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Sample records for 3d microfluidic devices

  1. 3D-printed microfluidic devices.

    PubMed

    Amin, Reza; Knowlton, Stephanie; Hart, Alexander; Yenilmez, Bekir; Ghaderinezhad, Fariba; Katebifar, Sara; Messina, Michael; Khademhosseini, Ali; Tasoglu, Savas

    2016-06-01

    Microfluidics is a flourishing field, enabling a wide range of biochemical and clinical applications such as cancer screening, micro-physiological system engineering, high-throughput drug testing, and point-of-care diagnostics. However, fabrication of microfluidic devices is often complicated, time consuming, and requires expensive equipment and sophisticated cleanroom facilities. Three-dimensional (3D) printing presents a promising alternative to traditional techniques such as lithography and PDMS-glass bonding, not only by enabling rapid design iterations in the development stage, but also by reducing the costs associated with institutional infrastructure, equipment installation, maintenance, and physical space. With the recent advancements in 3D printing technologies, highly complex microfluidic devices can be fabricated via single-step, rapid, and cost-effective protocols, making microfluidics more accessible to users. In this review, we discuss a broad range of approaches for the application of 3D printing technology to fabrication of micro-scale lab-on-a-chip devices. PMID:27321137

  2. 3D printed microfluidic devices: enablers and barriers.

    PubMed

    Waheed, Sidra; Cabot, Joan M; Macdonald, Niall P; Lewis, Trevor; Guijt, Rosanne M; Paull, Brett; Breadmore, Michael C

    2016-05-24

    3D printing has the potential to significantly change the field of microfluidics. The ability to fabricate a complete microfluidic device in a single step from a computer model has obvious attractions, but it is the ability to create truly three dimensional structures that will provide new microfluidic capability that is challenging, if not impossible to make with existing approaches. This critical review covers the current state of 3D printing for microfluidics, focusing on the four most frequently used printing approaches: inkjet (i3DP), stereolithography (SLA), two photon polymerisation (2PP) and extrusion printing (focusing on fused deposition modeling). It discusses current achievements and limitations, and opportunities for advancement to reach 3D printing's full potential. PMID:27146365

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

    PubMed

    Kalish, Brent; Tsutsui, Hideaki

    2016-01-01

    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. PMID:27077551

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

    PubMed

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

    2016-01-01

    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. PMID:26332914

  5. 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.

  6. Photo-crosslinkable hydrogel-based 3D microfluidic culture device.

    PubMed

    Lee, Youlee; Lee, Jong Min; Bae, Pan-Kee; Chung, Il Yup; Chung, Bong Hyun; Chung, Bong Geun

    2015-04-01

    We developed the photo-crosslinkable hydrogel-based 3D microfluidic device to culture neural stem cells (NSCs) and tumors. The photo-crosslinkable gelatin methacrylate (GelMA) polymer was used as a physical barrier in the microfluidic device and collagen type I gel was employed to culture NSCs in a 3D manner. We demonstrated that the pore size was inversely proportional to concentrations of GelMA hydrogels, showing the pore sizes of 5 and 25 w/v% GelMA hydrogels were 34 and 4 μm, respectively. It also revealed that the morphology of pores in 5 w/v% GelMA hydrogels was elliptical shape, whereas we observed circular-shaped pores in 25 w/v% GelMA hydrogels. To culture NSCs and tumors in the 3D microfluidic device, we investigated the molecular diffusion properties across GelMA hydrogels, indicating that 25 w/v% GelMA hydrogels inhibited the molecular diffusion for 6 days in the 3D microfluidic device. In contrast, the chemicals were diffused in 5 w/v% GelMA hydrogels. Finally, we cultured NSCs and tumors in the hydrogel-based 3D microfluidic device, showing that 53-75% NSCs differentiated into neurons, while tumors were cultured in the collagen gels. Therefore, this photo-crosslinkable hydrogel-based 3D microfluidic culture device could be a potentially powerful tool for regenerative tissue engineering applications. PMID:25641332

  7. 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

  8. 3D Printed Microfluidic Device with Integrated Biosensors for Online Analysis of Subcutaneous Human Microdialysate.

    PubMed

    Gowers, Sally A N; Curto, Vincenzo F; Seneci, Carlo A; Wang, Chu; Anastasova, Salzitsa; Vadgama, Pankaj; Yang, Guang-Zhong; Boutelle, Martyn G

    2015-08-01

    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

  9. 3D-printing of transparent bio-microfluidic devices in PEG-DA.

    PubMed

    Urrios, Arturo; Parra-Cabrera, Cesar; Bhattacharjee, Nirveek; Gonzalez-Suarez, Alan M; Rigat-Brugarolas, Luis G; Nallapatti, Umashree; Samitier, Josep; DeForest, Cole A; Posas, Francesc; Garcia-Cordero, José L; Folch, Albert

    2016-06-21

    The vast majority of microfluidic systems are molded in poly(dimethylsiloxane) (PDMS) by soft lithography due to the favorable properties of PDMS: biocompatible, elastomeric, transparent, gas-permeable, inexpensive, and copyright-free. However, PDMS molding involves tedious manual labor, which makes PDMS devices prone to assembly failures and difficult to disseminate to research and clinical settings. Furthermore, the fabrication procedures limit the 3D complexity of the devices to layered designs. Stereolithography (SL), a form of 3D-printing, has recently attracted attention as a way to customize the fabrication of biomedical devices due to its automated, assembly-free 3D fabrication, rapidly decreasing costs, and fast-improving resolution and throughput. However, existing SL resins are not biocompatible and patterning transparent resins at high resolution remains difficult. Here we report procedures for the preparation and patterning of a transparent resin based on low-MW poly(ethylene glycol) diacrylate (MW 250) (PEG-DA-250). The 3D-printed devices are highly transparent and cells can be cultured on PEG-DA-250 prints for several days. This biocompatible SL resin and printing process solves some of the main drawbacks of 3D-printed microfluidic devices: biocompatibility and transparency. In addition, it should also enable the production of non-microfluidic biomedical devices. PMID:27217203

  10. 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.

  11. 3D-Printed Microfluidics.

    PubMed

    Au, Anthony K; Huynh, Wilson; Horowitz, Lisa F; Folch, Albert

    2016-03-14

    The advent of soft lithography allowed for an unprecedented expansion in the field of microfluidics. However, the vast majority of PDMS microfluidic devices are still made with extensive manual labor, are tethered to bulky control systems, and have cumbersome user interfaces, which all render commercialization difficult. On the other hand, 3D printing has begun to embrace the range of sizes and materials that appeal to the developers of microfluidic devices. Prior to fabrication, a design is digitally built as a detailed 3D CAD file. The design can be assembled in modules by remotely collaborating teams, and its mechanical and fluidic behavior can be simulated using finite-element modeling. As structures are created by adding materials without the need for etching or dissolution, processing is environmentally friendly and economically efficient. We predict that in the next few years, 3D printing will replace most PDMS and plastic molding techniques in academia. PMID:26854878

  12. 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. PMID:25962351

  13. 3D printed microfluidic devices with integrated versatile and reusable electrodes.

    PubMed

    Erkal, Jayda L; Selimovic, Asmira; Gross, Bethany C; Lockwood, Sarah Y; Walton, Eric L; McNamara, Stephen; Martin, R Scott; Spence, Dana M

    2014-06-21

    We report two 3D printed devices that can be used for electrochemical detection. In both cases, the electrode is housed in commercially available, polymer-based fittings so that the various electrode materials (platinum, platinum black, carbon, gold, silver) can be easily added to a threaded receiving port printed on the device; this enables a module-like approach to the experimental design, where the electrodes are removable and can be easily repolished for reuse after exposure to biological samples. The first printed device represents a microfluidic platform with a 500 × 500 μm channel and a threaded receiving port to allow integration of either polyetheretherketone (PEEK) nut-encased glassy carbon or platinum black (Pt-black) electrodes for dopamine and nitric oxide (NO) detection, respectively. The embedded 1 mm glassy carbon electrode had a limit of detection (LOD) of 500 nM for dopamine and a linear response (R(2) = 0.99) for concentrations between 25-500 μM. When the glassy carbon electrode was coated with 0.05% Nafion, significant exclusion of nitrite was observed when compared to signal obtained from equimolar injections of dopamine. When using flow injection analysis with a Pt/Pt-black electrode and standards derived from NO gas, a linear correlation (R(2) = 0.99) over a wide range of concentrations (7.6-190 μM) was obtained, with the LOD for NO being 1 μM. The second application showcases a 3D printed fluidic device that allows collection of the biologically relevant analyte adenosine triphosphate (ATP) while simultaneously measuring the release stimulus (reduced oxygen concentration). The hypoxic sample (4.8 ± 0.5 ppm oxygen) released 2.4 ± 0.4 times more ATP than the normoxic sample (8.4 ± 0.6 ppm oxygen). Importantly, the results reported here verify the reproducible and transferable nature of using 3D printing as a fabrication technique, as devices and electrodes were moved between labs multiple times during completion of the study. PMID

  14. 3D Printed Microfluidic Devices with Integrated Versatile and Reusable Electrodes

    PubMed Central

    Erkal, Jayda L.; Selimovic, Asmira; Gross, Bethany C.; Lockwood, Sarah Y.; Walton, Eric L.; McNamara, Stephen; Martin, R. Scott; Spence, Dana M.

    2014-01-01

    We report two 3D printed devices that can be used for electrochemical detection. In both cases, the electrode is housed in commercially available, polymer-based fittings so that the various electrode materials (platinum, platinum black, carbon, gold, silver) can be easily added to a threaded receiving port printed on the device; this enables a module-like approach to the experimental design, where the electrodes are removable and can be easily repolished for reuse after exposure to biological samples. The first printed device represents a microfluidic platform with a 500 × 500 μm channel and a threaded receiving port to allow integration of either polyetheretherketone (PEEK) nut-encased glassy carbon or platinum black (Pt-black) electrodes for dopamine and nitric oxide (NO) detection, respectively. The embedded 1 mm glassy carbon electrode had a limit of detection (LOD) of 500 nM for dopamine and a linear response (R2= 0.99) for concentrations between 25-500 μM. When the glassy carbon electrode was coated with 0.05% Nafion, significant exclusion of nitrite was observed when compared to signal obtained from equimolar injections of dopamine. When using flow injection analysis with a Pt/Pt-black electrode and standards derived from NO gas, a linear correlation (R2 = 0.99) over a wide range of concentrations (7.6 - 190 μM) was obtained, with the LOD for NO being 1 μM. The second application showcases a 3D printed fluidic device that allows collection of the biologically relevant analyte adenosine triphosphate (ATP) while simultaneously measuring the release stimulus (reduced oxygen concentration). The hypoxic sample (4.76 ± 0.53 ppm oxygen) released 2.37 ± 0.37 times more ATP than the normoxic sample (8.22 ± 0.60 ppm oxygen). Importantly, the results reported here verify the reproducible and transferable nature of using 3D printing as a fabrication technique, as devices and electrodes were moved between labs multiple times during completion of the study. PMID

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

    NASA Astrophysics Data System (ADS)

    Roberts, John

    2005-11-01

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

  16. Configurable 3D-Printed millifluidic and microfluidic 'lab on a chip' reactionware devices.

    PubMed

    Kitson, Philip J; Rosnes, Mali H; Sans, Victor; Dragone, Vincenza; Cronin, Leroy

    2012-09-21

    We utilise 3D design and 3D printing techniques to fabricate a number of miniaturised fluidic 'reactionware' devices for chemical syntheses in just a few hours, using inexpensive materials producing reliable and robust reactors. Both two and three inlet reactors could be assembled, as well as one-inlet devices with reactant 'silos' allowing the introduction of reactants during the fabrication process of the device. To demonstrate the utility and versatility of these devices organic (reductive amination and alkylation reactions), inorganic (large polyoxometalate synthesis) and materials (gold nanoparticle synthesis) processes were efficiently carried out in the printed devices. PMID:22875258

  17. 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.

  18. 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. PMID:26237523

  19. One-layer microfluidic device for hydrodynamic 3D self-flow-focusing operating in low flow speed

    NASA Astrophysics Data System (ADS)

    Daghighi, Yasaman; Gnyawali, Vaskar; Strohm, Eric M.; Tsai, Scott S. H.; Kolios, Michael C.

    2016-03-01

    Hydrodynamic 3D flow-focusing techniques in microfluidics are categorized as (a) sheathless techniques which require high flow rates and long channels, resulting in high operating cost and high flow rates which are inappropriate for applications with flow rate limitations, and (b) sheath-flow based techniques which usually require excessive sheath flow rate to achieve hydrodynamic 3D flow-focusing. Many devices based on these principles use complicated fabrication methods to create multi-layer microchannels. We have developed a sheath-flow based microfluidic device that is capable of hydrodynamic 3D self-flow-focusing. In this device the main flow (black ink) in a low speed, and a sheath flow, enter through two inlets and enter a 180 degree curved channel (300 × 300 μm cross-section). Main flow migrates outwards into the sheath-flow due to centrifugal effects and consequently, vertical focusing is achieved at the end of the curved channel. Then, two other sheath flows horizontally confine the main flow to achieve horizontal focusing. Thus, the core flow is three-dimensionally focused at the center of the channel at the downstream. Using centrifugal force for 3D flow-focusing in a single-layer fabricated microchannel has been previously investigated by few groups. However, their demonstrated designs required high flow speed (>1 m/s) which is not suitable for many applications that live biomedical specie are involved. Here, we introduce a new design which is operational in low flow speed (<0.05 m/s) and is suitable for applications involving live cells. This microfluidic device can be used in detecting, counting and isolating cells in many biomedical applications.

  20. 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. PMID:25808433

  1. 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

  2. 3D Printed Multimaterial Microfluidic Valve.

    PubMed

    Keating, Steven J; Gariboldi, Maria Isabella; 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

  3. 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

  4. A 3-D microfluidic combinatorial cell array.

    PubMed

    Liu, Mike C; Tai, Yu-Chong

    2011-02-01

    We present the development of a three-dimensional (3-D) combinatorial cell culture array device featured with integrated three-input, eight-output combinatorial mixer and cell culture chambers. The device is designed for cell-based screening of multiple compounds simultaneously on a microfluidic platform. The final assembled device is composed of a porous membrane integrated in between a Parylene 3-D microfluidic chip and a PDMS microfluidic chip. The membrane turned the cell culture chambers into two-level configuration to facilitate cell loading and to maintain cells in a diffusion dominated space during device operation. Experimentally, we first characterized the combined compound concentration profile at each chamber using a fluorescence method. We then successfully demonstrated the functionality of the quantitative cell-based assay by culturing B35 rat neuronal cells on this device and screening the ability of three compounds (1,5-dihydroxyisoquinoline, deferoxamine, and 3-aminobenzoic acid) to attenuate cell death caused by cytotoxic hydrogen peroxide. In another experiment, we assayed for the combinatorial effects of three chemotherapeutic compound exposures (vinorelbine, paclitaxel, and γ-linolenic acid) on human breast cancer cells, MDA-MB-231. The same technology will enable the construction of inexpensive lab-on-a-chip devices with high-input combinatorial mixer for performing high-throughput cell-based assay and highly parallel and combinatorial chemical or biochemical reactions. PMID:21063783

  5. 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

  6. 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.

  7. 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.

  8. 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

    2012-09-01

    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. PMID:22763468

  9. 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. PMID:27101171

  10. 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.

  11. 3D imaging of flow patterns in an internally-pumped microfluidic device: redox magnetohydrodynamics and electrochemically-generated density gradients.

    PubMed

    Gao, Feng; Kreidermacher, Adam; Fritsch, Ingrid; Heyes, Colin D

    2013-05-01

    Redox magnetohydrodynamics (MHD) is a promising technique for developing new electrochemical-based microfluidic flow devices with unique capabilities, such as easily switching flow direction and adjusting flow speeds and flow patterns as well as avoiding bubble formation. However, a detailed description of all the forces involved and predicting flow patterns in confined geometries is lacking. In addition to redox-MHD, density gradients caused by the redox reactions also play important roles. Flow in these devices with small fluid volumes has mainly been characterized by following microbead motion by optical microscopy either by particle tracking velocimetry (PTV) or by processing the microbead images by particle image velocimetry (PIV) software. This approach has limitations in spatial resolution and dimensionality. Here we use fluorescence correlation spectroscopy (FCS) to quantitatively and accurately measure flow speeds and patterns in the ~5-50 μm/s range in redox-MHD-based microfluidic devices, from which 3D flow maps are obtained with a spatial resolution down to 2 μm. The 2 μm spatial resolution flow speeds map revealed detailed flow profiles during redox-MHD in which the velocity increases linearly from above the electrode and reaches a plateau across the center of the cell. By combining FCS and video-microscopy (with PTV and PIV processing approaches), we are able to quantify a vertical flow of ~10 μm/s above the electrodes as a result of density gradients caused by the redox reactions and follow convection flow patterns. Overall, combining FCS, PIV, and PTV analysis of redox-MHD is a powerful combination to more thoroughly characterize the underlying forces in these promising microfluidic devices. PMID:23537496

  12. 3D Imaging of Flow Patterns in an Internally-Pumped Microfluidic Device: Redox Magnetohydrodynamics and Electrochemically-Generated Density Gradients

    PubMed Central

    Gao, Feng; Kreidermacher, Adam; Fritsch, Ingrid; Heyes, Colin D.

    2013-01-01

    Redox magnetohydrodynamics (MHD) is a promising technique for developing new electrochemical-based microfluidic flow devices with unique capabilities, such as easily switching flow direction, adjusting flow speeds and flow patterns as well as avoiding bubble formation. However, a detailed description of all the forces involved and predicting flow patterns in confined geometries is lacking. In addition to redox-MHD, density gradients caused by the redox reactions also play important roles. Flow in these devices with small fluid volumes has mainly been characterized by following microbead motion by optical microscopy either by particle tracking velocimetry (PTV) or by processing the microbead images by particle image velocimetry (PIV) software. This approach has limitations in spatial resolution and dimensionality. Here we use fluorescence correlation spectroscopy (FCS) to quantitatively and accurately measure flow speeds and patterns in the ~5-50 μm/s range in redox-MHD-based microfluidic devices, from which 3D flow maps are obtained with a spatial resolution down to 2 μm. The 2 μm spatial resolution flow speeds map revealed detailed flow profiles during redox-MHD in which the velocity increases linearly from above the electrode, and reaches a plateau across the center of the channel. By combining FCS and video-microscopy (with PTV and PIV processing approaches), we are able to quantify a vertical flow of ~10 μm/s above the electrodes as a result of density gradients caused by the redox reactions and follow convection flow patterns. Overall, combining FCS, PIV and PTV analysis of redox-MHD is a powerful combination to more thoroughly characterize the underlying forces in these promising microfluidic devices. PMID:23537496

  13. Wax-bonding 3D microfluidic chips.

    PubMed

    Gong, Xiuqing; Yi, Xin; Xiao, Kang; Li, Shunbo; Kodzius, Rimantas; Qin, Jianhua; Wen, Weijia

    2010-10-01

    We report a simple, low-cost and detachable microfluidic chip incorporating easily accessible paper, glass slides or other polymer films as the chip materials along with adhesive wax as the recycling bonding material. We use a laser to cut through the paper or film to form patterns and then sandwich the paper and film between glass sheets or polymer membranes. The hot-melt adhesive wax can realize bridge bonding between various materials, for example, paper, polymethylmethacrylate (PMMA) film, glass sheets, or metal plate. The bonding process is reversible and the wax is reusable through a melting and cooling process. With this process, a three-dimensional (3D) microfluidic chip is achievable by vacuating and venting the chip in a hot-water bath. To study the biocompatibility and applicability of the wax-based microfluidic chip, we tested the PCR compatibility with the chip materials first. Then we applied the wax-paper based microfluidic chip to HeLa cell electroporation (EP). Subsequently, a prototype of a 5-layer 3D chip was fabricated by multilayer wax bonding. To check the sealing ability and the durability of the chip, green fluorescence protein (GFP) recombinant Escherichia coli (E. coli) bacteria were cultured, with which the chemotaxis of E. coli was studied in order to determine the influence of antibiotic ciprofloxacin concentration on the E. coli migration. PMID:20689865

  14. 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. PMID:25041926

  15. 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.

  16. 3D-printed bioanalytical devices.

    PubMed

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

    2016-07-15

    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. PMID:27250897

  17. A 3D printed microfluidic device for production of functionalized hydrogel microcapsules for culture and differentiation of human Neuronal Stem Cells (hNSC).

    PubMed

    Alessandri, Kevin; Feyeux, Maxime; Gurchenkov, Basile; Delgado, Christophe; Trushko, Anastasiya; Krause, Karl-Heinz; Vignjević, Daniela; Nassoy, Pierre; Roux, Aurélien

    2016-04-26

    We present here a microfluidic device that generates sub-millimetric hollow hydrogel spheres, encapsulating cells and coated internally with a layer of reconstituted extracellular matrix (ECM) of a few microns thick. The spherical capsules, composed of alginate hydrogel, originate from the spontaneous instability of a multi-layered jet formed by co-extrusion using a coaxial flow device. We provide a simple design to manufacture this device using a DLP (digital light processing) 3D printer. Then, we demonstrate how the inner wall of the capsules can be decorated with a continuous ECM layer that is anchored to the alginate gel and mimics the basal membrane of a cellular niche. Finally, we used this approach to encapsulate human Neural Stem Cells (hNSC) derived from human Induced Pluripotent Stem Cells (hIPSC), which were further differentiated into neurons within the capsules with negligible loss of viability. Altogether, we show that these capsules may serve as cell micro-containers compatible with complex cell culture conditions and applications. These developments widen the field of research and biomedical applications of the cell encapsulation technology. PMID:27025278

  18. 3D-printed microfluidic chips with patterned, cell-laden hydrogel constructs.

    PubMed

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

    2016-06-01

    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. PMID:27321481

  19. 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

    2015-07-01

    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. PMID:26088776

  20. 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.

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

    PubMed

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

    2016-07-01

    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. PMID:27242064

  2. 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. PMID:25686903

  3. 3D medical thermography device

    NASA Astrophysics Data System (ADS)

    Moghadam, Peyman

    2015-05-01

    In this paper, a novel handheld 3D medical thermography system is introduced. The proposed system consists of a thermal-infrared camera, a color camera and a depth camera rigidly attached in close proximity and mounted on an ergonomic handle. As a practitioner holding the device smoothly moves it around the human body parts, the proposed system generates and builds up a precise 3D thermogram model by incorporating information from each new measurement in real-time. The data is acquired in motion, thus it provides multiple points of view. When processed, these multiple points of view are adaptively combined by taking into account the reliability of each individual measurement which can vary due to a variety of factors such as angle of incidence, distance between the device and the subject and environmental sensor data or other factors influencing a confidence of the thermal-infrared data when captured. Finally, several case studies are presented to support the usability and performance of the proposed system.

  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. 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. PMID:27050661

  6. Hot embossing for fabrication of a microfluidic 3D cell culture platform

    PubMed Central

    Jeon, Jessie S.; Chung, Seok; Kamm, Roger D.; Charest, Joseph L.

    2011-01-01

    Clinically relevant studies of cell function in vitro require a physiologically-representative microenvironment possessing aspects such as a 3D extracellular matrix (ECM) and controlled biochemical and biophysical parameters. A polydimethylsiloxane (PDMS) microfluidic system with a 3D collagen gel has previously served for analysis of factors inducing different responses of cells in a 3D microenvironment under controlled biochemical and biophysical parameters. In the present study, applying the known commercially-viable manufacturing methods to a cyclic olefin copolymer (COC) material resulted in a microfluidic device with enhanced 3D gel capabilities, controlled surface properties, and improved potential to serve high-volume applications. Hot embossing and roller lamination molded and sealed the microfluidic device. A combination of oxygen plasma and thermal treatments enhanced the sealing, ensured proper placement of the 3D gel, and created controlled and stable surface properties within the device. Culture of cells in the new device indicated no adverse effects of the COC material or processing as compared to previous PDMS devices. The results demonstrate a methodology to transition microfludic devices for 3D cell culture from scientific research to high-volume applications with broad clinical impact. PMID:21113663

  7. 3D Printed Micro Free-Flow Electrophoresis Device.

    PubMed

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

    2016-08-01

    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. PMID:27377354

  8. Sub-micrometer-precision, three-dimensional (3D) hydrodynamic focusing via “microfluidic drifting”

    PubMed Central

    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

    2014-01-01

    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 by 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 by 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. PMID:24287742

  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. PMID:24287742

  10. Microfluidic 3D cell culture: from tools to tissue models.

    PubMed

    van Duinen, Vincent; Trietsch, Sebastiaan J; Joore, Jos; Vulto, Paul; Hankemeier, Thomas

    2015-12-01

    The transition from 2D to 3D cell culture techniques is an important step in a trend towards better biomimetic tissue models. Microfluidics allows spatial control over fluids in micrometer-sized channels has become a valuable tool to further increase the physiological relevance of 3D cell culture by enabling spatially controlled co-cultures, perfusion flow and spatial control over of signaling gradients. This paper reviews most important developments in microfluidic 3D culture since 2012. Most efforts were exerted in the field of vasculature, both as a tissue on its own and as part of cancer models. We observe that the focus is shifting from tool building to implementation of specific tissue models. The next big challenge for the field is the full validation of these models and subsequently the implementation of these models in drug development pipelines of the pharmaceutical industry and ultimately in personalized medicine applications. PMID:26094109

  11. Evaluating Biomaterial- and Microfluidic-Based 3D Tumor Models.

    PubMed

    Carvalho, Mariana R; Lima, Daniela; Reis, Rui L; Correlo, Vitor M; Oliveira, Joaquim M

    2015-11-01

    Cancer is a major cause of morbidity and mortality worldwide, with a disease burden estimated to increase over the coming decades. Disease heterogeneity and limited information on cancer biology and disease mechanisms are aspects that 2D cell cultures fail to address. Here, we review the current ‘state-of-the-art’ in 3D tissue-engineering (TE) models developed for, and used in, cancer research. We assess the potential for scaffold-based TE models and microfluidics to fill the gap between 2D models and clinical application. We also discuss recent advances in combining the principles of 3D TE models and microfluidics, with a special focus on biomaterials and the most promising chip-based 3D models. PMID:26603572

  12. 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.

  13. 3D-Printed Microfluidic Device for the Detection of Pathogenic Bacteria Using Size-based Separation in Helical Channel with Trapezoid Cross-Section

    PubMed Central

    Lee, Wonjae; Kwon, Donghoon; Choi, Woong; Jung, Gyoo Yeol; Jeon, Sangmin

    2015-01-01

    A facile method has been developed to detect pathogenic bacteria using magnetic nanoparticle clusters (MNCs) and a 3D-printed helical microchannel. Antibody-functionalized MNCs were used to capture E. coli (EC) bacteria in milk, and the free MNCs and MNC-EC complexes were separated from the milk using a permanent magnet. The free MNCs and MNC-EC complexes were dispersed in a buffer solution, then the solution was injected into a helical microchannel device with or without a sheath flow. The MNC-EC complexes were separated from the free MNCs via the Dean drag force and lift force, and the separation was facilitated in the presence of a sheath flow. The concentration of the E. coli bacteria was determined using a light absorption spectrometer, and the limit of detection was found to be 10 cfu/mL in buffer solution and 100 cfu/mL in milk. PMID:25578942

  14. 3D-printed microfluidic device for the detection of pathogenic bacteria using size-based separation in helical channel with trapezoid cross-section.

    PubMed

    Lee, Wonjae; Kwon, Donghoon; Choi, Woong; Jung, Gyoo Yeol; Jeon, Sangmin

    2015-01-01

    A facile method has been developed to detect pathogenic bacteria using magnetic nanoparticle clusters (MNCs) and a 3D-printed helical microchannel. Antibody-functionalized MNCs were used to capture E. coli (EC) bacteria in milk, and the free MNCs and MNC-EC complexes were separated from the milk using a permanent magnet. The free MNCs and MNC-EC complexes were dispersed in a buffer solution, then the solution was injected into a helical microchannel device with or without a sheath flow. The MNC-EC complexes were separated from the free MNCs via the Dean drag force and lift force, and the separation was facilitated in the presence of a sheath flow. The concentration of the E. coli bacteria was determined using a light absorption spectrometer, and the limit of detection was found to be 10 cfu/mL in buffer solution and 100 cfu/mL in milk. PMID:25578942

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

    PubMed

    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

  17. 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.

  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. 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

  20. 3D nanoporous optofluidic device for high sensitivity SERS detection

    NASA Astrophysics Data System (ADS)

    H. Yazdi, Soroush; White, Ian M.

    2012-03-01

    We report the demonstration of an optofluidic surface enhanced Raman spectroscopy (SERS) device that leverages nanoporous microfluidics to dramatically increase the SERS performance. A number of optofluidic approaches have been used to improve the detection limit of SERS in microfluidic channels, including active concentration of nanoparticles and/or analyte and passive concentration of nanoparticles. Previous reports have used a single nanofabricated fluidic channel to trap metal nanoparticles and adsorbed analytes. In this work, we utilize a significantly simpler fabrication approach by packing silica beads in a microfluidic channel to create a 3D nanofluidic concentration matrix. The device is fabricated using polydimethylsiloxane (PDMS) on glass using typical soft lithography methods. Due to the larger area of the nanoporous fluidic channel, this approach should be less prone to clogging than single nanofluidic inlets, and the loading time is decreased compared to previous reports. Using this microfluidic device, we achieved a detection limit of 4 femtomoles of Rhodamine 6G in 2 minutes. Compared to an open microfluidic channel, the 3D nanoporous concentration matrix increased the SERS signal by a factor of 250 due to the trapping of silver nanoclusters. Fiber optic cables are integrated into the PDMS to deliver excitation light directly to the detection volume and to collect Raman-scattered photons. As a result, the use of a laser diode and alignment-free integrated fiber optics implies the potential for the device to be used in portable and automated applications, such as the on-site detection of pesticides, water contaminants, and explosives.

  1. 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.

  2. Open-Source Wax RepRap 3-D Printer for Rapid Prototyping Paper-Based Microfluidics.

    PubMed

    Pearce, J M; Anzalone, N C; Heldt, C L

    2016-08-01

    The open-source release of self-replicating rapid prototypers (RepRaps) has created a rich opportunity for low-cost distributed digital fabrication of complex 3-D objects such as scientific equipment. For example, 3-D printable reactionware devices offer the opportunity to combine open hardware microfluidic handling with lab-on-a-chip reactionware to radically reduce costs and increase the number and complexity of microfluidic applications. To further drive down the cost while improving the performance of lab-on-a-chip paper-based microfluidic prototyping, this study reports on the development of a RepRap upgrade capable of converting a Prusa Mendel RepRap into a wax 3-D printer for paper-based microfluidic applications. An open-source hardware approach is used to demonstrate a 3-D printable upgrade for the 3-D printer, which combines a heated syringe pump with the RepRap/Arduino 3-D control. The bill of materials, designs, basic assembly, and use instructions are provided, along with a completely free and open-source software tool chain. The open-source hardware device described here accelerates the potential of the nascent field of electrochemical detection combined with paper-based microfluidics by dropping the marginal cost of prototyping to nearly zero while accelerating the turnover between paper-based microfluidic designs. PMID:26763294

  3. 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. PMID:26980159

  4. 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.

  5. Microfluidic Bioprinting of Heterogeneous 3D Tissue Constructs Using Low-Viscosity Bioink.

    PubMed

    Colosi, Cristina; Shin, Su Ryon; Manoharan, Vijayan; Massa, Solange; Costantini, Marco; Barbetta, Andrea; Dokmeci, Mehmet Remzi; Dentini, Mariella; Khademhosseini, Ali

    2016-01-27

    A novel bioink and a dispensing technique for 3D tissue-engineering applications are presented. The technique incorporates a coaxial extrusion needle using a low-viscosity cell-laden bioink to produce highly defined 3D biostructures. The extrusion system is then coupled to a microfluidic device to control the bioink arrangement deposition, demonstrating the versatility of the bioprinting technique. This low-viscosity cell-responsive bioink promotes cell migration and alignment within each fiber organizing the encapsulated cells. PMID:26606883

  6. Metrological characterization of 3D imaging devices

    NASA Astrophysics Data System (ADS)

    Guidi, G.

    2013-04-01

    Manufacturers often express the performance of a 3D imaging device in various non-uniform ways for the lack of internationally recognized standard requirements for metrological parameters able to identify the capability of capturing a real scene. For this reason several national and international organizations in the last ten years have been developing protocols for verifying such performance. Ranging from VDI/VDE 2634, published by the Association of German Engineers and oriented to the world of mechanical 3D measurements (triangulation-based devices), to the ASTM technical committee E57, working also on laser systems based on direct range detection (TOF, Phase Shift, FM-CW, flash LADAR), this paper shows the state of the art about the characterization of active range devices, with special emphasis on measurement uncertainty, accuracy and resolution. Most of these protocols are based on special objects whose shape and size are certified with a known level of accuracy. By capturing the 3D shape of such objects with a range device, a comparison between the measured points and the theoretical shape they should represent is possible. The actual deviations can be directly analyzed or some derived parameters can be obtained (e.g. angles between planes, distances between barycenters of spheres rigidly connected, frequency domain parameters, etc.). This paper shows theoretical aspects and experimental results of some novel characterization methods applied to different categories of active 3D imaging devices based on both principles of triangulation and direct range detection.

  7. Fabrication of 3D high aspect ratio PDMS microfluidic networks with a hybrid stamp.

    PubMed

    Kung, Yu-Chun; Huang, Kuo-Wei; Fan, Yu-Jui; Chiou, Pei-Yu

    2015-04-21

    We report a novel methodology for fabricating large-area, multilayer, thin-film, high aspect ratio, 3D microfluidic structures with through-layer vias and open channels that can be bonded between hard substrates. It is realized by utilizing a hybrid stamp with a thin plastic sheet embedded underneath a PDMS surface. This hybrid stamp solves an important edge protrusion issue during PDMS molding while maintaining necessary stamp elasticity to ensure the removal of PDMS residues at through-layer regions. Removing edge protrusion is a significant progress toward fabricating 3D structures since high aspect ratio PDMS structures with flat interfaces can be realized to facilitate multilayer stacking and bonding to hard substrates. Our method also allows for the fabrication of 3D deformable channels, which can lead to profound applications in electrokinetics, optofluidics, inertial microfluidics, and other fields where the shape of the channel cross section plays a key role in device physics. To demonstrate, as an example, we have fabricated a microfluidic channel by sandwiching two 20 μm wide, 80 μm tall PDMS membranes between two featureless ITO glass substrates. By applying electrical bias to the two ITO substrates and pressure to deform the thin membrane sidewalls, strong electric field enhancement can be generated in the center of a channel to enable 3D sheathless dielectrophoretic focusing of biological objects including mammalian cells and bacteria at a flow speed up to 14 cm s(-1). PMID:25710255

  8. 3D flow focusing for microfluidic flow cytometry with ultrasonics

    NASA Astrophysics Data System (ADS)

    Gnyawali, Vaskar; Strohm, Eric M.; Daghighi, Yasaman; van de Vondervoort, Mia; Kolios, Michael C.; Tsai, Scott S. H.

    2015-11-01

    We are developing a flow cytometer that detects unique acoustic signature waves generated from single cells due to interactions between the cells and ultrasound waves. The generated acoustic waves depend on the size and biomechanical properties of the cells and are sufficient for identifying cells in the medium. A microfluidic system capable of focusing cells through a 10 x 10 μm ultrasound beam cross section was developed to facilitate acoustic measurements of single cells. The cells are streamlined in a hydro-dynamically 3D focused flow in a 300 x 300 μm channel made using PDMS. 3D focusing is realized by lateral sheath flows and an inlet needle (inner diameter 100 μm). The accuracy of the 3D flow focusing is measured using a dye and detecting its localization using confocal microscopy. Each flowing cell would be probed by an ultrasound pulse, which has a center frequency of 375 MHz and bandwidth of 250 MHz. The same probe would also be used for recording the scattered waves from the cells, which would be processed to distinguish the physical and biomechanical characteristics of the cells, eventually identifying them. This technique has potential applications in detecting circulating tumor cells, blood cells and blood-related diseases.

  9. Generation and functional assessment of 3D multicellular spheroids in droplet based microfluidics platform.

    PubMed

    Sabhachandani, P; Motwani, V; Cohen, N; Sarkar, S; Torchilin, V; Konry, T

    2016-02-01

    Here we describe a robust, microfluidic technique to generate and analyze 3D tumor spheroids, which resembles tumor microenvironment and can be used as a more effective preclinical drug testing and screening model. Monodisperse cell-laden alginate droplets were generated in polydimethylsiloxane (PDMS) microfluidic devices that combine T-junction droplet generation and external gelation for spheroid formation. The proposed approach has the capability to incorporate multiple cell types. For the purposes of our study, we generated spheroids with breast cancer cell lines (MCF-7 drug sensitive and resistant) and co-culture spheroids of MCF-7 together with a fibroblast cell line (HS-5). The device has the capability to house 1000 spheroids on chip for drug screening and other functional analysis. Cellular viability of spheroids in the array part of the device was maintained for two weeks by continuous perfusion of complete media into the device. The functional performance of our 3D tumor models and a dose dependent response of standard chemotherapeutic drug, doxorubicin (Dox) and standard drug combination Dox and paclitaxel (PCT) was analyzed on our chip-based platform. Altogether, our work provides a simple and novel, in vitro platform to generate, image and analyze uniform, 3D monodisperse alginate hydrogel tumors for various omic studies and therapeutic efficiency screening, an important translational step before in vivo studies. PMID:26686985

  10. 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. PMID:27452498

  11. 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

  12. 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

  13. 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.

  14. 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

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

    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.

  16. 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.

  17. 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

  18. 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.

  19. 3D printing of liquid metals as fugitive inks for fabrication of 3D microfluidic channels.

    PubMed

    Parekh, Dishit P; Ladd, Collin; Panich, Lazar; Moussa, Khalil; Dickey, Michael D

    2016-05-21

    This paper demonstrates a simple method to fabricate 3D microchannels and microvasculature at room temperature by direct-writing liquid metal as a sacrificial template. The formation of a surface oxide skin on the low-viscosity liquid metal stabilizes the shape of the printed metal for planar and out-of-plane structures. The printed structures can be embedded in a variety of soft (e.g. elastomeric) and rigid (e.g. thermoset) polymers. Both acid and electrochemical reduction are capable of removing the oxide skin that forms on the metal, which destabilizes the ink so that it withdraws from the encapsulating material due to capillary forces, resulting in nearly full recovery of the fugitive ink at room temperature. Whereas conventional fabrication procedures typically confine microchannels to 2D planes, the geometry of the printed microchannels can be varied from a simple 2D network to complex 3D architectures without using lithography. The method produces robust monolithic structures without the need for any bonding or assembling techniques that often limit the materials of construction of conventional microchannels. Removing select portions of the metal leaves behind 3D metal features that can be used as antennas, interconnects, or electrodes for interfacing with lab-on-a-chip devices. This paper describes the capabilities and limitations of this simple process. PMID:27025537

  20. 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.

  1. Creating 3D chemical gradients with self-folding microfluidic networks

    NASA Astrophysics Data System (ADS)

    Jamal, Mustapha; Kalinin, Yevgeniy; Zarafshar, Aasiyeh; Gracias, David

    2012-02-01

    We describe the reversible self-folding of polymeric films into intricate three-dimensional (3D) microfluidic networks and investigate their utility as bio-inspired synthetic vasculature for in vitro tissue culture models. Our fabrication methodology relies on patterning of channels inside the films at the planar microfabrication stage followed by programmable self-folding of the two-dimensional patterned structures. Here self-folding action is enabled by stress gradients which develop in the films due to differential ultraviolet cross-linking and subsequent solvent conditioning. We achieved wafer-scale assembly of micropatterned geometries including helices, polyhedra and corrugated sheets. To demonstrate utility of such self-folded microfluidic devices we present localized chemical delivery of biochemicals in 3D to discrete regions of cells cultured on the curved self-assembled surfaces and in a thick, surrounding hydrogel. We believe that the devices can be used to mimic such natural self-assembled systems as leaves and tissues. Reference: M. Jamal et al., Nature Communications (2011; in press).

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

    PubMed Central

    Shen, Richang; Gurkan, Umut A.

    2016-01-01

    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.

  3. Osteocyte culture in microfluidic devices.

    PubMed

    Wei, Chao; Fan, Beiyuan; Chen, Deyong; Liu, Chao; 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

  4. 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

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

    PubMed

    Munshi, Akash S; Martin, R Scott

    2016-02-01

    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 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. PMID:26649363

  6. 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.

  7. 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.

  8. Microfluidic ion-sensing devices.

    PubMed

    Johnson, R Daniel; Gavalas, Vasilis G; Daunert, Sylvia; Bachas, Leonidas G

    2008-04-14

    Quantitative determinations of ions in a variety of media have been performed traditionally via one of three approaches: optical instrumental methods (e.g., atomic absorption, and inductively-coupled plasma-optical emission or mass spectrometry), "wet" methods, or ion-selective sensors. Each of the approaches, though, possesses limitations including: power/reagent consumption and lack of portability for instrumental techniques; laborious sample-treatment steps for wet methods; and lack of selectivity and sensitivity with sensors when employed with complex samples. Microfluidic device have emerged as a solution to some of these challenges associated with ion analysis. Such systems can integrate multiple sample handling, calibration, and detection steps ("lab-on-a-chip" concept) into a footprint amenable to portability, while requiring small amounts of sample and power. Furthermore, devices can be constructed for multi-analyte detection, either through multiple parallel fluidic architectures or by using arrays of detection elements. This paper reviews recent progress in the development of total-analysis systems for ionic species. Fabrication techniques and various fluid-handling operations are discussed briefly, followed by a number of more mature strategies for microfluidic ion analysis. A variety of approaches expected to comprise the next generation of devices are also presented. PMID:18374698

  9. 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

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

    PubMed

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

    2015-01-01

    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

  11. 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.

  12. 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

  13. 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.

  14. Inkjet 3D printing of microfluidic structures—on the selection of the printer towards printing your own microfluidic chips

    NASA Astrophysics Data System (ADS)

    Walczak, Rafał; Adamski, Krzysztof

    2015-08-01

    This article reports, for the first time, the results of detailed research on the application of inkjet 3D printing for the fabrication of microfluidic structures. CAD designed test structures were printed with four different printers. Dimensional fidelity, shape conformity, and surface roughness were studied for each printout. It was found that the minimum dimension (width or depth) for a properly printed microfluidic channel was approximately 200 μm. Although the nominal resolution of the printers was one order of magnitude better, smaller structures were significantly deformed or not printed at all. It was also found that a crucial step in one-step fabrication of embedded microchannels is the removal of the support material. We also discuss the source of print error and present a way to evaluate other printers. The printouts obtained from the four different printers were compared, and the optimal printing technique and printer were used to fabricate a microfluidic structure for the spectrophotometric characterisation of beverages. UV/VIS absorbance characteristics were collected using this microfluidic structure, demonstrating that the fabricated spectrophotometric chip operated properly. Thus, a proof-of-concept for using inkjet 3D printing for the fabrication of microfluidic structures was obtained.

  15. Development of an Efficient Quasi-3D Microfluidic Flow Model and Fabrication and Characterization of an All-PDMS Opto-Microfluidic Flow Cytometer

    NASA Astrophysics Data System (ADS)

    Islam, Md Zahurul

    In this thesis, development of a novel microfluidic flow model, and, fabrication and testing of microfluidic cytometer for potential cell detection and sorting applications are described. The model is formulated by decomposing the flow profile along the height of microfluidic device into a Fourier series that converts the 3D flow equations into a series of coupled 2D equations and is applicable to planar microfluidic devices only. It is validated against the analytical solution for flow in a straight rectangular channel and the full 3D solution of a commercial Navier-Stokes solver for flow in a T-channel. Comparable accuracy to the full 3D numerical solution is achieved by using only three Fourier terms with significant decrease in computation time. The model is also extended to the problems with time-varying boundary conditions. We fabricated two first generation miniaturized cytometer prototypes and used them for preliminary proof-of-concepts experiments. They were built by cutting fluidic channels into two different polymer materials and bonding them between two standard glass slides with epoxy and fusion bonding. We fabricated a second generation of flow cytometer chip consisting of an integrated 2D hydrodynamic focusing system, solid-core optical waveguides and a hydrodynamic side-flow switching system on an all-PDMS platform. Optical propagation losses of the integrated waveguides and signal-to-noise ratio (SNR) of its detection system were characterized. The propagation losses were found to be 1.6 and 1.5 dB/cm for the green and red light, respectively. Detection of fluorescent signal through the waveguide yielded improved SNR than the conventional method of under-chip detection. Fluid flow speeds were estimated from volumetric flow measurements and fluorescent particle tracking experiments and the width of the hydrodynamically focused stream was extracted from microscope flow images. The results were compared to the simulation values obtained from the Q3D

  16. Creation of hydrophilic microfluidic devices for biomedical application through stereolithography

    NASA Astrophysics Data System (ADS)

    Brandhoff, Lukas; van den Driesche, Sander; Lucklum, Frieder; Vellekoop, Michael J.

    2015-06-01

    We present a method to graft a layer of poly-ethylene-glycol (PEG) to the surface of stereo-lithography fabricated or 3D-printed microfluidic devices rendering it hydrophilic and repellent to the adhesion of proteins. The PEG forms a rigid bond with the surface that is more stable than many coatings or surface treatments. This makes stereolithography much more attractive as a prototyping platform for microfluidics. The method has been proven with two different resins by different manufacturers, showing the universality of said treatment.

  17. 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. PMID:24110985

  18. Laser Ablation of Polymer Microfluidic Devices

    NASA Astrophysics Data System (ADS)

    Killeen, Kevin

    2004-03-01

    Microfluidic technology is ideal for processing precious samples of limited volumes. Some of the most important classes of biological samples are both high in sample complexity and low in concentration. Combining the elements of sample pre-concentration, chemical separation and high sensitivity detection with chemical identification is essential for realizing a functional microfluidic based analysis system. Direct write UV laser ablation has been used to rapidly fabricate microfluidic devices capable of high performance liquid chromatography (HPLC)-MS. These chip-LC/MS devices use bio-compatible, solvent resistant and flexible polymer materials such as polyimide. A novel microfluidic to rotary valve interface enables, leak free, high pressure fluid switching between multiple ports of the microfluidic chip-LC/MS device. Electrospray tips with outer dimension of 50 um and inner of 15 um are formed by ablating the polymer material concentrically around a multilayer laminated channel structure. Biological samples of digested proteins were used to evaluate the performance of these microfluidic devices. Liquid chromatography separation and similar sample pretreatments have been performed using polymeric microfluidic devices with on-chip separation channels. Mass spectrometry was performed using an Agilent Technologies 1100 series ion trap mass spectrometer. Low fmol amounts of protein samples were positively and routinely identified by searching the MS/MS spectral data against protein databases. The sensitivity and separation performance of the chip-LC devices has been found to be comparable to state of the art nano-electrospray systems.

  19. 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.

  20. Microfluidic devices for construction of contractile skeletal muscle microtissues.

    PubMed

    Shimizu, Kazunori; Araki, Hiroyuki; Sakata, Kohei; Tonomura, Wataru; Hashida, Mitsuru; Konishi, Satoshi

    2015-02-01

    Cell-culture microchips mimicking tissue/organ-specific functions are required as alternatives to animal testing for drug discovery and disease models. Although three-dimensional (3D) cell culture microfluidic devices can create more biologically relevant cellular microenvironments and higher throughput analysis platforms of cell behavior than conventional techniques, devices for skeletal muscle cells have not been developed. In the present study, we aimed to develop microfluidic devices for 3D cultures of skeletal muscle cells. Skeletal muscle cells mixed with a collagen type-I solution was introduced into the microchannel for cells (MC-C) and was gelated. Then, the medium was introduced into the microchannel for medium (MC-M). During this process, connecting microchannels (Con-MCs) prevented leakage of the collagen solution mixed with cells from MC-C to MC-M and supplied the nutrients from the medium in MC-M to the cells in MC-C. Skeletal muscle microtissues cultured in the microchannel for a week consisted of myotubes were confirmed by histological analysis and immunofluorescence staining. The skeletal muscle microtissues in the microchannel contracted in response to externally applied electrical stimulation (1 and 50 Hz). These results indicate that the functional skeletal muscle microtissues were constructed in the microchannel. Thus, the microfluidic device for culturing 3D skeletal muscle microtissues presented in this study has a potential to be used for drug discovery and toxicological tests. PMID:25085533

  1. 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.

  2. 3D pulsed laser-triggered high-speed microfluidic fluorescence-activated cell sorter.

    PubMed

    Chen, Yue; Wu, Ting-Hsiang; Kung, Yu-Chun; Teitell, Michael A; Chiou, Pei-Yu

    2013-11-12

    We report a 3D microfluidic pulsed laser-triggered fluorescence-activated cell sorter capable of sorting at a throughput of 23 000 cells per s with 90% purity in high-purity mode and at a throughput of 45 000 cells per s with 45% purity in enrichment mode in one stage and in a single channel. This performance is realized by exciting laser-induced cavitation bubbles in a 3D PDMS microfluidic channel to generate high-speed liquid jets that deflect detected fluorescent cells and particles focused by 3D sheath flows. The ultrafast switching mechanism (20 μs complete on-off cycle), small liquid jet perturbation volume, and three-dimensional sheath flow focusing for accurate timing control of fast (1.5 m s(-1)) passing cells and particles are three critical factors enabling high-purity sorting at high-throughput in this sorter. PMID:23844418

  3. Microfluidic Devices in Advanced Caenorhabditis elegans Research.

    PubMed

    Muthaiyan Shanmugam, Muniesh; Subhra Santra, Tuhin

    2016-01-01

    The study of model organisms is very important in view of their potential for application to human therapeutic uses. One such model organism is the nematode worm, Caenorhabditis elegans. As a nematode, C. elegans have ~65% similarity with human disease genes and, therefore, studies on C. elegans can be translated to human, as well as, C. elegans can be used in the study of different types of parasitic worms that infect other living organisms. In the past decade, many efforts have been undertaken to establish interdisciplinary research collaborations between biologists, physicists and engineers in order to develop microfluidic devices to study the biology of C. elegans. Microfluidic devices with the power to manipulate and detect bio-samples, regents or biomolecules in micro-scale environments can well fulfill the requirement to handle worms under proper laboratory conditions, thereby significantly increasing research productivity and knowledge. The recent development of different kinds of microfluidic devices with ultra-high throughput platforms has enabled researchers to carry out worm population studies. Microfluidic devices primarily comprises of chambers, channels and valves, wherein worms can be cultured, immobilized, imaged, etc. Microfluidic devices have been adapted to study various worm behaviors, including that deepen our understanding of neuromuscular connectivity and functions. This review will provide a clear account of the vital involvement of microfluidic devices in worm biology. PMID:27490525

  4. 3D Printed Microscope for Mobile Devices that Cost Pennies

    ScienceCinema

    Erikson, Rebecca; Baird, Cheryl; Hutchinson, Janine

    2015-06-23

    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.

  5. 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.

  6. Microfluidic vias enable nested bioarrays and autoregulatory devices in Newtonian fluids

    PubMed Central

    Kartalov, Emil P.; Walker, Christopher; Taylor, Clive R.; Anderson, W. French; Scherer, Axel

    2006-01-01

    We report on a fundamental technological advance for multilayer polydimethylsiloxane (PDMS) microfluidics. Vertical passages (vias), connecting channels located in different layers, are fabricated monolithically, in parallel, by simple and easy means. The resulting 3D connectivity greatly expands the potential complexity of microfluidic architecture. We apply the vias to printing nested bioarrays and building autoregulatory devices. A current source is demonstrated, while a diode and a rectifier are derived; all are building blocks for analog circuitry in Newtonian fluids. We also describe microfluidic septa and their applications. Vias lay the foundation for a new generation of microfluidic devices. PMID:16888040

  7. 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

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

    PubMed

    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

  9. 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.

  10. 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

    2016-02-01

    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

  11. 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.

  12. Monolithic multilayer microfluidics via sacrificial molding of 3D-printed isomalt†

    PubMed Central

    Gelber, Matthew K.

    2015-01-01

    Here we demonstrate a method for creating multilayer or 3D microfluidics by casting a curable resin around a water-soluble, freestanding sacrificial mold. We use a purpose-built 3D printer to pattern self-supporting filaments of the sugar alcohol isomalt, which we then back-fill with a transparent epoxy resin. Dissolving the sacrificial mold leaves a network of cylindrical channels as well as input and output ports. We use this technique to fabricate a combinatorial mixer capable of producing 8 combinations of two fluids in ratios ranging from 1 : 100 to 100 : 1. This approach allows rapid iteration on microfluidic chip design and enables the use of geometry and materials not accessible using conventional soft lithography. The ability to precisely pattern round channels in all three dimensions in hard and soft media may prove enabling for many organ-on-chip systems. PMID:25671493

  13. Monolithic multilayer microfluidics via sacrificial molding of 3D-printed isomalt.

    PubMed

    Gelber, Matthew K; Bhargava, Rohit

    2015-04-01

    Here we demonstrate a method for creating multilayer or 3D microfluidics by casting a curable resin around a water-soluble, freestanding sacrificial mold. We use a purpose-built 3D printer to pattern self-supporting filaments of the sugar alcohol isomalt, which we then back-fill with a transparent epoxy resin. Dissolving the sacrificial mold leaves a network of cylindrical channels as well as input and output ports. We use this technique to fabricate a combinatorial mixer capable of producing 8 combinations of two fluids in ratios ranging from 1 : 100 to 100 : 1. This approach allows rapid iteration on microfluidic chip design and enables the use of geometry and materials not accessible using conventional soft lithography. The ability to precisely pattern round channels in all three dimensions in hard and soft media may prove enabling for many organ-on-chip systems. PMID:25671493

  14. Microfluidic Generation of Monodisperse, Structurally Homogeneous Alginate Microgels for Cell Encapsulation and 3D Cell Culture.

    PubMed

    Utech, Stefanie; Prodanovic, Radivoje; Mao, Angelo S; Ostafe, Raluca; Mooney, David J; Weitz, David A

    2015-08-01

    Monodisperse alginate microgels (10-50 μm) are created via droplet-based microfluidics by a novel crosslinking procedure. Ionic crosslinking of alginate is induced by release of chelated calcium ions. The process separates droplet formation and gelation reaction enabling excellent control over size and homogeneity under mild reaction conditions. Living mesenchymal stem cells are encapsulated and cultured in the generated 3D microenvironments. PMID:26039892

  15. Time domain topology optimization of 3D nanophotonic devices

    NASA Astrophysics Data System (ADS)

    Elesin, Y.; Lazarov, B. S.; Jensen, J. S.; Sigmund, O.

    2014-02-01

    We present an efficient parallel topology optimization framework for design of large scale 3D nanophotonic devices. The code shows excellent scalability and is demonstrated for optimization of broadband frequency splitter, waveguide intersection, photonic crystal-based waveguide and nanowire-based waveguide. The obtained results are compared to simplified 2D studies and we demonstrate that 3D topology optimization may lead to significant performance improvements.

  16. 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. PMID:25971059

  17. Fabrication of 3D microfluidic structures inside glass by femtosecond laser micromachining

    NASA Astrophysics Data System (ADS)

    Sugioka, Koji; Cheng, Ya

    2014-01-01

    Femtosecond lasers have opened up new avenues in materials processing due to their unique characteristics of ultrashort pulse widths and extremely high peak intensities. One of the most important features of femtosecond laser processing is that a femtosecond laser beam can induce strong absorption in even transparent materials due to nonlinear multiphoton absorption. This makes it possible to directly create three-dimensional (3D) microfluidic structures in glass that are of great use for fabrication of biochips. For fabrication of the 3D microfluidic structures, two technical approaches are being attempted. One of them employs femtosecond laser-induced internal modification of glass followed by wet chemical etching using an acid solution (Femtosecond laser-assisted wet chemical etching), while the other one performs femtosecond laser 3D ablation of the glass in distilled water (liquid-assisted femtosecond laser drilling). This paper provides a review on these two techniques for fabrication of 3D micro and nanofluidic structures in glass based on our development and experimental results.

  18. 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. PMID:20199381

  19. 3D hybrid wound devices for spatiotemporally controlled release kinetics.

    PubMed

    Ozbolat, Ibrahim T; Koc, Bahattin

    2012-12-01

    This paper presents localized and temporal control of release kinetics over 3-dimensional (3D) hybrid wound devices to improve wound-healing process. Imaging study is performed to extract wound bed geometry in 3D. Non-Uniform Rational B-Splines (NURBS) based surface lofting is applied to generate functionally graded regions. Diffusion-based release kinetics model is developed to predict time-based release of loaded modifiers for functionally graded regions. Multi-chamber single nozzle solid freeform dispensing system is used to fabricate wound devices with controlled dispensing concentration. Spatiotemporal control of biological modifiers thus enables a way to achieve target delivery to improve wound healing. PMID:22672934

  20. 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

  1. Forming particle chains in inertial microfluidic devices

    NASA Astrophysics Data System (ADS)

    Hood, Kaitlyn; Liu, Lawrence; Roper, Marcus

    2015-11-01

    Particles in microfluidic devices at finite Reynolds number self-assemble into evenly-spaced chains, which can be exploited in inertial microfluidic devices for flow cytometry, high speed imaging, and entrapment. While the location and number of chains can be manipulated by changing the channel geometry, the particle interactions are not understood well enough to manipulate the spacing between particles. We present a mathematical model of particle interactions and the formation of particle chains. We will address the following questions: Is there a preferred particle spacing? What are the conditions needed for chain formation?

  2. 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.

  3. 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

  4. 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.

  5. A Microfluidic Bioreactor for Toxicity Testing of Stem Cell Derived 3D Cardiac Bodies.

    PubMed

    Christoffersson, Jonas; Bergström, Gunnar; Schwanke, Kristin; Kempf, Henning; Zweigerdt, Robert; Mandenius, Carl-Fredrik

    2016-01-01

    Modeling tissues and organs using conventional 2D cell cultures is problematic as the cells rapidly lose their in vivo phenotype. In microfluidic bioreactors the cells reside in microstructures that are continuously perfused with cell culture medium to provide a dynamic environment mimicking the cells natural habitat. These micro scale bioreactors are sometimes referred to as organs-on-chips and are developed in order to improve and extend cell culture experiments. Here, we describe the two manufacturing techniques photolithography and soft lithography that are used in order to easily produce microfluidic bioreactors. The use of these bioreactors is exemplified by a toxicity assessment on 3D clustered human pluripotent stem cells (hPSC)-derived cardiomyocytes by beating frequency imaging. PMID:27052611

  6. 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.

  7. 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.

  8. 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

  9. 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. PMID:26725379

  10. 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.

  11. Microfluidic device for acoustic cell lysis

    DOEpatents

    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.

  12. Double emulsions in a microfluidic device

    NASA Astrophysics Data System (ADS)

    Pannacci, Nicolas; Lockhart, Thibaut; Willaime, Hervé; Tabeling, Patrick

    2007-11-01

    Double emulsions (emulsion of two liquids dispersed in a third liquid phase) are widely used in cosmetics, medicine or food industry. We are interested in producing very well controlled double emulsions in a microfluidic device and predicting the morphology (complete engulfing, non-engulfing or partial engulfing called ``janus'') from classical energetic considerations. We use a double flow focusing geometry with a 100 micrometers cross section for the PDMS microsystem. We compare theoretical and experimental morphologies flowing thirty triplets of immiscible fluids. We observe quite a good agreement and show that microfluidic technology may permit to get non standard objects.

  13. 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.

  14. 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.

  15. Microfluidic Generation of Haptotactic Gradients through 3D Collagen Gels for Enhanced Neurite Growth

    PubMed Central

    Sundararaghavan, Harini G.; Masand, Shirley N.

    2011-01-01

    Abstract We adapted a microfluidic system used previously to generate durotactic gradients of stiffness in a 3D collagen gel, to produce haptotactic gradients of adhesive ligands through the collagen gel. Oligopeptide sequences that included bioactive peptide sequences from laminin, YIGSR, or IKVAV, were grafted separately onto type I collagen using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC). Solutions of peptide-grafted collagen and untreated collagen were then used as source and sink input solutions, respectively, in an H-shaped microfluidic network fabricated using traditional soft lithography. One-dimensional gradients of the peptide-grafted collagen solution were generated in the channel that connected the source and sink channels, and these gradients became immobilized upon self-assembly of the collagen into a 3D fibrillar gel. The slope and average concentration of the gradients were adjusted by changing the concentration of the source solutions and by changing the length of the cross-channel. A separate, underlying channel in the microfluidic construct allowed the introduction of a chick embryo dorsal root ganglion into the network. Neurites from these explants grew significantly longer up steep gradients of YIGSR, but shallow gradients of IKVAV in comparison to untreated collagen controls. When these two gradients were presented in combination, the bias in growth acceleration was the largest and most consistent. No differences were observed in the number of neurites choosing to grow up or down the gradients in any condition. These results suggest that the incorporation of distinct gradients of multiple bioactive ligands can improve directional acceleration of regenerating axons. PMID:21473683

  16. Microfluidic device capable of sensing ultrafast chemiluminescence.

    PubMed

    Kim, Young-Teck; Ko, Seok Oh; Lee, Ji Hoon

    2009-05-15

    Based on the principle of liquid core waveguide, a novel microfluidic device with micro-scale detection window capable of sensing flashlight emitted from rapid 1,1'-oxalyldi-4-methylimidazole (OD4MI) chemiluminescence (CL) reaction was fabricated. Light emitted from OD4MI CL reaction occurring in the micro-dimensional pentagonal detection window (length of each line segment: 900.0 microm, depth: 50.0 microm) of the microfluidic device with two inlets and one outlet was so bright that it was possible to take an image every 1/30 s at the optimal focusing distance (60 cm) using a commercial digital camera. Peaks obtained using a flow injection analysis (FIA) system with the micro-scale detection window and OD4MI CL detection show excellent resolution and reproducibility without any band-broadening observed in analytical devices having additional reaction channel(s) to measure light generated from slow CL reaction. Maximum height (H(max)) and area (A) of peak, reproducibility and sensitivity observed in the FIA system with the microfluidic device and OD4MI CL detection depends on (1) the mole ratio between bis(2,4,6-trichlorophenyl) oxalate and 4-methyl imidazole yielding OD4MI, (2) the flow rate to mix OD4MI, H(2)O(2) and 1-AP in the detection window of the microfluidic device, and (3) H(2)O(2) concentration. We obtained linear calibration curves with wide dynamic ranges using H(max) and A. The detection limit of 1-AP determined with H(max) and A was as low as 0.05 fmole/injection (signal/background=3.0). PMID:19269463

  17. 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

  18. 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. PMID:24816615

  19. 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.

  20. 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.

  1. 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.

  2. 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. PMID:23774994

  3. 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

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

    PubMed

    Bai, Jing; Tu, Ting-Yuan; Kim, Choong; Thiery, Jean Paul; Kamm, Roger D

    2015-11-01

    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

  5. 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

  6. 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. PMID:26696441

  7. Thermal Measurement Techniques in Analytical Microfluidic Devices.

    PubMed

    Davaji, Benyamin; Lee, Chung Hoon

    2015-01-01

    Thermal measurement techniques have been used for many applications such as thermal characterization of materials and chemical reaction detection. Micromachining techniques allow reduction of the thermal mass of fabricated structures and introduce the possibility to perform high sensitivity thermal measurements in the micro-scale and nano-scale devices. Combining thermal measurement techniques with microfluidic devices allows performing different analytical measurements with low sample consumption and reduced measurement time by integrating the miniaturized system on a single chip. The procedures of thermal measurement techniques for particle detection, material characterization, and chemical detection are introduced in this paper. PMID:26066563

  8. 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

  9. 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. PMID:22740459

  10. 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”.

  11. In situ patterned micro 3D liver constructs for parallel toxicology testing in a fluidic device.

    PubMed

    Skardal, Aleksander; Devarasetty, Mahesh; Soker, Shay; Hall, Adam R

    2015-09-01

    3D tissue models are increasingly being implemented for drug and toxicology testing. However, the creation of tissue-engineered constructs for this purpose often relies on complex biofabrication techniques that are time consuming, expensive, and difficult to scale up. Here, we describe a strategy for realizing multiple tissue constructs in a parallel microfluidic platform using an approach that is simple and can be easily scaled for high-throughput formats. Liver cells mixed with a UV-crosslinkable hydrogel solution are introduced into parallel channels of a sealed microfluidic device and photopatterned to produce stable tissue constructs in situ. The remaining uncrosslinked material is washed away, leaving the structures in place. By using a hydrogel that specifically mimics the properties of the natural extracellular matrix, we closely emulate native tissue, resulting in constructs that remain stable and functional in the device during a 7-day culture time course under recirculating media flow. As proof of principle for toxicology analysis, we expose the constructs to ethyl alcohol (0-500 mM) and show that the cell viability and the secretion of urea and albumin decrease with increasing alcohol exposure, while markers for cell damage increase. PMID:26355538

  12. Particle motion past cylindrical flow-obstacles in microfluidic devices

    NASA Astrophysics Data System (ADS)

    Mustin, Benjamin; Drazer, German; Stoeber, Boris

    2011-11-01

    A microfluidic device has been developed for the systematic investigation of particle trajectories near micro-flow obstacles. The device incorporates a 3D stream-focusing concept that focuses a micro-particle suspension into a thin stream by means of four sheath flows before sending it towards an obstacle. Stream focusing is used to control the initial position of each particle in the unidirectional flow field upstream of the obstacle. Two types of obstacles often met in practice are considered in this work: a single cylinder and a pair of cylinders in a straight micro-channel. The particle trajectories are observed with a high-speed camera connected to an inverted epi-fluorescence microscope. The motion of non-Brownian polystyrene particles near the obstacles is investigated for different initial particle positions, particle sizes and obstacle configurations. For a given initial position, the role of the particle velocity is investigated by performing experiments at different flow rates.

  13. PCR microfluidic devices for DNA amplification.

    PubMed

    Zhang, Chunsun; Xu, Jinliang; Ma, Wenli; Zheng, Wenling

    2006-01-01

    The miniaturization of biological and chemical analytical devices by micro-electro-mechanical-systems (MEMS) technology has posed a vital influence on such fields as medical diagnostics, microbial detection and other bio-analysis. Among many miniaturized analytical devices, the polymerase chain reaction (PCR) microchip/microdevices are studied extensively, and thus great progress has been made on aspects of on-chip micromachining (fabrication, bonding and sealing), choice of substrate materials, surface chemistry and architecture of reaction vessel, handling of necessary sample fluid, controlling of three or two-step temperature thermocycling, detection of amplified nucleic acid products, integration with other analytical functional units such as sample preparation, capillary electrophoresis (CE), DNA microarray hybridization, etc. However, little has been done on the review of above-mentioned facets of the PCR microchips/microdevices including the two formats of flow-through and stationary chamber in spite of several earlier reviews [Zorbas, H. Miniature continuous-flow polymerase chain reaction: a breakthrough? Angew Chem Int Ed 1999; 38 (8):1055-1058; Krishnan, M., Namasivayam, V., Lin, R., Pal, R., Burns, M.A. Microfabricated reaction and separation systems. Curr Opin Biotechnol 2001; 12:92-98; Schneegabeta, I., Köhler, J.M. Flow-through polymerase chain reactions in chip themocyclers. Rev Mol Biotechnol 2001; 82:101-121; deMello, A.J. DNA amplification: does 'small' really mean 'efficient'? Lab Chip 2001; 1: 24N-29N; Mariella, Jr. R. MEMS for bio-assays. Biomed Microdevices 2002; 4 (2):77-87; deMello AJ. Microfluidics: DNA amplification moves on. Nature 2003; 422:28-29; Kricka, L.J., Wilding, P. Microchip PCR. Anal BioAnal Chem 2003; 377:820-825]. In this review, we survey the advances of the above aspects among the PCR microfluidic devices in detail. Finally, we also illuminate the potential and practical applications of PCR microfluidics to some fields such

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

    PubMed

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

    2014-04-01

    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

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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. PMID:25231706

  20. Method for forming polymerized microfluidic devices

    SciTech Connect

    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.

  1. Solvent-resistant elastomeric microfluidic devices and applications

    NASA Astrophysics Data System (ADS)

    van Dam, Robert Michael

    Microfluidics is increasingly being used in many areas of biotechnology and chemistry to achieve reduced reagent volumes, improved performance, integration, and parallelism, among other advantages. Though early devices were based on rigid materials such as glass and silicon, elastomeric materials such as polydiznethylsiloxane (PDMS) are rapidly emerging as a ubiquitous platform for applications in biotechnology. This is due, in part, to simpler fabrication procedures and to the ability to integrate mechanical microvalves at vastly greater densities. For many applications in the areas of chemical synthesis and analysis, however, PDMS cannot replace glass and silicon due to its incompatibility with many solvents and reagents. Such areas could benefit tremendously from the development of an elastomeric microfluidic device technology that combines the advantages of PDMS with the property of solvent resistance. Simplified fabrication could increase the accessibility of microfluidics, and the possibility of dense valve integration could lead to significant advances in device sophistication. Applications could be more rapidly developed by design re-use due to the independence of mechanical valves on fluid properties (unlike electrokinetic pumping), and the property of permeability could enable novel fluidic functions for accessing a broader range of reactions than is possible in glass and silicon. The first half of this thesis describes our strategies and efforts to develop this new enabling technology. Several approaches are presented in Chapter 3, and two particularly successful ones, based on new elastomers (FNB and PFPE), are described in Chapters 4 and 5. Chapter 6 describes a novel method of fabricating devices from 3D molds that could expand the range of useful clastomers. The second half of this thesis discusses microfluidic combinatorial synthesis and high throughput screening-applications that take particular advantage of the ability to integrate thousands of

  2. Development of a 3D graphene electrode dielectrophoretic device.

    PubMed

    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

  3. 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

  4. 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.

  5. Non-linear electrohydrodynamics in microfluidic devices.

    PubMed

    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

  6. 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

  7. 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

  8. 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

  9. Three-dimensional, paper-based microfluidic devices containing internal timers for running time-based diagnostic assays.

    PubMed

    Phillips, Scott T; Thom, Nicole K

    2013-01-01

    This chapter describes a method for fabricating three-dimensional (3D), paper-based microfluidic devices that contain internal timers for running quantitative, time-based assays. The method involves patterning microfluidic channels into paper, and cutting double-sided adhesive tape into defined patterns. Patterned paper and tape are assembled layer by layer to create 3D microfluidic devices that are capable of distributing microliter volumes of a sample into multiple regions on a device for conducting multiple assays simultaneously. Paraffin wax is incorporated into defined regions within the device to provide control over the distribution rate of a sample, and food coloring is included in defined regions within the device to provide an unambiguous readout when the sample has reached the bottom of the device (this latter feature is the endpoint of the timer). PMID:23329444

  10. Physicochemical regulation of endothelial sprouting in a 3D microfluidic angiogenesis model.

    PubMed

    Verbridge, Scott S; Chakrabarti, Anirikh; DelNero, Peter; Kwee, Brian; Varner, Jeffrey D; Stroock, Abraham D; Fischbach, Claudia

    2013-10-01

    Both physiological and pathological tissue remodeling (e.g., during wound healing and cancer, respectively) require new blood vessel formation via angiogenesis, but the underlying microenvironmental mechanisms remain poorly defined due in part to the lack of biologically relevant in vitro models. Here, we present a biomaterials-based microfluidic 3D platform for analysis of endothelial sprouting in response to morphogen gradients. This system consists of three lithographically defined channels embedded in type I collagen hydrogels. A central channel is coated with endothelial cells, and two parallel side channels serve as a source and a sink for the steady-state generation of biochemical gradients. Gradients of vascular endothelial growth factor (VEGF) promoted sprouting, whereby endothelial cell responsiveness was markedly dependent on cell density and vessel geometry regardless of treatment conditions. These results point toward mechanical and/or autocrine mechanisms that may overwhelm pro-angiogenic paracrine signaling under certain conditions. To date, neither geometrical effects nor cell density have been considered critical determinants of angiogenesis in health and disease. This biomimetic vessel platform demonstrated utility for delineating hitherto underappreciated contributors of angiogenesis, and future studies may enable important new mechanistic insights that will inform anti-angiogenic cancer therapy. PMID:23559519

  11. Study of a 3D DEP-based microfluidic system for selective nanoparticle manipulation

    NASA Astrophysics Data System (ADS)

    Lungu, M.; Balasiu, S.; Bunoiu, M. O.; Neculae, A.

    2014-11-01

    Manipulation of nanoparticle using dielectrophoresis (DEP) is an emerging technique to separate particles solely according to their dielectric properties and size, used in different forms to control the position, their orientation and velocity, to filtrate chemical compounds contained in the gas resulting from combustion processes, etc. This contribution presents the results of a simulation study which aims to characterize the functionality of a 3D DEP-based microsystem for the selective manipulation of nanometric particles. The use of 3D geometry of the device represents an important improvement in the description of the behavior of a nanoparticle suspension subjected to dielectrophoretic forces. The numerical solutions of the electric potential, electric field, DEP force and particle concentration distribution for a typical interdigitated electrodes array are calculated using the COMSOL Multiphysics finite element solver. The presented results demonstrate that dielectrophoresis can be successfully used for the manipulation of nanometric particles and give important information for the optimization of the experimental setup.

  12. 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.

  13. 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

  14. Patient-specific 3D microfluidic tissue model for multiple myeloma.

    PubMed

    Zhang, Wenting; Lee, Woo Y; Siegel, David S; Tolias, Peter; Zilberberg, Jenny

    2014-08-01

    In vitro culturing of primary multiple myeloma cells (MMC) has been a major challenge as this plasma cell malignancy depends on the bone marrow environment for its survival. Using a microfluidic platform to emulate the dynamic physiology of the bone marrow microenvironment, we report here a new approach for culturing difficult to preserve primary human MMC. The system uses a three-dimensional ossified tissue to mimic the tumor niche and recapitulate interactions between bone marrow cells and osteoblasts (OSB). To this end, the human fetal OSB cell line hFOB 1.19 was cultured in an eight-chamber microfluidic culture device to facilitate the seeding of mononuclear cells from bone marrow aspirates from three multiple myeloma patients. Optical microscopy, used for real-time monitoring of mononuclear cell interactions with the ossified tissue, confirmed that these are drawn toward the OSB layer. After 3 weeks, cocultures were characterized by flow cytometry to evaluate the amount of expansion of primary MMC (with CD138(+) and CD38(+)CD56(+) phenotypes) in this system. For each of the three patients analyzed, bone marrow mononuclear cells underwent, on an average, 2 to 5 expansions; CD38(+)CD56(+) cells underwent 1 to 3 expansions and CD138(+) cells underwent 2.5 to 4.6 expansions. This approach is expected to provide a new avenue that can facilitate: (1) testing of personalized therapeutics for multiple myeloma patients; (2) evaluation of new drugs without the need for costly animal models; and (3) studying the biology of multiple myeloma, and in particular, the mechanisms responsible for drug resistance and relapse. PMID:24294886

  15. 3D microfluidic chips with integrated functional microelements fabricated by a femtosecond laser for studying the gliding mechanism of cyanobacteria.

    PubMed

    Hanada, Yasutaka; Sugioka, Koji; Shihira-Ishikawa, Ikuko; Kawano, Hiroyuki; Miyawaki, Atsushi; Midorikawa, Katsumi

    2011-06-21

    Phormidium, a genus of filamentous cyanobacteria, forms endosymbiotic associations with seedling roots that accelerate the growth of the vegetable seedlings. Understanding the gliding mechanism of Phormidium will facilitate improved formation of this association and increased vegetable production. To observe the gliding movements, we fabricated various microfluidic chips termed nanoaquariums using a femtosecond (fs) laser. Direct fs laser writing, followed by annealing and successive wet etching in dilute hydrofluoric acid solution, can easily produce three-dimensional (3D) microfluidics with different structures embedded in a photostructurable glass. Using the fs laser, optical waveguides and filters were integrated with the microfluidic structures in the microchips, allowing the gliding mechanism to be more easily clarified. Using this apparatus, we found that CO(2) secreted from the seedling root attracts Phormidium in the presence of light, and determined the light intensity and specific wavelength necessary for gliding. PMID:21562650

  16. Passive Microfluidic device for Sub Millisecond Mixing

    PubMed Central

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

    2009-01-01

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

  17. Intrinsic FGF2 and FGF5 promotes angiogenesis of human aortic endothelial cells in 3D microfluidic angiogenesis system

    PubMed Central

    Seo, Ha-Rim; Jeong, Hyo Eun; Joo, Hyung Joon; Choi, Seung-Cheol; Park, Chi-Yeon; Kim, Jong-Ho; Choi, Ji-Hyun; Cui, Long-Hui; Hong, Soon Jun; Chung, Seok; Lim, Do-Sun

    2016-01-01

    The human body contains different endothelial cell types and differences in their angiogenic potential are poorly understood. We compared the functional angiogenic ability of human aortic endothelial cells (HAECs) and human umbilical vein endothelial cells (HUVECs) using a three-dimensional (3D) microfluidic cell culture system. HAECs and HUVECs exhibited similar cellular characteristics in a 2D culture system; however, in the 3D microfluidic angiogenesis system, HAECs exhibited stronger angiogenic potential than HUVECs. Interestingly, the expression level of fibroblast growth factor (FGF)2 and FGF5 under vascular endothelial growth factor (VEGF)-A stimulation was significantly higher in HAECs than in HUVECs. Moreover, small interfering RNA-mediated knockdown of FGF2 and FGF5 more significantly attenuated vascular sprouting induced from HAECs than HUVECs. Our results suggest that HAECs have greater angiogenic potential through FGF2 and FGF5 upregulation and could be a compatible endothelial cell type to achieve robust angiogenesis. PMID:27357248

  18. Intrinsic FGF2 and FGF5 promotes angiogenesis of human aortic endothelial cells in 3D microfluidic angiogenesis system.

    PubMed

    Seo, Ha-Rim; Jeong, Hyo Eun; Joo, Hyung Joon; Choi, Seung-Cheol; Park, Chi-Yeon; Kim, Jong-Ho; Choi, Ji-Hyun; Cui, Long-Hui; Hong, Soon Jun; Chung, Seok; Lim, Do-Sun

    2016-01-01

    The human body contains different endothelial cell types and differences in their angiogenic potential are poorly understood. We compared the functional angiogenic ability of human aortic endothelial cells (HAECs) and human umbilical vein endothelial cells (HUVECs) using a three-dimensional (3D) microfluidic cell culture system. HAECs and HUVECs exhibited similar cellular characteristics in a 2D culture system; however, in the 3D microfluidic angiogenesis system, HAECs exhibited stronger angiogenic potential than HUVECs. Interestingly, the expression level of fibroblast growth factor (FGF)2 and FGF5 under vascular endothelial growth factor (VEGF)-A stimulation was significantly higher in HAECs than in HUVECs. Moreover, small interfering RNA-mediated knockdown of FGF2 and FGF5 more significantly attenuated vascular sprouting induced from HAECs than HUVECs. Our results suggest that HAECs have greater angiogenic potential through FGF2 and FGF5 upregulation and could be a compatible endothelial cell type to achieve robust angiogenesis. PMID:27357248

  19. 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

  20. 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

    2012-01-01

    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. PMID:22089026

  1. One-Step Microfluidic Generation of Pre-Hatching Embryo-Like Core-Shell Microcapsules for Miniaturized 3D Culture of Pluripotent Stem Cells

    PubMed Central

    Agarwal, Pranay; Zhao, Shuting; Bielecki, Peter; Rao, Wei; Choi, Jung K.; Zhao, Yi; Yu, Jianhua; Zhang, Wujie; He, Xiaoming

    2013-01-01

    A novel core-shell microcapsule system is developed in this study to mimic the miniaturized 3D architecture of pre-hatching embryos with an aqueous liquid core of embryonic cells and a hydrogel-shell of zona pellucida. This is done by microfabricating a non-planar microfluidic flow-focusing device that enables one-step generation of microcapsules with an alginate hydrogel shell and an aqueous liquid core of cells from two aqueous fluids. Mouse embryonic stem (ES) cells encapsulated in the liquid core are found to survive well (> 92 %). Moreover, ~ 20 ES cells in the core can proliferate to form a single ES cell aggregate in each microcapsule within 7 days while at least a few hundred cells are usually needed by the commonly used hanging-drop method to form an embryoid body (EB) in each hanging drop. Quantitative RT-PCR analyses show significantly higher expression of pluripotency marker genes in the 3D aggregated ES cells compared to the cells under 2D culture. The aggregated ES cells can be efficiently differentiated into beating cardiomyocytes using a small molecule (cardiogenol C) without complex combination of multiple growth factors. Taken together, the novel 3D microfluidic and pre-hatching embryo-like microcapsule systems are of importance to facilitate in vitro culture of pluripotent stem cells for their ever-increasing use in modern cell-based medicine. PMID:24113543

  2. 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. PMID:23921454

  3. 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. PMID:25801423

  4. Electrochemical sensing in paper-based microfluidic devices.

    PubMed

    Nie, Zhihong; Nijhuis, Christian A; Gong, Jinlong; Chen, Xin; Kumachev, Alexander; Martinez, Andres W; Narovlyansky, Max; Whitesides, George M

    2010-02-21

    This paper describes the fabrication and the performance of microfluidic paper-based electrochemical sensing devices (we call the microfluidic paper-based electrochemical devices, microPEDs). The microPEDs comprise paper-based microfluidic channels patterned by photolithography or wax printing, and electrodes screen-printed from conducting inks (e.g., carbon or Ag/AgCl). We demonstrated that the microPEDs are capable of quantifying the concentrations of various analytes (e.g., heavy-metal ions and glucose) in aqueous solutions. This low-cost analytical device should be useful for applications in public health, environmental monitoring, and the developing world. PMID:20126688

  5. A microfluidic device for uniform-sized cell spheroids formation, culture, harvesting and flow cytometry analysis.

    PubMed

    Patra, Bishnubrata; Chen, Ying-Hua; Peng, Chien-Chung; Lin, Shiang-Chi; Lee, Chau-Hwang; Tung, Yi-Chung

    2013-01-01

    Culture of cells as three-dimensional (3D) aggregates, named spheroids, possesses great potential to improve in vitro cell models for basic biomedical research. However, such cell spheroid models are often complicated, cumbersome, and expensive compared to conventional Petri-dish cell cultures. In this work, we developed a simple microfluidic device for cell spheroid formation, culture, and harvesting. Using this device, cells could form uniformly sized spheroids due to strong cell-cell interactions and the spatial confinement of microfluidic culture chambers. We demonstrated cell spheroid formation and culture in the designed devices using embryonic stem cells, carcinoma cells, and fibroblasts. We further scaled up the device capable of simultaneously forming and culturing 5000 spheroids in a single chip. Finally, we demonstrated harvesting of the cultured spheroids from the device with a simple setup. The harvested spheroids possess great integrity, and the cells can be exploited for further flow cytometry assays due to the ample cell numbers. PMID:24396525

  6. 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. PMID:27273436

  7. 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

  8. 3D spherical microtissues and microfluidic technology for multi-tissue experiments and analysis.

    PubMed

    Kim, Jin-Young; Fluri, David A; Marchan, Rosemarie; Boonen, Kurt; Mohanty, Soumyaranjan; Singh, Prateek; Hammad, Seddik; Landuyt, Bart; Hengstler, Jan G; Kelm, Jens M; Hierlemann, Andreas; Frey, Olivier

    2015-07-10

    Rational development of more physiologic in vitro models includes the design of robust and flexible 3D-microtissue-based multi-tissue devices, which allow for tissue-tissue interactions. The developed device consists of multiple microchambers interconnected by microchannels. Pre-formed spherical microtissues are loaded into the microchambers and cultured under continuous perfusion. Gravity-driven flow is generated from on-chip reservoirs through automated chip-tilting without any need for additional tubing and external pumps. This tilting concept allows for operating up to 48 devices in parallel in order to test various drug concentrations with a sufficient number of replicates. For a proof of concept, rat liver and colorectal tumor microtissues were interconnected on the chip and cultured during 8 days in the presence of the pro-drug cyclophosphamide. Cyclophosphamide has a significant impact on tumor growth but only after bio-activation by the liver. This effect was only observed in the perfused and interconnected co-cultures of different microtissue types on-chip, whereas the discontinuous transfer of supernatant via pipetting from static liver microtissues that have been treated with cyclophosphamide did not significantly affect tumor growth. The results indicate the utility and multi-tissue functionality of this platform. The importance of continuous medium circulation and tissue interaction is highlighted. PMID:25592049

  9. Fabrication of gravity-driven microfluidic device

    NASA Astrophysics Data System (ADS)

    Yamada, H.; Yoshida, Y.; Terada, N.; Hagihara, S.; Komatsu, T.; Terasawa, A.

    2008-12-01

    We have studied the micro total analysis system as a blood test. A microfluidic device with a three-pronged microchannel and artificial capillary vessels was fabricated. The microchannel is to transport blood, focus blood cells, and line them up. The vessels are to observe red blood cell deformation. An excimer laser was used to form grooves and so on. Numbers of thermosetting resin film and fluororesin were piled up on a cover glass. A laser fabricated part of the channel at the each film every lamination, and then a three-dimensional structure microchannel was fabricated. The channel sizes have widths of 50-150 μm and depths of 45 μm. Through holes used as artificial capillary vessels are made in the fluororesin having a minimum diameter of 5 μm and a length of 100 μm. As blood and a physiological saline are injected into the microchannel, the device stands upward facing the channel, and blood cells go into the vessels by the force of gravity and sheath flow of the saline. By gravity various groove patterns were made changing the width and length for measurement of blood focusing. Moreover, the red blood cell deformation was observed in the vessels with a microscope.

  10. Cell loss in integrated microfluidic device.

    PubMed

    Zhu, Liang; Peh, Xue Li; Ji, Hong Miao; Teo, Cheng Yong; Feng, Han Hua; Liu, Wen-Tso

    2007-10-01

    Cell loss during sample transporting from macro-components to micro-components in integrated microfluidic devices can considerably deteriorate cell detection sensitivity. This intrinsic cell loss was studied and effectively minimized through (a) increasing the tubing diameter connecting the sample storage and the micro-device, (b) applying a hydrodynamic focusing approach for sample delivering to reduce cells contacting and adhesion on the walls of micro-channel and chip inlet; (c) optimizing the filter design with a zigzag arrangement of pillars (13 microm in chamber depth and 0.8 microm in gap) to prolong the effective filter length, and iv) the use of diamond shaped pillar instead of normally used rectangular shape to reduce the gap length between any two given pillar (i.e. pressure drop) at the filter region. Cell trapping and immunofluorescent detection of 12 Giardia lamblia and 12 Cryptosporidium parvum cells in 150 microl solution and 50 MCF-7 breast cancer cells in 150 microl solution was completed within 15 min with trapping efficiencies improved from 79+/-11%, 50.8+/-5.5% and 41.3+/-3.6% without hydrodynamic focusing, respectively, to 90.8+/-5.8%, 89.8+/-16.6% and 77.0+/-9.2% with hydrodynamic focusing. PMID:17541747

  11. 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.

  12. 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

  13. Use of Vacuum Bagging for Fabricating Thermoplastic Microfluidic Devices

    PubMed Central

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

    2014-01-01

    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. PMID:25329244

  14. High-performance UV-curable epoxy resin-based microarray and microfluidic immunoassay devices.

    PubMed

    Yu, Ling; Liu, Yingshuai; Gan, Ye; Li, Chang Ming

    2009-06-15

    Immunoassay devices including microarray and microfluidic systems were fabricated with an UV-curable resin by a new economic approach, which can not only simply produce a 3-dimensional (3D) patterned structure, but also simultaneously introduce functional epoxide groups for efficient protein immobilization. The performance of the epoxy resin-based microarray was improved by optimization of printing buffer, probe concentration, and immobilization time, showing a detection dynamic range of 5 orders of magnitude and a limit of detection (LOD) of 10 pg mL(-1) for immunoglobulin G (IgG). The developed microfluidic immunoassay device demonstrates a LOD of 100 pg mL(-1) for IL-5 detection. The device can also be used to colorimetrically detect proteins via naked human eyes for immunoassays. This work provides a simple and inexpensive method to fabricate a sensitive immunoassay device, especially a 3D microfluidic system, which has great potential to develop a portable immunoassay device via human eye detection for point-of-care service and/or high throughput screening of infectious diseases. PMID:19346122

  15. 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.

  16. Monitoring time course of human whole blood coagulation using a microfluidic dielectric sensor with a 3D capacitive structure.

    PubMed

    Maji, Debnath; Suster, Michael A; Stavrou, Evi; Gurkan, Umut A; Mohseni, Pedram

    2015-08-01

    This paper reports on the design, fabrication, and testing of a microfluidic sensor for dielectric spectroscopy (DS) of human whole blood during coagulation. The sensor employs a three-dimensional (3D), parallel-plate, capacitive sensing structure with a floating electrode integrated into a microfluidic channel. Using an impedance analyzer and after a 5-point calibration, the sensor is shown to measure the real part of complex relative dielectric permittivity of human whole blood in a frequency range of 10kHz to 100MHz. The temporal variation of dielectric permittivity at 1MHz for human whole blood from three different healthy donors shows a peak in permittivity at ~ 4 to 5 minutes, which also corresponds to the onset of CaCl2-initiated coagulation of the blood sample verified visually. PMID:26737635

  17. Preparation and 3D Tracking of Catalytic Swimming Devices.

    PubMed

    Campbell, Andrew; Archer, Richard; Ebbens, Stephen

    2016-01-01

    We report a method to prepare catalytically active Janus colloids that "swim" in fluids and describe how to determine their 3D motion using fluorescence microscopy. One commonly deployed method for catalytically active colloids to produce enhanced motion is via an asymmetrical distribution of catalyst. Here this is achieved by spin coating a dispersed layer of fluorescent polymeric colloids onto a flat planar substrate, and then using directional platinum vapor deposition to half coat the exposed colloid surface, making a two faced "Janus" structure. The Janus colloids are then re-suspended from the planar substrate into an aqueous solution containing hydrogen peroxide. Hydrogen peroxide serves as a fuel for the platinum catalyst, which is decomposed into water and oxygen, but only on one side of the colloid. The asymmetry results in gradients that produce enhanced motion, or "swimming". A fluorescence microscope, together with a video camera is used to record the motion of individual colloids. The center of the fluorescent emission is found using image analysis to provide an x and y coordinate for each frame of the video. While keeping the microscope focal position fixed, the fluorescence emission from the colloid produces a characteristic concentric ring pattern which is subject to image analysis to determine the particles relative z position. In this way 3D trajectories for the swimming colloid are obtained, allowing swimming velocity to be accurately measured, and physical phenomena such as gravitaxis, which may bias the colloids motion to be detected. PMID:27404327

  18. 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.

  19. 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. PMID:26842949

  20. 3-D Coldtest Simulations of W-Band Devices

    NASA Astrophysics Data System (ADS)

    Petillo, John J.

    1998-04-01

    Recent advances in the simulation and modeling of vacuum electronic devices has opened up the door for the much-anticipated ``first-pass design success" of these devices by computational means. For W-band, this is an exciting prospect since many current designs begin with scaling from lower-frequency devices. The next step is trial and error by fabrication and experimental testing, which demands high precision machining practices as well as reproducible assembly procedures. This can be a very time-consuming, expensive, and error-prone undertaking. Aside from the unit-to-unit variances in dimensions between prototypes, the repeatability of material properties (e.g., dielectric constant and resistivity) in this frequency band is difficult to measure, predict, and ensure. Computers have no such repeatability problems, and run-to-run differences can be predefined, and subsequently analyzed. The computational limitations include setup difficulty, computer time, computer power, and fidelity of the calculation. For W-band devices with 1% or lower bandwidth, fidelity of the numerical solution is critical in the search for ``first-pass design success" capability. The codes have to not only be up to the task, but the appropriate application of these codes becomes an essential ingredient to predicting the accuracy of the results. These issues as well as cross validation between computational models will be discussed. Several recent simulation results of W-band devices will be presented, along with comparisons with data. These will include the NRL/Litton/CPI gyroklystron input coupler and several CPI Coupled Cavity Tube designs.

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

    PubMed

    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

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

    PubMed

    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

  3. 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

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

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

    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.

  5. SIERRA - A 3-D device simulator for reliability modeling

    NASA Astrophysics Data System (ADS)

    Chern, Jue-Hsien; Arledge, Lawrence A., Jr.; Yang, Ping; Maeda, John T.

    1989-05-01

    SIERRA is a three-dimensional general-purpose semiconductor-device simulation program which serves as a foundation for investigating integrated-circuit (IC) device and reliability issues. This program solves the Poisson and continuity equations in silicon under dc, transient, and small-signal conditions. Executing on a vector/parallel minisupercomputer, SIERRA utilizes a matrix solver which uses an incomplete LU (ILU) preconditioned conjugate gradient square (CGS, BCG) method. The ILU-CGS method provides a good compromise between memory size and convergence rate. The authors have observed a 5x to 7x speedup over standard direct methods in simulations of transient problems containing highly coupled Poisson and continuity equations such as those found in reliability-oriented simulations. The application of SIERRA to parasitic CMOS latchup and dynamic random-access memory single-event-upset studies is described.

  6. Absolute 3D reconstruction of thin films topography in microfluidic channels by interference reflection microscopy.

    PubMed

    Huerre, A; Jullien, M-C; Theodoly, O; Valignat, M-P

    2016-03-01

    The travel of droplets, bubbles, vesicles, capsules, living cells or small organisms in microchannels is a hallmark in microfluidics applications. A full description of the dynamics of such objects requires a quantitative understanding of the complex hydrodynamic and interfacial interactions between objects and channel walls. In this paper, we present an interferometric method that allows absolute topographic reconstruction of the interspace between an object and channel walls for objects confined in microfluidic channels. Wide field microscopic imaging in reflection interference contrast mode (RICM) is directly performed at the bottom wall of microfluidic chips. Importantly, we show that the reflections at both the lower and upper surface of the microchannel have to be considered in the quantitative analysis of the optical signal. More precisely, the contribution of the reflection at the upper surface is weighted depending on the light coherence length and channel height. Using several wavelengths and illumination apertures, our method allows reconstructing the topography of thin films on channel walls in a range of 0-500 nm, with a precision as accurate as 2 nm for the thinnest films. A complete description of the protocol is exemplified for oil in water droplets travelling in channels of height 10-400 μm at a speed up to 5 mm s(-1). PMID:26830018

  7. 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. PMID:26368165

  8. Did ``Minority Report'' Get It Wrong? Superiority of the Mouse over 3D Input Devices in a 3D Placement Task

    NASA Astrophysics Data System (ADS)

    Bérard, François; Ip, Jessica; Benovoy, Mitchel; El-Shimy, Dalia; Blum, Jeffrey R.; Cooperstock, Jeremy R.

    Numerous devices have been invented with three or more degrees of freedom (DoF) to compensate for the assumed limitations of the 2 DoF mouse in the execution of 3D tasks. Nevertheless, the mouse remains the dominant input device in desktop 3D applications, which leads us to pose the following question: is the dominance of the mouse due simply to its widespread availability and long-term user habituation, or is the mouse, in fact, more suitable than dedicated 3D input devices to an important subset of 3D tasks? In the two studies reported in this paper, we measured performance efficiency of a group of subjects in accomplishing a 3D placement task and also observed physiological indicators through biosignal measurements. Subjects used both a standard 2D mouse and three other 3 DoF input devices. Much to our surprise, the standard 2D mouse outperformed the 3D input devices in both studies.

  9. Biomimetic microfluidic device for in vitro antihypertensive drug evaluation.

    PubMed

    Li, Lei; Lv, Xiaoqing; Ostrovidov, Serge; Shi, Xuetao; Zhang, Ning; Liu, Jing

    2014-07-01

    Microfluidic devices have emerged as revolutionary, novel platforms for in vitro drug evaluation. In this work, we developed a facile method for evaluating antihypertensive drugs using a microfluidic chip. This microfluidic chip was generated using the elastic material poly(dimethylsiloxane) (PDMS) and a microchannel structure that simulated a blood vessel as fabricated on the chip. We then cultured human umbilical vein endothelial cells (HUVECs) inside the channel. Different pressures and shear stresses could be applied on the cells. The generated vessel mimics can be used for evaluating the safety and effects of antihypertensive drugs. Here, we used hydralazine hydrochloride as a model drug. The results indicated that hydralazine hydrochloride effectively decreased the pressure-induced dysfunction of endothelial cells. This work demonstrates that our microfluidic system provides a convenient and cost-effective platform for studying cellular responses to drugs under mechanical pressure. PMID:24673554

  10. A microfluidic device for efficient chemical testing using Caenorhabditis elegans.

    PubMed

    Song, Pengfei; Zhang, Weize; Sobolevski, Alexandre; Bernard, Kristine; Hekimi, Siegfried; Liu, Xinyu

    2015-04-01

    The nematode worm Caenorhabditis elegans has been employed as a popular model organism in many fields of biological research. In this paper, we present a microfluidic device for facilitating chemical testing using C. elegans. For testing chemicals on chip, the device houses single nematodes in microfluidic chambers and precisely adjusts the chamber's chemical environment during experiments. Eight nematodes can be readily loaded into the chambers through separate loading channels in a quick and gentle manner. In addition, a custom-made software with a graphic user interface is also created for quantitative analysis of locomotion parameters (swimming frequency and bend amplitude) of the nematodes in response to chemical stimuli, thus greatly enhancing the efficiency of data collection. We perform proof-of-concept experiments using two chemicals, zinc ion (Zn(2+)) and glucose, to demonstrate the effectiveness of the microfluidic device. PMID:25744157

  11. 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

  12. Exploiting droplet formation in microfluidic devices to create functional particles

    NASA Astrophysics Data System (ADS)

    Nowak, Emilia; Simmons, Mark

    2014-11-01

    Microfluidic devices offer excellent capabilities for the formation of microstructured particles which have functional attributes e.g. in controlled delivery of pharmaceuticals, enhanced nutrition and flavours in food. In this work, a microfluidic device is employed to form microstructured particles in two steps: (i) by formation of single/double emulsions and (ii) solidification of the droplet by either gelation or solvent evaporation. Both may impart non-Newtonian properties to the component phases. The influence of phase flow rates (capillary number), surfactant type/concentration and the rheology of the component phases upon the particle formation and hydrodynamic behaviour are described. EPSRC Programme Grant, MEMPHIS, EP/K0039761/1.

  13. Virtual 3D interactive system with embedded multiwavelength optical sensor array and sequential devices

    NASA Astrophysics Data System (ADS)

    Wang, Guo-Zhen; Huang, Yi-Pai; Hu, Kuo-Jui

    2012-06-01

    We proposed a virtual 3D-touch system by bare finger, which can detect the 3-axis (x, y, z) information of finger. This system has multi-wavelength optical sensor array embedded on the backplane of TFT panel and sequentail devices on the border of TFT panel. We had developed reflecting mode which can be worked by bare finger for the 3D interaction. A 4-inch mobile 3D-LCD with this proposed system was successfully been demonstrated already.

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

    PubMed

    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

  15. 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. PMID:26192108

  16. 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.

  17. High-throughput rheology in a microfluidic device

    NASA Astrophysics Data System (ADS)

    Furst, Eric; Schultz, Kelly; Han, Hyejin; Kim, Chongyoup

    2011-11-01

    High-throughput rheological measurements in a microfluidic device are demonstrated. A series of microrheology samples is generated as droplets in an immiscible spacer fluid using a microfluidic T-junction. The compositions of the sample droplets are continuously varied over a wide range. Rheology measurements are made in each droplet using multiple particle tracking microrheology. We review critical design and operating parameters, including the droplet size, flow rates and rapid fabrication methods. Validation experiments are performed by measuring the solution viscosity of glycerine and the biopolymer heparin as a function of concentration. Finally, an analysis of droplet mixing is performed in order to optimize the device performance. Overall, the combination of microrheology with microfluidics maximizes the number of rheological measurements while simultaneously minimizing the sample preparation time and amount of material, and should be particularly suited to the characterization of scarce or expensive materials. We acknowledge financial support from the NSF (CBET-0730292).

  18. 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.

  19. Full 3D morphology of diatoms flowing in a microfluidic channel by digital holographic microscopy

    NASA Astrophysics Data System (ADS)

    Savoia, Roberto; Memmolo, Pasquale; Merola, Francesco; Miccio, Lisa; D'Ippolito, Giuliana; Fontana, Angelo; Ferraro, Pietro

    2015-07-01

    In this paper, we present a new approach for three-dimensional reconstruction and biovolume estimation of some species of diatoms. An optofluidic platform, composed by an optical tweezer and holographic modulus, is employed to retrieve several holograms at different angular positions, which are processed by the shape from silhouette algorithm to estimate the 3D shape of the cells.

  20. Recapitulation of in vivo-like paracrine signals of human mesenchymal stem cells for functional neuronal differentiation of human neural stem cells in a 3D microfluidic system.

    PubMed

    Yang, Kisuk; Park, Hyun-Ji; Han, Sewoon; Lee, Joan; Ko, Eunkyung; Kim, Jin; Lee, Jong Seung; Yu, Ji Hea; Song, Ki Yeong; Cheong, Eunji; Cho, Sung-Rae; Chung, Seok; Cho, Seung-Woo

    2015-09-01

    Paracrine signals produced from stem cells influence tissue regeneration by inducing the differentiation of endogenous stem or progenitor cells. However, many recent studies that have investigated paracrine signaling of stem cells have relied on either two-dimensional transwell systems or conditioned medium culture, neither of which provide optimal culture microenvironments for elucidating the effects of paracrine signals in vivo. In this study, we recapitulated in vivo-like paracrine signaling of human mesenchymal stem cells (hMSCs) to enhance functional neuronal differentiation of human neural stem cells (hNSCs) in three-dimensional (3D) extracellular matrices (ECMs) within a microfluidic array platform. In order to amplify paracrine signaling, hMSCs were genetically engineered using cationic polymer nanoparticles to overexpress glial cell-derived neurotrophic factor (GDNF). hNSCs were cultured in 3D ECM hydrogel used to fill central channels of the microfluidic device, while GDNF-overexpressing hMSCs (GDNF-hMSCs) were cultured in channels located on both sides of the central channel. This setup allowed for mimicking of paracrine signaling between genetically engineered hMSCs and endogenous hNSCs in the brain. Co-culture of hNSCs with GDNF-hMSCs in the 3D microfluidic system yielded reduced glial differentiation of hNSCs while significantly enhancing differentiation into neuronal cells including dopaminergic neurons. Neuronal cells produced from hNSCs differentiating in the presence of GDNF-hMSCs exhibited functional neuron-like electrophysiological features. The enhanced paracrine ability of GDNF-hMSCs was finally confirmed using an animal model of hypoxic-ischemic brain injury. This study demonstrates the presented 3D microfluidic array device can provide an efficient co-culture platform and provide an environment for paracrine signals from transplanted stem cells to control endogenous neuronal behaviors in vivo. PMID:26113074

  1. 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.

  2. 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. PMID:21293829

  3. 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. PMID:26243449

  4. 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.

  5. 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.

  6. Microcontact printing-based fabrication of digital microfluidic devices.

    PubMed

    Watson, Michael W L; Abdelgawad, Mohamed; Ye, George; Yonson, Neal; Trottier, Justin; Wheeler, Aaron R

    2006-11-15

    Digital microfluidics is a fluid manipulation technique in which discrete droplets are actuated on patterned arrays of electrodes. Although there is great enthusiasm for the application of this technique to chemical and biological assays, development has been hindered by the requirement of clean room fabrication facilities. Here, we present a new fabrication scheme, relying on microcontact printing (microCP), an inexpensive technique that does not require clean room facilities. In microCP, an elastomeric poly(dimethylsiloxane) stamp is used to deposit patterns of self-assembled monolayers onto a substrate. We report three different microCP-based fabrication techniques: (1) selective etching of gold-on-glass substrates; (2) direct printing of a suspension of palladium colloids; and (3) indirect trapping of gold colloids from suspension. In method 1, etched gold electrodes are used for droplet actuation; in methods 2 and 3, colloid patterns are used to seed electroless deposition of copper. We demonstrate, for the first time, that digital microfluidic devices can be formed by microCP and are capable of the full range of digital microfluidics operations: dispensing, merging, motion, and splitting. Devices formed by the most robust of the new techniques were comparable in performance to devices formed by conventional methods, at a fraction of the fabrication time. These new techniques for digital microfluidics device fabrication have the potential to facilitate expansion of this technology to any research group, even those without access to conventional microfabrication tools and facilities. PMID:17105183

  7. A microfluidic device for dry sample preservation in remote settings.

    PubMed

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

    2013-11-21

    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. PMID:24056744

  8. 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

  9. Magnetophoretic-based microfluidic device for DNA isolation

    PubMed Central

    Hale, C.; Darabi, J.

    2014-01-01

    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. PMID:25379103

  10. Flow control concepts for thread-based microfluidic devices

    PubMed Central

    Ballerini, David R.; Li, Xu; Shen, Wei

    2011-01-01

    The emerging concept of thread-based microfluidics has shown great promise for application to inexpensive disease detection and environmental monitoring. To allow the creation of more sophisticated and functional thread-based sensor designs, the ability to better control and understand the flow of fluids in the devices is required. To meet this end, various mechanisms for controlling the flow of reagents and samples in thread-based microfluidic devices are investigated in this study. A study of fluid penetration in single threads and in twined threads provides greater practical understanding of fluid velocity and ultimate penetration for the design of devices. “Switches” which control when or where flow can occur, or allow the mixing of multiple fluids, have been successfully prototyped from multifilament threads, plastic films, and household adhesive. This advancement allows the fabrication of more functional sensory devices which can incorporate more complex detection chemistries, while maintaining low production cost and simplicity of construction. PMID:21483659

  11. 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.

  12. A Sensitive Chemotaxis Assay Using a Novel Microfluidic Device

    PubMed Central

    Zhang, Chen; Jang, Sunyoung; Amadi, Ovid C.; Shimizu, Koichi; Lee, Richard T.; Mitchell, Richard N.

    2013-01-01

    Existing chemotaxis assays do not generate stable chemotactic gradients and thus—over time—functionally measure only nonspecific random motion (chemokinesis). In comparison, microfluidic technology has the capacity to generate a tightly controlled microenvironment that can be stably maintained for extended periods of time and is, therefore, amenable to adaptation for assaying chemotaxis. We describe here a novel microfluidic device for sensitive assay of cellular migration and show its application for evaluating the chemotaxis of smooth muscle cells in a chemokine gradient. PMID:24151597

  13. 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

  14. Mapping of Enzyme Kinetics on a Microfluidic Device.

    PubMed

    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

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

    PubMed

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

    2015-01-01

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

  16. 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

  17. 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.

  18. 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

  19. 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. PMID:25893395

  20. A Microfluidic Device for Multiplex Single-Nucleotide Polymorphism Genotyping

    PubMed Central

    Zhu, Jing; Qiu, Chunmei; Palla, Mirkó; Nguyen, ThaiHuu; Russo, James J.; Ju, Jingyue; Lin, Qiao

    2015-01-01

    Single-nucleotide polymorphisms (SNPs) are the most abundant type of genetic variations; they provide the genetic fingerprint of individuals and are essential for genetic biomarker discoveries. Accurate detection of SNPs is of great significance for disease prevention, diagnosis and prognosis, and for prediction of drug response and clinical outcomes in patients. Nevertheless, conventional SNP genotyping methods are still limited by insufficient accuracy or labor-, time-, and resource-intensive procedures. Microfluidics has been increasingly utilized to improve efficiency; however, the currently available microfluidic genotyping systems still have shortcomings in accuracy, sensitivity, throughput and multiplexing capability. To address these challenges, we developed a multi-step SNP genotyping microfluidic device, which performs single-base extension of SNP specific primers and solid-phase purification of the extension products on a temperature-controlled chip. The products are ready for immediate detection by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), providing identification of the alleles at the target loci. The integrated device enables efficient and automated operation, while maintaining the high accuracy and sensitivity provided by MS. The multiplex genotyping capability was validated by performing rapid, accurate and simultaneous detection of 4 loci on a synthetic template. The microfluidic device has the potential to perform automatic, accurate, quantitative and high-throughput assays covering a broad spectrum of applications in biological and clinical research, drug development and forensics. PMID:26594354

  1. Optimization of device geometry in single-plate digital microfluidics

    NASA Astrophysics Data System (ADS)

    Abdelgawad, Mohamed; Park, Philip; Wheeler, Aaron R.

    2009-05-01

    Digital microfluidics is a popular tool for lab-on-a-chip applications and is typically implemented in one of two formats: single-plate ("open") devices or two-plate ("closed") devices. Single-plate devices have some advantages relative to the more common two-plate format such as faster mixing, the capacity to move larger volumes on a given footprint, and easier access to droplets for handling or optical detection. In contrast with the two-plate format, in which ground potential is generally supplied via a top electrode, in the single-plate format, many different geometries of ground wires/electrodes have been used. Until the present study, there has been no metric to determine which of these geometries is best suited for droplet actuation. Here, we present a combination of numerical simulations and experimental tests to compare six different single-plate designs. We applied finite element analysis, using the commercially available COMSOL software package to calculate the electrodynamic actuation forces in each of the different designs and used the results to optimize device design. Forces predicted by the electrodynamic model were in agreement with forces predicted using electromechanical models. More importantly, results were verified experimentally using a unique technique that permits indirect estimation of actuation forces on digital microfluidic devices. This work illustrates the promise of using numerical modeling to enhance the design and performance of digital microfluidic devices.

  2. Microfluidic device fabrication by thermoplastic hot-embossing.

    PubMed

    Yang, Shuang; Devoe, Don L

    2013-01-01

    Due to their low cost compatibility with replication-based fabrication methods, thermoplastics represent an exceptionally attractive family of materials for the fabrication of lab-on-a-chip platforms. A diverse range of thermoplastic materials suitable for microfluidic fabrication is available, offering a wide selection of mechanical and chemical properties that can be leveraged and further tailored for specific applications. While high-throughput embossing methods such as reel-to-reel processing of thermoplastics is an attractive method for industrial microfluidic chip production, the use of single chip hot embossing is a cost-effective technique for realizing high-quality microfluidic devices during the prototyping stage. Here we describe methods for the replication of microscale features in two thermoplastics, polymethylmethacrylate (PMMA) and polycarbonate (PC), using hot embossing from a silicon template fabricated by deep reactive-ion etching. PMID:23329439

  3. 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

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

    PubMed

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

    2014-09-01

    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

  5. A low resistance microfluidic system for the creation of stable concentration gradients in a defined 3D microenvironment

    PubMed Central

    Amadi, Ovid C.; Steinhauser, Matthew L.; Nishi, Yuichi; Chung, Seok; Kamm, Roger D.; McMahon, Andrew P.

    2011-01-01

    The advent of microfluidic technology allows control and interrogation of cell behavior by defining the local microenvironment with an assortment of biochemical and biophysical stimuli. Many approaches have been developed to create gradients of soluble factors, but the complexity of such systems or their inability to create defined and controllable chemical gradients has limited their widespread implementation. Here we describe a new microfluidic device which employs a parallel arrangement of wells and channels to create stable, linear concentration gradients in a gel region between a source and a sink well. Pressure gradients between the source and sink wells are dissipated through low resistance channels in parallel with the gel channel, thus minimizing the convection of solute in this region. We demonstrate the ability of the new device to quantitate chemotactic responses in a variety of cell types, yielding a complete profile of the migratory response and representing the total number of migrating cells and the distance each cell has migrated. Additionally we show the effect of concentration gradients of the morphogen Sonic hedgehog on the specification of differentiating neural progenitors in a 3-dimensional matrix. PMID:20661647

  6. A Microfluidic Device for Mixing of Capillary-Driven Liquids

    NASA Astrophysics Data System (ADS)

    Hosokawa, Kazuo; Maeda, Mizuo

    In this paper, a novel microfluidic device for mixing liquids is described. Main feature of this device is that the liquids are passively pumped through microchannels only by capillary action, and therefore no external power is required for the pumping. This feature brings extremely simple hardware setup and easy operation. In this device, a pneumatically-actuated, normally-closed microvalve regulates capillary-driven flow. The device has been fabricated with polydimethylsiloxane (PDMS) elastomer, and tested using fluorescent dye and fluorescent particle solutions. A simple method for controlling the mixing ratio is also demonstrated.

  7. 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. PMID:25925683

  8. 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

  9. 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.…

  10. 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.

  11. Microwave temperature measurement in microfluidic devices.

    PubMed

    Wong, David; Yesiloz, Gurkan; Boybay, Muhammed S; Ren, Carolyn L

    2016-06-21

    In spite of various existing thermometry methods for microfluidic applications, it remains challenging to measure the temperature of individual droplets in segmented flow since fast moving droplets do not allow sufficient exposure time demanded by both fluorescence based techniques and resistance temperature detectors. In this contribution, we present a microwave thermometry method that is non-intrusive and requires minimal external equipment. This technique relies on the correlation of fluid temperature with the resonance frequency of a microwave sensor that operates at a GHz frequency range. It is a remote yet direct sensing technique, eliminating the need for mixing fluorescent dyes with the working fluid. We demonstrated that the sensor operates reliably over multiple tests and is capable of both heating and sensing. It measures temperature to within ±1.2 °C accuracy and can detect the temperature of individual droplets. PMID:27199210

  12. Development of a biomimetic microfluidic oxygen transfer device.

    PubMed

    Gimbel, A A; Flores, E; Koo, A; García-Cardeña, G; Borenstein, J T

    2016-08-16

    Blood oxygenators provide crucial life support for patients suffering from respiratory failure, but their use is severely limited by the complex nature of the blood circuit and by complications including bleeding and clotting. We have fabricated and tested a multilayer microfluidic blood oxygenation prototype designed to have a lower blood prime volume and improved blood circulation relative to current hollow fiber cartridge oxygenators. Here we address processes for scaling the device toward clinically relevant oxygen transfer rates while maintaining a low prime volume of blood in the device, which is required for clinical applications in cardiopulmonary support and ultimately for chronic use. Approaches for scaling the device toward clinically relevant gas transfer rates, both by expanding the active surface area of the network of blood microchannels in a planar layer and by increasing the number of microfluidic layers stacked together in a three-dimensional device are addressed. In addition to reducing prime volume and enhancing gas transfer efficiency, the geometric properties of the microchannel networks are designed to increase device safety by providing a biomimetic and physiologically realistic flow path for the blood. Safety and hemocompatibility are also influenced by blood-surface interactions within the device. In order to further enhance device safety and hemocompatibility, we have demonstrated successful coating of the blood flow pathways with human endothelial cells, in order to confer the ability of the endothelium to inhibit coagulation and thrombus formation. Blood testing results provide confirmation of fibrin clot formation in non-endothelialized devices, while negligible clot formation was documented in cell-coated devices. Gas transfer testing demonstrates that the endothelial lining does not reduce the transfer efficiency relative to acellular devices. This process of scaling the microfluidic architecture and utilizing autologous cells to

  13. Recent developments in PDMS surface modification for microfluidic devices.

    PubMed

    Zhou, Jinwen; Ellis, Amanda Vera; Voelcker, Nicolas Hans

    2010-01-01

    PDMS is enjoying continued and ever increasing popularity as the material of choice for microfluidic devices due to its low cost, ease of fabrication, oxygen permeability and optical transparency. However, PDMS's hydrophobicity and fast hydrophobic recovery after surface hydrophilization, attributed to its low glass transition temperature of less than -120 degrees C, negatively impacts on the performance of PDMS-based microfluidic device components. This issue has spawned a flurry of research to devise longer lasting surface modifications of PDMS, with particular emphasis on microfluidic applications. This review will present recent research on surface modifications of PDMS using techniques ranging from metal layer coatings and layer-by-layer depositions to dynamic surfactant treatments and the adsorption of amphipathic proteins. We will also discuss significant advances that have been made with a broad palette of gas-phase processing methods including plasma processing, sol-gel coatings and chemical vapor deposition. Finally, we will present examples of applications and future prospects of modified PDMS surfaces in microfluidics, in areas such as molecular separations, cell culture in microchannels and biomolecular detection via immunoassays. PMID:20039289

  14. 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

  15. 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.

  16. Cell-free protein synthesis in microfluidic array devices.

    PubMed

    Mei, Qian; Fredrickson, Carl K; Simon, Andrew; Khnouf, Ruba; Fan, Z Hugh

    2007-01-01

    We report the development of a microfluidic array device for continuous-exchange, cell-free protein synthesis. The advantages of protein expression in the microfluidic array include (1) the potential to achieve high-throughput protein expression, matching the throughput of gene discovery; (2) more than 2 orders of magnitude reduction in reagent consumption, decreasing the cost of protein synthesis; and (3) the possibility to integrate with detection for rapid protein analysis, eliminating the need to harvest proteins. The device consists of an array of units, and each unit can be used for production of an individual protein. The unit comprises a tray chamber for in vitro protein expression and a well chamber as a nutrient reservoir. The tray is nested in the well, and they are separated by a dialysis membrane and connected through a microfluidic connection that provides a means to supply nutrients and remove the reaction byproducts. The device is demonstrated by synthesis of green fluorescent protein, chloramphenicol acetyl-transferase, and luciferase. Protein expression in the device lasts 5-10 times longer and the production yield is 13-22 times higher than in a microcentrifuge tube. In addition, we studied the effects of the operation temperature and hydrostatic flow on the protein production yield. PMID:17924644

  17. 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.

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

    SciTech Connect

    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.

  19. Magnetically driven solid sample preparation for centrifugal microfluidic devices.

    PubMed

    Duford, David A; Peng, Dan D; Salin, Eric D

    2009-06-01

    A prototype for solid sample preparation on centrifugal microfluidic devices has been designed and characterized. The system uses NdFeB magnets in both the centrifugal device and a fixed base. As the centrifugal device rotates, the magnets move and spin in their chambers creating a pulverizing mechanical motion. This technique was successfully applied to the dissolution of potassium ferricyanide (K(3)[Fe(CN)(6)]), a hard colored crystal. A 0.10 g sample was completely dissolved in 3 s in 1.0 mL of water while rotating at 1000 rpm. This is a 300-fold improvement over static dissolution. PMID:19422186

  20. 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.

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

    PubMed Central

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

    2011-01-01

    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. PMID:21799715

  2. Real-time detection of neurite outgrowth using microfluidic device

    NASA Astrophysics Data System (ADS)

    Kim, Samhwan; Jang, Jongmoon; Choi, Hongsoo; Moon, Cheil

    2013-05-01

    We developed a simple method for real-time detection of the neurite outgrowth using microfluidic device. Our microfluidic device contains three compartmentalized channels which are for cell seeding, hydrogel and growth factors. Collagen gel is filled in the middle channel and pheochromocytoma (PC12) cells are seeded in the left channel. To induce differentiation of PC12 cells, 50 ng/ml to1000 ng/ml of nerve growth factor (NGF) is introduced into the right channel. After three days of NGF treatment, PC12 cells begin to extend neurites and formed neurite network from sixth day. Quantification of neurite outgrowth is analyzed by measuring the total area of neurites. On sixth day, the area is doubled compared to the area on third day and increases by 20 times on ninth day.

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

    PubMed

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

    2014-06-01

    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. PMID:24722827

  4. 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.

  5. 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.

  6. 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

    2015-11-01

    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

  7. 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.

  8. 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

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

    SciTech Connect

    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.

  10. Study of Chemotaxis and Cell-Cell Interactions in Cancer with Microfluidic Devices.

    PubMed

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

    2016-01-01

    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

  11. 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

  12. 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.

  13. A Versatile Microfluidic Device for Automating Synthetic Biology.

    PubMed

    Shih, Steve C C; Goyal, Garima; Kim, Peter W; Koutsoubelis, Nicolas; Keasling, Jay D; Adams, Paul D; Hillson, Nathan J; Singh, Anup K

    2015-10-16

    New microbes are being engineered that contain the genetic circuitry, metabolic pathways, and other cellular functions required for a wide range of applications such as producing biofuels, biobased chemicals, and pharmaceuticals. Although currently available tools are useful in improving the synthetic biology process, further improvements in physical automation would help to lower the barrier of entry into this field. We present an innovative microfluidic platform for assembling DNA fragments with 10× lower volumes (compared to that of current microfluidic platforms) and with integrated region-specific temperature control and on-chip transformation. Integration of these steps minimizes the loss of reagents and products compared to that with conventional methods, which require multiple pipetting steps. For assembling DNA fragments, we implemented three commonly used DNA assembly protocols on our microfluidic device: Golden Gate assembly, Gibson assembly, and yeast assembly (i.e., TAR cloning, DNA Assembler). We demonstrate the utility of these methods by assembling two combinatorial libraries of 16 plasmids each. Each DNA plasmid is transformed into Escherichia coli or Saccharomyces cerevisiae using on-chip electroporation and further sequenced to verify the assembly. We anticipate that this platform will enable new research that can integrate this automated microfluidic platform to generate large combinatorial libraries of plasmids and will help to expedite the overall synthetic biology process. PMID:26075958

  14. Tunable microfluidic optical devices with an integrated microlens array

    NASA Astrophysics Data System (ADS)

    Hong, Kuang-Sheng; Wang, Jing; Sharonov, Alexey; Chandra, Dinesh; Aizenberg, Joanna; Yang, Shu

    2006-08-01

    Interest in dynamically tuning light has attracted great attention to the fabrication of tunable microlens arrays. Here we discuss the fabrication and characterization of a simple, robust, yet tunable microfluidic optical device with an integrated microlens array. The microfluidic device with a desired channel structure was micromachined on a polycarbonate plate with a resolution of up to 100 µm, followed by thermal bonding two plates above their glass transition temperature. The microlens arrays were replica molded on a glass slide, which was then attached to the polycarbonate plates. By simply actuating the liquids with variable refractive index into the fluidic channel to immerse the lens arrays without moving or deformation of microlenses, a large change of focal length of more than ten times (f = 0.74-8.53) was achieved. When a dye-containing liquid was pumped into the microfluidic channel to cover the lenses, the light transmission through the lenses was reduced from about 95% to 55% when the dye concentration was increased to 10 w/v%. The knowledge we gain from these studies will provide important insights to construct new, adaptive, micro-scale optical devices with multiple functionalities.

  15. Microwave dielectric heating of drops in microfluidic devices.

    PubMed

    Issadore, David; Humphry, Katherine J; Brown, Keith A; Sandberg, Lori; Weitz, David A; Westervelt, Robert M

    2009-06-21

    We present a technique to locally and rapidly heat water drops in microfluidic devices with microwave dielectric heating. Water absorbs microwave power more efficiently than polymers, glass, and oils due to its permanent molecular dipole moment that has large dielectric loss at GHz frequencies. The relevant heat capacity of the system is a single thermally isolated picolitre-scale drop of water, enabling very fast thermal cycling. We demonstrate microwave dielectric heating in a microfluidic device that integrates a flow-focusing drop maker, drop splitters, and metal electrodes to locally deliver microwave power from an inexpensive, commercially available 3.0 GHz source and amplifier. The temperature change of the drops is measured by observing the temperature dependent fluorescence intensity of cadmium selenide nanocrystals suspended in the water drops. We demonstrate characteristic heating times as short as 15 ms to steady-state temperature changes as large as 30 degrees C above the base temperature of the microfluidic device. Many common biological and chemical applications require rapid and local control of temperature and can benefit from this new technique. PMID:19495453

  16. 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.

  17. 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.

  18. Microfluidic paper-based devices for bioanalytical applications.

    PubMed

    Santhiago, Murilo; Nery, Emilia W; Santos, Glauco P; Kubota, Lauro T

    2014-01-01

    Paper has become increasingly recognized as a very interesting substrate for the construction of microfluidic devices, with potential application in a variety of areas, including health diagnosis, environmental monitoring, immunoassays and food safety. The aim of this review is to present a short history of analytical systems constructed from paper, summarize the main advantages and disadvantages of fabrication techniques, exploit alternative methods of detection such as colorimetric, electrochemical, photoelectrochemical, chemiluminescence and electrochemiluminescence, as well as to take a closer look at the novel achievements in the field of bioanalysis published during the last 2 years. Finally, the future trends for production of such devices are discussed. PMID:24341497

  19. 3D imaging LADAR with linear array devices: laser, detector and ROIC

    NASA Astrophysics Data System (ADS)

    Kameyama, Shumpei; Imaki, Masaharu; Tamagawa, Yasuhisa; Akino, Yosuke; Hirai, Akihito; Ishimura, Eitaro; Hirano, Yoshihito

    2009-07-01

    This paper introduces the recent development of 3D imaging LADAR (LAser Detection And Ranging) in Mitsubishi Electric Corporation. The system consists of in-house-made key devices which are linear array: the laser, the detector and the ROIC (Read-Out Integrated Circuit). The laser transmitter is the high power and compact planar waveguide array laser at the wavelength of 1.5 micron. The detector array consists of the low excess noise Avalanche Photo Diode (APD) using the InAlAs multiplication layer. The analog ROIC array, which is fabricated in the SiGe- BiCMOS process, includes the Trans-Impedance Amplifiers (TIA), the peak intensity detectors, the Time-Of-Flight (TOF) detectors, and the multiplexers for read-out. This device has the feature in its detection ability for the small signal by optimizing the peak intensity detection circuit. By combining these devices with the one dimensional fast scanner, the real-time 3D range image can be obtained. After the explanations about the key devices, some 3D imaging results are demonstrated using the single element key devices. The imaging using the developed array devices is planned in the near future.

  20. 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.

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

    SciTech Connect

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

    2011-11-10

    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.

  2. Inkjet printing of UV-curable adhesive and dielectric inks for microfluidic devices.

    PubMed

    Hamad, E M; Bilatto, S E R; Adly, N Y; Correa, D S; Wolfrum, B; Schöning, M J; Offenhäusser, A; Yakushenko, A

    2016-01-01

    Bonding of polymer-based microfluidics to polymer substrates still poses a challenge for Lab-On-a-Chip applications. Especially, when sensing elements are incorporated, patterned deposition of adhesives with curing at ambient conditions is required. Here, we demonstrate a fabrication method for fully printed microfluidic systems with sensing elements using inkjet and stereolithographic 3D-printing. PMID:26627046

  3. 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.

  4. 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. PMID:26899965

  5. Femtosecond laser-drilled capillary integrated into a microfluidic device

    SciTech Connect

    Kim, Tyson N.; Campbell, Kyle; Groisman, Alex; Kleinfeld, David; Schaffer, Chris B.

    2005-05-16

    Recent growth in microfluidic technology is, to a large extent, driven by soft lithography, a high-throughput fabrication technique where polymer materials, such as poly(dimethyl) siloxane (PDMS), are molded to form microscopic channel networks. Nevertheless, the channel architectures that can be obtained by molding are limited. We address this limitation by using femtosecond laser micromachining to add unmoldable features to the microfluidic devices. We apply laser ablation to drill microcapillaries, with diameters as small as 0.5 {mu}m and aspect ratios as high as 800:1, in the walls of molded PDMS channels. Finally, we use a laser-drilled microcapillary to trap a polystyrene bead by suction and hold it against a shear flow.

  6. Forward electrohydrodynamic inkjet printing of optical microlenses on microfluidic devices.

    PubMed

    Vespini, V; Coppola, S; Todino, M; Paturzo, M; Bianco, V; Grilli, S; Ferraro, P

    2016-01-21

    We report a novel method for direct printing of viscous polymers based on a pyro-electrohydrodynamic repulsion system capable of overcoming limitations on the material type, geometry and thickness of the receiving substrate. In fact, the results demonstrate that high viscosity polymers can be easily manipulated for optical functionalizing of lab-on-a-chip devices through demonstration of direct printing of polymer microlenses onto microfluidic chips and optical fibre terminations. The present system has great potential for applications from biomolecules to nano-electronics. Moreover, in order to prove the effectiveness of the system, the optical performance of such microlenses has been characterized by testing their imaging capabilities when the fibroblast cells were allowed to flow inside the microfluidic channel, showing one of their possible applications on-board a LoC platform. PMID:26660423

  7. 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.

  8. Bubble-induced acoustic mixing in a microfluidic device

    NASA Astrophysics Data System (ADS)

    Chen, Huaying; Petkovic-Duran, Karolina; Best, Michael; Zhu, Yonggang

    2015-12-01

    Homogeneous and fast mixing of samples at microscale is a critical requirement for successful applications of microfluidics in biochemical analysis, chemical synthesis, drug delivery and nanomaterial synthesis. This paper reports the optimisation of bubble-induced mixing in a microfluidic device in terms of voltage, driving frequency, piezo transducer position and PDMS thickness. The microfluidic device consists of a microwell (with the diameter of 1mm and volume of ~95 nL) with two rectangular bubble traps (400×400μm) on both sides of the well. After the injection of liquid, air bubbles were spontaneously trapped in two rectangular traps. When the frequency of a piezo was equal to the resonance frequency of air bubbles, strong liquid recirculation formed (so called acoustic microstreaming) in the vicinity of the interface of air bubbles and water. The acoustic induced flow of microbeads and mixing of water and fluorescence dye were imaged to study the mixing efficiency. For a given voltage and PDMS thickness, when the piezo was placed on top of the well, the mixing was most vigorous. For a given frequency, the mixing efficiency was directly proportional to the voltage (4-20V) and inversely proportional to the PDMS thickness (0.3-2mm). When the frequency driving the piezo was approaching the resonance frequency of air bubbles, the mixing efficiency was maximal, while when it was far away from the resonance frequency of air bubbles, the mixing efficiency was much lower. This work provides guidance to the design and the application of bubble-induced acoustic mixing in microfluidics.

  9. 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.

    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.

  10. 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.

  11. 3D strain measurement in electronic devices using through-focal annular dark-field imaging.

    PubMed

    Kim, Suhyun; Jung, Younheum; Lee, Sungho; Jung Kim, Joong; Byun, Gwangseon; Lee, Sunyoung; Lee, Haebum

    2014-11-01

    Spherical aberration correction in high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) allows us to form an electron probe with reduced depth of field. Using through-focal HAADF imaging, we experimentally demonstrated 3D strain measurement in a strained-channel transistor. The strain field distribution in the channel region was obtained by scanning an electron beam over a plan-view specimen. Furthermore, the decrease in the strain fields toward the silicon substrate was revealed at different focal planes with a 5-nm focal step. These results demonstrate that it is possible to reconstruct the 3D strain field in electronic devices. PMID:24859824

  12. 3D-printed devices for continuous-flow organic chemistry

    PubMed Central

    Dragone, Vincenza; Sans, Victor; Rosnes, Mali H; Kitson, Philip J

    2013-01-01

    Summary We present a study in which the versatility of 3D-printing is combined with the processing advantages of flow chemistry for the synthesis of organic compounds. Robust and inexpensive 3D-printed reactionware devices are easily connected using standard fittings resulting in complex, custom-made flow systems, including multiple reactors in a series with in-line, real-time analysis using an ATR-IR flow cell. As a proof of concept, we utilized two types of organic reactions, imine syntheses and imine reductions, to show how different reactor configurations and substrates give different products. PMID:23766811

  13. 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. PMID:17594014

  14. 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.

  15. Acoustophoretic sorting of viable mammalian cells in a microfluidic device.

    PubMed

    Yang, Allen H J; Soh, H Tom

    2012-12-18

    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 10(6) 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

  16. A novel in vitro angiogenesis model based on a microfluidic device.

    PubMed

    Xiaozhen, Dai; Shaoxi, Cai; Qunfang, Ye; Jiahuan, Jiang; Xiaoqing, Yan; Xin, Xiong; Qifeng, Jiang; Albert Chih-Lueh, Wang; Yi, Tan

    2011-11-01

    Angiogenesis is very important for many physiological and pathological processes. However, the molecular mechanisms of angiogenesis are unclear. To elucidate the molecular mechanisms of angiogenesis and to develop treatments for "angiogenesis- dependent" diseases, it is essential to establish a suitable in vitro angiogenesis model. In this study, we created a novel in vitro angiogenesis model based on a microfluidic device. Our model provides an in vivo-like microenvironment for endothelial cells (ECs) cultures and monitors the response of ECs to changes in their microenvironment in real time. To evaluate the potential of this microfluidic device for researching angiogenesis, the effects of pro-angiogenic factors on ECs proliferation, migration and tube-like structure formation were investigated. Our results showed the proliferation rate of ECs in 3D matrix was significantly promoted by the pro-angiogenic factors (with an increase of 59.12%). With the stimulation of pro-angiogenic factors gradients, ECs directionally migrated into the Matrigel from low concentrations to high concentrations and consequently formed multi-cell chords and tube-like structures. These results suggest that the device can provide a suitable platform for elucidating the mechanisms of angiogenesis and for screening pro-angiogenic or anti-angiogenic drugs for "angiogenesis-dependent" diseases. PMID:22247609

  17. Transport Mechanisms of Circulating Tumor Cells in Microfluidic Devices

    NASA Astrophysics Data System (ADS)

    Rangharajan, Kaushik; Conlisk, A. T.; Prakash, Shaurya

    2014-11-01

    Lab-on-a-chip (LoC) devices are becoming an essential tool for several emerging point-of-care healthcare needs and applications. Among the plethora of challenging problems in the personalized healthcare domain, early detection of cancer continues to be a challenge. For instance, identification of most tumors occurs by the time the tumor comprises approximately 1 billion cells, with poor prognosis for metastatic disease. The key obstacle in identifying and subsequent capture of circulating tumor cells (CTCs) is that the amount of CTCs in the blood stream is ~1 in 109 cells. The fundamental challenge in design and fabrication of microfluidic devices arises due to lack of information on suitable sorting needed for sample preparation before any labeling or capture scheme can be employed. Moreover, the ability to study these low concentration cells relies on knowledge of their physical and chemical properties, of which the physical properties are poorly understood. Also, nearly all existing microfluidic mixers were developed for aqueous electrolyte solutions to enhance mixing in traditional low Re flows. However, no systematic studies have developed design rules for particle mixing. Therefore, we present a numerical model to discuss design rules for microscale mixers and sorters for particle sorting for high efficiency antibody labeling of CTCs along with presenting a pathway for a device to capture CTCs without the need for labeling based on particle electrical properties. NSF Nanoscale Science and Engineering Center (NSEC) for the Affordable Nanoengineering of Polymeric Biomedical Devices EEC-0914790.

  18. Isolating single stranded DNA using a microfluidic dialysis device

    PubMed Central

    Sheng, Yixiao

    2013-01-01

    Isolating a particular strand of DNA from a double stranded DNA duplex is an important step in aptamer generation as well as many other biotechnology applications. Here we describe a microfluidic, flow-through, dialysis device for isolating single-stranded DNA (ssDNA) from double-stranded DNA (dsDNA). The device consists of two channels fabricated in polydimethylsiloxane (PDMS) separated by a track etched polycarbonate membrane (800 nm pore size). To isolate ssDNA, dual-biotin labelled dsDNA was immobilized onto streptavidin-coated polystyrene beads. Alkaline treatment was used to denature dsDNA, releasing the non-biotinylated ssDNA. In the flow-through dialysis device the liberated ssDNA was able to cross the membrane and was collected in an outlet channel. The complementary sequence bound to the bead was unable to cross the membrane and was directed to a waste channel. The effect of NaOH concentration and flow rate on purity and yield were compared. >95% ssDNA purity was achieved at 25mM NaOH. However, lower flow rates were necessary to achieve ssDNA yields approaching the 50% theoretical maximum of the concurrent-flow device. Under optimized conditions the microfluidic isolation achieved even higher purity ssDNA than analogous manual procedures. PMID:24213273

  19. 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.

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

    PubMed

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

    2010-04-01

    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. 2D array transducers for real-time 3D ultrasound guidance of interventional devices

    NASA Astrophysics Data System (ADS)

    Light, Edward D.; Smith, Stephen W.

    2009-02-01

    We describe catheter ring arrays for real-time 3D ultrasound guidance of devices such as vascular grafts, heart valves and vena cava filters. We have constructed several prototypes operating at 5 MHz and consisting of 54 elements using the W.L. Gore & Associates, Inc. micro-miniature ribbon cables. We have recently constructed a new transducer using a braided wiring technology from Precision Interconnect. This transducer consists of 54 elements at 4.8 MHz with pitch of 0.20 mm and typical -6 dB bandwidth of 22%. In all cases, the transducer and wiring assembly were integrated with an 11 French catheter of a Cook Medical deployment device for vena cava filters. Preliminary in vivo and in vitro testing is ongoing including simultaneous 3D ultrasound and x-ray fluoroscopy.

  2. 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.

  3. Temporal analysis of protozoan lysis in a microfluidic device.

    PubMed

    Santillo, Michael F; Heien, Michael L; Ewing, Andrew G

    2009-10-01

    A microfluidic device was fabricated and characterized for studying cell lysis of Arcella vulgaris, a nonpathogenic amoeba, over time. The device contains a series of chambers which capture cells allowing them to be subsequently exposed to a constant flow of biocidal agent. With this microfluidic system, individual cells are observed as they undergo lysis. This allows high-throughput measurements of individual lysis events, which are not possible with conventional techniques. Differences in lysis and decay times for Arcella were seen at different flow rates and concentrations of benzalkonium chloride, a biocidal detergent. The efficacy of benzalkonium chloride, chlorhexidine digluconate, phenol, sodium dodecyl sulfate, and Triton X-100 were compared, revealing information on their mechanisms of action. The presented device allows cell capture, controlled exposure to chemical biocides, and observation of lysis with single-cell resolution. Observations at the single cell level give insight into the mechanistic details of the lysis of individual Arcella cells vs. the population; decay times for individual Arcella cells were much shorter when compared to a population of 15 cells. PMID:19967116

  4. NMR analysis on microfluidic devices by remote detection

    SciTech Connect

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

    2005-08-15

    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.

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

    PubMed

    Lebedev, Artem; 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 (18)F-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 [(18)F]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 [(18)F]fallypride, a neuroimaging radiopharmaceutical under IND Application #109,880. PMID:23135409

  6. 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

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

    PubMed

    Jin, D; Deng, B; Li, J X; 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-cm(2) scale area, as a promising tool to pattern large-scale single cells on specific

  8. "Off-the-shelf" microfluidic devices for the production of liposomes for drug delivery.

    PubMed

    Bottaro, E; Nastruzzi, C

    2016-07-01

    An "off-the-shelf" microfluidic chip approach, utilizing lowcost, commercially available components, for liposome production, is presented. Microfluidic devices with different geometries have been conveniently designed and assembled, allowing the production of narrowly dispersed unilamellar and very reproducible liposomes. The presented results indicate that off-the-shelf microfluidic devices can hold great promises for the efficient preparation of different lipid based colloidal systems for biomedical applications. PMID:27127025

  9. Three-dimensional parallel UNIPIC-3D code for simulations of high-power microwave devices

    NASA Astrophysics Data System (ADS)

    Wang, Jianguo; Chen, Zaigao; Wang, Yue; Zhang, Dianhui; Liu, Chunliang; Li, Yongdong; Wang, Hongguang; Qiao, Hailiang; Fu, Meiyan; Yuan, Yuan

    2010-07-01

    This paper introduces a self-developed, three-dimensional parallel fully electromagnetic particle simulation code UNIPIC-3D. In this code, the electromagnetic fields are updated using the second-order, finite-difference time-domain method, and the particles are moved using the relativistic Newton-Lorentz force equation. The electromagnetic field and particles are coupled through the current term in Maxwell's equations. Two numerical examples are used to verify the algorithms adopted in this code, numerical results agree well with theoretical ones. This code can be used to simulate the high-power microwave (HPM) devices, such as the relativistic backward wave oscillator, coaxial vircator, and magnetically insulated line oscillator, etc. UNIPIC-3D is written in the object-oriented C++ language and can be run on a variety of platforms including WINDOWS, LINUX, and UNIX. Users can use the graphical user's interface to create the complex geometric structures of the simulated HPM devices, which can be automatically meshed by UNIPIC-3D code. This code has a powerful postprocessor which can display the electric field, magnetic field, current, voltage, power, spectrum, momentum of particles, etc. For the sake of comparison, the results computed by using the two-and-a-half-dimensional UNIPIC code are also provided for the same parameters of HPM devices, the numerical results computed from these two codes agree well with each other.

  10. Microfluidics 3D gel-island chip for single cell isolation and lineage-dependent drug responses study.

    PubMed

    Zhang, Zhixiong; Chen, Yu-Chih; Cheng, Yu-Heng; Luan, Yi; Yoon, Euisik

    2016-07-01

    3D cell culture in the extracellular matrix (ECM), which not only provides structural support to cellular constituents, but also initiates regulatory biochemical cues for a variety of important cell functions in tissue, has become more and more important in understanding cancer pathology and drug testing. Although the ECM-gel has been used in cell culture both in bulk and on-chip, previous studies focused on collective cell behavior rather than single-cell heterogeneity. To track the behavior of each individual cell, we have developed a gel-island chip, which can form thousands of islands containing single cells encapsulated by the desired ECM. Optimized by Poisson's distribution, the device can attain 34% single cell capture efficiency of the exact number of single cells per island. A good culture media exchange rate and high cell viability can be achieved in the gel-islands. The cells in the islands can be automatically counted for high-throughput analysis. As a proof of concept, we monitored the proliferation and differentiation of single Notch+ (stem-like) T47D breast cancer cells. The 3D collagen gel environment was found to be favorable for the stem-like phenotype through better self-renewal and de-differentiation (Notch- to Notch+ transition). More interestingly, we found that the Notch- de-differentiated cells were more resistant to doxorubicin and cisplatin than the Notch+ cells. Combining the 3D ECM culture and single cell resolution, the presented platform can automatically analyze the individual cell behaviors of hundreds of cells using a small amount of drug and reagents. PMID:27270563

  11. 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.

  12. A microfluidic electrochemiluminescent device for detecting cancer biomarker proteins.

    PubMed

    Sardesai, Naimish P; Kadimisetty, Karteek; Faria, Ronaldo; Rusling, James F

    2013-04-01

    We describe an electrochemiluminescence (ECL) immunoarray incorporated into a prototype microfluidic device for highly sensitive protein detection and apply this system to accurate, sensitive measurements of prostate-specific antigen (PSA) and interleukin-6 (IL-6) in serum. The microfluidic system employed three molded polydimethylsiloxane (PDMS) channels on a conductive pyrolytic graphite chip (2.5 × 2.5 cm) inserted into a machined chamber and interfaced with a pump, switching valve, and sample injector. Each of the three PDMS channels encompasses three 3 μL analytical wells. Capture-antibody-decorated single-wall carbon nanotube forests are fabricated in the bottom of the wells. The antigen is captured by these antibodies on the well bottoms. Then, a RuBPY-silica-secondary antibody (Ab2) label is injected to bind to antigen on the array, followed by injection of sacrificial reductant tripropylamine (TPrA) to produce ECL. For detection, the chip is placed into an open-top ECL measuring cell, and the channels are in contact with electrolyte in the chamber. Potential applied at 0.95 V versus Ag/AgCl oxidizes TPrA to produce ECL by redox cycling the RuBPY species in the particles, and ECL light is measured by a charge-coupled device camera. This approach achieved ultralow detection limits of 100 fg mL(-1) for PSA (9 zeptomole) and 10 fg mL(-1) (1 zeptomole) for IL-6 in calf serum, a 10-25-fold improvement of a similar non-microfluidic array. PSA and IL-6 in synthetic cancer patient serum samples were detected in 1.1 h and results correlated well with single-protein enzyme-linked immunosorbent assays. PMID:23307128

  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. 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

  15. Active Microfluidic Devices for Single-Molecule Experiments

    NASA Astrophysics Data System (ADS)

    Chen, Hao; Meiners, Jens-Christian

    2003-03-01

    Microfluidic chips have become an increasingly powerful and versatile tool in the life sciences. Multilayer devices fabricated from soft silicone elastomers in a replication molding technique are especially promising, because they permit flexible integration of active elements such as valves and pumps. In addition, they are fairly easy and inexpensive to produce. In a wide range of applications, microfluidic chips are used in conjunction with optical detection and manipulation techniques. However their widespread use has been hampered due to problems with interconnect stability, optical accessibility, and ability to perform surface chemistry. We have developed a packaging technique that encapsulates the elastomer in an epoxy resin of high optical quality. This stabilizes the interconnects so that a chip can be repeatedly plugged in and out of a socket. Our technique also eliminates the need for a baking step that is conventionally used to attach a glass cover slip to the elastomer surface. This allows us to assemble devices that contain a cover slip coated with proteins, thereby permitting subsequent in situ attachment of DNA molecules to the bottom of the flow channels. We demonstrate the utility of our chips in single-molecule applications involving tethered-particles and optical tweezers. Support: NIH R01 GM065934 & Research Corporation

  16. A novel high accuracy 3D scanning device for rock-art sites

    NASA Astrophysics Data System (ADS)

    Höll, T.; Holler, G.; Pinz, A.

    2014-06-01

    We are currently developing a novel 3D scanning device for rock-art. Within the European project 3D-Pitoti, this scanner shall be used to acquire 3D structure and radiometric surface properties of ancient rock-art sites in Valcamonica. Overall design goals include high spatial accuracy and precision, as well as radiometric quality beyond phototexture. This paper is devoted to the geometric measurement principle of the new scanner. We present a novel scanning scheme based on various constraints to Structure from Motion, that guarantees high accuracy of the resulting scans by combining tachymeter-based tracking of the scanner, stereo, and structure-from-motion. This method provides scale information (by calibrated stereo), and does not require ground control points, because outside-in tracking avoids the typical issues of drift in structure-from-motion. The system is designed for flexibility, high throughput, approx. 0.1 mm precision, and an overall accuracy of the reconstructed 3D structure that conforms with the specifications of the tachymeter.

  17. Separating Beads and Cells in Multi-channel Microfluidic Devices Using Dielectrophoresis and Laminar Flow

    PubMed Central

    Millet, Larry J.; Park, Kidong; Watkins, Nicholas N.; Hsia, K. Jimmy; Bashir, Rashid

    2011-01-01

    Microfluidic devices have advanced cell studies by providing a dynamic fluidic environment on the scale of the cell for studying, manipulating, sorting and counting cells. However, manipulating the cell within the fluidic domain remains a challenge and requires complicated fabrication protocols for forming valves and electrodes, or demands specialty equipment like optical tweezers. Here, we demonstrate that conventional printed circuit boards (PCB) can be used for the non-contact manipulation of cells by employing dielectrophoresis (DEP) for bead and cell manipulation in laminar flow fields for bioactuation, and for cell and bead separation in multichannel microfluidic devices. First, we present the protocol for assembling the DEP electrodes and microfluidic devices, and preparing the cells for DEP. Then, we characterize the DEP operation with polystyrene beads. Lastly, we show representative results of bead and cell separation in a multichannel microfluidic device. In summary, DEP is an effective method for manipulating particles (beads or cells) within microfluidic devices. PMID:21339720

  18. Rapid microfabrication of solvent-resistant biocompatible microfluidic devices.

    PubMed

    Hung, Lung-Hsin; Lin, Robert; Lee, Abraham Phillip

    2008-06-01

    This paper presents a rapid, simple, and low-cost fabrication method to prepare solvent resistant and biocompatible microfluidic devices with three-dimensional geometries. The devices were fabricated in thiolene and replicated from PDMS master with high molding fidelity. Good chemical compatibility for organic solvents allows volatile chemicals in synthesis and analysis applications. The surface can be processed to be hydrophobic or hydrophilic for water-in-oil and oil-in-water emulsions. Monodisperse organic solvent droplet generation is demonstrated to be reproducible in thiolene microchannels without swelling. The thiolene surface prevents cell adhesion but normal cell growth and adhesion on glass substrates is not affected by the adjacent thiolene patterns. PMID:18497921

  19. Paper-based microfluidic device with upconversion fluorescence assay.

    PubMed

    He, Mengyuan; Liu, Zhihong

    2013-12-17

    A paper-based microfluidic device with upconversion fluorescence assay (named as UC-μPAD) is proposed. The device is fabricated on a normal office printing sheet with a simple plotting method. Upconversion phosphors (UCPs) tagged with specific probes are spotted to the test zones on the μPAD, followed by the introduction of assay targets. Upconversion fluorescence measurements are directly conducted on the test zones after the completion of the probe-to-target reactions, without any post-treatments. The UC-μPAD features very easy fabrication and operation, simple and fast detection, low cost, and high sensitivity. UC-μPAD is a promising prospect for a clinical point-of-care test. PMID:24308347

  20. 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

  1. 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.

  2. A 3D visualization and guidance system for handheld optical imaging devices

    NASA Astrophysics Data System (ADS)

    Azar, Fred S.; de Roquemaurel, Benoit; Cerussi, Albert; Hajjioui, Nassim; Li, Ang; Tromberg, Bruce J.; Sauer, Frank

    2007-03-01

    We have developed a novel 3D visualization and guidance system for handheld optical imaging devices. In this paper, the system is applied to measurements of breast/cancerous tissue optical properties using a handheld diffuse optical spectroscopy (DOS) instrument. The combined guidance system/DOS instrument becomes particularly useful for monitoring neoadjuvant chemotherapy in breast cancer patients and for longitudinal studies where measurement reproducibility is critical. The system uses relatively inexpensive hardware components and comprises a 6 degrees-of-freedom (DOF) magnetic tracking device including a DC field generator, three sensors, and a PCI card running on a PC workstation. A custom-built virtual environment combined with a well-defined workflow provide the means for image-guided measurements, improved longitudinal studies of breast optical properties, 3D reconstruction of optical properties within the anatomical map, and serial data registration. The DOS instrument characterizes tissue function such as water, lipid and total hemoglobin concentration. The patient lies on her back at a 45-degrees angle. Each spectral measurement requires consistent contact with the skin, and lasts about 5-10 seconds. Therefore a limited number of positions may be studied. In a reference measurement session, the physician acquires surface points on the breast. A Delaunay-based triangulation algorithm is used to build the virtual breast surface from the acquired points. 3D locations of all DOS measurements are recorded. All subsequently acquired surfaces are automatically registered to the reference surface, thus allowing measurement reproducibility through image guidance using the reference measurements.

  3. 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

  4. 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. PMID:26319168

  5. Vapor deposition of cross-linked fluoropolymer barrier coatings onto pre-assembled microfluidic devices.

    PubMed

    Riche, Carson T; Marin, Brandon C; Malmstadt, Noah; Gupta, Malancha

    2011-09-21

    The interior surfaces of pre-assembled poly(dimethylsiloxane) (PDMS) microfluidic devices were modified with a cross-linked fluoropolymer barrier coating that significantly increased the chemical compatibility of the devices. PMID:21850298

  6. Engineered three-dimensional microfluidic device for interrogating cell-cell interactions in the tumor microenvironment

    PubMed Central

    Hockemeyer, K.; Janetopoulos, C.; Terekhov, A.; Hofmeister, W.; Vilgelm, A.; Costa, Lino; Wikswo, J. P.; Richmond, A.

    2014-01-01

    Stromal cells in the tumor microenvironment play a key role in the metastatic properties of a tumor. It is recognized that cancer-associated fibroblasts (CAFs) and endothelial cells secrete factors capable of influencing tumor cell migration into the blood or lymphatic vessels. We developed a microfluidic device that can be used to image the interactions between stromal cells and tumor cell spheroids in a three dimensional (3D) microenvironment while enabling external control of interstitial flow at an interface, which supports endothelial cells. The apparatus couples a 200-μm channel with a semicircular well to mimic the interface of a blood vessel with the stroma, and the design allows for visualization of the interactions of interstitial flow, endothelial cells, leukocytes, and fibroblasts with the tumor cells. We observed that normal tissue-associated fibroblasts (NAFs) contribute to the “single file” pattern of migration of tumor cells from the spheroid in the 3D microenvironment. In contrast, CAFs induce a rapid dispersion of tumor cells out of the spheroid with migration into the 3D matrix. Moreover, treatment of tumor spheroid cultures with the chemokine CXCL12 mimics the effect of the CAFs, resulting in similar patterns of dispersal of the tumor cells from the spheroid. Conversely, addition of CXCL12 to co-cultures of NAFs with tumor spheroids did not mimic the effects observed with CAF co-cultures, suggesting that NAFs produce factors that stabilize the tumor spheroids to reduce their migration in response to CXCL12. PMID:25379090

  7. Engineered three-dimensional microfluidic device for interrogating cell-cell interactions in the tumor microenvironment.

    PubMed

    Hockemeyer, K; Janetopoulos, C; Terekhov, A; Hofmeister, W; Vilgelm, A; Costa, Lino; Wikswo, J P; Richmond, A

    2014-07-01

    Stromal cells in the tumor microenvironment play a key role in the metastatic properties of a tumor. It is recognized that cancer-associated fibroblasts (CAFs) and endothelial cells secrete factors capable of influencing tumor cell migration into the blood or lymphatic vessels. We developed a microfluidic device that can be used to image the interactions between stromal cells and tumor cell spheroids in a three dimensional (3D) microenvironment while enabling external control of interstitial flow at an interface, which supports endothelial cells. The apparatus couples a 200-μm channel with a semicircular well to mimic the interface of a blood vessel with the stroma, and the design allows for visualization of the interactions of interstitial flow, endothelial cells, leukocytes, and fibroblasts with the tumor cells. We observed that normal tissue-associated fibroblasts (NAFs) contribute to the "single file" pattern of migration of tumor cells from the spheroid in the 3D microenvironment. In contrast, CAFs induce a rapid dispersion of tumor cells out of the spheroid with migration into the 3D matrix. Moreover, treatment of tumor spheroid cultures with the chemokine CXCL12 mimics the effect of the CAFs, resulting in similar patterns of dispersal of the tumor cells from the spheroid. Conversely, addition of CXCL12 to co-cultures of NAFs with tumor spheroids did not mimic the effects observed with CAF co-cultures, suggesting that NAFs produce factors that stabilize the tumor spheroids to reduce their migration in response to CXCL12. PMID:25379090

  8. A microfluidic electrochemiluminescent device for detecting cancer biomarker proteins

    PubMed Central

    Sardesai, Naimish P.; Kadimisetty, Karteek; Faria, Ronaldo; Rusling, James F.

    2013-01-01

    We describe an electrochemiluminescence (ECL) immunoarray incorporated into a prototype microfluidic device for highly sensitive protein detection, and apply this system to accurate, sensitive measurements of prostate specific antigen (PSA) and interleukin-6 (IL-6) in serum. The microfluidic system employed three molded polydimethylsiloxane (PDMS) channels on a conductive pyrolytic graphite chip (PG) (2.5 × 2.5 cm) inserted into a machined chamber and interfaced with a pump, switching valve and sample injector. Each of the three PDMS channels encompasses three 3 μL analytical wells. Capture-antibody-decorated single-wall carbon nanotube (SWCNT) forests are fabricated in the bottom of the wells. The antigen is captured by these antibodies on the well bottoms. Then a RuBPY-silica-secondary antibody (Ab2) label is injected to bind to antigen on the array, followed by injection of sacrificial reductant tripropylamine (TPrA) to produce ECL. For detection, the chip is placed into an open-top ECL measuring cell, and the channels are in contact with electrolyte in the chamber. Potential applied at 0.95 V vs. SCE oxidizes TPrA to produce ECL by redox cycling the RuBPY species in the particles, and ECL light is measured by a CCD camera. This approach achieved ultralow detection limits (DL) of 100 fg mL-1 for PSA (9 zeptomol) and 10 fg mL-1 (1 zeptomol) for IL-6 in calf serum, a 10-25 fold improvement of a similar non-microfluidic array. PSA and IL-6 in synthetic cancer patient serum samples were detected in 1.1 h and results correlated well with single-protein ELISAs. PMID:23307128

  9. Simple and cheap microfluidic devices for the preparation of monodisperse emulsions.

    PubMed

    Deng, Nan-Nan; Meng, Zhi-Jun; Xie, Rui; Ju, Xiao-Jie; Mou, Chuan-Lin; Wang, Wei; Chu, Liang-Ying

    2011-12-01

    Droplet microfluidics, which can generate monodisperse droplets or bubbles in unlimited numbers, at high speed and with complex structures, have been extensively investigated in chemical and biological fields. However, most current methods for fabricating microfluidic devices, such as glass etching, soft lithography in polydimethylsiloxane (PDMS) or assembly of glass capillaries, are usually either expensive or complicated. Here we report the fabrication of simple and cheap microfluidic devices based on patterned coverslips and microscope glass slides. The advantages of our approach for fabricating microfluidic devices lie in a simple process, inexpensive processing equipment and economical laboratory supplies. The fabricated microfluidic devices feature a flexible design of microchannels, easy spatial patterning of surface wettability, and good chemical compatibility and optical properties. We demonstrate their utilities for generation of monodisperse single and double emulsions with highly controllable flexibility. PMID:22025190

  10. Electrodes for microfluidic devices produced by laser induced forward transfer

    NASA Astrophysics Data System (ADS)

    Germain, Chris; Charron, Luc; Lilge, Lothar; Tsui, Ying Y.

    2007-07-01

    The laser induced forward transfer (LIFT) process was used to create conductive lines and pads for rapid prototyping and repairing microdevices. Single 0.1-10 μJ pulses from a 120 fs 800 nm titanium:sapphire laser were used to transfer films consisting of 40-80 nm thick gold to create the lines. Experiments were conducted in air ambient. The laser was focused using 4× and 10× microscope objectives and produced 5-20 μm diameter metal spots which were overlapped to produce conductive lines. Electrodes with widths between 10 and 50 μm have been produced and their resistances have been measured. The resistivities of these LIFT produced Au electrodes were found to be approximately (1-4) × 10 -6 Ω m. It has also been shown that the conductivity of the lines can be further improved by electrical curing. The LIFT process was used to repair heaters for microfluidic applications and preliminarily create electrodes for control of electro-osmotic flow in microfluidic devices.

  11. 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.

  12. Stem cell derived in vivo-like human cardiac bodies in a microfluidic device for toxicity testing by beating frequency imaging.

    PubMed

    Bergström, Gunnar; Christoffersson, Jonas; Schwanke, Kristin; Zweigerdt, Robert; Mandenius, Carl-Fredrik

    2015-08-01

    Beating in vivo-like human cardiac bodies (CBs) were used in a microfluidic device for testing cardiotoxicity. The CBs, cardiomyocyte cell clusters derived from induced pluripotent stem cells, exhibited typical structural and functional properties of the native human myocardium. The CBs were captured in niches along a perfusion channel in the device. Video imaging was utilized for automatic monitoring of the beating frequency of each individual CB. The device allowed assessment of cardiotoxic effects of drug substances doxorubicin, verapamil and quinidine on the 3D clustered cardiomyocytes. Beating frequency data recorded over a period of 6 hours are presented and compared to literature data. The results indicate that this microfluidic setup with imaging of CB characteristics provides a new opportunity for label-free, non-invasive investigation of toxic effects in a 3D microenvironment. PMID:26135270

  13. 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.

  14. 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.

  15. Inducing chemotactic and haptotactic cues in microfluidic devices for three-dimensional in vitro assays

    PubMed Central

    Moreno-Arotzena, O.; Mendoza, G.; Cóndor, M.; Rüberg, T.

    2014-01-01

    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. PMID:25587374

  16. Integrated microwave resonant device for dielectric analysis of microfluidic systems

    NASA Astrophysics Data System (ADS)

    Rowe, D. J.; Porch, A.; Barrow, D. A.; Allender, C. J.

    2011-08-01

    Herein we present a device for performing non-contact dielectric spectroscopy upon liquids in a microfluidic environment. The device is comprised of a compression-sealed polytetrafluoroethylene (PTFE) chip with an embedded coaxial resonator, which is overmoded for dielectric measurements at six discrete frequencies between 1 and 8 GHz. A novel capacitive coupling structure allows transmission measurements to be taken from one end of the resonator, and an optimised microchannel design maximises sensitivity and repeatability. The use of a PTFE substrate and a non-contact measurement gives excellent chemical and biological compatibility. A simple 'fingerprint' method for identifying solvents is demonstrated, whereby a sample is characterised by air-referenced changes in complex frequency. Complex permittivity values are also obtained via a perturbation theory-based inversion. A combination of experimental and simulated results is used to characterise the device behaviour, limits of operation and measurement uncertainty. The high stability of temporal measurements, coupled with the robustness of the design, make this device ideal for analytical chemistry and industrial process control.

  17. High-Throughput Microfluidic Device for Rare Cell Isolation

    PubMed Central

    Yang, Daniel; Leong, Serena; Lei, Andy; Sohn, Lydia L.

    2016-01-01

    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. PMID:26937065

  18. 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.

  19. 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.

  20. 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.

  1. Large-area polymer replication for microfluidic devices

    NASA Astrophysics Data System (ADS)

    Heckele, Mathias; Gerlach, Andreas; Guber, Andreas E.; Schaller, Thomas

    2001-04-01

    A huge market development is expected for modern drug discovery and genomic analysis when rapid parallel analysis of a large number of samples gets available at affordable costs. The state of the art shows that low cost devices can be fabricated in mass production by micromolding of polymers. In close collaboration, Greiner Bio-One and Forschungszentrum Karlsruhe have developed a single-use plastic microfluidic capillary electrophoresis (CE) array in the standardized microplate footprint. This paper presents the results of experiences which show that hot embossing with a mechanically micromachined molding tool is the appropriate technology for low cost mass fabrication. A subsequent sealing of the microchannels allows sub-microliter sample volumes in 96- channel multiplexed microstructures.

  2. 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.

  3. 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. PMID:21821908

  4. Parameter modeling for nanopore lonic field effect transistors in 3-D device simulation.

    PubMed

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

    2014-11-01

    An Ion Field Effect Transistor (IFET) with nanopore structure was modeled in a conventional 3-dimensional (3-D) device simulator to understand current-voltage (I-V) characteristics and underlying physics of the device. Since the nanopore was filled with positive ions (K+) ions due to the negative interface charge on the insulator surface and negative gate bias condition, we could successfully simulate the IFET structure using modified p-type silicon to mimic KCl solution. We used p-type silicon with a doping concentration of 6.022 x 10(16) cm(-3) which has the same concentration of positive carriers (hole) as in 10(-4) M KCl. By controlling gate electric field effect on the mobility, the I-V curves obtained by the parameter modeling matched very well with the measured data. In addition, the decrease of [V(th)] with increasing V(DS) was physically analyzed. PMID:25958494

  5. 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.

  6. Simultaneous 3D-vibration measurement using a single laser beam device

    NASA Astrophysics Data System (ADS)

    Brecher, Christian; Guralnik, Alexander; Baümler, Stephan

    2012-06-01

    Today's commercial solutions for vibration measurement and modal analysis are 3D-scanning laser doppler vibrometers, mainly used for open surfaces in the automotive and aerospace industries and the classic three-axial accelerometers in civil engineering, for most industrial applications in manufacturing environments, and particularly for partially closed structures. This paper presents a novel measurement approach using a single laser beam device and optical reflectors to simultaneously perform 3D-dynamic measurement as well as geometry measurement of the investigated object. We show the application of this so called laser tracker for modal testing of structures on a mechanical manufacturing shop floor. A holistic measurement method is developed containing manual reflector placement, semi-automated geometric modeling of investigated objects and fully automated vibration measurement up to 1000 Hz and down to few microns amplitude. Additionally the fast set up dynamic measurement of moving objects using a tracking technique is presented that only uses the device's own functionalities and does neither require a predefined moving path of the target nor an electronic synchronization to the moving object.

  7. 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

  8. 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

  9. Microfluidic shear devices for quantitative analysis of cell adhesion.

    PubMed

    Lu, Hang; Koo, Lily Y; Wang, Wechung M; Lauffenburger, Douglas A; Griffith, Linda G; Jensen, Klavs F

    2004-09-15

    We describe the design, construction, and characterization of microfluidic devices for studying cell adhesion and cell mechanics. The method offers multiple advantages over previous approaches, including a wide range of distractive forces, high-throughput performance, simplicity in experimental setup and control, and potential for integration with other microanalytic modules. By manipulating the geometry and surface chemistry of the microdevices, we are able to vary the shear force and the biochemistry during an experiment. The dynamics of cell detachment under different conditions can be captured simultaneously using time-lapse videomicroscopy. We demonstrate assessment of cell adhesion to fibronectin-coated substrates as a function of the shear stress or fibronectin concentration in microchannels. Furthermore, a combined perfusion-shear device is designed to maintain cell viability for long-term culture as well as to introduce exogenous reagents for biochemical studies of cell adhesion regulation. In agreement with established literature, we show that fibroblasts cultured in the combined device reduced their adhesion strength to the substrate in response to epidermal growth factor stimulation. PMID:15362881

  10. 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.

  11. Switchable pH actuators and 3D integrated salt bridges as new strategies for reconfigurable microfluidic free-flow electrophoretic separation.

    PubMed

    Cheng, Li-Jing; Chang, Hsueh-Chia

    2014-03-01

    We present novel strategies for reconfigurable, high-throughput microfluidic free-flow electrophoretic separation using electrically switchable pH actuators and 3D integrated salt bridges to allow rapid formation of stable pH gradients and efficient electrophoresis. The pH actuator is achieved by microfluidic integration of bipolar membranes which change electrolyte pH by injecting excess H(+) or OH(-) ions produced by a field-enhanced water dissociation phenomenon at the membrane junction upon voltage bias. The technique does not require conventional multiple buffer inflows and leaves no gas production as experienced in electrolysis, thus providing stable pH gradients for isoelectric focusing (IEF) separation. With the pH actuator inactivated, the platform can perform zone electrophoretic (ZE) separation in a medium of constant pH. We also describe the use of 3D integrated ion conductive polymers that serve as salt bridges for improving the voltage efficiency of electrophoresis and to allow high throughput. The proof of concept was successfully demonstrated for free-flow IEF and ZE separation of protein mixtures showing the potential and the simplicity of the platform for high-throughput and high-precision sample separation. PMID:24430103

  12. 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

  13. Exploration of microfluidic devices based on multi-filament threads and textiles: A review.

    PubMed

    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

  14. Microfluidic device for the formation of optically excitable, three-dimensional, compartmentalized motor units.

    PubMed

    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

    2016-08-01

    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

  15. 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

  16. Underwater 3D Surface Measurement Using Fringe Projection Based Scanning Devices.

    PubMed

    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

  17. 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.

  18. 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

  19. Microfluidic Devices with Templated Regular Macroporous Structures for HIV Viral Capture

    PubMed Central

    Surawathanawises, Krissada; Kundrod, Kathryn; Cheng, Xuanhong

    2016-01-01

    There is a need to develop inexpensive, portable and easy-to-use devices for viral sample processing for resource-limited settings. Here we offer a solution to efficient virus capture by incorporating macroporous materials with regular structures into microfluidic devices for affinity chromatography. Two-dimensional simulations were first conducted to investigate the effects of two structures, a nanopost array and a spherical pore network, on nanoparticle capture. Then, the two structures were created in polymers by templating anodic aluminum oxide films and 3D close-packed silica particles, respectively. When the microdevices containing functionalized porous materials were tested for human immunodeficiency virus (HIV) isolation, capture efficiencies of 80–99% were achieved under a continuous flow. Comparatively, functionalized flatbed microchannels captured around 10% of HIV particles. As the characteristic dimensions of the nanostructures are tunable, such devices can be adapted for the capture of different submicron bioparticles. The high capture efficiency and easy-to-operate nature suit the need of resource-limited settings and may find applications for point-of-care diagnostics. PMID:26899457

  20. Numerical analysis of wave generation and propagation in a focused surface acoustic wave device for potential microfluidics applications.

    PubMed

    Sankaranarayanan, Subramanian K R S; Bhethanabotla, Venkat R

    2009-03-01

    We develop a 3-D finite element model of a focused surface acoustic wave (F-SAW) device based on LiNbO(3) to analyze the wave generation and propagation characteristics for devices operating at MHz frequencies with varying applied input voltages. We compare the F-SAW device to a conventional SAW device with similar substrate dimensions and transducer finger periodicity. SAW devices with concentrically shaped focused interdigital transducer fingers (F-IDTs) are found to excite waves with high intensity and high beam-width compression ratio, confined to a small localized area. F-SAW devices are more sensitive to amplitude variations at regions close to the focal point than conventional SAW devices having uniform IDT configuration. We compute F-SAW induced streaming forces and velocity fields by applying a successive approximation technique to the Navier-Stokes equation (Nyborg's theory). The maximum streaming force obtained at the focal point varies as the square of the applied input voltage. Computed streaming velocities at the focal point in F-SAW devices are at least an order of magnitude higher than those in conventional SAW devices. Simulated frequency response indicates higher insertion losses in F-SAW devices than in conventional devices, reflecting their greater utility as actuators than as sensors. Our simulation findings suggest that F-SAW devices can be utilized effectively for actuation in microfluidic applications involving diffusion limited transport processes. PMID:19411221

  1. Nonlinear dynamics in a microfluidic loop device: Chaos and Fractals

    NASA Astrophysics Data System (ADS)

    Maddala, Jeevan; Rengaswamy, Raghunathan

    2012-11-01

    Discrete decision making and resistive interactions between droplets in a microfluidic loop device induces fascinating nonlinear dynamics such as multi-stability and period doubling. Droplets entering the device at fixed time intervals can exit at different periods or chaotically. One of the periodic behaviors that is observed in a loop is the three-period behavior; this is consistent with the notion that three period behavior implies chaos. Switching between these different dynamical regimes is achieved by changing the inlet droplet feeding frequency. Chaotic behavior is observed between islands of periodic behavior. We show through simulations and experimental observations that the transitions between periods are indeed chaotic. Network model is used to study the dynamic behavior for different inlet feeding frequencies resulting in the development of a bifurcation map. The bifurcation map shows that the three period dynamics is preceded by chaos. A Lyapunov exponent is used to further validate these results. The exit droplet spacing shows several fascinating patterns when the model is simulated for a large number of droplets in the chaotic regime. One such chaotic regime produces a fractal that has a boundary of cardioid. The correlation dimension for a fractal pattern produced by this particular loop system is calculated to be 0.7.

  2. 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.

  3. 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.

  4. 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.

  5. Thermoplastic microfluidic devices and their applications in protein and DNA analysis

    PubMed Central

    Liu, Ke; Fan, Z. Hugh

    2013-01-01

    Microfluidics is a platform technology that has been used for genomics, proteomics, chemical synthesis, environment monitoring, cellular studies, and other applications. The fabrication materials of microfluidic devices have traditionally included silicon and glass, but plastics have gained increasing attention in the past few years. We focus this review on thermoplastic microfluidic devices and their applications in protein and DNA analysis. We outline the device design and fabrication methods, followed by discussion on the strategies of surface treatment. We then concentrate on several significant advancements in applying thermoplastic microfluidic devices to protein separation, immunoassays, and DNA analysis. Comparison among numerous efforts, as well as the discussion on the challenges and innovation associated with detection, is presented. PMID:21274478

  6. Integration of a bioMEMS device into a disposable microfluidic cartridge for medical diagnostics

    NASA Astrophysics Data System (ADS)

    Ortiz, Pedro; Keegan, Neil; Spoors, Julia; Hedley, John; Harris, Alun; Burdess, Jim; Burnett, Richard; Velten, Thomas; Biehl, Margit; Knoll, Thorsten; Haberer, Werner; Solomon, Matthew; Campitelli, Andrew; McNeil, Calum

    2009-02-01

    A microfluidic system for cancer diagnostics based around a core MEMS biosensor technology is presented in this paper. The principle of the MEMS biosensor is introduced and the functionalisation strategy for cancer marker recognition is described. In addition, the successful packaging and integration of functional MEMS biosensor devices are reported herein. This ongoing work represents one of the first hybrid systems to integrate a PCB packaged silicon MEMS device into a disposable microfluidic cartridge.

  7. 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

  8. Ionic current devices-Recent progress in the merging of electronic, microfluidic, and biomimetic structures.

    PubMed

    Koo, Hyung-Jun; Velev, Orlin D

    2013-01-01

    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. PMID:24404020

  9. Paper-based three-dimensional microfluidic device for monitoring of heavy metals with a camera cell phone.

    PubMed

    Wang, Hu; Li, Ya-jie; Wei, Jun-feng; Xu, Ji-run; Wang, Yun-hua; Zheng, Guo-xia

    2014-05-01

    A 3D paper-based microfluidic device has been developed for colorimetric determination of selected heavy metals in water samples by stacking layers of wax patterned paper and double-sided adhesive tape. It has the capability of wicking fluids and distributing microliter volumes of samples from single inlet into affrays of detection zones without external pumps, thus a range of metal assays can be simply and inexpensively performed. We demonstrate a prototype of four sample inlets for up to four heavy metal assays each, with detection limits as follows: Cu (II) = 0.29 ppm, Ni(II) = 0.33 ppm, Cd (II) = 0.19 ppm, and Cr (VI) = 0.35 ppm, which provided quantitative data that were in agreement with values gained from atomic absorption. It has the ability to identify these four metals in mixtures and is immune to interferences from either nontoxic metal ions such as Na(I) and K(I) or components found in reservoir or beach water. With the incorporation of a portable detector, a camera mobile phone, this 3D paper-based microfluidic device should be useful as a simple, rapid, and on-site screening approach of heavy metals in aquatic environments. PMID:24618990

  10. 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.

  11. 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.

  12. 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.

  13. Additively Manufactured Device for Dynamic Culture of Large Arrays of 3D Tissue Engineered Constructs.

    PubMed

    Costa, Pedro F; Hutmacher, Dietmar W; Theodoropoulos, Christina; Gomes, Manuela E; Reis, Rui L; Vaquette, Cédryck

    2015-04-22

    The ability to test large arrays of cell and biomaterial combinations in 3D environments is still rather limited in the context of tissue engineering and regenerative medicine. This limitation can be generally addressed by employing highly automated and reproducible methodologies. This study reports on the development of a highly versatile and upscalable method based on additive manufacturing for the fabrication of arrays of scaffolds, which are enclosed into individualized perfusion chambers. Devices containing eight scaffolds and their corresponding bioreactor chambers are simultaneously fabricated utilizing a dual extrusion additive manufacturing system. To demonstrate the versatility of the concept, the scaffolds, while enclosed into the device, are subsequently surface-coated with a biomimetic calcium phosphate layer by perfusion with simulated body fluid solution. 96 scaffolds are simultaneously seeded and cultured with human osteoblasts under highly controlled bidirectional perfusion dynamic conditions over 4 weeks. Both coated and noncoated resulting scaffolds show homogeneous cell distribution and high cell viability throughout the 4 weeks culture period and CaP-coated scaffolds result in a significantly increased cell number. The methodology developed in this work exemplifies the applicability of additive manufacturing as a tool for further automation of studies in the field of tissue engineering and regenerative medicine. PMID:25721231

  14. 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

  15. 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

  16. Microfluidic paper-based analytical device for particulate metals.

    PubMed

    Mentele, Mallory M; Cunningham, Josephine; Koehler, Kirsten; Volckens, John; Henry, Charles S

    2012-05-15

    A microfluidic paper-based analytical device (μPAD) fabricated by wax printing was designed to assess occupational exposure to metal-containing aerosols. This method employs rapid digestion of particulate metals using microliters of acid added directly to a punch taken from an air sampling filter. Punches were then placed on a μPAD, and digested metals were transported to detection reservoirs upon addition of water. These reservoirs contained reagents for colorimetric detection of Fe, Cu, and Ni. Dried buffer components were used to set the optimal pH in each detection reservoir, while precomplexation agents were deposited in the channels between the sample and detection zones to minimize interferences from competing metals. Metal concentrations were quantified from color intensity images using a scanner in conjunction with image processing software. Reproducible, log-linear calibration curves were generated for each metal, with method detection limits ranging from 1.0 to 1.5 μg for each metal (i.e., total mass present on the μPAD). Finally, a standard incineration ash sample was aerosolized, collected on filters, and analyzed for the three metals of interest. Analysis of this collected aerosol sample using a μPAD showed good correlation with known amounts of the metals present in the sample. This technology can provide rapid assessment of particulate metal concentrations at or below current regulatory limits and at dramatically reduced cost. PMID:22489881

  17. 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

  18. Tip-multi-breaking in Capillary Microfluidic Devices.

    PubMed

    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

  19. Tip-multi-breaking in Capillary Microfluidic Devices

    NASA Astrophysics Data System (ADS)

    Zhu, Pingan; Kong, Tiantian; Kang, Zhanxiao; Tian, Xiaowei; Wang, Liqiu

    2015-06-01

    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.

  20. 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

  1. Evaluation of the correctness of a 3D recording device for mandibular functional movement in laboratory

    NASA Astrophysics Data System (ADS)

    Zhao, Tian; Sui, Huaxin; Yang, Huifang; Wang, Yong; Sun, Yuchun

    2015-07-01

    Objectives: To quantitatively evaluate the correctness of a computer binocular vision mandibular 3D trajectory recording device. Methods: A specialized target shooting paper was neatly pasted on a high-precision three-axis electronic translation stage. A linear one-way movement was set at a speed of 1 mm/s along the X, Y, and Z directions for a distance of 10 mm each. The coordinates of 3 pre-set target points were recorded at the start and end by a computer binocular vision system with a frequency of 10 FPS and stored in TXT format. The TXT files were imported to Imageware 13.0, and the straight-line lengths between the start and end were measured. The mean difference between each length and 10 mm were calculated to evaluate the correctness of the distance measurement. The linear movement and recording procedure was repeated 3 times, but the speed was changed to 5 mm/s to simulate the human mandibular movement speed. The trajectories of the 3 target points were fitted and the vertical dimensions from each track point to the fitted lines were measured. The mean difference was calculated between the vertical dimensions and 0 mm to evaluate the correctness of recording trajectories using this device. Results: The correctness of distance measurements of the points 1, 2, and 3 were 0.06 mm, 0.16 mm, and 0.08 mm, respectively. The correctness of the trajectories of the points 1, 2, and 3 were 0.11 mm, 0.11 mm, and 0.10 mm, respectively. Conclusion: Using this computer binocular vision device, the correctness of the recorded linear trajectories in the range of 10 mm was better than 0.20 mm.

  2. 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

  3. 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…

  4. Attenuated total reflection-Fourier transform infrared spectroscopic imaging of pharmaceuticals in microfluidic devices.

    PubMed

    Ewing, Andrew V; Clarke, Graham S; Kazarian, Sergei G

    2016-03-01

    The poor aqueous solubility of many active pharmaceutical ingredients presents challenges for effective drug delivery. In this study, the combination of attenuated total reflection (ATR)-FTIR spectroscopic imaging with specifically designed polydimethylsiloxane microfluidic devices to study drug release from pharmaceutical formulations has been developed. First, the high-throughput analysis of the dissolution of micro-formulations studied under flowing conditions has been introduced using a model formulation of ibuprofen and polyethylene glycol. The behaviour and release of the drug was monitored in situ under different pH conditions. In contrast to the neutral solution, where both the drug and excipient dissolved at a similar rate, structural change from the molecularly dispersed to a crystalline form of ibuprofen was characterised in the obtained spectroscopic images and the corresponding ATR-FTIR spectra for the experiments carried out in the acidic medium. Further investigations into the behaviour of the drug after its release from formulations (i.e., dissolved drug) were also undertaken. Different solutions of sodium ibuprofen dissolved in a neutral medium were studied upon contact with acidic conditions. The phase transition from a dissolved species of sodium ibuprofen to the formation of solid crystalline ibuprofen was revealed in the microfluidic channels. This innovative approach could offer a promising platform for high-throughput analysis of a range of micro-formulations, which are of current interest due to the advent of 3D printed pharmaceutical and microparticulate delivery systems. Furthermore, the ability to study dissolved drug in solution under flowing conditions can be useful for the studies of the diffusion of drugs into tissues or live cells. PMID:27158293

  5. 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

    2016-03-01

    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. PMID:26862603

  6. A versatile and flexible low-temperature full-wafer bonding process of monolithic 3D microfluidic structures in SU-8

    NASA Astrophysics Data System (ADS)

    Steigert, J.; Brett, O.; Müller, C.; Strasser, M.; Wangler, N.; Reinecke, H.; Daub, M.; Zengerle, R.

    2008-09-01

    We present a versatile fabrication process for the precise fabrication of embedded three-dimensional microfluidic structures in SU-8 photoresist. The full-wafer bond process based on a polyester (PET) handling layer enhances the previous low-temperature bonding technology. We achieved an extremely high bond strength of 45 MPa while requiring only small anchoring structures. Small channel structures with an aspect ratio >2 as well as wide membranes with an aspect ratio <0.02 were successfully bonded to realize precisely defined channel structures. Furthermore, the developed process features high yields (>80%) and enables the integration of microelectronics. The flexibility of the fabrication process is presented in two contrary applications. A completely freestanding and transparent SU-8 foil with a thickness of 225 µm featuring embedded 3D microchannels was fabricated. Also, high quality ink-jet dispensers were successfully fabricated whereas the dispenser quality mainly depends on the channel quality.

  7. Nanoscale surface modifications to control capillary flow characteristics in PMMA microfluidic devices.

    PubMed

    Mukhopadhyay, Subhadeep; Roy, Susanta S; D'Sa, Raechelle A; Mathur, Ashish; Holmes, Richard J; McLaughlin, James A

    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

  8. 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. PMID:26232932

  9. 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).

  10. 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.

  11. Drug penetration and metabolism in 3D cell cultures treated in a 3D printed fluidic device: assessment of irinotecan via MALDI imaging mass spectrometry.

    PubMed

    LaBonia, Gabriel J; Lockwood, Sarah Y; Heller, Andrew A; Spence, Dana M; Hummon, Amanda B

    2016-06-01

    Realistic in vitro models are critical in the drug development process. In this study, a novel in vitro platform is employed to assess drug penetration and metabolism. This platform, which utilizes a 3D printed fluidic device, allows for dynamic dosing of three dimensional cell cultures, also known as spheroids. The penetration of the chemotherapeutic irinotecan into HCT 116 colon cancer spheroids was examined with MALDI imaging mass spectrometry (IMS). The active metabolite of irinotecan, SN-38, was also detected. After twenty-four hours of treatment, SN-38 was concentrated to the outside of the spheroid, a region of actively dividing cells. The irinotecan prodrug localization contrasted with SN-38 and was concentrated to the necrotic core of the spheroids, a region containing mostly dead and dying cells. These results demonstrate that this unique in vitro platform is an effective means to assess drug penetration and metabolism in 3D cell cultures. This innovative system can have a transformative impact on the preclinical evaluation of drug candidates due to its cost effectiveness and high throughput. PMID:27198560

  12. 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

  13. 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. PMID:26402320

  14. 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

    2014-10-01

    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. PMID:25102283

  15. 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

  16. Microfluidic-SERS devices for one shot limit-of-detection.

    PubMed

    Kim, Donghyuk; Campos, Antonio R; 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

    2014-07-01

    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

  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. 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…

  19. Control of 3-dimensional collagen matrix polymerization for reproducible human mammary fibroblast cell culture in microfluidic devices.

    PubMed

    Sung, Kyung Eun; Su, Gui; Pehlke, Carolyn; Trier, Steven M; Eliceiri, Kevin W; Keely, Patricia J; Friedl, Andreas; Beebe, David J

    2009-09-01

    Interest in constructing a reliable 3-dimensional (3D) collagen culture platform in microfabricated systems is increasing as researchers strive to investigate reciprocal interaction between extracellular matrix (ECM) and cells under various conditions. However, in comparison to conventional 2-dimensional (2D) cell culture research, relatively little work has been reported about the polymerization of collagen type I matrix in microsystems. We, thus, present a study of 3D collagen polymerization to achieve reproducible 3D cell culture in microfluidic devices. Array-based microchannels are employed to efficiently examine various polymerization conditions, providing more replicates with less sample volume than conventional means. Collagen fibers assembled in microchannels were almost two-times thinner than those in conventional gels prepared under similar conditions, and the fiber thickness difference influenced viability and morphology of embedded human mammary fibroblast (HMF) cells. HMF cells contained more actin stress fibers and showed increased viability in 3D collagen matrix composed of thicker collagen fibers. Relatively low pH of the collagen solution within a physiological pH range (6.5-8.5) and pre-incubation at low temperature (approximately 4 degrees C) before polymerization at 37 degrees C allow sufficient time for molecular assembly, generating thicker collagen fibers and enhancing HMF cell viability. The results provide the basis for improved process control and reproducibility of 3D collagen matrix culture in microchannels, allowing predictable modifications to provide optimum conditions for specific cell types. In addition, the presented method lays the foundation for high throughput 3D cellular screening. PMID:19540580

  20. 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.

  1. Development, characterization, and analytical applications of microfluidic devices and nanostructured materials

    NASA Astrophysics Data System (ADS)

    Bhakta, Samir A.

    Compared to conventional benchtop instruments, microfluidic devices possess advantageous characteristics including portability, reduced analysis time, and relatively inexpensive production, making them attractive analytical devices. The goals of our research lab include the design, operation, and application of microfluidic techniques and the rational design of biosensors. In line with these goals, the objectives of my research are to develop and characterize novel microfluidic platforms and to improve their overall efficiency towards the analysis of a wide range of biologically active and environmentally-relevant compounds. Specifically, the research projects discussed herein are based on the development of novel strategies enabling the miniaturization of traditional analytical protocols using microfluidic devices. In addition, the development and characterization of novel biosensors incorporating thin-films of nanoporous materials that can be potentially used in series with the microfluidic platforms is discussed. A critical review of the field involving adsorption of proteins to nanomaterials for the use of biosensors is also discussed. Results related to the design, characterization, and applications of the devices and biosensors are discussed along with the advantages of these technologies.

  2. 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.

  3. 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

  4. 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

  5. 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

  6. Multilayer soft lithography of perfluoropolyether based elastomer for microfluidic device fabrication.

    PubMed

    Devaraju, Naga Sai Gopi Krishna; Unger, Marc Alexander

    2011-06-01

    The compatibility of microfluidic devices with solvents and other chemicals is extremely important for many applications such as organic synthesis in microreactors and drug screening. We report the successful fabrication of microfluidic devices from a novel perfluoropolyether based polymer utilizing the Multilayer Soft Lithography™ (MSL) technique with simple, straightforward processing. The perfluorinated polymer SIFEL X-71 8115 is a highly chemically resistant elastomeric material. We demonstrate fabrication of a microfluidic device using an off-ratio bonding technique to bond multiple SIFEL layers, each patterned lithographically. The mechanical properties of the SIFEL MSL valves (including actuation pressures) are similar to PDMS MSL valves of the same geometry. Chemical compatibility tests highlight SIFEL's remarkable resistance to organic solvents, acids and alkalis. PMID:21503367

  7. 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.

  8. A review on recent developments for biomolecule separation at analytical scale using microfluidic devices.

    PubMed

    Tetala, Kishore K R; Vijayalakshmi, M A

    2016-02-01

    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. PMID:26772122

  9. Theory and experiment on resonant frequencies of liquid-air interfaces trapped in microfluidic devices

    NASA Astrophysics Data System (ADS)

    Chindam, Chandraprakash; Nama, Nitesh; Ian Lapsley, Michael; Costanzo, Francesco; Jun Huang, Tony

    2013-11-01

    Bubble-based microfluidic devices have been proven to be useful for many biological and chemical studies. These bubble-based microdevices are particularly useful when operated at the trapped bubbles' resonance frequencies. In this work, we present an analytical expression that can be used to predict the resonant frequency of a bubble trapped over an arbitrary shape. Also, the effect of viscosity on the dispersion characteristics of trapped bubbles is determined. A good agreement between experimental data and theoretical results is observed for resonant frequency of bubbles trapped over different-sized rectangular-shaped structures, indicating that our expression can be valuable in determining optimized operational parameters for many bubble-based microfluidic devices. Furthermore, we provide a close estimate for the harmonics and a method to determine the dispersion characteristics of a bubble trapped over circular shapes. Finally, we present a new method to predict fluid properties in microfluidic devices and complement the explanation of acoustic microstreaming.

  10. 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. PMID:24753723

  11. 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…

  12. 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

  13. An inkjet-printed microfluidic device for liquid-liquid extraction.

    PubMed

    Watanabe, Masashi

    2011-04-01

    A microfluidic device for liquid-liquid extraction was quickly produced using an office inkjet printer. An advantage of this method is that normal end users, who are not familiar with microfabrication, can produce their original microfluidic devices by themselves. In this method, the printer draws a line on a hydrophobic and oil repellent surface using hydrophilic ink. This line directs a fluid, such as water or xylene, to form a microchannel along the printed line. Using such channels, liquid-liquid extraction was successfully performed under concurrent and countercurrent flow conditions. PMID:21290076

  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. PMID:26659997

  15. Performance and scaling effects in a multilayer microfluidic extracorporeal lung oxygenation device

    PubMed Central

    Kniazeva, Tatiana; Epshteyn, Alla A.; Hsiao, James C.; Kim, Ernest S.; Kolachalama, Vijaya B.; Charest, Joseph L.

    2012-01-01

    Microfluidic fabrication technologies are emerging as viable platforms for extracorporeal lung assist devices and oxygenators for cardiac surgical support and critical care medicine, based in part on their ability to more closely mimic the architecture of the human vasculature than existing technologies. In comparison with current hollow fiber oxygenator technologies, microfluidic systems have more physiologically-representative blood flow paths, smaller cross section blood conduits and thinner gas transfer membranes. These features can enable smaller device sizes and a reduced blood volume in the oxygenator, enhanced gas transfer efficiencies, and may also reduce the tendency for clotting in the system. Several critical issues need to be addressed in order to advance this technology from its current state and implement it in an organ-scale device for clinical use. Here we report on the design, fabrication and characterization of multilayer microfluidic oxygenators, investigating scaling effects associated with fluid mechanical resistance, oxygen transfer efficiencies, and other parameters in multilayer devices. Important parameters such as the fluidic resistance of interconnects are shown to become more predominant as devices are scaled towards many layers, while other effects such as membrane distensibility become less significant. The present study also probes the relationship between blood channel depth and membrane thickness on oxygen transfer, as well as the rate of oxygen transfer on the number of layers in the device. These results contribute to our understanding of the complexity involved in designing three-dimensional microfluidic oxygenators for clinical applications. PMID:22418858

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. Fabrication of PDMS-Based Microfluidic Devices: Application for Synthesis of Magnetic Nanoparticles

    NASA Astrophysics Data System (ADS)

    Thu, Vu Thi; Mai, An Ngoc; Le The Tam; Van Trung, Hoang; Thu, Phung Thi; Tien, Bui Quang; Thuat, Nguyen Tran; Lam, Tran Dai

    2016-05-01

    In this work, we have developed a convenient approach to synthesize magnetic nanoparticles with relatively high magnetization and controllable sizes. This was realized by combining the traditional co-precipitation method and microfluidic techniques inside microfluidic devices. The device was first designed, and then fabricated using simplified soft-lithography techniques. The device was utilized to synthesize magnetite nanoparticles. The synthesized nanomaterials were thoroughly characterized using field emission scanning electron microscopy and a vibrating sample magnetometer. The results demonstrated that the as-prepared device can be utilized as a simple and effective tool to synthesize magnetic nanoparticles with the sizes less than 10 nm and magnetization more than 50 emu/g. The development of these devices opens new strategies to synthesize nanomaterials with more precise dimensions at narrow size-distribution and with controllable behaviors.

  2. UV-nanoimprint lithography as a tool to develop flexible microfluidic devices for electrochemical detection.

    PubMed

    Chen, Juhong; Zhou, Yiliang; Wang, Danhui; He, Fei; Rotello, Vincent M; Carter, Kenneth R; Watkins, James J; Nugen, Sam R

    2015-07-21

    Research in microfluidic biosensors has led to dramatic improvements in sensitivities. Very few examples of these devices have been commercially successful, keeping this methodology out of the hands of potential users. In this study, we developed a method to fabricate a flexible microfluidic device containing electrowetting valves and electrochemical transduction. The device was designed to be amenable to a roll-to-roll manufacturing system, allowing a low manufacturing cost. Microchannels with high fidelity were structured on a PET film using UV-NanoImprint Lithography (UV-NIL). The electrodes were inkjet-printed and photonically sintered on second flexible PET film. The film containing electrodes was bonded directly to the channel-containing layer to form sealed fluidic device. Actuation of the multivalve system with food dye in PBS buffer was performed to demonstrate automated fluid delivery. The device was then used to detect Salmonella in a liquid sample. PMID:26095586

  3. Engineering controllable architecture in matrigel for 3D cell alignment.

    PubMed

    Jang, Jae Myung; Tran, Si-Hoai-Trung; Na, Sang Cheol; Jeon, Noo Li

    2015-02-01

    We report a microfluidic approach to impart alignment in ECM components in 3D hydrogels by continuously applying fluid flow across the bulk gel during the gelation process. The microfluidic device where each channel can be independently filled was tilted at 90° to generate continuous flow across the Matrigel as it gelled. The presence of flow helped that more than 70% of ECM components were oriented along the direction of flow, compared with randomly cross-linked Matrigel. Following the oriented ECM components, primary rat cortical neurons and mouse neural stem cells showed oriented outgrowth of neuronal processes within the 3D Matrigel matrix. PMID:25585718

  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. Thermal Blood Clot Formation and use in Microfluidic Device Valving Applications

    NASA Technical Reports Server (NTRS)

    Tai, Yu-Chong (Inventor); Shi, Wendian (Inventor); Guo, Luke (Inventor)

    2014-01-01

    The present invention provides a method of forming a blood-clot microvalve by heating blood in a capillary tube of a microfluidic device. Also described are methods of modulating liquid flow in a capillary tube by forming and removing a blood-clot microvalve.

  6. A Serial Sample Loading System: Interfacing Multi-well plates with Microfluidic Devices

    PubMed Central

    Rane, Tushar D.; Zec, Helena; Wang, Jeff Tza-Huei

    2013-01-01

    There is an increasing demand for novel high-throughput screening (HTS) technologies in the pharmaceutical and biotechnological industries. The robotic sample handling techniques currently used in these industries, although fast, are still limited to operating in multi-well plates with the sample volumes per reaction in the microliter regime. Digital microfluidics offers an alternative for reduction in sample volume consumption for HTS but lacks a reliable technique for transporting large number of samples to the microfluidic device. In this report, we develop a technique for serial delivery of sample arrays to a microfluidic device from multi-well plates, through a single sample inlet. Under this approach, a serial array of sample plugs, separated by an immiscible carrier fluid, is loaded into a capillary and delivered to a microfluidic device. Similar approaches have been attempted in the past, however, either with a slower sample loading device like syringe pump or vacuum based sample loading with limited driving pressure. We demonstrated the application of our positive pressure based ‘Serial Sample Loading’ (SSL) system to load a series of sample plugs into a capillary. The adaptability of the SSL system to generate sample plugs with a variety of volumes in a predictable manner was also demonstrated. PMID:22885789

  7. Student-Fabricated Microfluidic Devices as Flow Reactors for Organic and Inorganic Synthesis

    ERIC Educational Resources Information Center

    Feng, Z. Vivian; Edelman, Kate R.; Swanson, Benjamin P.

    2015-01-01

    Flow synthesis in microfluidic devices has been rapidly adapted in the pharmaceutical industry and in many research laboratories. Yet, the cost of commercial flow reactors is a major factor limiting the dissemination of this technology in the undergraduate curriculum. Here, we present a laboratory activity where students design and fabricate…

  8. Low-Cost Rapid Prototyping of Whole-Glass Microfluidic Devices

    ERIC Educational Resources Information Center

    Yuen, Po Ki; Goral, Vasiliy N.

    2012-01-01

    A low-cost, straightforward, rapid prototyping of whole-glass microfluidic devices is presented using glass-etching cream that can be easily purchased in local stores. A self-adhered vinyl stencil cut out by a desktop digital craft cutter was used as an etching mask for patterning microstructures in glass using the glass-etching cream. A specific…

  9. FLASH: a rapid method for prototyping paper-based microfluidic devices.

    PubMed

    Martinez, Andres W; Phillips, Scott T; Wiley, Benjamin J; Gupta, Malancha; Whitesides, George M

    2008-12-01

    This article describes FLASH (Fast Lithographic Activation of Sheets), a rapid method for laboratory prototyping of microfluidic devices in paper. Paper-based microfluidic devices are emerging as a new technology for applications in diagnostics for the developing world, where low cost and simplicity are essential. FLASH is based on photolithography, but requires only a UV lamp and a hotplate; no clean-room or special facilities are required (FLASH patterning can even be performed in sunlight if a UV lamp and hotplate are unavailable). The method provides channels in paper with dimensions as small as 200 microm in width and 70 microm in height; the height is defined by the thickness of the paper. Photomasks for patterning paper-based microfluidic devices can be printed using an ink-jet printer or photocopier, or drawn by hand using a waterproof black pen. FLASH provides a straightforward method for prototyping paper-based microfluidic devices in regions where the technological support for conventional photolithography is not available. PMID:19023478

  10. Generating Electric Fields in PDMS Microfluidic Devices with Salt Water Electrodes

    PubMed Central

    Sciambi, Adam; Abate, Adam R.

    2014-01-01

    Droplet merging and sorting in microfluidic devices usually rely on electric fields generated by solid metal electrodes. We show that simpler and more reliable salt water electrodes, despite their lower conductivity, can perform the same droplet manipulations at the same voltages. PMID:24671446

  11. Microfluidics in the Undergraduate Laboratory: Device Fabrication and an Experiment to Mimic Intravascular Gas Embolism

    ERIC Educational Resources Information Center

    Jablonski, Erin L.; Vogel, Brandon M.; Cavanagh, Daniel P.; Beers, Kathryn L.

    2010-01-01

    A method to fabricate microfluidic devices and an experimental protocol to model intravascular gas embolism for undergraduate laboratories are presented. The fabrication process details how to produce masters on glass slides; these masters serve as molds to pattern channels in an elastomeric polymer that can be adhered to a substrate, resulting in…

  12. From 1D to 3D: Tunable Sub-10 nm Gaps in Large Area Devices.

    PubMed

    Zhou, Ziwei; Zhao, Zhiyuan; Yu, Ye; Ai, Bin; Möhwald, Helmuth; Chiechi, Ryan C; Yang, Joel K W; Zhang, Gang

    2016-04-20

    Tunable sub-10 nm 1D nanogaps are fabricated based on nanoskiving. The electric field in different sized nanogaps is investigated theoretically and experimentally, yielding nonmonotonic dependence and an optimized gap-width (5 nm). 2D nanogap arrays are fabricated to pack denser gaps combining surface patterning techniques. Innovatively, 3D multistory nanogaps are built via a stacking procedure, processing higher integration, and much improved electric field. PMID:26890027

  13. Producing 3D neuronal networks in hydrogels for living bionic device interfaces.

    PubMed

    Aregueta-Robles, Ulises A; Lim, Khoon S; Martens, Penny J; Lovell, Nigel H; Poole-Warren, Laura A; Green, Rylie

    2015-08-01

    Hydrogels hold significant promise for supporting cell based therapies in the field of bioelectrodes. It has been proposed that tissue engineering principles can be used to improve the integration of neural interfacing electrodes. Degradable hydrogels based on poly (vinyl alcohol) functionalised with tyramine (PVA-Tyr) have been shown to support covalent incorporation of non-modified tyrosine rich proteins within synthetic hydrogels. PVA-Tyr crosslinked with such proteins, were explored as a scaffold for supporting development of neural tissue in a three dimensional (3D) environment. In this study a model neural cell line (PC12) and glial accessory cell line, Schwann cell (SC) were encapsulated in PVA-Tyr crosslinked with gelatin and sericin. Specifically, this study aimed to examine the growth and function of SC and PC12 co-cultures when translated from a two dimensional (2D) environment to a 3D environment. PC12 differentiation was successfully promoted in both 2D and 3D at 25 days post-culture. SC encapsulated as a single cell line and in co-culture were able to produce both laminin and collagen-IV which are required to support neuronal development. Neurite outgrowth in the 3D environment was confirmed by immunocytochemical staining. PVA-Tyr/sericin/gelatin hydrogel showed mechanical properties similar to nerve tissue elastic modulus. It is suggested that the mechanical properties of the PVA-Tyr hydrogels with native protein components are providing with a compliant substrate that can be used to support the survival and differentiation of neural networks. PMID:26736824

  14. 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.

  15. 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).

  16. A Two-Stage Microfluidic Device for the Isolation and Capture of Circulating Tumor Cells

    NASA Astrophysics Data System (ADS)

    Cook, Andrew; Belsare, Sayali; Giorgio, Todd; Mu, Richard

    2014-11-01

    Analysis of circulating tumor cells (CTCs) can be critical for studying how tumors grow and metastasize, in addition to personalizing treatment for cancer patients. CTCs are rare events in blood, making it difficult to remove CTCs from the blood stream. Two microfluidic devices have been developed to separate CTCs from blood. The first is a double spiral device that focuses cells into streams, the positions of which are determined by cell diameter. The second device uses ligand-coated magnetic nanoparticles that selectively attach to CTCs. The nanoparticles then pull CTCs out of solution using a magnetic field. These two devices will be combined into a single 2-stage microfluidic device that will capture CTCs more efficiently than either device on its own. The first stage depletes the number of blood cells in the sample by size-based separation. The second stage will magnetically remove CTCs from solution for study and culturing. Thus far, size-based separation has been achieved. Research will also focus on understanding the equations that govern fluid dynamics and magnetic fields in order to determine how the manipulation of microfluidic parameters, such as dimensions and flow rate, will affect integration and optimization of the 2-stage device. NSF-CREST: Center for Physics and Chemistry of Materials. HRD-0420516; Department of Defense, Peer Reviewed Medical Research Program Award W81XWH-13-1-0397.

  17. Biomedical microfluidic devices by using low-cost fabrication techniques: A review.

    PubMed

    Faustino, Vera; Catarino, Susana O; Lima, Rui; Minas, Graça

    2016-07-26

    One of the most popular methods to fabricate biomedical microfluidic devices is by using a soft-lithography technique. However, the fabrication of the moulds to produce microfluidic devices, such as SU-8 moulds, usually requires a cleanroom environment that can be quite costly. Therefore, many efforts have been made to develop low-cost alternatives for the fabrication of microstructures, avoiding the use of cleanroom facilities. Recently, low-cost techniques without cleanroom facilities that feature aspect ratios more than 20, for fabricating those SU-8 moulds have been gaining popularity among biomedical research community. In those techniques, Ultraviolet (UV) exposure equipment, commonly used in the Printed Circuit Board (PCB) industry, replaces the more expensive and less available Mask Aligner that has been used in the last 15 years for SU-8 patterning. Alternatively, non-lithographic low-cost techniques, due to their ability for large-scale production, have increased the interest of the industrial and research community to develop simple, rapid and low-cost microfluidic structures. These alternative techniques include Print and Peel methods (PAP), laserjet, solid ink, cutting plotters or micromilling, that use equipment available in almost all laboratories and offices. An example is the xurography technique that uses a cutting plotter machine and adhesive vinyl films to generate the master moulds to fabricate microfluidic channels. In this review, we present a selection of the most recent lithographic and non-lithographic low-cost techniques to fabricate microfluidic structures, focused on the features and limitations of each technique. Only microfabrication methods that do not require the use of cleanrooms are considered. Additionally, potential applications of these microfluidic devices in biomedical engineering are presented with some illustrative examples. PMID:26671220

  18. A numerical study of droplet trapping in microfluidic devices

    NASA Astrophysics Data System (ADS)

    Nagel, Mathias; Brun, P.-T.; Gallaire, François

    2014-03-01

    Microfluidic channels are powerful means of control of minute volumes such as droplets. These droplets are usually conveyed at will in an externally imposed flow which follows the geometry of the micro-channel. It has recently been pointed out by Dangla et al. ["Trapping microfluidic drops in wells of surface energy," Phys. Rev. Lett. 107(12), 124501 (2011)] that the motion of transported droplets may also be stopped in the flow, when they are anchored to grooves which are etched in the channels top wall. This feature of the channel geometry explores a direction that is usually uniform in microfluidics. Herein, this anchoring effect exploiting the three spatial directions is studied combining a depth averaged fluid description and a geometrical model that accounts for the shape of the droplet in the anchor. First, the presented method is shown to enable the capture and release droplets in numerical simulations. Second, this tool is used in a numerical investigation of the physical mechanisms at play in the capture of the droplet: a localized reduced Laplace pressure jump is found on its interface when the droplet penetrates the groove. This modified boundary condition helps the droplet cope with the linear pressure drop in the surrounding fluid. Held on the anchor the droplet deforms and stretches in the flow. The combination of these ingredients leads to recover the scaling law for the critical capillary number at which the droplets exit the anchors C a^{star} ∝ h2/R2 where h is the channel height and R the droplet undeformed radius.

  19. Polymer Coatings in 3D-Printed Fluidic Device Channels for Improved Cellular Adherence Prior to Electrical Lysis.

    PubMed

    Gross, Bethany C; Anderson, Kari B; Meisel, Jayda E; McNitt, Megan I; Spence, Dana M

    2015-06-16

    This paper describes the design and fabrication of a polyjet-based three-dimensional (3D)-printed fluidic device where poly(dimethylsiloxane) (PDMS) or polystyrene (PS) were used to coat the sides of a fluidic channel within the device to promote adhesion of an immobilized cell layer. The device was designed using computer-aided design software and converted into an .STL file prior to printing. The rigid, transparent material used in the printing process provides an optically transparent path to visualize endothelial cell adherence and supports integration of removable electrodes for electrical cell lysis in a specified portion of the channel (1 mm width × 0.8 mm height × 2 mm length). Through manipulation of channel geometry, a low-voltage power source (500 V max) was used to selectively lyse adhered endothelial cells in a tapered region of the channel. Cell viability was maintained on the device over a 5 day period (98% viable), though cell coverage decreased after day 4 with static media delivery. Optimal lysis potentials were obtained for the two fabricated device geometries, and selective cell clearance was achieved with cell lysis efficiencies of 94 and 96%. The bottleneck of unknown surface properties from proprietary resin use in fabricating 3D-printed materials is overcome through techniques to incorporate PDMS and PS. PMID:25973637

  20. A microfluidic device for epigenomic profiling using 100 cells.

    PubMed

    Cao, Zhenning; Chen, Changya; He, Bing; Tan, Kai; Lu, Chang

    2015-10-01

    The sensitivity of chromatin immunoprecipitation (ChIP) assays poses a major obstacle for epigenomic studies of low-abundance cells. Here we present a microfluidics-based ChIP-seq protocol using as few as 100 cells via drastically improved collection of high-quality ChIP-enriched DNA. Using this technology, we uncovered many new enhancers and super enhancers in hematopoietic stem and progenitor cells from mouse fetal liver, suggesting that enhancer activity is highly dynamic during early hematopoiesis. PMID:26214128

  1. In situ serial Laue diffraction on a microfluidic crystallization device

    PubMed Central

    Perry, Sarah L.; Guha, Sudipto; Pawate, Ashtamurthy S.; Henning, Robert; Kosheleva, Irina; Srajer, Vukica; Kenis, Paul J. A.; Ren, Zhong

    2014-01-01

    Renewed interest in room-temperature diffraction has been prompted by the desire to observe structural dynamics of proteins as they function. Serial crystallography, an experimental strategy that aggregates small pieces of data from a large uniform pool of crystals, has been demonstrated at synchrotrons and X-ray free-electron lasers. This work utilizes a microfluidic crystallization platform for serial Laue diffraction from macroscopic crystals and proposes that a collection of small slices of Laue data from many individual crystals is a realistic solution to the difficulties in dynamic studies of irreversible biochemical reactions. PMID:25484843

  2. A microfluidic device for epigenomic profiling using 100 cells

    PubMed Central

    Cao, Zhenning; Chen, Changya; He, Bing; Tan, Kai; Lu, Chang

    2015-01-01

    The sensitivity of chromatin immunoprecipitation (ChIP) assays poses a major obstacle for epigenomic studies of low-abundance cells. Here we present a microfluidics-based ChIP-Seq protocol using as few as 100 cells via drastically improved collection of high-quality ChIP-enriched DNA. Using this technology, we uncovered many novel enhancers and super enhancers in hematopoietic stem and progenitor cells from mouse fetal liver, suggesting that enhancer activity is highly dynamic during early hematopoiesis. PMID:26214128

  3. Modeling the geometric effects on programming characteristics for the TANOS device by developing a 3D self-consistent simulation

    NASA Astrophysics Data System (ADS)

    Jeon, Kwang Sun; Choe, Kyu Sik; Choi, Seongwook; Park, Sang Yong; Park, Young-June

    2013-01-01

    This paper reports a study on the programming characteristics of the TANOS (Ti gate - Al2O3-Si3N4-SiO2-Si) device using a 3-dimensional self-consistent numerical simulation. The STI (Shallow Trench Isolation) structure is considered in TANOS device simulation. The program characteristics are investigated in various active space and gate dimensions (width and channel length) using numerical simulation. It is found from the simulation that the STI effect becomes more important as the device size is scaled down. Since the STI effect is dependent on the channel width, length, and STI width, the framework of 3D simulation is crucial for scaled TANOS device design.

  4. 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. PMID:26626777

  5. High-Throughput Microfluidic Device for Circulating Tumor Cell Isolation from Whole Blood

    PubMed Central

    Yang, Daniel K.; Leong, Serena; Sohn, Lydia L.

    2016-01-01

    Circulating tumor cells (CTCs) are promising markers to determine cancer patient prognosis and track disease response to therapy. We present a multi-stage microfluidic device we have developed that utilizes inertial and Dean drag forces for isolating CTCs from whole blood. We demonstrate a 94.2% ± 2.1% recovery of cancer cells with our device when screening whole blood spiked with MCF-7 GFP cells.

  6. Photoinitiated grafting of porous polymer monoliths and thermoplastic polymers for microfluidic devices

    DOEpatents

    Frechet, Jean M. J.; Svec, Frantisek; Rohr, Thomas

    2008-10-07

    A microfluidic device preferably made of a thermoplastic polymer that includes a channel or a multiplicity of channels whose surfaces are modified by photografting. The device further includes a porous polymer monolith prepared via UV initiated polymerization within the channel, and functionalization of the pore surface of the monolith using photografting. Processes for making such surface modifications of thermoplastic polymers and porous polymer monoliths are set forth.

  7. 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. PMID:26838854

  8. Epitaxial MoS2/GaN structures to enable vertical 2D/3D semiconductor heterostructure devices

    NASA Astrophysics Data System (ADS)

    Ruzmetov, D.; Zhang, K.; Stan, G.; Kalanyan, B.; Eichfeld, S.; Burke, R.; Shah, P.; O'Regan, T.; Crowne, F.; Birdwell, A. G.; Robinson, J.; Davydov, A.; Ivanov, T.

    MoS2/GaN structures are investigated as a building block for vertical 2D/3D semiconductor heterostructure devices that utilize a 3D substrate (GaN) as an active component of the semiconductor device without the need of mechanical transfer of the 2D layer. Our CVD-grown monolayer MoS2 has been shown to be epitaxially aligned to the GaN lattice which is a pre-requisite for high quality 2D/3D interfaces desired for efficient vertical transport and large area growth. The MoS2 coverage is nearly 50 % including isolated triangles and monolayer islands. The GaN template is a double-layer grown by MOCVD on sapphire and allows for measurement of transport perpendicular to the 2D layer. Photoluminescence, Raman, XPS, Kelvin force probe microscopy, and SEM analysis identified high quality monolayer MoS2. The MoS2/GaN structures electrically conduct in the out-of-plane direction and across the van der Waals gap, as measured with conducting AFM (CAFM). The CAFM current maps and I-V characteristics are analyzed to estimate the MoS2/GaN contact resistivity to be less than 4 Ω-cm2 and current spreading in the MoS2 monolayer to be approx. 1 μm in diameter. Epitaxial MoS2/GaN heterostructures present a promising platform for the design of energy-efficient, high-speed vertical devices incorporating 2D layered materials with 3D semiconductors.

  9. Demonstration of an integrated electroactive polymer actuator on a microfluidic electrophoresis device.

    PubMed

    Price, Alexander K; Anderson, Kristen M; Culbertson, Christopher T

    2009-07-21

    The construction of microfluidic devices from siloxane-based polymers is widely reported in the current literature. While the use of these materials is primarily due to their rapid and facile fabrication, low cost and robustness, they also have the ability to function as smart materials. This feature, however, has not been commonly exploited in conjunction with their fluid-handling capabilities. Siloxanes are considered smart materials because their shapes can be modified in the presence of an electric field. The energy in the electric field can be transduced into mechanical energy and directly coupled with a microfabricated channel network in order to affect or initiate the movement of fluids. Here, we present a novel microfluidic device into which an electroactive polymer (EAP) actuation unit is integrated. The EAP actuation unit features a microfluidic channel placed above a patterned electrode. The patterned electrode is insulated from the channel by an EAP layer that is composed of PDMS. When a potential is applied across the EAP layer, it changes shape, which also changes the volume of the microfluidic channel above it. With this proof-of-concept device we demonstrated the ability to inject plugs of sample on a standard electrophoresis cross chip solely by changing the magnitude of the electric field between the channel and the electrode. Using an EAP actuation unit, the size of the injection plugs can be varied as a function of the electric field, the active area of the EAP actuation unit and the softness of the EAP. PMID:19568678

  10. Microfluidic Reactor Array Device for Massively Parallel In-situ Synthesis of Oligonucleotides

    PubMed Central

    Srivannavit, Onnop; Gulari, Mayurachat; Hua, Zhishan.; Gao, Xiaolian; Zhou, Xiaochuan; Hong, Ailing; Zhou, Tiecheng; Gulari, Erdogan

    2009-01-01

    We have designed and fabricated a microfluidic reactor array device for massively parallel in-situ synthesis of oligonucleotides (oDNA). The device is made of glass anodically bonded to silicon consisting of three level features: microreactors, microchannels and through inlet/outlet holes. Main challenges in the design of this device include preventing diffusion of photogenerated reagents upon activation and achieving uniform reagent flow through thousands of parallel reactors. The device embodies a simple and effective dynamic isolation mechanism which prevents the intermixing of active reagents between discrete microreactors. Depending on the design parameters, it is possible to achieve uniform flow and synthesis reaction in all of the reactors by proper design of the microreactors and the microchannels. We demonstrated the use of this device on a solution-based, light-directed parallel in-situ oDNA synthesis. We were able to synthesize long oDNA, up to 120 mers at stepwise yield of 98 %. The quality of our microfluidic oDNA microarray including sensitivity, signal noise, specificity, spot variation and accuracy was characterized. Our microfluidic reactor array devices show a great potential for genomics and proteomics researches. PMID:20161215

  11. Mammosphere culture of cancer stem cells in a microfluidic device

    NASA Astrophysics Data System (ADS)

    Saadin, Katayoon; White, Ian M.

    2012-03-01

    It is known that tumor-initiating cells with stem-like properties will form spherical colonies - termed mammospheres - when cultured in serum-free media on low-attachment substrates. Currently this assay is performed in commercially available 96-well trays with low-attachment surfaces. Here we report a novel microsystem that features on-chip mammosphere culture on low attachment surfaces. We have cultured mammospheres in this microsystem from well-studied human breast cancer cell lines. To enable the long-term culture of these unattached cells, we have integrated diffusion-based delivery columns that provide zero-convection delivery of reagents, such as fresh media, staining agents, or drugs. The multi-layer system consists of parallel cell-culture chambers on top of a low-attachment surface, connected vertically with a microfluidic reagent delivery layer. This design incorporates a reagent reservoir, which is necessary to reduce evaporation from the cell culture micro-chambers. The development of this microsystem will lead to the integration of mammosphere culture with other microfluidic functions, including circulating tumor cell recovery and high throughput drug screening. This will enable the cancer research community to achieve a much greater understanding of these tumor initiating cancer stem cells.

  12. Microwave dielectric heating of fluids in an integrated microfluidic device

    NASA Astrophysics Data System (ADS)

    Shah, Jayna J.; Sundaresan, Siddarth G.; Geist, Jon; Reyes, Darwin R.; Booth, James C.; Rao, Mulpuri V.; Gaitan, Michael

    2007-11-01

    The ability to selectively and precisely control the temperature of fluid volumes ranging from a few microliters to sub-nanoliters in microfluidic networks is vital for a wide range of applications in micro total analysis systems (μTAS). In this work, we characterize and model the performance of a thin film microwave transmission line integrated with a microfluidic channel to heat fluids with relevant buffer salt concentrations over a wide range of frequencies. A microchannel fabricated in poly(dimethylsiloxane) (PDMS) is aligned with a thin film microwave transmission line in a coplanar waveguide (CPW) configuration. The electromagnetic fields localized in the gap between the signal and ground lines of the transmission line dielectrically heat the fluid in the selected region of the microchannel. Microwave S-parameter measurements and optical fluorescence-based temperature measurements are used with a theoretical model developed based on classical microwave absorption theory to fully characterize the temperature rise of the fluid. We observe a 0.95 °C mW-1 temperature rise at 15 GHz and confirm that the temperature rise of the fluid is predominantly due to microwave dielectric heating.

  13. Fabrication and characterization of polymer microfluidic devices for bio-agent detection

    NASA Astrophysics Data System (ADS)

    Morales, Alfredo M.; Brazzle, John D.; Crocker, Robert W.; Domeier, Linda A.; Goods, Eric B.; Hachman, John T., Jr.; Harnett, Cindy K.; Hunter, Marion C.; Mani, Seethambal S.; Mosier, Bruce P.; Simmons, Blake A.

    2004-12-01

    Sandia and Lawrence Livermore National Laboratories are developing a briefcase-sized, broad-spectrum bioagent detection system. This autonomous instrument, the BioBriefcase, will monitor the environment and warn against bacterium, virus, and toxin based biological attacks. At the heart of this device, inexpensive polymer microfluidic chips will carry out sample preparation and analysis. Fabrication of polymer microfluidic chips involves the creation of a master in etched glass; plating of the master to produce a nickel stamp; large lot chip replication by injection molding; and thermal chip sealing. Since the performance and reliability of microfluidic chips are very sensitive to fluidic impedance and to electromagnetic fluxes, the microchannel dimensions and shape have to be tightly controlled during chip fabrication. In this talk, we will present an overview of chip design and fabrication. Metrology data collected at different fabrication steps and the dimensional deviations of the polymer chip from the original design will be discussed.

  14. Fabrication and characterization of polymer microfluidic devices for bio-agent detection

    NASA Astrophysics Data System (ADS)

    Morales, Alfredo M.; Brazzle, John D.; Crocker, Robert W.; Domeier, Linda A.; Goods, Eric B.; Hachman, John T., Jr.; Harnett, Cindy K.; Hunter, Marion C.; Mani, Seethambal S.; Mosier, Bruce P.; Simmons, Blake A.

    2005-01-01

    Sandia and Lawrence Livermore National Laboratories are developing a briefcase-sized, broad-spectrum bioagent detection system. This autonomous instrument, the BioBriefcase, will monitor the environment and warn against bacterium, virus, and toxin based biological attacks. At the heart of this device, inexpensive polymer microfluidic chips will carry out sample preparation and analysis. Fabrication of polymer microfluidic chips involves the creation of a master in etched glass; plating of the master to produce a nickel stamp; large lot chip replication by injection molding; and thermal chip sealing. Since the performance and reliability of microfluidic chips are very sensitive to fluidic impedance and to electromagnetic fluxes, the microchannel dimensions and shape have to be tightly controlled during chip fabrication. In this talk, we will present an overview of chip design and fabrication. Metrology data collected at different fabrication steps and the dimensional deviations of the polymer chip from the original design will be discussed.

  15. A spheroid toxicity assay using magnetic 3D bioprinting and real-time mobile device-based imaging.

    PubMed

    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

  16. 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

  17. Real-time Functional Analysis of Inertial Microfluidic Devices via Spectral Domain Optical Coherence Tomography.

    PubMed

    Dong, Biqin; Chen, Siyu; Zhou, Fan; Chan, Christina H Y; Yi, Ji; Zhang, Hao F; Sun, Cheng

    2016-01-01

    We report the application of spectral-domain optical coherence tomography (SD-OCT) technology that enables real-time functional analysis of sorting microparticles and cells in an inertial microfluidic device. We demonstrated high-speed, high-resolution acquisition of cross-sectional images at a frame rate of 350 Hz, with a lateral resolution of 3 μm and an axial resolution of 1 μm within the microfluidic channel filled with water. We analyzed the temporal sequence of cross-sectional SD-OCT images to determine the position and diameter of microspheres in a spiral microfluidic channel under various flow rates. We used microspheres with known diameters to validate the sub-micrometer precision of the particle size analysis based on a scattering model of spherical microparticles. An additional investigation of sorting live HT-29 cells in the spiral microfluidic channel indicated that the distribution of cells within in the microchannel has a close correspondence with the cells' size distribution. The label-free real-time imaging and analysis of microscale particles in flow offers robustness for practical applications with live cells and allows us to better understand the mechanisms of particle separations in microfluidic sorting systems. PMID:27619202

  18. 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.

  19. Novel developments in mobile sensing based on the integration of microfluidic devices and smartphones.

    PubMed

    Yang, Ke; Peretz-Soroka, Hagit; Liu, Yong; Lin, Francis

    2016-03-21

    Portable electronic devices and wireless communication systems enable a broad range of applications such as environmental and food safety monitoring, personalized medicine and healthcare management. Particularly, hybrid smartphone and microfluidic devices provide an integrated solution for the new generation of mobile sensing applications. Such mobile sensing based on microfluidic devices (broadly defined) and smartphones (MS(2)) offers a mobile laboratory for performing a wide range of bio-chemical detection and analysis functions such as water and food quality analysis, routine health tests and disease diagnosis. MS(2) offers significant advantages over traditional platforms in terms of test speed and control, low cost, mobility, ease-of-operation and data management. These improvements put MS(2) in a promising position in the fields of interdisciplinary basic and applied research. In particular, MS(2) enables applications to remote in-field testing, homecare, and healthcare in low-resource areas. The marriage of smartphones and microfluidic devices offers a powerful on-chip operating platform to enable various bio-chemical tests, remote sensing, data analysis and management in a mobile fashion. The implications of such integration are beyond telecommunication and microfluidic-related research and technology development. In this review, we will first provide the general background of microfluidic-based sensing, smartphone-based sensing, and their integration. Then, we will focus on several key application areas of MS(2) by systematically reviewing the important literature in each area. We will conclude by discussing our perspectives on the opportunities, issues and future directions of this emerging novel field. PMID:26899264

  20. A versatile valving toolkit for automating fluidic operations in paper microfluidic devices

    PubMed Central

    Toley, Bhushan J.; Wang, Jessica A.; Gupta, Mayuri; Buser, Joshua R.; Lafleur, Lisa K.; Lutz, Barry R.; Fu, Elain; Yager, Paul

    2015-01-01

    Failure to utilize valving and automation techniques has restricted the complexity of fluidic operations that can be performed in paper microfluidic devices. We developed a toolkit of paper microfluidic valves and methods for automatic valve actuation using movable paper strips and fluid-triggered expanding elements. To the best of our knowledge, this is the first functional demonstration of this valving strategy in paper microfluidics. After introduction of fluids on devices, valves can actuate automatically a) after a certain period of time, or b) after the passage of a certain volume of fluid. Timing of valve actuation can be tuned with greater than 8.5% accuracy by changing lengths of timing wicks, and we present timed on-valves, off-valves, and diversion (channel-switching) valves. The actuators require ~30 μl fluid to actuate and the time required to switch from one state to another ranges from ~5 s for short to ~50s for longer wicks. For volume-metered actuation, the size of a metering pad can be adjusted to tune actuation volume, and we present two methods – both methods can achieve greater than 9% accuracy. Finally, we demonstrate the use of these valves in a device that conducts a multi-step assay for the detection of the malaria protein PfHRP2. Although slightly more complex than devices that do not have moving parts, this valving and automation toolkit considerably expands the capabilities of paper microfluidic devices. Components of this toolkit can be used to conduct arbitrarily complex, multi-step fluidic operations on paper-based devices, as demonstrated in the malaria assay device. PMID:25606810

  1. 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. PMID:25962333

  2. Low cost production of 3D-printed devices and electrostimulation chambers for the culture of primary neurons

    PubMed Central

    Wardyn, Joanna D.; Sanderson, Chris; Swan, Laura E.; Stagi, Massimiliano

    2015-01-01

    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. PMID:25962333

  3. Organization of Endothelial Cells, Pericytes, and Astrocytes into a 3D Microfluidic in Vitro Model of the Blood-Brain Barrier.

    PubMed

    Wang, Jack D; Khafagy, El-Sayed; Khanafer, Khalil; Takayama, Shuichi; ElSayed, Mohamed E H

    2016-03-01

    The endothelial cells lining the capillaries supplying the brain with oxygen and nutrients form a formidable barrier known as the blood-brain barrier (BBB), which exhibits selective permeability to small drug molecules and virtually impermeable to macromolecular therapeutics. Current in vitro BBB models fail to replicate this restrictive behavior due to poor integration of the endothelial cells with supporting cells (pericytes and astrocytes) following the correct anatomical organization observed in vivo. We report the coculture of mouse brain microvascular endothelial cells (b.End3), pericytes, with/without C8-D1A astrocytes in layered microfluidic channels forming three-dimensional (3D) bi- and triculture models of the BBB. The live/dead assay indicated high viability of all cultured cells up to 21 days. Trans-endothelial electrical resistance (TEER) values confirmed the formation of intact monolayers after 3 days in culture and showed statistically higher values for the triculture model compared to the single and biculture models. Screening the permeability of [(14)C]-mannitol and [(14)C]-urea showed the ability of bi- and triculture models to discriminate between different markers based on their size. Further, permeability of [(14)C]-mannitol across the triculture model after 18 days in culture matched its reported permeability across the BBB in vivo. Mathematical calculations also showed that the radius of the tight junctions pores (R) in the triculture model is similar to the reported diameter of the BBB in vivo. Finally, both the bi- and triculture models exhibited functional expression of the P-glycoprotein efflux pump, which increased with the increase in the number of days in culture. These results collectively indicate that the triculture model is a robust in vitro model of the BBB. PMID:26751280

  4. Use of electrospinning and dynamic air focusing to create three-dimensional cell culture scaffolds in microfluidic devices.

    PubMed

    Chen, Chengpeng; Mehl, Benjamin T; Sell, Scott A; Martin, R Scott

    2016-09-21

    those cultured on a thin layer of PCL in a channel or directly on the inner channel wall. Overall, this study represents a new approach for in vitro cell studies, where electrospinning can be used to easily and quickly create 3D scaffolds that can improve the culture conditions in microfluidic devices. PMID:27373715

  5. Development of a PMMA Electrochemical Microfluidic Device for Carcinoembryonic Antigen Detection

    NASA Astrophysics Data System (ADS)

    Van Anh, Nguyen; Van Trung, Hoang; Tien, Bui Quang; Binh, Nguyen Hai; Ha, Cao Hong; Le Huy, Nguyen; Loc, Nguyen Thai; Thu, Vu Thi; Lam, Tran Dai

    2016-05-01

    In this study, a poly(methyl methacrylate) (PMMA) microfluidic device fabricated by an inexpensive CO2 laser etching system was developed for detection of carcino-embryonic antigens (CEA). The device was capable of working in continuous mode and was designed with the aid of numerical simulation. The detection of target CEA was based on immuno-assay via magnetic particles and electrochemical sensing. The as-prepared microfluidic can be used to detect CEA at the relatively low concentration of 150 pg mL-1. The device could be reused many times, since the capture and removal of magnetic particles in the assay could be manipulated by an external magnetic field. The proposed approach appears to be suitable for high-throughput and automated analysis of large biomolecules such as tumor markers and pathogens.

  6. Microfluidic LC Device with Orthogonal Sample Extraction for On-Chip MALDI-MS Detection

    PubMed Central

    Lazar, Iulia M.; Kabulski, Jarod L.

    2013-01-01

    A microfluidic device that enables on-chip matrix assisted laser desorption ionization-mass spectrometry (MALDI-MS) detection for liquid chromatography (LC) separations is described. The device comprises an array of functional elements to carry out LC separations, integrates a novel microchip-MS interface to facilitate the orthogonal transposition of the microfluidic LC channel into an array of reservoirs, and enables sensitive MALDI-MS detection directly from the chip. Essentially, the device provides a snapshot MALDI-MS map of the content of the separation channel present on the chip. The detection of proteins with biomarker potential from MCF10A breast epithelial cell extracts, and detection limits in the low fmol range, are demonstrated. In addition, the design of the novel LC-MALDI-MS chip entices the promotion of a new concept for performing sample separations within the limited time-frame that accompanies the dead-volume of a separation channel. PMID:23592150

  7. Characterization of light-controlled Volvox as movable microvalve element assembled in multilayer microfluidic device

    NASA Astrophysics Data System (ADS)

    Nagai, Moeto; Oguri, Michihito; Shibata, Takayuki

    2015-06-01

    We report a model of a light-controlled microvalve driven by Volvox and characterization of Volvox as a movable microvalve element in a multilayer microfluidic device for development of the valve. First, a three-layer microfluidic device having a single through-hole was fabricated by a replica molding process. The fabricated devices met the requirements for experiments using Volvox. Second, we used the phototactic behavior of V. carteri and controlled its motions in a microchannel by illuminating light. V. carteri migrated to the light source in the channel. Third, a colony of V. carteri was placed on a microhole, and the colony was found to stop the flow compared to the flow without Volvox on the hole. The integration of all of the obtained findings is expected to lead to the fabrication of the proposed microvalve.

  8. Rapid fabrication of microfluidic PDMS devices from reusable PDMS molds using laser ablation

    NASA Astrophysics Data System (ADS)

    Isiksacan, Ziya; Tahsin Guler, M.; Aydogdu, Berkan; Bilican, Ismail; Elbuken, Caglar

    2016-03-01

    The conventional fabrication methods for microfluidic devices require cleanroom processes that are costly and time-consuming. We present a novel, facile, and low-cost method for rapid fabrication of polydimethylsiloxane (PDMS) molds and devices. The method consists of three main fabrication steps: female mold (FM), male mold (MM), and chip fabrication. We use a CO2 laser cutter to pattern a thin, spin-coated PDMS layer for FM fabrication. We then obtain reusable PDMS MM from the FM using PDMS/PDMS casting. Finally, a second casting step is used to replicate PDMS devices from the MM. Demolding of one PDMS layer from another is carried out without any potentially hazardous chemical surface treatment. We have successfully demonstrated that this novel method allows fabrication of microfluidic molds and devices with precise dimensions (thickness, width, length) using a single material, PDMS, which is very common across microfluidic laboratories. The whole process, from idea to device testing, can be completed in 1.5 h in a standard laboratory.

  9. Design of a microfluidic device to quantify dynamic intra-nuclear deformation during cell migration through confining environments

    PubMed Central

    Davidson, Patricia M.; Sliz, Josiah; Isermann, Philipp; Denais, Celine; Lammerding, Jan

    2015-01-01

    The ability of cells to migrate through tissues and interstitial space is an essential factor during development and tissue homeostasis, immune cell mobility, and in various human diseases. Deformation of the nucleus and its associated lamina during 3-D migration is gathering increasing interest in the context of cancer metastasis, with the underlying hypothesis that a softer nucleus, resulting from reduced levels of lamin A/C, may aid tumour spreading. However, current methods to study the migration of cells in confining three dimensional (3-D) environments are limited by their imprecise control over the confinement, physiological relevance, and/or compatibility with high resolution imaging techniques. We describe the design of a polydimethylsiloxane (PDMS) microfluidic device composed of channels with precisely-defined constrictions mimicking physiological environments that enable high resolution imaging of live and fixed cells. The device promotes easy cell loading and rapid, yet long-lasting (>24 hours) chemotactic gradient formation without the need for continuous perfusion. Using this device, we obtained detailed, quantitative measurements of dynamic nuclear deformation as cells migrate through tight spaces, revealing distinct phases of nuclear translocation through the constriction, buckling of the nuclear lamina, and severe intranuclear strain. Furthermore, we found that lamin A/C-deficient cells exhibited increased and more plastic nuclear deformations compared to wild-type cells but only minimal changes in nuclear volume, implying that low lamin A/C levels facilitate migration through constrictions by increasing nuclear deformability rather than compressibility. The integration of our migration devices with high resolution time-lapse imaging provides a powerful new approach to study intracellular mechanics and dynamics in a variety of physiologically-relevant applications, ranging from cancer cell invasion to immune cell recruitment. PMID:26549481

  10. Remote Detection of Explosive Molecules by a Microfluidic SERS Device

    NASA Astrophysics Data System (ADS)

    Piorek, Brian; Lee, Seung Joon; Moskovits, Martin; Banerjee, Sanjoy; Meinhart, Carl

    2007-11-01

    Free-surface microfluidics (FSF) is combined with surface-enhanced Raman spectroscopy (SERS) to detect trace explosives vapors at room temperature and pressure. A free surface, with a large surface to volume ratio, is created using an open microchannel. Since surface tension is a dominant force at the microscale, it can be used to confine the fluid in the microchannel and create a pressure gradient to drive the flow with velocities ranging from ˜ 1um/s - 1mm/s. The curvature of the free surface is measured by confocal microscopy in order to determine the local Laplace pressure in the free-surface microchannel flow. The system has been used for the molecular-specific detection of vapor emanated from explosives such as DNT, TNT and picric acid. The system does not show signs of performance degradation from common interferents such as saturated gasoline vapor and perfume.

  11. Towards time-resolved serial crystallography in a microfluidic device

    PubMed Central

    Pawate, Ashtamurthy S.; Šrajer, Vukica; Schieferstein, Jeremy; Guha, Sudipto; Henning, Robert; Kosheleva, Irina; Schmidt, Marius; Ren, Zhong; Kenis, Paul J. A.; Perry, Sarah L.

    2015-01-01

    Serial methods for crystallography have the potential to enable dynamic structural studies of protein targets that have been resistant to single-crystal strategies. The use of serial data-collection strategies can circumvent challenges associated with radiation damage and repeated reaction initiation. This work utilizes a microfluidic crystallization platform for the serial time-resolved Laue diffraction analysis of macroscopic crystals of photoactive yellow protein (PYP). Reaction initiation was achieved via pulsed laser illumination, and the resultant electron-density difference maps clearly depict the expected pR1/pRE46Q and pR2/pRCW states at 10 µs and the pB1 intermediate at 1 ms. The strategies presented here have tremendous potential for extension to chemical triggering methods for reaction initiation and for extension to dynamic, multivariable analyses. PMID:26144226

  12. Accurate and rapid micromixer for integrated microfluidic devices

    SciTech Connect

    Van Dam, R. Michael; Liu, Kan; Shen, Kwang -Fu Clifton; Tseng, Hsian -Rong

    2015-09-22

    The invention may provide a microfluidic mixer having a droplet generator and a droplet mixer in selective fluid connection with the droplet generator. The droplet generator comprises first and second fluid chambers that are structured to be filled with respective first and second fluids that can each be held in isolation for a selectable period of time. The first and second fluid chambers are further structured to be reconfigured into a single combined chamber to allow the first and second fluids in the first and second fluid chambers to come into fluid contact with each other in the combined chamber for a selectable period of time prior to being brought into the droplet mixer.

  13. Novel low-cost 2D/3D switchable autostereoscopic system for notebook computers and other portable devices

    NASA Astrophysics Data System (ADS)

    Eichenlaub, Jesse B.

    1995-03-01

    Mounting a lenticular lens in front of a flat panel display is a well known, inexpensive, and easy way to create an autostereoscopic system. Such a lens produces half resolution 3D images because half the pixels on the LCD are seen by the left eye and half by the right eye. This may be acceptable for graphics, but it makes full resolution text, as displayed by common software, nearly unreadable. Very fine alignment tolerances normally preclude the possibility of removing and replacing the lens in order to switch between 2D and 3D applications. Lenticular lens based displays are therefore limited to use as dedicated 3D devices. DTI has devised a technique which removes this limitation, allowing switching between full resolution 2D and half resolution 3D imaging modes. A second element, in the form of a concave lenticular lens array whose shape is exactly the negative of the first lens, is mounted on a hinge so that it can be swung down over the first lens array. When so positioned the two lenses cancel optically, allowing the user to see full resolution 2D for text or numerical applications. The two lenses, having complementary shapes, naturally tend to nestle together and snap into perfect alignment when pressed together--thus obviating any need for user operated alignment mechanisms. This system represents an ideal solution for laptop and notebook computer applications. It was devised to meet the stringent requirements of a laptop computer manufacturer including very compact size, very low cost, little impact on existing manufacturing or assembly procedures, and compatibility with existing full resolution 2D text- oriented software as well as 3D graphics. Similar requirements apply to high and electronic calculators, several models of which now use LCDs for the display of graphics.

  14. Nanoelectronics Meets Biology: From Novel Nanoscale Devices for Live Cell Recording to 3D Innervated Tissues†

    PubMed Central

    Duan, Xiaojie; Lieber, Charles M.

    2013-01-01

    High spatio-temporal resolution interfacing between electrical sensors and biological systems, from single live cells to tissues, is crucial for many areas, including fundamental biophysical studies as well as medical monitoring and intervention. This focused review summarizes recent progresses in the development and application of novel nanoscale devices for intracellular electrical recordings of action potentials, and the effort of merging electronic and biological systems seamlessly in three dimension using macroporous nanoelectronic scaffolds. The uniqueness of these nanoscale devices for minimally invasive, large scale, high spatial resolution, and three dimensional neural activity mapping will be highlighted. PMID:23946279

  15. An electric stimulation system for electrokinetic particle manipulation in microfluidic devices

    NASA Astrophysics Data System (ADS)

    Lopez-de la Fuente, M. S.; Moncada-Hernandez, H.; Perez-Gonzalez, V. H.; Lapizco-Encinas, B. H.; Martinez-Chapa, S. O.

    2013-03-01

    Microfluidic devices have grown significantly in the number of applications. Microfabrication techniques have evolved considerably; however, electric stimulation systems for microdevices have not advanced at the same pace. Electric stimulation of micro-fluidic devices is an important element in particle manipulation research. A flexible stimulation instrument is desired to perform configurable, repeatable, automated, and reliable experiments by allowing users to select the stimulation parameters. The instrument presented here is a configurable and programmable stimulation system for electrokinetic-driven microfluidic devices; it consists of a processor, a memory system, and a user interface to deliver several types of waveforms and stimulation patterns. It has been designed to be a flexible, highly configurable, low power instrument capable of delivering sine, triangle, and sawtooth waveforms with one single frequency or two superimposed frequencies ranging from 0.01 Hz to 40 kHz, and an output voltage of up to 30 Vpp. A specific stimulation pattern can be delivered over a single time period or as a sequence of different signals for different time periods. This stimulation system can be applied as a research tool where manipulation of particles suspended in liquid media is involved, such as biology, medicine, environment, embryology, and genetics. This system has the potential to lead to new schemes for laboratory procedures by allowing application specific and user defined electric stimulation. The development of this device is a step towards portable and programmable instrumentation for electric stimulation on electrokinetic-based microfluidic devices, which are meant to be integrated with lab-on-a-chip devices.

  16. Comparison of Chip Inlet Geometry in Microfluidic Devices for Cell Studies.

    PubMed

    Sun, Yung-Shin

    2016-01-01

    Micro-fabricated devices integrated with fluidic components provide an in vitro platform for cell studies best mimicking the in vivo micro-environment. These devices are capable of creating precise and controllable surroundings of pH value, temperature, salt concentration, and other physical or chemical stimuli. Various cell studies such as chemotaxis and electrotaxis can be performed by using such devices. Moreover, microfluidic chips are designed and fabricated for applications in cell separations such as circulating tumor cell (CTC) chips. Usually, there are two most commonly used inlets in connecting the microfluidic chip to sample/reagent loading tubes: the vertical (top-loading) inlet and the parallel (in-line) inlet. Designing this macro-to-micro interface is believed to play an important role in device performance. In this study, by using the commercial COMSOL Multiphysics software, we compared the cell capture behavior in microfluidic devices with different inlet types and sample flow velocities. Three different inlets were constructed: the vertical inlet, the parallel inlet, and the vertically parallel inlet. We investigated the velocity field, the flow streamline, the cell capture rate, and the laminar shear stress in these inlets. It was concluded that the inlet should be designed depending on the experimental purpose, i.e., one wants to maximize or minimize cell capture. Also, although increasing the flow velocity could reduce cell sedimentation, too high shear stresses are thought harmful to cells. Our findings indicate that the inlet design and flow velocity are crucial and should be well considered in fabricating microfluidic devices for cell studies. PMID:27314318

  17. A monolithically three-dimensional flow-focusing device for formation of single/double emulsions in closed/open microfluidic systems

    NASA Astrophysics Data System (ADS)

    Huang, Shih-Hao; Tan, Wei-Heong; Tseng, Fan-Gang; Takeuchi, Shoji

    2006-11-01

    This paper proposes a design concept and fabrication method of a planar three-dimensional (3D) microfluidic flow-focusing device (MFFD) that can produce monodisperse single/double emulsions in a closed/open microfluidic system. The device consists of three layers of SU-8 resist structures to form coaxial embedded orifices at the center of the microchannel with dimensions ranging from 50 µm to 200 µm by means of the black photoresist shadow method. Two or three immiscible fluids can be focused through the coaxial orifices, producing monodispersed droplets with a coefficient of variance (CV) of less than 4.1%. At the orifice, the inner liquid thread stays confined to the central axis of the microchannel, surrounded by the continuous phase. As the dispensed phase (inner fluid thread) does not wet channel walls, our proposed 3D MFFD can produce single emulsions for both water-in-oil (W/O) and oil-in-water (O/W) droplets utilizing the same device. The droplet diameter ranges from 50 µm to 300 µm. Also, double emulsions containing one to several internal droplets were successfully produced in the closed channel configuration. In addition, we demonstrated for the first time the feasibility of forming W/O droplets and polymer particles in an open channel configuration by withdrawing the fluid from the outlet channel. W/O droplets and polymer particles, smaller than 10 µm and 40 µm, respectively, were successfully produced. In contrast to the closed channel configuration where the droplet size decreases with an increasing flow rate, in an open channel configuration, the droplet size increases with an increasing withdrawal rate. The unique fabrication of the monolithic 3D MFFD device utilizing SU-8 resist overcomes problems regarding orifice sizes/shapes, alignment and assembly for current axisymmetric flow-focusing devices (AFFD) based on capillary microtubes, and provides flexibility for the future development of an integrated miniaturized lab-on-a-chip microsystem.

  18. A simple microfluidic device for the deformability assessment of blood cells in a continuous flow.

    PubMed

    Rodrigues, Raquel O; Pinho, Diana; Faustino, Vera; Lima, Rui

    2015-12-01

    Blood flow presents several interesting phenomena in microcirculation that can be used to develop microfluidic devices capable to promote blood cells separation and analysis in continuous flow. In the last decade there have been numerous microfluidic studies focused on the deformation of red blood cells (RBCs) flowing through geometries mimicking microvessels. In contrast, studies focusing on the deformation of white blood cells (WBCs) are scarce despite this phenomenon often happens in the microcirculation. In this work, we present a novel integrative microfluidic device able to perform continuous separation of a desired amount of blood cells, without clogging or jamming, and at the same time, capable to assess the deformation index (DI) of both WBCs and RBCs. To determine the DI of both WBCs and RBCs, a hyperbolic converging microchannel was used, as well as a suitable image analysis technique to measure the DIs of these blood cells along the regions of interest. The results show that the WBCs have a much lower deformability than RBCs when subjected to the same in vitro flow conditions, which is directly related to their cytoskeleton and nucleus contents. The proposed strategy can be easily transformed into a simple and inexpensive diagnostic microfluidic system to simultaneously separate and assess blood cells deformability. PMID:26482154

  19. Electric Field Directed Collection and Metering of DNA in Microfluidic Devices

    NASA Astrophysics Data System (ADS)

    Shaikh, Faisal; Ugaz, Victor

    2004-03-01

    Microfluidic technology is a key component in the development of microfabricated lab-on-a-chip systems for use in bioanalytical and biosensing applications. These devices continue to be developed to perform a variety of DNA analysis assays, however many of these applications deal with such minute amounts of DNA that it must first be pre-concentrated to a detectable level. On the macroscale, this pre-concentration is typically performed using centrifugation processes which are difficult to miniaturize and interface with other microfluidic components. In order to address this issue, we have developed microfluidic devices incorporating arrays of on-chip electrodes to locally increase the concentration of DNA in solution. By applying a low voltage between neighboring electrodes positioned inside a microfluidic channel, the negatively charged DNA fragments are induced to migrate toward and collect the anode, thereby allowing the quantity of accumulated DNA to be precisely metered. We demonstrate the application of this technique in electrophoresis microchips to inject a narrow and well-defined DNA plug into an electrophoresis gel. This loading scheme both increases the concentration of the sample to be separated and significantly reduces the degradation in separation resolution due the size of the injected sample plug.

  20. Oxygen-Purged Microfluidic Device to Enhance Cell Viability in Photopolymerized PEG Hydrogel Microparticles.

    PubMed

    Xia, Bingzhao; Krutkramelis, Kaspars; Oakey, John

    2016-07-11

    Encapsulating cells within biocompatible materials is a widely used strategy for cell delivery and tissue engineering. While cells are commonly suspended within bulk hydrogel-forming solutions during gelation, substantial interest in the microfluidic fabrication of miniaturized cell encapsulation vehicles has more recently emerged. Here, we utilize multiphase microfluidics to encapsulate cells within photopolymerized picoliter-volume water-in-oil droplets at high production rates. The photoinitiated polymerization of polyethylene glycol diacrylate (PEGDA) is used to continuously produce solid particles from aqueous liquid drops containing cells and hydrogel forming solution. It is well understood that this photoinitiated addition reaction is inhibited by oxygen. In contrast to bulk polymerization in which ambient oxygen is rapidly and harmlessly consumed, allowing the polymerization reaction to proceed, photopolymerization within air permeable polydimethylsiloxane (PDMS) microfluidic devices allows oxygen to be replenished by diffusion as it is depleted. This sustained presence of oxygen and the consequential accumulation of peroxy radicals produce a dramatic effect upon both droplet polymerization and post-encapsulation cell viability. In this work we employ a nitrogen microjacketed microfluidic device to purge oxygen from flowing fluids during photopolymerization. By increasing the purging nitrogen pressure, oxygen concentration was attenuated, and increased post-encapsulation cell viability was achieved. A reaction-diffusion model was used to predict the cumulative intradroplet concentration of peroxy radicals, which corresponded directly to post-encapsulation cell viability. The nitrogen-jacketed microfluidic device presented here allows the droplet oxygen concentration to be finely tuned during cell encapsulation, leading to high post-encapsulation cell viability. PMID:27285343

  1. Surface Modification of Droplet Polymeric Microfluidic Devices for the Stable and Continuous Generation of Aqueous Droplets

    PubMed Central

    Subramanian, Balamurugan; Kim, Namwon; Lee, Wonbae; Spivak, David A.; Nikitopoulos, Dimitris E.; McCarley, Robin L.; Soper, Steven A.

    2012-01-01

    Droplet microfluidics performed in poly(methylmethacrylate), PMMA, microfluidic devices resulted in significant wall wetting by water droplets formed in a liquid-liquid segmented flow when using a hydrophobic carrier fluid, such as perfluorotripropylamine (FC-3283). This wall wetting led to water droplets with non-uniform sizes that were often trapped on the wall surfaces leading to unstable and poorly controlled liquid-liquid segmented flow. To circumvent this problem, we developed a two-step procedure to hydrophobically modify the surfaces of PMMA and other thermoplastic materials commonly used for making microfluidic devices. The surface modification route involved the introduction of hydroxyl groups by oxygen plasma treatment of the polymer surface followed by a solution phase reaction with heptadecafluoro-1,1,2,2–tetrahydrodecyl trichlorosilane dissolved in the fluorocarbon solvent FC-3283. This procedure was found to be useful for the modification of PMMA and other thermoplastic surfaces, including polycyclic olefin copolymer (COC) and polycarbonate (PC). Angle-resolved X-ray photoelectron spectroscopy indicated that the fluorination of these polymers took place with high surface selectivity. This procedure was used to modify the surface of a PMMA droplet microfluidic device (DMFD) and was shown to be useful to reduce the wetting problem during the generation of aqueous droplets in a perfluorotripropylamine (FC-3283) carrier fluid and could generate stable segmented flows for hours of operation. In the case of the PMMA DMFD, oxygen plasma treatment was carried out after the PMMA cover plate was thermally fusion bonded to the PMMA microfluidic chip. Because the appended chemistry to the channel wall created a hydrophobic surface, it will accommodate the use of other carrier fluids that are hydrophobic as well, such as hexadecane or mineral oils. PMID:21608975

  2. Exploring protein-DNA interactions in 3D using in situ construction, manipulation, and visualization of individual DNA-dumbbells with optical traps, microfluidics, and fluorescence microscopy

    PubMed Central

    Forget, Anthony L.; Dombrowski, Christopher C.; Amitani, Ichiro; Kowalczykowski, Stephen C.

    2015-01-01

    In this Protocol, we describe a procedure to generate ‘DNA-dumbbells’ — single molecules of DNA with a microscopic bead attached at each end — and techniques for manipulating individual DNA-dumbbells. We also detail the design and fabrication of a microfluidic device (flow cell) used in conjunction with dual optical trapping to manipulate DNA-dumbbells and to visualize individual protein–DNA complexes by single-molecule epifluorescence microscopy. Our design of the flow cell enables the rapid movement of trapped molecules between laminar flow channels and a flow-free ‘reservoir’. The reservoir provides the means to examine formation of DNA–protein complexes in solution in the absence of external flow forces, while still maintaining a predetermined end-to-end extension of the DNA. These features facilitate examination of the role of three-dimensional DNA conformation and dynamics in protein–DNA interactions. Preparation of flow cells and reagents requires two days each; in situ DNA-dumbbell assembly and imaging of single protein–DNA complexes requires another day. PMID:23411634

  3. Highly efficient full-wave electromagnetic analysis of 3-D arbitrarily shaped waveguide microwave devices using an integral equation technique

    NASA Astrophysics Data System (ADS)

    Vidal, A.; San-Blas, A. A.; Quesada-Pereira, F. D.; Pérez-Soler, J.; Gil, J.; Vicente, C.; Gimeno, B.; Boria, V. E.

    2015-07-01

    A novel technique for the full-wave analysis of 3-D complex waveguide devices is presented. This new formulation, based on the Boundary Integral-Resonant Mode Expansion (BI-RME) method, allows the rigorous full-wave electromagnetic characterization of 3-D arbitrarily shaped metallic structures making use of extremely low CPU resources (both time and memory). The unknown electric current density on the surface of the metallic elements is represented by means of Rao-Wilton-Glisson basis functions, and an algebraic procedure based on a singular value decomposition is applied to transform such functions into the classical solenoidal and nonsolenoidal basis functions needed by the original BI-RME technique. The developed tool also provides an accurate computation of the electromagnetic fields at an arbitrary observation point of the considered device, so it can be used for predicting high-power breakdown phenomena. In order to validate the accuracy and efficiency of this novel approach, several new designs of band-pass waveguides filters are presented. The obtained results (S-parameters and electromagnetic fields) are successfully compared both to experimental data and to numerical simulations provided by a commercial software based on the finite element technique. The results obtained show that the new technique is specially suitable for the efficient full-wave analysis of complex waveguide devices considering an integrated coaxial excitation, where the coaxial probes may be in contact with the metallic insets of the component.

  4. A novel 3D embedded gate field effect transistor - Screen-grid FET - Device concept and modelling

    NASA Astrophysics Data System (ADS)

    Fobelets, K.; Ding, P. W.; Velazquez-Perez, J. E.

    2007-05-01

    A novel 3D field effect transistor on SOI - screen-grid FET (SGrFET) - is proposed and an analysis of its DC behaviour is presented by means of 2D TCAD analysis. The novel feature of the SGrFET is the design of 3D insulated gate cylinders embedded in the SOI body. This novel gate topology improves efficiency and allows great flexibility in device and gate geometry to optimize DC performance. The floating body effect is avoided and the double gating row configuration controls short channel effects. The traditional intimate relationship between gate length and source-drain distance is removed, resulting in easy control of drain induced barrier lowering, improved output conductance and ideal sub-threshold slope. The separation between the gate fingers in each row is the key factor to optimize the performance, whilst downscaling of the source-drain distance and oxide thickness is not essential from an operational point of view. The device exhibits a huge potential in low power electronics as given by an efficiency of transconductance " gm/ Id" of 39 S/A at VDS = 100 mV over a large gate voltage range and at a source-drain distance of 825 nm. We present the modelling results of the influence of gate cylinder distribution in the channel, channel doping, gate oxide thickness, gate finger distance and source-drain distance on the characteristics of the device.

  5. Development of AN Innovative Three-Dimensional Complete Body Screening Device - 3D-CBS

    NASA Astrophysics Data System (ADS)

    Crosetto, D. B.

    2004-07-01

    This article describes an innovative technological approach that increases the efficiency with which a large number of particles (photons) can be detected and analyzed. The three-dimensional complete body screening (3D-CBS) combines the functional imaging capability of the Positron Emission Tomography (PET) with those of the anatomical imaging capability of Computed Tomography (CT). The novel techniques provide better images in a shorter time with less radiation to the patient. A primary means of accomplishing this is the use of a larger solid angle, but this requires a new electronic technique capable of handling the increased data rate. This technique, combined with an improved and simplified detector assembly, enables executing complex real-time algorithms and allows more efficiently use of economical crystals. These are the principal features of this invention. A good synergy of advanced techniques in particle detection, together with technological progress in industry (latest FPGA technology) and simple, but cost-effective ideas provide a revolutionary invention. This technology enables over 400 times PET efficiency improvement at once compared to two to three times improvements achieved every five years during the past decades. Details of the electronics are provided, including an IBM PC board with a parallel-processing architecture implemented in FPGA, enabling the execution of a programmable complex real-time algorithm for best detection of photons.

  6. DNA Assembly in 3D Printed Fluidics.

    PubMed

    Patrick, William G; Nielsen, Alec A K; Keating, Steven J; Levy, Taylor J; Wang, Che-Wei; Rivera, Jaime J; Mondragón-Palomino, Octavio; Carr, Peter A; Voigt, Christopher A; Oxman, Neri; Kong, David S

    2015-01-01

    The process of connecting genetic parts-DNA assembly-is a foundational technology for synthetic biology. Microfluidics present an attractive solution for minimizing use of costly reagents, enabling multiplexed reactions, and automating protocols by integrating multiple protocol steps. However, microfluidics fabrication and operation can be expensive and requires expertise, limiting access to the technology. With advances in commodity digital fabrication tools, it is now possible to directly print fluidic devices and supporting hardware. 3D printed micro- and millifluidic devices are inexpensive, easy to make and quick to produce. We demonstrate Golden Gate DNA assembly in 3D-printed fluidics with reaction volumes as small as 490 nL, channel widths as fine as 220 microns, and per unit part costs ranging from $0.61 to $5.71. A 3D-printed syringe pump with an accompanying programmable software interface was designed and fabricated to operate the devices. Quick turnaround and inexpensive materials allowed for rapid exploration of device parameters, demonstrating a manufacturing paradigm for designing and fabricating hardware for synthetic biology. PMID:26716448

  7. DNA Assembly in 3D Printed Fluidics

    PubMed Central

    Patrick, William G.; Nielsen, Alec A. K.; Keating, Steven J.; Levy, Taylor J.; Wang, Che-Wei; Rivera, Jaime J.; Mondragón-Palomino, Octavio; Carr, Peter A.; Voigt, Christopher A.; Oxman, Neri; Kong, David S.

    2015-01-01

    The process of connecting genetic parts—DNA assembly—is a foundational technology for synthetic biology. Microfluidics present an attractive solution for minimizing use of costly reagents, enabling multiplexed reactions, and automating protocols by integrating multiple protocol steps. However, microfluidics fabrication and operation can be expensive and requires expertise, limiting access to the technology. With advances in commodity digital fabrication tools, it is now possible to directly print fluidic devices and supporting hardware. 3D printed micro- and millifluidic devices are inexpensive, easy to make and quick to produce. We demonstrate Golden Gate DNA assembly in 3D-printed fluidics with reaction volumes as small as 490 nL, channel widths as fine as 220 microns, and per unit part costs ranging from $0.61 to $5.71. A 3D-printed syringe pump with an accompanying programmable software interface was designed and fabricated to operate the devices. Quick turnaround and inexpensive materials allowed for rapid exploration of device parameters, demonstrating a manufacturing paradigm for designing and fabricating hardware for synthetic biology. PMID:26716448

  8. Fully Integrated Microfluidic Device for Direct Sample-to-Answer Genetic Analysis

    NASA Astrophysics Data System (ADS)

    Liu, Robin H.; Grodzinski, Piotr

    Integration of microfluidics technology with DNA microarrays enables building complete sample-to-answer systems that are useful in many applications such as clinic diagnostics. In this chapter, a fully integrated microfluidic device [1] that consists of microfluidic mixers, valves, pumps, channels, chambers, heaters, and a DNA microarray sensor to perform DNA analysis of complex biological sample solutions is present. This device can perform on-chip sample preparation (including magnetic bead-based cell capture, cell preconcentration and purification, and cell lysis) of complex biological sample solutions (such as whole blood), polymerase chain reaction, DNA hybridization, and electrochemical detection. A few novel microfluidic techniques were developed and employed. A micromix-ing technique based on a cavitation microstreaming principle was implemented to enhance target cell capture from whole blood samples using immunomagnetic beads. This technique was also employed to accelerate DNA hybridization reaction. Thermally actuated paraffin-based microvalves were developed to regulate flows. Electrochemical pumps and thermopneumatic pumps were integrated on the chip to provide pumping of liquid solutions. The device is completely self-contained: no external pressure sources, fluid storage, mechanical pumps, or valves are necessary for fluid manipulation, thus eliminating possible sample contamination and simplifying device operation. Pathogenic bacteria detection from ~mL whole blood samples and single-nucleotide polymorphism analysis directly from diluted blood were demonstrated. The device provides a cost-effective solution to direct sample-to-answer genetic analysis, and thus has a potential impact in the fields of point-of-care genetic analysis, environmental testing, and biological warfare agent detection.

  9. Microfluidic devices with permeable polymer barriers for capture and transport of biomolecules and cells

    PubMed Central

    Lee, Ho Suk; Chu, Wai Keung; Zhang, Kun

    2013-01-01

    We report a method for fabricating permeable polymer microstructure barriers in polydimethylsiloxane (PDMS) microfluidic devices and the use of the devices to capture and transport DNA and cells. The polymer microstructure in a desired location in a fluidic channel is formed in situ by the polymerization of acrylamide and polyethylene diacrylate cross-linker (PEG-DA) monomer in a solution which is trapped in the location using a pair of PDMS valves. The porous polymer microstructure provides a mechanical barrier to convective fluid flow in the channel or between two microfluidic chambers while it still conducts ions or small charged species under an electric field, allowing for the rapid capture and transport of biomolecules and cells by electrophoresis. We have demonstrated the application of the devices for the rapid capture and efficient release of bacteriophage λ genomic DNA, solution exchange and for the transport and capture of HeLa cells. Our devices will enable the multi-step processing of biomolecules and cells or individual cells within a single microfluidic chamber. PMID:23828542

  10. An integrated fiberoptic-microfluidic device for agglutination detection and blood typing.

    PubMed

    Ramasubramanian, Melur K; Alexander, Stewart P

    2009-02-01

    In this paper, an integrated fiberoptic-microfluidic device for the detection of agglutination for blood type cross-matching has been described. The device consists of a straight microfluidic channel through with a reacted RBC suspension is pumped with the help of a syringe pump. The flow intersects an optical path created by an emitter-received fiber optic pair integrated into the microfluidic device. A 650 nm laser diode is used as the light source and a silicon photodiode is used to detect the light intensity. The spacing between the tips of the two optic fibers can be adjusted. When fiber spacing is large and the concentration of the suspension is high, scattering phenomenon becomes the dominant mechanism for agglutination detection while at low concentrations and small spacing, optointerruption becomes the dominant mechanism. An agglutination strength factor (ASF) is calculated from the data. Studies with a variety of blood types indicate that the sensing method correctly identifies the agglutination reaction in all cases. A disposable integrated device can be designed for future implementation of the method for near-bedside pre-transfusion check. PMID:18815884

  11. Generation of Gradients on a Microfluidic Device: Toward a High-Throughput Investigation of Spermatozoa Chemotaxis

    PubMed Central

    Zou, Wei; Tang, Yun; Ding, Jinli; Yang, Jing

    2015-01-01

    Various research tools have been used for in vitro detection of sperm chemotaxis. However, they are typically poor in maintenance of gradient stability, not to mention their low efficiency. Microfluidic device offers a new experimental platform for better control over chemical concentration gradient than traditional ones. In the present study, an easy-handle diffusion-based microfluidic chip was established. This device allowed for conduction of three parallel experiments on the same chip, and improved the performance of sperm chemotaxis research. In such a chip, there were six channels surrounding a hexagonal pool. The channels are connected to the hexagon by microchannels. Firstly, the fluid flow in the system was characterized; secondly, fluorescein solution was used to calibrate gradient profiles formed in the central hexagon; thirdly, sperm behavior was observed under two concentration gradients of progesterone (100 pM and 1 mM, respectively) as a validation of the device. Significant differences in chemotactic parameters were recognized between experimental and control groups (p < 0.05). Compared with control group, sperm motility was greatly enhanced in 1 mM group (p < 0.05), but no significant difference was found in 100 pM group. In conclusion, we proposed a microfluidic device for the study of sperm chemotaxis that was capable of generating multi-channel gradients on a chip and would help reduce experimental errors and save time in experiment. PMID:26555941

  12. A polymeric master replication technology for mass fabrication of poly(dimethylsiloxane) microfluidic devices.

    PubMed

    Li, Hai-Fang; Lin, Jin-Ming; Su, Rong-Guo; Cai, Zong Wei; Uchiyama, Katsumi

    2005-05-01

    A protocol of producing multiple polymeric masters from an original glass master mold has been developed, which enables the production of multiple poly(dimethylsiloxane) (PDMS)-based microfluidic devices in a low-cost and efficient manner. Standard wet-etching techniques were used to fabricate an original glass master with negative features, from which more than 50 polymethylmethacrylate (PMMA) positive replica masters were rapidly created using the thermal printing technique. The time to replicate each PMMA master was as short as 20 min. The PMMA replica masters have excellent structural features and could be used to cast PDMS devices for many times. An integration geometry designed for laser-induced fluorescence (LIF) detection, which contains normal deep microfluidic channels and a much deeper optical fiber channel, was successfully transferred into PDMS devices. The positive relief on seven PMMA replica masters is replicated with regard to the negative original glass master, with a depth average variation of 0.89% for 26-microm deep microfluidic channels and 1.16% for the 90 mum deep fiber channel. The imprinted positive relief in PMMA from master-to-master is reproducible with relative standard deviations (RSDs) of 1.06% for the maximum width and 0.46% for depth in terms of the separation channel. T