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Sample records for 3d microfluidic devices

  1. Using Adhesive Patterning to Construct 3D Paper Microfluidic Devices.

    PubMed

    Kalish, Brent; Tsutsui, Hideaki

    2016-04-01

    We demonstrate the use of patterned aerosol adhesives to construct both planar and nonplanar 3D paper microfluidic devices. By spraying an aerosol adhesive through a metal stencil, the overall amount of adhesive used in assembling paper microfluidic devices can be significantly reduced. We show on a simple 4-layer planar paper microfluidic device that the optimal adhesive application technique and device construction style depends heavily on desired performance characteristics. By moderately increasing the overall area of a device, it is possible to dramatically decrease the wicking time and increase device success rates while also reducing the amount of adhesive required to keep the device together. Such adhesive application also causes the adhesive to form semi-permanent bonds instead of permanent bonds between paper layers, enabling single-use devices to be non-destructively disassembled after use. Nonplanar 3D origami devices also benefit from the semi-permanent bonds during folding, as it reduces the likelihood that unrelated faces may accidently stick together. Like planar devices, nonplanar structures see reduced wicking times with patterned adhesive application vs uniformly applied adhesive.

  2. 3D thermoplastic elastomer microfluidic devices for biological probe immobilization.

    PubMed

    Brassard, Daniel; Clime, Liviu; Li, Kebin; Geissler, Matthias; Miville-Godin, Caroline; Roy, Emmanuel; Veres, Teodor

    2011-12-07

    Microfluidics has emerged as a valuable tool for the high-resolution patterning of biological probes on solid supports. Yet, its widespread adoption as a universal biological immobilization tool is still limited by several technical challenges, particularly for the patterning of isolated spots using three-dimensional (3D) channel networks. A key limitation arises from the difficulties to adapt the techniques and materials typically used in prototyping to low-cost mass-production. In this paper, we present the fabrication of thin thermoplastic elastomer membranes with microscopic through-holes using a hot-embossing process that is compatible with high-throughput manufacturing. The membranes provide the basis for the fabrication of highly integrated 3D microfluidic devices with a footprint of only 1 × 1 cm(2). When placed on a solid support, the device allows for the immobilization of up to 96 different probes in the form of a 10 × 10 array comprising isolated spots of 50 × 50 μm(2). The design of the channel network is optimized using 3D simulations based on the Lattice-Boltzmann method to promote capillary action as the sole force distributing the liquid in the device. Finally, we demonstrate the patterning of DNA and protein arrays on hard thermoplastic substrates yielding spots of excellent definition that prove to be highly specific in subsequent hybridization experiments.

  3. Engineering-Aligned 3D Neural Circuit in Microfluidic Device.

    PubMed

    Bang, Seokyoung; Na, Sangcheol; Jang, Jae Myung; Kim, Jinhyun; Jeon, Noo Li

    2016-01-07

    The brain is one of the most important and complex organs in the human body. Although various neural network models have been proposed for in vitro 3D neuronal networks, it has been difficult to mimic functional and structural complexity of the in vitro neural circuit. Here, a microfluidic model of a simplified 3D neural circuit is reported. First, the microfluidic device is filled with Matrigel and continuous flow is delivered across the device during gelation. The fluidic flow aligns the extracellular matrix (ECM) components along the flow direction. Following the alignment of ECM fibers, neurites of primary rat cortical neurons are grown into the Matrigel at the average speed of 250 μm d(-1) and form axon bundles approximately 1500 μm in length at 6 days in vitro (DIV). Additionally, neural networks are developed from presynaptic to postsynaptic neurons at 14 DIV. The establishment of aligned 3D neural circuits is confirmed with the immunostaining of PSD-95 and synaptophysin and the observation of calcium signal transmission.

  4. A microfluidic device for 2D to 3D and 3D to 3D cell navigation

    NASA Astrophysics Data System (ADS)

    Shamloo, Amir; Amirifar, Leyla

    2016-01-01

    Microfluidic devices have received wide attention and shown great potential in the field of tissue engineering and regenerative medicine. Investigating cell response to various stimulations is much more accurate and comprehensive with the aid of microfluidic devices. In this study, we introduced a microfluidic device by which the matrix density as a mechanical property and the concentration profile of a biochemical factor as a chemical property could be altered. Our microfluidic device has a cell tank and a cell culture chamber to mimic both 2D to 3D and 3D to 3D migration of three types of cells. Fluid shear stress is negligible on the cells and a stable concentration gradient can be obtained by diffusion. The device was designed by a numerical simulation so that the uniformity of the concentration gradients throughout the cell culture chamber was obtained. Adult neural cells were cultured within this device and they showed different branching and axonal navigation phenotypes within varying nerve growth factor (NGF) concentration profiles. Neural stem cells were also cultured within varying collagen matrix densities while exposed to NGF concentrations and they experienced 3D to 3D collective migration. By generating vascular endothelial growth factor concentration gradients, adult human dermal microvascular endothelial cells also migrated in a 2D to 3D manner and formed a stable lumen within a specific collagen matrix density. It was observed that a minimum absolute concentration and concentration gradient were required to stimulate migration of all types of the cells. This device has the advantage of changing multiple parameters simultaneously and is expected to have wide applicability in cell studies.

  5. 3D Printed Microfluidic Device with Integrated Biosensors for Online Analysis of Subcutaneous Human Microdialysate

    PubMed Central

    2015-01-01

    This work presents the design, fabrication, and characterization of a robust 3D printed microfluidic analysis system that integrates with FDA-approved clinical microdialysis probes for continuous monitoring of human tissue metabolite levels. The microfluidic device incorporates removable needle type integrated biosensors for glucose and lactate, which are optimized for high tissue concentrations, housed in novel 3D printed electrode holders. A soft compressible 3D printed elastomer at the base of the holder ensures a good seal with the microfluidic chip. Optimization of the channel size significantly improves the response time of the sensor. As a proof-of-concept study, our microfluidic device was coupled to lab-built wireless potentiostats and used to monitor real-time subcutaneous glucose and lactate levels in cyclists undergoing a training regime. PMID:26070023

  6. Arbitrarily Accessible 3D Microfluidic Device for Combinatorial High-Throughput Drug Screening

    PubMed Central

    Chen, Zhuofa; Li, Weizhi; Choi, Gihoon; Yang, Xiaonan; Miao, Jun; Cui, Liwang; Guan, Weihua

    2016-01-01

    Microfluidics-based drug-screening systems have enabled efficient and high-throughput drug screening, but their routine uses in ordinary labs are limited due to the complexity involved in device fabrication and system setup. In this work, we report an easy-to-use and low-cost arbitrarily accessible 3D microfluidic device that can be easily adopted by various labs to perform combinatorial assays for high-throughput drug screening. The device is capable of precisely performing automatic and simultaneous reagent loading and aliquoting tasks and performing multistep assays with arbitrary sequences. The device is not intended to compete with other microfluidic technologies regarding ultra-low reaction volume. Instead, its freedom from tubing or pumping systems and easy operation makes it an ideal platform for routine high-throughput drug screening outside traditional microfluidic labs. The functionality and quantitative reliability of the 3D microfluidic device were demonstrated with a histone acetyltransferase-based drug-screening assay using the recombinant Plasmodium falciparum GCN5 enzyme, benchmarked with a traditional microtiter plate-based method. This arbitrarily accessible, multistep capable, low-cost, and easy-to-use device can be widely adopted in various combinatorial assays beyond high-throughput drug screening. PMID:27690055

  7. Developing a protocol for creating microfluidic devices with a 3D printer, PDMS, and glass

    NASA Astrophysics Data System (ADS)

    Collette, Robyn; Novak, Eric; Shirk, Kathryn

    2015-03-01

    Microfluidics research requires the design and fabrication of devices that have the ability to manipulate small volumes of fluid, typically ranging from microliters to picoliters. These devices are used for a wide range of applications including the assembly of materials and testing of biological samples. Many methods have been previously developed to create microfluidic devices, including traditional nanolithography techniques. However, these traditional techniques are cost-prohibitive for many small-scale laboratories. This research explores a relatively low-cost technique using a 3D printed master, which is used as a template for the fabrication of polydimethylsiloxane (PDMS) microfluidic devices. The masters are designed using computer aided design (CAD) software and can be printed and modified relatively quickly. We have developed a protocol for creating simple microfluidic devices using a 3D printer and PDMS adhered to glass. This relatively simple and lower-cost technique can now be scaled to more complicated device designs and applications. Funding provided by the Undergraduate Research Grant Program at Shippensburg University and the Student/Faculty Research Engagement Grants from the College of Arts and Sciences at Shippensburg University.

  8. 3-D LTCC microfluidic device as a tool for studying nanoprecipitation

    NASA Astrophysics Data System (ADS)

    Schianti, J. N.; Cerize, N. P. N.; Oliveira, A. M.; Derenzo, S.; Góngora-Rubio, M. R.

    2013-03-01

    Nanoparticles have been used to improve the properties of many cosmetic products, mainly the sunscreens materials using nanoencapsulation or nanosuspensions, improving the contact with active molecules, enhancing the sun protection effect and facilitating formulations in industrial products. Microfluidic devices offer an important possibility in producing nanoparticles in a simple way, in one step bottom up technique, continuum process with low polidispersivity, low consumption of reagents and additives. In this work, we microfabricated a 3-D LTCC microfluidic device to study the nanoprecipitation of Benzophenone-3, used as a sunscreen in pharmaceutical products. It was observed that some parameters influence the particle size related to the total fluid flow on device, the ratio between phases, and the Benzophenone-3 initial concentration. The influence of applied voltages on particle sizes was tested also. For the processing, a high voltage was applied in a Kovar tube inserted in the 3D device. The use of microfluidic device resulted in particles with 100 up to 800 nm of size, with polispersivity index below 0.3 and offering an interesting way to obtain nanoparticles. These studies are still ongoing, but early results indicate the possibility of obtaining B-3 nanostructured material.

  9. Rollable Microfluidic Systems with Microscale Bending Radius and Tuning of Device Function with Reconfigurable 3D Channel Geometry.

    PubMed

    Kim, Jihye; You, Jae Bem; Nam, Sung Min; Seo, Sumin; Im, Sung Gap; Lee, Wonhee

    2017-03-29

    Flexible microfluidic system is an essential component of wearable biosensors to handle body fluids. A parylene-based, thin-film microfluidic system is developed to achieve flexible microfluidics with microscale bending radius. A new molding and bonding technique is developed for parylene microchannel fabrication. Bonding with nanoadhesive layers deposited by initiated chemical vapor deposition (iCVD) enables the construction of microfluidic channels with short fabrication time and high bonding strength. The high mechanical strength of parylene allows less channel deformation from the internal pressure for the thin-film parylene channel than bulk PDMS channel. At the same time, negligible channel sagging or collapse is observed during channel bending down to a few hundreds of micrometers due to stress relaxation by prestretch structure. The flexible parylene channels are also developed into a rollable microfluidic system. In a rollable microfluidics format, 2D parylene channels can be rolled around a capillary tubing working as inlets to minimize the device footprint. In addition, we show that creating reconfigurable 3D channel geometry with microscale bending radius can lead to tunable device function: tunable Dean-flow mixer is demonstrated using reconfigurable microscale 3D curved channel. Flexible parylene microfluidics with microscale bending radius is expected to provide an important breakthrough for many fields including wearable biosensors and tunable 3D microfluidics.

  10. Continuous dielectrophoretic particle separation using a microfluidic device with 3D electrodes and vaulted obstacles.

    PubMed

    Jia, Yankai; Ren, Yukun; Jiang, Hongyuan

    2015-08-01

    This paper reports a microfluidic separation device combining 3D electrodes and vaulted obstacles to continuously separate particles experiencing strong positive dielectrophoresis (DEP) from particles experiencing weak positive DEP, or from particles experiencing negative DEP. The separation is achieved by first focusing the particle mixture into a narrow stream by a hydrodynamic focusing flow, and then deviating them into different outlets by AC DEP. The vaulted obstacles facilitate the separation by both increasing the non-uniformity of the electric field, and influencing the particles to move in regions strongly affected by DEP. The 3D electrodes give rise to a spatially non-uniform electric field and extend DEP effect to the channel height. Numerical simulations are performed to investigate the effects of the obstacles on electric field distribution and particle trajectories so as to optimize the obstacle height and compare with the experimental results. The performance of the device is assessed by separating 25 μm gold-coated particles from 10 μm particles in different flow rates by positive DEP and negative DEP, and also separating 25 μm gold-coated particles from yeast cells using only positive DEP. The experimental observation shows a reasonable agreement with numerical simulation results.

  11. Quasi-3D Modeling and Efficient Simulation of Laminar Flows in Microfluidic Devices.

    PubMed

    Islam, Md Zahurul; Tsui, Ying Yin

    2016-10-03

    A quasi-3D model has been developed to simulate the flow in planar microfluidic systems with low Reynolds numbers. The model was developed by decomposing the flow profile along the height of a microfluidic system into a Fourier series. It was validated against the analytical solution for flow in a straight rectangular channel and the full 3D numerical COMSOL Navier-Stokes solver for flow in a T-channel. Comparable accuracy to the full 3D numerical solution was achieved by using only three Fourier terms with a significant decrease in computation time. The quasi-3D model was used to model flows in a micro-flow cytometer chip on a desktop computer and good agreement between the simulation and the experimental results was found.

  12. Quasi-3D Modeling and Efficient Simulation of Laminar Flows in Microfluidic Devices

    PubMed Central

    Islam, Md. Zahurul; Tsui, Ying Yin

    2016-01-01

    A quasi-3D model has been developed to simulate the flow in planar microfluidic systems with low Reynolds numbers. The model was developed by decomposing the flow profile along the height of a microfluidic system into a Fourier series. It was validated against the analytical solution for flow in a straight rectangular channel and the full 3D numerical COMSOL Navier-Stokes solver for flow in a T-channel. Comparable accuracy to the full 3D numerical solution was achieved by using only three Fourier terms with a significant decrease in computation time. The quasi-3D model was used to model flows in a micro-flow cytometer chip on a desktop computer and good agreement between the simulation and the experimental results was found. PMID:27706104

  13. Single-layer microfluidic device to realize hydrodynamic 3D flow focusing.

    PubMed

    Eluru, Gangadhar; Julius, Lourdes Albina Nirupa; Gorthi, Sai Siva

    2016-10-18

    The recent rapid growth of microfluidic applications has witnessed the emergence of several particle flow focusing techniques for analysis and/or further processing. The majority of flow focusing techniques employ an external sheath fluid to achieve sample flow focusing independent of the flow rate, in contrast to sheath-free techniques. However, the introduction of a sheath fluid to surround the sample fluid has complicated the device design and fabrication, generally involving multi-layer fabrication and bonding of multiple polydimethylsiloxane (PDMS) layers. Several promising efforts have been made to reduce the complexity of fabrication. However, most of these methods involved the use of inertial/Dean effects, which in turn demanded the use of higher sample flow rates. In this paper, we report a method of flow focusing that uses a sheath fluid to enclose the sample in a single layer of PDMS, and that possesses applicability for a wide range of sample flow rates. This method of flow focusing uses abrupt channel depth variation and a shift of one of the sample-sheath junctions (termed as 'junction-shift') against the direction of the sample flow. This configuration serves to manipulate the sample fluid with respect to the sheath fluid and achieve the desired flow focusing. This design facilitates the attainment of 3D flow focusing in two sequential steps (depth-wise and then along the lateral direction) and in distinct regions, hence enabling the regions to be used in imaging and non-imaging flow cytometric applications, respectively. Simulations were performed to characterize and determine the optimum set of design parameters. Experimental demonstrations of this technique were carried out by focusing fluorescein dye and blood cells in flow.

  14. Fabrication of a three dimensional particle focusing microfluidic device using a 3D printer, PDMS, and glass

    NASA Astrophysics Data System (ADS)

    Collette, Robyn; Rosen, Daniel; Shirk, Kathryn

    Microfluidic devices have high importance in fields such as bioanalysis because they can manipulate volumes of fluid in the range of microliters to picoliters. Small samples can be quickly and easily tested using complex microfluidic devices. Typically, these devices are created through lithography techniques, which can be costly and time consuming. It has been shown that inexpensive microfluidic devices can be produced quickly using a 3D printer and PDMS. However, a size limitation prohibits the fabrication of precisely controlled microchannels. By using shrinking materials in combination with 3D printing of flow-focusing geometries, this limitation can be overcome. This research seeks to employ these techniques to quickly fabricate an inexpensive, working device with three dimensional particle focusing capabilities. By modifying the channel geometry, colloidal particles in a solution will be focused into a single beam when passed through this device. The ability to focus particles is necessary for a variety of biological applications which requires precise detection and characterization of particles in a sample. We would like to thank the Shippensburg University Undergraduate Research Grant Program for their generous funding.

  15. One-Step Fabrication of a Microfluidic Device with an Integrated Membrane and Embedded Reagents by Multimaterial 3D Printing.

    PubMed

    Li, Feng; Smejkal, Petr; Macdonald, Niall P; Guijt, Rosanne M; Breadmore, Michael C

    2017-04-05

    One of the largest impediments in the development of microfluidic-based smart sensing systems is the manufacturability of integrated, complex devices. Here we propose multimaterial 3D printing for the fabrication of such devices in a single step. A microfluidic device containing an integrated porous membrane and embedded liquid reagents was made by 3D printing and applied for the analysis of nitrate in soil. The manufacture of the integrated, sealed device was realized as a single print within 30 min. The body of the device was printed in transparent acrylonitrile butadiene styrene (ABS) and contained a 400 μm wide structure printed from a commercially available composite filament. The composite filament can be turned into a porous material through dissolution of a water-soluble material. Liquid reagents were integrated by briefly pausing the printing before resuming for sealing the device. The devices were evaluated by the determination of nitrate in a soil slurry containing zinc particles for the reduction of nitrate to nitrite using the Griess reagent. Using a consumer digital camera, the linear range of the detector response ranged from 0 to 60 ppm, covering the normal range of nitrate in soil. To ensure that the sealing of the reagent chamber is maintained, aqueous reagents should be avoided. When using the nonaqueous reagent, the multimaterial device containing the Griess reagent could be stored for over 4 days but increased the detection range to 100-500 ppm. Multimaterial 3D printing is a potentially new approach for the manufacture of microfluidic devices with multiple integrated functional components.

  16. 3D printed microfluidics for biological applications.

    PubMed

    Ho, Chee Meng Benjamin; Ng, Sum Huan; Li, King Ho Holden; Yoon, Yong-Jin

    2015-01-01

    The term "Lab-on-a-Chip," is synonymous with describing microfluidic devices with biomedical applications. Even though microfluidics have been developing rapidly over the past decade, the uptake rate in biological research has been slow. This could be due to the tedious process of fabricating a chip and the absence of a "killer application" that would outperform existing traditional methods. In recent years, three dimensional (3D) printing has been drawing much interest from the research community. It has the ability to make complex structures with high resolution. Moreover, the fast building time and ease of learning has simplified the fabrication process of microfluidic devices to a single step. This could possibly aid the field of microfluidics in finding its "killer application" that will lead to its acceptance by researchers, especially in the biomedical field. In this paper, a review is carried out of how 3D printing helps to improve the fabrication of microfluidic devices, the 3D printing technologies currently used for fabrication and the future of 3D printing in the field of microfluidics.

  17. Numerical simulation of 3D boundary-driven acoustic streaming in microfluidic devices.

    PubMed

    Lei, Junjun; Hill, Martyn; Glynne-Jones, Peter

    2014-02-07

    This article discusses three-dimensional (3D) boundary-driven streaming in acoustofluidic devices. Firstly, the 3D Rayleigh streaming pattern in a microchannel is simulated and its effect on the movement of microparticles of various sizes is demonstrated. The results obtained from this model show good comparisons with 3D experimental visualisations and demonstrate the fully 3D nature of the acoustic streaming field and the associated acoustophoretic motion of microparticles in acoustofluidic devices. This method is then applied to another acoustofluidic device in order to gain insights into an unusual in-plane streaming pattern. The origin of this streaming has not been fully described and its characteristics cannot be explained from the classical theory of Rayleigh streaming. The simulated in-plane streaming pattern was in good agreement with the experimental visualisation. The mechanism behind it is shown to be related to the active sound intensity field, which supports our previous findings on the mechanism of the in-plane acoustic streaming pattern visualised and modelled in a thin-layered capillary device.

  18. Fabrication of continuous flow microfluidics device with 3D electrode structures for high throughput DEP applications using mechanical machining.

    PubMed

    Zeinali, Soheila; Çetin, Barbaros; Oliaei, Samad Nadimi Bavil; Karpat, Yiğit

    2015-07-01

    Microfluidics is the combination of micro/nano fabrication techniques with fluid flow at microscale to pursue powerful techniques in controlling and manipulating chemical and biological processes. Sorting and separation of bio-particles are highly considered in diagnostics and biological analyses. Dielectrophoresis (DEP) has offered unique advantages for microfluidic devices. In DEP devices, asymmetric pair of planar electrodes could be employed to generate non-uniform electric fields. In DEP applications, facing 3D sidewall electrodes is considered to be one of the key solutions to increase device throughput due to the generated homogeneous electric fields along the height of microchannels. Despite the advantages, fabrication of 3D vertical electrodes requires a considerable challenge. In this study, two alternative fabrication techniques have been proposed for the fabrication of a microfluidic device with 3D sidewall electrodes. In the first method, both the mold and the electrodes are fabricated using high precision machining. In the second method, the mold with tilted sidewalls is fabricated using high precision machining and the electrodes are deposited on the sidewall using sputtering together with a shadow mask fabricated by electric discharge machining. Both fabrication processes are assessed as highly repeatable and robust. Moreover, the two methods are found to be complementary with respect to the channel height. Only the manipulation of particles with negative-DEP is demonstrated in the experiments, and the throughput values up to 105 particles / min is reached in a continuous flow. The experimental results are compared with the simulation results and the limitations on the fabrication techniques are also discussed.

  19. 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.

  20. 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

  1. 3D Printed Multimaterial Microfluidic Valve

    PubMed Central

    Patrick, William G.; Sharma, Sunanda; Kong, David S.; Oxman, Neri

    2016-01-01

    We present a novel 3D printed multimaterial microfluidic proportional valve. The microfluidic valve is a fundamental primitive that enables the development of programmable, automated devices for controlling fluids in a precise manner. We discuss valve characterization results, as well as exploratory design variations in channel width, membrane thickness, and membrane stiffness. Compared to previous single material 3D printed valves that are stiff, these printed valves constrain fluidic deformation spatially, through combinations of stiff and flexible materials, to enable intricate geometries in an actuated, functionally graded device. Research presented marks a shift towards 3D printing multi-property programmable fluidic devices in a single step, in which integrated multimaterial valves can be used to control complex fluidic reactions for a variety of applications, including DNA assembly and analysis, continuous sampling and sensing, and soft robotics. PMID:27525809

  2. A simple method to produce 2D and 3D microfluidic paper-based analytical devices for clinical analysis.

    PubMed

    de Oliveira, Ricardo A G; Camargo, Fiamma; Pesquero, Naira C; Faria, Ronaldo Censi

    2017-03-08

    This paper describes the fabrication of 2D and 3D microfluidic paper-based analytical devices (μPADs) for monitoring glucose, total protein, and nitrite in blood serum and artificial urine. A new method of cutting and sealing filter paper to construct μPADs was demonstrated. Using an inexpensive home cutter printer soft cellulose-based filter paper was easily and precisely cut to produce pattern hydrophilic microchannels. 2D and 3D μPADs were designed with three detection zones each for the colorimetric detection of the analytes. A small volume of samples was added to the μPADs, which was photographed after 15 min using a digital camera. Both μPADs presented an excellent analytical performance for all analytes. The 2D device was applied in artificial urine samples and reached limits of detection (LODs) of 0.54 mM, 5.19 μM, and 2.34 μM for glucose, protein, and nitrite, respectively. The corresponding LODs of the 3D device applied for detecting the same analytes in artificial blood serum were 0.44 mM, 1.26 μM, and 4.35 μM.

  3. Improving sample distribution homogeneity in Three-Dimensional Microfluidic Paper-Based Analytical Devices (3D-μPAD) by rational device design.

    PubMed

    Morbioli, Giorgio Gianini; Mazzu-Nascimento, Thiago; Milan, Luis Aparecido; Stockton, Amanda M; Carrilho, Emanuel

    2017-04-12

    Paper-based devices are a portable, user-friendly and affordable technology that is one of the best analytical tools for inexpensive diagnostic devices. Three-dimensional microfluidic paper-based analytical devices (3D-μPADs) are an evolution of single layer devices and they permit effective sample dispersion, individual layer treatment, and multiplex analytical assays. Here, we present the rational design of a wax-printed 3D-μPAD that enables more homogeneous permeation of fluids along the cellulose matrix than other existing designs in the literature. Moreover, we show the importance of the rational design of channels on these devices using glucose oxidase, peroxidase, and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) reactions. We present an alternative method for layer stacking using a magnetic apparatus, which facilitates fluidic dispersion and improves the reproducibility of tests performed on 3D-μPADs. We also provide the optimized designs for printing, facilitating further studies using 3D-μPADs.

  4. Discrete elements for 3D microfluidics

    PubMed Central

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

    2014-01-01

    Microfluidic systems are rapidly becoming commonplace tools for high-precision materials synthesis, biochemical sample preparation, and biophysical analysis. Typically, microfluidic systems are constructed in monolithic form by means of microfabrication and, increasingly, by additive techniques. These methods restrict the design and assembly of truly complex systems by placing unnecessary emphasis on complete functional integration of operational elements in a planar environment. Here, we present a solution based on discrete elements that liberates designers to build large-scale microfluidic systems in three dimensions that are modular, diverse, and predictable by simple network analysis techniques. We develop a sample library of standardized components and connectors manufactured using stereolithography. We predict and validate the flow characteristics of these individual components to design and construct a tunable concentration gradient generator with a scalable number of parallel outputs. We show that these systems are rapidly reconfigurable by constructing three variations of a device for generating monodisperse microdroplets in two distinct size regimes and in a high-throughput mode by simple replacement of emulsifier subcircuits. Finally, we demonstrate the capability for active process monitoring by constructing an optical sensing element for detecting water droplets in a fluorocarbon stream and quantifying their size and frequency. By moving away from large-scale integration toward standardized discrete elements, we demonstrate the potential to reduce the practice of designing and assembling complex 3D microfluidic circuits to a methodology comparable to that found in the electronics industry. PMID:25246553

  5. Discrete elements for 3D microfluidics.

    PubMed

    Bhargava, Krisna C; Thompson, Bryant; Malmstadt, Noah

    2014-10-21

    Microfluidic systems are rapidly becoming commonplace tools for high-precision materials synthesis, biochemical sample preparation, and biophysical analysis. Typically, microfluidic systems are constructed in monolithic form by means of microfabrication and, increasingly, by additive techniques. These methods restrict the design and assembly of truly complex systems by placing unnecessary emphasis on complete functional integration of operational elements in a planar environment. Here, we present a solution based on discrete elements that liberates designers to build large-scale microfluidic systems in three dimensions that are modular, diverse, and predictable by simple network analysis techniques. We develop a sample library of standardized components and connectors manufactured using stereolithography. We predict and validate the flow characteristics of these individual components to design and construct a tunable concentration gradient generator with a scalable number of parallel outputs. We show that these systems are rapidly reconfigurable by constructing three variations of a device for generating monodisperse microdroplets in two distinct size regimes and in a high-throughput mode by simple replacement of emulsifier subcircuits. Finally, we demonstrate the capability for active process monitoring by constructing an optical sensing element for detecting water droplets in a fluorocarbon stream and quantifying their size and frequency. By moving away from large-scale integration toward standardized discrete elements, we demonstrate the potential to reduce the practice of designing and assembling complex 3D microfluidic circuits to a methodology comparable to that found in the electronics industry.

  6. Microfluidic Device

    NASA Technical Reports Server (NTRS)

    Tai, Yu-Chong (Inventor); Zheng, Siyang (Inventor); Lin, Jeffrey Chun-Hui (Inventor); Kasdan, Harvey L. (Inventor)

    2017-01-01

    Described herein are particular embodiments relating to a microfluidic device that may be utilized for cell sensing, counting, and/or sorting. Particular aspects relate to a microfabricated device that is capable of differentiating single cell types from dense cell populations. One particular embodiment relates a device and methods of using the same for sensing, counting, and/or sorting leukocytes from whole, undiluted blood samples.

  7. Microfluidic Device

    NASA Technical Reports Server (NTRS)

    Tai, Yu-Chong (Inventor); Zheng, Siyang (Inventor); Lin, Jeffrey Chun-Hui (Inventor); Kasdan, Harvey (Inventor)

    2015-01-01

    Described herein are particular embodiments relating to a microfluidic device that may be utilized for cell sensing, counting, and/or sorting. Particular aspects relate to a microfabricated device that is capable of differentiating single cell types from dense cell populations. One particular embodiment relates a device and methods of using the same for sensing, counting, and/or sorting leukocytes from whole, undiluted blood samples.

  8. Microfluidic Device

    NASA Technical Reports Server (NTRS)

    Tai, Yu-Chong (Inventor); Zheng, Siyang (Inventor); Lin, Jeffrey Chun-Hui (Inventor); Kasdan, Harvey L. (Inventor)

    2016-01-01

    Described herein are particular embodiments relating to a microfluidic device that may be utilized for cell sensing, counting, and/or sorting. Particular aspects relate to a microfabricated device that is capable of differentiating single cell types from dense cell populations. One particular embodiment relates a device and methods of using the same for sensing, counting, and/or sorting leukocytes from whole, undiluted blood samples.

  9. 3D Printed Microfluidic Device with Microporous Mn2O3-Modified Screen Printed Electrode for Real-Time Determination of Heavy Metal Ions.

    PubMed

    Hong, Ying; Wu, Meiyan; Chen, Guangwei; Dai, Ziyang; Zhang, Yizhou; Chen, Guosong; Dong, Xiaochen

    2016-12-07

    Fabricating portable devices for the determination of heavy metal ions is an ongoing challenge. Here, a 3D printing approach was adopted to fabricate a microfluidic electrochemical sensor with the desired shape in which the model for velocity profiles in microfluidic cells was built and optimized by the finite element method (FEM). The electrode in the microfluidic cell was a flexible screen-printed electrode (SPE) modified with porous Mn2O3 derived from manganese containing metal-organic framework (Mn-MOF). The microfluidic device presented superior electrochemical detection properties toward heavy metal ions. The calibration curves at the modified SPE for Cd(II) and Pb(II) covered two linear ranges varying from 0.5 to 8 and 10 to 100 μg L(-1), respectively. The limits of detection were estimated to be 0.5 μg L(-1) for Cd(II) and 0.2 μg L(-1) for Pb(II), which were accordingly about 6 and 50 times lower than the guideline values proposed by the World Health Organization. Furthermore, the microfluidic device was connected to iPad via a USB to enable real-time household applications. Additionally, the sensing system exhibited a better stability and reproducibility compared with traditional detecting system which offered a promising prospect for the detection of heavy metal ions especially in household and resource-limited occasions.

  10. Analysis of 3D multi-layer microfluidic gradient generator.

    PubMed

    Ha, Jang Ho; Kim, Tae Hyeon; Lee, Jong Min; Ahrberg, Christian D; Chung, Bong Geun

    2017-01-01

    We developed a three-dimensional (3D) simple multi-layer microfluidic gradient generator to create molecular gradients on the centimeter scale with a wide range of flow rates. To create the concentration gradients, a main channel (MC) was orthogonally intersected with vertical side microchannel (SC) in a 3D multi-layer microfluidic device. Through sequential dilution from the SC, a spatial gradient was generated in the MC. Two theoretical models were created to assist in the design of the 3D multi-layer microfluidic gradient generator and to compare its performance against a two-dimensional equivalent. A first mass balance model was used to predict the steady-state concentrations reached, while a second computational fluid dynamic model was employed to predict spatial development of the gradient by considering convective as well as diffusive mass transport. Furthermore, the theoretical simulations were verified through experiments to create molecular gradients in a 3D multi-layer microfluidic gradient generator.

  11. 3D origami-based multifunction-integrated immunodevice: low-cost and multiplexed sandwich chemiluminescence immunoassay on microfluidic paper-based analytical device.

    PubMed

    Ge, Lei; Wang, Shoumei; Song, Xianrang; Ge, Shenguang; Yu, Jinghua

    2012-09-07

    A novel 3D microfluidic paper-based immunodevice, integrated with blood plasma separation from whole blood samples, automation of rinse steps, and multiplexed CL detections, was developed for the first time based on the principle of origami (denoted as origami-based device). This 3D origami-based device, comprised of one test pad surrounded by four folding tabs, could be patterned and fabricated by wax-printing on paper in bulk. In this work, a sandwich-type chemiluminescence (CL) immunoassay was introduced into this 3D origami-based immunodevice, which could separate the operational procedures into several steps including (i) folding pads above/below and (ii) addition of reagent/buffer under a specific sequence. The CL behavior, blood plasma separation, washing protocol, and incubation time were investigated in this work. The developed 3D origami-based CL immunodevice, combined with a typical luminuol-H(2)O(2) CL system and catalyzed by Ag nanoparticles, showed excellent analytical performance for the simultaneous detection of four tumor markers. The whole blood samples were assayed and the results obtained were in agreement with the reference values from the parallel single-analyte test. This paper-based microfluidic origami CL detection system provides a new strategy for a low-cost, sensitive, simultaneous multiplex immunoassay and point-of-care diagnostics.

  12. The upcoming 3D-printing revolution in microfluidics.

    PubMed

    Bhattacharjee, Nirveek; Urrios, Arturo; Kang, Shawn; Folch, Albert

    2016-05-21

    In the last two decades, the vast majority of microfluidic systems have been built in poly(dimethylsiloxane) (PDMS) by soft lithography, a technique based on PDMS micromolding. A long list of key PDMS properties have contributed to the success of soft lithography: PDMS is biocompatible, elastomeric, transparent, gas-permeable, water-impermeable, fairly inexpensive, copyright-free, and rapidly prototyped with high precision using simple procedures. However, the fabrication process typically involves substantial human labor, which tends to make PDMS devices difficult to disseminate outside of research labs, and the layered molding limits the 3D complexity of the devices that can be produced. 3D-printing has recently attracted attention as a way to fabricate microfluidic systems due to its automated, assembly-free 3D fabrication, rapidly decreasing costs, and fast-improving resolution and throughput. Resins with properties approaching those of PDMS are being developed. Here we review past and recent efforts in 3D-printing of microfluidic systems. We compare the salient features of PDMS molding with those of 3D-printing and we give an overview of the critical barriers that have prevented the adoption of 3D-printing by microfluidic developers, namely resolution, throughput, and resin biocompatibility. We also evaluate the various forces that are persuading researchers to abandon PDMS molding in favor of 3D-printing in growing numbers.

  13. Pathology in a tube: Step 1. Fixing, staining, and transporting pancreatic core biopsies in a microfluidic device for 3D imaging

    NASA Astrophysics Data System (ADS)

    Das, Ronnie; Burfeind, Chris W.; Kramer, Greg M.; Seibel, Eric J.

    2014-03-01

    A minimally-invasive diagnosis of pancreatic cancer is accomplished by obtaining a fine needle aspirate and observing the cell preparations under conventional optical microscopy. As an unavoidable artifact, native tissue architecture is lost, making definite diagnosis of malignancy, or invasive neoplasm, impossible. One solution is the preparation of core biopsies (CBs) within a microfluidic device that are subsequently imaged in 3D. In this paper, porcine pancreas CBs (L = 1-2 cm, D = 0.4-2.0 mm) were formalin-fixed, stained and optically cleared (FocusClear®). In brightfield at 40x, light transmission through the ordinarily opaque CBs was increased 5-15x, and internal islet structures were easily identified 250-300 μm beneath the tissue surface. Typically, specimen preparation is time intensive and requires precise handling since CBs are delicate; thus, fixative, absorptive stain and FocusClear® diffusion were done slowly and manually. To significantly speed up tissue processing, we developed a microfluidic device consisting of both a main channel (L = 12.5 cm, D = 1.415 mm) with a circular cross section used for fixing and transporting the CB and an intersecting U-channel employed for staining. Space between the CB and channel wall provided a key feature not traditionally employed in microfluidic devices, such that at low flow rates (5-10 mL/min) CBs were fixed and stained while the specimen remained stationary. By switching quickly to higher flow rates (15-20 mL/min), we could precisely overcome adhesion and transport the specimen within the channel towards the imaging platform for 3D pathology.

  14. 3D-printed bioanalytical devices

    NASA Astrophysics Data System (ADS)

    Bishop, Gregory W.; Satterwhite-Warden, Jennifer E.; Kadimisetty, Karteek; Rusling, James F.

    2016-07-01

    While 3D printing technologies first appeared in the 1980s, prohibitive costs, limited materials, and the relatively small number of commercially available printers confined applications mainly to prototyping for manufacturing purposes. As technologies, printer cost, materials, and accessibility continue to improve, 3D printing has found widespread implementation in research and development in many disciplines due to ease-of-use and relatively fast design-to-object workflow. Several 3D printing techniques have been used to prepare devices such as milli- and microfluidic flow cells for analyses of cells and biomolecules as well as interfaces that enable bioanalytical measurements using cellphones. This review focuses on preparation and applications of 3D-printed bioanalytical devices.

  15. 3D hydrodynamic focusing microfluidics for emerging sensing technologies.

    PubMed

    Daniele, Michael A; Boyd, Darryl A; Mott, David R; Ligler, Frances S

    2015-05-15

    While the physics behind laminar flows has been studied for 200 years, understanding of how to use parallel flows to augment the capabilities of microfluidic systems has been a subject of study primarily over the last decade. The use of one flow to focus another within a microfluidic channel has graduated from a two-dimensional to a three-dimensional process and the design principles are only now becoming established. This review explores the underlying principles for hydrodynamic focusing in three dimensions (3D) using miscible fluids and the application of these principles for creation of biosensors, separation of cells and particles for sample manipulation, and fabrication of materials that could be used for biosensors. Where sufficient information is available, the practicality of devices implementing fluid flows directed in 3D is evaluated and the advantages and limitations of 3D hydrodynamic focusing for the particular application are highlighted.

  16. 3D-printed microfluidic chips with patterned, cell-laden hydrogel constructs.

    PubMed

    Knowlton, Stephanie; Yu, Chu Hsiang; Ersoy, Fulya; Emadi, Sharareh; Khademhosseini, Ali; Tasoglu, Savas

    2016-06-20

    Three-dimensional (3D) printing offers potential to fabricate high-throughput and low-cost fabrication of microfluidic devices as a promising alternative to traditional techniques which enables efficient design iterations in the development stage. In this study, we demonstrate a single-step fabrication of a 3D transparent microfluidic chip using two alternative techniques: a stereolithography-based desktop 3D printer and a two-step fabrication using an industrial 3D printer based on polyjet technology. This method, compared to conventional fabrication using relatively expensive materials and labor-intensive processes, presents a low-cost, rapid prototyping technique to print functional 3D microfluidic chips. We enhance the capabilities of 3D-printed microfluidic devices by coupling 3D cell encapsulation and spatial patterning within photocrosslinkable gelatin methacryloyl (GelMA). The platform presented here serves as a 3D culture environment for long-term cell culture and growth. Furthermore, we have demonstrated the ability to print complex 3D microfluidic channels to create predictable and controllable fluid flow regimes. Here, we demonstrate the novel use of 3D-printed microfluidic chips as controllable 3D cell culture environments, advancing the applicability of 3D printing to engineering physiological systems for future applications in bioengineering.

  17. Development of paper-based microfluidic analytical device for iron assay using photomask printed with 3D printer for fabrication of hydrophilic and hydrophobic zones on paper by photolithography.

    PubMed

    Asano, Hitoshi; Shiraishi, Yukihide

    2015-07-09

    This paper describes a paper-based microfluidic analytical device for iron assay using a photomask printed with a 3D printer for fabrication of hydrophilic and hydrophobic zones on the paper by photolithography. Several designed photomasks for patterning paper-based microfluidic analytical devices can be printed with a 3D printer easily, rapidly and inexpensively. A chromatography paper was impregnated with the octadecyltrichlorosilane n-hexane solution and hydrophobized. After the hydrophobic zone of the paper was exposed to the UV light through the photomask, the hydrophilic zone was generated. The smallest functional hydrophilic channel and hydrophobic barrier were ca. 500 μm and ca. 100 μm in width, respectively. The fabrication method has high stability, resolution and precision for hydrophilic channel and hydrophobic barrier. This test paper was applied to the analysis of iron in water samples using a colorimetry with phenanthroline.

  18. Construction of programmable interconnected 3D microfluidic networks

    NASA Astrophysics Data System (ADS)

    Hunziker, Patrick R.; Wolf, Marc P.; Wang, Xueya; Zhang, Bei; Marsch, Stephan; Salieb-Beugelaar, Georgette B.

    2015-02-01

    Microfluidic systems represent a key-enabling platform for novel diagnostic tools for use at the point-of-care in clinical contexts as well as for evolving single cell diagnostics. The design of 3D microfluidic systems is an active field of development, but construction of true interconnected 3D microfluidic networks is still a challenge, in particular when the goal is rapid prototyping, accurate design and flexibility. We report a novel approach for the construction of programmable 3D microfluidic systems consisting of modular 3D template casting of interconnected threads to allow user-programmable flow paths and examine its structural characteristics and its modular function. To overcome problems with thread template casting reported in the literature, low-surface-energy polymer threads were used, that allow solvent-free production. Connected circular channels with excellent roundness and low diameter variability were created. Variable channel termination allowed programming a flow path on-the-fly, thus rendering the resulting 3D microfluidic systems highly customizable even after production. Thus, construction of programmable/reprogrammable fully 3D microfluidic systems by template casting of a network of interconnecting threads is feasible, leads to high-quality and highly reproducible, complex 3D geometries.

  19. 3D printing of soft lithography mold for rapid production of polydimethylsiloxane-based microfluidic devices for cell stimulation with concentration gradients.

    PubMed

    Kamei, Ken-ichiro; Mashimo, Yasumasa; Koyama, Yoshie; Fockenberg, Christopher; Nakashima, Miyuki; Nakajima, Minako; Li, Junjun; Chen, Yong

    2015-04-01

    Three-dimensional (3D) printing is advantageous over conventional technologies for the fabrication of sophisticated structures such as 3D micro-channels for future applications in tissue engineering and drug screening. We aimed to apply this technology to cell-based assays using polydimethylsiloxane (PDMS), the most commonly used material for fabrication of micro-channels used for cell culture experiments. Useful properties of PDMS include biocompatibility, gas permeability and transparency. We developed a simple and robust protocol to generate PDMS-based devices using a soft lithography mold produced by 3D printing. 3D chemical gradients were then generated to stimulate cells confined to a micro-channel. We demonstrate that concentration gradients of growth factors, important regulators of cell/tissue functions in vivo, influence the survival and growth of human embryonic stem cells. Thus, this approach for generation of 3D concentration gradients could have strong implications for tissue engineering and drug screening.

  20. High density 3D printed microfluidic valves, pumps, and multiplexers.

    PubMed

    Gong, Hua; Woolley, Adam T; Nordin, Gregory P

    2016-07-07

    In this paper we demonstrate that 3D printing with a digital light processor stereolithographic (DLP-SLA) 3D printer can be used to create high density microfluidic devices with active components such as valves and pumps. Leveraging our previous work on optical formulation of inexpensive resins (RSC Adv., 2015, 5, 106621), we demonstrate valves with only 10% of the volume of our original 3D printed valves (Biomicrofluidics, 2015, 9, 016501), which were already the smallest that have been reported. Moreover, we show that incorporation of a thermal initiator in the resin formulation along with a post-print bake can dramatically improve the durability of 3D printed valves up to 1 million actuations. Using two valves and a valve-like displacement chamber (DC), we also create compact 3D printed pumps. With 5-phase actuation and a 15 ms phase interval, we obtain pump flow rates as high as 40 μL min(-1). We also characterize maximum pump back pressure (i.e., maximum pressure the pump can work against), maximum flow rate (flow rate when there is zero back pressure), and flow rate as a function of the height of the pump outlet. We further demonstrate combining 5 valves and one DC to create a 3-to-2 multiplexer with integrated pump. In addition to serial multiplexing, we also show that the device can operate as a mixer. Importantly, we illustrate the rapid fabrication and test cycles that 3D printing makes possible by implementing a new multiplexer design to improve mixing, and fabricate and test it within one day.

  1. Sequential assembly of 3D perfusable microfluidic hydrogels.

    PubMed

    He, Jiankang; Zhu, Lin; Liu, Yaxiong; Li, Dichen; Jin, Zhongmin

    2014-11-01

    Bottom-up tissue engineering provides a promising way to recreate complex structural organizations of native organs in artificial constructs by assembling functional repeating modules. However, it is challenging for current bottom-up strategies to simultaneously produce a controllable and immediately perfusable microfluidic network in modularly assembled 3D constructs. Here we presented a bottom-up strategy to produce perfusable microchannels in 3D hydrogels by sequentially assembling microfluidic modules. The effects of agarose-collagen composition on microchannel replication and 3D assembly of hydrogel modules were investigated. The unique property of predefined microchannels in transporting fluids within 3D assemblies was evaluated. Endothelial cells were incorporated into the microfluidic network of 3D hydrogels for dynamic culture in a house-made bioreactor system. The results indicated that the sequential assembly method could produce interconnected 3D predefined microfluidic networks in optimized agarose-collagen hydrogels, which were fully perfusable and successfully functioned as fluid pathways to facilitate the spreading of endothelial cells. We envision that the presented method could be potentially used to engineer 3D vascularized parenchymal constructs by encapsulating primary cells in bulk hydrogels and incorporating endothelial cells in predefined microchannels.

  2. 3D Printed Micro Free-Flow Electrophoresis Device.

    PubMed

    Anciaux, Sarah K; Geiger, Matthew; Bowser, Michael T

    2016-08-02

    The cost, time, and restrictions on creative flexibility associated with current fabrication methods present significant challenges in the development and application of microfluidic devices. Additive manufacturing, also referred to as three-dimensional (3D) printing, provides many advantages over existing methods. With 3D printing, devices can be made in a cost-effective manner with the ability to rapidly prototype new designs. We have fabricated a micro free-flow electrophoresis (μFFE) device using a low-cost, consumer-grade 3D printer. Test prints were performed to determine the minimum feature sizes that could be reproducibly produced using 3D printing fabrication. Microfluidic ridges could be fabricated with dimensions as small as 20 μm high × 640 μm wide. Minimum valley dimensions were 30 μm wide × 130 μm wide. An acetone vapor bath was used to smooth acrylonitrile-butadiene-styrene (ABS) surfaces and facilitate bonding of fully enclosed channels. The surfaces of the 3D-printed features were profiled and compared to a similar device fabricated in a glass substrate. Stable stream profiles were obtained in a 3D-printed μFFE device. Separations of fluorescent dyes in the 3D-printed device and its glass counterpart were comparable. A μFFE separation of myoglobin and cytochrome c was also demonstrated on a 3D-printed device. Limits of detection for rhodamine 110 were determined to be 2 and 0.3 nM for the 3D-printed and glass devices, respectively.

  3. Simple and Versatile 3D Printed Microfluidics Using Fused Filament Fabrication.

    PubMed

    Morgan, Alex J L; Hidalgo San Jose, Lorena; Jamieson, William D; Wymant, Jennifer M; Song, Bing; Stephens, Phil; Barrow, David A; Castell, Oliver K

    2016-01-01

    The uptake of microfluidics by the wider scientific community has been limited by the fabrication barrier created by the skills and equipment required for the production of traditional microfluidic devices. Here we present simple 3D printed microfluidic devices using an inexpensive and readily accessible printer with commercially available printer materials. We demonstrate that previously reported limitations of transparency and fidelity have been overcome, whilst devices capable of operating at pressures in excess of 2000 kPa illustrate that leakage issues have also been resolved. The utility of the 3D printed microfluidic devices is illustrated by encapsulating dental pulp stem cells within alginate droplets; cell viability assays show the vast majority of cells remain live, and device transparency is sufficient for single cell imaging. The accessibility of these devices is further enhanced through fabrication of integrated ports and by the introduction of a Lego®-like modular system facilitating rapid prototyping whilst offering the potential for novices to build microfluidic systems from a database of microfluidic components.

  4. Simple and Versatile 3D Printed Microfluidics Using Fused Filament Fabrication

    PubMed Central

    Morgan, Alex J. L.; Hidalgo San Jose, Lorena; Jamieson, William D.; Wymant, Jennifer M.; Song, Bing; Stephens, Phil

    2016-01-01

    The uptake of microfluidics by the wider scientific community has been limited by the fabrication barrier created by the skills and equipment required for the production of traditional microfluidic devices. Here we present simple 3D printed microfluidic devices using an inexpensive and readily accessible printer with commercially available printer materials. We demonstrate that previously reported limitations of transparency and fidelity have been overcome, whilst devices capable of operating at pressures in excess of 2000 kPa illustrate that leakage issues have also been resolved. The utility of the 3D printed microfluidic devices is illustrated by encapsulating dental pulp stem cells within alginate droplets; cell viability assays show the vast majority of cells remain live, and device transparency is sufficient for single cell imaging. The accessibility of these devices is further enhanced through fabrication of integrated ports and by the introduction of a Lego®-like modular system facilitating rapid prototyping whilst offering the potential for novices to build microfluidic systems from a database of microfluidic components. PMID:27050661

  5. In-air microfluidics: Drop and jet coalescence enables rapid multi-phase 3D printing

    NASA Astrophysics Data System (ADS)

    Visser, Claas Willem; Kamperman, Tom; Lohse, Detlef; Karperien, Marcel; University of Twente Collaboration

    2016-11-01

    For the first time, we connect and integrate the fields of microfluidics and additive manufacturing, by presenting a unifying technology that we call In-air microfluidics (IAMF). We impact two liquid jets or a jet and a droplet train while flying in-air, and control their coalescence and solidification. This approach enables producing monodisperse emulsions, particles, and fibers with controlled shape and size (10 to 300 µm) and production rates 100x higher than droplet microfluidics. A single device is sufficient to process a variety of materials, and to produce different particle or fiber shapes, in marked contrast to current microfluidic devices or printers. In-air microfluidics also enables rapid deposition onto substrates, for example to form 3D printed (bio)materials which are partly-liquid but still shape-stable.

  6. 3D elastic control for mobile devices.

    PubMed

    Hachet, Martin; Pouderoux, Joachim; Guitton, Pascal

    2008-01-01

    To increase the input space of mobile devices, the authors developed a proof-of-concept 3D elastic controller that easily adapts to mobile devices. This embedded device improves the completion of high-level interaction tasks such as visualization of large documents and navigation in 3D environments. It also opens new directions for tomorrow's mobile applications.

  7. Microfluidic Printheads for Multimaterial 3D Printing of Viscoelastic Inks.

    PubMed

    Hardin, James O; Ober, Thomas J; Valentine, Alexander D; Lewis, Jennifer A

    2015-06-03

    Multimaterial 3D printing using microfluidic printheads specifically designed for seamless switching between two visco-elastic materials "on-the-fly" during fabrication is demonstrated. This approach opens new avenues for the digital assembly of functional matter with controlled compositional and property gradients at the microscale.

  8. Single-layer planar on-chip flow cytometer using microfluidic drifting based three-dimensional (3D) hydrodynamic focusing.

    PubMed

    Mao, Xiaole; Lin, Sz-Chin Steven; Dong, Cheng; Huang, Tony Jun

    2009-06-07

    In this work, we demonstrate an on-chip microfluidic flow cytometry system based on a three-dimensional (3D) hydrodynamic focusing technique, microfluidic drifting. By inducing Dean flow in a curved microfluidic channel, microfluidic drifting can be used to hydrodynamically focus cells or particles in the vertical direction and enables the 3D hydrodynamic focusing in a single-layer planar microfluidic device. Through theoretical calculation, numerical simulation, and experimental characterization, we found that the microfluidic drifting technique can be effectively applied to three-dimensionally focus microparticles with density and size equivalent to those of human CD4+ T lymphocytes. In addition, we developed a flow cytometry platform by integrating the 3D focusing device with a laser-induced fluorescence (LIF) detection system. The system was shown to provide effective high-throughput flow cytometry measurements at a rate of greater than 1700 cells s(-1).

  9. Sub-micrometer-precision, three-dimensional (3D) hydrodynamic focusing via "microfluidic drifting".

    PubMed

    Nawaz, Ahmad Ahsan; Zhang, Xiangjun; Mao, Xiaole; Rufo, Joseph; Lin, Sz-Chin Steven; Guo, Feng; Zhao, Yanhui; Lapsley, Michael; Li, Peng; McCoy, J Philip; Levine, Stewart J; Huang, Tony Jun

    2014-01-21

    In this article, we demonstrate single-layered, "microfluidic drifting" based three-dimensional (3D) hydrodynamic focusing devices with particle/cell focal positioning approaching submicron precision along both lateral and vertical directions. By systematically optimizing channel geometries and sample/sheath flow rates, a series of "microfluidic drifting" based 3D hydrodynamic focusing devices with different curvature angles are designed and fabricated. Their performances are then evaluated using confocal microscopy, fast camera imaging, and side-view imaging techniques. Using a device with a curvature angle of 180°, we have achieved a standard deviation of ±0.45 μm in particle focal position and a coefficient of variation (CV) of 2.37% in flow cytometric measurements. To the best of our knowledge, this is the best CV that has been achieved using a microfluidic flow cytometry device. Moreover, the device showed the capability to distinguish 8 peaks when subjected to a stringent 8-peak rainbow calibration test, signifying the ability to perform sensitive, accurate tests similar to commercial flow cytometers. We have further tested and validated our device by detection of HEK-293 cells. With its advantages in simple fabrication (i.e., single-layered device), precise 3D hydrodynamic focusing (i.e., submicrometer precision along both lateral and vertical directions), and high detection resolution (i.e., low CV), our method could serve as an important basis for high-performance, mass-producible microfluidic flow cytometry.

  10. 3D Droplet Microfluidic Systems for High-Throughput Biological Experimentation.

    PubMed

    Kang, Dong-Ku; Gong, Xiuqing; Cho, Soongwon; Kim, Jin-young; Edel, Joshua B; Chang, Soo-Ik; Choo, Jaebum; deMello, Andrew J

    2015-11-03

    Herein, we describe the development of a multilayer droplet microfluidic system for creating concentration gradients and generating microdroplets of varying composition for high-throughput biochemical and cell-based screening applications. The 3D droplet-based microfluidic device consists of multiple PDMS layers, which are used to generate logarithmic concentration gradient reagent profiles. Parallel flow focusing structures are used to form picoliter-sized droplets of defined volumes but of varying composition. As proof of concept, we demonstrate rapid enzymatic activity assays and drug cytotoxicity assays on bacteria. The 3D droplet-based microfluidic platform has the potential to allow for high-efficiency and high-throughput analysis, overcoming the structural limitations of single layer microfluidic systems.

  11. Microfluidic vascular channels in gels using commercial 3D printers

    NASA Astrophysics Data System (ADS)

    Selvaganapathy, P. Ravi; Attalla, Rana

    2016-03-01

    This paper details the development of a three dimensional (3D) printing system with a modified microfluidic printhead used for the generation of complex vascular tissue scaffolds. The print-head features an integrated coaxial nozzle that allows the fabrication of hollow, calcium-polymerized alginate tubes that can easily be patterned using 3Dbioprinting techniques. This microfluidic design allows the incorporation of a wide range of scaffold materials as well as biological constituents such as cells, growth factors, and ECM material. With this setup, gel constructs with embedded arrays of hollow channels can be created and used as a potential substitute for blood vessel networks.

  12. Comparing Microfluidic Performance of Three-Dimensional (3D) Printing Platforms.

    PubMed

    Macdonald, Niall P; Cabot, Joan M; Smejkal, Petr; Guijt, Rosanne M; Paull, Brett; Breadmore, Michael C

    2017-03-24

    Three-dimensional (3D) printing has emerged as a potential revolutionary technology for the fabrication of microfluidic devices. A direct experimental comparison of the three 3D printing technologies dominating microfluidics was conducted using a Y-junction microfluidic device, the design of which was optimized for each printer: fused deposition molding (FDM), Polyjet, and digital light processing stereolithography (DLP-SLA). Printer performance was evaluated in terms of feature size, accuracy, and suitability for mass manufacturing; laminar flow was studied to assess their suitability for microfluidics. FDM was suitable for microfabrication with minimum features of 321 ± 5 μm, and rough surfaces of 10.97 μm. Microfluidic devices >500 μm, rapid mixing (71% ± 12% after 5 mm, 100 μL/min) was observed, indicating a strength in fabricating micromixers. Polyjet fabricated channels with a minimum size of 205 ± 13 μm, and a surface roughness of 0.99 μm. Compared with FDM, mixing decreased (27% ± 10%), but Polyjet printing is more suited for microfluidic applications where flow splitting is not required, such as cell culture or droplet generators. DLP-SLA fabricated a minimum channel size of 154 ± 10 μm, and 94 ± 7 μm for positive structures such as soft lithography templates, with a roughness of 0.35 μm. These results, in addition to low mixing (8% ± 1%), showed suitability for microfabrication, and microfluidic applications requiring precise control of flow. Through further discussion of the capabilities (and limitations) of these printers, we intend to provide guidance toward the selection of the 3D printing technology most suitable for specific microfluidic applications.

  13. Structural and functional imaging of 3D microfluidic mixers using optical coherence tomography.

    PubMed

    Xi, Chuanwu; Marks, Daniel L; Parikh, Devang S; Raskin, Lutgarde; Boppart, Stephen A

    2004-05-18

    To achieve high mixing efficiency in microfluidic devices, complex designs are often required. Microfluidic devices have been evaluated with light and confocal microscopy, but fluid-flow characteristics at different depths are difficult to separate from the en face images produced. By using optical coherence tomography (OCT), an imaging modality capable of imaging 3D microstructures at micrometer-scale resolutions over millimeter-size scales, we obtained 3D dynamic functional and structural data for three representative microfluidic mixers: a Y channel mixer, a 3D serpentine mixer, and a vortex mixer. In the serpentine mixer, OCT image analysis revealed that the mixing efficiency was linearly dependent on the Reynolds number, whereas it appeared to have exponential dependence when imaged with light microscopy. The visual overlap of fluid flows in light-microscopy images leads to an overestimation of the mixing efficiency, an effect that was eliminated with OCT imaging. Doppler OCT measurements determined velocity profiles at various points in the serpentine mixer. Mixing patterns in the vortex mixer were compared with light-microscopy and OCT image analysis. These results demonstrate that OCT can significantly improve the characterization of 3D microfluidic device structure and function.

  14. On-chip Microfluidic Multimodal Swimmer toward 3D Navigation

    NASA Astrophysics Data System (ADS)

    Barbot, Antoine; Decanini, Dominique; Hwang, Gilgueng

    2016-01-01

    Mobile microrobots have a promising future in various applications. These include targeted drug delivery, local measurement, biopsy or microassembly. Studying mobile microrobots inside microfluidics is an essential step towards such applications. But in this environment that was not designed for the robot, integration process and propulsion robustness still pose technological challenges. In this paper, we present a helical microrobot with three different motions, designed to achieve these goals. These motions are rolling, spintop motion and swimming. Through these multiple motions, microrobots are able to selectively integrate a chip through a microfluidic channel. This enables them to perform propulsion characterizations, 3D (Three Dimensional) maneuverability, particle cargo transport manipulation and exit from the chip. The microrobot selective integration inside microfluidics could lead to various in-vitro biologic or in-vivo biomedical applications.

  15. On-chip Microfluidic Multimodal Swimmer toward 3D Navigation

    PubMed Central

    Barbot, Antoine; Decanini, Dominique; Hwang, Gilgueng

    2016-01-01

    Mobile microrobots have a promising future in various applications. These include targeted drug delivery, local measurement, biopsy or microassembly. Studying mobile microrobots inside microfluidics is an essential step towards such applications. But in this environment that was not designed for the robot, integration process and propulsion robustness still pose technological challenges. In this paper, we present a helical microrobot with three different motions, designed to achieve these goals. These motions are rolling, spintop motion and swimming. Through these multiple motions, microrobots are able to selectively integrate a chip through a microfluidic channel. This enables them to perform propulsion characterizations, 3D (Three Dimensional) maneuverability, particle cargo transport manipulation and exit from the chip. The microrobot selective integration inside microfluidics could lead to various in-vitro biologic or in-vivo biomedical applications. PMID:26791433

  16. Microfluidic techniques for development of 3D vascularized tissue.

    PubMed

    Hasan, Anwarul; Paul, Arghya; Vrana, Nihal E; Zhao, Xin; Memic, Adnan; Hwang, Yu-Shik; Dokmeci, Mehmet R; Khademhosseini, Ali

    2014-08-01

    Development of a vascularized tissue is one of the key challenges for the successful clinical application of tissue engineered constructs. Despite the significant efforts over the last few decades, establishing a gold standard to develop three dimensional (3D) vascularized tissues has still remained far from reality. Recent advances in the application of microfluidic platforms to the field of tissue engineering have greatly accelerated the progress toward the development of viable vascularized tissue constructs. Numerous techniques have emerged to induce the formation of vascular structure within tissues which can be broadly classified into two distinct categories, namely (1) prevascularization-based techniques and (2) vasculogenesis and angiogenesis-based techniques. This review presents an overview of the recent advancements in the vascularization techniques using both approaches for generating 3D vascular structure on microfluidic platforms.

  17. Microfluidic Techniques for Development of 3D Vascularized Tissue

    PubMed Central

    Hasan, Anwarul; Paul, Arghya; Vrana, Nihal Engin; Zhao, Xin; Memic, Adnan; Hwang, Yu-Shik; Dokmeci, Mehmet R.; Khademhosseini, Ali

    2014-01-01

    Development of a vascularized tissue is one of the key challenges for the successful clinical application of tissue engineered constructs. Despite the significant efforts over the last few decades, establishing a gold standard to develop three dimensional (3D) vascularized tissues has still remained far from reality. Recent advances in the application of microfluidic platforms to the field of tissue engineering have greatly accelerated the progress toward the development of viable vascularized tissue constructs. Numerous techniques have emerged to induce the formation of vascular structure within tissues which can be broadly classified into two distinct categories, namely (1) prevascularization-based techniques and (2) vasculogenesis and angiogenesis-based techniques. This review presents an overview of the recent advancements in the vascularization techniques using both approaches for generating 3D vascular structure on microfluidic platforms. PMID:24906345

  18. Microfluidic Cell Culture Device

    NASA Technical Reports Server (NTRS)

    Takayama, Shuichi (Inventor); Cabrera, Lourdes Marcella (Inventor); Heo, Yun Seok (Inventor); Smith, Gary Daniel (Inventor)

    2014-01-01

    Microfluidic devices for cell culturing and methods for using the same are disclosed. One device includes a substrate and membrane. The substrate includes a reservoir in fluid communication with a passage. A bio-compatible fluid may be added to the reservoir and passage. The reservoir is configured to receive and retain at least a portion of a cell mass. The membrane acts as a barrier to evaporation of the bio-compatible fluid from the passage. A cover fluid may be added to cover the bio-compatible fluid to prevent evaporation of the bio-compatible fluid.

  19. Controllable organization and high throughput production of recoverable 3D tumors using pneumatic microfluidics.

    PubMed

    Liu, Wenming; Wang, Jian-Chun; Wang, Jinyi

    2015-02-21

    Three-dimensional tumor culture methods offer a high degree of biological and clinical relevance to in vitro models as well as cancer therapy. However, a straightforward, dynamic, and high-throughput method for micro-manipulation of 3D tumors is not yet well established. In this study, we present a novel and simple strategy for producing biomimetic 3D tumors in a controllable, high throughput manner based on an integrated microfluidic system with well-established pneumatic microstructures. Serial manipulations, including one-step cell localization, array-like self-assembly, and real-time analysis of 3D tumors, are accomplished smoothly in the microfluidic device. The recovery of tumor products from the chip is performed by dynamic off-switch of the pneumatic microstructures. In addition, this microfluidic platform is demonstrated to be capable of producing multiple types of 3D tumors and performing the evaluation of tumor targeting by nanomedicine. The pneumatic microfluidic-based 3D tumor production shows potential for research on tumor biology, tissue engineering, and drug delivery.

  20. Microplasma fabrication: from semiconductor technology for 2D-chips and microfluidic channels to rapid prototyping and 3D-printing of microplasma devices

    NASA Astrophysics Data System (ADS)

    Shatford, R.; Karanassios, Vassili

    2014-05-01

    Microplasmas are receiving attention in recent conferences and current scientific literature. In our laboratory, microplasmas-on-chips proved to be particularly attractive. The 2D- and 3D-chips we developed became hybrid because they were fitted with a quartz plate (quartz was used due to its transparency to UV). Fabrication of 2D- and 3D-chips for microplasma research is described. The fabrication methods described ranged from semiconductor fabrication technology, to Computer Numerical Control (CNC) machining, to 3D-printing. These methods may prove to be useful for those contemplating in entering microplasma research but have no access to expensive semiconductor fabrication equipment.

  1. 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.

  2. Fabrication and optimisation of a fused filament 3D-printed microfluidic platform

    NASA Astrophysics Data System (ADS)

    Tothill, A. M.; Partridge, M.; James, S. W.; Tatam, R. P.

    2017-03-01

    A 3D-printed microfluidic device was designed and manufactured using a low cost (2000) consumer grade fusion deposition modelling (FDM) 3D printer. FDM printers are not typically used, or are capable, of producing the fine detailed structures required for microfluidic fabrication. However, in this work, the optical transparency of the device was improved through manufacture optimisation to such a point that optical colorimetric assays can be performed in a 50 µl device. A colorimetric enzymatic cascade assay was optimised using glucose oxidase and horseradish peroxidase for the oxidative coupling of aminoantipyrine and chromotropic acid to produce a blue quinoneimine dye with a broad absorbance peaking at 590 nm for the quantification of glucose in solution. For comparison the assay was run in standard 96 well plates with a commercial plate reader. The results show the accurate and reproducible quantification of 0–10 mM glucose solution using a 3D-printed microfluidic optical device with performance comparable to that of a plate reader assay.

  3. Microfluidic device, and related methods

    NASA Technical Reports Server (NTRS)

    Wong, Eric W. (Inventor)

    2010-01-01

    A method of making a microfluidic device is provided. The method features patterning a permeable wall on a substrate, and surrounding the permeable wall with a solid, non-permeable boundary structure to establish a microfluidic channel having a cross-sectional dimension less than 5,000 microns and a cross-sectional area at least partially filled with the permeable wall so that fluid flowing through the microfluidic channel at least partially passes through the permeable wall.

  4. Simple, Expendable, 3D-Printed Microfluidic Systems for Sample Preparation of Petroleum.

    PubMed

    Kataoka, Érica M; Murer, Rui C; Santos, Jandyson M; Carvalho, Rogério M; Eberlin, Marcos N; Augusto, Fabio; Poppi, Ronei J; Gobbi, Angelo L; Hantao, Leandro W

    2017-03-21

    In this study, we introduce a simple protocol to manufacture disposable, 3D-printed microfluidic systems for sample preparation of petroleum. This platform is produced with a consumer-grade 3D-printer, using fused deposition modeling. Successful incorporation of solid-phase extraction (SPE) to microchip was ensured by facile 3D element integration using proposed approach. This 3D-printed μSPE device was applied to challenging matrices in oil and gas industry, such as crude oil and oil-brine emulsions. Case studies investigated important limitations of nonsilicon and nonglass microchips, namely, resistance to nonpolar solvents and conservation of sample integrity. Microfluidic features remained fully functional even after prolonged exposure to nonpolar solvents (20 min). Also, 3D-printed μSPE devices enabled fast emulsion breaking and solvent deasphalting of petroleum, yielding high recovery values (98%) without compromising maltene integrity. Such finding was ascertained by high-resolution molecular analyses using comprehensive two-dimensional gas chromatography and gas chromatography/mass spectrometry by monitoring important biomarker classes, such as C10 demethylated terpanes, ααα-steranes, and monoaromatic steroids. 3D-Printed chips enabled faster and reliable preparation of maltenes by exhibiting a 10-fold reduction in sample processing time, compared to the reference method. Furthermore, polar (oxygen-, nitrogen-, and sulfur-containing) analytes found in low-concentrations were analyzed by Fourier transform ion cyclotron resonance mass spectrometry. Analysis results demonstrated that accurate characterization may be accomplished for most classes of polar compounds, except for asphaltenes, which exhibited lower recoveries (82%) due to irreversible adsorption to sorbent phase. Therefore, 3D-printing is a compelling alternative to existing microfabrication solutions, as robust devices were easy to prepare and operate.

  5. Customisable 3D printed microfluidics for integrated analysis and optimisation.

    PubMed

    Monaghan, T; Harding, M J; Harris, R A; Friel, R J; Christie, S D R

    2016-08-16

    The formation of smart Lab-on-a-Chip (LOC) devices featuring integrated sensing optics is currently hindered by convoluted and expensive manufacturing procedures. In this work, a series of 3D-printed LOC devices were designed and manufactured via stereolithography (SL) in a matter of hours. The spectroscopic performance of a variety of optical fibre combinations were tested, and the optimum path length for performing Ultraviolet-visible (UV-vis) spectroscopy determined. The information gained in these trials was then used in a reaction optimisation for the formation of carvone semicarbazone. The production of high resolution surface channels (100-500 μm) means that these devices were capable of handling a wide range of concentrations (9 μM-38 mM), and are ideally suited to both analyte detection and process optimisation. This ability to tailor the chip design and its integrated features as a direct result of the reaction being assessed, at such a low time and cost penalty greatly increases the user's ability to optimise both their device and reaction. As a result of the information gained in this investigation, we are able to report the first instance of a 3D-printed LOC device with fully integrated, in-line monitoring capabilities via the use of embedded optical fibres capable of performing UV-vis spectroscopy directly inside micro channels.

  6. In situ fabrication of 3D Ag@ZnO nanostructures for microfluidic surface-enhanced Raman scattering systems.

    PubMed

    Xie, Yuliang; Yang, Shikuan; Mao, Zhangming; Li, Peng; Zhao, Chenglong; Cohick, Zane; Huang, Po-Hsun; Huang, Tony Jun

    2014-12-23

    In this work, we develop an in situ method to grow highly controllable, sensitive, three-dimensional (3D) surface-enhanced Raman scattering (SERS) substrates via an optothermal effect within microfluidic devices. Implementing this approach, we fabricate SERS substrates composed of Ag@ZnO structures at prescribed locations inside microfluidic channels, sites within which current fabrication of SERS structures has been arduous. Conveniently, properties of the 3D Ag@ZnO nanostructures such as length, packing density, and coverage can also be adjusted by tuning laser irradiation parameters. After exploring the fabrication of the 3D nanostructures, we demonstrate a SERS enhancement factor of up to ∼2×10(6) and investigate the optical properties of the 3D Ag@ZnO structures through finite-difference time-domain simulations. To illustrate the potential value of our technique, low concentrations of biomolecules in the liquid state are detected. Moreover, an integrated cell-trapping function of the 3D Ag@ZnO structures records the surface chemical fingerprint of a living cell. Overall, our optothermal-effect-based fabrication technique offers an effective combination of microfluidics with SERS, resolving problems associated with the fabrication of SERS substrates in microfluidic channels. With its advantages in functionality, simplicity, and sensitivity, the microfluidic-SERS platform presented should be valuable in many biological, biochemical, and biomedical applications.

  7. In Situ Fabrication of 3D Ag@ZnO Nanostructures for Microfluidic Surface-Enhanced Raman Scattering Systems

    PubMed Central

    2015-01-01

    In this work, we develop an in situ method to grow highly controllable, sensitive, three-dimensional (3D) surface-enhanced Raman scattering (SERS) substrates via an optothermal effect within microfluidic devices. Implementing this approach, we fabricate SERS substrates composed of Ag@ZnO structures at prescribed locations inside microfluidic channels, sites within which current fabrication of SERS structures has been arduous. Conveniently, properties of the 3D Ag@ZnO nanostructures such as length, packing density, and coverage can also be adjusted by tuning laser irradiation parameters. After exploring the fabrication of the 3D nanostructures, we demonstrate a SERS enhancement factor of up to ∼2 × 106 and investigate the optical properties of the 3D Ag@ZnO structures through finite-difference time-domain simulations. To illustrate the potential value of our technique, low concentrations of biomolecules in the liquid state are detected. Moreover, an integrated cell-trapping function of the 3D Ag@ZnO structures records the surface chemical fingerprint of a living cell. Overall, our optothermal-effect-based fabrication technique offers an effective combination of microfluidics with SERS, resolving problems associated with the fabrication of SERS substrates in microfluidic channels. With its advantages in functionality, simplicity, and sensitivity, the microfluidic-SERS platform presented should be valuable in many biological, biochemical, and biomedical applications. PMID:25402207

  8. Microfluidic devices for cell cultivation and proliferation

    PubMed Central

    Tehranirokh, Masoomeh; Kouzani, Abbas Z.; Francis, Paul S.; Kanwar, Jagat R.

    2013-01-01

    Microfluidic technology provides precise, controlled-environment, cost-effective, compact, integrated, and high-throughput microsystems that are promising substitutes for conventional biological laboratory methods. In recent years, microfluidic cell culture devices have been used for applications such as tissue engineering, diagnostics, drug screening, immunology, cancer studies, stem cell proliferation and differentiation, and neurite guidance. Microfluidic technology allows dynamic cell culture in microperfusion systems to deliver continuous nutrient supplies for long term cell culture. It offers many opportunities to mimic the cell-cell and cell-extracellular matrix interactions of tissues by creating gradient concentrations of biochemical signals such as growth factors, chemokines, and hormones. Other applications of cell cultivation in microfluidic systems include high resolution cell patterning on a modified substrate with adhesive patterns and the reconstruction of complicated tissue architectures. In this review, recent advances in microfluidic platforms for cell culturing and proliferation, for both simple monolayer (2D) cell seeding processes and 3D configurations as accurate models of in vivo conditions, are examined. PMID:24273628

  9. Microfluidic device for drug delivery

    NASA Technical Reports Server (NTRS)

    Beebe, David J. (Inventor); MacDonald, Michael J. (Inventor); Eddington, David T. (Inventor); Mensing, Glennys A. (Inventor)

    2010-01-01

    A microfluidic device is provided for delivering a drug to an individual. The microfluidic device includes a body that defines a reservoir for receiving the drug therein. A valve interconnects the reservoir to an output needle that is insertable into the skin of an individual. A pressure source urges the drug from the reservoir toward the needle. The valve is movable between a closed position preventing the flow of the drug from the reservoir to the output needle and an open position allowing for the flow of the drug from the reservoir to the output needle in response to a predetermined condition in the physiological fluids of the individual.

  10. Sandwich-format 3D printed microfluidic mixers: a flexible platform for multi-probe analysis

    PubMed Central

    Kise, Drew P; Reddish, Michael J; Dyer, R Brian

    2015-01-01

    We report on a microfluidic mixer fabrication platform that increases the versatility and flexibility of mixers for biomolecular applications. A sandwich-format design allows the application of multiple spectroscopic probes to the same mixer. A polymer spacer is ‘sandwiched’ between two transparent windows, creating a closed microfluidic system. The channels of the mixer are defined by regions in the polymer spacer that lack material and therefore the polymer need not be transparent in the spectral region of interest. Suitable window materials such as CaF2 make the device accessible to a wide range of optical probe wavelengths, from the deep UV to the mid-IR. In this study, we use a commercially available 3D printer to print the polymer spacers to apply three different channel designs into the passive, continuous-flow mixer, and integrated them with three different spectroscopic probes. All three spectroscopic probes are applicable to each mixer without further changes. The sandwich-format mixer coupled with cost-effective 3D printed fabrication techniques could increase the applicability and accessibility of microfluidic mixing to intricate kinetic schemes and monitoring chemical synthesis in cases where only one probe technique proves insufficient. PMID:26855478

  11. Monolithic cell counter based on 3D hydrodynamic focusing in microfluidic channels

    NASA Astrophysics Data System (ADS)

    Paiè, Petra; Bragheri, Francesca; Osellame, Roberto

    2014-03-01

    Hydrodynamic focusing is a powerful technique frequently used in microfluidics that presents a wide range of applications since it allows focusing the sample flowing in the device to a narrow region in the center of the microchannel. In fact thanks to the laminarity of the fluxes in microchannels it is possible to confine the sample solution with a low flow rate by using a sheath flow with a higher flow rate. This in turn allows the flowing of one sample element at a time in the detection region, thus enabling analysis on single particles. Femtosecond laser micromachining is ideally suited to fabricate device integrating full hydrodynamic focusing functionalities thanks to the intrinsic 3D nature of this technique, especially if compared to expensive and complicated lithographic multi-step fabrication processes. Furthermore, because of the possibility to fabricate optical waveguides with the same technology, it is possible to obtain compact optofluidic devices to perform optical analysis of the sample even at the single cell level, as is the case for optical cell stretchers and sorters. In this work we show the fabrication and the fluidic characterization of extremely compact devices having only two inlets for 2D (both in vertical and horizontal planes) as well as full 3D symmetric hydrodynamic focusing. In addition we prove one of the possible application of the hydrodynamic focusing module, by fabricating and validating (both with polystyrene beads and erythrocytes) a monolithic cell counter obtained by integrating optical waveguides in the 3D hydrodynamic focusing device.

  12. Desktop aligner for fabrication of multilayer microfluidic devices

    PubMed Central

    Li, Xiang; Yu, Zeta Tak For; Geraldo, Dalton; Weng, Shinuo; Alve, Nitesh; Dun, Wu; Kini, Akshay; Patel, Karan; Shu, Roberto; Zhang, Feng; Li, Gang; Jin, Qinghui; Fu, Jianping

    2015-01-01

    Multilayer assembly is a commonly used technique to construct multilayer polydimethylsiloxane (PDMS)-based microfluidic devices with complex 3D architecture and connectivity for large-scale microfluidic integration. Accurate alignment of structure features on different PDMS layers before their permanent bonding is critical in determining the yield and quality of assembled multilayer microfluidic devices. Herein, we report a custom-built desktop aligner capable of both local and global alignments of PDMS layers covering a broad size range. Two digital microscopes were incorporated into the aligner design to allow accurate global alignment of PDMS structures up to 4 in. in diameter. Both local and global alignment accuracies of the desktop aligner were determined to be about 20 μm cm−1. To demonstrate its utility for fabrication of integrated multilayer PDMS microfluidic devices, we applied the desktop aligner to achieve accurate alignment of different functional PDMS layers in multilayer microfluidics including an organs-on-chips device as well as a microfluidic device integrated with vertical passages connecting channels located in different PDMS layers. Owing to its convenient operation, high accuracy, low cost, light weight, and portability, the desktop aligner is useful for microfluidic researchers to achieve rapid and accurate alignment for generating multilayer PDMS microfluidic devices. PMID:26233409

  13. Desktop aligner for fabrication of multilayer microfluidic devices

    NASA Astrophysics Data System (ADS)

    Li, Xiang; Yu, Zeta Tak For; Geraldo, Dalton; Weng, Shinuo; Alve, Nitesh; Dun, Wu; Kini, Akshay; Patel, Karan; Shu, Roberto; Zhang, Feng; Li, Gang; Jin, Qinghui; Fu, Jianping

    2015-07-01

    Multilayer assembly is a commonly used technique to construct multilayer polydimethylsiloxane (PDMS)-based microfluidic devices with complex 3D architecture and connectivity for large-scale microfluidic integration. Accurate alignment of structure features on different PDMS layers before their permanent bonding is critical in determining the yield and quality of assembled multilayer microfluidic devices. Herein, we report a custom-built desktop aligner capable of both local and global alignments of PDMS layers covering a broad size range. Two digital microscopes were incorporated into the aligner design to allow accurate global alignment of PDMS structures up to 4 in. in diameter. Both local and global alignment accuracies of the desktop aligner were determined to be about 20 μm cm-1. To demonstrate its utility for fabrication of integrated multilayer PDMS microfluidic devices, we applied the desktop aligner to achieve accurate alignment of different functional PDMS layers in multilayer microfluidics including an organs-on-chips device as well as a microfluidic device integrated with vertical passages connecting channels located in different PDMS layers. Owing to its convenient operation, high accuracy, low cost, light weight, and portability, the desktop aligner is useful for microfluidic researchers to achieve rapid and accurate alignment for generating multilayer PDMS microfluidic devices.

  14. Microfluidic devices for droplet injection

    NASA Astrophysics Data System (ADS)

    Aubrecht, Donald; Akartuna, Ilke; Weitz, David

    2012-02-01

    As picoliter-scale reaction vessels, microfluidic water-in-oil emulsions have found application for high-throughput, large-sample number analyses. Often, the biological or chemical system under investigation needs to be encapsulated into droplets to prevent cross contamination prior to the introduction of reaction reagents. Previous techniques of picoinjection or droplet synchronization and merging enable the addition of reagents to individual droplets, but present limitations on what can be added to each droplet. We present microfluidic devices that couple the strengths of picoinjection and droplet merging, allowing us to selectively add precise volume to our droplet reactions.

  15. Improving the Resolution of 3D-Printed Molds for Microfluidics by Iterative Casting-Shrinkage Cycles.

    PubMed

    Sun, Miao; Xie, Yanbo; Zhu, Jihong; Li, Jun; Eijkel, Jan C T

    2017-02-21

    Breaking through technical barriers and cost reduction are critical issues for the development of microfluidic devices, and both rely greatly on the innovation of fabrication techniques and use of new materials. The application of 3D printing definitely accelerated the prototyping of microfluidic chips by its versatility and functionality. However, the resolution of existing 3D printing techniques is still far below that of lithography, which makes it difficult to work on the scale of single cells and near impossible for single molecule work. In this paper, we present a facile way to increase the resolution of 3D printed microstructures to minimally 4 μm by casting-shrinkage cycles of a polyurethane (PU) polymer. A water-PU liquid mixture poured on a 3D printed template quickly solidifies replicating the structures, which then isometrically shrink to half its size after solvent evaporation, downscaling the replicated structures. By repeating the casting-shrinkage cycles, we could downscale the (sub)millimeter structures of 3D printed structures on demand, until the working limit posed by the polymer properties, which we demonstrate by fabricating a micromixer. Moreover, we can even fabricate microfluidic chips from millimeter-scale manually assembled templates, fully independent of any micromachining facilities, significantly reducing the technical barriers and costs, thus opening up the microfluidics field to low-resource areas.

  16. A rapid, straightforward, and print house compatible mass fabrication method for integrating 3D paper-based microfluidics.

    PubMed

    Xiao, Liangpin; Liu, Xianming; Zhong, Runtao; Zhang, Kaiqing; Zhang, Xiaodi; Zhou, Xiaomian; Lin, Bingcheng; Du, Yuguang

    2013-11-01

    Three-dimensional (3D) paper-based microfluidics, which is featured with high performance and speedy determination, promise to carry out multistep sample pretreatment and orderly chemical reaction, which have been used for medical diagnosis, cell culture, environment determination, and so on with broad market prospect. However, there are some drawbacks in the existing fabrication methods for 3D paper-based microfluidics, such as, cumbersome and time-consuming device assembly; expensive and difficult process for manufacture; contamination caused by organic reagents from their fabrication process. Here, we present a simple printing-bookbinding method for mass fabricating 3D paper-based microfluidics. This approach involves two main steps: (i) wax-printing, (ii) bookbinding. We tested the delivery capability, diffusion rate, homogeneity and demonstrated the applicability of the device to chemical analysis by nitrite colorimetric assays. The described method is rapid (<30 s), cheap, easy to manipulate, and compatible with the flat stitching method that is common in a print house, making itself an ideal scheme for large-scale production of 3D paper-based microfluidics.

  17. Direct digital manufacturing of autonomous centrifugal microfluidic device

    NASA Astrophysics Data System (ADS)

    Ukita, Yoshiaki; Takamura, Yuzuru; Utsumi, Yuichi

    2016-06-01

    This paper presents strategies that attempt to solve two key problems facing the commercialization of microfluidics: cost reduction in microfluidic chip manufacturing and microfluidic device driver development. To reduce the cost of microfluidic chip manufacturing, we propose to use of three-dimensional (3D) printers for direct digital manufacturing (DDM). An evaluation of 3D micro-scale structure printing using several 3D printers is reported, and some of the technical issues to be addressed in the future are suggested. To evaluate micro-scale printing, three types of 3D printers, with the ability to print structures on the scale of several hundred meters, were selected by first screening six 3D printers. Line and space patterns with line widths of 100-500 µm and an aspect ratio of one were printed and evaluated. The estimated critical dimension was around 200 µm. The manufacturing of a monolithic microfluidic chip with embedded channels was also demonstrated. Monolithic microfluidic chips with embedded microchannels having 500 × 500 and 250 × 250 µm2 cross sections and 2-20 mm lengths were printed, and the fidelity of the channel shape, residual supporting material, and flow of liquid water were evaluated. The liquid flow evaluation showed that liquid water could flow through all of the microchannels with the 500 × 500 µm2 cross section, whereas this was not possible through some of the channels with the 250 × 250 µm2 cross section because of the residual resin or supporting material. To reduce the device-driver cost, we propose to use of the centrifugal microfluidic concept. An autonomous microfluidic device that could implement sequential flow control under a steadily rotating condition was printed. Four-step flow injection under a steadily rotating condition at 1500 rpm was successfully demonstrated without any external triggering such as changing the rotational speed.

  18. Three-Dimensional Printing Based Hybrid Manufacturing of Microfluidic Devices.

    PubMed

    Alapan, Yunus; Hasan, Muhammad Noman; Shen, Richang; Gurkan, Umut A

    2015-05-01

    Microfluidic platforms offer revolutionary and practical solutions to challenging problems in biology and medicine. Even though traditional micro/nanofabrication technologies expedited the emergence of the microfluidics field, recent advances in advanced additive manufacturing hold significant potential for single-step, stand-alone microfluidic device fabrication. One such technology, which holds a significant promise for next generation microsystem fabrication is three-dimensional (3D) printing. Presently, building 3D printed stand-alone microfluidic devices with fully embedded microchannels for applications in biology and medicine has the following challenges: (i) limitations in achievable design complexity, (ii) need for a wider variety of transparent materials, (iii) limited z-resolution, (iv) absence of extremely smooth surface finish, and (v) limitations in precision fabrication of hollow and void sections with extremely high surface area to volume ratio. We developed a new way to fabricate stand-alone microfluidic devices with integrated manifolds and embedded microchannels by utilizing a 3D printing and laser micromachined lamination based hybrid manufacturing approach. In this new fabrication method, we exploit the minimized fabrication steps enabled by 3D printing, and reduced assembly complexities facilitated by laser micromachined lamination method. The new hybrid fabrication method enables key features for advanced microfluidic system architecture: (i) increased design complexity in 3D, (ii) improved control over microflow behavior in all three directions and in multiple layers, (iii) transverse multilayer flow and precisely integrated flow distribution, and (iv) enhanced transparency for high resolution imaging and analysis. Hybrid manufacturing approaches hold great potential in advancing microfluidic device fabrication in terms of standardization, fast production, and user-independent manufacturing.

  19. Osteocyte culture in microfluidic devices

    PubMed Central

    Wei, Chao; Fan, Beiyuan; Chen, Deyong; Wei, Yuanchen; Huo, Bo; You, Lidan; Wang, Junbo; Chen, Jian

    2015-01-01

    This paper presents a microfluidic device (poly-dimethylsiloxane micro channels bonded with glass slides) enabling culture of MLO-Y4 osteocyte like cells. In this study, on-chip collagen coating, cell seeding and culture, as well as staining were demonstrated in a tubing-free manner where gravity was used as the driving force for liquid transportation. MLO-Y4 cells were cultured in microfluidic channels with and without collagen coating where cellular images in a time sequence were taken and analyzed, confirming the positive effect of collagen coating on phenotype maintaining of MLO-Y4 cells. The proliferating cell nuclear antigen based proliferation assay was used to study cellular proliferation, revealing a higher proliferation rate of MLO-Y4 cells seeded in microfluidic channels without collagen coating compared to the substrates coated with collagen. Furthermore, the effects of channel dimensions (variations in width and height) on the viability of MLO-Y4 cells were explored based on the Calcein-AM and propidium iodide based live/dead assay and the Hoechst 33258 based apoptosis assay, locating the correlation between the decrease in channel width or height and the decrease in cell viability. As a platform technology, this microfluidic device may function as a new cell culture model enabling studies of osteocytes. PMID:25713691

  20. Microchip-Based Electrochemical Detection using a 3-D Printed Wall-Jet Electrode Device

    PubMed Central

    Munshi, Akash S.; Martin, R. Scott

    2016-01-01

    Three dimensional (3-D) printing technology has evolved dramatically in the last few years, offering the capability of printing objects with a variety of materials. Printing microfluidic devices using this technology offers various advantages such as ease and uniformity of fabrication, file sharing between laboratories, and increased device-to-device reproducibility. One unique aspects of this technology, when used with electrochemical detection, is the ability to produce a microfluidic device as one unit while also allowing the reuse of the device and electrode for multiple analyses. Here we present an alternate electrode configuration for microfluidic devices, a wall-jet electrode (WJE) approach, created by 3-D printing. Using microchip-based flow injection analysis, we compared the WJE design with the conventionally used thin-layer electrode (TLE) design. It was found that the optimized WJE system enhances analytical performance (as compared to the TLE design), with improvements in sensitivity and the limit of detection. Experiments were conducted using two working electrodes – 500 μm platinum and 1 mm glassy carbon. Using the 500 μm platinum electrode the calibration sensitivity was 16 times higher for the WJE device (as compared to the TLE design). In addition, use of the 1 mm glassy carbon electrode led to limit of detection of 500 nM for catechol, as compared to 6 μM for the TLE device. Finally, to demonstrate the versatility and applicability of the 3-D printed WJE approach, the device was used as an inexpensive electrochemical detector for HPLC. The number of theoretical plates was comparable to the use of commercially available UV and MS detectors, with the WJE device being inexpensive to utilize. These results show that 3D-printing can be a powerful tool to fabricate reusable and integrated microfluidic detectors in configurations that are not easily achieved with more traditional lithographic methods. PMID:26649363

  1. Microchip-based electrochemical detection using a 3-D printed wall-jet electrode device.

    PubMed

    Munshi, Akash S; Martin, R Scott

    2016-02-07

    Three dimensional (3-D) printing technology has evolved dramatically in the last few years, offering the capability of printing objects with a variety of materials. Printing microfluidic devices using this technology offers various advantages such as ease and uniformity of fabrication, file sharing between laboratories, and increased device-to-device reproducibility. One unique aspect of this technology, when used with electrochemical detection, is the ability to produce a microfluidic device as one unit while also allowing the reuse of the device and electrode for multiple analyses. Here we present an alternate electrode configuration for microfluidic devices, a wall-jet electrode (WJE) approach, created by 3-D printing. Using microchip-based flow injection analysis, we compared the WJE design with the conventionally used thin-layer electrode (TLE) design. It was found that the optimized WJE system enhances analytical performance (as compared to the TLE design), with improvements in sensitivity and the limit of detection. Experiments were conducted using two working electrodes - 500 μm platinum and 1 mm glassy carbon. Using the 500 μm platinum electrode the calibration sensitivity was 16 times higher for the WJE device (as compared to the TLE design). In addition, use of the 1 mm glassy carbon electrode led to limit of detection of 500 nM for catechol, as compared to 6 μM for the TLE device. Finally, to demonstrate the versatility and applicability of the 3-D printed WJE approach, the device was used as an inexpensive electrochemical detector for HPLC. The number of theoretical plates was comparable to the use of commercially available UV and MS detectors, with the WJE device being inexpensive to utilize. These results show that 3-D-printing can be a powerful tool to fabricate reusable and integrated microfluidic detectors in configurations that are not easily achieved with more traditional lithographic methods.

  2. Surface-micromachined microfluidic devices

    DOEpatents

    Galambos, Paul C.; Okandan, Murat; Montague, Stephen; Smith, James H.; Paul, Phillip H.; Krygowski, Thomas W.; Allen, James J.; Nichols, Christopher A.; Jakubczak, II, Jerome F.

    2003-01-01

    Microfluidic devices are disclosed which can be manufactured using surface-micromachining. These devices utilize an electroosmotic force or an electromagnetic field to generate a flow of a fluid in a microchannel that is lined, at least in part, with silicon nitride. Additional electrodes can be provided within or about the microchannel for separating particular constituents in the fluid during the flow based on charge state or magnetic moment. The fluid can also be pressurized in the channel. The present invention has many different applications including electrokinetic pumping, chemical and biochemical analysis (e.g. based on electrophoresis or chromatography), conducting chemical reactions on a microscopic scale, and forming hydraulic actuators.

  3. Straightforward 3D hydrodynamic focusing in femtosecond laser fabricated microfluidic channels.

    PubMed

    Paiè, Petra; Bragheri, Francesca; Vazquez, Rebeca Martinez; Osellame, Roberto

    2014-06-07

    We report on the use of femtosecond laser irradiation followed by chemical etching as a microfabrication tool for innovative microfluidic networks that implement hydrodynamic focusing. The capability of our microfabrication technology to interconnect microchannels in three dimensions was exploited to demonstrate 2D hydrodynamic focusing, either in the horizontal or in the vertical plane, and full 3D hydrodynamic focusing. In all cases only two inlets were required, one for the sample and one for the sheath flows. Fluidic characterization of all devices was provided. In addition, taking advantage of the possibility to write optical waveguides using the same technology, a monolithic cell counter based on 3D hydrodynamic focusing and integrated optical detection was validated. Counting rates up to 5000 cells s(-1) were achieved in this very compact device, where focusing and counting operations were implemented in less than 1 mm(3). Integration of this hydrodynamic focusing module into several devices fabricated by the same technology as optical cell stretchers and cell sorters is envisaged.

  4. Autonomous microfluidic capillaric circuits replicated from 3D-printed molds.

    PubMed

    Olanrewaju, A O; Robillard, A; Dagher, M; Juncker, D

    2016-09-21

    We recently developed capillaric circuits (CCs) - advanced capillary microfluidic devices assembled from capillary fluidic elements in a modular manner similar to the design of electric circuits (Safavieh & Juncker, Lab Chip, 2013, 13, 4180-4189). CCs choreograph liquid delivery operations according to pre-programmed capillary pressure differences with minimal user intervention. CCs were thought to require high-precision micron-scale features manufactured by conventional photolithography, which is slow and expensive. Here we present CCs manufactured rapidly and inexpensively using 3D-printed molds. Molds for CCs were fabricated with a benchtop 3D-printer, poly(dimethylsiloxane) replicas were made, and fluidic functionality was verified with aqueous solutions. We established design rules for CCs by a combination of modelling and experimentation. The functionality and reliability of trigger valves - an essential fluidic element that stops one liquid until flow is triggered by a second liquid - was tested for different geometries and different solutions. Trigger valves with geometries up to 80-fold larger than cleanroom-fabricated ones were found to function reliably. We designed retention burst valves that encode sequential liquid delivery using capillary pressure differences encoded by systematically varied heights and widths. Using an electrical circuit analogue of the CC, we established design rules to ensure strictly sequential liquid delivery. CCs autonomously delivered eight liquids in a pre-determined sequence in <7 min. Taken together, our results demonstrate that 3D-printing lowers the bar for other researchers to access capillary microfluidic valves and CCs for autonomous liquid delivery with applications in diagnostics, research and education.

  5. Surface-Micromachined Microfluidic Devices

    DOEpatents

    Galambos, Paul C.; Okandan, Murat; Montague, Stephen; Smith, James H.; Paul, Phillip H.; Krygowski, Thomas W.; Allen, James J.; Nichols, Christopher A.; Jakubczak, II, Jerome F.

    2004-09-28

    Microfluidic devices are disclosed which can be manufactured using surface-micromachining. These devices utilize an electroosmotic force or an electromagnetic field to generate a flow of a fluid in a microchannel that is lined, at least in part, with silicon nitride. Additional electrodes can be provided within or about the microchannel for separating particular constituents in the fluid during the flow based on charge state or magnetic moment. The fluid can also be pressurized in the channel. The present invention has many different applications including electrokinetic pumping, chemical and biochemical analysis (e.g. based on electrophoresis or chromatography), conducting chemical reactions on a microscopic scale, and forming hydraulic actuators. Microfluidic devices are disclosed which can be manufactured using surface-micromachining. These devices utilize an electroosmotic force or an electromagnetic field to generate a flow of a fluid in a microchannel that is lined, at least in part, with silicon nitride. Additional electrodes can be provided within or about the microchannel for separating particular constituents in the fluid during the flow based on charge state or magnetic moment. The fluid can also be pressurized in the channel. The present invention has many different applications including electrokinetic pumping, chemical and biochemical analysis (e.g. based on electrophoresis or chromatography), conducting chemical reactions on a microscopic scale, and forming hydraulic actuators.

  6. 3D tracking and phase-contrast imaging by twin-beams digital holographic microscope in microfluidics

    NASA Astrophysics Data System (ADS)

    Miccio, L.; Memmolo, P.; Finizio, A.; Paturzo, M.; Merola, F.; Grilli, S.; Ferraro, P.

    2012-06-01

    A compact twin-beam interferometer that can be adopted as a flexible diagnostic tool in microfluidic platforms is presented. The devise has two functionalities, as explained in the follow, and can be easily integrated in microfluidic chip. The configuration allows 3D tracking of micro-particles and, at same time, furnishes Quantitative Phase-Contrast maps of tracked micro-objects by interference microscopy. Experimental demonstration of its effectiveness and compatibility with biological field is given on for in vitro cells in microfluidic environment. Nowadays, several microfluidic configuration exist and many of them are commercially available, their development is due to the possibility for manipulating droplets, handling micro and nano-objects, visualize and quantify processes occurring in small volumes and, clearly, for direct applications on lab-on-a chip devices. In microfluidic research field, optical/photonics approaches are the more suitable ones because they have various advantages as to be non-contact, full-field, non-invasive and can be packaged thanks to the development of integrable optics. Moreover, phase contrast approaches, adapted to a lab-on-a-chip configurations, give the possibility to get quantitative information with remarkable lateral and vertical resolution directly in situ without the need to dye and/or kill cells. Furthermore, numerical techniques for tracking of micro-objects needs to be developed for measuring velocity fields, trajectories patterns, motility of cancer cell and so on. Here, we present a compact holographic microscope that can ensure, by the same configuration and simultaneously, accurate 3D tracking and quantitative phase-contrast analysis. The system, simple and solid, is based on twin laser beams coming from a single laser source. Through a easy conceptual design, we show how these two different functionalities can be accomplished by the same optical setup. The working principle, the optical setup and the mathematical

  7. Tuning 3D topography on biomimetic surface for efficient self-cleaning and microfluidic manipulation

    NASA Astrophysics Data System (ADS)

    Guan, Wei-Sheng; Huang, Han-Xiong; Chen, An-Fu

    2015-03-01

    Currently, micro-/nanotopography on polymeric replica is generally limited to 2D when a mechanical demolding approach is applied. In this work, one-step replication of bio-inspired 3D topography is achieved using microinjection compression molding with novel dual-layer molds. Using a proposed flexible template, the replica topography and wettability are highly tunable during molding. Moreover, dual-scale topography on the mold is developed by coating the micropatterned insert with submicron silica particles. Contact angle and roll-off angle measurements indicate the lotus leaf, rose petal and rice leaf effects on biomimetic surfaces. Among the three kinds of surfaces, the petal-inspired surface possesses the superior performance in self-cleaning submicron contaminants and mechanical robustness, which is highly correlated to the low roughness-induced adhesive superhydrophobicity and the absence of fragile submicron-/nanostructure, respectively. Furthermore, a multi-layer mold structure is proposed for fabricating the open microfluidic devices. The embedment of the hydrophilic and hydrophobic silica particles in the microstructured open channel and the hydrophobic silica particles in the background area during replication renders the wettability contrast sharp, realizing the self-driven flow of microfluid confined within the open microchannel.

  8. Will true 3d display devices aid geologic interpretation. [Mirage

    SciTech Connect

    Nelson, H.R. Jr.

    1982-04-01

    A description is given of true 3D display devices and techniques that are being evaluated in various research laboratories around the world. These advances are closely tied to the expected application of 3D display devices as interpretational tools for explorationists. 34 refs.

  9. Layer-by-layer Collagen Deposition in Microfluidic Devices for Microtissue Stabilization

    PubMed Central

    McCarty, William J.; Prodanov, Ljupcho; Bale, Shyam Sundhar; Bhushan, Abhinav; Jindal, Rohit; Yarmush, Martin L.; Usta, O. Berk

    2016-01-01

    Although microfluidics provides exquisite control of the cellular microenvironment, culturing cells within microfluidic devices can be challenging. 3D culture of cells in collagen type I gels helps to stabilize cell morphology and function, which is necessary for creating microfluidic tissue models in microdevices. Translating traditional 3D culture techniques for tissue culture plates to microfluidic devices is often difficult because of the limited channel dimensions. In this method, we describe a technique for modifying native type I collagen to generate polycationic and polyanionic collagen solutions that can be used with layer-by-layer deposition to create ultrathin collagen assemblies on top of cells cultured in microfluidic devices. These thin collagen layers stabilize cell morphology and function, as shown using primary hepatocytes as an example cell, allowing for the long term culture of microtissues in microfluidic devices. PMID:26485274

  10. Microfluidic 3D cell culture: potential application for tissue-based bioassays

    PubMed Central

    Li, XiuJun (James); Valadez, Alejandra V.; Zuo, Peng; Nie, Zhihong

    2014-01-01

    Current fundamental investigations of human biology and the development of therapeutic drugs, commonly rely on two-dimensional (2D) monolayer cell culture systems. However, 2D cell culture systems do not accurately recapitulate the structure, function, physiology of living tissues, as well as highly complex and dynamic three-dimensional (3D) environments in vivo. The microfluidic technology can provide micro-scale complex structures and well-controlled parameters to mimic the in vivo environment of cells. The combination of microfluidic technology with 3D cell culture offers great potential for in vivo-like tissue-based applications, such as the emerging organ-on-a-chip system. This article will review recent advances in microfluidic technology for 3D cell culture and their biological applications. PMID:22793034

  11. Microfluidic titer plate for stratified 3D cell culture.

    PubMed

    Trietsch, Sebastiaan J; Israëls, Guido D; Joore, Jos; Hankemeier, Thomas; Vulto, Paul

    2013-09-21

    Human tissues and organs are inherently heterogeneous. Their functionality is determined by the interplay between different cell types, their secondary architecture, vascular system and gradients of signaling molecules and metabolites. Here we propose a stratified 3D cell culture platform, in which adjacent lanes of gels and liquids are patterned by phaseguides to capture this tissue heterogeneity. We demonstrate 3D cell culture of HepG2 hepatocytes under continuous perfusion, a rifampicin toxicity assay and co-culture with fibroblasts. 4T1 breast cancer cells are used to demonstrate invasion and aggregation models. The platform is incorporated in a microtiter plate format that renders it fully compatible with automation and high-content screening equipment. The extended functionality, ease of handling and full compatibility to standard equipment is an important step towards adoption of Organ-on-a-Chip technology for screening in an industrial setting.

  12. Femtosecond laser fabricated electrofluidic devices in glass for 3D manipulation of biological samples

    NASA Astrophysics Data System (ADS)

    Xu, Jian; Midorikawa, Katsumi; Sugioka, Koji

    2016-03-01

    Novel electrofluidic microdevices based on monolithic integration of 3D metal electrodes into 3D glass microchannels have been prepared by femtosecond (fs) laser hybrid microfabrication. 3D microchannels with smooth internal walls are first prepared in photosensitive glass by fs laser-assisted chemical wet etching process combined with post-annealing. Then, 3D electrode patterning in prepared glass channels is carried out by water-assisted fs-laser direct-write ablation using the same laser followed by electroless metal plating. Laser processing parameters are optimized and the roles of water during the laser irradiation are discussed. The fabricated electrofluidic devices are applied to demonstrate 3D electro-orientation of cells in microfluidic environments.

  13. Enzymatic Reactions in Microfluidic Devices

    NASA Astrophysics Data System (ADS)

    Ristenpart, W. D.; Wan, J.; Stone, H. A.

    2008-11-01

    We establish simple scaling laws for enzymatic reactions in microfluidic devices, and we demonstrate that kinetic parameters obtained conventionally using multiple stop-flow experiments may instead be extracted from a single microfluidic experiment. Introduction of an enzyme and substrate species in different arms of a Y-shaped channel allows the two species to diffuse across the parallel streamlines and to begin reacting. Measurements of the product concentration versus distance down the channel provide information about the kinetics of the reaction. In the limit where the enzyme is much larger (and thus less diffusive) than the substrate, we show that near the entrance the total amount of product (P) formed varies as a power law in the distance x down the channel. For reactions that follow standard Michaelis-Menten kinetics, the power law takes the form P˜(Vmax/Km) x^5/2, where Vmax and Km are the maximum reaction rate and Michaelis constant respectively. If a large excess of substrate is used, then Km is identified by measuring Vmax far downstream where the different species are completely mixed by diffusion. Numerical simulations and experiments using the bioluminescent reaction between luciferase and ATP as a model system are both shown to accord with the model. We discuss the implications for significant savings in the amount of time and enzyme required for determination of kinetic parameters.

  14. Optimization Techniques for 3D Graphics Deployment on Mobile Devices

    NASA Astrophysics Data System (ADS)

    Koskela, Timo; Vatjus-Anttila, Jarkko

    2015-03-01

    3D Internet technologies are becoming essential enablers in many application areas including games, education, collaboration, navigation and social networking. The use of 3D Internet applications with mobile devices provides location-independent access and richer use context, but also performance issues. Therefore, one of the important challenges facing 3D Internet applications is the deployment of 3D graphics on mobile devices. In this article, we present an extensive survey on optimization techniques for 3D graphics deployment on mobile devices and qualitatively analyze the applicability of each technique from the standpoints of visual quality, performance and energy consumption. The analysis focuses on optimization techniques related to data-driven 3D graphics deployment, because it supports off-line use, multi-user interaction, user-created 3D graphics and creation of arbitrary 3D graphics. The outcome of the analysis facilitates the development and deployment of 3D Internet applications on mobile devices and provides guidelines for future research.

  15. Multi-level 3D implementation of thermo-pneumatic pumping on centrifugal microfluidic CD platforms.

    PubMed

    Thio, Tzer Hwai Gilbert; Ibrahim, Fatimah; Al-Faqheri, Wisam; Soin, Norhayati; Abdul Kahar, Maria Kahar Bador; Madou, Marc

    2013-01-01

    Thermo-pneumatic (TP) pumping is a method employing the principle of expanding heated air to transfer fluids back towards the CD center on the centrifugal microfluidic CD platform. While the TP features are easy to fabricate as no moving parts are involved, it consumes extra real estate on the CD, and because heating is involved, it introduces unnecessary heating to the fluids on the CD. To overcome these limitations, we introduce a multi-level 3D approach and implement forced convection heating. In a multi-level 3D CD, the TP features are relocated to a separate top level, while the microfluidic process remains on a lower bottom level. This allows for heat shielding of the fluids in the microfluidic process level, and also improve usage of space on the CD. To aid in future implementations of TP pumping on a multi-level 3D CD, studies on the effect of heat source setting, and the effect of positioning the TP feature (it distance from the CD center) on CD surface heating are also presented. In this work, we successfully demonstrate a multi-level 3D approach to implement TP pumping on the microfluidic CD platform.

  16. Kilo-scale droplet generation in three-dimensional monolithic elastomer device (3D MED).

    PubMed

    Jeong, Heon-Ho; Yelleswarapu, Venkata R; Yadavali, Sagar; Issadore, David; Lee, Daeyeon

    2015-12-07

    Droplet-based microfluidics has led to transformational new approaches in diverse areas including materials synthesis and high-throughput biological assays. However, the translation of droplet microfluidics technology into commercial applications requires scale-up of droplet generation from the laboratory (<10 mL h(-1)) to the industrial (>1 L h(-1)) scale. To address this challenge, we develop a three-dimensional monolithic elastomer device (3D MED) for mass production of monodisperse emulsion droplets. Using double-sided imprinting, 3D microchannels are formed in a single elastomer piece that has 1000 parallel flow focusing generators (k-FFGs). Compared to previous work that parallelizes droplet generation, the 3D MED eliminates the needs for alignment and bonding of multiple pieces and thus makes it possible to achieve the high flow rates and pressure necessary for the kilo-scale generation of droplets. Using this approach, we demonstrate mass production of water-in-oil (W/O) emulsion droplets at production rates as high as 1.5 L h(-1) (>30 billion 45 μm diameter droplets per hour), with a coefficient of variation of droplet diameter of only 6.6%. Because of the simplicity, robustness, and manufacturability of our 3D MED architecture, it is well suited to bridge the gap between the continuously growing library of promising microfluidic technologies to generate microparticles that have been demonstrated in laboratory settings and their successful application in industry.

  17. Laser direct writing 3D structures for microfluidic channels: flow meter and mixer

    NASA Astrophysics Data System (ADS)

    Lin, Chih-Lang; Liu, Yi-Jui; Lin, Zheng-Da; Wu, Bo-Long; Lee, Yi-Hsiung; Shin, Chow-Shing; Baldeck, Patrice L.

    2015-03-01

    The 3D laser direct-writing technology is aimed at the modeling of arbitrary three-dimensional (3D) complex microstructures by scanning a laser-focusing point along predetermined trajectories. Through the perspective technique, the details of designed 3D structures can be properly fabricated in a microchannel. This study introduces a direct reading flow meter and a 3D passive mixer fabricated by laser direct writing for microfluidic applications. The flow meter consists of two rod-shaped springs, a pillar, an anchor, and a wedge-shaped indicator, installed inside a microfluidic channel. The indicator is deflected by the flowing fluid while restrained by the spring to establish an equilibrium indication according to the flow rate. The measurement is readily carried out by optical microscopy observation. The 3D passive Archimedes-screw-shaped mixer is designed to disturb the laminar flow 3D direction for enhancing the mixing efficiency. The simulation results indicate that the screw provides 3D disturbance of streamlines in the microchannel. The mixing demonstration for fluids flowing in the micrchannel approximately agrees with the simulation result. Thanks to the advantage of the laser direct writing technology, this study performs the ingenious applications of 3D structures for microchannels.

  18. 3D Printed Microscope for Mobile Devices that Cost Pennies

    ScienceCinema

    Erikson, Rebecca; Baird, Cheryl; Hutchinson, Janine

    2016-07-12

    Scientists at PNNL have designed a 3D-printable microscope for mobile devices using pennies worth of plastic and glass materials. The microscope has a wide range of uses, from education to in-the-field science.

  19. 3D Printed Microscope for Mobile Devices that Cost Pennies

    SciTech Connect

    Erikson, Rebecca; Baird, Cheryl; Hutchinson, Janine

    2014-09-15

    Scientists at PNNL have designed a 3D-printable microscope for mobile devices using pennies worth of plastic and glass materials. The microscope has a wide range of uses, from education to in-the-field science.

  20. Electronic Sensing for Microfluidic Devices

    DTIC Science & Technology

    2005-10-08

    D. J. Insect cell culture in microfluidic channels. Biomedical Microdevices 4, 161-166 (2002). 8 20. Walker, G. M., Zeringue, H. C. & Beebe, D. J...engineering. Biomedical Microdevices 4, 167-175 (2002). 23. Moorthy, J. & Beebe, D. J. Organic and biomimetic designs for microfluidic systems

  1. Engineering a 3D microfluidic culture platform for tumor-treating field application

    PubMed Central

    Pavesi, Andrea; Adriani, Giulia; Tay, Andy; Warkiani, Majid Ebrahimi; Yeap, Wei Hseun; Wong, Siew Cheng; Kamm, Roger D.

    2016-01-01

    The limitations of current cancer therapies highlight the urgent need for a more effective therapeutic strategy. One promising approach uses an alternating electric field; however, the mechanisms involved in the disruption of the cancer cell cycle as well as the potential adverse effects on non-cancerous cells must be clarified. In this study, we present a novel microfluidic device with embedded electrodes that enables the application of an alternating electric field therapy to cancer cells in a 3D extracellular matrix. To demonstrate the potential of our system to aid in designing and testing new therapeutic approaches, cancer cells and cancer cell aggregates were cultured individually or co-cultured with endothelial cells. The metastatic potential of the cancer cells was reduced after electric field treatment. Moreover, the proliferation rate of the treated cancer cells was lower compared with that of the untreated cells, whereas the morphologies and proliferative capacities of the endothelial cells were not significantly affected. These results demonstrate that our novel system can be used to rapidly screen the effect of an alternating electric field on cancer and normal cells within an in vivo-like microenvironment with the potential to optimize treatment protocols and evaluate synergies between tumor-treating field treatment and chemotherapy. PMID:27215466

  2. Engineering a 3D microfluidic culture platform for tumor-treating field application

    NASA Astrophysics Data System (ADS)

    Pavesi, Andrea; Adriani, Giulia; Tay, Andy; Warkiani, Majid Ebrahimi; Yeap, Wei Hseun; Wong, Siew Cheng; Kamm, Roger D.

    2016-05-01

    The limitations of current cancer therapies highlight the urgent need for a more effective therapeutic strategy. One promising approach uses an alternating electric field; however, the mechanisms involved in the disruption of the cancer cell cycle as well as the potential adverse effects on non-cancerous cells must be clarified. In this study, we present a novel microfluidic device with embedded electrodes that enables the application of an alternating electric field therapy to cancer cells in a 3D extracellular matrix. To demonstrate the potential of our system to aid in designing and testing new therapeutic approaches, cancer cells and cancer cell aggregates were cultured individually or co-cultured with endothelial cells. The metastatic potential of the cancer cells was reduced after electric field treatment. Moreover, the proliferation rate of the treated cancer cells was lower compared with that of the untreated cells, whereas the morphologies and proliferative capacities of the endothelial cells were not significantly affected. These results demonstrate that our novel system can be used to rapidly screen the effect of an alternating electric field on cancer and normal cells within an in vivo-like microenvironment with the potential to optimize treatment protocols and evaluate synergies between tumor-treating field treatment and chemotherapy.

  3. Beating heart on a chip: a novel microfluidic platform to generate functional 3D cardiac microtissues.

    PubMed

    Marsano, Anna; Conficconi, Chiara; Lemme, Marta; Occhetta, Paola; Gaudiello, Emanuele; Votta, Emiliano; Cerino, Giulia; Redaelli, Alberto; Rasponi, Marco

    2016-02-07

    In the past few years, microfluidic-based technology has developed microscale models recapitulating key physical and biological cues typical of the native myocardium. However, the application of controlled physiological uniaxial cyclic strains on a defined three-dimension cellular environment is not yet possible. Two-dimension mechanical stimulation was particularly investigated, neglecting the complex three-dimensional cell-cell and cell-matrix interactions. For this purpose, we developed a heart-on-a-chip platform, which recapitulates the physiologic mechanical environment experienced by cells in the native myocardium. The device includes an array of hanging posts to confine cell-laden gels, and a pneumatic actuation system to induce homogeneous uniaxial cyclic strains to the 3D cell constructs during culture. The device was used to generate mature and highly functional micro-engineered cardiac tissues (μECTs), from both neonatal rat and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM), strongly suggesting the robustness of our engineered cardiac micro-niche. Our results demonstrated that the cyclic strain was effectively highly uniaxial and uniformly transferred to cells in culture. As compared to control, stimulated μECTs showed superior cardiac differentiation, as well as electrical and mechanical coupling, owing to a remarkable increase in junction complexes. Mechanical stimulation also promoted early spontaneous synchronous beating and better contractile capability in response to electric pacing. Pacing analyses of hiPSC-CM constructs upon controlled administration of isoprenaline showed further promising applications of our platform in drug discovery, delivery and toxicology fields. The proposed heart-on-a-chip device represents a relevant step forward in the field, providing a standard functional three-dimensional cardiac model to possibly predict signs of hypertrophic changes in cardiac phenotype by mechanical and biochemical co-stimulation.

  4. Macro-to-micro interfacing to microfluidic channels using 3D-printed templates: application to time-resolved secretion sampling of endocrine tissue.

    PubMed

    Brooks, Jessica C; Ford, Katarena I; Holder, Dylan H; Holtan, Mark D; Easley, Christopher J

    2016-10-21

    Employing 3D-printed templates for macro-to-micro interfacing, a passively operated polydimethysiloxane (PDMS) microfluidic device was designed for time-resolved secretion sampling from primary murine islets and epidiymal white adipose tissue explants. Interfacing in similar devices is typically accomplished through manually punched or drilled fluidic reservoirs. We previously introduced the concept of using hand fabricated polymer inserts to template cell culture and sampling reservoirs into PDMS devices, allowing rapid stimulation and sampling of endocrine tissue. However, fabrication of the fluidic reservoirs was time consuming, tedious, and was prone to errors during device curing. Here, we have implemented computer-aided design and 3D printing to circumvent these fabrication obstacles. In addition to rapid prototyping and design iteration advantages, the ability to match these 3D-printed interface templates with channel patterns is highly beneficial. By digitizing the template fabrication process, more robust components can be produced with reduced fabrication variability. Herein, 3D-printed templates were used for sculpting millimetre-scale reservoirs into the above-channel, bulk PDMS in passively-operated, eight-channel devices designed for time-resolved secretion sampling of murine tissue. Devices were proven functional by temporally assaying glucose-stimulated insulin secretion from <10 pancreatic islets and glycerol secretion from 2 mm adipose tissue explants, suggesting that 3D-printed interface templates could be applicable to a variety of cells and tissue types. More generally, this work validates desktop 3D printers as versatile interfacing tools in microfluidic laboratories.

  5. 3D Printed Graphene Based Energy Storage Devices.

    PubMed

    Foster, Christopher W; Down, Michael P; Zhang, Yan; Ji, Xiaobo; Rowley-Neale, Samuel J; Smith, Graham C; Kelly, Peter J; Banks, Craig E

    2017-03-03

    3D printing technology provides a unique platform for rapid prototyping of numerous applications due to its ability to produce low cost 3D printed platforms. Herein, a graphene-based polylactic acid filament (graphene/PLA) has been 3D printed to fabricate a range of 3D disc electrode (3DE) configurations using a conventional RepRap fused deposition moulding (FDM) 3D printer, which requires no further modification/ex-situ curing step. To provide proof-of-concept, these 3D printed electrode architectures are characterised both electrochemically and physicochemically and are advantageously applied as freestanding anodes within Li-ion batteries and as solid-state supercapacitors. These freestanding anodes neglect the requirement for a current collector, thus offering a simplistic and cheaper alternative to traditional Li-ion based setups. Additionally, the ability of these devices' to electrochemically produce hydrogen via the hydrogen evolution reaction (HER) as an alternative to currently utilised platinum based electrodes (with in electrolysers) is also performed. The 3DE demonstrates an unexpectedly high catalytic activity towards the HER (-0.46 V vs. SCE) upon the 1000th cycle, such potential is the closest observed to the desired value of platinum at (-0.25 V vs. SCE). We subsequently suggest that 3D printing of graphene-based conductive filaments allows for the simple fabrication of energy storage devices with bespoke and conceptual designs to be realised.

  6. Rapid Protein Separations in Microfluidic Devices

    NASA Technical Reports Server (NTRS)

    Fan, Z. H.; Das, Champak; Xia, Zheng; Stoyanov, Alexander V.; Fredrickson, Carl K.

    2004-01-01

    This paper describes fabrication of glass and plastic microfluidic devices for protein separations. Although the long-term goal is to develop a microfluidic device for two-dimensional gel electrophoresis, this paper focuses on the first dimension-isoelectric focusing (IEF). A laser-induced fluorescence (LIF) imaging system has been built for imaging an entire channel in an IEF device. The whole-channel imaging eliminates the need to migrate focused protein bands, which is required if a single-point detector is used. Using the devices and the imaging system, we are able to perform IEF separations of proteins within minutes rather than hours in traditional bench-top instruments.

  7. 3D integration of microfluidics and microoptics inside photosensitive glass by femtosecond laser direct writing for photonic biosensing

    NASA Astrophysics Data System (ADS)

    Sugioka, Koji; Wang, Zhongke; Midorikawa, Katsumi

    2008-02-01

    Optical waveguides with a propagation loss of around 0.5 dB/cm are written inside photosensitive Foturan glass by internal modification of refractive index using femtosecond (fs) laser. Integration of the optical wafveguides with a micromirror enables us to bend the guided laser beam at an angle of 90° with a bending loss of less than 0.3 dB. In the meanwhile, a plano-convex microlens is completely embedded inside the Foturan glass chip via formation of a three-dimensional (3D) hollow microstructure using fs laser direct writing followed by heat treatment and successive wet etching. This technique can also be used to fabricate microfluidic devices and therefore realizes 3D integration of microoptical and microfluidic components by one continuous procedure. Subsequently, microoptical waveguides are further integrated into the single glass chip. Demonstration of optical measurements using the integrated microchip reveals that photonic biosensing can be performed with an efficiency increased by a factor of 8 for fluorescence detection and by a factor of 3 for absorption detection.

  8. 3D Printed Graphene Based Energy Storage Devices

    PubMed Central

    Foster, Christopher W.; Down, Michael P.; Zhang, Yan; Ji, Xiaobo; Rowley-Neale, Samuel J.; Smith, Graham C.; Kelly, Peter J.; Banks, Craig E.

    2017-01-01

    3D printing technology provides a unique platform for rapid prototyping of numerous applications due to its ability to produce low cost 3D printed platforms. Herein, a graphene-based polylactic acid filament (graphene/PLA) has been 3D printed to fabricate a range of 3D disc electrode (3DE) configurations using a conventional RepRap fused deposition moulding (FDM) 3D printer, which requires no further modification/ex-situ curing step. To provide proof-of-concept, these 3D printed electrode architectures are characterised both electrochemically and physicochemically and are advantageously applied as freestanding anodes within Li-ion batteries and as solid-state supercapacitors. These freestanding anodes neglect the requirement for a current collector, thus offering a simplistic and cheaper alternative to traditional Li-ion based setups. Additionally, the ability of these devices’ to electrochemically produce hydrogen via the hydrogen evolution reaction (HER) as an alternative to currently utilised platinum based electrodes (with in electrolysers) is also performed. The 3DE demonstrates an unexpectedly high catalytic activity towards the HER (−0.46 V vs. SCE) upon the 1000th cycle, such potential is the closest observed to the desired value of platinum at (−0.25 V vs. SCE). We subsequently suggest that 3D printing of graphene-based conductive filaments allows for the simple fabrication of energy storage devices with bespoke and conceptual designs to be realised. PMID:28256602

  9. 3D Printed Graphene Based Energy Storage Devices

    NASA Astrophysics Data System (ADS)

    Foster, Christopher W.; Down, Michael P.; Zhang, Yan; Ji, Xiaobo; Rowley-Neale, Samuel J.; Smith, Graham C.; Kelly, Peter J.; Banks, Craig E.

    2017-03-01

    3D printing technology provides a unique platform for rapid prototyping of numerous applications due to its ability to produce low cost 3D printed platforms. Herein, a graphene-based polylactic acid filament (graphene/PLA) has been 3D printed to fabricate a range of 3D disc electrode (3DE) configurations using a conventional RepRap fused deposition moulding (FDM) 3D printer, which requires no further modification/ex-situ curing step. To provide proof-of-concept, these 3D printed electrode architectures are characterised both electrochemically and physicochemically and are advantageously applied as freestanding anodes within Li-ion batteries and as solid-state supercapacitors. These freestanding anodes neglect the requirement for a current collector, thus offering a simplistic and cheaper alternative to traditional Li-ion based setups. Additionally, the ability of these devices’ to electrochemically produce hydrogen via the hydrogen evolution reaction (HER) as an alternative to currently utilised platinum based electrodes (with in electrolysers) is also performed. The 3DE demonstrates an unexpectedly high catalytic activity towards the HER (‑0.46 V vs. SCE) upon the 1000th cycle, such potential is the closest observed to the desired value of platinum at (‑0.25 V vs. SCE). We subsequently suggest that 3D printing of graphene-based conductive filaments allows for the simple fabrication of energy storage devices with bespoke and conceptual designs to be realised.

  10. Preparation of 3D electrode microarrays of multi-walled carbon nanotubes/nafion nanocomposites for microfluidic biofuel cells.

    PubMed

    Choi, Jin Ho; Kim, Young Ho; Choi, Sung Deuk; Kim, Gyu Man

    2014-12-01

    Three-dimensional (3D) electrode microarrays with multi-walled carbon nanotubes (MWCNTs) reinforced Nafion nanocomposites were prepared for microfluidic biofuel cells. The oxidized MWCNTs (ox-MWCNTs) were prepared using chemical reactions with 60% nitric acid solution with pristine MWCNTs at 120 degrees C for 12 hrs with a nitrogen gas flow environment. Ox-MWCNTs in the range of 1 to 20 wt.% based on the Nafion polymer weight were reinforced to Nafion nanocomposites by solution casting. The micro-porous structure of the ox-MWCNTs reinforced Nafion nanocomposites was prepared by plasma etching for 5 to 20 min. The 10 wt.% ox-MWCNTs reinforced Nafion nanocomposite produced stable micro-porous structures of 3D electrodes by 10 min plasma etching. Micro-scale 3D structures of MWCNTs reinforced Nafion nanocomposites in a diameter range of 47 to 300 μm were prepared by the micro-stencil assisted casting. To characterize the 3D electrode microarrays, the physical geometry and the reinforced MWCNT dispersion in the nanocomposite structure were examined using a scanning electron microscope (SEM) and an optical microscope. Thermal property measurements of the ox-MWCNTs reinforced Nafion nanocomposites with 10 min of plasma etching, and without plasma etching were made. Both showed stable thermal properties over 300 degrees C. The proposed 3D electrode microarray of MWCNT/Nafion nanocomposites with micro-porous structures can be applied to miniaturized fuel cell devices.

  11. Development of a 3-D Pen Input Device

    DTIC Science & Technology

    2008-09-01

    remote sites. Compared to other distance learning technologies such as video cameras, the 3-D pen input device would require much less bandwidth. The...other form of eLearning portal. However with a pen-type input device, the professors are saved the trouble of either rewriting their notes or copying...and scanning the notes then uploading them into a form of eLearning , then broadcasting them for the distance learning students. Instead, the

  12. Paper/PMMA Hybrid 3D Cell Culture Microfluidic Platform for the Study of Cellular Crosstalk.

    PubMed

    Lei, Kin Fong; Chang, Chih-Hsuan; Chen, Ming-Jie

    2017-04-06

    Studying cellular crosstalk is important for understanding tumor initiation, progression, metastasis, and therapeutic resistance. Moreover, a three-dimensional (3D) cell culture model can provide a more physiologically meaningful culture microenvironment. However, studying cellular crosstalk in a 3D cell culture model involves tedious processing. In this study, a paper/poly(methyl methacrylate) (PMMA) hybrid 3D cell culture microfluidic platform was successfully developed for the study of cellular crosstalk. The platform was a paper substrate with culture microreactors placed on a PMMA substrate with hydrogel-infused channels. Different types of cells were directly seeded and cultured in the microreactors. Aberrant cell proliferation of the affected cells was induced by secretions from transfected cells, and the proliferation ratios were investigated using a colorimetric method. The results showed that the responses of cellular crosstalk were different in different types of cells. Moreover, neutralizing and competitive assays were performed to show the functionality of the platform. Additionally, the triggered signaling pathways of the affected cells were directly analyzed by a subsequent immunoassay. The microfluidic platform provides a simple method for studying cellular crosstalk and the corresponding signaling pathways in a 3D culture model.

  13. MEMS and microfluidics for diagnostics devices.

    PubMed

    Rosen, Y; Gurman, P

    2010-06-01

    There are conditions in clinical medicine demanding critical therapeutic decisions. These conditions necessitate accuracy, rapidity, accessibility, cost-effectiveness and mobility. New technologies have been developed in order to address these challenges. Microfluidics and Micro Electro-Mechanical Systems are two of such technologies. Microfluidics, a discipline that involves processing fluids at the microscale in etched microchannels, is being used to build lab- on-a-chip systems to run chemical and biological assays. These systems are being transformed into handheld devices designed to be used at remote settings or at the bedside. MEMS are microscale electromechanical elements integrated in lab chip systems or used as individual components. MEMS based sensors represents a highly developed field with successful commercialized products currently being incorporated into vitro,ex vivo and in vivo devices. In the present paper several examples of microfluidic devices and MEMS sensors are introduced together with some current examples of commercialized products. Future challenges and trends will be discussed.

  14. Mixing in polymeric microfluidic devices.

    SciTech Connect

    Schunk, Peter Randall; Sun, Amy Cha-Tien; Davis, Robert H.; Brotherton, Christopher M. (University of Colorado at Boulder, Boulder, CO)

    2006-04-01

    This SAND report describes progress made during a Sandia National Laboratories sponsored graduate fellowship. The fellowship was funded through an LDRD proposal. The goal of this project is development and characterization of mixing strategies for polymeric microfluidic devices. The mixing strategies under investigation include electroosmotic flow focusing, hydrodynamic focusing, physical constrictions and porous polymer monoliths. For electroosmotic flow focusing, simulations were performed to determine the effect of electroosmotic flow in a microchannel with heterogeneous surface potential. The heterogeneous surface potential caused recirculations to form within the microchannel. These recirculations could then be used to restrict two mixing streams and reduce the characteristic diffusion length. Maximum mixing occurred when the ratio of the mixing region surface potential to the average channel surface potential was made large in magnitude and negative in sign, and when the ratio of the characteristic convection time to the characteristic diffusion time was minimized. Based on these results, experiments were performed to evaluate the manipulation of surface potential using living-radical photopolymerization. The material chosen to manipulate typically exhibits a negative surface potential. Using living-radical surface grafting, a positive surface potential was produced using 2-(Dimethylamino)ethyl methacrylate and a neutral surface was produced using a poly(ethylene glycol) surface graft. Simulations investigating hydrodynamic focusing were also performed. For this technique, mixing is enhanced by using a tertiary fluid stream to constrict the two mixing streams and reduce the characteristic diffusion length. Maximum mixing occurred when the ratio of the tertiary flow stream flow-rate to the mixing streams flow-rate was maximized. Also, like the electroosmotic focusing mixer, mixing was also maximized when the ratio of the characteristic convection time to the

  15. Gradient Static-Strain Stimulation in a Microfluidic Chip for 3D Cellular Alignment

    PubMed Central

    Hsieh, Hsin-Yi; Camci-Unal, Gulden; Huang, Tsu-Wei; Liao, Ronglih; Chen, Tsung-Ju; Paul, Arghya; Tseng, Fan-Gang; Khademhosseini, Ali

    2014-01-01

    Cell alignment is a critical factor to govern cellular behavior and function for various tissue engineering applications ranging from cardiac to neural regeneration. In addition to physical geometry, strain is a crucial parameter to manipulate cellular alignment for functional tissue formation. In this paper, we introduce a simple approach to generate a range of gradient static strains without external mechanical control for the stimulation of cellular behavior within 3D biomimetic hydrogel microenvironments. A glass-supported microfluidic chip with a convex flexible polydimethylsiloxane (PDMS) membrane on the top was employed for loading the cells suspended in a prepolymer solution. Following UV crosslinking through a photomask with a concentric circular pattern, the cell-laden hydrogels were formed in a height gradient from the center (maximum) to the boundary (minimum). When the convex PDMS membrane retracted back to a flat surface, it applied compressive gradient forces on the cell-laden hydrogels. The concentric circular hydrogel patterns confined the direction of hydrogel elongation, and the compressive strain on the hydrogel therefore resulted in elongation stretch in the radial direction to guide cell alignment. NIH3T3 cells were cultured in the chip for 3 days with compressive strains that varied from ~65% (center) to ~15% (boundary) on hydrogels. We found that the hydrogel geometry dominated the cell alignment near the outside boundary, where cells aligned along the circular direction, and the compressive strain dominated the cell alignment near the center, where cells aligned radially. This study developed a new and simple approach to facilitate cellular alignment based on hydrogel geometry and strain stimulation for tissue engineering applications. This platform offers unique advantages and is significantly different than the existing approaches owing to the fact that gradient generation was accomplished in a miniature device without using an external

  16. From Microscale Devices to 3D Printing: Advances in Fabrication of 3D Cardiovascular Tissues.

    PubMed

    Borovjagin, Anton V; Ogle, Brenda M; Berry, Joel L; Zhang, Jianyi

    2017-01-06

    Current strategies for engineering cardiovascular cells and tissues have yielded a variety of sophisticated tools for studying disease mechanisms, for development of drug therapies, and for fabrication of tissue equivalents that may have application in future clinical use. These efforts are motivated by the need to extend traditional 2-dimensional (2D) cell culture systems into 3D to more accurately replicate in vivo cell and tissue function of cardiovascular structures. Developments in microscale devices and bioprinted 3D tissues are beginning to supplant traditional 2D cell cultures and preclinical animal studies that have historically been the standard for drug and tissue development. These new approaches lend themselves to patient-specific diagnostics, therapeutics, and tissue regeneration. The emergence of these technologies also carries technical challenges to be met before traditional cell culture and animal testing become obsolete. Successful development and validation of 3D human tissue constructs will provide powerful new paradigms for more cost effective and timely translation of cardiovascular tissue equivalents.

  17. Micro-Fluidic Device for Drug Delivery

    NASA Technical Reports Server (NTRS)

    Beebe, David J. (Inventor); MacDonald, Michael J. (Inventor); Eddington, David T. (Inventor); Mensing, Glennys A. (Inventor)

    2014-01-01

    A microfluidic device is provided for delivering a drug to an individual. The microfluidic device includes a body that defines a reservoir for receiving the drug therein. A valve interconnects the reservoir to an output needle that is insertable into the skin of an individual. A pressure source urges the drug from the reservoir toward the needle. The valve is movable between a closed position preventing the flow of the drug from the reservoir to the output needle and an open position allowing for the flow of the drug from the reservoir to the output needle in response to a predetermined condition in the physiological fluids of the individual.

  18. Fluid control in microfluidic devices using a fluid conveyance extension and an absorbent microfluidic flow modulator.

    PubMed

    Yuen, Po Ki

    2013-05-07

    This article presents a simple method for controlling fluid in microfluidic devices without the need for valves or pumps. A fluid conveyance extension is fluidly coupled to the enclosed outlet chamber of a microfluidic device. After a fluid is introduced into the microfluidic device and saturates the fluid conveyance extension, a fluid flow in the microfluidic device is generated by contacting an absorbent microfluidic flow modulator with the fluid conveyance extension to absorb the fluid from the fluid conveyance extension through capillary action. Since the fluid in the microfluidic device is fluidly coupled with the fluid conveyance extension and the fluid conveyance extension is fluidly coupled with the absorbent microfluidic flow modulator, the absorption rate of the absorbent microfluidic flow modulator, which is the rate at which the absorbent microfluidic flow modulator absorbs fluid, matches the fluid flow rate in the microfluidic device. Thus, the fluid flow rate in the microfluidic device is set by the absorption rate of the absorbent microfluidic flow modulator. Sheath flow and fluid switching applications are demonstrated using this simple fluid control method without the need for valves or pumps. Also, the ability to control the fluid flow rate in the microfluidic device is demonstrated using absorbent microfluidic flow modulators with various absorbent characteristics and dimensions.

  19. 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.

  20. Diamond Pixel Detectors and 3D Diamond Devices

    NASA Astrophysics Data System (ADS)

    Venturi, N.

    2016-12-01

    Results from detectors of poly-crystalline chemical vapour deposited (pCVD) diamond are presented. These include the first analysis of data of the ATLAS Diamond Beam Monitor (DBM). The DBM module consists of pCVD diamond sensors instrumented with pixellated FE-I4 front-end electronics. Six diamond telescopes, each with three modules, are placed symmetrically around the ATLAS interaction point. The DBM tracking capabilities allow it to discriminate between particles coming from the interaction point and background particles passing through the ATLAS detector. Also, analysis of test beam data of pCVD DBM modules are presented. A new low threshold tuning algorithm based on noise occupancy was developed which increases the DBM module signal to noise ratio significantly. Finally first results from prototypes of a novel detector using pCVD diamond and resistive electrodes in the bulk, forming a 3D diamond device, are discussed. 3D devices based on pCVD diamond were successfully tested with test beams at CERN. The measured charge is compared to that of a strip detector mounted on the same pCVD diamond showing that the 3D device collects significantly more charge than the planar device.

  1. Understanding the mixing process in 3D microfluidic nozzle/diffuser systems: simulations and experiments

    NASA Astrophysics Data System (ADS)

    Sayah, Abdeljalil; Gijs, Martin A. M.

    2016-11-01

    We characterise computationally and experimentally a three-dimensional (3D) microfluidic passive mixer for various Reynolds numbers ranging from 1 to 100, corresponding to primary flow rates of 10-870 µl min-1. The 3D mixing channel is composed of multiple curved segments: circular arcs situated in the substrate plane and curved nozzle/diffuser elements normal to the substrate plane. Numerical simulation provides a detailed understanding of the mixing mechanism resulting from the geometrical topology of the mixer. These Comsol software-based simulations reveal the development of two secondary flows perpendicular to the primary flow: a swirling flow resulting from tangential injection of the flow into the nozzle holes and Dean vortices present in the circular arcs. These phenomena are particularly important at a Reynolds number larger than 30, where mixing occurs by chaotic advection. Experimentally, the 3D mixer is fabricated in a monolithic glass substrate by powder blasting machining, exploiting eroding powder beams at various angles of impact with respect to the substrate plane. Experimental mixing was characterised using two coloured dyes, showing nearly perfect mixing for a microfluidic footprint of the order of a few mm2, in good agreement with the simulations.

  2. Packaging of electro-microfluidic devices

    DOEpatents

    Benavides, Gilbert L.; Galambos, Paul C.; Emerson, John A.; Peterson, Kenneth A.; Giunta, Rachel K.; Watson, Robert D.

    2002-01-01

    A new architecture for packaging surface micromachined electro-microfluidic devices is presented. This architecture relies on two scales of packaging to bring fluid to the device scale (picoliters) from the macro-scale (microliters). The architecture emulates and utilizes electronics packaging technology. The larger package consists of a circuit board with embedded fluidic channels and standard fluidic connectors (e.g. Fluidic Printed Wiring Board). The embedded channels connect to the smaller package, an Electro-Microfluidic Dual-Inline-Package (EMDIP) that takes fluid to the microfluidic integrated circuit (MIC). The fluidic connection is made to the back of the MIC through Bosch-etched holes that take fluid to surface micromachined channels on the front of the MIC. Electrical connection is made to bond pads on the front of the MIC.

  3. Packaging of electro-microfluidic devices

    DOEpatents

    Benavides, Gilbert L.; Galambos, Paul C.; Emerson, John A.; Peterson, Kenneth A.; Giunta, Rachel K.; Zamora, David Lee; Watson, Robert D.

    2003-04-15

    A new architecture for packaging surface micromachined electro-microfluidic devices is presented. This architecture relies on two scales of packaging to bring fluid to the device scale (picoliters) from the macro-scale (microliters). The architecture emulates and utilizes electronics packaging technology. The larger package consists of a circuit board with embedded fluidic channels and standard fluidic connectors (e.g. Fluidic Printed Wiring Board). The embedded channels connect to the smaller package, an Electro-Microfluidic Dual-Inline-Package (EMDIP) that takes fluid to the microfluidic integrated circuit (MIC). The fluidic connection is made to the back of the MIC through Bosch-etched holes that take fluid to surface micromachined channels on the front of the MIC. Electrical connection is made to bond pads on the front of the MIC.

  4. 3D printed microfluidic circuitry via multijet-based additive manufacturing†

    PubMed Central

    Sochol, R. D.; Sweet, E.; Glick, C. C.; Venkatesh, S.; Avetisyan, A.; Ekman, K. F.; Raulinaitis, A.; Tsai, A.; Wienkers, A.; Korner, K.; Hanson, K.; Long, A.; Hightower, B. J.; Slatton, G.; Burnett, D. C.; Massey, T. L.; Iwai, K.; Lee, L. P.; Pister, K. S. J.; Lin, L.

    2016-01-01

    The miniaturization of integrated fluidic processors affords extensive benefits for chemical and biological fields, yet traditional, monolithic methods of microfabrication present numerous obstacles for the scaling of fluidic operators. Recently, researchers have investigated the use of additive manufacturing or “three-dimensional (3D) printing” technologies – predominantly stereolithography – as a promising alternative for the construction of submillimeter-scale fluidic components. One challenge, however, is that current stereolithography methods lack the ability to simultaneously print sacrificial support materials, which limits the geometric versatility of such approaches. In this work, we investigate the use of multijet modelling (alternatively, polyjet printing) – a layer-by-layer, multi-material inkjetting process – for 3D printing geometrically complex, yet functionally advantageous fluidic components comprised of both static and dynamic physical elements. We examine a fundamental class of 3D printed microfluidic operators, including fluidic capacitors, fluidic diodes, and fluidic transistors. In addition, we evaluate the potential to advance on-chip automation of integrated fluidic systems via geometric modification of component parameters. Theoretical and experimental results for 3D fluidic capacitors demonstrated that transitioning from planar to non-planar diaphragm architectures improved component performance. Flow rectification experiments for 3D printed fluidic diodes revealed a diodicity of 80.6 ± 1.8. Geometry-based gain enhancement for 3D printed fluidic transistors yielded pressure gain of 3.01 ± 0.78. Consistent with additional additive manufacturing methodologies, the use of digitally-transferrable 3D models of fluidic components combined with commercially-available 3D printers could extend the fluidic routing capabilities presented here to researchers in fields beyond the core engineering community. PMID:26725379

  5. 3D printed microfluidic circuitry via multijet-based additive manufacturing.

    PubMed

    Sochol, R D; Sweet, E; Glick, C C; Venkatesh, S; Avetisyan, A; Ekman, K F; Raulinaitis, A; Tsai, A; Wienkers, A; Korner, K; Hanson, K; Long, A; Hightower, B J; Slatton, G; Burnett, D C; Massey, T L; Iwai, K; Lee, L P; Pister, K S J; Lin, L

    2016-02-21

    The miniaturization of integrated fluidic processors affords extensive benefits for chemical and biological fields, yet traditional, monolithic methods of microfabrication present numerous obstacles for the scaling of fluidic operators. Recently, researchers have investigated the use of additive manufacturing or "three-dimensional (3D) printing" technologies - predominantly stereolithography - as a promising alternative for the construction of submillimeter-scale fluidic components. One challenge, however, is that current stereolithography methods lack the ability to simultaneously print sacrificial support materials, which limits the geometric versatility of such approaches. In this work, we investigate the use of multijet modelling (alternatively, polyjet printing) - a layer-by-layer, multi-material inkjetting process - for 3D printing geometrically complex, yet functionally advantageous fluidic components comprised of both static and dynamic physical elements. We examine a fundamental class of 3D printed microfluidic operators, including fluidic capacitors, fluidic diodes, and fluidic transistors. In addition, we evaluate the potential to advance on-chip automation of integrated fluidic systems via geometric modification of component parameters. Theoretical and experimental results for 3D fluidic capacitors demonstrated that transitioning from planar to non-planar diaphragm architectures improved component performance. Flow rectification experiments for 3D printed fluidic diodes revealed a diodicity of 80.6 ± 1.8. Geometry-based gain enhancement for 3D printed fluidic transistors yielded pressure gain of 3.01 ± 0.78. Consistent with additional additive manufacturing methodologies, the use of digitally-transferrable 3D models of fluidic components combined with commercially-available 3D printers could extend the fluidic routing capabilities presented here to researchers in fields beyond the core engineering community.

  6. Push pull microfluidics on a multi-level 3D CD.

    PubMed

    Thio, Tzer Hwai Gilbert; Ibrahim, Fatimah; Al-Faqheri, Wisam; Moebius, Jacob; Khalid, Noor Sakinah; Soin, Norhayati; Kahar, Maria Kahar Bador Abdul; Madou, Marc

    2013-08-21

    A technique known as thermo-pneumatic (TP) pumping is used to pump fluids on a microfluidic compact disc (CD) back towards the CD center against the centrifugal force that pushes liquids from the center to the perimeter of the disc. Trapped air expands in a TP air chamber during heating, and this creates positive pressure on liquids located in chambers connected to that chamber. While the TP air chamber and connecting channels are easy to fabricate in a one-level CD manufacturing technique, this approach provides only one way pumping between two chambers, is real-estate hungry and leads to unnecessary heating of liquids in close proximity to the TP chamber. In this paper, we present a novel TP push and pull pumping method which allows for pumping of liquid in any direction between two connected liquid chambers. To ensure that implementation of TP push and pull pumping also addresses the issue of space and heating challenges, a multi-level 3D CD design is developed, and localized forced convection heating, rather than infra-red (IR) is applied. On a multi-level 3D CD, the TP features are placed on a top level separate from the rest of the microfluidic processes that are implemented on a lower separate level. This approach allows for heat shielding of the microfluidic process level, and efficient usage of space on the CD for centrifugal handling of liquids. The use of localized forced convection heating, rather than infra-red (IR) or laser heating in earlier implementations allows not only for TP pumping of liquids while the CD is spinning but also makes heat insulation for TP pumping and other fluidic functions easier. To aid in future implementations of TP push and pull pumping on a multi-level 3D CD, study on CD surface heating is also presented. In this contribution, we also demonstrate an advanced application of pull pumping through the implementation of valve-less switch pumping.

  7. Differences in morphogenesis of 3D cultured primary human osteoblasts under static and microfluidic growth conditions.

    PubMed

    Altmann, Brigitte; Löchner, Anne; Swain, Michael; Kohal, Ralf-Joachim; Giselbrecht, Stefan; Gottwald, Eric; Steinberg, Thorsten; Tomakidi, Pascal

    2014-03-01

    As information on osteoblast mechanosensitivity response to biomechanical cues in three-dimensional (3D) in vitro microenvironments is sparse, the present study compared morphogenesis of primary human alveolar bone osteoblasts (PHABO) under microchip-based 3D-static conditions, and 3D-fluid flow-mediated biomechanical stimulation in perfusion bioreactors. Discrimination of the respective microenvironment by differential morphogenesis was evident from fluid flow-induced PHABO reorganization into rotund bony microtissue, comprising more densely packed multicellular 3D-aggregates, while viability of microtissues was flow rate dependent. Time-lapse microscopy and simple modeling of biomechanical conditions revealed that physiologically relevant fluid flow-mediated PHABO stimulation was associated with formation of mulberry-like PHABO aggregates within the first 24 h. Differential extracellular matrix deposition patterns and gene expression modulation in PHABO aggregates at day 7 further indicates progressive osteoblast differentiation exclusively in perfusion culture-developed bony microtissues. The results of our study strongly suggest PHABO morphogenesis as discriminator of microenvironmental growth conditions, which in case of the microfluidic 3D microchip-bioreactor are substantiated by triggering in vitro bone microtissue formation concomitant with progressive osteoblastic differentiation. Such microtissue outcomes provide unique insight for mechanobiological studies in response to biomechanical fluid flow cues, and clinically appear promising for in vitro PHABO preconditioning, enabling innovative bone augmentation procedures.

  8. 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.

  9. Formation of interconnections to microfluidic devices

    DOEpatents

    Matzke, Carolyn M.; Ashby, Carol I. H.; Griego, Leonardo

    2003-07-29

    A method is disclosed to form external interconnections to a microfluidic device for coupling of a fluid or light or both into a microchannel of the device. This method can be used to form optical or fluidic interconnections to microchannels previously formed on a substrate, or to form both the interconnections and microchannels during the same process steps. The optical and fluidic interconnections are formed parallel to the plane of the substrate, and are fluid tight.

  10. Microfluidic device for acoustic cell lysis

    SciTech Connect

    Branch, Darren W.; Cooley, Erika Jane; Smith, Gennifer Tanabe; James, Conrad D.; McClain, Jaime L.

    2015-08-04

    A microfluidic acoustic-based cell lysing device that can be integrated with on-chip nucleic acid extraction. Using a bulk acoustic wave (BAW) transducer array, acoustic waves can be coupled into microfluidic cartridges resulting in the lysis of cells contained therein by localized acoustic pressure. Cellular materials can then be extracted from the lysed cells. For example, nucleic acids can be extracted from the lysate using silica-based sol-gel filled microchannels, nucleic acid binding magnetic beads, or Nafion-coated electrodes. Integration of cell lysis and nucleic acid extraction on-chip enables a small, portable system that allows for rapid analysis in the field.

  11. Aerial obstacle detection with 3-D mobile devices.

    PubMed

    Sáez, Juan Manuel; Escolano, Francisco; Lozano, Miguel Angel

    2015-01-01

    In this paper, we present a novel approach for aerial obstacle detection (e.g., branches or awnings) using a 3-D smartphone in the context of the visually impaired (VI) people assistance. This kind of obstacles are especially challenging because they cannot be detected by the walking stick or the guide dog.The algorithm captures the 3-D data of the scene through stereo vision. To our knowledge, this is the first work that presents a technology able to obtain real 3-D measures with smartphones in real time. The orientation sensors of the device (magnetometer and accelerometer) are used to approximate the walking direction of the user, in order to look for the obstacles only in such a direction. The obtained 3-D data are compressed and then linearized for detecting the potential obstacles. Potential obstacles are tracked in order to accumulate enough evidence to alert the user only when a real obstacle is found.In the experimental section, we show the results of the algorithm in several situations using real data and helped by VI users.

  12. A Laminar Flow-Based Microfluidic Tesla Pump via Lithography Enabled 3D Printing.

    PubMed

    Habhab, Mohammed-Baker; Ismail, Tania; Lo, Joe Fujiou

    2016-11-23

    Tesla turbine and its applications in power generation and fluid flow were demonstrated by Nicholas Tesla in 1913. However, its real-world implementations were limited by the difficulty to maintain laminar flow between rotor disks, transient efficiencies during rotor acceleration, and the lack of other applications that fully utilize the continuous flow outputs. All of the aforementioned limits of Tesla turbines can be addressed by scaling to the microfluidic flow regime. Demonstrated here is a microscale Tesla pump designed and fabricated using a Digital Light Processing (DLP) based 3D printer with 43 µm lateral and 30 µm thickness resolutions. The miniaturized pump is characterized by low Reynolds number of 1000 and a flow rate of up to 12.6 mL/min at 1200 rpm, unloaded. It is capable of driving a mixer network to generate microfluidic gradient. The continuous, laminar flow from Tesla turbines is well-suited to the needs of flow-sensitive microfluidics, where the integrated pump will enable numerous compact lab-on-a-chip applications.

  13. A Laminar Flow-Based Microfluidic Tesla Pump via Lithography Enabled 3D Printing

    PubMed Central

    Habhab, Mohammed-Baker; Ismail, Tania; Lo, Joe Fujiou

    2016-01-01

    Tesla turbine and its applications in power generation and fluid flow were demonstrated by Nicholas Tesla in 1913. However, its real-world implementations were limited by the difficulty to maintain laminar flow between rotor disks, transient efficiencies during rotor acceleration, and the lack of other applications that fully utilize the continuous flow outputs. All of the aforementioned limits of Tesla turbines can be addressed by scaling to the microfluidic flow regime. Demonstrated here is a microscale Tesla pump designed and fabricated using a Digital Light Processing (DLP) based 3D printer with 43 µm lateral and 30 µm thickness resolutions. The miniaturized pump is characterized by low Reynolds number of 1000 and a flow rate of up to 12.6 mL/min at 1200 rpm, unloaded. It is capable of driving a mixer network to generate microfluidic gradient. The continuous, laminar flow from Tesla turbines is well-suited to the needs of flow-sensitive microfluidics, where the integrated pump will enable numerous compact lab-on-a-chip applications. PMID:27886051

  14. Research on 3-D device for infrared temperature detection

    NASA Astrophysics Data System (ADS)

    Chen, Shuxin; Jiang, Shaohua; Hou, Jie; Chen, Shuwang

    2007-12-01

    In a certain field, it is important to measure temperature information in variable direction at the same time. However, there are few instruments to accomplish the function now. To implement the measure in 3 dimensions, an experimental table of temperature detection by infrared is designed. It is the integration of detection, control and monitor. The infrared device in the table can detect and measure temperature in real time, and the three dimension electric motional device can adjust the detection distance by the user. The mechanical bar for displacement is controlled by a circuit with the control button. The infrared temperature sensor is fixed on the bar, so it can move along with the bar controlled by the circuit. The method of temperature detection is untouched, so it can detect small object and its tiny variable temperature, which can not be detected by the thermometer or the electronic temperature sensor. In terms of the 3-D parallel motion control, the device can implement temperature measurement in variable directions. According to the results of the temperature values, the 3-D temperature distributed curve can be described. By using of the detection device, temperature of some special objects can be detected, such as the live anatomical animal, small sensor, nondestructive object, and so on.

  15. Simple Check Valves for Microfluidic Devices

    NASA Technical Reports Server (NTRS)

    Willis, Peter A.; Greer, Harold F.; Smith, J. Anthony

    2010-01-01

    A simple design concept for check valves has been adopted for microfluidic devices that consist mostly of (1) deformable fluorocarbon polymer membranes sandwiched between (2) borosilicate float glass wafers into which channels, valve seats, and holes have been etched. The first microfluidic devices in which these check valves are intended to be used are micro-capillary electrophoresis (microCE) devices undergoing development for use on Mars in detecting compounds indicative of life. In this application, it will be necessary to store some liquid samples in reservoirs in the devices for subsequent laboratory analysis, and check valves are needed to prevent cross-contamination of the samples. The simple check-valve design concept is also applicable to other microfluidic devices and to fluidic devices in general. These check valves are simplified microscopic versions of conventional rubber- flap check valves that are parts of numerous industrial and consumer products. These check valves are fabricated, not as separate components, but as integral parts of microfluidic devices. A check valve according to this concept consists of suitably shaped portions of a deformable membrane and the two glass wafers between which the membrane is sandwiched (see figure). The valve flap is formed by making an approximately semicircular cut in the membrane. The flap is centered over a hole in the lower glass wafer, through which hole the liquid in question is intended to flow upward into a wider hole, channel, or reservoir in the upper glass wafer. The radius of the cut exceeds the radius of the hole by an amount large enough to prevent settling of the flap into the hole. As in a conventional rubber-flap check valve, back pressure in the liquid pushes the flap against the valve seat (in this case, the valve seat is the adjacent surface of the lower glass wafer), thereby forming a seal that prevents backflow.

  16. Evaluation of Manufacturing Processes for Microfluidic Devices

    NASA Astrophysics Data System (ADS)

    Laura Jáuregui, Ana; Siller, Héctor R.; Rodriguez, Ciro A.; Elías-Zúñiga, Alex

    2009-11-01

    In this paper several micro-mechanical manufacturing technologies were studied in order to characterize their performance for making miniaturized geometries known as micro-channels, which are the main geometric features of micro-fluidic devices. The technologies used were Micro-End Milling, Wire Electro Discharge Machiningesol Sandblasting and Abrasive Water Jet. Their capabilities were compared with Lithography capabilities, which is the conventional process for micro-channel manufacturing. The evaluation consists in a comprehensive study of surface quality and topography, made with the help of advanced contact and non-contact devices over each prototype made by each technology. Also economical considerations have been taken into account in order to choose the most appropriate manufacturing process for the prototyping of micro-fluidic devices. The results show that Micro-End Milling process can compete with Lithography, in terms of achieving acceptable levels of product quality and economics.

  17. Microfluidic devices for terahertz spectroscopy of biomolecules.

    PubMed

    George, Paul A; Hui, Wallace; Rana, Farhan; Hawkins, Benjamin G; Smith, A Ezekiel; Kirby, Brian J

    2008-02-04

    We demonstrate microfluidic devices for terahertz spectroscopy of biomolecules in aqueous solutions. The devices are fabricated out of a plastic material that is both mechanically rigid and optically transparent with near-zero dispersion in the terahertz frequency range. Using a lowpower terahertz time-domain spectrometer, we experimentally measure the absorption spectra of the vibrational modes of bovine serum albumin from 0.5 - 2.5 THz and find good agreement with previously reported data obtained using large-volume solutions and a high-power free-electron laser. Our results demonstrate the feasibility of performing high sensitivity terahertz spectroscopy of biomolecules in aqueous solutions with detectable molecular quantities as small as 10 picomoles using microfluidic devices.

  18. Microfluidic devices fabricated using fast wafer-scale LED-lithography patterning.

    PubMed

    Challa, Pavan K; Kartanas, Tadas; Charmet, Jérôme; Knowles, Tuomas P J

    2017-01-01

    Current lithography approaches underpinning the fabrication of microfluidic devices rely on UV exposure of photoresists to define microstructures in these materials. Conventionally, this objective is achieved with gas discharge mercury lamps, which are capable of producing high intensity UV radiation. However, these sources are costly, have a comparatively short lifetime, necessitate regular calibration, and require significant time to warm up prior to exposure taking place. To address these limitations we exploit advances in solid state sources in the UV range and describe a fast and robust wafer-scale laboratory exposure system relying entirely on UV-Light emitting diode (UV-LED) illumination. As an illustration of the potential of this system for fast and low-cost microfluidic device production, we demonstrate the microfabrication of a 3D spray-drying microfluidic device and a 3D double junction microdroplet maker device.

  19. 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

  20. 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.

  1. Mixing in microfluidic devices and enhancement methods

    NASA Astrophysics Data System (ADS)

    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.

  2. Microfluidic 3D bone tissue model for high-throughput evaluation of wound-healing and infection-preventing biomaterials.

    PubMed

    Lee, Joung-Hyun; Gu, Yexin; Wang, Hongjun; Lee, Woo Y

    2012-02-01

    We report the use of a microfluidic 3D bone tissue model, as a high-throughput means of evaluating the efficacy of biomaterials aimed at accelerating orthopaedic implant-related wound-healing while preventing bacterial infection. As an example of such biomaterials, inkjet-printed micropatterns were prepared to contain antibiotic and biphasic calcium phosphate (BCP) nanoparticles dispersed in a poly(D,L-lactic-co-glycolic) acid matrix. The micropatterns were integrated with a microfluidic device consisting of eight culture chambers. The micropatterns immediately and completely killed Staphylococcus epidermidis upon inoculation, and enhanced the calcified extracellular matrix production of osteoblasts. Without antibiotic elution, bacteria rapidly proliferated to result in an acidic microenvironment which was detrimental to osteoblasts. These results were used to demonstrate the tissue model's potential in: (i) significantly reducing the number of biomaterial samples and culture experiments required to assess in vitro efficacy for wound-healing and infection prevention and (ii) in situ monitoring of dynamic interactions of biomaterials with bacteria as wells as with tissue cells simultaneously.

  3. Microfluidic Gradients Reveal Enhanced Neurite Outgrowth but Impaired Guidance within 3D Matrices with High Integrin Ligand Densities

    PubMed Central

    Romano, Nicole H.; Lampe, Kyle J.; Xu, Hui; Ferreira, Meghaan M.

    2015-01-01

    The density of integrin-binding ligands in an extracellular matrix (ECM) is known to regulate cell migration speed by imposing a balance of traction forces between the leading and trailing edges of the cell, but the effect of cell-adhesive ligands on neurite chemoattraction is not well understood. We present a platform that combines gradient-generating microfluidic devices with three-dimensional (3D) protein-engineered hydrogels to study the effect of RGD ligand density on neurite pathfinding from chick dorsal root ganglia-derived spheroids. Spheroids are encapsulated in elastin-like polypeptide (ELP) hydrogels presenting either 3.2 or 1.6 mM RGD ligands and exposed to a microfluidic gradient of nerve growth factor (NGF). While the higher ligand density matrix enhanced neurite initiation and persistence of neurite outgrowth, the lower ligand density matrix significantly improved neurite pathfinding and increased the frequency of growth cone turning up the NGF gradient. The apparent trade-off between neurite extension and neurite guidance is reminiscent of the well-known parabolic relationship between cell adhesion and migration speed, implying that a similar matrix-mediated balance of forces regulate neurite elongation and growth cone turning. These results have implications in the design of engineered materials for in vitro models of neural tissue and in vivo nerve guidance channels. PMID:25315156

  4. Using Living Radical Polymerization to Enable Facile Incorporation of Materials in Microfluidic Cell Culture Devices

    PubMed Central

    Simms, Helen M.; Bowman, Christopher M.; Anseth, Kristi S.

    2008-01-01

    High throughput screening tools are expediting cell culture studies with applications in drug discovery and tissue engineering. This contribution demonstrates a method to incorporate 3D cell culture sites into microfluidic devices and enables the fabrication of high throughput screening tools with uniquely addressable culture environments. Contact Lithographic Photopolymerization (CLiPP) was used to fabricate microfluidic devices with two types of 3D culture sites: macroporous rigid polymer cell scaffolds and poly(ethylene glycol) (PEG) encapsulated cell matrices. Cells were cultured on-device with both types of culture sites, demonstrating material cytocompatibility. Multilayer microfluidic devices were fabricated with channels passing the top and bottom sides of a series of rigid porous polymer scaffolds. Cells were seeded and cultured on-device, demonstrating the ability to deliver cells and culture cells on multiple scaffolds along the length of a single channel. Flow control through these rigid porous polymer scaffolds was demonstrated. Finally, devices were modified by grafting of PEG methacrylate from surfaces to prevent non-specific protein adsorption and ultimately cell adhesion to channel surfaces. The living radical component of this CLiPP device fabrication platform enables facile incorporation of 3D culture sites into microfluidic cell culture devices, which can be utilized for high throughput screening of cell material interactions. PMID:18294686

  5. Optimization of monolithic columns for microfluidic devices

    NASA Astrophysics Data System (ADS)

    Pagaduan, Jayson V.; Yang, Weichun; Woolley, Adam T.

    2011-06-01

    Monolithic columns offer advantages as solid-phase extractors because they offer high surface area that can be tailored to a specific function, fast mass transport, and ease of fabrication. Porous glycidyl methacrylate-ethylene glycol dimethacrylate monoliths were polymerized in-situ in microfluidic devices, without pre-treatment of the poly(methyl methacrylate) channel surface. Cyclohexanol, 1-dodecanol and Tween 20 were used to control the pore size of the monoliths. The epoxy groups on the monolith surface can be utilized to immobilize target-specific probes such as antibodies, aptamers, or DNA for biomarker detection. Microfluidic devices integrated with solid-phase extractors should be useful for point-of-care diagnostics in detecting specific biomarkers from complex biological fluids.

  6. Streamline-based microfluidic device

    NASA Technical Reports Server (NTRS)

    Tai, Yu-Chong (Inventor); Zheng, Siyang (Inventor); Kasdan, Harvey (Inventor)

    2013-01-01

    The present invention provides a streamline-based device and a method for using the device for continuous separation of particles including cells in biological fluids. The device includes a main microchannel and an array of side microchannels disposed on a substrate. The main microchannel has a plurality of stagnation points with a predetermined geometric design, for example, each of the stagnation points has a predetermined distance from the upstream edge of each of the side microchannels. The particles are separated and collected in the side microchannels.

  7. A Microfluidic DNA Sensor Based on Three-Dimensional (3D) Hierarchical MoS2/Carbon Nanotube Nanocomposites

    PubMed Central

    Yang, Dahou; Tayebi, Mahnoush; Huang, Yinxi; Yang, Hui Ying; Ai, Ye

    2016-01-01

    In this work, we present a novel microfluidic biosensor for sensitive fluorescence detection of DNA based on 3D architectural MoS2/multi-walled carbon nanotube (MWCNT) nanocomposites. The proposed platform exhibits a high sensitivity, selectivity, and stability with a visible manner and operation simplicity. The excellent fluorescence quenching stability of a MoS2/MWCNT aqueous solution coupled with microfluidics will greatly simplify experimental steps and reduce time for large-scale DNA detection. PMID:27854247

  8. 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.

  9. Fluid control structures in microfluidic devices

    NASA Technical Reports Server (NTRS)

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

  10. Three-dimensional microfluidic devices fabricated in layered paper and tape

    PubMed Central

    Martinez, Andres W.; Phillips, Scott T.; Whitesides, George M.

    2008-01-01

    This article describes a method for fabricating 3D microfluidic devices by stacking layers of patterned paper and double-sided adhesive tape. Paper-based 3D microfluidic devices have capabilities in microfluidics that are difficult to achieve using conventional open-channel microsystems made from glass or polymers. In particular, 3D paper-based devices wick fluids and distribute microliter volumes of samples from single inlet points into arrays of detection zones (with numbers up to thousands). This capability makes it possible to carry out a range of new analytical protocols simply and inexpensively (all on a piece of paper) without external pumps. We demonstrate a prototype 3D device that tests 4 different samples for up to 4 different analytes and displays the results of the assays in a side-by-side configuration for easy comparison. Three-dimensional paper-based microfluidic devices are especially appropriate for use in distributed healthcare in the developing world and in environmental monitoring and water analysis. PMID:19064929

  11. Identification of drugs as single agents or in combination to prevent carcinoma dissemination in a microfluidic 3D environment

    PubMed Central

    Kim, Choong; Thiery, Jean Paul; Kamm, Roger D.

    2015-01-01

    Experiments were performed in a modified microfluidic platform recapitulating part of the in vivo tumor microenvironment by co-culturing carcinoma cell aggregates embedded in a three-dimensional (3D) collagen scaffold with human umbilical vein endothelial cells (HUVECs). HUVECs were seeded in one channel of the device to initiate vessel-like structures in vitro prior to introducing the aggregates. The lung adenocarcinoma cell line A549 and the bladder carcinoma cell line T24 were tested. Dose-response assays of four drugs known to interfere with Epithelial Mesenchymal Transition (EMT) signaling pathways were quantified using relative dispersion as a metric of EMT progression. The presence of HUVECs in one channel induces cell dispersal in A549 which then can be inhibited by each of the four drugs. Complete inhibition of T24 aggregate dispersal, however, is not achieved with any single agent, although partial inhibition was observed with 10 μM of the Src inhibitor, AZD-0530. Almost complete inhibition of T24 dispersal in monoculture was achieved only when the four drugs were added in combination, each at 10 μM concentration. Coculture of T24 with HUVECs forfeits the almost-complete inhibition. The enhanced dispersal observed in the presence of HUVECs is a consequence of secretion of growth factors, including HGF and FGF-2, by endothelial cells. This 3D microfluidic co-culture platform provides an in vivo-like surrogate for anti-invasive and anti-metastatic drug screening. It will be particularly useful for defining combination therapies for aggressive tumors such as invasive bladder carcinoma. PMID:26474384

  12. Regulation of mesenchymal stem cell 3D microenvironment: From macro to microfluidic bioreactors.

    PubMed

    Sart, Sébastien; Agathos, Spiros N; Li, Yan; Ma, Teng

    2016-01-01

    Human mesenchymal stem cells (hMSCs) have emerged as an important cell type in cell therapy and tissue engineering. In these applications, maintaining the therapeutic properties of hMSCs requires tight control of the culture environments and the structural cell organizations. Bioreactor systems are essential tools to achieve these goals in the clinical-scale expansion and tissue engineering applications. This review summarizes how different bioreactors provide cues to regulate the structure and the chemico-mechanical microenvironment of hMSCs with a focus on 3D organization. In addition to conventional bioreactors, recent advances in microfluidic bioreactors as a novel approach to better control the hMSC microenvironment are also discussed. These advancements highlight the key role of bioreactor systems in preserving hMSC's functional properties by providing dynamic and temporal regulation of in vitro cellular microenvironment.

  13. Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation

    PubMed Central

    Jeon, Jessie S.; Bersini, Simone; Gilardi, Mara; Dubini, Gabriele; Charest, Joseph L.; Moretti, Matteo; Kamm, Roger D.

    2015-01-01

    A key aspect of cancer metastases is the tendency for specific cancer cells to home to defined subsets of secondary organs. Despite these known tendencies, the underlying mechanisms remain poorly understood. Here we develop a microfluidic 3D in vitro model to analyze organ-specific human breast cancer cell extravasation into bone- and muscle-mimicking microenvironments through a microvascular network concentrically wrapped with mural cells. Extravasation rates and microvasculature permeabilities were significantly different in the bone-mimicking microenvironment compared with unconditioned or myoblast containing matrices. Blocking breast cancer cell A3 adenosine receptors resulted in higher extravasation rates of cancer cells into the myoblast-containing matrices compared with untreated cells, suggesting a role for adenosine in reducing extravasation. These results demonstrate the efficacy of our model as a drug screening platform and a promising tool to investigate specific molecular pathways involved in cancer biology, with potential applications to personalized medicine. PMID:25524628

  14. Long Term Maintenance of a Microfluidic 3-D Human Liver Sinusoid

    PubMed Central

    Prodanov, Ljupcho; Jindal, Rohit; Bale, Shyam Sundhar; Hegde, Manjunath; McCarty, William J.; Golberg, Inna; Bhushan, Abhinav; Yarmush, Martin L.; Usta, O. Berk

    2016-01-01

    The development of long-term human organotypic liver-on-a-chip models for successful prediction of toxic response is one of the most important and urgent goals of the NIH/DARPA’s initiative to replicate and replace chronic and acute drug testing in animals. For this purpose we developed a microfluidic chip that consists of two microfluidic chambers separated by a porous membrane. The aim of this communication is to demonstrate the recapitulation of a liver sinusoid-on-a-chip using human cells only for a period of 28 days. Using a step-by-step method for building a 3D microtissue on-a-chip, we demonstrate that an organotypic in vitro model that reassembles the liver sinusoid microarchitecture can be maintained successfully for a period of 28 days. In addition, higher albumin synthesis (synthetic), urea excretion (detoxification) was observed under flow compared to static cultures. This human liver-on-a-chip should be further evaluated in drug-related studies. PMID:26152452

  15. Long-term maintenance of a microfluidic 3D human liver sinusoid.

    PubMed

    Prodanov, Ljupcho; Jindal, Rohit; Bale, Shyam Sundhar; Hegde, Manjunath; McCarty, William J; Golberg, Inna; Bhushan, Abhinav; Yarmush, Martin L; Usta, Osman Berk

    2016-01-01

    The development of long-term human organotypic liver-on-a-chip models for successful prediction of toxic response is one of the most important and urgent goals of the NIH/DARPA's initiative to replicate and replace chronic and acute drug testing in animals. For this purpose, we developed a microfluidic chip that consists of two microfluidic chambers separated by a porous membrane. The aim of this communication is to demonstrate the recapitulation of a liver sinusoid-on-a-chip, using human cells only for a period of 28 days. Using a step-by-step method for building a 3D microtissue on-a-chip, we demonstrate that an organotypic in vitro model that reassembles the liver sinusoid microarchitecture can be maintained successfully for a period of 28 days. In addition, higher albumin synthesis (synthetic) and urea excretion (detoxification) were observed under flow compared to static cultures. This human liver-on-a-chip should be further evaluated in drug-related studies.

  16. Fabrication of microfluidic system for the assessment of cell migration on 3D micropatterned substrates.

    PubMed

    Lee, Eun-Joong; Hwang, Chang-Mo; Baek, Dong-Hyun; Lee, Sang-Hoon

    2009-01-01

    Cell migration and proliferation are major process in wound healing, cancer metastasis and organogenesis during development. Many cells are related to recovery process of wound. Especially, fibroblasts act an important role in wound healing. Various cytokines such as platelet derived growth factor (PDGF) can induce fibroblast migration and widely studied to investigate the cell response under controlled cytokine microenvironments during wound healing. In real tissue healing process, cell microenvironments change with tissue types and anatomical characteristics of organs. With microfluidic system, we tried to mimic the natural microenvironment of wound healing, with gradient of PDGF, a fibroblast migration inducing cytokine, and patterned substrate with different orientation to PDGF gradient. Fibroblasts cultured in PDGF gradient micro fluidic chip showed cell migration under various micro environmental gradient conditions. Cells were cultured under PDGF gradient condition and different substrate pattern. Mouse fibroblast L929 cells were cultured in the microfluidic gradient. The results showed that most cells migrated along the substrate topological patterns under high concentration of PDGF. We developed long range sustaining micro fluidic channel and could analyze cell migration along the gradient of PDGF. Also, the cell migration on patterned extracellular environment shows that cells migrate along the extracellular 3D pattern rather than directly along the cytokine gradient when the pattern height is less than 1 microm. In this study, we could demonstrate that the extracellular pattern is more dominant to cell migration in combination with cytokine gradient in the wounded tissue when the environmental cues are 20 microm.

  17. Detection of unlabeled particles in the low micrometer size range using light scattering and hydrodynamic 3D focusing in a microfluidic system.

    PubMed

    Zhuang, Guisheng; Jensen, Thomas G; Kutter, Jörg P

    2012-07-01

    In this paper, we describe a microfluidic device composed of integrated microoptical elements and a two-layer microchannel structure for highly sensitive light scattering detection of micro/submicrometer-sized particles. In the two-layer microfluidic system, a sample flow stream is first constrained in the out-of-plane direction into a narrow sheet, and then focused in-plane into a small core region, obtaining on-chip three-dimensional (3D) hydrodynamic focusing. All the microoptical elements, including waveguides, microlens, and fiber-to-waveguide couplers, and the in-plane focusing channels are fabricated in one SU-8 layer by standard photolithography. The channels for out-of-plane focusing are made in a polydimethylsiloxane (PDMS) layer by a single cast using a SU-8 master. Numerical and experimental results indicate that the device can realize 3D hydrodynamic focusing reliably over a wide range of Reynolds numbers (0.5 < Re < 20). Polystyrene particles of three sizes (2, 1, and 0.5 μm) were measured in the microfluidic device with integrated optics, demonstrating the feasibility of this approach to detect particles in the low micrometer size range by light scattering detection.

  18. Recent progress in printed 2/3D electronic devices

    NASA Astrophysics Data System (ADS)

    Klug, Andreas; Patter, Paul; Popovic, Karl; Blümel, Alexander; Sax, Stefan; Lenz, Martin; Glushko, Oleksandr; Cordill, Megan J.; List-Kratochvil, Emil J. W.

    2015-09-01

    New, energy-saving, efficient and cost-effective processing technologies such as 2D and 3D inkjet printing (IJP) for the production and integration of intelligent components will be opening up very interesting possibilities for industrial applications of molecular materials in the near future. Beyond the use of home and office based printers, "inkjet printing technology" allows for the additive structured deposition of photonic and electronic materials on a wide variety of substrates such as textiles, plastics, wood, stone, tiles or cardboard. Great interest also exists in applying IJP in industrial manufacturing such as the manufacturing of PCBs, of solar cells, printed organic electronics and medical products. In all these cases inkjet printing is a flexible (digital), additive, selective and cost-efficient material deposition method. Due to these advantages, there is the prospect that currently used standard patterning processes can be replaced through this innovative material deposition technique. A main issue in this research area is the formulation of novel functional inks or the adaptation of commercially available inks for specific industrial applications and/or processes. In this contribution we report on the design, realization and characterization of novel active and passive inkjet printed electronic devices including circuitry and sensors based on metal nanoparticle ink formulations and the heterogeneous integration into 2/3D printed demonstrators. The main emphasis of this paper will be on how to convert scientific inkjet knowledge into industrially relevant processes and applications.

  19. Microfab-less Microfluidic Capillary Electrophoresis Devices

    PubMed Central

    Segato, Thiago P.; Bhakta, Samir A.; Gordon, Matthew; Carrilho, Emanuel; Willis, Peter A.; Jiao, Hong; Garcia, Carlos D.

    2013-01-01

    Compared to conventional bench-top instruments, microfluidic devices possess advantageous characteristics including great portability potential, reduced analysis time (minutes), and relatively inexpensive production, putting them on the forefront of modern analytical chemistry. Fabrication of these devices, however, often involves polymeric materials with less-than-ideal surface properties, specific instrumentation, and cumbersome fabrication procedures. In order to overcome such drawbacks, a new hybrid platform is proposed. The platform is centered on the use of 5 interconnecting microfluidic components that serve as the injector or reservoirs. These plastic units are interconnected using standard capillary tubing, enabling in-channel detection by a wide variety of standard techniques, including capacitively-coupled contactless conductivity detection (C4D). Due to the minimum impact on the separation efficiency, the plastic microfluidic components used for the experiments discussed herein were fabricated using an inexpensive engraving tool and standard Plexiglas. The presented approach (named 52-platform) offers a previously unseen versatility: enabling the assembly of the platform within minutes using capillary tubing that differs in length, diameter, or material. The advantages of the proposed design are demonstrated by performing the analysis of inorganic cations by capillary electrophoresis on soil samples from the Atacama Desert. PMID:23585815

  20. Microfluidic device for unidirectional axon growth

    NASA Astrophysics Data System (ADS)

    Malishev, E.; Pimashkin, A.; Gladkov, A.; Pigareva, Y.; Bukatin, A.; Kazantsev, V.; Mukhina, I.; Dubina, M.

    2015-11-01

    In order to better understand the communication and connectivity development of neuron networks, we designed microfluidic devices with several chambers for growing dissociated neuronal cultures from mice fetal hippocampus (E18). The chambers were connected with microchannels providing unidirectional axonal growth between “Source” and “Target” neural sub-networks. Experiments were performed in a hippocampal cultures plated in a poly-dimethylsiloxane (PDMS) microfluidic chip, aligned with a 60 microelectrode array (MEA). Axonal growth through microchannels was observed with brightfield, phase-contrast and fluorescence microscopy, and after 7 days in vitro electrical activity was recorded. Visual inspection and spike propagation analysis showed the predominant axonal growth in microchannels in a direction from “Source” to “Target”.

  1. 3D FaceCam: a fast and accurate 3D facial imaging device for biometrics applications

    NASA Astrophysics Data System (ADS)

    Geng, Jason; Zhuang, Ping; May, Patrick; Yi, Steven; Tunnell, David

    2004-08-01

    Human faces are fundamentally three-dimensional (3D) objects, and each face has its unique 3D geometric profile. The 3D geometric features of a human face can be used, together with its 2D texture, for rapid and accurate face recognition purposes. Due to the lack of low-cost and robust 3D sensors and effective 3D facial recognition (FR) algorithms, almost all existing FR systems use 2D face images. Genex has developed 3D solutions that overcome the inherent problems in 2D while also addressing limitations in other 3D alternatives. One important aspect of our solution is a unique 3D camera (the 3D FaceCam) that combines multiple imaging sensors within a single compact device to provide instantaneous, ear-to-ear coverage of a human face. This 3D camera uses three high-resolution CCD sensors and a color encoded pattern projection system. The RGB color information from each pixel is used to compute the range data and generate an accurate 3D surface map. The imaging system uses no moving parts and combines multiple 3D views to provide detailed and complete 3D coverage of the entire face. Images are captured within a fraction of a second and full-frame 3D data is produced within a few seconds. This described method provides much better data coverage and accuracy in feature areas with sharp features or details (such as the nose and eyes). Using this 3D data, we have been able to demonstrate that a 3D approach can significantly improve the performance of facial recognition. We have conducted tests in which we have varied the lighting conditions and angle of image acquisition in the "field." These tests have shown that the matching results are significantly improved when enrolling a 3D image rather than a single 2D image. With its 3D solutions, Genex is working toward unlocking the promise of powerful 3D FR and transferring FR from a lab technology into a real-world biometric solution.

  2. Microfluidic control using colloidal devices.

    PubMed

    Terray, Alex; Oakey, John; Marr, David W M

    2002-06-07

    By manipulating colloidal microspheres within customized channels, we have created micrometer-scale fluid pumps and particulate valves. We describe two positive-displacement designs, a gear and a peristaltic pump, both of which are about the size of a human red blood cell. Two colloidal valve designs are also demonstrated, one actuated and one passive, for the direction of cells or small particles. The use of colloids as both valves and pumps will allow device integration at a density far beyond what is currently achievable by other approaches and may provide a link between fluid manipulation at the macro- and nanoscale.

  3. Microfluidic Control Using Colloidal Devices

    NASA Astrophysics Data System (ADS)

    Terray, Alex; Oakey, John; Marr, David W. M.

    2002-06-01

    By manipulating colloidal microspheres within customized channels, we have created micrometer-scale fluid pumps and particulate valves. We describe two positive-displacement designs, a gear and a peristaltic pump, both of which are about the size of a human red blood cell. Two colloidal valve designs are also demonstrated, one actuated and one passive, for the direction of cells or small particles. The use of colloids as both valves and pumps will allow device integration at a density far beyond what is currently achievable by other approaches and may provide a link between fluid manipulation at the macro- and nanoscale.

  4. 3D-printed microfluidic microdissector for high-throughput studies of cellular aging.

    PubMed

    Spivey, Eric C; Xhemalce, Blerta; Shear, Jason B; Finkelstein, Ilya J

    2014-08-05

    Due to their short lifespan, rapid division, and ease of genetic manipulation, yeasts are popular model organisms for studying aging in actively dividing cells. To study replicative aging over many cell divisions, individual cells must be continuously separated from their progeny via a laborious manual microdissection procedure. Microfluidics-based soft-lithography devices have recently been used to automate microdissection of the budding yeast Saccharomyces cerevisiae. However, little is known about replicative aging in Schizosaccharomyces pombe, a rod-shaped yeast that divides by binary fission and shares many conserved biological functions with higher eukaryotes. In this report, we develop a versatile multiphoton lithography method that enables rapid fabrication of three-dimensional master structures for polydimethylsiloxane (PDMS)-based microfluidics. We exploit the rapid prototyping capabilities of multiphoton lithography to create and characterize a cell-capture device that is capable of high-resolution microscopic observation of hundreds of individual S. pombe cells. By continuously removing the progeny cells, we demonstrate that cell growth and protein aggregation can be tracked in individual cells for over ~100 h. Thus, the fission yeast lifespan microdissector (FYLM) provides a powerful on-chip microdissection platform that will enable high-throughput studies of aging in rod-shaped cells.

  5. Development of a 3D Graphene Electrode Dielectrophoretic Device

    PubMed Central

    Xie, Hongyu; Tewari, Radheshyam; Fukushima, Hiroyuki; Narendra, Jeffri; Heldt, Caryn; King, Julia; Minerick, Adrienne R.

    2014-01-01

    The design and fabrication of a novel 3D electrode microdevice using 50 µm thick graphene paper and 100 µm double sided tape is described. The protocol details the procedures to construct a versatile, reusable, multiple layer, laminated dielectrophoresis chamber. Specifically, six layers of 50 µm x 0.7 cm x 2 cm graphene paper and five layers of double sided tape were alternately stacked together, then clamped to a glass slide. Then a 700 μm diameter micro-well was drilled through the laminated structure using a computer-controlled micro drilling machine. Insulating properties of the tape layer between adjacent graphene layers were assured by resistance tests. Silver conductive epoxy connected alternate layers of graphene paper and formed stable connections between the graphene paper and external copper wire electrodes. The finished device was then clamped and sealed to a glass slide. The electric field gradient was modeled within the multi-layer device. Dielectrophoretic behaviors of 6 μm polystyrene beads were demonstrated in the 1 mm deep micro-well, with medium conductivities ranging from 0.0001 S/m to 1.3 S/m, and applied signal frequencies from 100 Hz to 10 MHz. Negative dielectrophoretic responses were observed in three dimensions over most of the conductivity-frequency space and cross-over frequency values are consistent with previously reported literature values. The device did not prevent AC electroosmosis and electrothermal flows, which occurred in the low and high frequency regions, respectively. The graphene paper utilized in this device is versatile and could subsequently function as a biosensor after dielectrophoretic characterizations are complete. PMID:24998694

  6. Mail-order microfluidics: evaluation of stereolithography for the production of microfluidic devices.

    PubMed

    Au, Anthony K; Lee, Wonjae; Folch, Albert

    2014-04-07

    The vast majority of microfluidic devices are developed in PDMS by molding ("soft lithography") because PDMS is an inexpensive material, has physicochemical properties that are well suited for biomedical and physical sciences applications, and design cycle lengths are generally adequate for prototype development. However, PDMS molding is tediously slow and thus cannot provide the high- or medium-volume production required for the commercialization of devices. While high-throughput plastic molding techniques (e.g. injection molding) exist, the exorbitant cost of the molds and/or the equipment can be a serious obstacle for device commercialization, especially for small startups. High-volume production is not required to reach niche markets such as clinical trials, biomedical research supplies, customized research equipment, and classroom projects. Crucially, both PDMS and plastic molding are layer-by-layer techniques where each layer is produced as a result of physicochemical processes not specified in the initial photomask(s) and where the final device requires assembly by bonding, all resulting in a cost that is very hard to predict at the start of the project. By contrast, stereolithography (SL) is an automated fabrication technique that allows for the production of quasi-arbitrary 3D shapes in a single polymeric material at medium-volume throughputs (ranging from a single part to hundreds of parts). Importantly, SL devices can be designed between several groups using CAD tools, conveniently ordered by mail, and their cost precisely predicted via a web interface. Here we evaluate the resolution of an SL mail-order service and the main causes of resolution loss; the optical clarity of the devices and how to address the lack of clarity for imaging in the channels; and the future role that SL could play in the commercialization of microfluidic devices.

  7. Mail-Order Microfluidics: Evaluation of Stereolithography for the Production of Microfluidic Devices

    PubMed Central

    Au, Anthony K.; Lee, Wonjae; Folch, Albert

    2015-01-01

    The vast majority of microfluidic devices are developed in PDMS by molding (“soft lithography”) because PDMS is an inexpensive material, has physicochemical properties that are well suited for biomedical and physical sciences applications, and design cycle lengths are generally adequate for prototype development. However, PDMS molding is tediously slow and thus cannot provide the high- or medium-volume production required for the commercialization of devices. While high-throughput plastic molding techniques (e.g. injection molding) exist, the exorbitant cost of the molds and/or the equipment can be a serious obstacle for device commercialization, especially for small startups. High-volume production is not required to reach niche markets such as clinical trials, biomedical research supplies, customized research equipment, and classroom projects. Crucially, both PDMS and plastic molding are layer-by-layer techniques where each layer is produced as a result of physicochemical processes not specified in the initial photomask(s) and where the final device requires assembly by bonding, all resulting in a cost that is very hard to predict at the start of the project. By contrast, stereolithography (SL) is an automated fabrication technique that allows for the production of quasi-arbitrary 3D shapes in a single polymeric material at medium-volume throughputs (ranging from a single part to hundreds of parts). Importantly, SL devices can be designed between several groups using CAD tools, conveniently ordered by mail, and their cost precisely predicted via a web interface. Here we evaluate the resolution of an SL mail-order service and the main causes of resolution loss; the optical clarity of the devices and how to address the lack of clarity for imaging in the channels; and the future role that SL could play in the commercialization of microfluidic devices. PMID:24510161

  8. Comparison of production methods of a spiral inertial microfluidic cell separation device

    NASA Astrophysics Data System (ADS)

    Robinson, Mitchell; Marks, Haley; Coté, Gerard L.

    2016-03-01

    From the miniaturization of large sample processing machines to the creation of handheld point-of-care devices, microfluidics has the potential to be a powerful tool in the advancement of diagnostic technologies. Here, we compare different prototyping modalities towards the generation of an inertial microfluidic blood filter: i.e. a 'centrifuge-on-a-chip'. While photolithography is currently the method of choice for soft lithography mold fabrication, offering high design fidelity, we believe simpler methods, such as milling or 3D printing, will soon become equally viable options in the field of microfluidic device fabrication. Three modalities for optofluidic PDMS chip fabrication were compared: micromachining, 3D printing, and SU8 photolithography. The filtration efficiency of the chips were tested with whole blood and compared spectroscopically by monitoring the outlet absorbance at the 540 nm peak intrinsic to oxyhemoglobin at the outlet of each filter chip.

  9. Device level 3D characterization using PeakForce AFM

    NASA Astrophysics Data System (ADS)

    Timoney, Padraig; Zhang, Xiaoxiao; Vaid, Alok; Hand, Sean; Osborne, Jason; Milligan, Eric; Feinstein, Adam

    2016-03-01

    Traditional metrology solutions face a range of challenges at the 1X node such as three dimensional (3D) measurement capabilities, shrinking overlay and critical dimension (CD) error budgets driven by multi-patterning and via in trench CD measurements. With advent of advanced technology nodes and 3D processing, an increasing need is emerging for in-die metrology including across-structure and structure-to-structure characterization. A myriad of work has emerged in the past few years intending to address these challenges from various aspects; in-die OCD with reduced spot size and tilt beam on traditional critical dimension scanning electron microscopy (CDSEM) for height measurements. This paper explores the latest capability offered by PeakForceTM Tapping Atomic Force Microscopy (PFT-AFM). The use of traditional harmonic tapping mode for scanning high aspect ratio, and complex "3D" wafer structures, results in limited depth probing capability as well as excessive tip wear. These limitations arise due to the large tip-sample interaction volume in such confined spaces. PeakForce Tapping eliminates these limitations through direct real time control of the tip-sample interaction contact force. The ability of PeakForce to measure, and respond directly to tip- sample interaction forces results in more detailed feature resolution, reduced tip wear, and improved depth capability. In this work, the PFT-AFM tool was applied for multiple applications, including the 14nm fin and replacement metal gate (RMG) applications outlined below. Results from DOE wafers, detailed measurement precision studies and correlation to reference metrology are presented for validation of this methodology. With the fin application, precision of 0.3nm is demonstrated by measuring 5 dies with 10 consecutive runs. Capability to resolve within-die and localized within-macro height variation is also demonstrated. Results obtained from the fin measurements support the increasing trend that measurements

  10. The pumping lid: investigating multi-material 3D printing for equipment-free, programmable generation of positive and negative pressures for microfluidic applications.

    PubMed

    Begolo, Stefano; Zhukov, Dmitriy V; Selck, David A; Li, Liang; Ismagilov, Rustem F

    2014-12-21

    Equipment-free pumping is a challenging problem and an active area of research in microfluidics, with applications for both laboratory and limited-resource settings. This paper describes the pumping lid method, a strategy to achieve equipment-free pumping by controlled generation of pressure. Pressure was generated using portable, lightweight, and disposable parts that can be integrated with existing microfluidic devices to simplify workflow and eliminate the need for pumping equipment. The development of this method was enabled by multi-material 3D printing, which allows fast prototyping, including composite parts that combine materials with different mechanical properties (e.g. both rigid and elastic materials in the same part). The first type of pumping lid we describe was used to produce predictable positive or negative pressures via controlled compression or expansion of gases. A model was developed to describe the pressures and flow rates generated with this approach and it was validated experimentally. Pressures were pre-programmed by the geometry of the parts and could be tuned further even while the experiment was in progress. Using multiple lids or a composite lid with different inlets enabled several solutions to be pumped independently in a single device. The second type of pumping lid, which relied on vapor-liquid equilibrium to generate pressure, was designed, modeled, and experimentally characterized. The pumping lid method was validated by controlling flow in different types of microfluidic applications, including the production of droplets, control of laminar flow profiles, and loading of SlipChip devices. We believe that applying the pumping lid methodology to existing microfluidic devices will enhance their use as portable diagnostic tools in limited resource settings as well as accelerate adoption of microfluidics in laboratories.

  11. Rapid Reconstitution Packages (RRPs) implemented by integration of computational fluid dynamics (CFD) and 3D printed microfluidics.

    PubMed

    Chi, Albert; Curi, Sebastian; Clayton, Kevin; Luciano, David; Klauber, Kameron; Alexander-Katz, Alfredo; D'hers, Sebastian; Elman, Noel M

    2014-08-01

    Rapid Reconstitution Packages (RRPs) are portable platforms that integrate microfluidics for rapid reconstitution of lyophilized drugs. Rapid reconstitution of lyophilized drugs using standard vials and syringes is an error-prone process. RRPs were designed using computational fluid dynamics (CFD) techniques to optimize fluidic structures for rapid mixing and integrating physical properties of targeted drugs and diluents. Devices were manufactured using stereo lithography 3D printing for micrometer structural precision and rapid prototyping. Tissue plasminogen activator (tPA) was selected as the initial model drug to test the RRPs as it is unstable in solution. tPA is a thrombolytic drug, stored in lyophilized form, required in emergency settings for which rapid reconstitution is of critical importance. RRP performance and drug stability were evaluated by high-performance liquid chromatography (HPLC) to characterize release kinetics. In addition, enzyme-linked immunosorbent assays (ELISAs) were performed to test for drug activity after the RRPs were exposed to various controlled temperature conditions. Experimental results showed that RRPs provided effective reconstitution of tPA that strongly correlated with CFD results. Simulation and experimental results show that release kinetics can be adjusted by tuning the device structural dimensions and diluent drug physical parameters. The design of RRPs can be tailored for a number of applications by taking into account physical parameters of the active pharmaceutical ingredients (APIs), excipients, and diluents. RRPs are portable platforms that can be utilized for reconstitution of emergency drugs in time-critical therapies.

  12. Microfluidic devices using thiol-ene polymers

    NASA Astrophysics Data System (ADS)

    Bou, Simon J. M. C.; Ellis, Amanda V.

    2013-12-01

    Here, a new polymeric microfluidic platform using off-stoichiometric thiol-ene (OSTE) polymers was developed. Thiolene polymers were chosen as they afford rapid UV curing, low volume shrinkage and optical transparency for use in microfluidic devices. Three different off-stoichiometric thiol-ene polymers with 30% excess allyl, 50% excess thiol and a 90% excess thiol (OSTE Allyl-30, OSTE-50 and OSTE-90, respectively) were fabricated. Attenuated reflectance Fourier transform infrared (ATR-FTIR) spectroscopy and solid-state cross polarisation-magic angle spinning (CP-MAS) nuclear magnetic resonance (NMR) spectroscopy confirmed which functional groups (thiol or allyl) were present in excess in the OSTE polymers. The polymers were shown to have a more hydrophilic surface (water contact angle of 65°+/- 3) compared to polydimethylsiloxane (water contact angle of 105° +/- 5). Testing of the mechanical properties showed the glass transition temperatures to be 15.09 °C, 43.15 °C and, 57.48 °C for OSTE-90, OSTE Allyl-30 and, OSTE-50, respectively. The storage modulus was shown to be less than 10 MPa for the OSTE-90 polymer and approximately 1750 MPa for the OSTE Allyl-30 and OSTE-50 polymers. The polymers were then utilised to fabricate microfluidic devices via soft lithography practices and devices sealed using a one-step UV lamination "click" reaction technique. Finally, gold nanoparticles were used to form gold films on the OSTE-90 and OSTE-50 polymers as potential electrodes. Atomic force microscopy and sheet resistances were used to characterise the films.

  13. A microfluidic device for characterizing nuclear deformations.

    PubMed

    Hodgson, Andrew C; Verstreken, Christophe M; Fisher, Cynthia L; Keyser, Ulrich F; Pagliara, Stefano; Chalut, Kevin J

    2017-02-28

    Cell nuclei experience and respond to a wide range of forces, both in vivo and in vitro. In order to characterize the nuclear response to physical stress, we developed a microfluidic chip and used it to apply mechanical stress to live cells and measure their nuclear deformability. The device design is optimized for the detection of both nucleus and cytoplasm, which can then be conveniently quantified using a custom-written Matlab program. We measured nuclear sizes and strains of embryonic stem cells, for which we observed negative Poisson ratios in the nuclei. In addition, we were able to detect changes in the nuclear response after treatment with actin depolymerizing and chromatin decondensing agents. Finally, we showed that the device can be used for biologically relevant high-resolution confocal imaging of cells under compression. Thus, the device presented here allows for accurate physical phenotyping at high throughput and has the potential to be applied to a range of cell types.

  14. Method for forming polymerized microfluidic devices

    DOEpatents

    Sommer, Gregory J.; Hatch, Anson V.; Wang, Ying-Chih; Singh, Anup K.; Renzi, Ronald F.; Claudnic, Mark R.

    2013-03-12

    Methods for making a microfluidic device according to embodiments of the present invention include defining.about.cavity. Polymer precursor solution is positioned in the cavity, and exposed to light to begin the polymerization process and define a microchannel. In some embodiments, after the polymerization process is partially complete, a solvent rinse is performed, or fresh polymer precursor introduced into the microchannel. This may promote removal of unpolymerized material from the microchannel and enable smaller feature sizes. The polymer precursor solution may contain an iniferter. Polymerized features therefore may be capped with the iniferter, which is photoactive. The iniferter may aid later binding of a polyacrylamide gel to the microchannel surface.

  15. Microfluidic devices and methods for integrated flow cytometry

    DOEpatents

    Srivastava, Nimisha; Singh, Anup K.

    2011-08-16

    Microfluidic devices and methods for flow cytometry are described. In described examples, various sample handling and preparation steps may be carried out within a same microfluidic device as flow cytometry steps. A combination of imaging and flow cytometry is described. In some examples, spiral microchannels serve as incubation chambers. Examples of automated sample handling and flow cytometry are described.

  16. Non-Linear Electrohydrodynamics in Microfluidic Devices

    PubMed Central

    Zeng, Jun

    2011-01-01

    Since the inception of microfluidics, the electric force has been exploited as one of the leading mechanisms for driving and controlling the movement of the operating fluid and the charged suspensions. Electric force has an intrinsic advantage in miniaturized devices. Because the electrodes are placed over a small distance, from sub-millimeter to a few microns, a very high electric field is easy to obtain. The electric force can be highly localized as its strength rapidly decays away from the peak. This makes the electric force an ideal candidate for precise spatial control. The geometry and placement of the electrodes can be used to design electric fields of varying distributions, which can be readily realized by Micro-Electro-Mechanical Systems (MEMS) fabrication methods. In this paper, we examine several electrically driven liquid handling operations. The emphasis is given to non-linear electrohydrodynamic effects. We discuss the theoretical treatment and related numerical methods. Modeling and simulations are used to unveil the associated electrohydrodynamic phenomena. The modeling based investigation is interwoven with examples of microfluidic devices to illustrate the applications. PMID:21673912

  17. 3D site specific sample preparation and analysis of 3D devices (FinFETs) by atom probe tomography.

    PubMed

    Kambham, Ajay Kumar; Kumar, Arul; Gilbert, Matthieu; Vandervorst, Wilfried

    2013-09-01

    With the transition from planar to three-dimensional device architectures such as Fin field-effect-transistors (FinFETs), new metrology approaches are required to meet the needs of semiconductor technology. It is important to characterize the 3D-dopant distributions precisely as their extent, positioning relative to gate edges and absolute concentration determine the device performance in great detail. At present the atom probe has shown its ability to analyze dopant distributions in semiconductor and thin insulating materials with sub-nm 3D-resolution and good dopant sensitivity. However, so far most reports have dealt with planar devices or restricted the measurements to 2D test structures which represent only limited challenges in terms of localization and site specific sample preparation. In this paper we will discuss the methodology to extract the dopant distribution from real 3D-devices such as a 3D-FinFET device, requiring the sample preparation to be carried out at a site specific location with a positioning accuracy ∼50 nm.

  18. Microfluidic assay of endothelial cell migration in 3D interpenetrating polymer semi-network HA-Collagen hydrogel.

    PubMed

    Jeong, Gi Seok; Kwon, Gu Han; Kang, Ah Ran; Jung, Bo Young; Park, Yongdoo; Chung, Seok; Lee, Sang-Hoon

    2011-08-01

    Cell migration through the extracellular matrix (ECM) is one of the key features for physiological and pathological processes such as angiogenesis, cancer metastasis, and wound healing. In particular, the quantitative assay of endothelial cell migration under the well-defined three dimensional (3D) microenvironment is important to analyze the angiogenesis mechanism. In this study, we report a microfluidic assay of endothelial cell sprouting and migration into an interpenetrating polymer semi-network HA-Collagen (SIPNs CH) hydrogel as ECM providing an enhanced in vivo mimicking 3D microenvironment to cells. The microfluidic chip could provide a well-controlled gradient of growth factor to cells, whereas the hydrogel could mimic a well-defined 3D microenvironment in vivo. (In addition/Furthermore, the microfluidic chip gives a well-controlled gradient of growth factor to cells) For this reason, three types of hydrogel, composed of semi-interpenetrating networks of collagen and hyaluronic acid were prepared, and firstly we proved the role of the hydrogel in endothelial cell migration. The diffusion property and swelling ratio of the hydrogel were characterized. It modulated the migration of endothelial cells in quantified manner, also being influenced by additional synthesis of Matrix metalloproteinase(MMP)-sensitive remodeling peptides and Arginine-glycine-lycinee (RGD) cell adhesion peptides. We successfully established a novel cell migration platform by changing major determinants such as ECM material under biochemical synthesis and under growth factor gradients in a microfluidic manner.

  19. Investigation of nerve injury through microfluidic devices

    PubMed Central

    Siddique, Rezina; Thakor, Nitish

    2014-01-01

    Traumatic injuries, both in the central nervous system (CNS) and peripheral nervous system (PNS), can potentially lead to irreversible damage resulting in permanent loss of function. Investigating the complex dynamics involved in these processes may elucidate the biological mechanisms of both nerve degeneration and regeneration, and may potentially lead to the development of new therapies for recovery. A scientific overview on the biological foundations of nerve injury is presented. Differences between nerve regeneration in the central and PNS are discussed. Advances in microtechnology over the past several years have led to the development of invaluable tools that now facilitate investigation of neurobiology at the cellular scale. Microfluidic devices are explored as a means to study nerve injury at the necessary simplification of the cellular level, including those devices aimed at both chemical and physical injury, as well as those that recreate the post-injury environment. PMID:24227311

  20. A 3D microfluidic chip for electrochemical detection of hydrolysed nucleic bases by a modified glassy carbon electrode.

    PubMed

    Vlachova, Jana; Tmejova, Katerina; Kopel, Pavel; Korabik, Maria; Zitka, Jan; Hynek, David; Kynicky, Jindrich; Adam, Vojtech; Kizek, Rene

    2015-01-22

    Modification of carbon materials, especially graphene-based materials, has wide applications in electrochemical detection such as electrochemical lab-on-chip devices. A glassy carbon electrode (GCE) modified with chemically alternated graphene oxide was used as a working electrode (glassy carbon modified by graphene oxide with sulphur containing compounds and Nafion) for detection of nucleobases in hydrolysed samples (HCl pH = 2.9, 100 °C, 1 h, neutralization by NaOH). It was found out that modification, especially with trithiocyanuric acid, increased the sensitivity of detection in comparison with pure GCE. All processes were finally implemented in a microfluidic chip formed with a 3D printer by fused deposition modelling technology. As a material for chip fabrication, acrylonitrile butadiene styrene was chosen because of its mechanical and chemical stability. The chip contained the one chamber for the hydrolysis of the nucleic acid and another for the electrochemical detection by the modified GCE. This chamber was fabricated to allow for replacement of the GCE.

  1. A 3D Microfluidic Chip for Electrochemical Detection of Hydrolysed Nucleic Bases by a Modified Glassy Carbon Electrode

    PubMed Central

    Vlachova, Jana; Tmejova, Katerina; Kopel, Pavel; Korabik, Maria; Zitka, Jan; Hynek, David; Kynicky, Jindrich; Adam, Vojtech; Kizek, Rene

    2015-01-01

    Modification of carbon materials, especially graphene-based materials, has wide applications in electrochemical detection such as electrochemical lab-on-chip devices. A glassy carbon electrode (GCE) modified with chemically alternated graphene oxide was used as a working electrode (glassy carbon modified by graphene oxide with sulphur containing compounds and Nafion) for detection of nucleobases in hydrolysed samples (HCl pH = 2.9, 100 °C, 1 h, neutralization by NaOH). It was found out that modification, especially with trithiocyanuric acid, increased the sensitivity of detection in comparison with pure GCE. All processes were finally implemented in a microfluidic chip formed with a 3D printer by fused deposition modelling technology. As a material for chip fabrication, acrylonitrile butadiene styrene was chosen because of its mechanical and chemical stability. The chip contained the one chamber for the hydrolysis of the nucleic acid and another for the electrochemical detection by the modified GCE. This chamber was fabricated to allow for replacement of the GCE. PMID:25621613

  2. Direct synthesis and integration of functional nanostructures in microfluidic devices.

    PubMed

    Kim, Jung; Li, Zhiyong; Park, Inkyu

    2011-06-07

    Integration of functional nanostructures within a microfluidic device can synergize the advantages of both unique properties of nanomaterials and diverse functionalities of microfluidics. In this paper, we report a novel and simple method for the in situ synthesis and integration of ZnO nanowires by controlled hydrothermal reaction within microfluidic devices. By modulating synthesis parameters such as the seed preparation, synthesis time, and heating locations, the morphology and location of synthesized nanowires can be easily controlled. The applications of such nanostructure-integrated microfluidics for particle trapping and chemiresistive pH sensing were demonstrated.

  3. Embellishment of microfluidic devices via femtosecond laser micronanofabrication for chip functionalization.

    PubMed

    Wang, Juan; He, Yan; Xia, Hong; Niu, Li-Gang; Zhang, Ran; Chen, Qi-Dai; Zhang, Yong-Lai; Li, Yan-Feng; Zeng, Shao-Jiang; Qin, Jian-Hua; Lin, Bing-Cheng; Sun, Hong-Bo

    2010-08-07

    This paper demonstrates the embellishment of existing microfluidic devices with integrated three dimensional (3D) micronanostructures via femtosecond laser micronanofabrication, which, for the first time, proves two-photon photopolymerization (TPP) to be a powerful technology for chip functionalization. As representative examples, microsieves with various pore shape and adjustable pore size were successfully fabricated inside a conventional glass-based microfluidic channel prepared by wet etching for microparticle separation. Moreover, a fish scale like microfilter was also fabricated and appointed as a one-way valve, which showed excellent performance as we expected. These results indicate that such embellishment of microfluidic devices is simple, low cost, flexible and easy to access. We believe that, combined with TPP, the application of lab-on-chip devices would be further extended.

  4. Development of microfluidic devices for in situ investigation of cells using surface-enhanced Raman spectroscopy (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Ho, Yu-Han; Galvan, Daniel D.; Yu, Qiuming

    2016-03-01

    Surface-enhanced Raman spectroscopy (SERS) has immerged as a power analytical and sensing technique for many applications in biomedical diagnosis, life sciences, food safety, and environment monitoring because of its molecular specificity and high sensitivity. The inactive Raman scattering of water molecule makes SERS a suitable tool for studying biological systems. Microfluidic devices have also attracted a tremendous interest for the aforementioned applications. By integrating SERS-active substrates with microfluidic devices, it offers a new capability for in situ investigation of biological systems, their dynamic behaviors, and response to drugs or microenvironment changes. In this work, we designed and fabricated a microfluidic device with SERS-active substrates surrounding by cell traps in microfluidic channels for in situ study of live cells using SERS. The SERS-active substrates are quasi-3D plasmonic nanostructure array (Q3D-PNA) made in h-PDMS/PMDS with physically separated gold film with nanoholes op top and gold nanodisks at the bottom of nanowells. 3D finite-difference time-domain (3D-FDTD) electromagnetic simulations were performed to design Q3D-PNAs with the strongest local electric fields (hot spots) at the top or bottom water/Au interfaces for sensitive analysis of cells and small components, respectively. The Q3D-PNAs with the hot spots on top and bottom were placed at the up and down stream of the microfluidic channel, respectively. Each Q3D-PNA pattern was surrounded with cell trapping structures. The microfluidic device was fabricated via soft lithography. We demonstrated that normal (COS-7) and cancer (HpeG2) cells were captured on the Q3D-PNAs and investigated in situ using SERS.

  5. Advantages and challenges of microfluidic cell culture in polydimethylsiloxane devices.

    PubMed

    Halldorsson, Skarphedinn; Lucumi, Edinson; Gómez-Sjöberg, Rafael; Fleming, Ronan M T

    2015-01-15

    Culture of cells using various microfluidic devices is becoming more common within experimental cell biology. At the same time, a technological radiation of microfluidic cell culture device designs is currently in progress. Ultimately, the utility of microfluidic cell culture will be determined by its capacity to permit new insights into cellular function. Especially insights that would otherwise be difficult or impossible to obtain with macroscopic cell culture in traditional polystyrene dishes, flasks or well-plates. Many decades of heuristic optimization have gone into perfecting conventional cell culture devices and protocols. In comparison, even for the most commonly used microfluidic cell culture devices, such as those fabricated from polydimethylsiloxane (PDMS), collective understanding of the differences in cellular behavior between microfluidic and macroscopic culture is still developing. Moving in vitro culture from macroscopic culture to PDMS based devices can come with unforeseen challenges. Changes in device material, surface coating, cell number per unit surface area or per unit media volume may all affect the outcome of otherwise standard protocols. In this review, we outline some of the advantages and challenges that may accompany a transition from macroscopic to microfluidic cell culture. We focus on decisive factors that distinguish macroscopic from microfluidic cell culture to encourage a reconsideration of how macroscopic cell culture principles might apply to microfluidic cell culture.

  6. Microwave welding of polymeric-microfluidic devices

    NASA Astrophysics Data System (ADS)

    Yussuf, A. A.; Sbarski, I.; Hayes, J. P.; Solomon, M.; Tran, N.

    2005-09-01

    This paper describes a novel technique for bonding polymeric-microfluidic devices using microwave energy and a conductive polymer (polyaniline). The bonding is achieved by patterning the polyaniline features at the polymer joint interface by filling of milled microchannels. The absorbed electromagnetic energy is then converted into heat, facilitating the localized microwave bonding of two polymethylmethacrylate (PMMA) substrates. A coaxial open-ended probe was used to study the dielectric properties at 2.45 GHz of the PMMA and polyaniline at a range of temperatures up to 120 °C. The measurements confirm a difference in the dielectric loss factor of the PMMA substrate and the polyaniline, which means that differential heating using microwaves is possible. Microfluidic channels of 200 µm and 400 µm widths were sealed using a microwave power of 300 W for 15 s. The results of the interface evaluations and leak test show that strong bonding is formed at the polymer interface, and there is no fluid leak up to a pressure of 1.18 MPa. Temperature field of microwave heating was found by using direct measurement techniques. A numerical simulation was also conducted by using the finite-element method, which confirmed and validated the experimental results. These results also indicate that no global deformation of the PMMA substrate occurred during the bonding process.

  7. 3D Printing: 3D Printing of Shape Memory Polymers for Flexible Electronic Devices (Adv. Mater. 22/2016).

    PubMed

    Zarek, Matt; Layani, Michael; Cooperstein, Ido; Sachyani, Ela; Cohn, Daniel; Magdassi, Shlomo

    2016-06-01

    On page 4449, D. Cohn, S. Magdassi, and co-workers describe a general and facile method based on 3D printing of methacrylated macromonomers to fabricate shape-memory objects that can be used in flexible and responsive electrical circuits. Such responsive objects can be used in the fabrication of soft robotics, minimal invasive medical devices, sensors, and wearable electronics. The use of 3D printing overcomes the poor processing characteristics of thermosets and enables complex geometries that are not easily accessible by other techniques.

  8. Finite Element Model of Oxygen Transport for the Design of Geometrically Complex Microfluidic Devices Used in Biological Studies

    PubMed Central

    Fraser, Graham M.; Goldman, Daniel; Ellis, Christopher G.

    2016-01-01

    Red blood cells play a crucial role in the local regulation of oxygen supply in the microcirculation through the oxygen dependent release of ATP. Since red blood cells serve as an oxygen sensor for the circulatory system, the dynamics of ATP release determine the effectiveness of red blood cells to relate the oxygen levels to the vessels. Previous work has focused on the feasibility of developing a microfluidic system to measure the dynamics of ATP release. The objective was to determine if a steep oxygen gradient could be developed in the channel to cause a rapid decrease in hemoglobin oxygen saturation in order to measure the corresponding levels of ATP released from the red blood cells. In the present study, oxygen transport simulations were used to optimize the geometric design parameters for a similar system which is easier to fabricate. The system is composed of a microfluidic device stacked on top of a large, gas impermeable flow channel with a hole to allow gas exchange. The microfluidic device is fabricated using soft lithography in polydimethyl-siloxane, an oxygen permeable material. Our objective is twofold: (1) optimize the parameters of our system and (2) develop a method to assess the oxygen distribution in complex 3D microfluidic device geometries. 3D simulations of oxygen transport were performed to simulate oxygen distribution throughout the device. The simulations demonstrate that microfluidic device geometry plays a critical role in molecule exchange, for instance, changing the orientation of the short wide microfluidic channel results in a 97.17% increase in oxygen exchange. Since microfluidic devices have become a more prominent tool in biological studies, understanding the transport of oxygen and other biological molecules in microfluidic devices is critical for maintaining a physiologically relevant environment. We have also demonstrated a method to assess oxygen levels in geometrically complex microfluidic devices. PMID:27829071

  9. Parallel microfluidic synthesis of size-tunable polymeric nanoparticles using 3D flow focusing towards in vivo study

    PubMed Central

    Lim, Jong-Min; Bertrand, Nicolas; Valencia, Pedro M.; Rhee, Minsoung; Langer, Robert; Jon, Sangyong; Farokhzad, Omid C.; Karnik, Rohit

    2014-01-01

    Microfluidic synthesis of nanoparticles (NPs) can enhance the controllability and reproducibility in physicochemical properties of NPs compared to bulk synthesis methods. However, applications of microfluidic synthesis are typically limited to in vitro studies due to low production rates. Herein, we report the parallelization of NP synthesis by 3D hydrodynamic flow focusing (HFF) using a multilayer microfluidic system to enhance the production rate without losing the advantages of reproducibility, controllability, and robustness. Using parallel 3D HFF, polymeric poly(lactide-co-glycolide)-b-polyethyleneglycol (PLGA-PEG) NPs with sizes tunable in the range of 13–150 nm could be synthesized reproducibly with high production rate. As a proof of concept, we used this system to perform in vivo pharmacokinetic and biodistribution study of small (20 nm diameter) PLGA-PEG NPs that are otherwise difficult to synthesize. Microfluidic parallelization thus enables synthesis of NPs with tunable properties with production rates suitable for both in vitro and in vivo studies. PMID:23969105

  10. Probing cell mechanical properties with microfluidic devices

    NASA Astrophysics Data System (ADS)

    Rowat, Amy

    2012-02-01

    Exploiting flow on the micron-scale is emerging as a method to probe cell mechanical properties with 10-1000x advances in throughput over existing technologies. The mechanical properties of cells and the cell nucleus are implicated in a wide range of biological contexts: for example, the ability of white blood cells to deform is central to immune response; and malignant cells show decreased stiffness compared to benign cells. We recently developed a microfluidic device to probe cell and nucleus mechanical properties: cells are forced to deform through a narrow constrictions in response to an applied pressure; flowing cells through a series of constrictions enables us to probe the ability of hundreds of cells to deform and relax during flow. By tuning the constriction width so it is narrower than the width of the cell nucleus, we can specifically probe the effects of nuclear physical properties on whole cell deformability. We show that the nucleus is the rate-limiting step in cell passage: inducing a change in its shape to a multilobed structure results in cells that transit more quickly; increased levels of lamin A, a nuclear protein that is key for nuclear shape and mechanical stability, impairs the passage of cells through constrictions. We are currently developing a new class of microfluidic devices to simultaneously probe the deformability of hundreds of cell samples in parallel. Using the same soft lithography techniques, membranes are fabricated to have well-defined pore distribution, width, length, and tortuosity. We design the membranes to interface with a multiwell plate, enabling simultaneous measurement of hundreds of different samples. Given the wide spectrum of diseases where altered cell and nucleus mechanical properties are implicated, such a platform has great potential, for example, to screen cells based on their mechanical phenotype against a library of drugs.

  11. Flexible microfluidic cloth-based analytical devices using a low-cost wax patterning technique.

    PubMed

    Nilghaz, Azadeh; Wicaksono, Dedy H B; Gustiono, Dwi; Abdul Majid, Fadzilah Adibah; Supriyanto, Eko; Abdul Kadir, Mohammed Rafiq

    2012-01-07

    This paper describes the fabrication of microfluidic cloth-based analytical devices (μCADs) using a simple wax patterning method on cotton cloth for performing colorimetric bioassays. Commercial cotton cloth fabric is proposed as a new inexpensive, lightweight, and flexible platform for fabricating two- (2D) and three-dimensional (3D) microfluidic systems. We demonstrated that the wicking property of the cotton microfluidic channel can be improved by scouring in soda ash (Na(2)CO(3)) solution which will remove the natural surface wax and expose the underlying texture of the cellulose fiber. After this treatment, we fabricated narrow hydrophilic channels with hydrophobic barriers made from patterned wax to define the 2D microfluidic devices. The designed pattern is carved on wax-impregnated paper, and subsequently transferred to attached cotton cloth by heat treatment. To further obtain 3D microfluidic devices having multiple layers of pattern, a single layer of wax patterned cloth can be folded along a predefined folding line and subsequently pressed using mechanical force. All the fabrication steps are simple and low cost since no special equipment is required. Diagnostic application of cloth-based devices is shown by the development of simple devices that wick and distribute microvolumes of simulated body fluids along the hydrophilic channels into reaction zones to react with analytical reagents. Colorimetric detection of bovine serum albumin (BSA) in artificial urine is carried out by direct visual observation of bromophenol blue (BPB) colour change in the reaction zones. Finally, we show the flexibility of the novel microfluidic platform by conducting a similar reaction in a bent pinned μCAD.

  12. Synthesis of a 3D graphite microball using a microfluidic droplet generator and its polymer composite with core-shell structure.

    PubMed

    Han, Dong Ju; Jung, Jae Hwan; Choi, Jong Seob; Kim, Yong Tae; Seo, Tae Seok

    2013-10-21

    Spherical 3D graphite microballs (3D GMs) and their nanohybrids (3D GM-Fe3O4 nanoparticles) were synthesized by using a microfluidic droplet generator and a thermal evaporation-induced capillary compression method. Using the 3D GM-Fe3O4 nanoparticle as a support for polymerization, 3D GM-polypyrrole composites were produced with a unique core-shell structure.

  13. Rare Cell Capture in Microfluidic Devices

    PubMed Central

    Pratt, Erica D.; Huang, Chao; Hawkins, Benjamin G.; Gleghorn, Jason P.; Kirby, Brian J.

    2010-01-01

    This article reviews existing methods for the isolation, fractionation, or capture of rare cells in microfluidic devices. Rare cell capture devices face the challenge of maintaining the efficiency standard of traditional bulk separation methods such as flow cytometers and immunomagnetic separators while requiring very high purity of the target cell population, which is typically already at very low starting concentrations. Two major classifications of rare cell capture approaches are covered: (1) non-electrokinetic methods (e.g., immobilization via antibody or aptamer chemistry, size-based sorting, and sheath flow and streamline sorting) are discussed for applications using blood cells, cancer cells, and other mammalian cells, and (2) electrokinetic (primarily dielectrophoretic) methods using both electrode-based and insulative geometries are presented with a view towards pathogen detection, blood fractionation, and cancer cell isolation. The included methods were evaluated based on performance criteria including cell type modeled and used, number of steps/stages, cell viability, and enrichment, efficiency, and/or purity. Major areas for improvement are increasing viability and capture efficiency/purity of directly processed biological samples, as a majority of current studies only process spiked cell lines or pre-diluted/lysed samples. Despite these current challenges, multiple advances have been made in the development of devices for rare cell capture and the subsequent elucidation of new biological phenomena; this article serves to highlight this progress as well as the electrokinetic and non-electrokinetic methods that can potentially be combined to improve performance in future studies. PMID:21532971

  14. Vascular smooth muscle cell culture in microfluidic devices

    PubMed Central

    Wei, Y. C.; Chen, F.; Zhang, T.; Chen, D. Y.; Jia, X.; Wang, J. B.; Guo, W.; Chen, J.

    2014-01-01

    This paper presents a microfluidic device enabling culture of vascular smooth muscle cells (VSMCs) where extracellular matrix coating, VSMC seeding, culture, and immunostaining are demonstrated in a tubing-free manner. By optimizing droplet volume differences between inlets and outlets of micro channels, VSMCs were evenly seeded into microfluidic devices. Furthermore, the effects of extracellular matrix (e.g., collagen, poly-l-Lysine (PLL), and fibronectin) on VSMC proliferation and phenotype expression were explored. As a platform technology, this microfluidic device may function as a new VSMC culture model enabling VSMC studies. PMID:25379109

  15. Recent microfluidic devices for studying gamete and embryo biomechanics.

    PubMed

    Lai, David; Takayama, Shuichi; Smith, Gary D

    2015-06-25

    The technical challenges of biomechanic research such as single cell analysis at a high monetary cost, labor, and time for just a small number of measurements is a good match to the strengths of microfluidic devices. New scientific discoveries in the fertilization and embryo development process, of which biomechanics is a major subset of interest, is crucial to fuel the continual improvement of clinical practice in assisted reproduction. The following review will highlight some recent microfluidic devices tailored for gamete and embryo biomechanics where biomimicry arises as a major theme of microfluidic device design and function, and the application of fundamental biomechanic principles are used to improve outcomes of cryopreservation.

  16. A facile route to the synthesis of monodisperse nanoscale liposomes using 3D microfluidic hydrodynamic focusing in a concentric capillary array.

    PubMed

    Hood, Renee R; DeVoe, Don L; Atencia, Javier; Vreeland, Wyatt N; Omiatek, Donna M

    2014-07-21

    A novel microscale device has been developed to enable the one-step continuous flow assembly of monodisperse nanoscale liposomes using three-dimensional microfluidic hydrodynamic focusing (3D-MHF) in a concentric capillary array. The 3D-MHF flow technique displays patent advantages over conventional methods for nanoscale liposome manufacture (i.e., bulk-scale alcohol injection and/or sonication) through the on-demand synthesis of consistently uniform liposomes without the need for post-processing strategies. Liposomes produced by the 3D-MHF device are of tunable size, have a factor of two improvement in polydispersity, and a production rate that is four orders of magnitude higher than previous MHF methods, which can be attributed to entirely radially symmetric diffusion of alcohol-solvated lipid into an aqueous flow stream. Moreover, the 3D-MHF platform is simple to construct from low-cost, commercially-available components, which obviates the need for advanced microfabrication strategies necessitated by previous MHF nanoparticle synthesis platforms.

  17. Microfluidic Devices for Studying Biomolecular Interactions

    NASA Technical Reports Server (NTRS)

    Wilson, Wilbur W.; Garcia, Carlos d.; Henry, Charles S.

    2006-01-01

    Microfluidic devices for monitoring biomolecular interactions have been invented. These devices are basically highly miniaturized liquid-chromatography columns. They are intended to be prototypes of miniature analytical devices of the laboratory on a chip type that could be fabricated rapidly and inexpensively and that, because of their small sizes, would yield analytical results from very small amounts of expensive analytes (typically, proteins). Other advantages to be gained by this scaling down of liquid-chromatography columns may include increases in resolution and speed, decreases in the consumption of reagents, and the possibility of performing multiple simultaneous and highly integrated analyses by use of multiple devices of this type, each possibly containing multiple parallel analytical microchannels. The principle of operation is the same as that of a macroscopic liquid-chromatography column: The column is a channel packed with particles, upon which are immobilized molecules of the protein of interest (or one of the proteins of interest if there are more than one). Starting at a known time, a solution or suspension containing molecules of the protein or other substance of interest is pumped into the channel at its inlet. The liquid emerging from the outlet of the channel is monitored to detect the molecules of the dissolved or suspended substance(s). The time that it takes these molecules to flow from the inlet to the outlet is a measure of the degree of interaction between the immobilized and the dissolved or suspended molecules. Depending on the precise natures of the molecules, this measure can be used for diverse purposes: examples include screening for solution conditions that favor crystallization of proteins, screening for interactions between drugs and proteins, and determining the functions of biomolecules.

  18. Diffusion phenomena of cells and biomolecules in microfluidic devices

    PubMed Central

    Yildiz-Ozturk, Ece; Yesil-Celiktas, Ozlem

    2015-01-01

    Biomicrofluidics is an emerging field at the cross roads of microfluidics and life sciences which requires intensive research efforts in terms of introducing appropriate designs, production techniques, and analysis. The ultimate goal is to deliver innovative and cost-effective microfluidic devices to biotech, biomedical, and pharmaceutical industries. Therefore, creating an in-depth understanding of the transport phenomena of cells and biomolecules becomes vital and concurrently poses significant challenges. The present article outlines the recent advancements in diffusion phenomena of cells and biomolecules by highlighting transport principles from an engineering perspective, cell responses in microfluidic devices with emphases on diffusion- and flow-based microfluidic gradient platforms, macroscopic and microscopic approaches for investigating the diffusion phenomena of biomolecules, microfluidic platforms for the delivery of these molecules, as well as the state of the art in biological applications of mammalian cell responses and diffusion of biomolecules. PMID:26180576

  19. Diffusion phenomena of cells and biomolecules in microfluidic devices.

    PubMed

    Yildiz-Ozturk, Ece; Yesil-Celiktas, Ozlem

    2015-09-01

    Biomicrofluidics is an emerging field at the cross roads of microfluidics and life sciences which requires intensive research efforts in terms of introducing appropriate designs, production techniques, and analysis. The ultimate goal is to deliver innovative and cost-effective microfluidic devices to biotech, biomedical, and pharmaceutical industries. Therefore, creating an in-depth understanding of the transport phenomena of cells and biomolecules becomes vital and concurrently poses significant challenges. The present article outlines the recent advancements in diffusion phenomena of cells and biomolecules by highlighting transport principles from an engineering perspective, cell responses in microfluidic devices with emphases on diffusion- and flow-based microfluidic gradient platforms, macroscopic and microscopic approaches for investigating the diffusion phenomena of biomolecules, microfluidic platforms for the delivery of these molecules, as well as the state of the art in biological applications of mammalian cell responses and diffusion of biomolecules.

  20. Clear Castable Polyurethane Elastomer for Fabrication of Microfluidic Devices

    PubMed Central

    Domansky, Karel; Leslie, Daniel C.; McKinney, James; Fraser, Jacob P.; Sliz, Josiah D.; Hamkins-Indik, Tiama; Hamilton, Geraldine A.; Bahinski, Anthony; Ingber, Donald E.

    2013-01-01

    Polydimethylsiloxane (PDMS) has numerous desirable properties for fabricating microfluidic devices, including optical transparency, flexibility, biocompatibility, and fabrication by casting; however, partitioning of small hydrophobic molecules into the bulk of PDMS hinders industrial acceptance of PDMS microfluidic devices for chemical processing and drug development applications. Here we describe an attractive alternative material that is similar to PDMS in terms of optical transparency, flexibility and castability, but that is also resistant to absorption of small hydrophobic molecules. PMID:23954953

  1. Use of vacuum bagging for fabricating thermoplastic microfluidic devices.

    PubMed

    Cassano, Christopher L; Simon, Andrew J; Liu, Wei; Fredrickson, Carl; Fan, Z Hugh

    2015-01-07

    In this work we present a novel thermal bonding method for thermoplastic microfluidic devices. This simple method employs a modified vacuum bagging technique, a concept borrowed from the aerospace industry, to produce conventional thick substrate microfluidic devices, as well as multi-layer film devices. The bonds produced using this method are superior to those obtained using conventional thermal bonding methods, including thermal lamination, and are capable of sustaining burst pressures in excess of 550 kPa. To illustrate the utility of this method, thick substrate devices were produced, as well as a six-layer film device that incorporated several complex features.

  2. Real-time PCR in microfluidic devices

    NASA Astrophysics Data System (ADS)

    Becker, Holger; Hlawatsch, Nadine; Klemm, Richard; Moche, Christian; Hansen-Hagge, Thomas; Gärtner, Claudia

    2014-03-01

    A central method in a standard biochemical laboratory is represented by the polymerase chain reaction (PCR), therefore many attempts have been performed so far to implement this technique in lab-on-a-chip (LOC) devices. PCR is an ideal candidate for miniaturization because of a reduction of assay time and decreased costs for expensive bio-chemicals. In case of the "classical" PCR, detection is done by identification of DNA fragments electrophoretically separated in agarose gels. This method is meanwhile frequently replaced by the so-called Real-Time-PCR because here the exponential increase of amplificates can be observed directly by measurement of DNA interacting fluorescent dyes. Two main methods for on-chip PCRs are available: traditional "batch" PCR in chambers on a chip using thermal cycling, requiring about 30 minutes for a typical PCR protocol and continuous-flow PCR, where the liquid is guided over stationary temperature zones. In the latter case, the PCR protocol can be as fast as 5 minutes. In the presented work, a proof of concept is demonstrated for a real-time-detection of PCR products in microfluidic systems.

  3. Micro-scale and microfluidic devices for neurobiology.

    PubMed

    Taylor, Anne M; Jeon, Noo Li

    2010-10-01

    The precise spatial and temporal control afforded by microfluidic devices make them uniquely suited as experimental tools for cellular neuroscience. Micro-structures have been developed to direct the placement of cells and small organisms within a device. Microfluidics can precisely define pharmacological microenvironments, mimicking conditions found in vivo with the advantage of defined parameters which are usually difficult to control and manipulate in vivo. These devices are compatible with high-resolution microscopy, are simple to assemble, and are reproducible. In this review we will focus on microfluidic devices that have recently been developed for small, whole organisms such as C. elegans and dissociated cultured neurons. These devices have improved control over the placement of cells or organisms and allowed unprecedented experimental access, enabling novel investigations in neurobiology.

  4. Design of 3D isotropic metamaterial device using smart transformation optics.

    PubMed

    Shin, Dongheok; Kim, Junhyun; Yoo, Do-Sik; Kim, Kyoungsik

    2015-08-24

    We report here a design method for a 3 dimensional (3D) isotropic transformation optical device using smart transformation optics. Inspired by solid mechanics, smart transformation optics regards a transformation optical medium as an elastic solid and deformations as coordinate transformations. Further developing from our previous work on 2D smart transformation optics, we introduce a method of 3D smart transformation optics to design 3D transformation optical devices by maintaining isotropic materials properties for all types of polarizations imposing free or nearly free boundary conditions. Due to the material isotropy, it is possible to fabricate such devices with structural metamaterials made purely of common dielectric materials. In conclusion, the practical importance of the method reported here lies in the fact that it enables us to fabricate, without difficulty, arbitrarily shaped 3D devices with existing 3D printing technology.

  5. Origami microfluidic paper-analytical-devices (omPAD) for sensing and diagnostics.

    PubMed

    Punjiya, Meera; Chung Hee Moon; Yu Chen; Sonkusale, Sameer

    2016-08-01

    Recent research activities in the area of low-cost sensing and diagnostics that are realized on cellulosic paper substrate are presented. First a three-dimensional origami paper-based analytical device (omPAD) with multiple electrochemical sensors, an integrated sample reservoir and tight integration with a custom CMOS potentiostat is presented. Second, an optical sensor array with built-in microfluidic channel for sample delivery is presented. The sensors are fabricated using a combination of wax printing and screen-printing using a solution based approach in ambient conditions without the need for expensive fabrication equipment or a cleanroom. Readout is based on using existing consumer grade electronic devices like flatbed scanner (for optical sensor) or custom designed CMOS potentiostat (for electrochemical sensors). Together the 3D paper-based analytical device with integrated sensor, microfluidics and portable readout instrumentation demonstrates a low-cost, self-contained system suitable for sensing and point-of-care diagnostics.

  6. Method for making electro-fluidic connections in microfluidic devices

    DOEpatents

    Frye-Mason, Gregory C.; Martinez, David; Manginell, Ronald P.; Heller, Edwin J.; Chanchani, Rajen

    2004-08-10

    A method for forming electro-fluidic interconnections in microfluidic devices comprises forming an electrical connection between matching bond pads on a die containing an active electrical element and a microfluidic substrate and forming a fluidic seal ring that circumscribes the active electrical element and a fluidic feedthrough. Preferably, the electrical connection and the seal ring are formed in a single bonding step. The simple method is particularly useful for chemical microanalytical systems wherein a plurality of microanalytical components, such as a chemical preconcentrator, a gas chromatography column, and a surface acoustic wave detector, are fluidically interconnected on a hybrid microfluidic substrate having electrical connection to external support electronics.

  7. Fabrication and characterization of gels with integrated channels using 3D printing with microfluidic nozzle for tissue engineering applications.

    PubMed

    Attalla, R; Ling, C; Selvaganapathy, P

    2016-02-01

    The lack of a simple and effective method to integrate vascular network with engineered scaffolds and tissue constructs remains one of the biggest challenges in true 3D tissue engineering. Here, we detail the use of a commercially available, low-cost, open-source 3D printer modified with a microfluidic print-head in order to develop a method for the generation of instantly perfusable vascular network integrated with gel scaffolds seeded with cells. The print-head features an integrated coaxial nozzle that allows the fabrication of hollow, calcium-polymerized alginate tubes that can be easily patterned using 3D printing techniques. The diameter of the hollow channel can be precisely controlled and varied between 500 μm - 2 mm by changing applied flow rates or print-head speed. These channels are integrated into gel layers with a thickness of 800 μm - 2.5 mm. The structural rigidity of these constructs allows the fabrication of multi-layered structures without causing the collapse of hollow channels in lower layers. The 3D printing method was fully characterized at a range of operating speeds (0-40 m/min) and corresponding flow rates (1-30 mL/min) were identified to produce precise definition. This microfluidic design also allows the incorporation of a wide range of scaffold materials as well as biological constituents such as cells, growth factors, and ECM material. Media perfusion of the channels causes a significant viability increase in the bulk of cell-laden structures over the long-term. With this setup, gel constructs with embedded arrays of hollow channels can be created and used as a potential substitute for blood vessel networks.

  8. Cell-Based Biosensors: Electrical Sensing in Microfluidic Devices

    PubMed Central

    Kiilerich-Pedersen, Katrine; Rozlosnik, Noemi

    2012-01-01

    Cell-based biosensors provide new horizons for medical diagnostics by adopting complex recognition elements such as mammalian cells in microfluidic devices that are simple, cost efficient and disposable. This combination renders possible a new range of applications in the fields of diagnostics and personalized medicine. The review looks at the most recent developments in cell-based biosensing microfluidic systems with electrical and electrochemical transduction, and relevance to medical diagnostics. PMID:26859401

  9. High-Throughput Microfluidic Platform for 3D Cultures of Mesenchymal Stem Cells, Towards Engineering Developmental Processes

    PubMed Central

    Occhetta, Paola; Centola, Matteo; Tonnarelli, Beatrice; Redaelli, Alberto; Martin, Ivan; Rasponi, Marco

    2015-01-01

    The development of in vitro models to screen the effect of different concentrations, combinations and temporal sequences of morpho-regulatory factors on stem/progenitor cells is crucial to investigate and possibly recapitulate developmental processes with adult cells. Here, we designed and validated a microfluidic platform to (i) allow cellular condensation, (ii) culture 3D micromasses of human bone marrow-derived mesenchymal stromal cells (hBM-MSCs) under continuous flow perfusion, and (ii) deliver defined concentrations of morphogens to specific culture units. Condensation of hBM-MSCs was obtained within 3 hours, generating micromasses in uniform sizes (56.2 ± 3.9 μm). As compared to traditional macromass pellet cultures, exposure to morphogens involved in the first phases of embryonic limb development (i.e. Wnt and FGF pathways) yielded more uniform cell response throughout the 3D structures of perfused micromasses (PMMs), and a 34-fold higher percentage of proliferating cells at day 7. The use of a logarithmic serial dilution generator allowed to identify an unexpected concentration of TGFβ3 (0.1 ng/ml) permissive to hBM-MSCs proliferation and inductive to chondrogenesis. This proof-of-principle study supports the described microfluidic system as a tool to investigate processes involved in mesenchymal progenitor cells differentiation, towards a ‘developmental engineering’ approach for skeletal tissue regeneration. PMID:25983217

  10. Holographic microscopy and microfluidics platform for measuring wall stress and 3D flow over surfaces textured by micro-pillars

    PubMed Central

    Bocanegra Evans, Humberto; Gorumlu, Serdar; Aksak, Burak; Castillo, Luciano; Sheng, Jian

    2016-01-01

    Understanding how fluid flow interacts with micro-textured surfaces is crucial for a broad range of key biological processes and engineering applications including particle dispersion, pathogenic infections, and drag manipulation by surface topology. We use high-speed digital holographic microscopy (DHM) in combination with a correlation based de-noising algorithm to overcome the optical interference generated by surface roughness and to capture a large number of 3D particle trajectories in a microfluidic channel with one surface patterned with micropillars. It allows us to obtain a 3D ensembled velocity field with an uncertainty of 0.06% and 2D wall shear stress distribution at the resolution of ~65 μPa. Contrary to laminar flow in most microfluidics, we find that the flow is three-dimensional and complex for the textured microchannel. While the micropillars affect the velocity flow field locally, their presence is felt globally in terms of wall shear stresses at the channel walls. These findings imply that micro-scale mixing and wall stress sensing/manipulation can be achieved through hydro-dynamically smooth but topologically rough micropillars. PMID:27353632

  11. Integrated microfluidic test-bed for energy conversion devices.

    PubMed

    Modestino, Miguel A; Diaz-Botia, Camilo A; Haussener, Sophia; Gomez-Sjoberg, Rafael; Ager, Joel W; Segalman, Rachel A

    2013-05-21

    Energy conversion devices require the parallel functionality of a variety of components for efficient operation. We present a versatile microfluidic test-bed for facile testing of integrated catalysis and mass transport components for energy conversion via water electrolysis. This system can be readily extended to solar-fuels generators and fuel-cell devices.

  12. Oxygen Levels in Thermoplastic Microfluidic Devices during Cell Culture

    PubMed Central

    Ochs, Christopher J.; Kasuya, Junichi; Pavesi, Andrea; Kamm, Roger D.

    2015-01-01

    We developed a computational model to predict oxygen levels in microfluidic plastic devices during cell culture. This model is based on experimental evaluation of oxygen levels. Conditions are determined that provide adequate oxygen supply to two cell types, hepatocytes and endothelial cells, either by diffusion through the plastic device, or by supplying a low flow rate of medium. PMID:24302467

  13. Oxygen levels in thermoplastic microfluidic devices during cell culture.

    PubMed

    Ochs, Christopher J; Kasuya, Junichi; Pavesi, Andrea; Kamm, Roger D

    2014-02-07

    We developed a computational model to predict oxygen levels in microfluidic plastic devices during cell culture. This model is based on experimental evaluation of oxygen levels. Conditions are determined that provide adequate oxygen supply to two cell types, hepatocytes and endothelial cells, either by diffusion through the plastic device, or by supplying a low flow rate of medium.

  14. High fidelity digital inline holographic PTV for 3D flow measurements: from microfluidics to wall-bounded turbulence

    NASA Astrophysics Data System (ADS)

    Hong, Jiarong; Toloui, Mostafa; Mallery, Kevin

    2016-11-01

    Three-dimensional PIV and PTV provides the most comprehensive flow information for unraveling the physical phenomena in a wide range of fluid problems, from microfluidics to wall-bounded turbulent flows. Compared with other commercialized 3D PIV techniques, such as tomographic PIV and defocusing PIV, the digital inline holographic PTV (namely DIH-PTV) provides 3D flow measurement solution with high spatial resolution, low cost optical setup, and easy alignment and calibration. Despite these advantages, DIH-PTV suffers from major limitations including poor longitudinal resolution, human intervention (i.e. requirement for manually determined tuning parameters during tracer field reconstruction and extraction), limited tracer concentration, small sampling volume and expensive computations, limiting its broad use for 3D flow measurements. Here we will report our latest work on improving DIH-PTV method through an integration of deconvolution algorithm, iterative removal method and GPU computation to overcome some of abovementioned limitations. We will also present the application of our DIH-PTV for measurements in the following sample cases: (i) flows in bio-filmed microchannel with 50-60 μm vector spacing within sampling volumes of 1 mm (streamwise) x 1 mm (wall-normal) x 1 mm (spanwise); (ii) turbulent flows over smooth and rough surfaces (1.1 mm vector spacing within 15 mm x 50 mm x 15 mm); (iii) 3D distribution and kinematics of inertial particles in turbulent air duct flow.

  15. Micro Electromechanical Systems (MEMS) Based Microfluidic Devices for Biomedical Applications.

    PubMed

    Ashraf, Muhammad Waseem; Tayyaba, Shahzadi; Afzulpurkar, Nitin

    2011-01-01

    Micro Electromechanical Systems (MEMS) based microfluidic devices have gained popularity in biomedicine field over the last few years. In this paper, a comprehensive overview of microfluidic devices such as micropumps and microneedles has been presented for biomedical applications. The aim of this paper is to present the major features and issues related to micropumps and microneedles, e.g., working principles, actuation methods, fabrication techniques, construction, performance parameters, failure analysis, testing, safety issues, applications, commercialization issues and future prospects. Based on the actuation mechanisms, the micropumps are classified into two main types, i.e., mechanical and non-mechanical micropumps. Microneedles can be categorized according to their structure, fabrication process, material, overall shape, tip shape, size, array density and application. The presented literature review on micropumps and microneedles will provide comprehensive information for researchers working on design and development of microfluidic devices for biomedical applications.

  16. Micro Electromechanical Systems (MEMS) Based Microfluidic Devices for Biomedical Applications

    PubMed Central

    Ashraf, Muhammad Waseem; Tayyaba, Shahzadi; Afzulpurkar, Nitin

    2011-01-01

    Micro Electromechanical Systems (MEMS) based microfluidic devices have gained popularity in biomedicine field over the last few years. In this paper, a comprehensive overview of microfluidic devices such as micropumps and microneedles has been presented for biomedical applications. The aim of this paper is to present the major features and issues related to micropumps and microneedles, e.g., working principles, actuation methods, fabrication techniques, construction, performance parameters, failure analysis, testing, safety issues, applications, commercialization issues and future prospects. Based on the actuation mechanisms, the micropumps are classified into two main types, i.e., mechanical and non-mechanical micropumps. Microneedles can be categorized according to their structure, fabrication process, material, overall shape, tip shape, size, array density and application. The presented literature review on micropumps and microneedles will provide comprehensive information for researchers working on design and development of microfluidic devices for biomedical applications. PMID:21747700

  17. Towards fabrication of 3D printed medical devices to prevent biofilm formation.

    PubMed

    Sandler, Niklas; Salmela, Ida; Fallarero, Adyary; Rosling, Ari; Khajeheian, Mohammad; Kolakovic, Ruzica; Genina, Natalja; Nyman, Johan; Vuorela, Pia

    2014-01-01

    The use of three-dimensional (3D) printing technologies is transforming the way that materials are turned into functional devices. We demonstrate in the current study the incorporation of anti-microbial nitrofurantoin in a polymer carrier material and subsequent 3D printing of a model structure, which resulted in an inhibition of biofilm colonization. The approach taken is very promising and can open up new avenues to manufacture functional medical devices in the future.

  18. Control and automation of multilayered integrated microfluidic device fabrication.

    PubMed

    Kipper, Sarit; Frolov, Ludmila; Guy, Ortal; Pellach, Michal; Glick, Yair; Malichi, Asaf; Knisbacher, Binyamin A; Barbiro-Michaely, Efrat; Avrahami, Dorit; Yavets-Chen, Yehuda; Levanon, Erez Y; Gerber, Doron

    2017-01-31

    Integrated microfluidics is a sophisticated three-dimensional (multi layer) solution for high complexity serial or parallel processes. Fabrication of integrated microfluidic devices requires soft lithography and the stacking of thin-patterned PDMS layers. Precise layer alignment and bonding is crucial. There are no previously reported standards for alignment of the layers, which is mostly performed using uncontrolled processes with very low alignment success. As a result, integrated microfluidics is mostly used in academia rather than in the many potential industrial applications. We have designed and manufactured a semiautomatic Microfluidic Device Assembly System (μDAS) for full device production. μDAS comprises an electrooptic mechanical system consisting of four main parts: optical system, smart media holder (for PDMS), a micropositioning xyzθ system and a macropositioning XY mechanism. The use of the μDAS yielded valuable information regarding PDMS as the material for device fabrication, revealed previously unidentified errors, and enabled optimization of a robust fabrication process. In addition, we have demonstrated the utilization of the μDAS technology for fabrication of a complex 3 layered device with over 12 000 micromechanical valves and an array of 64 × 64 DNA spots on a glass substrate with high yield and high accuracy. We increased fabrication yield from 25% to about 85% with an average layer alignment error of just ∼4 μm. It also increased our protein expression yields from 80% to over 90%, allowing us to investigate more proteins per experiment. The μDAS has great potential to become a valuable tool for both advancing integrated microfluidics in academia and producing and applying microfluidic devices in the industry.

  19. Regulatory Considerations in the Design and Manufacturing of Implantable 3D-Printed Medical Devices

    PubMed Central

    Morrison, Robert J.; Kashlan, Khaled N.; Flanangan, Colleen L.; Wright, Jeanne K.; Green, Glenn E.; Hollister, Scott J.; Weatherwax, Kevin J.

    2015-01-01

    Three-dimensional (3D) printing, or additive manufacturing, technology has rapidly penetrated the medical device industry over the past several years, and innovative groups have harnessed it to create devices with unique composition, structure, and customizability. These distinctive capabilities afforded by 3D printing have introduced new regulatory challenges. The customizability of 3D-printed devices introduces new complexities when drafting a design control model for FDA consideration of market approval. The customizability and unique build processes of 3D-printed medical devices pose unique challenges in meeting regulatory standards related to the manufacturing quality assurance. Consistent material powder properties and optimal printing parameters such as build orientation and laser power must be addressed and communicated to the FDA to ensure a quality build. Post-printing considerations unique to 3D-printed devices, such as cleaning, finishing and sterilization are also discussed. In this manuscript we illustrate how such regulatory hurdles can be navigated by discussing our experience with our group’s 3D-printed bioresorbable implantable device. PMID:26243449

  20. Regulatory Considerations in the Design and Manufacturing of Implantable 3D-Printed Medical Devices.

    PubMed

    Morrison, Robert J; Kashlan, Khaled N; Flanangan, Colleen L; Wright, Jeanne K; Green, Glenn E; Hollister, Scott J; Weatherwax, Kevin J

    2015-10-01

    Three-dimensional (3D) printing, or additive manufacturing, technology has rapidly penetrated the medical device industry over the past several years, and innovative groups have harnessed it to create devices with unique composition, structure, and customizability. These distinctive capabilities afforded by 3D printing have introduced new regulatory challenges. The customizability of 3D-printed devices introduces new complexities when drafting a design control model for FDA consideration of market approval. The customizability and unique build processes of 3D-printed medical devices pose unique challenges in meeting regulatory standards related to the manufacturing quality assurance. Consistent material powder properties and optimal printing parameters such as build orientation and laser power must be addressed and communicated to the FDA to ensure a quality build. Postprinting considerations unique to 3D-printed devices, such as cleaning, finishing and sterilization are also discussed. In this manuscript we illustrate how such regulatory hurdles can be navigated by discussing our experience with our group's 3D-printed bioresorbable implantable device.

  1. Metering and routing of liquid quanta in microfluidic devices

    NASA Astrophysics Data System (ADS)

    Cole, Matthew Charles

    Microchemical systems have become increasingly more intricate and complex, and have been used in a wide variety of interesting applications in recent years. However, further advancement of these devices is currently limited by their lack of any significant detection, routing, and scheduling capabilities for the materials moving throughout them. This limited level of control becomes a significant issue when scaling simple, single-channel microfluidic devices to large arrays. The overall goal of this thesis, therefore, is to create and improve several fundamental microfluidic capabilities, including droplet generation, routing, sensing, and scheduling. The integration of these components into larger arrays will also be demonstrated, and will provide a significant step towards more robust and capable heterogeneous microchemical systems. This thesis describes the development of a number of microfluidic handling techniques, including; (i) the detection of individual liquid droplets using electrical position sensors; (ii) the generation and control over the three major microfluidic segmented laminar flow regimes; (iii) the creation of discrete liquid quanta by entirely chip-driven techniques, including on-chip valves and pumps; (iv) the driving around of those resulting liquid quanta; and (v) the combining of multiple microfluidic peristaltic pumps into a multiplexed arrangement, allowing for many pumps to be controlled by a limited number of external pneumatic connections. These techniques were integrated to create an overall microfluidic droplet routing platform, capable of generating and directing individual liquid elements to arbitrary locations within a large microfluidic A I array, using completely chip-driven actuations. As a testbed application, the microfluidic capabilities developed here were utilized in conjunction with an electrohydrodynamic-jet printing process to generate a high resolution heterogeneous printhead.

  2. A Microfluidic Flow-switching Device Powered by Vorticella Stalk

    NASA Astrophysics Data System (ADS)

    Nagai, M.; Tanizaki, K.; Hayasaka, Y.; Kawashima, T.; Shibata, T.

    2013-04-01

    Bioactuators are an attractive alternative for mechanical components of MEMS devices. We propose a flow-switching device active to calcium ion based on bioactuator of Vorticella. We develop a fundamental procedure for immobilization of Vorticella in a microfluidic chamber and control of contraction and extension of stalks. Cells were trapped in microfluidic chambers and allowed to adhere. After treatment of cells, stalks were contracted and extended by injecting solutions. Flow speed changed during the motion. Our developed method presents a strategy for application of bioactuator.

  3. Microfluidic devices for DNA sequencing: sample preparation and electrophoretic analysis.

    PubMed

    Paegel, Brian M; Blazej, Robert G; Mathies, Richard A

    2003-02-01

    Modern DNA sequencing 'factories' have revolutionized biology by completing the human genome sequence, but in the race to completion we are left with inefficient, cumbersome, and costly macroscale processes and supporting facilities. During the same period, microfabricated DNA sequencing, sample processing and analysis devices have advanced rapidly toward the goal of a 'sequencing lab-on-a-chip'. Integrated microfluidic processing dramatically reduces analysis time and reagent consumption, and eliminates costly and unreliable macroscale robotics and laboratory apparatus. A microfabricated device for high-throughput DNA sequencing that couples clone isolation, template amplification, Sanger extension, purification, and electrophoretic analysis in a single microfluidic circuit is now attainable.

  4. Numerical Optimization Strategy for Determining 3D Flow Fields in Microfluidics

    NASA Astrophysics Data System (ADS)

    Eden, Alex; Sigurdson, Marin; Mezic, Igor; Meinhart, Carl

    2015-11-01

    We present a hybrid experimental-numerical method for generating 3D flow fields from 2D PIV experimental data. An optimization algorithm is applied to a theory-based simulation of an alternating current electrothermal (ACET) micromixer in conjunction with 2D PIV data to generate an improved representation of 3D steady state flow conditions. These results can be used to investigate mixing phenomena. Experimental conditions were simulated using COMSOL Multiphysics to solve the temperature and velocity fields, as well as the quasi-static electric fields. The governing equations were based on a theoretical model for ac electrothermal flows. A Nelder-Mead optimization algorithm was used to achieve a better fit by minimizing the error between 2D PIV experimental velocity data and numerical simulation results at the measurement plane. By applying this hybrid method, the normalized RMS velocity error between the simulation and experimental results was reduced by more than an order of magnitude. The optimization algorithm altered 3D fluid circulation patterns considerably, providing a more accurate representation of the 3D experimental flow field. This method can be generalized to a wide variety of flow problems. This research was supported by the Institute for Collaborative Biotechnologies through grant W911NF-09-0001 from the U.S. Army Research Office.

  5. Fabrication of polyimide based microfluidic channels for biosensor devices

    NASA Astrophysics Data System (ADS)

    Zulfiqar, Azeem; Pfreundt, Andrea; Svendsen, Winnie Edith; Dimaki, Maria

    2015-03-01

    The ever-increasing complexity of the fabrication process of Point-of-care (POC) devices, due to high demand of functional versatility, compact size and ease-of-use, emphasizes the need of multifunctional materials that can be used to simplify this process. Polymers, currently in use for the fabrication of the often needed microfluidic channels, have limitations in terms of their physicochemical properties. Therefore, the use of a multipurpose biocompatible material with better resistance to the chemical, thermal and electrical environment, along with capability of forming closed channel microfluidics is inevitable. This paper demonstrates a novel technique of fabricating microfluidic devices using polyimide (PI) which fulfills the aforementioned properties criteria. A fabrication process to pattern microfluidic channels, using partially cured PI, has been developed by using a dry etching method. The etching parameters are optimized and compared to those used for fully cured PI. Moreover, the formation of closed microfluidic channel on wafer level by bonding two partially cured PI layers or a partially cured PI to glass with high bond strength has been demonstrated. The reproducibility in uniformity of PI is also compared to the most commonly used SU8 polymer, which is a near UV sensitive epoxy resin. The potential applications of PI processing are POC and biosensor devices integrated with microelectronics.

  6. Microfluidic Devices for Forensic DNA Analysis: A Review

    PubMed Central

    Bruijns, Brigitte; van Asten, Arian; Tiggelaar, Roald; Gardeniers, Han

    2016-01-01

    Microfluidic devices may offer various advantages for forensic DNA analysis, such as reduced risk of contamination, shorter analysis time and direct application at the crime scene. Microfluidic chip technology has already proven to be functional and effective within medical applications, such as for point-of-care use. In the forensic field, one may expect microfluidic technology to become particularly relevant for the analysis of biological traces containing human DNA. This would require a number of consecutive steps, including sample work up, DNA amplification and detection, as well as secure storage of the sample. This article provides an extensive overview of microfluidic devices for cell lysis, DNA extraction and purification, DNA amplification and detection and analysis techniques for DNA. Topics to be discussed are polymerase chain reaction (PCR) on-chip, digital PCR (dPCR), isothermal amplification on-chip, chip materials, integrated devices and commercially available techniques. A critical overview of the opportunities and challenges of the use of chips is discussed, and developments made in forensic DNA analysis over the past 10–20 years with microfluidic systems are described. Areas in which further research is needed are indicated in a future outlook. PMID:27527231

  7. Microfluidic Devices for Forensic DNA Analysis: A Review.

    PubMed

    Bruijns, Brigitte; van Asten, Arian; Tiggelaar, Roald; Gardeniers, Han

    2016-08-05

    Microfluidic devices may offer various advantages for forensic DNA analysis, such as reduced risk of contamination, shorter analysis time and direct application at the crime scene. Microfluidic chip technology has already proven to be functional and effective within medical applications, such as for point-of-care use. In the forensic field, one may expect microfluidic technology to become particularly relevant for the analysis of biological traces containing human DNA. This would require a number of consecutive steps, including sample work up, DNA amplification and detection, as well as secure storage of the sample. This article provides an extensive overview of microfluidic devices for cell lysis, DNA extraction and purification, DNA amplification and detection and analysis techniques for DNA. Topics to be discussed are polymerase chain reaction (PCR) on-chip, digital PCR (dPCR), isothermal amplification on-chip, chip materials, integrated devices and commercially available techniques. A critical overview of the opportunities and challenges of the use of chips is discussed, and developments made in forensic DNA analysis over the past 10-20 years with microfluidic systems are described. Areas in which further research is needed are indicated in a future outlook.

  8. Microfluidic Fabrication of Bio-Inspired Microfibers with Controllable Magnetic Spindle-Knots for 3D Assembly and Water Collection.

    PubMed

    He, Xiao-Heng; Wang, Wei; Liu, Ying-Mei; Jiang, Ming-Yue; Wu, Fang; Deng, Ke; Liu, Zhuang; Ju, Xiao-Jie; Xie, Rui; Chu, Liang-Yin

    2015-08-12

    A simple and flexible approach is developed for controllable fabrication of spider-silk-like microfibers with tunable magnetic spindle-knots from biocompatible calcium alginate for controlled 3D assembly and water collection. Liquid jet templates with volatile oil drops containing magnetic Fe3O4 nanoparticles are generated from microfluidics for fabricating spider-silk-like microfibers. The structure of jet templates can be precisely adjusted by simply changing the flow rates to tailor the structures of the resultant spider-silk-like microfibers. The microfibers can be well manipulated by external magnetic fields for controllably moving, and patterning and assembling into different 2D and 3D structures. Moreover, the dehydrated spider-silk-like microfibers, with magnetic spindle-knots for collecting water drops, can be controllably assembled into spider-web-like structures for excellent water collection. These spider-silk-like microfibers are promising as functional building blocks for engineering complex 3D scaffolds for water collection, cell culture, and tissue engineering.

  9. Microfluidic paper-based analytical devices fabricated by low-cost photolithography and embossing of Parafilm®.

    PubMed

    Yu, Ling; Shi, Zhuan Zhuan

    2015-04-07

    Microfluidic paper-based analytical devices (μPADs) attract tremendous attention as an economical tool for in-field diagnosis, food safety and environmental monitoring. We innovatively fabricated 2D and 3D μPADs by photolithography-patterning microchannels on a Parafilm® and subsequently embossing them to paper. This truly low-cost, wax printer and cutter plotter independent approach offers the opportunity for researchers from resource-limited laboratories to work on paper-based analytical devices.

  10. An architecture for integrating planar and 3D cQED devices

    NASA Astrophysics Data System (ADS)

    Axline, C.; Reagor, M.; Heeres, R.; Reinhold, P.; Wang, C.; Shain, K.; Pfaff, W.; Chu, Y.; Frunzio, L.; Schoelkopf, R. J.

    2016-07-01

    Numerous loss mechanisms can limit coherence and scalability of planar and 3D-based circuit quantum electrodynamics (cQED) devices, particularly due to their packaging. The low loss and natural isolation of 3D enclosures make them good candidates for coherent scaling. We introduce a coaxial transmission line device architecture with coherence similar to traditional 3D cQED systems. Measurements demonstrate well-controlled external and on-chip couplings, a spectrum absent of cross-talk or spurious modes, and excellent resonator and qubit lifetimes. We integrate a resonator-qubit system in this architecture with a seamless 3D cavity, and separately pattern a qubit, readout resonator, Purcell filter, and high-Q stripline resonator on a single chip. Device coherence and its ease of integration make this a promising tool for complex experiments.

  11. A novel device to concurrently assess leukocyte extravasation and interstitial migration within a defined 3D environment.

    PubMed

    Molteni, Raffaella; Bianchi, Elena; Patete, Paolo; Fabbri, Monica; Baroni, Guido; Dubini, Gabriele; Pardi, Ruggero

    2015-01-07

    Leukocyte extravasation and interstitial migration are key events during inflammation. Traditional in vitro techniques address only specific steps of cell recruitment to tissues and fail to recapitulate the whole process in an appropriate three-dimensional (3D) microenvironment. Herein, we describe a device that enables us to qualitatively and quantitatively assess in 4D the interdependent steps underlying leukocyte trafficking in a close-to-physiology in vitro context. Real-time tracking of cells, from initial adhesion to the endothelium and subsequent diapedesis to interstitial migration towards the source of the chemoattractant within the 3D collagen matrix, is enabled by the use of optically transparent porous membranes laid over the matrix. Unique features of the device, such as the use of non-planar surfaces and the contribution of physiological flow to the establishment of a persistent chemoattractant gradient, were assessed by numerical simulations and validated by proof-of-concept, simultaneous testing of differentially treated primary mouse neutrophils. This microfluidic platform offers new and versatile tools to thoroughly investigate the stepwise process of circulating cell recruitment to target tissues in vitro and to test novel therapeutics targeting various steps of the process.

  12. Method Of Packaging And Assembling Electro-Microfluidic Devices

    DOEpatents

    Benavides, Gilbert L.; Galambos, Paul C.; Emerson, John A.; Peterson, Kenneth A.; Giunta, Rachel K.; Zamora, David Lee; Watson, Robert D.

    2004-11-23

    A new architecture for packaging surface micromachined electro-microfluidic devices is presented. This architecture relies on two scales of packaging to bring fluid to the device scale (picoliters) from the macro-scale (microliters). The architecture emulates and utilizes electronics packaging technology. The larger package consists of a circuit board with embedded fluidic channels and standard fluidic connectors (e.g. Fluidic Printed Wiring Board). The embedded channels connect to the smaller package, an Electro-Microfluidic Dual-Inline-Package (EMDIP) that takes fluid to the microfluidic integrated circuit (MIC). The fluidic connection is made to the back of the MIC through Bosch-etched holes that take fluid to surface micromachined channels on the front of the MIC. Electrical connection is made to bond pads on the front of the MIC.

  13. Diffusionless fluid transport and routing using novel microfluidic devices.

    SciTech Connect

    Barrett, Louise Mary; Shediac, Renee; Reichmuth, David S.

    2006-11-01

    Microfluidic devices have been proposed for 'Lab-on-a-Chip' applications for nearly a decade. Despite the unquestionable promise of these devices to allow rapid, sensitive and portable biochemical analysis, few practical devices exist. It is often difficult to adapt current laboratory techniques to the microscale because bench-top methods use discrete liquid volumes, while most current microfluidic devices employ streams of liquid confined in a branching network of micron-scale channels. The goal of this research was to use two phase liquid flows, creating discrete packets of liquid. Once divided into discrete packets, the packets can be moved controllably within the microchannels without loss of material. Each packet is equivalent to a minute test tube, holding a fraction from a separation or an aliquot to be reacted. We report on the fabrication of glass and PDMS (polydimethylsiloxane) devices that create and store packets.

  14. Wirelessly powered microfluidic dielectrophoresis devices using printable RF circuits.

    PubMed

    Qiao, Wen; Cho, Gyoujin; Lo, Yu-Hwa

    2011-03-21

    We report the first microfluidic device integrated with a printed RF circuit so the device can be wirelessly powered by a commercially available RFID reader. For conventional dielectrophoresis devices, electrical wires are needed to connect the electric components on the microchip to external equipment such as power supplies, amplifiers, function generators, etc. Such a procedure is unfamiliar to most clinicians and pathologists who are used to working with a microscope for examination of samples on microscope slides. The wirelessly powered device reported here eliminates the entire need for wire attachments and external instruments so the operators can use the device in essentially the same manner as they do with microscope slides. The integrated circuit can be fabricated on a flexible plastic substrate at very low cost using a roll-to-roll printing method. Electrical power at 13.56 MHz transmitted by a radio-frequency identification (RFID) reader is inductively coupled to the printed RFIC and converted into 10 V DC (direct current) output, which provides sufficient power to drive a microfluidic device to manipulate biological particles such as beads and proteins via the DC dielectrophoresis (DC-DEP) effect. To our best knowledge, this is the first wirelessly powered microfluidic dielectrophoresis device. Although the work is preliminary, the device concept, the architecture, and the core technology are expected to stimulate many efforts in the future and transform the technology to a wide range of clinical and point-of-care applications.

  15. Mitigation of Tracheobronchomalacia with 3D-Printed Personalized Medical Devices in Pediatric Patients

    PubMed Central

    Morrison, Robert J.; Hollister, Scott J.; Niedner, Matthew F.; Mahani, Maryam Ghadimi; Park, Albert H.; Mehta, Deepak K.; Ohye, Richard G.; Green, Glenn E.

    2015-01-01

    Three-dimensional (3D) printing offers the potential for rapid customization of medical devices. The advent of 3D-printable biomaterials has created the potential for device control in the fourth dimension: 3D-printed objects that exhibit a designed shape change under tissue growth and resorption conditions over time. Tracheobronchomalacia (TBM) is a condition of excessive collapse of the airways during respiration that can lead to life-threatening cardiopulmonary arrests. Here we demonstrate the successful application of 3D printing technology to produce a personalized medical device for treatment of TBM, designed to accommodate airway growth while preventing external compression over a pre-determined time period before bioresorption. We implanted patient-specific 3D-printed external airway splints in three infants with severe TBM. At the time of publication, these infants no longer exhibited life-threatening airway disease and had demonstrated resolution of both pulmonary and extra-pulmonary complications of their TBM. Long-term data show continued growth of the primary airways. This process has broad application for medical manufacturing of patient-specific 3D-printed devices that adjust to tissue growth through designed mechanical and degradation behaviors over time. PMID:25925683

  16. Mitigation of tracheobronchomalacia with 3D-printed personalized medical devices in pediatric patients.

    PubMed

    Morrison, Robert J; Hollister, Scott J; Niedner, Matthew F; Mahani, Maryam Ghadimi; Park, Albert H; Mehta, Deepak K; Ohye, Richard G; Green, Glenn E

    2015-04-29

    Three-dimensional (3D) printing offers the potential for rapid customization of medical devices. The advent of 3D-printable biomaterials has created the potential for device control in the fourth dimension: 3D-printed objects that exhibit a designed shape change under tissue growth and resorption conditions over time. Tracheobronchomalacia (TBM) is a condition of excessive collapse of the airways during respiration that can lead to life-threatening cardiopulmonary arrests. We demonstrate the successful application of 3D printing technology to produce a personalized medical device for treatment of TBM, designed to accommodate airway growth while preventing external compression over a predetermined time period before bioresorption. We implanted patient-specific 3D-printed external airway splints in three infants with severe TBM. At the time of publication, these infants no longer exhibited life-threatening airway disease and had demonstrated resolution of both pulmonary and extrapulmonary complications of their TBM. Long-term data show continued growth of the primary airways. This process has broad application for medical manufacturing of patient-specific 3D-printed devices that adjust to tissue growth through designed mechanical and degradation behaviors over time.

  17. Microfluidic devices and methods including porous polymer monoliths

    DOEpatents

    Hatch, Anson V; Sommer, Gregory J; Singh, Anup K; Wang, Ying-Chih; Abhyankar, Vinay V

    2014-04-22

    Microfluidic devices and methods including porous polymer monoliths are described. Polymerization techniques may be used to generate porous polymer monoliths having pores defined by a liquid component of a fluid mixture. The fluid mixture may contain iniferters and the resulting porous polymer monolith may include surfaces terminated with iniferter species. Capture molecules may then be grafted to the monolith pores.

  18. Microfluidic devices and methods including porous polymer monoliths

    SciTech Connect

    Hatch, Anson V.; Sommer, Gregory j.; Singh, Anup K.; Wang, Ying-Chih; Abhyankar, Vinay

    2015-12-01

    Microfluidic devices and methods including porous polymer monoliths are described. Polymerization techniques may be used to generate porous polymer monoliths having pores defined by a liquid component of a fluid mixture. The fluid mixture may contain iniferters and the resulting porous polymer monolith may include surfaces terminated with iniferter species. Capture molecules may then be grafted to the monolith pores.

  19. A Microfluidic Device for Dry Sample Preservation in Remote Settings

    PubMed Central

    Begolo, Stefano; Shen, Feng; Ismagilov, Rustem F.

    2013-01-01

    Summary This paper describes a microfluidic device for dry preservation of biological specimens at room temperature that incorporates chemical stabilization matrices. Long-term stabilization of samples is crucial for remote medical analysis, biosurveillance, and archiving, but the current paradigm for transporting remotely obtained samples relies on the costly “cold chain” to preserve analytes within biospecimens. We propose an alternative approach that involves the use of microfluidics to preserve samples in the dry state with stabilization matrices, developed by others, that are based on self-preservation chemistries found in nature. We describe a SlipChip-based device that allows minimally trained users to preserve samples with the three simple steps of placing a sample at an inlet, closing a lid, and slipping one layer of the device. The device fills automatically, and a pre-loaded desiccant dries the samples. Later, specimens can be rehydrated and recovered for analysis in a laboratory. This device is portable, compact, and self-contained, so it can be transported and operated by untrained users even in limited-resource settings. Features such as dead-end and sequential filling, combined with a “pumping lid” mechanism, enable precise quantification of the original sample’s volume while avoiding overfilling. In addition, we demonstrated that the device can be integrated with a plasma filtration module, and we validated device operations and capabilities by testing the stability of purified RNA solutions. These features and the modularity of this platform (which facilitates integration and simplifies operation) would be applicable to other microfluidic devices beyond this application. We envision that as the field of stabilization matrices develops, microfluidic devices will be useful for cost-effectively facilitating remote analysis and biosurveillance while also opening new opportunities for diagnostics, drug development, and other medical fields

  20. Magnetophoretic-based microfluidic device for DNA isolation.

    PubMed

    Hale, C; Darabi, J

    2014-07-01

    This paper presents a continuous flow microfluidic device for the separation of DNA from blood using magnetophoresis for biological applications and analysis. This microfluidic bio-separation device has several benefits, including decreased sample handling, smaller sample and reagent volumes, faster isolation time, and decreased cost to perform DNA isolation. One of the key features of this device is the use of short-range magnetic field gradients, generated by a micro-patterned nickel array on the bottom surface of the separation channel. In addition, the device utilizes an array of oppositely oriented, external permanent magnets to produce strong long-range field gradients at the interfaces between magnets, further increasing the effectiveness of the device. A comprehensive simulation is performed using COMSOL Multiphysics to study the effect of various parameters on the magnetic flux within the separation channel. Additionally, a microfluidic device is designed, fabricated, and tested to isolate DNA from blood. The results show that the device has the capability of separating DNA from a blood sample with a purity of 1.8 or higher, a yield of up to 33 μg of polymerase chain reaction ready DNA per milliliter of blood, and a volumetric throughput of up to 50 ml/h.

  1. 3D functional and perfusable microvascular networks for organotypic microfluidic models.

    PubMed

    Bersini, Simone; Moretti, Matteo

    2015-05-01

    The metastatic dissemination of cancer cells from primary tumors to secondary loci is a complex and multistep process including local invasion, intravasation, survival in the blood stream and extravasation towards the metastatic site. It is well known cancer metastases follow organ-specific pathways with selected primary tumors mainly metastasizing towards a specific panel of secondary organs (Steven Paget's theory 1889). However, circulatory patterns and microarchitecture of capillary networks play a key role in the metastatic spread as well (James Ewing's theory 1929). Taking into account both these factors would be critical to develop more complex and physiologically relevant in vitro cancer models. This review presents recent advances in the generation of microvascularized systems through microfluidic approaches and discusses promising results achieved by organ-on-a-chip platforms mimicking the pathophysiology of the functional units of specific organs. The combination of physiologically-like microvascular networks and organotypic microenvironments would foster a new generation of in vitro cancer models to more effectively screen new therapeutics, design personalized medicine treatments and investigate molecular pathways involved in cancer metastases.

  2. A Biochip with a 3D microfluidic architecture for trapping white blood cells

    PubMed Central

    Tripathi, Anurag; Riddell, James; Chronis, Nikos

    2013-01-01

    We present a microfluidic biochip for trapping single white blood cells (WBCs). The novel biochip, microfabricated using standard surface micromachining processes, consists of an array of precisely engineered microholes that confine single cells in a tight, three dimensional space and mechanically immobilize them. A high (> 87%) trapping efficiency was achieved when WBC-containing samples were delivered to the biochip at the optimal pressure of 3 psi. The biochip can efficiently trap up to 7,500 cells, maintaining a high trapping efficiency even when the number of cells is extremely low (~200 cells). We believe that the developed biochip can be used as a standalone unit in a biology/clinical lab for trapping WBCs as well as other cell types and imaging them using a standard fluorescent microscope at the single cell level. Furthermore, it can be integrated with other miniaturized optical modules to construct a portable platform for counting a wide variety of cells and therefore it can be an excellent tool for monitoring human diseases at the point-of-care. PMID:23935241

  3. Microfluidic device for the assembly and transport of microparticles

    DOEpatents

    James, Conrad D.; Kumar, Anil; Khusid, Boris; Acrivos, Andreas

    2010-06-29

    A microfluidic device comprising independently addressable arrays of interdigitated electrodes can be used to assembly and transport large-scale microparticle structures. The device and method uses collective phenomena in a negatively polarized suspension exposed to a high-gradient strong ac electric field to assemble the particles into predetermined locations and then transport them collectively to a work area for final assembly by sequentially energizing the electrode arrays.

  4. Electrochemical fields within 3D reconstructed microstructures of mixed ionic and electronic conducting devices

    NASA Astrophysics Data System (ADS)

    Zhang, Yanxiang; Chen, Yu; Lin, Ye; Yan, Mufu; Harris, William M.; Chiu, Wilson K. S.; Ni, Meng; Chen, Fanglin

    2016-11-01

    The performance and stability of the mixed ionic and electronic conducting (MIEC) membrane devices, such as solid oxide cells (SOCs) and oxygen separation membranes (OSMs) interplay tightly with the transport properties and the three-dimensional (3D) microstructure of the membrane. However, development of the MIEC devices is hindered by the limited knowledge about the distribution of electrochemical fields within the 3D local microstructures, especially at surface and interface. In this work, a generic model conforming to local thermodynamic equilibrium is developed to calculate the electrochemical fields, such as electric potential and oxygen chemical potential, within the 3D microstructure of the MIEC membrane. Stability of the MIEC membrane is evaluated by the distribution of oxygen partial pressure. The cell-level performance such as polarization resistance and voltage vs. current curve can be further calculated. Case studies are performed to demonstrate the capability of the framework by using X-ray computed tomography reconstructed 3D microstructures of a SOC and an OSM. The calculation method demonstrates high computational efficiency for large size 3D tomographic microstructures, and permits parallel calculation. The framework can serve as a powerful tool for correlating the transport properties and the 3D microstructure to the performance and the stability of MIEC devices.

  5. 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

  6. Mapping of Enzyme Kinetics on a Microfluidic Device

    PubMed Central

    Rho, Hoon Suk; Hanke, Alexander Thomas; Ottens, Marcel; Gardeniers, Han

    2016-01-01

    A microfluidic platform or “microfluidic mapper” is demonstrated, which in a single experiment performs 36 parallel biochemical reactions with 36 different combinations of two reagents in stepwise concentration gradients. The volume used in each individual reaction was 36 nl. With the microfluidic mapper, we obtained a 3D enzyme reaction plot of horseradish peroxidase (HRP) with Amplex Red (AR) and hydrogen peroxide (H2O2), for concentration ranges of 11.7 μM to 100.0 μM and 11.1 μM to 66.7 μM for AR and H2O2, respectively. This system and methodology could be used as a fast analytical tool to evaluate various chemical and biochemical reactions especially where two or more reagents interact with each other. The generation of dual concentration gradients in the present format has many advantages such as parallelization of reactions in a nanoliter-scale volume and the real-time monitoring of processes leading to quick concentration gradients. The microfluidic mapper could be applied to various problems in analytical chemistry such as revealing of binding kinetics, and optimization of reaction kinetics. PMID:27082243

  7. Microfluidic device for multimodal characterization of pancreatic islets.

    PubMed

    Mohammed, Javeed Shaikh; Wang, Yong; Harvat, Tricia A; Oberholzer, Jose; Eddington, David T

    2009-01-07

    A microfluidic device to perfuse pancreatic islets while simultaneously characterizing their functionality through fluorescence imaging of the mitochondrial membrane potential and intracellular calcium ([Ca(2+)](i)) in addition to enzyme linked immunosorbent assay (ELISA) quantification of secreted insulin was developed and characterized. This multimodal characterization of islet function will facilitate rapid assessment of tissue quality immediately following isolation from donor pancreas and allow more informed transplantation decisions to be made which may improve transplantation outcomes. The microfluidic perfusion chamber allows flow rates of up to 1 mL min(-1), without any noticeable perturbation or shear of islets. This multimodal quantification was done on both mouse and human islets. The ability of this simple microfluidic device to detect subtle variations in islet responses in different functional assays performed in short time-periods demonstrates that the microfluidic perfusion chamber device can be used as a new gold standard to perform comprehensive islet analysis and obtain a more meaningful predictive value for islet functionality prior to transplantation into recipients, which is currently difficult to predict using a single functional assay.

  8. Partitioning microfluidic channels with hydrogel to construct tunable 3-D cellular microenvironments.

    PubMed

    Wong, Amy P; Perez-Castillejos, Raquel; Christopher Love, J; Whitesides, George M

    2008-04-01

    Accurate modeling of the cellular microenvironment is important for improving studies of cell biology in vitro. Here, we demonstrate a flexible method for creating a cellular microenvironment in vitro that allows (i) controlled spatial distribution (patterning) of multiple types of cells within three-dimensional (3-D) matrices of a biologically derived, thermally curable hydrogel (Matrigel) and (ii) application of gradients of soluble factors, such as cytokines, across the hydrogel. The technique uses laminar flow to divide a microchannel into multiple subchannels separated by microslabs of hydrogel. It does not require the use of UV light or photoinitiators and is compatible with cell culture in the hydrogel. This technique makes it possible to design model systems to study cellular communication mediated by the diffusion of soluble factors within 3-D matrices. Such factors can originate either from secretions of neighboring cells patterned within the microchannel, or from an external source -- e.g., a solution of growth factors injected into a subchannel. This method is particularly useful for studying cells such as those of the immune system, which are often weakly adherent and difficult to position precisely with standard systems for cell culture. We demonstrated this application by co-culturing two types of macrophage-like cells (BAC1.2F5 and LADMAC cell lines) within spatially separated regions of a slab of hydrogel. This pair of cell lines represents a simple model system for intercellular communication: the LADMAC cells produce colony-stimulating factor 1 (CSF-1), which is required by the BAC cells for survival.

  9. Partitioning Microfluidic Channels with Hydrogel to Construct Tunable 3-D Cellular Microenvironments

    PubMed Central

    Wong, Amy P.; Perez-Castillejos, Raquel; Love, J. Christopher; Whitesides, George M.

    2008-01-01

    Accurate modeling of the cellular microenvironment is important for improving studies of cell biology in vitro. Here, we demonstrate a flexible method for creating a cellular microenvironment in vitro that allows i) controlled spatial distribution (patterning) of multiple types of cells within three-dimensional (3-D) matrices of a biologically-derived, thermally-curable hydrogel (Matrigel) and ii) application of gradients of soluble factors, such as cytokines, across the hydrogel. The technique uses laminar flow to divide a microchannel into multiple subchannels separated by microslabs of hydrogel. It does not require the use of UV light or photoinitiators, and is compatible with cell culture in the hydrogel. This technique makes it possible to design model systems to study cellular communication mediated by the diffusion of soluble factors within 3-D matrices. Such factors can originate either from secretions of neighboring cells patterned within the microchannel, or from an external source—e.g., a solution of growth factors injected into a subchannel. This method is particularly useful for studying cells such as those of the immune system, which are often weakly adherent and difficult to position precisely with standard systems for cell culture. We demonstrated this application by co-culturing two types of macrophage-like cells (BAC1.2F5 and LADMAC cell lines) within spatially separated regions of a slab of hydrogel. This pair of cell lines represents a simple model system for intercellular communication: the LADMAC cells produce colony-stimulating factor 1 (CSF-1), which is required by the BAC cells for survival. PMID:18243301

  10. Advances in three-dimensional rapid prototyping of microfluidic devices for biological applications

    PubMed Central

    O'Neill, P. F.; Ben Azouz, A.; Vázquez, M.; Liu, J.; Marczak, S.; Slouka, Z.; Chang, H. C.; Diamond, D.; Brabazon, D.

    2014-01-01

    The capability of 3D printing technologies for direct production of complex 3D structures in a single step has recently attracted an ever increasing interest within the field of microfluidics. Recently, ultrafast lasers have also allowed developing new methods for production of internal microfluidic channels within the bulk of glass and polymer materials by direct internal 3D laser writing. This review critically summarizes the latest advances in the production of microfluidic 3D structures by using 3D printing technologies and direct internal 3D laser writing fabrication methods. Current applications of these rapid prototyped microfluidic platforms in biology will be also discussed. These include imaging of cells and living organisms, electrochemical detection of viruses and neurotransmitters, and studies in drug transport and induced-release of adenosine triphosphate from erythrocytes. PMID:25538804

  11. 3D Printing of Medicines: Engineering Novel Oral Devices with Unique Design and Drug Release Characteristics.

    PubMed

    Goyanes, Alvaro; Wang, Jie; Buanz, Asma; Martínez-Pacheco, Ramón; Telford, Richard; Gaisford, Simon; Basit, Abdul W

    2015-11-02

    Three dimensional printing (3D printing) was used to fabricate novel oral drug delivery devices with specialized design configurations. Each device was loaded with multiple actives, with the intent of applying this process to the production of personalized medicines tailored at the point of dispensing or use. A filament extruder was used to obtain drug-loaded--paracetamol (acetaminophen) or caffeine--filaments of poly(vinyl alcohol) with characteristics suitable for use in fused-deposition modeling 3D printing. A multinozzle 3D printer enabled fabrication of capsule-shaped solid devices containing the drug with different internal structures. The design configurations included a multilayer device, with each layer containing drug, whose identity was different to the drug in the adjacent layers, and a two-compartment device comprising a caplet embedded within a larger caplet (DuoCaplet), with each compartment containing a different drug. Raman spectroscopy was used to collect 2-dimensional hyper spectral arrays across the entire surface of the devices. Processing of the arrays using direct classical least-squares component matching to produce false color representations of distribution of the drugs was used. This clearly showed a definitive separation between the drug layers of paracetamol and caffeine. Drug release tests in biorelevant bicarbonate media showed unique drug release profiles dependent on the macrostructure of the devices. In the case of the multilayer devices, release of both paracetamol and caffeine was simultaneous and independent of drug solubility. With the DuoCaplet design, it was possible to engineer either rapid drug release or delayed release by selecting the site of incorporation of the drug in the device; the lag-time for release from the internal compartment was dependent on the characteristics of the external layer. The study confirms the potential of 3D printing to fabricate multiple-drug containing devices with specialized design

  12. A Comprehensive Microfluidics Device Construction and Characterization Module for the Advanced Undergraduate Analytical Chemistry Laboratory

    ERIC Educational Resources Information Center

    Piunno, Paul A. E.; Zetina, Adrian; Chu, Norman; Tavares, Anthony J.; Noor, M. Omair; Petryayeva, Eleonora; Uddayasankar, Uvaraj; Veglio, Andrew

    2014-01-01

    An advanced analytical chemistry undergraduate laboratory module on microfluidics that spans 4 weeks (4 h per week) is presented. The laboratory module focuses on comprehensive experiential learning of microfluidic device fabrication and the core characteristics of microfluidic devices as they pertain to fluid flow and the manipulation of samples.…

  13. Microfluidic device for capture and isolation of single cells

    NASA Astrophysics Data System (ADS)

    Hsiao, Alexander P.; Barbee, Kristopher D.; Huang, Xiaohua

    2010-08-01

    We describe a microfluidic device capable of trapping, isolating, and lysing individual cells in parallel using dielectrophoretic forces and a system of PDMS channels and valves. The device consists of a glass substrate patterned with electrodes and two PDMS layers comprising of the microfluidic channels and valve control channels. Individual cells are captured by positive dielectrophoresis using the microfabricated electrode pairs. The cells are then isolated into nanoliter compartments using pneumatically actuated PDMS valves. Following isolation, the cells are lysed open by applying an electric field using the same electrode pairs. With the ability to capture and compartmentalize single cells our device may be combined with analytical methods for in situ molecular analysis of cellular components from single cells in a highly parallel manner.

  14. Modelling of a microfluidic device with piezoelectric actuators

    NASA Astrophysics Data System (ADS)

    Seitz, Hermann; Heinzl, Joachim

    2004-08-01

    This paper presents the modelling of a given microfluidic device, that is applied as a drop-on-demand printhead for different printing tasks. Piezoelectric bend mode actuators are used to eject a droplet from the respective nozzle on demand. The device is considered as a coupled system consisting of an electric, a mechanical and a fluidic part. The electric and mechanical parts of the piezoelectric actuator are described by conventional lumped elements, while the complex three-dimensional fluid analysis is performed by a commercial computational fluid dynamics (CFD) free-surface modelling package. The model helps one to understand the fluid dynamics and thus to study different design and operating parameter aspects. The general approach to the problem of modelling a microfluidic device as presented here can also be applied in various other modelling tasks.

  15. Microfluidic photocatalytic device exploiting PDMS/TiO2 nanocomposite

    NASA Astrophysics Data System (ADS)

    Lamberti, Andrea

    2015-04-01

    A microfluidic device exploiting PDMS/TiO2 nanocomposite has been used for photocatalytic degradation studies of organic dye. By using commercial P25 TiO2 nanoparticles (NPs) and conventional PDMS casting and replication techniques, high density and well-dispersed TiO2 NPs were embedded in the elastomeric surface. The obtained nanocomposite membranes were characterized by morphological, chemical, and physical points of view. The fabrication process allows an easy integration of the membrane into an all-PDMS microfluidic device for pollutant photodegradation. The high surface-to-volume ratio intrinsic in nanoparticles and the functional properties of the proposed nanocomposite substrate are responsible for the interesting photocatalytic device performance.

  16. Three-dimensional paper-based microfluidic device for assays of protein and glucose in urine.

    PubMed

    Sechi, Deidre; Greer, Brady; Johnson, Jesse; Hashemi, Nastaran

    2013-11-19

    The first step in curing a disease is being able to detect the disease effectively. Paper-based microfluidic devices are biodegradable and can make diagnosing diseases cost-effective and easy in almost all environments. We created a three-dimesnional (3D) paper device using wax printing fabrication technique and basic principles of origami. This design allows for a versatile fabrication technique over previously reported patterning of SU-8 photoresist on chromatography paper by employing a readily available wax printer. The design also utilizes multiple colorimetric assays that can accommodate one or more analytes including urine, blood, and saliva. In this case to demonstrate the functionality of the 3D paper-based microfluidic system, a urinalysis of protein and glucose assays is conducted. The amounts of glucose and protein introduced to the device are found to be proportional to the color change of each assay. This color change was quantified by use of Adobe Photoshop. Urine samples from participants with no pre-existing health conditions and one person with diabetes were collected and compared against synthetic urine samples with predetermined glucose and protein levels. Utilizing this method, we were able to confirm that both protein and glucose levels were in fact within healthy ranges for healthy participants. For the participant with diabetes, glucose was found to be above the healthy range while the protein level was in the healthy range.

  17. A photonic-microfluidic integrated device for reliable fluorescence detection and counting.

    PubMed

    Watts, Benjamin R; Zhang, Zhiyi; Xu, Chang Qing; Cao, Xudong; Lin, Min

    2012-11-01

    A photonic-microfluidic integrated device is demonstrated with excellent and reliable fluorescence detection performance. CV values of 8% for 2.5-μm beads and 14% for 6-μm beads were achieved through the correct deployment of carefully formed excitation beam shapes via integrated on-chip optics even without the use of 3D hydrodynamic focusing or a high-quality laser source and single mode beam propagation. The devices are fabricated in a monolithic planar fashion using a system of microlenses and waveguides integrated with microfluidic channels on-chip and packaged using a high-quality and low-cost channel sealing and high-performance interconnecting technology developed from our earlier works. Beam geometry in the excitation region is shown to affect the variation of fluorescence intensity from specimens, hence configurations of beam geometry targeted for a specific bead sizes are examined to ensure proper deployment of the lens designs. The formed high-quality optical excitation regions ensure reliable detection even with relaxed hydrodynamic focusing to ensure applicability with multiple specimen sizes. Device performance with each bead size was found to be acceptable for a range of beam geometries with a different ideal configuration for each bead size. These device designs help to form a device that will supplement conventional flow cytometry in point-of-care and remote detection applications by performing specific detections with an inexpensive and replaceable device.

  18. Microfluidic devices for modeling cell-cell and particle-cell interactions in the microvasculature

    PubMed Central

    Prabhakarpandian, Balabhaskar; Shen, Ming-Che; Pant, Kapil; Kiani, Mohammad F.

    2011-01-01

    Cell-fluid and cell-cell interactions are critical components of many physiological and pathological conditions in the microvasculature. Similarly, particle-cell interactions play an important role in targeted delivery of therapeutics to tissue. Development of in vitro fluidic devices to mimic these microcirculatory processes has been a critical step forward in our understanding of the inflammatory process, development of nano-particulate drug carriers, and developing realistic in vitro models of the microvasculature and its surrounding tissue. However, widely used parallel plate flow based devices and assays have a number of important limitations for studying the physiological conditions in vivo. In addition, these devices are resource hungry and time consuming for performing various assays. Recently developed, more realistic, microfluidic based devices have been able to overcome many of these limitations. In this review, an overview of the fluidic devices and their use in studying the effects of shear forces on cell-cell and cell-particle interactions is presented. In addition, use of mathematical models and Computational Fluid Dynamics (CFD) based models for interpreting the complex flow patterns in the microvasculature are highlighted. Finally, the potential of 3D microfluidic devices and imaging for better representing in vivo conditions under which cell-cell and cell-particle interactions take place are discussed. PMID:21763328

  19. Prototyping of microfluidic devices in poly(dimethylsiloxane) using solid-object printing.

    PubMed

    McDonald, J Cooper; Chabinyc, Michael L; Metallo, Steven J; Anderson, Janelle R; Stroock, Abraham D; Whitesides, George M

    2002-04-01

    A solid-object printer was used to produce masters for the fabrication of microfluidic devices in poly(dimethylsiloxane) (PDMS). The printer provides an alternative to photolithography for applications where features of > 250 microm are needed. Solid-object printing is capable of delivering objects that have dimensions as large as 250 x 190 x 200 mm (x, y, z) with feature sizes that can range from 10 cm to 250 microm. The user designs a device in 3-D in a CAD program, and the CAD file is used by the printer to fabricate a master directly without the need for a mask. The printer can produce complex structures, including multilevel features, in one unattended printing. The masters are robust and inexpensive and can be fabricated rapidly. Once a master was obtained, a PDMS replica was fabricated by molding against it and used to fabricate a microfluidic device. The capabilities of this method are demonstrated by fabricating devices that contain multilevel and tall features, devices that cover a large area (approximately 150 cm2), and devices that contain nonintersecting, crossing channels.

  20. Integration of isothermal amplification methods in microfluidic devices: Recent advances.

    PubMed

    Giuffrida, Maria Chiara; Spoto, Giuseppe

    2017-04-15

    The integration of nucleic acids detection assays in microfluidic devices represents a highly promising approach for the development of convenient, cheap and efficient diagnostic tools for clinical, food safety and environmental monitoring applications. Such tools are expected to operate at the point-of-care and in resource-limited settings. The amplification of the target nucleic acid sequence represents a key step for the development of sensitive detection protocols. The integration in microfluidic devices of the most popular technology for nucleic acids amplifications, polymerase chain reaction (PCR), is significantly limited by the thermal cycling needed to obtain the target sequence amplification. This review provides an overview of recent advances in integration of isothermal amplification methods in microfluidic devices. Isothermal methods, that operate at constant temperature, have emerged as promising alternative to PCR and greatly simplify the implementation of amplification methods in point-of-care diagnostic devices and devices to be used in resource-limited settings. Possibilities offered by isothermal methods for digital droplet amplification are discussed.

  1. Customizable 3D Printed ‘Plug and Play’ Millifluidic Devices for Programmable Fluidics

    PubMed Central

    Tsuda, Soichiro; Jaffery, Hussain; Doran, David; Hezwani, Mohammad; Robbins, Phillip J.; Yoshida, Mari; Cronin, Leroy

    2015-01-01

    Three dimensional (3D) printing is actively sought after in recent years as a promising novel technology to construct complex objects, which scope spans from nano- to over millimeter scale. Previously we utilized Fused deposition modeling (FDM)-based 3D printer to construct complex 3D chemical fluidic systems, and here we demonstrate the construction of 3D milli-fluidic structures for programmable liquid handling and control of biological samples. Basic fluidic operation devices, such as water-in-oil (W/O) droplet generators for producing compartmentalized mono-disperse droplets, sensor-integrated chamber for online monitoring of cellular growth, are presented. In addition, chemical surface treatment techniques are used to construct valve-based flow selector for liquid flow control and inter-connectable modular devices for networking fluidic parts. As such this work paves the way for complex operations, such as mixing, flow control, and monitoring of reaction / cell culture progress can be carried out by constructing both passive and active components in 3D printed structures, which designs can be shared online so that anyone with 3D printers can reproduce them by themselves. PMID:26558389

  2. Customizable 3D Printed 'Plug and Play' Millifluidic Devices for Programmable Fluidics.

    PubMed

    Tsuda, Soichiro; Jaffery, Hussain; Doran, David; Hezwani, Mohammad; Robbins, Phillip J; Yoshida, Mari; Cronin, Leroy

    2015-01-01

    Three dimensional (3D) printing is actively sought after in recent years as a promising novel technology to construct complex objects, which scope spans from nano- to over millimeter scale. Previously we utilized Fused deposition modeling (FDM)-based 3D printer to construct complex 3D chemical fluidic systems, and here we demonstrate the construction of 3D milli-fluidic structures for programmable liquid handling and control of biological samples. Basic fluidic operation devices, such as water-in-oil (W/O) droplet generators for producing compartmentalized mono-disperse droplets, sensor-integrated chamber for online monitoring of cellular growth, are presented. In addition, chemical surface treatment techniques are used to construct valve-based flow selector for liquid flow control and inter-connectable modular devices for networking fluidic parts. As such this work paves the way for complex operations, such as mixing, flow control, and monitoring of reaction / cell culture progress can be carried out by constructing both passive and active components in 3D printed structures, which designs can be shared online so that anyone with 3D printers can reproduce them by themselves.

  3. Mimicking liver sinusoidal structures and functions using a 3D-configured microfluidic chip.

    PubMed

    Du, Yu; Li, Ning; Yang, Hao; Luo, Chunhua; Gong, Yixin; Tong, Chunfang; Gao, Yuxin; Lü, Shouqin; Long, Mian

    2017-02-28

    Physiologically, four major types of hepatic cells - the liver sinusoidal endothelial cells, Kupffer cells, hepatic stellate cells, and hepatocytes - reside inside liver sinusoids and interact with flowing peripheral cells under blood flow. It is hard to mimic an in vivo liver sinusoid due to its complex multiple cell-cell interactions, spatiotemporal construction, and mechanical microenvironment. Here we developed an in vitro liver sinusoid chip by integrating the four types of primary murine hepatic cells into two adjacent fluid channels separated by a porous permeable membrane, replicating liver's key structures and configurations. Each type of cells was identified with its respective markers, and the assembled chip presented the liver-specific unique morphology of fenestration. The flow field in the liver chip was quantitatively analyzed by computational fluid dynamics simulations and particle tracking visualization tests. Intriguingly, co-culture and shear flow enhance albumin secretion independently or cooperatively, while shear flow alone enhances HGF production and CYP450 metabolism. Under lipopolysaccharide (LPS) stimulations, the hepatic cell co-culture facilitated neutrophil recruitment in the liver chip. Thus, this 3D-configured in vitro liver chip integrates the two key factors of shear flow and the four types of primary hepatic cells to replicate key structures, hepatic functions, and primary immune responses and provides a new in vitro model to investigate the short-duration hepatic cellular interactions under a microenvironment mimicking the physiology of a liver.

  4. Synergistic Effects of 3D ECM and Chemogradients on Neurite Outgrowth and Guidance: A Simple Modeling and Microfluidic Framework

    PubMed Central

    Srinivasan, Parthasarathy; Zervantonakis, Ioannis K.; Kothapalli, Chandrasekhar R.

    2014-01-01

    During nervous system development, numerous cues within the extracellular matrix microenvironment (ECM) guide the growing neurites along specific pathways to reach their intended targets. Neurite motility is controlled by extracellular signal sensing through the growth cone at the neurite tip, including chemoattractive and repulsive cues. However, it is difficult to regenerate and restore neurite tracts, lost or degraded due to an injury or disease, in the adult central nervous system. Thus, it is important to evaluate the dynamic interplay between ECM and the concentration gradients of these cues, which would elicit robust neuritogenesis. Such information is critical in understanding the processes involved in developmental biology, and in developing high-fidelity neurite regenerative strategies post-injury, and in drug discovery and targeted therapeutics for neurodegenerative conditions. Here, we quantitatively investigated this relationship using a combination of mathematical modeling and in vitro experiments, and determined the synergistic role of guidance cues and ECM on neurite outgrowth and turning. Using a biomimetic microfluidic system, we have shown that cortical neurite outgrowth and turning under chemogradients (IGF-1 or BDNF) within 3D scaffolds is highly regulated by the source concentration of the guidance cue and the physical characteristics of the scaffold. A mechanistic-driven partial differential equation model of neurite outgrowth has been proposed, which could also be used prospectively as a predictive tool. The parameters for the chemotaxis term in the model are determined from the experimental data using our microfluidic assay. Resulting model simulations demonstrate how neurite outgrowth was critically influenced by the experimental variables, which was further supported by experimental data on cell-surface-receptor expressions. The model results are in excellent agreement with the experimental findings. This integrated approach represents a

  5. Device and methods for "gold standard" registration of clinical 3D and 2D cerebral angiograms

    NASA Astrophysics Data System (ADS)

    Madan, Hennadii; Likar, Boštjan; Pernuš, Franjo; Å piclin, Žiga

    2015-03-01

    Translation of any novel and existing 3D-2D image registration methods into clinical image-guidance systems is limited due to lack of their objective validation on clinical image datasets. The main reason is that, besides the calibration of the 2D imaging system, a reference or "gold standard" registration is very difficult to obtain on clinical image datasets. In the context of cerebral endovascular image-guided interventions (EIGIs), we present a calibration device in the form of a headband with integrated fiducial markers and, secondly, propose an automated pipeline comprising 3D and 2D image processing, analysis and annotation steps, the result of which is a retrospective calibration of the 2D imaging system and an optimal, i.e., "gold standard" registration of 3D and 2D images. The device and methods were used to create the "gold standard" on 15 datasets of 3D and 2D cerebral angiograms, whereas each dataset was acquired on a patient undergoing EIGI for either aneurysm coiling or embolization of arteriovenous malformation. The use of the device integrated seamlessly in the clinical workflow of EIGI. While the automated pipeline eliminated all manual input or interactive image processing, analysis or annotation. In this way, the time to obtain the "gold standard" was reduced from 30 to less than one minute and the "gold standard" of 3D-2D registration on all 15 datasets of cerebral angiograms was obtained with a sub-0.1 mm accuracy.

  6. Synthesis of Bioactive Microcapsules Using a Microfluidic Device

    PubMed Central

    Kim, Byeong Il; Jeong, Soon Woo; Lee, Kyoung G.; Park, Tae Jung; Park, Jung Youn; Song, Jae Jun; Lee, Seok Jae; Lee, Chang-Soo

    2012-01-01

    Bioactive microcapsules containing Bacillus thuringiensis (BT) spores were generated by a combination of a hydro gel, microfluidic device and chemical polymerization method. As a proof-of-principle, we used BT spores displaying enhanced green fluorescent protein (EGFP) on the spore surface to spatially direct the EGFP-presenting spores within microcapsules. BT spore-encapsulated microdroplets of uniform size and shape are prepared through a flow-focusing method in a microfluidic device and converted into microcapsules through hydrogel polymerization. The size of microdroplets can be controlled by changing both the dispersion and continuous flow rate. Poly(N-isoproplyacrylamide) (PNIPAM), known as a hydrogel material, was employed as a biocompatible material for the encapsulation of BT spores and long-term storage and outstanding stability. Due to these unique properties of PNIPAM, the nutrients from Luria-Bertani complex medium diffused into the microcapsules and the microencapsulated spores germinated into vegetative cells under adequate environmental conditions. These results suggest that there is no limitation of transferring low-molecular-weight-substrates through the PNIPAM structures, and the viability of microencapsulated spores was confirmed by the culture of vegetative cells after the germinations. This microfluidic-based microencapsulation methodology provides a unique way of synthesizing bioactive microcapsules in a one-step process. This microfluidic-based strategy would be potentially suitable to produce microcapsules of various microbial spores for on-site biosensor analysis. PMID:23112592

  7. Tuning of the droplet motion in interconnected microfluidic devices

    NASA Astrophysics Data System (ADS)

    Hu, Guoqing; Song, Kui; Zhang, Li

    2010-11-01

    The problem of controlling the droplet motions in multiphase flows on the microscale has gained increasing attention because the droplet-based microfluidic devices provide great potentials for chemical/biological applications such as drug discovery, chemical kinetics study, material synthesis, and DNA/cell assays. It is critical to understand the relevant physics on droplet hydrodynamics and thus control the generation, motion, splitting, and coalescence of droplets in complex microfluidic networks. The operation of those applications sometimes requires the arrival of droplets from different branch microchannels at a designated location within a transit time. We propose a simple design for interconnected microfluidic devices that implement the feedback mechanism to synchronize the droplet motion via a passive way. Numerical simulations using the Volume of Fluid (VOF) algorithm are conducted to investigate the time-dependent dynamics of droplets in both gas-liquid and liquid-liquid systems. An analytical mode based on the electronic-hydraulic analogy is also developed to describe the transit behavior of the droplet traffic. Both the numerical and theoretical results agree well with the corresponding experimental results. Furthermore, we optimize the microfluidic networks to control the motion of a series of droplets.

  8. Microfluidic Devices for Chemical and Biochemical Analysis in Microgravity

    NASA Technical Reports Server (NTRS)

    Roman, Gregory T.; Culbertson, Christopher T.; Meyer, Amanda; Ramsey, J. Michael; Gonda, Steven R.

    2004-01-01

    One often touted benefit of "Lab-on-a-Chip" devices is their potential for use in remote environments. The ultimate remote environment is outer space, and NASA has multiple needs in the area of analytical sensing capability in such an environment. In particular, we are interested in integrating microfluidic devices with NASA bioreactor systems. In such an integrated system, the microfluidic device will serve as a biosensor and be used for both feedback control and for detecting various bioproducts produced by cells cultured in the NASA bioreactors. As a first step in demonstrating the ability of microfluidic devices to operate under the extreme environmental conditions found in outer space, we constructed a portable, battery operated platform for testing under reduced gravity conditions on a NASA KC-135 reduced gravity research aircraft, (AKA "the vomit comet"). The test platform consisted of a microchip, two 0-8kV high voltage power supplies, a high voltage switch, a solid-state diode-pumped green laser, a channel photomultiplier, and an inertial mass measurement unit, all under the control of a laptop computer and powered by 10 D-cell alkaline batteries. Over the course of 4 KC-135 flights, 1817 fast electrophoretic separations of 4 amino acids and/or proteins were performed in a variety of gravitational environments including zero-G, Martian-G, lunar-G, and 2-G. Results from these experiments will be presented and discussed.

  9. An integrated microfluidic device for influenza and other genetic analyses.

    PubMed

    Pal, R; Yang, M; Lin, R; Johnson, B N; Srivastava, N; Razzacki, S Z; Chomistek, K J; Heldsinger, D C; Haque, R M; Ugaz, V M; Thwar, P K; Chen, Z; Alfano, K; Yim, M B; Krishnan, M; Fuller, A O; Larson, R G; Burke, D T; Burns, M A

    2005-10-01

    An integrated microfluidic device capable of performing a variety of genetic assays has been developed as a step towards building systems for widespread dissemination. The device integrates fluidic and thermal components such as heaters, temperature sensors, and addressable valves to control two nanoliter reactors in series followed by an electrophoretic separation. This combination of components is suitable for a variety of genetic analyses. As an example, we have successfully identified sequence-specific hemagglutinin A subtype for the A/LA/1/87 strain of influenza virus. The device uses a compact design and mass production technologies, making it an attractive platform for a variety of widely disseminated applications.

  10. Microfluidic structures and methods for integrating a functional component into a microfluidic device

    DOEpatents

    Simmons, Blake; Domeier, Linda; Woo, Noble; Shepodd, Timothy; Renzi, Ronald F.

    2008-04-01

    Injection molding is used to form microfluidic devices with integrated functional components. One or more functional components are placed in a mold cavity which is then closed. Molten thermoplastic resin is injected into the mold and then cooled, thereby forming a solid substrate including the functional component(s). The solid substrate including the functional component(s) is then bonded to a second substrate which may include microchannels or other features.

  11. Polymeric salt bridges for conducting electric current in microfluidic devices

    DOEpatents

    Shepodd, Timothy J.; Tichenor, Mark S.; Artau, Alexander

    2009-11-17

    A "cast-in-place" monolithic microporous polymer salt bridge for conducting electrical current in microfluidic devices, and methods for manufacture thereof is disclosed. Polymeric salt bridges are formed in place in capillaries or microchannels. Formulations are prepared with monomer, suitable cross-linkers, solvent, and a thermal or radiation responsive initiator. The formulation is placed in a desired location and then suitable radiation such as UV light is used to polymerize the salt bridge within a desired structural location. Embodiments are provided wherein the polymeric salt bridges have sufficient porosity to allow ionic migration without bulk flow of solvents therethrough. The salt bridges form barriers that seal against fluid pressures in excess of 5000 pounds per square inch. The salt bridges can be formulated for carriage of suitable amperage at a desired voltage, and thus microfluidic devices using such salt bridges can be specifically constructed to meet selected analytical requirements.

  12. Mobile monolithic polymer elements for flow control in microfluidic devices

    DOEpatents

    Hasselbrink, Jr., Ernest F.; Rehm, Jason E.; Shepodd, Timothy J.; Kirby, Brian J.

    2005-11-11

    A cast-in-place and lithographically shaped mobile, monolithic polymer element for fluid flow control in microfluidic devices and method of manufacture. Microfluid flow control devices, or microvalves that provide for control of fluid or ionic current flow can be made incorporating a cast-in-place, mobile monolithic polymer element, disposed within a microchannel, and driven by fluid pressure (either liquid or gas) against a retaining or sealing surface. The polymer elements are made by the application of lithographic methods to monomer mixtures formulated in such a way that the polymer will not bond to microchannel walls. The polymer elements can seal against pressures greater than 5000 psi, and have a response time on the order of milliseconds. By the use of energetic radiation it is possible to depolymerize selected regions of the polymer element to form shapes that cannot be produced by conventional lithographic patterning and would be impossible to machine.

  13. Mobile monolithic polymer elements for flow control in microfluidic devices

    DOEpatents

    Hasselbrink, Jr., Ernest F.; Rehm, Jason E.; Shepodd, Timothy J.

    2004-08-31

    A cast-in-place and lithographically shaped mobile, monolithic polymer element for fluid flow control in microfluidic devices and method of manufacture. Microfluid flow control devices, or microvalves that provide for control of fluid or ionic current flow can be made incorporating a cast-in-place, mobile monolithic polymer element, disposed within a microchannel, and driven by either fluid or gas pressure against a retaining or sealing surface. The polymer elements are made by the application of lithographic methods to monomer mixtures formulated in such a way that the polymer will not bond to microchannel walls. The polymer elements can seal against pressures greater than 5000 psi, and have a response time on the order of milliseconds. By the use of energetic radiation it is possible to depolymerize selected regions of the polymer element to form shapes that cannot be produced by conventional lithographic patterning and would be impossible to machine.

  14. Femtosecond fabricated photomasks for fabrication of microfluidic devices.

    PubMed

    Day, Daniel; Gu, Min

    2006-10-30

    This paper describes the direct write laser fabrication of a photolithography mask for prototyping of microfluidic devices in polydimethylsiloxane. An amplified femtosecond pulse laser is used to selectively remove the aluminium metal layer from the poly(methyl methacrylate) photomask substrate. The use of a femtosecond pulse laser to selectively etch a metal layer has several advantages over other conventional methods for binary photomask fabrication, namely rapid prototyping of microfluidic devices using soft lightography. Control of the energy density and defocus position of the focusing objective lens results in the etching of features with widths ranging from 2 microm to 35 microm when using an objective lens with numerical aperture of 0.25.

  15. Shrink-film microfluidic education modules: Complete devices within minutes.

    PubMed

    Nguyen, Diep; McLane, Jolie; Lew, Valerie; Pegan, Jonathan; Khine, Michelle

    2011-06-01

    As advances in microfluidics continue to make contributions to diagnostics and life sciences, broader awareness of this expanding field becomes necessary. By leveraging low-cost microfabrication techniques that require no capital equipment or infrastructure, simple, accessible, and effective educational modules can be made available for a broad range of educational needs from middle school demonstrations to college laboratory classes. These modules demonstrate key microfluidic concepts such as diffusion and separation as well as "laboratory on-chip" applications including chemical reactions and biological assays. These modules are intended to provide an interdisciplinary hands-on experience, including chip design, fabrication of functional devices, and experiments at the microscale. Consequently, students will be able to conceptualize physics at small scales, gain experience in computer-aided design and microfabrication, and perform experiments-all in the context of addressing real-world challenges by making their own lab-on-chip devices.

  16. Fluoropolymer surface coatings to control droplets in microfluidic devices.

    PubMed

    Riche, Carson T; Zhang, Chuchu; Gupta, Malancha; Malmstadt, Noah

    2014-06-07

    We have demonstrated the application of low surface energy fluoropolymer coatings onto poly(dimethylsiloxane) (PDMS) microfluidic devices for droplet formation and extraction-induced merger of droplets. Initiated chemical vapor deposition (iCVD) was used to pattern fluoropolymer coatings within microchannels based on geometrical constraints. In a two-phase flow system, the range of accessible flow rates for droplet formation was greatly enhanced in the coated devices. The ability to controllably apply the coating only at the inlet facilitated a method for merging droplets. An organic spacer droplet was extracted from between a pair of aqueous droplets. The size of the organic droplet and the flow rate controlled the time to merge the aqueous droplets; the process of merging was independent of the droplet sizes. Extraction-induced droplet merging is a robust method for manipulating droplets that could be applied in translating multi-step reactions to microfluidic platforms.

  17. Stress-induced Effects Caused by 3D IC TSV Packaging in Advanced Semiconductor Device Performance

    NASA Astrophysics Data System (ADS)

    Sukharev, V.; Kteyan, A.; Choy, J.-H.; Hovsepyan, H.; Markosian, A.; Zschech, E.; Huebner, R.

    2011-11-01

    Potential challenges with managing mechanical stress and the consequent effects on device performance for advanced 3D through-silicon-via (TSV) based technologies are outlined. The paper addresses the growing need in a simulation-based design verification flow capable to analyze a design of 3D IC stacks and to determine across-die out-of-spec variations in device electrical characteristics caused by the layout and through-silicon-via (TSV)/package-induced mechanical stress. The limited characterization/measurement capabilities for 3D IC stacks and a strict "good die" requirement make this type of analysis critical for the achievement of an acceptable level of functional and parametric yield and reliability. The paper focuses on the development of a design-for-manufacturability (DFM) type of methodology for managing mechanical stresses during a sequence of designs of 3D TSV-based dies, stacks and packages. A set of physics-based compact models for a multi-scale simulation to assess the mechanical stress across the device layers in silicon chips stacked and packaged with the 3D TSV technology is proposed. A calibration technique based on fitting to measured stress components and electrical characteristics of the test-chip devices is presented. A strategy for generation of a simulation feeding data and respective materials characterization approach are proposed, with the goal to generate a database for multi-scale material parameters of wafer-level and package-level structures. For model validation, high-resolution strain measurements in Si channels of the test-chip devices are needed. At the nanoscale, the transmission electron microscopy (TEM) is the only technique available for sub-10 nm strain measurements so far.

  18. A Pneumatic Actuated Microfluidic Beads-Trapping Device

    SciTech Connect

    Shao, Guocheng; Cai, Ziliang; Wang, Jun; Wang, Wanjun; Lin, Yuehe

    2011-08-20

    The development of a polydimethylsiloxane (PDMS) microfluidic microbeads trapping device is reported in this paper. Besides fluid channels, the proposed device includes a pneumatic control chamber and a beads-trapping chamber with a filter array structure. The pneumatic flow control chamber and the beads-trapping chamber are vertically stacked and separated by a thin membrane. By adjusting the pressure in the pneumatic control chamber, the membrane can either be pushed against the filter array to set the device in trapping mode or be released to set the device in releasing mode. In this paper, a computational fluid dynamics simulation was conducted to optimize the geometry design of the filter array structure; the device fabrication was also carried out. The prototype device was tested and the preliminary experimental results showed that it can be used as a beads-trapping unit for various biochemistry and analytical chemistry applications, especially for flow injection analysis systems.

  19. A microfluidic device based on an evaporation-driven micropump.

    PubMed

    Nie, Chuan; Frijns, Arjan J H; Mandamparambil, Rajesh; den Toonder, Jaap M J

    2015-04-01

    In this paper we introduce a microfluidic device ultimately to be applied as a wearable sweat sensor. We show proof-of-principle of the microfluidic functions of the device, namely fluid collection and continuous fluid flow pumping. A filter-paper based layer, that eventually will form the interface between the device and the skin, is used to collect the fluid (e.g., sweat) and enter this into the microfluidic device. A controllable evaporation driven pump is used to drive a continuous fluid flow through a microfluidic channel and over a sensing area. The key element of the pump is a micro-porous membrane mounted at the channel outlet, such that a pore array with a regular hexagonal arrangement is realized through which the fluid evaporates, which drives the flow within the channel. The system is completely fabricated on flexible polyethylene terephthalate (PET) foils, which can be the backbone material for flexible electronics applications, such that it is compatible with volume production approaches like Roll-to-Roll technology. The evaporation rate can be controlled by varying the outlet geometry and the temperature. The generated flows are analyzed experimentally using Particle Tracking Velocimetry (PTV). Typical results show that with 1 to 61 pores (diameter = 250 μm, pitch = 500 μm) flow rates of 7.3 × 10(-3) to 1.2 × 10(-1) μL/min are achieved. When the surface temperature is increased by 9.4°C, the flow rate is increased by 130 %. The results are theoretically analyzed using an evaporation model that includes an evaporation correction factor. The theoretical and experimental results are in good agreement.

  20. Methods for integrating a functional component into a microfluidic device

    DOEpatents

    Simmons, Blake; Domeier, Linda; Woo, Noble; Shepodd, Timothy; Renzi, Ronald F.

    2014-08-19

    Injection molding is used to form microfluidic devices with integrated functional components. One or more functional components are placed in a mold cavity, which is then closed. Molten thermoplastic resin is injected into the mold and then cooled, thereby forming a solid substrate including the functional component(s). The solid substrate including the functional component(s) is then bonded to a second substrate, which may include microchannels or other features.

  1. Acoustofluidics 14: Applications of acoustic streaming in microfluidic devices.

    PubMed

    Wiklund, Martin; Green, Roy; Ohlin, Mathias

    2012-07-21

    In part 14 of the tutorial series "Acoustofluidics--exploiting ultrasonic standing wave forces and acoustic streaming in microfluidic systems for cell and particle manipulation", we provide a qualitative description of acoustic streaming and review its applications in lab-on-a-chip devices. The paper covers boundary layer driven streaming, including Schlichting and Rayleigh streaming, Eckart streaming in the bulk fluid, cavitation microstreaming and surface-acoustic-wave-driven streaming.

  2. Drug testing and flow cytometry analysis on a large number of uniform sized tumor spheroids using a microfluidic device

    PubMed Central

    Patra, Bishnubrata; Peng, Chien-Chung; Liao, Wei-Hao; Lee, Chau-Hwang; Tung, Yi-Chung

    2016-01-01

    Three-dimensional (3D) tumor spheroid possesses great potential as an in vitro model to improve predictive capacity for pre-clinical drug testing. In this paper, we combine advantages of flow cytometry and microfluidics to perform drug testing and analysis on a large number (5000) of uniform sized tumor spheroids. The spheroids are formed, cultured, and treated with drugs inside a microfluidic device. The spheroids can then be harvested from the device without tedious operation. Due to the ample cell numbers, the spheroids can be dissociated into single cells for flow cytometry analysis. Flow cytometry provides statistical information in single cell resolution that makes it feasible to better investigate drug functions on the cells in more in vivo-like 3D formation. In the experiments, human hepatocellular carcinoma cells (HepG2) are exploited to form tumor spheroids within the microfluidic device, and three anti-cancer drugs: Cisplatin, Resveratrol, and Tirapazamine (TPZ), and their combinations are tested on the tumor spheroids with two different sizes. The experimental results suggest the cell culture format (2D monolayer vs. 3D spheroid) and spheroid size play critical roles in drug responses, and also demonstrate the advantages of bridging the two techniques in pharmaceutical drug screening applications. PMID:26877244

  3. Drug testing and flow cytometry analysis on a large number of uniform sized tumor spheroids using a microfluidic device

    NASA Astrophysics Data System (ADS)

    Patra, Bishnubrata; Peng, Chien-Chung; Liao, Wei-Hao; Lee, Chau-Hwang; Tung, Yi-Chung

    2016-02-01

    Three-dimensional (3D) tumor spheroid possesses great potential as an in vitro model to improve predictive capacity for pre-clinical drug testing. In this paper, we combine advantages of flow cytometry and microfluidics to perform drug testing and analysis on a large number (5000) of uniform sized tumor spheroids. The spheroids are formed, cultured, and treated with drugs inside a microfluidic device. The spheroids can then be harvested from the device without tedious operation. Due to the ample cell numbers, the spheroids can be dissociated into single cells for flow cytometry analysis. Flow cytometry provides statistical information in single cell resolution that makes it feasible to better investigate drug functions on the cells in more in vivo-like 3D formation. In the experiments, human hepatocellular carcinoma cells (HepG2) are exploited to form tumor spheroids within the microfluidic device, and three anti-cancer drugs: Cisplatin, Resveratrol, and Tirapazamine (TPZ), and their combinations are tested on the tumor spheroids with two different sizes. The experimental results suggest the cell culture format (2D monolayer vs. 3D spheroid) and spheroid size play critical roles in drug responses, and also demonstrate the advantages of bridging the two techniques in pharmaceutical drug screening applications.

  4. Study of Chemotaxis and Cell–Cell Interactions in Cancer with Microfluidic Devices

    PubMed Central

    Sai, Jiqing; Rogers, Matthew; Hockemeyer, Kathryn; Wikswo, John P.; Richmond, Ann

    2017-01-01

    Microfluidic devices have very broad applications in biological assays from simple chemotaxis assays to much more complicated 3D bioreactors. In this chapter, we describe the design and methods for performing chemotaxis assays using simple microfluidic chemotaxis chambers. With these devices, using real-time video microscopy we can examine the chemotactic responses of neutrophil-like cells under conditions of varying gradient steepness or flow rate and then utilize software programs to calculate the speed and angles of cell migration as gradient steepness and flow are varied. Considering the shearing force generated on the cells by the constant flow that is required to produce and maintain a stable gradient, the trajectories of the cell migration will reflect the net result of both shear force generated by flow and the chemotactic force resulting from the chemokine gradient. Moreover, the effects of mutations in chemokine receptors or the presence of inhibitors of intracellular signals required for gradient sensing can be evaluated in real time. We also describe a method to monitor intracellular signals required for cells to alter cell polarity in response to an abrupt switch in gradient direction. Lastly, we demonstrate an in vitro method for studying the interactions of human cancer cells with human endothelial cells, fibroblasts, and leukocytes, as well as environmental chemokines and cytokines, using 3D microbioreactors that mimic the in vivo microenvironment. PMID:26921940

  5. Microfluidic devices to enrich and isolate circulating tumor cells

    PubMed Central

    Myung, J. H.; Hong, S.

    2015-01-01

    Given the potential clinical impact of circulating tumor cells (CTCs) in blood as a clinical biomarker for diagnosis and prognosis of various cancers, a myriad of detection methods for CTCs have been recently introduced. Among those, a series of microfluidic devices are particularly promising as these uniquely offer micro-scale analytical systems that are highlighted by low consumption of samples and reagents, high flexibility to accommodate other cutting-edge technologies, precise and well-defined flow behaviors, and automation capability, presenting significant advantages over the conventional larger scale systems. In this review, we highlight the advantages of microfluidic devices and their translational potential into CTC detection methods, categorized by miniaturization of bench-top analytical instruments, integration capability with nanotechnologies, and in situ or sequential analysis of captured CTCs. This review provides a comprehensive overview of recent advances in the CTC detection achieved through application of microfluidic devices and their challenges that these promising technologies must overcome to be clinically impactful. PMID:26549749

  6. Buckling delamination induced microchannel: Flow regulation in microfluidic devices

    NASA Astrophysics Data System (ADS)

    Kang, Jingtian; Wang, Changguo; Xue, Zhiming; Liu, Mengxiong; Tan, Huifeng

    2016-09-01

    The buckling delamination induced microchannel is employed to regulate fluid flow as a microvalve which can be utilized in microfluidic devices. This microvalve consists of a soft substrate and a stiff thin film, between which there is a pre-set small imperfection. Two critical strain values, namely, on-off strain and failure strain, have been proposed to determine the working strain interval using analytical predictions. Within this interval, the cross-sectional area of the microchannel can be controlled and predicted by different compressive strains of the film/substrate system. The fluid flow rate within this microchannel can be then estimated by both analytical and numerical simulations and adjusted to satisfy different values by alternating the compressive strain. In addition, a demonstrative experiment has been taken to verify the feasibility of this approach. This flexible microvalve has potential in the application where the use of traditional rigid microvalves is improper in flexible microfluidic devices. The method and approach of this paper can provide a general guide for flow rate control in microfluidic devices.

  7. Microfluidic device integration of electrostatic corral trapping systems

    NASA Astrophysics Data System (ADS)

    Amin-Patel, Alaknanda P.

    This thesis describes the development, characterization, and application of the microfluidics device integration of electrostatic corral trapping systems. Optical traps or "laser tweezers", which are capable of trapping microscopic dielectric particles through the production of steep electromagnetic field gradients, have been significant in the development of the field of biophysics and the manipulation of microscopic objects. This method of trapping unfortunately has a fundamental size limitation, making it incapable of trapping molecular-scale objects. We have developed a new tool for the trapping and manipulation of nanoscale objects including single molecules, the corral trap, which has distinct characteristics that set it apart from other trapping techniques. In order to increase the versatility of this new trapping tool, steps have been taken to integrate corral traps in a microfluidic cell. The production of such integrated devices based on optical lithography techniques will be presented in detail. Corral trapping in microfluidics device is expected to have important future applications in areas such as biomedical assays, ultra-sensitive biochemical analysis, and DNA manipulation and screening. Novelty: A novel method for the trapping of single molecules has been successfully used for the trapping of single ssDNA molecules.

  8. Microfluidic structures for LOC devices designed by laser lithography

    NASA Astrophysics Data System (ADS)

    Figurova, M.; Pudis, D.; Gaso, P.

    2016-12-01

    Nowadays, lab on a chip (LOC) applications are very popular in the field of biomedicine. LOC device works with biological materials and enables to arrange conventional laboratory operations on a small chip. Philosophy of LOC applications stands on quick and precise diagnostics process and technology, which uses cheap materials with possibility of rapid prototyping. LOC, as a time saving application, works with small volume of samples and reagents and enables better control over the sample. We present fabrication method of functional LOC chip for different biomedical microfluidic applications based on direct laser writing (DLW) lithography. We present fabrication of few types of microfluidic and micro-optic structures with different capabilities created by DLW system. The combination of DLW lithography in photoresist layer deposited on glass substrate and polydimethylsiloxane (PDMS) replica molding process were used for patterning of designed microstructures. Prepared microfluidic and micro-optic structures were observed by confocal microscope and microfluidic flow observations were investigated by conventional optical microscope and CCD camera.

  9. 3D-FBK Pixel Sensors: Recent Beam Tests Results with Irradiated Devices

    SciTech Connect

    Micelli, A.; Helle, K.; Sandaker, H.; Stugu, B.; Barbero, M.; Hugging, F.; Karagounis, M.; Kostyukhin, V.; Kruger, H.; Tsung, J.W.; Wermes, N.; Capua, M.; Fazio, S.; Mastroberardino, A.; Susinno, G.; Gallrapp, C.; Di Girolamo, B.; Dobos, D.; La Rosa, A.; Pernegger, H.; Roe, S.; /CERN /Prague, Tech. U. /Prague, Tech. U. /Freiburg U. /Freiburg U. /Freiburg U. /INFN, Genoa /Genoa U. /INFN, Genoa /Genoa U. /INFN, Genoa /Genoa U. /INFN, Genoa /Genoa U. /INFN, Genoa /Genoa U. /Glasgow U. /Glasgow U. /Glasgow U. /Hawaii U. /Barcelona, IFAE /Barcelona, IFAE /LBL, Berkeley /Barcelona, IFAE /LBL, Berkeley /LBL, Berkeley /Manchester U. /Manchester U. /Manchester U. /Manchester U. /Manchester U. /Manchester U. /Manchester U. /Manchester U. /Manchester U. /New Mexico U. /New Mexico U. /Oslo U. /Oslo U. /Oslo U. /Oslo U. /Oslo U. /SLAC /SLAC /SLAC /SLAC /SLAC /SLAC /SLAC /SLAC /SLAC /SUNY, Stony Brook /SUNY, Stony Brook /SUNY, Stony Brook /INFN, Trento /Trento U. /INFN, Trento /Trento U. /INFN, Trento /Trento U. /INFN, Trieste /Udine U. /INFN, Trieste /Udine U. /INFN, Trieste /Udine U. /INFN, Trieste /Udine U. /INFN, Trieste /Udine U. /INFN, Trieste /Udine U. /Barcelona, Inst. Microelectron. /Barcelona, Inst. Microelectron. /Barcelona, Inst. Microelectron. /Fond. Bruno Kessler, Trento /Fond. Bruno Kessler, Trento /Fond. Bruno Kessler, Trento /Fond. Bruno Kessler, Trento /Fond. Bruno Kessler, Trento /SINTEF, Oslo /SINTEF, Oslo /SINTEF, Oslo /SINTEF, Oslo /VTT Electronics, Espoo /VTT Electronics, Espoo

    2012-04-30

    The Pixel Detector is the innermost part of the ATLAS experiment tracking device at the Large Hadron Collider, and plays a key role in the reconstruction of the primary vertices from the collisions and secondary vertices produced by short-lived particles. To cope with the high level of radiation produced during the collider operation, it is planned to add to the present three layers of silicon pixel sensors which constitute the Pixel Detector, an additional layer (Insertable B-Layer, or IBL) of sensors. 3D silicon sensors are one of the technologies which are under study for the IBL. 3D silicon technology is an innovative combination of very-large-scale integration and Micro-Electro-Mechanical-Systems where electrodes are fabricated inside the silicon bulk instead of being implanted on the wafer surfaces. 3D sensors, with electrodes fully or partially penetrating the silicon substrate, are currently fabricated at different processing facilities in Europe and USA. This paper reports on the 2010 June beam test results for irradiated 3D devices produced at FBK (Trento, Italy). The performance of these devices, all bump-bonded with the ATLAS pixel FE-I3 read-out chip, is compared to that observed before irradiation in a previous beam test.

  10. Scalable Iterative Solvers Applied to 3D Parallel Simulation of Advanced Semiconductor Devices

    NASA Astrophysics Data System (ADS)

    García-Loureiro, A. J.; Aldegunde, M.; Seoane, N.

    2009-08-01

    We have studied the performance of a preconditioned iterative solver to speed up a 3D semiconductor device simulator. Since 3D simulations necessitate large computing resources, the choice of algorithms and their parameters become of utmost importance. This code uses a density gradient drift-diffusion semiconductor transport model based on the finite element method which is one of the most general and complex discretisation techniques. It has been implemented for a distributed memory multiprocessor environment using the Message Passing Interface (MPI) library. We have applied this simulator to a 67 nm effective gate length Si MOSFET.

  11. Method for a microfluidic weaklink device

    DOEpatents

    Shepodd, Timothy J.; Duncan, Matthew P.

    2009-12-01

    The present invention relates to an electrokinetic (EK) pump capable of creating high pressures electroosmotically, and capable of retaining high pressures. Both pressure creation and retention are accomplished without the need for moving parts. The EK pump uses a polymerizable fluid that creates the pressure-retaining seal within the EK pump when polymerization is initiated, typically by exposure to UV radiation. Weaklink devices are advantageously constructed including such a pressure-retaining EK pump since, among other advantages, the response of the weaklink device relies on predictable and reliable chemical polymerization reactions.

  12. Fabrication of microfluidic devices containing patterned microwell arrays.

    PubMed

    Henley, W Hampton; Dennis, Patty J; Ramsey, J Michael

    2012-02-07

    A rapid fabrication and prototyping technique to incorporate microwell arrays with sub-10 μm features within a single layer of microfluidic circuitry is presented. Typically, the construction of devices that incorporate very small architecture within larger components has required the assembly of multiple elements to form a working device. Rapid, facile production of a working device using only a single layer of molded polydimethylsiloxane (PDMS) and a glass support substrate is achieved with the reported fabrication technique. A combination of conventional wet-chemical etching for larger (≥20 μm) microchannel features and focused ion beam (FIB) milling for smaller (≤10 μm) microwell features was used to fabricate a monolithic glass master mold. PDMS/glass hybrid chips were then produced using simple molding and oxygen plasma bonding methods. Microwell structures were loaded with 3 μm antibody-functionalized dye-encoded polystyrene spheres, and a sandwich immunoassay for common cytokines was performed to demonstrate proof-of-principle. Potential applications for this device include highly parallel multiplexed sandwich immunoassays, DNA/RNA hybridization analyses, and enzyme linked immunosorbent assay (ELISA). The fabrication technique described can be used for rapid prototyping of devices wherever submicrometer- to micrometer-sized features are incorporated into a microfluidic device.

  13. An integrated microfluidic device for two-dimensional combinatorial dilution†

    PubMed Central

    Jang, Yun-Ho; Hancock, Matthew J.; Kim, Sang Bok; Selimović, Šeila; Sim, Woo Young; Bae, Hojae; Khademhosseini, Ali

    2012-01-01

    High-throughput preparation of multi-component solutions is an integral process in biology, chemistry and materials science for screening, diagnostics and analysis. Compact microfluidic systems enable such processing with low reagent volumes and rapid testing. Here we present a microfluidic device that incorporates two gradient generators, a tree-like generator and a new microfluidic active injection system, interfaced by intermediate solution reservoirs to generate diluted combinations of input solutions within an 8 × 8 or 10 × 10 array of isolated test chambers. Three input solutions were fed into the device, two to the tree-like gradient generator and one to pre-fill the test chamber array. The relative concentrations of these three input solutions in the test chambers completely characterized device behaviour and were controlled by the number of injection cycles and the flow rate. Device behaviour was modelled by computational fluid dynamics simulations and an approximate analytic formula. The device may be used for two-dimensional (2D) combinatorial dilution by adding two solutions in different relative concentrations to each of its three inputs. By appropriate choice of the two-component input solutions, test chamber concentrations that span any triangle in 2D concentration space may be obtained. In particular, explicit inputs are given for a coarse screening of a large region in concentration space followed by a more refined screening of a smaller region, including alternate inputs that span the same concentration region but with different distributions. The ability to probe arbitrary subspaces of concentration space and to control the distribution of discrete test points within those subspaces makes the device of potential benefit for high-throughput cell biology studies and drug screening. PMID:21837312

  14. Continuous separation of blood cells in spiral microfluidic devices

    PubMed Central

    Nivedita, Nivedita; Papautsky, Ian

    2013-01-01

    Blood cell sorting is critical to sample preparation for both clinical diagnosis and therapeutic research. The spiral inertial microfluidic devices can achieve label-free, continuous separation of cell mixtures with high throughput and efficiency. The devices utilize hydrodynamic forces acting on cells within laminar flow, coupled with rotational Dean drag due to curvilinear microchannel geometry. Here, we report on optimized Archimedean spiral devices to achieve cell separation in less than 8 cm of downstream focusing length. These improved devices are small in size (<1 in.2), exhibit high separation efficiency (∼95%), and high throughput with rates up to 1 × 106 cells per minute. These device concepts offer a path towards possible development of a lab-on-chip for point-of-care blood analysis with high efficiency, low cost, and reduced analysis time. PMID:24404064

  15. Devices for the production and sorting of microfluidic droplets

    NASA Astrophysics Data System (ADS)

    Aubrecht, Donald; Heyman, John; Agresti, Jeremy; Köster, Sarah; Weitz, David

    2010-03-01

    Droplets produced in microfluidic devices are a great set of tools for studying large cell populations and permutations of reactions. Sample populations of 10^6 - 10^7 can be studied with relative ease, as encapsulation and screening rates in the kHz range are accessible. Previous droplet work has shown encapsulation of cells in droplets allows individual cells and their products to be studied. Advantages include correlation between detected products and initial drop contents, as well as minimized sample cross-contamination. Most microfluidic-based biological assays rely on fluorescent labeling of cells or use of cellular products to initiate a fluorescence-producing reaction. Detection of the fluorescence provides a trigger for sorting those cells or cell-containing droplets away from the general population. Though this allows some cellular processes to be studied, detection and quantification of all products, not just those expressed to the cell surface or those that catalyze reactions, would impact development of better therapeutics. We are currently working to adapt benchtop biological assays that label and detect cellular products for use in a droplet-based system. The work presented here details the chain of modular microfluidic devices we use to encapsulate, incubate, interrogate, and sort a population of droplets containing a model system.

  16. Super resolution imaging and nanoscale magnetic detection in microfluidic device

    NASA Astrophysics Data System (ADS)

    Lim, Kangmook

    Nanoscale sensing and imaging tools are the most emerging techniques in fields of nanoscience research and engineering. To demonstrate nanoscale sensing and imaging tools, it is required to achieve high sensitivity and spatial resolution simultaneously. By fulfilling the requirements, this thesis describes mainly two different scanning applications employing quantum probes and nanoparticle positioning technique using fluid flow control. First, we develop a method that can systematically probe the distortion of an emitter's diffraction spot near a nanoparticle in a microfluidic device. The results provide a better fundamental understanding of near-field coupling between emitters and nanophotonic structures. We demonstrate that by monitoring the distortion of the diffraction spot we can perform highly accurate imaging of the nanoparticle with 8 nm spatial precision. Next, we develop a method to perform localized magnetometry in a microfluidic device with a 48 nm spatial precision. We map out the local field distribution of a magnetic nanoparticle by manipulating it in the vicinity of an immobilized single NV center and optically detecting the induced Zeeman shift with a magnetic field sensitivity of 17.5 muT Hz-1/2. Finally, we introduce a scanning magnetic field technique that employs multiple NV centers in diamond nanocrystals suspended in microfluidic channels. This technique has advantages of short acquisition time over wide-field with nanoscale spatial resolution. The advantages make our technique attractive to a wide range of magnetic imaging applications in fluidic environments and biophysical systems.

  17. Adhesion and formation of microbial biofilms in complex microfluidic devices

    SciTech Connect

    Kumar, Aloke; Karig, David K; Neethirajan, Suresh; Suresh, Anil K; Srijanto, Bernadeta R; Mukherjee, Partha P; Retterer, Scott T; Doktycz, Mitchel John

    2012-01-01

    Shewanella oneidensis is a metal reducing bacterium, which is of interest for bioremediation and clean energy applications. S. oneidensis biofilms play a critical role in several situations such as in microbial energy harvesting devices. Here, we use a microfluidic device to quantify the effects of hydrodynamics on the biofilm morphology of S. oneidensis. For different rates of fluid flow through a complex microfluidic device, we studied the spatiotemporal dynamics of biofilms, and we quantified several morphological features such as spatial distribution, cluster formation and surface coverage. We found that hydrodynamics resulted in significant differences in biofilm dynamics. The baffles in the device created regions of low and high flow in the same device. At higher flow rates, a nonuniform biofilm develops, due to unequal advection in different regions of the microchannel. However, at lower flow rates, a more uniform biofilm evolved. This depicts competition between adhesion events, growth and fluid advection. Atomic force microscopy (AFM) revealed that higher production of extra-cellular polymeric substances (EPS) occurred at higher flow velocities.

  18. Magnetophoretic-based microfluidic device for DNA Concentration.

    PubMed

    Shim, Sangjo; Shim, Jiwook; Taylor, William R; Kosari, Farhad; Vasmatzis, George; Ahlquist, David A; Bashir, Rashid

    2016-04-01

    Nucleic acids serve as biomarkers of disease and it is highly desirable to develop approaches to extract small number of such genomic extracts from human bodily fluids. Magnetic particles-based nucleic acid extraction is widely used for concentration of small amount of samples and is followed by DNA amplification in specific assays. However, approaches to integrate such magnetic particles based capture with micro and nanofluidic based assays are still lacking. In this report, we demonstrate a magnetophoretic-based approach for target-specific DNA extraction and concentration within a microfluidic device. This device features a large chamber for reducing flow velocity and an array of μ-magnets for enhancing magnetic flux density. With this strategy, the device is able to collect up to 95 % of the magnetic particles from the fluidic flow and to concentrate these magnetic particles in a collection region. Then an enzymatic reaction is used to detach the DNA from the magnetic particles within the microfluidic device, making the DNA available for subsequent analysis. Concentrations of over 1000-fold for 90 bp dsDNA molecules is demonstrated. This strategy can bridge the gap between detection of low concentration analytes from clinical samples and a range of micro and nanofluidic sensors and devices including nanopores, nano-cantilevers, and nanowires.

  19. Multilayer Microfluidic Devices Created From A Single Photomask

    SciTech Connect

    Kelly, Ryan T.; Sheen, Allison M.; Jambovane, Sachin R.

    2013-08-28

    The time and expense associated with high quality photomask production can discourage the creation of multilayer microfluidic devices, as each layer currently requires a separate photomask. Here we describe an approach in which multilayer microfabricated devices can be created from a single photomask. The separate layers and their corresponding alignment marks are arranged in separate halves of the mask for two layer devices or quadrants for four layer devices. Selective exposure of the photomask features and rotation of the device substrate between exposures result in multiple copies of the devices on each wafer. Subsequent layers are aligned to patterned features on the substrate with the same alignment accuracy as when multiple photomasks are used. We demonstrate this approach for fabricating devices employing multilayer soft lithography (MSL) for pneumatic valving. MSL devices containing as many as 5 layers (4 aligned fluidic layers plus a manually aligned control layer) were successfully created using this approach. Device design is also modularized, enabling the presence or absence of features as well as channel heights to be selected independently from one another. The use of a single photomask to create multilayer devices results in a dramatic savings of time and/or money required to advance from device design to completed prototype.

  20. High-resolution real-time 3D shape measurement on a portable device

    NASA Astrophysics Data System (ADS)

    Karpinsky, Nikolaus; Hoke, Morgan; Chen, Vincent; Zhang, Song

    2013-09-01

    Recent advances in technology have enabled the acquisition of high-resolution 3D models in real-time though the use of structured light scanning techniques. While these advances are impressive, they require large amounts of computing power, thus being limited to using large desktop computers with high end CPUs and sometimes GPUs. This is undesirable in making high-resolution real-time 3D scanners ubiquitous in our mobile lives. To address this issue, this work describes and demonstrates a real-time 3D scanning system that is realized on a mobile device, namely a laptop computer, which can achieve speeds of 20fps 3D at a resolution of 640x480 per frame. By utilizing a graphics processing unit (GPU) as a multipurpose parallel processor, along with a parallel phase shifting technique, we are able to realize the entire 3D processing pipeline in parallel. To mitigate high speed camera transfer problems, which typically require a dedicated frame grabber, we make use of USB 3.0 along with direct memory access (DMA) to transfer camera images to the GPU. To demonstrate the effectiveness of the technique, we experiment with the scanner on both static geometry of a statue and dynamic geometry of a deforming material sample in front of the system.

  1. Enzymatic reactions in microfluidic devices: Michaelis-Menten kinetics.

    PubMed

    Ristenpart, William D; Wan, Jiandi; Stone, Howard A

    2008-05-01

    Kinetic rate constants for enzymatic reactions are typically measured with a series of experiments at different substrate concentrations in a well-mixed container. Here we demonstrate a microfluidic technique for measuring Michaelis-Menten rate constants with only a single experiment. Enzyme and substrate are brought together in a coflow microfluidic device, and we establish analytically and numerically that the initial concentration of product scales with the distance x along the channel as x5/2. Measurements of the initial rate of product formation, combined with the quasi-steady rate of product formation further downstream, yield the rate constants. We corroborate the x5/2 scaling result experimentally using the bioluminescent reaction between ATP and luciferase/luciferin as a model system.

  2. Electrostatic charging and control of droplets in microfluidic devices.

    PubMed

    Zhou, Hongbo; Yao, Shuhuai

    2013-03-07

    Precharged droplets can facilitate manipulation and control of low-volume liquids in droplet-based microfluidics. In this paper, we demonstrate non-contact electrostatic charging of droplets by polarizing a neutral droplet and splitting it into two oppositely charged daughter droplets in a T-junction microchannel. We performed numerical simulation to analyze the non-contact charging process and proposed a new design with a notch at the T-junction in aid of droplet splitting for more efficient charging. We experimentally characterized the induced charge in droplets in microfabricated devices. The experimental results agreed well with the simulation. Finally, we demonstrated highly effective droplet manipulation in a path selection unit appending to the droplet charging. We expect our work could enable precision manipulation of droplets for more complex liquid handling in microfluidics and promote electric-force based manipulation in 'lab-on-a-chip' systems.

  3. An efficient solid modeling system based on a hand-held 3D laser scan device

    NASA Astrophysics Data System (ADS)

    Xiong, Hanwei; Xu, Jun; Xu, Chenxi; Pan, Ming

    2014-12-01

    The hand-held 3D laser scanner sold in the market is appealing for its port and convenient to use, but price is expensive. To develop such a system based cheap devices using the same principles as the commercial systems is impossible. In this paper, a simple hand-held 3D laser scanner is developed based on a volume reconstruction method using cheap devices. Unlike convenient laser scanner to collect point cloud of an object surface, the proposed method only scan few key profile curves on the surface. Planar section curve network can be generated from these profile curves to construct a volume model of the object. The details of design are presented, and illustrated by the example of a complex shaped object.

  4. Method for forming polymerized microfluidic devices

    DOEpatents

    Sommer, Gregory J [Livermore, CA; Hatch, Anson V [Tracy, CA; Wang, Ying-Chih [Pleasanton, CA; Singh, Anup K [Danville, CA; Renzi, Ronald F [Tracy, CA; Claudnic, Mark R [Livermore, CA

    2011-11-01

    Methods for making a micofluidic device according to embodiments of the present invention include defining a cavity. Polymer precursor solution is positioned in the cavity, and exposed to light to begin the polymerization process and define a microchannel. In some embodiments, after the polymerization process is partially complete, a solvent rinse is performed, or fresh polymer precursor introduced into the microchannel. This may promote removal of unpolymerized material from the microchannel and enable smaller feature sizes. The polymer precursor solution may contain an iniferter. Polymerized features therefore may be capped with the iniferter, which is photoactive. The iniferter may aid later binding of a polyacrylamide gel to the microchannel surface.

  5. [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.

  6. Fabrication improvements for thermoset polyester (TPE) microfluidic devices.

    PubMed

    Fiorini, Gina S; Yim, Moonbin; Jeffries, Gavin D M; Schiro, Perry G; Mutch, Sarah A; Lorenz, Robert M; Chiu, Daniel T

    2007-07-01

    Thermoset polyester (TPE) microfluidic devices were previously developed as an alternative to poly(dimethylsiloxane) (PDMS) devices, fabricated similarly by replica molding, yet offering stable surface properties and good chemical compatibility with some organics that are incompatible with PDMS. This paper describes a number of improvements in the fabrication of TPE chips. Specifically, we describe methods to form TPE devices with a thin bottom layer for use with high numerical aperture (NA) objectives for sensitive fluorescence detection and optical manipulation. We also describe plasma-bonding of TPE to glass to create hybrid TPE-glass devices. We further present a simple master-pretreatment method to replace our original technique that required the use of specialized equipment.

  7. Acoustophoretic Sorting of Viable Mammalian Cells in a Microfluidic Device

    PubMed Central

    Yang, Allen H. J.; Soh, H. Tom

    2013-01-01

    We report the first use of ultrasonic acoustophoresis for the label-free separation of viable and nonviable mammalian cells within a microfluidic device. Cells that have undergone apoptosis are physically smaller than viable cells, and our device exploits this fact to achieve efficient sorting based on the strong size dependence of acoustic radiation forces within a microchannel. As a model, we have selectively enriched viable MCF-7 breast tumor cells from heterogeneous mixtures of viable and nonviable cells. We found that this mode of separation is gentle and enables efficient, label-free isolation of viable cells from mixed samples containing 106 cells/mL at flow rates of up to 12 mL/h. We have extensively characterized the device, and we report the effects of piezoelectric voltage and sample flow rate on device performance and describe how these parameters can be tuned to optimize recovery, purity, or throughput. PMID:23157478

  8. Intracavity Microfluidic Laser Device for Single Cell Analysis

    NASA Astrophysics Data System (ADS)

    Gourley, Paul

    2015-03-01

    An intracavity microfluidic laser device has been developed to study bioparticles ranging in size from 50 nm to 20 μm (virons to organelles to whole cells). The versatile device can be operated used in several modes including static or flowing fluids, with or without molecular labels, and microscopic imaging and/or spectroscopy. It enables advantageous new ways to perform analyses of bioparticles for applications including cell biology, detection of disease and pathogens, environmental monitoring, pharmaceuticals, agriculture, and food processing. This talk will briefly summarize the physics of the device including its laser optics, fluid dynamics, and intracavity light interaction with cells. The talk will then focus on results of a study of mitochondria in normal and cancer liver cells. The study examines the transformation of intracellular and isolated mitochondria from the normal to disease state. The results highlight the unique utility of the device to rapidly assess biophysical changes arising from altered biomolecular states of cells and organelles.

  9. Analysis of Uncertainty in a Middle-Cost Device for 3D Measurements in BIM Perspective

    PubMed Central

    Sánchez, Alonso; Naranjo, José-Manuel; Jiménez, Antonio; González, Alfonso

    2016-01-01

    Medium-cost devices equipped with sensors are being developed to get 3D measurements. Some allow for generating geometric models and point clouds. Nevertheless, the accuracy of these measurements should be evaluated, taking into account the requirements of the Building Information Model (BIM). This paper analyzes the uncertainty in outdoor/indoor three-dimensional coordinate measures and point clouds (using Spherical Accuracy Standard (SAS) methods) for Eyes Map, a medium-cost tablet manufactured by e-Capture Research & Development Company, Mérida, Spain. To achieve it, in outdoor tests, by means of this device, the coordinates of targets were measured from 1 to 6 m and cloud points were obtained. Subsequently, these were compared to the coordinates of the same targets measured by a Total Station. The Euclidean average distance error was 0.005–0.027 m for measurements by Photogrammetry and 0.013–0.021 m for the point clouds. All of them satisfy the tolerance for point cloud acquisition (0.051 m) according to the BIM Guide for 3D Imaging (General Services Administration); similar results are obtained in the indoor tests, with values of 0.022 m. In this paper, we establish the optimal distances for the observations in both, Photogrammetry and 3D Photomodeling modes (outdoor) and point out some working conditions to avoid in indoor environments. Finally, the authors discuss some recommendations for improving the performance and working methods of the device. PMID:27669245

  10. Analysis of Uncertainty in a Middle-Cost Device for 3D Measurements in BIM Perspective.

    PubMed

    Sánchez, Alonso; Naranjo, José-Manuel; Jiménez, Antonio; González, Alfonso

    2016-09-22

    Medium-cost devices equipped with sensors are being developed to get 3D measurements. Some allow for generating geometric models and point clouds. Nevertheless, the accuracy of these measurements should be evaluated, taking into account the requirements of the Building Information Model (BIM). This paper analyzes the uncertainty in outdoor/indoor three-dimensional coordinate measures and point clouds (using Spherical Accuracy Standard (SAS) methods) for Eyes Map, a medium-cost tablet manufactured by e-Capture Research & Development Company, Mérida, Spain. To achieve it, in outdoor tests, by means of this device, the coordinates of targets were measured from 1 to 6 m and cloud points were obtained. Subsequently, these were compared to the coordinates of the same targets measured by a Total Station. The Euclidean average distance error was 0.005-0.027 m for measurements by Photogrammetry and 0.013-0.021 m for the point clouds. All of them satisfy the tolerance for point cloud acquisition (0.051 m) according to the BIM Guide for 3D Imaging (General Services Administration); similar results are obtained in the indoor tests, with values of 0.022 m. In this paper, we establish the optimal distances for the observations in both, Photogrammetry and 3D Photomodeling modes (outdoor) and point out some working conditions to avoid in indoor environments. Finally, the authors discuss some recommendations for improving the performance and working methods of the device.

  11. Microfluidic Devices with Photodefinable Pseudo-valves for Protein Separation

    NASA Astrophysics Data System (ADS)

    Fan, Z. Hugh

    Plastic microfluidic devices are fabricated with an array of pseudo-valves for two-dimensional (2D) protein separation. The devices are made by compression molding; the mold is created by electroplating on a glass master fabricated by photolithography. Each device consists of one channel for isoelectric focusing (IEF) and multiple parallel channels for polyacrylamide gel electrophoresis (PAGE). The IEF channel (first dimension) is orthogonal to the PAGE channels (second dimension). Microfluidic pseudo-valves are created at the intersections of orthogonal channels by photodefinable, in situ gel polymerization. These valves enable the introduction of two types of separation media into orthogonal channels for performing 2D protein separation in the device. The presence of the pseudo-valves prevents one separation medium from being contaminated by the other medium, although proteins are allowed to transfer from the first to the second dimension under an electric field. Two-dimensional protein separation is achieved in less than 10 min, an improvement of two orders of magnitude compared with the conventional 2D gel electrophoresis using an IEF strip and a PAGE slab.

  12. 3D microfilter device for viable circulating tumor cell (CTC) enrichment from blood.

    PubMed

    Zheng, Siyang; Lin, Henry K; Lu, Bo; Williams, Anthony; Datar, Ram; Cote, Richard J; Tai, Yu-Chong

    2011-02-01

    Detection of circulating tumor cells has emerged as a promising minimally invasive diagnostic and prognostic tool for patients with metastatic cancers. We report a novel three dimensional microfilter device that can enrich viable circulating tumor cells from blood. This device consists of two layers of parylene membrane with pores and gap precisely defined with photolithography. The positions of the pores are shifted between the top and bottom membranes. The bottom membrane supports captured cells and minimize the stress concentration on cell membrane and sustain cell viability during filtration. Viable cell capture on device was investigated with scanning electron microscopy, confocal microscopy, and immunofluorescent staining using model systems of cultured tumor cells spiked in blood or saline. The paper presents and validates this new 3D microfiltration concept for circulation tumor cell enrichment application. The device provides a highly valuable tool for assessing and characterizing viable enriched circulating tumor cells in both research and clinical settings.

  13. Testing a Novel 3D Printed Radiographic Imaging Device for Use in Forensic Odontology.

    PubMed

    Newcomb, Tara L; Bruhn, Ann M; Giles, Bridget; Garcia, Hector M; Diawara, Norou

    2017-01-01

    There are specific challenges related to forensic dental radiology and difficulties in aligning X-ray equipment to teeth of interest. Researchers used 3D printing to create a new device, the combined holding and aiming device (CHAD), to address the positioning limitations of current dental X-ray devices. Participants (N = 24) used the CHAD, soft dental wax, and a modified external aiming device (MEAD) to determine device preference, radiographer's efficiency, and technique errors. Each participant exposed six X-rays per device for a total of 432 X-rays scored. A significant difference was found at the 0.05 level between the three devices (p = 0.0015), with the MEAD having the least amount of total errors and soft dental wax taking the least amount of time. Total errors were highest when participants used soft dental wax-both the MEAD and the CHAD performed best overall. Further research in forensic dental radiology and use of holding devices is needed.

  14. Interpretation and mapping of geological features using mobile devices for 3D outcrop modelling

    NASA Astrophysics Data System (ADS)

    Buckley, Simon J.; Kehl, Christian; Mullins, James R.; Howell, John A.

    2016-04-01

    Advances in 3D digital geometric characterisation have resulted in widespread adoption in recent years, with photorealistic models utilised for interpretation, quantitative and qualitative analysis, as well as education, in an increasingly diverse range of geoscience applications. Topographic models created using lidar and photogrammetry, optionally combined with imagery from sensors such as hyperspectral and thermal cameras, are now becoming commonplace in geoscientific research. Mobile devices (tablets and smartphones) are maturing rapidly to become powerful field computers capable of displaying and interpreting 3D models directly in the field. With increasingly high-quality digital image capture, combined with on-board sensor pose estimation, mobile devices are, in addition, a source of primary data, which can be employed to enhance existing geological models. Adding supplementary image textures and 2D annotations to photorealistic models is therefore a desirable next step to complement conventional field geoscience. This contribution reports on research into field-based interpretation and conceptual sketching on images and photorealistic models on mobile devices, motivated by the desire to utilise digital outcrop models to generate high quality training images (TIs) for multipoint statistics (MPS) property modelling. Representative training images define sedimentological concepts and spatial relationships between elements in the system, which are subsequently modelled using artificial learning to populate geocellular models. Photorealistic outcrop models are underused sources of quantitative and qualitative information for generating TIs, explored further in this research by linking field and office workflows through the mobile device. Existing textured models are loaded to the mobile device, allowing rendering in a 3D environment. Because interpretation in 2D is more familiar and comfortable for users, the developed application allows new images to be captured

  15. Process monitor of 3D-device features by using FIB and CD-SEM

    NASA Astrophysics Data System (ADS)

    Kawada, Hiroki; Ikota, Masami; Sakai, Hideo; Torikawa, Shota; Tomimatsu, Satoshi; Onishi, Tsuyoshi

    2016-03-01

    For yield improvement of 3D-device manufacturing, metrology for the variability of individual device-features is on hot issue. Transmission Electron Microscope (TEM) can be used for monitoring the individual cross-section. However, efficiency of process monitoring is limited by the speed of measurement including preparation of lamella sample. In this work we demonstrate speedy 3D-profile measurement of individual line-features without the lamella sampling. For instance, we make a-few-micrometer-wide and 45-degree-descending slope in dense line-features by using Focused Ion Beam (FIB) tool capable of 300mm-wafer. On the descending slope, obliquely cut cross-section of the line features appears. Then, we transfer the wafer to Critical-Dimension Secondary Electron Microscope (CDSEM) to measure the oblique cross-section in normal top-down view. As the descending angle is 45 degrees, the oblique cross-section looks like a cross-section normal to the wafer surface. For every single line-features the 3D dimensions are measured. To the reference metrology of the Scanning TEM (STEM), nanometric linearity and precision are confirmed for the height and the width under the hard mask of the line features. Without cleaving wafer the 60 cells on the wafer can be measured in 3 hours, which allows us of near-line process monitor of in-wafer uniformity.

  16. A serial dilution microfluidic device for cytotoxicity assays.

    PubMed

    O'Neill, Adrian T; Monteiro-Riviere, Nancy; Walker, Glenn M

    2006-01-01

    A novel microfluidic device is presented which creates a linear serial dilution of two input fluid streams. This platform facilitates higher productivity as a component of a high throughput cytotoxicity testing strategy. A modeling solution is presented to create custom linear dilution schemes. The featured device creates a serial dilution of two solutions in the range of 1:9 through 9:1 across nine discrete dilutions. It has been validated to create a highly linear progression of dilutions with an R2 value of 0.9993. The device functions equivalently over a wide range of flow rates. The standard deviation of dilution values averages 0.76% over six flow rates spanning 0.5 to 16 microl min(-1).

  17. Microfluidic whole genome amplification device for single cell sequencing.

    PubMed

    Yu, Zhilong; Lu, Sijia; Huang, Yanyi

    2014-10-07

    We developed a microfluidic device to perform multiplex single-cell whole-genome amplification (WGA) using multiple annealing and looping-based amplification cycles (MALBAC). This device, made of polydimethylsiloxane (PDMS), allows us to monitor the whole process of cell loading and single-cell WGA for sequencing. We show that the genome coverage of MALBAC amplifications is reproducible between chambers on a single chip and between different chips, which enables data normalization using standard samples to accurately identify copy number variations (CNVs). This device provides an easy-to-operate approach to perform single cell sequencing library preparation with minimum hands-on time. It reduces the requirement of manual expertise as well as the risk of contamination, which is essential in future applications especially the medical diagnosis.

  18. Investigation of bacterial chemotaxis in flow-based microfluidic devices.

    PubMed

    Englert, Derek L; Manson, Michael D; Jayaraman, Arul

    2010-05-01

    The plug-in-pond and capillary assays are convenient methods for measuring attractant and repellent bacterial chemotaxis. However, these assays do not provide quantitative information on the extent of migration and are not well-suited for investigating repellent taxis. Here, we describe a protocol for a flow-based microfluidic system (microFlow) to quantitatively investigate chemotaxis in response to concentration gradients of attractants and repellents. The microFlow device uses diffusive mixing to generate concentration gradients that are stable throughout the chemotaxis chamber and for the duration of the experiment. The gradients may be of any desired absolute concentration and gradient strength. GFP-expressing bacteria immediately encounter a stable concentration gradient when they enter the chemotaxis chamber, and the migration in response to the gradient is monitored by microscopy. The effects of different parameters that influence the extent of migration in the microFlow device-preparation of the motile bacterial population preparation, strength of the concentration gradient and duration of exposure to the gradient-are discussed in the context of repellent taxis of chemotactically wild-type Escherichia coli cells in a gradient of NiSO(4). Fabrication of the microfluidic device takes 1 d while preparing motile cells and carrying out the chemotaxis experiment takes 4-6 h to complete.

  19. NMR analysis on microfluidic devices by remote detection.

    PubMed

    McDonnell, Erin E; Han, SongI; Hilty, Christian; Pierce, Kimberly L; Pines, Alexander

    2005-12-15

    We present a novel approach to perform high-sensitivity NMR imaging and spectroscopic analysis on microfluidic devices. The application of NMR, the most information-rich spectroscopic technique, to microfluidic devices remains a challenge because the inherently low sensitivity of NMR is aggravated by small fluid volumes leading to low NMR signal and geometric constraints resulting in poor efficiency for inductive detection. We address the latter by physically separating signal detection from encoding of information with remote detection. Thereby, we use a commercial imaging probe with sufficiently large diameter to encompass the entire device, enabling encoding of NMR information at any location on the chip. Because large-diameter coils are too insensitive for detection, we store the encoded information as longitudinal magnetization and flow it into the outlet capillary. There, we detect the signal with optimal sensitivity, using a solenoidal microcoil, and reconstruct the information encoded in the fluid. We present a generally applicable design for a detection-only microcoil probe that can be inserted into the bore of a commercial imaging probe. Using hyperpolarized 129Xe gas, we show that this probe enables sensitive reconstruction of NMR spectroscopic information encoded by the large imaging probe while keeping the flexibility of a large coil.

  20. Wireless induction heating in a microfluidic device for cell lysis.

    PubMed

    Baek, Seung-ki; Min, Junghong; Park, Jung-Hwan

    2010-04-07

    A wireless induction heating system in a microfluidic device was devised for cell lysis to extract DNA and RNA from Escherichia coli. The thermal responses of nickel, iron and copper heating units were studied by applying an alternating magnetic field as a function of geometry of unit, strength of magnetic field, and kind of metal. Heating units were prepared by cutting metal film using a fiber laser, and the units were integrated into a microchannel system using a soft lithographic process. Variation and distribution of temperature on the surface of the heating units was observed using a thermographic camera and temperature labels. The amount of protein released from E. coli by thermal lysis was determined by protein concentration measurement. Hemoglobin released from red blood cells was observed using colorimetric intensity measurement. Extracted DNA was quantified by real-time polymerase chain reaction, and the profile was compared with that of a positive control of ultrasonically disrupted E. coli. The stability of RNA extracted by induction heating was quantified by the measurement of 23S/16S rRNA ratio and comparison with that by normal RNA extraction kit as a gold standard. A solid-shaped nickel structure was selected as the induction heating element in the microfluidic device because of the relatively small influence of geometries and faster thermal response.The amount of protein extracted from E. coli and hemoglobin released from red blood cells by induction heating of the nickel unit in the microfluidic device was proportional to the strength of the applied magnetic field. The lysis of E. coli by induction heating was as effective as lysis of DNA by the ultrasonication method because the threshold cycle values of the sample were compatible with those of the positive control as measured by ultrasonication. Thermal lysis of E. coli by induction heating represents a reasonable alternative to a commercial RNA extraction method as shown by the comparative

  1. Pressure-driven microfluidic perfusion culture device for integrated dose-response assays.

    PubMed

    Hattori, Koji; Sugiura, Shinji; Kanamori, Toshiyuki

    2013-12-01

    Cell-based assays are widely used in the various stages of drug discovery. Advances in microfluidic systems over the past two decades have enabled them to become a powerful tool for cell-based assays to achieve both reliability and high throughput. The interface between the micro-world and macro-world is important in industrial assay processes. Therefore, microfluidic cell-based assays using pressure-driven liquid handling are an ideal platform for integrated assays. The aim of this article is to review recent advancements in microfluidic cell-based assays focusing on a pressure-driven perfusion culture device. Here, we review the development of microfluidic cell-based assay devices and discuss the techniques involved in designing a microfluidic network, device fabrication, liquid and cell manipulation, and detection schemes for pressure-driven perfusion culture devices. Finally, we describe recent progress in semiautomatic and reliable pressure-driven microfluidic cell-based assays.

  2. Electrochemiluminescence at Bare and DNA-Coated Graphite Electrodes in 3D-Printed Fluidic Devices.

    PubMed

    Bishop, Gregory W; Satterwhite-Warden, Jennifer E; Bist, Itti; Chen, Eric; Rusling, James F

    Clear plastic fluidic devices with ports for incorporating electrodes to enable electrochemiluminescence (ECL) measurements were prepared using a low-cost, desktop three-dimensional (3D) printer based on stereolithography. Electrodes consisted of 0.5 mm pencil graphite rods and 0.5 mm silver wires inserted into commercially available 1/4 in.-28 threaded fittings. A bioimaging system equipped with a CCD camera was used to measure ECL generated at electrodes and small arrays using 0.2 M phosphate buffer solutions containing tris(2,2'-bipyridyl)dichlororuthenium(II) hexahydrate ([Ru(bpy)3](2+)) with 100 mM tri-n-propylamine (TPA) as the coreactant. ECL signals produced at pencil graphite working electrodes were linear with respect to [Ru(bpy)3](2+) concentration for 9-900 μM [Ru(bpy)3](2+). The detection limit was found to be 7 μM using the CCD camera with exposure time set at 10 s. Electrode-to-electrode ECL signals varied by ±7.5%. Device performance was further evaluated using pencil graphite electrodes coated with multilayer poly(diallyldimethylammonium chloride) (PDDA)/DNA films. In these experiments, ECL resulted from the reaction of [Ru(bpy)3](3+) with guanines of DNA. ECL produced at these thin-film electrodes was linear with respect to [Ru(bpy)3](2+) concentration from 180 to 800 μM. These studies provide the first demonstration of ECL measurements obtained using a 3D-printed closed-channel fluidic device platform. The affordable, high-resolution 3D printer used in these studies enables easy, fast, and adaptable prototyping of fluidic devices capable of incorporating electrodes for measuring ECL.

  3. A microfluidic device enabling high-efficiency single cell trapping

    PubMed Central

    Jin, D.; Deng, B.; Cai, W.; Tu, L.; Chen, J.; Wu, Q.; Wang, W. H.

    2015-01-01

    Single cell trapping increasingly serves as a key manipulation technique in single cell analysis for many cutting-edge cell studies. Due to their inherent advantages, microfluidic devices have been widely used to enable single cell immobilization. To further improve the single cell trapping efficiency, this paper reports on a passive hydrodynamic microfluidic device based on the “least flow resistance path” principle with geometry optimized in line with corresponding cell types. Different from serpentine structure, the core trapping structure of the micro-device consists of a series of concatenated T and inverse T junction pairs which function as bypassing channels and trapping constrictions. This new device enhances the single cell trapping efficiency from three aspects: (1) there is no need to deploy very long or complicated channels to adjust flow resistance, thus saving space for each trapping unit; (2) the trapping works in a “deterministic” manner, thus saving a great deal of cell samples; and (3) the compact configuration allows shorter flowing path of cells in multiple channels, thus increasing the speed and throughput of cell trapping. The mathematical model of the design was proposed and optimization of associated key geometric parameters was conducted based on computational fluid dynamics (CFD) simulation. As a proof demonstration, two types of PDMS microfluidic devices were fabricated to trap HeLa and HEK-293T cells with relatively significant differences in cell sizes. Experimental results showed 100% cell trapping and 90% single cell trapping over 4 × 100 trap sites for these two cell types, respectively. The space saving is estimated to be 2-fold and the cell trapping speed enhancement to be 3-fold compared to previously reported devices. This device can be used for trapping various types of cells and expanded to trap cells in the order of tens of thousands on 1-cm2 scale area, as a promising tool to pattern large-scale single cells on

  4. Batch-reactor microfluidic device: first human use of a microfluidically produced PET radiotracer†

    PubMed Central

    Miraghaie, Reza; Kotta, Kishore; Ball, Carroll E.; Zhang, Jianzhong; Buchsbaum, Monte S.; Kolb, Hartmuth C.; Elizarov, Arkadij

    2013-01-01

    The very first microfluidic device used for the production of 18F-labeled tracers for clinical research is reported along with the first human Positron Emission Tomography scan obtained with a microfluidically produced radiotracer. The system integrates all operations necessary for the transformation of [18F]fluoride in irradiated cyclotron target water to a dose of radiopharmaceutical suitable for use in clinical research. The key microfluidic technologies developed for the device are a fluoride concentration system and a microfluidic batch reactor assembly. Concentration of fluoride was achieved by means of absorption of the fluoride anion on a micro ion-exchange column (5 μL of resin) followed by release of the radioactivity with 45 μL of the release solution (95 ± 3% overall efficiency). The reactor assembly includes an injection-molded reactor chip and a transparent machined lid press-fitted together. The resulting 50 μL cavity has a unique shape designed to minimize losses of liquid during reactor filling and liquid evaporation. The cavity has 8 ports for gases and liquids, each equipped with a 2-way on-chip mechanical valve rated for pressure up to 20.68 bar (300 psi). The temperature is controlled by a thermoelectric heater capable of heating the reactor up to 180 °C from RT in 150 s. A camera captures live video of the processes in the reactor. HPLC-based purification and reformulation units are also integrated in the device. The system is based on “split-box architecture”, with reagents loaded from outside of the radiation shielding. It can be installed either in a standard hot cell, or as a self-shielded unit. Along with a high level of integration and automation, split-box architecture allowed for multiple production runs without the user being exposed to radiation fields. The system was used to support clinical trials of [18F]fallypride, a neuroimaging radiopharmaceutical under IND Application #109,880. PMID:23135409

  5. Optical absorption enhancement in 3D nanofibers coated on polymer substrate for photovoltaic devices.

    PubMed

    Kiani, Amirkianoosh; Venkatakrishnan, Krishnan; Tan, Bo

    2015-06-01

    Recent research in the field of photovoltaics has shown that polymer solar cells have great potential to provide low-cost, lightweight and flexible electronic devices to harvest solar energy. In this paper, we propose a new method for the generation of three-dimensional nanofibers coated on polymer substrate induced by femtosecond laser pulses. In this new method, a thin layer of polymer is irradiated by megahertz femtosecond laser pulses under ambient conditions, and a thin fibrous layer is generated on top of the polymer substrate. This method is single step; no additional materials are added, and the layers of the three-dimensional (3D) polymer nanofibrous structures are grown on top of the substrate after laser irradiation. Light spectroscopy results show significant enhancement of light absorption in the generated 3D nanofibrous layers of polymer. Finally, we suggest how to maximize the light trapping and optical absorption of the generated nanofiber cells by optimizing the laser parameters.

  6. A porous 3D cell culture micro device for cell migration study.

    PubMed

    Ma, Liang; Zhou, Changchun; Lin, Biaoyang; Li, Wei

    2010-08-01

    Cell migration under chemoattractant is an important biological step in cancer metastasis that causes the spread of malignant tumor cells. Porous polymeric materials are widely used to mimic the extracellular matrix (ECM) environment for applications such as three dimensional (3D) cell culturing and tissue engineering. In this paper we report a novel 3D cell culture device based on porous polymeric material to study cancer migration. We fabricated a porous channel on a polymeric chip using a selective ultrasonic foaming method. We demonstrate that a chemical concentration gradient could be established through the porous channel due to the slow diffusion process. We show that significant cell migration could be observed through the porous channel within 1-2 weeks of cell culturing when metastatic M4A4-GFP breast cancer cells were induced by 20% fetal bovine serum (FBS).We also developed a mathematical model to evaluate the diffusivity and concentration gradient through the fabricated porous structure.

  7. Particle-Based Microfluidic Device for Providing High Magnetic Field Gradients

    NASA Technical Reports Server (NTRS)

    Lin, Adam Y. (Inventor); Wong, Tak S. (Inventor)

    2013-01-01

    A microfluidic device for manipulating particles in a fluid has a device body that defines a main channel therein, in which the main channel has an inlet and an outlet. The device body further defines a particulate diverting channel therein, the particulate diverting channel being in fluid connection with the main channel between the inlet and the outlet of the main channel and having a particulate outlet. The microfluidic device also has a plurality of microparticles arranged proximate or in the main channel between the inlet of the main channel and the fluid connection of the particulate diverting channel to the main channel. The plurality of microparticles each comprises a material in a composition thereof having a magnetic susceptibility suitable to cause concentration of magnetic field lines of an applied magnetic field while in operation. A microfluidic particle-manipulation system has a microfluidic particle-manipulation device and a magnet disposed proximate the microfluidic particle-manipulation device.

  8. Thermoplastic elastomers for microfluidics: towards a high-throughput fabrication method of multilayered microfluidic devices.

    PubMed

    Roy, Emmanuel; Galas, Jean-Christophe; Veres, Teodor

    2011-09-21

    Multilayer soft lithography of polydimethylsiloxane (PDMS) is a well-known method for the fabrication of complex fluidic functions. With advantages and drawbacks, this technique allows fabrication of valves, pumps and micro-mixers. However, the process is inadequate for industrial applications. Here, we report a rapid prototyping technique for the fabrication of multilayer microfluidic devices, using a different and promising class of polymers. Using styrenic thermoplastic elastomers (TPE), we demonstrate a rapid technique for the fabrication and assembly of pneumatically driven valves in a multilayer microfluidic device made completely from thermoplastics. This material solution is transparent, biocompatible and as flexible as PDMS, and has high throughput thermoforming processing characteristics. We established a proof of principle for valving and mixing with three different grades of TPE using an SU-8 master mold. Specific viscoelastic properties of each grade allow us to report enhanced bonding capabilities from room temperature bonding to free pressure thermally assisted bonding. In terms of microfabrication, beyond classically embossing means, we demonstrate a high-throughput thermoforming method, where TPE molding experiments have been carried out without applied pressure and vacuum assistance within an overall cycle time of 180 s. The quality of the obtained thermoplastic systems show robust behavior and an opening/closing frequency of 5 Hz.

  9. Novel microfluidic devices for Raman spectroscopy and optical trapping

    NASA Astrophysics Data System (ADS)

    Ottevaere, Heidi; Liu, Qing; de Coster, Diane; Van Erps, Jürgen; Vervaeke, Michael; Thienpont, Hugo

    2016-09-01

    Traditionally, Raman spectroscopy is done in a specialized lab, with considerable requirements in terms of equipment, time and manual sampling of substances of interest. We present the modeling, the design and the fabrication process of a microfluidic device incorporation Raman spectroscopy, from which one enables confocal Raman measurements on-chip. The latter is fabricated using ultra precision diamond tooling and is tested in a proof-of-concept setup, by for example measuring Raman spectra of urea solutions with various concentrations. If one wants to analyze single cells instead of a sample solution, precautions need to be taken. Since Raman scattering is a weak process, the molecular fingerprint of flowing particles would be hard to measure. One method is to stably position the cell under test in the detection area during acquisition of the Raman scattering such that the acquisition time can be increased. Positioning of cells can be done through optical trapping and leads to an enhanced signal-to-noise ratio and thus a more reliable cell identification. Like Raman spectroscopy, optical trapping can also be miniaturized. We present the modeling, design process and fabrication of a mass-manufacturable polymer microfluidic device for dual fiber optical trapping using two counterpropagating singlemode beams. We use a novel fabrication process that consists of a premilling step and ultraprecision diamond tooling for the manufacturing of the molds and double-sided hot embossing for replication, resulting in a robust microfluidic chip for optical trapping. In a proof-of-concept demonstration, we characterize the trapping capabilities of the hot embossed chip.

  10. 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

  11. Investigation of hydrodynamic focusing in a microfluidic coulter counter device.

    PubMed

    Zhang, Muheng; Lian, Yongsheng; Harnett, Cindy; Brehob, Ellen

    2012-08-01

    The Coulter technique enables rapid analysis of particles or cells suspended in a fluid stream. In this technique, the cells are suspended in an electrically conductive solution, which is hydrodynamically focused by nonconducting sheath flows. The cells produce a characteristic voltage signal when they interrupt an electrical path. The population and size of the cells can be obtained through analyzing the voltage signal. In a microfluidic Coulter counter device, the hydrodynamic focusing technique is used to position the conducting sample stream and the cells and also to separate close cells to generate distinct signals for each cell and avoid signal jam. The performance of hydrodynamic focusing depends on the relative flow ratio between the sample stream and sheath stream. We use a numerical approach to study the hydrodynamic focusing in a microfluidic Coulter counter device. In this approach, the flow field is described by solving the incompressible Navier-Stokes equations. The sample stream concentration is modeled by an advection-diffusion equation. The motion of the cells is governed by the Newton-Euler equations of motion. Particle motion through the flow field is handled using an overlapping grid technique. A numerical model for studying a microfluidic Coulter counter has been validated. Using the model, the impact of relative flow rate on the performance of hydrodynamic focusing was studied. Our numerical results show that the position of the sample stream can be controlled by adjusting the relative flow rate. Our simulations also show that particles can be focused into the stream and initially close particles can be separated by the hydrodynamic focusing. From our study, we conclude that hydrodynamic focusing provides an effective way to control the position of the sample stream and cells and it also can be used to separate cells to avoid signal jam.

  12. 3D printing of tissue-simulating phantoms for calibration of biomedical optical devices

    NASA Astrophysics Data System (ADS)

    Zhao, Zuhua; Zhou, Ximing; Shen, Shuwei; Liu, Guangli; Yuan, Li; Meng, Yuquan; Lv, Xiang; Shao, Pengfei; Dong, Erbao; Xu, Ronald X.

    2016-10-01

    Clinical utility of many biomedical optical devices is limited by the lack of effective and traceable calibration methods. Optical phantoms that simulate biological tissues used for optical device calibration have been explored. However, these phantoms can hardly simulate both structural and optical properties of multi-layered biological tissue. To address this limitation, we develop a 3D printing production line that integrates spin coating, light-cured 3D printing and Fused Deposition Modeling (FDM) for freeform fabrication of optical phantoms with mechanical and optical heterogeneities. With the gel wax Polydimethylsiloxane (PDMS), and colorless light-curable ink as matrix materials, titanium dioxide (TiO2) powder as the scattering ingredient, graphite powder and black carbon as the absorption ingredient, a multilayer phantom with high-precision is fabricated. The absorption and scattering coefficients of each layer are measured by a double integrating sphere system. The results demonstrate that the system has the potential to fabricate reliable tissue-simulating phantoms to calibrate optical imaging devices.

  13. A Student-Made Microfluidic Device for Electrophoretic Separation of Food Dyes

    ERIC Educational Resources Information Center

    Teerasong, Saowapak; McClain, Robert L.

    2011-01-01

    We have developed an undergraduate laboratory activity to introduce students to microfluidics. In the activity, each student constructs their own microfluidic device using simple photolithographic techniques and then uses the device to separate a food dye mixture by electrophoresis. Dyes are used so that students are able to visually observe the…

  14. Bifurcation to 3D helical magnetic equilibrium in an axisymmetric toroidal device.

    PubMed

    Bergerson, W F; Auriemma, F; Chapman, B E; Ding, W X; Zanca, P; Brower, D L; Innocente, P; Lin, L; Lorenzini, R; Martines, E; Momo, B; Sarff, J S; Terranova, D

    2011-12-16

    We report the first direct measurement of the internal magnetic field structure associated with a 3D helical equilibrium generated spontaneously in the core of an axisymmetric toroidal plasma containment device. Magnetohydrodynamic equilibrium bifurcation occurs in a reversed-field pinch when the innermost resonant magnetic perturbation grows to a large amplitude, reaching up to 8% of the mean field strength. Magnetic topology evolution is determined by measuring the Faraday effect, revealing that, as the perturbation grows, toroidal symmetry is broken and a helical equilibrium is established.

  15. Purification of DNA/RNA in a microfluidic device.

    PubMed

    Fan, Andy; Byrnes, Samantha; Klapperich, Catherine

    2013-01-01

    Often, modern diagnostic techniques require the isolation and purification of nucleic acids directly from patient samples such as blood or stool. Many diagnostic tests are being miniaturized onto micro-sized platforms and integrated into microfluidic devices due to the economies resulting from smaller sample and reagent volumes. Often, these devices perform sample preparation in series with the diagnostic tests. The sample preparation steps are vital in order to purify the desired genetic material from potential inhibitors that can interfere with the outcome of the test. There are various techniques used to selectively capture the nucleic acids while washing away potential contamination (proteins, enzymes, lipids, etc.). Two of the most common forms of selective capture are based on nucleic acid binding to silica surface or on the precipitation of nucleic acids with or without the presence of a carrier species. Each of these methods can be performed in liquid phase or in a solid support such as an extraction column. Here we discuss both methods and address microfluidic applications.

  16. Single vegetal cell handling and fixing in a microfluidic device

    NASA Astrophysics Data System (ADS)

    Denoual, Matthieu J.; Koh, Aoki; Mita-Tixier, Agnes; Fujita, Hiroyuki

    2003-04-01

    The basic advantage of the microfluidic systems is that they enable reducing consumption of biological material and chemicals. But another major advantage of the microfluidic systems, not widely explored so far, is that with feature sizes reduced toward the size of cells, one can easily handle and fix a single cell. The interest of single cell handling and fixing appears when one wants to study biochemical exchanges between single cells or internal biochemical reactions inside an isolated cell. This work uses the shape of the microfluidc device to control the migration and placement of single vegetal cells. Three-dimensional micro-molding and poly-dimethylsiloxane (PDMS) patterning techniques have been used to realize device prototypes. Double-height micro-molds are made of thick negative photoresist (SU8) Experiments have been undergone to optimize fluid rate flow and cell concentration regarding to right cell placement percentage. The PDMS prototypes systems confirm the good operation of the design to migrate cells, place and fix them. The placement rate, even if it is enough for statistical biochemical experiments, will be improved by the use of new material. New material will allow to get rid of air bubbles due to PDMS long-term hydrophobicity that render up to 25% settlement places unserviceable.

  17. Microfluidic Device for Automated Synchronization of Bacterial Cells

    PubMed Central

    Madren, Seth M.; Hoffman, Michelle D.; Brown, Pamela J.B.; Kysela, David T.; Brun, Yves V.; Jacobson, Stephen C.

    2012-01-01

    We report the development of an automated microfluidic “baby machine” to synchronize the bacterium Caulobacter crescentus on-chip and to move the synchronized populations downstream for analysis. The microfluidic device is fabricated from three-layers of poly(dimethylsiloxane) and has integrated pumps and valves to control the movement of cells and media. This synchronization method decreases incubation time and media consumption and improves synchrony quality compared to the conventional plate-release technique. Synchronized populations are collected from the device at intervals as short as 10 min and at any time over four days. Flow cytometry and fluorescence cell tracking are used to determine synchrony quality, and cell populations synchronized in M2G and PYE media contain >70% and >80% swarmer cells, respectively. Our on-chip method overcomes limitations with conventional physical separation methods that consume large volumes of media, require manual manipulations, have lengthy incubation times, are limited to one collection, and lack precise temporal control of collection times. PMID:23030473

  18. Manufacturing and wetting low-cost microfluidic cell separation devices

    PubMed Central

    Pawell, Ryan S.; Inglis, David W.; Barber, Tracie J.; Taylor, Robert A.

    2013-01-01

    Deterministic lateral displacement (DLD) is a microfluidic size-based particle separation or filter technology with applications in cell separation and enrichment. Currently, there are no cost-effective manufacturing methods for this promising microfluidic technology. In this fabrication paper, however, we develop a simple, yet robust protocol for thermoplastic DLD devices using regulatory-approved materials and biocompatible methods. The final standalone device allowed for volumetric flow rates of 660 μl min−1 while reducing the manufacturing time to <1 h. Optical profilometry and image analysis were employed to assess manufacturing accuracy and precision; the average replicated post height was 0.48% less than the average post height on the master mold and the average replicated array pitch was 1.1% less than the original design with replicated posts heights of 62.1 ± 5.1 μm (mean ± 6 standard deviations) and replicated array pitches of 35.6 ± 0.31 μm. PMID:24404077

  19. Rapid prototyping of three-dimensional microfluidic mixers in glass by femtosecond laser direct writing.

    PubMed

    Liao, Yang; Song, Jiangxin; Li, En; Luo, Yong; Shen, Yinglong; Chen, Danping; Cheng, Ya; Xu, Zhizhan; Sugioka, Koji; Midorikawa, Katsumi

    2012-02-21

    The creation of complex three-dimensional (3D) microfluidic systems has attracted significant attention from both scientific and applied research communities. However, it is still a formidable challenge to build 3D microfluidic structures with arbitrary configurations using conventional planar lithographic fabrication methods. Here, we demonstrate rapid fabrication of high-aspect-ratio microfluidic channels with various 3D configurations in glass substrates by femtosecond laser direct writing. Based on this approach, we demonstrate a 3D passive microfluidic mixer and characterize its functionalities. This technology will enable rapid construction of complex 3D microfluidic devices for a wide array of lab-on-a-chip applications.

  20. Microfluidic Device for Studying Controllable Hydrodynamic Flow Induced Cellular Responses.

    PubMed

    Zheng, Chunhong; Zhang, Xiannian; Li, Chunmei; Pang, Yuhong; Huang, Yanyi

    2017-03-07

    Hydrodynamic flow is an essential stimulus in many cellular functions, regulating many mechanical sensitive pathways and closely associating with human health status and diseases. The flow pattern of blood in vessels is the key factor in causing atherosclerosis. Hemodynamics has great effect on endothelial cells' gene expression and biological functions. There are various tools that can be used for studying flow-induced cellular responses but most of them are either bulky or lack precise controllability. We develop an integrated microfluidic device that can precisely generate different flow patterns to human endothelial cells cultured on-chip. We monitored cell morphology and used small-input RNA-seq technology to depict the transcriptome profiles of human umbilical vein endothelial cells under uni- or bidirectional flow. Such integrated and miniatured device has greatly facilitated our understanding of endothelial functions with shear stimulus, not only providing new data on the transcriptomic scale but also building the connection between cell phenotypic changes and expression alternations.

  1. Femtosecond laser fabrication of microfluidic channels for organic photonic devices.

    PubMed

    Chaitanya Vishnubhatla, Krishna; Clark, Jenny; Lanzani, Guglielmo; Ramponi, Roberta; Osellame, Roberto; Virgili, Tersilla

    2009-11-01

    We report on innovative application of microchannels with access holes fabricated by femtosecond laser irradiation followed by chemical etching. This technique allows us to demonstrate a novel approach to the achievement of organic photonic devices in which the properties of a conjugated polymer in solution are exploited in a microfluidic configuration to produce an easy-to-integrate photonic device. Filling the microchannel with a diluted polyfluorene solution, we exploit the unique properties of isolated polymeric chains such as ultrafast gain switching (switching response time of 150 fs) with a 100% on-off ratio. In addition, by dispersing nanoparticles in the polymeric solution we are able to achieve random lasing in the microchannel.

  2. Particle sorting using a porous membrane in a microfluidic device.

    PubMed

    Wei, Huibin; Chueh, Bor-han; Wu, Huiling; Hall, Eric W; Li, Cheuk-wing; Schirhagl, Romana; Lin, Jin-Ming; Zare, Richard N

    2011-01-21

    Porous membranes have been fabricated based on the development of the perforated membrane mold [Y. Luo and R. N. Zare, Lab Chip, 2008, 8, 1688-1694] to create a single filter that contains multiple pore sizes ranging from 6.4 to 16.6 µm inside a monolithic three-dimensional poly(dimethylsiloxane) microfluidic structure. By overlapping two filters we are able to achieve smaller pore size openings (2.5 to 3.3 µm). This filter operates without any detectable irreversible clogging, which is achieved using a cross-flow placed in front of each filtration section. The utility of a particle-sorting device that contains this filter is demonstrated by separating polystyrene beads of different diameters with an efficiency greater than 99.9%. Additionally, we demonstrate the effectiveness of this particle-sorting device by separating whole blood samples into white blood cells and red blood cells with platelets.

  3. The electrochemical detection of droplets in microfluidic devices.

    PubMed

    Liu, Shujuan; Gu, Yunfeng; Le Roux, Rudolph B; Matthews, Sinéad M; Bratton, Daniel; Yunus, Kamran; Fisher, Adrian C; Huck, Wilhelm T S

    2008-11-01

    This paper presents a new electrochemical method for the detection and characterisation of aqueous droplets in an organic carrier fluid (1,2-dichloroethane) formed in flow-focusing microfluidic devices. The devices consist of a conventional flow-focusing channel 250 microm wide and 250 microm deep cast out of poly(dimethylsiloxane) (PDMS) which is sealed onto a glass substrate containing a set of microelectrodes 100 microm long. Chronoamperometric analysis of a suitable electrolyte contained in the organic phase is presented for characterising the droplet frequency and size. This chronoamperometric method is then extended to a dual working electrode approach in order to determine the velocity of the droplet. Good agreement between experimental measurements and theory was observed.

  4. Wnt5a-mediating neurogenesis of human adipose tissue-derived stem cells in a 3D microfluidic cell culture system.

    PubMed

    Choi, Jeein; Kim, Sohyeun; Jung, Jinsun; Lim, Youngbin; Kang, Kyungsun; Park, Seungsu; Kang, Sookyung

    2011-10-01

    In stem cell biology, cell plasticity refers to the ability of stem cells to differentiate into a variety of cell lineages. Recently, cell plasticity has been used to refer to the ability of a given cell type to reversibly de-differentiate, re-differentiate, or transdifferentiate in response to specific stimuli. These processes are regulated by multiple intracellular and extracellular growth and differentiation factors, including low oxygen. Our recent study showed that 3D microfluidic cell culture induces activation of the Wnt5A/β-catenin signaling pathway in hATSCs (human Adipose Tissue-derived Stem Cells). This resulted in self renewal and transdifferentiation of hATSCs into neurons. To improve neurogenic potency of hATSCs in response to low oxygen and other unknown physical factors, we developed a gel-free 3D microfluidic cell culture system (3D-μFCCS). The functional structure was developed for the immobilization of 3D multi-cellular aggregates in a microfluidic channel without the use of a matrix on the chip. Growth of hATSCs neurosphere grown on a chip was higher than the growth of control cells grown in a culture dish. Induction of differentiation in the Chip system resulted in a significant increase in the induction of neuronal-like cell structures and the presentation of TuJ or NF160 positive long neuritis compared to control cells after active migration from the center of the microfluidic channel layer to the outside of the microfluidic channel layer. We also observed that the chip neurogenesis system induced a significantly higher level of GABA secreting neurons and, in addition, almost 60% of cells were GABA + cells. Finally, we observed that 1 month of after the transplantation of each cell type in a mouse SCI lesion, chip cultured and neuronal differentiated hATSCs exhibited the ability to effectively transdifferentiate into NF160 + motor neurons at a high ratio. Interestingly, our CHIP/PCR analysis revealed that HIF1α-induced hATSCs neurogenesis

  5. User-friendly 3D bioassays with cell-containing hydrogel modules: narrowing the gap between microfluidic bioassays and clinical end-users' needs.

    PubMed

    Lee, Do-Hyun; Bae, Chae Yun; Kwon, Seyong; Park, Je-Kyun

    2015-06-07

    Cell-containing hydrogel modules as cell-hydrogel microunits for creating a physiologically relevant 3D in vivo-like microenvironment with multiple cell types and unique extracellular matrix (ECM) compositions facilitate long-term cell maintenance and bioassays. To date, there have been many important advances in microfluidic bioassays, which incorporate hydrogel scaffolds into surface-accessible microchambers, driven by the strong demand for the application of spatiotemporally defined biochemical stimuli to construct in vivo-like conditions and perform real-time imaging of cell-matrix interactions. In keeping with the trend of fostering collaborations among biologists, clinicians, and microfluidic engineers, it is essential to create a simpler approach for coupling cell-containing hydrogel modules and an automated bioassay platform in a user-friendly format. In this article, we review recent progress in hydrogel-incorporated microfluidics for long-term cell maintenance and discuss some of the simpler and user-friendly 3D bioassay techniques combined with cell-containing hydrogel modules that can be applied to mutually beneficial collaborations with non-engineers. We anticipate that this modular and user-friendly format interfaced with existing laboratory infrastructure will help address several clinical questions in ways that extend well beyond the current 2D cell-culture systems.

  6. Electrochemiluminescence detection in microfluidic cloth-based analytical devices.

    PubMed

    Guan, Wenrong; Liu, Min; Zhang, Chunsun

    2016-01-15

    This work describes the first approach at combining microfluidic cloth-based analytical devices (μCADs) with electrochemiluminescence (ECL) detection. Wax screen-printing is employed to make cloth-based microfluidic chambers which are patterned with carbon screen-printed electrodes (SPEs) to create truly disposable, simple, inexpensive sensors which can be read with a low-cost, portable charge coupled device (CCD) imaging sensing system. And, the two most commonly used ECL systems of tris(2,2'-bipyridyl)ruthenium(II)/tri-n-propylamine (Ru(bpy)3(2+)/TPA) and 3-aminophthalhydrazide/hydrogen peroxide (luminol/H2O2) are applied to demonstrate the quantitative ability of the ECL μCADs. In this study, the proposed devices have successfully fulfilled the determination of TPA with a linear range from 2.5 to 2500μM with a detection limit of 1.265μM. In addition, the detection of H2O2 can be performed in the linear range of 0.05-2.0mM, with a detection limit of 0.027mM. It has been shown that the ECL emission on the wax-patterned cloth device has an acceptable sensitivity, stability and reproducibility. Finally, the applicability of cloth-based ECL is demonstrated for determination of glucose in phosphate buffer solution (PBS) and artificial urine (AU) samples, with the detection limits of 0.032mM and 0.038mM, respectively. It can be foreseen, therefore, that μCADs with ECL detection could provide a new sensing platform for point-of-care testing, public health, food safety detection and environmental monitoring in remote regions, developing or developed countries.

  7. Facial expression identification using 3D geometric features from Microsoft Kinect device

    NASA Astrophysics Data System (ADS)

    Han, Dongxu; Al Jawad, Naseer; Du, Hongbo

    2016-05-01

    Facial expression identification is an important part of face recognition and closely related to emotion detection from face images. Various solutions have been proposed in the past using different types of cameras and features. Microsoft Kinect device has been widely used for multimedia interactions. More recently, the device has been increasingly deployed for supporting scientific investigations. This paper explores the effectiveness of using the device in identifying emotional facial expressions such as surprise, smile, sad, etc. and evaluates the usefulness of 3D data points on a face mesh structure obtained from the Kinect device. We present a distance-based geometric feature component that is derived from the distances between points on the face mesh and selected reference points in a single frame. The feature components extracted across a sequence of frames starting and ending by neutral emotion represent a whole expression. The feature vector eliminates the need for complex face orientation correction, simplifying the feature extraction process and making it more efficient. We applied the kNN classifier that exploits a feature component based similarity measure following the principle of dynamic time warping to determine the closest neighbors. Preliminary tests on a small scale database of different facial expressions show promises of the newly developed features and the usefulness of the Kinect device in facial expression identification.

  8. Study of 3D printing method for GRIN micro-optics devices

    NASA Astrophysics Data System (ADS)

    Wang, P. J.; Yeh, J. A.; Hsu, W. Y.; Cheng, Y. C.; Lee, W.; Wu, N. H.; Wu, C. Y.

    2016-03-01

    Conventional optical elements are based on either refractive or reflective optics theory to fulfill the design specifications via optics performance data. In refractive optical lenses, the refractive index of materials and radius of curvature of element surfaces determine the optical power and wavefront aberrations so that optical performance can be further optimized iteratively. Although gradient index (GRIN) phenomenon in optical materials is well studied for more than a half century, the optics theory in lens design via GRIN materials is still yet to be comprehensively investigated before realistic GRIN lenses are manufactured. In this paper, 3D printing method for manufacture of micro-optics devices with special features has been studied based on methods reported in the literatures. Due to the additive nature of the method, GRIN lenses in micro-optics devices seem to be readily achievable if a design methodology is available. First, derivation of ray-tracing formulae is introduced for all possible structures in GRIN lenses. Optics simulation program is employed for characterization of GRIN lenses with performance data given by aberration coefficients in Zernike polynomial. Finally, a proposed structure of 3D printing machine is described with conceptual illustration.

  9. Integrated Interventional Devices For Real Time 3D Ultrasound Imaging and Therapy

    NASA Astrophysics Data System (ADS)

    Smith, Stephen W.; Lee, Warren; Gentry, Kenneth L.; Pua, Eric C.; Light, Edward D.

    2006-05-01

    Two recent advances have expanded the potential of medical ultrasound: the introduction of real-time 3-D ultrasound imaging with catheter, transesophageal and laparoscopic probes and the development of interventional ultrasound therapeutic systems for focused ultrasound surgery, ablation and ultrasound enhanced drug delivery. This work describes devices combining both technologies. A series of transducer probes have been designed, fabricated and tested including: 1) a 12 French side scanning catheter incorporating a 64 element matrix array for imaging at 5MHz and a piston ablation transducer operating at 10 MHz. 2) a 14 Fr forward-scanning catheter integrating a 112 element 2-D array for imaging at 5 MHz encircled by an ablation annulus operating at 10 MHz. Finite element modeling was then used to simulate catheter annular and linear phased array transducers for ablation. 3) Linear phased array transducers were built to confirm the finite element analysis at 4 and 8 MHz including a mechanically focused 86 element 9 MHz array which transmits an ISPTA of 29.3 W/cm2 and creates a lesion in 2 minutes. 4) 2-D arrays of 504 channels operating at 5 MHz have been developed for transesophageal and laparascopic 3D imaging as well as therapeutic heating. All the devices image the heart anatomy including atria, valves, septa and en face views of the pulmonary veins.

  10. Coated microfluidic devices for improved chiral separations in microchip electrophoresis.

    PubMed

    Ludwig, Martin; Belder, Detlev

    2003-08-01

    Chiral separations of fluorescein isothiocyanate-labeled amines have been performed in poly(vinyl alcohol) (PVA)-coated microfluidic glass chips. Baseline separation of enantiomers could be realized in coated devices while they could not be resolved in uncoated chips. The electroosmotic flow (EOF) in PVA-coated channels is suppressed over a wide pH range which leads to a considerable improved reproducibility of migration times in repetitive analysis. Due to the high resolution obtained in such devices, it was possible to reliable determine the enantiomeric purity with high accuracy. One percent of the minor enantiomer could be determined in the presence of large excess of the other enantiomer. As the EOF was suppressed, the anionic compounds were detected at the anode whereas the dominant EOF in uncoated devices resulted in an effective mobility to the cathode. Applying PVA-coated channels considerable improved precision of migration times was found. The relative standard deviation of migration times was below 1% in PVA-coated devices. Accordingly, excessive rinsing or etching steps in order to stabilize the EOF could be omitted while this was necessary for a reliable operation of uncoated devices.

  11. Cholera toxin subunit B detection in microfluidic devices.

    PubMed

    Bunyakul, Natinan; Edwards, Katie A; Promptmas, Chamras; Baeumner, Antje J

    2009-01-01

    Fluorescence and electrochemical microfluidic biosensors were developed for the detection of cholera toxin subunit B (CTB) as a model analyte. The microfluidic devices were made from polydimethylsiloxane (PDMS) using soft lithography from silicon templates. The polymer channels were sealed with a glass plate and packaged in a polymethylmethacrylate housing that provided leakproof sealing and a connection to a syringe pump. In the electrochemical format, an interdigitated ultramicroelectrode array (IDUA) was patterned onto the glass slide using photolithography, gold evaporation and lift-off processes. For CTB recognition, CTB-specific antibodies were immobilized onto superparamagnetic beads and ganglioside GM(1) was incorporated into liposomes. The fluorescence dye sulforhodamine B (SRB) and the electroactive compounds potassium hexacyanoferrate (II)/hexacyanoferrate (III) were used as detection markers that were encapsulated inside the liposomes for the fluorescence and electrochemical detection formats, respectively. Initial optimization experiments were carried out by applying the superparamagnetic beads in microtiter plate assays and SRB liposomes before they were transferred to the microfluidic systems. The limits of detection (LoD) of both assay formats for CTB were found to be 6.6 and 1.0 ng mL(-1) for the fluorescence and electrochemical formats, respectively. Changing the detection system was very easy, requiring only the synthesis of different marker-encapsulating liposomes, as well as the exchange of the detection unit. It was found that, in addition to a lower LoD, the electrochemical format assay showed advantages over the fluorescence format in terms of flexibility and reliability of signal recording.

  12. Development of a 3D circular microfluidic centrifuge for the separation of mixed particles by using their different centrifuge times

    NASA Astrophysics Data System (ADS)

    Jeon, H. J.; Kim, D. I.; Kim, M. J.; Nguyen, X. D.; Park, D. H.; Go, J. S.

    2015-11-01

    This paper presents a circular microfluidic centrifuge with two inlets and two outlets to separate mixed microparticles with a specially designed sample injection hole. To separate the mixed particles, it uses a rotational flow, generated in a chamber by counter primary flows in the microchannels. The shape and sizes of the circular microfluidic centrifuge have been designed through numerical evaluation to have a large relative centrifugal force. The difference of centrifuge times of the mixed particles of 1 μm and 6 μm was determined to be 8.2 s at an inlet Reynolds number of 500 and a sample Reynolds number of 20. In the experiment, this was measured to be about 10 s. From the separation of the two polymer particles analogous to the representative sizes of platelets and red blood cells, the circular microfluidic centrifuge shows a potential to separate human blood cells size-selectively by using the difference of centrifuge times.

  13. Study nanoparticle delivery in microcirculation through a microfluidic device

    NASA Astrophysics Data System (ADS)

    Liu, Yaling; Thomas, Antony; Tan, Jifu

    2013-11-01

    This work focuses on the characterization of nanoparticle (NP) delivery in microcirculation through a microfluidic device. In microvasculature the vessel size is comparable to that of red blood cells (RBCs) and the existence of blood cells largely influences the dispersion and binding distribution of NPs. We perform an in vitro study in a mimetic microfluidic chip considering the various factors that influence NP distribution and delivery such as the vessel geometry, shear rate, blood cells, particle size, and particle antibody density. Around 10% higher particle binding density is observed at bifurcation regions of the mimetic microvasculature geometry. Particle binding density is found to decrease linearly for 210 nm particles and nonlinearly for 2 μm particles with increased shear rates. Particle flow along with RBCs enhances the binding of both 210 nm and 2 μm particles at all shear rates. The particle binding density increases about 4-8 times and 6-10 times when flowing in a 25% RBC in plasma solution compared to the pure particle case, for 210 nm and 2 μm particles respectively. Larger enhancement in particle binding density is observed for 2 μm particles in RBC flow case compared to that for 210 nm particles, which indicates size dependent exclusion of 2 μm particles to the cell free layer. An increase in particle antibody coating density leads to increase in the particle binding density for both 210 nm and 2 μm particles.

  14. AC Electrokinetic Cell Separation on a Microfluidic Device

    NASA Astrophysics Data System (ADS)

    Gagnon, Zachary; Chang, Hsueh-Chia

    2009-03-01

    Rapid cell separation and collection is demonstrated through the integration of electrokinetic pumps, dielectrophoretic (DEP) traps and field driven valves into a well designed microfluidic channel loop. We present the ground-up design and analysis of this fully functional microfluidic device for the rapid separation and collection of live and dead yeast cells and malaria red blood cells (RBCs) at low concentrations. DEP cell sorting and concentration schemes are based on the exploitation of cell specific DEP crossover frequencies (cof's). A rigorous DEP study of yeast and RBCs is presented and used to determine optimal conditions for cell separation. By utilizing a glutaraldehyde crosslinking cell fixation reaction that is sensitive to cell membrane protein concentration, we demonstrate the ability to further amplify these differences between healthy and unhealthy cells as well as stabilize their DEP cof's. Pumping is achieved with a new type of electrokinetic flow, AC electrothermal electro-osmosis (ETEO) and is shown to scale inversely with the field induced debye length and drive fluid velocities in excess of 6 mm/sec. The well characterized electrokinetic phenomena are integrated into a microchannel loop with a specifically designed electrode field penetration length for low concentration cell separation and concentration.

  15. Measuring Cell Viscoelastic Properties Using a Microfluidic Extensional Flow Device.

    PubMed

    Guillou, Lionel; Dahl, Joanna B; Lin, Jung-Ming G; Barakat, AbduI I; Husson, Julien; Muller, Susan J; Kumar, Sanjay

    2016-11-01

    The quantification of cellular mechanical properties is of tremendous interest in biology and medicine. Recent microfluidic technologies that infer cellular mechanical properties based on analysis of cellular deformations during microchannel traversal have dramatically improved throughput over traditional single-cell rheological tools, yet the extraction of material parameters from these measurements remains quite complex due to challenges such as confinement by channel walls and the domination of complex inertial forces. Here, we describe a simple microfluidic platform that uses hydrodynamic forces at low Reynolds number and low confinement to elongate single cells near the stagnation point of a planar extensional flow. In tandem, we present, to our knowledge, a novel analytical framework that enables determination of cellular viscoelastic properties (stiffness and fluidity) from these measurements. We validated our system and analysis by measuring the stiffness of cross-linked dextran microparticles, which yielded reasonable agreement with previously reported values and our micropipette aspiration measurements. We then measured viscoelastic properties of 3T3 fibroblasts and glioblastoma tumor initiating cells. Our system captures the expected changes in elastic modulus induced in 3T3 fibroblasts and tumor initiating cells in response to agents that soften (cytochalasin D) or stiffen (paraformaldehyde) the cytoskeleton. The simplicity of the device coupled with our analytical model allows straightforward measurement of the viscoelastic properties of cells and soft, spherical objects.

  16. Microfluidic devices obtained by thermal toner transferring on glass substrate.

    PubMed

    do Lago, Claudimir L; Neves, Carlos A; Pereira de Jesus, Dosil; da Silva, Heron D T; Brito-Neto, José G A; Fracassi da Silva, José A

    2004-11-01

    A new process for the manufacture of microfluidic devices based on deposition of laser-printing toner on glass substrates is described. It is an alternative method to the toner on polyester film (toner-polyester) one, previously introduced. Commercial laser printers cannot print directly on glass, thus the toner must first be printed on a special paper and then transferred by heating under pressure to the glass surface. Although this procedure is more complex than the toner-polyester one, it can be repeated several times, yielding multiple toner layers. Even without special alignment equipment, up to four layers could be satisfactorily piled up. Characterization tests revealed that the toner-glass devices have similar behavior as toner-polyester ones regarding the toner layer porosity. The main advantages of the toner-glass technology are improved mechanical stability, possibility of multiple toner layers, augmented electroosmotic flow (EOF), and improved heat transfer. On the other hand, toner adhesion to glass is weaker than to polyester, which limits the device lifetime and usable liquid media. The measured EOF mobility (3.5 x 10(-4) cm2.V(-1).s(-1) for pH 7) suggests that it is mainly determined by the glass surface, being little influenced by the toner walls. Microchip electrophoresis with contactless conductivity detection and photometric detection were implemented using toner-glass devices.

  17. Inducing chemotactic and haptotactic cues in microfluidic devices for three-dimensional in vitro assays.

    PubMed

    Moreno-Arotzena, O; Mendoza, G; Cóndor, M; Rüberg, T; García-Aznar, J M

    2014-11-01

    Microfluidic devices allow for the production of physiologically relevant cellular microenvironments by including biomimetic hydrogels and generating controlled chemical gradients. During transport, the biomolecules interact in distinct ways with the fibrillar networks: as purely diffusive factors in the soluble fluid or bound to the matrix proteins. These two main mechanisms may regulate distinct cell responses in order to guide their directional migration: caused by the substrate-bound chemoattractant gradient (haptotaxis) or by the gradient established within the soluble fluid (chemotaxis). In this work 3D diffusion experiments, in combination with ELISA assays, are performed using microfluidic platforms in order to quantify the distribution of PDGF-BB and TGF-β1 across collagen and fibrin gels. Furthermore, to gain a deeper understanding of the fundamental processes, the experiments are reproduced by computer simulations based on a reaction-diffusion transport model. This model yields an accurate prediction of the experimental results, confirming that diffusion and binding phenomena are established within the microdevice.

  18. Microfluidic devices with thick-film electrochemical detection

    DOEpatents

    Wang, Joseph; Tian, Baomin; Sahlin, Eskil

    2005-04-12

    An apparatus for conducting a microfluidic process and analysis, including at least one elongated microfluidic channel, fluidic transport means for transport of fluids through the microfluidic channel, and at least one thick-film electrode in fluidic connection with the outlet end of the microfluidic channel. The present invention includes an integrated on-chip combination reaction, separation and thick-film electrochemical detection microsystem, for use in detection of a wide range of analytes, and methods for the use thereof.

  19. High-throughput microfluidic device for rare cell isolation

    NASA Astrophysics Data System (ADS)

    Yang, Daniel; Leong, Serena; Lei, Andy; Sohn, Lydia L.

    2015-06-01

    Enumerating and analyzing circulating tumor cells (CTCs)—cells that have been shed from primary solid tumors—can potentially be used to determine patient prognosis and track the progression of disease. There is a great challenge to create an effective platform that can isolate these cells, as they are extremely rare: only 1-10 CTCs are present in a 7.5mL of a cancer patient's peripheral blood. We have developed a novel microfluidic system that can isolate CTC populations label free. Our system consists of a multistage separator that employs inertial migration to sort cells based on size. We demonstrate the feasibility of our device by sorting colloids that are comparable in size to red blood cells (RBCs) and CTCs.

  20. From screen to structure with a harvestable microfluidic device

    SciTech Connect

    Stojanoff V.; Jakonic, J.; Oren, D.A.; Nagarajan, V.; Navarro Poulsen, J.C.; Adams-Cioaba, M.A.; Bergfors, T. and Sommer, M.O.A.

    2011-06-21

    Advances in automation have facilitated the widespread adoption of high-throughput vapor-diffusion methods for initial crystallization screening. However, for many proteins, screening thousands of crystallization conditions fails to yield crystals of sufficient quality for structural characterization. Here, the rates of crystal identification for thaumatin, catalase and myoglobin using microfluidic Crystal Former devices and sitting-drop vapour-diffusion plates are compared. It is shown that the Crystal Former results in a greater number of identified initial crystallization conditions compared with vapor diffusion. Furthermore, crystals of thaumatin and lysozyme obtained in the Crystal Former were used directly for structure determination both in situ and upon harvesting and cryocooling. On the basis of these results, a crystallization strategy is proposed that uses multiple methods with distinct kinetic trajectories through the protein phase diagram to increase the output of crystallization pipelines.

  1. Nanolaminate microfluidic device for mobility selection of particles

    SciTech Connect

    Surh, Michael P.; Wilson, William D.; Barbee, Jr., Troy W.; Lane, Stephen M.

    2006-10-10

    A microfluidic device made from nanolaminate materials that are capable of electrophoretic selection of particles on the basis of their mobility. Nanolaminate materials are generally alternating layers of two materials (one conducting, one insulating) that are made by sputter coating a flat substrate with a large number of layers. Specific subsets of the conducting layers are coupled together to form a single, extended electrode, interleaved with other similar electrodes. Thereby, the subsets of conducting layers may be dynamically charged to create time-dependent potential fields that can trap or transport charge colloidal particles. The addition of time-dependence is applicable to all geometries of nanolaminate electrophoretic and electrochemical designs from sinusoidal to nearly step-like.

  2. Microscale Confinement features in microfluidic devices can affect biofilm

    SciTech Connect

    Kumar, Aloke; Karig, David K; Neethirajan, Suresh; Acharya, Rajesh K; Mukherjee, Partha P; Retterer, Scott T; Doktycz, Mitchel John

    2013-01-01

    Biofilms are aggregations of microbes that are encased by extra-cellular polymeric substances (EPS) and adhere to surfaces and interfaces. Biofilm development on abiotic surfaces is a dynamic process, which typically proceeds through an initial phase of adhesion of plankntonic microbes to the substrate, followed by events such as growth, maturation and EPS secretion. However, the coupling of hydrodynamics, microbial adhesion and biofilm growth remain poorly understood. Here, we investigate the effect of semiconfined features on biofilm formation. Using a microfluidic device and fluorescent time-lapse microscopy, we establish that confinement features can significantly affect biofilm formation. Biofilm dynamics change not only as a function of confinement features, but also of the total fluid flow rate, and our combination of experimental results and numerical simulations reveal insights into the link between hydrodynamics and biofilm formation.

  3. Laser induced fluorescence photobleaching anemometer for microfluidic devices.

    PubMed

    Wang, G R

    2005-04-01

    We have developed a novel, non-intrusive fluid velocity measurement method based on photobleaching of a fluorescent dye for microfluidic devices. The residence time of the fluorescent dye in a laser beam depends on the flow velocity and approximately corresponds to the decaying time of the photobleaching of the dye in the laser beam. The residence time is inversely proportional to the flow velocity. The fluorescence intensity increases with the flow velocity due to the decrease of the residence time. A calibration curve between fluorescence intensity and known flow velocity should be obtained first. The calibration relationship is then used to calculate the flow velocity directly from the measured fluorescence intensity signal. The new method can measure the velocity very quickly and is easy to use. It is demonstrated for both pressure driven flow and electroosmotic flow.

  4. Surface geometry based hydrophobicity of the PDMS for microfluidic devices

    NASA Astrophysics Data System (ADS)

    Pelayo, J. C.; Badiola, R. A.; Castañares, J.; Pili, U.; Violanda, R.; Bacabac, R.

    2015-06-01

    In this report, the surface hydrophobicity of PDMS was investigated using two methods of preparations. The first method was performed by changing the surface roughness through the use of different molds. The second method was performed by varying the reconstitution ratio (volume of elastomer base to volume of elastomer curing) of the PDMS. Variation in the hydrophobicity of the PDMS was characterized by measuring the contact angle of a liquid droplet against the surface of the PDMS. The results showed that both the surface roughness and the reconstitution ratio of the PDMS positively correlated with the contact angle measured regardless of the liquid used. The maximum and minimum contact angle obtained were θr = (138 ± 3)° and θr = (99 ± 3)°, respectively. The results demonstrate a straightforward way of fabricating microfluidic devices using PDMS with controlled hydrophobicity.

  5. From screen to structure with a harvestable microfluidic device.

    PubMed

    Stojanoff, Vivian; Jakoncic, Jean; Oren, Deena A; Nagarajan, V; Poulsen, Jens-Christian Navarro; Adams-Cioaba, Melanie A; Bergfors, Terese; Sommer, Morten O A

    2011-08-01

    Advances in automation have facilitated the widespread adoption of high-throughput vapour-diffusion methods for initial crystallization screening. However, for many proteins, screening thousands of crystallization conditions fails to yield crystals of sufficient quality for structural characterization. Here, the rates of crystal identification for thaumatin, catalase and myoglobin using microfluidic Crystal Former devices and sitting-drop vapour-diffusion plates are compared. It is shown that the Crystal Former results in a greater number of identified initial crystallization conditions compared with vapour diffusion. Furthermore, crystals of thaumatin and lysozyme obtained in the Crystal Former were used directly for structure determination both in situ and upon harvesting and cryocooling. On the basis of these results, a crystallization strategy is proposed that uses multiple methods with distinct kinetic trajectories through the protein phase diagram to increase the output of crystallization pipelines.

  6. Protocol for Biofilm Streamer Formation in a Microfluidic Device with Micro-pillars

    PubMed Central

    Hassanpourfard, Mahtab; Sun, Xiaohui; Valiei, Amin; Mukherjee, Partha; Thundat, Thomas; Liu, Yang; Kumar, Aloke

    2014-01-01

    Several bacterial species possess the ability to attach to surfaces and colonize them in the form of thin films called biofilms. Biofilms that grow in porous media are relevant to several industrial and environmental processes such as wastewater treatment and CO2 sequestration. We used Pseudomonas fluorescens, a Gram-negative aerobic bacterium, to investigate biofilm formation in a microfluidic device that mimics porous media. The microfluidic device consists of an array of micro-posts, which were fabricated using soft-lithography. Subsequently, biofilm formation in these devices with flow was investigated and we demonstrate the formation of filamentous biofilms known as streamers in our device. The detailed protocols for fabrication and assembly of microfluidic device are provided here along with the bacterial culture protocols. Detailed procedures for experimentation with the microfluidic device are also presented along with representative results. PMID:25178035

  7. 3D quantitative imaging of the microvasculature with the Texas Instruments Digital Micromirror Device

    NASA Astrophysics Data System (ADS)

    Fainman, Yeshaiahu; Botvinick, Elliott L.; Price, Jeffrey H.; Gough, David A.

    2001-11-01

    There is a growing need for developing 3D quantitative imaging tools that can operate at high speed enabling real-time visualization for the field of biology, material science, and the semiconductor industry. We will present our 3D quantitative imaging system based on a confocal microscope built with a Texas Instruments Digital Micromirror Device (DMD). By using the DMD as a spatial light modulator, confocal transverse surface (x, y) scanning can be performed in parallel at speeds faster than video rate without physical movement of the sample. The DMD allows us to programmably configure the source and the detection pinhole array in the lateral direction to achieve the best signal and to reduce the crosstalk noise. Investigations of the microcirculation were performed on 40 g to 45 g golden Syrian hamsters fit with dorsal skin fold window chambers. FITC-Dextran or Red blood cells from donor hamsters, stained with Celltracker CM-DiI, were injected into the circulation and imaged with the confocal microscope. We will present the measured results for the axial resolution, in vivo, as well as experimental results from imaging the window chamber.

  8. Underwater 3D Surface Measurement Using Fringe Projection Based Scanning Devices

    PubMed Central

    Bräuer-Burchardt, Christian; Heinze, Matthias; Schmidt, Ingo; Kühmstedt, Peter; Notni, Gunther

    2015-01-01

    In this work we show the principle of optical 3D surface measurements based on the fringe projection technique for underwater applications. The challenges of underwater use of this technique are shown and discussed in comparison with the classical application. We describe an extended camera model which takes refraction effects into account as well as a proposal of an effective, low-effort calibration procedure for underwater optical stereo scanners. This calibration technique combines a classical air calibration based on the pinhole model with ray-based modeling and requires only a few underwater recordings of an object of known length and a planar surface. We demonstrate a new underwater 3D scanning device based on the fringe projection technique. It has a weight of about 10 kg and the maximal water depth for application of the scanner is 40 m. It covers an underwater measurement volume of 250 mm × 200 mm × 120 mm. The surface of the measurement objects is captured with a lateral resolution of 150 μm in a third of a second. Calibration evaluation results are presented and examples of first underwater measurements are given. PMID:26703624

  9. A Disposable Microfluidic Virus Concentration Device Based on Evaporation and Interfacial Tension

    PubMed Central

    Zhang, Jane Yuqian; Mahalanabis, Madhumita; Liu, Lena; Chang, Jessie; Pollock, Nira R.; Klapperich, Catherine M.

    2013-01-01

    We report a disposable and highly effective polymeric microfluidic viral sample concentration device capable of increasing the concentration of virus in a human nasopharyngeal specimen more than one order of magnitude in less than 30 min without the use of a centrifuge. The device is fabricated using 3D maskless xurography method using commercially available polymeric materials, which require no cleanroom operations. The disposable components can be fabricated and assembled in five minutes. The device can concentrate a few milliliters (mL) of influenza virus in solution from tissue culture or clinical nasopharyngeal swab specimens, via reduction of the fluid volume, to tens of microliters μL). The performance of the device was evaluated by nucleic acid extraction from the concentrated samples, followed by a real-time quantitative polymerase chain reaction (qRT-PCR). The viral RNA concentration in each sample was increased on average over 10-fold for both cultured and patient specimens compared to the starting samples, with recovery efficiencies above 60% for all input concentrations. Highly concentrated samples in small fluid volumes can increase the downstream process speed of on-chip nucleic acid extraction, and result in improvements in the sensitivity of many diagnostic platforms that interrogate small sample volumes. PMID:26617991

  10. Development and characterization of 3D, nano-confined multicellular constructs for advanced biohybrid devices.

    SciTech Connect

    Kaehr, Bryan James

    2011-09-01

    This is the final report for the President Harry S. Truman Fellowship in National Security Science and Engineering (LDRD project 130813) awarded to Dr. Bryan Kaehr from 2008-2011. Biological chemistries, cells, and integrated systems (e.g., organisms, ecologies, etc.) offer important lessons for the design of synthetic strategies and materials. The desire to both understand and ultimately improve upon biological processes has been a driving force for considerable scientific efforts worldwide. However, to impart the useful properties of biological systems into modern devices and materials requires new ideas and technologies. The research herein addresses aspects of these issues through the development of (1) a rapid-prototyping methodology to build 3D bio-interfaces and catalytic architectures, (2) a quantitative method to measure cell/material mechanical interactions in situ and at the microscale, and (3) a breakthrough approach to generate functional biocomposites from bacteria and cultured cells.

  11. A practical guide for the fabrication of microfluidic devices using glass and silicon.

    PubMed

    Iliescu, Ciprian; Taylor, Hayden; Avram, Marioara; Miao, Jianmin; Franssila, Sami

    2012-03-01

    This paper describes the main protocols that are used for fabricating microfluidic devices from glass and silicon. Methods for micropatterning glass and silicon are surveyed, and their limitations are discussed. Bonding methods that can be used for joining these materials are summarized and key process parameters are indicated. The paper also outlines techniques for forming electrical connections between microfluidic devices and external circuits. A framework is proposed for the synthesis of a complete glass/silicon device fabrication flow.

  12. A practical guide for the fabrication of microfluidic devices using glass and silicon

    PubMed Central

    Iliescu, Ciprian; Taylor, Hayden; Avram, Marioara; Miao, Jianmin; Franssila, Sami

    2012-01-01

    This paper describes the main protocols that are used for fabricating microfluidic devices from glass and silicon. Methods for micropatterning glass and silicon are surveyed, and their limitations are discussed. Bonding methods that can be used for joining these materials are summarized and key process parameters are indicated. The paper also outlines techniques for forming electrical connections between microfluidic devices and external circuits. A framework is proposed for the synthesis of a complete glass/silicon device fabrication flow. PMID:22662101

  13. 3D sensitive voxel detector of ionizing radiation based on Timepix device

    NASA Astrophysics Data System (ADS)

    Soukup, P.; Jakubek, J.; Vykydal, Z.

    2011-01-01

    Position sensitive detectors are evolving towards higher segmentation geometries from 0D (single pad) over 1D (strip) to 2D (pixel) detectors. Each step has brought up substantial expansion in the field of applications. The next logical step in this evolution is to design a 3D, i.e. voxel detector. The voxel detector can be constructed from 2D volume element detectors arranged in layers forming a 3D matrix of sensitive elements — voxels. Such detectors can effectively record tracks of energetic particles. By proper analysis of these tracks it is possible to determine the type, direction and energy of the primary particle. One of the prominent applications of such device is in the localization and identification of gamma and neutron sources in the environment. It can be also used for emission and transmission radiography in many fields where standard imagers are currently utilized. The qualitative properties of current imagers such as: spatial resolution, efficiency, directional sensitivity, energy sensitivity and selectivity (background suppression) can be improved. The first prototype of a voxel detector was built using a number of Timepix devices. Timepix is hybrid semiconductor detector consisting of a segmented semiconductor sensor bump-bonded to a readout chip. Each sensor contains 256x256 square pixels of 55 μm size. The voxel detector prototype was successfully tested to prove the concept functionality. The detector has a modular architecture with a daisy chain connection of the individual detector layers. This permits easy rearrangement due to its modularity, while keeping a single readout system for a variable number of detector layers. A limitation of this approach is the relatively large inter-layer distance (4 mm) compared to the pixel thickness (0.3 mm). Therefore the next step in the design is to decrease the space between the 2D detectors.

  14. A microfluidic paper-based device to assess acetylcholinesterase activity.

    PubMed

    Liu, Chunye; Gomez, Frank A

    2017-04-01

    Neurotransmitters play key roles in cell-to-cell communication. These chemical messengers are involved in many functional processes, including growth, reproduction, memory, and behavior. In this communication, we describe a novel microfluidic paper-based analytical device (μPAD) to detect acetylcholinesterase (AChE) activity and inhibitor screening through a colorimetric analysis. The μPAD is easily fabricated via a wax printing process whereby wax is deposited onto the surface of chromatographic paper, and heated to create a hydrophobic barrier. Separate solutions of 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) and samples containing AChE and acetylthiocholine iodide (ATC) (or cysteine, Cys), respectively, are directly spotted onto the μPAD. DTNB and AChE/ATC (or Cys) flow towards each other where a reaction occurs to form the yellow colored 2-nitro-5-thiobenzoic acid anion (TNB(2-) ). The device is dried, scanned, and analyzed yielding a linear range of average inverse yellow intensities versus substrate concentration. An IC50 value (0.045 nM) with a known inhibitor, neostigmine bromide (NB), is obtained on the device. μPADs are low cost and easy to fabricate and have great potential to quantify neurotransmitter activity.

  15. Autonomous microfluidic capillaric circuits replicated from 3D-printed molds† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c6lc00764c Click here for additional data file. Click here for additional data file.

    PubMed Central

    Olanrewaju, A. O.; Robillard, A.; Dagher, M.

    2016-01-01

    We recently developed capillaric circuits (CCs) – advanced capillary microfluidic devices assembled from capillary fluidic elements in a modular manner similar to the design of electric circuits (Safavieh & Juncker, Lab Chip, 2013, 13, 4180–4189). CCs choreograph liquid delivery operations according to pre-programmed capillary pressure differences with minimal user intervention. CCs were thought to require high-precision micron-scale features manufactured by conventional photolithography, which is slow and expensive. Here we present CCs manufactured rapidly and inexpensively using 3D-printed molds. Molds for CCs were fabricated with a benchtop 3D-printer, poly(dimethylsiloxane) replicas were made, and fluidic functionality was verified with aqueous solutions. We established design rules for CCs by a combination of modelling and experimentation. The functionality and reliability of trigger valves – an essential fluidic element that stops one liquid until flow is triggered by a second liquid – was tested for different geometries and different solutions. Trigger valves with geometries up to 80-fold larger than cleanroom-fabricated ones were found to function reliably. We designed retention burst valves that encode sequential liquid delivery using capillary pressure differences encoded by systematically varied heights and widths. Using an electrical circuit analogue of the CC, we established design rules to ensure strictly sequential liquid delivery. CCs autonomously delivered eight liquids in a pre-determined sequence in <7 min. Taken together, our results demonstrate that 3D-printing lowers the bar for other researchers to access capillary microfluidic valves and CCs for autonomous liquid delivery with applications in diagnostics, research and education. PMID:27722504

  16. Blood separation on microfluidic paper-based analytical devices.

    PubMed

    Songjaroen, Temsiri; Dungchai, Wijitar; Chailapakul, Orawon; Henry, Charles S; Laiwattanapaisal, Wanida

    2012-09-21

    A microfluidic paper-based analytical device (μPAD) for the separation of blood plasma from whole blood is described. The device can separate plasma from whole blood and quantify plasma proteins in a single step. The μPAD was fabricated using the wax dipping method, and the final device was composed of a blood separation membrane combined with patterned Whatman No.1 paper. Blood separation membranes, LF1, MF1, VF1 and VF2 were tested for blood separation on the μPAD. The LF1 membrane was found to be the most suitable for blood separations when fabricating the μPAD by wax dipping. For blood separation, the blood cells (both red and white) were trapped on blood separation membrane allowing pure plasma to flow to the detection zone by capillary force. The LF1-μPAD was shown to be functional with human whole blood of 24-55% hematocrit without dilution, and effectively separated blood cells from plasma within 2 min when blood volumes of between 15-22 μL were added to the device. Microscopy was used to confirm that the device isolated plasma with high purity with no blood cells or cell hemolysis in the detection zone. The efficiency of blood separation on the μPAD was studied by plasma protein detection using the bromocresol green (BCG) colorimetric assay. The results revealed that protein detection on the μPAD was not significantly different from the conventional method (p > 0.05, pair t-test). The colorimetric measurement reproducibility on the μPAD was 2.62% (n = 10) and 5.84% (n = 30) for within-day and between day precision, respectively. Our proposed blood separation on μPAD has the potential for reducing turnaround time, sample volume, sample preparation and detection processes for clinical diagnosis and point-of care testing.

  17. High-throughput compound evaluation on 3D networks of neurons and glia in a microfluidic platform

    PubMed Central

    Wevers, Nienke R.; van Vught, Remko; Wilschut, Karlijn J.; Nicolas, Arnaud; Chiang, Chiwan; Lanz, Henriette L.; Trietsch, Sebastiaan J.; Joore, Jos; Vulto, Paul

    2016-01-01

    With great advances in the field of in vitro brain modelling, the challenge is now to implement these technologies for development and evaluation of new drug candidates. Here we demonstrate a method for culturing three-dimensional networks of spontaneously active neurons and supporting glial cells in a microfluidic platform. The high-throughput nature of the platform in combination with its compatibility with all standard laboratory equipment allows for parallel evaluation of compound effects. PMID:27934939

  18. 3D-printed microfluidic magnetic preconcentrator for the detection of bacterial pathogen using an ATP luminometer and antibody-conjugated magnetic nanoparticles.

    PubMed

    Park, Chanyong; Lee, Jinyeop; Kim, Yonghee; Kim, Jaewon; Lee, Jinkee; Park, Sungsu

    2017-01-01

    Various types of microfluidic systems have been developed to detect bacterial pathogens. However, most of these require enrichment steps that take at least several hours when detecting bacteria that are present with a low number of cells and, in addition, fabrication requires complicated assembly steps. In this study, we report the development of 3D microfluidic magnetic preconcentrator (3DμFMP) made of plastic via 3D printing without the need for any assembly. 3DμFMP could selectively preconcentrate enterohemorrhagic Escherichia coli O157:H7 in 100mL by a factor of 700 within 1h using antibody-conjugated magnetic nanoparticles (Ab-MNPs). With the combined use of an ATP luminometer, as low as 10 E. coli O157:H7 CFU (colony forming unit)/mL could be detected in blood. These results demonstrate the feasibility of 3DμFMP as a preconcentrator to improve the detection limit of existing bacterial detection systems.

  19. An easy-to-use microfluidic interconnection system to create quick and reversibly interfaced simple microfluidic devices

    NASA Astrophysics Data System (ADS)

    Pfreundt, Andrea; Brandt Andersen, Karsten; Dimaki, Maria; Svendsen, Winnie E.

    2015-11-01

    The presented microfluidic interconnection system provides an alternative for the individual interfacing of simple microfluidic devices fabricated in polymers such as polymethylmethacrylate, polycarbonate and cyclic olefin polymer. A modification of the device inlet enables the direct attachment of tubing (such as polytetrafluoroethylene tubing) secured and sealed by using a small plug, without the need for additional assembly, glue or o-rings. This provides a very clean connection that does not require additional, potentially incompatible, materials. The tightly sealed connection can withstand pressures above 250 psi and therefore supports applications with high flow rates or highly viscous fluids. The ease of incorporation, configuration, fabrication and use make this interconnection system ideal for the rapid prototyping of simple microfluidic devices or other integrated systems that require microfluidic interfaces. It provides a valuable addition to the toolbox of individual and small arrays of connectors suitable for micromachined or template-based injection molded devices since it does not require protruding, threaded or glued modifications on the inlet and avoids bulky and expensive fittings.

  20. C-peptide and zinc delivery to erythrocytes requires the presence of albumin: implications in diabetes explored with a 3D-printed fluidic device.

    PubMed

    Liu, Yueli; Chen, Chengpeng; Summers, Suzanne; Medawala, Wathsala; Spence, Dana M

    2015-05-01

    People with type 1 diabetes (T1D) must administer insulin exogenously due to the destruction of their pancreatic β-cells. Endogenous insulin is stored in β-cell granules along with C-peptide, a 31 amino acid peptide that is secreted from these granules in amounts equal to insulin. Exogenous co-administration of C-peptide with insulin has proven to reduce diabetes-associated complications in animals and humans. The exact mechanism of C-peptide's beneficial effects after secretion from the β-cell granules is not completely understood, thus hindering its development as an exogenously administered hormone. Monitoring tissue-to-tissue communication using a 3D-printed microfluidic device revealed that zinc and C-peptide are being delivered to erythrocytes by albumin. Upon delivery, erythrocyte-derived ATP increased by >50%, as did endothelium-derived NO, which was measured downstream in the 3D-printed device. Our results suggest that hormone replacement therapy in diabetes may be improved by exogenous administration of a C-peptide ensemble that includes zinc and albumin.

  1. Microwave sensing and heating of individual droplets in microfluidic devices.

    PubMed

    Boybay, Muhammed S; Jiao, Austin; Glawdel, Tomasz; Ren, Carolyn L

    2013-10-07

    Droplet-based microfluidics is an emerging high-throughput screening technology finding applications in a variety of areas such as life science research, drug discovery and material synthesis. In this paper we present a cost-effective, scalable microwave system that can be integrated with microfluidic devices enabling remote, simultaneous sensing and heating of individual nanoliter-sized droplets generated in microchannels. The key component of this microwave system is an electrically small resonator that is able to distinguish between materials with different electrical properties (i.e. permittivity, conductivity). The change in these properties causes a shift in the operating frequency of the resonator, which can be used for sensing purposes. Alternatively, if microwave power is delivered to the sensing region at the frequency associated with a particular material (i.e. droplet), then only this material receives the power while passing the resonator leaving the surrounding materials (i.e. carrier fluid and chip material) unaffected. Therefore this method allows sensing and heating of individual droplets to be inherently synchronized, eliminating the need for external triggers. We confirmed the performance of the sensor by applying it to differentiate between various dairy fluids, identify salt solutions and detect water droplets with different glycerol concentrations. We experimentally verified that this system can increase the droplet temperature from room temperature by 42 °C within 5.62 ms with an input power of 27 dBm. Finally we employed this system to thermally initiate the formation of hydrogel particles out of the droplets that are being heated by this system.

  2. Microfluidic device for the formation of optically excitable, three-dimensional, compartmentalized motor units

    PubMed Central

    Uzel, Sebastien G. M.; Platt, Randall J.; Subramanian, Vidya; Pearl, Taylor M.; Rowlands, Christopher J.; Chan, Vincent; Boyer, Laurie A.; So, Peter T. C.; Kamm, Roger D.

    2016-01-01

    Motor units are the fundamental elements responsible for muscle movement. They are formed by lower motor neurons and their muscle targets, synapsed via neuromuscular junctions (NMJs). The loss of NMJs in neurodegenerative disorders (such as amyotrophic lateral sclerosis or spinal muscle atrophy) or as a result of traumatic injuries affects millions of lives each year. Developing in vitro assays that closely recapitulate the physiology of neuromuscular tissues is crucial to understand the formation and maturation of NMJs, as well as to help unravel the mechanisms leading to their degeneration and repair. We present a microfluidic platform designed to coculture myoblast-derived muscle strips and motor neurons differentiated from mouse embryonic stem cells (ESCs) within a three-dimensional (3D) hydrogel. The device geometry mimics the spinal cord–limb physical separation by compartmentalizing the two cell types, which also facilitates the observation of 3D neurite outgrowth and remote muscle innervation. Moreover, the use of compliant pillars as anchors for muscle strips provides a quantitative functional readout of force generation. Finally, photosensitizing the ESC provides a pool of source cells that can be differentiated into optically excitable motor neurons, allowing for spatiodynamic, versatile, and noninvasive in vitro control of the motor units. PMID:27493991

  3. Exploration of microfluidic devices based on multi-filament threads and textiles: A review

    PubMed Central

    Nilghaz, A.; Ballerini, D. R.; Shen, W.

    2013-01-01

    In this paper, we review the recent progress in the development of low-cost microfluidic devices based on multifilament threads and textiles for semi-quantitative diagnostic and environmental assays. Hydrophilic multifilament threads are capable of transporting aqueous and non-aqueous fluids via capillary action and possess desirable properties for building fluid transport pathways in microfluidic devices. Thread can be sewn onto various support materials to form fluid transport channels without the need for the patterned hydrophobic barriers essential for paper-based microfluidic devices. Thread can also be used to manufacture fabrics which can be patterned to achieve suitable hydrophilic-hydrophobic contrast, creating hydrophilic channels which allow the control of fluids flow. Furthermore, well established textile patterning methods and combination of hydrophilic and hydrophobic threads can be applied to fabricate low-cost microfluidic devices that meet the low-cost and low-volume requirements. In this paper, we review the current limitations and shortcomings of multifilament thread and textile-based microfluidics, and the research efforts to date on the development of fluid flow control concepts and fabrication methods. We also present a summary of different methods for modelling the fluid capillary flow in microfluidic thread and textile-based systems. Finally, we summarized the published works of thread surface treatment methods and the potential of combining multifilament thread with other materials to construct devices with greater functionality. We believe these will be important research focuses of thread- and textile-based microfluidics in future. PMID:24086179

  4. Pyro-EHD ink-jet printing for direct functionalization of 3D lab-on-chip devices

    NASA Astrophysics Data System (ADS)

    Coppola, S.; Vespini, V.; Bianco, V.; Mecozzi, L.; Olivieri, F.; Todino, M.; Paturzo, M.; Grilli, S.; Ferraro, P.

    2016-03-01

    A challenging request in the fabrication of microfluidics and biomedical microsystems is a flexible ink-jet printing for breaking the rigidity of classical lithography. A pyroelectric-EHD system is presented. The system has proved challenging spatial resolution down to nanoscale, printing of high ordered patterns, capability of dispensing bio-ink as DNA and protein array for biosensing fabrication, single cells printing and direct printing of nanoparticles. With the method proposed high viscous polymers could be easily printed at high resolution in 2D or in 3D configuration. The pyro-EHD process has been proved for the fabrication of biodegradable microneedles for trasndermal drug delivery and 3D optical waveguides.

  5. Microfluidic Device for Studying Tumor Cell Extravasation in Cancer Metastasis

    SciTech Connect

    Lin, Henry K; Thundat, Thomas George; Evans III, Boyd Mccutchen; Datar, Ram H; Reese, Benjamin E; Zheng, Siyang

    2010-01-01

    Metastasis is the process by which cancer spreads to form secondary tumors at downstream locations throughout the body. This uncontrolled spreading is the leading cause of death in patients with epithelial cancers and is the main reason that suppressing and targeting cancer has proven to be so challenging. Tumor cell extravasation is one of the key steps in cancer s progression towards a metastatic state. This occurs when circulating tumor cells found within the blood stream are able to transmigrate through the endothelium lining and basement membrane of the vasculature to form metastatic tumors at secondary sites within the body. Predicting the likelihood of this occurrence in patients, or being able to determine specific markers involved in this process could lead to preventative measures targeting these types of cancer; moreover, this may lead to the discovery of novel anti-metastatic drugs. We have developed a microfluidic device that has shown the extravasation of fluorescently labeled tumor cells across an endothelial cell lined membrane coated with matrigel followed by the formation of colonies. This device provides the advantages of combining a controlled environment, mimicking that found within the body, with real-time monitoring capabilities allowing for the study of these biomarkers and cellular interactions along with other potential mechanisms involved in the process of extravasation.

  6. A novel MR-guided interventional device for 3D circumferential access to breast tissue

    PubMed Central

    Smith, Matthew; Zhai, Xu; Harter, Ray; Sisney, Gale; Elezaby, Mai; Fain, Sean

    2008-01-01

    MRI is rapidly growing as a tool for image-guided procedures in the breast such as needle localizations, biopsy, and cryotherapy. The ability of MRI to resolve small (<1 cm) lesions allows earlier detection and diagnosis than with ultrasound. Most MR-guidance methods perform a two-dimensional compression of the breast that distorts tissue anatomy and limits medial access. This work presents a system for localizing breast lesions with 360° access to breast tissue. A novel system has been developed to perform breast lesion localization using MR guidance that uses a 3D radial coordinate system with four degrees of freedom. The device is combined with a novel breast RF coil for improved signal to noise and rotates 360° around the breast to allow medial, lateral, superior, and inferior access minimizing insertion depth to the target. Coil performance was evaluated using a human volunteer by comparing signal to noise from both the developed breast RF coil and a commercial seven-channel breast coil. The system was tested with a breast-shaped gel phantom containing randomly distributed MR-visible targets. MR-compatible localization needles were used to demonstrate the accuracy and feasibility of the concept for breast biopsy. Localization results were classified based on the relationship between the final needle tip position and the lesion. A 3D bladder concept was also tested using animal tissue to evaluate the device’s ability to immobilize deformable breast tissue during a needle insertion. The RF breast coil provided signal to noise values comparable to a seven-channel breast coil. The needle tip was in contact with the targeted lesion in 89% (25∕28) of all the trials and 100% (6∕6) of the trials with targeted lesions >6 mm. Target lesions were 3–4 mm in diameter for 47% (13∕28), 5–6 mm in diameter for 32% (9∕28), and over 6 mm in diameter for 21% (6∕28) of the trials, respectively. The 3D bladder concept was shown to immobilize a deformable animal

  7. MEVA - An Interactive Visualization Application for Validation of Multifaceted Meteorological Data with Multiple 3D Devices

    PubMed Central

    Helbig, Carolin; Bilke, Lars; Bauer, Hans-Stefan; Böttinger, Michael; Kolditz, Olaf

    2015-01-01

    Background To achieve more realistic simulations, meteorologists develop and use models with increasing spatial and temporal resolution. The analyzing, comparing, and visualizing of resulting simulations becomes more and more challenging due to the growing amounts and multifaceted character of the data. Various data sources, numerous variables and multiple simulations lead to a complex database. Although a variety of software exists suited for the visualization of meteorological data, none of them fulfills all of the typical domain-specific requirements: support for quasi-standard data formats and different grid types, standard visualization techniques for scalar and vector data, visualization of the context (e.g., topography) and other static data, support for multiple presentation devices used in modern sciences (e.g., virtual reality), a user-friendly interface, and suitability for cooperative work. Methods and Results Instead of attempting to develop yet another new visualization system to fulfill all possible needs in this application domain, our approach is to provide a flexible workflow that combines different existing state-of-the-art visualization software components in order to hide the complexity of 3D data visualization tools from the end user. To complete the workflow and to enable the domain scientists to interactively visualize their data without advanced skills in 3D visualization systems, we developed a lightweight custom visualization application (MEVA - multifaceted environmental data visualization application) that supports the most relevant visualization and interaction techniques and can be easily deployed. Specifically, our workflow combines a variety of different data abstraction methods provided by a state-of-the-art 3D visualization application with the interaction and presentation features of a computer-games engine. Our customized application includes solutions for the analysis of multirun data, specifically with respect to data

  8. 3D electro-thermal Monte Carlo study of transport in confined silicon devices

    NASA Astrophysics Data System (ADS)

    Mohamed, Mohamed Y.

    The simultaneous explosion of portable microelectronics devices and the rapid shrinking of microprocessor size have provided a tremendous motivation to scientists and engineers to continue the down-scaling of these devices. For several decades, innovations have allowed components such as transistors to be physically reduced in size, allowing the famous Moore's law to hold true. As these transistors approach the atomic scale, however, further reduction becomes less probable and practical. As new technologies overcome these limitations, they face new, unexpected problems, including the ability to accurately simulate and predict the behavior of these devices, and to manage the heat they generate. This work uses a 3D Monte Carlo (MC) simulator to investigate the electro-thermal behavior of quasi-one-dimensional electron gas (1DEG) multigate MOSFETs. In order to study these highly confined architectures, the inclusion of quantum correction becomes essential. To better capture the influence of carrier confinement, the electrostatically quantum-corrected full-band MC model has the added feature of being able to incorporate subband scattering. The scattering rate selection introduces quantum correction into carrier movement. In addition to the quantum effects, scaling introduces thermal management issues due to the surge in power dissipation. Solving these problems will continue to bring improvements in battery life, performance, and size constraints of future devices. We have coupled our electron transport Monte Carlo simulation to Aksamija's phonon transport so that we may accurately and efficiently study carrier transport, heat generation, and other effects at the transistor level. This coupling utilizes anharmonic phonon decay and temperature dependent scattering rates. One immediate advantage of our coupled electro-thermal Monte Carlo simulator is its ability to provide an accurate description of the spatial variation of self-heating and its effect on non

  9. Cooperative roles of SDF-1α and EGF gradients on tumor cell migration revealed by a robust 3D microfluidic model.

    PubMed

    Kim, Beum Jun; Hannanta-anan, Pimkhuan; Chau, Michelle; Kim, Yoon Soo; Swartz, Melody A; Wu, Mingming

    2013-01-01

    Chemokine-mediated directed tumor cell migration within a three dimensional (3D) matrix, or chemoinvasion, is an important early step in cancer metastasis. Despite its clinical importance, it is largely unknown how cytokine and growth factor gradients within the tumor microenvironment regulate chemoinvasion. We studied tumor cell chemoinvasion in well-defined and stable chemical gradients using a robust 3D microfluidic model. We used CXCL12 (also known as SDF-1α) and epidermal growth factor (EGF), two well-known extracellular signaling molecules that co-exist in the tumor microenvironment (e.g. lymph nodes or intravasation sites), and a malignant breast tumor cell line, MDA-MB-231, embedded in type I collagen. When subjected to SDF-1α gradients alone, MDA-MB-231 cells migrated up the gradient, and the measured chemosensitivity (defined as the average cell velocity along the direction of the gradient) followed the ligand - receptor (SDF-1α - CXCR4) binding kinetics. On the other hand, when subjected to EGF gradients alone, tumor cells increased their overall motility, but without statistically significant chemotactic (directed) migration, in contrast to previous reports using 2D chemotaxis assays. Interestingly, we found that the chemoinvasive behavior to SDF-1α gradients was abrogated or even reversed in the presence of uniform concentrations of EGF; however, the presence of SDF-1α and EGF together modulated tumor cell motility cooperatively. These findings demonstrate the capabilities of our microfluidic model in re-creating complex microenvironments for cells, and the importance of cooperative roles of multiple cytokine and growth factor gradients in regulating cell migration in 3D environments.

  10. Cooperative Roles of SDF-1α and EGF Gradients on Tumor Cell Migration Revealed by a Robust 3D Microfluidic Model

    PubMed Central

    Kim, Beum Jun; Hannanta-anan, Pimkhuan; Chau, Michelle; Kim, Yoon Soo; Swartz, Melody A.; Wu, Mingming

    2013-01-01

    Chemokine-mediated directed tumor cell migration within a three dimensional (3D) matrix, or chemoinvasion, is an important early step in cancer metastasis. Despite its clinical importance, it is largely unknown how cytokine and growth factor gradients within the tumor microenvironment regulate chemoinvasion. We studied tumor cell chemoinvasion in well-defined and stable chemical gradients using a robust 3D microfluidic model. We used CXCL12 (also known as SDF-1α) and epidermal growth factor (EGF), two well-known extracellular signaling molecules that co-exist in the tumor microenvironment (e.g. lymph nodes or intravasation sites), and a malignant breast tumor cell line, MDA-MB-231, embedded in type I collagen. When subjected to SDF-1α gradients alone, MDA-MB-231 cells migrated up the gradient, and the measured chemosensitivity (defined as the average cell velocity along the direction of the gradient) followed the ligand – receptor (SDF-1α – CXCR4) binding kinetics. On the other hand, when subjected to EGF gradients alone, tumor cells increased their overall motility, but without statistically significant chemotactic (directed) migration, in contrast to previous reports using 2D chemotaxis assays. Interestingly, we found that the chemoinvasive behavior to SDF-1α gradients was abrogated or even reversed in the presence of uniform concentrations of EGF; however, the presence of SDF-1α and EGF together modulated tumor cell motility cooperatively. These findings demonstrate the capabilities of our microfluidic model in re-creating complex microenvironments for cells, and the importance of cooperative roles of multiple cytokine and growth factor gradients in regulating cell migration in 3D environments. PMID:23869217

  11. Using a microfluidic device for high-content analysis of cell signaling.

    PubMed

    Cheong, Raymond; Wang, Chiaochun Joanne; Levchenko, Andre

    2009-06-16

    Quantitative analysis and understanding of signaling networks require measurements of the location and activities of key proteins over time, at the level of single cells, in response to various perturbations. Microfluidic devices enable such analyses to be conducted in a high-throughput and in a highly controlled manner. We describe in detail how to design and use a microfluidic device to perform such information-rich experiments.

  12. Optimizing design and fabrication of microfluidic devices for cell cultures: An effective approach to control cell microenvironment in three dimensions

    PubMed Central

    Pagano, G.; Ventre, M.; Iannone, M.; Greco, F.; Maffettone, P. L.; Netti, P. A.

    2014-01-01

    The effects of gradients of bioactive molecules on the cell microenvironment are crucial in several biological processes, such as chemotaxis, angiogenesis, and tumor progression. The elucidation of the basic mechanisms regulating cell responses to gradients requires a tight control of the spatio-temporal features of such gradients. Microfluidics integrating 3D gels are useful tools to fulfill this requirement. However, even tiny flaws in the design or in the fabrication process may severely impair microenvironmental control, thus leading to inconsistent results. Here, we report a sequence of actions aimed at the design and fabrication of a reliable and robust microfluidic device integrated with collagen gel for cell culturing in 3D, subjected to a predetermined gradient of biomolecular signals. In particular, we developed a simple and effective solution to the frequently occurring technical problems of gas bubble formation and 3D matrix collapsing or detaching from the walls. The device here proposed, in Polydimethylsiloxane, was designed to improve the stability of the cell-laden hydrogel, where bubble deprived conditioning media flow laterally to the gel. We report the correct procedure to fill the device with the cell populated gel avoiding the entrapment of gas bubbles, yet maintaining cell viability. Numerical simulations and experiments with fluorescent probes demonstrated the establishment and stability of a concentration gradient across the gel. Finally, chemotaxis experiments of human Mesenchymal Stem Cells under the effects of Bone Morphogenetic Protein-2 gradients were performed in order to demonstrate the efficacy of the system in controlling cell microenvironment. The proposed procedure is sufficiently versatile and simple to be used also for different device geometries or experimental setups. PMID:25379108

  13. Bacterial Response to Antibiotic Gradients in a Porous Microfluidic Device

    NASA Astrophysics Data System (ADS)

    Deng, J.; Shechtman, L. A.; Sanford, R. A.; Dong, Y.; Werth, C. J.; Fouke, B. W.

    2015-12-01

    Microorganisms in nature have evolved survival strategies to cope with a wide variety of environmental stresses, including gradients in temperature, pH, substrate availability and aqueous chemistry. Microfluidic devices provide a consistently reliable real-time means to quantitatively measure, control and reproduce the dynamic nature of these stresses. As an example, accelerated adaptation from genetic mutations have been observed in E. coli as it responds to gradients of Ciprofloxacin (Zhang et. al. 2011). However, the mechanisms by which bacteria respond to antibiotic gradients, as well as the effect of changes in how the stressor is applied, have not been systematically studied. In this study, newly designed and fabricated microfluidic devices with porous media have been utilized to determine the chemical stress fields that enhance adaptation and thus to test how E. coli bacterial communities adapt to antibiotic stresses. By applying antibiotic and nutrient into inlet channels adjacent to either side of the porous media inoculated with E. coli, a gradient of antibiotic was formed. Hydrogel barriers were selectively photo-polymerized in between of the inlet channels and the porous media to prevent any undesired convection. Hence, chemical solute can only be transported by diffusion, creating a reproducible antibiotic gradient over the porous media. The bacteria were also constrained by the hydrogel boundary barriers from escaping the porous media. Preliminary results suggest that E. coli moves freely with respect to Ciprofloxacin concentrations. In addition, and unexpectedly, the E. coli colonies exhibit a concentric pulsed growth front radiating away from the point of inoculation within the micromodel ecosystem and pulse over the porous media containing antibiotic. The bacteria at the growth front grow into long filaments (up to 100μm) while the bacteria in the inner concentric area are normal size. We hypothesize that the frontier bacteria, which are first

  14. Ionic current devices-Recent progress in the merging of electronic, microfluidic, and biomimetic structures.

    PubMed

    Koo, Hyung-Jun; Velev, Orlin D

    2013-05-09

    We review the recent progress in the emerging area of devices and circuits operating on the basis of ionic currents. These devices operate at the intersection of electrochemistry, electronics, and microfluidics, and their potential applications are inspired by essential biological processes such as neural transmission. Ionic current rectification has been demonstrated in diode-like devices containing electrolyte solutions, hydrogel, or hydrated nanofilms. More complex functions have been realized in ionic current based transistors, solar cells, and switching memory devices. Microfluidic channels and networks-an intrinsic component of the ionic devices-could play the role of wires and circuits in conventional electronics.

  15. Microfluidics on compliant substrates: recent developments in foldable and bendable devices and system packaging

    NASA Astrophysics Data System (ADS)

    Gray, Bonnie L.

    2012-04-01

    Microfluidics is revolutionizing laboratory methods and biomedical devices, offering new capabilities and instrumentation in multiple areas such as DNA analysis, proteomics, enzymatic analysis, single cell analysis, immunology, point-of-care medicine, personalized medicine, drug delivery, and environmental toxin and pathogen detection. For many applications (e.g., wearable and implantable health monitors, drug delivery devices, and prosthetics) mechanically flexible polymer devices and systems that can conform to the body offer benefits that cannot be achieved using systems based on conventional rigid substrate materials. However, difficulties in implementing active devices and reliable packaging technologies have limited the success of flexible microfluidics. Employing highly compliant materials such as PDMS that are typically employed for prototyping, we review mechanically flexible polymer microfluidic technologies based on free-standing polymer substrates and novel electronic and microfluidic interconnection schemes. Central to these new technologies are hybrid microfabrication methods employing novel nanocomposite polymer materials and devices. We review microfabrication methods using these materials, along with demonstrations of example devices and packaging schemes that employ them. We review these recent developments and place them in the context of the fields of flexible microfluidics and conformable systems, and discuss cross-over applications to conventional rigid-substrate microfluidics.

  16. A new UV-curing elastomeric substrate for rapid prototyping of microfluidic devices

    NASA Astrophysics Data System (ADS)

    Alvankarian, Jafar; Yeop Majlis, Burhanuddin

    2012-03-01

    Rapid prototyping in the design cycle of new microfluidic devices is very important for shortening time-to-market. Researchers are facing the challenge to explore new and suitable substrates with simple and efficient microfabrication techniques. In this paper, we introduce and characterize a UV-curing elastomeric polyurethane methacrylate (PUMA) for rapid prototyping of microfluidic devices. The swelling and solubility of PUMA in different chemicals is determined. Time-dependent measurements of water contact angle show that the native PUMA is hydrophilic without surface treatment. The current monitoring method is used for measurement of the electroosmotic flow mobility in the microchannels made from PUMA. The optical, physical, thermal and mechanical properties of PUMA are evaluated. The UV-lithography and molding process is used for making micropillars and deep channel microfluidic structures integrated to the supporting base layer. Spin coating is characterized for producing different layer thicknesses of PUMA resin. A device is fabricated and tested for examining the strength of different bonding techniques such as conformal, corona treating and semi-curing of two PUMA layers in microfluidic application and the results show that the bonding strengths are comparable to that of PDMS. We also report fabrication and testing of a three-layer multi inlet/outlet microfluidic device including a very effective fluidic interconnect for application demonstration of PUMA as a promising new substrate. A simple micro-device is developed and employed for observing the pressure deflection of membrane made from PUMA as a very effective elastomeric valve in microfluidic devices.

  17. A 3D character animation engine for multimodal interaction on mobile devices

    NASA Astrophysics Data System (ADS)

    Sandali, Enrico; Lavagetto, Fabio; Pisano, Paolo

    2005-03-01

    Talking virtual characters are graphical simulations of real or imaginary persons that enable natural and pleasant multimodal interaction with the user, by means of voice, eye gaze, facial expression and gestures. This paper presents an implementation of a 3D virtual character animation and rendering engine, compliant with the MPEG-4 standard, running on Symbian-based SmartPhones. Real-time animation of virtual characters on mobile devices represents a challenging task, since many limitations must be taken into account with respect to processing power, graphics capabilities, disk space and execution memory size. The proposed optimization techniques allow to overcome these issues, guaranteeing a smooth and synchronous animation of facial expressions and lip movements on mobile phones such as Sony-Ericsson's P800 and Nokia's 6600. The animation engine is specifically targeted to the development of new "Over The Air" services, based on embodied conversational agents, with applications in entertainment (interactive story tellers), navigation aid (virtual guides to web sites and mobile services), news casting (virtual newscasters) and education (interactive virtual teachers).

  18. Split and flow: reconfigurable capillary connection for digital microfluidic devices.

    PubMed

    Lapierre, Florian; Harnois, Maxime; Coffinier, Yannick; Boukherroub, Rabah; Thomy, Vincent

    2014-09-21

    Supplying liquid to droplet-based microfluidic microsystems remains a delicate task facing the problems of coupling continuous to digital or macro- to microfluidic systems. Here, we take advantage of superhydrophobic microgrids to address this problem. Insertion of a capillary tube inside a microgrid aperture leads to a simple and reconfigurable droplet generation setup.

  19. Methodology of the determination of the uncertainties by using the biometric device the broadway 3D

    NASA Astrophysics Data System (ADS)

    Jasek, Roman; Talandova, Hana; Adamek, Milan

    2016-06-01

    The biometric identification by face is among one of the most widely used methods of biometric identification. Due to it provides a faster and more accurate identification; it was implemented into area of security 3D face reader by Broadway manufacturer was used to measure. It is equipped with the 3D camera system, which uses the method of structured light scanning and saves the template into the 3D model of face. The obtained data were evaluated by software Turnstile Enrolment Application (TEA). The measurements were used 3D face reader the Broadway 3D. First, the person was scanned and stored in the database. Thereafter person has already been compared with the stored template in the database for each method. Finally, a measure of reliability was evaluated for the Broadway 3D face reader.

  20. Tip-multi-breaking in Capillary Microfluidic Devices

    PubMed Central

    Zhu, Pingan; Kong, Tiantian; Kang, Zhanxiao; Tian, Xiaowei; Wang, Liqiu

    2015-01-01

    We report tip-multi-breaking (TMB) mode of droplet breakup in capillary microfluidic devices. This new mode appears in a region embraced by Cai = 0 and lg(Cai) = − 8.371(Ca0) −7.36 with Ca0 varying from 0.35 to 0.63 on the Cai – Ca0 phase diagram, Cai and Ca0 being the capillary numbers of inner and outer fluids, respectively. The mode is featured with a periodic, constant-speed thinning of the inner liquid tip and periodic formation of a sequence of droplets. The droplet number n in a sequence is determined by and increases with outer phase capillary number, and varies from two to over ten. The distribution of both pinch-off time and size of the droplets in a sequence is a geometric progression of common ratio that depends exclusively on and increases monotonically with the droplet number from its minimum value of 0.5 at n = 2 to its maximum value of 1 as n tends to infinity. These features can help identify the unique geometric morphology of droplet clusters and make them promising candidates for encryption and anti-fake identification. PMID:26077155

  1. Calculation of Acoustic Radiation Force and Moment in Microfluidic Devices

    NASA Astrophysics Data System (ADS)

    Lim, Kian-Meng; Rahnama, Shahrokh Sepehri

    2014-11-01

    The ability to compute the acoustic radiation force and torque acting on a particle is critical to the design of microfluidic devices and the operating conditions for separation of different species of particles or biological cells using this force field. Closed-form formulae had been reported in the literature for calculating the acoustic radiation force acting on simple geometries such as spheres and ellipsoids. Also, these analytical formulae are limited to objects that are small compared to the wavelength of sound in the surrounding fluid. Numerical methods provide a more flexible way to calculate the acoustic radiation force and torque on suspended objects of arbitrary shape and size. In this paper, we will present results of using the finite element method and the multipole expansion method to calculate the acoustic radiation force and moment. For harmonic excitation, the Helmholtz equation is solved for the velocity potential of the acoustic field with the appropriate boundary conditions imposed on the surface of the spherical or ellipsoidal objects. The resultant force and torque were then calculated by performing a surface integral of the second order, time-averaged Brillouin stress over the object. The numerical results show good agreement with the analytical results for small size spheres and ellipsoids. When the object size is comparable to the wavelength of the acoustic field, the analytical results breakdown and numerical methods are necessary to obtain accurate results.

  2. Development of a Microfluidics-Based Intracochlear Drug Delivery Device

    PubMed Central

    Sewell, William F.; Borenstein, Jeffrey T.; Chen, Zhiqiang; Fiering, Jason; Handzel, Ophir; Holmboe, Maria; Kim, Ernest S.; Kujawa, Sharon G.; McKenna, Michael J.; Mescher, Mark M.; Murphy, Brian; Leary Swan, Erin E.; Peppi, Marcello; Tao, Sarah

    2009-01-01

    Background Direct delivery of drugs and other agents into the inner ear will be important for many emerging therapies, including the treatment of degenerative disorders and guiding regeneration. Methods We have taken a microfluidics/MEMS (MicroElectroMechanical Systems) technology approach to develop a fully implantable reciprocating inner-ear drug-delivery system capable of timed and sequenced delivery of agents directly into perilymph of the cochlea. Iterations of the device were tested in guinea pigs to determine the flow characteristics required for safe and effective delivery. For these tests, we used the glutamate receptor blocker DNQX, which alters auditory nerve responses but not cochlear distortion product otoacoustic emissions. Results We have demonstrated safe and effective delivery of agents into the scala tympani. Equilibration of the drug in the basal turn occurs rapidly (within tens of minutes) and is dependent on reciprocating flow parameters. Conclusion We have described a prototype system for the direct delivery of drugs to the inner ear that has the potential to be a fully implantable means for safe and effective treatment of hearing loss and other diseases. PMID:19923811

  3. Studies of bacterial aerotaxis in a microfluidic device

    PubMed Central

    Adler, Micha; Erickstad, Michael; Gutierrez, Edgar; Groisman, Alex

    2012-01-01

    Aerotaxis, the directional motion of bacteria in gradients of oxygen, was discovered in late 19th century and has since been reported in a variety of bacterial species. Nevertheless, quantitative studies of aerotaxis have been complicated by the lack of tools for generation of stable gradients of oxygen concentration, [O2]. Here we report a series of experiments on aerotaxis of Escherichia coli in a specially built experimental setup consisting of a computer-controlled gas mixer and a two-layer microfluidic device made of polydimethylsiloxane (PDMS). The setup enables generation of a variety of stable linear profiles of [O2] across a long gradient channel, with characteristic [O2] ranging from aerobic to microaerobic conditions. A suspension of E. coli cells is perfused through the gradient channel at a low speed, allowing cells enough time to explore the [O2] gradient, and the distribution of cells across the channel is analyzed near the channel outlet at a throughput of >105 cells per hour. Aerotaxis experiments are performed in [O2] gradients with identical logarithmic slopes and varying mean concentrations, as well as in gradients with identical mean concentrations and varying slopes. Experiments in gradients with [O2] ranging from 0 to ~11.5% indicate that, in contrast to some previous reports, E. coli cells do not congregate at some intermediate level of [O2], but rather prefer the highest accessible [O2]. The presented technology can be applied to studies of aerotaxis of other aerobic and microaerobic bacteria. PMID:23010909

  4. Super-Resolution Imaging of Bacteria in a Microfluidics Device

    PubMed Central

    Valeri, Alessandro; Mignot, Tâm; Nöllmann, Marcelo

    2013-01-01

    Bacteria have evolved complex, highly-coordinated, multi-component cellular engines to achieve high degrees of efficiency, accuracy, adaptability, and redundancy. Super-resolution fluorescence microscopy methods are ideally suited to investigate the internal composition, architecture, and dynamics of molecular machines and large cellular complexes. These techniques require the long-term stability of samples, high signal-to-noise-ratios, low chromatic aberrations and surface flatness, conditions difficult to meet with traditional immobilization methods. We present a method in which cells are functionalized to a microfluidics device and fluorophores are injected and imaged sequentially. This method has several advantages, as it permits the long-term immobilization of cells and proper correction of drift, avoids chromatic aberrations caused by the use of different filter sets, and allows for the flat immobilization of cells on the surface. In addition, we show that different surface chemistries can be used to image bacteria at different time-scales, and we introduce an automated cell detection and image analysis procedure that can be used to obtain cell-to-cell, single-molecule localization and dynamic heterogeneity as well as average properties at the super-resolution level. PMID:24146850

  5. A wavelike buffer for introducing samples into autonomous capillary microfluidic devices

    NASA Astrophysics Data System (ADS)

    Li, Jingmin; Liang, Chao; Wang, Shuai; Guo, Lihua; Liu, Ziyang; Liu, Chong

    2017-01-01

    The microfluidic technique has gained attention due to its advantages in providing a rapid diagnostic result for on-site diagnosis and treatment. To obtain a quantitative and reproducible diagnostic result the fluid flow in the microfluidic device must be steady. However, a non-specific flow will always form due to the disturbances introduced during the sample injecting process. Here, a wavelike sample introduction buffer is presented. The buffer can change the longitudinal flow of the injected sample to a transverse flow, which will consume the kinetic energy and eliminate disturbances. By using the buffer, fluid flow within a microfluidic device can become steady. The effects of the buffer parameters on buffering performance have been studied. Results show that the buffering performance increases as the waved peak height and peak number decrease. This buffer has a simple structure. It requires no external power supplies or complicated fabrication process. It will be helpful in improving the diagnostic accuracy of microfluidic devices.

  6. Low density cell culture of locust neurons in closed-channel microfluidic devices.

    PubMed

    Göbbels, Katrin; Thiebes, Anja Lena; van Ooyen, André; Schnakenberg, Uwe; Bräunig, Peter

    2010-08-01

    Microfluidic channel systems were fabricated out of polydimethylsiloxane (PDMS) and used as culture vessels for primary culture of neurons from locust thoracic ganglia. In a biocompatibility study it was shown that cell adhesion and neuronal cell growth of locust neurons on uncoated PDMS was restricted. Coating with concanavalin A improved cell adhesion. In closed-channel microfluidic devices neurons were grown in static-bath culture conditions for more than 15 days. Cell densities of up to 20 cells/channel were not exceeded in low-density cultures but we also found optimal cell growth of single neurons inside individual channels. The first successful cultivation of insect neurons in closed-channel microfluidic devices provides a prerequisite for the development of low density neuronal networks on multi electrode arrays combined with microfluidic devices.

  7. Study of local intracellular signals regulating axonal morphogenesis using a microfluidic device

    PubMed Central

    Uryu, Daiki; Tamaru, Tomohiro; Suzuki, Azusa; Sakai, Rie; Konishi, Yoshiyuki

    2016-01-01

    Abstract The establishment and maintenance of axonal patterning is crucial for neuronal function. To identify the molecular systems that operate locally to control axonal structure, it is important to manipulate molecular functions in restricted subcellular areas for a long period of time. Microfluidic devices can be powerful tools for such purposes. In this study, we demonstrate the application of a microfluidic device to clarify the function of local Ca2+ signals in axons. Membrane depolarization significantly induced axonal branch-extension in cultured cerebellar granule neurons (CGNs). Local application of nifedipine using a polydimethylsiloxane (PDMS)-based microfluidic device demonstrated that Ca2+ entry from the axonal region via L-type voltage-dependent calcium channels (L-VDCC) is required for branch extension. Furthermore, we developed a method for locally controlling protein levels by combining genetic techniques and use of a microfluidic culture system. A vector for enhanced green fluorescent protein (EGFP) fused to a destabilizing domain derived from E. coli dihydrofolate reductase (ecDHFR) is introduced in neurons by electroporation. By local application of the DHFR ligand, trimethoprim (TMP) using a microfluidic device, we were able to manipulate differentially the level of fusion protein between axons and somatodendrites. The present study revealed the effectiveness of microfluidic devices to address fundamental biological issues at subcellular levels, and the possibility of their development in combination with molecular techniques. PMID:27877916

  8. 3D Printing of Shape Memory Polymers for Flexible Electronic Devices.

    PubMed

    Zarek, Matt; Layani, Michael; Cooperstein, Ido; Sachyani, Ela; Cohn, Daniel; Magdassi, Shlomo

    2016-06-01

    The formation of 3D objects composed of shape memory polymers for flexible electronics is described. Layer-by-layer photopolymerization of methacrylated semicrystalline molten macromonomers by a 3D digital light processing printer enables rapid fabrication of complex objects and imparts shape memory functionality for electrical circuits.

  9. A novel ultrathin collagen nanolayer assembly for 3-D microtissue engineering: Layer-by-layer collagen deposition for long-term stable microfluidic hepatocyte culture.

    PubMed

    McCarty, William J; Usta, O Berk; Luitje, Martha; Bale, Shyam Sundhar; Bhushan, Abhinav; Hegde, Manjunath; Golberg, Inna; Jindal, Rohit; Yarmush, Martin L

    2014-03-01

    The creation of stable hepatocyte cultures using cell-matrix interactions has proven difficult in microdevices due to dimensional constraints limiting the utility of classic tissue culture techniques that involve the use of hydrogels such as the collagen "double gel" or "overlay". To translate the collagen overlay technique into microdevices, we modified collagen using succinylation and methylation reactions to create polyanionic and polycationic collagen solutions, and deposited them layer-by-layer to create ultrathin collagen nanolayers on hepatocytes. These ultrathin collagen layers covered hepatocytes in microdevices and 1) maintained cell morphology, viability, and polarity, 2) induced bile canalicular formation and actin reorganization, and 3) maintained albumin and urea secretions and CYP activity similar to those observed in hepatocytes in collagen double gel hepatocytes in plate cultures. Beyond the immediate applications of this technique to create stable, in vitro microfluidic hepatocyte cultures for drug toxicity testing, this technique is generally applicable as a thin biomaterial for other 3D microtissues.

  10. A microfluidic opto-caloric switch for sorting of particles by using 3D-hydrodynamic focusing based on SLE fabrication capabilities.

    PubMed

    Meineke, G; Hermans, M; Klos, J; Lenenbach, A; Noll, R

    2016-03-07

    In a miniaturised flow switch fluid flows are controlled by reducing the local viscosity via absorption of laser radiation. Through this, the local flow rates are increased to switch the outlet port of a fluid flow carrying the analyte. The microfluidic chip is fabricated using Selective Laser-Induced Etching (SLE). SLE allows novel 3D-hydrodynamic focusing, realising circular shaped channel cross-sections and adapting interaction volume geometries to the profile of the laser radiation for optimised absorption. The performance of the switch is validated experimentally with a dyed analyte and video image processing. The ability to sort particles like cells is demonstrated at 8 Hz using polystyrene beads having a diameter of 8 μm.

  11. A low cost solution for the fabrication of dielectrophoretic microfluidic devices and embedded electrodes.

    PubMed

    Sano, Michael B; Caldwell, John L; Davalos, Rafael V

    2011-01-01

    The versatility of a simple method for producing microfluidic devices with embedded electrodes is demonstrated through the fabrication and operation of two dielectrophoretic devices; one employing interdigitated electrode structures on glass and the other employing contactless electrode reservoirs. Device manufacture is based on the precipitation of silver and subsequent photolithography of thin film resists conducted outside of a cleanroom environment. In current experiments, minimum channel widths of 50 microns and electrode widths of 25 microns are achieved when the distance between features is 40 microns or greater. These results illustrate this technique's potential to produce microfluidic devices with embedded electrodes for lab on chip applications while significantly reducing fabrication expense.

  12. The integration of 3D carbon-electrode dielectrophoresis on a CD-like centrifugal microfluidic platform.

    PubMed

    Martinez-Duarte, Rodrigo; Gorkin, Robert A; Abi-Samra, Kameel; Madou, Marc J

    2010-04-21

    We introduce the integration of a novel dielectrophoresis (DEP)-assisted filter with a compact disk (CD)-based centrifugal platform. Carbon-electrode dielectrophoresis (carbon-DEP) refers to the use of carbon electrodes to induce DEP. In this work, 3D carbon electrodes are fabricated using the C-MEMS technique and are used to implement a DEP-enabled active filter to trap particles of interest. Compared to traditional planar metal electrodes, 3D carbon electrodes allow for superior filtering efficiency. The system includes mounting modular 3D carbon-DEP chips on an electrically interfaced rotating disk. This allows simple centrifugal pumping to replace the large footprint syringe pump approaches commonly used in DEP systems. The advantages of the CD setup include not only a reduced footprint, but also complexity and cost reduction by eliminating expensive precision pumps and fluidic interconnects. To demonstrate the viability of this system we quantified the filter efficiency in the DEP trapping of yeast cells from a mix of latex and yeast cells. Results demonstrate selective filtering at flow rates up to 35 microl min(-1). The impact of electrode height, DEP chip misalignment and particle sedimentation on filter efficiency and the advantages this system represents are analyzed. The ultimate goal is to obtain an automated platform for bioparticle sorting with application in different fields such as point-of-care diagnostics and cell-based therapies.

  13. Fabrication, Metrology, and Transport Characteristics of Single Polymeric Nanopores in Three-Dimensional Hybrid Microfluidic/Nanofluidic Devices

    ERIC Educational Resources Information Center

    King, Travis L.

    2009-01-01

    The incorporation of nanofluidic elements between microfluidic channels to form hybrid microfluidic/nanofluidic architectures allows the extension of microfluidic systems into the third dimension, thus removing the constraints imposed by planarity. Measuring and understanding the behavior of these devices creates new analytical challenges due to…

  14. 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.

  15. Nanoscale surface modifications to control capillary flow characteristics in PMMA microfluidic devices

    PubMed Central

    2011-01-01

    Polymethylmethacrylate (PMMA) microfluidic devices have been fabricated using a hot embossing technique to incorporate micro-pillar features on the bottom wall of the device which when combined with either a plasma treatment or the coating of a diamond-like carbon (DLC) film presents a range of surface modification profiles. Experimental results presented in detail the surface modifications in the form of distinct changes in the static water contact angle across a range from 44.3 to 81.2 when compared to pristine PMMA surfaces. Additionally, capillary flow of water (dyed to aid visualization) through the microfluidic devices was recorded and analyzed to provide comparison data between filling time of a microfluidic chamber and surface modification characteristics, including the effects of surface energy and surface roughness on the microfluidic flow. We have experimentally demonstrated that fluid flow and thus filling time for the microfluidic device was significantly faster for the device with surface modifications that resulted in a lower static contact angle, and also that the incorporation of micro-pillars into a fluidic device increases the filling time when compared to comparative devices. PMID:21711936

  16. Colorimetric analysis of the decomposition of S-nitrosothiols on paper-based microfluidic devices.

    PubMed

    Ismail, Abdulghani; Araújo, Marillya O; Chagas, Cyro L S; Griveau, Sophie; D'Orlyé, Fanny; Varenne, Anne; Bedioui, Fethi; Coltro, Wendell K T

    2016-10-24

    A disposable microfluidic paper-based analytical device (μPAD) was developed to easily analyse different S-nitrosothiols (RSNOs) through colorimetric measurements. RSNOs are carriers of nitric oxide (NO) that play several physiological and physiopathological roles. The quantification of RSNOs relies on their decomposition using several protocols and the colorimetric detection of the final product, NO or nitrite. μPADs were fabricated by wax printing technology in a geometry containing one central zone for the sample inlet and eight circular detection zones interconnected by microfluidic channels for decomposition and posterior detection of decayed products. Different decomposition protocols including mercuric ions and light (UV, visible, and infrared) were tested on μPADs. For this purpose, a 3D printed holder was coupled with μPADs to easily design a simultaneous decomposition procedure using different light sources. The Griess reagent was added to detect NO and nitrite produced by the different decomposition methods. μPADs were then scanned using a flat board scanner and calibration curves based on color intensity were plotted. The limit of detection (LOD) values achieved for nitrite (used as a reference compound) and S-nitrosoglutathione (GSNO) using mercuric decomposition were 3 and 4 μM, respectively. The LOD reported herein for nitrite is considered among the lowest LODs already reported for this compound using μPADs. The results also show that low-molecular-weight RSNO, namely S-nitrosocysteine, decomposes more easily than high-molecular-weight RSNOs with light. As a proof of concept, RSNOs in human plasma were successfully detected on μPADs. For this purpose, a preliminary treatment step was optimized and the presence of high-molecular-weight (HMW) RSNOs was evidenced in the available plasma samples. The concentrations of HMW-RSNOs and nitrite in the various samples ranged from 5 to 16 μM and from 37 to 58 μM, respectively.

  17. Software architecture as a freedom for 3D content providers and users along with independency on purposes and used devices

    NASA Astrophysics Data System (ADS)

    Sultana, Razia; Christ, Andreas; Meyrueis, Patrick

    2014-05-01

    The improvements in the hardware and software of communication devices have allowed running Virtual Reality (VR) and Augmented Reality (AR) applications on those. Nowadays, it is possible to overlay synthetic information on real images, or even to play 3D on-line games on smart phones or some other mobile devices. Hence the use of 3D data for business and specially for education purposes is ubiquitous. Due to always available at hand and always ready to use properties of mobile phones, those are considered as most potential communication devices. The total numbers of mobile phone users are increasing all over the world every day and that makes mobile phones the most suitable device to reach a huge number of end clients either for education or for business purposes. There are different standards, protocols and specifications to establish the communication among different communication devices but there is no initiative taken so far to make it sure that the send data through this communication process will be understood and used by the destination device. Since all the devices are not able to deal with all kind of 3D data formats and it is also not realistic to have different version of the same data to make it compatible with the destination device, it is necessary to have a prevalent solution. The proposed architecture in this paper describes a device and purpose independent 3D data visibility any time anywhere to the right person in suitable format. There is no solution without limitation. The architecture is implemented in a prototype to make an experimental validation of the architecture which also shows the difference between theory and practice.

  18. Optimal invasive key-hole neurosurgery with a miniaturized 3D chip on the tip: Microendoscopic device

    PubMed Central

    Charalampaki, Patra; Igressa, Alhadi; Mahvash, Mehran; Pechlivanis, Ioannis; Schick, Bernhard

    2013-01-01

    Objective: The goal of the performed study was to evaluate the possibility of a three-dimensional endoscope to become a combined microscope-endoscope device in one. We analyzed the ergonomy of the device, the implementation into the surgical workflow, the image quality, and the future perspectives such devices could have for the next generation of neurosurgeons. Materials and Methods: Within 6 months, 22 patients (10 male, 12 female, 20-65 age) underwent surgery in neuroaxis using the new 3D-microendoscope (ME). The new 3D-ME has (a) the ability to visualize the surgical field from out- to inside with all advantages offered by a microscope, and in the same moment, (b) its design is like a small diameter endoscope that allows stereoscopic views extracorporal, intracorporal, and panoramic “para-side” of the lesion. Results: In general, transcranial 3D-“microendoscopy” was performed in all patients with high-resolution 3D quality. No severe complications were observed intra- or postoperatively. With the addition of depth perception, the anatomic structures were well seen and observed. Conclusion: The 3D-microendoscopy is a very promising surgical concept associated with new technological developments. The surgeon is able to switch to a modern visualization instrument reaching the most optimal surgical approach without compromising safety, effectiveness, and visual information. PMID:24403954

  19. A guiding light: spectroscopy on digital microfluidic devices using in-plane optical fibre waveguides.

    PubMed

    Choi, Kihwan; Mudrik, Jared M; Wheeler, Aaron R

    2015-09-01

    We present a novel method for in-plane digital microfluidic spectroscopy. In this technique, a custom manifold (.stl file available online as ESM) aligns optical fibres with a digital microfluidic device, allowing optical measurements to be made in the plane of the device. Because of the greater width vs thickness of a droplet on-device, the in-plane alignment of this technique allows it to outperform the sensitivity of vertical absorbance measurements on digital microfluidic (DMF) devices by ∼14×. The new system also has greater calibration sensitivity for thymol blue measurements than the popular NanoDrop system by ∼2.5×. The improvements in absorbance sensitivity result from increased path length, as well as from additional effects likely caused by liquid lensing, in which the presence of a water droplet between optical fibres increases fibre-to-fibre transmission of light by ∼2× through refraction and internal reflection. For interrogation of dilute samples, stretching of droplets using digital microfluidic electrodes and adjustment of fibre-to-fibre gap width allows absorbance path length to be changed on-demand. We anticipate this new digital microfluidic optical fibre absorbance and fluorescence measurement system will be useful for a wide variety of analytical applications involving microvolume samples with digital microfluidics.

  20. Integration of microfluidic chip with biomimetic hydrogel for 3D controlling and monitoring of cell alignment and migration.

    PubMed

    Lee, Kwang Ho; Lee, Ki Hwa; Lee, Jeonghoon; Choi, Hyuk; Lee, Donghee; Park, Yongdoo; Lee, Sang-Hoon

    2014-04-01

    A biomimetic hydrogel was integrated into microfluidic chips to monitor glioma cell alignment and migration. The extracellular matrix-based biomimetic hydrogel was remodeled by matrix metalloprotease (MMP) secreted by glioma cells and the hydrogel could thus be used to assess cellular behavior. Both static and dynamic cell growth conditions (flow rate of 0.1 mL/h) were used. Cell culture medium with and without vascular endothelial growth factor (VEGF), insensitive VEGF and tissue inhibitor of metalloproteinases (TIMP) were employed to monitor cell behavior. A concentration gradient formed in the hydrogel resulted in differences in cell behavior. Glioma cell viability in the microchannel was 75-85%. Cells in the VEGF-loaded microchannels spread extensively, degrading the MMP-sensitive hydrogel, and achieved cell sizes almost fivefold larger than seen in the control medium. Our integrated system can be used as a model for the study of cellular behavior in a controlled microenvironment generated by fluidic conditions in a biomimetic matrix.

  1. Microfluidic device for continuous single cells analysis via Raman spectroscopy enhanced by integrated plasmonic nanodimers.

    PubMed

    Perozziello, Gerardo; Candeloro, Patrizio; De Grazia, Antonio; Esposito, Francesco; Allione, Marco; Coluccio, Maria Laura; Tallerico, Rossana; Valpapuram, Immanuel; Tirinato, Luca; Das, Gobind; Giugni, Andrea; Torre, Bruno; Veltri, Pierangelo; Kruhne, Ulrich; Della Valle, Giuseppe; Di Fabrizio, Enzo

    2016-01-25

    In this work a Raman flow cytometer is presented. It consists of a microfluidic device that takes advantages of the basic principles of Raman spectroscopy and flow cytometry. The microfluidic device integrates calibrated microfluidic channels- where the cells can flow one-by-one -, allowing single cell Raman analysis. The microfluidic channel integrates plasmonic nanodimers in a fluidic trapping region. In this way it is possible to perform Enhanced Raman Spectroscopy on single cell. These allow a label-free analysis, providing information about the biochemical content of membrane and cytoplasm of the each cell. Experiments are performed on red blood cells (RBCs), peripheral blood lymphocytes (PBLs) and myelogenous leukemia tumor cells (K562).

  2. Reduction of surface roughness for optical quality microfluidic devices in PMMA and COC

    NASA Astrophysics Data System (ADS)

    Ogilvie, I. R. G.; Sieben, V. J.; Floquet, C. F. A.; Zmijan, R.; Mowlem, M. C.; Morgan, H.

    2010-06-01

    A rapid and low-cost technique is presented for the fabrication of optical quality microfluidic devices in poly(methyl methacrylate) (PMMA) or cyclic olefin copolymer (COC). When polymer microfluidic devices are manufactured by rapid prototyping techniques, such as micromilling, the surface roughness is typically in the region of hundreds of nanometres reducing the overall optical efficiency of many microfluidic-based systems. Here we demonstrate a novel solvent vapour treatment that is used to irreversibly bond microfluidic chips while simultaneously reducing the channel surface roughness, yielding optical grade (less than 15 nm surface roughness) channel walls. We characterize this vapour bonding method and optimize the process parameters to avoid channel collapse, while achieving reflow of polymer and uniformity of bonding. The reflow of polymer is the key to enabling a fabrication process that takes less than a day and produces optical quality surfaces with low-cost rapid prototyping tools.

  3. Incorporation of prefabricated screw, pneumatic, and solenoid valves into microfluidic devices

    PubMed Central

    Hulme, S. Elizabeth; Shevkoplyas, Sergey S.

    2011-01-01

    This paper describes a method for prefabricating screw, pneumatic, and solenoid valves and embedding them in microfluidic devices. This method of prefabrication and embedding is simple, requires no advanced fabrication, and is compatible with soft lithography. Because prefabrication allows many identical valves to be made at one time, the performance across different valves made in the same manner is reproducible. In addition, the performance of a single valve is reproducible over many cycles of opening and closing: an embedded solenoid valve opened and closed a microfluidic channel more than 100,000 times with no apparent deterioration in its function. It was possible to combine all three types of prefabricated valves in a single microfluidic device to control chemical gradients in a microfluidic channel temporally and spatially. PMID:19209338

  4. Implementation of tetra-poly(ethylene glycol) hydrogel with high mechanical strength into microfluidic device technology

    PubMed Central

    Takehara, Hiroaki; Nagaoka, Akira; Noguchi, Jun; Akagi, Takanori; Sakai, Takamasa; Chung, Ung-il; Kasai, Haruo; Ichiki, Takanori

    2013-01-01

    Hydrogels have several excellent characteristics suitable for biomedical use such as softness, biological inertness and solute permeability. Hence, integrating hydrogels into microfluidic devices is a promising approach for providing additional functions such as biocompatibility and porosity, to microfluidic devices. However, the poor mechanical strength of hydrogels has severely limited device design and fabrication. A tetra-poly(ethylene glycol) (tetra-PEG) hydrogel synthesized recently has high mechanical strength and is expected to overcome such a limitation. In this research, we have comprehensively studied the implementation of tetra-PEG gel into microfluidic device technology. First, the fabrication of tetra-PEG gel/PDMS hybrid microchannels was established by developing a simple and robust bonding technique. Second, some fundamental features of tetra-PEG gel/PDMS hybrid microchannels, particularly fluid flow and mass transfer, were studied. Finally, to demonstrate the unique application of tetra-PEG-gel-integrated microfluidic devices, the generation of patterned chemical modulation with the maximum concentration gradient: 10% per 20 μm in a hydrogel was performed. The techniques developed in this study are expected to provide fundamental and beneficial methods of developing various microfluidic devices for life science and biomedical applications. PMID:24404072

  5. Interventional left atrial appendage occlusion: added value of 3D transesophageal echocardiography for device sizing.

    PubMed

    Goebel, Björn; Wieg, Stephanie; Hamadanchi, Ali; Otto, Sylvia; Jung, Christian; Kretzschmar, Daniel; Figulla, Hans R; Christian Schulze, P; Poerner, Tudor C

    2016-09-01

    Aim of this study was the assessment of left atrial appendage (LAA) dimensions comparing 2D- to 3D-TEE measurements in patients with nonvalvular atrial fibrillation undergoing percutaneous LAA occlusion. Patients underwent transesophageal echocardiography (TEE) before, during and 45 days after intervention. The maximal LAA orifice diameters in 2D-TEE (LODmax 2D) were obtained from multiple views. Test-retest reliability (screening vs. implantation), inter- and intra-observer variability for echocardiographic parameters were assessed by two independent examiners. Overall, 74 patients underwent percutaneous LAA occlusion. 2D-TEE significantly underestimated the maximal LAA orifice diameter compared with 3D-TEE (screening LODmax 2D 21.11 ± 2.75 mm vs. 22.52 ± 3.45 mm for LODmax 3D, p < 0.001; during implantation LODmax 2D 21.56 ± 3.48 mm vs. 22.99 ± 3.24 mm for LODmax 3D, p < 0.001). The intraobserver and interobserver variability calculated as coefficient of variation (CV) were both lower for the 3D-TEE quantification of the maximal orifice diameter (intraobserver CV for 3D-TEE 6.07 % vs. 9.31 % for 2D-TEE; interobserver CV for 3D-TEE 6.73 % vs. 9.69 % for 2D-TEE). Compared to 3D-TEE the test-retest reliability of 2D-TEE showed a lower intraclass correlation coefficient calculated as average of raters (0.92 for 3D-TEE vs. for 2D-TEE 0.78). Firstly, 2D-TEE significantly underestimates the maximal LAA orifice diameter compared to 3D-TEE. Secondly, 3D-TEE measurements are associated with a lower observer variability and higher reliability than 2D-TEE.

  6. Light-driven 3D droplet manipulation on flexible optoelectrowetting devices fabricated by a simple spin-coating method.

    PubMed

    Jiang, Dongyue; Park, Sung-Yong

    2016-05-21

    Technical advances in electrowetting-on-dielectric (EWOD) over the past few years have extended our attraction to three-dimensional (3D) devices capable of providing more flexibility and functionality with larger volumetric capacity than conventional 2D planar ones. However, typical 3D EWOD devices require complex and expensive fabrication processes for patterning and wiring of pixelated electrodes that also restrict the minimum droplet size to be manipulated. Here, we present a flexible single-sided continuous optoelectrowetting (SCOEW) device which is not only fabricated by a spin-coating method without the need for patterning and wiring processes, but also enables light-driven 3D droplet manipulations. To provide photoconductive properties, previous optoelectrowetting (OEW) devices have used amorphous silicon (a-Si) typically fabricated through high-temperature processes over 300 °C such as CVD or PECVD. However, most of the commercially-available flexible substrates such as polyethylene terephthalate (PET) and polyethylene naphthalate (PEN) experience serious thermal deformation under such high-temperature processes. Because of this compatibility issue of conventional OEW devices with flexible substrates, light-driven 3D droplet manipulations have not yet been demonstrated on flexible substrates. Our study overcomes this compatibility issue by using a polymer-based photoconductive material, titanium oxide phthalocyanine (TiOPc) and thus SCOEW devices can be simply fabricated on flexible substrates through a low-cost, spin-coating method. In this paper, analytical studies were conducted to understand the effects of light patterns on static contact angles and EWOD forces. For experimental validations of our study, flexible SCOEW devices were successfully fabricated through the TiOPc-based spin-coating method and light-driven droplet manipulations (e.g. transportation, merging, and splitting) have been demonstrated on various 3D terrains such as inclined

  7. Foil assisted replica molding for fabrication of microfluidic devices and their application in vitro.

    PubMed

    Micheal, Issac J; Vidyasagar, Aditya J; Bokara, Kiran Kumar; Mekala, Naveen Kumar; Asthana, Amit; Rao, Ch Mohan

    2014-10-07

    We present a simple, rapid, benchtop, Foil Assisted Rapid Molding (FARM) method for the fabrication of microfluidic devices. This novel technique involves the use of aluminium foil, pen and an X-Y plotter to create semi-circular or plano-concave, shallow microchannels. It is an easy do-it-yourself (DIY) technique for creating a microfluidic device in three simple steps: (1) create a channel design using the CAD software, (2) plot the patterns on aluminium foil and (3) use the reverse of the engraved foil as a mold to create microfluidic devices. In this report, we present a detailed study of the proposed method by varying a range of parameters such as foil thickness, tip material, and tip sizes and by investigating their effect on the creation of channels with varying geometry. Furthermore, we demonstrated the cytocompatibility of these devices in vitro.

  8. Microfluidic-SERS Devices for One Shot Limit-of-Detection

    PubMed Central

    Datt, Ashish; Gao, Zhe; Rycenga, Matthew; Burrows, Nathan D.; Greeneltch, Nathan G.; Mirkin, Chad A.; Murphy, Catherine J.; Van Duyne, Richard P.; Haynes, Christy L.

    2014-01-01

    Microfluidic sensing platforms facilitate parallel, low sample volume detection using various optical signal transduction mechanisms. Herein, we introduce a simple mixing microfluidic device, enabling serial dilution of introduced analyte solution that terminates in five discrete sensing elements. We demonstrate the utility of this device with on-chip fluorescence and surface-enhanced Raman scattering (SERS) detection of analytes, and we demonstrate device use both when combined with a traditional inflexible SERS substrate and with SERS-active nanoparticles that are directly incorporated into microfluidic channels to create a flexible SERS platform. The results indicate, with varying sensitivities, that either flexible or inflexible devices can be easily used to create a calibration curve and perform a limit of detection study with a single experiment. PMID:24756225

  9. Flow shear stress regulates endothelial barrier function and expression of angiogenic factors in a 3D microfluidic tumor vascular model

    PubMed Central

    Buchanan, Cara F; Verbridge, Scott S; Vlachos, Pavlos P; Rylander, Marissa Nichole

    2014-01-01

    Endothelial cells lining blood vessels are exposed to various hemodynamic forces associated with blood flow. These include fluid shear, the tangential force derived from the friction of blood flowing across the luminal cell surface, tensile stress due to deformation of the vessel wall by transvascular flow, and normal stress caused by the hydrodynamic pressure differential across the vessel wall. While it is well known that these fluid forces induce changes in endothelial morphology, cytoskeletal remodeling, and altered gene expression, the effect of flow on endothelial organization within the context of the tumor microenvironment is largely unknown. Using a previously established microfluidic tumor vascular model, the objective of this study was to investigate the effect of normal (4 dyn/cm2), low (1 dyn/cm2), and high (10 dyn/cm2) microvascular wall shear stress (WSS) on tumor-endothelial paracrine signaling associated with angiogenesis. It is hypothesized that high WSS will alter the endothelial phenotype such that vascular permeability and tumor-expressed angiogenic factors are reduced. Results demonstrate that endothelial permeability decreases as a function of increasing WSS, while co-culture with tumor cells increases permeability relative to mono-cultures. This response is likely due to shear stress-mediated endothelial cell alignment and tumor-VEGF-induced permeability. In addition, gene expression analysis revealed that high WSS (10 dyn/cm2) significantly down-regulates tumor-expressed MMP9, HIF1, VEGFA, ANG1, and ANG2, all of which are important factors implicated in tumor angiogenesis. This result was not observed in tumor mono-cultures or static conditioned media experiments, suggesting a flow-mediated paracrine signaling mechanism exists with surrounding tumor cells that elicits a change in expression of angiogenic factors. Findings from this work have significant implications regarding low blood velocities commonly seen in the tumor vasculature

  10. Microfluidic Emulation of Mechanical Circulatory Support Device Shear-Mediated Platelet Activation

    PubMed Central

    Dimasi, A.; Rasponi, M.; Sheriff, J.; Chiu, W.-C.; Bluestein, D.; Tran, P.L.; Slepian, M. J.; Redaelli, A.

    2016-01-01

    Thrombosis of ventricular assist devices (VADs) compromises their performance, with associated risks of systemic embolization, stroke, pump stop and possible death. Anti-thrombotic (AT) drugs, utilized to limit thrombosis, are largely dosed empirically, with limited testing of their efficacy. Further, such testing, if performed, typically examines efficacy under static conditions, which is not reflective of actual shear-mediated flow. Here we adopted our previously developed Device Thrombogenicity Emulation methodology to design microfluidic platforms able to emulate representative shear stress profiles of mechanical circulatory support (MCS) devices. Our long-term goal is to utilize these systems for point-of-care (POC) personalized testing of AT efficacy under specific, individual shear profiles. First, we designed different types of microfluidic channels able to replicate sample shear stress patterns observed in MCS devices. Second, we explored the flexibility of microfluidic technology in generating dynamic shear stress profiles by modulating the geometrical features of the channels. Finally, we designed microfluidic channel systems able to emulate the shear stress profiles of two commercial VADs. From CFD analyses, the VAD-emulating microfluidic systems were able to replicate the main characteristics of the shear stress waveforms of the macroscale VADs (i.e. shear stress peaks and duration). Our results establish the basis for development of a lab-on-chip POC system able to perform device-specific and patient-specific platelet activation state assays. PMID:26578003

  11. Hydrogel microfluidic co-culture device for photothermal therapy and cancer migration.

    PubMed

    Lee, Jong Min; Seo, Hye In; Bae, Jun Hyuk; Chung, Bong Geun

    2017-02-07

    We developed the photo-crosslinkable hydrogel microfluidic co-culture device to study photothermal therapy and cancer cell migration. To culture MCF7 human breast carcinoma cells and metastatic U87MG human glioblastoma in the microfluidic device, we used 10 w/v% gelatin methacrylate (GelMA) hydrogels as a semi-permeable physical barrier. We demonstrated the effect of gold nanorod on photothermal therapy of cancer cells in the microfluidic co-culture device. Interestingly, we observed that metastatic U87MG human glioblastoma largely migrated toward vascular endothelial growth factor (VEGF)-treated GelMA hydrogel-embedding microchannels. The main advantage of this hydrogel microfluidic co-culture device is to simultaneously analyze the physiological migration behaviors of two cancer cells with different physiochemical motilities and study gold nanorod-mediated photothermal therapy effect. Therefore, this hydrogel microfluidic co-culture device could be a potentially powerful tool for photothermal therapy and cancer cell migration applications. This article is protected by copyright. All rights reserved.

  12. Graphics to H.264 video encoding for 3D scene representation and interaction on mobile devices using region of interest

    NASA Astrophysics Data System (ADS)

    Le, Minh Tuan; Nguyen, Congdu; Yoon, Dae-Il; Jung, Eun Ku; Jia, Jie; Kim, Hae-Kwang

    2007-12-01

    In this paper, we propose a method of 3D graphics to video encoding and streaming that are embedded into a remote interactive 3D visualization system for rapidly representing a 3D scene on mobile devices without having to download it from the server. In particular, a 3D graphics to video framework is presented that increases the visual quality of regions of interest (ROI) of the video by performing more bit allocation to ROI during H.264 video encoding. The ROI are identified by projection 3D objects to a 2D plane during rasterization. The system offers users to navigate the 3D scene and interact with objects of interests for querying their descriptions. We developed an adaptive media streaming server that can provide an adaptive video stream in term of object-based quality to the client according to the user's preferences and the variation of network bandwidth. Results show that by doing ROI mode selection, PSNR of test sample slightly change while visual quality of objects increases evidently.

  13. Cost Effective Paper-Based Colorimetric Microfluidic Devices and Mobile Phone Camera Readers for the Classroom

    ERIC Educational Resources Information Center

    Koesdjojo, Myra T.; Pengpumkiat, Sumate; Wu, Yuanyuan; Boonloed, Anukul; Huynh, Daniel; Remcho, Thomas P.; Remcho, Vincent T.

    2015-01-01

    We have developed a simple and direct method to fabricate paper-based microfluidic devices that can be used for a wide range of colorimetric assay applications. With these devices, assays can be performed within minutes to allow for quantitative colorimetric analysis by use of a widely accessible iPhone camera and an RGB color reader application…

  14. Co-integrated microfluidic and THz functions for biochip devices

    NASA Astrophysics Data System (ADS)

    Laurette, S.; Treizebre, A.; Bocquet, B.

    2011-06-01

    TeraHertz (THz) spectroscopy is becoming an alternative way to probe biological interactions in real-time conditions. However, accurate and reproducible THz measurements of aqueous solutions, largely represented in life sciences, remain difficult. A THz microsystem which couples both electromagnetic and microfluidic integrated functions is presented here. Its technological process is accurately detailed and enables easy designs of advanced THz and microfluidic functions. It is composed of the deposition of gold wires on a glass wafer to guide the THz waves. Then, a whole silicon wafer is bonded by using a thermosensitive-polymer thermo-compression. Silicon is deep-etched to create the microchannels which are finally covered with a second glass wafer. This bonding-etching process enables huge freedom and independence for electromagnetic and microfluidic designs. The technological process characterization has shown that the manufactured biochip is compatible with pressures up to 37 bar. First measurements with empty and water-filled channels have been carried out and have shown the ability to perform THz spectroscopy inside the chip. Then, first measurements on proteins have been performed and shown the system ability to probe protein concentration. This kind of microfluidic microsystem, allowing complex design for integrated electronic and microfluidic circuits, defines a true new instrumental way for life science investigations.

  15. Fabricating process of hollow out-of-plane Ni microneedle arrays and properties of the integrated microfluidic device

    NASA Astrophysics Data System (ADS)

    Zhu, Jun; Cao, Ying; Wang, Hong; Li, Yigui; Chen, Xiang; Chen, Di

    2013-07-01

    Although microfluidic devices that integrate microfluidic chips with hollow out-of-plane microneedle arrays have many advantages in transdermal drug delivery applications, difficulties exist in their fabrication due to the special three-dimensional structures of hollow out-of-plane microneedles. A new, cost-effective process for the fabrication of a hollow out-of-plane Ni microneedle array is presented. The integration of PDMS microchips with the Ni hollow microneedle array and the properties of microfluidic devices are also presented. The integrated microfluidic devices provide a new approach for transdermal drug delivery.

  16. Rapid Prototyping of a Cyclic Olefin Copolymer Microfluidic Device for Automated Oocyte Culturing.

    PubMed

    Berenguel-Alonso, Miguel; Sabés-Alsina, Maria; Morató, Roser; Ymbern, Oriol; Rodríguez-Vázquez, Laura; Talló-Parra, Oriol; Alonso-Chamarro, Julián; Puyol, Mar; López-Béjar, Manel

    2017-01-01

    Assisted reproductive technology (ART) can benefit from the features of microfluidic technologies, such as the automation of time-consuming labor-intensive procedures, the possibility to mimic in vivo environments, and the miniaturization of the required equipment. To date, most of the proposed approaches are based on polydimethylsiloxane (PDMS) as platform substrate material due to its widespread use in academia, despite certain disadvantages, such as the elevated cost of mass production. Herein, we present a rapid fabrication process for a cyclic olefin copolymer (COC) monolithic microfluidic device combining hot embossing-using a low-temperature cofired ceramic (LTCC) master-and micromilling. The microfluidic device was suitable for trapping and maturation of bovine oocytes, which were further studied to determine their ability to be fertilized. Furthermore, another COC microfluidic device was fabricated to store sperm and assess its quality parameters over time. The study herein presented demonstrates a good biocompatibility of the COC when working with gametes, and it exhibits certain advantages, such as the nonabsorption of small molecules, gas impermeability, and low fabrication costs, all at the prototyping and mass production scale, thus taking a step further toward fully automated microfluidic devices in ART.

  17. One step antibody-mediated isolation and patterning of multiple cell types in microfluidic devices

    PubMed Central

    Bavli, Danny; Ezra, Elishai; Kitsberg, Daniel; Murthy, Shashi K.; Nahmias, Yaakov

    2016-01-01

    Cell-cell interactions play a key role in regeneration, differentiation, and basic tissue function taking place under physiological shear forces. However, current solutions to mimic such interactions by micro-patterning cells within microfluidic devices have low resolution, high fabrication complexity, and are limited to one or two cell types. Here, we present a microfluidic platform capable of laminar patterning of any biotin-labeled peptide using streptavidin-based surface chemistry. The design permits the generation of arbitrary cell patterns from heterogeneous mixtures in microfluidic devices. We demonstrate the robust co-patterning of α-CD24, α-ASGPR-1, and α-Tie2 antibodies for rapid isolation and co-patterning of mixtures of hepatocytes and endothelial cells. In addition to one-step isolation and patterning, our design permits step-wise patterning of multiple cell types and empty spaces to create complex cellular geometries in vitro. In conclusion, we developed a microfluidic device that permits the generation of perfusable tissue-like patterns in microfluidic devices by directly injecting complex cell mixtures such as differentiated stem cells or tissue digests with minimal sample preparation. PMID:27051469

  18. Separation of biological cells in a microfluidic device using surface acoustic waves (SAWs)

    NASA Astrophysics Data System (ADS)

    Ai, Ye; Marrone, Babetta L.

    2014-03-01

    In this study, a surface acoustic wave (SAW)-based microfluidic device has been developed to separate heterogeneous particle or cell mixtures in a continuous flow using acoustophoresis. The microfluidic device is comprised of two components, a SAW transducer and a microfluidic channel made of polydimethylsiloxane (PDMS). The SAW transducer was fabricated by patterning two pairs of interdigital electrodes on a lithium niobate (LiNbO3) piezoelectric substrate. When exciting the SAW transducer by AC signals, a standing SAW is generated along the cross-section of the channel. Solid particles immersed in the standing SAW field are accordingly pushed to the pressure node arising from the acoustic radiation force acting on the particles, referring to the acoustic particle-focusing phenomenon. Acoustic radiation force highly depends on the particle properties, resulting in different acoustic responses for different types of cells. A numerical model, coupling the piezoelectric effect in the solid substrate and acoustic pressure in the fluid, was developed to provide a better understanding of SAW-based particle manipulation. Separation of two types of fluorescent particles has been demonstrated using the developed SAW-based microfluidic device. An efficient separation of E. coli bacteria from peripheral blood mononuclear cell (PBMC) samples has also been successfully achieved. The purity of separated E. coli bacteria and separated PBMCs were over 95% and 91%, respectively, obtained by a flow cytometric analysis. The developed microfluidic device can efficiently separate E. coli bacteria from biological samples, which has potential applications in biomedical analysis and clinical diagnosis.

  19. 3D Visualization of Cultural Heritage Artefacts with Virtual Reality devices

    NASA Astrophysics Data System (ADS)

    Gonizzi Barsanti, S.; Caruso, G.; Micoli, L. L.; Covarrubias Rodriguez, M.; Guidi, G.

    2015-08-01

    Although 3D models are useful to preserve the information about historical artefacts, the potential of these digital contents are not fully accomplished until they are not used to interactively communicate their significance to non-specialists. Starting from this consideration, a new way to provide museum visitors with more information was investigated. The research is aimed at valorising and making more accessible the Egyptian funeral objects exhibited in the Sforza Castle in Milan. The results of the research will be used for the renewal of the current exhibition, at the Archaeological Museum in Milan, by making it more attractive. A 3D virtual interactive scenario regarding the "path of the dead", an important ritual in ancient Egypt, was realized to augment the experience and the comprehension of the public through interactivity. Four important artefacts were considered for this scope: two ushabty, a wooden sarcophagus and a heart scarab. The scenario was realized by integrating low-cost Virtual Reality technologies, as the Oculus Rift DK2 and the Leap Motion controller, and implementing a specific software by using Unity. The 3D models were implemented by adding responsive points of interest in relation to important symbols or features of the artefact. This allows highlighting single parts of the artefact in order to better identify the hieroglyphs and provide their translation. The paper describes the process for optimizing the 3D models, the implementation of the interactive scenario and the results of some test that have been carried out in the lab.

  20. Ultra-rapid prototyping of flexible, multi-layered microfluidic devices via razor writing.

    PubMed

    Cosson, Steffen; Aeberli, Luc G; Brandenberg, Nathalie; Lutolf, Matthias P

    2015-01-07

    The fabrication of microfluidic devices is often still a time-consuming and costly process. Here we introduce a very simple and cheap microfabrication process based on "razor writing", also termed xurography, for the ultra-rapid prototyping of microfluidic devices. Thin poly(dimethylsiloxane) (PDMS) membranes are spin-coated on flexible plastic foil and cut into user-defined shapes with a bench-top cutter plotter. The PDMS membranes can then be assembled into desirable microdevices via plasma bonding. The plastic foil allows manipulation of exceptionally thin (30-300 μm) PDMS layers and can be readily peeled after fabrication. This versatile technique can be used to produce a wide variety of microfluidic device prototypes within just a few hours.

  1. Tunable Microfluidic Devices for Hydrodynamic Fractionation of Cells and Beads: A Review

    PubMed Central

    Alvankarian, Jafar; Majlis, Burhanuddin Yeop

    2015-01-01

    The adjustable microfluidic devices that have been developed for hydrodynamic-based fractionation of beads and cells are important for fast performance tunability through interaction of mechanical properties of particles in fluid flow and mechanically flexible microstructures. In this review, the research works reported on fabrication and testing of the tunable elastomeric microfluidic devices for applications such as separation, filtration, isolation, and trapping of single or bulk of microbeads or cells are discussed. Such microfluidic systems for rapid performance alteration are classified in two groups of bulk deformation of microdevices using external mechanical forces, and local deformation of microstructures using flexible membrane by pneumatic pressure. The main advantage of membrane-based tunable systems has been addressed to be the high capability of integration with other microdevice components. The stretchable devices based on bulk deformation of microstructures have in common advantage of simplicity in design and fabrication process. PMID:26610519

  2. Latex immunoagglutination assay for bovine viral diarrhea virus utilizing forward light scattering in a microfluidic device

    NASA Astrophysics Data System (ADS)

    Heinze, Brian C.; Song, Jae-Young; Han, Jin-Hee; Yoon, Jeong-Yeol

    2008-02-01

    We have investigated the utilization of particle agglutination assays using forward light scattering measurements in a microfluidic device towards detecting viral particles. The model viral target was bovine viral diarrhea virus (BVDV). Highly carboxylated polystyrene microspheres (510 nm) were coated with anti-BVDV monoclonal antibodies. This solution was in turn used to detect live modified BVDV. This assay was first performed in a two well slide for proof of concept and then in a simple y-channel microfluidic device with optical fibers arranged in a close proximity setup. Particle immunoagglutination was detected through static light scattering measurements taken at 45° to incident light. In the microfluidic device, modified live BVDV was detected with a detection limit of 0.5 TCID 50 mL -1.

  3. A review on recent developments for biomolecule separation at analytical scale using microfluidic devices.

    PubMed

    Tetala, Kishore K R; Vijayalakshmi, M A

    2016-02-04

    Microfluidic devices with their inherent advantages like the ability to handle 10(-9) to 10(-18) L volume, multiplexing of microchannels, rapid analysis and on-chip detection are proving to be efficient systems in various fields of life sciences. This review highlights articles published since 2010 that reports the use of microfluidic devices to separate biomolecules (DNA, RNA and proteins) using chromatography principles (size, charge, hydrophobicity and affinity) along with microchip capillary electrophoresis, isotachophoresis etc. A detailed overview of stationary phase materials and the approaches to incorporate them within the microchannels of microchips is provided as well as a brief overview of chemical methods to immobilize ligand(s). Furthermore, we review research articles that deal with microfluidic devices as analytical tools for biomolecule (DNA, RNA and protein) separation.

  4. Stimulus-active polymer actuators for next-generation microfluidic devices

    NASA Astrophysics Data System (ADS)

    Hilber, Wolfgang

    2016-08-01

    Microfluidic devices have not yet evolved into commercial off-the-shelf products. Although highly integrated microfluidic structures, also known as lab-on-a-chip (LOC) and micrototal-analysis-system (µTAS) devices, have consistently been predicted to revolutionize biomedical assays and chemical synthesis, they have not entered the market as expected. Studies have identified a lack of standardization and integration as the main obstacles to commercial breakthrough. Soft microfluidics, the utilization of a broad spectrum of soft materials (i.e., polymers) for realization of microfluidic components, will make a significant contribution to the proclaimed growth of the LOC market. Recent advances in polymer science developing novel stimulus-active soft-matter materials may further increase the popularity and spreading of soft microfluidics. Stimulus-active polymers and composite materials change shape or exert mechanical force on surrounding fluids in response to electric, magnetic, light, thermal, or water/solvent stimuli. Specifically devised actuators based on these materials may have the potential to facilitate integration significantly and hence increase the operational advantage for the end-user while retaining cost-effectiveness and ease of fabrication. This review gives an overview of available actuation concepts that are based on functional polymers and points out promising concepts and trends that may have the potential to promote the commercial success of microfluidics.

  5. A medical application integrating remote 3D visualization tools to access picture archiving and communication system on mobile devices.

    PubMed

    He, Longjun; Ming, Xing; Liu, Qian

    2014-04-01

    With computing capability and display size growing, the mobile device has been used as a tool to help clinicians view patient information and medical images anywhere and anytime. However, for direct interactive 3D visualization, which plays an important role in radiological diagnosis, the mobile device cannot provide a satisfactory quality of experience for radiologists. This paper developed a medical system that can get medical images from the picture archiving and communication system on the mobile device over the wireless network. In the proposed application, the mobile device got patient information and medical images through a proxy server connecting to the PACS server. Meanwhile, the proxy server integrated a range of 3D visualization techniques, including maximum intensity projection, multi-planar reconstruction and direct volume rendering, to providing shape, brightness, depth and location information generated from the original sectional images for radiologists. Furthermore, an algorithm that changes remote render parameters automatically to adapt to the network status was employed to improve the quality of experience. Finally, performance issues regarding the remote 3D visualization of the medical images over the wireless network of the proposed application were also discussed. The results demonstrated that this proposed medical application could provide a smooth interactive experience in the WLAN and 3G networks.

  6. Custom fabrication of biomass containment devices using 3-D printing enables bacterial growth analyses with complex insoluble substrates

    SciTech Connect

    Nelson, Cassandra E.; Beri, Nina R.; Gardner, Jeffrey G.

    2016-09-21

    Physiological studies of recalcitrant polysaccharide degradation are challenging for several reasons, one of which is the difficulty in obtaining a reproducibly accurate real-time measurement of bacterial growth using insoluble substrates. Current methods suffer from several problems including (i) high background noise due to the insoluble material interspersed with cells, (ii) high consumable and reagent cost and (iii) significant time delay between sampling and data acquisition. A customizable substrate and cell separation device would provide an option to study bacterial growth using optical density measurements. To test this hypothesis we used 3-D printing to create biomass containment devices that allow interaction between insoluble substrates and microbial cells but do not interfere with spectrophotometer measurements. Evaluation of materials available for 3-D printing indicated that UV-cured acrylic plastic was the best material, being superior to nylon or stainless steel when examined for heat tolerance, reactivity, and ability to be sterilized. Cost analysis of the 3-D printed devices indicated they are a competitive way to quantitate bacterial growth compared to viable cell counting or protein measurements, and experimental conditions were scalable over a 100-fold range. The presence of the devices did not alter growth phenotypes when using either soluble substrates or insoluble substrates. Furthermore, we applied biomass containment to characterize growth of Cellvibrio japonicus on authentic lignocellulose (non-pretreated corn stover), and found physiological evidence that xylan is a significant nutritional source despite an abundance of cellulose present.

  7. Custom fabrication of biomass containment devices using 3-D printing enables bacterial growth analyses with complex insoluble substrates

    DOE PAGES

    Nelson, Cassandra E.; Beri, Nina R.; Gardner, Jeffrey G.

    2016-09-21

    Physiological studies of recalcitrant polysaccharide degradation are challenging for several reasons, one of which is the difficulty in obtaining a reproducibly accurate real-time measurement of bacterial growth using insoluble substrates. Current methods suffer from several problems including (i) high background noise due to the insoluble material interspersed with cells, (ii) high consumable and reagent cost and (iii) significant time delay between sampling and data acquisition. A customizable substrate and cell separation device would provide an option to study bacterial growth using optical density measurements. To test this hypothesis we used 3-D printing to create biomass containment devices that allow interactionmore » between insoluble substrates and microbial cells but do not interfere with spectrophotometer measurements. Evaluation of materials available for 3-D printing indicated that UV-cured acrylic plastic was the best material, being superior to nylon or stainless steel when examined for heat tolerance, reactivity, and ability to be sterilized. Cost analysis of the 3-D printed devices indicated they are a competitive way to quantitate bacterial growth compared to viable cell counting or protein measurements, and experimental conditions were scalable over a 100-fold range. The presence of the devices did not alter growth phenotypes when using either soluble substrates or insoluble substrates. Furthermore, we applied biomass containment to characterize growth of Cellvibrio japonicus on authentic lignocellulose (non-pretreated corn stover), and found physiological evidence that xylan is a significant nutritional source despite an abundance of cellulose present.« less

  8. Technical Note: Immunohistochemical evaluation of mouse brain irradiation targeting accuracy with 3D-printed immobilization device

    SciTech Connect

    Zarghami, Niloufar Jensen, Michael D.; Talluri, Srikanth; Dick, Frederick A.; Foster, Paula J.; Chambers, Ann F.; Wong, Eugene

    2015-11-15

    Purpose: Small animal immobilization devices facilitate positioning of animals for reproducible imaging and accurate focal radiation therapy. In this study, the authors demonstrate the use of three-dimensional (3D) printing technology to fabricate a custom-designed mouse head restraint. The authors evaluate the accuracy of this device for the purpose of mouse brain irradiation. Methods: A mouse head holder was designed for a microCT couch using CAD software and printed in an acrylic based material. Ten mice received half-brain radiation while positioned in the 3D-printed head holder. Animal placement was achieved using on-board image guidance and computerized asymmetric collimators. To evaluate the precision of beam localization for half-brain irradiation, mice were sacrificed approximately 30 min after treatment and brain sections were stained for γ-H2AX, a marker for DNA breaks. The distance and angle of the γ-H2AX radiation beam border to longitudinal fissure were measured on histological samples. Animals were monitored for any possible trauma from the device. Results: Visualization of the radiation beam on ex vivo brain sections with γ-H2AX immunohistochemical staining showed a sharp radiation field within the tissue. Measurements showed a mean irradiation targeting error of 0.14 ± 0.09 mm (standard deviation). Rotation between the beam axis and mouse head was 1.2° ± 1.0° (standard deviation). The immobilization device was easily adjusted to accommodate different sizes of mice. No signs of trauma to the mice were observed from the use of tooth block and ear bars. Conclusions: The authors designed and built a novel 3D-printed mouse head holder with many desired features for accurate and reproducible radiation targeting. The 3D printing technology was found to be practical and economical for producing a small animal imaging and radiation restraint device and allows for customization for study specific needs.

  9. Grafting of antibodies inside integrated microfluidic-microoptic devices by means of automated microcontact printing

    PubMed Central

    Bou Chakra, Elie; Hannes, Benjamin; Vieillard, Julien; Mansfield, Colin D.; Mazurczyk, Radoslav; Bouchard, Aude; Potempa, Jan; Krawczyk, Stanislas; Cabrera, Michel

    2009-01-01

    A novel approach to integrating biochip and microfluidic devices is reported in which microcontact printing is a key fabrication technique. The process is performed using an automated microcontact printer that has been developed as an application-specific tool. As proof-of-concept the instrument is used to consecutively and selectively graft patterns of antibodies at the bottom of a glass channel for use in microfluidic immunoassays. Importantly, feature collapse due to over compression of the PDMS stamp is avoided by fine control of the stamp’s compression during contact. The precise alignment of biomolecules at the intersection of microfluidic channel and integrated optical waveguides has been achieved, with antigen detection performed via fluorescence excitation. Thus, it has been demonstrated that this technology permits sequential microcontact printing of isolated features consisting of functional biomolecules at any position along a microfluidic channel and also that it is possible to precisely align these features with existing components. PMID:20161128

  10. Electrical measurement of red blood cell deformability on a microfluidic device.

    PubMed

    Zheng, Yi; Nguyen, John; Wang, Chen; Sun, Yu

    2013-08-21

    This paper describes a microfluidic system and a technique for electrically measuring the deformability of red blood cells (RBCs). RBCs are deformed when they flow through a small capillary (microfluidic channel). The microfluidic device consists of two stages of microchannels as two measurement units for measuring cell size/volume and cell deformability. A low frequency voltage signal is established across the microfluidic channel, and electrical current signal is sampled continuously when RBCs pass through the measurement areas. Mechanical opacity is defined to mitigate the coupled effect of cell size/volume and deformability. The system performed tests on controlled, glutaraldehyde-treated, and heated RBCs using a number of driving pressures. The experimental results proved the capability of the system for distinguishing different RBC populations based on their deformability with a throughput of ~10 cells s(-1).

  11. Bubble-free and pulse-free fluid delivery into microfluidic devices.

    PubMed

    Kang, Yang Jun; Yeom, Eunseop; Seo, Eunseok; Lee, Sang-Joon

    2014-01-01

    The bubble-free and pulse-free fluid delivery is critical to reliable operation of microfluidic devices. In this study, we propose a new method for stable bubble-free and pulse-free fluid delivery in a microfluidic device. Gas bubbles are separated from liquid by using the density difference between liquid and gas in a closed cavity. The pulsatile flow caused by a peristaltic pump is stabilized via gas compressibility. To demonstrate the proposed method, a fluidic chamber which is composed of two needles for inlet and outlet, one needle for a pinch valve and a closed cavity is carefully designed. By manipulating the opening or closing of the pinch valve, fluids fill up the fluidic chamber or are delivered into a microfluidic device through the fluidic chamber in a bubble-free and pulse-free manner. The performance of the proposed method in bubble-free and pulse-free fluid delivery is quantitatively evaluated. The proposed method is then applied to monitor the temporal variations of fluidic flows of rat blood circulating within a complex fluidic network including a rat, a pinch valve, a reservoir, a peristaltic pump, and the microfluidic device. In addition, the deformability of red blood cells and platelet aggregation are quantitatively evaluated from the information on the temporal variations of blood flows in the microfluidic device. These experimental demonstrations confirm that the proposed method is a promising tool for stable, bubble-free, and pulse-free supply of fluids, including whole blood, into a microfluidic device. Furthermore, the proposed method will be used to quantify the biophysical properties of blood circulating within an extracorporeal bypass loop of animal models.

  12. Quantitative analysis of Caenorhabditis elegans chemotaxis using a microfluidic device.

    PubMed

    Hu, Liang; Ye, Jinjuan; Tan, Haowei; Ge, Anle; Tang, Lichun; Feng, Xiaojun; Du, Wei; Liu, Bi-Feng

    2015-08-05

    Caenorhabditis elegans, one of the widely studied model organisms, sense external chemical cues and perform relative chemotaxis behaviors through its simple chemosensory neuronal system. To study the mechanism underlying chemosensory behavior, a rapid and reliable method for quantitatively analyzing the worms' behaviors is essential. In this work, we demonstrated a microfluidic approach for investigating chemotaxis responses of worms to chemical gradients. The flow-based microfluidic chip was consisted of circular tree-like microchannels, which was able to generate eight flow streams containing stepwise chemical concentrations without the difference in flow velocity. Worms' upstream swimming into microchannels with various concentrations was monitored for quantitative analysis of the chemotaxis behavior. By using this microfluidic chip, the attractive and repellent responses of C. elegans to NaCl were successfully quantified within several minutes. The results demonstrated the wild type-like repellent responses and severely impaired attractive responses in grk-2 mutant animals with defects in calcium influx. In addition, the chemotaxis analysis of the third stage larvae revealed that its gustatory response was different from that in the adult stage. Thus, our microfluidic method provided a useful platform for studying the chemosensory behaviors of C. elegans and screening of chemosensation-related chemical drugs.

  13. Open-channel, water-in-oil emulsification in paper-based microfluidic devices.

    PubMed

    Li, C; Boban, M; Tuteja, A

    2017-04-11

    Open-channel microfluidic devices have shown great potential in achieving a high degree of fluid control, at relatively low-cost, while enabling the opportunity for rapid fabrication. However, thus far, work in open channel microfluidics has largely focused on controlling the flow of water or other aqueous solutions. In this work we present new open channel microfluidic devices based on surfaces with patterned wettabilty that are capable of controlling the flow of virtually all high and low surface tension liquids. The fabricated open channel devices are capable of constraining a variety of low surface tension oils at high enough flow rates to enable, for the first time, water-in-oil microfluidic emulsification in an open channel device. By changing the flow rates for both the aqueous (dispersed) and organic (continuous) phases, we show that it is possible to vary the size of the emulsified droplets produced in the open channel device. Finally, we utilized the fabricated devices to synthesize relatively monodisperse, hydrogel microparticles that could incorporate a drug molecule. We also investigated the drug release characteristics of the fabricated particles.

  14. Low cost microfluidic device based on cotton threads for electroanalytical application.

    PubMed

    Agustini, Deonir; Bergamini, Márcio F; Marcolino-Junior, Luiz Humberto

    2016-01-21

    Microfluidic devices are an interesting alternative for performing analytical assays, due to the speed of analyses, reduced sample, reagent and solvent consumption and less waste generation. However, the high manufacturing costs still prevent the massive use of these devices worldwide. Here, we present the construction of a low cost microfluidic thread-based electroanalytical device (μTED), employing extremely cheap materials and a manufacturing process free of equipment. The microfluidic channels were built with cotton threads and the estimated cost per device was only $0.39. The flow of solutions (1.12 μL s(-1)) is generated spontaneously due to the capillary forces, eliminating the use of any pumping system. To demonstrate the analytical performance of the μTED, a simultaneous determination of acetaminophen (ACT) and diclofenac (DCF) was performed by multiple pulse amperometry (MPA). A linear dynamic range (LDR) of 10 to 320 μmol L(-1) for both species, a limit of detection (LOD) and a limit of quantitation (LOQ) of 1.4 and 4.7 μmol L(-1) and 2.5 and 8.3 μmol L(-1) for ACT and DCF, respectively, as well as an analytical frequency of 45 injections per hour were reached. Thus, the proposed device has shown potential to extend the use of microfluidic analytical devices, due to its simplicity, low cost and good analytical performance.

  15. Fabrication of a Paper-Based Microfluidic Device to Readily Determine Nitrite Ion Concentration by Simple Colorimetric Assay

    ERIC Educational Resources Information Center

    Wang, Bo; Lin, Zhiqiang; Wang, Min

    2015-01-01

    Paper-based microfluidic devices (µPAD) are a burgeoning platform of microfluidic analysis technology. The method described herein is for use in undergraduate and high school chemistry laboratories. A simple and convenient µPAD was fabricated by easy patterning of filter paper using a permanent marker pen. The usefulness of the device was…

  16. Microfluidic Device to Quantify the Behavior of Therapeutic Bacteria in Three-Dimensional Tumor Tissue

    PubMed Central

    Brackett, Emily L.; Swofford, Charles A.; Forbes, Neil S.

    2016-01-01

    Summary Microfluidic devices enable precise quantification of the interactions between anticancer bacteria and tumor tissue. Direct observation of bacterial movement and gene expression in tissue is not possible with either monolayers of cells or tumor-bearing mice. Quantification of these interactions is necessary to understand the inherent mechanisms of bacterial targeting and to develop modified organisms with enhanced therapeutic properties. Here we describe the procedures for designing, printing and assembling microfluidic tumor-on-a-chip devices. We also describe the procedures for inserting three- dimensional tumor-cell masses, exposing to bacteria, and analyzing the resultant images. PMID:26846800

  17. 3D interactive augmented reality-enhanced digital learning systems for mobile devices

    NASA Astrophysics Data System (ADS)

    Feng, Kai-Ten; Tseng, Po-Hsuan; Chiu, Pei-Shuan; Yang, Jia-Lin; Chiu, Chun-Jie

    2013-03-01

    With enhanced processing capability of mobile platforms, augmented reality (AR) has been considered a promising technology for achieving enhanced user experiences (UX). Augmented reality is to impose virtual information, e.g., videos and images, onto a live-view digital display. UX on real-world environment via the display can be e ectively enhanced with the adoption of interactive AR technology. Enhancement on UX can be bene cial for digital learning systems. There are existing research works based on AR targeting for the design of e-learning systems. However, none of these work focuses on providing three-dimensional (3-D) object modeling for en- hanced UX based on interactive AR techniques. In this paper, the 3-D interactive augmented reality-enhanced learning (IARL) systems will be proposed to provide enhanced UX for digital learning. The proposed IARL systems consist of two major components, including the markerless pattern recognition (MPR) for 3-D models and velocity-based object tracking (VOT) algorithms. Realistic implementation of proposed IARL system is conducted on Android-based mobile platforms. UX on digital learning can be greatly improved with the adoption of proposed IARL systems.

  18. Wide-viewing-angle 3D/2D convertible display system using two display devices and a lens array.

    PubMed

    Choi, Heejin; Park, Jae-Hyeung; Kim, Joohwan; Cho, Seong-Woo; Lee, Byoungho

    2005-10-17

    A wide-viewing-angle 3D/2D convertible display system with a thin structure is proposed that is able to display three-dimensional and two-dimensional images. With the use of a transparent display device in front of a conventional integral imaging system, it is possible to display planar images using the conventional system as a backlight source. By experiments, the proposed method is proven and compared with the conventional one.

  19. Impact of continuing scaling on the device performance of 3D cylindrical junction-less charge trapping memory

    NASA Astrophysics Data System (ADS)

    Xinkai, Li; Zongliang, Huo; Lei, Jin; Dandan, Jiang; Peizhen, Hong; Qiang, Xu; Zhaoyun, Tang; Chunlong, Li; Tianchun, Ye

    2015-09-01

    This work presents a comprehensive analysis of 3D cylindrical junction-less charge trapping memory device performance regarding continuous scaling of the structure dimensions. The key device performance, such as program/erase speed, vertical charge loss, and lateral charge migration under high temperature are intensively studied using the Sentaurus 3D device simulator. Although scaling of channel radius is beneficial for operation speed improvement, it leads to a retention challenge due to vertical leakage, especially enhanced charge loss through TPO. Scaling of gate length not only decreases the program/erase speed but also leads to worse lateral charge migration. Scaling of spacer length is critical for the interference of adjacent cells and should be carefully optimized according to specific cell operation conditions. The gate stack shape is also found to be an important factor affecting the lateral charge migration. Our results provide guidance for high density and high reliability 3D CTM integration. Project supported by the National Natural Science Foundation of China (Nos. 61474137, 61176073, 61306107).

  20. Experimental Studies of Surface-Driven Capillary Flow in PMMA Microfluidic Devices Prepared by Direct Bonding Technique and Passive Separation of Microparticles in Microfluidic Laboratory-On Systems

    NASA Astrophysics Data System (ADS)

    Mukhopadhyay, Subhadeep; Banerjee, J. P.; Mathur, Ashish; Tweedie, M.; McLaughlin, J. A.; Roy, Susanta Sinha

    2015-05-01

    Proper bonding technique is investigated to achieve leakage-free surface-driven capillary flow in polymethylmethacrylate (PMMA) microfluidic devices. SU-8-based silicon stamp is fabricated by maskless lithography. This stamp is used to produce PMMA microchannel structure by hot embossing lithography. A direct bonding technique is mainly employed for leakage-free sealing inside PMMA microfluidic devices. The effect of surface wettability on surface-driven capillary flow is also investigated in PMMA microfluidic devices. The separation of polystyrene microparticles in PMMA laboratory-on-a-chip systems is investigated with the reduction of separation time by air dielectric barrier discharge (DBD) plasma processing of channel surfaces. This study is useful to fabricate the microfluidic laboratory-on-a-chip systems and to understand the surface-driven capillary flow.

  1. A novel ultrathin collagen nanolayer assembly for 3-D microtissue engineering: Layer-by-layer collagen deposition for long-term stable microfluidic hepatocyte culture

    PubMed Central

    McCarty, William J.; Usta, O. Berk; Luitje, Martha; Bale, Shyam Sundhar; Bhushan, Abhinav; Hegde, Manjunath; Golberg, Inna; Jindal, Rohit; Yarmush, Martin L.

    2014-01-01

    The creation of stable hepatocyte cultures using cell-matrix interactions has proven difficult in microdevices due to dimensional constraints limiting the utility of classic tissue culture techniques that involve the use of hydrogels such as the collagen “double gel” or “overlay”. To translate the collagen overlay technique into microdevices, we modified collagen using succinylation and methylation reactions to create polyanionic and polycationic collagen solutions, and deposited them layer-by-layer to create ultrathin collagen nanolayers on hepatocytes. These ultrathin collagen layers covered hepatocytes in microdevices and 1) maintained cell morphology, viability, and polarity, 2) induced bile canalicular formation and actin reorganization, and 3) maintained albumin and urea secretions and CYP activity similar to those observed in hepatocytes in collagen double gel hepatocytes in plate cultures. Beyond the immediate applications of this technique to create stable, in vitro microfluidic hepatocyte cultures for drug toxicity testing, this technique is generally applicable as a thin biomaterial for other 3D microtissues. PMID:24932459

  2. Reproducible preparation of nanospray tips for capillary electrophoresis coupled to mass spectrometry using 3D printed grinding device.

    PubMed

    Tycova, Anna; Prikryl, Jan; Foret, Frantisek

    2016-04-01

    The use of high quality fused silica capillary nanospray tips is critical for obtaining reliable and reproducible electrospray/MS data; however, reproducible laboratory preparation of such tips is a challenging task. In this work, we report on the design and construction of low-cost grinding device assembled from 3D printed and commercially easily available components. Detailed description and characterization of the grinding device is complemented by freely accessible files in stl and skp format allowing easy laboratory replication of the device. The process of sharpening is aimed at achieving maximal symmetricity, surface smoothness and repeatability of the conus shape. Moreover, the presented grinding device brings possibility to fabricate the nanospray tips of desired dimensions regardless of the commercial availability. On several samples of biological nature (reserpine, rabbit plasma, and the mixture of three aminoacids), performance of fabricated tips is shown on CE coupled to MS analysis. The special interest is paid to the effect of tip sharpness.

  3. A 3D-Printed Oxygen Control Insert for a 24-Well Plate.

    PubMed

    Brennan, Martin D; Rexius-Hall, Megan L; Eddington, David T

    2015-01-01

    3D printing has emerged as a method for directly printing complete microfluidic devices, although printing materials have been limited to oxygen-impermeable materials. We demonstrate the addition of gas permeable PDMS (Polydimethylsiloxane) membranes to 3D-printed microfluidic devices as a means to enable oxygen control cell culture studies. The incorporation of a 3D-printed device and gas-permeable membranes was demonstrated on a 24-well oxygen control device for standard multiwell plates. The direct printing allows integrated distribution channels and device geometries not possible with traditional planar lithography. With this device, four different oxygen conditions were able to be controlled, and six wells were maintained under each oxygen condition. We demonstrate enhanced transcription of the gene VEGFA (vascular endothelial growth factor A) with decreasing oxygen levels in human lung adenocarcinoma cells. This is the first 3D-printed device incorporating gas permeable membranes to facilitate oxygen control in cell culture.

  4. A 3D-Printed Oxygen Control Insert for a 24-Well Plate

    PubMed Central

    Brennan, Martin D.; Rexius-Hall, Megan L.; Eddington, David T.

    2015-01-01

    3D printing has emerged as a method for directly printing complete microfluidic devices, although printing materials have been limited to oxygen-impermeable materials. We demonstrate the addition of gas permeable PDMS (Polydimethylsiloxane) membranes to 3D-printed microfluidic devices as a means to enable oxygen control cell culture studies. The incorporation of a 3D-printed device and gas-permeable membranes was demonstrated on a 24-well oxygen control device for standard multiwell plates. The direct printing allows integrated distribution channels and device geometries not possible with traditional planar lithography. With this device, four different oxygen conditions were able to be controlled, and six wells were maintained under each oxygen condition. We demonstrate enhanced transcription of the gene VEGFA (vascular endothelial growth factor A) with decreasing oxygen levels in human lung adenocarcinoma cells. This is the first 3D-printed device incorporating gas permeable membranes to facilitate oxygen control in cell culture. PMID:26360882

  5. Micromilling: A method for ultra-rapid prototyping of plastic microfluidic devices

    PubMed Central

    Guckenberger, David J.; de Groot, Theodorus E.; Wan, Alwin M.D.; Beebe, David J.; Young, Edmond W. K.

    2015-01-01

    This tutorial review offers protocols, tips, insight, and considerations for practitioners interested in using micromilling to create microfluidic devices. The objective is to provide a potential user with information to guide them on whether micromilling would fill a specific need within their overall fabrication strategy. Comparisons are made between micromilling and other common fabrication methods for plastics in terms of technical capabilities and cost. The main discussion focuses on “how-to” aspects of micromilling, to enable a user to select proper equipment and tools, and obtain usable microfluidic parts with minimal start-up time and effort. The supplementary information provides more extensive discussion on CNC mill setup, alignment, and programming. We aim to reach an audience with minimal prior experience in milling, but with strong interests in fabrication of microfluidic devices. PMID:25906246

  6. Particle Migration due to Viscoelasticity of the Suspending Liquid and Its Relevance in Microfluidic Devices

    NASA Astrophysics Data System (ADS)

    D'Avino, Gaetano; Greco, Francesco; Maffettone, Pier Luca

    2017-01-01

    The fast growth of microfluidic applications based on complex fluids is a result of the unique fluid dynamics of these systems, enabling the creation of devices for health care or biological and chemical analysis. Microchannels designed to focus, concentrate, or separate particles suspended in viscoelastic liquids are becoming common. The key fluid dynamical issue on which such devices work is viscoelasticity-induced lateral migration. This phenomenon was discovered in the 1960s in macroscopic channels and has received great attention within the microfluidic community in the past decade. This review presents the current understanding, both from experiments and theoretical analysis, of viscoelasticity-driven cross-flow migration. Examples of promising microfluidic applications show the unprecedented capabilities offered by such technology based on geometrically simple microchannels and rheologically complex liquids.

  7. Microfluidic device and method for focusing, segmenting, and dispensing of a fluid stream

    DOEpatents

    Jacobson, Stephen C.; Ramsey, J. Michael

    2004-09-14

    A microfluidic device for forming and/or dispensing minute volume segments of a material is described. In accordance with one aspect of the present invention, a microfluidic device and method is provided for spatially confining the material in a focusing element. The device is also capable of segmenting the confined material into minute volume segments, and dispensing a volume segment to a waste or collection channel. The device further includes means for driving the respective streams of sample and focusing fluids through respective channels into a chamber, such that the focusing fluid streams spatially confine the sample material. The device may also include additional means for driving a minute volume segment of the spatially confined sample material into a collection channel in fluid communication with the waste reservoir.

  8. Microfluidic device and method for focusing, segmenting, and dispensing of a fluid stream

    DOEpatents

    Jacobson, Stephen C [Knoxville, TN; Ramsey, J Michael [Knoxville, TN

    2008-09-09

    A microfluidic device and method for forming and dispensing minute volume segments of a material are described. In accordance with the present invention, a microfluidic device and method are provided for spatially confining the material in a focusing element. The device is also adapted for segmenting the confined material into minute volume segments, and dispensing a volume segment to a waste or collection channel. The device further includes means for driving the respective streams of sample and focusing fluids through respective channels into a chamber, such that the focusing fluid streams spatially confine the sample material. The device may also include additional means for driving a minute volume segment of the spatially confined sample material into a collection channel in fluid communication with the waste reservoir.

  9. Digital micromirror device (DMD)-based 3D printing of poly(propylene fumarate) scaffolds.

    PubMed

    Mott, Eric J; Busso, Mallory; Luo, Xinyi; Dolder, Courtney; Wang, Martha O; Fisher, John P; Dean, David

    2016-04-01

    Our recent investigations into the 3D printing of poly(propylene fumarate) (PPF), a linear polyester, using a DMD-based system brought us to a resin that used titanium dioxide (TiO2) as an ultraviolet (UV) filter for controlling cure depth. However, this material hindered the 3D printing process due to undesirable lateral or "dark" curing (i.e., in areas not exposed to light from the DMD chip). Well known from its use in sunscreen, another UV filter, oxybenzone, has previously been used in conjunction with TiO2. In this study we hypothesize that combining these two UV filters will result in a synergistic effect that controls cure depth and avoids dark cure. A resin mixture (i.e., polymer, initiator, UV filters) was identified that worked well. The resin was then further characterized through mechanical testing, cure testing, and cytotoxicity testing to investigate its use as a material for bone tissue engineering scaffolds. Results show that the final resin eliminated dark cure as shown through image analysis. Mechanically the new scaffolds proved to be far weaker than those printed from previous resins, with compressive strengths of 7.8 ± 0.5 MPa vs. 36.5 ± 1.6 MPa, respectively. The new scaffolds showed a 90% reduction in elastic modulus and a 74% increase in max strain. These properties may be useful in tissue engineering applications where resorption is required. Initial cytotoxicity evaluation was negative. As hypothesized, the use of TiO2 and oxybenzone showed synergistic effects in the 3D printing of PPF tissue engineering scaffolds.

  10. Injection molded microfluidic devices for biological sample separation and detection

    NASA Astrophysics Data System (ADS)

    Morales, Alfredo M.; Simmons, Blake A.; Wallow, Thomas I.; Campbell, K. Jeffery; Mani, Seethambal S.; Mittal, Brita; Crocker, Robert W.; Cummings, Eric B.; Davalos, Rafael V.; Domeier, Linda A.; Hunter, Marion C.; Krafcik, Karen L.; McGraw, Gregory J.; Mosier, Bruce P.; Sickafoose, Shane M.

    2006-01-01

    We are developing a variety of microsystems for the separation and detection of biological samples. At the heart of these systems, inexpensive polymer microfluidic chips carry out sample preparation and analysis. Fabrication of polymer microfluidic chips involves the creation of a master in etched silicon or glass; plating of the master to produce a nickel stamp; large lot chip replication by injection molding; precision chip sealing; and chemical modification of channel surfaces. Separation chips rely on insulator-based dielectrophoresis for the separation of biological particles. Detection chips carry out capillary electrophoresis to detect fluorescent tags that identify specific biological samples. Since the performance and reliability of these microfluidic chips are very sensitive to fluidic impedance, electromagnetic flux, and zeta potential, the microchannel dimensions, shape, and surface chemistry have to be tightly controlled during chip fabrication and use. This paper will present an overview of chip design, fabrication, and testing. Dimensional metrology data, surface chemistry characterization, and chip performance data will be discussed in detail.

  11. Simulating The Technological Movements Of The Equipment Used For Manufacturing Prosthetic Devices Using 3D Models

    NASA Astrophysics Data System (ADS)

    Chicea, Anca-Lucia

    2015-09-01

    The paper presents the process of building geometric and kinematic models of a technological equipment used in the process of manufacturing devices. First, the process of building the model for a six axes industrial robot is presented. In the second part of the paper, the process of building the model for a five-axis CNC milling machining center is also shown. Both models can be used for accurate cutting processes simulation of complex parts, such as prosthetic devices.

  12. A spheroid toxicity assay using magnetic 3D bioprinting and real-time mobile device-based imaging

    PubMed Central

    Tseng, Hubert; Gage, Jacob A.; Shen, Tsaiwei; Haisler, William L.; Neeley, Shane K.; Shiao, Sue; Chen, Jianbo; Desai, Pujan K.; Liao, Angela; Hebel, Chris; Raphael, Robert M.; Becker, Jeanne L.; Souza, Glauco R.

    2015-01-01

    An ongoing challenge in biomedical research is the search for simple, yet robust assays using 3D cell cultures for toxicity screening. This study addresses that challenge with a novel spheroid assay, wherein spheroids, formed by magnetic 3D bioprinting, contract immediately as cells rearrange and compact the spheroid in relation to viability and cytoskeletal organization. Thus, spheroid size can be used as a simple metric for toxicity. The goal of this study was to validate spheroid contraction as a cytotoxic endpoint using 3T3 fibroblasts in response to 5 toxic compounds (all-trans retinoic acid, dexamethasone, doxorubicin, 5′-fluorouracil, forskolin), sodium dodecyl sulfate (+control), and penicillin-G (−control). Real-time imaging was performed with a mobile device to increase throughput and efficiency. All compounds but penicillin-G significantly slowed contraction in a dose-dependent manner (Z’ = 0.88). Cells in 3D were more resistant to toxicity than cells in 2D, whose toxicity was measured by the MTT assay. Fluorescent staining and gene expression profiling of spheroids confirmed these findings. The results of this study validate spheroid contraction within this assay as an easy, biologically relevant endpoint for high-throughput compound screening in representative 3D environments. PMID:26365200

  13. Low cost production of 3D-printed devices and electrostimulation chambers for the culture of primary neurons.

    PubMed

    Wardyn, Joanna D; Sanderson, Chris; Swan, Laura E; Stagi, Massimiliano

    2015-08-15

    The analysis of primary neurons is a basic requirement for many areas of neurobiology. However, the range of commercial systems available for culturing primary neurons is functionally limiting, and the expense of these devices is a barrier to both exploratory and large-scale studies. This is especially relevant as primary neurons often require unusual geometries and specialised coatings for optimum growth. Fortunately, the recent revolution in 3D printing offers the possibility to generate customised devices, which can support neuronal growth and constrain neurons in defined paths, thereby enabling many aspects of neuronal physiology to be studied with relative ease. In this article, we provide a detailed description of the system hardware and software required to produce affordable 3D-printed culture devices, which are also compatible with live-cell imaging. In addition, we also describe how to use these devices to grow and stimulate neurons within geometrically constrained compartments and provide examples to illustrate the practical utility and potential that these protocols offer for many aspects of experimental neurobiology.