nL and below. We attained excellent thermal resolution via on-chip vacuum encapsulation, which provides unprecedented thermal isolation of the minute microfluidic reaction chambers. We demonstrate performance of these calorimeters by resolving measurements of the heat of reaction of urea hydrolysis and the enthalpy of mixing of water with methanol. The device structure can be adapted easily to enable a wide variety of other standard calorimeter operations; one example, a flow calorimeter, is described.

Microfluidic Diatomite Analytical Devices for Illicit Drug Sensing with ppb-Level Sensitivity.

PubMed

Kong, Xianming; Chong, Xinyuan; Squire, Kenny; Wang, Alan X

2018-04-15

The escalating research interests in porous media microfluidics, such as microfluidic paper-based analytical devices, have fostered a new spectrum of biomedical devices for point-of-care (POC) diagnosis and biosensing. In this paper, we report microfluidic diatomite analytical devices (μDADs), which consist of highly porous photonic crystal biosilica channels, as an innovative lab-on-a-chip platform to detect illicit drugs. The μDADs in this work are fabricated by spin-coating and tape-stripping diatomaceous earth on regular glass slides with cross section of 400×30µm 2 . As the most unique feature, our μDADs can simultaneously perform on-chip chromatography to separate small molecules from complex biofluidic samples and acquire the surface-enhanced Raman scattering spectra of the target chemicals with high specificity. Owing to the ultra-small dimension of the diatomite microfluidic channels and the photonic crystal effect from the fossilized diatom frustules, we demonstrate unprecedented sensitivity down to part-per-billion (ppb) level when detecting pyrene (1ppb) from mixed sample with Raman dye and cocaine (10 ppb) from human plasma. This pioneering work proves the exclusive advantage of μDADs as emerging microfluidic devices for chemical and biomedical sensing, especially for POC drug screening.

Determination of cell metabolite VEGF₁₆₅ and dynamic analysis of protein-DNA interactions by combination of microfluidic technique and luminescent switch-on probe.

PubMed

Lin, Xuexia; Leung, Ka-Ho; Lin, Ling; Lin, Luyao; Lin, Sheng; Leung, Chung-Hang; Ma, Dik-Lung; Lin, Jin-Ming

2016-05-15

In this paper, we rationally design a novel G-quadruplex-selective luminescent iridium (III) complex for rapid detection of oligonucleotide and VEGF165 in microfluidics. This new probe is applied as a convenient biosensor for label-free quantitative analysis of VEGF165 protein from cell metabolism, as well as for studying the kinetics of the aptamer-protein interaction combination with a microfluidic platform. As a result, we have successfully established a quantitative analysis of VEGF165 from cell metabolism. Furthermore, based on the principles of hydrodynamic focusing and diffusive mixing, different transient states during kinetics process were monitored and recorded. Thus, the combination of microfluidic technique and G-quadruplex luminescent probe will be potentially applied in the studies of intramolecular interactions and molecule recognition in the future. Copyright © 2015 Elsevier B.V. All rights reserved.

Automated centrifugal-microfluidic platform for DNA purification using laser burst valve and coriolis effect.

PubMed

Choi, Min-Seong; Yoo, Jae-Chern

2015-04-01

We report a fully automated DNA purification platform with a micropored membrane in the channel utilizing centrifugal microfluidics on a lab-on-a-disc (LOD). The microfluidic flow in the LOD, into which the reagents are injected for DNA purification, is controlled by a single motor and laser burst valve. The sample and reagents pass successively through the micropored membrane in the channel when each laser burst valve is opened. The Coriolis effect is used by rotating the LOD bi-directionally to increase the purity of the DNA, thereby preventing the mixing of the waste and elution solutions. The total process from the lysed sample injection into the LOD to obtaining the purified DNA was finished within 7 min with only one manual step. The experimental result for Salmonella shows that the proposed microfluidic platform is comparable to the existing devices in terms of the purity and yield of DNA.

3D-Printed Microfluidic Automation

PubMed Central

Au, Anthony K.; Bhattacharjee, Nirveek; Horowitz, Lisa F.; Chang, Tim C.; Folch, Albert

2015-01-01

Microfluidic automation – the automated routing, dispensing, mixing, and/or separation of fluids through microchannels – generally remains a slowly-spreading technology because device fabrication requires sophisticated facilities and the technology’s use demands expert operators. Integrating microfluidic automation in devices has involved specialized multi-layering and bonding approaches. Stereolithography is an assembly-free, 3D-printing technique that is emerging as an efficient alternative for rapid prototyping of biomedical devices. Here we describe fluidic valves and pumps that can be stereolithographically printed in optically-clear, biocompatible plastic and integrated within microfluidic devices at low cost. User-friendly fluid automation devices can be printed and used by non-engineers as replacement for costly robotic pipettors or tedious manual pipetting. Engineers can manipulate the designs as digital modules into new devices of expanded functionality. Printing these devices only requires the digital file and electronic access to a printer. PMID:25738695

Microfluidics-based integrated airborne pathogen detection systems

NASA Astrophysics Data System (ADS)

Northrup, M. Allen; Alleman-Sposito, Jennifer; Austin, Todd; Devitt, Amy; Fong, Donna; Lin, Phil; Nakao, Brian; Pourahmadi, Farzad; Vinas, Mary; Yuan, Bob

2006-09-01

Microfluidic Systems is focused on building microfluidic platforms that interface front-end mesofluidics to handle real world sample volumes for optimal sensitivity coupled to microfluidic circuitry to process small liquid volumes for complex reagent metering, mixing, and biochemical analysis, particularly for pathogens. MFSI is the prime contractor on two programs for the US Department of Homeland Security: BAND (Bioagent Autonomous Networked Detector) and IBADS (Instantaneous Bio-Aerosol Detection System). The goal of BAND is to develop an autonomous system for monitoring the air for known biological agents. This consists of air collection, sample lysis, sample purification, detection of DNA, RNA, and toxins, and a networked interface to report the results. For IBADS, MFSI is developing the confirmatory device which must verify the presence of a pathogen with 5 minutes of an air collector/trigger sounding an alarm. Instrument designs and biological assay results from both BAND and IBADS will be presented.

Electroosmotic mixing in microchannels.

PubMed

Glasgow, Ian; Batton, John; Aubry, Nadine

2004-12-01

Mixing is an essential, yet challenging, process step for many Lab on a Chip (LOC) applications. This paper presents a method of mixing for microfluidic devices that relies upon electroosmotic flow. In physical tests and in computer simulations, we periodically vary the electric field with time to mix two aqueous solutions. Good mixing is shown to occur when the electroosmotic flow at the two inlets pulse out of phase, the Strouhal number is on the order of 1, and the pulse volumes are on the order of the intersection volume.

An acoustofluidic micromixer based on oscillating sidewall sharp-edges†

PubMed Central

Huang, Po-Hsun; Xie, Yuliang; Ahmed, Daniel; Rufo, Joseph; Nama, Nitesh; Chen, Yuchao; Chan, Chung Yu; Huang, Tony Jun

2014-01-01

Rapid and homogeneous mixing inside a microfluidic channel is demonstrated via the acoustic streaming phenomenon induced by the oscillation of sidewall sharp-edges. By optimizing the design of the sharp-edges, excellent mixing performance and fast mixing speed can be achieved in a simple device, making our sharp-edge-based acoustic micromixer a promising candidate for a wide variety of applications. PMID:23896797

On-chip gradient generation in 256 microfluidic cell cultures: simulation and experimental validation.

PubMed

Somaweera, Himali; Haputhanthri, Shehan O; Ibraguimov, Akif; Pappas, Dimitri

2015-08-07

A microfluidic diffusion diluter was used to create a stable concentration gradient for dose response studies. The microfluidic diffusion diluter used in this study consisted of 128 culture chambers on each side of the main fluidic channel. A calibration method was used to find unknown concentrations with 12% error. Flow rate dependent studies showed that changing the flow rates generated different gradient patterns. Mathematical simulations using COMSOL Multi-physics were performed to validate the experimental data. The experimental data obtained for the flow rate studies agreed with the simulation results. Cells could be loaded into culture chambers using vacuum actuation and cultured for long times under low shear stress. Decreasing the size of the culture chambers resulted in faster gradient formation (20 min). Mass transport into the side channels of the microfluidic diffusion diluter used in this study is an important factor in creating the gradient using diffusional mixing as a function of the distance. To demonstrate the device's utility, an H2O2 gradient was generated while culturing Ramos cells. Cell viability was assayed in the 256 culture chambers, each at a discrete H2O2 concentration. As expected, the cell viability for the high concentration side channels increased (by injecting H2O2) whereas the cell viability in the low concentration side channels decreased along the chip due to diffusional mixing as a function of distance. COMSOL simulations were used to identify the effective concentration of H2O2 for cell viability in each side chamber at 45 min. The gradient effects were confirmed using traditional H2O2 culture experiments. Viability of cells in the microfluidic device under gradient conditions showed a linear relationship with the viability of the traditional culture experiment. Development of the microfluidic device used in this study could be used to study hundreds of concentrations of a compound in a single experiment.

A single microfluidic chip with dual surface properties for protein drug delivery.

PubMed

Bokharaei, Mehrdad; Saatchi, Katayoun; Häfeli, Urs O

2017-04-15

Principles of double emulsion generation were incorporated in a glass microfluidic chip fabricated with two different surface properties in order to produce protein loaded polymer microspheres. The microspheres were produced by integrating two microfluidic flow focusing systems and a multi-step droplet splitting and mixing system into one chip. The chip consists of a hydrophobic and a hydrophilic section with two different heights, 12μm and 45μm, respectively. As a result, the protein is homogenously distributed throughout the polymer microsphere matrix, not just in its center (which has been studied before). In our work, the inner phase was bovine serum albumin (BSA) in phosphate buffered saline, the disperse phase was poly (lactic acid) in chloroform and the continuous phase was an aqueous solution of poly(vinyl alcohol). After solvent removal, BSA loaded microspheres with an encapsulation efficiency of up to 96% were obtained. Our results show the feasibility of producing microspheres loaded with a hydrophilic drug in a microfluidic system that integrates different microfluidic units into one chip. Copyright © 2017 Elsevier B.V. All rights reserved.

Quantitative comparison of inflammatory infiltrate and linear contraction in human skin treated with 90-microsecond pulsed and 900-microsecond dwell time carbon dioxide lasers.

PubMed

Bucalo, B D; Moy, R L

1998-12-01

Skin resurfacing with 90-microsecond pulse duration carbon dioxide (CO2) resurfacing lasers has been reported to have shorter duration of erythema compared with skin resurfacing with 900-microsecond dwell time lasers. The presence of inflammatory infiltrate following resurfacing may correlate with the persistence of this erythema. Furthermore, skin treated with the 90-microsecond pulse duration laser and the 900-microsecond dwell time lasers both result in equivalent improvement of rhytids in the treated skin. To quantitative the inflammatory cell infiltrate and linear contraction of skin treated with the 90-microsecond pulsed and 900-microsecond dwell time CO2 lasers at intervals of 2 and 4 weeks after treatment. Volunteers were recruited from patients who were planning to undergo full face laser resurfacing under general anesthesia. Informed consent was obtained from all volunteers. In the posterior auricular areas of all volunteers, four separate rectangular areas were marked using a skin marking pen and a template. Two rectangular areas behind the right ear were treated with 6 passes of the 90-microsecond laser and two rectangular areas behind the left ear were treated with the 900-microsecond dwell time laser. The resurfaced areas were wiped with a moist cotton swab and then patted dry with dry gauze between passes. Contraction measurements of the resurfaced areas were taken before and immediately after laser treatment and again at 2 and 4 weeks following treatment. Punch biopsies were also performed at 2 and 4 weeks after treatment in an area of skin different from where contraction measurements were taken. The number of inflammatory cells present in the skin at 2 and 4 weeks after laser resurfacing are greater for skin resurfaced with a 900-microsecond dwell time laser than a 90-microsecond pulse time laser. Linear contraction of skin immediately after treatment was 18% greater with the 900-microsecond dwell time laser than with the 90-microsecond pulsed laser. The difference in the amount of contraction produced by the lasers tended to decrease over time. At 4 weeks there was a 10% difference in mean linear contraction between the two laser types. Increased numbers of inflammatory cells in skin resurfaced with the 900-microsecond dwell time laser may explain the observed persistence of erythema associated with the 900-microsecond dwell time laser. Measurable linear contraction produced by the 900-microsecond dwell time laser was initially 18% greater than the 90-microsecond pulse laser. This difference tends to decrease over time.

An effective splitting-and-recombination micromixer with self-rotated contact surface for wide Reynolds number range applications

PubMed Central

Feng, Xiangsong; Ren, Yukun; Jiang, Hongyuan

2013-01-01

It is difficult to mix two liquids on a microfluidic chip because the small dimensions and velocities effectively prevent the turbulence. This paper describes two 2-layer PDMS passive micromixers based on the concept of splitting and recombining the flow that exploits a self-rotated contact surface to increase the concentration gradients to obtain fast and efficient mixing. The designed micromixers were simulated and the mixing performance was assessed. The mixers have shown excellent mixing efficiency over a wide range of Reynolds number. The mixers were reasonably fabricated by multilayer soft lithography, and the experimental measurements were performed to qualify the mixing performance of the realized mixer. The results show that the mixing efficiency for one realized mixer is from 91.8% to 87.7% when the Reynolds number increases from 0.3 to 60, while the corresponding value for another mixer is from 89.4% to 72.9%. It is rather interesting that the main mechanism for the rapid mixing is from diffusion to chaotic advection when the flow rate increases, but the mixing efficiency has not obvious decline. The smart geometry of the mixers with total length of 10.25 mm makes it possible to be integrated with many microfluidic devices for various applications in μ-TAS and Lab-on-a-chip systems. PMID:24396530

An effective splitting-and-recombination micromixer with self-rotated contact surface for wide Reynolds number range applications.

PubMed

Feng, Xiangsong; Ren, Yukun; Jiang, Hongyuan

2013-01-01

It is difficult to mix two liquids on a microfluidic chip because the small dimensions and velocities effectively prevent the turbulence. This paper describes two 2-layer PDMS passive micromixers based on the concept of splitting and recombining the flow that exploits a self-rotated contact surface to increase the concentration gradients to obtain fast and efficient mixing. The designed micromixers were simulated and the mixing performance was assessed. The mixers have shown excellent mixing efficiency over a wide range of Reynolds number. The mixers were reasonably fabricated by multilayer soft lithography, and the experimental measurements were performed to qualify the mixing performance of the realized mixer. The results show that the mixing efficiency for one realized mixer is from 91.8% to 87.7% when the Reynolds number increases from 0.3 to 60, while the corresponding value for another mixer is from 89.4% to 72.9%. It is rather interesting that the main mechanism for the rapid mixing is from diffusion to chaotic advection when the flow rate increases, but the mixing efficiency has not obvious decline. The smart geometry of the mixers with total length of 10.25 mm makes it possible to be integrated with many microfluidic devices for various applications in μ-TAS and Lab-on-a-chip systems.

Design of Interactively Time-Pulsed Microfluidic Mixers in Microchips using Numerical Simulation

NASA Astrophysics Data System (ADS)

Fu, Lung-Ming; Tsai, Chien-Hsiung

2007-01-01

In this paper, we propose a novel technique in which driving voltages are applied interactively to the respective inlet fluid flows of three configurations of a microfluidic device, namely T-shaped, double-T-shaped, and double-cross-shaped configurations, to induce electroosmotic flow (EOF) velocity variations in such a way as to develop a rapid mixing effect in the microchannel. In these configurations a microfluidic mixer apply only one electrokinetic driving force, which drives the sample fluids and simultaneously produces a periodic switching frequency. It requires no other external driving force to induce perturbations to the flow field. The effects of the main applied electric field, the interactive frequency, and the pullback electric field on the mixing performance are thoroughly examined numerically. The optimal interactive frequency range for a given set of micromixer parameters is identified for each type of control mode. The numerical results confirm that micromixers operating at an optimal interactive frequency are capable of delivering a significantly enhanced mixing performance. Furthermore, it is shown that the optimal interactive frequency depends upon the magnitude of the main applied electric field. The interactively pulsed mixers developed in this study have a strong potential for use in lab-on-a-chip systems. They involve a simpler fabrication process than either passive or active on-chip mixers and require less human intervention in operation than their bulky external counterparts.

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.

Optimized open-flow mixing: insights from microbubble streaming

NASA Astrophysics Data System (ADS)

Rallabandi, Bhargav; Wang, Cheng; Guo, Lin; Hilgenfeldt, Sascha

2015-11-01

Microbubble streaming has been developed into a robust and powerful flow actuation technique in microfluidics. Here, we study it as a paradigmatic system for microfluidic mixing under a continuous throughput of fluid (open-flow mixing), providing a systematic optimization of the device parameters in this practically important situation. Focusing on two-dimensional advective stirring (neglecting diffusion), we show through numerical simulation and analytical theory that mixing in steady streaming vortices becomes ineffective beyond a characteristic time scale, necessitating the introduction of unsteadiness. By duty cycling the streaming, such unsteadiness is introduced in a controlled fashion, leading to exponential refinement of the advection structures. The rate of refinement is then optimized for particular parameters of the time modulation, i.e. a particular combination of times for which the streaming is turned ``on'' and ``off''. The optimized protocol can be understood theoretically using the properties of the streaming vortices and the throughput Poiseuille flow. We can thus infer simple design principles for practical open flow micromixing applications, consistent with experiments. Current Address: Mechanical and Aerospace Engineering, Princeton University.

Rapid and Quantitative Detection of Vibrio parahemolyticus by the Mixed-Dye-Based Loop-Mediated Isothermal Amplification Assay on a Self-Priming Compartmentalization Microfluidic Chip.

PubMed

Pang, Bo; Ding, Xiong; Wang, Guoping; Zhao, Chao; Xu, Yanan; Fu, Kaiyue; Sun, Jingjing; Song, Xiuling; Wu, Wenshuai; Liu, Yushen; Song, Qi; Hu, Jiumei; Li, Juan; Mu, Ying

2017-12-27

Vibrio parahemolyticus (VP) mostly isolated from aquatic products is one of the major causes of bacterial food-poisoning events worldwide, which could be reduced using a promising on-site detection method. Herein, a rapid and quantitative method for VP detection was developed by applying a mixed-dye-loaded loop-mediated isothermal amplification (LAMP) assay on a self-priming compartmentalization (SPC) microfluidic chip, termed on-chip mixed-dye-based LAMP (CMD-LAMP). In comparison to conventional approaches, CMD-LAMP was advantageous on the limit of detection, which reached down to 1 × 10 3 CFU/mL in food-contaminated samples without the pre-enrichment of bacteria. Additionally, as a result of the use of a mixed dye and SPC chip, the quantitative result could be easily acquired, avoiding the requirement of sophisticated instruments and tedious operation. Also, CMD-LAMP was rapid and cost-effective. Conclusively, CMD-LAMP has great potential in realizing the on-site quantitative analysis of VP for food safety.

Impact of Motile Bacterial Suspensions on Viscous Fingering and Mixing

NASA Astrophysics Data System (ADS)

Chui, Jane; Auradou, Harold; de Anna, Pietro; Fahrner, Karen; Berg, Howard; Juanes, Ruben

2017-11-01

Viscous fingering is a hydrodynamic instability that occurs when a less viscous fluid displaces a more viscous one. Instead of progressing as a uniform front, the less viscous fluid forms fingers to create complex patterns. Understanding how these patterns and their associated gradients evolve over time is of critical importance in characterizing the mixing of two fluids, which in turn is important to applications such as enhanced oil recovery, bioremediation, and microfluidics. Here, we investigate the impact of replacing the less viscous fluid with an active suspension of motile bacteria. In this series of experiments, a suspension of motile Escherichia coli capable of collective swimming is injected into a microfluidic Hele-Shaw cell under viscous fingering conditions. Through videomicroscopy, we obtain high-resolution concentration fields to determine the evolution of the mixing zone (region with concentration gradients). We quantify the impact that active suspensions have on the formation of viscous fingering patterns and mixing efficiency between the two fluids, and-conversely-report details of the collective swimming behavior in the presence of a viscous-gradient front.

Microfluidic Chips Controlled with Elastomeric Microvalve Arrays

PubMed Central

Li, Nianzhen; Sip, Chris; Folch, Albert

2007-01-01

Miniaturized microfluidic systems provide simple and effective solutions for low-cost point-of-care diagnostics and high-throughput biomedical assays. Robust flow control and precise fluidic volumes are two critical requirements for these applications. We have developed microfluidic chips featuring elastomeric polydimethylsiloxane (PDMS) microvalve arrays that: 1) need no extra energy source to close the fluidic path, hence the loaded device is highly portable; and 2) allow for microfabricating deep (up to 1 mm) channels with vertical sidewalls and resulting in very precise features. The PDMS microvalves-based devices consist of three layers: a fluidic layer containing fluidic paths and microchambers of various sizes, a control layer containing the microchannels necessary to actuate the fluidic path with microvalves, and a middle thin PDMS membrane that is bound to the control layer. Fluidic layer and control layers are made by replica molding of PDMS from SU-8 photoresist masters, and the thin PDMS membrane is made by spinning PDMS at specified heights. The control layer is bonded to the thin PDMS membrane after oxygen activation of both, and then assembled with the fluidic layer. The microvalves are closed at rest and can be opened by applying negative pressure (e.g., house vacuum). Microvalve closure and opening are automated via solenoid valves controlled by computer software. Here, we demonstrate two microvalve-based microfluidic chips for two different applications. The first chip allows for storing and mixing precise sub-nanoliter volumes of aqueous solutions at various mixing ratios. The second chip allows for computer-controlled perfusion of microfluidic cell cultures. The devices are easy to fabricate and simple to control. Due to the biocompatibility of PDMS, these microchips could have broad applications in miniaturized diagnostic assays as well as basic cell biology studies. PMID:18989408

Design and Parameter Study of Integrated Microfluidic Platform for CTC Isolation and Enquiry; A Numerical Approach.

PubMed

Shamloo, Amir; Ahmad, Saba; Momeni, Maede

2018-06-18

Being the second cause of mortality across the globe, there is now a persistent effort to establish new cancer medication and therapies. Any accomplishment in treating cancers entails the existence of accurate identification systems empowering the early diagnosis. Recent studies indicate CTCs’ potential in cancer prognosis as well as therapy monitoring. The chief shortcoming with CTCs is that they are exceedingly rare cells in their clinically relevant concentration. Here, we simulated a microfluidic construct devised for immunomagnetic separation of the particles of interest from the background cells. This separation unit is integrated with a mixer subunit. The mixer is envisioned for mixing the CTC enriched stream with lysis buffer to extract the biological material of the cell. Some modification was proposed on mixing geometry improving the efficacy of the functional unit. A valuation of engaged forces was made and some forces were neglected due to their order of magnitude. The position of the magnet was also optimized by doing parametric study. For the mixer unit, the effect of applied voltage and frequency on mixing index was studied to find the optimal voltage and frequency which provides better mixing. Above-mentioned studies were done on isolated units and the effect of each functional unit on the other is not studied. As the final step, an integrated microfluidic platform composed of both functional subunits was simulated simultaneously. To ensure the independence of results from the grid, grid studies were also performed. The studies carried out on the construct reveal its potential for diagnostic application.

Active Mixing in Microchannels using Surface Acoustic Wave Streaming on Lithium Niobate

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

Branch, Darren W.; Meyer, Grant D.; Bourdon, Christopher Jay

2005-11-01

We present an active method for mixing fluid streams in microchannels at low Reynolds number with no dead volume. To overcome diffusion limited mixing in microchannels, surface acoustic wave streaming offers an extremely effective approach to rapidly homogenize fluids. This is a pivotal improvement over mixers based on complex 3D microchannels which have significant dead volume resulting in trapping or loss of sample. Our micromixer is integrable and highly adaptable for use within existing microfluidic devices. Surface acoustic wave devices fabricated on 128° YX LiNbO 3 permitted rapid mixing of flow streams as evidenced by fluorescence microscopy. Longitudinal waves createdmore » at the solid-liquid interface were capable of inducing strong nonlinear gradients within the bulk fluid. In the highly laminar regime (Re = 2), devices achieved over 93% mixing efficacy in less than a second. Micro-particle imaging velicometry was used to determine the mixing behavior in the microchannels and indicated that the liquid velocity can be controlled by varying the input power. Fluid velocities in excess of 3 cm•s -1 were measured in the main excitation region at low power levels (2.8mW). We believe that this technology will be pivotal in the development and advancement of microfluidic devices and applications.« less

Optimization of multiplexed PCR on an integrated microfluidic forensic platform for rapid DNA analysis.

PubMed

Estes, Matthew D; Yang, Jianing; Duane, Brett; Smith, Stan; Brooks, Carla; Nordquist, Alan; Zenhausern, Frederic

2012-12-07

This study reports the design, prototyping, and assay development of multiplexed polymerase chain reaction (PCR) on a plastic microfluidic device. Amplification of 17 DNA loci is carried out directly on-chip as part of a system for continuous workflow processing from sample preparation (SP) to capillary electrophoresis (CE). For enhanced performance of on-chip PCR amplification, improved control systems have been developed making use of customized Peltier assemblies, valve actuators, software, and amplification chemistry protocols. Multiple enhancements to the microfluidic chip design have been enacted to improve the reliability of sample delivery through the various on-chip modules. This work has been enabled by the encapsulation of PCR reagents into a solid phase material through an optimized Solid Phase Encapsulating Assay Mix (SPEAM) bead-based hydrogel fabrication process. SPEAM bead technology is reliably coupled with precise microfluidic metering and dispensing for efficient amplification and subsequent DNA short tandem repeat (STR) fragment analysis. This provides a means of on-chip reagent storage suitable for microfluidic automation, with the long shelf-life necessary for point-of-care (POC) or field deployable applications. This paper reports the first high quality 17-plex forensic STR amplification from a reference sample in a microfluidic chip with preloaded solid phase reagents, that is designed for integration with up and downstream processing.

Controlled droplet microfluidic systems for multistep chemical and biological assays.

PubMed

Kaminski, T S; Garstecki, P

2017-10-16

Droplet microfluidics is a relatively new and rapidly evolving field of science focused on studying the hydrodynamics and properties of biphasic flows at the microscale, and on the development of systems for practical applications in chemistry, biology and materials science. Microdroplets present several unique characteristics of interest to a broader research community. The main distinguishing features include (i) large numbers of isolated compartments of tiny volumes that are ideal for single cell or single molecule assays, (ii) rapid mixing and negligible thermal inertia that all provide excellent control over reaction conditions, and (iii) the presence of two immiscible liquids and the interface between them that enables new or exotic processes (the synthesis of new functional materials and structures that are otherwise difficult to obtain, studies of the functions and properties of lipid and polymer membranes and execution of reactions at liquid-liquid interfaces). The most frequent application of droplet microfluidics relies on the generation of large numbers of compartments either for ultrahigh throughput screens or for the synthesis of functional materials composed of millions of droplets or particles. Droplet microfluidics has already evolved into a complex field. In this review we focus on 'controlled droplet microfluidics' - a portfolio of techniques that provide convenient platforms for multistep complex reaction protocols and that take advantage of automated and passive methods of fluid handling on a chip. 'Controlled droplet microfluidics' can be regarded as a group of methods capable of addressing and manipulating droplets in series. The functionality and complexity of controlled droplet microfluidic systems can be positioned between digital microfluidics (DMF) addressing each droplet individually using 2D arrays of electrodes and ultrahigh throughput droplet microfluidics focused on the generation of hundreds of thousands or even millions of picoliter droplets that cannot be individually addressed by their location on a chip.

Digital hydraulic drive for microfluidics and miniaturized cell culture devices based on shape memory alloy actuators

NASA Astrophysics Data System (ADS)

Tsai, Cheng-Han; Wu, Xuanye; Kuan, Da-Han; Zimmermann, Stefan; Zengerle, Roland; Koltay, Peter

2018-08-01

In order to culture and analyze individual living cells, microfluidic cultivation and manipulation of cells become an increasingly important topic. Such microfluidic systems allow for exploring the phenotypic differences between thousands of genetically identical cells or pharmacological tests in parallel, which is impossible to achieve by traditional macroscopic cell culture methods. Therefore, plenty of microfluidic systems and devices have been developed for cell biological studies like cell culture, cell sorting, and cell lysis in the past. However, these microfluidic systems are still limited by the external pressure sources which most of the time are large in size and have to be connected by fluidic tubing leading to complex and delicate systems. In order to provide a miniaturized, more robust actuation system a novel, compact and low power consumption digital hydraulic drive (DHD) has been developed that is intended for use in portable and automated microfluidic systems for various applications. The DHD considered in this work consists of a shape memory alloy (SMA) actuator and a pneumatic cylinder. The switching time of the digital modes (pressure ON versus OFF) can be adjusted from 1 s to min. Thus, the DHDs might have many applications for driving microfluidic devices. In this work, different implementations of DHDs are presented and their performance is characterized by experiments. In particular, it will be shown that DHDs can be used for microfluidic large-scale integration (mLSI) valve control (256 valves in parallel) as well as potentially for droplet-based microfluidic systems. As further application example, high-throughput mixing of cell cultures (96 wells in parallel) is demonstrated employing the DHD to drive a so-called ‘functional lid’ (FL), to enable a miniaturized micro bioreactor in a regular 96-well micro well plate.

Design and development of a microfluidic platform for use with colorimetric gold nanoprobe assays

NASA Astrophysics Data System (ADS)

Bernacka-Wojcik, Iwona

Due to the importance and wide applications of the DNA analysis, there is a need to make genetic analysis more available and more affordable. As such, the aim of this PhD thesis is to optimize a colorimetric DNA biosensor based on gold nanoprobes developed in CEMOP by reducing its price and the needed volume of solution without compromising the device sensitivity and reliability, towards the point of care use. Firstly, the price of the biosensor was decreased by replacing the silicon photodetector by a low cost, solution processed TiO2 photodetector. To further reduce the photodetector price, a novel fabrication method was developed: a cost-effective inkjet printing technology that enabled to increase TiO2 surface area. Secondly, the DNA biosensor was optimized by means of microfluidics that offer advantages of miniaturization, much lower sample/reagents consumption, enhanced system performance and functionality by integrating different components. In the developed microfluidic platform, the optical path length was extended by detecting along the channel and the light was transmitted by optical fibres enabling to guide the light very close to the analysed solution. Microfluidic chip of high aspect ratio ( 13), smooth and nearly vertical sidewalls was fabricated in PDMS using a SU-8 mould for patterning. The platform coupled to the gold nanoprobe assay enabled detection of Mycobacterium tuberculosis using 3 mul on DNA solution, i.e. 20 times less than in the previous state-of-the-art. Subsequently, the bio-microfluidic platform was optimized in terms of cost, electrical signal processing and sensitivity to colour variation, yielding 160% improvement of colorimetric AuNPs analysis. Planar microlenses were incorporated to converge light into the sample and then to the output fibre core increasing 6 times the signal-to-losses ratio. The optimized platform enabled detection of single nucleotide polymorphism related with obesity risk (FTO) using target DNA concentration below the limit of detection of the conventionally used microplate reader (i.e. 15 ng/mul) with 10 times lower solution volume (3 mul). The combination of the unique optical properties of gold nanoprobes with microfluidic platform resulted in sensitive and accurate sensor for single nucleotide polymorphism detection operating using small volumes of solutions and without the need for substrate functionalization or sophisticated instrumentation. Simultaneously, to enable on chip reagents mixing, a PDMS micromixer was developed and optimized for the highest efficiency, low pressure drop and short mixing length. The optimized device shows 80% of mixing efficiency at Re = 0.1 in 2.5 mm long mixer with the pressure drop of 6 Pa, satisfying requirements for the application in the microfluidic platform for DNA analysis.

Facile fabrication of a rigid and chemically resistant micromixer system from photocurable inorganic polymer by static liquid photolithography (SLP).

PubMed

Fang, Qingling; Kim, Dong-Pyo; Li, Xiaodong; Yoon, Tae-Ho; Li, Yihe

2011-08-21

Highly effective mixing in microchannels is important for most chemical reactions conducted in microfluidic chips. To obtain a rigid and chemically resistant micromixer system at low cost, we fabricated a Y-shaped microchannel with built-in mixer structures by static liquid photolithography (SLP) from methacrylated polyvinylsilazane (MPVSZ) as an inorganic polymer photoresist which was then converted to a silicate phase by hydrolysis in vaporized ammonia atmosphere at 80 °C. The microchannel incorporating herringbone mixer structures was bonded with a matching polydimethylsiloxane (PDMS) open channel which was pre-coated by perhydropolysilazane (PHPS)-based mixture, and finally treated by additional hydrolysis at room temperature to convert the PHPS layer to a silica phase. Finally, the chemical resistance of the microfluidic system with embedded micromixer was confirmed with various solvents, and the excellent mixing performance in a short mixing length of 2.3 cm was demonstrated by injecting two different colored fluids into the microchannel. This journal is © The Royal Society of Chemistry 2011

High-throughput manufacturing of size-tuned liposomes by a new microfluidics method using enhanced statistical tools for characterization.

PubMed

Kastner, Elisabeth; Kaur, Randip; Lowry, Deborah; Moghaddam, Behfar; Wilkinson, Alexander; Perrie, Yvonne

2014-12-30

Microfluidics has recently emerged as a new method of manufacturing liposomes, which allows for reproducible mixing in miliseconds on the nanoliter scale. Here we investigate microfluidics-based manufacturing of liposomes. The aim of these studies was to assess the parameters in a microfluidic process by varying the total flow rate (TFR) and the flow rate ratio (FRR) of the solvent and aqueous phases. Design of experiment and multivariate data analysis were used for increased process understanding and development of predictive and correlative models. High FRR lead to the bottom-up synthesis of liposomes, with a strong correlation with vesicle size, demonstrating the ability to in-process control liposomes size; the resulting liposome size correlated with the FRR in the microfluidics process, with liposomes of 50 nm being reproducibly manufactured. Furthermore, we demonstrate the potential of a high throughput manufacturing of liposomes using microfluidics with a four-fold increase in the volumetric flow rate, maintaining liposome characteristics. The efficacy of these liposomes was demonstrated in transfection studies and was modelled using predictive modeling. Mathematical modelling identified FRR as the key variable in the microfluidic process, with the highest impact on liposome size, polydispersity and transfection efficiency. This study demonstrates microfluidics as a robust and high-throughput method for the scalable and highly reproducible manufacture of size-controlled liposomes. Furthermore, the application of statistically based process control increases understanding and allows for the generation of a design-space for controlled particle characteristics. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Punch card programmable microfluidics.

PubMed

Korir, George; Prakash, Manu

2015-01-01

Small volume fluid handling in single and multiphase microfluidics provides a promising strategy for efficient bio-chemical assays, low-cost point-of-care diagnostics and new approaches to scientific discoveries. However multiple barriers exist towards low-cost field deployment of programmable microfluidics. Incorporating multiple pumps, mixers and discrete valve based control of nanoliter fluids and droplets in an integrated, programmable manner without additional required external components has remained elusive. Combining the idea of punch card programming with arbitrary fluid control, here we describe a self-contained, hand-crank powered, multiplex and robust programmable microfluidic platform. A paper tape encodes information as a series of punched holes. A mechanical reader/actuator reads these paper tapes and correspondingly executes operations onto a microfluidic chip coupled to the platform in a plug-and-play fashion. Enabled by the complexity of codes that can be represented by a series of holes in punched paper tapes, we demonstrate independent control of 15 on-chip pumps with enhanced mixing, normally-closed valves and a novel on-demand impact-based droplet generator. We demonstrate robustness of operation by encoding a string of characters representing the word "PUNCHCARD MICROFLUIDICS" using the droplet generator. Multiplexing is demonstrated by implementing an example colorimetric water quality assays for pH, ammonia, nitrite and nitrate content in different water samples. With its portable and robust design, low cost and ease-of-use, we envision punch card programmable microfluidics will bring complex control of microfluidic chips into field-based applications in low-resource settings and in the hands of children around the world.

Electrokinetic micro-fluid mixer

DOEpatents

Paul, Phillip H.; Rakestraw, David J.

2000-01-01

A method and apparatus for efficiently and rapidly mixing liquids in a system operating in the creeping flow regime such as would be encountered in capillary-based systems. By applying an electric field to each liquid, the present invention is capable of mixing together fluid streams in capillary-based systems, where mechanical or turbulent stirring cannot be used, to produce a homogeneous liquid.

A mix-and-read drop-based in vitro two-hybrid method for screening high-affinity peptide binders

PubMed Central

Cui, Naiwen; Zhang, Huidan; Schneider, Nils; Tao, Ye; Asahara, Haruichi; Sun, Zhiyi; Cai, Yamei; Koehler, Stephan A.; de Greef, Tom F. A.; Abbaspourrad, Alireza; Weitz, David A.; Chong, Shaorong

2016-01-01

Drop-based microfluidics have recently become a novel tool by providing a stable linkage between phenotype and genotype for high throughput screening. However, use of drop-based microfluidics for screening high-affinity peptide binders has not been demonstrated due to the lack of a sensitive functional assay that can detect single DNA molecules in drops. To address this sensitivity issue, we introduced in vitro two-hybrid system (IVT2H) into microfluidic drops and developed a streamlined mix-and-read drop-IVT2H method to screen a random DNA library. Drop-IVT2H was based on the correlation between the binding affinity of two interacting protein domains and transcriptional activation of a fluorescent reporter. A DNA library encoding potential peptide binders was encapsulated with IVT2H such that single DNA molecules were distributed in individual drops. We validated drop-IVT2H by screening a three-random-residue library derived from a high-affinity MDM2 inhibitor PMI. The current drop-IVT2H platform is ideally suited for affinity screening of small-to-medium-sized libraries (103–106). It can obtain hits within a single day while consuming minimal amounts of reagents. Drop-IVT2H simplifies and accelerates the drop-based microfluidics workflow for screening random DNA libraries, and represents a novel alternative method for protein engineering and in vitro directed protein evolution. PMID:26940078

Microfluidics—from fundamental research to industrial applications

NASA Astrophysics Data System (ADS)

Köster, Sarah

2013-03-01

The advance of microfluidics started in the early 1980s. At the time, researchers realized that many processes and reactions in chemistry and biology, which typically take place on small length scales, can be defined, controlled and understood much better when using tools on equally small length scales. Reactions and reaction kinetics rely on (gradual) concentration differences and microfluidics provides the unique possibility to establish exactly such gradients of solutes, ion concentrations, pH value and so on. Nowadays the variety of specific microfluidic methods is large. In principle, they can be divided into two groups: (i) monophase flow, where miscible (e.g. aqueous) fluids are mixed, mostly by diffusion owing to the laminar flow on small length scales and (ii) multiphase flow, the most prominent example of which is probably droplet microfluidics, where water-in-oil or oil-in-water emulsions are used to encapsulate chemical or biological systems and separate them from each other, much like in 'micron-scale test tubes'. Now, 30 years later, microfluidic techniques are seriously considered for industrial applications, although some important steps in the upscaling process are still missing. The purpose of this special issue is to shed light on the different aspects in microfluidics research starting from fundamental research reaching all the way to industrial applications. The study by Toma and co-workers takes advantage of the controlled diffusive mixing when co-flowing aqueous, miscible solutions. They combine microfluidics with optical, spectroscopic and scattering techniques to study DNA packing. Nunes et al review the different regimes when replacing one of the fluids by an oil phase and varying flow rates and device geometries with a particular emphasis on using multiphase microfluidics for synthesis of particles or fibres. Going into the third dimension by fabricating microfluidic devices with several layers, producing emulsions can also be achieved by so-called 'step emulsification', the physical mechanisms behind which are described by Dangla et al. Tran and co-workers move a considerable step towards applicability of water-in-oil emulsions for biological research and review ultrahigh-throughput methods used for bio-assays. The article by Lagus et al focuses this topic specifically on single-cell experiments. Whereas it is very popular to use emulsions with drop sizes of a few tens of micrometers as 'tiny test tubes' they may also serve as templates for materials fabrication. Gundabala and co-workers combine both aspects by producing so-called 'celloidosomes', which consist of liquid drops decorated with yeast cells at the outer interface. Wang et al fabricate microcrawlers that can be thermally set in motion. Finally, Holtze gives a perspective on the possibility to upscale and apply such methods in industry. The choice of papers shows the wide and diverse applicability of microfluidics in various fields of research. While microfluidics started out as a 'niche' technique for very specific applications and as a tool in fundamental soft and biological matter research, the advancements made during recent years promise further progress in the chemical industry, biomedicine and pharmacology. Advantages such as low sample consumption, single cell accessibility and controlled experimental parameters in general may in the future be exploited for real industrial sized applications. In Journal of Physics D: Applied Physics we find a journal that is ideally positioned to give applied microfluidics research a wide readership across many disciplines. In the publication of this special issue we hope to inspire and encourage microfluidics researchers, and to promote interdisciplinary collaborations. We would like to thank all of the authors for their excellent contributions to this special issue.

Droplet based microfluidics.

PubMed

Seemann, Ralf; Brinkmann, Martin; Pfohl, Thomas; Herminghaus, Stephan

2012-01-01

Droplet based microfluidics is a rapidly growing interdisciplinary field of research combining soft matter physics, biochemistry and microsystems engineering. Its applications range from fast analytical systems or the synthesis of advanced materials to protein crystallization and biological assays for living cells. Precise control of droplet volumes and reliable manipulation of individual droplets such as coalescence, mixing of their contents, and sorting in combination with fast analysis tools allow us to perform chemical reactions inside the droplets under defined conditions. In this paper, we will review available drop generation and manipulation techniques. The main focus of this review is not to be comprehensive and explain all techniques in great detail but to identify and shed light on similarities and underlying physical principles. Since geometry and wetting properties of the microfluidic channels are crucial factors for droplet generation, we also briefly describe typical device fabrication methods in droplet based microfluidics. Examples of applications and reaction schemes which rely on the discussed manipulation techniques are also presented, such as the fabrication of special materials and biophysical experiments.

Windowless microfluidic platform based on capillary burst valves for high intensity x-ray measurements.

PubMed

Vig, Asger Laurberg; Haldrup, Kristoffer; Enevoldsen, Nikolaj; Thilsted, Anil Haraksingh; Eriksen, Johan; Kristensen, Anders; Feidenhans'l, Robert; Nielsen, Martin Meedom

2009-11-01

We propose and describe a microfluidic system for high intensity x-ray measurements. The required open access to a microfluidic channel is provided by an out-of-plane capillary burst valve (CBV). The functionality of the out-of-plane CBV is characterized with respect to the diameter of the windowless access hole, ranging from 10 to 130 microm. Maximum driving pressures from 22 to 280 mbar corresponding to refresh rates of the exposed sample from 300 Hz to 54 kHz is demonstrated. The microfluidic system is tested at beamline ID09b at the ESRF synchrotron radiation facility in Grenoble, and x-ray scattering measurements are shown to be feasible and to require only very limited amounts of sample, <1 ml/h of measurements without recapturing of sample. With small adjustments of the present chip design, scattering angles up to 30 degrees can be achieved without shadowing effects and integration on-chip mixing and spectroscopy appears straightforward.

Windowless microfluidic platform based on capillary burst valves for high intensity x-ray measurements

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

Vig, Asger Laurberg; Enevoldsen, Nikolaj; Thilsted, Anil Haraksingh

2009-11-15

We propose and describe a microfluidic system for high intensity x-ray measurements. The required open access to a microfluidic channel is provided by an out-of-plane capillary burst valve (CBV). The functionality of the out-of-plane CBV is characterized with respect to the diameter of the windowless access hole, ranging from 10 to 130 {mu}m. Maximum driving pressures from 22 to 280 mbar corresponding to refresh rates of the exposed sample from 300 Hz to 54 kHz is demonstrated. The microfluidic system is tested at beamline ID09b at the ESRF synchrotron radiation facility in Grenoble, and x-ray scattering measurements are shown tomore » be feasible and to require only very limited amounts of sample, <1 ml/h of measurements without recapturing of sample. With small adjustments of the present chip design, scattering angles up to 30 deg. can be achieved without shadowing effects and integration on-chip mixing and spectroscopy appears straightforward.« less

Integrated printed circuit board device for cell lysis and nucleic acid extraction.

PubMed

Marshall, Lewis A; Wu, Liang Li; Babikian, Sarkis; Bachman, Mark; Santiago, Juan G

2012-11-06

Preparation of raw, untreated biological samples remains a major challenge in microfluidics. We present a novel microfluidic device based on the integration of printed circuit boards and an isotachophoresis assay for sample preparation of nucleic acids from biological samples. The device has integrated resistive heaters and temperature sensors as well as a 70 μm × 300 μm × 3.7 cm microfluidic channel connecting two 15 μL reservoirs. We demonstrated this device by extracting pathogenic nucleic acids from 1 μL dispensed volume of whole blood spiked with Plasmodium falciparum. We dispensed whole blood directly onto an on-chip reservoir, and the system's integrated heaters simultaneously lysed and mixed the sample. We used isotachophoresis to extract the nucleic acids into a secondary buffer via isotachophoresis. We analyzed the convective mixing action with micro particle image velocimetry (micro-PIV) and verified the purity and amount of extracted nucleic acids using off-chip quantitative polymerase chain reaction (PCR). We achieved a clinically relevant limit of detection of 500 parasites per microliter. The system has no moving parts, and the process is potentially compatible with a wide range of on-chip hybridization or amplification assays.

Hyaluronic Acid Surface Modified Liposomes Prepared via Orthogonal Aminoxy Coupling: Synthesis of Nontoxic Aminoxylipids Based on Symmetrically α-Branched Fatty Acids, Preparation of Liposomes by Microfluidic Mixing, and Targeting to Cancer Cells Expressing CD44.

PubMed

Bartheldyová, Eliška; Effenberg, Roman; Mašek, Josef; Procházka, Lubomír; Knötigová, Pavlína Turánek; Kulich, Pavel; Hubatka, František; Velínská, Kamila; Zelníčková, Jaroslava; Zouharová, Darina; Fojtíková, Martina; Hrebík, Dominik; Plevka, Pavel; Mikulík, Robert; Miller, Andrew D; Macaulay, Stuart; Zyka, Daniel; Drož, Ladislav; Raška, Milan; Ledvina, Miroslav; Turánek, Jaroslav

2018-06-25

New synthetic aminoxy lipids are designed and synthesized as building blocks for the formulation of functionalized nanoliposomes by microfluidization using a NanoAssemblr. Orthogonal binding of hyaluronic acid onto the outer surface of functionalized nanoliposomes via aminoxy coupling ( N-oxy ligation) is achieved at hemiacetal function of hyaluronic acid and the structure of hyaluronic acid-liposomes is visualized by transmission electron microscopy and cryotransmission electron microscopy. Observed structures are in a good correlation with data obtained by dynamic light scattering (size and ζ-potential). In vitro experiments on cell lines expressing CD44 receptors demonstrate selective internalization of fluorochrome-labeled hyaluronic acid-liposomes, while cells with down regulated CD44 receptor levels exhibit very low internalization of hyaluronic acid-liposomes. A method based on microfluidization mixing was developed for preparation of monodispersive unilamellar liposomes containing aminoxy lipids and orthogonal binding of hyaluronic acid onto the liposomal surface was demonstrated. These hyaluronic acid-liposomes represent a potentially new drug delivery platform for CD44-targeted anticancer drugs as well as for immunotherapeutics and vaccines.

About Small Streams and Shiny Rocks: Macromolecular Crystal Growth in Microfluidics

NASA Technical Reports Server (NTRS)

vanderWoerd, Mark; Ferree, Darren; Spearing, Scott; Monaco, Lisa; Molho, Josh; Spaid, Michael; Brasseur, Mike; Curreri, Peter A. (Technical Monitor)

2002-01-01

We are developing a novel technique with which we have grown diffraction quality protein crystals in very small volumes, utilizing chip-based, microfluidic ("LabChip") technology. With this technology volumes smaller than achievable with any laboratory pipette can be dispensed with high accuracy. We have performed a feasibility study in which we crystallized several proteins with the aid of a LabChip device. The protein crystals are of excellent quality as shown by X-ray diffraction. The advantages of this new technology include improved accuracy of dispensing for small volumes, complete mixing of solution constituents without bubble formation, highly repeatable recipe and growth condition replication, and easy automation of the method. We have designed a first LabChip device specifically for protein crystallization in batch mode and can reliably dispense and mix from a range of solution constituents. We are currently testing this design. Upon completion additional crystallization techniques, such as vapor diffusion and liquid-liquid diffusion will be accommodated. Macromolecular crystallization using microfluidic technology is envisioned as a fully automated system, which will use the 'tele-science' concept of remote operation and will be developed into a research facility aboard the International Space Station.

Microfluidics Integrated Biosensors: A Leading Technology towards Lab-on-a-Chip and Sensing Applications

PubMed Central

Luka, George; Ahmadi, Ali; Najjaran, Homayoun; Alocilja, Evangelyn; DeRosa, Maria; Wolthers, Kirsten; Malki, Ahmed; Aziz, Hassan; Althani, Asmaa; Hoorfar, Mina

2015-01-01

A biosensor can be defined as a compact analytical device or unit incorporating a biological or biologically derived sensitive recognition element immobilized on a physicochemical transducer to measure one or more analytes. Microfluidic systems, on the other hand, provide throughput processing, enhance transport for controlling the flow conditions, increase the mixing rate of different reagents, reduce sample and reagents volume (down to nanoliter), increase sensitivity of detection, and utilize the same platform for both sample preparation and detection. In view of these advantages, the integration of microfluidic and biosensor technologies provides the ability to merge chemical and biological components into a single platform and offers new opportunities for future biosensing applications including portability, disposability, real-time detection, unprecedented accuracies, and simultaneous analysis of different analytes in a single device. This review aims at representing advances and achievements in the field of microfluidic-based biosensing. The review also presents examples extracted from the literature to demonstrate the advantages of merging microfluidic and biosensing technologies and illustrate the versatility that such integration promises in the future biosensing for emerging areas of biological engineering, biomedical studies, point-of-care diagnostics, environmental monitoring, and precision agriculture. PMID:26633409

Ultrasensitive microfluidic solid-phase ELISA using an actuatable microwell-patterned PDMS chip.

PubMed

Wang, Tanyu; Zhang, Mohan; Dreher, Dakota D; Zeng, Yong

2013-11-07

Quantitative detection of low abundance proteins is of significant interest for biological and clinical applications. Here we report an integrated microfluidic solid-phase ELISA platform for rapid and ultrasensitive detection of proteins with a wide dynamic range. Compared to the existing microfluidic devices that perform affinity capture and enzyme-based optical detection in a constant channel volume, the key novelty of our design is two-fold. First, our system integrates a microwell-patterned assay chamber that can be pneumatically actuated to significantly reduce the volume of chemifluorescent reaction, markedly improving the sensitivity and speed of ELISA. Second, monolithic integration of on-chip pumps and the actuatable assay chamber allow programmable fluid delivery and effective mixing for rapid and sensitive immunoassays. Ultrasensitive microfluidic ELISA was demonstrated for insulin-like growth factor 1 receptor (IGF-1R) across at least five orders of magnitude with an extremely low detection limit of 21.8 aM. The microwell-based solid-phase ELISA strategy provides an expandable platform for developing the next-generation microfluidic immunoassay systems that integrate and automate digital and analog measurements to further improve the sensitivity, dynamic ranges, and reproducibility of proteomic analysis.

Microfluidic Pneumatic Logic Circuits and Digital Pneumatic Microprocessors for Integrated Microfluidic Systems

PubMed Central

Rhee, Minsoung

2010-01-01

We have developed pneumatic logic circuits and microprocessors built with microfluidic channels and valves in polydimethylsiloxane (PDMS). The pneumatic logic circuits perform various combinational and sequential logic calculations with binary pneumatic signals (atmosphere and vacuum), producing cascadable outputs based on Boolean operations. A complex microprocessor is constructed from combinations of various logic circuits and receives pneumatically encoded serial commands at a single input line. The device then decodes the temporal command sequence by spatial parallelization, computes necessary logic calculations between parallelized command bits, stores command information for signal transportation and maintenance, and finally executes the command for the target devices. Thus, such pneumatic microprocessors will function as a universal on-chip control platform to perform complex parallel operations for large-scale integrated microfluidic devices. To demonstrate the working principles, we have built 2-bit, 3-bit, 4-bit, and 8-bit microprecessors to control various target devices for applications such as four color dye mixing, and multiplexed channel fluidic control. By significantly reducing the need for external controllers, the digital pneumatic microprocessor can be used as a universal on-chip platform to autonomously manipulate microfluids in a high throughput manner. PMID:19823730

Lab-on-a-chip workshop activities for secondary school students

PubMed Central

Esfahani, Mohammad M. N.; Tarn, Mark D.; Choudhury, Tahmina A.; Hewitt, Laura C.; Mayo, Ashley J.; Rubin, Theodore A.; Waller, Mathew R.; Christensen, Martin G.; Dawson, Amy; Pamme, Nicole

2016-01-01

The ability to engage and inspire younger generations in novel areas of science is important for bringing new researchers into a burgeoning field, such as lab-on-a-chip. We recently held a lab-on-a-chip workshop for secondary school students, for which we developed a number of hands-on activities that explained various aspects of microfluidic technology, including fabrication (milling and moulding of microfluidic devices, and wax printing of microfluidic paper-based analytical devices, so-called μPADs), flow regimes (gradient formation via diffusive mixing), and applications (tissue analysis and μPADs). Questionnaires completed by the students indicated that they found the workshop both interesting and informative, with all activities proving successful, while providing feedback that could be incorporated into later iterations of the event. PMID:26865902

Uniform integration of gold nanoparticles in PDMS microfluidics with 3D micromixing

NASA Astrophysics Data System (ADS)

SadAbadi, H.; Packirisamy, M.; Wuthrich, R.

2015-09-01

The integration of gold nanoparticles (AuNPs) on the surface of polydimethylsiloxane (PDMS) microfluidics for biosensing applications is a challenging task. In this paper we address this issue by integration of pre-synthesized AuNPs (in a microreactor) into a microfluidic system. This method explored the affinity of AuNPs toward the PDMS surface so that the pre-synthesized particles will be adsorbed onto the channel walls. AuNPs were synthesized inside a microreactor before integration. In order to improve the size uniformity of the synthesized AuNPs and also to provide full mixing of reactants, a 3D-micromixer was designed, fabricated and then integrated with the microreactor in a single platform. SEM and UV/Vis spectroscopy were used to characterize the AuNPs on the PDMS surface.

Magnetic Tethering of Microswimmers in Microfluidic Devices

NASA Astrophysics Data System (ADS)

Chawan, Aschvin; Jana, Saikat; Ghosh, Suvojit; Jung, Sunghwan; Puri, Ishwar

2013-03-01

Exercising control over animal locomotion is well known in the macro world. In the micro-scale world, such methods require more sophistication. We magnetize Paramecium multimicronucleatum by internalization of magnetite nanoparticles coated with bovine serum albumin (BSA). This enables control of their motion in a microfluidic device using a magnetic field. Miniature permanent magnets embedded within the device are used to tether the magnetized organisms to specific locations along a micro-channel. Ciliary beatings of the microswimmer generate shear flows nearby. We apply this setup to enhance cross-stream mixing in a microfluidic device by supplementing molecular diffusion. The device is similar to an active micromixer but requires no external power sources or artificial actuators. We optically characterize the effectiveness of the mechanism in a variety of flow situations.

Patterned-wettability-induced alteration of electro-osmosis over charge-modulated surfaces in narrow confinements.

PubMed

Ghosh, Uddipta; Chakraborty, Suman

2012-04-01

In the present study, we focus on alterations in flow physics as a consequence of interactions between patterned-wettability gradients on microfluidic substrates with modulated surface charge distributions, giving rise to an intricate electrohydrodynamic coupling over small scales. We demonstrate that by exploiting such intricate coupling, it may be possible to pattern vortices occurring in the fluidic confinement by exploiting an interplay between the Navier slip and electro-osmotic transport. Our studies do reveal that the resultant flow structure originating out of the spatially periodic variations in the surface charge and surface wettability may depend critically on several independently tunable controlling parameters, such as the amplitudes and frequencies of the respective patterning functions, the phase shift between the two, an asymmetry factor, and the channel height to Debye length ratio. We show that judicious choices with regard to the combinations of these parameters may result in significant augmentations in the corresponding mixing efficiency without any appreciable compromise in the net microfluidic throughput. Furthermore, our studies reveal an optimum patterning frequency, which results in the most efficient microfluidic mixing within the constraints of achieving a desired volumetric flow rate. Our results also demonstrate that the net flow rate is maximized when the surface wettability variation functions and surface charge-density functions are in phase, whereas mixing is best facilitated when they are in opposite phase. In practice, therefore, one may select an intermediate value of the phase angle depending on the extent of compromise necessary between flow rate and mixing characteristics, yielding far-ranging scientific and technological advances toward an improved design of miniaturized fluidic devices of practical relevance.

Rigorous buoyancy driven bubble mixing for centrifugal microfluidics.

PubMed

Burger, S; Schulz, M; von Stetten, F; Zengerle, R; Paust, N

2016-01-21

We present batch-mode mixing for centrifugal microfluidics operated at fixed rotational frequency. Gas is generated by the disk integrated decomposition of hydrogen peroxide (H2O2) to liquid water (H2O) and gaseous oxygen (O2) and inserted into a mixing chamber. There, bubbles are formed that ascent through the liquid in the artificial gravity field and lead to drag flow. Additionaly, strong buoyancy causes deformation and rupture of the gas bubbles and induces strong mixing flows in the liquids. Buoyancy driven bubble mixing is quantitatively compared to shake mode mixing, mixing by reciprocation and vortex mixing. To determine mixing efficiencies in a meaningful way, the different mixers are employed for mixing of a lysis reagent and human whole blood. Subsequently, DNA is extracted from the lysate and the amount of DNA recovered is taken as a measure for mixing efficiency. Relative to standard vortex mixing, DNA extraction based on buoyancy driven bubble mixing resulted in yields of 92 ± 8% (100 s mixing time) and 100 ± 8% (600 s) at 130g centrifugal acceleration. Shake mode mixing yields 96 ± 11% and is thus equal to buoyancy driven bubble mixing. An advantage of buoyancy driven bubble mixing is that it can be operated at fixed rotational frequency, however. The additional costs of implementing buoyancy driven bubble mixing are low since both the activation liquid and the catalyst are very low cost and no external means are required in the processing device. Furthermore, buoyancy driven bubble mixing can easily be integrated in a monolithic manner and is compatible to scalable manufacturing technologies such as injection moulding or thermoforming. We consider buoyancy driven bubble mixing an excellent alternative to shake mode mixing, in particular if the processing device is not capable of providing fast changes of rotational frequency or if the low average rotational frequency is challenging for the other integrated fluidic operations.

Experimental investigations of the use of an erbium:YAG laser on temporomandibular joint (TMJ) structures: first experimental results

NASA Astrophysics Data System (ADS)

Nuebler-Moritz, Michael; Niederdellmann, Herbert; Hering, Peter; Deuerling, Christian; Dammer, Ralf; Behr, M.

1995-04-01

The following paper introduces the results of an interdisciplinary research project. With the aid of photomacroscopic examination, light and scanning electron microscope investigations, changes to temporomandibular joint structures were detected in vitro after irradiation with an Erbium:YAG laser system. The solid-state Erbium:YAG laser, operating at a wavelength of 2.94 micrometers was used in the normal- spiking mode. The free-running laser beam was focussed onto freshly excised porcine tissue samples using a 108-mm sapphire lens. In this study the output was generally pulsed at a repetition rate of 4 Hz, with a pulse duration varying from 120 microsecond(s) to 500 microsecond(s) . Between 50 mJ and 500 mJ per pulse were applied to create pinpoint lesions. The optimum average energy density and pulse duration of the Erbium:YAG laser radiation for the purpose of TMJ-surgery (as far as it concerns meniscus and articulating facets) - which means efficient etch rate and minimal adjacent injury - seems to be about 24-42 J/cm2 and 120 microsecond(s) -240 microsecond(s) , respectively.

Enhancing the chemiluminescence intensity of a KMnO4 formaldehyde system for estimating the total phenolic content in honey samples using a novel nanodroplet mixing approach in a microfluidics platform.

PubMed

Al Lawati, Haider A J; Al Mughairy, Baqia; Al Lawati, Iman; Suliman, FakhrEldin O

2018-04-30

A novel mixing approach was utilized with a highly sensitive chemiluminescence (CL) method to determine the total phenolic content (TPC) in honey samples using an acidic potassium permanganate-formaldehyde system. The mixing approach was based on exploiting the mixing efficiency of nanodroplets generated in a microfluidic platform. Careful optimization of the instrument setup and various experimental conditions were employed to obtain excellent sensitivity. The mixing efficiency of the droplets was compared with the CL signal intensity obtained using the common serpentine chip design, with both approaches using at a total flow rate of 15 μl min -1 ; the results showed that the nanodroplets provided 600% higher CL signal intensity at this low flow rate. Using the optimum conditions, calibration equations, limits of detection (LOD) and limits of quantification (LOQ) for gallic acid (GA), caffeic acid (CA), kaempferol (KAM), quercetin (QRC) and catechin (CAT) were obtained. The LOD ranged from 6.2 ppb for CA to 11.0 ppb for QRC. Finally, the method was applied for the determination of TPC in several local and commercial honey samples. Copyright © 2018 John Wiley & Sons, Ltd.

Design, fabrication and characterization of an arrayable all-polymer microfluidic valve employing highly magnetic rare-earth composite polymer

NASA Astrophysics Data System (ADS)

Rahbar, Mona; Shannon, Lesley; Gray, Bonnie L.

2016-05-01

We present a new magnetically actuated microfluidic valve that employs a highly magnetic composite polymer (M-CP) containing rare-earth hard-magnetic powder for its actuating element and for its valve seat. The M-CP offers much higher magnetization compared to the soft-magnetic, ferrite-based composite polymers typically used in microfluidic applications. Each valve consists of a permanently magnetized M-CP flap and valve seat mounted on a microfluidic channel system fabricated in poly(dimethylsiloxane) (PDMS). Each valve is actuated under a relatively small external magnetic field of 80 mT provided by a small permanent magnet mounted on a miniature linear actuator. The performance of the valve with different flap thicknesses is characterized. In addition, the effect of the magnetic valve seat on the valve’s performance is also characterized. It is experimentally shown that a valve with a 2.3 mm flap thickness, actuated under an 80 mT magnetic field, is capable of completely blocking liquid flow at a flow rate of 1 ml min-1 for pressures up to 9.65 kPa in microfluidic channels 200 μm wide and 200 μm deep. The valve can also be fabricated into an array for flow switching between multiple microfluidic channels under continuous flow conditions. The performance of arrays of valves for flow routing is demonstrated for flow rates up to 5 ml min-1 with larger microfluidic channels of up to 1 mm wide and 500 μm deep. The design of the valves is compatible with other commonly used polymeric microfluidic components, as well as other components that use the same novel permanently magnetic composite polymer, such as our previously reported cilia-based mixing devices.

Use of Patterned CNT Arrays for Display Purposes

NASA Technical Reports Server (NTRS)

Delzeit, Lance D. (Inventor); Schipper, John F. (Inventor)

2009-01-01

Method and system for providing a dynamically reconfigurable display having nanometer-scale resolution, using a patterned array of multi-wall carbon nanotube (MWCNT) clusters. A diode, phosphor or other light source on each MWCNT cluster is independently activated, and different color light sources (e.g., red, green, blue, grey scale, infrared) can be mixed if desired. Resolution is estimated to be 40-100 nm, and reconfiguration time for each MWCNT cluster is no greater than one microsecond.

Punch Card Programmable Microfluidics

PubMed Central

Korir, George; Prakash, Manu

2015-01-01

Small volume fluid handling in single and multiphase microfluidics provides a promising strategy for efficient bio-chemical assays, low-cost point-of-care diagnostics and new approaches to scientific discoveries. However multiple barriers exist towards low-cost field deployment of programmable microfluidics. Incorporating multiple pumps, mixers and discrete valve based control of nanoliter fluids and droplets in an integrated, programmable manner without additional required external components has remained elusive. Combining the idea of punch card programming with arbitrary fluid control, here we describe a self-contained, hand-crank powered, multiplex and robust programmable microfluidic platform. A paper tape encodes information as a series of punched holes. A mechanical reader/actuator reads these paper tapes and correspondingly executes operations onto a microfluidic chip coupled to the platform in a plug-and-play fashion. Enabled by the complexity of codes that can be represented by a series of holes in punched paper tapes, we demonstrate independent control of 15 on-chip pumps with enhanced mixing, normally-closed valves and a novel on-demand impact-based droplet generator. We demonstrate robustness of operation by encoding a string of characters representing the word “PUNCHCARD MICROFLUIDICS” using the droplet generator. Multiplexing is demonstrated by implementing an example colorimetric water quality assays for pH, ammonia, nitrite and nitrate content in different water samples. With its portable and robust design, low cost and ease-of-use, we envision punch card programmable microfluidics will bring complex control of microfluidic chips into field-based applications in low-resource settings and in the hands of children around the world. PMID:25738834

Temperature change rate actuated bubble mixing for homogeneous rehydration of dry pre-stored reagents in centrifugal microfluidics.

PubMed

Hin, S; Paust, N; Keller, M; Rombach, M; Strohmeier, O; Zengerle, R; Mitsakakis, K

2018-01-16

In centrifugal microfluidics, dead volumes in valves downstream of mixing chambers can hardly be avoided. These dead volumes are excluded from mixing processes and hence cause a concentration gradient. Here we present a new bubble mixing concept which avoids such dead volumes. The mixing concept employs heating to create a temperature change rate (TCR) induced overpressure in the air volume downstream of mixing chambers. The main feature is an air vent with a high fluidic resistance, representing a low pass filter with respect to pressure changes. Fast temperature increase causes rapid pressure increase in downstream structures pushing the liquid from downstream channels into the mixing chamber. As air further penetrates into the mixing chamber, bubbles form, ascend due to buoyancy and mix the liquid. Slow temperature/pressure changes equilibrate through the high fluidic resistance air vent enabling sequential heating/cooling cycles to repeat the mixing process. After mixing, a complete transfer of the reaction volume into the downstream fluidic structure is possible by a rapid cooling step triggering TCR actuated valving. The new mixing concept is applied to rehydrate reagents for loop-mediated isothermal amplification (LAMP). After mixing, the reaction mix is aliquoted into several reaction chambers for geometric multiplexing. As a measure for mixing efficiency, the mean coefficient of variation (C[combining macron]V[combining macron], n = 4 LabDisks) of the time to positivity (t p ) of the LAMP reactions (n = 11 replicates per LabDisk) is taken. The C[combining macron]V[combining macron] of the t p is reduced from 18.5% (when using standard shake mode mixing) to 3.3% (when applying TCR actuated bubble mixing). The bubble mixer has been implemented in a monolithic fashion without the need for any additional actuation besides rotation and temperature control, which are needed anyhow for the assay workflow.

Optical calorimetry in microfluidic droplets.

PubMed

Chamoun, Jacob; Pattekar, Ashish; Afshinmanesh, Farzaneh; Martini, Joerg; Recht, Michael I

2018-05-29

A novel microfluidic calorimeter that measures the enthalpy change of reactions occurring in 100 μm diameter aqueous droplets in fluoropolymer oil has been developed. The aqueous reactants flow into a microfluidic droplet generation chip in separate fluidic channels, limiting contact between the streams until immediately before they form the droplet. The diffusion-driven mixing of reactants is predominantly restricted to within the droplet. The temperature change in droplets due to the heat of reaction is measured optically by recording the reflectance spectra of encapsulated thermochromic liquid crystals (TLC) that are added to one of the reactant streams. As the droplets travel through the channel, the spectral characteristics of the TLC represent the internal temperature, allowing optical measurement with a precision of ≈6 mK. The microfluidic chip and all fluids are temperature controlled, and the reaction heat within droplets raises their temperature until thermal diffusion dissipates the heat into the surrounding oil and chip walls. Position resolved optical temperature measurement of the droplets allows calculation of the heat of reaction by analyzing the droplet temperature profile over time. Channel dimensions, droplet generation rate, droplet size, reactant stream flows and oil flow rate are carefully balanced to provide rapid diffusional mixing of reactants compared to thermal diffusion, while avoiding thermal "quenching" due to contact between the droplets and the chip walls. Compared to conventional microcalorimetry, which has been used in this work to provide reference measurements, this new continuous flow droplet calorimeter has the potential to perform titrations ≈1000-fold faster while using ≈400-fold less reactants per titration.

Sample to answer visualization pipeline for low-cost point-of-care blood cell counting

NASA Astrophysics Data System (ADS)

Smith, Suzanne; Naidoo, Thegaran; Davies, Emlyn; Fourie, Louis; Nxumalo, Zandile; Swart, Hein; Marais, Philip; Land, Kevin; Roux, Pieter

2015-03-01

We present a visualization pipeline from sample to answer for point-of-care blood cell counting applications. Effective and low-cost point-of-care medical diagnostic tests provide developing countries and rural communities with accessible healthcare solutions [1], and can be particularly beneficial for blood cell count tests, which are often the starting point in the process of diagnosing a patient [2]. The initial focus of this work is on total white and red blood cell counts, using a microfluidic cartridge [3] for sample processing. Analysis of the processed samples has been implemented by means of two main optical visualization systems developed in-house: 1) a fluidic operation analysis system using high speed video data to determine volumes, mixing efficiency and flow rates, and 2) a microscopy analysis system to investigate homogeneity and concentration of blood cells. Fluidic parameters were derived from the optical flow [4] as well as color-based segmentation of the different fluids using a hue-saturation-value (HSV) color space. Cell count estimates were obtained using automated microscopy analysis and were compared to a widely accepted manual method for cell counting using a hemocytometer [5]. The results using the first iteration microfluidic device [3] showed that the most simple - and thus low-cost - approach for microfluidic component implementation was not adequate as compared to techniques based on manual cell counting principles. An improved microfluidic design has been developed to incorporate enhanced mixing and metering components, which together with this work provides the foundation on which to successfully implement automated, rapid and low-cost blood cell counting tests.

Centrifugal microfluidic platforms: advanced unit operations and applications.

PubMed

Strohmeier, O; Keller, M; Schwemmer, F; Zehnle, S; Mark, D; von Stetten, F; Zengerle, R; Paust, N

2015-10-07

Centrifugal microfluidics has evolved into a mature technology. Several major diagnostic companies either have products on the market or are currently evaluating centrifugal microfluidics for product development. The fields of application are widespread and include clinical chemistry, immunodiagnostics and protein analysis, cell handling, molecular diagnostics, as well as food, water, and soil analysis. Nevertheless, new fluidic functions and applications that expand the possibilities of centrifugal microfluidics are being introduced at a high pace. In this review, we first present an up-to-date comprehensive overview of centrifugal microfluidic unit operations. Then, we introduce the term "process chain" to review how these unit operations can be combined for the automation of laboratory workflows. Such aggregation of basic functionalities enables efficient fluidic design at a higher level of integration. Furthermore, we analyze how novel, ground-breaking unit operations may foster the integration of more complex applications. Among these are the storage of pneumatic energy to realize complex switching sequences or to pump liquids radially inward, as well as the complete pre-storage and release of reagents. In this context, centrifugal microfluidics provides major advantages over other microfluidic actuation principles: the pulse-free inertial liquid propulsion provided by centrifugal microfluidics allows for closed fluidic systems that are free of any interfaces to external pumps. Processed volumes are easily scalable from nanoliters to milliliters. Volume forces can be adjusted by rotation and thus, even for very small volumes, surface forces may easily be overcome in the centrifugal gravity field which enables the efficient separation of nanoliter volumes from channels, chambers or sensor matrixes as well as the removal of any disturbing bubbles. In summary, centrifugal microfluidics takes advantage of a comprehensive set of fluidic unit operations such as liquid transport, metering, mixing and valving. The available unit operations cover the entire range of automated liquid handling requirements and enable efficient miniaturization, parallelization, and integration of assays.

Inherently aligned microfluidic electrodes composed of liquid metal.

PubMed

So, Ju-Hee; Dickey, Michael D

2011-03-07

This paper describes the fabrication and characterization of microelectrodes that are inherently aligned with microfluidic channels and in direct contact with the fluid in the channels. Injecting low melting point alloys, such as eutectic gallium indium (EGaIn), into microchannels at room temperature (or just above room temperature) offers a simple way to fabricate microelectrodes. The channels that define the shape and position of the microelectrodes are fabricated simultaneously with other microfluidic channels (i.e., those used to manipulate fluids) in a single step; consequently, all of the components are inherently aligned. In contrast, conventional techniques require multiple fabrication steps and registration (i.e., alignment of the electrodes with the microfluidic channels), which are technically challenging. The distinguishing characteristic of this work is that the electrodes are in direct contact with the fluid in the microfluidic channel, which is useful for a number of applications such as electrophoresis. Periodic posts between the microelectrodes and the microfluidic channel prevent the liquid metal from entering the microfluidic channel during injection. A thin oxide skin that forms rapidly and spontaneously on the surface of the metal stabilizes mechanically the otherwise low viscosity, high surface tension fluid within the channel. Moreover, the injected electrodes vertically span the sidewalls of the channel, which allows for the application of uniform electric field lines throughout the height of the channel and perpendicular to the direction of flow. The electrodes are mechanically stable over operating conditions commonly used in microfluidic applications; the mechanical stability depends on the magnitude of the applied bias, the nature of the bias (DC vs. AC), and the conductivity of the solutions in the microfluidic channel. Electrodes formed using alloys with melting points above room temperature ensure mechanical stability over all of the conditions explored. As a demonstration of their utility, the fluidic electrodes are used for electrohydrodynamic mixing, which requires extremely high electric fields (~10(5) V m(-1)).

Microfluidics Expanding the Frontiers of Microbial Ecology

PubMed Central

Rusconi, Roberto; Garren, Melissa; Stocker, Roman

2014-01-01

The ability afforded by microfluidics to observe the behaviors of microbes in highly controlled and confined microenvironments, across scales from a single cell to mixed communities, has significantly contributed to expand the frontiers of microbial ecology over the last decade. Spatially and temporally varying distributions of organisms and chemical cues that mimic natural microbial habitats can now be established by exploiting physics at the micrometer scale and by incorporating structures with specific geometries and materials. Here we review applications of microfluidics that have resulted in highly insightful discoveries on fundamental aspects of microbial life, ranging from growth and sensing to cell-cell interactions and population dynamics. We anticipate that this flexible, multidisciplinary technology will continue to facilitate discoveries regarding the ecology of microorganisms and help uncover strategies to control phenomena such as biofilm formation and antibiotic resistance. PMID:24773019

Acoustically enhanced microfluidic mixer to synthesize highly uniform nanodrugs without the addition of stabilizers.

PubMed

Le, Nguyen Hoai An; Van Phan, Hoang; Yu, Jiaqi; Chan, Hak-Kim; Neild, Adrian; Alan, Tuncay

2018-01-01

This article presents an acoustically enhanced microfluidic mixer to generate highly uniform and ultra-fine nanoparticles, offering significant advantages over conventional liquid antisolvent techniques. The method employed a 3D microfluidic geometry whereby two different phases - solvent and antisolvent - were introduced at either side of a 1 μm thick resonating membrane, which contained a through-hole. The vibration of the membrane rapidly and efficiently mixed the two phases, at the location of the hole, leading to the formation of nanoparticles. The versatility of the device was demonstrated by synthesizing budesonide (a common asthma drug) with a mean diameter of 135.7 nm and a polydispersity index of 0.044. The method offers a 40-fold reduction in the size of synthesized particles combined with a substantial improvement in uniformity, achieved without the need of stabilizers.

Microfluidics expanding the frontiers of microbial ecology.

PubMed

Rusconi, Roberto; Garren, Melissa; Stocker, Roman

2014-01-01

Microfluidics has significantly contributed to the expansion of the frontiers of microbial ecology over the past decade by allowing researchers to observe the behaviors of microbes in highly controlled microenvironments, across scales from a single cell to mixed communities. Spatially and temporally varying distributions of organisms and chemical cues that mimic natural microbial habitats can now be established by exploiting physics at the micrometer scale and by incorporating structures with specific geometries and materials. In this article, we review applications of microfluidics that have resulted in insightful discoveries on fundamental aspects of microbial life, ranging from growth and sensing to cell-cell interactions and population dynamics. We anticipate that this flexible multidisciplinary technology will continue to facilitate discoveries regarding the ecology of microorganisms and help uncover strategies to control microbial processes such as biofilm formation and antibiotic resistance.

Bridging kinematics and concentration content in a chaotic micromixer.

PubMed

Villermaux, E; Stroock, A D; Stone, H A

2008-01-01

We analyze the mixing properties of the microfluidic herringbone configuration introduced to mix scalar substances in a narrow channel at low Reynolds but large Péclet numbers. Because of the grooves sculpted on the channel floor, substantial transverse motions are superimposed onto the usual longitudinal Poiseuille dispersion along the channel, whose impact on both the mixing rate and mixture content is quantified. We demonstrate the direct link between the flow kinematics and the deformation rate of the mixture's concentration distribution, whose overall shape is also determined.

Complex-Shaped Microcomponents by the Reactive Conversion of Biology Templates

DTIC Science & Technology

2003-12-15

luminescent Eu-doped BaTiO3) and as structures for microfluidic mixing devices (e.g., based on electroosmotic flow). Optimization of the MgO conversion...ends of the iron tube. The tube was then crimped in the middle (to avoid physical mixing of the reactants) and the ends were welded shut. Upon heating...luminescent coatings (i.e., Eu-doped BaTiO 3 coatings on MgO), and ii) 3-D micro-structures for incorporation in electro-osmotic mixing devices (i.e., to

Silicon micromachined pumps employing piezoelectric membrane actuation for microfluidic systems

NASA Astrophysics Data System (ADS)

Koch, Michael

Microsystems technology is a rapidly expanding area that comprises electronics, mechanics and optics. In this field, physical/chemical sensing, fluid handling and optical communication are emerging as potential markets. Microfluidic systems like an implantable insulin pump, a drug delivery system and a total chemical analysis system are currently being developed by academia and industry around the world. This project contributes to the area of microfluidics in that a novel thick-film-on-silicon membrane actuator has been developed to allow inexpensive mass production of micropumps. To date piezoelectric plates have been surface mounted onto a silicon membrane. This single chip fabrication method can now be replaced by screen printing thick piezoelectric layers onto 4 inch silicon substrates. Two different pump types have been developed. These are membrane pumps with either cantilever valves or diffuser/nozzle valves. Pump rates between 100 and 200 μl min-1 and backpressures up to 4 kPa have been achieved with these pumps. Along with the technology of micropumps, simulators have been developed. A novel coupled FEM-CFD solver was realised by a computer controlled coupling of two commercially available packages (ANSYS and CFX-Flow3D). The results of this simulator were in good agreement with measurements on micromachined cantilever valves. CFX- Flow3D was also used to successfully model the behaviour of the diffuser/nozzle valve. Finally, the pump has been simulated using a continuity equation. A behavioural dynamic extension of the cantilever valve was necessary to achieve better prediction of the pump rates for higher frequencies. As well, a common process has been developed for microfluidic devices like micromixers, particle counters and sorters as well as flow sensors. The micromixer has been tested already and achieves mixing for input pressures between 2 and 7 kPa. This agrees with simulations of the diffusive mixing with CFX-Flow3D. Together with the micropump, a combination of these devices allows future development of microfluidic systems for the medical and (bio)chemical market.

An electrohydrodynamic technique for rapid mixing in stationary droplets on digital microfluidic platforms.

PubMed

Samiei, Ehsan; de Leon Derby, Maria Diaz; den Berg, Andre Van; Hoorfar, Mina

2017-01-17

This paper presents an electrohydrodynamic technique for rapid mixing of droplets in open and closed digital microfluidic (DMF) platforms. Mixing is performed by applying a high frequency AC voltage to the coplanar or parallel electrodes, inducing circulation zones inside the droplet which results in rapid mixing of the content. The advantages of the proposed method in comparison to conventional mixing methods that operate based on transporting the droplet back and forth and side to side include 1) a shorter mixing time (as fast as 0.25 s), 2) the use of a fewer number of electrodes, reducing the size of the chip, and 3) the stationary nature of the technique which reduces the chance of cross-contamination and surface biofouling. Mixing using the proposed method is performed to create a uniform mixture after merging a water droplet with another droplet containing either particles or dye. The results show that increasing the frequency, and or the amplitude of the applied voltage, enhances the mixing process. However, actuation with a very high frequency and voltage may result in shedding pico-liter satellite droplets. Therefore, for each frequency there is an effective range of the amplitude which provides rapid mixing and avoids shedding satellite droplets. Also, the increase in the gap height between the two plates (for the closed DMF platforms) significantly enhances the mixing efficiency due to the lower viscous effects. Effects of the addition of salts and DNA to the samples were also studied. The electrothermal effect decreased for these cases, which was solved by increasing the frequency of the applied voltage. To assure the high frequency actuation does not increase the sample temperature excessively, the temperature change was monitored using a thermal imaging camera and it was found that the increase in temperature is negligible.

Active micromixer using surface acoustic wave streaming

DOEpatents

Branch,; Darren W. , Meyer; Grant D. , Craighead; Harold, G [Ithaca, NY

2011-05-17

An active micromixer uses a surface acoustic wave, preferably a Rayleigh wave, propagating on a piezoelectric substrate to induce acoustic streaming in a fluid in a microfluidic channel. The surface acoustic wave can be generated by applying an RF excitation signal to at least one interdigital transducer on the piezoelectric substrate. The active micromixer can rapidly mix quiescent fluids or laminar streams in low Reynolds number flows. The active micromixer has no moving parts (other than the SAW transducer) and is, therefore, more reliable, less damaging to sensitive fluids, and less susceptible to fouling and channel clogging than other types of active and passive micromixers. The active micromixer is adaptable to a wide range of geometries, can be easily fabricated, and can be integrated in a microfluidic system, reducing dead volume. Finally, the active micromixer has on-demand on/off mixing capability and can be operated at low power.

Electroosmotic flow and mixing in microchannels with the lattice Boltzmann method

NASA Astrophysics Data System (ADS)

Tang, G. H.; Li, Zhuo; Wang, J. K.; He, Y. L.; Tao, W. Q.

2006-11-01

Understanding the electroosmotic flow in microchannels is of both fundamental and practical significance for the design and optimization of various microfluidic devices to control fluid motion. In this paper, a lattice Boltzmann equation, which recovers the nonlinear Poisson-Boltzmann equation, is used to solve the electric potential distribution in the electrolytes, and another lattice Boltzmann equation, which recovers the Navier-Stokes equation including the external force term, is used to solve the velocity fields. The method is validated by the electric potential distribution in the electrolytes and the pressure driven pulsating flow. Steady-state and pulsating electroosmotic flows in two-dimensional parallel uniform and nonuniform charged microchannels are studied with this lattice Boltzmann method. The simulation results show that the heterogeneous surface potential distribution and the electroosmotic pulsating flow can induce chaotic advection and thus enhance the mixing in microfluidic systems efficiently.

Acoustic actuation of in situ fabricated artificial cilia

NASA Astrophysics Data System (ADS)

Orbay, Sinem; Ozcelik, Adem; Bachman, Hunter; Huang, Tony Jun

2018-02-01

We present on-chip acoustic actuation of in situ fabricated artificial cilia. Arrays of cilia structures are UV polymerized inside a microfluidic channel using a photocurable polyethylene glycol (PEG) polymer solution and photomasks. During polymerization, cilia structures are attached to a silane treated glass surface inside the microchannel. Then, the cilia structures are actuated using acoustic vibrations at 4.6 kHz generated by piezo transducers. As a demonstration of a practical application, DI water and fluorescein dye solutions are mixed inside a microfluidic channel. Using pulses of acoustic excitations, and locally fabricated cilia structures within a certain region of the microchannel, a waveform of mixing behavior is obtained. This result illustrates one potential application wherein researchers can achieve spatiotemporal control of biological microenvironments in cell stimulation studies. These acoustically actuated, in situ fabricated, cilia structures can be used in many on-chip applications in biological, chemical and engineering studies.

Simulation of electrokinetic flow in microfluidic channels

NASA Astrophysics Data System (ADS)

Sabur, Romena; Matin, M.

2005-08-01

Electrokinetic phenomena become an increasingly efficient fluid transport mechanism in micro- and nano-fluidic fields. These phenomena have also been applied successfully in microfluidic devices to achieve particle separation, pre-concentration and mixing. Electrokinetic is the flow produced by the action of an electric field on a fluid with a net charge, where the charged ions of fluid are able to drag the whole solution through the channels in the microfluidic device from one analyzing point to the other. We will present the simulation results of electrokinetic transports of fluid in various typical micro-channel geometries such as T-channel, Y-channel, cross channel and straight channel. In practice, high-speed micro-PIV technique is used to measure transient fluidic phenomena in a microfluidic channel. Particle Image Velocimetry (PIV) systems provide two- or three-dimensional velocity maps in flows using whole field techniques based on imaging the light scattered by small particles in the flow illuminated by a laser light sheet. The system generally consists of an epifluorescent microscope, CW laser and a high-speed CMOS of CCD camera. The flow of a liquid, (water for example), containing fluorescent particle is then analyzed in a counter microchannel by the highly accurate PIV method. One can then compare the simulated and experimental microfluidic flow due to electroosmotic effect.

Electronic modification of Pt via Ti and Se as tolerant cathodes in air-breathing methanol microfluidic fuel cells.

PubMed

Ma, Jiwei; Habrioux, Aurélien; Morais, Cláudia; Alonso-Vante, Nicolas

2014-07-21

We reported herein on the use of tolerant cathode catalysts such as carbon supported Pt(x)Ti(y) and/or Pt(x)Se(y) nanomaterials in an air-breathing methanol microfluidic fuel cell. In order to show the improvement of mixed-reactant fuel cell (MRFC) performances obtained with the developed tolerant catalysts, a classical Pt/C nanomaterial was used for comparison. Using 5 M methanol concentration in a situation where the fuel crossover is 100% (MRFC-mixed reactant fuel cell application), the maximum power density of the fuel cell with a Pt/C cathodic catalyst decreased by 80% in comparison with what is observed in the laminar flow fuel cell (LFFC) configuration. With Pt(x)Ti(y)/C and Pt(x)Se(y)/C cathode nanomaterials, the performance loss was only 55% and 20%, respectively. The evaluation of the tolerant cathode catalysts in an air-breathing microfluidic fuel cell suggests the development of a novel nanometric system that will not be size restricted. These interesting results are the consequence of the high methanol tolerance of these advanced electrocatalysts via surface electronic modification of Pt. Herein we used X-ray photoelectron and in situ FTIR spectroscopies to investigate the origin of the high methanol tolerance on modified Pt catalysts.

Novel and facile viscometer using a paper-based microfluidic device

NASA Astrophysics Data System (ADS)

Kang, Hyunwoong; Jang, Ilhoon; Song, Simon

2017-11-01

In clinical applications, it is important to rapidly estimate the blood viscosity of a patient with a high accuracy and a small sample consumption. Unfortunately, ordinary mechanical viscometers require long analysis time, large volume of sample and skilled person. To address this issue, silicon-based viscometers have been developed, but they are still far from prevail usage in clinical environments due to complexity in process and analysis. Recently, a paper-based microfluidic device is emerged as a new platform for a facile point-of-care diagnostic device due to low cost, disposability and ease of use. Thus, we propose a novel and facile method of measuring a viscosity with a paper-based microfluidic devices and a smartphone. This viscometer utilizes mixing characteristics of two fluid flows in a T-shape channel: one for reference and the other for test fluid. The mixing strongly depends on viscosity difference between the two fluids. Also, the fluids are dyed for colorimetric analysis with a smartphone. We found that the accuracy of viscometer is about 3 percent when it was tested for various glycerin aqueous solutions. More detailed information will be discussed in the presentation. This work was supported by the National Research Foundation of Korea(NRF) Grant funded by the Korea government(MSIP) (No. 2016R1A2B3009541).

Synthesis of Cesium Lead Halide Perovskite Nanocrystals in a Droplet-Based Microfluidic Platform: Fast Parametric Space Mapping.

PubMed

Lignos, Ioannis; Stavrakis, Stavros; Nedelcu, Georgian; Protesescu, Loredana; deMello, Andrew J; Kovalenko, Maksym V

2016-03-09

Prior to this work, fully inorganic nanocrystals of cesium lead halide perovskite (CsPbX3, X = Br, I, Cl and Cl/Br and Br/I mixed halide systems), exhibiting bright and tunable photoluminescence, have been synthesized using conventional batch (flask-based) reactions. Unfortunately, our understanding of the parameters governing the formation of these nanocrystals is still very limited due to extremely fast reaction kinetics and multiple variables involved in ion-metathesis-based synthesis of such multinary halide systems. Herein, we report the use of a droplet-based microfluidic platform for the synthesis of CsPbX3 nanocrystals. The combination of online photoluminescence and absorption measurements and the fast mixing of reagents within such a platform allows the rigorous and rapid mapping of the reaction parameters, including molar ratios of Cs, Pb, and halide precursors, reaction temperatures, and reaction times. This translates into enormous savings in reagent usage and screening times when compared to analogous batch synthetic approaches. The early-stage insight into the mechanism of nucleation of metal halide nanocrystals suggests similarities with multinary metal chalcogenide systems, albeit with much faster reaction kinetics in the case of halides. Furthermore, we show that microfluidics-optimized synthesis parameters are also directly transferrable to the conventional flask-based reaction.

In Vitro Studies on a Microfluidic Sensor with Embedded Obstacles Using New Antibacterial Synthetic Compounds (1-TDPPO) Mixed Prop-2-en-1-one with Difluoro Phenyl.

PubMed

Roh, Changhyun; Lee, Jaewoong; Kinger, Mayank; Kang, Chankyu

2017-04-08

This paper describes the use of an analytical microfluidic sensor for accelerating chemo-repellent response and strong anti-bacterial 1-(Thien-2-yl)-3-(2, 6-difluoro phenyl) prop-2-en-1-one (1-TDPPO). The chemically-synthesized antimicrobial agent, which included prop-2-en-1-one and difluoro phenyl groups, was moving through an optically transparent polydimethylsiloxane (PDMS) microfluidic sensor with circular obstacles arranged evenly. The response, growth and distribution of fluorescent labeling Pseudomonas aeruginosa PAO1 against the antimicrobial agent were monitored by confocal laser scanning microscope (CLSM). The microfluidic sensor along with 1-TDPPOin this study exhibits the following advantages: (i) Real-time chemo-repellent responses of cell dynamics; (ii) Rapid eradication of biofilm by embedded obstacles and powerful antibacterial agents, which significantly reduce the response time compared to classical methods; (iii) Minimal consumption of cells and antimicrobial agents; and (iv) Simplifying the process of the normalization of the fluorescence intensity and monitoring of biofilm by captured images and datasets.

Microfluidics for High School Chemistry Students.

PubMed

Hemling, Melissa; Crooks, John A; Oliver, Piercen M; Brenner, Katie; Gilbertson, Jennifer; Lisensky, George C; Weibel, Douglas B

2014-01-14

We present a laboratory experiment that introduces high school chemistry students to microfluidics while teaching fundamental properties of acid-base chemistry. The procedure enables students to create microfluidic systems using nonspecialized equipment that is available in high school classrooms and reagents that are safe, inexpensive, and commercially available. The experiment is designed to ignite creativity and confidence about experimental design in a high school chemistry class. This experiment requires a computer program (e.g., PowerPoint), Shrinky Dink film, a readily available silicone polymer, weak acids, bases, and a colorimetric pH indicator. Over the span of five 45-min class periods, teams of students design and prepare devices in which two different pH solutions mix in a predictable way to create five different pH solutions. Initial device designs are instructive but rarely optimal. During two additional half-class periods, students have the opportunity to use their initial observations to redesign their microfluidic systems to optimize the outcome. The experiment exposes students to cutting-edge science and the design process, and solidifies introductory chemistry concepts including laminar flow, neutralization of weak acids-bases, and polymers.

Microfluidics platform for single-shot dose-response analysis of chloride channel-modulating compounds.

PubMed

Jin, Byung-Ju; Ko, Eun-A; Namkung, Wan; Verkman, A S

2013-10-07

We previously developed cell-based kinetics assays of chloride channel modulators utilizing genetically encoded yellow fluorescent proteins. Fluorescence platereader-based high-throughput screens yielded small-molecule activators and inhibitors of the cAMP-activated chloride channel CFTR and calcium-activated chloride channels, including TMEM16A. Here, we report a microfluidics platform for single-shot determination of concentration-activity relations in which a 1.5 × 1.5 mm square area of adherent cultured cells is exposed for 5-10 min to a pseudo-logarithmic gradient of test compound generated by iterative, two-component channel mixing. Cell fluorescence is imaged following perfusion with an iodide-containing solution to give iodide influx rate at each location in the image field, thus quantifying modulator effects over a wide range of concentrations in a single measurement. IC50 determined for CFTR and TMEM16A activators and inhibitors by single-shot microfluidics were in agreement with conventional plate reader measurements. The microfluidics approach developed here may accelerate the discovery and characterization of chloride channel-targeted drugs.

Microfluidic based high throughput synthesis of lipid-polymer hybrid nanoparticles with tunable diameters

PubMed Central

Feng, Qiang; Zhang, Lu; Liu, Chao; Li, Xuanyu; Hu, Guoqing; Sun, Jiashu; Jiang, Xingyu

2015-01-01

Core-shell hybrid nanoparticles (NPs) for drug delivery have attracted numerous attentions due to their enhanced therapeutic efficacy and good biocompatibility. In this work, we fabricate a two-stage microfluidic chip to implement a high-throughput, one-step, and size-tunable synthesis of mono-disperse lipid-poly (lactic-co-glycolic acid) NPs. The size of hybrid NPs is tunable by varying the flow rates inside the two-stage microfluidic chip. To elucidate the mechanism of size-controllable generation of hybrid NPs, we observe the flow field in the microchannel with confocal microscope and perform the simulation by a numerical model. Both the experimental and numerical results indicate an enhanced mixing effect at high flow rate, thus resulting in the assembly of small and mono-disperse hybrid NPs. In vitro experiments show that the large hybrid NPs are more likely to be aggregated in serum and exhibit a lower cellular uptake efficacy than the small ones. This microfluidic chip shows great promise as a robust platform for optimization of nano drug delivery system. PMID:26180574

Microfluidics for High School Chemistry Students

PubMed Central

Hemling, Melissa; Crooks, John A.; Oliver, Piercen M.; Brenner, Katie; Gilbertson, Jennifer; Lisensky, George C.; Weibel, Douglas B.

2014-01-01

We present a laboratory experiment that introduces high school chemistry students to microfluidics while teaching fundamental properties of acid–base chemistry. The procedure enables students to create microfluidic systems using nonspecialized equipment that is available in high school classrooms and reagents that are safe, inexpensive, and commercially available. The experiment is designed to ignite creativity and confidence about experimental design in a high school chemistry class. This experiment requires a computer program (e.g., PowerPoint), Shrinky Dink film, a readily available silicone polymer, weak acids, bases, and a colorimetric pH indicator. Over the span of five 45-min class periods, teams of students design and prepare devices in which two different pH solutions mix in a predictable way to create five different pH solutions. Initial device designs are instructive but rarely optimal. During two additional half-class periods, students have the opportunity to use their initial observations to redesign their microfluidic systems to optimize the outcome. The experiment exposes students to cutting-edge science and the design process, and solidifies introductory chemistry concepts including laminar flow, neutralization of weak acids–bases, and polymers. PMID:25584013

Fluorimetric urease inhibition assay on a multilayer microfluidic chip with immunoaffinity immobilized enzyme reactors.

PubMed

Zhang, Qin; Tang, Xiuwen; Hou, Fenghua; Yang, Jianping; Xie, Zhiyong; Cheng, Zhiyi

2013-10-01

We fabricated a three-layer polydimethylsiloxane (PDMS)-based microfluidic chip for realizing urease inhibition assay with sensitive fluorescence detection. Procedures such as sample prehandling, enzyme reaction, reagent mixing, fluorescence derivatization, and detection can be readily carried out. Urease reactors were prepared by adsorption of rabbit immunoglobulin G (IgG) and immunoreaction with urease-conjugated goat anti-rabbit IgG. Acetohydroxamic acid (AHA) as a competitive inhibitor of urease was tested on the chip. Microfluidically generated gradient concentrations of AHA with substrate (urea) were loaded into urease reactors. After incubation, the produced ammonia was transported out of reactors and then reacted with o-phthalaldehyde (OPA) to generate fluorescent products. Urease inhibition was indicated by a decrease in fluorescence signal detected by microplate reader. The IC50 value of AHA was determined and showed good agreement with that obtained in microplate. The presented device combines several steps of the analytical process with advantages of low reagent consumption, reduced analysis time, and ease of manipulation. This microfluidic approach can be extended to the screening of inhibitory compounds in drug discovery. Copyright © 2013 Elsevier Inc. All rights reserved.

Combining Whispering-Gallery Mode Optical Biosensors with Microfluidics for Real-Time Detection of Protein Secretion from Living Cells in Complex Media.

PubMed

Chen, Ying-Jen; Schoeler, Ulrike; Huang, Chung-Hsuan Benjamin; Vollmer, Frank

2018-05-01

The noninvasive monitoring of protein secretion of cells responding to drug treatment is an effective and essential tool in latest drug development and for cytotoxicity assays. In this work, a surface functionalization method is demonstrated for specific detection of protein released from cells and a platform that integrates highly sensitive optical devices, called whispering-gallery mode biosensors, with precise microfluidics control to achieve label-free and real-time detection. Cell biomarker release is measured in real time and with nanomolar sensitivity. The surface functionalization method allows for antibodies to be immobilized on the surface for specific detection, while the microfluidics system enables detection in a continuous flow with a negligible compromise between sensitivity and flow control over stabilization and mixing. Cytochrome c detection is used to illustrate the merits of the system. Jurkat cells are treated with the toxin staurosporine to trigger cell apoptosis and cytochrome c released into the cell culture medium is monitored via the newly invented optical microfluidic platform. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

An integrated optics microfluidic device for detecting single DNA molecules.

PubMed

Krogmeier, Jeffrey R; Schaefer, Ian; Seward, George; Yantz, Gregory R; Larson, Jonathan W

2007-12-01

A fluorescence-based integrated optics microfluidic device is presented, capable of detecting single DNA molecules in a high throughput and reproducible manner. The device integrates microfluidics for DNA stretching with two optical elements for single molecule detection (SMD): a plano-aspheric refractive lens for fluorescence excitation (illuminator) and a solid parabolic reflective mirror for fluorescence collection (collector). Although miniaturized in size, both optical components were produced and assembled onto the microfluidic device by readily manufacturable fabrication techniques. The optical resolution of the device is determined by the small and relatively low numerical aperture (NA) illuminator lens (0.10 effective NA, 4.0 mm diameter) that delivers excitation light to a diffraction limited 2.0 microm diameter spot at full width half maximum within the microfluidic channel. The collector (0.82 annular NA, 15 mm diameter) reflects the fluorescence over a large collection angle, representing 71% of a hemisphere, toward a single photon counting module in an infinity-corrected scheme. As a proof-of-principle experiment for this simple integrated device, individual intercalated lambda-phage DNA molecules (48.5 kb) were stretched in a mixed elongational-shear microflow, detected, and sized with a fluorescence signal to noise ratio of 9.9 +/-1.0. We have demonstrated that SMD does not require traditional high numerical aperture objective lenses and sub-micron positioning systems conventionally used in many applications. Rather, standard manufacturing processes can be combined in a novel way that promises greater accessibility and affordability for microfluidic-based single molecule applications.

Magneto-Hydrodynamics Based Microfluidics

PubMed Central

Qian, Shizhi; Bau, Haim H.

2009-01-01

In microfluidic devices, it is necessary to propel samples and reagents from one part of the device to another, stir fluids, and detect the presence of chemical and biological targets. Given the small size of these devices, the above tasks are far from trivial. Magnetohydrodynamics (MHD) offers an elegant means to control fluid flow in microdevices without a need for mechanical components. In this paper, we review the theory of MHD for low conductivity fluids and describe various applications of MHD such as fluid pumping, flow control in fluidic networks, fluid stirring and mixing, circular liquid chromatography, thermal reactors, and microcoolers. PMID:20046890

Rapid magnetic microfluidic mixer utilizing AC electromagnetic field.

PubMed

Wen, Chih-Yung; Yeh, Cheng-Peng; Tsai, Chien-Hsiung; Fu, Lung-Ming

2009-12-01

This paper presents a novel simple micromixer based on stable water suspensions of magnetic nanoparticles (i.e. ferrofluids). The micromixer chip is built using standard microfabrication and simple soft lithography, and the design can be incorporated as a subsystem into any chemical microreactor or a miniaturized biological sensor. An electromagnet driven by an AC power source is used to induce transient interactive flows between a ferrofluid and Rhodamine B. The alternative magnetic field causes the ferrofluid to expand significantly and uniformly toward Rhodamine B, associated with a great number of extremely fine fingering structures on the interface in the upstream and downstream regions of the microchannel. These pronounced fingering patterns, which have not been observed by other active mixing methods utilizing only magnetic force, increase the mixing interfacial length dramatically. Along with the dominant diffusion effects occurring around the circumferential regions of the fine finger structures, the mixing efficiency increases significantly. The miscible fingering instabilities are observed and applied in the microfluidics for the first time. This work is carried with a view to developing functionalized ferrofluids that can be used as sensitive pathogen detectors and the present experimental results demonstrate that the proposed micromixer has excellent mixing capabilities. The mixing efficiency can be as high as 95% within 2.0 s and a distance of 3.0 mm from the inlet of the mixing channel, when the applied peak magnetic field is higher than 29.2 Oe and frequency ranges from 45 to 300 Hz.

A millisecond micromixer via single-bubble-based acoustic streaming.

PubMed

Ahmed, Daniel; Mao, Xiaole; Shi, Jinjie; Juluri, Bala Krishna; Huang, Tony Jun

2009-09-21

We present ultra-fast homogeneous mixing inside a microfluidic channel via single-bubble-based acoustic streaming. The device operates by trapping an air bubble within a "horse-shoe" structure located between two laminar flows inside a microchannel. Acoustic waves excite the trapped air bubble at its resonance frequency, resulting in acoustic streaming, which disrupts the laminar flows and triggers the two fluids to mix. Due to this technique's simple design, excellent mixing performance, and fast mixing speed (a few milliseconds), our single-bubble-based acoustic micromixer may prove useful for many biochemical studies and applications.

Carbon nanotube sensors integrated inside a microfluidic channel for water quality monitoring

NASA Astrophysics Data System (ADS)

Liu, Yu; Li, Xinghui; Dokmeci, Mehmet R.; Wang, Ming L.

2011-04-01

Single-walled carbon nanotubes (SWNTs) with their unique electrical properties and large surface area are remarkable materials for detecting low concentration of toxic and hazardous chemicals (both from the gaseous and liquid phases). Ionic adsorbates in water will attach on to SWNTs and drastically alter their electrical properties. Several SWNTs based pH and chemical sensors have been demonstrated. However, most of them require external components to test and analyze the response of SWNTs to ions inside the liquid samples. Here, we report a water quality monitoring sensor composed of SWNTs integrated inside microfluidic channels and on-chip testing components with a wireless transmission board. To detect multiple analytes in water requires the functionalization of SWNTs with different chemistries. In addition, microfluidic channels are used to guide liquid samples to individual nanotube sensors in an efficient manner. Furthermore, the microfluidic system enables sample mixing and separation before testing. To realize the nanosensors, first microelectrodes were fabricated on an oxidized silicon substrate. Next, PDMS micro channels were fabricated and bonded on the substrate. These channels can be incorporated with a microfluidic system which can be designed to manipulate different analytes for specific molecule detection. Low temperature, solution based Dielectrophoretic (DEP) assembly was conducted inside this microfluidic system which successfully bridged SWNTs between the microelectrodes. The SWNTs sensors were next characterized with different pH buffer solutions. The resistance of SWNTs had a linearly increase as the pH values ranged from 5 to 8. The nanosensor incorporated within the microfluidic system is a versatile platform and can be utilized to detect numerous water pollutants, including toxic organics and microorganisms down to low concentrations. On-chip processing and wireless transmission enables the realization of a full autonomous system for real time monitoring of water quality.

Assessment of three AC electroosmotic flow protocols for mixing in microfluidic channel.

PubMed

Chen, Jia-Kun; Weng, Chi-Neng; Yang, Ruey-Jen

2009-05-07

This study performs an experimental investigation into the micromixer capabilities of three different protocols of AC electroosmotic flow (AC EOF), namely capacitive charging (CC), Faradaic charging (FC) and asymmetric polarization (AP). The results reveal that the vortices generated by the FC protocol (the frequency is around 50-350 Hz) are stronger than those induced by the CC protocol (the frequency is higher than 350 Hz), and therefore provide an improved mixing effect. However, in the FC protocol, the frequency of the external AC voltage must be carefully controlled to avoid damaging electrodes as a result of Faradaic reactions. The experimental results indicate that the AP polarization effect (the applied voltage and frequency are V(1) = 1 V(pp) and V(2) = 20 V(pp)/5 kHz) induces more powerful vortices than either the CC protocol or the FC protocol, and therefore yields a better mixing performance. Two AP-based micromixers are fabricated with symmetric and asymmetric electrode configurations, respectively. The mixing indices achieved by the two devices after an elapsed time of 60 seconds are found to be 56.49 % and 71.77 %, respectively. This result shows that of the two devices, an asymmetric electrode configuration represents a more suitable choice for micromixer in microfluidic devices.

On-chip synthesis of fine-tuned bone-seeking hybrid nanoparticles.

PubMed

Hasani-Sadrabadi, Mohammad Mahdi; Dashtimoghadam, Erfan; Bahlakeh, Ghasem; Majedi, Fatemeh S; Keshvari, Hamid; Van Dersarl, Jules J; Bertsch, Arnaud; Panahifar, Arash; Renaud, Philippe; Tayebi, Lobat; Mahmoudi, Morteza; Jacob, Karl I

2015-01-01

Here we report a one-step approach for reproducible synthesis of finely tuned targeting multifunctional hybrid nanoparticles (HNPs). A microfluidic-assisted method was employed for controlled nanoprecipitation of bisphosphonate-conjugated poly(D,L-lactide-co-glycolide) chains, while coencapsulating superparamagnetic iron oxide nanoparticles and the anticancer drug Paclitaxel. Smaller and more compact HNPs with narrower size distribution and higher drug loading were obtained at microfluidic rapid mixing regimen compared with the conventional bulk method. The HNPs were shown to have a strong affinity for hydroxyapatite, as demonstrated in vitro bone-binding assay, which was further supported by molecular dynamics simulation results. In vivo proof of concept study verified the prolonged circulation of targeted microfluidic HNPs. Biodistribution as well as noninvasive bioimaging experiments showed high tumor localization and suppression of targeted HNPs to the bone metastatic tumor. The hybrid bone-targeting nanoparticles with adjustable characteristics can be considered as promising nanoplatforms for various theragnostic applications.

Fluidic conduits for highly efficient purification of target species in EWOD-driven droplet microfluidics.

PubMed

Shah, Gaurav J; Kim, Chang-Jin Cj

2009-08-21

Due to the lack of continuous flows that would wash unwanted specifies and impurities off from a target location, droplet microfluidics commonly employs a long serial dilution process to purify target species. In this work, we achieve high-purity separation for the case of electrowetting-on-dielectric (EWOD) based droplet microfluidics by introducing a "fluidic conduit" between a sample droplet and a buffer droplet. The long and slender fluidic path minimizes the diffusion and fluidic mixing between the two droplets (thus eliminating non-specific transport) but provides a conduit between them for actively transported particles (thus allowing the specific transport). The conduit is purely fluidic, stabilized chemically (e.g. using surfactants) and controlled by EWOD. The effectiveness of the technique is demonstrated by eliminating approximately 97% non-magnetic beads in just one purification step, while maintaining high collection efficiency (>99%) of magnetic beads.

Sequential bottom-up assembly of mechanically stabilized synthetic cells by microfluidics

NASA Astrophysics Data System (ADS)

Weiss, Marian; Frohnmayer, Johannes Patrick; Benk, Lucia Theresa; Haller, Barbara; Janiesch, Jan-Willi; Heitkamp, Thomas; Börsch, Michael; Lira, Rafael B.; Dimova, Rumiana; Lipowsky, Reinhard; Bodenschatz, Eberhard; Baret, Jean-Christophe; Vidakovic-Koch, Tanja; Sundmacher, Kai; Platzman, Ilia; Spatz, Joachim P.

2018-01-01

Compartments for the spatially and temporally controlled assembly of biological processes are essential towards cellular life. Synthetic mimics of cellular compartments based on lipid-based protocells lack the mechanical and chemical stability to allow their manipulation into a complex and fully functional synthetic cell. Here, we present a high-throughput microfluidic method to generate stable, defined sized liposomes termed `droplet-stabilized giant unilamellar vesicles (dsGUVs)’. The enhanced stability of dsGUVs enables the sequential loading of these compartments with biomolecules, namely purified transmembrane and cytoskeleton proteins by microfluidic pico-injection technology. This constitutes an experimental demonstration of a successful bottom-up assembly of a compartment with contents that would not self-assemble to full functionality when simply mixed together. Following assembly, the stabilizing oil phase and droplet shells are removed to release functional self-supporting protocells to an aqueous phase, enabling them to interact with physiologically relevant matrices.

Fast and sensitive detection of foodborne pathogen using electrochemical impedance analysis, urease catalysis and microfluidics.

PubMed

Chen, Qi; Wang, Dan; Cai, Gaozhe; Xiong, Yonghua; Li, Yuntao; Wang, Maohua; Huo, Huiling; Lin, Jianhan

2016-12-15

Early screening of pathogenic bacteria is a key to prevent and control of foodborne diseases. In this study, we developed a fast and sensitive bacteria detection method integrating electrochemical impedance analysis, urease catalysis with microfluidics and using Listeria as model. The Listeria cells, the anti-Listeria monoclonal antibodies modified magnetic nanoparticles (MNPs), and the anti-Listeria polyclonal antibodies and urease modified gold nanoparticles (AuNPs) were incubated in a fluidic separation chip with active mixing to form the MNP-Listeria-AuNP-urease sandwich complexes. The complexes were captured in the separation chip by applying a high gradient magnetic field, and the urea was injected to resuspend the complexes and hydrolyzed under the catalysis of the urease on the complexes into ammonium ions and carbonate ions, which were transported into a microfluidic detection chip with an interdigitated microelectrode for impedance measurement to determine the amount of the Listeria cells. The capture efficiency of the Listeria cells in the separation chip was ∼93% with a shorter time of 30min due to the faster immuno-reaction using the active magnetic mixing. The changes on both impedance magnitude and phase angle were demonstrated to be able to detect the Listeria cells as low as 1.6×10(2)CFU/mL. The detection time was reduced from original ∼2h to current ∼1h. The recoveries of the spiked lettuce samples ranged from 82.1% to 89.6%, indicating the applicability of this proposed biosensor. This microfluidic impedance biosensor has shown the potential for online, automatic and sensitive bacteria separation and detection. Copyright © 2016 Elsevier B.V. All rights reserved.

Acoustically and Electrokinetically Driven Transport in Microfluidic Devices

NASA Astrophysics Data System (ADS)

Sayar, Ersin

Electrokinetically driven flows are widely employed as a primary method for liquid pumping in micro-electromechanical systems. Mixing of analytes and reagents is limited in microfluidic devices due to the low Reynolds number of the flows. Acoustic excitations have recently been suggested to promote mixing in the microscale flow systems. Electrokinetic flows through straight microchannels were investigated using the Poisson-Boltzmann and Nernst-Planck models. The acoustic wave/fluid flow interactions in a microchannel were investigated via the development of two and three-dimensional dynamic predictive models for flows with field couplings of the electrical, mechanical and fluid flow quantities. The effectiveness and applicability of electrokinetic augmentation in flexural plate wave micropumps for enhanced capabilities were explored. The proposed concept can be exploited to integrate micropumps into complex microfluidic chips improving the portability of micro-total-analysis systems along with the capabilities of actively controlling acoustics and electrokinetics for micro-mixer applications. Acoustically excited flows in microchannels consisting of flexural plate wave devices and thin film resonators were considered. Compressible flow fields were considered to accommodate the acoustic excitations produced by a vibrating wall. The velocity and pressure profiles for different parameters including frequency, channel height, wave amplitude and length were investigated. Coupled electrokinetics and acoustics cases were investigated while the electric field intensity of the electrokinetic body forces and actuation frequency of acoustic excitations were varied. Multifield analysis of a piezoelectrically actuated valveless micropump was also presented. The effect of voltage and frequency on membrane deflection and flow rate were investigated. Detailed fluid/solid deformation coupled simulations of piezoelectric valveless micropump have been conducted to predict the generated time averaged flow rates. Developed coupled solid and fluid mechanics models can be utilized to integrate flow-through sensors with microfluidic chips.

An optical manometer-on-a-chip

NASA Astrophysics Data System (ADS)

Jin, Yuhang; Crozier, Kenneth B.

2011-10-01

The rapid development of microfluidic devices in recent years has led to a huge number of applications in chemistry, biology and interdisciplinary areas. This is because they act as miniaturized platforms in which sorting, mixing, reaction and measurement can be achieved in a precise and rapid manner. Being able to both understand and measure the pressure of fluids inside these devices is very important, especially in the cases where multiphase flows are involved. For example, certain advanced micromixing technologies demand accurate evaluations of bubble-induced extra pressure, since the pressure contribution from one bubble is likely to impact the velocity and residence time of others, affecting the mixing efficiency and quality in a complicated manner. Similarly, in some microfluidics-based biochemical analysis, extra pressure brought about by droplets is a critical factor in the design of on-chip pumping, as high throughput experiments involving continuous supply of large numbers of droplets often require a considerable enhancement in the pumping pressure necessary to maintain the droplet flow3. Last, state-of-the-art microfluidic logic devices rely heavily on the pressure distribution inside the channels, which automatically controls the paths of each droplet in the microfluidic network and as a result determines the "on" and "off" of each switch. A few techniques to measure pressure change or pressure drop in microfluidic channels have been developed. Examples include connecting the device to commercially available pressure sensors and comparing pressures of different areas by analyzing the position of fluid-fluid interface. However, all of those methods have intrinsic drawbacks in one or more aspects that considerably limit their applications. A significant one is that they are primarily aiming at measuring or comparing pressures over relatively long channels (~10 mm), and are hence only designed to work in the highpressure range, i.e. to detect a pressure change on the order of tens or hundreds of Pascals. Moreover, the long channels make it rather challenging to look into the detailed dynamics of pressure variations caused by inhomogeneous emulsions, since such a long section invariably contains multiple elements, for instance droplets, of the emulsion flow, and the measurements average out the behavior of one single element. Consequently, to further reveal the characteristics of flows in microfluidics, it is highly desirable for a pressure measurement device to work in the low-pressure range, and to resolve pressure changes "locally", i.e. within small spatial regions.

Instantaneous velocity measurement of AC electroosmotic flows by laser induced fluorescence photobleaching anemometer with high temporal resolution

NASA Astrophysics Data System (ADS)

Zhao, Wei; Yang, Fang; Qiao, Rui; Wang, Guiren; Rui Qiao Collaboration

2015-11-01

Understanding the instantaneous response of flows to applied AC electric fields may help understand some unsolved issues in induced-charge electrokinetics and enhance performance of microfluidic devices. Since currently available velocimeters have difficulty in measuring velocity fluctuations with frequency higher than 1 kHz, most experimental studies so far focus only on the average velocity measurement in AC electrokinetic flows. Here, we present measurements of AC electroosmotic flow (AC-EOF) response time in microchannels by a novel velocimeter with submicrometer spatial resolution and microsecond temporal resolution, i.e. laser-induced fluorescence photobleaching anemometer (LIFPA). Several parameters affecting the AC-EOF response time to the applied electric signal were investigated, i.e. channel length, transverse position and solution conductivity. The experimental results show that the EOF response time under a pulsed electric field decreases with the reduction of the microchannel length, distance between the detection position to the wall and the conductivity of the solution. This work could provide a new powerful tool to measure AC electrokinetics and enhance our understanding of AC electrokinetic flows.

Reconfigurable virtual electrowetting channels.

PubMed

Banerjee, Ananda; Kreit, Eric; Liu, Yuguang; Heikenfeld, Jason; Papautsky, Ian

2012-02-21

Lab-on-a-chip systems rely on several microfluidic paradigms. The first uses a fixed layout of continuous microfluidic channels. Such lab-on-a-chip systems are almost always application specific and far from a true "laboratory." The second involves electrowetting droplet movement (digital microfluidics), and allows two-dimensional computer control of fluidic transport and mixing. The merging of the two paradigms in the form of programmable electrowetting channels takes advantage of both the "continuous" functionality of rigid channels based on which a large number of applications have been developed to date and the "programmable" functionality of digital microfluidics that permits electrical control of on-chip functions. In this work, we demonstrate for the first time programmable formation of virtual microfluidic channels and their continuous operation with pressure driven flows using an electrowetting platform. Experimental, theoretical, and numerical analyses of virtual channel formation with biologically relevant electrolyte solutions and electrically-programmable reconfiguration are presented. We demonstrate that the "wall-less" virtual channels can be formed reliably and rapidly, with propagation rates of 3.5-3.8 mm s(-1). Pressure driven transport in these virtual channels at flow rates up to 100 μL min(-1) is achievable without distortion of the channel shape. We further demonstrate that these virtual channels can be switched on-demand between multiple inputs and outputs. Ultimately, we envision a platform that would provide rapid prototyping of microfluidic concepts and would be capable of a vast library of functions and benefitting applications from clinical diagnostics in resource-limited environments to rapid system prototyping to high throughput pharmaceutical applications.

An X-ray transparent microfluidic platform for screening of the phase behavior of lipidic mesophases

PubMed Central

Khvostichenko, Daria S.; Kondrashkina, Elena; Perry, Sarah L.; Pawate, Ashtamurthy S.; Brister, Keith

2013-01-01

Lipidic mesophases are a class of highly ordered soft materials that form when certain lipids are mixed with water. Understanding the relationship between the composition and the microstructure of mesophases is necessary for fundamental studies of self-assembly in amphiphilic systems and for applications, such as crystallization of membrane proteins. However, the laborious formulation protocol for highly viscous mesophases and the large amounts of material required for sample formulation are significant obstacles in such studies. Here we report a microfluidic platform that facilitates investigations of the phase behavior of mesophases by reducing sample consumption, and automating and parallelizing sample formulation. The mesophases were formulated on-chip using less than 40 nL of material per sample and their microstructure was analyzed in situ using small-angle X-ray scattering (SAXS). The 220 μm-thick X-ray compatible platform was comprised of thin polydimethylsiloxane (PDMS) layers sandwiched between cyclic olefin copolymer (COC) sheets. Uniform mesophases were prepared using an active on-chip mixing strategy coupled with periodic cooling of the sample to reduce the viscosity. We validated the platform by preparing and analyzing mesophases of lipid monoolein (MO) mixed with aqueous solutions of different concentrations of β-octylglucoside (βOG), a detergent frequently used in membrane protein crystallization. Four samples were prepared in parallel on chip, by first metering and automatically diluting βOG to obtain detergent solutions of different concentration, then metering MO, and finally mixing by actuation of pneumatic valves. Integration of detergent dilution and subsequent mixing significantly reduced the number of manual steps needed for sample preparation. Three different types of mesophases typical for monoolein were successfully identified in SAXS data from on-chip samples. Microstructural parameters of identical samples formulated in different chips showed excellent agreement. Phase behavior observed on-chip corresponded well with that of samples prepared via the traditional coupled-syringe method (“off-chip”) using 300-fold larger amount of material, further validating the utility of the microfluidic platform for on-chip characterization of mesophase behavior. PMID:23882463

Microfluidic systems with ion-selective membranes.

PubMed

Slouka, Zdenek; Senapati, Satyajyoti; Chang, Hsueh-Chia

2014-01-01

When integrated into microfluidic chips, ion-selective nanoporous polymer and solid-state membranes can be used for on-chip pumping, pH actuation, analyte concentration, molecular separation, reactive mixing, and molecular sensing. They offer numerous functionalities and are hence superior to paper-based devices for point-of-care biochips, with only slightly more investment in fabrication and material costs required. In this review, we first discuss the fundamentals of several nonequilibrium ion current phenomena associated with ion-selective membranes, many of them revealed by studies with fabricated single nanochannels/nanopores. We then focus on how the plethora of phenomena has been applied for transport, separation, concentration, and detection of biomolecules on biochips.

Microfluidic Systems with Ion-Selective Membranes

NASA Astrophysics Data System (ADS)

Slouka, Zdenek; Senapati, Satyajyoti; Chang, Hsueh-Chia

2014-06-01

When integrated into microfluidic chips, ion-selective nanoporous polymer and solid-state membranes can be used for on-chip pumping, pH actuation, analyte concentration, molecular separation, reactive mixing, and molecular sensing. They offer numerous functionalities and are hence superior to paper-based devices for point-of-care biochips, with only slightly more investment in fabrication and material costs required. In this review, we first discuss the fundamentals of several nonequilibrium ion current phenomena associated with ion-selective membranes, many of them revealed by studies with fabricated single nanochannels/nanopores. We then focus on how the plethora of phenomena has been applied for transport, separation, concentration, and detection of biomolecules on biochips.

Material-Efficient Microfluidic Platform for Exploratory Studies of Visible-Light Photoredox Catalysis.

PubMed

Coley, Connor W; Abolhasani, Milad; Lin, Hongkun; Jensen, Klavs F

2017-08-07

We present an automated microfluidic platform for in-flow studies of visible-light photoredox catalysis in liquid or gas-liquid reactions at the 15 μL scale. An oscillatory flow strategy enables a flexible residence time while preserving the mixing and heat transfer advantages of flow systems. The adjustable photon flux made possible with the platform is characterized using actinometry. Case studies of oxidative hydroxylation of phenylboronic acids and dimerization of thiophenol demonstrate the capabilities and advantages of the system. Reaction conditions identified through droplet screening translate directly to continuous synthesis with minor platform modifications. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bubble-driven mixer integrated with a microfluidic bead-based ELISA for rapid bladder cancer biomarker detection.

PubMed

Lin, Yen-Heng; Wang, Chia-Chu; Lei, Kin Fong

2014-04-01

In this study, fine bubbles were successfully generated and used as a simple, low-cost driving force for mixing fluids in an integrated microfluidic bead-based enzyme-linked immunosorbent assay (ELISA) to rapidly and quantitatively detect apolipoprotein A1 (APOA1), a biomarker highly correlated with bladder cancer. A wooden gas diffuser was embedded underneath a microfluidic chip to refine injected air and generate bubbles of less than 0.3 mm. The rising bubbles caused disturbances and convection in the fluid, increasing the probability of analyte interaction. This setup not only simplifies the micromixer design but also achieves rapid mixing with a small airflow as a force. We used this bubble-driven micromixer in a bead-based ELISA that targeted APOA1. The results indicate that this micromixer reduced the time for each incubation from 60 min in the conventional assay to 8 min with the chip, resulting in a reduction of total ELISA reaction time from 3-4 h to 30-40 min. Furthermore, the concentration detection limit was 9.16 ng/mL, which was lower than the detection cut-off value (11.16 ng/mL) for bladder cancer diagnosis reported in the literature. Therefore, this chip can be used to achieve rapid low-cost bladder cancer detection and may be used in point-of-care cancer monitoring.

Macromolecular Crystal Growth by Means of Microfluidics

NASA Technical Reports Server (NTRS)

vanderWoerd, Mark; Ferree, Darren; Spearing, Scott; Monaco, Lisa; Molho, Josh; Spaid, Michael; Brasseur, Mike; Curreri, Peter A. (Technical Monitor)

2002-01-01

We have performed a feasibility study in which we show that chip-based, microfluidic (LabChip(TM)) technology is suitable for protein crystal growth. This technology allows for accurate and reliable dispensing and mixing of very small volumes while minimizing bubble formation in the crystallization mixture. The amount of (protein) solution remaining after completion of an experiment is minimal, which makes this technique efficient and attractive for use with proteins, which are difficult or expensive to obtain. The nature of LabChip(TM) technology renders it highly amenable to automation. Protein crystals obtained in our initial feasibility studies were of excellent quality as determined by X-ray diffraction. Subsequent to the feasibility study, we designed and produced the first LabChip(TM) device specifically for protein crystallization in batch mode. It can reliably dispense and mix from a range of solution constituents into two independent growth wells. We are currently testing this design to prove its efficacy for protein crystallization optimization experiments. In the near future we will expand our design to incorporate up to 10 growth wells per LabChip(TM) device. Upon completion, additional crystallization techniques such as vapor diffusion and liquid-liquid diffusion will be accommodated. Macromolecular crystallization using microfluidic technology is envisioned as a fully automated system, which will use the 'tele-science' concept of remote operation and will be developed into a research facility for the International Space Station as well as on the ground.

Computerized microfluidic cell culture using elastomeric channels and Braille displays.

PubMed

Gu, Wei; Zhu, Xiaoyue; Futai, Nobuyuki; Cho, Brenda S; Takayama, Shuichi

2004-11-09

Computer-controlled microfluidics would advance many types of cellular assays and microscale tissue engineering studies wherever spatiotemporal changes in fluidics need to be defined. However, this goal has been elusive because of the limited availability of integrated, programmable pumps and valves. This paper demonstrates how a refreshable Braille display, with its grid of 320 vertically moving pins, can power integrated pumps and valves through localized deformations of channel networks within elastic silicone rubber. The resulting computerized fluidic control is able to switch among: (i) rapid and efficient mixing between streams, (ii) multiple laminar flows with minimal mixing between streams, and (iii) segmented plug-flow of immiscible fluids within the same channel architecture. The same control method is used to precisely seed cells, compartmentalize them into distinct subpopulations through channel reconfiguration, and culture each cell subpopulation for up to 3 weeks under perfusion. These reliable microscale cell cultures showed gradients of cellular behavior from C2C12 myoblasts along channel lengths, as well as differences in cell density of undifferentiated myoblasts and differentiation patterns, both programmable through different flow rates of serum-containing media. This technology will allow future microscale tissue or cell studies to be more accessible, especially for high-throughput, complex, and long-term experiments. The microfluidic actuation method described is versatile and computer programmable, yet simple, well packaged, and portable enough for personal use.

Computerized microfluidic cell culture using elastomeric channels and Braille displays

PubMed Central

Gu, Wei; Zhu, Xiaoyue; Futai, Nobuyuki; Cho, Brenda S.; Takayama, Shuichi

2004-01-01

Computer-controlled microfluidics would advance many types of cellular assays and microscale tissue engineering studies wherever spatiotemporal changes in fluidics need to be defined. However, this goal has been elusive because of the limited availability of integrated, programmable pumps and valves. This paper demonstrates how a refreshable Braille display, with its grid of 320 vertically moving pins, can power integrated pumps and valves through localized deformations of channel networks within elastic silicone rubber. The resulting computerized fluidic control is able to switch among: (i) rapid and efficient mixing between streams, (ii) multiple laminar flows with minimal mixing between streams, and (iii) segmented plug-flow of immiscible fluids within the same channel architecture. The same control method is used to precisely seed cells, compartmentalize them into distinct subpopulations through channel reconfiguration, and culture each cell subpopulation for up to 3 weeks under perfusion. These reliable microscale cell cultures showed gradients of cellular behavior from C2C12 myoblasts along channel lengths, as well as differences in cell density of undifferentiated myoblasts and differentiation patterns, both programmable through different flow rates of serum-containing media. This technology will allow future microscale tissue or cell studies to be more accessible, especially for high-throughput, complex, and long-term experiments. The microfluidic actuation method described is versatile and computer programmable, yet simple, well packaged, and portable enough for personal use. PMID:15514025

Lab on a CD.

PubMed

Madou, Marc; Zoval, Jim; Jia, Guangyao; Kido, Horacio; Kim, Jitae; Kim, Nahui

2006-01-01

In this paper, centrifuge-based microfluidic platforms are reviewed and compared with other popular microfluidic propulsion methods. The underlying physical principles of centrifugal pumping in microfluidic systems are presented and the various centrifuge fluidic functions, such as valving, decanting, calibration, mixing, metering, heating, sample splitting, and separation, are introduced. Those fluidic functions have been combined with analytical measurement techniques, such as optical imaging, absorbance, and fluorescence spectroscopy and mass spectrometry, to make the centrifugal platform a powerful solution for medical and clinical diagnostics and high throughput screening (HTS) in drug discovery. Applications of a compact disc (CD)-based centrifuge platform analyzed in this review include two-point calibration of an optode-based ion sensor, an automated immunoassay platform, multiple parallel screening assays, and cellular-based assays. The use of modified commercial CD drives for high-resolution optical imaging is discussed as well. From a broader perspective, we compare technical barriers involved in applying microfluidics for sensing and diagnostic use and applying such techniques to HTS. The latter poses less challenges and explains why HTS products based on a CD fluidic platform are already commercially available, whereas we might have to wait longer to see commercial CD-based diagnostics.

Microfluidic cell disruption system employing a magnetically actuated diaphragm.

PubMed

Huh, Yun Suk; Choi, Jong Hyun; Huh, Kyoung Ae Kim; Kim, Kyoung Ae; Park, Tae Jung; Hong, Yeon Ki; Kim, Do Hyun; Hong, Won Hi; Lee, Sang Yup

2007-12-01

A microfluidic cell lysis chip equipped with a micromixer and SPE unit was developed and used for quantitative analysis of intracellular proteins. This miniaturized sample preparation system can be employed for any purpose where cell disruption is needed to obtain intracellular constituents for the subsequent analysis. This system comprises a magnetically actuated micromixer to disrupt cells, a hydrophobic valve to manipulate the cell lysate, and a packed porous polymerized monolith chamber for SPE and filtering debris from the cell lysate. Using recombinant Escherichia coli expressing intracellular enhanced green fluorescent protein (EGFP) and lipase as model bacteria, we optimized the cell disruption condition with respect to the lysis buffer composition, mixing time, and the frequency of the diaphragm in the micromixer, which was magnetically actuated by an external magnetic stirrer in the micromixer chamber. The lysed sample prepared under the optimal condition was purified by the packed SPE in the microfluidic chip. At a frequency of 1.96 Hz, the final cell lysis efficiency and relative fluorescence intensity of EGFP after the cell disruption process were greater than 90 and 94%, respectively. Thus, this microfluidic cell disruption chip can be used for the efficient lysis of cells for further analysis of intracellular contents in many applications.

Electroacoustics: A New Mechanism for Driving Individually Addressable Jetting and Other Microfluidic Manipulations in Multiwell Arrays

NASA Astrophysics Data System (ADS)

Yeo, Leslie; Rezk, Amgad

2017-11-01

The low take-up of microfluidic technology at the laboratory bench despite 25 years of advances can be attributed to the reluctance of practitioners to adopt new and sophisticated technology, which requires substantial retraining, as well as the large investments that have already been made in the vast array of existing laboratory equipment. A way to circumvent this is to design microfluidic technology to retrofit existing laboratory technology such as microscope stages, microplate readers, etc. This is however not without challenge as existing microfluidic devices themselves often require large ancillary equipment to drive fluidic actuation/detection, which are not always amenable to integration into these existing laboratory formats. We have developed a low-cost and scalable modular plug-and-play microplatform that facilitates individual addressability of each well in a microarray plate for sample dispensing, mixing and preconcentration, as well as its ejection via jetting/nebulisation for subsequent analysis. As this cannot be achieved using standard acoustofluidics, we have developed a new electroacoustic mechanism that allows the transmission of high frequency sound waves into each well while uniquely confining the electric field off the piezoelectric chip.

A novel in-plane passive microfluidic mixer with modified Tesla structures.

PubMed

Hong, Chien-Chong; Choi, Jin-Woo; Ahn, Chong H

2004-04-01

An innovative in-plane passive micromixer using modified Tesla structures, which are used as passive valves, has been designed, simulated, fabricated and successfully characterized in this paper. Simulation and experimental results of the developed novel micromixer have shown excellent mixing performance over a wide range of flow conditions in the micro scale. The micromixer realized in this work has achieved even better mixing performance at a higher flow rate, and its pressure drop is less than 10 KPa at the flow rate of 100 microl min(-1). This micromixer shows characteristics similar to Taylor dispersion, with contributions from both diffusion and convection. The mixer has a diffusion domain region at low flow rate, but it moves to a convection domain region at high flow rate. Due to the simple in-plane structure of the novel micromixer explored in this work, the mixer can be easily realized and integrated with on-chip microfluidic devices and micro total analysis systems (micro-TAS).

Design and Optimization of Coin-Shaped Microreactor Chips for PET Radiopharmaceutical Synthesis

PubMed Central

Elizarov, Arkadij M.; van Dam, R. Michael; Shin, Young Shik; Kolb, Hartmuth C.; Padgett, Henry C.; Stout, David; Shu, Jenny; Huang, Jiang; Daridon, Antoine; Heath, James R.

2010-01-01

An integrated elastomeric microfluidic device, with a footprint the size of a postage stamp, has been designed and optimized for multistep radiosynthesis of PET tracers. Methods The unique architecture of the device is centered around a 5-μL coin-shaped reactor, which yields reaction efficiency and speed from a combination of high reagent concentration, pressurized reactions, and rapid heat and mass transfer. Its novel features facilitate mixing, solvent exchange, and product collection. New mixing mechanisms assisted by vacuum, pressure, and chemical reactions are exploited. Results The architecture of the reported reactor is the first that has allowed batch-mode microfluidic devices to produce radiopharmaceuticals of sufficient quality and quantity to be validated by in vivo imaging. Conclusion The reactor has the potential to produce multiple human doses of 18F-FDG; the most impact, however, is expected in the synthesis of PET radiopharmaceuticals that can be made only with low yields by currently available equipment. PMID:20124050

Digital microfluidics and delivery of molecular payloads with magnetic porous silicon chaperones.

PubMed

Dorvee, Jason R; Sailor, Michael J; Miskelly, Gordon M

2008-02-14

Digital microfluidics involves the manipulation of molecules and materials in discrete packages. This paper reviews our work using amphiphilic magnetic microparticles constructed from porous silicon. An individual porous particle can be used to carry a nanomole or smaller quantities of a reagent, and assemblies of the particles can encapsulate and transport microliter droplets of liquid containing inorganic, organic, or biological molecules. The tracking and identification of each particle can be accomplished with spectral labels that are encoded into the particles during their synthesis. When used to chaperone liquid droplets, the labels can identify the separate droplets prior to mixing and also the combined droplets after mixing. Magnetic iron oxide nanoparticles encapsulated in the porous matrix allow the manipulation of the particles or whole droplet assemblies with a magnetic field, and they also allow heating of the particle's payload by means of an externally applied RF field. Examples of organic, inorganic, and biomolecular addition reactions, catalytic reactions, and thermolysis reactions are described.

Monolithic Microfluidic Mixing-Spraying Devices for Time-Resolved Cryo-Electron Microscopy

PubMed Central

Lu, Zonghuan; Shaikh, Tanvir R.; Barnard, David; Meng, Xing; Mohamed, Hisham; Yassin, Aymen; Mannella, Carmen A.; Agrawal, Rajendra K.; Lu, Toh-Ming

2009-01-01

The goal of time-resolved cryo-electron microscopy is to determine structural models for transient functional states of large macromolecular complexes such as ribosomes and viruses. The challenge of time-resolved cryo-electron microscopy is to rapidly mix reactants, and then, following a defined time interval, to rapidly deposit them as a thin film and freeze the sample to the vitreous state. Here we describe a methodology in which reaction components are mixed and allowed to react, and are then sprayed onto an EM grid as it is being plunged into cryogen. All steps are accomplished by a monolithic, microfabricated silicon device that incorporates a mixer, reaction channel, and pneumatic sprayer in a single chip. We have found that microdroplets produced by air atomization spread to sufficiently thin films on a millisecond time scale provided that the carbon supporting film is made suitably hydrophilic. The device incorporates two T-mixers flowing into a single channel of four butterfly-shaped mixing elements that ensure effective mixing, followed by a microfluidic reaction channel whose length can be varied to achieve the desired reaction time. The reaction channel is flanked by two ports connected to compressed humidified nitrogen gas (at 50 psi) to generate the spray. The monolithic mixer-sprayer is incorporated into a computer-controlled plunging apparatus. To test the mixing performance and the suitability of the device for preparation of biological macromolecules for cryo-EM, ribosomes and ferritin were mixed in the device and sprayed onto grids. Three-dimensional reconstructions of the ribosomes demonstrated retention of native structure, and 30S and 50S subunits were shown to be capable of reassociation into ribosomes after passage through the device. PMID:19683579

Complex Microfluidic Systems Architectures and Applications to Micropower Generation

DTIC Science & Technology

2010-07-07

signal. Images are recorded via an Hamamatsu Orca camera and processed with Matlab. The observed results show the ability of the micromixer to distribute...Generator was produced. References [1] F. Bottausci, C. Cardonne, C. Meinhart, and I. Mezić. An ultrashort mixing length micromixer : The shear superposition... micromixer . Lab on a Chip, 7(3):396–398, 2007. [2] F. Bottausci, I. Mezić, C.D. Meinhart, and C. Cardonne. Mixing in the shear superposition

Optical analysis of cirrhotic liver by near infrared time resolved spectroscopy

NASA Astrophysics Data System (ADS)

Nishio, Toshihiro; Kitai, Toshiyuki; Miwa, Mitsuharu; Takahashi, Rei; Yamaoka, Yoshio

1999-10-01

The severity of liver cirrhosis was related with the optical properties of liver tissue. Various grades of liver cirrhosis were produced in rats by intraperitoneal injection of thioacetamide (TAA) for different periods: 4 weeks, 8 weeks, 12 weeks, and 16 weeks. Optical properties of the liver, absorption, coefficient ((mu) a) and scattering coefficient (microsecond(s) '), were measured by near-infrared time- resolved spectroscopy. Histological examination confirmed cirrhotic changes in the liver, which were more severe in rats with TAA administration for longer periods. The (mu) a increased in 4- and 8-week rats, and then decreased in 12- and 16-week rats. The (mu) a of blood-free liver decreased as liver cirrhosis progressed. The hemoglobin content in the liver calculated from the (mu) a values increased in 4- and 8-week rats and decreased in 12- and 16-week rats. The microsecond(s) ' decreased in the cirrhotic liver, probably reflecting the decrease in the mitochondria content. It was shown that (mu) a and microsecond(s) ' determination is useful to assess the severity of liver cirrhosis.

Biochemical analysis with microfluidic systems.

PubMed

Bilitewski, Ursula; Genrich, Meike; Kadow, Sabine; Mersal, Gaber

2003-10-01

Microfluidic systems are capillary networks of varying complexity fabricated originally in silicon, but nowadays in glass and polymeric substrates. Flow of liquid is mainly controlled by use of electroosmotic effects, i.e. application of electric fields, in addition to pressurized flow, i.e. application of pressure or vacuum. Because electroosmotic flow rates depend on the charge densities on the walls of capillaries, they are influenced by substrate material, fabrication processes, surface pretreatment procedures, and buffer additives. Microfluidic systems combine the properties of capillary electrophoretic systems and flow-through analytical systems, and thus biochemical analytical assays have been developed utilizing and integrating both aspects. Proteins, peptides, and nucleic acids can be separated because of their different electrophoretic mobility; detection is achieved with fluorescence detectors. For protein analysis, in particular, interfaces between microfluidic chips and mass spectrometers were developed. Further levels of integration of required sample-treatment steps were achieved by integration of protein digestion by immobilized trypsin and amplification of nucleic acids by the polymerase chain reaction. Kinetic constants of enzyme reactions were determined by adjusting different degrees of dilution of enzyme substrates or inhibitors within a single chip utilizing mainly the properties of controlled dosing and mixing liquids within a chip. For analysis of kinase reactions, however, a combination of a reaction step (enzyme with substrate and inhibitor) and a separation step (enzyme substrate and reaction product) was required. Microfluidic chips also enable separation of analytes from sample matrix constituents, which can interfere with quantitative determination, if they have different electrophoretic mobilities. In addition to analysis of nucleic acids and enzymes, immunoassays are the third group of analytical assays performed in microfluidic chips. They utilize either affinity capillary electrophoresis as a homogeneous assay format, or immobilized antigens or antibodies in heterogeneous assays with serial supply of reagents and washing solutions.

SAXS on a chip: from dynamics of phase transitions to alignment phenomena at interfaces studied with microfluidic devices.

PubMed

Silva, Bruno F B

2017-09-13

The field of microfluidics offers attractive possibilities to perform novel experiments that are difficult (or even impossible) to perform using conventional bulk and surface-based methods. Such attractiveness comes from several important aspects inherent to these miniaturized devices. First, the flow of fluids under submillimeter confinement typically leads to a drop of inertial forces, meaning that turbulence is practically suppressed. This leads to predictable and controllable flow profiles, along with well-defined chemical gradients and stress fields that can be used for controlled mixing and actuation on the micro and nanoscale. Secondly, intricate microfluidic device designs can be fabricated using cleanroom standard procedures. Such intricate geometries can take diverse forms, designed by researchers to perform complex tasks, that require exquisite control of flow of several components and gradients, or to mimic real world examples, facilitating the establishment of more realistic models. Thirdly, microfluidic devices are usually compatible with in situ or integrated characterization methods that allow constant real-time monitoring of the processes occurring inside the microchannels. This is very different from typical bulk-based methods, where usually one can only observe the final result, or otherwise, take quick snapshots of the evolving process or take aliquots to be analyzed separately. Altogether, these characteristics inherent to microfluidic devices provide researchers with a set of tools that allow not only exquisite control and manipulation of materials at the micro and nanoscale, but also observation of these effects. In this review, we will focus on the use and prospects of combining microfluidic devices with in situ small-angle X-ray scattering (and related techniques such as small-angle neutron scattering and X-ray photon correlation spectroscopy), and their enormous potential for physical-chemical research, mainly in self-assembly and phase-transitions, and surface characterization.

A review of the theory, methods and recent applications of high-throughput single-cell droplet microfluidics

NASA Astrophysics Data System (ADS)

Lagus, Todd P.; Edd, Jon F.

2013-03-01

Most cell biology experiments are performed in bulk cell suspensions where cell secretions become diluted and mixed in a contiguous sample. Confinement of single cells to small, picoliter-sized droplets within a continuous phase of oil provides chemical isolation of each cell, creating individual microreactors where rare cell qualities are highlighted and otherwise undetectable signals can be concentrated to measurable levels. Recent work in microfluidics has yielded methods for the encapsulation of cells in aqueous droplets and hydrogels at kilohertz rates, creating the potential for millions of parallel single-cell experiments. However, commercial applications of high-throughput microdroplet generation and downstream sensing and actuation methods are still emerging for cells. Using fluorescence-activated cell sorting (FACS) as a benchmark for commercially available high-throughput screening, this focused review discusses the fluid physics of droplet formation, methods for cell encapsulation in liquids and hydrogels, sensors and actuators and notable biological applications of high-throughput single-cell droplet microfluidics.

Prediction and validation of concentration gradient generation in a paper-based microfluidic channel

NASA Astrophysics Data System (ADS)

Jang, Ilhoon; Kim, Gang-June; Song, Simon

2016-11-01

A paper-based microfluidic channel has obtained attention as a diagnosis device that can implement various chemical or biological reactions. With benefits of thin, flexible, and strong features of paper devices, for example, it is often utilized for cell culture where controlling oxygen, nutrients, metabolism, and signaling molecules gradient affects the growth and movement of the cells. Among various features of paper-based microfluidic devices, we focus on establishment of concentration gradient in a paper channel. The flow is subject to dispersion and capillary effects because a paper is a porous media. In this presentation, we describe facile, fast and accurate method of generating a concentration gradient by using flow mixing of different concentrations. Both theoretical prediction and experimental validation are discussed along with inter-diffusion characteristics of porous flows. This work was supported by the National Research Foundation of Korea(NRF) Grant funded by the Korea government(MSIP) (No. 2016R1A2B3009541).

Spatiotemporal periodicity of dislocation dynamics in a two-dimensional microfluidic crystal flowing in a tapered channel

DOE PAGES

Gai, Ya; Min Leong, Chia; Cai, Wei; ...

2016-10-10

When a many-body system is driven away from equilibrium, order can spontaneously emerge in places where disorder might be expected. Here we report an unexpected order in the flow of a concentrated emulsion in a tapered microfluidic channel. The velocity profiles of individual drops in the emulsion show periodic patterns in both space and time. Such periodic patterns appear surprising from both a fluid and a solid mechanics point of view. In particular, when the emulsion is considered as a soft crystal under extrusion, a disordered scenario might be expected based on the stochastic nature of dislocation dynamics in microscopicmore » crystals. However, an orchestrated sequence of dislocation nucleation and migration is observed to give rise to a highly ordered deformation mode. This discovery suggests that nanocrystals can be made to deform more controllably than previously thought. It can also lead to novel flow control and mixing strategies in droplet microfluidics.« less

Real-time isothermal RNA amplification of toxic marine microalgae using preserved reagents on an integrated microfluidic platform.

PubMed

Tsaloglou, Maria-Nefeli; Laouenan, Florian; Loukas, Christos-Moritz; Monsalve, Lisandro Gabriel; Thanner, Christine; Morgan, Hywel; Ruano-López, Jesus M; Mowlem, Matthew C

2013-01-21

Quantitation of specific RNA sequences is a useful technique in marine biology that can elucidate cell abundance, speciation and viability, especially for early detection of harmful algal blooms. We are thus developing an integrated microfluidic system for cell concentration and lysis, RNA extraction/purification and quantitative RNA detection for environmental applications. The portable system is based on a microfluidic cartridge, or "lab-card", using a low-cost injection moulded device, with a laminated lid. Here we present real-time isothermal RNA amplification using reagent master-mixes preserved on-chip in a gel at 4 °C for up to eight months. We demonstrate quantitation by reference to an internal control in a competitive assay with 500 cell equivalents of the toxic microalga Karenia brevis. Annealing of primers, amplification at 41 °C and real-time fluorescence detection of the internal control and target using sequence-specific molecular beacons were all performed on-chip.

Droplet microfluidics with a nanoemulsion continuous phase.

PubMed

Gu, Tonghan; Yeap, Eunice W Q; Somasundar, Ambika; Chen, Ran; Hatton, T Alan; Khan, Saif A

2016-07-05

We present the first study of a novel, generalizable method that uses a water-in-oil nanoemulsion as the continuous phase to generate uniform aqueous micro-droplets in a capillary-based microfluidic system. We first study the droplet generation mechanism in this system and compare it to the more conventional case where a simple oil/solvent (with surfactant) is used as the continuous phase. Next, we present two versatile methods - adding demulsifying chemicals and heat treatment - to allow active online chemical interaction between the continuous and dispersed phases. These methods allow each generated micro-droplet to act as a well-mixed micro-reactor with walls that are 'permeable' to the nanoemulsion droplets and their contents. Finally, we demonstrate an application of this system in the fabrication of uniform hydrogel (alginate) micro-beads with control over particle properties such as size and swelling. Our work expands the toolbox of droplet-based microfluidics, enabling new opportunities and applications involving active colloidal continuous phases carrying chemical payloads, both in advanced materials synthesis and droplet-based screening and diagnostic methods.

Droplet microfluidics with magnetic beads: a new tool to investigate drug-protein interactions.

PubMed

Lombardi, Dario; Dittrich, Petra S

2011-01-01

In this study, we give the proof of concept for a method to determine binding constants of compounds in solution. By implementing a technique based on magnetic beads with a microfluidic device for segmented flow generation, we demonstrate, for individual droplets, fast, robust and complete separation of the magnetic beads. The beads are used as a carrier for one binding partner and hence, any bound molecule is separated likewise, while the segmentation into small microdroplets ensures fast mixing, and opens future prospects for droplet-wise analysis of drug candidate libraries. We employ the method for characterization of drug-protein binding, here warfarin to human serum albumin. The approach lays the basis for a microfluidic droplet-based screening device aimed at investigating the interactions of drugs with specific targets including enzymes and cells. Furthermore, the continuous method could be employed for various applications, such as binding assays, kinetic studies, and single cell analysis, in which rapid removal of a reactive component is required.

Lattice Boltzmann Simulation of Electroosmotic Micromixing by Heterogeneous Surface Charge

NASA Astrophysics Data System (ADS)

Tang, G. H.; Wang, F. F.; Tao, W. Q.

Microelectroosmotic flow is usually restricted to low Reynolds number regime, and mixing in these microfluidic systems becomes problematic due to the negligible inertial effects. To gain an improved understanding of mixing enhancement in microchannels patterned with heterogeneous surface charge, the lattice Boltzmann method has been employed to obtain the electric potential distribution in the electrolyte, the flow field, and the species concentration distribution, respectively. The simulation results show that heterogeneous surfaces can significantly disturb the streamlines leading to apparently substantial improvements in mixing. However, the introduction of such a feature can reduce the mass flow rate in the channel. The reduction in flow rate effectively prolongs the available mixing time when the flow passes through the channel and the observed mixing enhancement by heterogeneous surfaces partly results from longer mixing time.

Theoretical and numerical studies of chaotic mixing

NASA Astrophysics Data System (ADS)

Kim, Ho Jun

Theoretical and numerical studies of chaotic mixing are performed to circumvent the difficulties of efficient mixing, which come from the lack of turbulence in microfluidic devices. In order to carry out efficient and accurate parametric studies and to identify a fully chaotic state, a spectral element algorithm for solution of the incompressible Navier-Stokes and species transport equations is developed. Using Taylor series expansions in time marching, the new algorithm employs an algebraic factorization scheme on multi-dimensional staggered spectral element grids, and extends classical conforming Galerkin formulations to nonconforming spectral elements. Lagrangian particle tracking methods are utilized to study particle dispersion in the mixing device using spectral element and fourth order Runge-Kutta discretizations in space and time, respectively. Comparative studies of five different techniques commonly employed to identify the chaotic strength and mixing efficiency in microfluidic systems are presented to demonstrate the competitive advantages and shortcomings of each method. These are the stirring index based on the box counting method, Poincare sections, finite time Lyapunov exponents, the probability density function of the stretching field, and mixing index inverse, based on the standard deviation of scalar species distribution. Series of numerical simulations are performed by varying the Peclet number (Pe) at fixed kinematic conditions. The mixing length (lm) is characterized as function of the Pe number, and lm ∝ ln(Pe) scaling is demonstrated for fully chaotic cases. Employing the aforementioned techniques, optimum kinematic conditions and the actuation frequency of the stirrer that result in the highest mixing/stirring efficiency are identified in a zeta potential patterned straight micro channel, where a continuous flow is generated by superposition of a steady pressure driven flow and time periodic electroosmotic flow induced by a stream-wise AC electric field. Finally, it is shown that the invariant manifold of hyperbolic periodic point determines the geometry of fast mixing zones in oscillatory flows in two-dimensional cavity.

On micro-electrokinetic scalar turbulence in microfluidics at a low Reynolds number.

PubMed

Wang, Guiren; Yang, Fang; Zhao, Wei; Chen, Chien-Pin

2016-03-21

We recently demonstrated the direct observation of micro-electrokinetic turbulence in a microchannel at a low Reynolds number (Re) when a pressure-driven flow was forced electrokinetically. Here, we characterize the corresponding scalar turbulence and surprisingly find that the corresponding turbulent mixing has some typical and important features of scalar turbulence, such as the Obukhov-Corrsin (O-C) -5/3 spectrum of concentration fluctuation, which can commonly be realized only at high Re in macroflows. This discovery could provide a new perspective of scalar turbulence and an avenue for control of transport phenomena in lab-on-a-chip platforms. This will deepen our fundamental understanding of transport phenomena in microfluidics.

Microsecond protein dynamics observed at the single-molecule level

NASA Astrophysics Data System (ADS)

Otosu, Takuhiro; Ishii, Kunihiko; Tahara, Tahei

2015-07-01

How polypeptide chains acquire specific conformations to realize unique biological functions is a central problem of protein science. Single-molecule spectroscopy, combined with fluorescence resonance energy transfer, is utilized to study the conformational heterogeneity and the state-to-state transition dynamics of proteins on the submillisecond to second timescales. However, observation of the dynamics on the microsecond timescale is still very challenging. This timescale is important because the elementary processes of protein dynamics take place and direct comparison between experiment and simulation is possible. Here we report a new single-molecule technique to reveal the microsecond structural dynamics of proteins through correlation of the fluorescence lifetime. This method, two-dimensional fluorescence lifetime correlation spectroscopy, is applied to clarify the conformational dynamics of cytochrome c. Three conformational ensembles and the microsecond transitions in each ensemble are indicated from the correlation signal, demonstrating the importance of quantifying microsecond dynamics of proteins on the folding free energy landscape.

Microsecond protein dynamics observed at the single-molecule level

PubMed Central

Otosu, Takuhiro; Ishii, Kunihiko; Tahara, Tahei

2015-01-01

How polypeptide chains acquire specific conformations to realize unique biological functions is a central problem of protein science. Single-molecule spectroscopy, combined with fluorescence resonance energy transfer, is utilized to study the conformational heterogeneity and the state-to-state transition dynamics of proteins on the submillisecond to second timescales. However, observation of the dynamics on the microsecond timescale is still very challenging. This timescale is important because the elementary processes of protein dynamics take place and direct comparison between experiment and simulation is possible. Here we report a new single-molecule technique to reveal the microsecond structural dynamics of proteins through correlation of the fluorescence lifetime. This method, two-dimensional fluorescence lifetime correlation spectroscopy, is applied to clarify the conformational dynamics of cytochrome c. Three conformational ensembles and the microsecond transitions in each ensemble are indicated from the correlation signal, demonstrating the importance of quantifying microsecond dynamics of proteins on the folding free energy landscape. PMID:26151767

Flow Field Analysis of Micromixer Powered by Ciliary Motion of Vorticella

NASA Astrophysics Data System (ADS)

Hayasaka, Yo; Nagai, Moeto; Matsumoto, Nobuyoshi; Kawashima, Takahiro; Shibata, Takayuki

We demonstrate the observation of a flow field generated by ciliary motion of Vorticella in a microfluidic chamber. We applied the property that Vorticella vibrates its cilia and create a flow field to a micromixer. The stability and mixing performance of Vorticella were measured by PIV (Particle Image Velocimetry). One cell of Vorticella mixed the half area of the microchamber. We revealed that the flow field of a single cell in a chamber was more stable than that of multiple cells.

Flow control for a paper-based microfluidic device by adjusting permeability of paper

NASA Astrophysics Data System (ADS)

Jang, Ilhoon; Kim, Gangjune; Song, Simon

2014-11-01

The paper-based microfluidics has attracted intensive attention as a prospective substitute for conventional microfluidic substrates used for a point-of-care diagnostics due to its superior advantages such as the cost effectiveness and production simplicity. Generally, a paper-based microfluidic device utilizes capillary force to drive a flow. Recent studies on flow control in such a device aimed at obtaining accurate and quantitative results by varying a channel geometry like width and length. According to the Darcy's law describing a flow in a porous media like paper, a flow rate can be adjusted the permeability of paper. In this study, we investigate a flow control method by adjusting the permeability of paper. We utilize the wax printing for the adjustment and the fabrication of paper channels. A rectangular wax pattern was printed on one inlet channel of a Y-channel geometry. By varying the brightness of the wax pattern, a relationship between the flow rate and permeability changes due to the wax was investigated. As a result, we obtained an effective permeability contour with respect to the wax pattern length and brightness. In addition, we developed a paper-based micromixer of which the mixing ratio was controlled precisely by adjusting the permeability.

Plasma treatments of wool fiber surface for microfluidic applications

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

Jeon, So-Hyoun; Hwang, Ki-Hwan; Lee, Jin Su

Highlights: • We used atmospheric plasma for tuning the wettability of wool fibers. • The wicking rates of the wool fibers increased with increasing treatment time. • The increasing of wettability results in removement of fatty acid on the wool surface. - Abstract: Recent progress in health diagnostics has led to the development of simple and inexpensive systems. Thread-based microfluidic devices allow for portable and inexpensive field-based technologies enabling medical diagnostics, environmental monitoring, and food safety analysis. However, controlling the flow rate of wool thread, which is a very important part of thread-based microfluidic devices, is quite difficult. For thismore » reason, we focused on thread-based microfluidics in the study. We developed a method of changing the wettability of hydrophobic thread, including wool thread. Thus, using natural wool thread as a channel, we demonstrate herein that the manipulation of the liquid flow, such as micro selecting and micro mixing, can be achieved by applying plasma treatment to wool thread. In addition to enabling the flow control of the treated wool channels consisting of all natural substances, this procedure will also be beneficial for biological sensing devices. We found that wools treated with various gases have different flow rates. We used an atmospheric plasma with O{sub 2}, N{sub 2} and Ar gases.« less

Laser-bulge based ultrasonic bonding method for fabricating multilayer thermoplastic microfluidic devices

NASA Astrophysics Data System (ADS)

Liang, Chao; Liu, Chong; Liu, Ziyang; Meng, Fanjian; Li, Jingmin

2017-11-01

Ultrasonic bonding is a commonly-used method for fabrication of thermoplastic microfluidic devices. However, due to the existence of the energy director (a convex structure to concentrate the ultrasonic energy), it is difficult to control its molten polymer flow, which may result in a small gap between the bonding interface or microchannel clogging. In this paper, we present an approach to address these issues. Firstly, the microchannels were patterned onto the PMMA sheets using hot embossing with the wire electrical discharge machined molds. Then, a small bulge, which was formed at the edge of the laser-ablated groove (LG), was generated around the microchannel using a CO2 laser ablation system. By using the bulge to concentrate the ultrasonic energy, there was no need for fabricating the complicated and customized energy director. When the bulge was melted, it was able to flow into the LG which overcame the ‘gap’ and ‘clogging’ problems. Here, two types of two-layer microfluidic devices and a five-layer micromixer were fabricated to validate its performance. Our results showed that these thermoplastic microdevices can be successfully bonded by using this method. The liquid leakage was not observed in both the capillary-driven flowing test and the pressure-driven mixing experiments. It is a potential method for bonding the thermoplastic microfluidic devices.

Easy route to superhydrophobic copper-based wire-guided droplet microfluidic systems.

PubMed

Mumm, Florian; van Helvoort, Antonius T J; Sikorski, Pawel

2009-09-22

Droplet-based microfluidic systems are an expansion of the lab on a chip concept toward flexible, reconfigurable setups based on the modification and analysis of individual droplets. Superhydrophobic surfaces are one suitable candidate for the realization of droplet-based microfluidic systems as the high mobility of aqueous liquids on such surfaces offers possibilities to use novel or more efficient approaches to droplet movement. Here, copper-based superhydrophobic surfaces were produced either by the etching of polycrystalline copper samples along the grain boundaries using etchants common in the microelectronics industry, by electrodeposition of copper films with subsequent nanowire decoration based on thermal oxidization, or by a combination of both. The surfaces could be easily hydrophobized with thiol-modified fluorocarbons, after which the produced surfaces showed a water contact angle as high as 171 degrees +/- 2 degrees . As copper was chosen as the base material, established patterning techniques adopted from printed circuit board fabrication could be used to fabricate macrostructures on the surfaces with the intention to confine the droplets and, thus, to reduce the system's sensitivity to tilting and vibrations. A simple droplet-based microfluidic chip with inlets, outlets, sample storage, and mixing areas was produced. Wire guidance, a relatively new actuation method applicable to aqueous liquids on superhydrophobic surfaces, was applied to move the droplets.

Micro Machining of Injection Mold Inserts for Fluidic Channel of Polymeric Biochips

PubMed Central

Jung, Woo-Chul; Heo, Young-Moo; Yoon, Gil-Sang; Shin, Kwang-Ho; Chang, Sung-Ho; Kim, Gun-Hee; Cho, Myeong-Woo

2007-01-01

Recently, the polymeric micro-fluidic biochip, often called LOC (lab-on-a-chip), has been focused as a cheap, rapid and simplified method to replace the existing biochemical laboratory works. It becomes possible to form miniaturized lab functionalities on a chip with the development of MEMS technologies. The micro-fluidic chips contain many micro-channels for the flow of sample and reagents, mixing, and detection tasks. Typical substrate materials for the chip are glass and polymers. Typical techniques for microfluidic chip fabrication are utilizing various micro pattern forming methods, such as wet-etching, micro-contact printing, and hot-embossing, micro injection molding, LIGA, and micro powder blasting processes, etc. In this study, to establish the basis of the micro pattern fabrication and mass production of polymeric micro-fluidic chips using injection molding process, micro machining method was applied to form micro-channels on the LOC molds. In the research, a series of machining experiments using micro end-mills were performed to determine optimum machining conditions to improve surface roughness and shape accuracy of designed simplified micro-channels. Obtained conditions were used to machine required mold inserts for micro-channels using micro end-mills. Test injection processes using machined molds and COC polymer were performed, and then the results were investigated.

Continuous-Flow Production of Injectable Liposomes via a Microfluidic Approach

PubMed Central

Zizzari, Alessandra; Bianco, Monica; Perrone, Elisabetta; Amato, Francesco; Maruccio, Giuseppe; Rendina, Filippo; Arima, Valentina

2017-01-01

Injectable liposomes are characterized by a suitable size and unique lipid mixtures, which require time-consuming and nonstraightforward production processes. The complexity of the manufacturing methods may affect liposome solubility, the phase transition temperatures of the membranes, the average particle size, and the associated particle size distribution, with a possible impact on the drug encapsulation and release. By leveraging the precise steady-state control over the mixing of miscible liquids and a highly efficient heat transfer, microfluidic technology has proved to be an effective and direct methodology to produce liposomes. This approach results particularly efficient in reducing the number of the sizing steps, when compared to standard industrial methods. Here, Microfluidic Hydrodynamic Focusing chips were produced and used to form liposomes upon tuning experimental parameters such as lipids concentration and Flow-Rate-Ratios (FRRs). Although modelling evidenced the dependence of the laminar flow on the geometric constraints and the FRR conditions, for the specific formulation investigated in this study, the lipids concentration was identified as the primary factor influencing the size of the liposomes and their polydispersity index. This was attributed to a predominance of the bending elasticity modulus over the vesiculation index in the lipid mixture used. Eventually, liposomes of injectable size were produced using microfluidic one-pot synthesis in continuous flow. PMID:29232873

Spontaneous Self-Assembly of Polymeric Nanoparticles in Aqueous Media: New Insights From Microfluidics, In Situ Size Measurements, and Individual Particle Tracking.

PubMed

Li, Xue; Salzano, Giuseppina; Zhang, Jiwen; Gref, Ruxandra

2017-01-01

Supramolecular cyclodextrin-based nanoparticles (CD-NPs) mediated by host-guest interactions have gained increased popularity because of their "green" and simple preparation procedure, as well as their versatility in terms of inclusion of active molecules. Herein, we showed that original CD-NPs of around 100 nm are spontaneously formed in water, by mixing 2 aqueous solutions of (1) a CD polymer and (2) dextran grafted with benzophenone moieties. For the first time, CD-NPs were instantaneously produced in a microfluidic interaction chamber by mixing 2 aqueous solutions of neutral polymers, in the absence of organic solvents. Whatever the mixing conditions, CD-NPs with narrow size distributions were immediately formed upon contact of the 2 polymeric solutions. In situ size measurements showed that the CD-NPs were spontaneously formed. Nanoparticle tracking analysis was used to individually follow the CD-NPs in their Brownian motions, to gain insights on their size distribution, concentration, and stability on extreme dilution. Nanoparticle tracking analysis allowed to establish that despite their non-covalent nature, and the CD-NPs were remarkably stable in terms of concentration and size distribution, even on extreme dilution (concentrations as low as 100 ng/mL). Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Microfluidic Reactors for the Controlled Synthesis of Nanoparticles

NASA Astrophysics Data System (ADS)

Erdem, Emine Yegan

Nanoparticles have attracted a lot of attention in the past few decades due to their unique, size-dependent properties. In order to use these nanoparticles in devices or sensors effectively, it is important to maintain uniform properties throughout the system; therefore nanoparticles need to have uniform sizes -- or monodisperse. In order to achieve monodispersity, an extreme control over the reaction conditions is required during their synthesis. These reaction conditions such as temperature, concentration of reagents, residence times, etc. affect the structure of nanoparticles dramatically; therefore when the conditions vary locally in the reaction vessel, different sized nanoparticles form, causing polydispersity. In widely-used batch wise synthesis techniques, large sized reaction vessels are used to mix and heat reagents. In these types of systems, it is very hard to avoid thermal gradients and to achieve rapid mixing times as well as to control residence times. Also it is not possible to make rapid changes in the reaction parameters during the synthesis. The other drawback of conventional methods is that it is not possible to separate the nucleation of nanoparticles from their growth; this leads to combined nucleation and growth and subsequently results in polydisperse size distributions. Microfluidics is an alternative method by which the limitations of conventional techniques can be addressed. Due to the small size, it is possible to control temperature and concentration of reagents precisely as well as to make rapid changes in mixing ratios of reagents or temperature of the reaction zones. There have been several microfluidic reactors -- (microreactors) in literature that were designed to improve the size distribution of nanoparticles. In this work, two novel microfluidic systems were developed for achieving controlled synthesis of nanoparticles. The first microreactor was made out of a chemically robust polymer, polyurethane, and it was used for low temperature nanoparticle synthesis. This microreactor was fabricated by using a CO 2-laser printer, which is an inexpensive method for fabricating microfluidic devices and it is a relatively fast way compared to other fabrication techniques. Iron oxide nanoparticle synthesis was demonstrated using this reactor and size distributions with a standard deviation of 10% was obtained. The second microreactor presented in this work was designed to produce monodisperse nanoparticles by utilizing thermally isolated heated and cooled regions for separating nucleation and growth processes. This microreactor was made out of silicon and it was used to demonstrate the synthesis of TiO 2 nanoparticles. Size distributions with less than 10% standard deviation were achieved. This microreactor also provides a platform for studying the effects of temperature and residence times which is very important to understand the reaction kinetics of nanoparticle synthesis. In this work, two microfluidic techniques for retrieving nanoparticles from the microreactors were also discussed. The first method was based on trapping the aqueous droplet phase inside the microchannel and the second method was utilizing a micropost array to direct droplets from the oil solution to the pure water. As a final step, a printing technique was used to print nanoparticles synthesized inside the microreactors for future applications. This ability is important for achieving smart surfaces that can utilize the properties of nanoparticles for sensing applications in the future.

Improvements in Mixing Time and Mixing Uniformity in Devices Designed for Studies of Protein Folding Kinetics

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

Yao, Shuhuai; Bakajin, Olgica

2007-08-01

Using a microfluidic laminar flow mixer designed for studies of protein folding kinetics, we demonstrate a mixing time of 1 +/- 1 micros with sample consumption on the order of femtomoles. We recognize two limitations of previously proposed designs: (1) size and shape of the mixing region, which limits mixing uniformity and (2) the formation of Dean vortices at high flow rates, which limits the mixing time. We address these limitations by using a narrow shape-optimized nozzle and by reducing the bend of the side channel streamlines. The final design, which combines both of these features, achieves the best performance.more » We quantified the mixing performance of the different designs by numerical simulation of coupled Navier-Stokes and convection-diffusion equations and experiments using fluorescence resonance energy-transfer (FRET)-labeled DNA.« less

Chaotic mixing by microswimmers moving on quasiperiodic orbits

NASA Astrophysics Data System (ADS)

Jalali, Mir Abbas; Khoshnood, Atefeh; Alam, Mohammad-Reza

2015-11-01

Life on the Earth is strongly dependent upon mixing across a vast range of scales. For example, mixing distributes nutrients for microorganisms in aquatic environments, and balances the spatial energy distribution in the oceans and the atmosphere. From industrial point of view, mixing is essential in many microfluidic processes and lab-on-a-chip operations, polymer engineering, pharmaceutics, food engineering, petroleum engineering, and biotechnology. Efficient mixing, typically characterized by chaotic advection, is hard to achieve in low Reynolds number conditions because of the linear nature of the Stokes equation that governs the motion. We report the first demonstration of chaotic mixing induced by a microswimmer that strokes on quasiperiodic orbits with multi-loop turning paths. Our findings can be utilized to understand the interactions of microorganisms with their environments, and to design autonomous robotic mixers that can sweep and mix an entire volume of complex-geometry containers.

Use of Buckling Instabilities in Micro Pumps, Valves, and Mixers

NASA Astrophysics Data System (ADS)

Tavakol, Behrouz; Chawan, Aschvin; Holmes, Douglas

2014-03-01

We use the buckling of thin, flexible plates for pumping fluids, controlling the flow rate, and mixing different media within a microfluidic channel. A dielectric elastomeric film with a confined geometry buckles out of the plane when exposed to an electric field. Solid or grease electrodes have traditionally been used as conductive materials to aid in voltage application to both sides of the film. In this work, we use an electrolytic fluid solution as the electrode to enable buckling at relatively low voltages, and to enhance the rate of deformation. We show that this mechanism can be implemented as a microvalve that controls flow rate, or as a micropump that operates over a range of frequencies. A similar mechanism can be used to aid diffusion between two adjacent laminar streams and improve mixing. These low-cost micropumps, microvalves, and micromixers rely on the reversible buckling of thin plates, are easily embeddable in a microfluidic chip, and can potentially be used in variety of applications to accurately control and manipulate fluid flow in a microchannel.

Three-Dimensional Phenomena in Microbubble Acoustic Streaming

NASA Astrophysics Data System (ADS)

Marin, Alvaro; Rossi, Massimiliano; Rallabandi, Bhargav; Wang, Cheng; Hilgenfeldt, Sascha; Kähler, Christian J.

2015-04-01

Ultrasound-driven oscillating microbubbles are used as active actuators in microfluidic devices to perform manifold tasks such as mixing, sorting, and manipulation of microparticles. A common configuration consists of side bubbles created by trapping air pockets in blind channels perpendicular to the main channel direction. This configuration consists of acoustically excited bubbles with a semicylindrical shape that generate significant streaming flow. Because of the geometry of the channels, such flows are generally considered as quasi-two-dimensional. Similar assumptions are often made in many other microfluidic systems based on flat microchannels. However, in this Letter we show that microparticle trajectories actually present a much richer behavior, with particularly strong out-of-plane dynamics in regions close to the microbubble interface. Using astigmatism particle-tracking velocimetry, we reveal that the apparent planar streamlines are actually projections of a stream surface with a pseudotoroidal shape. We, therefore, show that acoustic streaming cannot generally be assumed as a two-dimensional phenomenon in confined systems. The results have crucial consequences for most of the applications involving acoustic streaming such as particle trapping, sorting, and mixing.

High-throughput combinatorial cell co-culture using microfluidics.

PubMed

Tumarkin, Ethan; Tzadu, Lsan; Csaszar, Elizabeth; Seo, Minseok; Zhang, Hong; Lee, Anna; Peerani, Raheem; Purpura, Kelly; Zandstra, Peter W; Kumacheva, Eugenia

2011-06-01

Co-culture strategies are foundational in cell biology. These systems, which serve as mimics of in vivo tissue niches, are typically poorly defined in terms of cell ratios, local cues and supportive cell-cell interactions. In the stem cell niche, the ability to screen cell-cell interactions and identify local supportive microenvironments has a broad range of applications in transplantation, tissue engineering and wound healing. We present a microfluidic platform for the high-throughput generation of hydrogel microbeads for cell co-culture. Encapsulation of different cell populations in microgels was achieved by introducing in a microfluidic device two streams of distinct cell suspensions, emulsifying the mixed suspension, and gelling the precursor droplets. The cellular composition in the microgels was controlled by varying the volumetric flow rates of the corresponding streams. We demonstrate one of the applications of the microfluidic method by co-encapsulating factor-dependent and responsive blood progenitor cell lines (MBA2 and M07e cells, respectively) at varying ratios, and show that in-bead paracrine secretion can modulate the viability of the factor dependent cells. Furthermore, we show the application of the method as a tool to screen the impact of specific growth factors on a primary human heterogeneous cell population. Co-encapsulation of IL-3 secreting MBA2 cells with umbilical cord blood cells revealed differential sub-population responsiveness to paracrine signals (CD14+ cells were particularly responsive to locally delivered IL-3). This microfluidic co-culture platform should enable high throughput screening of cell co-culture conditions, leading to new strategies to manipulate cell fate. This journal is © The Royal Society of Chemistry 2011

A novel microfluidic rapid freeze-quench device for trapping reactions intermediates for high field EPR analysis.

PubMed

Kaufmann, Royi; Yadid, Itamar; Goldfarb, Daniella

2013-05-01

Rapid freeze quench electron paramagnetic resonance (RFQ)-EPR is a method for trapping short lived intermediates in chemical reactions and subjecting them to EPR spectroscopy investigation for their characterization. Two (or more) reacting components are mixed at room temperature and after some delay the mixture is sprayed into a cold trap and transferred into the EPR tube. A major caveat in using commercial RFQ-EPR for high field EPR applications is the relatively large amount of sample needed for each time point, a major part of which is wasted as the dead volume of the instrument. The small sample volume (∼2μl) needed for high field EPR spectrometers, such as W-band (∼3.5T, 95GHz), that use cavities calls for the development of a microfluidic based RFQ-EPR apparatus. This is particularly important for biological applications because of the difficulties often encountered in producing large amounts of intrinsically paramagnetic proteins and spin labeled nucleic acid and proteins. Here we describe a dedicated microfluidic based RFQ-EPR apparatus suitable for small volume samples in the range of a few μl. The device is based on a previously published microfluidic mixer and features a new ejection mechanism and a novel cold trap that allows collection of a series of different time points in one continuous experiment. The reduction of a nitroxide radical with dithionite, employing the signal of Mn(2+) as an internal standard was used to demonstrate the performance of the microfluidic RFQ apparatus. Copyright © 2013 Elsevier Inc. All rights reserved.

Microfluidic magnetic fluidized bed for DNA analysis in continuous flow mode.

PubMed

Hernández-Neuta, Iván; Pereiro, Iago; Ahlford, Annika; Ferraro, Davide; Zhang, Qiongdi; Viovy, Jean-Louis; Descroix, Stéphanie; Nilsson, Mats

2018-04-15

Magnetic solid phase substrates for biomolecule manipulation have become a valuable tool for simplification and automation of molecular biology protocols. However, the handling of magnetic particles inside microfluidic chips for miniaturized assays is often challenging due to inefficient mixing, aggregation, and the advanced instrumentation required for effective actuation. Here, we describe the use of a microfluidic magnetic fluidized bed approach that enables dynamic, highly efficient and simplified magnetic bead actuation for DNA analysis in a continuous flow platform with minimal technical requirements. We evaluate the performance of this approach by testing the efficiency of individual steps of a DNA assay based on padlock probes and rolling circle amplification. This assay comprises common nucleic acid analysis principles, such as hybridization, ligation, amplification and restriction digestion. We obtained efficiencies of up to 90% for these reactions with high throughput processing up to 120μL of DNA dilution at flow rates ranging from 1 to 5μL/min without compromising performance. The fluidized bed was 20-50% more efficient than a commercially available solution for microfluidic manipulation of magnetic beads. Moreover, to demonstrate the potential of this approach for integration into micro-total analysis systems, we optimized the production of a low-cost polymer based microarray and tested its analytical performance for integrated single-molecule digital read-out. Finally, we provide the proof-of-concept for a single-chamber microfluidic chip that combines the fluidized bed with the polymer microarray for a highly simplified and integrated magnetic bead-based DNA analyzer, with potential applications in diagnostics. Copyright © 2017 Elsevier B.V. All rights reserved.

A new electrowetting lab-on-a-chip platform based on programmable and virtual wall-less channels

NASA Astrophysics Data System (ADS)

Banerjee, Ananda; Kreit, Eric; Dhindsa, Manjeet; Heikenfeld, Jason; Papautsky, Ian

2011-02-01

Microscale liquid handling based on electrowetting has been previously demonstrated by several groups. Such liquid manipulation however is limited to control of individual droplets, aptly termed digital microfluidics. The inability to form continuous channels thus prevents conventional microfluidic sample manipulation and analysis approaches, such as electroosmosis and electrophoresis. In this paper, we discuss our recent progress on the development of electrowettingbased virtual channels. These channels can be created and reconfigured on-demand and preserve their shape without external stimulus. We also discuss recent progress towards demonstrating electroosmotic flows in such microchannels for fluid transport. This would permit a variety of basic functionalities in this new platform including sample transport and mixing between various functional areas of the chip.

Automated microfluidic platform for systematic studies of colloidal perovskite nanocrystals: towards continuous nano-manufacturing.

PubMed

Epps, Robert W; Felton, Kobi C; Coley, Connor W; Abolhasani, Milad

2017-11-21

Colloidal organic/inorganic metal-halide perovskite nanocrystals have recently emerged as a potential low-cost replacement for the semiconductor materials in commercial photovoltaics and light emitting diodes. However, unlike III-V and IV-VI semiconductor nanocrystals, studies of colloidal perovskite nanocrystals have yet to develop a fundamental and comprehensive understanding of nucleation and growth kinetics. Here, we introduce a modular and automated microfluidic platform for the systematic studies of room-temperature synthesized cesium-lead halide perovskite nanocrystals. With abundant data collection across the entirety of four orders of magnitude reaction time span, we comprehensively characterize nanocrystal growth within a modular microfluidic reactor. The developed high-throughput screening platform features a custom-designed three-port flow cell with translational capability for in situ spectral characterization of the in-flow synthesized perovskite nanocrystals along a tubular microreactor with an adjustable length, ranging from 3 cm to 196 cm. The translational flow cell allows for sampling of twenty unique residence times at a single equilibrated flow rate. The developed technique requires an average total liquid consumption of 20 μL per spectra and as little as 2 μL at the time of sampling. It may continuously sample up to 30 000 unique spectra per day in both single and multi-phase flow formats. Using the developed plug-and-play microfluidic platform, we study the growth of cesium lead trihalide perovskite nanocrystals through in situ monitoring of their absorption and emission band-gaps at residence times ranging from 100 ms to 17 min. The automated microfluidic platform enables a systematic study of the effect of mixing enhancement on the quality of the synthesized nanocrystals through a direct comparison between single- and multi-phase flow systems at similar reaction time scales. The improved mixing characteristics of the multi-phase flow format results in high-quality perovskite nanocrystals with kinetically tunable emission wavelength, ranging as much as 25 nm at equivalent residence times. Further application of this unique platform would allow rapid parameter optimization in the colloidal synthesis of a wide range of nanomaterials (e.g., metal or semiconductor), that is directly transferable to continuous manufacturing in a numbered-up platform with a similar characteristic length scale.

A smog chamber comparison of a microfluidic derivatisation measurement of gas-phase glyoxal and methylglyoxal with other analytical techniques

NASA Astrophysics Data System (ADS)

Pang, xiaobing; Lewis, Alastair; Rickard, Andrew R.; Baeza-Romero, Maria Teresa; Adams, Thomas J.; Ball, Stephen M.; Goodall, Iain C. A.; Monks, Paul S.; Peppe, Salvatore; Ródenas García, Milagros; Sánchez, Pilar; Muñoz, Amalia

2014-05-01

A microfluidic lab-on-a-chip derivatisation technique has been developed to measure part per billion (ppbV) mixing ratios of gaseous glyoxal (GLY) and methylglyoxal (MGLY), and the method is compared with other techniques in a smog chamber experiment. The method uses o-(2,3,4,5,6-pentafluorobenzyl) hydroxylamine (PFBHA) as a derivatisation reagent and a microfabricated planar glass micro-reactor comprising an inlet, gas and fluid splitting and combining channels, mixing junctions, and a heated capillary reaction microchannel. The enhanced phase contact area-to-volume ratio and the high heat transfer rate in the micro-reactor result in a fast and highly efficient derivatisation reaction, generating an effluent stream ready for direct introduction to a gas chromatograph-mass spectrometer (GC-MS). A linear response for GLY was observed over a calibration range 0.7 to 400 ppbV, and for MGLY of 1.2 to 300 ppbV, when derivatised under optimal reaction conditions. The analytical performance shows good accuracy (6.6 % for GLY and 7.5 % for MGLY), suitable precision (< 12.0 %) and method detection limits (MDLs) (75 pptV for GLY and 185 pptV for MGLY) with a time resolution of 30 minutes. These MDLs are below or close to typical concentrations of these compounds observed in ambient air. The microfluidic derivatisation technique would be appropriate for ambient α-dicarbonyl measurements in a range of field environments based on its performance in a large-scale outdoor atmospheric simulation chamber (EUPHORE). The feasibility of the technique was assessed by applying the methodology to quantify of α-dicarbonyls formed during the photo-oxidation of isoprene in the EUPHORE chamber. Good correlations were found between microfluidic measurements and Fourier Transform InfraRed spectroscopy (FTIR) with the correlation coefficient (r2) of 0.84, Broad Band Cavity Enhanced Absorption Spectroscopy (BBCEAS) (r2 = 0.75), solid phase micro extraction (SPME) (r2 = 0.89), and a photochemical chamber box modelling calculation (r2 = 0.79) in GLY measurements. For MGLY measurements, the microfluidic technique showed good agreement with BBCEAS (r2 = 0.87), SPME (r2 = 0.76), and modeling simulation (r2 = 0.83), FTIR (r2 = 0.72) but displayed a discrepancy with Proton-Transfer Reaction Time-of-Flight Mass Spectrometry (PTR-ToF-MS) with r2 value of 0.39.

Microfluidic mixing for sperm activation and motility analysis of pearl Danio zebrafish

PubMed Central

Park, Daniel S.; Egnatchik, Robert A.; Bordelon, Hali; Tiersch, Terrence R.; Monroe, W. Todd

2013-01-01

Sperm viability in aquatic species is increasingly being evaluated by motility analysis via computer-assisted sperm analysis (CASA) following activation of sperm with manual dilution and mixing by hand. User variation can limit the speed and control over the activation process, preventing consistent motility analysis. This is further complicated by the short interval (i.e., less than 15 s) of burst motility in these species. The objectives of this study were to develop a staggered herringbone microfluidic mixer to: 1) activate small volumes of Danio pearl zebrafish (Danio albolineatus) sperm by rapid mixing with diluent, and 2) position sperm in a viewing chamber for motility evaluation using a standard CASA system. A herringbone micromixer was fabricated in polydimethylsiloxane (PDMS) to yield high quality smooth surfaces. Based on fluorescence microscopy, mixing efficiency exceeding 90% was achieved within 5 s for a range of flow rates (from 50 to 250 μL/h), with a correlation of mixing distances and mixing efficiency. For example, at the nominal flow rate of 100 μL/h, there was a significant difference in mixing efficiency between 3.5 mm (75 ± 4%; mean ± SD) and 7 mm (92 ± 2%; P = 0.002). The PDMS micromixer, integrated with standard volumetric slides, demonstrated activation of fresh zebrafish sperm with reduced user variation, greater control, and without morphologic damage to sperm. Analysis of zebrafish sperm viability by CASA revealed a statistically higher motility rate for activation by micromixing (56 ± 4%) than manual activation (45 ± 7%; n = 5, P = 0.011). This micromixer represented a first step in streamlining methods for consistent, rapid assessment of sperm quality for zebrafish and other aquatic species. The capability to rapidly activate sperm and consistently measure motility with CASA using the PDMS micromixer described herein will improve studies of germplasm physiology and cryopreservation. PMID:22494680

Microfluidic mixing for sperm activation and motility analysis of pearl Danio zebrafish.

PubMed

Park, Daniel S; Egnatchik, Robert A; Bordelon, Hali; Tiersch, Terrence R; Monroe, W Todd

2012-07-15

Sperm viability in aquatic species is increasingly being evaluated by motility analysis via computer-assisted sperm analysis (CASA) following activation of sperm with manual dilution and mixing by hand. User variation can limit the speed and control over the activation process, preventing consistent motility analysis. This is further complicated by the short interval (i.e., less than 15 s) of burst motility in these species. The objectives of this study were to develop a staggered herringbone microfluidic mixer to: 1) activate small volumes of Danio pearl zebrafish (Danio albolineatus) sperm by rapid mixing with diluent, and 2) position sperm in a viewing chamber for motility evaluation using a standard CASA system. A herringbone micromixer was fabricated in polydimethylsiloxane (PDMS) to yield high quality smooth surfaces. Based on fluorescence microscopy, mixing efficiency exceeding 90% was achieved within 5 s for a range of flow rates (from 50 to 250 μL/h), with a correlation of mixing distances and mixing efficiency. For example, at the nominal flow rate of 100 μL/h, there was a significant difference in mixing efficiency between 3.5 mm (75±4%; mean±SD) and 7 mm (92±2%; P=0.002). The PDMS micromixer, integrated with standard volumetric slides, demonstrated activation of fresh zebrafish sperm with reduced user variation, greater control, and without morphologic damage to sperm. Analysis of zebrafish sperm viability by CASA revealed a statistically higher motility rate for activation by micromixing (56±4%) than manual activation (45±7%; n=5, P=0.011). This micromixer represented a first step in streamlining methods for consistent, rapid assessment of sperm quality for zebrafish and other aquatic species. The capability to rapidly activate sperm and consistently measure motility with CASA using the PDMS micromixer described herein will improve studies of germplasm physiology and cryopreservation. Copyright © 2012 Elsevier Inc. All rights reserved.

Characterization and optimization of slanted well designs for microfluidic mixing under electroosmotic flow.

PubMed

Johnson, Timothy J; Locascio, Laurie E

2002-08-01

Recently, a series of slanted wells on the floor of a microfluidic channel were experimentally shown to successfully induce off-axis transport and mixing of two confluent streams when operating under electroosmotic (EO) flow. This paper will further explore, through numerical simulations, the parameters that affect off-axis transport under EO flow with an emphasis on optimizing the mixing rate of (a). two confluent streams in steady-state or (b). the transient scenario of two confluent plugs of material, which simulates mixing after an injection. For the steady-state scenario, the degree of mixing was determined to increase by changing any of the following parameters: (1). increasing the well depth, (2). decreasing the well angle relative to the axis of the channel, and (3). increasing the EO mobility of the well walls relative to the mobility of the main channel. Also, it will be shown that folding of the fluid can occur when the well angle is sufficiently reduced and/or when the EO mobility of the wells is increased relative to the channel. The optimum configuration for the transient problem of mixing two confluent plugs includes shallow wells to minimize the well residence time, and an increased EO mobility of the well walls relative to the main channel as well as small well angles to maximize off-axis transport. The final design reported here for the transient study reduces the standard deviation of the concentration across the channel by 72% while only increasing the axial dispersion of the injected plug by 8.6 % when compared to a plug injected into a channel with no wells present. These results indicate that a series of slanted wells on the wall of a microchannel provides a means for controlling and achieving a high degree of off-axis transport and mixing in a passive manner for micro total analysis system (microTAS) devices that are driven by electroosmosis.

Flow-based analysis using microfluidics-chemiluminescence systems.

PubMed

Al Lawati, Haider A J

2013-01-01

This review will discuss various approaches and techniques in which analysis using microfluidics-chemiluminescence systems (MF-CL) has been reported. A variety of applications is examined, including environmental, pharmaceutical, biological, food and herbal analysis. Reported uses of CL reagents, sample introduction techniques, sample pretreatment methods, CL signal enhancement and detection systems are discussed. A hydrodynamic pumping system is predominately used for these applications. However, several reports are available in which electro-osmotic (EO) pumping has been implemented. Various sample pretreatment methods have been used, including liquid-liquid extraction, solid-phase extraction and molecularly imprinted polymers. A wide range of innovative techniques has been reported for CL signal enhancement. Most of these techniques are based on enhancement of the mixing process in the microfluidics channels, which leads to enhancement of the CL signal. However, other techniques are also reported, such as mirror reaction, liquid core waveguide, on-line pre-derivatization and the use of an opaque white chip with a thin transparent seal. Photodetectors are the most commonly used detectors; however, other detection systems have also been used, including integrated electrochemiluminescence (ECL) and organic photodiodes (OPDs). Copyright © 2012 John Wiley & Sons, Ltd.

A microfluidic chip containing multiple 3D nanofibrous scaffolds for culturing human pluripotent stem cells

NASA Astrophysics Data System (ADS)

Wertheim, Lior; Shapira, Assaf; Amir, Roey J.; Dvir, Tal

2018-04-01

In microfluidics-based lab-on-a-chip systems, which are used for investigating the effect of drugs and growth factors on cells, the latter are usually cultured within the device’s channels in two-dimensional, and not in their optimal three-dimensional (3D) microenvironment. Herein, we address this shortfall by designing a microfluidic system, comprised of two layers. The upper layer of the system consists of multiple channels generating a gradient of soluble factors. The lower layer is comprised of multiple wells, each deposited with 3D, nanofibrous scaffold. We first used a mathematical model to characterize the fluid flow within the system. We then show that induced pluripotent stem cells can be seeded within the 3D scaffolds and be exposed to a well-mixed gradient of soluble factors. We believe that utilizing such system may enable in the future to identify new differentiation factors, investigate drug toxicity, and eventually allow to perform analyses on patient-specific tissues, in order to fit the appropriate combination and concentration of drugs.

Self-Powered Forward Error-Correcting Biosensor Based on Integration of Paper-Based Microfluidics and Self-Assembled Quick Response Codes.

PubMed

Yuan, Mingquan; Liu, Keng-Ku; Singamaneni, Srikanth; Chakrabartty, Shantanu

2016-10-01

This paper extends our previous work on silver-enhancement based self-assembling structures for designing reliable, self-powered biosensors with forward error correcting (FEC) capability. At the core of the proposed approach is the integration of paper-based microfluidics with quick response (QR) codes that can be optically scanned using a smart-phone. The scanned information is first decoded to obtain the location of a web-server which further processes the self-assembled QR image to determine the concentration of target analytes. The integration substrate for the proposed FEC biosensor is polyethylene and the patterning of the QR code on the substrate has been achieved using a combination of low-cost ink-jet printing and a regular ballpoint dispensing pen. A paper-based microfluidics channel has been integrated underneath the substrate for acquiring, mixing and flowing the sample to areas on the substrate where different parts of the code can self-assemble in presence of immobilized gold nanorods. In this paper we demonstrate the proof-of-concept detection using prototypes of QR encoded FEC biosensors.

Characterization of C-PDMS electrodes for electrokinetic applications in microfluidic systems

NASA Astrophysics Data System (ADS)

Deman, A.-L.; Brun, M.; Quatresous, M.; Chateaux, J.-F.; Frenea-Robin, M.; Haddour, N.; Semet, V.; Ferrigno, R.

2011-09-01

This paper reports on the integration of thick carbon-polydimethylsiloxane (C-PDMS) electrodes in microfluidic systems for electrokinetic operations. The C-PDMS material, obtained by mixing carbon nanopowder and PDMS, preserves PDMS processing properties such as O2 plasma activation and soft-lithography patternability in thick or 3D electrodes. Conductivity in the order of 10 S m-1 was reached for a carbon concentration of 25 wt%. To evaluate the adhesion between PDMS and C-PDMS, we prepared bi-material strips and carried out a manual pull test. The cohesion and robustness of C-PDMS were also evaluated by applying a large range of electric field conditions from dc to ac (300 kHz). No damage to the electrodes or release of carbon was noticed. The use of such a material for electrokinetic manipulation was validated on polystyrene particles and cells. Here, we demonstrate that C-PDMS seems to be a valuable technological solution for electrokinetic in microfluidic and particularly for biological applications such as cell electrofusion, lysis and trapping, which are favored by uniform lateral electric fields across the microchannel section.

Microbiological-enhanced mixing across scales during in-situ bioreduction of metals and radionuclides at Department of Energy Sites

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

Valocchi, Albert; Werth, Charles; Liu, Wen-Tso

Bioreduction is being actively investigated as an effective strategy for subsurface remediation and long-term management of DOE sites contaminated by metals and radionuclides (i.e. U(VI)). These strategies require manipulation of the subsurface, usually through injection of chemicals (e.g., electron donor) which mix at varying scales with the contaminant to stimulate metal reducing bacteria. There is evidence from DOE field experiments suggesting that mixing limitations of substrates at all scales may affect biological growth and activity for U(VI) reduction. Although current conceptual models hold that biomass growth and reduction activity is limited by physical mixing processes, a growing body of literaturemore » suggests that reaction could be enhanced by cell-to-cell interaction occurring over length scales extending tens to thousands of microns. Our project investigated two potential mechanisms of enhanced electron transfer. The first is the formation of single- or multiple-species biofilms that transport electrons via direct electrical connection such as conductive pili (i.e. ‘nanowires’) through biofilms to where the electron acceptor is available. The second is through diffusion of electron carriers from syntrophic bacteria to dissimilatory metal reducing bacteria (DMRB). The specific objectives of this work are (i) to quantify the extent and rate that electrons are transported between microorganisms in physical mixing zones between an electron donor and electron acceptor (e.g. U(IV)), (ii) to quantify the extent that biomass growth and reaction are enhanced by interspecies electron transport, and (iii) to integrate mixing across scales (e.g., microscopic scale of electron transfer and macroscopic scale of diffusion) in an integrated numerical model to quantify these mechanisms on overall U(VI) reduction rates. We tested these hypotheses with five tasks that integrate microbiological experiments, unique micro-fluidics experiments, flow cell experiments, and multi-scale numerical models. Continuous fed-batch reactors were used to derive kinetic parameters for DMRB, and to develop an enrichment culture for elucidation of syntrophic relationships in a complex microbial community. Pore and continuum scale experiments using microfluidic and bench top flow cells were used to evaluate the impact of cell-to-cell and microbial interactions on reaction enhancement in mixing-limited bioactive zones, and the mechanisms of this interaction. Some of the microfluidic experiments were used to develop and test models that considers direct cell-to-cell interactions during metal reduction. Pore scale models were incorporated into a multi-scale hybrid modeling framework that combines pore scale modeling at the reaction interface with continuum scale modeling. New computational frameworks for combining continuum and pore-scale models were also developed« less

Optical enhanced luminescent measurements and sequential reagent mixing on a centrifugal microfluidic device for multi-analyte point-of-care applications

NASA Astrophysics Data System (ADS)

Bartholomeusz, Daniel A.; Davies, Rupert H.; Andrade, Joseph D.

2006-02-01

A centrifugal-based microfluidic device1 was built with lyophilized bioluminescent reagents for measuring multiple metabolites from a sample of less than 15 μL. Microfluidic channels, reaction wells, and valves were cut in adhesive vinyl film using a knife plotter with features down to 30 μm and transferred to metalized polycarbonate compact disks (CDs). The fabrication method was simple enough to test over 100 prototypes within a few months. It also allowed enzymes to be packaged in microchannels without exposure to heat or chemicals. The valves were rendered hydrophobic using liquid phase deposition. Microchannels were patterned using soft lithography to make them hydrophilic. Reagents and calibration standards were deposited and lyophilized in different wells before being covered with another adhesive film. Sample delivery was controlled by a modified CD ROM. The CD was capable of distributing 200 nL sample aliquots to 36 channels, each with a different set of reagents that mixed with the sample before initiating the luminescent reactions. Reflection of light from the metalized layer and lens configuration allowed for 20% of the available light to be collected from each channel. ATP was detected down to 0.1 μM. Creatinine, glucose, and galactose were also measured in micro and milliMolar ranges. Other optical-based analytical assays can easily be incorporated into the device design. The minimal sample size needed and expandability of the device make it easier to simultaneously measure a variety of clinically relevant analytes in point-of-care settings.

Twisting microfluidics in a planetary centrifuge.

PubMed

Yasuda, Shoya; Hayakawa, Masayuki; Onoe, Hiroaki; Takinoue, Masahiro

2017-03-15

This paper reports a twisting microfluidic method utilising a centrifuge-based fluid extruding system in a planetary centrifuge which simultaneously generates an orbital rotation and an axial spin. In this method, fluid extrusion from a micro-scale capillary to an 'open-space' solution or air enables release of the fluid from the capillary-based microchannel, which physically means that there is a release of fluids from a confined low-Reynolds-number environment to an open non-low-Reynolds-number environment. As a result, the extruded fluids are separated from the axial spin of the capillary, and the difference in the angular rates of the axial spin between the capillary and the extruded fluids produces the 'twisting' of the fluid. In this study, we achieve control of the twist of highly viscous fluids, and we construct a simple physical model for the fluid twist. In addition, we demonstrate the formation of twisted hydrogel microstructures (stripe-patterned microbeads and multi-helical microfibres) with control over the stripe pattern and the helical pitch length. We believe that this method will enable the generation of more sophisticated microstructures which cannot easily be formed by usual channel-based microfluidic devices. This method can also provide advanced control of microfluids, as in the case of rapid mixing of highly viscous fluids. This method can contribute to a wide range of applications in materials science, biophysics, biomedical science, and microengineering in the future.

A novel 3D micron-scale DPTV (Defocused Particle Tracking Velocimetry) and its applications in microfluidic devices

NASA Astrophysics Data System (ADS)

Roberts, John

2005-11-01

The rapid advancements in micro/nano biotechnology demand quantitative tools for characterizing microfluidic flows in lab-on-a-chip applications, validation of computational results for fully 3D flows in complex micro-devices, and efficient observation of cellular dynamics in 3D. We present a novel 3D micron-scale DPTV (defocused particle tracking velocimetry) that is capable of mapping out 3D Lagrangian, as well as 3D Eulerian velocity flow fields at sub-micron resolution and with one camera. The main part of the imaging system is an epi-fluorescent microscope (Olympus IX 51), and the seeding particles are fluorescent particles with diameter range 300nm - 10um. A software package has been developed for identifying (x,y,z,t) coordinates of the particles using the defocused images. Using the imaging system, we successfully mapped the pressure driven flow fields in microfluidic channels. In particular, we measured the Laglangian flow fields in a microfluidic channel with a herring bone pattern at the bottom, the later is used to enhance fluid mixing in lateral directions. The 3D particle tracks revealed the flow structure that has only been seen in numerical computation. This work is supported by the National Science Foundation (CTS - 0514443), the Nanobiotechnology Center at Cornell, and The New York State Center for Life Science Enterprise.

Distillation and detection of SO2 using a microfluidic chip.

PubMed

Ju, Wei-Jhong; Fu, Lung-Ming; Yang, Ruey-Jen; Lee, Chia-Lun

2012-02-07

A miniaturized distillation system is presented for separating sulfurous acid (H(2)SO(3)) into sulfur dioxide (SO(2)) and water (H(2)O). The major components of the proposed system include a microfluidic distillation chip, a power control module, and a carrier gas pressure control module. The microfluidic chip is patterned using a commercial CO(2) laser and comprises a serpentine channel, a heating zone, a buffer zone, a cooling zone, and a collection tank. In the proposed device, the H(2)SO(3) solution is injected into the microfluidic chip and is separated into SO(2) and H(2)O via an appropriate control of the distillation time and temperature. The gaseous SO(2) is then transported into the collection chamber by the carrier gas and is mixed with DI water. Finally, the SO(2) concentration is deduced from the absorbance measurements obtained using a spectrophotometer. The experimental results show that a correlation coefficient of R(2) = 0.9981 and a distillation efficiency as high as 94.6% are obtained for H(2)SO(3) solutions with SO(2) concentrations in the range of 100-500 ppm. The SO(2) concentrations of two commercial red wines are successfully detected using the developed device. Overall, the results presented in this study show that the proposed system provides a compact and reliable tool for SO(2) concentration measurement purposes.

Microtechnology in Space: NASA's Lab-on-a-Chip Applications Development Program

NASA Technical Reports Server (NTRS)

Monaco, Lisa; Spearing, Scott; Jenkins, Andy; Symonds, Wes; Mayer, Derek; Gouldie, Edd; Wainwright, Norm; Fries, Marc; Maule, Jake; Toporski, Jan

2004-01-01

NASA's Marshall Space Flight Center (MSFC) Lab on a Chip Application Development LOCAD) team has worked with microfluidic technology for the past few years in an effort to support NASA's Mission. In that time, such microfluidic based Lab-on-a-Chip (LOC) systems have become common technology in clinical and diagnostic laboratories. The approach is most attractive due to its highly miniaturized platform and ability to perform reagent handling (i-e., dilution, mixing, separation) and diagnostics for multiple reactions in an integrated fashion. LOCAD, along with Caliper Life Sciences has successfully developed the first LOC device for macromolecular crystallization using a workstation acquired specifically for designing custom chips, the Caliper 42. LOCAD uses this, along with a novel MSFC-designed and built workstation for microfluidic development. The team has a cadre of LOC devices that can be used to perform initial feasibility testing to determine the efficacy of the LOC approach for a specific application. Once applicability has been established, the LOCAD team, along with the Army's Aviation and Missile Command microfabrication facility, can then begin to custom design and fabricate a device per the user's specifications. This presentation will highlight the LOCAD team's proven and unique expertise that has been utilized to provide end to end capabilities associated with applying microfluidics for applications that include robotic life detection instrumentation, crew health monitoring and microbial and environmental monitoring for human Exploration.

Microfluidics for Synthetic Biology: From Design to Execution

PubMed Central

Ferry, M. S.; Razinkov, I. A.; Hasty, J.

2016-01-01

With the expanding interest in cellular responses to dynamic environments, microfluidic devices have become important experimental platforms for biological research. Microfluidic “microchemostat” devices enable precise environmental control while capturing high quality, single-cell gene expression data. For studies of population heterogeneity and gene expression noise, these abilities are crucial. Here, we describe the necessary steps for experimental microfluidics using devices created in our lab as examples. First, we discuss the rational design of microchemostats and the tools available to predict their performance. We carefully analyze the critical parts of an example device, focusing on the most important part of any microchemostat: the cell trap. Next, we present a method for generating on-chip dynamic environments using an integrated fluidic junction coupled to linear actuators. Our system relies on the simple modulation of hydrostatic pressure to alter the mixing ratio between two source reservoirs and we detail the software and hardware behind it. To expand the throughput of microchemostat experiments, we describe how to build larger, parallel versions of simpler devices. To analyze the large amounts of data, we discuss methods for automated cell tracking, focusing on the special problems presented by Saccharomyces cerevisiae cells. The manufacturing of microchemostats is described in complete detail: from the photolithographic processing of the wafer to the final bonding of the PDMS chip to glass coverslip. Finally, the procedures for conducting Escherichia coli and S. cerevisiae microchemostat experiments are addressed. PMID:21601093

Heterogeneous surface charge enhanced micromixing for electrokinetic flows.

PubMed

Biddiss, Elaine; Erickson, David; Li, Dongqing

2004-06-01

Enhancing the species mixing in microfluidic applications is key to reducing analysis time and increasing device portability. The mixing in electroosmotic flow is usually diffusion-dominated. Recent numerical studies have indicated that the introduction of electrically charged surface heterogeneities may augment mixing efficiencies by creating localized regions of flow circulation. In this study, we experimentally visualized the effects of surface charge patterning and developed an optimized electrokinetic micromixer applicable to the low Reynolds number regime. Using the optimized micromixer, mixing efficiencies were improved between 22 and 68% for the applied potentials ranging from 70 to 555 V/cm when compared with the negatively charged homogeneous case. For producing a 95% mixture, this equates to a potential decrease in the required mixing channel length of up to 88% for flows with Péclet numbers between 190 and 1500.

High-Throughput Incubation and Quantification of Agglutination Assays in a Microfluidic System.

PubMed

Castro, David; Conchouso, David; Kodzius, Rimantas; Arevalo, Arpys; Foulds, Ian G

2018-06-04

In this paper, we present a two-phase microfluidic system capable of incubating and quantifying microbead-based agglutination assays. The microfluidic system is based on a simple fabrication solution, which requires only laboratory tubing filled with carrier oil, driven by negative pressure using a syringe pump. We provide a user-friendly interface, in which a pipette is used to insert single droplets of a 1.25-µL volume into a system that is continuously running and therefore works entirely on demand without the need for stopping, resetting or washing the system. These assays are incubated by highly efficient passive mixing with a sample-to-answer time of 2.5 min, a 5⁻10-fold improvement over traditional agglutination assays. We study system parameters such as channel length, incubation time and flow speed to select optimal assay conditions, using the streptavidin-biotin interaction as a model analyte quantified using optical image processing. We then investigate the effect of changing the concentration of both analyte and microbead concentrations, with a minimum detection limit of 100 ng/mL. The system can be both low- and high-throughput, depending on the rate at which assays are inserted. In our experiments, we were able to easily produce throughputs of 360 assays per hour by simple manual pipetting, which could be increased even further by automation and parallelization. Agglutination assays are a versatile tool, capable of detecting an ever-growing catalog of infectious diseases, proteins and metabolites. A system such as this one is a step towards being able to produce high-throughput microfluidic diagnostic solutions with widespread adoption. The development of analytical techniques in the microfluidic format, such as the one presented in this work, is an important step in being able to continuously monitor the performance and microfluidic outputs of organ-on-chip devices.

Microsecond kinetics in model single- and double-stranded amylose polymers.

PubMed

Sattelle, Benedict M; Almond, Andrew

2014-05-07

Amylose, a component of starch with increasing biotechnological significance, is a linear glucose polysaccharide that self-organizes into single- and double-helical assemblies. Starch granule packing, gelation and inclusion-complex formation result from finely balanced macromolecular kinetics that have eluded precise experimental quantification. Here, graphics processing unit (GPU) accelerated multi-microsecond aqueous simulations are employed to explore conformational kinetics in model single- and double-stranded amylose. The all-atom dynamics concur with prior X-ray and NMR data while surprising and previously overlooked microsecond helix-coil, glycosidic linkage and pyranose ring exchange are hypothesized. In a dodecasaccharide, single-helical collapse was correlated with linkages and rings transitioning from their expected syn and (4)C1 chair conformers. The associated microsecond exchange rates were dependent on proximity to the termini and chain length (comparing hexa- and trisaccharides), while kinetic features of dodecasaccharide linkage and ring flexing are proposed to be a good model for polymers. Similar length double-helices were stable on microsecond timescales but the parallel configuration was sturdier than the antiparallel equivalent. In both, tertiary organization restricted local chain dynamics, implying that simulations of single amylose strands cannot be extrapolated to dimers. Unbiased multi-microsecond simulations of amylose are proposed as a valuable route to probing macromolecular kinetics in water, assessing the impact of chemical modifications on helical stability and accelerating the development of new biotechnologies.

Final Project Report, DE-SC0001280, Characterizing the Combined Roles of Iron and Transverse Mixing on Uranium Bioremediation in Groundwater using Microfluidic Devices

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

Finneran, Kevin; Werth, Charles; Strathmann, Timothy

2015-01-10

In situ bioremediation of U(VI) involves amending groundwater with an appropriate electron donor and limiting nutrients to promote biological reduction to the less soluble and mobile U(IV) oxidation state. Groundwater flow is laminar; mixing is controlled by hydrodynamic dispersion. Recent studies indicate that transverse dispersion along plume margins can limit mixing of the amended electron donor and accepter (such as U(VI) in remediation applications). As a result, microbial growth, and subsequently contaminant reaction, may be limited to these transverse mixing zones during bioremediation. The primary objective of this work was to characterize the combined effects of hydrology, geochemistry, and biologymore » on the (bio)remediation of U(VI). Our underlying hypothesis was that U(VI) reaction in groundwater is controlled by transverse mixing with an electron donor along plume margins, and that iron bioavailability in these zones affects U(VI) reduction kinetics and U(IV) re-oxidation. Our specific objectives were to a) quantify reaction kinetics mediated by biological versus geochemical reactions leading to U(VI) reduction and U(IV) re-oxidation, b) understand the influence of bioavailable iron on U(VI) reduction and U(IV) re-oxidation along the transverse mixing zones, c) determine how transverse mixing limitations and the presence of biomass in pores affects these reactions, and d) identify how microbial populations that develop along transverse mixing zones are influenced by the presence of iron and the concentration of electron donor. In the completed work, transverse mixing zones along plume margins were re-created in microfluidic pore networks, referred to as micromodels. We conducted a series of experiments that allowed us to distinguish among the hydraulic, biological, and geochemical mechanisms that contribute to U(VI) reduction, U(IV) re-oxidation, and U(VI) abiotic reaction with the limiting biological nutrient HP042-. This systematic approach may lead to a better understanding of U(VI) remediation, and better strategies for groundwater amendments to maximize remediation efficiency.« less

From cellular lysis to microarray detection, an integrated thermoplastic elastomer (TPE) point of care Lab on a Disc.

PubMed

Roy, Emmanuel; Stewart, Gale; Mounier, Maxence; Malic, Lidija; Peytavi, Régis; Clime, Liviu; Madou, Marc; Bossinot, Maurice; Bergeron, Michel G; Veres, Teodor

2015-01-21

We present an all-thermoplastic integrated sample-to-answer centrifugal microfluidic Lab-on-Disc system (LoD) for nucleic acid analysis. The proposed CD system and engineered platform were employed for analysis of Bacillus atrophaeus subsp. globigii spores. The complete assay comprised cellular lysis, polymerase chain reaction (PCR) amplification, amplicon digestion, and microarray hybridization on a plastic support. The fluidic robustness and operating efficiency of the assay were ensured through analytical optimization of microfluidic tools enabling beneficial implementation of capillary valves and accurate control of all flow timing procedures. The assay reliability was further improved through the development of two novel microfluidic strategies for reagents mixing and flow delay on the CD platform. In order to bridge the gap between the proof-of-concept LoD and production prototype demonstration, low-cost thermoplastic elastomer (TPE) was selected as the material for CD fabrication and assembly, allowing the use of both, high quality hot-embossing and injection molding processes. Additionally, the low-temperature and pressure-free assembly and bonding properties of TPE material offer a pertinent solution for simple and efficient loading and storage of reagents and other on-board components. This feature was demonstrated through integration and conditioning of microbeads, magnetic discs, dried DNA buffer reagents and spotted DNA array inserts. Furthermore, all microfluidic functions and plastic parts were designed according to the current injection mold-making knowledge for industrialization purposes. Therefore, the current work highlights a seamless strategy that promotes a feasible path for the transfer from prototype toward realistic industrialization. This work aims to establish the full potential for TPE-based centrifugal system as a mainstream microfluidic diagnostic platform for clinical diagnosis, water and food safety, and other molecular diagnostic applications.

A study of EWOD-driven droplets by PIV investigation.

PubMed

Lu, Hsiang-Wei; Bottausci, Frederic; Fowler, Jesse D; Bertozzi, Andrea L; Meinhart, Carl; Kim, Chang-Jin C J

2008-03-01

Despite the recent interest in droplet-based microfluidics using electrowetting-on-dielectric (EWOD), fundamental understanding of the fluid dynamics remains limited to two-dimensional (2D) reduction of the Navier-Stokes equation. Experimental data are in dire need to verify the predictions and advance the field. We report an investigation of the flow inside droplets actuated by EWOD in air using micro particle image velocimetry (micro-PIV). Using the continuity equation, we reconstruct the 3D velocity field from the 2D PIV experimental data. We present some fundamental findings and build valuable insights that will help design sophisticated EWOD microfluidic devices. For example, the results confirm that efficient mixing in a droplet may be achieved by moving the droplet along an irreversible pattern that breaks the symmetry of the two circulating inner flows.

Cell stimulus and lysis in a microfluidic device with segmented gas-liquid flow.

PubMed

El-Ali, Jamil; Gaudet, Suzanne; Günther, Axel; Sorger, Peter K; Jensen, Klavs F

2005-06-01

We describe a microfluidic device with rapid stimulus and lysis of mammalian cells for resolving fast transient responses in cell signaling networks. The device uses segmented gas-liquid flow to enhance mixing and has integrated thermoelectric heaters and coolers to control the temperature during cell stimulus and lysis. Potential negative effects of segmented flow on cell responses are investigated in three different cell types, with no morphological changes and no activation of the cell stress-sensitive mitogen activated protein kinases observed. Jurkat E6-1 cells are stimulated in the device using alpha-CD3, and the resulting activations of ERK and JNK are presented for different time points. Stimulation of cells performed on chip results in pathway activation identical to that of conventionally treated cells under the same conditions.

Engineering and analysis of surface interactions in a microfluidic herringbone micromixer.

PubMed

Forbes, Thomas P; Kralj, Jason G

2012-08-07

We developed a computational model and theoretical framework to investigate the geometrical optimization of particle-surface interactions in a herringbone micromixer. The enhancement of biomolecule- and particle-surface interactions in microfluidic devices through mixing and streamline disruption holds promise for a variety of applications. This analysis provides guidelines for optimizing the frequency and specific location of surface interactions based on the flow pattern and relative hydraulic resistance between a groove and the effective channel. The channel bottom, i.e., channel surface between grooves, was identified as the dominant location for surface contact. In addition, geometries that decrease the groove-to-channel hydraulic resistance improve contact with the channel top. Thus, herringbone mixers appear useful for a variety of surface-interaction applications, yet they have largely not been employed in an optimized fashion.

Flow optimization study of a batch microfluidics PET tracer synthesizing device

PubMed Central

Elizarov, Arkadij M.; Meinhart, Carl; van Dam, R. Michael; Huang, Jiang; Daridon, Antoine; Heath, James R.; Kolb, Hartmuth C.

2010-01-01

We present numerical modeling and experimental studies of flow optimization inside a batch microfluidic micro-reactor used for synthesis of human-scale doses of Positron Emission Tomography (PET) tracers. Novel techniques are used for mixing within, and eluting liquid out of, the coin-shaped reaction chamber. Numerical solutions of the general incompressible Navier Stokes equations along with time-dependent elution scalar field equation for the three dimensional coin-shaped geometry were obtained and validated using fluorescence imaging analysis techniques. Utilizing the approach presented in this work, we were able to identify optimized geometrical and operational conditions for the micro-reactor in the absence of radioactive material commonly used in PET related tracer production platforms as well as evaluate the designed and fabricated micro-reactor using numerical and experimental validations. PMID:21072595

Probing individual environmental bacteria for viruses by using microfluidic digital PCR.

PubMed

Tadmor, Arbel D; Ottesen, Elizabeth A; Leadbetter, Jared R; Phillips, Rob

2011-07-01

Viruses may very well be the most abundant biological entities on the planet. Yet neither metagenomic studies nor classical phage isolation techniques have shed much light on the identity of the hosts of most viruses. We used a microfluidic digital polymerase chain reaction (PCR) approach to physically link single bacterial cells harvested from a natural environment with a viral marker gene. When we implemented this technique on the microbial community residing in the termite hindgut, we found genus-wide infection patterns displaying remarkable intragenus selectivity. Viral marker allelic diversity revealed restricted mixing of alleles between hosts, indicating limited lateral gene transfer of these alleles despite host proximity. Our approach does not require culturing hosts or viruses and provides a method for examining virus-bacterium interactions in many environments.

High-throughput single-cell PCR using microfluidic emulsions

NASA Astrophysics Data System (ADS)

Guo, Mira; Mazutis, Linas; Agresti, Jeremy; Sommer, Morten; Dantas, Gautam; Church, George; Turnbaugh, Peter; Weitz, David

2012-02-01

The human gut and other environmental samples contain large populations of diverse bacteria that are poorly characterized and unculturable, yet have many functions relevant to human health. Our goal is to identify exactly which species carry some gene of interest, such as a carbohydrate metabolism gene. Conventional metagenomic assays sequence DNA extracted in bulk from populations of mixed cell types, and are therefore unable to associate a gene of interest with a species-identifying 16S gene, to determine that the two genes originated from the same cell. We solve this problem by microfluidically encapsulating single bacteria cells in drops, using PCR to amplify the two genes inside any drop whose encapsulated cell contains both genes, and sequencing the DNA from those drops that contain both amplification products.

Probing Individual Environmental Bacteria for Viruses by Using Microfluidic Digital PCR

PubMed Central

Tadmor, Arbel D.; Ottesen, Elizabeth A.; Leadbetter, Jared R.; Phillips, Rob

2012-01-01

Viruses may very well be the most abundant biological entities on the planet. Yet neither metagenomic studies nor classical phage isolation techniques have shed much light on the identity of the hosts of most viruses. We used a microfluidic digital polymerase chain reaction (PCR) approach to physically link single bacterial cells harvested from a natural environment with a viral marker gene. When we implemented this technique on the microbial community residing in the termite hindgut, we found genus-wide infection patterns displaying remarkable intragenus selectivity. Viral marker allelic diversity revealed restricted mixing of alleles between hosts, indicating limited lateral gene transfer of these alleles despite host proximity. Our approach does not require culturing hosts or viruses and provides a method for examining virus-bacterium interactions in many environments. PMID:21719670

Microfluidic mixing for non-equilibrium single-molecule optical spectroscopy

NASA Astrophysics Data System (ADS)

Pfeil, Shawn H.

We describe a series of experiments made possible by the combination of single-molecule fluorescence spectroscopy and microfluidic mixing. To perform these measurements, a microfluidic sample handling system was developed and characterized. This system allows observation at times as early as 2.4 ms after a reaction is triggered, which is an more than an order of magnitude earlier than previous microfabricated devices. Dilutions as high as 1:19 (v/v) are achieved, allowing measurements of molecular refolding in native conditions. The interconversion of subpopulations, masked by averaging in ensemble measurements, is observed. This technology also facilitates ultra-sensitive chemiluminescence measurements, using only microliters of sample. Microfluidics are designed and fabricated to extend single-molecule measurements to samples out of equilibrium. The system is optimized for sensitive optical detection and experimental convenience. Channels are replica-molded in poly-dimethyl-siloxane (PDMS) elastomer and sealed to coverglass. The resulting devices are compatible with a broad range of chemicals, and exhibit low background fluorescence. The combination of continuous flow, which decouples reaction progress from measurement duration, with low background enables single molecules to be probed at well defined times after a reaction is triggered. Fluid delivery and pressure connections are made using an interface optimized for rapid assembly, rapid sample exchange, and modular device replacement, while providing access for high numerical aperture optics. The kinetics of Csp, the cold shock protein from Thermotoga maritima, are studied with the mixer. An order of magnitude decrease in deadtime puts a new upper limit of 4.6 ms on the time required for collapse after mixing. This result is in agreement with indirect measurements of chain reconfiguration time, which suggest collapse happens on the timescale of 10--100 ns. Measurements of the kinetics of a DNA sequence that binds cocaine put a lower bound on its folding rate of 100 s-1. Single-Molecule measurements at equilibrium, in conjunction with ensemble measurements, demonstrate that this system can be described thermodynamically with a two-state model. In addition, standard free energy changes for folding, in the presence and absence of 1 mM cocaine, are obtained. Ensemble chemiluminescence experiments demonstrate the broad applicability of themixing system. The luciferase-luciferin system from Photinus pyralis, the North American firefly, is studied. Kinetically resolved chemiluminescence measurements are performed using only 50 femtomoles of target, and microliters of sample. This compares favorably to stopped-flow, which requires milliliters of sample and picomoles of target.

Kilohertz and Low-Frequency Electrical Stimulation With the Same Pulse Duration Have Similar Efficiency for Inducing Isometric Knee Extension Torque and Discomfort.

PubMed

Medeiros, Flávia Vanessa; Bottaro, Martim; Vieira, Amilton; Lucas, Tiago Pires; Modesto, Karenina Arrais; Bo, Antonio Padilha L; Cipriano, Gerson; Babault, Nicolas; Durigan, João Luiz Quagliotti

2017-06-01

To test the hypotheses that, as compared with pulsed current with the same pulse duration, kilohertz frequency alternating current would not differ in terms of evoked-torque production and perceived discomfort, and as a result, it would show the same current efficiency. A repeated-measures design with 4 stimuli presented in random order was used to test 25 women: (1) 500-microsecond pulse duration, (2) 250-microsecond pulse duration, (3) 500-microsecond pulse duration and low carrier frequency (1 kHz), (4) 250-microsecond pulse duration and high carrier frequency (4 kHz). Isometric peak torque of quadriceps muscle was measured using an isokinetic dynamometer. Discomfort was measured using a visual analog scale. Currents with long pulse durations induced approximately 21% higher evoked torque than short pulse durations. In addition, currents with 500 microseconds delivered greater amounts of charge than stimulation patterns using 250-microsecond pulse durations (P < 0.05). All currents presented similar discomfort. There was no difference on stimulation efficiency with the same pulse duration. Both kilohertz frequency alternating current and pulsed current, with the same pulse duration, have similar efficiency for inducing isometric knee extension torque and discomfort. However, neuromuscular electrical stimulation (NMES) with longer pulse duration induces higher NMES-evoked torque, regardless of the carrier frequency. Pulse duration is an important variable that should receive more attention for an optimal application of NMES in clinical settings.

Sample injection and electrophoretic separation on a simple laminated paper based analytical device.

PubMed

Xu, Chunxiu; Zhong, Minghua; Cai, Longfei; Zheng, Qingyu; Zhang, Xiaojun

2016-02-01

We described a strategy to perform multistep operations on a simple laminated paper-based separation device by using electrokinetic flow to manipulate the fluids. A laminated crossed-channel paper-based separation device was fabricated by cutting a filter paper sheet followed by lamination. Multiple function units including sample loading, sample injection, and electrophoretic separation were integrated on a single paper based analytical device for the first time, by applying potential at different reservoirs for sample, sample waste, buffer, and buffer waste. As a proof-of-concept demonstration, mixed sample solution containing carmine and sunset yellow were loaded in the sampling channel, and then injected into separation channel followed by electrophoretic separation, by adjusting the potentials applied at the four terminals of sampling and separation channel. The effects of buffer pH, buffer concentration, channel width, and separation time on resolution of electrophoretic separation were studied. This strategy may be used to perform multistep operations such as reagent dilution, sample injection, mixing, reaction, and separation on a single microfluidic paper based analytical device, which is very attractive for building micro total analysis systems on microfluidic paper based analytical devices. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Size-based sorting of micro-particles using microbubble streaming

NASA Astrophysics Data System (ADS)

Wang, Cheng; Jalikop, Shreyas; Hilgenfeldt, Sascha

2009-11-01

Oscillating microbubbles driven by ultrasound have shown great potential in microfluidic applications, such as transporting particles and promoting mixing [1-3]. The oscillations generate secondary steady streaming that can also trap particles. We use the streaming to develop a method of sorting particles of different sizes in an initially well-mixed solution. The solution is fed into a channel consisting of bubbles placed periodically along a side wall. When the bubbles are excited by an ultrasound piezo-electric transducer to produce steady streaming, the flow field is altered by the presence of the particles. This effect is dependent on particle size and results in size-based sorting of the particles. The effectiveness of the separation depends on the dimensions of the bubbles and particles as well as on the ultrasound frequency. Our experimental studies are aimed at a better understanding of the design and control of effective microfluidic separating devices. Ref: [1] P. Marmottant and S. Hilgenfeldt, Nature 423, 153 (2003). [2] P. Marmottant and S. Hilgenfeldt, Proc. Natl. Acad. Science USA, 101, 9523 (2004). [3] P. Marmottant, J.-P. Raven, H. Gardeniers, J. G. Bomer, and S. Hilgenfeldt, J. Fluid Mech., vol.568, 109 (2006).

ALL-ELECTRONIC DROPLET GENERATION ON-CHIP WITH REAL-TIME FEEDBACK CONTROL FOR EWOD DIGITIAL MICROFLUIDICS

PubMed Central

Gong, Jian; Kim, Chang-Jin “CJ”

2009-01-01

Electrowetting-on-dielectric (EWOD) actuation enables digital (or droplet) microfluidics where small packets of liquids are manipulated on a two-dimensional surface. Due to its mechanical simplicity and low energy consumption, EWOD holds particular promise for portable systems. To improve volume precision of the droplets, which is desired for quantitative applications such as biochemical assays, existing practices would require near-perfect device fabricaion and operation conditions unless the droplets are generated under feedback control by an extra pump setup off of the chip. In this paper, we develop an all-electronic (i.e., no ancillary pumping) real-time feedback control of on-chip droplet generation. A fast voltage modulation, capacitance sensing, and discrete-time PID feedback controller are integrated on the operating electronic board. A significant improvement is obtained in the droplet volume uniformity, compared with an open loop control as well as the previous feedback control employing an external pump. Furthermore, this new capability empowers users to prescribe the droplet volume even below the previously considered minimum, allowing, for example, 1:x (x < 1) mixing, in comparison to the previously considered n:m mixing (i.e., n and m unit droplets). PMID:18497909

All-electronic droplet generation on-chip with real-time feedback control for EWOD digital microfluidics.

PubMed

Gong, Jian; Kim, Chang-Jin C J

2008-06-01

Electrowetting-on-dielectric (EWOD) actuation enables digital (or droplet) microfluidics where small packets of liquids are manipulated on a two-dimensional surface. Due to its mechanical simplicity and low energy consumption, EWOD holds particular promise for portable systems. To improve volume precision of the droplets, which is desired for quantitative applications such as biochemical assays, existing practices would require near-perfect device fabrication and operation conditions unless the droplets are generated under feedback control by an extra pump setup off of the chip. In this paper, we develop an all-electronic (i.e., no ancillary pumping) real-time feedback control of on-chip droplet generation. A fast voltage modulation, capacitance sensing, and discrete-time PID feedback controller are integrated on the operating electronic board. A significant improvement is obtained in the droplet volume uniformity, compared with an open loop control as well as the previous feedback control employing an external pump. Furthermore, this new capability empowers users to prescribe the droplet volume even below the previously considered minimum, allowing, for example, 1 : x (x < 1) mixing, in comparison to the previously considered n : m mixing (i.e., n and m unit droplets).

Replication of microchannel structures in WC-Co feedstock using elastomeric replica moulds by hot embossing process.

PubMed

Sahli, M; Gelin, J-C; Barrière, T

2015-10-01

Hot embossing is a net shaping process that is able to produce the micro-components of polymers with intrinsic and complex shapes at lower cost compared with machining and injection moulding. However, the emboss of hard metals, such as WC-Co, is more challenging due to their high thermal conductivity and ease of agglomeration. Thus, a WC-Co alloy mixed with a wax-based binder feedstock was selected. The formed feedstock exhibited pseudo-plastic flow and was successfully embossed (green part). Here, we developed a novel process that is used to replicate polymer microfluidic chips while simultaneously reducing the channel surface roughness of the mould insert, yielding optical-grade (less than 100 nm surface roughness) channels and reservoirs. This paper concerns the replication of metallic microfluidic mould inserts in WC-Co and the parameters associated with feedstock formation via a hot embossing process. A suitable formulation for micro-powder hot embossing has been established and characterised by thermogravimetric analyses and measurements of mixing torques to verify and quantify the homogeneity of the proposed feedstocks. The relative density of the samples increased with processing temperature, and almost fully dense materials were obtained. In this work, the effects of the sintering temperature on the physical properties were systematically analysed. The evolution of the metal surface morphology during the hot embossing process was also investigated. The results indicate that the feedstock can be used to manufacture micro-fluidic die mould cavities with a low roughness, proper dimensions and good shape retention. The shrinkage of the sintered part was approximately 19-24% compared with that of the brown part. Copyright © 2015 Elsevier B.V. All rights reserved.

Airborne Network Camera Standard

DTIC Science & Technology

2015-06-01

SS is the second in the minute from 0 to 59; TTT is the millisecond from 0 to 999; UUU are the microseconds. 5.3.5.7 Trigger Delay Enable Feature...to 59; SS is the second in the minute from 0 to 59; TTT is the millisecond from 0 to 999; UUU are the microseconds. 5.3.5.12 Acquisition Start Time...0 to 59; SS is the second in the minute from 0 to 59; TTT is the millisecond from 0 to 999; UUU are the microseconds. 5.3.5.13 Acquisition Arm

Microfluidics for synthetic biology: from design to execution.

PubMed

Ferry, M S; Razinkov, I A; Hasty, J

2011-01-01

With the expanding interest in cellular responses to dynamic environments, microfluidic devices have become important experimental platforms for biological research. Microfluidic "microchemostat" devices enable precise environmental control while capturing high quality, single-cell gene expression data. For studies of population heterogeneity and gene expression noise, these abilities are crucial. Here, we describe the necessary steps for experimental microfluidics using devices created in our lab as examples. First, we discuss the rational design of microchemostats and the tools available to predict their performance. We carefully analyze the critical parts of an example device, focusing on the most important part of any microchemostat: the cell trap. Next, we present a method for generating on-chip dynamic environments using an integrated fluidic junction coupled to linear actuators. Our system relies on the simple modulation of hydrostatic pressure to alter the mixing ratio between two source reservoirs and we detail the software and hardware behind it. To expand the throughput of microchemostat experiments, we describe how to build larger, parallel versions of simpler devices. To analyze the large amounts of data, we discuss methods for automated cell tracking, focusing on the special problems presented by Saccharomyces cerevisiae cells. The manufacturing of microchemostats is described in complete detail: from the photolithographic processing of the wafer to the final bonding of the PDMS chip to glass coverslip. Finally, the procedures for conducting Escherichia coli and S. cerevisiae microchemostat experiments are addressed. Copyright © 2011 Elsevier Inc. All rights reserved.

Microfluidics and numerical simulation as methods for standardization of zebrafish sperm cell activation

PubMed Central

Scherr, Thomas; Knapp, Gerald L.; Guitreau, Amy; Park, Daniel Sang-Won; Tiersch, Terrence; Nandakumar, Krishnaswamy

2017-01-01

Sperm cell activation plays a critical role in a range of biological and engineering processes, from fertilization to cryopreservation protocol evaluation. Across a range of species, ionic and osmotic effects have been discovered that lead to activation. Sperm cells of zebrafish (Danio rerio) initiate motility in a hypoosmotic environment. In this study, we employ a microfluidic mixer for the purpose of rapidly diluting the extracellular medium to initiate the onset of cell motility. The use of a microchannel offers a rapid and reproducible mixing profile throughout the device. This greatly reduces variability from trial to trial relative to the current methods of analysis. Coupling these experiments with numerical simulations, we were able to investigate the dynamics of intracellular osmolality as each cell moves along its path through the micromixer. Our results suggest that intracellular osmolality, and hence intracellular ion concentration, only slightly decreases, contrary to the common thought that larger changes in these parameters are required for activation. Utilizing this framework, microfluidics for controlled extracellular environments and associated numerical modeling, has practical applicability in standardizing high-throughput aquatic sperm activation, and more fundamentally, investigations of the intracellular environment leading to motility. PMID:26026298

Turning the Page: Advancing Paper-Based Microfluidics for Broad Diagnostic Application.

PubMed

Gong, Max M; Sinton, David

2017-06-28

Infectious diseases are a major global health issue. Diagnosis is a critical first step in effectively managing their spread. Paper-based microfluidic diagnostics first emerged in 2007 as a low-cost alternative to conventional laboratory testing, with the goal of improving accessibility to medical diagnostics in developing countries. In this review, we examine the advances in paper-based microfluidic diagnostics for medical diagnosis in the context of global health from 2007 to 2016. The theory of fluid transport in paper is first presented. The next section examines the strategies that have been employed to control fluid and analyte transport in paper-based assays. Tasks such as mixing, timing, and sequential fluid delivery have been achieved in paper and have enabled analytical capabilities comparable to those of conventional laboratory methods. The following section examines paper-based sample processing and analysis. The most impactful advancement here has been the translation of nucleic acid analysis to a paper-based format. Smartphone-based analysis is another exciting development with potential for wide dissemination. The last core section of the review highlights emerging health applications, such as male fertility testing and wearable diagnostics. We conclude the review with the future outlook, remaining challenges, and emerging opportunities.

Droplet-based pyrosequencing using digital microfluidics.

PubMed

Boles, Deborah J; Benton, Jonathan L; Siew, Germaine J; Levy, Miriam H; Thwar, Prasanna K; Sandahl, Melissa A; Rouse, Jeremy L; Perkins, Lisa C; Sudarsan, Arjun P; Jalili, Roxana; Pamula, Vamsee K; Srinivasan, Vijay; Fair, Richard B; Griffin, Peter B; Eckhardt, Allen E; Pollack, Michael G

2011-11-15

The feasibility of implementing pyrosequencing chemistry within droplets using electrowetting-based digital microfluidics is reported. An array of electrodes patterned on a printed-circuit board was used to control the formation, transportation, merging, mixing, and splitting of submicroliter-sized droplets contained within an oil-filled chamber. A three-enzyme pyrosequencing protocol was implemented in which individual droplets contained enzymes, deoxyribonucleotide triphosphates (dNTPs), and DNA templates. The DNA templates were anchored to magnetic beads which enabled them to be thoroughly washed between nucleotide additions. Reagents and protocols were optimized to maximize signal over background, linearity of response, cycle efficiency, and wash efficiency. As an initial demonstration of feasibility, a portion of a 229 bp Candida parapsilosis template was sequenced using both a de novo protocol and a resequencing protocol. The resequencing protocol generated over 60 bp of sequence with 100% sequence accuracy based on raw pyrogram levels. Excellent linearity was observed for all of the homopolymers (two, three, or four nucleotides) contained in the C. parapsilosis sequence. With improvements in microfluidic design it is expected that longer reads, higher throughput, and improved process integration (i.e., "sample-to-sequence" capability) could eventually be achieved using this low-cost platform.

Toward a microfluidic-based rapid amylase assay system.

PubMed

Holmes, Richard J; Summersgil, Philip; Ryan, Timothy; Brown, Bernard J Treves; Mockbil, Amal; Grieve, Bruce D; Fielden, Peter R

2009-08-01

This article describes work into a prototype system for the assay of amylase, using microfludic technologies. The new system has a significantly shorter cycle time than the current laboratory methods, which generally use microtitre plates, yet is capable of generating significantly superior results. As such, we have shown that sensitivity is enhanced by a factor of 10 in the standard assay trials, and by a factor of 2 in the real-sample lab trials. In both assays, the use of a microreactor system reduced the reaction time by a factor of 6.2, from 20 min incubation to 3.2 min. Basing the conclusion on the Megazyme Cerealpha Standard Method, and using the Cerealpha units as a measure of assay efficiency, the typical response for the microfluidic assay was shown to be 1.0 x 10(-3) CU/mL (standard deviation [SD] 2.5 x 10(-4) CU/mL), compared to 2.56 x 10(-4) CU/mL (SD 5.94 x 10(-5) CU/mL) for the standard macroassay. It is believed that this improvement in the reaction schematics is due to the inherent advantages of microfluidic devices such as superior mixing, higher thermal efficiency, and enhanced reaction kinetics.

Self-Powered Wireless Affinity-Based Biosensor Based on Integration of Paper-Based Microfluidics and Self-Assembled RFID Antennas.

PubMed

Yuan, Mingquan; Alocilja, Evangelyn C; Chakrabartty, Shantanu

2016-08-01

This paper presents a wireless, self-powered, affinity-based biosensor based on the integration of paper-based microfluidics with our previously reported method for self-assembling radio-frequency (RF) antennas. At the core of the proposed approach is a silver-enhancement technique that grows portions of a RF antenna in regions where target antigens hybridize with target specific affinity probes. The hybridization regions are defined by a network of nitrocellulose based microfluidic channels which implement a self-powered approach to sample the reagent and control its flow and mixing. The integration substrate for the biosensor has been constructed using polyethylene and the patterning of the antenna on the substrate has been achieved using a low-cost ink-jet printing technique. The substrate has been integrated with passive radio-frequency identification (RFID) tags to demonstrate that the resulting sensor-tag can be used for continuous monitoring in a food supply-chain where direct measurement of analytes is typically considered to be impractical. We validate the proof-of-concept operation of the proposed sensor-tag using IgG as a model analyte and using a 915 MHz Ultra-high-frequency (UHF) RFID tagging technology.

Microfluidic lab-on-a-foil for nucleic acid analysis based on isothermal recombinase polymerase amplification (RPA).

PubMed

Lutz, Sascha; Weber, Patrick; Focke, Max; Faltin, Bernd; Hoffmann, Jochen; Müller, Claas; Mark, Daniel; Roth, Günter; Munday, Peter; Armes, Niall; Piepenburg, Olaf; Zengerle, Roland; von Stetten, Felix

2010-04-07

For the first time we demonstrate a self-sufficient lab-on-a-foil system for the fully automated analysis of nucleic acids which is based on the recently available isothermal recombinase polymerase amplification (RPA). The system consists of a novel, foil-based centrifugal microfluidic cartridge including prestored liquid and dry reagents, and a commercially available centrifugal analyzer for incubation at 37 degrees C and real-time fluorescence detection. The system was characterized with an assay for the detection of the antibiotic resistance gene mecA of Staphylococcus aureus. The limit of detection was <10 copies and time-to-result was <20 min. Microfluidic unit operations comprise storage and release of liquid reagents, reconstitution of lyophilized reagents, aliquoting the sample into < or = 30 independent reaction cavities, and mixing of reagents with the DNA samples. The foil-based cartridge was produced by blow-molding and sealed with a self-adhesive tape. The demonstrated system excels existing PCR based lab-on-a-chip platforms in terms of energy efficiency and time-to-result. Applications are suggested in the field of mobile point-of-care analysis, B-detection, or in combination with continuous monitoring systems.

Droplet-Based Pyrosequencing Using Digital Microfluidics

PubMed Central

Boles, Deborah J.; Benton, Jonathan L.; Siew, Germaine J.; Levy, Miriam H.; Thwar, Prasanna K.; Sandahl, Melissa A.; Rouse, Jeremy L.; Perkins, Lisa C.; Sudarsan, Arjun P.; Jalili, Roxana; Pamula, Vamsee K.; Srinivasan, Vijay; Fair, Richard B.; Griffin, Peter B.; Eckhardt, Allen E.; Pollack, Michael G.

2013-01-01

The feasibility of implementing pyrosequencing chemistry within droplets using electrowetting-based digital microfluidics is reported. An array of electrodes patterned on a printed-circuit board was used to control the formation, transportation, merging, mixing, and splitting of submicroliter-sized droplets contained within an oil-filled chamber. A three-enzyme pyrosequencing protocol was implemented in which individual droplets contained enzymes, deoxyribonucleotide triphosphates (dNTPs), and DNA templates. The DNA templates were anchored to magnetic beads which enabled them to be thoroughly washed between nucleotide additions. Reagents and protocols were optimized to maximize signal over background, linearity of response, cycle efficiency, and wash efficiency. As an initial demonstration of feasibility, a portion of a 229 bp Candida parapsilosis template was sequenced using both a de novo protocol and a resequencing protocol. The resequencing protocol generated over 60 bp of sequence with 100% sequence accuracy based on raw pyrogram levels. Excellent linearity was observed for all of the homopolymers (two, three, or four nucleotides) contained in the C. parapsilosis sequence. With improvements in microfluidic design it is expected that longer reads, higher throughput, and improved process integration (i.e., “sample-to-sequence” capability) could eventually be achieved using this low-cost platform. PMID:21932784

Effects of pulsed mid-IR lasers on bovine knee joint tissues

NASA Astrophysics Data System (ADS)

Vari, Sandor G.; Shi, Wei-Qiang; Pergadia, Vani R.; Duffy, J. T.; Miller, J. M.; van der Veen, Maurits J.; Weiss, Andrew B.; Fishbein, Michael C.; Grundfest, Warren S.

1993-07-01

We investigated the effect of varying Tm:YAG (2.014 micrometers ) and Ho:YAG (2.130 micrometers ) laser parameters on ablation rate and consequent thermal damage. Mid-infrared wavelengths are strongly absorbed by most biological tissues due to the tissue's high water content. The ablation rate of fresh bovine knee joint tissues (fibrous cartilage, hyaline cartilage, and bone) in saline was assessed as a function of radiant exposure (160 - 950 J/cm2), at pulse widths of 200 microsecond(s) ec for Tm:YAG and 250 microsecond(s) ec for Ho:YAG and a repetition rate of 2 Hz. All tissues used in this study could be efficiently ablated using two micron lasers. The mechanism of action is likely related to the formation and collapse of cavitation bubbles, associated with mid-infrared lasers. We concluded that the Tm:YAG and Ho:YAG lasers are capable of effective knee joint tissue ablation.

An acoustofluidic micromixer via bubble inception and cavitation from microchannel sidewalls.

PubMed

Ozcelik, Adem; Ahmed, Daniel; Xie, Yuliang; Nama, Nitesh; Qu, Zhiguo; Nawaz, Ahmad Ahsan; Huang, Tony Jun

2014-05-20

During the deep reactive ion etching process, the sidewalls of a silicon mold feature rough wavy structures, which can be transferred onto a polydimethylsiloxane (PDMS) microchannel through the soft lithography technique. In this article, we utilized the wavy structures of PDMS microchannel sidewalls to initiate and cavitate bubbles in the presence of acoustic waves. Through bubble cavitation, this acoustofluidic approach demonstrates fast, effective mixing in microfluidics. We characterized its performance by using viscous fluids such as poly(ethylene glycol) (PEG). When two PEG solutions with a resultant viscosity 54.9 times higher than that of water were used, the mixing efficiency was found to be 0.92, indicating excellent, homogeneous mixing. The acoustofluidic micromixer presented here has the advantages of simple fabrication, easy integration, and capability to mix high-viscosity fluids (Reynolds number: ~0.01) in less than 100 ms.

Secondary electroosmotic flow in microchannels with nonuniform and asymmetric Zeta potential

NASA Astrophysics Data System (ADS)

Zhang, Jinbai; He, Guowei; Liu, Feng

2004-11-01

Microfluidics has a broad range of applications in biotechnology, such as sample injection, drug delivering, solution mixing, and separations. All of these techniques require handling fluids in the low Reynolds number (Re) regime. Electroosmotic flow (EOF) or electroosmocitcs is the bulk movement of liquid relative to a stationary surface due to an externally applied electronic field. It is an alternative to pressure-driven flows with convenient implementation The driving force for EOF is dependent on the zeta potential. Previous reseraches focus on the nonuniform Zeta potential. In the present work, we consider nonuniform and asymmetric Zeta potential. The effects of asymmetric Zeta potential on the EOF are investigated analytically and simulated numerically. It is demonstrated that the nonuniform and asymmetric Zeta potential can generate more flow patterns for microfluidic control compared to symmetric Zeta potential.

Method And Apparatus For Reducing Sample Dispersion In Turns And Junctions Of Micro-Channel Systems

DOEpatents

Griffiths, Stewart K. , Nilson, Robert H.

2004-05-11

What is disclosed pertains to improvement in the performance of microchannel devices by providing turns, wyes, tees, and other junctions that produce little dispersion of a sample as it traverses the turn or junction. The reduced dispersion results from contraction and expansion regions that reduce the cross-sectional area over some portion of the turn or junction. By carefully designing the geometries of these regions, sample dispersion in turns and junctions is reduced to levels comparable to the effects of ordinary diffusion. The low dispersion features are particularly suited for microfluidic devices and systems using either electromotive force, pressure, or combinations thereof as the principle of fluid transport. Such microfluidic devices and systems are useful for separation of components, sample transport, reaction, mixing, dilution or synthesis, or combinations thereof.

Microfluidic microbial fuel cells: from membrane to membrane free

NASA Astrophysics Data System (ADS)

Yang, Yang; Ye, Dingding; Li, Jun; Zhu, Xun; Liao, Qiang; Zhang, Biao

2016-08-01

Microfluidic microbial fuel cells (MMFCs) are small carbon-neutral devices that use self-organized bacteria to degrade organic substrates and harness energy from the waste water. Conventional MMFCs have made great strides in the past decade and have overcome some limitations, such as high capital costs and low energy output. A co-laminar flow MFC has been first proposed in 2011 with the potential to be an attractively power source to niche applications. Co-laminar MFCs typically operate without any physical membranes separating the reactants, and bacterial ecosystems can be easily manipulated by regulating the inlet conditions. This paper highlights recent accomplishments in the development of co-laminar MFCs, emphasizing basic principles, mass transport and fluid dynamics including boundary layer theory, entrance conditions and mixing zone issues. Furthermore, the development of current techniques, major challenges and the potential research directions are discussed.

Recirculating, passive micromixer with a novel sawtooth structure.

PubMed

Nichols, Kevin P; Ferullo, Julia R; Baeumner, Antje J

2006-02-01

A microfluidic device capable of recirculating nano to microlitre volumes in order to efficiently mix solutions is described. The device consists of molded polydimethyl siloxane (PDMS) channels with pressure inlet and outlet holes sealed by a glass lid. Recirculation is accomplished by a repeatedly reciprocated flow over an iterated sawtooth structure. The sawtooth structure serves to change the fluid velocity of individual streamlines differently depending on whether the fluid is flowing backwards or forward over the structure. Thus, individual streamlines can be accelerated or decelerated relative to the other streamlines to allow sections of the fluid to interact that would normally be linearly separated. Low Reynolds numbers imply that the process is reversible, neglecting diffusion. Computer simulations were carried out using FLUENT. Subsequently, fluorescent indicators were employed to experimentally verify these numerical simulations of the recirculation principal. Finally, mixing of a carboxyfluorescein labeled DMSO plug with an unlabeled DMSO plug across an immiscible hydrocarbon plug was investigated. At cycling rates of 1 Hz across five sawtooth units, the time was recorded to reach steady state in the channels, i.e. until both DMSO plugs had the same fluorescence intensity. In the case of the sawtooth structures, steady state was reached five times faster than in channels without sawtooth structures, which verified what would be expected based on numerical simulations. The microfluidic mixer is unique due to its versatility with respect to scaling, its potential to also mix solutions containing small particles such as beads and cells, and its ease of fabrication and use.

Micromixer based on viscoelastic flow instability at low Reynolds number.

PubMed

Lam, Y C; Gan, H Y; Nguyen, N T; Lie, H

2009-03-30

We exploited the viscoelasticity of biocompatible dilute polymeric solutions, namely, dilute poly(ethylene oxide) solutions, to significantly enhance mixing in microfluidic devices at a very small Reynolds number, i.e., Re approximately 0.023, but large Peclet and elasticity numbers. With an abrupt contraction microgeometry (8:1 contraction ratio), two different dilute poly(ethylene oxide) solutions were successfully mixed with a short flow length at a relatively fast mixing time of <10 mus. Microparticle image velocimetry was employed in our investigations to characterize the flow fields. The increase in velocity fluctuation with an increase in flow rate and Deborah number indicates the increase in viscoelastic flow instability. Mixing efficiency was characterized by fluorescent concentration measurements. Our results showed that enhanced mixing can be achieved through viscoelastic flow instability under situations where molecular-diffusion and inertia effects are negligible. This approach bypasses the laminar flow limitation, usually associated with a low Reynolds number, which is not conducive to mixing.

Micromixer based on viscoelastic flow instability at low Reynolds number

PubMed Central

Lam, Y. C.; Gan, H. Y.; Nguyen, N. T.; Lie, H.

2009-01-01

We exploited the viscoelasticity of biocompatible dilute polymeric solutions, namely, dilute poly(ethylene oxide) solutions, to significantly enhance mixing in microfluidic devices at a very small Reynolds number, i.e., Re≈0.023, but large Peclet and elasticity numbers. With an abrupt contraction microgeometry (8:1 contraction ratio), two different dilute poly(ethylene oxide) solutions were successfully mixed with a short flow length at a relatively fast mixing time of <10 μs. Microparticle image velocimetry was employed in our investigations to characterize the flow fields. The increase in velocity fluctuation with an increase in flow rate and Deborah number indicates the increase in viscoelastic flow instability. Mixing efficiency was characterized by fluorescent concentration measurements. Our results showed that enhanced mixing can be achieved through viscoelastic flow instability under situations where molecular-diffusion and inertia effects are negligible. This approach bypasses the laminar flow limitation, usually associated with a low Reynolds number, which is not conducive to mixing. PMID:19693399

The Effects of Micromixing Two Solutions of Two Concentrations in a Two Tier PDMS Micromixer

NASA Astrophysics Data System (ADS)

Sundra, Sargunan; Fhong Soon, Chin; Zainal, Nurfarina; Sek Tee, Kian; Ahmad, Nornabihah; Gan, Siew Hua

2017-08-01

Micromixing technology has drastically advanced in the past few decades. Micromixers are one of the elements in integrated microfluidic systems for chemical, analytical chemistry, pharmaceutical, and biological applications. In this study, two tier micromixer was used to mix and dilute two solutions of similar and different concentration in order to investigate performance of micromixer’s mixing. This paper presents the fabrication of a designed micromixer using polydimethylsiloxane (PDMS) and vinyl tape methods which reduce time, cost and complexity of prototyping. The serpentine structure of the microchannels was designed to enhance both mixing and dilution. Two types of food dyes and distilled water were used to investigate the mixing performance of the micromixer followed by spectrophotometry analysis. It is observed that the single dye solution and distilled water shows better mixing performance compared to the micromixing of two dye solutions which was supported by the diffusion theory. 2.00 ml/min was the optimum flow rate that allow optimum mixing and dilution between two different concentrated liquids.

Broadband spectroscopy of dynamic impedances with short chirp pulses.

PubMed

Min, M; Land, R; Paavle, T; Parve, T; Annus, P; Trebbels, D

2011-07-01

An impedance spectrum of dynamic systems is time dependent. Fast impedance changes take place, for example, in high throughput microfluidic devices and in operating cardiovascular systems. Measurements must be as short as possible to avoid significant impedance changes during the spectrum analysis, and as long as possible for enlarging the excitation energy and obtaining a better signal-to-noise ratio (SNR). The authors propose to use specific short chirp pulses for excitation. Thanks to the specific properties of the chirp function, it is possible to meet the needs for a spectrum bandwidth, measurement time and SNR so that the most accurate impedance spectrogram can be obtained. The chirp wave excitation can include thousands of cycles when the impedance changes slowly, but in the case of very high speed changes it can be shorter than a single cycle, preserving the same excitation bandwidth. For example, a 100 kHz bandwidth can be covered by the chirp pulse with durations from 10 µs to 1 s; only its excitation energy differs also 10(5) times. After discussing theoretical short chirp properties in detail, the authors show how to generate short chirps in the microsecond range with a bandwidth up to a few MHz by using digital synthesis architectures developed inside a low-cost standard field programmable gate array.

MULTI-PLATE IONIZATION CHAMBER FOR THE DETECTION OF SLOW NEUTRONS

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

Bubzanowski, A.; Grotowski, K.

1957-01-01

A description is given of an ionization chamber, the electrodes of which are coated with a layer of natural boron of thickness 3 mg/cm/sup 2/. Each electrode of the chamber consists of three disks, placed between plates of the other electrodes. The capacitance between the electrodes does not exceed 15 micromicrofarads. The technology of coating the layer is as follows: the boron is mixed with alcohol and a small amount of Canada balsam and is coated in the form of an emulsion on the plates. The chamber efficiency is approximately 2%. The filler is argon at atmospheric pressure. The durationmore » of the output pulses after forming is approximately 5 microseconds.« less

An Acoustofluidic Micromixer via Bubble Inception and Cavitation from Microchannel Sidewalls

PubMed Central

2015-01-01

During the deep reactive ion etching process, the sidewalls of a silicon mold feature rough wavy structures, which can be transferred onto a polydimethylsiloxane (PDMS) microchannel through the soft lithography technique. In this article, we utilized the wavy structures of PDMS microchannel sidewalls to initiate and cavitate bubbles in the presence of acoustic waves. Through bubble cavitation, this acoustofluidic approach demonstrates fast, effective mixing in microfluidics. We characterized its performance by using viscous fluids such as poly(ethylene glycol) (PEG). When two PEG solutions with a resultant viscosity 54.9 times higher than that of water were used, the mixing efficiency was found to be 0.92, indicating excellent, homogeneous mixing. The acoustofluidic micromixer presented here has the advantages of simple fabrication, easy integration, and capability to mix high-viscosity fluids (Reynolds number: ∼0.01) in less than 100 ms. PMID:24754496

Development of a 1000V, 200A, low-loss, fast-switching, gate-assisted turn-off thyristor

NASA Technical Reports Server (NTRS)

Schlegel, E. S.; Lowry, L. R.; Moore, D. L.

1977-01-01

The results of a program to develop a fast high power thyristor that can operate in switching circuits at frequencies of 10 to 20 kHz with very low power loss are given. Feasibility was demonstrated for a thyristor that blocks 1000V forward and reverse, conducts 200A, turns on in little more than 2 more microseconds with only 2A of gate drive, turns off in 3 microseconds with 2A of gate assist current and has an energy dissipation of only 12 mJ per pulse for a 20 microsecond half sine wave 200A pulse. Data were generated that clearly showed the tradeoffs that can be made between the turn off time and forward drop. The understanding of this relationship is necessary in the selection of deliverable thyristors with turn off times up to 7 microseconds to give improved efficiency in a series resonant dc to dc inverter application.

a New Approach for Complete Mixing by Transverse and Streamwise Flow Motions in Micro-Channels

NASA Astrophysics Data System (ADS)

Wang, Muh-Rong; Dai, Chiau-Yi; Huang, Yang-Sheng

Mixing control is an important issue in micro-fluid chip applications, such as μTAS (Micro-Total Analysis System) or LOC (Lab-on-Chip) because the flow at micro-scale is highly laminar. Several flow control schemes had been developed for complete mixing in the micro-channels in the past decades. However, most of the mixing control schemes are performed by utilizing specific excitation devices, such as electrokinetic, magnetic or pressure drivers. This paper investigates a new control scheme which is composed of a series of flow manipulation by changing the pressure at the two inlets of the micromixer as the external excitation. The fluids from two inlets are introduced to a square mixing chamber, which provides a space where the streamwise and transverse flow motions take place. The results show that the micromixer can be used to produce a large recirculation zone with series of small transverse fringes under external excitations. It is found that this new flow pattern enhances mixing processes at the micro-scale. A complete mixing can be achieved under appropriate flow control with the corresponding design.

A novel effective micromixer having horizontal and vertical weaving flow motion

NASA Astrophysics Data System (ADS)

Yoo, Won-Sul; Go, Jung Sang; Park, Seonghun; Park, Sang-Hu

2012-03-01

The need for small-scale product-related biotechnology (BT) is rapidly increasing. An important product among these is high-performance biochips. In these devices, many microchannels are used for separation, filtering and mixing of various materials; therefore, for compactness, these reactions should be carried out in the small space of microfluidic systems. However, there is no turbulence that can induce materials to be mixed or reacted in the microchannel, especially with low Reynolds number laminar flow. Hence, it is difficult to sufficiently mix different materials. To address this problem, we propose the HVW (horizontal and vertical weaving) micromixer having crossed barriers inside of a microchannel, for effective mixing and reacting different materials. From CFD analysis, we have evaluated the mixing mechanism and efficiency of the HVW mixer. In this work, it is shown that the HVW mixer has the maximum mixing efficiency of 89.9% with a short mixing distance of 450 µm at a Reynolds number of 5 with the barrier angle of 30°, when water and water combined with Rhodamine B figment were used as fluids.

Passive micromixer using by convection and surface tension effects with air-liquid interface.

PubMed

Ju, Jongil; Warrick, Jay

2013-12-01

This article describes a passive micromixer that utilizes an air-liquid interface and surface tension effects to enhance fluid mixing via convection and Marangoni effects. Performance of the microfluidic component is tested within a passive-pumping-based device that consists of three microchannels connected in succession using passive micro-mixers. Mixing was quantified at 5 key points along the length of the device using microscope images of patterned streams of Alexa 488 fluorescent-dyed water and pure DI water flowing through the device. The passive micro-mixer mixed fluid 15-20 times more effectively than diffusion between laminar flow streams alone and is a novel micro-mixer embodiment that provides an additional strategy for removing external components from microscale devices for simpler, autonomous operation.

Passive micromixer using by convection and surface tension effects with air-liquid interface

PubMed Central

Ju, Jongil; Warrick, Jay

2014-01-01

This article describes a passive micromixer that utilizes an air-liquid interface and surface tension effects to enhance fluid mixing via convection and Marangoni effects. Performance of the microfluidic component is tested within a passive-pumping-based device that consists of three microchannels connected in succession using passive micro-mixers. Mixing was quantified at 5 key points along the length of the device using microscope images of patterned streams of Alexa 488 fluorescent-dyed water and pure DI water flowing through the device. The passive micro-mixer mixed fluid 15–20 times more effectively than diffusion between laminar flow streams alone and is a novel micro-mixer embodiment that provides an additional strategy for removing external components from microscale devices for simpler, autonomous operation. PMID:25104979

Active micromixer for microfluidic systems using lead-zirconate-titanate (PZT)-generated ultrasonic vibration.

PubMed

Yang, Z; Goto, H; Matsumoto, M; Maeda, R

2000-01-01

A micromixer using direct ultrasonic vibration is first reported in this paper. The ultrasonic vibration was induced by a bulk lead-zirconate-titanate (PZT; 5 x 4 x 0.2 mm), which was excited by a 48 kHz square wave at 150 V (peak-to-peak). Liquids were mixed in a chamber (6 x 6 x 0.06 mm) with an oscillating diaphragm driven by the PZT. The oscillating diaphragm was in the size of 6 x 6 x 0.15 mm. Ethanol and water were used to test the mixing effectiveness. The laminar flows of ethanol (115 microL/min) and water (100 microL/min) were mixed effectively when the PZT was excited. The entire process was recorded using a video camera.

Flow characterization and patch clamp dose responses using jet microfluidics in a tubeless microfluidic device.

PubMed

Resto, Pedro J; Bhat, Abhishek; Stava, Eric; Lor, Chong; Merriam, Elliot; Diaz-Rivera, Ruben E; Pearce, Robert; Blick, Robert; Williams, Justin C

2017-11-01

Surface tension passive pumping is a way to actuate flow without the need for pumps, tubing or valves by using the pressure inside small drop to move liquid via a microfluidic channel. These types of tubeless devices have typically been used in cell biology. Herein we present the use of tubeless devices as a fluid exchange platform for patch clamp electrophysiology. Inertia from high-speed droplets and jets is used to create flow and perform on-the-fly mixing of solutions. These are then flowed over GABA transfected HEK cells under patch in order to perform a dose response analysis. TIRF imaging and electrical recordings are used to study the fluid exchange properties of the microfluidic device, resulting in 0-90% fluid exchange times of hundreds of milliseconds. COMSOL is used to model flow and fluid exchange within the device. Patch-clamping experiments show the ability to use high-speed passive pumping and its derivatives for studying peak dose responses, but not for studying ion channel kinetics. Our system results in fluid exchange times slower than when using a standard 12-barrel application system and is not as stable as traditional methods, but it offers a new platform with added functionality. Surface tension passive pumping and tubeless devices can be used in a limited fashion for electrophysiology. Users may obtain peak dose responses but the system, in its current form, is not capable of fluid exchange fast enough to study the kinetics of most ion channels. Copyright © 2017 Elsevier B.V. All rights reserved.

Continuous-flow, microfluidic, qRT-PCR system for RNA virus detection.

PubMed

Fernández-Carballo, B Leticia; McBeth, Christine; McGuiness, Ian; Kalashnikov, Maxim; Baum, Christoph; Borrós, Salvador; Sharon, Andre; Sauer-Budge, Alexis F

2018-01-01

One of the main challenges in the diagnosis of infectious diseases is the need for rapid and accurate detection of the causative pathogen in any setting. Rapid diagnosis is key to avoiding the spread of the disease, to allow proper clinical decisions to be made in terms of patient treatment, and to mitigate the rise of drug-resistant pathogens. In the last decade, significant interest has been devoted to the development of point-of-care reverse transcription polymerase chain reaction (PCR) platforms for the detection of RNA-based viral pathogens. We present the development of a microfluidic, real-time, fluorescence-based, continuous-flow reverse transcription PCR system. The system incorporates a disposable microfluidic chip designed to be produced industrially with cost-effective roll-to-roll embossing methods. The chip has a long microfluidic channel that directs the PCR solution through areas heated to different temperatures. The solution first travels through a reverse transcription zone where RNA is converted to complementary DNA, which is later amplified and detected in real time as it travels through the thermal cycling area. As a proof of concept, the system was tested for Ebola virus detection. Two different master mixes were tested, and the limit of detection of the system was determined, as was the maximum speed at which amplification occurred. Our results and the versatility of our system suggest its promise for the detection of other RNA-based viruses such as Zika virus or chikungunya virus, which constitute global health threats worldwide. Graphical abstract Photograph of the RT-PCR thermoplastic chip.

Flow of wormlike micellar solutions around confined microfluidic cylinders.

PubMed

Zhao, Ya; Shen, Amy Q; Haward, Simon J

2016-10-26

Wormlike micellar (WLM) solutions are frequently used in enhanced oil and gas recovery applications in porous rock beds where complex microscopic geometries result in mixed flow kinematics with strong shear and extensional components. Experiments with WLM solutions through model microfluidic porous media have revealed a variety of complex flow phenomena, including the formation of stable gel-like structures known as a Flow-Induced Structured Phase (FISP), which undoubtedly play an important role in applications of WLM fluids, but are still poorly understood. A first step in understanding flows of WLM fluids through porous media can be made by examining the flow around a single micro-scale cylinder aligned on the flow axis. Here we study flow behavior of an aqueous WLM solution consisting of cationic surfactant cetyltrimethylammonium bromide (CTAB) and a stable hydrotropic salt 3-hydroxy naphthalene-2-carboxylate (SHNC) in microfluidic devices with three different cylinder blockage ratios, β. We observe a rich sequence of flow instabilities depending on β as the Weissenberg number (Wi) is increased to large values while the Reynolds number (Re) remains low. Instabilities upstream of the cylinder are associated with high stresses in fluid that accelerates into the narrow gap between the cylinder and the channel wall; vortex growth upstream is reminiscent of that seen in microfluidic contraction geometries. Instability downstream of the cylinder is associated with stresses generated at the trailing stagnation point and the resulting flow modification in the wake, coupled with the onset of time-dependent flow upstream and the asymmetric division of flow around the cylinder.

Characterization of Nanoparticles by Capillary Electrophoresis and Trapping of Nanoparticles in Microfluidics Device

DTIC Science & Technology

2009-08-01

tubular mode driven by electroosmotic flow and the inherent electrophoretic mobility of the analytes under the influence of an applied electric field...could be due to unlabeled beads. Figure 3 (C and D) also shows electropherogram of a neutral electroosmotic flow (EOF) marker dye BODIPY and...internal turbulent mixing . The current microfabricated electromagnets cannot produce sufficient fields to trap the NPs against a large flow forces

Micro-Fluidic Chemical Reactor Systems: Development, Scale-Up and Demonstration

DTIC Science & Technology

2002-11-01

B) A ) Figure 1: Gas Phase Microreactor . ( A ) Photograph of device. (B) Top view schematic. (C) Side view across channel. ( D ) Side view along... Microreactor system showing controller, heater power, fluid mixing, and microreactor cards (as in Figure 14) in a PCI chassis... microreactor design used for gas-phase heterogeneous reactions is a microchannel device that can be integrated with a heat exchange layer for highly

High-speed pulsed mixing in a short distance with high-frequency switching of pumping from three inlets

NASA Astrophysics Data System (ADS)

Sugano, K.; Nakata, A.; Tsuchiya, T.; Tabata, O.

2015-08-01

In this study, we propose a mixing method using alternate pulsed flows from three inlets with flow direction control. In conventional pulsed mixing, a residual flow near the sidewalls inhibits the rapid mixing of two solutions at high switching frequency. In this study, we addressed this issue in order to perform rapid mixing in a short distance with a low Reynolds number. We fabricated a microfluidic mixing device consisting of a cross-shaped mixing channel with three inlet microchannels and three valveless micropumps. In conventional T-shaped or Y-shaped mixing channels, a residual flow is observed because of the incomplete switching of solutions. The three inlet configuration enabled us to split the residual flow at a switching frequency of pumping of up to 200 Hz, thus resulting in rapid mixing. Furthermore, by controlling the flow direction at the confluent area using the reverse flow of the micropump, the mixing speed was dramatically increased because of the complete switching of the two solutions. As a result, we achieved the mixing time of 3.6 ms and the mixing length of 20.7 µm, which were necessary to achieve a 90% mixing ratio at a high micropump switching frequency of 400 Hz and reverse flow ratio of 1/4.

Nonlinear dynamic phase contrast microscopy for microfluidic and microbiological applications

NASA Astrophysics Data System (ADS)

Denz, C.; Holtmann, F.; Woerdemann, M.; Oevermann, M.

2008-08-01

In live sciences, the observation and analysis of moving living cells, molecular motors or motion of micro- and nano-objects is a current field of research. At the same time, microfluidic innovations are needed for biological and medical applications on a micro- and nano-scale. Conventional microscopy techniques are reaching considerable limits with respect to these issues. A promising approach for this challenge is nonlinear dynamic phase contrast microscopy. It is an alternative full field approach that allows to detect motion as well as phase changes of living unstained micro-objects in real-time, thereby being marker free, without contact and non destructive, i.e. fully biocompatible. The generality of this system allows it to be combined with several other microscope techniques such as conventional bright field or fluorescence microscopy. In this article we will present the dynamic phase contrast technique and its applications in analysis of micro organismic dynamics, micro flow velocimetry and micro-mixing analysis.

Analysis of microfluidic flow driven by electrokinetic and pressure forces

NASA Astrophysics Data System (ADS)

Chen, Chien-Hsin

2011-12-01

This work presents an analysis of microfluidic flow introduced by mixed electrokinetic force and pressure gradient. Analytical solutions are presented for the case of constant surface heat flux, taking the Joule heating effect into account. The present problem is governed by two scale ratios and the dimensionless source term. The two important ratios are the length scale ratio e (the ratio of Debye length to the tube radius R) and the velocity scale ratio Γ (the ratio of the pressuredriven velocity scale for Poiseuille flow to Helmholtz-Smoluchowski velocity for electroosmotic flow). For mixed electroosmotic and pressure-driven flow, the resulting velocity profile is the superimposed effect of both electroosmotic and Poiseuille flow phenomena. It is found that the velocity profile decreases as e increases and the normalized temperature profiles across the tube increases monotonously form the core to the wall. The maximum dimensionless temperature is observed at the wall and the wall temperature increases with increasing Joule heating. Also, the temperature is increased with increasing the value of ɛ . The fully developed Nusselt number takes the maximum value at the limiting case of ɛ --> 0 , and then decreases with increasing ɛ . Moreover, the Nusselt number decreases with Γ and then goes asymptotically to the limit of Poiseuille flow as Γ --> ∞ , where the flow is dominated by the pressure force.

Optimized Mixing in Microchannels with Integrated Microactuators

NASA Astrophysics Data System (ADS)

Folk, Christopher Richard

Microscale valves and pumps have been designed and fabricated for integration into a microfluidic circuit. Furthermore, a micromixer for this circuit has been designed and optimized. N-isopropylacrylamide (NIPA) gels have been fabricated and actuated directly with heat and indirectly by laser. A new method for photopatterning these gels based on photoinitiation has been used to fabricate hydrogel valves down to 50 mum in diameter. Hydrogel valves have been fabricated in situ in a microfluidic network. The valves open in 27 seconds and close via diffusion of water into the gel in 128 seconds, which is faster than other optically-driven polymers used for large displacements. In this research, azobis-isobutyronitrile (AIBN) is incorporated into a variety of polydimethylsiloxane (PDMS) pump chambers. The AIBN is heated via integrated resistive heaters and decomposes to release nitrogen gas. The nitrogen gas provides impulse power to a PDMS diaphragm to displace the fluid. The pump devices have been built and characterized. Lastly, in this work, we describe the use of combined fluid dynamic and diffusion modeling to simulate a micromixer based on the elements above. The micromixer is optimized via Design of Experiments to produce an optimized geometry for mixing. The optimization is validated via comparison to previous work through the Strouhal number.

Assay for Listeria monocytogenes cells in whole blood using isotachophoresis and recombinase polymerase amplification.

PubMed

Eid, Charbel; Santiago, Juan G

2016-12-19

We present a new approach which enables lysis, extraction, and detection of inactivated Listeria monocytogenes cells from blood using isotachophoresis (ITP) and recombinase polymerase amplification (RPA). We use an ITP-compatible alkaline and proteinase K approach for rapid and effective lysis. We then perform ITP purification to separate bacterial DNA from whole blood contaminants using a microfluidic device that processes 25 μL sample volume. Lysis, mixing, dispensing, and on-chip ITP purification are completed in a total of less than 50 min. We transfer extracted DNA directly into RPA master mix for isothermal incubation and detection, an additional 25 min. We first validate our assay in the detection of purified genomic DNA spiked into whole blood, and demonstrate a limit of detection of 16.7 fg μL -1 genomic DNA, the equivalent of 5 × 10 3 cells per mL. We then show detection of chemically-inactivated L. monocytogenes cells spiked into whole blood, and demonstrate a limit of detection of 2 × 10 4 cells per mL. Lastly, we show preliminary experimental data demonstrating the feasibility of the integration of ITP purification with RPA detection on a microfluidic chip. Our results suggest that ITP purification is compatible with RPA detection, and has potential to extend the applicability of RPA to whole blood.

Design of micro-second pulsed laser mode for ophthalmological CW self-raman laser

NASA Astrophysics Data System (ADS)

Mota, Alessandro D.; Rossi, Giuliano; Ortega, Tiago A.; Costal, Glauco Z.; Fontes, Yuri C.; Yasuoka, Fatima M. M.; Stefani, Mario A.; de Castro N., Jarbas C.; Paiva, Maria S. V.

2011-02-01

This work presents the mechanisms adopted for the design of micro-second pulsed laser mode for a CW Self-Raman laser cavity in 586nm and 4W output power. The new technique for retina disease treatment discharges laser pulses on the retina tissue, in laser sequences of 200 μs pulse duration at each 2ms. This operation mode requires the laser to discharge fast electric pulses, making the system control velocity of the electronic system cavity vital. The control procedures to keep the laser output power stable and the laser head behavior in micro-second pulse mode are presented.

Numerical and experimental characterization of a novel modular passive micromixer.

PubMed

Pennella, Francesco; Rossi, Massimiliano; Ripandelli, Simone; Rasponi, Marco; Mastrangelo, Francesco; Deriu, Marco A; Ridolfi, Luca; Kähler, Christian J; Morbiducci, Umberto

2012-10-01

This paper reports a new low-cost passive microfluidic mixer design, based on a replication of identical mixing units composed of microchannels with variable curvature (clothoid) geometry. The micromixer presents a compact and modular architecture that can be easily fabricated using a simple and reliable fabrication process. The particular clothoid-based geometry enhances the mixing by inducing transversal secondary flows and recirculation effects. The role of the relevant fluid mechanics mechanisms promoting the mixing in this geometry were analysed using computational fluid dynamics (CFD) for Reynolds numbers ranging from 1 to 110. A measure of mixing potency was quantitatively evaluated by calculating mixing efficiency, while a measure of particle dispersion was assessed through the lacunarity index. The results show that the secondary flow arrangement and recirculation effects are able to provide a mixing efficiency equal to 80 % at Reynolds number above 70. In addition, the analysis of particles distribution promotes the lacunarity as powerful tool to quantify the dispersion of fluid particles and, in turn, the overall mixing. On fabricated micromixer prototypes the microscopic-Laser-Induced-Fluorescence (μLIF) technique was applied to characterize mixing. The experimental results confirmed the mixing potency of the microdevice.

Foundations of chaotic mixing.

PubMed

Wiggins, Stephen; Ottino, Julio M

2004-05-15

The simplest mixing problem corresponds to the mixing of a fluid with itself; this case provides a foundation on which the subject rests. The objective here is to study mixing independently of the mechanisms used to create the motion and review elements of theory focusing mostly on mathematical foundations and minimal models. The flows under consideration will be of two types: two-dimensional (2D) 'blinking flows', or three-dimensional (3D) duct flows. Given that mixing in continuous 3D duct flows depends critically on cross-sectional mixing, and that many microfluidic applications involve continuous flows, we focus on the essential aspects of mixing in 2D flows, as they provide a foundation from which to base our understanding of more complex cases. The baker's transformation is taken as the centrepiece for describing the dynamical systems framework. In particular, a hierarchy of characterizations of mixing exist, Bernoulli --> mixing --> ergodic, ordered according to the quality of mixing (the strongest first). Most importantly for the design process, we show how the so-called linked twist maps function as a minimal picture of mixing, provide a mathematical structure for understanding the type of 2D flows that arise in many micromixers already built, and give conditions guaranteeing the best quality mixing. Extensions of these concepts lead to first-principle-based designs without resorting to lengthy computations.

Optimization of ultrahigh-speed multiplex PCR for forensic analysis.

PubMed

Gibson-Daw, Georgiana; Crenshaw, Karin; McCord, Bruce

2018-01-01

In this paper, we demonstrate the design and optimization of an ultrafast PCR amplification technique, used with a seven-locus multiplex that is compatible with conventional capillary electrophoresis systems as well as newer microfluidic chip devices. The procedure involves the use of a high-speed polymerase and a rapid cycling protocol to permit multiplex PCR amplification of forensic short tandem repeat loci in 6.5 min. We describe the selection and optimization of master mix reagents such as enzyme, buffer, MgCl 2 , and dNTPs, as well as primer ratios, total volume, and cycle conditions, in order to get the best profile in the shortest time possible. Sensitivity and reproducibility studies are also described. The amplification process utilizes a small high-speed thermocycler and compact laptop, making it portable and potentially useful for rapid, inexpensive on-site genotyping. The seven loci of the multiplex were taken from conventional STR genotyping kits and selected for their size and lack of overlap. Analysis was performed using conventional capillary electrophoresis and microfluidics with fluorescent detection. Overall, this technique provides a more rapid method for rapid sample screening of suspects and victims. Graphical abstract Rapid amplification of forensic DNA using high speed thermal cycling followed by capillary or microfluidic electrophoresis.

Manufacturing of three-dimensionally microstructured nanocomposites through microfluidic infiltration.

PubMed

Dermanaki-Farahani, Rouhollah; Lebel, Louis Laberge; Therriault, Daniel

2014-03-12

Microstructured composite beams reinforced with complex three-dimensionally (3D) patterned nanocomposite microfilaments are fabricated via nanocomposite infiltration of 3D interconnected microfluidic networks. The manufacturing of the reinforced beams begins with the fabrication of microfluidic networks, which involves layer-by-layer deposition of fugitive ink filaments using a dispensing robot, filling the empty space between filaments using a low viscosity resin, curing the resin and finally removing the ink. Self-supported 3D structures with other geometries and many layers (e.g. a few hundreds layers) could be built using this method. The resulting tubular microfluidic networks are then infiltrated with thermosetting nanocomposite suspensions containing nanofillers (e.g. single-walled carbon nanotubes), and subsequently cured. The infiltration is done by applying a pressure gradient between two ends of the empty network (either by applying a vacuum or vacuum-assisted microinjection). Prior to the infiltration, the nanocomposite suspensions are prepared by dispersing nanofillers into polymer matrices using ultrasonication and three-roll mixing methods. The nanocomposites (i.e. materials infiltrated) are then solidified under UV exposure/heat cure, resulting in a 3D-reinforced composite structure. The technique presented here enables the design of functional nanocomposite macroscopic products for microengineering applications such as actuators and sensors.

An Incompressible, Depth-Averaged Lattice Boltzmann Method for Liquid Flow in Microfluidic Devices with Variable Aperture

DOE PAGES

Laleian, Artin; Valocchi, Albert J.; Werth, Charles J.

2015-11-24

Two-dimensional (2D) pore-scale models have successfully simulated microfluidic experiments of aqueous-phase flow with mixing-controlled reactions in devices with small aperture. A standard 2D model is not generally appropriate when the presence of mineral precipitate or biomass creates complex and irregular three-dimensional (3D) pore geometries. We modify the 2D lattice Boltzmann method (LBM) to incorporate viscous drag from the top and bottom microfluidic device (micromodel) surfaces, typically excluded in a 2D model. Viscous drag from these surfaces can be approximated by uniformly scaling a steady-state 2D velocity field at low Reynolds number. We demonstrate increased accuracy by approximating the viscous dragmore » with an analytically-derived body force which assumes a local parabolic velocity profile across the micromodel depth. Accuracy of the generated 2D velocity field and simulation permeability have not been evaluated in geometries with variable aperture. We obtain permeabilities within approximately 10% error and accurate streamlines from the proposed 2D method relative to results obtained from 3D simulations. Additionally, the proposed method requires a CPU run time approximately 40 times less than a standard 3D method, representing a significant computational benefit for permeability calculations.« less

Microfluidic-based photocatalytic microreactor for environmental application: a review of fabrication substrates and techniques, and operating parameters.

PubMed

Das, Susmita; Srivastava, Vimal Chandra

2016-06-08

Photochemical technology with microfluidics is emerging as a new platform in environmental science. Microfluidic technology has various advantages, like better mixing and a shorter diffusion distance for the reactants and products; and uniform distribution of light on the photocatalyst. Depending on the material type and related applications, several fabrication techniques have been adopted by various researchers. Microreactors have been prepared by various techniques, such as lithography, etching, mechanical microcutting technology, etc. Lithography can be classified into photolithography, soft lithography and X-ray lithography techniques whereas the etching process is divided into wet etching (chemical etching) and dry etching (plasma etching) techniques. Several substrates, like polymers, such as polydimethyl-siloxane (PDMS), polymethyle-methacrylate (PMMA), hydrogel, etc.; metals, such as stainless steel, titanium foil, etc.; glass, such as silica capillary, glass slide, etc.; and ceramics have been used for microchannel fabrication. During degradation in a microreactor, the degradation efficiency is affected by few important parameters such as flow rate, initial concentration of the target compound, microreactor dimensions, light intensity, photocatalyst structure and catalyst support. The present paper discusses and critically reviews fabrication techniques and substrates used for microchannel fabrication and critical operating parameters for organics, especially dye degradation in the microreactor. The kinetics of degradation has also been discussed.

X-ray transparent microfluidic chips for high-throughput screening and optimization of in meso membrane protein crystallization

PubMed Central

Schieferstein, Jeremy M.; Pawate, Ashtamurthy S.; Wan, Frank; Sheraden, Paige N.; Broecker, Jana; Ernst, Oliver P.; Gennis, Robert B.

2017-01-01

Elucidating and clarifying the function of membrane proteins ultimately requires atomic resolution structures as determined most commonly by X-ray crystallography. Many high impact membrane protein structures have resulted from advanced techniques such as in meso crystallization that present technical difficulties for the set-up and scale-out of high-throughput crystallization experiments. In prior work, we designed a novel, low-throughput X-ray transparent microfluidic device that automated the mixing of protein and lipid by diffusion for in meso crystallization trials. Here, we report X-ray transparent microfluidic devices for high-throughput crystallization screening and optimization that overcome the limitations of scale and demonstrate their application to the crystallization of several membrane proteins. Two complementary chips are presented: (1) a high-throughput screening chip to test 192 crystallization conditions in parallel using as little as 8 nl of membrane protein per well and (2) a crystallization optimization chip to rapidly optimize preliminary crystallization hits through fine-gradient re-screening. We screened three membrane proteins for new in meso crystallization conditions, identifying several preliminary hits that we tested for X-ray diffraction quality. Further, we identified and optimized the crystallization condition for a photosynthetic reaction center mutant and solved its structure to a resolution of 3.5 Å. PMID:28469762

Controllable liquid colour-changing lenses with microfluidic channels for vision protection, camouflage and optical filtering based on soft lithography fabrication.

PubMed

Zhang, Min; Li, Songjing

2016-01-01

In this work, liquid colour-changing lenses for vision protection, camouflage and optical filtering are developed by circulating colour liquids through microfluidic channels on the lenses manually. Soft lithography technology is applied to fabricate the silicone liquid colour-changing layers with microfluidic channels on the lenses instead of mechanical machining. To increase the hardness and abrasion resistance of the silicone colour-changing layers on the lenses, proper fabrication parameters such as 6:1 (mass ration) mixing proportion and 100 °C curing temperature for 2 h are approved for better soft lithography process of the lenses. Meanwhile, a new surface treatment for the irreversible bonding of silicone colour-changing layer with optical resin (CR39) substrate lens by using 5 % (volume ratio) 3-Aminopropyltriethoxysilane solution is proposed. Vision protection, camouflage and optical filtering functions of the lenses are investigated with different designs of the channels and multi-layer structures. Each application can not only well achieve their functional demands, but also shows the advantages of functional flexibility, rapid prototyping and good controllability compared with traditional ways. Besides optometry, some other designs and applications of the lenses are proposed for potential utility in the future.

Manufacturing of Three-dimensionally Microstructured Nanocomposites through Microfluidic Infiltration

PubMed Central

Dermanaki-Farahani, Rouhollah; Lebel, Louis Laberge; Therriault, Daniel

2014-01-01

Microstructured composite beams reinforced with complex three-dimensionally (3D) patterned nanocomposite microfilaments are fabricated via nanocomposite infiltration of 3D interconnected microfluidic networks. The manufacturing of the reinforced beams begins with the fabrication of microfluidic networks, which involves layer-by-layer deposition of fugitive ink filaments using a dispensing robot, filling the empty space between filaments using a low viscosity resin, curing the resin and finally removing the ink. Self-supported 3D structures with other geometries and many layers (e.g. a few hundreds layers) could be built using this method. The resulting tubular microfluidic networks are then infiltrated with thermosetting nanocomposite suspensions containing nanofillers (e.g. single-walled carbon nanotubes), and subsequently cured. The infiltration is done by applying a pressure gradient between two ends of the empty network (either by applying a vacuum or vacuum-assisted microinjection). Prior to the infiltration, the nanocomposite suspensions are prepared by dispersing nanofillers into polymer matrices using ultrasonication and three-roll mixing methods. The nanocomposites (i.e. materials infiltrated) are then solidified under UV exposure/heat cure, resulting in a 3D-reinforced composite structure. The technique presented here enables the design of functional nanocomposite macroscopic products for microengineering applications such as actuators and sensors. PMID:24686754

Comprehensive Study of the Flow Control Strategy in a Wirelessly Charged Centrifugal Microfluidic Platform with Two Rotation Axes.

PubMed

Zhu, Yunzeng; Chen, Yiqi; Meng, Xiangrui; Wang, Jing; Lu, Ying; Xu, Youchun; Cheng, Jing

2017-09-05

Centrifugal microfluidics has been widely applied in the sample-in-answer-out systems for the analyses of nucleic acids, proteins, and small molecules. However, the inherent characteristic of unidirectional fluid propulsion limits the flexibility of these fluidic chips. Providing an extra degree of freedom to allow the unconstrained and reversible pumping of liquid is an effective strategy to address this limitation. In this study, a wirelessly charged centrifugal microfluidic platform with two rotation axes has been constructed and the flow control strategy in such platform with two degrees of freedom was comprehensively studied for the first time. Inductively coupled coils are installed on the platform to achieve wireless power transfer to the spinning stage. A micro servo motor is mounted on both sides of the stage to alter the orientation of the device around a secondary rotation axis on demand during stage rotation. The basic liquid operations on this platform, including directional transport of liquid, valving, metering, and mixing, are comprehensively studied and realized. Finally, a chip for the simultaneous determination of hexavalent chromium [Cr(VI)] and methanal in water samples is designed and tested based on the strategy presented in this paper, demonstrating the potential use of this platform for on-site environmental monitoring, food safety testing, and other life science applications.

Microfluidic control of droplet formation from stable emulsions formed by aqueous two-phase systems

NASA Astrophysics Data System (ADS)

Teixeira, Alyne G.; Tsai, Meng-Chiao; Frampton, John P.

2018-02-01

Aqueous two-phase systems (ATPSs) form from the thermodynamic separation of two dissolved incompatible solutes, such as two polymers, a polymer and a salt, and a polymer and a surfactant. At most supercritical concentrations, ATPS emulsions can be formed by vigorous mixing. These emulsions typically settle into distinct layers in minutes to hours. However, it is also possible to choose ATPS compositions with extremely long settling times that resemble stable emulsions. Here, we generated stable emulsions from a polyethylene glycol (PEG)-dextran ATPS by selecting ATPS compositions at the extreme ends of the tie lines connecting the binodal curve delineating phase-separating compositions. Droplets of PEG in a continuous dextran phase did not coalesce appreciably over the course of several days when stored in a conical tube or syringe. However, upon exposure to laminar flow conditions in a microfluidic channel, droplets were observed to coalesce. Through microscopic characterization of droplet volume, an increase in droplet size and decrease in overall droplet number was observed as a function of channel distance, suggesting a progressive droplet merging phenomenon. This novel approach to control droplet size by encouraging coalescence of stable emulsions under laminar flow in a microfluidic channel enables the production of droplets ranging from fL to several pL, which may enable various future biotechnology applications.

Self-assembled materials and supramolecular chemistry within microfluidic environments: from common thermodynamic states to non-equilibrium structures.

PubMed

Sevim, S; Sorrenti, A; Franco, C; Furukawa, S; Pané, S; deMello, A J; Puigmartí-Luis, J

2018-05-01

Self-assembly is a crucial component in the bottom-up fabrication of hierarchical supramolecular structures and advanced functional materials. Control has traditionally relied on the use of encoded building blocks bearing suitable moieties for recognition and interaction, with targeting of the thermodynamic equilibrium state. On the other hand, nature leverages the control of reaction-diffusion processes to create hierarchically organized materials with surprisingly complex biological functions. Indeed, under non-equilibrium conditions (kinetic control), the spatio-temporal command of chemical gradients and reactant mixing during self-assembly (the creation of non-uniform chemical environments for example) can strongly affect the outcome of the self-assembly process. This directly enables a precise control over material properties and functions. In this tutorial review, we show how the unique physical conditions offered by microfluidic technologies can be advantageously used to control the self-assembly of materials and of supramolecular aggregates in solution, making possible the isolation of intermediate states and unprecedented non-equilibrium structures, as well as the emergence of novel functions. Selected examples from the literature will be used to confirm that microfluidic devices are an invaluable toolbox technology for unveiling, understanding and steering self-assembly pathways to desired structures, properties and functions, as well as advanced processing tools for device fabrication and integration.

Parallel line raster eliminates ambiguities in reading timing of pulses less than 500 microseconds apart

NASA Technical Reports Server (NTRS)

Horne, A. P.

1966-01-01

Parallel horizontal line raster is used for precision timing of events occurring less than 500 microseconds apart for observation of hypervelocity phenomena. The raster uses a staircase vertical deflection and eliminates ambiguities in reading timing of pulses close to the end of each line.

Sub-microsecond-resolution probe microscopy

DOEpatents

Ginger, David; Giridharagopal, Rajiv; Moore, David; Rayermann, Glennis; Reid, Obadiah

2014-04-01

Methods and apparatus are provided herein for time-resolved analysis of the effect of a perturbation (e.g., a light or voltage pulse) on a sample. By operating in the time domain, the provided method enables sub-microsecond time-resolved measurement of transient, or time-varying, forces acting on a cantilever.

DC-biased AC-electroosmotic and AC-electrothermal flow mixing in microchannels.

PubMed

Ng, Wee Yang; Goh, Shireen; Lam, Yee Cheong; Yang, Chun; Rodríguez, Isabel

2009-03-21

This paper presents a novel approach of mixing two laminar flowing streams in microchannels. The mixer consists of a pair of electrodes disposed along a fluidic channel. By energizing the electrodes with a DC-biased (2.5 V) AC voltage (20 Vpp), an electrokinetic flow is induced with a flow profile perpendicular to that of the incoming laminar streams of liquids to be mixed. As a result, the flow lines of the incoming streams and the induced flow are forced to crossover and very efficient stirring and mixing at short mixing length can be achieved. The mixer can be operated from the AC-electroosmotic (ACEO) (sigma=1 mS/m, f=100 kHz) to the AC-electrothermal (ACET) (sigma=500 mS/m, f=500 kHz) flow regimes. The mixing efficiency in the ACEO regime was 92%, with a mixing length of 600 microm (Q=2 microL/min), an estimated mixing time of 69 ms and an induced ACEO flow velocity of approximately 725 microm/s. The mixing efficiency in the ACET regime was 65% for a mixing length of approximately 1200 microm. The mixer is efficient and suitable for mixing reagents in a fluid media from low to high conductivity as required in diverse microfluidic applications.

Analysis of Electrokinetic Mixing Using AC Electric Field and Patchwise Surface Heterogeneities

NASA Astrophysics Data System (ADS)

Luo, Win-Jet; Yarn, Kao-Feng; Hsu, Shou-Ping

2007-04-01

In this paper, the authors investigate the use of an applied AC electric field and microchannel surface heterogeneities to carry out the microfluidic mixing of two-dimensional, time-dependent electroosmotic flows. The time-dependent flow fields within the microchannel are simulated using the backwards-Euler time-stepping numerical method. The mixing efficiencies obtained in microchannels with two different patchwise surface heterogeneity patterns are investigated. In general, the results show that the application of an AC electric field significantly reduces the required mixing length compared with the use of a DC electric field. Furthermore, the presence of oppositely charged surface heterogeneities on the microchannel walls results in the formation of localized flow circulation regions within the bulk flow. These circulation regions grow and decay periodically in accordance with the periodic variation of the AC electric field intensity and provide an effective means of enhancing species mixing in the microchannel. Consequently, the use of an AC electric field together with patchwise surface heterogeneities permits a significant reduction in both the mixing channel length and the retention time required to attain a homogeneous solution.

Rapid microfluidic mixing and liquid jets for studying biomolecular chemical dynamics

NASA Astrophysics Data System (ADS)

Langley, Daniel; Abbey, Brian

2018-01-01

X-ray Free-Electron Lasers (XFELs) offer a unique opportunity to study the structural dynamics of proteins on a femtosecond time-scale. To realize the full potential of XFEL sources for studying time-resolved biomolecular processes however, requires the optimization and development of devices that can both act as a trigger and a delivery mechanism for the system of interest. Here we present numerical simulations and actual devices exploring the conditions required for the development of successful mixing and injection devices for tracking the molecular dynamics of proteins in solution on micro to nanosecond timescales using XFELs. The mechanism for combining reagents employs a threefold combination of pico-liter volumes, lamination and serpentine mixing. Focusing and delivering the sample in solution is achieved using the Gas Dynamic Virtual Nozzle (GDVN), which was specifically developed to produce a micrometer diameter, in-vacuum liquid jet. We explore the influence of parameters such as flow rate and gas pressure on the mixing time and jet stability, and explore the formation of rapid homogeneously mixed jets for `mix-and-inject' liquid scattering experiments at Synchrotron and XFEL facilities.

In vitro study of the variable square pulse Er:YAG laser cutting efficacy for apicectomy.

PubMed

Grgurević, Josko; Grgurević, Lovro; Miletić, Ivana; Karlović, Zoran; Krmek, Silvana Jukić; Anić, Ivica

2005-06-01

Variable square pulse (VSP) Er:YAG laser should be quicker than older Er:YAG lasers. The objectives were: (1) comparison of VSP laser and mechanical handpiece efficacy for apicectomy and (2) determination of optimal pulse width/energy/frequency combination. Sixty extracted, single-rooted mature human teeth with round apical parts were instrumented, root filled, cleaned, and divided into four groups. Apical 2 mm of each root were apicectomized with mechanical handpiece and Er:YAG laser with three different settings (LaserA = 200 mJ/300 microseconds/ 8 Hz; LaserB = 200 mJ/100 microseconds/8 Hz; LaserC = 380 mJ/100 microseconds/20 Hz). Timing results were statistically compared. LaserC was the most efficient setting. Differences between groups were significant except between LaserC-Mechanical and LaserA-LaserC (P < 0.05). VSP Er:YAG laser used for apicectomy is slower by a factor of 7-31 than mechanical handpiece, but treatment outcome is acceptable. Optimal settings for apicectomy with VSP laser are 380 mJ/100 microseconds/20 Hz. Copyright 2005 Wiley-Liss, Inc.

Passive micromixers with dual helical channels

NASA Astrophysics Data System (ADS)

Liu, Keyin; Yang, Qing; Chen, Feng; Zhao, Yulong; Meng, Xiangwei; Shan, Chao; Li, Yanyang

2015-02-01

In this study, a three-dimensional (3D) micromixer with cross-linked double helical microchannels is studied to achieve rapid mixing of fluids at low Reynolds numbers (Re). The 3D micromixer takes full advantages of the chaotic advection model with helical microchannels; meanwhile, the proposed crossing structure of double helical microchannels enables two flow patterns of repelling flow and straight flow in the fluids to promote the agitation effect. The complex 3D micromixer is realized by an improved femtosecond laser wet etching (FLWE) technology embedded in fused silica. The mixing results show that cross-linked double helical microchannels can achieve excellent mixing within 3 cycles (300 μm) over a wide range of low Re (1.5×10-3~600), which compare well with the conventional passive micromixers. This highly-effective micromixer is hoped to contribute to the integration of microfluidic systems.

Mix-and-diffuse serial synchrotron crystallography

DOE PAGES

Beyerlein, Kenneth R.; Dierksmeyer, Dennis; Mariani, Valerio; ...

2017-10-09

Unravelling the interaction of biological macromolecules with ligands and substrates at high spatial and temporal resolution remains a major challenge in structural biology. The development of serial crystallography methods at X-ray free-electron lasers and subsequently at synchrotron light sources allows new approaches to tackle this challenge. Here, a new polyimide tape drive designed for mix-and-diffuse serial crystallography experiments is reported. The structure of lysozyme bound by the competitive inhibitor chitotriose was determined using this device in combination with microfluidic mixers. The electron densities obtained from mixing times of 2 and 50 s show clear binding of chitotriose to the enzymemore » at a high level of detail. Here, the success of this approach shows the potential for high-throughput drug screening and even structural enzymology on short timescales at bright synchrotron light sources.« less

Mix-and-diffuse serial synchrotron crystallography

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

Beyerlein, Kenneth R.; Dierksmeyer, Dennis; Mariani, Valerio

Unravelling the interaction of biological macromolecules with ligands and substrates at high spatial and temporal resolution remains a major challenge in structural biology. The development of serial crystallography methods at X-ray free-electron lasers and subsequently at synchrotron light sources allows new approaches to tackle this challenge. Here, a new polyimide tape drive designed for mix-and-diffuse serial crystallography experiments is reported. The structure of lysozyme bound by the competitive inhibitor chitotriose was determined using this device in combination with microfluidic mixers. The electron densities obtained from mixing times of 2 and 50 s show clear binding of chitotriose to the enzymemore » at a high level of detail. Here, the success of this approach shows the potential for high-throughput drug screening and even structural enzymology on short timescales at bright synchrotron light sources.« less

Stimuli-Responsive Reagent System for Enabling Microfluidic Immunoassays with Biomarker Purification and Enrichment

PubMed Central

2015-01-01

Immunoassays have been translated into microfluidic device formats, but significant challenges relating to upstream sample processing still limit their applications. Here, stimuli-responsive polymer–antibody conjugates are utilized in a microfluidic immunoassay to enable rapid biomarker purification and enrichment as well as sensitive detection. The conjugates were constructed by covalently grafting poly(N-isopropylacrylamide) (PNIPAAm), a thermally responsive polymer, to the lysine residues of anti-prostate specific antigen (PSA) Immunoglobulin G (IgG) using carbodiimide chemistry via the polymer end-carboxylate. The antibody-PNIPAAm (capture) conjugates and antibody-alkaline phosphatase (detection) conjugates formed sandwich immunocomplexes via PSA binding in 50% human plasma. The complexes were loaded into a recirculating poly(dimethylsiloxane) microreactor, equipped with micropumps and transverse flow features, for subsequent separation, enrichment, and quantification. The immunocomplexes were captured by heating the solution to 39 °C, mixed over the transverse features for 2 min, and washed with warm buffer. In one approach, the assay utilized immunocomplex solution that was contained in an 80 nL microreactor, which was loaded with solution at room temperature and subsequently heated to 39 °C. The assay took 25 min and resulted in 37 pM PSA limit of detection (LOD), which is comparable to a plate ELISA employing the same antibody pair. In another approach, the microreactor was preheated to 39 °C, and immunocomplex solution was flowed through the reactor, mixed, and washed. When the specimen volume was increased to 7.5 μL by repeating the capture process three times, the higher specimen volume led to immunocomplex enrichment within the microreactor. The resulting assay LOD was 0.5 pM, which is 2 orders of magnitude lower than the plate ELISA. Both approaches generate antigen specific signal over a clinically significant range. The sample processing capabilities and subsequent utility in a biomarker assay demonstrate the opportunity for stimuli-responsive polymer–protein conjugates in novel diagnostic technologies. PMID:25405605

A smog chamber comparison of a microfluidic derivatization measurement of gas-phase glyoxal and methylglyoxal with other analytical techniques

NASA Astrophysics Data System (ADS)

Pang, X.; Lewis, A. C.; Richard, A.; Baeza-Romero, M. T.; Adams, T. J.; Ball, S. M.; Daniels, M. J. S.; Goodall, I. C. A.; Monks, P. S.; Peppe, S.; Ródenas García, M.; Sánchez, P.; Muñoz, A.

2013-06-01

A microfluidic lab-on-a-chip derivatization technique has been developed to measure part per billion volume (ppbV) mixing ratios of gaseous glyoxal (GLY) and methylglyoxal (MGLY), and the method compared with other techniques in a smog chamber experiment. The method uses o-(2,3,4,5,6-pentafluorobenzyl) hydroxylamine (PFBHA) as a derivatization reagent and a microfabricated planar glass micro-reactor comprising an inlet, gas and fluid splitting and combining channels, mixing junctions, and a heated capillary reaction microchannel. The enhanced phase contact area-to-volume ratio and the high heat transfer rate in the micro-reactor result in a fast and highly efficient derivatization reaction, generating an effluent stream ready for direct introduction to a gas chromatograph-mass spectrometer (GC-MS). A linear response for GLY was observed over a calibration range 0.7 to 400 ppbV, and for MGLY of 1.2 to 300 ppbV, when derivatized under optimal reaction conditions. The method detection limits (MDLs) were 80 pptV and 200 pptV for GLY and MGLY respectively, calculated as 3 times the standard deviation of the S/N of the blank sample chromatograms. These MDLs are below or close to typical concentrations in clean ambient air. The feasibility of the technique was assessed by applying the methodology under controlled conditions to quantify of α-dicarbonyls formed during the photo-oxidation of isoprene in a large scale outdoor atmospheric simulation chamber (EUPHORE). Good general agreement was seen between microfluidic measurements and Fourier Transform Infra Red (FTIR), Broad Band Cavity Enhanced Absorption Spectroscopy (BBCEAS) and a detailed photochemical chamber box modelling calculation for both GLY and MGLY. Less good agreement was found with Proton-Transfer Reaction Time-of-Flight Mass Spectrometry (PTR-ToF-MS) and Solid Phase Microextraction (SPME) derivatization methods for MGLY measurement.

Fuel-Air Mixing and Combustion in Scramjets. Chapter 6

NASA Technical Reports Server (NTRS)

Drummond, J. Philip; Diskin, Glenn S.; Cutler, Andrew D.

2006-01-01

At flight speeds, the residence time for atmospheric air ingested into a scramjet inlet and exiting from the engine nozzle is on the order of a millisecond. Therefore, fuel injected into the air must efficiently mix within tens of microseconds and react to release its energy in the combustor. The overall combustion process should be mixing controlled to provide a stable operating environment; in reality, however, combustion in the upstream portion of the combustor, particularly at higher Mach numbers, is kinetically controlled where ignition delay times are on the same order as the fluid scale. Both mixing and combustion time scales must be considered in a detailed study of mixing and reaction in a scramjet to understand the flow processes and to ultimately achieve a successful design. Although the geometric configuration of a scramjet is relatively simple compared to a turbomachinery design, the flow physics associated with the simultaneous injection of fuel from multiple injector configurations, and the mixing and combustion of that fuel downstream of the injectors is still quite complex. For this reason, many researchers have considered the more tractable problem of a spatially developing, primarily supersonic, chemically reacting mixing layer or jet that relaxes only the complexities introduced by engine geometry. All of the difficulties introduced by the fluid mechanics, combustion chemistry, and interactions between these phenomena can be retained in the reacting mixing layer, making it an ideal problem for the detailed study of supersonic reacting flow in a scramjet. With a good understanding of the physics of the scramjet internal flowfield, the designer can then return to the actual scramjet geometry with this knowledge and apply engineering design tools that more properly account for the complex physics. This approach will guide the discussion in the remainder of this section.

Electrokinetic dispersion in microfluidic separation systems

NASA Astrophysics Data System (ADS)

Molho, Joshua Irving

Numerous efforts have focused on engineering miniaturized chemical analysis devices that are faster, more portable and consume smaller volumes of expensive reagents than their macroscale counterparts. Many of these analysis devices employ electrokinetic effects to transport picoliter volumes of liquids and to separate chemical species from an initially mixed sample volume. In these microfluidic separation systems, dispersion must be minimized to obtain the highest resolution separation possible. This work focuses on modeling, simulation and experimental measurement of two electrokinetic dispersion mechanisms that can reduce the effectiveness of microfluidic separation systems: dispersion resulting from non-uniform wall zeta-potential, and dispersion caused by microchannel turns. When the surface of a microchannel has non-uniform zeta-potential (e.g., if the surface charge varies along the length of the microchannel), an applied electric field creates both electroosmotic and pressure-driven flow. A caged-fluorescence imaging technique was used to visualize the dispersion caused by this electrokinetically induced pressure-driven flow. A simple model for a single channel with an axially varying surface charge is presented and compared to experimental measurements. Microchannel turns have been shown to create dispersion of electrokinetically transported analyte bands. Using a method of moments analysis, a model is developed that quantifies this dispersion and identifies the conditions under which turn dispersion limits the resolution of a microfluidic separation system. Measurements using the caged-fluorescence visualization technique were used to verify this model. New turn geometries are presented and were optimized using both a reduced parameter technique as well as a more generalized, numerical shape optimization approach. These improved turn designs were manufactured using two fabrication techniques and then tested experimentally. The turn optimization approaches and resulting turn geometries described here are shown to reduce turn dispersion to less than 1% of the dispersion caused by unoptimized, constant-width turns.

Inertial microfluidic physics.

PubMed

Amini, Hamed; Lee, Wonhee; Di Carlo, Dino

2014-08-07

Microfluidics has experienced massive growth in the past two decades, and especially with advances in rapid prototyping researchers have explored a multitude of channel structures, fluid and particle mixtures, and integration with electrical and optical systems towards solving problems in healthcare, biological and chemical analysis, materials synthesis, and other emerging areas that can benefit from the scale, automation, or the unique physics of these systems. Inertial microfluidics, which relies on the unconventional use of fluid inertia in microfluidic platforms, is one of the emerging fields that make use of unique physical phenomena that are accessible in microscale patterned channels. Channel shapes that focus, concentrate, order, separate, transfer, and mix particles and fluids have been demonstrated, however physical underpinnings guiding these channel designs have been limited and much of the development has been based on experimentally-derived intuition. Here we aim to provide a deeper understanding of mechanisms and underlying physics in these systems which can lead to more effective and reliable designs with less iteration. To place the inertial effects into context we also discuss related fluid-induced forces present in particulate flows including forces due to non-Newtonian fluids, particle asymmetry, and particle deformability. We then highlight the inverse situation and describe the effect of the suspended particles acting on the fluid in a channel flow. Finally, we discuss the importance of structured channels, i.e. channels with boundary conditions that vary in the streamwise direction, and their potential as a means to achieve unprecedented three-dimensional control over fluid and particles in microchannels. Ultimately, we hope that an improved fundamental and quantitative understanding of inertial fluid dynamic effects can lead to unprecedented capabilities to program fluid and particle flow towards automation of biomedicine, materials synthesis, and chemical process control.

Fully solution-processed organic light-emitting electrochemical cells (OLEC) with inkjet-printed micro-lenses for disposable lab-on-chip applications at ambient conditions

NASA Astrophysics Data System (ADS)

Shu, Zhe; Pabst, Oliver; Beckert, Erik; Eberhardt, Ramona; Tünnermann, Andreas

2016-02-01

Microfluidic lab-on-chip devices can be used for chemical and biological analyses such as DNA tests or environmental monitoring. Such devices integrate most of the basic functionalities needed for scientific analysis on a microfluidic chip. When using such devices, cost and space-intensive lab equipment is no longer necessary. However, in order to make a monolithic and cost-efficient/disposable microfluidic sensing device, direct integration of the excitation light source for fluorescent sensing is often required. To achieve this, we introduce a fully solution processable deviation of OLEDs, organic light-emitting electrochemical cells (OLECs), as a low-cost excitation light source for a disposable microfluidic sensing platform. By mixing metal ions and a solid electrolyte with light-emitting polymers as active materials, an in-situ doping and in-situ PN-junction can be generated within a three layer sandwich device. Thanks to this doping effect, work function adaptation is not necessary and air-stable electrode can be used. An ambient manufacturing process for fully solution-processed OLECs is presented, which consist of a spin-coated blue light-emitting polymer plus dopants on an ITO cathode and an inkjet-printed PEDOT:PSS transparent top anode. A fully transparent blue OLEC is able to obtain light intensity > 2500 cd/m2 under pulsed driving mode and maintain stable after 1000 cycles, which fulfils requirements for simple fluorescent on-chip sensing applications. However, because of the large refractive index difference between substrates and air, about 80% of emitted light is trapped inside the device. Therefore, inkjet printed micro-lenses on the rear side are introduced here to further increase light-emitting brightness.

Electrolytic Valving Isolation for Cell Co-Culture Microenvironment with Controlled Cell Pairing Ratios

PubMed Central

Chen, Yu-Chih; Ingram, Patrick; Yoon, Euisik

2016-01-01

Cancer-stromal interaction is a critical process in tumorigenesis. Conventional dish-based co-culture assays simply mix two cell types in the same dish; thus, they are deficient in controlling cell locations and precisely tracking single cell behavior from heterogeneous cell populations. Microfluidic technology can provide a good spatial temporal control of microenvironments, but the control has been typically realized by using external pumps, making long-term cultures cumbersome and bulky. In this work, we present a cell-cell interaction microfluidic platform that can accurately control co-culture microenvironment by using a novel electrolytic cell isolation scheme without using any valves or pneumatic pumps. The proposed microfluidic platform can also precisely control the number of interacting cells and pairing ratios to emulate cancer niches. More than 80% of the chambers captured the desired number of cells. The duration of cell isolation can be adjusted by electrolytic bubble generation and removal. We verified that electrolytic process has a negligible effect on cell viability and proliferation in our platform. To the best of our knowledge, this work is the first attempt to incorporate electrolytic bubble generation as a cell isolation method in microfluidics. For proof of feasibility, we performed cell-cell interaction assays between prostate cancer (PC3) cells and myoblast (C2C12) cells. The preliminary results demonstrated the potential of using electrolysis for micro-environmental control during cell culture. Also, the ratio controlled cell-cell interaction assays was successfully performed showing that the cell pairing ratios of PC3 to C2C12 affected the proliferation rate of myoblast cells due to increased secretion of growth factors from prostate cancer cells. PMID:25118341

Numerical Analysis of Micromixers for Optimization of Mixing Action

NASA Astrophysics Data System (ADS)

Panta, Yogendra; Adhikari, Param

2011-03-01

Micro-bio/chemical applications often require rapid and uniform mixing of a number of fluid streams that carries bio/chemical species in the solution. At microscale, fluid flow is highly laminar with low Reynolds number, fluids mixing mechanism is primarily by diffusion and free from any turbulence. Demand for highly efficient micromixers for microfluidic networks is due to slower mixing process for larger bio-molecules such as peptides, proteins, and nucleic acids compared to micro-scale molecules. Passive and active mixers are two basic mixers that are currently in use for these applications. Passive mixers often require very long mixing channels where are most active mixers require bulky moving parts to stir the fluids. In this study, electroosmotic effects orthogonally aligned with the fluid flowstream are utilized for optimum mixing effect in various micromixers. Cross-dependencies among several geometrical, electrical, and fluid parameters and their significance are studied in order to achieve an optimum mixing effect. It has been planned to optimize the mixer by non-moving stirring actions provided by an external magnetic field. Acknowledgements to School of Graduate Studies and Research at YSU for URC Grant and RP Award 2009-2010.

Revisiting the Least Force Required to Keep a Block from Sliding

ERIC Educational Resources Information Center

De, Subhranil

2013-01-01

This article pertains to a problem on static friction that concerns a block of mass "M" resting on a rough inclined plane. The coefficient of static friction is microsecond and the inclination angle theta is greater than tan[superscript -1] microsecond. This means that some force "F" must be applied (see Fig. 1) to keep the…

14 CFR 171.311 - Signal format requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... zero state of the data filed represents the lower limit of the absolute range of the coded parameter... transmitted as a “zero” DPSK signal lasting for a six-bit period (see Tables 4a and 4b). Table 4a—Approach... microsecond. T0=Time separation in microseconds between TO and FRO beam centers corresponding to zero degrees...

14 CFR 171.311 - Signal format requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... zero state of the data filed represents the lower limit of the absolute range of the coded parameter... transmitted as a “zero” DPSK signal lasting for a six-bit period (see Tables 4a and 4b). Table 4a—Approach... microsecond. T0=Time separation in microseconds between TO and FRO beam centers corresponding to zero degrees...

14 CFR 171.311 - Signal format requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... zero state of the data filed represents the lower limit of the absolute range of the coded parameter... transmitted as a “zero” DPSK signal lasting for a six-bit period (see Tables 4a and 4b). Table 4a—Approach... microsecond. T0=Time separation in microseconds between TO and FRO beam centers corresponding to zero degrees...

14 CFR 171.311 - Signal format requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

... zero state of the data filed represents the lower limit of the absolute range of the coded parameter... transmitted as a “zero” DPSK signal lasting for a six-bit period (see Tables 4a and 4b). Table 4a—Approach... microsecond. T0=Time separation in microseconds between TO and FRO beam centers corresponding to zero degrees...

Nanoliter-droplet acoustic streaming via ultra high frequency surface acoustic waves.

PubMed

Shilton, Richie J; Travagliati, Marco; Beltram, Fabio; Cecchini, Marco

2014-08-06

The relevant length scales in sub-nanometer amplitude surface acoustic wave-driven acoustic streaming are demonstrated. We demonstrate the absence of any physical limitations preventing the downscaling of SAW-driven internal streaming to nanoliter microreactors and beyond by extending SAW microfluidics up to operating frequencies in the GHz range. This method is applied to nanoliter scale fluid mixing. © 2014 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Isolation of circulating tumor cells using a microvortex-generating herringbone-chip.

PubMed

Stott, Shannon L; Hsu, Chia-Hsien; Tsukrov, Dina I; Yu, Min; Miyamoto, David T; Waltman, Belinda A; Rothenberg, S Michael; Shah, Ajay M; Smas, Malgorzata E; Korir, George K; Floyd, Frederick P; Gilman, Anna J; Lord, Jenna B; Winokur, Daniel; Springer, Simeon; Irimia, Daniel; Nagrath, Sunitha; Sequist, Lecia V; Lee, Richard J; Isselbacher, Kurt J; Maheswaran, Shyamala; Haber, Daniel A; Toner, Mehmet

2010-10-26

Rare circulating tumor cells (CTCs) present in the bloodstream of patients with cancer provide a potentially accessible source for detection, characterization, and monitoring of nonhematological cancers. We previously demonstrated the effectiveness of a microfluidic device, the CTC-Chip, in capturing these epithelial cell adhesion molecule (EpCAM)-expressing cells using antibody-coated microposts. Here, we describe a high-throughput microfluidic mixing device, the herringbone-chip, or "HB-Chip," which provides an enhanced platform for CTC isolation. The HB-Chip design applies passive mixing of blood cells through the generation of microvortices to significantly increase the number of interactions between target CTCs and the antibody-coated chip surface. Efficient cell capture was validated using defined numbers of cancer cells spiked into control blood, and clinical utility was demonstrated in specimens from patients with prostate cancer. CTCs were detected in 14 of 15 (93%) patients with metastatic disease (median = 63 CTCs/mL, mean = 386 ± 238 CTCs/mL), and the tumor-specific TMPRSS2-ERG translocation was readily identified following RNA isolation and RT-PCR analysis. The use of transparent materials allowed for imaging of the captured CTCs using standard clinical histopathological stains, in addition to immunofluorescence-conjugated antibodies. In a subset of patient samples, the low shear design of the HB-Chip revealed microclusters of CTCs, previously unappreciated tumor cell aggregates that may contribute to the hematogenous dissemination of cancer.

Concentration and purification of HIV-1 virions by microfluidic separation of superparamagnetic nanoparticles

PubMed Central

Chen, Grace Dongqing; Alberts, Catharina Johanna

2009-01-01

The low concentration and complex sample matrix of many clinical and environmental viral samples presents a significant challenge in the development of low cost, point-of-care viral assays. To address this problem, we investigated the use of a microfluidic passive magnetic separator combined with on-chip mixer to both purify and concentrate whole particle HIV-1 virions. Virus-containing plasma samples are first mixed to allow specific binding of the viral particles with antibody-conjugated superparamagnetic nanoparticles, and several passive mixer geometries were assessed for their mixing efficiencies. The virus-nanoparticle complexes are then separated from the plasma in a novel magnetic separation chamber, where packed micron-sized ferromagnetic particles serve as high magnetic gradient concentrators for an externally applied magnetic field. Thereafter, a viral lysis buffer was flowed through the chip and the released HIV proteins were assayed off-chip. Viral protein extraction efficiencies of 62% and 45% were achieved at 10uL/min and 30uL/min throughputs respectively. More importantly, an 80-fold concentration was observed for an initial sample volume of 1mL, and a 44-fold concentration for an initial sample volume of 0.5mL. The system is broadly applicable to microscale sample preparation of any viral sample and can be used for nucleic acid extraction as well as 40–80 fold enrichment of target viruses. PMID:19954210

3D printed auto-mixing chip enables rapid smartphone diagnosis of anemia

PubMed Central

Plevniak, Kimberly; Campbell, Matthew; Hodges, Abby; He, Mei

2016-01-01

Clinical diagnosis requiring central facilities and site visits can be burdensome for patients in resource-limited or rural areas. Therefore, development of a low-cost test that utilizes smartphone data collection and transmission would beneficially enable disease self-management and point-of-care (POC) diagnosis. In this paper, we introduce a low-cost iPOC3D diagnostic strategy which integrates 3D design and printing of microfluidic POC device with smartphone-based disease diagnosis in one process as a stand-alone system, offering strong adaptability for establishing diagnostic capacity in resource-limited areas and low-income countries. We employ smartphone output (AutoCAD 360 app) and readout (color-scale analytical app written in-house) functionalities for rapid 3D printing of microfluidic auto-mixers and colorimetric detection of blood hemoglobin levels. The auto-mixing of reagents with blood via capillary force has been demonstrated in 1 second without the requirement of external pumps. We employed this iPOC3D system for point-of-care diagnosis of anemia using a training set of patients (nanemia = 16 and nhealthy = 6), which showed consistent measurements of blood hemoglobin levels (a.u.c. = 0.97) and comparable diagnostic sensitivity and specificity, compared with standard clinical hematology analyzer. Capable of 3D fabrication flexibility and smartphone compatibility, this work presents a novel diagnostic strategy for advancing personalized medicine and mobile healthcare. PMID:27733894

Pulsed laser activated cell sorter (PLACS) for high-throughput fluorescent mammalian cell sorting

NASA Astrophysics Data System (ADS)

Chen, Yue; Wu, Ting-Hsiang; Chung, Aram; Kung, Yu-Chung; Teitell, Michael A.; Di Carlo, Dino; Chiou, Pei-Yu

2014-09-01

We present a Pulsed Laser Activated Cell Sorter (PLACS) realized by exciting laser induced cavitation bubbles in a PDMS microfluidic channel to create high speed liquid jets to deflect detected fluorescent samples for high speed sorting. Pulse laser triggered cavitation bubbles can expand in few microseconds and provide a pressure higher than tens of MPa for fluid perturbation near the focused spot. This ultrafast switching mechanism has a complete on-off cycle less than 20 μsec. Two approaches have been utilized to achieve 3D sample focusing in PLACS. One is relying on multilayer PDMS channels to provide 3D hydrodynamic sheath flows. It offers accurate timing control of fast (2 m sec-1) passing particles so that synchronization with laser bubble excitation is possible, an critically important factor for high purity and high throughput sorting. PLACS with 3D hydrodynamic focusing is capable of sorting at 11,000 cells/sec with >95% purity, and 45,000 cells/sec with 45% purity using a single channel in a single step. We have also demonstrated 3D focusing using inertial flows in PLACS. This sheathless focusing approach requires 10 times lower initial cell concentration than that in sheath-based focusing and avoids severe sample dilution from high volume sheath flows. Inertia PLACS is capable of sorting at 10,000 particles sec-1 with >90% sort purity.

Flow characterization of electroconvective micromixer with a nanoporous polymer membrane in-situ fabricated using a laser polymerization technique

PubMed Central

Hwang, Sangbeom; Song, Simon

2015-01-01

Electroconvection is known to cause strong convective mixing in a microchannel near a nanoporous membrane or a nanochannel in contact with an electrolyte solution due to the external electric field. This study addresses micromixer behavior subject to electroconvection occurring near a nanoporous membrane in-situ fabricated by a laser polymerization technique on a microfluidic chip. We found that the micromixer behavior can be categorized into three regimes. Briefly, the weak electroconvection regime is characterized by weak mixing performance at a low applied voltage and KCl concentration, whereas the strong electroconvection regime has a high mixing performance when the applied voltage and KCl concentration are moderately high. Finally, the incomplete electroconvection regime has an incomplete electric double-layer overlap in the nanopores of the membrane when the electrolyte concentration is very high. The mixing index reached 0.92 in the strong electroconvection regime. The detailed fabrication methods for the micromixer and characterization results are discussed in this paper. PMID:26064195

Flow characterization of electroconvective micromixer with a nanoporous polymer membrane in-situ fabricated using a laser polymerization technique.

PubMed

Hwang, Sangbeom; Song, Simon

2015-05-01

Electroconvection is known to cause strong convective mixing in a microchannel near a nanoporous membrane or a nanochannel in contact with an electrolyte solution due to the external electric field. This study addresses micromixer behavior subject to electroconvection occurring near a nanoporous membrane in-situ fabricated by a laser polymerization technique on a microfluidic chip. We found that the micromixer behavior can be categorized into three regimes. Briefly, the weak electroconvection regime is characterized by weak mixing performance at a low applied voltage and KCl concentration, whereas the strong electroconvection regime has a high mixing performance when the applied voltage and KCl concentration are moderately high. Finally, the incomplete electroconvection regime has an incomplete electric double-layer overlap in the nanopores of the membrane when the electrolyte concentration is very high. The mixing index reached 0.92 in the strong electroconvection regime. The detailed fabrication methods for the micromixer and characterization results are discussed in this paper.

Chaotic micromixers using two-layer crossing channels to exhibit fast mixing at low Reynolds numbers.

PubMed

Xia, H M; Wan, S Y M; Shu, C; Chew, Y T

2005-07-01

We report two chaotic micromixers that exhibit fast mixing at low Reynolds numbers in this paper. Passive mixers usually use the channel geometry to stir the fluids, and many previously reported designs rely on inertial effects which are only available at moderate Re. In this paper, we propose two chaotic micromixers using two-layer crossing channels. Both numerical and experimental studies show that the mixers are very efficient for fluid manipulation at low Reynolds numbers, such as stretching and splitting, folding and recombination, through which chaotic advection can be generated and the mixing is significantly promoted. More importantly, the generation of chaotic advection does not rely on the fluid inertial forces, so the mixers work well at very low Re. The mixers are benchmarked against a three-dimensional serpentine mixer. Results show that the latter is inefficient at Re = 0.2, while the new design exhibits rapid mixing at Re = 0.2 and at Re of O(10(-2)). The new mixer design will benefit various microfluidic systems.

A microfluidic chip with a staircase pH gradient generator, a packed column and a fraction collector for chromatofocusing of proteins.

PubMed

Rho, Hoon Suk; Hanke, Alexander Thomas; Ottens, Marcel; Gardeniers, Han J G E

2018-04-01

A microfluidic device for pH gradient chromatofocusing is presented, which performs creation of a micro-column, pH gradient generation, and fraction collection in a single device. Using a sieve micro-valve, anion exchange particles were packed into a microchannel in order to realize a solid-phase absorption column. To fractionate proteins according to their isoelectric points, elution buffer solutions with a stepwise pH gradient were prepared in 16 parallel mixing reactors and flowed through the micro-column, wherein a protein mixture was previously loaded. The volume of the column is only 20 nL, hence it allows extremely low sample consumption and fast analysis compared with a conventional system. We demonstrated separation of two proteins, albumin-fluorescein isothiocyanate conjugate (FITC-BSA) and R-Phycoerythrin (R-PE), by using a microcolumn of commercial charged polymeric particles (Source 15Q). The microfluidic device can be used as a rapid diagnostic tool to analyse crude mixtures of proteins or nucleic acids and determine adsorption/desorption characteristics of various biochemical products, which can be helpful for scientific fundamental understanding as well as instrumental in various industrial applications, especially in early stage screening and process development. © 2018 The Authors Electrophoresis Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Single-Monomer Formulation of Polymerized Polyethylene Glycol Diacrylate as a Nonadsorptive Material for Microfluidics

PubMed Central

Rogers, Chad I.; Pagaduan, Jayson V.; Nordin, Gregory P.; Woolley, Adam T.

2011-01-01

Nonspecific adsorption in microfluidic systems can deplete target molecules in solution and prevent analytes, especially those at low concentrations, from reaching the detector. Polydimethylsiloxane (PDMS) is a widely used material for microfluidics, but is prone to nonspecific adsorption, necessitating complex chemical modification processes to address this issue. An alternative material to PDMS that does not require subsequent chemical modification is presented here. Poly(ethylene glycol) diacrylate (PEGDA) mixed with photoinitiator forms on exposure to UV radiation a polymer with inherent resistance to nonspecific adsorption. Optimization of the polymerized PEGDA (poly-PEGDA) formula imbues this material with some of the same properties, including optical clarity, water stability, and low background fluorescence, that make PDMS so popular. Poly-PEGDA demonstrates less nonspecific adsorption than PDMS over a range of concentrations of flowing fluorescently tagged bovine serum albumin solutions, and poly-PEGDA has greater resistance to permeation by small hydrophobic molecules than PDMS. Poly-PEGDA also exhibits long-term (hour scale) resistance to nonspecific adsorption compared to PDMS when exposed to a low (1 µg/mL) concentration of a model adsorptive protein. Electrophoretic separations of amino acids and proteins resulted in symmetrical peaks and theoretical plate counts as high as 4 × 105/m. Poly-PEGDA, which displays resistance to nonspecific adsorption, could have broad use in small volume analysis and biomedical research. PMID:21728310

Polymer microfluidic device replacing fluids using only capillary force

NASA Astrophysics Data System (ADS)

Chung, Kwang Hyo; Lee, Dae Sik; Yang, Haesik; Kim, Sung Jin; Pyo, Hyun Bong

2005-02-01

A novel polymer microfluidic device for self-wash using only capillary force is presented. A liquid filled in a reaction chamber is replaced by another liquid with no external actuation. All the fluidic actuations in the device is pre-programmed about time and sequence, and accomplished by capillary force naturally. Careful design is necessary for exact actions. The fluidic conduits were designed by the newly derived theoretical equations about the capillary stop pressure and flow time. Simulations using CFD-ACE+ were conducted to check the validity of theory and the performance of the chip. These analytic results were consistent with experimental ones. The chip was made of polymers for the purpose of single use and low price. It was fabricated by sealing the hot-embossed PMMA substrate with a PET film. For simpler fabrication, the chip was of a single height. The embossing master was produced from a nickel-electroplating on a SU8-patterned Ni-plate followed by CMP. The contact angles of liquids on substrates were manipulated through the mixing of surfactants, and the temporal variations were monitored for a more exact design. The real actuation steps in experiment revealed the stable performance of selfwash, and coincided well with the designed ones. The presented microfluidic method can be applicable to other LOCs of special purposes through simple modification. For example, array or serial types would be possible for multiple selfwashes.

An Integrated Microfluidic Processor for DNA-Encoded Combinatorial Library Functional Screening

PubMed Central

2017-01-01

DNA-encoded synthesis is rekindling interest in combinatorial compound libraries for drug discovery and in technology for automated and quantitative library screening. Here, we disclose a microfluidic circuit that enables functional screens of DNA-encoded compound beads. The device carries out library bead distribution into picoliter-scale assay reagent droplets, photochemical cleavage of compound from the bead, assay incubation, laser-induced fluorescence-based assay detection, and fluorescence-activated droplet sorting to isolate hits. DNA-encoded compound beads (10-μm diameter) displaying a photocleavable positive control inhibitor pepstatin A were mixed (1920 beads, 729 encoding sequences) with negative control beads (58 000 beads, 1728 encoding sequences) and screened for cathepsin D inhibition using a biochemical enzyme activity assay. The circuit sorted 1518 hit droplets for collection following 18 min incubation over a 240 min analysis. Visual inspection of a subset of droplets (1188 droplets) yielded a 24% false discovery rate (1166 pepstatin A beads; 366 negative control beads). Using template barcoding strategies, it was possible to count hit collection beads (1863) using next-generation sequencing data. Bead-specific barcodes enabled replicate counting, and the false discovery rate was reduced to 2.6% by only considering hit-encoding sequences that were observed on >2 beads. This work represents a complete distributable small molecule discovery platform, from microfluidic miniaturized automation to ultrahigh-throughput hit deconvolution by sequencing. PMID:28199790

An Integrated Microfluidic Processor for DNA-Encoded Combinatorial Library Functional Screening.

PubMed

MacConnell, Andrew B; Price, Alexander K; Paegel, Brian M

2017-03-13

DNA-encoded synthesis is rekindling interest in combinatorial compound libraries for drug discovery and in technology for automated and quantitative library screening. Here, we disclose a microfluidic circuit that enables functional screens of DNA-encoded compound beads. The device carries out library bead distribution into picoliter-scale assay reagent droplets, photochemical cleavage of compound from the bead, assay incubation, laser-induced fluorescence-based assay detection, and fluorescence-activated droplet sorting to isolate hits. DNA-encoded compound beads (10-μm diameter) displaying a photocleavable positive control inhibitor pepstatin A were mixed (1920 beads, 729 encoding sequences) with negative control beads (58 000 beads, 1728 encoding sequences) and screened for cathepsin D inhibition using a biochemical enzyme activity assay. The circuit sorted 1518 hit droplets for collection following 18 min incubation over a 240 min analysis. Visual inspection of a subset of droplets (1188 droplets) yielded a 24% false discovery rate (1166 pepstatin A beads; 366 negative control beads). Using template barcoding strategies, it was possible to count hit collection beads (1863) using next-generation sequencing data. Bead-specific barcodes enabled replicate counting, and the false discovery rate was reduced to 2.6% by only considering hit-encoding sequences that were observed on >2 beads. This work represents a complete distributable small molecule discovery platform, from microfluidic miniaturized automation to ultrahigh-throughput hit deconvolution by sequencing.

On controlling the flow behavior driven by induction electrohydrodynamics in microfluidic channels.

PubMed

Li, Yanbo; Ren, Yukun; Liu, Weiyu; Chen, Xiaoming; Tao, Ye; Jiang, Hongyuan

2017-04-01

In this study, we develop a nondimensional physical model to demonstrate fluid flow at the micrometer dimension driven by traveling-wave induction electrohydrodynamics (EHD) through direct numerical simulation. In order to realize an enhancement in the pump flow rate as well as a flexible adjustment of anisotropy of flow behavior generated by induction EHD in microchannels, while not adding the risk of causing dielectric breakdown of working solution and material for insulation, a pair of synchronized traveling-wave voltage signals are imposed on double-sided electrode arrays that are mounted on the top and bottom insulating substrate, respectively. Accordingly, we present a model evidence, that not only the pump performance is improved evidently, but a variety of flow profiles, including the symmetrical and parabolic curve, plug-like shape and even biased flow behavior of quite high anisotropy are produced by the device design of "mix-type", "superimposition-type" and "adjustable-type" proposed herein as well, with the resulting controllable fluid motion being able to greatly facilitate an on-demand transportation mode of on-chip bio-microfluidic samples. Besides, automatic conversion in the direction of pump flow is achievable by switching on and off a second voltage wave. Our results provide utilitarian guidelines for constructing flexible electrokinetic framework useful in controllable transportation of particle and fluid samples in modern microfluidic systems. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

MicrofluIdic circuit designs for performing electrokinetic manipulations that reduce the number of voltage sources and fluid reservoirs

DOEpatents

Jacobson, Stephen C.; Ramsey, J. Michael

2000-01-01

A microfabricated device and method for proportioning and mixing electrokinetically manipulated biological or chemical materials is disclosed. The microfabricated device mixes a plurality of materials in volumetric proportions controlled by the electrical resistances of tributary reagent channels through which the materials are transported. The microchip includes two or more tributary reagent channels combining at one or more junctions to form one or more mixing channels. By varying the geometries of the channels (length, cross section, etc.), a plurality of reagent materials can be mixed at a junction such that the proportions of the reagent materials in the mixing channel depend on a ratio of the channel geometries and material properties. Such an approach facilitates voltage division on the microchip without relying on external wiring schemes and voltage division techniques external to the microchip. Microchannel designs that provide the necessary voltage division to accomplish electrokinetic valving operations using a single voltage source and a switch are also described. In addition, microchannel designs that accomplish fluidic operation utilizing a minimal number of fluidic reservoirs are disclosed.

Microfluidic circuit designs for performing fluidic manipulations that reduce the number of pumping sources and fluid reservoirs

DOEpatents

Jacobson, Stephen C [Knoxville, TN; Ramsey, J Michael [Knoxville, TN

2001-01-01

A microfabricated device and method for proportioning and mixing biological or chemical materials by pressure- or vacuum-driven flow is disclosed. The microfabricated device mixes a plurality of materials in volumetric proportions controlled by the flow resistances of tributary reagent channels through which the materials are transported. The microchip includes two or more tributary reagent channels combining at one or more junctions to form one or more mixing channels. By varying the geometries of the channels (length, cross section, etc.), a plurality of reagent materials can be mixed at a junction such that the proportions of the reagent materials in the mixing channel depend on a ratio of the channel geometries and material properties. Such an approach facilitates flow division on the microchip without relying on techniques external to the microchip. Microchannel designs that provide the necessary flow division to accomplish valving operations using a minimum of pressure or vacuum sources are also described. In addition, microchannel designs that accomplish fluidic operation utilizing a minimal number of fluidic reservoirs are disclosed.

Modeling of optical mirror and electromechanical behavior

NASA Astrophysics Data System (ADS)

Wang, Fang; Lu, Chao; Liu, Zishun; Liu, Ai Q.; Zhang, Xu M.

2001-10-01

This paper presents finite element (FE) simulation and theoretical analysis of novel MEMS fiber-optical switches actuated by electrostatic attraction. FE simulation for the switches under static and dynamic loading are first carried out to reveal the mechanical characteristics of the minimum or critical switching voltages, the natural frequencies, mode shapes and response under different levels of electrostatic attraction load. To validate the FE simulation results, a theoretical (or analytical) model is then developed for one specific switch, i.e., Plate_40_104. Good agreement is found between the FE simulation and the analytical results. From both FE simulation and theoretical analysis, the critical switching voltage for Plate_40_104 is derived to be 238 V for the switching angel of 12 degree(s). The critical switching on and off times are 431 microsecond(s) and 67 microsecond(s) , respectively. The present study not only develops good FE and analytical models, but also demonstrates step by step a method to simplify a real optical switch structure with reference to the FE simulation results for analytical purpose. With the FE and analytical models, it is easy to obtain any information about the mechanical behaviors of the optical switches, which are helpful in yielding optimized design.

An easily integrative and efficient micromixer and its application to the spectroscopic detection of glucose-catalyst reactions.

PubMed

Kim, D J; Oh, H J; Park, T H; Choo, J B; Lee, S H

2005-03-01

The focus of this paper is on the fabrication of a PDMS-based passive efficient micromixer to be easily integrated into the other on-chip microfluidic system. The mixing is achieved by "strong stretching and folding," which employs a three-dimensional microchannel structure. By the simultaneously vertical and transversal dispersion of fluids, strong advection is developed. Owing to this powerful mixing performance (more than 70% of the mixing is accomplished within 2.3 mm over a wide range of Reynold number (Re)), the smaller integrative mixer can be realized. The feasibility and the potential usefulness of an integrative micromixer were evaluated by incorporating two mixers into the microchannel for the spectroscopic detection of a glucose-catalyst reaction. The results demonstrate a promising performance for diverse applications in the assay or synthesis of biological or chemical materials.

Electrokinetically driven microfluidic mixing with patchwise surface heterogeneity and AC applied electric field

NASA Astrophysics Data System (ADS)

Luo, Win-Jet; Yue, Cheng-Feng

2004-12-01

This paper investigates two-dimensional, time-dependent electroosmotic flows driven by an AC electric field via patchwise surface heterogeneities distributed along the microchannel walls. The time-dependent flow fields through the microchannel are simulated for various patchwise heterogeneous surface patterns using the backwards-Euler time stepping numerical method. Different heterogeneous surface patterns are found to create significantly different electrokinetic transport phenomena. It is shown that the presence of oppositely charged surface heterogeneities on the microchannel walls results in the formation of localized flow circulations within the bulk flow. These circulation regions grow and decay periodically in accordance with the applied periodic AC electric field intensity. The circulations provide an effective means of enhancing species mixing in the microchannel. A suitable design of the patchwise heterogeneous surface pattern permits the mixing channel length and the retention time required to attain a homogeneous solution to be reduced significantly.

Cell fusion through a microslit between adhered cells and observation of their nuclear behavior.

PubMed

Wada, Ken-Ichi; Hosokawa, Kazuo; Kondo, Eitaro; Ito, Yoshihiro; Maeda, Mizuo

2014-07-01

This paper describes a novel cell fusion method which induces cell fusion between adhered cells through a microslit for preventing nuclear mixing. For this purpose, a microfluidic device which had ∼ 100 cell pairing structures (CPSs) making cell pairs through microslits with 2.1 ± 0.3 µm width was fabricated. After trapping NIH3T3 cells with hydrodynamic forces at the CPSs, the cells were fused through the microslit by the Sendai virus envelope method. With following timelapse observation, we discovered that the spread cells were much less susceptible to nuclear migration passing through the microslit compared with round cells, and that cytoplasmic fraction containing mitochondria was transferred through the microslit without nuclear mixing. These findings will provide an effective method for cell fusion without nuclear mixing, and will lead to an efficient method for reprograming and transdifferentiation of target cells toward regenerative medicine. © 2014 Wiley Periodicals, Inc.

Development of Biopolymer Composite Films Using a Microfluidization Technique for Carboxymethylcellulose and Apple Skin Particles

PubMed Central

Choi, Inyoung; Chang, Yoonjee; Shin, So-Hyang; Joo, Eunmi; Song, Hyun Ju; Eom, Haeyoung; Han, Jaejoon

2017-01-01

Biopolymer films based on apple skin powder (ASP) and carboxymethylcellulose (CMC) were developed with the addition of apple skin extract (ASE) and tartaric acid (TA). ASP/CMC composite films were prepared by mixing CMC with ASP solution using a microfluidization technique to reduce particle size. Then, various concentrations of ASE and TA were incorporated into the film solution as an antioxidant and an antimicrobial agent, respectively. Fourier transform infrared (FTIR), optical, mechanical, water barrier, and solubility properties of the developed films were then evaluated to determine the effects of ASE and TA on physicochemical properties. The films were also analyzed for antioxidant effect on 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity and antimicrobial activities against Listeria monocytogenes, Staphylococcus aureus, Salmonella enterica, and Shigella flexneri. From the results, the ASP/CMC film containing ASE and TA was revealed to enhance the mechanical, water barrier, and solubility properties. Moreover, it showed the additional antioxidant and antimicrobial properties for application as an active packaging film. PMID:28617325

Label-free isolation of a prostate cancer cell among blood cells and the single-cell measurement of drug accumulation using an integrated microfluidic chip.

PubMed

Khamenehfar, A; Beischlag, T V; Russell, P J; Ling, M T P; Nelson, C; Li, P C H

2015-11-01

Circulating tumor cells (CTCs) are found in the blood of patients with cancer. Although these cells are rare, they can provide useful information for chemotherapy. However, isolation of these rare cells from blood is technically challenging because they are small in numbers. An integrated microfluidic chip, dubbed CTC chip, was designed and fabricated for conducting tumor cell isolation. As CTCs usually show multidrug resistance (MDR), the effect of MDR inhibitors on chemotherapeutic drug accumulation in the isolated single tumor cell is measured. As a model of CTC isolation, human prostate cancer cells were mixed with mouse blood cells and the label-free isolation of the tumor cells was conducted based on cell size difference. The major advantages of the CTC chip are the ability for fast cell isolation, followed by multiple rounds of single-cell measurements, suggesting a potential assay for detecting the drug responses based on the liquid biopsy of cancer patients.

A rapid, maskless 3D prototyping for fabrication of capillary circuits: Toward urinary protein detection.

PubMed

Yan, Sheng; Zhu, Yuanqing; Tang, Shi-Yang; Li, Yuxing; Zhao, Qianbin; Yuan, Dan; Yun, Guolin; Zhang, Jun; Zhang, Shiwu; Li, Weihua

2018-04-01

Proteinuria is an established risk marker for progressive renal function loss and patients would significantly benefit from a point-of-care testing. Although extensive work has been done to develop the microfluidic devices for the detection of urinary protein, they need the complicated operation and bulky peripherals. Here, we present a rapid, maskless 3D prototyping for fabrication of capillary fluidic circuits using laser engraving. The capillary circuits can be fabricated in a short amount of time (<10 min) without the requirements of clean-room facilities and photomasks. The advanced capillary components (e.g., trigger valves, retention valves and retention bursting valves) were fabricated, enabling the sequential liquid delivery and sample-reagent mixing. With the integration of smartphone-based detection platform, the microfluidic device can quantify the urinary protein via a colorimetric analysis. By eliminating the bulky and expensive equipment, this smartphone-based detection platform is portable for on-site quantitative detection. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Designing a Micromixer for Rolling Circle Amplification in Cancer Biomarker Detection

NASA Astrophysics Data System (ADS)

Altural, Hayriye

2015-03-01

Rolling circle amplification (RCA) is an alternative method to the Polymerase Chain Reaction based amplification for point-of-care (POC) diagnosis. In future personalized cancer diagnostic for POC applications, smaller, faster and cheaper methods are needed instead of costly and time-consuming laboratory tests. Microfluidic chips can perform the detection of cancer biomarkers within less analysis time, and provide for improvement in the sensitivity and specificity required for biochemical analysis as well. Rapid mixing is essential in the chips used in cancer diagnostic. The goal of this study is to design a micromixer for rapid RCA-based analysis and develop the assay time in cancer biomarker detection. By combining assays with micromixers, multi-step bioreactions in microfluidic chips may be achieved with minimal external control. Here, simulation results related to the micromixer are obtained by COMSOL software. The Scientific and Technological Research Council of Turkey (TUBITAK) is acknowledged for granting of H. Altural postdoctoral study in the framework of TUBITAK-BIDEB 2219-International Postdoctoral Research Scholarship Program.

Optimized holographic femtosecond laser patterning method towards rapid integration of high-quality functional devices in microchannels.

PubMed

Zhang, Chenchu; Hu, Yanlei; Du, Wenqiang; Wu, Peichao; Rao, Shenglong; Cai, Ze; Lao, Zhaoxin; Xu, Bing; Ni, Jincheng; Li, Jiawen; Zhao, Gang; Wu, Dong; Chu, Jiaru; Sugioka, Koji

2016-09-13

Rapid integration of high-quality functional devices in microchannels is in highly demand for miniature lab-on-a-chip applications. This paper demonstrates the embellishment of existing microfluidic devices with integrated micropatterns via femtosecond laser MRAF-based holographic patterning (MHP) microfabrication, which proves two-photon polymerization (TPP) based on spatial light modulator (SLM) to be a rapid and powerful technology for chip functionalization. Optimized mixed region amplitude freedom (MRAF) algorithm has been used to generate high-quality shaped focus field. Base on the optimized parameters, a single-exposure approach is developed to fabricate 200 × 200 μm microstructure arrays in less than 240 ms. Moreover, microtraps, QR code and letters are integrated into a microdevice by the advanced method for particles capture and device identification. These results indicate that such a holographic laser embellishment of microfluidic devices is simple, flexible and easy to access, which has great potential in lab-on-a-chip applications of biological culture, chemical analyses and optofluidic devices.

Optimized holographic femtosecond laser patterning method towards rapid integration of high-quality functional devices in microchannels

NASA Astrophysics Data System (ADS)

Zhang, Chenchu; Hu, Yanlei; Du, Wenqiang; Wu, Peichao; Rao, Shenglong; Cai, Ze; Lao, Zhaoxin; Xu, Bing; Ni, Jincheng; Li, Jiawen; Zhao, Gang; Wu, Dong; Chu, Jiaru; Sugioka, Koji

2016-09-01

Rapid integration of high-quality functional devices in microchannels is in highly demand for miniature lab-on-a-chip applications. This paper demonstrates the embellishment of existing microfluidic devices with integrated micropatterns via femtosecond laser MRAF-based holographic patterning (MHP) microfabrication, which proves two-photon polymerization (TPP) based on spatial light modulator (SLM) to be a rapid and powerful technology for chip functionalization. Optimized mixed region amplitude freedom (MRAF) algorithm has been used to generate high-quality shaped focus field. Base on the optimized parameters, a single-exposure approach is developed to fabricate 200 × 200 μm microstructure arrays in less than 240 ms. Moreover, microtraps, QR code and letters are integrated into a microdevice by the advanced method for particles capture and device identification. These results indicate that such a holographic laser embellishment of microfluidic devices is simple, flexible and easy to access, which has great potential in lab-on-a-chip applications of biological culture, chemical analyses and optofluidic devices.

Path-programmable water droplet manipulations on an adhesion controlled superhydrophobic surface

PubMed Central

Seo, Jungmok; Lee, Seoung-Ki; Lee, Jaehong; Seung Lee, Jung; Kwon, Hyukho; Cho, Seung-Woo; Ahn, Jong-Hyun; Lee, Taeyoon

2015-01-01

Here, we developed a novel and facile method to control the local water adhesion force of a thin and stretchable superhydrophobic polydimethylsiloxane (PDMS) substrate with micro-pillar arrays that allows the individual manipulation of droplet motions including moving, merging and mixing. When a vacuum pressure was applied below the PDMS substrate, a local dimple structure was formed and the water adhesion force of structure was significantly changed owing to the dynamically varied pillar density. With the help of the lowered water adhesion force and the slope angle of the formed dimple structure, the motion of individual water droplets could be precisely controlled, which facilitated the creation of a droplet-based microfluidic platform capable of a programmable manipulation of droplets. We showed that the platform could be used in newer and emerging microfluidic operations such as surface-enhanced Raman spectroscopy with extremely high sensing capability (10−15 M) and in vitro small interfering RNA transfection with enhanced transfection efficiency of ~80%. PMID:26202206

Microfluidic PDMS on paper (POP) devices.

PubMed

Shangguan, Jin-Wen; Liu, Yu; Pan, Jian-Bin; Xu, Bi-Yi; Xu, Jing-Juan; Chen, Hong-Yuan

2016-12-20

In this paper, we propose a generalized concept of microfluidic polydimethylsiloxane (PDMS) on paper (POP) devices, which combines well the merits of paper chips and PDMS chips. First, we optimized the conditions for accurate PDMS spatial patterning on paper, based on screen printing and a high temperature enabled superfast curing technique, which enables PDMS patterning to an accuracy of tens of microns in less than ten seconds. This, in turn, makes it available for seamless, reversible and reliable integration of the resulting paper layer with other PDMS channel structures. The integrated POP devices allow for both porous paper and smooth channels to be spatially defined on the devices, greatly extending the flexibility for designers to be able to construct powerful functional structures. To demonstrate the versatility of this design, a prototype POP device for the colorimetric analysis of liver function markers, serum protein, alkaline phosphatase (ALP) and aspartate aminotransferase (AST), was constructed. On this POP device, quantitative sample loading, mixing and multiplex analysis have all been realized.

Information transmission and signal permutation in active flow networks

NASA Astrophysics Data System (ADS)

Woodhouse, Francis G.; Fawcett, Joanna B.; Dunkel, Jörn

2018-03-01

Recent experiments show that both natural and artificial microswimmers in narrow channel-like geometries will self-organise to form steady, directed flows. This suggests that networks of flowing active matter could function as novel autonomous microfluidic devices. However, little is known about how information propagates through these far-from-equilibrium systems. Through a mathematical analogy with spin-ice vertex models, we investigate here the input–output characteristics of generic incompressible active flow networks (AFNs). Our analysis shows that information transport through an AFN is inherently different from conventional pressure or voltage driven networks. Active flows on hexagonal arrays preserve input information over longer distances than their passive counterparts and are highly sensitive to bulk topological defects, whose presence can be inferred from marginal input–output distributions alone. This sensitivity further allows controlled permutations on parallel inputs, revealing an unexpected link between active matter and group theory that can guide new microfluidic mixing strategies facilitated by active matter and aid the design of generic autonomous information transport networks.

Photothermal heating in metal-embedded microtools for material transport

NASA Astrophysics Data System (ADS)

Villangca, Mark; Palima, Darwin; Bañas, Andrew; Glückstad, Jesper

2016-03-01

Material transport is an important mechanism in microfluidics and drug delivery. The methods and solutions found in literature involve passively diffusing structures, microneedles and chemically fueled structures. In this work, we make use of optically actuated microtools with embedded metal layer as heating element for controlled loading and release. The new microtools take advantage of the photothermal-induced convection current to load and unload cargo. We also discuss some challenges encountered in realizing a self-contained polymerized microtool. Microfluidic mixing, fluid flow control and convection currents have been demonstrated both experimentally and numerically for static metal thin films or passively floating nanoparticles. Here we show an integration of aforementioned functionalities in an optically fabricated and actuated microtool. As proof of concept, we demonstrate loading and unloading of beads. This can be extended to controlled transport and release of genetic material, bio-molecules, fluorescent dyes. We envisioned these microtools to be an important addition to the portfolio of structure-mediated contemporary biophotonics.

Microfluidic networks embedded in a printed circuit board

NASA Astrophysics Data System (ADS)

Dong, Liangwei; Hu, Yueli

2017-07-01

In order to improve the robustness of microfluidic networks in printed circuit board (PCB)-based microfluidic platforms, a new method was presented. A pattern in a PCB was formed using hollowed-out technology. Polydimethylsiloxane was partly filled in the hollowed-out fields after mounting an adhesive tape on the bottom of the PCB, and solidified in an oven. Then, microfluidic networks were built using soft lithography technology. Microfluidic transportation and dilution operations were demonstrated using the fabricated microfluidic platform. Results show that this method can embed microfluidic networks into a PCB, and microfluidic operations can be implemented in the microfluidic networks embedded into the PCB.

Slightly uneven electric field trigatron employed in tens of microseconds charging time.

PubMed

Lin, Jiajin; Yang, Jianhua; Zhang, Jiande; Zhang, Huibo; Yang, Xiao

2014-09-01

To solve the issue of operation instability for the trigatron switch in the application of tens of microseconds or even less charging time, a novel trigatron spark gap with slightly uneven electric field was presented. Compared with the conventional trigatron, the novel trigatron was constructed with an obvious field enhancement on the edge of the opposite electrode. The selection of the field enhancement was analyzed based on the theory introduced by Martin. A low voltage trigatron model was constructed and tested on the tens of microseconds charging time platform. The results show that the character of relative range was improved while the trigger character still held a high level. This slightly uneven electric field typed trigatron is willing to be employed in the Tesla transformer - pulse forming line system.

A Planar Microfluidic Mixer Based on Logarithmic Spirals

PubMed Central

Scherr, Thomas; Quitadamo, Christian; Tesvich, Preston; Park, Daniel Sang-Won; Tiersch, Terrence; Hayes, Daniel; Choi, Jin-Woo; Nandakumar, Krishnaswamy

2013-01-01

A passive, planar micromixer design based on logarithmic spirals is presented. The device was fabricated using polydimethylsiloxane soft photolithography techniques, and mixing performance was characterized via numerical simulation and fluorescent microscopy. Mixing efficiency initially declined as Reynolds number increased, and this trend continued until a Reynolds number of 15 where a minimum was reached at 53%. Mixing efficiency then began to increase reaching a maximum mixing efficiency of 86% at Re = 67. Three-dimensional simulations of fluid mixing in this design were compared to other planar geometries such as the Archimedes spiral and Meandering-S mixers. The implementation of logarithmic curvature offers several unique advantages that enhance mixing, namely a variable cross-sectional area and a logarithmically varying radius of curvature that creates 3-D Dean vortices. These flow phenomena were observed in simulations with multilayered fluid folding and validated with confocal microscopy. This design provides improved mixing performance over a broader range of Reynolds numbers than other reported planar mixers, all while avoiding external force fields, more complicated fabrication processes, and the introduction of flow obstructions or cavities that may unintentionally affect sensitive or particulate-containing samples. Due to the planar design requiring only single-step lithographic features, this compact geometry could be easily implemented into existing micro-total analysis systems requiring effective rapid mixing. PMID:23956497

A planar microfluidic mixer based on logarithmic spirals

NASA Astrophysics Data System (ADS)

Scherr, Thomas; Quitadamo, Christian; Tesvich, Preston; Sang-Won Park, Daniel; Tiersch, Terrence; Hayes, Daniel; Choi, Jin-Woo; Nandakumar, Krishnaswamy; Monroe, W. Todd

2012-05-01

A passive, planar micromixer design based on logarithmic spirals is presented. The device was fabricated using polydimethylsiloxane soft photolithography techniques, and mixing performance was characterized via numerical simulation and fluorescent microscopy. Mixing efficiency initially declined as the Reynolds number increased, and this trend continued until a Reynolds number of 15 where a minimum was reached at 53%. Mixing efficiency then began to increase reaching a maximum mixing efficiency of 86% at Re = 67. Three-dimensional (3D) simulations of fluid mixing in this design were compared to other planar geometries such as the Archimedes spiral and Meandering-S mixers. The implementation of logarithmic curvature offers several unique advantages that enhance mixing, namely a variable cross-sectional area and a logarithmically varying radius of curvature that creates 3D Dean vortices. These flow phenomena were observed in simulations with multilayered fluid folding and validated with confocal microscopy. This design provides improved mixing performance over a broader range of Reynolds numbers than other reported planar mixers, all while avoiding external force fields, more complicated fabrication processes and the introduction of flow obstructions or cavities that may unintentionally affect sensitive or particulate-containing samples. Due to the planar design requiring only single-step lithographic features, this compact geometry could be easily implemented into existing micro-total analysis systems requiring effective rapid mixing.

Measurement of diurnal and semidiurnal rotational variations and tidal parameters of Earth

NASA Technical Reports Server (NTRS)

Herring, Thomas A.; Dong, Danan

1994-01-01

We discuss the determination of diurnal and semidiurnal variations in the rotation rate and the direction of rotation axis of Earth from the analysis of 8 years of very long baseline interferometry (VLBI) data. This analysis clearly show that these variations are largely periodic and tidally driven; that is, the periods of the variations correspond to the periods of the largest lunar and solar tides. For rotation rate variations, expressed in terms of changes in universal time (UT), the tidal lines with the largest observed signals are O1 (amplitude 23.5 microseconds in time (microseconds), period 25.82 solar hours); KL (18.9 microseconds, 23.93 hours); M2 (17.9 microseconds, 12.54 hours); and S2 (8.6 microseconds, 12.00 hours). For variations in the direction of the rotation axis (polar motion), significant signals exist in the retrograde semidiurnal band at the M2 and S2 tides (amplitudes 265 and 119 microarc seconds (microarc seconds, respectively); the prograde diurnal band at the O1, K1, and P1 tides (amplitudes 199, 152, and 60 microarc seconds, respectively); and the prograde semidiurnal band at the M2 and K2 tides (amplitudes 58 and 39 microarc seconds, respectively). Variations in the retrograde diurnal band are represented by corrections with previous estimates except that a previously noted discrepancy in the 13.66-day nutation (corresponding to the O1 tide) is largely removed in this new analysis. We estimate that the standard deviations of these estimates are 1.0 microseconds for the UT1 variations and 14-16 microarc seconds for the polar motion terms. These uncertainties correspond to surface displacements of approximately 0.5 mm. From the analysis of atmospheric angular momentum data we conclude that variations in UT1 excited by the atmosphere with subdaily periods are small (approximately 1 microsecond). We find that the average radial tidal displacements of the VLBI sites in the diurnal band are largely consistent with known deficiencies in current tidal models, i.e., deficiencies of up to 0.9 mm in the treatment of the free core nutation resonance. In the semidiurnal band, our analysis yields estimates of the second-degree harmonic radial Love number h(sub 2) at the M2 tide of 0.604 + i0.005 +/- 0.002. The most likely explanation for the rotational variations are the effects of ocean tides, but there may also be some contributions from atmospheric tides, the effects of triaxiality of Earth, and the equatorial second-degree-harmonic components of the core- mantle boundary.

Modelling, fabrication and characterization of a polymeric micromixer based on sequential segmentation.

PubMed

Nguyen, Nam-Trung; Huang, Xiaoyang

2006-06-01

Effective and fast mixing is important for many microfluidic applications. In many cases, mixing is limited by molecular diffusion due to constrains of the laminar flow in the microscale regime. According to scaling law, decreasing the mixing path can shorten the mixing time and enhance mixing quality. One of the techniques for reducing mixing path is sequential segmentation. This technique divides solvent and solute into segments in axial direction. The so-called Taylor-Aris dispersion can improve axial transport by three orders of magnitudes. The mixing path can be controlled by the switching frequency and the mean velocity of the flow. Mixing ratio can be controlled by pulse width modulation of the switching signal. This paper first presents a simple time-dependent one-dimensional analytical model for sequential segmentation. The model considers an arbitrary mixing ratio between solute and solvent as well as the axial Taylor-Aris dispersion. Next, a micromixer was designed and fabricated based on polymeric micromachining. The micromixer was formed by laminating four polymer layers. The layers are micro machined by a CO(2) laser. Switching of the fluid flows was realized by two piezoelectric valves. Mixing experiments were evaluated optically. The concentration profile along the mixing channel agrees qualitatively well with the analytical model. Furthermore, mixing results at different switching frequencies were investigated. Due to the dynamic behavior of the valves and the fluidic system, mixing quality decreases with increasing switching frequency.

Unconventional microfluidics: expanding the discipline.

PubMed

Nawaz, Ahmad Ahsan; Mao, Xiaole; Stratton, Zackary S; Huang, Tony Jun

2013-04-21

Since its inception, the discipline of microfluidics has been harnessed for innovations in the biomedicine/chemistry fields-and to great effect. This success has had the natural side-effect of stereotyping microfluidics as a platform for medical diagnostics and miniaturized lab processes. But microfluidics has more to offer. And very recently, some researchers have successfully applied microfluidics to fields outside its traditional domains. In this Focus article, we highlight notable examples of such "unconventional" microfluidics applications (e.g., robotics, electronics). It is our hope that these early successes in unconventional microfluidics prompt further creativity, and inspire readers to expand the microfluidics discipline.

Accelerated Biofluid Filling in Complex Microfluidic Networks by Vacuum-Pressure Accelerated Movement (V-PAM).

PubMed

Yu, Zeta Tak For; Cheung, Mei Ki; Liu, Shirley Xiaosu; Fu, Jianping

2016-09-01

Rapid fluid transport and exchange are critical operations involved in many microfluidic applications. However, conventional mechanisms used for driving fluid transport in microfluidics, such as micropumping and high pressure, can be inaccurate and difficult for implementation for integrated microfluidics containing control components and closed compartments. Here, a technology has been developed termed Vacuum-Pressure Accelerated Movement (V-PAM) capable of significantly enhancing biofluid transport in complex microfluidic environments containing dead-end channels and closed chambers. Operation of the V-PAM entails a pressurized fluid loading into microfluidic channels where gas confined inside can rapidly be dissipated through permeation through a thin, gas-permeable membrane sandwiched between microfluidic channels and a network of vacuum channels. Effects of different structural and operational parameters of the V-PAM for promoting fluid filling in microfluidic environments have been studied systematically. This work further demonstrates the applicability of V-PAM for rapid filling of temperature-sensitive hydrogels and unprocessed whole blood into complex irregular microfluidic networks such as microfluidic leaf venation patterns and blood circulatory systems. Together, the V-PAM technology provides a promising generic microfluidic tool for advanced fluid control and transport in integrated microfluidics for different microfluidic diagnosis, organs-on-chips, and biomimetic studies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Microfluidic electrochemical reactors

DOEpatents

Nuzzo, Ralph G [Champaign, IL; Mitrovski, Svetlana M [Urbana, IL

2011-03-22

A microfluidic electrochemical reactor includes an electrode and one or more microfluidic channels on the electrode, where the microfluidic channels are covered with a membrane containing a gas permeable polymer. The distance between the electrode and the membrane is less than 500 micrometers. The microfluidic electrochemical reactor can provide for increased reaction rates in electrochemical reactions using a gaseous reactant, as compared to conventional electrochemical cells. Microfluidic electrochemical reactors can be incorporated into devices for applications such as fuel cells, electrochemical analysis, microfluidic actuation, pH gradient formation.

A review of satellite time-transfer technology: Accomplishments and future applications

NASA Technical Reports Server (NTRS)

Cooper, R. S.; Chi, A. R.

1978-01-01

The research accomplishments by NASA in meeting the needs of the space program for precise time in satellite tracking are presented. As a major user of precise time signals for clock synchronization of NASA's worldwide satellite tracking networks, the agency provides much of the necessary impetus for the development of stable frequency sources and time synchronization technology. The precision time required for both satellite tracking and space science experiments has increased at a rate of about one order of magnitude per decade from 1 millisecond in the 1950's to 100 microseconds during the Apollo era in the 1960's to 10 microseconds in the 1970's. For the Tracking and Data Relay Satellite System, satellite timing requirements will be extended to 1 microsecond and below. These requirements are needed for spacecraft autonomy and data packeting.

Evaluation of electrical conductivity of Cu and Al through sub microsecond underwater electrical wire explosion

NASA Astrophysics Data System (ADS)

Sheftman, D.; Shafer, D.; Efimov, S.; Krasik, Ya. E.

2012-03-01

Sub-microsecond timescale underwater electrical wire explosions using Cu and Al materials have been conducted. Current and voltage waveforms and time-resolved streak images of the discharge channel, coupled to 1D magneto-hydrodynamic simulations, have been used to determine the electrical conductivity of the metals for the range of conditions between hot liquid metal and strongly coupled non-ideal plasma, in the temperature range of 10-60 KK. The results of these studies showed that the conductivity values obtained are typically lower than those corresponding to modern theoretical electrical conductivity models and provide a transition between the conductivity values obtained in microsecond time scale explosions and those obtained in nanosecond time scale wire explosions. In addition, the measured wire expansion shows good agreement with equation of state tables.

Recent developments in microfluidics-based chemotaxis studies.

PubMed

Wu, Jiandong; Wu, Xun; Lin, Francis

2013-07-07

Microfluidic devices can better control cellular microenvironments compared to conventional cell migration assays. Over the past few years, microfluidics-based chemotaxis studies showed a rapid growth. New strategies were developed to explore cell migration in manipulated chemical gradients. In addition to expanding the use of microfluidic devices for a broader range of cell types, microfluidic devices were used to study cell migration and chemotaxis in complex environments. Furthermore, high-throughput microfluidic chemotaxis devices and integrated microfluidic chemotaxis systems were developed for medical and commercial applications. In this article, we review recent developments in microfluidics-based chemotaxis studies and discuss the new trends in this field observed over the past few years.

Microfluidic Lab-on-a-Chip Platforms: Requirements, Characteristics and Applications

NASA Astrophysics Data System (ADS)

Mark, D.; Haeberle, S.; Roth, G.; Von Stetten, F.; Zengerle, R.

This review summarizes recent developments in microfluidic platform approaches. In contrast to isolated application-specific solutions, a microfluidic platform provides a set of fluidic unit operations, which are designed for easy combination within a well-defined fabrication technology. This allows the implementation of different application-specific (bio-) chemical processes, automated by microfluidic process integration [1]. A brief introduction into technical advances, major market segments and promising applications is followed by a detailed characterization of different microfluidic platforms, comprising a short definition, the functional principle, microfluidic unit operations, application examples as well as strengths and limitations. The microfluidic platforms in focus are lateral flow tests, linear actuated devices, pressure driven laminar flow, microfluidic large scale integration, segmented flow microfluidics, centrifugal microfluidics, electro-kinetics, electrowetting, surface acoustic waves, and systems for massively parallel analysis. The review concludes with the attempt to provide a selection scheme for microfluidic platforms which is based on their characteristics according to key requirements of different applications and market segments. Applied selection criteria comprise portability, costs of instrument and disposable, sample throughput, number of parameters per sample, reagent consumption, precision, diversity of microfluidic unit operations and the flexibility in programming different liquid handling protocols.

Rapid microfluidic mixing.

PubMed

Johnson, Timothy J; Ross, David; Locascio, Laurie E

2002-01-01

A preformed T-microchannel imprinted in polycarbonate was postmodified with a pulsed UV excimer laser (KrF, 248 nm) to create a series of slanted wells at the junction. The presence of the wells leads to a high degree of lateral transport within the channel and rapid mixing of two confluent streams undergoing electroosmotic flow. Several mixer designs were fabricated and investigated. All designs were relatively successful at low flow rates (0.06 cm/s, > or = 75% mixing), but had varying degrees of success at high flow rates (0.81 cm/s, 45-80% mixing). For example, one design operating at high flow rates was able to split an incoming fluorescent stream into two streams of varying concentrations depending on the number of slanted wells present. The final mixer design was able to overcome stream splitting at high flow rates, and it was shown that the two incoming streams were 80% mixed within 443 microm of the T-junction for a flow rate of 0.81 cm/s. Without the presence of the mixer and at the same high flow rate, a channel length of 2.3 cm would be required to achieve the same extent of mixing when relying upon molecular diffusion entirely, while 6.9 cm would be required for 99% mixing.

Using Multiorder Time-Correlation Functions (TCFs) To Elucidate Biomolecular Reaction Pathways from Microsecond Single-Molecule Fluorescence Experiments.

PubMed

Phelps, Carey; Israels, Brett; Marsh, Morgan C; von Hippel, Peter H; Marcus, Andrew H

2016-12-29

Recent advances in single-molecule fluorescence imaging have made it possible to perform measurements on microsecond time scales. Such experiments have the potential to reveal detailed information about the conformational changes in biological macromolecules, including the reaction pathways and dynamics of the rearrangements involved in processes, such as sequence-specific DNA "breathing" and the assembly of protein-nucleic acid complexes. Because microsecond-resolved single-molecule trajectories often involve "sparse" data, that is, they contain relatively few data points per unit time, they cannot be easily analyzed using the standard protocols that were developed for single-molecule experiments carried out with tens-of-millisecond time resolution and high "data density." Here, we describe a generalized approach, based on time-correlation functions, to obtain kinetic information from microsecond-resolved single-molecule fluorescence measurements. This approach can be used to identify short-lived intermediates that lie on reaction pathways connecting relatively long-lived reactant and product states. As a concrete illustration of the potential of this methodology for analyzing specific macromolecular systems, we accompany the theoretical presentation with the description of a specific biologically relevant example drawn from studies of reaction mechanisms of the assembly of the single-stranded DNA binding protein of the T4 bacteriophage replication complex onto a model DNA replication fork.

Use of microsecond current prepulse for dramatic improvements of wire array Z-pinch implosion

NASA Astrophysics Data System (ADS)

Calamy, H.; Lassalle, F.; Loyen, A.; Zucchini, F.; Chittenden, J. P.; Hamann, F.; Maury, P.; Georges, A.; Bedoch, J. P.; Morell, A.

2008-01-01

The Sphinx machine [F. Lassalle et al., "Status on the SPHINX machine based on the 1microsecond LTD technology"] based on microsecond linear transformer driver (LTD) technology is used to implode an aluminium wire array with an outer diameter up to 140mm and maximum current from 3.5to5MA. 700to800ns implosion Z-pinch experiments are performed on this driver essentially with aluminium. Best results obtained before the improvement described in this paper were 1-3TW radial total power, 100-300kJ total yield, and 20-30kJ energy above 1keV. An auxiliary generator was added to the Sphinx machine in order to allow a multi microsecond current to be injected through the wire array load before the start of the main current. Amplitude and duration of this current prepulse are adjustable, with maxima ˜10kA and 50μs. This prepulse dramatically changes the ablation phase leading to an improvement of the axial homogeneity of both the implosion and the final radiating column. Total power was multiplied by a factor of 6, total yield by a factor of 2.5 with a reproducible behavior. This paper presents experimental results, magnetohydrodynamic simulations, and analysis of the effect of such a long current prepulse.

Pulsed Electron Beam Water Radiolysis for Sub-Microsecond Hydroxyl Radical Protein Footprinting

PubMed Central

Watson, Caroline; Janik, Ireneusz; Zhuang, Tiandi; Charvátová, Olga; Woods, Robert J.; Sharp, Joshua S.

2009-01-01

Hydroxyl radical footprinting is a valuable technique for studying protein structure, but care must be taken to ensure that the protein does not unfold during the labeling process due to oxidative damage. Footprinting methods based on sub-microsecond laser photolysis of peroxide that complete the labeling process faster than the protein can unfold have been recently described; however, the mere presence of large amounts of hydrogen peroxide can also cause uncontrolled oxidation and minor conformational changes. We have developed a novel method for sub-microsecond hydroxyl radical protein footprinting using a pulsed electron beam from a 2 MeV Van de Graaff electron accelerator to generate a high concentration of hydroxyl radicals by radiolysis of water. The amount of oxidation can be controlled by buffer composition, pulsewidth, dose, and dissolved nitrous oxide gas in the sample. Our results with ubiquitin and β-lactoglobulin A demonstrate that one sub-microsecond electron beam pulse produces extensive protein surface modifications. Highly reactive residues that are buried within the protein structure are not oxidized, indicating that the protein retains its folded structure during the labeling process. Time-resolved spectroscopy indicates that the major part of protein oxidation is complete in a timescale shorter than that of large scale protein motions. PMID:19265387

Synthetic microfluidic paper: high surface area and high porosity polymer micropillar arrays.

PubMed

Hansson, Jonas; Yasuga, Hiroki; Haraldsson, Tommy; van der Wijngaart, Wouter

2016-01-21

We introduce Synthetic Microfluidic Paper, a novel porous material for microfluidic applications that consists of an OSTE polymer that is photostructured in a well-controlled geometry of slanted and interlocked micropillars. We demonstrate the distinct benefits of Synthetic Microfluidic Paper over other porous microfluidic materials, such as nitrocellulose, traditional paper and straight micropillar arrays: in contrast to straight micropillar arrays, the geometry of Synthetic Microfluidic Paper was miniaturized without suffering capillary collapse during manufacturing and fluidic operation, resulting in a six-fold increased internal surface area and a three-fold increased porous fraction. Compared to commercial nitrocellulose materials for capillary assays, Synthetic Microfluidic Paper shows a wider range of capillary pumping speed and four times lower device-to-device variation. Compared to the surfaces of the other porous microfluidic materials that are modified by adsorption, Synthetic Microfluidic Paper contains free thiol groups and has been shown to be suitable for covalent surface chemistry, demonstrated here for increasing the material hydrophilicity. These results illustrate the potential of Synthetic Microfluidic Paper as a porous microfluidic material with improved performance characteristics, especially for bioassay applications such as diagnostic tests.

Passive microfluidic array card and reader

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

Dugan, Lawrence Christopher; Coleman, Matthew A

A microfluidic array card and reader system for analyzing a sample. The microfluidic array card includes a sample loading section for loading the sample onto the microfluidic array card, a multiplicity of array windows, and a transport section or sections for transporting the sample from the sample loading section to the array windows. The microfluidic array card reader includes a housing, a receiving section for receiving the microfluidic array card, a viewing section, and a light source that directs light to the array window of the microfluidic array card and to the viewing section.

EDITORIAL: Focus on Micro- and Nanofluidics FOCUS ON MICRO- AND NANOFLUIDICS

NASA Astrophysics Data System (ADS)

Ajdari, Armand; Stone, Howard A.

2009-07-01

This focus issue of New Journal of Physics concentrates on recent developments in microfluidics, and related small-scale flow themes. This subject touches on many areas with the common element that they are engaged with understanding, measuring or manipulating flows at the scale of a few hundred microns or smaller. Microfluidics is of interest to many scientists and engineers from many disciplines because it is a toolbox from which they can investigate basic questions in their respective fields. In particular, the field has led to new studies of small-scale fluid flows, especially those dominated by surface effects, which is crucial for understanding electrokinetics, chemical reactions and phase changes, and multiphase systems, including those involving dispersed liquid and gas phases, suspended particles, cells, vesicles, capsules, etc. The lower length scale of these kinds of flows concerns nanoscale manipulation of objects such as DNA or nanoparticles, nanofabrication of surfaces, studies of the flow within nanometers of substrates, etc. Microfluidics has also given rise to technologies because it enables design and implementation of new devices for sensing, detection, measurement, materials characterization, combinatorial discovery, cellular-scale manipulation, miniaturization of reactors, etc. The fact that these systems are small, cheap, physically flexible, portable, multifunctional, and, when they are working, produce measurements quickly, offers many new avenues for innovation. In this issue we highlight contributions from around the world that explore research directions inspired by the manifold possibilities of microfluidics. In particular, the papers include reports of single-phase flows that are driven by electrical fields, so-called electrokinetics. Although the field has its origins in the 19th century, if not even earlier, new theoretical ideas are required to understand dynamics close to charged surfaces, and new applications of the basic ideas are being introduced for driving flows and manipulating suspended particles (e.g. DNA). In addition, the subject of mixing and the study of transport processes coupling diffusion and convection is a necessary component of many studies aimed at lab-on-a-chip environments. At the other extreme from mixing there is interest in the precise placement of particles in microfluidic flows. Although the majority of microfluidic studies focus on the consequences of low Reynolds number motions, the flows can frequently have large enough particle-scale Reynolds numbers that inertial effects can appear. Also, chemical gradients, via osmotic effects, can be significant, and, where surface effects are significant, particle deposition can occur. Multiphase flows constitute another major area of microfluidic research. For example, there has been great interest in using drops as individual containers since both the chemical composition inside and outside the drop can be controlled. Also, the interface between the two phases provides both a natural chemical barrier (surfactants are generally added to reduce the probability of coalescence between drops) as well as potentially being the site for reactions or localized organization of particles suspended in solution. Thus, there is interest in both the controlled breakup of liquid threads, the dynamics of such a thread, which can fold or buckle, and application of these processes to fabricating new materials. Not surprisingly the themes mentioned in this short summary are just a small window into the myriad of ideas being investigated in the research world of small-scale flows that is the playground of micro- and nanofluidics. We are grateful to all of the contributors for their efforts and to the referees, whose feedback has added value to every contribution. We hope you, as readers, will find benefit in the many ideas discussed in this Focus on Micro- and Nanofluidics, which represents a sampling of current activity, including experiment, simulation and theory, in this rapidly developing field. Focus on Micro- and Nanofluidics Contents The anti-lotus leaf effect in nanohydrodynamic bump arrays Keith Morton, Ophelia K C Tsui, Chih-Kuan Tung, James C Sturm, Stephen Y Chou and Robert Austin Transport in nanofluidic systems: a review of theory and applications W Sparreboom, A van den Berg and J C T Eijkel The effects of polymer molecular weight on filament thinning and drop breakup in microchannels P E Arratia, L-A Cramer, J P Gollub and D J Durian Mass transfer and interfacial properties in two-phase microchannel flows Jeffrey D Martin and Steven D Hudson Temporal response of an initially deflected PDMS channel Priyadarshi Panda, Kai P Yuet, Dhananjay Dendukuri, T Alan Hatton and Patrick S Doyle Gas-liquid two-phase flow patterns in rectangular polymeric microchannels: effect of surface wetting properties D Huh, C-H Kuo, J B Grotberg and S Takayama Mixing via thermocapillary generation of flow patterns inside a microfluidic drop María Luisa Cordero, Hans Olav Rolfsnes, Daniel R Burnham, Paul A Campbell, David McGloin and Charles N Baroud Pressure-driven DNA transport across an artificial nanotopography J T Del Bonis-O'Donnell, W Reisner and D Stein Eulerian indicators for predicting and optimizing mixing quality Rob Sturman and Stephen Wiggins Asymmetric flows over symmetric surfaces: capacitive coupling in induced-charge electro-osmosis T S Mansuripur, A J Pascall and T M Squires High-viscosity fluid threads in weakly diffusive microfluidic systems T Cubaud and T G Mason Interfacial mass transport in steady three-dimensional flows in microchannels Joseph D Kirtland, Corey R Siegel and Abraham D Stroock Active connectors for microfluidic drops on demand Jean-Christophe Galas, Denis Bartolo and Vincent Studer Electrokinetic control of sample splitting at a channel bifurcation using isotachophoresis Alexandre Persat and Juan G Santiago Differential inertial focusing of particles in curved low-aspect-ratio microchannels Aman Russom, Amit K Gupta, Sunitha Nagrath, Dino Di Carlo, Jon F Edd and Mehmet Toner Capillary instability on a hydrophilic stripe Raymond L Speth and Eric Lauga Universal nanocolloid deposition patterns: can you see the harmonics of a Taylor cone? Xinguang Cheng and Hsueh-Chia Chang Osmotic manipulation of particles for microfluidic applications B Abécassis, C Cottin-Bizonne, C Ybert, A Ajdari and L Bocquet Scaling the drop size in coflow experiments E Castro-Hernández, V Gundabala, A Fernández-Nieves and J M Gordillo Pattern formation during the evaporation of a colloidal nanoliter drop: a numerical and experimental study Rajneesh Bhardwaj, Xiaohua Fang and Daniel Attinger Topology and shape optimization of induced-charge electro-osmotic micropumps M M Gregersen, F Okkels, M Z Bazant and H Bruus Fabrication of multiphasic and regio-specifically functionalized PRINT® particles of controlled size and shape H Zhang, J K Nunes, S E A Gratton, K P Herlihy, P D Pohlhaus and J M DeSimone Using TIRF microscopy to quantify and confirm efficient mass transfer at the substrate surface of the chemistrode Delai Chen, Wenbin Du and Rustem F Ismagilov Nonlinear electrokinetics at large voltages Martin Z Bazant, Mustafa Sabri Kilic, Brian D Storey and Armand Ajdari Interdiffusion of liquids of different viscosities in a microchannel J Dambrine, B Géraud and J-B Salmon Microfluidic fabrication of microparticles with structural complexity using photocurable emulsion droplets Shin-Hyun Kim, Jae Won Shim, Jong-Min Lim, Su Yeon Lee and Seung-Man Yang

A serpentine laminating micromixer combining splitting/recombination and advection.

PubMed

Kim, Dong Sung; Lee, Se Hwan; Kwon, Tai Hun; Ahn, Chong H

2005-07-01

Mixing enhancement has drawn great attention from designers of micromixers, since the flow in a microchannel is usually characterized by a low Reynolds number (Re) which makes the mixing quite a difficult task to accomplish. In this paper, a novel integrated efficient micromixer named serpentine laminating micromixer (SLM) has been designed, simulated, fabricated and fully characterized. In the SLM, a high level of efficient mixing can be achieved by combining two general chaotic mixing mechanisms: splitting/recombination and chaotic advection. The splitting and recombination (in other terms, lamination) mechanism is obtained by the successive arrangement of "F"-shape mixing units in two layers. The advection is induced by the overall three-dimensional serpentine path of the microchannel. The SLM was realized by SU-8 photolithography, nickel electroplating, injection molding and thermal bonding. Mixing performance of the SLM was fully characterized numerically and experimentally. The numerical mixing simulations show that the advection acts favorably to realize the ideal vertical lamination of fluid flow. The mixing experiments based on an average mixing color intensity change of phenolphthalein show a high level of mixing performance was obtained with the SLM. Numerical and experimental results confirm that efficient mixing is successfully achieved from the SLM over the wide range of Re. Due to the simple and mass producible geometry of the efficient micromixer, SLM proposed in this study, the SLM can be easily applied to integrated microfluidic systems, such as micro-total-analysis-systems or lab-on-a-chip systems.

Rapid microfluidic thermal cycler for nucleic acid amplification

DOEpatents

Beer, Neil Reginald; Vafai, Kambiz

2015-10-27

A system for thermal cycling a material to be thermal cycled including a microfluidic heat exchanger; a porous medium in the microfluidic heat exchanger; a microfluidic thermal cycling chamber containing the material to be thermal cycled, the microfluidic thermal cycling chamber operatively connected to the microfluidic heat exchanger; a working fluid at first temperature; a first system for transmitting the working fluid at first temperature to the microfluidic heat exchanger; a working fluid at a second temperature, a second system for transmitting the working fluid at second temperature to the microfluidic heat exchanger; a pump for flowing the working fluid at the first temperature from the first system to the microfluidic heat exchanger and through the porous medium; and flowing the working fluid at the second temperature from the second system to the heat exchanger and through the porous medium.

Design of an interface to allow microfluidic electrophoresis chips to drink from the fire hose of the external environment.

PubMed

Attiya, S; Jemere, A B; Tang, T; Fitzpatrick, G; Seiler, K; Chiem, N; Harrison, D J

2001-01-01

An interface design is presented that facilitates automated sample introduction into an electrokinetic microchip, without perturbing the liquids within the microfluidic device. The design utilizes an interface flow channel with a volume flow resistance that is 0.54-4.1 x 10(6) times lower than the volume flow resistance of the electrokinetic fluid manifold used for mixing, reaction, separation, and analysis. A channel, 300 microm deep, 1 mm wide and 15-20 mm long, was etched in glass substrates to create the sample introduction channel (SIC) for a manifold of electrokinetic flow channels in the range of 10-13 microm depth and 36-275 microm width. Volume flow rates of up to 1 mL/min were pumped through the SIC without perturbing the solutions within the electrokinetic channel manifold. Calculations support this observation, suggesting a leakage flow to electroosmotic flow ratio of 0.1:1% in the electrokinetic channels, arising from 66-700 microL/min pressure-driven flow rates in the SIC. Peak heights for capillary electrophoresis separations in the electrokinetic flow manifold showed no dependence on whether the SIC pump was on or off. On-chip mixing, reaction and separation of anti-ovalbumin and ovalbumin could be performed with good quantitative results, independent of the SIC pump operation. Reproducibility of injection performance, estimated from peak height variations, ranged from 1.5-4%, depending upon the device design and the sample composition.

Measurements of Elastic Moduli of Silicone Gel Substrates with a Microfluidic Device

PubMed Central

Gutierrez, Edgar; Groisman, Alex

2011-01-01

Thin layers of gels with mechanical properties mimicking animal tissues are widely used to study the rigidity sensing of adherent animal cells and to measure forces applied by cells to their substrate with traction force microscopy. The gels are usually based on polyacrylamide and their elastic modulus is measured with an atomic force microscope (AFM). Here we present a simple microfluidic device that generates high shear stresses in a laminar flow above a gel-coated substrate and apply the device to gels with elastic moduli in a range from 0.4 to 300 kPa that are all prepared by mixing two components of a transparent commercial silicone Sylgard 184. The elastic modulus is measured by tracking beads on the gel surface under a wide-field fluorescence microscope without any other specialized equipment. The measurements have small and simple to estimate errors and their results are confirmed by conventional tensile tests. A master curve is obtained relating the mixing ratios of the two components of Sylgard 184 with the resulting elastic moduli of the gels. The rigidity of the silicone gels is less susceptible to effects from drying, swelling, and aging than polyacrylamide gels and can be easily coated with fluorescent tracer particles and with molecules promoting cellular adhesion. This work can lead to broader use of silicone gels in the cell biology laboratory and to improved repeatability and accuracy of cell traction force microscopy and rigidity sensing experiments. PMID:21980487

3D printed auto-mixing chip enables rapid smartphone diagnosis of anemia.

PubMed

Plevniak, Kimberly; Campbell, Matthew; Myers, Timothy; Hodges, Abby; He, Mei

2016-09-01

Clinical diagnosis requiring central facilities and site visits can be burdensome for patients in resource-limited or rural areas. Therefore, development of a low-cost test that utilizes smartphone data collection and transmission would beneficially enable disease self-management and point-of-care (POC) diagnosis. In this paper, we introduce a low-cost i POC 3D diagnostic strategy which integrates 3D design and printing of microfluidic POC device with smartphone-based disease diagnosis in one process as a stand-alone system, offering strong adaptability for establishing diagnostic capacity in resource-limited areas and low-income countries. We employ smartphone output (AutoCAD 360 app) and readout (color-scale analytical app written in-house) functionalities for rapid 3D printing of microfluidic auto-mixers and colorimetric detection of blood hemoglobin levels. The auto-mixing of reagents with blood via capillary force has been demonstrated in 1 second without the requirement of external pumps. We employed this i POC 3D system for point-of-care diagnosis of anemia using a training set of patients (n anemia  = 16 and n healthy  = 6), which showed consistent measurements of blood hemoglobin levels (a.u.c. = 0.97) and comparable diagnostic sensitivity and specificity, compared with standard clinical hematology analyzer. Capable of 3D fabrication flexibility and smartphone compatibility, this work presents a novel diagnostic strategy for advancing personalized medicine and mobile healthcare.

Development of microLIPS (Luciferase Immunoprecipitation Systems): a novel microfluidic assay for rapid serum antibody detection

NASA Astrophysics Data System (ADS)

Chandrangsu, Matt; Burbelo, Peter D.; Iadarola, Michael J.; Smith, Paul D.; Morgan, Nicole Y.

2012-06-01

There is considerable interest in the development of rapid, point-of-care antibody detection for the diagnosis of infectious and auto-immune diseases. In this paper, we present work on the development of a self-contained microfluidic format for the Luciferase Immunoprecipitation Systems (LIPS) assay. Whereas the majority of immunoassays for antigen-specific antibodies employ either bacteria- or yeast-expressed proteins and require the use of secondary antibodies, the LIPS technique uses a fusion protein comprised of a Renilla luciferase reporter and the antigen of interest produced via mammalian cell culture, ensuring the addition of mammalian post-translational modifications. Patient serum is mixed with the fusion protein and passed over immobilized Protein A/G; after washing, the only remaining luciferase-tagged antigens are those retained by specific antibodies. These can be quantitatively measured using chemiluminescence upon the introduction of coelenterazine. The assay has been successfully employed for a wide variety of diseases in a microwell format. We report on a recent demonstration of rapid HSV-2 diagnosis with the LIPS assay in a microfluidic format, using one microliter of serum and obtaining results in under ten minutes. We will also discuss recent progress on two fronts, both aimed at the deployment of this technology in the field: first, simplifying assay operation through the automation of flow control using power-free means; and second, efforts to increase signal levels, primarily through strategies to increase antibody binding capacity, in order to move towards portable battery powered electronics.

Droplet-based microfluidic flow injection system with large-scale concentration gradient by a single nanoliter-scale injection for enzyme inhibition assay.

PubMed

Cai, Long-Fei; Zhu, Ying; Du, Guan-Sheng; Fang, Qun

2012-01-03

We described a microfluidic chip-based system capable of generating droplet array with a large scale concentration gradient by coupling flow injection gradient technique with droplet-based microfluidics. Multiple modules including sample injection, sample dispersion, gradient generation, droplet formation, mixing of sample and reagents, and online reaction within the droplets were integrated into the microchip. In the system, nanoliter-scale sample solution was automatically injected into the chip under valveless flow injection analysis mode. The sample zone was first dispersed in the microchannel to form a concentration gradient along the axial direction of the microchannel and then segmented into a linear array of droplets by immiscible oil phase. With the segmentation and protection of the oil phase, the concentration gradient profile of the sample was preserved in the droplet array with high fidelity. With a single injection of 16 nL of sample solution, an array of droplets with concentration gradient spanning 3-4 orders of magnitude could be generated. The present system was applied in the enzyme inhibition assay of β-galactosidase to preliminarily demonstrate its potential in high throughput drug screening. With a single injection of 16 nL of inhibitor solution, more than 240 in-droplet enzyme inhibition reactions with different inhibitor concentrations could be performed with an analysis time of 2.5 min. Compared with multiwell plate-based screening systems, the inhibitor consumption was reduced 1000-fold. © 2011 American Chemical Society

Development of Droplet Microfluidics Enabling High-Throughput Single-Cell Analysis.

PubMed

Wen, Na; Zhao, Zhan; Fan, Beiyuan; Chen, Deyong; Men, Dong; Wang, Junbo; Chen, Jian

2016-07-05

This article reviews recent developments in droplet microfluidics enabling high-throughput single-cell analysis. Five key aspects in this field are included in this review: (1) prototype demonstration of single-cell encapsulation in microfluidic droplets; (2) technical improvements of single-cell encapsulation in microfluidic droplets; (3) microfluidic droplets enabling single-cell proteomic analysis; (4) microfluidic droplets enabling single-cell genomic analysis; and (5) integrated microfluidic droplet systems enabling single-cell screening. We examine the advantages and limitations of each technique and discuss future research opportunities by focusing on key performances of throughput, multifunctionality, and absolute quantification.

Microfluidics and Raman microscopy: current applications and future challenges.

PubMed

Chrimes, Adam F; Khoshmanesh, Khashayar; Stoddart, Paul R; Mitchell, Arnan; Kalantar-Zadeh, Kourosh

2013-07-07

Raman microscopy systems are becoming increasingly widespread and accessible for characterising chemical species. Microfluidic systems are also progressively finding their way into real world applications. Therefore, it is anticipated that the integration of Raman systems with microfluidics will become increasingly attractive and practical. This review aims to provide an overview of Raman microscopy-microfluidics integrated systems for researchers who are actively interested in utilising these tools. The fundamental principles and application strengths of Raman microscopy are discussed in the context of microfluidics. Various configurations of microfluidics that incorporate Raman microscopy methods are presented, with applications highlighted. Data analysis methods are discussed, with a focus on assisting the interpretation of Raman-microfluidics data from complex samples. Finally, possible future directions of Raman-microfluidic systems are presented.

Dual-nozzle microfluidic droplet generator

NASA Astrophysics Data System (ADS)

Choi, Ji Wook; Lee, Jong Min; Kim, Tae Hyun; Ha, Jang Ho; Ahrberg, Christian D.; Chung, Bong Geun

2018-05-01

The droplet-generating microfluidics has become an important technique for a variety of applications ranging from single cell analysis to nanoparticle synthesis. Although there are a large number of methods for generating and experimenting with droplets on microfluidic devices, the dispensing of droplets from these microfluidic devices is a challenge due to aggregation and merging of droplets at the interface of microfluidic devices. Here, we present a microfluidic dual-nozzle device for the generation and dispensing of uniform-sized droplets. The first nozzle of the microfluidic device is used for the generation of the droplets, while the second nozzle can accelerate the droplets and increase the spacing between them, allowing for facile dispensing of droplets. Computational fluid dynamic simulations were conducted to optimize the design parameters of the microfluidic device.

Microfluidics on liquid handling stations (μF-on-LHS): an industry compatible chip interface between microfluidics and automated liquid handling stations.

PubMed

Waldbaur, Ansgar; Kittelmann, Jörg; Radtke, Carsten P; Hubbuch, Jürgen; Rapp, Bastian E

2013-06-21

We describe a generic microfluidic interface design that allows the connection of microfluidic chips to established industrial liquid handling stations (LHS). A molding tool has been designed that allows fabrication of low-cost disposable polydimethylsiloxane (PDMS) chips with interfaces that provide convenient and reversible connection of the microfluidic chip to industrial LHS. The concept allows complete freedom of design for the microfluidic chip itself. In this setup all peripheral fluidic components (such as valves and pumps) usually required for microfluidic experiments are provided by the LHS. Experiments (including readout) can be carried out fully automated using the hardware and software provided by LHS manufacturer. Our approach uses a chip interface that is compatible with widely used and industrially established LHS which is a significant advancement towards near-industrial experimental design in microfluidics and will greatly facilitate the acceptance and translation of microfluidics technology in industry.

Wavelet Domain Characterization & Localization of Modal Acoustic Emissions in Aircraft Aluminum

DTIC Science & Technology

1996-04-01

50 100 0 50 100 S0.5 05 •0.51777W W W-0ý5F: < 0 50 100 0 50 100 0.5 05 0KI ~A4 -0 oH 0 -0 50 100 0 50 100 Time (microseconds) Time (microseconds...of frequency with time. novel approach based on wide band processing. The method can be considered a time domain spectroscopy ( TDS ) technique where the

Investigations of large area electron beam diodes for excimer lasers. Final report

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

Not Available

1993-12-31

This report summarizes the results of a one year research program at the University of Michigan to investigate the physics and technology of microsecond electron beam diodes. These experiments were performed on the Michigan Electron Long Beam Accelerator (MELBA) at parameters: Voltage {equals} {minus}0.65 to {minus}0.9 MV, current {equals} 1 {minus}50 kA, and pulselength {equals} 0.5 {minus} 5 microseconds. Major accomplishments include: (1) the first two-wavelength (CO2 and HeNe) laser deflection measurements of diode plasma and neutrals; (2) measurements of the effects on magnetic field gradient on microsecond diode closure; (3) demonstration of good fidelity of processed x-ray signals asmore » a diagnostic of beam voltage; (4) extended-pulselength scaling of electron beam diode arcing and diode closure; and (5) innovative Cerenkov plate diagnostics of e-beam dynamics.« less

Analyzing ion distributions around DNA: sequence-dependence of potassium ion distributions from microsecond molecular dynamics

PubMed Central

Pasi, Marco; Maddocks, John H.; Lavery, Richard

2015-01-01

Microsecond molecular dynamics simulations of B-DNA oligomers carried out in an aqueous environment with a physiological salt concentration enable us to perform a detailed analysis of how potassium ions interact with the double helix. The oligomers studied contain all 136 distinct tetranucleotides and we are thus able to make a comprehensive analysis of base sequence effects. Using a recently developed curvilinear helicoidal coordinate method we are able to analyze the details of ion populations and densities within the major and minor grooves and in the space surrounding DNA. The results show higher ion populations than have typically been observed in earlier studies and sequence effects that go beyond the nature of individual base pairs or base pair steps. We also show that, in some special cases, ion distributions converge very slowly and, on a microsecond timescale, do not reflect the symmetry of the corresponding base sequence. PMID:25662221

Microsecond MD Simulations of Nano-patterned Polymer Brushes on Self-Assembled Monolayers

NASA Astrophysics Data System (ADS)

Buie, Creighton; Qiu, Liming; Cheng, Kwan; Park, Soyeun

2010-03-01

Nano-patterned polymer brushes end-grafted onto self-assembled monolayers have gained increasing research interests due to their unique thermodynamic properties and their chemical and biomedical applications in colloids, biosensing and tissue engineering. So far, the interactions between the polymer brushes with the surrounding environments such as the floor and solvent at the nanometer length scale and microsecond time scale are still difficult to obtained experimentally and computationally. Using a Coarse-Grained MD approach, polymer brushes of different monomeric lengths, grafting density and hydrophobicity of the monomers grafted on self-assembled monolayers and in explicit solvent were studied. Molecular level information, such as lateral diffusion, transverse height and volume contour of the brushes, were calculated from our microsecond-MD simulations. Our results demonstrated the significance of the hydration of the polymer in controlling the conformational arrangement of the polymer brushes.

High efficiency laser-assisted H - charge exchange for microsecond duration beams

DOE PAGES

Cousineau, Sarah; Rakhman, Abdurahim; Kay, Martin; ...

2017-12-26

Laser-assisted stripping is a novel approach to H - charge exchange that overcomes long-standing limitations associated with the traditional, foil-based method of producing high-intensity, time-structured beams of protons. This paper reports on the first successful demonstration of the laser stripping technique for microsecond duration beams. The experiment represents a factor of 1000 increase in the stripped pulse duration compared with the previous proof-of-principle demonstration. The central theme of the experiment is the implementation of methods to reduce the required average laser power such that high efficiency stripping can be accomplished for microsecond duration beams using conventional laser technology. In conclusion,more » the experiment was performed on the Spallation Neutron Source 1 GeV H - beam using a 1 MW peak power UV laser and resulted in ~95% stripping efficiency.« less

High efficiency laser-assisted H - charge exchange for microsecond duration beams

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

Cousineau, Sarah; Rakhman, Abdurahim; Kay, Martin

Laser-assisted stripping is a novel approach to H - charge exchange that overcomes long-standing limitations associated with the traditional, foil-based method of producing high-intensity, time-structured beams of protons. This paper reports on the first successful demonstration of the laser stripping technique for microsecond duration beams. The experiment represents a factor of 1000 increase in the stripped pulse duration compared with the previous proof-of-principle demonstration. The central theme of the experiment is the implementation of methods to reduce the required average laser power such that high efficiency stripping can be accomplished for microsecond duration beams using conventional laser technology. In conclusion,more » the experiment was performed on the Spallation Neutron Source 1 GeV H - beam using a 1 MW peak power UV laser and resulted in ~95% stripping efficiency.« less

Numerical investigation on layout optimization of obstacles in a three-dimensional passive micromixer.

PubMed

Chen, Xueye; Zhao, Zhongyi

2017-04-29

This paper aims at layout optimization design of obstacles in a three-dimensional T-type micromixer. Numerical analysis shows that the direction of flow velocity change constantly due to the obstacles blocking, which produces the chaotic convection and increases species mixing effectively. The orthogonal experiment method was applied for determining the effects of some key parameters on mixing efficiency. The weights in the order are: height of obstacles > geometric shape > symmetry = number of obstacles. Based on the optimized results, a multi-units obstacle micromixer was designed. Compared with T-type micromixer, the multi-units obstacle micromixer is more efficient, and more than 90% mixing efficiency were obtained for a wide range of peclet numbers. It can be demonstrated that the presented optimal design method of obstacles layout in three-dimensional microchannels is a simple and effective technology to improve species mixing in microfluidic devices. The obstacles layout methodology has the potential for applications in chemical engineering and bioengineering. Copyright © 2017 Elsevier B.V. All rights reserved.

Dynamics of a nuclear invasion

NASA Astrophysics Data System (ADS)

Roper, Marcus; Simonin, Anna; Glass, N. Louise

2009-11-01

Filamentous fungi grow as a network of continuous interconnected tubes, containing nuclei that move freely through a shared cytoplasm. Wild fungi are frequently chimerical: two nuclei from the same physiological individual may be genetically different. Such internal diversity can arise either from spontaneous mutations during nuclear division, or by nuclear exchange when two individuals fuse, sharing their resources and organelles to become a single individual. This diversity is thought to be essential to adaptation in plant pathogens, allowing, for instance, an invading fungus to present many different genetic identities against its host's immune response. However, it is clear that the presence of multiple genetic lineages within the same physiological individual can also pose challenges - lineages that are present in growing hyphal tips will multiply preferentially. Nuclei must therefore be kept well mixed across a growing front. By applying models developed to describe mixing of fluids in microfluidic reactors to experimental observations of lineage mixing in a growing Neurospora crassa colony, we show how this mixing is achieved. In particular we analyze the individual contributions from interdigitation of hyphae and from nuclear transport.

A Three-Dimensional Hydrodynamic Focusing Method for Polyplex Synthesis

PubMed Central

Lu, Mengqian; Ho, Yi-Ping; Grigsby, Christopher L.; Nawaz, Ahmad Ahsan; Leong, Kam W.; Huang, Tony Jun

2014-01-01

Successful intracellular delivery of nucleic acid therapeutics relies on multi-aspect optimization, one of which is formulation. While there has been ample innovation on chemical design of polymeric gene carriers, the same cannot be said for physical processing of polymer-DNA nanocomplexes (polyplexes). Conventional synthesis of polyplexes by bulk mixing depends on the operators’ experience. The poorly controlled bulk-mixing process may also lead to batch-to-batch variation and consequent irreproducibility. Here, we synthesize polyplexes by using a three-dimensional hydrodynamic focusing (3D-HF) technique in a single-layered, planar microfluidic device. Without any additional chemical treatment or post processing, the polyplexes prepared by the 3D-HF method show smaller size, slower aggregation rate, and higher transfection efficiency, while exhibiting reduced cytotoxicity compared to the ones synthesized by conventional bulk mixing. In addition, by introducing external acoustic perturbation, mixing can be further enhanced, leading to even smaller nanocomplexes. The 3D-HF method provides a simple and reproducible process for synthesizing high-quality polyplexes, addressing a critical barrier in the eventual translation of nucleic acid therapeutics. PMID:24341632

Tradeoff between mixing and transport for electroosmotic flow in heterogeneous microchannels with nonuniform surface potentials.

PubMed

Tian, Fuzhi; Li, Baoming; Kwok, Daniel Y

2005-02-01

Electroosmotic flow (EOF) is a phenomenon associated with the movement of an aqueous solution induced by the application of an electric field in microchannels. The characteristics of EOF depend on the nature of the surface potential, i.e., whether it is uniform or nonuniform. In this paper, a lattice Boltzmann model (LBM) combined with the Poisson-Boltzmann equation is used to simulate flow field in a rectangular microchannel with nonuniform (step change) surface potentials. The simulation results indicate that local circulations can occur near a heterogeneous region with nonuniform surface potentials, in agreement with those by other authors. Largest circulations, which imply a highest mixing efficiency due to convection and short-range diffusion, were found when the average surface potential is zero, regardless of whether the distribution of the heterogeneous patches is symmetric or asymmetric. In this work, we have illustrated that there is a trade-off between the mixing and liquid transport in EOF microfluidics. One should not simply focus on mixing and neglect liquid transport, as performed in the literature. Excellent mixing could lead to a poor transport of electroosmotic flow in microchannels.

Hydrophilic PEO-PDMS for microfluidic applications

NASA Astrophysics Data System (ADS)

Yao, Mingjin; Fang, Ji

2012-02-01

Polydimethylsiloxane (PDMS) is a popularly used nontoxic and biocompatible material in microfluidic systems, which is relatively cheap and does not break easily like glass. The simple fabrication, optical transparency and elastomeric property make PDMS a handy material to work with. In order to develop different applications of PDMS in microfluidics and bioengineering, it is necessary to modify the PDMS surface nature to improve wetting characteristics, and to have a better control in nonspecific binding of proteins and cells, as well as to increase adhesion. At the moment, the hydrophilic surface modification performance of PDMS is known to recover its hydrophobicity shortly after oxidation modification, which is not stable in the long term (Owen and Smith 1994 J. Adhes. Sci. Technol. 8 1063-75). This paper presents a long-term stable hydrophilic surface modification processing of PDMS. The poly(dimethylsiloxane-ethylene oxide polymeric) (PDMS-b-PEO) is used in this project as a surfactant additive to be added into the PDMS base and the curing agent mixture during polymerization and to create hydrophilic PEO-PDMS. The contact angle can be controlled at 21.5-80.9° with the different mixing ratios and the hydrophilicity will remain stable for two months and then slightly varied later. We also investigate the bonding conditions of the modified PDMS to a silicon wafer and a glass wafer. To demonstrate its applications, we designed a device which consists of microchannels on a silicon wafer, and PEO-PDMS is utilized as a cover sheet. The capillary function was investigated under the different contact angles of PED-PDMS and with different aspect ratios of microchannels. All of the processes and testing data are presented in detail. This easy and cost-effective modified PDMS with a good bonding property can be widely used in the capillary device and systems, and microfluidic devices for fluid flow control of the microchannels in biological, chemical, medical applications.

Deformability measurement of red blood cells using a microfluidic channel array and an air cavity in a driving syringe with high throughput and precise detection of subpopulations.

PubMed

Kang, Yang Jun; Ha, Young-Ran; Lee, Sang-Joon

2016-01-07

Red blood cell (RBC) deformability has been considered a potential biomarker for monitoring pathological disorders. High throughput and detection of subpopulations in RBCs are essential in the measurement of RBC deformability. In this paper, we propose a new method to measure RBC deformability by evaluating temporal variations in the average velocity of blood flow and image intensity of successively clogged RBCs in the microfluidic channel array for specific time durations. In addition, to effectively detect differences in subpopulations of RBCs, an air compliance effect is employed by adding an air cavity into a disposable syringe. The syringe was equally filled with a blood sample (V(blood) = 0.3 mL, hematocrit = 50%) and air (V(air) = 0.3 mL). Owing to the air compliance effect, blood flow in the microfluidic device behaved transiently depending on the fluidic resistance in the microfluidic device. Based on the transient behaviors of blood flows, the deformability of RBCs is quantified by evaluating three representative parameters, namely, minimum value of the average velocity of blood flow, clogging index, and delivered blood volume. The proposed method was applied to measure the deformability of blood samples consisting of homogeneous RBCs fixed with four different concentrations of glutaraldehyde solution (0%-0.23%). The proposed method was also employed to evaluate the deformability of blood samples partially mixed with normal RBCs and hardened RBCs. Thereafter, the deformability of RBCs infected by human malaria parasite Plasmodium falciparum was measured. As a result, the three parameters significantly varied, depending on the degree of deformability. In addition, the deformability measurement of blood samples was successfully completed in a short time (∼10 min). Therefore, the proposed method has significant potential in deformability measurement of blood samples containing hematological diseases with high throughput and precise detection of subpopulations in RBCs.

Convex Grooves in Staggered Herringbone Mixer Improve Mixing Efficiency of Laminar Flow in Microchannel.

PubMed

Kwak, Tae Joon; Nam, Young Gyu; Najera, Maria Alejandra; Lee, Sang Woo; Strickler, J Rudi; Chang, Woo-Jin

2016-01-01

The liquid streams in a microchannel are hardly mixed to form laminar flow, and the mixing issue is well described by a low Reynolds number scheme. The staggered herringbone mixer (SHM) using repeated patterns of grooves in the microchannel have been proved to be an efficient passive micro-mixer. However, only a negative pattern of the staggered herringbone mixer has been used so far after it was first suggested, to the best of our knowledge. In this study, the mixing efficiencies from negative and positive staggered herringbone mixer patterns as well as from opposite flow directions were tested to investigate the effect of the micro-structure geometry on the surrounding laminar flow. The positive herringbone pattern showed better mixing efficiency than the conventionally used negative pattern. Also, generally used forward flow gives better mixing efficiency than reverse flow. The mixing was completed after two cycles of staggered herringbone mixer with both forward and reverse flow in a positive pattern. The traditional negative pattern showed complete mixing after four and five cycles in forward and reverse flow direction, respectively. The mixing effect in all geometries was numerically simulated, and the results confirmed more efficient mixing in the positive pattern than the negative. The results can further enable the design of a more efficient microfluidic mixer, as well as in depth understanding of the phenomena of positive and negative patterns existing in nature with regards to the surrounding fluids.

Convex Grooves in Staggered Herringbone Mixer Improve Mixing Efficiency of Laminar Flow in Microchannel

PubMed Central

Nam, Young Gyu; Najera, Maria Alejandra; Lee, Sang Woo; Strickler, J. Rudi; Chang, Woo-Jin

2016-01-01

The liquid streams in a microchannel are hardly mixed to form laminar flow, and the mixing issue is well described by a low Reynolds number scheme. The staggered herringbone mixer (SHM) using repeated patterns of grooves in the microchannel have been proved to be an efficient passive micro-mixer. However, only a negative pattern of the staggered herringbone mixer has been used so far after it was first suggested, to the best of our knowledge. In this study, the mixing efficiencies from negative and positive staggered herringbone mixer patterns as well as from opposite flow directions were tested to investigate the effect of the micro-structure geometry on the surrounding laminar flow. The positive herringbone pattern showed better mixing efficiency than the conventionally used negative pattern. Also, generally used forward flow gives better mixing efficiency than reverse flow. The mixing was completed after two cycles of staggered herringbone mixer with both forward and reverse flow in a positive pattern. The traditional negative pattern showed complete mixing after four and five cycles in forward and reverse flow direction, respectively. The mixing effect in all geometries was numerically simulated, and the results confirmed more efficient mixing in the positive pattern than the negative. The results can further enable the design of a more efficient microfluidic mixer, as well as in depth understanding of the phenomena of positive and negative patterns existing in nature with regards to the surrounding fluids. PMID:27814386

Highly Stretchable and Transparent Microfluidic Strain Sensors for Monitoring Human Body Motions.

PubMed

Yoon, Sun Geun; Koo, Hyung-Jun; Chang, Suk Tai

2015-12-16

We report a new class of simple microfluidic strain sensors with high stretchability, transparency, sensitivity, and long-term stability with no considerable hysteresis and a fast response to various deformations by combining the merits of microfluidic techniques and ionic liquids. The high optical transparency of the strain sensors was achieved by introducing refractive-index matched ionic liquids into microfluidic networks or channels embedded in an elastomeric matrix. The microfluidic strain sensors offer the outstanding sensor performance under a variety of deformations induced by stretching, bending, pressing, and twisting of the microfluidic strain sensors. The principle of our microfluidic strain sensor is explained by a theoretical model based on the elastic channel deformation. In order to demonstrate its capability of practical usage, the simple-structured microfluidic strain sensors were performed onto a finger, wrist, and arm. The highly stretchable and transparent microfluidic strain sensors were successfully applied as potential platforms for distinctively monitoring a wide range of human body motions in real time. Our novel microfluidic strain sensors show great promise for making future stretchable electronic devices.

Bio-microfluidics: biomaterials and biomimetic designs.

PubMed

Domachuk, Peter; Tsioris, Konstantinos; Omenetto, Fiorenzo G; Kaplan, David L

2010-01-12

Bio-microfluidics applies biomaterials and biologically inspired structural designs (biomimetics) to microfluidic devices. Microfluidics, the techniques for constraining fluids on the micrometer and sub-micrometer scale, offer applications ranging from lab-on-a-chip to optofluidics. Despite this wealth of applications, the design of typical microfluidic devices imparts relatively simple, laminar behavior on fluids and is realized using materials and techniques from silicon planar fabrication. On the other hand, highly complex microfluidic behavior is commonplace in nature, where fluids with nonlinear rheology flow through chaotic vasculature composed from a range of biopolymers. In this Review, the current state of bio-microfluidic materials, designs and applications are examined. Biopolymers enable bio-microfluidic devices with versatile functionalization chemistries, flexibility in fabrication, and biocompatibility in vitro and in vivo. Polymeric materials such as alginate, collagen, chitosan, and silk are being explored as bulk and film materials for bio-microfluidics. Hydrogels offer options for mechanically functional devices for microfluidic systems such as self-regulating valves, microlens arrays and drug release systems, vital for integrated bio-microfluidic devices. These devices including growth factor gradients to study cell responses, blood analysis, biomimetic capillary designs, and blood vessel tissue culture systems, as some recent examples of inroads in the field that should lead the way in a new generation of microfluidic devices for bio-related needs and applications. Perhaps one of the most intriguing directions for the future will be fully implantable microfluidic devices that will also integrate with existing vasculature and slowly degrade to fully recapitulate native tissue structure and function, yet serve critical interim functions, such as tissue maintenance, drug release, mechanical support, and cell delivery.

A capillary-driven micromixer: idea and fabrication

NASA Astrophysics Data System (ADS)

Lee, Chun-Te; Lee, Chun-Che

2012-10-01

Microfluidic systems have been drawing attention upon the various branches of engineering science and the allied areas within biology and biomedicine. In this paper, a fabrication of a capillary-driven micromixer using photoresist JSR and glasses is proposed. We design three types of planar capillary-driven micormixers with different sizes of baffles in the channel. Flow tests have shown that the micromixer with a baffle gap of 100 μm and space of 100 μm reaches a best mixing performance of 93% in gray-level image analysis.

Continuous chemical operations and modifications on magnetic γ-Fe2O3 nanoparticles confined in nanoliter droplets for the assembly of fluorescent and magnetic SiO2@γ-Fe2O3.

PubMed

Ferraro, D; Lin, Y; Teste, B; Talbot, D; Malaquin, L; Descroix, S; Abou-Hassan, A

2015-12-11

We present a microfluidic platform that allows undergoing different chemical operations in a nanoliter droplet starting from the colloidal suspension of magnetic iron oxide (γ-Fe2O3) nanoparticles "NPs" (ferrofluid). These operations include: mixing, flocculation, magnetic decantation, colloidal redispersion, washing, surface functionalization, heating and colloidal assembly. To prove the platform capabilities, we produced fluorescent and magnetic nanoassemblies composed of fluorescent silica and magnetic NPs.

Microfluidic immunosensor with integrated liquid core waveguides for sensitive Mie scattering detection of avian influenza antigens in a real biological matrix.

PubMed

Heinze, Brian C; Gamboa, Jessica R; Kim, Keesung; Song, Jae-Young; Yoon, Jeong-Yeol

2010-11-01

This work presents the use of integrated, liquid core, optical waveguides for measuring immunoagglutination-induced light scattering in a microfluidic device, towards rapid and sensitive detection of avian influenza (AI) viral antigens in a real biological matrix (chicken feces). Mie scattering simulations were performed and tested to optimize the scattering efficiency of the device through proper scatter angle waveguide geometry. The detection limit is demonstrated to be 1 pg mL(-1) in both clean buffer and real biological matrix. This low detection limit is made possible through on-chip diffusional mixing of AI target antigens and high acid content microparticle assay reagents, coupled with real-time monitoring of immunoagglutination-induced forward Mie scattering via high refractive index liquid core optical waveguides in close proximity (100 μm) to the sample chamber. The detection time for the assay is <2 min. This device could easily be modified to detect trace levels of any biological molecules that antibodies are available for, moving towards a robust platform for point-of-care disease diagnostics.

Optimized holographic femtosecond laser patterning method towards rapid integration of high-quality functional devices in microchannels

PubMed Central

Zhang, Chenchu; Hu, Yanlei; Du, Wenqiang; Wu, Peichao; Rao, Shenglong; Cai, Ze; Lao, Zhaoxin; Xu, Bing; Ni, Jincheng; Li, Jiawen; Zhao, Gang; Wu, Dong; Chu, Jiaru; Sugioka, Koji

2016-01-01

Rapid integration of high-quality functional devices in microchannels is in highly demand for miniature lab-on-a-chip applications. This paper demonstrates the embellishment of existing microfluidic devices with integrated micropatterns via femtosecond laser MRAF-based holographic patterning (MHP) microfabrication, which proves two-photon polymerization (TPP) based on spatial light modulator (SLM) to be a rapid and powerful technology for chip functionalization. Optimized mixed region amplitude freedom (MRAF) algorithm has been used to generate high-quality shaped focus field. Base on the optimized parameters, a single-exposure approach is developed to fabricate 200 × 200 μm microstructure arrays in less than 240 ms. Moreover, microtraps, QR code and letters are integrated into a microdevice by the advanced method for particles capture and device identification. These results indicate that such a holographic laser embellishment of microfluidic devices is simple, flexible and easy to access, which has great potential in lab-on-a-chip applications of biological culture, chemical analyses and optofluidic devices. PMID:27619690

Population transcriptomics with single-cell resolution: a new field made possible by microfluidics: a technology for high throughput transcript counting and data-driven definition of cell types.

PubMed

Plessy, Charles; Desbois, Linda; Fujii, Teruo; Carninci, Piero

2013-02-01

Tissues contain complex populations of cells. Like countries, which are comprised of mixed populations of people, tissues are not homogeneous. Gene expression studies that analyze entire populations of cells from tissues as a mixture are blind to this diversity. Thus, critical information is lost when studying samples rich in specialized but diverse cells such as tumors, iPS colonies, or brain tissue. High throughput methods are needed to address, model and understand the constitutive and stochastic differences between individual cells. Here, we describe microfluidics technologies that utilize a combination of molecular biology and miniaturized labs on chips to study gene expression at the single cell level. We discuss how the characterization of the transcriptome of each cell in a sample will open a new field in gene expression analysis, population transcriptomics, that will change the academic and biomedical analysis of complex samples by defining them as quantified populations of single cells. Copyright © 2013 WILEY Periodicals, Inc.

Bubble formation during pulsed laser ablation: mechanism and implications

NASA Astrophysics Data System (ADS)

van Leeuwen, Ton G. J. M.; Jansen, E. Duco; Motamedi, Massoud; Welch, Ashley J.; Borst, Cornelius

1993-07-01

Holmium ((lambda) equals 2.09 micrometers ) and excimer ((lambda) equals 308 nm) lasers are used for ablation of tissue. In a previous study it was demonstrated that both excimer and holmium laser pulses produce fast expanding and collapsing vapor bubbles. To investigate whether the excimer induced bubble is caused by vaporization of water, the threshold fluence for bubble formation at a bare fiber tip in water was compared between the excimer laser (pulse length 115 ns) and the Q-switched and free-running holmium lasers (pulse length 1 microsecond(s) to 250 microsecond(s) , respectively). To induce bubble formation by excimer laser light in water, the absorber oxybuprocaine-hydrochloride (OBP-HCl) was added to the water. Fast flash photography was used to measure the threshold fluence as a function of the water temperature (6 - 90 degree(s)C) at environmental pressure. The ultraviolet excimer laser light is strongly absorbed by blood. Therefore, to document the implications of bubble formation at fluences above the tissue ablation threshold, excimer laser pulses were delivered in vitro in hemoglobin solution and in vivo in the femoral artery of the rabbit. We conclude that the principal content of the fast bubble induced by a 308 nm excimer laser pulse is water vapor. Therefore, delivery of excimer laser pulses in a water or blood environment will cause fast expanding water vapor bubbles, which may induce mechanical damage to adjacent tissue.

Acoustic transients in pulsed holmium laser ablation: effects of pulse duration

NASA Astrophysics Data System (ADS)

Asshauer, Thomas; Delacretaz, Guy P.; Jansen, E. Duco; Welch, Ashley J.; Frenz, Martin

1995-01-01

The goal of this work was to study the influence of pulse duration on acoustic transient generation in holmium laser ablation. For this, the generation and collapse of cavitation bubbles induced by Q-switched and free-running laser pulses delivered under water were investigated. Polyacrylamide gel of 84% water content served as a model for soft tissue. This gel is a more realistic tissue phantom than water because it mimics not only the optical properties but also the mechanical properties of tissue. The dynamics of bubble formation inside the clear gel were observed by 1 ns time resolved flash videography. A polyvinylidenefluoride (PVDF) needle probe transducer measured absolute values of pressure amplitudes. Pressure wave generation by cavitation bubble collapse was observed in all phantoms used. Maximum pressures of more than 180 bars at 1 mm from the collapse center were observed in water and high water-contents gels with a pulse energy of 200 mJ and a 400 micrometers fiber. A strong dependency of the bubble collapse pressure on the pulse duration for constant pulse energy was observed in gel as well as in water. For pulse durations longer than 400 microsecond(s) a 90% reduction of pressure amplitudes relative to 100 microsecond(s) pulses was found. This suggests that optimization of pulse duration offers a degree of freedom allowing us to minimize the risk of acoustical damage in medical applications like arthroscopy and angioplasty.

Acoustic transient generation in pulsed holmium laser ablation under water

NASA Astrophysics Data System (ADS)

Asshauer, Thomas; Rink, Klaus; Delacretaz, Guy P.; Salathe, Rene-Paul; Gerber, Bruno E.; Frenz, Martin; Pratisto, Hans; Ith, Michael; Romano, Valerio; Weber, Heinz P.

1994-08-01

In this study the role of acoustical transients during pulsed holmium laser ablation is addressed. For this the collapse of cavitation bubbles generated by 2.12 micrometers Cr:Tm:Ho:YAG laser pulses delivered via a fiber in water is investigated. Multiple consecutive collapses of a single bubble generating acoustic transients are documented. Pulse durations are varied from 130 - 230 microsecond(s) and pulse energies from 20 - 800 mJ. Fiber diameters of 400 and 600 micrometers are used. The bubble collapse behavior is observed by time resolved fast flash photography with 1 microsecond(s) strobe lamp or 5 ns 1064 nm Nd:YAG laser illumination. A PVDF needle probe transducer is used to observe acoustic transients and measure their pressure amplitudes. Under certain conditions, at the end of the collapse phase the bubbles emit spherical acoustic transients of up to several hundred bars amplitude. After the first collapse up to two rebounds leading to further acoustic transient emissions are observed. Bubbles generated near a solid surface under water are attracted towards the surface during their development. The final phase of the collapse generating the acoustic transients takes place directly on the surface, exposing it to maximum pressure amplitudes. Our results indicate a possible mechanism of unwanted tissue damage during holmium laser application in a liquid environment as in arthroscopy or angioplasty that may set limits to the choice of laser pulse duration and energies.

Microfluidic opportunities in the field of nutrition

PubMed Central

Li, Sixing; Kiehne, Justin; Sinoway, Lawrence I.; Cameron, Craig E.

2013-01-01

Nutrition has always been closely related to human health, which is a constant motivational force driving research in a variety of disciplines. Over the years, the rapidly emerging field of microfluidics has been pushing forward the healthcare industry with the development of microfluidic-based, point-of-care (POC) diagnostic devices. Though a great deal of work has been done in developing microfluidic platforms for disease diagnoses, potential microfluidic applications in the field of nutrition remain largely unexplored. In this Focus article, we would like to investigate the potential chances for microfluidics in the field of nutrition. We will first highlight some of the recent advances in microfluidic blood analysis systems that have the capacity to detect biomarkers of nutrition. Then we will examine existing examples of microfluidic devices for the detection of specific biomarkers of nutrition or nutrient content in food. Finally, we will discuss the challenges in this field and provide some insight into the future of applied microfluidics in nutrition. PMID:24056522

Principles, Techniques, and Applications of Tissue Microfluidics

NASA Technical Reports Server (NTRS)

Wade, Lawrence A.; Kartalov, Emil P.; Shibata, Darryl; Taylor, Clive

2011-01-01

The principle of tissue microfluidics and its resultant techniques has been applied to cell analysis. Building microfluidics to suit a particular tissue sample would allow the rapid, reliable, inexpensive, highly parallelized, selective extraction of chosen regions of tissue for purposes of further biochemical analysis. Furthermore, the applicability of the techniques ranges beyond the described pathology application. For example, they would also allow the posing and successful answering of new sets of questions in many areas of fundamental research. The proposed integration of microfluidic techniques and tissue slice samples is called "tissue microfluidics" because it molds the microfluidic architectures in accordance with each particular structure of each specific tissue sample. Thus, microfluidics can be built around the tissues, following the tissue structure, or alternatively, the microfluidics can be adapted to the specific geometry of particular tissues. By contrast, the traditional approach is that microfluidic devices are structured in accordance with engineering considerations, while the biological components in applied devices are forced to comply with these engineering presets.

Rapid wasted-free microfluidic fabrication based on ink-jet approach for microfluidic sensing applications

NASA Astrophysics Data System (ADS)

Jarujareet, Ungkarn; Amarit, Rattasart; Sumriddetchkajorn, Sarun

2016-11-01

Realizing that current microfluidic chip fabrication techniques are time consuming and labor intensive as well as always have material leftover after chip fabrication, this research work proposes an innovative approach for rapid microfluidic chip production. The key idea relies on a combination of a widely-used inkjet printing method and a heat-based polymer curing technique with an electronic-mechanical control, thus eliminating the need of masking and molds compared to typical microfluidic fabrication processes. In addition, as the appropriate amount of polymer is utilized during printing, there is much less amount of material wasted. Our inkjet-based microfluidic printer can print out the desired microfluidic chip pattern directly onto a heated glass surface, where the printed polymer is suddenly cured. Our proof-of-concept demonstration for widely-used single-flow channel, Y-junction, and T-junction microfluidic chips shows that the whole microfluidic chip fabrication process requires only 3 steps with a fabrication time of 6 minutes.

Mixed-Dimensionality VLSI-Type Configurable Tools for Virtual Prototyping of Biomicrofluidic Devices and Integrated Systems

NASA Astrophysics Data System (ADS)

Makhijani, Vinod B.; Przekwas, Andrzej J.

2002-10-01

This report presents results of a DARPA/MTO Composite CAD Project aimed to develop a comprehensive microsystem CAD environment, CFD-ACE+ Multiphysics, for bio and microfluidic devices and complete microsystems. The project began in July 1998, and was a three-year team effort between CFD Research Corporation, California Institute of Technology (CalTech), University of California, Berkeley (UCB), and Tanner Research, with Mr. Don Verlee from Abbott Labs participating as a consultant on the project. The overall objective of this project was to develop, validate and demonstrate several applications of a user-configurable VLSI-type mixed-dimensionality software tool for design of biomicrofluidics devices and integrated systems. The developed tool would provide high fidelity 3-D multiphysics modeling capability, l-D fluidic circuits modeling, and SPICE interface for system level simulations, and mixed-dimensionality design. It would combine tools for layouts and process fabrication, geometric modeling, and automated grid generation, and interfaces to EDA tools (e.g. Cadence) and MCAD tools (e.g. ProE).

Magnetic actuator for the control and mixing of magnetic bead-based reactions on-chip.

PubMed

Berenguel-Alonso, Miguel; Granados, Xavier; Faraudo, Jordi; Alonso-Chamarro, Julián; Puyol, Mar

2014-10-01

While magnetic bead (MB)-based bioassays have been implemented in integrated devices, their handling on-chip is normally either not optimal--i.e. only trapping is achieved, with aggregation of the beads--or requires complex actuator systems. Herein, we describe a simple and low-cost magnetic actuator to trap and move MBs within a microfluidic chamber in order to enhance the mixing of a MB-based reaction. The magnetic actuator consists of a CD-shaped plastic unit with an arrangement of embedded magnets which, when rotating, generate the mixing. The magnetic actuator has been used to enhance the amplification reaction of an enzyme-linked fluorescence immunoassay to detect Escherichia coli O157:H7 whole cells, an enterohemorrhagic strain, which have caused several outbreaks in food and water samples. A 2.7-fold sensitivity enhancement was attained with a detection limit of 603 colony-forming units (CFU) /mL, when employing the magnetic actuator.

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.

Suspended microfluidics.

PubMed

Casavant, Benjamin P; Berthier, Erwin; Theberge, Ashleigh B; Berthier, Jean; Montanez-Sauri, Sara I; Bischel, Lauren L; Brakke, Kenneth; Hedman, Curtis J; Bushman, Wade; Keller, Nancy P; Beebe, David J

2013-06-18

Although the field of microfluidics has made significant progress in bringing new tools to address biological questions, the accessibility and adoption of microfluidics within the life sciences are still limited. Open microfluidic systems have the potential to lower the barriers to adoption, but the absence of robust design rules has hindered their use. Here, we present an open microfluidic platform, suspended microfluidics, that uses surface tension to fill and maintain a fluid in microscale structures devoid of a ceiling and floor. We developed a simple and ubiquitous model predicting fluid flow in suspended microfluidic systems and show that it encompasses many known capillary phenomena. Suspended microfluidics was used to create arrays of collagen membranes, mico Dots (μDots), in a horizontal plane separating two fluidic chambers, demonstrating a transwell platform able to discern collective or individual cellular invasion. Further, we demonstrated that μDots can also be used as a simple multiplexed 3D cellular growth platform. Using the μDot array, we probed the combined effects of soluble factors and matrix components, finding that laminin mitigates the growth suppression properties of the matrix metalloproteinase inhibitor GM6001. Based on the same fluidic principles, we created a suspended microfluidic metabolite extraction platform using a multilayer biphasic system that leverages the accessibility of open microchannels to retrieve steroids and other metabolites readily from cell culture. Suspended microfluidics brings the high degree of fluidic control and unique functionality of closed microfluidics into the highly accessible and robust platform of open microfluidics.

Suspended microfluidics

PubMed Central

Casavant, Benjamin P.; Berthier, Erwin; Theberge, Ashleigh B.; Berthier, Jean; Montanez-Sauri, Sara I.; Bischel, Lauren L.; Brakke, Kenneth; Hedman, Curtis J.; Bushman, Wade; Keller, Nancy P.; Beebe, David J.

2013-01-01

Although the field of microfluidics has made significant progress in bringing new tools to address biological questions, the accessibility and adoption of microfluidics within the life sciences are still limited. Open microfluidic systems have the potential to lower the barriers to adoption, but the absence of robust design rules has hindered their use. Here, we present an open microfluidic platform, suspended microfluidics, that uses surface tension to fill and maintain a fluid in microscale structures devoid of a ceiling and floor. We developed a simple and ubiquitous model predicting fluid flow in suspended microfluidic systems and show that it encompasses many known capillary phenomena. Suspended microfluidics was used to create arrays of collagen membranes, mico Dots (μDots), in a horizontal plane separating two fluidic chambers, demonstrating a transwell platform able to discern collective or individual cellular invasion. Further, we demonstrated that μDots can also be used as a simple multiplexed 3D cellular growth platform. Using the μDot array, we probed the combined effects of soluble factors and matrix components, finding that laminin mitigates the growth suppression properties of the matrix metalloproteinase inhibitor GM6001. Based on the same fluidic principles, we created a suspended microfluidic metabolite extraction platform using a multilayer biphasic system that leverages the accessibility of open microchannels to retrieve steroids and other metabolites readily from cell culture. Suspended microfluidics brings the high degree of fluidic control and unique functionality of closed microfluidics into the highly accessible and robust platform of open microfluidics. PMID:23729815

Microfluidics on liquid handling stations (μF-on-LHS): a new industry-compatible microfluidic platform

NASA Astrophysics Data System (ADS)

Kittelmann, Jörg; Radtke, Carsten P.; Waldbaur, Ansgar; Neumann, Christiane; Hubbuch, Jürgen; Rapp, Bastian E.

2014-03-01

Since the early days microfluidics as a scientific discipline has been an interdisciplinary research field with a wide scope of potential applications. Besides tailored assays for point-of-care (PoC) diagnostics, microfluidics has been an important tool for large-scale screening of reagents and building blocks in organic chemistry, pharmaceutics and medical engineering. Furthermore, numerous potential marketable products have been described over the years. However, especially in industrial applications, microfluidics is often considered only an alternative technology for fluid handling, a field which is industrially mostly dominated by large-scale numerically controlled fluid and liquid handling stations. Numerous noteworthy products have dominated this field in the last decade and have been inhibited the widespread application of microfluidics technology. However, automated liquid handling stations and microfluidics do not have to be considered as mutually exclusive approached. We have recently introduced a hybrid fluidic platform combining an industrially established liquid handling station and a generic microfluidic interfacing module that allows probing a microfluidic system (such as an essay or a synthesis array) using the instrumentation provided by the liquid handling station. We term this technology "Microfluidic on Liquid Handling Stations (μF-on-LHS)" - a classical "best of both worlds"- approach that allows combining the highly evolved, automated and industry-proven LHS systems with any type of microfluidic assay. In this paper we show, to the best of our knowledge, the first droplet microfluidics application on an industrial LHS using the μF-on-LHS concept.

Microfluidic Impedance Flow Cytometry Enabling High-Throughput Single-Cell Electrical Property Characterization

PubMed Central

Chen, Jian; Xue, Chengcheng; Zhao, Yang; Chen, Deyong; Wu, Min-Hsien; Wang, Junbo

2015-01-01

This article reviews recent developments in microfluidic impedance flow cytometry for high-throughput electrical property characterization of single cells. Four major perspectives of microfluidic impedance flow cytometry for single-cell characterization are included in this review: (1) early developments of microfluidic impedance flow cytometry for single-cell electrical property characterization; (2) microfluidic impedance flow cytometry with enhanced sensitivity; (3) microfluidic impedance and optical flow cytometry for single-cell analysis and (4) integrated point of care system based on microfluidic impedance flow cytometry. We examine the advantages and limitations of each technique and discuss future research opportunities from the perspectives of both technical innovation and clinical applications. PMID:25938973

Ice matrix in reconfigurable microfluidic systems

NASA Astrophysics Data System (ADS)

Bossi, A. M.; Vareijka, M.; Piletska, E. V.; Turner, A. P. F.; Meglinski, I.; Piletsky, S. A.

2013-07-01

Microfluidic devices find many applications in biotechnologies. Here, we introduce a flexible and biocompatible microfluidic ice-based platform with tunable parameters and configuration of microfluidic patterns that can be changed multiple times during experiments. Freezing and melting of cavities, channels and complex relief structures created and maintained in the bulk of ice by continuous scanning of an infrared laser beam are used as a valve action in microfluidic systems. We demonstrate that pre-concentration of samples and transport of ions and dyes through the open channels created can be achieved in ice microfluidic patterns by IR laser-assisted zone melting. The proposed approach can be useful for performing separation and sensing processes in flexible reconfigurable microfluidic devices.

3D printed conformal microfluidics for isolation and profiling of biomarkers from whole organs.

PubMed

Singh, Manjot; Tong, Yuxin; Webster, Kelly; Cesewski, Ellen; Haring, Alexander P; Laheri, Sahil; Carswell, Bill; O'Brien, Timothy J; Aardema, Charles H; Senger, Ryan S; Robertson, John L; Johnson, Blake N

2017-07-25

The ability to interface microfluidic devices with native complex biological architectures, such as whole organs, has the potential to shift the paradigm for the study and analysis of biological tissue. Here, we show 3D printing can be used to fabricate bio-inspired conformal microfluidic devices that directly interface with the surface of whole organs. Structured-light scanning techniques enabled the 3D topographical matching of microfluidic device geometry to porcine kidney anatomy. Our studies show molecular species are spontaneously transferred from the organ cortex to the conformal microfluidic device in the presence of fluid flow through the organ-conforming microchannel. Large animal studies using porcine kidneys (n = 32 organs) revealed the profile of molecular species in the organ-conforming microfluidic stream was dependent on the organ preservation conditions. Enzyme-linked immunosorbent assay (ELISA) studies revealed conformal microfluidic devices isolate clinically relevant metabolic and pathophysiological biomarkers from whole organs, including heat shock protein 70 (HSP-70) and kidney injury molecule-1 (KIM-1), which were detected in the microfluidic device as high as 409 and 12 pg mL -1 , respectively. Overall, these results show conformal microfluidic devices enable a novel minimally invasive 'microfluidic biopsy' technique for isolation and profiling of biomarkers from whole organs within a clinically relevant interval. This achievement could shift the paradigm for whole organ preservation and assessment, thereby helping to relieve the organ shortage crisis through increased availability and quality of donor organs. Ultimately, this work provides a major advance in microfluidics through the design and manufacturing of organ-conforming microfluidic devices and a novel technique for microfluidic-based analysis of whole organs.

[Advances on enzymes and enzyme inhibitors research based on microfluidic devices].

PubMed

Hou, Feng-Hua; Ye, Jian-Qing; Chen, Zuan-Guang; Cheng, Zhi-Yi

2010-06-01

With the continuous development in microfluidic fabrication technology, microfluidic analysis has evolved from a concept to one of research frontiers in last twenty years. The research of enzymes and enzyme inhibitors based on microfluidic devices has also made great progress. Microfluidic technology improved greatly the analytical performance of the research of enzymes and enzyme inhibitors by reducing the consumption of reagents, decreasing the analysis time, and developing automation. This review focuses on the development and classification of enzymes and enzyme inhibitors research based on microfluidic devices.

Jack Rabbit Pretest 2021E PT3 Photonic Doppler Velocimetry Data Volume 3 Section 1

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

Hart, M M; Strand, O T; Bosson, S T

The Jack Rabbit Pretest (PT) 2021E PT3 was fired on March 12, 2008 at the Contained Firing Facility, Site 300, Lawrence Livermore National Laboratory. This experiment is part of an effort to determine the properties of LX-17 in a regime where corner-turning behavior and dead-zone formation are not well understood. Photonic Doppler Velocimetry (PDV) measured diagnostic plate velocities confirming the presence of a persistent LX-17 dead-zone formation and the resultant impulse gradient applied under the diagnostic plate. The Jack Rabbit Pretest 2021E PT3, 120 millimeter diameter experiment returned data on all eight PDV probes. The probes measured on the centralmore » axis and at 10, 20, 25, 30, 35, 40, 50 millimeters from the central axis. The experiment was shot at an ambient room temperature of 65 degrees Fahrenheit. The earliest PDV signal extinction was 41.7 microseconds at 30 millimeters. The latest PDV signal extinction time was 65.0 microseconds at 10 millimeters. The measured velocity ranged from meters per second to thousands of meters per second. First detonation wave induced jump-off was measured at 40 millimeters at 10.9 microseconds. The PDV data provided an unambiguous indication of dead-zone formation and an impulse gradient applied to the diagnostic plate. The central axis had a last measured velocity of 1636 meters per second. At 40 millimeters the last measured velocity was 2056 meters per second. The low-to-high velocity ratio was 0.80. Velocity data was integrated to compute diagnostic plate cross section profiles. Velocity data was differentiated to compute a peak pressure under the diagnostic plate at the central axis of 64.6 kilobars at 15.7 microseconds. Substantial motion (>1 m/s) of the diagnostic plate over the dead-zone is followed by detonation region motion within approximately 2.2 microseconds.« less

Jack Rabbit Pretest 2021E PT4 Photonic Doppler Velocimetry Data Volume 4 Section 1

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

Hart, M M; Strand, O T; Bosson, S T

The Jack Rabbit Pretest (PT) 2021E PT4 was fired on March 19, 2008 at the Contained Firing Facility, Site 300, Lawrence Livermore National Laboratory. This experiment is part of an effort to determine the properties of LX-17 in a regime where corner-turning behavior and dead-zone formation are not well understood. Photonic Doppler Velocimetry (PDV) measured diagnostic plate velocities confirming the presence of a persistent LX-17 dead-zone formation and the resultant impulse gradient applied under the diagnostic plate. The Jack Rabbit Pretest 2021E PT4, 120 millimeter diameter experiment returned data on all eight PDV probes. The probes measured on the centralmore » axis and at 10, 20, 25, 30, 35, 40, 50 millimeters from the central axis. The experiment was shot at an ambient room temperature of 64 degrees Fahrenheit. The earliest PDV signal extinction was 44.9 microseconds at 30 millimeters. The latest PDV signal extinction time was 69.5 microseconds at 10 millimeters. The measured velocity ranged from meters per second to thousands of meters per second. First detonation wave induced jump-off was measured at 50 millimeters at 13.3 microseconds. The PDV data provided an unambiguous indication of dead-zone formation and an impulse gradient applied to the diagnostic plate. The central axis had a last measured velocity of 1558 meters per second. At 40 millimeters the last measured velocity was 2019 meters per second. The low-to-high velocity ratio was 0.77. Velocity data was integrated to compute diagnostic plate cross section profiles. Velocity data was differentiated to compute a peak pressure under the diagnostic plate at the central axis of 98.6 kilobars at 15.0 microseconds. Substantial motion (>1 m/s) of the diagnostic plate over the dead-zone is followed by detonation region motion within approximately 0.7 microseconds.« less

Jack Rabbit Pretest 2021E PT6 Photonic Doppler Velocimetry Data Volume 6 Section 1

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

Hart, M M; Strand, O T; Bosson, S T

The Jack Rabbit Pretest (PT) 2021E PT6 experiment was fired on April 1, 2008 at the Contained Firing Facility, Site 300, Lawrence Livermore National Laboratory. This experiment is part of an effort to determine the properties of LX-17 in a regime where corner-turning behavior and dead-zone formation are not well understood. Photonic Doppler Velocimetry (PDV) measured diagnostic plate velocities confirming the presence of a persistent LX-17 dead-zone formation and the resultant impulse gradient applied under the diagnostic plate. The Jack Rabbit Pretest 2021E PT6, 160 millimeter diameter experiment returned data on all eight PDV probes. The probes measured on themore » central axis and at 20, 30, 35, 45, 55, 65, 75 millimeters from the central axis. The experiment was shot at an ambient room temperature of 65 degrees Fahrenheit. The earliest PDV signal extinction was 54.2 microseconds at 30 millimeters. The latest PDV signal extinction time was 64.5 microseconds at the central axis. The measured velocity ranged from meters per second to thousands of meters per second. First detonation wave induced jump-off was measured at 55 millimeters at 14.1 microseconds. The PDV data provided an unambiguous indication of dead-zone formation and an impulse gradient applied to the diagnostic plate. The central axis had a last measured velocity of 1860 meters per second. At 55 millimeters the last measured velocity was 2408 meters per second. The low-to-high velocity ratio was 0.77. Velocity data was integrated to compute diagnostic plate cross section profiles. Velocity data was differentiated to compute a peak pressure under the diagnostic plate at the central axis of 227 kilobars at 20.1 microseconds, indicating a late time chemical reaction in the LX-17 dead-zone. Substantial motion (>1 m/s) of the diagnostic plate over the dead-zone is followed by detonation region motion within approximately 1.7 microseconds.« less

Jack Rabbit Pretest 2021E PT5 Photonic Doppler Velocimetry Data Volume 5 Section 1

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

Hart, M M; Strand, O T; Bosson, S T

The Jack Rabbit Pretest (PT) 2021E PT5 was fired on March 17, 2008 at the Contained Firing Facility, Site 300, Lawrence Livermore National Laboratory. This experiment is part of an effort to determine the properties of LX-17 in a regime where corner-turning behavior and dead-zone formation are not well understood. Photonic Doppler Velocimetry (PDV) measured diagnostic plate velocities confirming the presence of a persistent LX-17 dead-zone formation and the resultant impulse gradient applied under the diagnostic plate. The Jack Rabbit Pretest 2021E PT5, 160 millimeter diameter experiment returned data on all eight PDV probes. The probes measured on the centralmore » axis and at 20, 30, 35, 45, 55, 65, 75 millimeters from the central axis. The experiment was shot at an ambient room temperature of 65 degrees Fahrenheit. The earliest PDV signal extinction was 40.0 microseconds at 45 millimeters. The latest PDV signal extinction time was 64.9 microseconds at 20 millimeters. The measured velocity ranged from meters per second to thousands of meters per second. First detonation wave induced jump-off was measured at 55 millimeters at 12.8 microseconds. The PDV data provided an unambiguous indication of dead-zone formation and an impulse gradient applied to the diagnostic plate. The central axis had a last measured velocity of 1877 meters per second. At 65 millimeters the last measured velocity was 2277 meters per second. The low-to-high velocity ratio was 0.82. Velocity data was integrated to compute diagnostic plate cross section profiles. Velocity data was differentiated to compute a peak pressure under the diagnostic plate at the central axis of 78 kilobars at 11.9 and 21.2 microseconds. Substantial motion (>1 m/s) of the diagnostic plate over the dead-zone is followed by detonation region motion within approximately 4.1 microseconds.« less

Jack Rabbit Pretest 2021E PT7 Photonic Doppler Velocimetry Data Volume 7 Section 1

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

Hart, M M; Strand, O T; Bosson, S T

The Jack Rabbit Pretest (PT) 2021E PT7 experiment was fired on April 3, 2008 at the Contained Firing Facility, Site 300, Lawrence Livermore National Laboratory. This experiment is part of an effort to determine the properties of LX-17 in a regime where corner-turning behavior and dead-zone formation are not well understood. Photonic Doppler Velocimetry (PDV) measured diagnostic plate velocities confirming the presence of a persistent LX-17 dead-zone formation and the resultant impulse gradient applied under the diagnostic plate. The Jack Rabbit Pretest 2021E PT7, 160 millimeter diameter experiment returned data on all eight PDV probes. The probes measured on themore » central axis and at 20, 30, 35, 45, 55, 65, 75 millimeters from the central axis. The experiment was shot at an ambient room temperature of 65 degrees Fahrenheit. The PDV earliest signal extinction was 50.7 microseconds at 45 millimeters. The latest PDV signal extinction time was 65.0 microseconds at 20 millimeters. The measured velocity ranged from meters per second to thousands of meters per second. First detonation wave induced jump-off was measured at 55 millimeters and at 15.2 microseconds. The PDV data provided an unambiguous indication of dead-zone formation and an impulse gradient applied to the diagnostic plate. The central axis had a last measured velocity of 1447 meters per second. At 65 millimeters the last measured velocity was 2360 meters per second. The low-to-high velocity ratio was 0.61. Velocity data was integrated to compute diagnostic plate cross section profiles. Velocity data was differentiated to compute a peak pressure under the diagnostic plate at the central axis of 49 kilobars at 23.3 microseconds. Substantial motion (>1 m/s) of the diagnostic plate over the dead-zone is followed by detonation region motion within approximately 4.6 microseconds.« less

Wire Array Z-pinches on Sphinx Machine: Experimental Results and Relevant Points of Microsecond Implosion Physics

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

Calamy, H.; Hamann, F.; Lassalle, F.

Centre d'Etudes de Gramat (France) has developed an efficient long implosion time (800 ns) Aluminum plasma radiation source (PRS). Based on the LTD technology, the SPHINX facility is developed as a 1-3MJ, 1{mu}s rise time, 4-10 MA current driver. In this paper, it was used in 1MJ, 4MA configuration to drive Aluminum nested wire arrays Z-pinches with K-shell yield up to 20 kJ and a FWHM of the x-ray pulse of about 50 ns. We present latest SPHINX experiments and some of the main physic issues of the microsecond regime. Experimental setup and results are described with the aim ofmore » giving trends that have been obtained. The main features of microsecond implosion of wire arrays can be analyzed thanks to same methods and theories as used for faster Z-pinches. The effect of load polarity was examined. The stability of the implosion , one of the critical point of microsecond wire arrays due to the load dimensions imposed by the time scale, is tackled. A simple scaling from 100 ns Z-pinch results to 800 ns ones gives good results and the use of nested arrays improves dramatically the implosion quality and the Kshell yield of the load. However, additional effects such as the impact of the return current can geometry on the implosion have to be taken into account on our loads. Axial inhomogeneity of the implosion the origin of which is not yet well understood occurs in some shots and impacts the radiation output. The shape of the radiative pulse is discussed and compared with the homogeneity of the implosion. Numerical 2D R-Z and R-{theta} simulations are used to highlight some experimental results and understand the plasma conditions during these microsecond wire arrays implosions.« less

Wire Array Z-pinches on Sphinx Machine: Experimental Results and Relevant Points of Microsecond Implosion Physics

NASA Astrophysics Data System (ADS)

Calamy, H.; Hamann, F.; Lassalle, F.; Bayol, F.; Mangeant, C.; Morell, A.; Huet, D.; Bedoch, J. P.; Chittenden, J. P.; Lebedev, S. V.; Jennings, C. A.; Bland, S. N.

2006-01-01

Centre d'Etudes de Gramat (France) has developed an efficient long implosion time (800 ns) Aluminum plasma radiation source (PRS). Based on the LTD technology, the SPHINX facility is developed as a 1-3MJ, 1μs rise time, 4-10 MA current driver. In this paper, it was used in 1MJ, 4MA configuration to drive Aluminum nested wire arrays Z-pinches with K-shell yield up to 20 kJ and a FWHM of the x-ray pulse of about 50 ns. We present latest SPHINX experiments and some of the main physic issues of the microsecond regime. Experimental setup and results are described with the aim of giving trends that have been obtained. The main features of microsecond implosion of wire arrays can be analyzed thanks to same methods and theories as used for faster Z-pinches. The effect of load polarity was examined. The stability of the implosion , one of the critical point of microsecond wire arrays due to the load dimensions imposed by the time scale, is tackled. A simple scaling from 100 ns Z-pinch results to 800 ns ones gives good results and the use of nested arrays improves dramatically the implosion quality and the Kshell yield of the load. However, additional effects such as the impact of the return current can geometry on the implosion have to be taken into account on our loads. Axial inhomogeneity of the implosion the origin of which is not yet well understood occurs in some shots and impacts the radiation output. The shape of the radiative pulse is discussed and compared with the homogeneity of the implosion. Numerical 2D R-Z and R-θ simulations are used to highlight some experimental results and understand the plasma conditions during these microsecond wire arrays implosions.

Rotational dynamics of spin-labeled F-actin during activation of myosin S1 ATPase using caged ATP.

PubMed Central

Ostap, E. M.; Thomas, D. D.

1991-01-01

The most probable source of force generation in muscle fibers in the rotation of the myosin head when bound to actin. This laboratory has demonstrated that ATP induces microsecond rotational motions of spin-labeled myosin heads bound to actin (Berger, C. L. E. C. Svensson, and D. D. Thomas. 1989. Proc. Natl. Acad. Sci. USA. 86:8753-8757). Our goal is to determine whether the observed ATP-induced rotational motions of actin-bound heads are accompanied by changes in actin rotational motions. We have used saturation transfer electron paramagnetic resonance (ST-EPR) and laser-induced photolysis of caged ATP to monitor changes in the microsecond rotational dynamics of spin-labeled F-actin in the presence of myosin subfragment-1 (S1). A maleimide spin label was attached selectively to cys-374 on actin. In the absence of ATP (with or without caged ATP), the ST-EPR spectrum (corresponding to an effective rotational time of approximately 150 microseconds) was essentially the same as observed for the same spin label bound to cys-707 (SH1) on S1, indicating that S1 is rigidly bound to actin in rigor. At normal ionic strength (micro = 186 mM), a decrease in ST-EPR intensity (increase in microsecond F-actin mobility) was clearly indicated upon photolysis of 1 mM caged ATP with a 50-ms, 351-nm laser pulse. This increase in mobility is due to the complete dissociation of Si from the actin filament. At low ionic strength (micro, = 36 mM), when about half the Si heads remain bound during ATP hydrolysis, no change in the actin mobility was detected, despite much faster motions of labeled S1 bound to actin. Therefore, we conclude that the active interaction of Si, actin,and ATP induces rotation of myosin heads relative to actin, but does not affect the microsecond rotational motion of actin itself, as detected at cys-374 of actin. PMID:1651780

Novel design and fabrication of a geometrical obstacle-embedded micromixer with notched wall

NASA Astrophysics Data System (ADS)

Wu, Shih-Jeh; Hsu, Hsiang-Chen; Feng, Wen-Jui

2014-09-01

A microfluidic embedded MEMS mixer with a Y-junction type channel and cylindrical obstructions was designed and fabricated for improving the fluid mixing mechanism under low Reynolds number (\\mathit{Re}) condition. The flow field was simulated numerically by software (COMSOL multiphysics®) first. The design was then realized through casting the device in PDMS by lithographed SU-8 photo-resistive mold on silicon wafer. Parametric experimental studies were conducted for optimal design. Two different fluids were pumped into the two legs of the Y-junction channel, and the fluids were broken-up by an embedded cylindrical obstacle in the middle of the tapered micro-channel. The chaotic convection took place in the mixing channel behind the embedded cylindrical obstacles. The flow motion was observed under CCD camera and analyzed by grey level. The developed micromixer in this study can enhance the fluid mixing by the interaction of diffusion and convection for wide range of Reynolds numbers (0.01 < \\mathit{Re} < 100). Experimental results showed that the mixing index reached the required value at 0.1 within 0.024 seconds when the inlet fluid velocity is 0.499 m/s (i.e., at 1200 µl/min flow rate) for merely four cylindrical obstacles. A shorter mixing distance can be accomplished compared to the current devices reported due to faster mixing and shorter mixing time.

Microfluidic electronics.

PubMed

Cheng, Shi; Wu, Zhigang

2012-08-21

Microfluidics, a field that has been well-established for several decades, has seen extensive applications in the areas of biology, chemistry, and medicine. However, it might be very hard to imagine how such soft microfluidic devices would be used in other areas, such as electronics, in which stiff, solid metals, insulators, and semiconductors have previously dominated. Very recently, things have radically changed. Taking advantage of native properties of microfluidics, advances in microfluidics-based electronics have shown great potential in numerous new appealing applications, e.g. bio-inspired devices, body-worn healthcare and medical sensing systems, and ergonomic units, in which conventional rigid, bulky electronics are facing insurmountable obstacles to fulfil the demand on comfortable user experience. Not only would the birth of microfluidic electronics contribute to both the microfluidics and electronics fields, but it may also shape the future of our daily life. Nevertheless, microfluidic electronics are still at a very early stage, and significant efforts in research and development are needed to advance this emerging field. The intention of this article is to review recent research outcomes in the field of microfluidic electronics, and address current technical challenges and issues. The outlook of future development in microfluidic electronic devices and systems, as well as new fabrication techniques, is also discussed. Moreover, the authors would like to inspire both the microfluidics and electronics communities to further exploit this newly-established field.

Principles, Techniques, and Applications of Tissue Microfluidics

NASA Technical Reports Server (NTRS)

Wade, Lawrence A.; Kartalov, Emil P.; Shibata, Darryl; Taylor, Clive

2011-01-01

The principle of tissue microfluidics and its resultant techniques has been applied to cell analysis. Building microfluidics to suit a particular tissue sample would allow the rapid, reliable, inexpensive, highly parallelized, selective extraction of chosen regions of tissue for purposes of further biochemical analysis. Furthermore, the applicability of the techniques ranges beyond the described pathology application. For example, they would also allow the posing and successful answering of new sets of questions in many areas of fundamental research. The proposed integration of microfluidic techniques and tissue slice samples is called tissue microfluidics because it molds the microfluidic architectures in accordance with each particular structure of each specific tissue sample. Thus, microfluidics can be built around the tissues, following the tissue structure, or alternatively, the microfluidics can be adapted to the specific geometry of particular tissues. By contrast, the traditional approach is that microfluidic devices are structured in accordance with engineering considerations, while the biological components in applied devices are forced to comply with these engineering presets. The proposed principles represent a paradigm shift in microfluidic technology in three important ways: Microfluidic devices are to be directly integrated with, onto, or around tissue samples, in contrast to the conventional method of off-chip sample extraction followed by sample insertion in microfluidic devices. Architectural and operational principles of microfluidic devices are to be subordinated to suit specific tissue structure and needs, in contrast to the conventional method of building devices according to fluidic function alone and without regard to tissue structure. Sample acquisition from tissue is to be performed on-chip and is to be integrated with the diagnostic measurement within the same device, in contrast to the conventional method of off-chip sample prep and subsequent insertion into a diagnostic device. A more advanced form of tissue integration with microfluidics is tissue encapsulation, wherein the sample is completely encapsulated within a microfluidic device, to allow for full surface access. The immediate applications of these approaches lie with diagnostics of tissue slices and biopsy samples e.g. for cancer but the approaches would also be very useful in comparative genomics and other areas of fundamental research involving heterogeneous tissue samples.