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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

    2016-06-20

    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.

  2. 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

  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.

  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.

  7. 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

  8. 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

  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.

  10. 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

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

    NASA Astrophysics Data System (ADS)

    Collette, Robyn; Novak, Eric; Shirk, Kathryn

    2015-03-01

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

  12. 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.

  13. 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.

  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. Femtosecond laser 3D micromachining: a powerful tool for the fabrication of microfluidic, optofluidic, and electrofluidic devices based on glass.

    PubMed

    Sugioka, Koji; Xu, Jian; Wu, Dong; Hanada, Yasutaka; Wang, Zhongke; Cheng, Ya; Midorikawa, Katsumi

    2014-09-21

    Femtosecond lasers have unique characteristics of ultrashort pulse width and extremely high peak intensity; however, one of the most important features of femtosecond laser processing is that strong absorption can be induced only at the focus position inside transparent materials due to nonlinear multiphoton absorption. This exclusive feature makes it possible to directly fabricate three-dimensional (3D) microfluidic devices in glass microchips by two methods: 3D internal modification using direct femtosecond laser writing followed by chemical wet etching (femtosecond laser-assisted etching, FLAE) and direct ablation of glass in water (water-assisted femtosecond laser drilling, WAFLD). Direct femtosecond laser writing also enables the integration of micromechanical, microelectronic, and microoptical components into the 3D microfluidic devices without stacking or bonding substrates. This paper gives a comprehensive review on the state-of-the-art femtosecond laser 3D micromachining for the fabrication of microfluidic, optofluidic, and electrofluidic devices. A new strategy (hybrid femtosecond laser processing) is also presented, in which FLAE is combined with femtosecond laser two-photon polymerization to realize a new type of biochip termed the ship-in-a-bottle biochip. PMID:25012238

  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. 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.

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

    PubMed

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

    2014-02-01

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

  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.

  1. 3D-printed microfluidic automation.

    PubMed

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

    2015-04-21

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

  2. 3D-printed microfluidic automation.

    PubMed

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

    2015-04-21

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

  3. 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

  4. Time lapse investigation of antibiotic susceptibility using a microfluidic linear gradient 3D culture device.

    PubMed

    Hou, Zining; An, Yu; Hjort, Karin; Hjort, Klas; Sandegren, Linus; Wu, Zhigang

    2014-09-01

    This study reports a novel approach to quantitatively investigate the antibacterial effect of antibiotics on bacteria using a three-dimensional microfluidic culture device. In particular, our approach is suitable for studying the pharmacodynamics effects of antibiotics on bacterial cells temporally and with a continuous range of concentrations in a single experiment. The responses of bacterial cells to a linear concentration gradient of antibiotics were observed using time-lapse photography, by encapsulating bacterial cells in an agarose-based gel located in a commercially available microfluidics chamber. This approach generates dynamic information with high resolution, in a single operation, e.g., growth curves and antibiotic pharmacodynamics, in a well-controlled environment. No pre-labelling of the cells is needed and therefore any bacterial sample can be tested in this setup. It also provides static information comparable to that of standard techniques for measuring minimum inhibitory concentration (MIC). Five antibiotics with different mechanisms were analysed against wild-type Escherichia coli, Staphylococcus aureus and Salmonella Typhimurium. The entire process, including data analysis, took 2.5-4 h and from the same analysis, high-resolution growth curves were obtained. As a proof of principle, a pharmacodynamic model of streptomycin against Salmonella Typhimurium was built based on the maximal effect model, which agreed well with the experimental results. Our approach has the potential to be a simple and flexible solution to study responding behaviours of microbial cells under different selection pressures both temporally and in a range of concentrations.

  5. 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.

  6. 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

  7. 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

  8. Discrete elements for 3D microfluidics.

    PubMed

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

    2014-10-21

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

  9. 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.

  10. 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.

  11. 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

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

    PubMed

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

    2016-05-21

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

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

  14. Microfluidic 3D models of cancer

    PubMed Central

    Sung, Kyung Eun; Beebe, David J.

    2014-01-01

    Despite advances in medicine and biomedical sciences, cancer still remains a major health issue. Complex interactions between tumors and their microenvironment contribute to tumor initiation and progression and also contribute to the development of drug resistant tumor cell populations. The complexity and heterogeneity of tumors and their microenvironment make it challenging to both study and treat cancer. Traditional animal cancer models and in vitro cancer models are limited in their ability to recapitulate human structures and functions, thus hindering the identification of appropriate drug targets and therapeutic strategies. The development and application of microfluidic 3D cancer models has the potential to overcome some of the limitations inherent to traditional models. This review summarizes the progress in microfluidic 3D cancer models, their benefits, and their broad application to basic cancer biology, drug screening, and drug discovery. PMID:25017040

  15. Microfluidic 3D models of cancer.

    PubMed

    Sung, Kyung Eun; Beebe, David J

    2014-12-15

    Despite advances in medicine and biomedical sciences, cancer still remains a major health issue. Complex interactions between tumors and their microenvironment contribute to tumor initiation and progression and also contribute to the development of drug resistant tumor cell populations. The complexity and heterogeneity of tumors and their microenvironment make it challenging to both study and treat cancer. Traditional animal cancer models and in vitro cancer models are limited in their ability to recapitulate human structures and functions, thus hindering the identification of appropriate drug targets and therapeutic strategies. The development and application of microfluidic 3D cancer models have the potential to overcome some of the limitations inherent to traditional models. This review summarizes the progress in microfluidic 3D cancer models, their benefits, and their broad application to basic cancer biology, drug screening, and drug discovery.

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. Sequential assembly of 3D perfusable microfluidic hydrogels.

    PubMed

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

    2014-11-01

    Bottom-up tissue engineering provides a promising way to recreate complex structural organizations of native organs in artificial constructs by assembling functional repeating modules. However, it is challenging for current bottom-up strategies to simultaneously produce a controllable and immediately perfusable microfluidic network in modularly assembled 3D constructs. Here we presented a bottom-up strategy to produce perfusable microchannels in 3D hydrogels by sequentially assembling microfluidic modules. The effects of agarose-collagen composition on microchannel replication and 3D assembly of hydrogel modules were investigated. The unique property of predefined microchannels in transporting fluids within 3D assemblies was evaluated. Endothelial cells were incorporated into the microfluidic network of 3D hydrogels for dynamic culture in a house-made bioreactor system. The results indicated that the sequential assembly method could produce interconnected 3D predefined microfluidic networks in optimized agarose-collagen hydrogels, which were fully perfusable and successfully functioned as fluid pathways to facilitate the spreading of endothelial cells. We envision that the presented method could be potentially used to engineer 3D vascularized parenchymal constructs by encapsulating primary cells in bulk hydrogels and incorporating endothelial cells in predefined microchannels. PMID:25027302

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 3D elastic control for mobile devices.

    PubMed

    Hachet, Martin; Pouderoux, Joachim; Guitton, Pascal

    2008-01-01

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

  16. 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.

  17. 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

  18. 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

  19. 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

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

    PubMed

    Barbot, Antoine; Decanini, Dominique; Hwang, Gilgueng

    2016-01-21

    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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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).

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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.

  17. 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

  18. 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.

  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. 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.

  1. Desktop aligner for fabrication of multilayer microfluidic devices.

    PubMed

    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.

  2. 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

  3. Desktop aligner for fabrication of multilayer microfluidic devices.

    PubMed

    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. PMID:26233409

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

    PubMed

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

    2013-11-01

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

  5. 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.

  6. 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.

  7. Microfluidic devices for droplet injection

    NASA Astrophysics Data System (ADS)

    Aubrecht, Donald; Akartuna, Ilke; Weitz, David

    2012-02-01

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

  8. Three-dimensional interconnected microporous poly(dimethylsiloxane) microfluidic devices.

    PubMed

    Yuen, Po Ki; Su, Hui; Goral, Vasiliy N; Fink, Katherine A

    2011-04-21

    This technical note presents a fabrication method and applications of three-dimensional (3D) interconnected microporous poly(dimethylsiloxane) (PDMS) microfluidic devices. Based on soft lithography, the microporous PDMS microfluidic devices were fabricated by molding a mixture of PDMS pre-polymer and sugar particles in a microstructured mold. After curing and demolding, the sugar particles were dissolved and washed away from the microstructured PDMS replica revealing 3D interconnected microporous structures. Other than introducing microporous structures into the PDMS replica, different sizes of sugar particles can be used to alter the surface wettability of the microporous PDMS replica. Oxygen plasma assisted bonding was used to enclose the microstructured microporous PDMS replica using a non-porous PDMS with inlet and outlet holes. A gas absorption reaction using carbon dioxide (CO(2)) gas acidified water was used to demonstrate the advantages and potential applications of the microporous PDMS microfluidic devices. We demonstrated that the acidification rate in the microporous PDMS microfluidic device was approximately 10 times faster than the non-porous PDMS microfluidic device under similar experimental conditions. The microporous PDMS microfluidic devices can also be used in cell culture applications where gas perfusion can improve cell survival and functions.

  9. 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. PMID:27512530

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 3D Structures: Microfluidic Stamping on Sheath Flow (Small 24/2016).

    PubMed

    Yoon, Dong Hyun; Tanaka, Daiki; Sekiguchi, Tetsushi; Shoji, Shuichi

    2016-06-01

    A microfluidic stamping method to form functional shapes on a cross section in fibre-shaped flow is presented by D. H. Yoon and co-workers on page 3224. Microfluidic stamping and overstamping allowed various cross sectional shapes on the three-dimensional flow. Dimension of the flows is controlled via a change in combination of 3D structures and fluidic conditions, which correspond to stamp type and stamping force. PMID:27306739

  16. 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.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2013-09-21

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

  19. 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.

  20. 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.

  1. 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.

  2. Microfluidic devices: useful tools for bioprocess intensification.

    PubMed

    Marques, Marco P C; Fernandes, Pedro

    2011-01-01

    The dawn of the new millennium saw a trend towards the dedicated use of microfluidic devices for process intensification in biotechnology. As the last decade went by, it became evident that this pattern was not a short-lived fad, since the deliverables related to this field of research have been consistently piling-up. The application of process intensification in biotechnology is therefore seemingly catching up with the trend already observed in the chemical engineering area, where the use of microfluidic devices has already been upgraded to production scale. The goal of the present work is therefore to provide an updated overview of the developments centered on the use of microfluidic devices for process intensification in biotechnology. Within such scope, particular focus will be given to different designs, configurations and modes of operation of microreactors, but reference to similar features regarding microfluidic devices in downstream processing will not be overlooked. Engineering considerations and fluid dynamics issues, namely related to the characterization of flow in microchannels, promotion of micromixing and predictive tools, will also be addressed, as well as reflection on the analytics required to take full advantage of the possibilities provided by microfluidic devices in process intensification. Strategies developed to ease the implementation of experimental set-ups anchored in the use of microfluidic devices will be briefly tackled. Finally, realistic considerations on the current advantages and limitation on the use of microfluidic devices for process intensification, as well as prospective near future developments in the field, will be presented.

  3. 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.

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

    ScienceCinema

    Erikson, Rebecca; Baird, Cheryl; Hutchinson, Janine

    2016-07-12

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

  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. 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

  7. 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.

  8. Low-cost rapid prototyping of flexible microfluidic devices using a desktop digital craft cutter.

    PubMed

    Yuen, Po Ki; Goral, Vasiliy N

    2010-02-01

    Low-cost and straight forward rapid prototyping of flexible microfluidic devices using a desktop digital craft cutter is presented. This rapid prototyping method can consistently achieve microchannels as thin as 200 microm in width and can be used to fabricate three-dimensional (3D) microfluidic devices using only double-sided pressure sensitive adhesive (PSA) tape and laser printer transparency film. Various functional microfluidic devices are demonstrated with this rapid prototyping method. The complete fabrication process from device design concept to working device can be completed in minutes without the need of expensive equipment. PMID:20091012

  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. 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

  11. 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-stimulation.

  12. 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

  13. 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

  14. A 3D printed fluidic device that enables integrated features.

    PubMed

    Anderson, Kari B; Lockwood, Sarah Y; Martin, R Scott; Spence, Dana M

    2013-06-18

    Fluidic devices fabricated using conventional soft lithography are well suited as prototyping methods. Three-dimensional (3D) printing, commonly used for producing design prototypes in industry, allows for one step production of devices. 3D printers build a device layer by layer based on 3D computer models. Here, a reusable, high throughput, 3D printed fluidic device was created that enables flow and incorporates a membrane above a channel in order to study drug transport and affect cells. The device contains 8 parallel channels, 3 mm wide by 1.5 mm deep, connected to a syringe pump through standard, threaded fittings. The device was also printed to allow integration with commercially available membrane inserts whose bottoms are constructed of a porous polycarbonate membrane; this insert enables molecular transport to occur from the channel to above the well. When concentrations of various antibiotics (levofloxacin and linezolid) are pumped through the channels, approximately 18-21% of the drug migrates through the porous membrane, providing evidence that this device will be useful for studies where drug effects on cells are investigated. Finally, we show that mammalian cells cultured on this membrane can be affected by reagents flowing through the channels. Specifically, saponin was used to compromise cell membranes, and a fluorescent label was used to monitor the extent, resulting in a 4-fold increase in fluorescence for saponin treated cells.

  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. 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

  17. 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.

  18. Slanted channel microfluidic chip for 3D fluorescence imaging of cells in flow.

    PubMed

    Jagannadh, Veerendra Kalyan; Mackenzie, Mark D; Pal, Parama; Kar, Ajoy K; Gorthi, Sai Siva

    2016-09-19

    Three-dimensional cellular imaging techniques have become indispensable tools in biological research and medical diagnostics. Conventional 3D imaging approaches employ focal stack collection to image different planes of the cell. In this work, we present the design and fabrication of a slanted channel microfluidic chip for 3D fluorescence imaging of cells in flow. The approach employs slanted microfluidic channels fabricated in glass using ultrafast laser inscription. The slanted nature of the microfluidic channels ensures that samples come into and go out of focus, as they pass through the microscope imaging field of view. This novel approach enables the collection of focal stacks in a straight-forward and automated manner, even with off-the-shelf microscopes that are not equipped with any motorized translation/rotation sample stages. The presented approach not only simplifies conventional focal stack collection, but also enhances the capabilities of a regular widefield fluorescence microscope to match the features of a sophisticated confocal microscope. We demonstrate the retrieval of sectioned slices of microspheres and cells, with the use of computational algorithms to enhance the signal-to-noise ratio (SNR) in the collected raw images. The retrieved sectioned images have been used to visualize fluorescent microspheres and bovine sperm cell nucleus in 3D while using a regular widefield fluorescence microscope. We have been able to achieve sectioning of approximately 200 slices per cell, which corresponds to a spatial translation of ∼ 15 nm per slice along the optical axis of the microscope. PMID:27661949

  19. Slanted channel microfluidic chip for 3D fluorescence imaging of cells in flow.

    PubMed

    Jagannadh, Veerendra Kalyan; Mackenzie, Mark D; Pal, Parama; Kar, Ajoy K; Gorthi, Sai Siva

    2016-09-19

    Three-dimensional cellular imaging techniques have become indispensable tools in biological research and medical diagnostics. Conventional 3D imaging approaches employ focal stack collection to image different planes of the cell. In this work, we present the design and fabrication of a slanted channel microfluidic chip for 3D fluorescence imaging of cells in flow. The approach employs slanted microfluidic channels fabricated in glass using ultrafast laser inscription. The slanted nature of the microfluidic channels ensures that samples come into and go out of focus, as they pass through the microscope imaging field of view. This novel approach enables the collection of focal stacks in a straight-forward and automated manner, even with off-the-shelf microscopes that are not equipped with any motorized translation/rotation sample stages. The presented approach not only simplifies conventional focal stack collection, but also enhances the capabilities of a regular widefield fluorescence microscope to match the features of a sophisticated confocal microscope. We demonstrate the retrieval of sectioned slices of microspheres and cells, with the use of computational algorithms to enhance the signal-to-noise ratio (SNR) in the collected raw images. The retrieved sectioned images have been used to visualize fluorescent microspheres and bovine sperm cell nucleus in 3D while using a regular widefield fluorescence microscope. We have been able to achieve sectioning of approximately 200 slices per cell, which corresponds to a spatial translation of ∼ 15 nm per slice along the optical axis of the microscope.

  20. 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

  1. 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.

  2. 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

  3. Reconfigurable microfluidic systems with reversible seals compatible with 2D and 3D surfaces of arbitrary chemical composition.

    PubMed

    Konda, Abhiteja; Taylor, Jay M; Stoller, Michael A; Morin, Stephen A

    2015-05-01

    Microfluidic channels are typically fabricated in polydimethylsiloxane (PDMS) using soft lithography and sealed against a support substrate using various irreversible/reversible techniques-the most widely used method is the irreversible bonding of PDMS to glass using oxygen plasma. These techniques are limited in their ability to seal channels against rough, uneven, and/or three-dimensional substrates. This manuscript describes the design and fabrication of soft microfluidic systems from combinations of silicone elastomers that can be reversibly sealed against an array of materials of various topographies/geometries using compression. These soft systems have channels with cross-sectional dimensions that can be decreased, reversibly, by hundreds of microns using compressive stress, and the ability to interface with virtually any support substrate. These capabilities go beyond that achievable with devices fabricated in PDMS alone and enable the integration of microfluidic functionality directly with rough and/or 3D surfaces, providing new opportunities in solution processing useful to, for example, materials science and the analytical/forensic sciences.

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Microfluidic device for acoustic cell lysis

    SciTech Connect

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

    2015-08-04

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

  14. 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.

  15. Simple Check Valves for Microfluidic Devices

    NASA Technical Reports Server (NTRS)

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

    2010-01-01

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

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

    PubMed Central

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

    2008-01-01

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

  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. 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.

  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. 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

  3. 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.

  4. A simple method for fabricating multi-layer PDMS structures for 3D microfluidic chips.

    PubMed

    Zhang, Mengying; Wu, Jinbo; Wang, Limu; Xiao, Kang; Wen, Weijia

    2010-05-01

    We report a simple methodology to fabricate PDMS multi-layer microfluidic chips. A PDMS slab was surface-treated by trichloro (1H,1H,2H,2H-perfluorooctyl) silane, and acts as a reusable transferring layer. Uniformity of the thickness of the patterned PDMS layer and the well-alignment could be achieved due to the transparency and proper flexibility of this transferring layer. Surface treatment results are confirmed by XPS and contact angle testing, while bonding forces between different layers were measured for better understanding of the transferring process. We have also designed and fabricated a few simple types of 3D PDMS chip, especially one consisting of 6 thin layers (each with thickness of 50 mum), to demonstrate the potential utilization of this technique. 3D fluorescence images were taken by a confocal microscope to illustrate the spatial characters of essential parts. This fabrication method is confirmed to be fast, simple, repeatable, low cost and possible to be mechanized for mass production.

  5. 3D-printed microfluidic microdissector for high-throughput studies of cellular aging.

    PubMed

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

    2014-08-01

    Due to their short lifespan, rapid division, and ease of genetic manipulation, yeasts are popular model organisms for studying aging in actively dividing cells. To study replicative aging over many cell divisions, individual cells must be continuously separated from their progeny via a laborious manual microdissection procedure. Microfluidics-based soft-lithography devices have recently been used to automate microdissection of the budding yeast Saccharomyces cerevisiae. However, little is known about replicative aging in Schizosaccharomyces pombe, a rod-shaped yeast that divides by binary fission and shares many conserved biological functions with higher eukaryotes. In this report, we develop a versatile multiphoton lithography method that enables rapid fabrication of three-dimensional master structures for polydimethylsiloxane (PDMS)-based microfluidics. We exploit the rapid prototyping capabilities of multiphoton lithography to create and characterize a cell-capture device that is capable of high-resolution microscopic observation of hundreds of individual S. pombe cells. By continuously removing the progeny cells, we demonstrate that cell growth and protein aggregation can be tracked in individual cells for over ~100 h. Thus, the fission yeast lifespan microdissector (FYLM) provides a powerful on-chip microdissection platform that will enable high-throughput studies of aging in rod-shaped cells. PMID:24992972

  6. 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”.

  7. 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

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  9. 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.

  10. 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

  11. 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

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

    PubMed

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

    2014-08-01

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

  13. 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.

  14. 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

  15. Microfluidic devices and methods for integrated flow cytometry

    DOEpatents

    Srivastava, Nimisha; Singh, Anup K.

    2011-08-16

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

  16. 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).

  17. 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

  18. 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

  19. 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.

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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.

  5. 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

  6. 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

  7. Neuromuscular junction in a microfluidic device.

    PubMed

    Park, Hyun Sung; Liu, Su; McDonald, John; Thakor, Nitish; Yang, In Hong

    2013-01-01

    Malfunctions at the site of neuromuscular junction (NMJ) of post-injuries or diseases are major barriers to recovery of function. The ability to efficiently derive motor neurons (MN) from embryonic stem cells has indicated promise toward the development of new therapies in increasing functional outcomes post injury. Recent advances in micro-technologies have provided advanced culture platforms allowing compartmentalization of sub-cellular components of neurons. In this study, we combined these advances in science and technology to develop a compartmentalized in vitro NMJ model. The developed NMJ system is between mouse embryonic stem cell (mESC)-derived MNs and c2c12 myotubes cultured in a compartmentalized polydimethylsiloxane (PDMS) microfluidic device. While some functional in vitro NMJ systems have been reported, this system would further contribute to research in NMJ-related diseases by providing a system to study the site of action of NMJ aimed at improving promoting better functional recovery. PMID:24110317

  8. 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.

  9. 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

  10. Microfluidic baker's transformation device for three-dimensional rapid mixing.

    PubMed

    Yasui, Takao; Omoto, Yusuke; Osato, Keiko; Kaji, Noritada; Suzuki, Norikazu; Naito, Toyohiro; Watanabe, Masaki; Okamoto, Yukihiro; Tokeshi, Manabu; Shamoto, Eiji; Baba, Yoshinobu

    2011-10-01

    We developed a new passive-type micromixer based on the baker's transformation and realized a fast mixing of a protein solution, which has lower diffusion constant. The baker's transformation is an ideal mixing method, but there is no report on the microfluidic baker's transformation (MBT), since it is required to fabricate the complicated three-dimensional (3D) structure to realize the MBT device. In this note, we successfully fabricate the MBT device by using precision diamond cutting of an oxygen-free copper substrate for the mould fabrication and PDMS replication. The MBT device with 10.4 mm mixing length enables us to achieve complete mixing of a FITC solution (D = 2.6 × 10(-10) m(2) s(-1)) within 51 ms and an IgG solution (D = 4.6 × 10(-11) m(2) s(-1)) within 306 ms. Its mixing speed is 70-fold higher for a FITC solution and 900-fold higher for an IgG solution than the mixing speed by the microchannel without MBT structures. The Péclet number to attain complete mixing in the MBT device is estimated to be 6.9 × 10(4).

  11. A polystyrene-based microfluidic device with three-dimensional interconnected microporous walls for perfusion cell culture

    PubMed Central

    Chan, Chung Yu; Goral, Vasiliy N.; DeRosa, Michael E.; Huang, Tony Jun

    2014-01-01

    In this article, we present a simple, rapid prototyped polystyrene-based microfluidic device with three-dimensional (3D) interconnected microporous walls for long term perfusion cell culture. Patterned 3D interconnected microporous structures were created by a chemical treatment together with a protective mask and the native hydrophobic nature of the microporous structures were selectively made hydrophilic using oxygen plasma treatment together with a protective mask. Using this polystyrene-based cell culture microfluidic device, we successfully demonstrated the support of four days perfusion cell culture of hepatocytes (C3A cells). PMID:25379110

  12. Probing cell mechanical properties with microfluidic devices

    NASA Astrophysics Data System (ADS)

    Rowat, Amy

    2012-02-01

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

  13. Hybrid chemical etching of femtosecond laser irradiated structures for engineered microfluidic devices

    NASA Astrophysics Data System (ADS)

    LoTurco, S.; Osellame, R.; Ramponi, R.; Vishnubhatla, K. C.

    2013-08-01

    We report on the fabrication of 3D buried micro-structures in fused silica glass using the selective chemical etching along femtosecond laser irradiated zones. Specifically, we have exploited a novel approach combining two different etching agents in successive steps. The widely used hydrofluoric acid solution, which provides fast volume removal, and potassium hydroxide solution, which exhibits high selectivity, are used to fabricate microfluidic structures. We demonstrate that this hybrid approach takes advantage of both of the individual etchants’ special characteristics and facilitates prototyping and fabrication of complex geometries for microfluidic devices.

  14. Polymeric infrared compatible microfluidic devices for spectrochemical analysis.

    PubMed

    Barich, Michael V; Krummel, Amber T

    2013-11-01

    An innovative fabrication method is presented that affords the combination of polydimethyl-siloxane (PDMS) microfluidic technology with vibrational spectroscopy. PDMS devices are produced with uniform thicknesses ranging from 25 to 400 μm. The optical characteristics of the microfluidic devices in the mid-infrared are reported. The broad utility of this approach is demonstrated through IR imaging of flows in functional gradient generators and flow-focusing devices. PMID:24099528

  15. Rare Cell Capture in Microfluidic Devices

    PubMed Central

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

    2010-01-01

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

  16. 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.

  17. 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

  18. 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

  19. 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.

  20. Fabrication of gravity-driven microfluidic device.

    PubMed

    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 microm and depths of 45 mum. Through holes used as artificial capillary vessels are made in the fluororesin having a minimum diameter of 5 microm and a length of 100 microm. 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.

  1. 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

  2. Polyurethane-based microfluidic devices for blood contacting applications.

    PubMed

    Wu, Wen-I; Sask, Kyla N; Brash, John L; Selvaganapathy, P Ravi

    2012-03-01

    Protein adsorption on PDMS surfaces poses a significant challenge in microfluidic devices that come into contact with biofluids such as blood. Polyurethane (PU) is often used for the construction of medical devices, but despite having several attractive properties for biointerfacing, it has not been widely used in microfluidic devices. In this work we developed two new fabrication processes for making thin, transparent and flexible PU-based microfluidic devices. Methods for the fabrication and bonding of microchannels, the integration of fluidic interconnections and surface modification with hydrophilic polyethylene oxide (PEO) to reduce protein adsorption are detailed. Using these processes, microchannels were produced having high transparency (96% that of glass in visible light), high bond strength (326.4 kPa) and low protein adsorption (80% reduction in fibrinogen adsorption vs. unmodified PDMS), which is critical for prevention of fouling. Our findings indicate that PEO modified PU could serve as an effective alternative to PDMS in blood contacting microfluidic applications.

  3. 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

  4. Preparation and 3D Tracking of Catalytic Swimming Devices

    PubMed Central

    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

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

    PubMed

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

    2015-01-01

    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.

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. 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.

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

    PubMed Central

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

    2015-01-01

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

  14. 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

  15. 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.

  16. Measurement of the hematocrit using paper-based microfluidic devices.

    PubMed

    Berry, Samuel B; Fernandes, Syrena C; Rajaratnam, Anjali; DeChiara, Nicholas S; Mace, Charles R

    2016-10-01

    The quantification of blood cells provides critical information about a patient's health status. Sophisticated analytical equipment, such as hematology analyzers, have been developed to perform these measurements, but limited-resource settings often lack the infrastructure required to purchase, operate, and maintain instrumentation. To address these practical challenges, paper-based microfluidic devices have emerged as a platform to develop diagnostic assays specifically for use at the point-of-care. To date, paper-based microfluidic devices have been used broadly in diagnostic assays that apply immunoassay, clinical chemistry, and electrochemistry techniques. The analysis of cells, however, has been largely overlooked. In this communication, we demonstrate a paper-based microfluidic device that enables the controlled transport of red blood cells (RBCs) and the measurement of the hematocrit-the ratio of RBC packed cell volume to total volume of whole blood. The properties of paper, device treatment, and device geometry affect the overall extent and reproducibility of transport of RBCs. Ultimately, we developed an inexpensive (US$0.03 per device) thermometer-styled device where the distance traveled by RBCs is proportional to the hematocrit. These results provide a foundation for the design of paper-based microfluidic devices that enable the separation and detection of cells in limited-resource settings. PMID:27604182

  17. Measurement of the hematocrit using paper-based microfluidic devices.

    PubMed

    Berry, Samuel B; Fernandes, Syrena C; Rajaratnam, Anjali; DeChiara, Nicholas S; Mace, Charles R

    2016-10-01

    The quantification of blood cells provides critical information about a patient's health status. Sophisticated analytical equipment, such as hematology analyzers, have been developed to perform these measurements, but limited-resource settings often lack the infrastructure required to purchase, operate, and maintain instrumentation. To address these practical challenges, paper-based microfluidic devices have emerged as a platform to develop diagnostic assays specifically for use at the point-of-care. To date, paper-based microfluidic devices have been used broadly in diagnostic assays that apply immunoassay, clinical chemistry, and electrochemistry techniques. The analysis of cells, however, has been largely overlooked. In this communication, we demonstrate a paper-based microfluidic device that enables the controlled transport of red blood cells (RBCs) and the measurement of the hematocrit-the ratio of RBC packed cell volume to total volume of whole blood. The properties of paper, device treatment, and device geometry affect the overall extent and reproducibility of transport of RBCs. Ultimately, we developed an inexpensive (US$0.03 per device) thermometer-styled device where the distance traveled by RBCs is proportional to the hematocrit. These results provide a foundation for the design of paper-based microfluidic devices that enable the separation and detection of cells in limited-resource settings.

  18. Comparison of Tomo-PIV and 3D-PTV for microfluidic flows

    NASA Astrophysics Data System (ADS)

    Kim, Hyoungsoo; Westerweel, Jerry; Elsinga, Gerrit E.

    2013-02-01

    Two 3D-3C velocimetry techniques for micro-scale measurements are compared: tomographic particle image velocimetry (Tomo-PIV) and 3D particle-tracking velocimetry (3D-PTV). Both methods are applied to experimental data from a confined shear-driven liquid droplet over a moving surface. The droplet has 200 μm height and 2 mm diameter. Micro 3D-PTV and Tomo-PIV are used to obtain the tracer particle distribution and the flow velocity field for the same set of images. It is shown that the reconstructed particle distributions are distinctly different, where Tomo-PIV returns a nearly uniform distribution over the height of the volume, as expected, and PTV reveals a clear peak in the particle distribution near the plane of focus. In Tomo-PIV, however, the reconstructed particle peak intensity decreases in proportion to the distance from the plane of focus. Due to the differences in particle distributions, the measured flow velocities are also different. In particular, we observe Tomo-PIV to be in closer agreement with mass conservation. Furthermore, the random noise level is found to increase with distance to the plane of focus at a higher rate for 3D-PTV as compared to Tomo-PIV. Thus, for a given noise threshold value, the latter method can measure reliably over a thicker volume.

  19. Droplets and Bubbles in Microfluidic Devices

    NASA Astrophysics Data System (ADS)

    Anna, Shelley Lynn

    2016-01-01

    Precise, tunable emulsions and foams produced in microfluidic geometries have found wide application in biochemical analysis and materials synthesis and characterization. Superb control of the volume, uniformity, and generation rate of droplets and bubbles arises from unique features of the microscale behavior of fluid interfaces. Fluid interfaces confined within microfluidic channels behave quite differently than their counterparts in unbounded flows. Confinement inhibits capillary instabilities so that breakup occurs by largely quasi-static mechanisms. The three-dimensional flow near confined interfaces in rectangular geometries and feedback effects from resistance changes in the entire microfluidic network play important roles in regulating the interfacial deformation. Timescales for transport of surfactants and particles to interfaces compete with flow timescales at the microscale, providing further opportunity for tuning the interfacial coverage and properties of individual droplets and bubbles.

  20. A PEG-DA microfluidic device for chemotaxis studies

    NASA Astrophysics Data System (ADS)

    Aziz Traore, Mahama; Behkam, Bahareh

    2013-08-01

    The study of cells in a well-defined and chemically programmable microenvironment is essential for a complete and fundamental understanding of the cell behaviors with respect to specific chemical compounds. Flow-free microfluidic devices that generate quasi-steady chemical gradients (spatially varying but temporally constant) have been demonstrated as effective chemotaxis assay platforms due to dissociating the effect of chemical cues from mechanical shear forces caused by fluid flow. In this work, we demonstrate the fabrication and characterization of a flow-free microfluidic platform made of polyethylene glycol diacrylate (PEG-DA) hydrogel. We have demonstrated that the mass transport properties of these devices can be customized by fabricating them from PEG-DA gels of four distinct molecular weights. In contrast to microfluidic devices developed using soft lithography; this class of devices can be realized using a more cost-effective approach of direct photopolymerization with fewer microfabrication steps. This microfluidic platform was tested by conducting a quantitative study of the chemotactic behavior of Escherichia coli (E. coli) RP437, a model microorganism, in presence of the chemo-effector, casamino-acids. Using the microfabrication and characterization methodology presented in this work, microfluidic platforms with well-defined and customizable diffusive properties can be developed to accommodate the study of a wide range of cell types.

  1. 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

  2. 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

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

    PubMed Central

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

    2015-01-01

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

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. High content screening in microfluidic devices

    PubMed Central

    Cheong, Raymond; Paliwal, Saurabh; Levchenko, Andre

    2011-01-01

    Importance of the field Miniaturization is key to advancing the state-of-the-art in high content screening (HCS), in order to enable dramatic cost savings through reduced usage of expensive biochemical reagents and to enable large-scale screening on primary cells. Microfluidic technology offers the potential to enable HCS to be performed with an unprecedented degree of miniaturization. Areas covered in this review This perspective highlights a real-world example from the authors’ work of HCS assays implemented in a highly miniaturized microfluidic format. Advantages of this technology are discussed, including cost savings, high throughput screening on primary cells, improved accuracy, the ability to study complex time-varying stimuli, and ease of automation, integration, and scaling. What the reader will gain The reader will understand the capabilities of a new microfluidics-based platform for HCS, and the advantages it provides over conventional plate-based HCS. Take home message Microfluidics technology will drive significant advancements and broader usage and applicability of HCS in drug discovery. PMID:21852997

  10. 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.

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

    PubMed

    Yu, Ling; Shi, Zhuan Zhuan

    2015-04-01

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

  13. 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.

  14. Microfluidic Devices for Forensic DNA Analysis: A Review

    PubMed Central

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

    2016-01-01

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

  15. Fabrication of polyimide based microfluidic channels for biosensor devices

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

  16. 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

  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. 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.

  19. 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.

  20. Controlling Mass Transport in Microfluidic Devices

    NASA Astrophysics Data System (ADS)

    Kuo, Jason S.; Chiu, Daniel T.

    2011-07-01

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

  1. 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

  2. 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.

  3. 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

  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. Adhesive-based bonding technique for PDMS microfluidic devices.

    PubMed

    Thompson, C Shea; Abate, Adam R

    2013-02-21

    We present a simple and inexpensive technique for bonding PDMS microfluidic devices. The technique uses only adhesive tape and an oven; plasma bonders and cleanroom facilities are not required. It also produces channels that are immediately hydrophobic, allowing formation of aqueous-in-oil emulsions.

  7. Nanoporous membrane-sealed microfluidic devices for improved cell viability.

    PubMed

    Masand, Shirley N; Mignone, Lindsay; Zahn, Jeffrey D; Shreiber, David I

    2011-12-01

    Cell-laden microfluidic devices have broad potential in various biomedical applications, including tissue engineering and drug discovery. However, multiple difficulties encountered while culturing cells within devices affecting cell viability, proliferation, and behavior has complicated their use. While active perfusion systems have been used to overcome the diffusive limitations associated with nutrient delivery into microchannels to support longer culture times, these systems can result in non-uniform oxygen and nutrient delivery and subject cells to shear stresses, which can affect cell behavior. Additionally, histological analysis of cell cultures within devices is generally laborious and yields inconsistent results due to difficulties in delivering labeling agents in microchannels. Herein, we describe a simple, cost-effective approach to preserve cell viability and simplify labeling within microfluidic networks without the need for active perfusion. Instead of bonding a microfluidic network to glass, PDMS, or other solid substrate, the network is bonded to a semi-permeable nanoporous membrane. The membrane-sealed devices allow free exchange of proteins, nutrients, buffers, and labeling reagents between the microfluidic channels and culture media in static culture plates under sterile conditions. The use of the semi-permeable membrane dramatically simplifies microniche cell culturing while avoiding many of the complications which arise from perfusion systems.

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

    NASA Astrophysics Data System (ADS)

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

    2016-11-01

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

  9. An integrated optics microfluidic device for detecting single DNA molecules.

    PubMed

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

    2007-12-01

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

  10. 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

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

    PubMed Central

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

    2008-01-01

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

  12. 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

  13. 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

  14. Effects of hydraulic pressure on cardiomyoblasts in a microfluidic device.

    PubMed

    Hsiao, Yu-Fang; Pan, Huei-Jyuan; Tung, Yi-Chung; Chen, Chien-Chang; Lee, Chau-Hwang

    2015-03-01

    We employed a microfluidic device to study the effects of hydraulic pressure on cardiomyoblast H9c2. The 170 mm Hg pressure increased the cellular area and the expression of atrial natriuretic peptide. With the same device, we demonstrated that the effects of hydraulic pressure on the cardiomyoblast could be reduced by the inhibitor of focal adhesion kinase. This mechanical-chemical antagonism could lead to a potential therapeutic strategy of hypertension-induced cardiac hypertrophy. PMID:25945137

  15. Isotachophoretic preconcenetration on paper-based microfluidic devices.

    PubMed

    Moghadam, Babak Y; Connelly, Kelly T; Posner, Jonathan D

    2014-06-17

    Paper substrates have been widely used to construct point-of-care lateral flow immunoassay (LFIA) diagnostic devices. Paper based microfluidic devices are robust and relatively simple to operate, compared to channel microfluidic devices, which is perhaps their greatest advantage and the reason they have reached a high level of commercial success. However, paper devices may not be well suited for integrated sample preparation, such as sample extraction and preconcentration, which is required in complex samples with low analyte concentrations. In this study, we investigate integration of isotachophoresis (ITP), an electrokinetic preconcentration and extraction technique, onto nitrocellulose-based paper microfluidic devices with the goal to improve the limit of detection of LFIA. ITP has been largely used in traditional capillary based microfluidic devices as a pretreatment method to preconcentrate and separate a variety of ionic compounds. Our findings show that ITP on nitrocellulose is capable of up to a 900 fold increase in initial sample concentration and up to 60% extraction from 100 μL samples and more than 80% extraction from smaller sample volumes. Paper based ITP is challenged by Joule heating and evaporation because it is open to the environment. We achieved high preconcentration by mitigating evaporation induced dispersion using novel cross-shaped device structures that keep the paper hydrated. We show that ITP on the nitrocellulose membrane can be powered and run several times by a small button battery suggesting that it could be integrated to a portable point-of-care diagnostic device. These results highlight the potential of ITP to increase the sensitivity of paper based LFIA under conditions where small analyte concentrations are present in complex biological samples.

  16. 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.

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2013-11-19

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

  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. 3-D microarray and its microfabrication-free fluidic immunoassay device.

    PubMed

    Liu, Yingshuai; Zhang, Yuanyuan; Lu, Zhisong; Li, Chang Ming

    2015-08-19

    Conventional 2-D microarray is known to have high-throughput detection capability; however, the sensing spots density is significantly hindered by the spot-to-spot distance (gap) requirement for eliminating cross-talks between adjacent spots. Herein a new conceptual 3-D microarray device is proposed to significantly improve the spots density. To demonstrate advantages of the 3-D array, a microfabrication-free fluidic immunoassay device is further made by simply coupling an antibodies-arrayed glass cuboid into a circular glass tube. Rapid, sensitive and high-throughput flow-through immunoassays were accomplished with the 3-D array-based device for detection limits of 10-100 pg mL(-1) and wide dynamic range over 4-5 orders of magnitude in human serum with cancer biomarkers α-fetoprotein (AFP) and carcinoembryonic antigen (CEA) as model targets, holding great promise for practical clinical applications. The 3-D microarray device not only significantly increases the density of sensing spots, but also greatly enhances the mass transport for rapid immunoassay when using in a flow-through device. PMID:26343442

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  13. 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

  14. 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.

  15. Paper-based inkjet-printed microfluidic analytical devices.

    PubMed

    Yamada, Kentaro; Henares, Terence G; Suzuki, Koji; Citterio, Daniel

    2015-04-27

    Rapid, precise, and reproducible deposition of a broad variety of functional materials, including analytical assay reagents and biomolecules, has made inkjet printing an effective tool for the fabrication of microanalytical devices. A ubiquitous office device as simple as a standard desktop printer with its multiple ink cartridges can be used for this purpose. This Review discusses the combination of inkjet printing technology with paper as a printing substrate for the fabrication of microfluidic paper-based analytical devices (μPADs), which have developed into a fast-growing new field in analytical chemistry. After introducing the fundamentals of μPADs and inkjet printing, it touches on topics such as the microfluidic patterning of paper, tailored arrangement of materials, and functionalities achievable exclusively by the inkjet deposition of analytical assay components, before concluding with an outlook on future perspectives.

  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. Molecular Probes for Thermometry in Microfluidic Devices

    NASA Astrophysics Data System (ADS)

    Gosse, Charlie; Bergaud, Christian; Löw, Peter

    The temperature is an important parameter with regard to chemical reactivity. It is therefore essential to ensure good thermal control within microsystems designed to carry out biological analysis. We begin by reviewing temperature measurement in the context of the lab-on-a-chip, and outlining the various generic strategies available. We then turnmore specifically to luminescentmolecular probes.We shall show that they all exploit the effect of temperature on a chemical reaction (in the broad sense of the term). More precisely, these probes can be divided in three main categories depending on whether one relies on a phase transition, the modification of a reaction rate, or a shift in an equilibrium. We shall also discuss the main experimental strategies used to transform the image obtained by fluorescence microscopy into a thermal map. Finally, we shall extend the discussion to a few other spectroscopic techniques and examine the prospects for this particular area of microfluidics.

  18. 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

  19. 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.

  20. 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.

  1. 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

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

    DOEpatents

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

    2008-04-01

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

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

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

    PubMed

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

    2015-04-01

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

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

    DOEpatents

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

    2014-08-19

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

  12. Single molecule imaging of NGF axonal transport in microfluidic devices

    PubMed Central

    Zhang, Kai; Osakada, Yasuko; Vrljic, Marija; Chen, Liang; Mudrakola, Harsha V.

    2010-01-01

    Nerve growth factor (NGF) signaling begins at the nerve terminal, where it binds and activates membrane receptors and subsequently carries the cell-survival signal to the cell body through the axon. A recent study revealed that the majority of endosomes contain a single NGF molecule, which makes single molecule imaging an essential tool for NGF studies. Despite being an increasingly popular technique, single molecule imaging in live cells is often limited by background fluorescence. Here, we employed a microfluidic culture platform to achieve background reduction for single molecule imaging in live neurons. Microfluidic devices guide the growth of neurons and allow separately-controlled microenvironment for cell bodies or axon termini. Designs of microfluidic devices were optimized and a three-compartment device successfully achieved direct observation of axonal transport of single NGF when quantum dot labeled NGF (Qdot-NGF) was applied only to the distal-axon compartment while imaging was carried out exclusively in the cell-body compartment. Qdot-NGF was shown to move exclusively toward the cell body with a characteristic stop-and-go pattern of movements. Measurements at various temperatures show that the rate of NGF retrograde transport decreased exponentially over the range of 36–14°C. A 10°C decrease in temperature resulted in a threefold decrease in the rate of NGF retrograde transport. Our successful measurements of NGF transport suggest that the microfluidic device can serve as a unique platform for single molecule imaging of molecular processes in neurons. PMID:20623041

  13. Remote control of reversible localized protein adsorption in microfluidic devices.

    PubMed

    Hao, Nan; Li, Jin-Yi; Xiong, Meng; Xia, Xing-Hua; Xu, Jing-Juan; Chen, Hong-Yuan

    2014-08-13

    We present a facilely prepared graphene oxide (GO)/ poly(dimethylsiloxane) (PDMS) composite by dispersing nanosized GO in PDMS. On the basis of the combination of photothermal effects of GO and grafted thermoresponsive polymer, poly(N-isopropylacrylamide) (PNIPAAm), an optical-driving approach for remote control of localized wettability is realized. And this method has been successfully applied in the spatially controlled reversible protein adsorption in microfluidic devices. PMID:25068799

  14. 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.

  15. 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

  16. 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.

  17. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-09-01

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

  19. 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

  20. 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.

  1. Fabrication of microfluidic devices containing patterned microwell arrays.

    PubMed

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

    2012-02-01

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

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

    PubMed Central

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

    2012-01-01

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

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Simulation of magnetic active polymers for versatile microfluidic devices

    NASA Astrophysics Data System (ADS)

    Gusenbauer, Markus; Özelt, Harald; Fischbacher, Johann; Reichel, Franz; Exl, Lukas; Bance, Simon; Kataeva, Nadezhda; Binder, Claudia; Brückl, Hubert; Schrefl, Thomas

    2013-01-01

    We propose to use a compound of magnetic nanoparticles (20-100 nm) embedded in a flexible polymer (Polydimethylsiloxane PDMS) to filter circulating tumor cells (CTCs). The analysis of CTCs is an emerging tool for cancer biology research and clinical cancer management including the detection, diagnosis and monitoring of cancer. The combination of experiments and simulations lead to a versatile microfluidic lab-on-chip device. Simulations are essential to understand the influence of the embedded nanoparticles in the elastic PDMS when applying a magnetic gradient field. It combines finite element calculations of the polymer, magnetic simulations of the embedded nanoparticles and the fluid dynamic calculations of blood plasma and blood cells. With the use of magnetic active polymers a wide range of tunable microfluidic structures can be created. The method can help to increase the yield of needed isolated CTCs.

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

    PubMed

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

    2016-09-22

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

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

    SciTech Connect

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

    2010-07-15

    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.

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

    PubMed

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

    2016-01-01

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

  15. [Advances on enzymes and enzyme inhibitors research based on microfluidic devices].

    PubMed

    Hou, Feng-Hua; Ye, Jian-Qing; Chen, Zuan-Guang; Cheng, Zhi-Yi

    2010-06-01

    With the continuous development in microfluidic fabrication technology, microfluidic analysis has evolved from a concept to one of research frontiers in last twenty years. The research of enzymes and enzyme inhibitors based on microfluidic devices has also made great progress. Microfluidic technology improved greatly the analytical performance of the research of enzymes and enzyme inhibitors by reducing the consumption of reagents, decreasing the analysis time, and developing automation. This review focuses on the development and classification of enzymes and enzyme inhibitors research based on microfluidic devices.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. Thermal loading in flow-through electroporation microfluidic devices.

    PubMed

    del Rosal, Blanca; Sun, Chen; Loufakis, Despina Nelie; Lu, Chang; Jaque, Daniel

    2013-08-01

    Thermal loading effects in flow-through electroporation microfluidic devices have been systematically investigated by using dye-based ratiometric luminescence thermometry. Fluorescence measurements have revealed the crucial role played by both the applied electric field and flow rate on the induced temperature increments at the electroporation sections of the devices. It has been found that Joule heating could raise the intra-channel temperature up to cytotoxic levels (>45 °C) only when conditions of low flow rates and high applied voltages are applied. Nevertheless, when flow rates and electric fields are set to those used in real electroporation experiments we have found that local heating is not larger than a few degrees, i.e. temperature is kept within the safe range (<32 °C). We also provide thermal images of electroporation devices from which the heat affected area can be elucidated. Experimental data have been found to be in excellent agreement with numerical simulations that have also revealed the presence of a non-homogeneous temperature distribution along the electroporation channel whose magnitude is critically dependent on both applied electric field and flow rate. Results included in this work will allow for full control over the electroporation conditions in flow-through microfluidic devices.

  3. 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

  4. 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

  5. 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.

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

    PubMed

    Yu, Ling; Shi, Zhuan Zhuan

    2015-04-01

    Microfluidic paper-based analytical devices (μPADs) attract tremendous attention as an economical tool for in-field diagnosis, food safety and environmental monitoring. We innovatively fabricated 2D and 3D μPADs by photolithography-patterning microchannels on a Parafilm® and subsequently embossing them to paper. This truly low-cost, wax printer and cutter plotter independent approach offers the opportunity for researchers from resource-limited laboratories to work on paper-based analytical devices. PMID:25710591

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

    PubMed

    Kiani, Amirkianoosh; Venkatakrishnan, Krishnan; Tan, Bo

    2015-06-01

    Recent research in the field of photovoltaics has shown that polymer solar cells have great potential to provide low-cost, lightweight and flexible electronic devices to harvest solar energy. In this paper, we propose a new method for the generation of three-dimensional nanofibers coated on polymer substrate induced by femtosecond laser pulses. In this new method, a thin layer of polymer is irradiated by megahertz femtosecond laser pulses under ambient conditions, and a thin fibrous layer is generated on top of the polymer substrate. This method is single step; no additional materials are added, and the layers of the three-dimensional (3D) polymer nanofibrous structures are grown on top of the substrate after laser irradiation. Light spectroscopy results show significant enhancement of light absorption in the generated 3D nanofibrous layers of polymer. Finally, we suggest how to maximize the light trapping and optical absorption of the generated nanofiber cells by optimizing the laser parameters. PMID:26072881

  8. 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.

  9. Imaging diffusion in a microfluidic device by third harmonic microscopy

    NASA Astrophysics Data System (ADS)

    Petzold, Uwe; Büchel, Andreas; Hardt, Steffen; Halfmann, Thomas

    2012-09-01

    We monitor and characterize near-surface diffusion of miscible, transparent liquids in a microfluidic device by third harmonic microscopy. The technique enables observations even of transparent or index-matched media without perturbation of the sample. In particular, we image concentrations of ethanol diffusing in water and estimate the diffusion coefficient from the third harmonic images. We obtain a diffusion coefficient D = (460 ± 30) μm2/s, which is consistent with theoretical predictions. The investigations clearly demonstrate the potential of harmonic microscopy also under the challenging conditions of transparent fluids.

  10. Microfluidic device for bacterial genome extraction and analysis

    NASA Astrophysics Data System (ADS)

    Galajda, Peter; Riehn, Robert; Wang, Yan-Mei; Keymer, Juan; Golding, Ido; Cox, Edward C.; Austin, Robert H.

    2006-03-01

    Although single molecule DNA manipulation and analysis techniques are emerging, methods for whole genome extraction from single cells, genomic length DNA handling and analytics is still to be developed. Here we present a microfabricated device to address some of these needs. This microfluidic chip is suitable for culturing bacteria and subsequently retrieve their genetic content. As a next step, the extracted DNA can be introduced in a nanostructured segment of the chip for precise handling, stretching and analysis. We hope that similar microdevices can be useful in studying genetic aspects of the cell lifecycle in a variety of organisms.

  11. 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

  12. Microfluidic devices for measuring gene network dynamics in single cells

    PubMed Central

    Bennett, Matthew R.; Hasty, Jeff

    2010-01-01

    The dynamics governing gene regulation have an important role in determining the phenotype of a cell or organism. From processing extracellular signals to generating internal rhythms, gene networks are central to many time-dependent cellular processes. Recent technological advances now make it possible to track the dynamics of gene networks in single cells under various environmental conditions using microfluidic ‘lab-on-a-chip’ devices, and researchers are using these new techniques to analyse cellular dynamics and discover regulatory mechanisms. These technologies are expected to yield novel insights and allow the construction of mathematical models that more accurately describe the complex dynamics of gene regulation. PMID:19668248

  13. 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

  14. "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

  15. 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.

  16. Front-end electronics for impedimetric microfluidic devices

    NASA Astrophysics Data System (ADS)

    Ojarand, Jaan; Giannitsis, Athanasios T.; Min, Mart; Land, Raul

    2011-05-01

    Impedance spectroscopy is a common approach in assessing passive electrical properties of biological matter, however, serious problems appear in microfluidic devices in connection with distortion free signal acquisition from microelectrodes. The quality of impedance measurements highly depends on the presence of stray capacitances, signal distortions, and accompanying noises. Measurement deficiencies may be minimized with optimized electronics and sensing electrodes. The quality can further be improved with appropriate selection of measuring signals and also with selection of measuring methods such as a choice between current or voltage sources and between differential or singleended techniques. The microfluidic device that we present here incorporates an impedance sensor, which consists of an array of two sequential pairs of parallel microelectrodes, embedded in a microfluidic channel. All electronics and fluidic components are placed inside a metal holder, which ensures electric and fluidic connections to peripheral instruments. This configuration provides short electric connections and proper shielding. The method that we are using to evaluate the sample's impedance is the differential measurement technique, capable of suppressing the common mode signals and interferences, appearing in the signal-conditioning front-end circuit. Besides, it opens the possibility for compensating stray effects of the electrodes. For excitation we employ wideband signals, such as chirps or multifreqyency signals, which allow fast measurements, essential in the most impedimetric experiments in biology. The impedance spectra cover the frequency range between 10kHz - 10MHz. This is essential for accessing information relating to β-dispersion, which characterizes the cell's structural properties. We present two measurement schemes: (i) an in-phase differential method, which employs two transimpedance amplifiers, and (ii) an anti-phase method, which uses one transimpedance amplifier

  17. 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

  18. Bifurcation to 3D Helical Magnetic Equilibrium in an Axisymmetric Toroidal Device

    NASA Astrophysics Data System (ADS)

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

    2011-12-01

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

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

    PubMed

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

    2011-12-16

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

  20. User-friendly 3D bioassays with cell-containing hydrogel modules: narrowing the gap between microfluidic bioassays and clinical end-users' needs.

    PubMed

    Lee, Do-Hyun; Bae, Chae Yun; Kwon, Seyong; Park, Je-Kyun

    2015-06-01

    Cell-containing hydrogel modules as cell-hydrogel microunits for creating a physiologically relevant 3D in vivo-like microenvironment with multiple cell types and unique extracellular matrix (ECM) compositions facilitate long-term cell maintenance and bioassays. To date, there have been many important advances in microfluidic bioassays, which incorporate hydrogel scaffolds into surface-accessible microchambers, driven by the strong demand for the application of spatiotemporally defined biochemical stimuli to construct in vivo-like conditions and perform real-time imaging of cell-matrix interactions. In keeping with the trend of fostering collaborations among biologists, clinicians, and microfluidic engineers, it is essential to create a simpler approach for coupling cell-containing hydrogel modules and an automated bioassay platform in a user-friendly format. In this article, we review recent progress in hydrogel-incorporated microfluidics for long-term cell maintenance and discuss some of the simpler and user-friendly 3D bioassay techniques combined with cell-containing hydrogel modules that can be applied to mutually beneficial collaborations with non-engineers. We anticipate that this modular and user-friendly format interfaced with existing laboratory infrastructure will help address several clinical questions in ways that extend well beyond the current 2D cell-culture systems.

  1. Fabrication techniques for microfluidic paper-based analytical devices and their applications for biological testing: A review.

    PubMed

    Xia, Yanyan; Si, Jin; Li, Zhiyang

    2016-03-15

    Paper is increasingly recognized as a user-friendly and ubiquitous substrate for construction of microfluidic devices. Microfluidic paper-based analytical devices (μPADs) provide an alternative technology for development of affordable, portable, disposable and low-cost diagnostic tools for improving point of care testing (POCT) and disease screening in the developing world, especially in those countries with no- or low-infrastructure and limited trained medical and health professionals. We in this review present fabrication techniques for microfluidic devices and their respective applications for biological detection as reported to date. These include: (i) fabrication techniques: examples of devices fabricated by using two-dimensional (2D) and three-dimensional (3D) methods; (ii) detection application: biochemical, immunological and molecular detection by incorporating efficient detection methods such as, colorimetric detection, electrochemical detection, fluorescence detection, chemiluminescence (CL) detection, electrochemiluninescence (ECL) detection, photoelectrochemi (PEC) detection and so on. In addition, main advantages, disadvantages and future trends for the devices are also discussed in this review.

  2. 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…

  3. PDMS and its suitability for analytical microfluidic devices.

    PubMed

    Kuncová-Kallio, Johana; Kallio, Pasi J

    2006-01-01

    Poly(dimethylsiloxane) also known as PDMS is used in a wide range of biomedical applications. These range from implants through catheters to soft contact lenses. Therefore, it is understandable that PDMS has been extensively tested for these purposes. In past years, the microfluidics has moved from predominantly silicon and glass structures towards polymers due to their ease of manufacturing and moderate cost. PDMS has gained a lot of attention in various analytical applications. However, the testing of its suitability for such applications has not been as thorough as in the biomedical applications, perhaps relying on the experiments from that field. Microfluidic PDMS structures are more and more popular in various analytical devices. Such devices consume less reagents and can work with lower sample volumes. On the other hand, the surface-to-sample-volume ratio becomes larger. That increases the influence of material properties on the actual measurement. Some of the challenges include adsorption, diffusion, surface roughness, permeability and elasticity of PDMS, which are discussed in this paper. PMID:17946118

  4. A microfluidic device for performing pressure-driven separations.

    PubMed

    Dutta, Debashis; Ramsey, J Michael

    2011-09-21

    Microchannels in microfluidic devices are frequently chemically modified to introduce specific functional elements or operational modalities. In this work, we describe a miniaturized hydraulic pump created by coating selective channels in a glass microfluidic manifold with a polyelectrolyte multilayer (PEM) that alters the surface charge of the substrate. Pressure-driven flow is generated due to a mismatch in the electroosmotic flow (EOF) rates induced upon the application of an electric field to a tee channel junction that has one arm coated with a positively charged PEM and the other arm left uncoated in its native state. In this design, the channels that generate the hydraulic pressure are interconnected via the third arm of the tee to a field-free analysis channel for performing pressure-driven separations. We have also shown that modifications in the cross-sectional area of the channels in the pumping unit can enhance the hydrodynamic flow through the separation section of the manifold. The integrated device has been demonstrated by separating Coumarin dyes in the field-free analysis channel using open-channel liquid chromatography under pressure-driven flow conditions. PMID:21789335

  5. 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

  6. Analysis of a vibrating interventional device to improve 3-D colormark tracking.

    PubMed

    Fronheiser, Matthew P; Smith, Stephen W

    2007-08-01

    Ultrasound guidance of interventional devices during minimally invasive surgical procedures has been investigated by many researchers. Previously, we extended the methods used by the Colormark tracking system to several interventional devices using a real-time, three-dimensional (3-D) ultrasound system. These results showed that we needed to improve the efficiency and reliability of the tracking. In this paper, we describe an analytical model to predict the transverse vibrations along the length of an atrial septal puncture needle to enable design improvements of the tracking system. We assume the needle can be modeled as a hollow bar with a circular cross section with a fixed proximal end and a free distal end that is suspended vertically to ignore gravity effects. The initial results show an ability to predict the natural nodes and antinodes along the needle using the characteristic equation for free vibrations. Simulations show that applying a forcing function to the device at a natural antinode yields an order of magnitude larger vibration than when driving the device at a node. Pulsed wave spectral Doppler data was acquired along the distal portion of the needle in a water tank using a 2-D matrix array transesophageal echocardiography probe. This data was compared to simulations of forced vibrations from the model. These initial results suggest that the model is a good first order approximation of the vibrating device in a water tank. It is our belief that knowing the location of the natural nodes and antinodes will improve our ability to drive the device to ensure the vibrations at the proximal end will reach the tip of the device, which in turn should improve our ability to track the device in vivo. PMID:17703675

  7. 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

  8. Facial expression identification using 3D geometric features from Microsoft Kinect device

    NASA Astrophysics Data System (ADS)

    Han, Dongxu; Al Jawad, Naseer; Du, Hongbo

    2016-05-01

    Facial expression identification is an important part of face recognition and closely related to emotion detection from face images. Various solutions have been proposed in the past using different types of cameras and features. Microsoft Kinect device has been widely used for multimedia interactions. More recently, the device has been increasingly deployed for supporting scientific investigations. This paper explores the effectiveness of using the device in identifying emotional facial expressions such as surprise, smile, sad, etc. and evaluates the usefulness of 3D data points on a face mesh structure obtained from the Kinect device. We present a distance-based geometric feature component that is derived from the distances between points on the face mesh and selected reference points in a single frame. The feature components extracted across a sequence of frames starting and ending by neutral emotion represent a whole expression. The feature vector eliminates the need for complex face orientation correction, simplifying the feature extraction process and making it more efficient. We applied the kNN classifier that exploits a feature component based similarity measure following the principle of dynamic time warping to determine the closest neighbors. Preliminary tests on a small scale database of different facial expressions show promises of the newly developed features and the usefulness of the Kinect device in facial expression identification.

  9. Recent applications of AC electrokinetics in biomolecular analysis on microfluidic devices.

    PubMed

    Sasaki, Naoki

    2012-01-01

    AC electrokinetics is a generic term that refers to an induced motion of particles and fluids under nonuniform AC electric fields. The AC electric fields are formed by application of AC voltages to microelectrodes, which can be easily integrated into microfluidic devices by standard microfabrication techniques. Moreover, the magnitude of the motion is large enough to control the mass transfer on the devices. These advantages are attractive for biomolecular analysis on the microfluidic devices, in which the characteristics of small space and microfluidics have been mainly employed. In this review, I describe recent applications of AC electrokinetics in biomolecular analysis on microfluidic devices. The applications include fluid pumping and mixing by AC electrokinetic flow, and manipulation of biomolecules such as DNA and proteins by various AC electrokinetic techniques. Future prospects for highly functional biomolecular analysis on microfluidic devices with the aid of AC electrokinetics are also discussed.

  10. 3D integration of planar crossbar memristive devices with CMOS substrate.

    PubMed

    Lin, Peng; Pi, Shuang; Xia, Qiangfei

    2014-10-10

    Planar memristive devices with bottom electrodes embedded into the substrates were integrated on top of CMOS substrates using nanoimprint lithography to implement hybrid circuits with a CMOL-like architecture. The planar geometry eliminated the mechanically and electrically weak parts, such as kinks in the top electrodes in a traditional crossbar structure, and allowed the use of thicker and thus less resistive metal wires as the bottom electrodes. Planar memristive devices integrated with CMOS have demonstrated much lower programing voltages and excellent switching uniformity. With the inclusion of the Moiré pattern, the integration process has sub-20 nm alignment accuracy, opening opportunities for 3D hybrid circuits in applications in the next generation of memory and unconventional computing.

  11. 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

  12. 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

  13. 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

  14. Study of 3D printing method for GRIN micro-optics devices

    NASA Astrophysics Data System (ADS)

    Wang, P. J.; Yeh, J. A.; Hsu, W. Y.; Cheng, Y. C.; Lee, W.; Wu, N. H.; Wu, C. Y.

    2016-03-01

    Conventional optical elements are based on either refractive or reflective optics theory to fulfill the design specifications via optics performance data. In refractive optical lenses, the refractive index of materials and radius of curvature of element surfaces determine the optical power and wavefront aberrations so that optical performance can be further optimized iteratively. Although gradient index (GRIN) phenomenon in optical materials is well studied for more than a half century, the optics theory in lens design via GRIN materials is still yet to be comprehensively investigated before realistic GRIN lenses are manufactured. In this paper, 3D printing method for manufacture of micro-optics devices with special features has been studied based on methods reported in the literatures. Due to the additive nature of the method, GRIN lenses in micro-optics devices seem to be readily achievable if a design methodology is available. First, derivation of ray-tracing formulae is introduced for all possible structures in GRIN lenses. Optics simulation program is employed for characterization of GRIN lenses with performance data given by aberration coefficients in Zernike polynomial. Finally, a proposed structure of 3D printing machine is described with conceptual illustration.

  15. 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.

  16. Rapid prototyping polymers for microfluidic devices and high pressure injections.

    PubMed

    Sollier, Elodie; Murray, Coleman; Maoddi, Pietro; Di Carlo, Dino

    2011-11-21

    Multiple methods of fabrication exist for microfluidic devices, with different advantages depending on the end goal of industrial mass production or rapid prototyping for the research laboratory. Polydimethylsiloxane (PDMS) has been the mainstay for rapid prototyping in the academic microfluidics community, because of its low cost, robustness and straightforward fabrication, which are particularly advantageous in the exploratory stages of research. However, despite its many advantages and its broad use in academic laboratories, its low elastic modulus becomes a significant issue for high pressure operation as it leads to a large alteration of channel geometry. Among other consequences, such deformation makes it difficult to accurately predict the flow rates in complex microfluidic networks, change flow speed quickly for applications in stop-flow lithography, or to have predictable inertial focusing positions for cytometry applications where an accurate alignment of the optical system is critical. Recently, other polymers have been identified as complementary to PDMS, with similar fabrication procedures being characteristic of rapid prototyping but with higher rigidity and better resistance to solvents; Thermoset Polyester (TPE), Polyurethane Methacrylate (PUMA) and Norland Adhesive 81 (NOA81). In this review, we assess these different polymer alternatives to PDMS for rapid prototyping, especially in view of high pressure injections with the specific example of inertial flow conditions. These materials are compared to PDMS, for which magnitudes of deformation and dynamic characteristics are also characterized. We provide a complete and systematic analysis of these materials with side-by-side experiments conducted in our lab that also evaluate other properties, such as biocompatibility, solvent compatibility, and ease of fabrication. We emphasize that these polymer alternatives, TPE, PUMA and NOA, have some considerable strengths for rapid prototyping when bond

  17. 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

  18. 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

  19. 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.

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

    PubMed

    Moreno-Arotzena, O; Mendoza, G; Cóndor, M; Rüberg, T; García-Aznar, J M

    2014-11-01

    Microfluidic devices allow for the production of physiologically relevant cellular microenvironments by including biomimetic hydrogels and generating controlled chemical gradients. During transport, the biomolecules interact in distinct ways with the fibrillar networks: as purely diffusive factors in the soluble fluid or bound to the matrix proteins. These two main mechanisms may regulate distinct cell responses in order to guide their directional migration: caused by the substrate-bound chemoattractant gradient (haptotaxis) or by the gradient established within the soluble fluid (chemotaxis). In this work 3D diffusion experiments, in combination with ELISA assays, are performed using microfluidic platforms in order to quantify the distribution of PDGF-BB and TGF-β1 across collagen and fibrin gels. Furthermore, to gain a deeper understanding of the fundamental processes, the experiments are reproduced by computer simulations based on a reaction-diffusion transport model. This model yields an accurate prediction of the experimental results, confirming that diffusion and binding phenomena are established within the microdevice.

  1. 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

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

    PubMed

    Moreno-Arotzena, O; Mendoza, G; Cóndor, M; Rüberg, T; García-Aznar, J M

    2014-11-01

    Microfluidic devices allow for the production of physiologically relevant cellular microenvironments by including biomimetic hydrogels and generating controlled chemical gradients. During transport, the biomolecules interact in distinct ways with the fibrillar networks: as purely diffusive factors in the soluble fluid or bound to the matrix proteins. These two main mechanisms may regulate distinct cell responses in order to guide their directional migration: caused by the substrate-bound chemoattractant gradient (haptotaxis) or by the gradient established within the soluble fluid (chemotaxis). In this work 3D diffusion experiments, in combination with ELISA assays, are performed using microfluidic platforms in order to quantify the distribution of PDGF-BB and TGF-β1 across collagen and fibrin gels. Furthermore, to gain a deeper understanding of the fundamental processes, the experiments are reproduced by computer simulations based on a reaction-diffusion transport model. This model yields an accurate prediction of the experimental results, confirming that diffusion and binding phenomena are established within the microdevice. PMID:25587374

  3. 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.

  4. 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.

  5. 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

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

    PubMed

    Bräuer-Burchardt, Christian; Heinze, Matthias; Schmidt, Ingo; Kühmstedt, Peter; Notni, Gunther

    2015-12-23

    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.

  7. 3D integration of photonic crystal devices: vertical coupling with a silicon waveguide.

    PubMed

    Ferrier, L; Romeo, P Rojo; Letartre, X; Drouard, E; Viktorovitch, P

    2010-07-19

    Two integrated devices based on the vertical coupling between a photonic crystal microcavity and a silicon (Si) ridge waveguide are presented in this paper. When the resonator is coupled to a single waveguide, light can be spectrally extracted from the waveguide to free space through the far field emission of the resonator. When the resonator is vertically coupled to two waveguides, a vertical add-drop filter can be realized. The dropping efficiency of these devices relies on a careful design of the resonator. In this paper, we use a Fabry-Perot (FP) microcavity composed of two photonic crystal (PhC) slab mirrors. Thanks to the unique dispersion properties of slow Bloch modes (SBM) at the flat extreme of the dispersion curve, it is possible to design a FP cavity exhibiting two quasi-degenerate modes. This specific configuration allows for a coupling efficiency that can theoretically achieve 100%. Using 3D FDTD calculations, we discuss the design of such devices and show that high dropping efficiency can be achieved between the Si waveguides and the PhC microcavity.

  8. Microwave-induced adjustable nonlinear temperature gradients in microfluidic devices

    NASA Astrophysics Data System (ADS)

    Shah, Jayna J.; Geist, Jon; Gaitan, Michael

    2010-10-01

    We describe on-chip microwave generation of spatial temperature gradients in a polymeric microfluidic device that includes an integrated microstrip transmission line. The transmission line was fabricated photolithographically on commercially available adhesive copper tape. The fluid temperature during microwave heating was measured by observing the temperature-dependent fluorescence intensity of a dye solution in the microchannel. Large interference effects, which were produced by superposition of a sinusoidal and two exponential temperature distributions, were measured at 12 GHz and 19 GHz. Temperature extremes of 31 °C and 53 °C at the minimum and maximum of the sinusoid were established within 1 s. The sinusoid also produced a quasilinear temperature gradient along a 2 mm distance with a slope of 7.3 °C mm-1. This technique has the potential to benefit many biological, chemical and physical applications requiring rapid temperature gradients.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. Protocol for Biofilm Streamer Formation in a Microfluidic Device with Micro-pillars

    PubMed Central

    Hassanpourfard, Mahtab; Sun, Xiaohui; Valiei, Amin; Mukherjee, Partha; Thundat, Thomas; Liu, Yang; Kumar, Aloke

    2014-01-01

    Several bacterial species possess the ability to attach to surfaces and colonize them in the form of thin films called biofilms. Biofilms that grow in porous media are relevant to several industrial and environmental processes such as wastewater treatment and CO2 sequestration. We used Pseudomonas fluorescens, a Gram-negative aerobic bacterium, to investigate biofilm formation in a microfluidic device that mimics porous media. The microfluidic device consists of an array of micro-posts, which were fabricated using soft-lithography. Subsequently, biofilm formation in these devices with flow was investigated and we demonstrate the formation of filamentous biofilms known as streamers in our device. The detailed protocols for fabrication and assembly of microfluidic device are provided here along with the bacterial culture protocols. Detailed procedures for experimentation with the microfluidic device are also presented along with representative results. PMID:25178035

  17. 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.

  18. 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.

  19. 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

  20. C-peptide and zinc delivery to erythrocytes requires the presence of albumin: implications in diabetes explored with a 3D-printed fluidic device.

    PubMed

    Liu, Yueli; Chen, Chengpeng; Summers, Suzanne; Medawala, Wathsala; Spence, Dana M

    2015-05-01

    People with type 1 diabetes (T1D) must administer insulin exogenously due to the destruction of their pancreatic β-cells. Endogenous insulin is stored in β-cell granules along with C-peptide, a 31 amino acid peptide that is secreted from these granules in amounts equal to insulin. Exogenous co-administration of C-peptide with insulin has proven to reduce diabetes-associated complications in animals and humans. The exact mechanism of C-peptide's beneficial effects after secretion from the β-cell granules is not completely understood, thus hindering its development as an exogenously administered hormone. Monitoring tissue-to-tissue communication using a 3D-printed microfluidic device revealed that zinc and C-peptide are being delivered to erythrocytes by albumin. Upon delivery, erythrocyte-derived ATP increased by >50%, as did endothelium-derived NO, which was measured downstream in the 3D-printed device. Our results suggest that hormone replacement therapy in diabetes may be improved by exogenous administration of a C-peptide ensemble that includes zinc and albumin. PMID:25825241

  1. 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.

  2. Control of sequential fluid delivery in a fully autonomous capillary microfluidic device.

    PubMed

    Novo, Pedro; Volpetti, Francesca; Chu, Virginia; Conde, João Pedro

    2013-02-21

    Microfluidics and miniaturization of biosensors are fundamental for the development of point-of-care (PoC) diagnostic and analytical tools with the potential of decreasing reagent consumption and time of analysis while increasing portability. However, interfacing microfluidics with fluid control systems is still a limiting factor in practical implementation. We demonstrate an innovative capillary microfluidic design that allows sequential insertion of controlled volumes of liquids into a microfluidic channel with general applicability. The system requires only the placing of liquids at the corresponding inlets. Subsequently, the different solutions flow inside the microfluidic device sequentially and autonomously without the use of valves using integrated capillary pumps. The capillary microfluidic system is demonstrated with a model immunoassay. PMID:23263650

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. Characterization of nanoparticle delivery in microcirculation using a microfluidic device.

    PubMed

    Thomas, Antony; Tan, Jifu; Liu, Yaling

    2014-07-01

    This work focuses on the characterization of particle delivery in microcirculation through a microfluidic device. In microvasculature the vessel size is comparable to that of red blood cells (RBCs) and the existence of blood cells largely influences the dispersion and binding distribution of drug loaded particles. The geometry of the microvasculature leads to non-uniform particle distribution and affects the particle binding characteristics. We perform an in vitro study in a microfluidic chip with micro vessel mimicking channels having a rectangular cross section. Various factors that influence particle distribution and delivery such as the vessel geometry, shear rate, blood cells, particle size, particle antibody density are considered in this study. Around 10% higher particle binding density is observed at bifurcation regions of the mimetic microvasculature geometry compared to straight regions. Particle binding density is found to decrease with increased shear rates. RBCs enhance particle binding for both 210 nm and 2 μm particles for shear rates between 200-1600 s(-1) studied. The particle binding density increases about 2-3 times and 6-10 times when flowing in whole blood at 25% RBC concentration compared to the pure particle case, for 210 nm and 2 μm particles respectively. With RBCs, the binding enhancement is more significant for 2 μm particles than that for 210 nm particles, which indicates an enhanced size dependent exclusion of 2 μm particles from the channel centre to the cell free layer (CFL). Increased particle antibody coating density leads to higher particle binding density for both 210 nm and 2 μm particles. PMID:24788074

  8. 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

  9. A novel MR-guided interventional device for 3D circumferential access to breast tissue

    PubMed Central

    Smith, Matthew; Zhai, Xu; Harter, Ray; Sisney, Gale; Elezaby, Mai; Fain, Sean

    2008-01-01

    MRI is rapidly growing as a tool for image-guided procedures in the breast such as needle localizations, biopsy, and cryotherapy. The ability of MRI to resolve small (<1 cm) lesions allows earlier detection and diagnosis than with ultrasound. Most MR-guidance methods perform a two-dimensional compression of the breast that distorts tissue anatomy and limits medial access. This work presents a system for localizing breast lesions with 360° access to breast tissue. A novel system has been developed to perform breast lesion localization using MR guidance that uses a 3D radial coordinate system with four degrees of freedom. The device is combined with a novel breast RF coil for improved signal to noise and rotates 360° around the breast to allow medial, lateral, superior, and inferior access minimizing insertion depth to the target. Coil performance was evaluated using a human volunteer by comparing signal to noise from both the developed breast RF coil and a commercial seven-channel breast coil. The system was tested with a breast-shaped gel phantom containing randomly distributed MR-visible targets. MR-compatible localization needles were used to demonstrate the accuracy and feasibility of the concept for breast biopsy. Localization results were classified based on the relationship between the final needle tip position and the lesion. A 3D bladder concept was also tested using animal tissue to evaluate the device’s ability to immobilize deformable breast tissue during a needle insertion. The RF breast coil provided signal to noise values comparable to a seven-channel breast coil. The needle tip was in contact with the targeted lesion in 89% (25∕28) of all the trials and 100% (6∕6) of the trials with targeted lesions >6 mm. Target lesions were 3–4 mm in diameter for 47% (13∕28), 5–6 mm in diameter for 32% (9∕28), and over 6 mm in diameter for 21% (6∕28) of the trials, respectively. The 3D bladder concept was shown to immobilize a deformable animal

  10. 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

  11. 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

  12. 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.

  13. Modification of Microfluidic Paper-Based Devices with Silica Nanoparticles

    PubMed Central

    Evans, Elizabeth; Gabriel, Ellen Flávia Moreira; Benavidez, Tomás E.; Coltro, Wendell Karlos Tomazelli; Garcia, Carlos D.

    2014-01-01

    This paper describes a silica nanoparticle-modified microfluidic paper-based analytical device (μPAD) with improved color intensity and uniformity for three different enzymatic reactions with clinical relevance (lactate, glucose, and glutamate). The μPADs were produced on Whatman grade 1 filter paper and using a CO2 laser engraver. Silica nanoparticles modified with 3-aminopropyltriethoxysilane (APTES) were then added to the paper devices to facilitate the adsorption of selected enzymes and prevent the washing away effect that creates color gradients in the colorimetric measurements. Here we show three different enzymatic assays for compounds. According to the results herein described, the addition of silica nanoparticles yielded to significant improvements in color intensity and uniformity. The resulting μPADs allowed for the detection of the three analytes in clinically-relevant concentration ranges with limits of detection (LOD) of 0.63 mM, 0.50 mM, and 0.25 mM for lactate, glucose, and glutamate, respectively. An example of an analytical application has been demonstrated for the semi-quantitative detection of all three analytes in artificial urine. The results demonstrate the potential of silica nanoparticles to avoid the washing away effect and improve the color uniformity and intensity in colorimetric bioassays performed on μPADs. PMID:25204446

  14. 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.

  15. Efficient coupling of acoustic modes in microfluidic channel devices.

    PubMed

    Bora, M; Shusteff, M

    2015-08-01

    This work introduces a new numerical simulation approach to acoustic microfluidic chip design based on coupled-resonator theory. A simplified acoustofluidic device operating in the transverse elastic mode is investigated and optimized for maximal pressure standing wave amplitude. This design approach provides insights into the symmetry and frequency characteristics of acoustic chip resonances that cannot be obtained from analysis based on wave propagation arguments. The new approach reveals that optimal performance requires spatial symmetry-matching and frequency-matching of the full device's elastic resonance to the channel's acoustic resonance. Symmetry selection is demonstrated for a three terminal piezoelectric transducer actuation scheme showing suppression of opposite-symmetry and enhancement of same-symmetry acoustic modes. Excitation of ultrasonic waves exhibits the anti-crossing behaviour predicted by coupled mode theory with the acoustic mode splitting into two distinct branches. Increased efficiency of energy transfer from the transducer into the fluid, with its corresponding increase in pressure amplitude, suggests a potential path toward significant increases in acoustic separator performance. PMID:26118358

  16. 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

  17. 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

  18. 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

  19. 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).

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

    PubMed

    Koo, Hyung-Jun; Velev, Orlin D

    2013-05-09

    We review the recent progress in the emerging area of devices and circuits operating on the basis of ionic currents. These devices operate at the intersection of electrochemistry, electronics, and microfluidics, and their potential applications are inspired by essential biological processes such as neural transmission. Ionic current rectification has been demonstrated in diode-like devices containing electrolyte solutions, hydrogel, or hydrated nanofilms. More complex functions have been realized in ionic current based transistors, solar cells, and switching memory devices. Microfluidic channels and networks-an intrinsic component of the ionic devices-could play the role of wires and circuits in conventional electronics.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. Split and flow: reconfigurable capillary connection for digital microfluidic devices.

    PubMed

    Lapierre, Florian; Harnois, Maxime; Coffinier, Yannick; Boukherroub, Rabah; Thomy, Vincent

    2014-09-21

    Supplying liquid to droplet-based microfluidic microsystems remains a delicate task facing the problems of coupling continuous to digital or macro- to microfluidic systems. Here, we take advantage of superhydrophobic microgrids to address this problem. Insertion of a capillary tube inside a microgrid aperture leads to a simple and reconfigurable droplet generation setup.

  6. Split and flow: reconfigurable capillary connection for digital microfluidic devices.

    PubMed

    Lapierre, Florian; Harnois, Maxime; Coffinier, Yannick; Boukherroub, Rabah; Thomy, Vincent

    2014-09-21

    Supplying liquid to droplet-based microfluidic microsystems remains a delicate task facing the problems of coupling continuous to digital or macro- to microfluidic systems. Here, we take advantage of superhydrophobic microgrids to address this problem. Insertion of a capillary tube inside a microgrid aperture leads to a simple and reconfigurable droplet generation setup. PMID:25058858

  7. 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.

  8. Manipulation of DNA for use in microfluidic devices

    SciTech Connect

    Belgrader, P; Bettencourt, K; Davidson, J C; Mariella, R P; Miles, R; Nasarabadi, NS; Wang, A

    1998-11-18

    MEMS microfluidic systems are becoming increasingly popular as a way to integrate sample preparation and biological assays on a single substrate. The resulting reduction in manual operations and reduced reagent use can lead to significant cost savings in performing biological tests. The authors have explored the use of small scale dielectrophoresis and electrophoresis as a way to manipulate DNA for sample preparation in DNA-based assays. The use of electric fields to manipulate DNA is readily achieved in MEMS devices using standard photolithography techniques to add electrodes to etched flow channels. Dielectrophoresis allows for manipulation of cells and DNA independently of the liquid. This ability is useful in small, valveless fluidic microchips. An advantage of the use of the dielectrophoretic force over an electrophoretic force is that dielectrophoresis works equally well using an AC field, thus reducing trapping of small ions and mitigating electrochemical effects at the electrodes. However, the dielectrophoretic force on the DNA is a function of the volume of the particle; thus, there is a lower practical limit to use of the dielectrophoretic force. Consequently they have also explored methods of manipulating smaller DNA fragments using what they refer to as a stepped electrophoresis method.

  9. 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

  10. Integrating Electronics and Microfluidics on Paper.

    PubMed

    Hamedi, Mahiar M; Ainla, Alar; Güder, Firat; Christodouleas, Dionysios C; Fernández-Abedul, M Teresa; Whitesides, George M

    2016-07-01

    Paper microfluidics and printed electronics have developed independently, and are incompatible in many aspects. Monolithic integration of microfluidics and electronics on paper is demonstrated. This integration makes it possible to print 2D and 3D fluidic, electrofluidic, and electrical components on paper, and to fabricate devices using them.

  11. Nanoparticle-based signal generation and amplification in microfluidic devices for bioanalysis.

    PubMed

    Hu, Chong; Yue, Wanqing; Yang, Mengsu

    2013-11-21

    Signal generation and amplification based on nanomaterials and microfluidic techniques have both attracted considerable attention separately due to the demands for ultrasensitive and high-throughput detection of biomolecules. This article reviews the latest development of signal amplification strategies based on nanoparticles for bioanalysis and their integration and applications in microfluidic systems. The applications of nanoparticles in bioanalysis were categorized based on the different approaches of signal amplification, and the microfluidic techniques were summarized based on cell analysis and biomolecule detection with a focus on the integration of nanoparticle-based amplification in microfluidic devices for ultrasensitive bioanalysis. The advantages and limitations of the combination of nanoparticles-based amplification with microfluidic techniques were evaluated, and the possible developments for future research were discussed.

  12. 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…

  13. 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.

  14. 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

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

    PubMed

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

    2015-09-01

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

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

    PubMed Central

    2011-01-01

    Polymethylmethacrylate (PMMA) microfluidic devices have been fabricated using a hot embossing technique to incorporate micro-pillar features on the bottom wall of the device which when combined with either a plasma treatment or the coating of a diamond-like carbon (DLC) film presents a range of surface modification profiles. Experimental results presented in detail the surface modifications in the form of distinct changes in the static water contact angle across a range from 44.3 to 81.2 when compared to pristine PMMA surfaces. Additionally, capillary flow of water (dyed to aid visualization) through the microfluidic devices was recorded and analyzed to provide comparison data between filling time of a microfluidic chamber and surface modification characteristics, including the effects of surface energy and surface roughness on the microfluidic flow. We have experimentally demonstrated that fluid flow and thus filling time for the microfluidic device was significantly faster for the device with surface modifications that resulted in a lower static contact angle, and also that the incorporation of micro-pillars into a fluidic device increases the filling time when compared to comparative devices. PMID:21711936

  17. Microfluidic Devices for Behavioral Analysis, Microscopy, and Neuronal Imaging in Caenorhabditis elegans.

    PubMed

    Lagoy, Ross C; Albrecht, Dirk R

    2015-01-01

    Microfluidic devices offer several advantages for C. elegans research, particularly for presenting precise physical and chemical environments, immobilizing animals during imaging, quantifying behavior, and automating screens. However, challenges to their widespread adoption in the field include increased complexity over conventional methods, operational problems (such as clogging, leaks, and bubbles), difficulty in obtaining or fabricating devices, and the need to characterize biological results obtained from new assay formats. Here we describe the preparation and operation of simple, reusable microfluidic devices for quantifying behavioral responses to chemical patterns, and single-use devices to arrange animals for time-lapse microscopy and to measure neuronal activity. We focus on details that eliminate or reduce the frustrations commonly experienced by new users of microfluidic devices. PMID:26423974

  18. Integration of microfluidic chip with biomimetic hydrogel for 3D controlling and monitoring of cell alignment and migration.

    PubMed

    Lee, Kwang Ho; Lee, Ki Hwa; Lee, Jeonghoon; Choi, Hyuk; Lee, Donghee; Park, Yongdoo; Lee, Sang-Hoon

    2014-04-01

    A biomimetic hydrogel was integrated into microfluidic chips to monitor glioma cell alignment and migration. The extracellular matrix-based biomimetic hydrogel was remodeled by matrix metalloprotease (MMP) secreted by glioma cells and the hydrogel could thus be used to assess cellular behavior. Both static and dynamic cell growth conditions (flow rate of 0.1 mL/h) were used. Cell culture medium with and without vascular endothelial growth factor (VEGF), insensitive VEGF and tissue inhibitor of metalloproteinases (TIMP) were employed to monitor cell behavior. A concentration gradient formed in the hydrogel resulted in differences in cell behavior. Glioma cell viability in the microchannel was 75-85%. Cells in the VEGF-loaded microchannels spread extensively, degrading the MMP-sensitive hydrogel, and achieved cell sizes almost fivefold larger than seen in the control medium. Our integrated system can be used as a model for the study of cellular behavior in a controlled microenvironment generated by fluidic conditions in a biomimetic matrix.

  19. Microfluidic device for continuous single cells analysis via Raman spectroscopy enhanced by integrated plasmonic nanodimers.

    PubMed

    Perozziello, Gerardo; Candeloro, Patrizio; De Grazia, Antonio; Esposito, Francesco; Allione, Marco; Coluccio, Maria Laura; Tallerico, Rossana; Valpapuram, Immanuel; Tirinato, Luca; Das, Gobind; Giugni, Andrea; Torre, Bruno; Veltri, Pierangelo; Kruhne, Ulrich; Della Valle, Giuseppe; Di Fabrizio, Enzo

    2016-01-25

    In this work a Raman flow cytometer is presented. It consists of a microfluidic device that takes advantages of the basic principles of Raman spectroscopy and flow cytometry. The microfluidic device integrates calibrated microfluidic channels- where the cells can flow one-by-one -, allowing single cell Raman analysis. The microfluidic channel integrates plasmonic nanodimers in a fluidic trapping region. In this way it is possible to perform Enhanced Raman Spectroscopy on single cell. These allow a label-free analysis, providing information about the biochemical content of membrane and cytoplasm of the each cell. Experiments are performed on red blood cells (RBCs), peripheral blood lymphocytes (PBLs) and myelogenous leukemia tumor cells (K562).

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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…

  5. 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.

  6. Fabricating process of hollow out-of-plane Ni microneedle arrays and properties of the integrated microfluidic device

    NASA Astrophysics Data System (ADS)

    Zhu, Jun; Cao, Ying; Wang, Hong; Li, Yigui; Chen, Xiang; Chen, Di

    2013-07-01

    Although microfluidic devices that integrate microfluidic chips with hollow out-of-plane microneedle arrays have many advantages in transdermal drug delivery applications, difficulties exist in their fabrication due to the special three-dimensional structures of hollow out-of-plane microneedles. A new, cost-effective process for the fabrication of a hollow out-of-plane Ni microneedle array is presented. The integration of PDMS microchips with the Ni hollow microneedle array and the properties of microfluidic devices are also presented. The integrated microfluidic devices provide a new approach for transdermal drug delivery.

  7. Custom fabrication of biomass containment devices using 3-D printing enables bacterial growth analyses with complex insoluble substrates

    DOE PAGES

    Nelson, Cassandra E.; Beri, Nina R.; Gardner, Jeffrey G.

    2016-09-21

    Physiological studies of recalcitrant polysaccharide degradation are challenging for several reasons, one of which is the difficulty in obtaining a reproducibly accurate real-time measurement of bacterial growth using insoluble substrates. Current methods suffer from several problems including (i) high background noise due to the insoluble material interspersed with cells, (ii) high consumable and reagent cost and (iii) significant time delay between sampling and data acquisition. A customizable substrate and cell separation device would provide an option to study bacterial growth using optical density measurements. To test this hypothesis we used 3-D printing to create biomass containment devices that allow interactionmore » between insoluble substrates and microbial cells but do not interfere with spectrophotometer measurements. Evaluation of materials available for 3-D printing indicated that UV-cured acrylic plastic was the best material, being superior to nylon or stainless steel when examined for heat tolerance, reactivity, and ability to be sterilized. Cost analysis of the 3-D printed devices indicated they are a competitive way to quantitate bacterial growth compared to viable cell counting or protein measurements, and experimental conditions were scalable over a 100-fold range. The presence of the devices did not alter growth phenotypes when using either soluble substrates or insoluble substrates. Furthermore, we applied biomass containment to characterize growth of Cellvibrio japonicus on authentic lignocellulose (non-pretreated corn stover), and found physiological evidence that xylan is a significant nutritional source despite an abundance of cellulose present.« less

  8. Technical Note: Immunohistochemical evaluation of mouse brain irradiation targeting accuracy with 3D-printed immobilization device

    SciTech Connect

    Zarghami, Niloufar Jensen, Michael D.; Talluri, Srikanth; Dick, Frederick A.; Foster, Paula J.; Chambers, Ann F.; Wong, Eugene

    2015-11-15

    Purpose: Small animal immobilization devices facilitate positioning of animals for reproducible imaging and accurate focal radiation therapy. In this study, the authors demonstrate the use of three-dimensional (3D) printing technology to fabricate a custom-designed mouse head restraint. The authors evaluate the accuracy of this device for the purpose of mouse brain irradiation. Methods: A mouse head holder was designed for a microCT couch using CAD software and printed in an acrylic based material. Ten mice received half-brain radiation while positioned in the 3D-printed head holder. Animal placement was achieved using on-board image guidance and computerized asymmetric collimators. To evaluate the precision of beam localization for half-brain irradiation, mice were sacrificed approximately 30 min after treatment and brain sections were stained for γ-H2AX, a marker for DNA breaks. The distance and angle of the γ-H2AX radiation beam border to longitudinal fissure were measured on histological samples. Animals were monitored for any possible trauma from the device. Results: Visualization of the radiation beam on ex vivo brain sections with γ-H2AX immunohistochemical staining showed a sharp radiation field within the tissue. Measurements showed a mean irradiation targeting error of 0.14 ± 0.09 mm (standard deviation). Rotation between the beam axis and mouse head was 1.2° ± 1.0° (standard deviation). The immobilization device was easily adjusted to accommodate different sizes of mice. No signs of trauma to the mice were observed from the use of tooth block and ear bars. Conclusions: The authors designed and built a novel 3D-printed mouse head holder with many desired features for accurate and reproducible radiation targeting. The 3D printing technology was found to be practical and economical for producing a small animal imaging and radiation restraint device and allows for customization for study specific needs.

  9. 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.

  10. An inertia enhanced passive pumping mechanism for fluid flow in microfluidic devices.

    PubMed

    Resto, Pedro J; Berthier, Erwin; Beebe, David J; Williams, Justin C

    2012-06-21

    We describe and characterize a pumping mechanism that leverages the momentum present in small droplets ejected from a micro-nozzle to drive flow in an open microfluidic device. This approach allows driving flow in a microfluidic device in a regime that offers unique features different to those achievable with typical passive pumping or syringe-pump driven flow. Two flow regimes with specific flow characteristics are described: inertia enhanced passive pumping, in which fluid exchange times in the channel are significantly reduced, and inertia actuated flow, in which it is possible to initiate flow in an empty channel or against natural pressure gradients. Momentum is leveraged to create rapid fluid exchanges, instantaneous flow reversal, filling and mixing inside the microfluidic device.

  11. Microfluidic devices for studying heterotypic cell-cell interactions and tissue specimen cultures under controlled microenvironments

    PubMed Central

    Zervantonakis, Ioannis K.; Kothapalli, Chandrasekhar R.; Chung, Seok; Sudo, Ryo; Kamm, Roger D.

    2011-01-01

    Microfluidic devices allow for precise control of the cellular and noncellular microenvironment at physiologically relevant length- and time-scales. These devices have been shown to mimic the complex in vivo microenvironment better than conventional in vitro assays, and allow real-time monitoring of homotypic or heterotypic cellular interactions. Microfluidic culture platforms enable new assay designs for culturing multiple different cell populations and∕or tissue specimens under controlled user-defined conditions. Applications include fundamental studies of cell population behaviors, high-throughput drug screening, and tissue engineering. In this review, we summarize recent developments in this field along with studies of heterotypic cell-cell interactions and tissue specimen culture in microfluidic devices from our own laboratory. PMID:21522496

  12. 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

  13. 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

  14. Ultra-rapid prototyping of flexible, multi-layered microfluidic devices via razor writing.

    PubMed

    Cosson, Steffen; Aeberli, Luc G; Brandenberg, Nathalie; Lutolf, Matthias P

    2015-01-01

    The fabrication of microfluidic devices is often still a time-consuming and costly process. Here we introduce a very simple and cheap microfabrication process based on "razor writing", also termed xurography, for the ultra-rapid prototyping of microfluidic devices. Thin poly(dimethylsiloxane) (PDMS) membranes are spin-coated on flexible plastic foil and cut into user-defined shapes with a bench-top cutter plotter. The PDMS membranes can then be assembled into desirable microdevices via plasma bonding. The plastic foil allows manipulation of exceptionally thin (30-300 μm) PDMS layers and can be readily peeled after fabrication. This versatile technique can be used to produce a wide variety of microfluidic device prototypes within just a few hours.

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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.

  20. Quantitative analysis of Caenorhabditis elegans chemotaxis using a microfluidic device.

    PubMed

    Hu, Liang; Ye, Jinjuan; Tan, Haowei; Ge, Anle; Tang, Lichun; Feng, Xiaojun; Du, Wei; Liu, Bi-Feng

    2015-08-01

    Caenorhabditis elegans, one of the widely studied model organisms, sense external chemical cues and perform relative chemotaxis behaviors through its simple chemosensory neuronal system. To study the mechanism underlying chemosensory behavior, a rapid and reliable method for quantitatively analyzing the worms' behaviors is essential. In this work, we demonstrated a microfluidic approach for investigating chemotaxis responses of worms to chemical gradients. The flow-based microfluidic chip was consisted of circular tree-like microchannels, which was able to generate eight flow streams containing stepwise chemical concentrations without the difference in flow velocity. Worms' upstream swimming into microchannels with various concentrations was monitored for quantitative analysis of the chemotaxis behavior. By using this microfluidic chip, the attractive and repellent responses of C. elegans to NaCl were successfully quantified within several minutes. The results demonstrated the wild type-like repellent responses and severely impaired attractive responses in grk-2 mutant animals with defects in calcium influx. In addition, the chemotaxis analysis of the third stage larvae revealed that its gustatory response was different from that in the adult stage. Thus, our microfluidic method provided a useful platform for studying the chemosensory behaviors of C. elegans and screening of chemosensation-related chemical drugs.

  1. Quantitative analysis of Caenorhabditis elegans chemotaxis using a microfluidic device.

    PubMed

    Hu, Liang; Ye, Jinjuan; Tan, Haowei; Ge, Anle; Tang, Lichun; Feng, Xiaojun; Du, Wei; Liu, Bi-Feng

    2015-08-01

    Caenorhabditis elegans, one of the widely studied model organisms, sense external chemical cues and perform relative chemotaxis behaviors through its simple chemosensory neuronal system. To study the mechanism underlying chemosensory behavior, a rapid and reliable method for quantitatively analyzing the worms' behaviors is essential. In this work, we demonstrated a microfluidic approach for investigating chemotaxis responses of worms to chemical gradients. The flow-based microfluidic chip was consisted of circular tree-like microchannels, which was able to generate eight flow streams containing stepwise chemical concentrations without the difference in flow velocity. Worms' upstream swimming into microchannels with various concentrations was monitored for quantitative analysis of the chemotaxis behavior. By using this microfluidic chip, the attractive and repellent responses of C. elegans to NaCl were successfully quantified within several minutes. The results demonstrated the wild type-like repellent responses and severely impaired attractive responses in grk-2 mutant animals with defects in calcium influx. In addition, the chemotaxis analysis of the third stage larvae revealed that its gustatory response was different from that in the adult stage. Thus, our microfluidic method provided a useful platform for studying the chemosensory behaviors of C. elegans and screening of chemosensation-related chemical drugs. PMID:26320797

  2. 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

    2015-01-01

    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

  3. 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…

  4. A modular cell culture device for generating arrays of gradients using stacked microfluidic flows

    PubMed Central

    Sip, Christopher G.; Bhattacharjee, Nirveek; Folch, Albert

    2011-01-01

    Microfluidics has become increasingly important for the study of biochemical cues because it enables exquisite spatiotemporal control of the microenvironment. Well-characterized, stable, and reproducible generation of biochemical gradients is critical for understanding the complex behaviors involved in many biological phenomena. Although many microfluidic devices have been developed which achieve these criteria, the ongoing challenge for these platforms is to provide a suitably benign and physiologically relevant environment for cell culture in a user-friendly format. To achieve this paradigm, microfluidic designs must consider the full scope of cell culture from substrate preparation, cell seeding, and long-term maintenance to properly observe gradient sensing behavior. In addition, designs must address the challenges associated with altered culture conditions and shear forces in flow-based devices. With this consideration, we have designed and characterized a microfluidic device based on the principle of stacked flows to achieve highly stable gradients of diffusible molecules over large areas with extremely low shear forces. The device utilizes a benign vacuum sealing strategy for reversible application to pre-established cell cultures. We apply this device to an existing culture of breast cancer cells to demonstrate the negligible effect of its shear flow on migratory behavior. Lastly, we extend the stacked-flow design to demonstrate its scalable architecture with a prototype device for generating an array of combinatorial gradients. PMID:21799716

  5. 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

  6. 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

  7. 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.

  8. Solvent-resistant photocurable liquid fluoropolymers for microfluidic device fabrication [corrected].

    PubMed

    Rolland, Jason P; Van Dam, R Michael; Schorzman, Derek A; Quake, Stephen R; DeSimone, Joseph M

    2004-03-01

    We report the first fabrication of a solvent-compatible microfluidic device based on photocurable "Liquid Teflon" materials. The materials are highly fluorinated functionalized perfluoropolyethers (PFPEs) that have liquidlike viscosities that can be cured into tough, highly durable elastomers that exhibit the remarkable chemical resistance of fluoropolymers such as Teflon. Poly(dimethylsiloxane) (PDMS) elastomers have rapidly become the material of choice for many recent microfluidic device applications. Despite the advantages of PDMS in relation to microfluidics technology, the material suffers from a serious drawback in that it swells in most organic solvents. The swelling of PDMS-based devices in organic solvents greatly disrupts the micrometer-sized features and makes it impossible for fluids to flow inside the channels. Our approach to this problem has been to replace PDMS with photocurable perfluoropolyethers. Device fabrication and valve actuation were accomplished using established procedures for PDMS devices. The additional advantage of photocuring allows fabrication time to be decreased from several hours to a matter of minutes. The PFPE-based device exhibited mechanical properties similar to those of Sylgard 184 before and after curing as well as remarkable resistance to organic solvents. This work has the potential to expand the field of microfluidics to many novel applications.

  9. 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.

  10. A new microfluidic device for electric lysis and separation of cells.

    PubMed

    Brun, M; Frénéa-Robin, M; Chateaux, J F; Haddour, N; Deman, A L; Ferrigno, R

    2012-01-01

    This paper demonstrates the potential use of a new microfluidic device embedding thick electrodes for cell lysis and cell separation applications. The system consists of a microfluidic channel featuring conductive walls made of a polydimethylsiloxane (PDMS) matrix mixed with carbon nanoparticles. Cell lysis was performed electrically by applying square pulses across the channel width, which was monitored by fluorimetry. Lysed and unlysed cells showed different dielectrophoretic behavior under appropriate experimental conditions, which suggests that the developed device is suitable to perform both cell lysis and subsequent sorting of viable and dead cells. PMID:23367365

  11. 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

  12. 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.

  13. Ordering Single Cells and Single Embryos in 3D Confinement: A New Device for High Content Screening.

    PubMed

    Wollrab, Viktoria; Caballero, David; Thiagarajan, Raghavan; Riveline, Daniel

    2016-01-01

    Biological cells are usually observed on flat (2D) surfaces. This condition is not physiological, and phenotypes and shapes are highly variable. Screening based on cells in such environments have therefore serious limitations: cell organelles show extreme phenotypes, cell morphologies and sizes are heterogeneous and/or specific cell organelles cannot be properly visualized. In addition, cells in vivo are located in a 3D environment; in this situation, cells show different phenotypes mainly because of their interaction with the surrounding extracellular matrix of the tissue. In order to standardize and generate order of single cells in a physiologically-relevant 3D environment for cell-based assays, we report here the microfabrication and applications of a device for in vitro 3D cell culture. This device consists of a 2D array of microcavities (typically 10(5) cavities/cm(2)), each filled with single cells or embryos. Cell position, shape, polarity and internal cell organization become then normalized showing a 3D architecture. We used replica molding to pattern an array of microcavities, 'eggcups', onto a thin polydimethylsiloxane (PDMS) layer adhered on a coverslip. Cavities were covered with fibronectin to facilitate adhesion. Cells were inserted by centrifugation. Filling percentage was optimized for each system allowing up to 80%. Cells and embryos viability was confirmed. We applied this methodology for the visualization of cellular organelles, such as nucleus and Golgi apparatus, and to study active processes, such as the closure of the cytokinetic ring during cell mitosis. This device allowed the identification of new features, such as periodic accumulations and inhomogeneities of myosin and actin during the cytokinetic ring closure and compacted phenotypes for Golgi and nucleus alignment. We characterized the method for mammalian cells, fission yeast, budding yeast, C. elegans with specific adaptation in each case. Finally, the characteristics of this

  14. Hard top soft bottom microfluidic devices for cell culture and chemical analysis.

    PubMed

    Mehta, Geeta; Lee, Jay; Cha, Wansik; Tung, Yi-Chung; Linderman, Jennifer J; Takayama, Shuichi

    2009-05-15

    We report fabrication and characterization of microfluidic devices made of thermoplastic and elastomeric polymers. These hard-soft hybrid material devices are motivated by the combined need for large scale manufacturability, enhanced barrier properties to gas permeation and evaporation of aqueous solutions compared to poly(dimethyl siloxane) (PDMS) devices, and compatibility with deformation-based actuation. Channel features are created on rigid polymers such as polyethylene terephthalate glycol (PETG), cyclic olefin copolymer (COC), and polystyrene (PS) by hot embossing. These "hard tops" are bonded to elastomeric "soft bottoms" (polyurethane (PU) or PDMS-parylene C-PDMS) to create devices that can be used for microfluidic cell culture where deformation-based fluid actuation schemes are used to perfuse and recirculate media. The higher barrier properties of this device compared to PDMS devices enable cell culture with less evaporation and creation of hypoxic conditions. PMID:19382754

  15. Functional characterization of circulating tumor cells with a prostate-cancer-specific microfluidic device.

    PubMed

    Kirby, Brian J; Jodari, Mona; Loftus, Matthew S; Gakhar, Gunjan; Pratt, Erica D; Chanel-Vos, Chantal; Gleghorn, Jason P; Santana, Steven M; Liu, He; Smith, James P; Navarro, Vicente N; Tagawa, Scott T; Bander, Neil H; Nanus, David M; Giannakakou, Paraskevi

    2012-01-01

    Cancer metastasis accounts for the majority of cancer-related deaths owing to poor response to anticancer therapies. Molecular understanding of metastasis-associated drug resistance remains elusive due to the scarcity of available tumor tissue. Isolation of circulating tumor cells (CTCs) from the peripheral blood of patients has emerged as a valid alternative source of tumor tissue that can be subjected to molecular characterization. However, issues with low purity and sensitivity have impeded adoption to clinical practice. Here we report a novel method to capture and molecularly characterize CTCs isolated from castrate-resistant prostate cancer patients (CRPC) receiving taxane chemotherapy. We have developed a geometrically enhanced differential immunocapture (GEDI) microfluidic device that combines an anti-prostate specific membrane antigen (PSMA) antibody with a 3D geometry that captures CTCs while minimizing nonspecific leukocyte adhesion. Enumeration of GEDI-captured CTCs (defined as intact, nucleated PSMA+/CD45- cells) revealed a median of 54 cells per ml identified in CRPC patients versus 3 in healthy donors. Direct comparison with the commercially available CellSearch® revealed a 2-400 fold higher sensitivity achieved with the GEDI device. Confocal microscopy of patient-derived GEDI-captured CTCs identified the TMPRSS2:ERG fusion protein, while sequencing identified specific androgen receptor point mutation (T868A) in blood samples spiked with only 50 PC C4-2 cells. On-chip treatment of patient-derived CTCs with docetaxel and paclitaxel allowed monitoring of drug-target engagement by means of microtubule bundling. CTCs isolated from docetaxel-resistant CRPC patients did not show any evidence of drug activity. These measurements constitute the first functional assays of drug-target engagement in living circulating tumor cells and therefore have the potential to enable longitudinal monitoring of target response and inform the development of new anticancer

  16. 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).

  17. 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

  18. Microfluidic-optical integrated CMOS compatible devices for label-free biochemical sensing

    NASA Astrophysics Data System (ADS)

    Blanco, F. J.; Agirregabiria, M.; Berganzo, J.; Mayora, K.; Elizalde, J.; Calle, A.; Dominguez, C.; Lechuga, L. M.

    2006-05-01

    The fabrication, characterization and packaging of novel microfluidic-optical integrated biosensors for label-free biochemical detection is presented in this paper. The integrated device consists of a three-dimensional embedded microchannel network fabricated using enhanced CMOS compatible SU-8 multilevel polymer technology on top of a wafer containing Mach-Zehnder Interferometer (MZI) nanophotonic biosensor devices. PMMA housing provides connection to the macro-world and ensures robust leakage-free flow operation of the devices. This macro-microfluidic module can operate at pressure drops up to 1000 kPa. Fluid flow experiments have been performed in order to demonstrate the robustness of our microfluidic devices. The devices have been designed to operate under continuous flow. Steady-state flow rates ranging from 1 to 100 µl min-1 at pressure drops ranging from 10 to 500 kPa were measured in the laminar flow regime. Experimental results are in good agreement with laminar flow theory. The first interferometric sensing measurements are presented in order to demonstrate the functionality of these novel integrated devices for lab-on-a-chip and label-free biosensing applications. A bulk refractive index detection limit of 3.8 × 10-6 was obtained, close to the minimum detected up to now by label-free biosensor devices without microfluidic integration. As far as we know, this is the first time that a label-free biosensor device is integrated within a microfluidic network using a wafer-level CMOS compatible process technology.

  19. Flip channel: A microfluidic device for uniform-sized embryoid body formation and differentiation

    PubMed Central

    Chen, Ying-Hua; Peng, Chien-Chung; Tung, Yi-Chung

    2015-01-01

    This paper reports a two-layered polydimethylsiloxane microfluidic device—Flip channel, capable of forming uniform-sized embryoid bodies (EBs) and performing stem cell differentiation within the same device after flipping the microfluidic channel. The size of EBs can be well controlled by designing the device geometries, and EBs with multiple sizes can be formed within a single device to study EB size-dependent stem cell differentiation. During operation of the device, cells are positioned in the designed positions. As a result, observation and monitoring specific population of cells can be achieved for further analysis. In addition, after flipping the microfluidic channel, stem cell differentiation from the EBs can be performed on an unconfined flat surface that is desired for various differentiation processes. In the experiments, murine embryonic stem cells (ES-D3) are cultured and formed EBs inside the developed device. The size of EBs is well controlled inside the device, and the neural differentiation is performed on the formed EBs after flipping the channel. The EB size-dependent stem cell differentiation is studied using the device to demonstrate its functions. The device provides a useful tool to study stem cell differentiation without complicated device fabrication and tedious cell handling under better-controlled microenvironments. PMID:26487897

  20. 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

  1. 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

  2. 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.

  3. Visualizing oil displacement with foam in a microfluidic device with permeability contrast.

    PubMed

    Conn, Charles A; Ma, Kun; Hirasaki, George J; Biswal, Sibani Lisa

    2014-10-21

    Foam mobility control and novel oil displacement mechanisms were observed in a microfluidic device representing a porous media system with layered permeability. Foam was pre-generated using a flow-focusing microfluidic device and injected into an oil-wet, oil-saturated 2-D PDMS microfluidic device. The device is designed with a central fracture flanked by high-permeability and low-permeability zones stratified in the direction of injection. A 1 : 1, 1% blend of alpha olefin sulfonate 14-16 (AOS) and lauryl betaine (LB) surfactants produced stable foam in the presence of paraffin oil. The oil saturation and pressure drop across the microfluidic device were measured as a function of time and the injected pore volume, indicating an increase in apparent viscosity for foam with an accompanying decrease in oil saturation. In contrast to the control experiments, foam was shown to more effectively mobilize trapped oil by increasing the flow resistance in the fracture and high-permeability zones and by diverting the surfactant solution into adjacent low-permeability zones. The foam was observed to separate into gas-rich and aqueous-rich phases depending on matrix permeability, suggesting that it is not appropriate to treat foam as a homogeneous dispersion of gas and liquid.

  4. 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

  5. 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.

  6. Cell separation by an aqueous two-phase system in a microfluidic device.

    PubMed

    Tsukamoto, Masatoshi; Taira, Shu; Yamamura, Shohei; Morita, Yasutaka; Nagatani, Naoki; Takamura, Yuzuru; Tamiya, Eiichi

    2009-10-01

    We generated an aqueous two-phase laminar flow in a microfluidic chip and used the system to isolate leukocyte and erythrocyte cells from whole blood cells. The microfluidic system reduced the effect of gravity in the aqueous two-phase system (ATPS). Poly(ethylene glycol) (PEG) and dextran (Dex) solutions were used as the two phases, and the independent flow rates of the solutions were both 2 microL/min. When hydrophobic and hydrophilic polystyrene beads were introduced into the microfluidic device, the hydrophilic beads moved to the Dex layer and the hydrophobic beads to the interface between the two phases. In the case of living cells, Jurkat cells and erythrocytes moved more efficiently to the PEG and Dex layers, respectively, than they move in a conventional ATPS. When whole blood cells were inserted into the microfluidic chip, leukocytes could be separated from erythrocytes because erythrocytes moved to the Dex layer while leukocytes remained outside of this layer in the microfluidic system. The reported microfluidic chip for the whole blood cell separation can effectively be integrated into a Micro Total Analysis System designed for cell-based clinical, forensic, and environmental analyses.

  7. 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.

  8. Microfluidic device and method for focusing, segmenting, and dispensing of a fluid stream

    DOEpatents

    Jacobson, Stephen C [Knoxville, TN; Ramsey, J Michael [Knoxville, TN

    2008-09-09

    A microfluidic device and method for forming and dispensing minute volume segments of a material are described. In accordance with the present invention, a microfluidic device and method are provided for spatially confining the material in a focusing element. The device is also adapted for segmenting the confined material into minute volume segments, and dispensing a volume segment to a waste or collection channel. The device further includes means for driving the respective streams of sample and focusing fluids through respective channels into a chamber, such that the focusing fluid streams spatially confine the sample material. The device may also include additional means for driving a minute volume segment of the spatially confined sample material into a collection channel in fluid communication with the waste reservoir.

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. 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…

  17. 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…

  18. 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.

  19. 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…

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. Identification of microfluidic two-phase flow patterns in lab-on-chip devices.

    PubMed

    Yang, Zhaochu; Dong, Tao; Halvorsen, Einar

    2014-01-01

    This work describes a capacitive sensor for identification of microfluidic two-phase flow in lab-on-chip devices. With interdigital electrodes and thin insulation layer utilized, this sensor is capable of being integrated with the microsystems easily. Transducing principle and design considerations are presented with respect to the microfluidic gas/liquid flow patterns. Numerical simulation results verify the operational principle. And the factors affecting the performance of the sensor are discussed. Besides, a feasible process flow for the fabrication is also proposed.

  6. Rapid prototyping of pneumatically actuated hydrocarbon gel valves for centrifugal microfluidic devices.

    PubMed

    Swayne, Laura; Kazarine, Alexei; Templeton, Erin J; Salin, Eric D

    2015-03-01

    A novel, easy to prototype hydrocarbon gel-based active valve was developed for use in centrifugal microfluidic devices. The valve has been demonstrated to restrict flow by an additional 1000 revolutions per minute (RPM) when compared to a passive capillary valve of the same size located at the same radius. Opening of the valve is accomplished in a contactless manner using a stream of focused compressed air. The ease of fabrication, low cost and small dimensions of the gel valve offer the potential for integration of multiple valves of this type into multi-process centrifugal microfluidic systems.

  7. Magnetophoretic continuous purification of single-walled carbon nanotubes from catalytic impurities in a microfluidic device.

    PubMed

    Kang, Joo H; Park, Je-Kyun

    2007-10-01

    A magnetophoretic continuous purification method is presented of single-walled carbon nanotubes (SWCNTs) from the superparamagnetic iron-catalyst impurities in a microfluidic device without any influence on inherent SWCNT properties. By employing microfluidics and a magnetic-field-induced saw-tooth nickel microstructure, a highly enhanced magnetic force in adjoining microchannels is exploited. The iron impurities of SWCNTs are attracted towards areas of higher magnetic-flux density in the microchannels where magnetic field was asymmetrically generated perpendicularly to the streamline. We obtained highly purified SWCNTs at a rate of 0.36 mg h(-1) and that are estimated to be about 99% purity.

  8. 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

  9. 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.

  10. 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.

  11. The use of an MEG device as 3D digitizer and motion monitoring system.

    PubMed

    de Munck, J C; Verbunt, J P; Van't Ent, D; Van Dijk, B W

    2001-08-01

    An algorithm is described that localizes a set of simultaneously activated coils using MEG detectors. These coil positions are used for continuous or intermittent head position registration during long MEG sessions, to coregistrate MR and MEG data and to localize EEG electrodes attached to the scalp, when EEG and MEG are recorded simultaneously. The algorithm is based on a mathematical model in which the coils are described as stationary magnetic dipoles with known source time functions. This knowledge makes it possible to detect and remove bad channels automatically. It is also assumed that the source time functions are orthogonal. Therefore, the localization problem splits into independent localization problems. for each coil. The method is validated in a phantom experiment, where the relative coil positions were known. From this experiment it is found that the average error is 0.25 cm. An error of 0.23 cm was found in an experiment where 64 electrode positions were measured four times independently. Examples of the applications of the method are presented. Our method eliminates the use of an external 3D digitizer and maps the MEG directly onto other modalities. This is not only a practical advantage, but it also reduces the gross registration error. Furthermore, head motions can be monitored and MEG data can be corrected for these motions.

  12. 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.

  13. Monte Carlo study of a 3D Compton imaging device with GEANT4

    NASA Astrophysics Data System (ADS)

    Lenti, M.; Veltri, M.

    2011-10-01

    In this paper we investigate, with a detailed Monte Carlo simulation based on Geant4, the novel approach of Lenti (2008) [1] to 3D imaging with photon scattering. A monochromatic and well collimated gamma beam is used to illuminate the object to be imaged and the photons Compton scattered are detected by means of a surrounding germanium strip detector. The impact position and the energy of the photons are measured with high precision and the scattering position along the beam axis is calculated. We study as an application of this technique the case of brain imaging but the results can be applied as well to situations where a lighter object, with localized variations of density, is embedded in a denser container. We report here the attainable sensitivity in the detection of density variations as a function of the beam energy, the depth inside the object and size and density of the inclusions. Using a 600 keV gamma beam, for an inclusion with a density increase of 30% with respect to the surrounding tissue and thickness along the beam of 5 mm, we obtain at midbrain position a resolution of about 2 mm and a contrast of 12%. In addition the simulation indicates that for the same gamma beam energy a complete brain scan would result in an effective dose of about 1 mSv.

  14. A microfluidic optical platform for real-time monitoring of pH and oxygen in microfluidic bioreactors and organ-on-chip devices.

    PubMed

    Mousavi Shaegh, Seyed Ali; De Ferrari, Fabio; Zhang, Yu Shrike; Nabavinia, Mahboubeh; Binth Mohammad, Niema; Ryan, John; Pourmand, Adel; Laukaitis, Eleanor; Banan Sadeghian, Ramin; Nadhman, Akhtar; Shin, Su Ryon; Nezhad, Amir Sanati; Khademhosseini, Ali; Dokmeci, Mehmet Remzi

    2016-07-01

    There is a growing interest to develop microfluidic bioreactors and organ-on-chip platforms with integrated sensors to monitor their physicochemical properties and to maintain a well-controlled microenvironment for cultured organoids. Conventional sensing devices cannot be easily integrated with microfluidic organ-on-chip systems with low-volume bioreactors for continual monitoring. This paper reports on the development of a multi-analyte optical sensing module for dynamic measurements of pH and dissolved oxygen levels in the culture medium. The sensing system was constructed using low-cost electro-optics including light-emitting diodes and silicon photodiodes. The sensing module includes an optically transparent window for measuring light intensity, and the module could be connected directly to a perfusion bioreactor without any specific modifications to the microfluidic device design. A compact, user-friendly, and low-cost electronic interface was developed to control the optical transducer and signal acquisition from photodiodes. The platform enabled convenient integration of the optical sensing module with a microfluidic bioreactor. Human dermal fibroblasts were cultivated in the bioreactor, and the values of pH and dissolved oxygen levels in the flowing culture medium were measured continuously for up to 3 days. Our integrated microfluidic system provides a new analytical platform with ease of fabrication and operation, which can be adapted for applications in various microfluidic cell culture and organ-on-chip devices. PMID:27648113

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. Micro 3D cell culture systems for cellular behavior studies: Culture matrices, devices, substrates, and in-situ sensing methods.

    PubMed

    Choi, Jonghoon; Lee, Eun Kyu; Choo, Jaebum; Yuh, Junhan; Hong, Jong Wook

    2015-09-01

    Microfabricated systems equipped with 3D cell culture devices and in-situ cellular biosensing tools can be a powerful bionanotechnology platform to investigate a variety of biomedical applications. Various construction substrates such as plastics, glass, and paper are used for microstructures. When selecting a construction substrate, a key consideration is a porous microenvironment that allows for spheroid growth and mimics the extracellular matrix (ECM) of cell aggregates. Various bio-functionalized hydrogels are ideal candidates that mimic the natural ECM for 3D cell culture. When selecting an optimal and appropriate microfabrication method, both the intended use of the system and the characteristics and restrictions of the target cells should be carefully considered. For highly sensitive and near-cell surface detection of excreted cellular compounds, SERS-based microsystems capable of dual modal imaging have the potential to be powerful tools; however, the development of optical reporters and nanoprobes remains a key challenge. We expect that the microsystems capable of both 3D cell culture and cellular response monitoring would serve as excellent tools to provide fundamental cellular behavior information for various biomedical applications such as metastasis, wound healing, high throughput screening, tissue engineering, regenerative medicine, and drug discovery and development. PMID:26358782

  3. Ethylene vinyl acetate (EVA) as a new drug carrier for 3D printed medical drug delivery devices.

    PubMed

    Genina, Natalja; Holländer, Jenny; Jukarainen, Harri; Mäkilä, Ermei; Salonen, Jarno; Sandler, Niklas

    2016-07-30

    The main purpose of this work was to investigate the printability of different grades of ethylene vinyl acetate (EVA) copolymers as new feedstock material for fused-deposition modeling (FDM™)-based 3D printing technology in fabrication of custom-made T-shaped intrauterine systems (IUS) and subcutaneous rods (SR). The goal was to select an EVA grade with optimal properties, namely vinyl acetate content, melting index, flexural modulus, for 3D printing of implantable prototypes with the drug incorporated within the entire matrix of the medical devices. Indomethacin was used as a model drug in this study. Out of the twelve tested grades of the EVA five were printable. One of them showed superior print quality and was further investigated by printing drug-loaded filaments, containing 5% and 15% indomethacin. The feedstock filaments were fabricated by hot-melt extrusion (HME) below the melting point of the drug substance and the IUS and SR were successfully printed at the temperature above the melting point of the drug. As a result, the drug substance in the printed prototypes showed to be at least partly amorphous, while the drug in the corresponding HME filaments was crystalline. This difference affected the drug release profiles from the filaments and printed prototype products: faster release from the prototypes over 30days in the in vitro tests. To conclude, this study indicates that certain grades of EVA were applicable feedstock material for 3D printing to produce drug-loaded implantable prototypes.

  4. 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

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

    PubMed

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

    2015-03-21

    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 after a) a certain period of time, or b) 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 ~50 s 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.

  6. 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

  7. 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

  8. Magnetic optical sensor particles: a flexible analytical tool for microfluidic devices.

    PubMed

    Ungerböck, Birgit; Fellinger, Siegfried; Sulzer, Philipp; Abel, Tobias; Mayr, Torsten

    2014-05-21

    In this study we evaluate magnetic optical sensor particles (MOSePs) with incorporated sensing functionalities regarding their applicability in microfluidic devices. MOSePs can be separated from the surrounding solution to form in situ sensor spots within microfluidic channels, while read-out is accomplished outside the chip. These magnetic sensor spots exhibit benefits of sensor layers (high brightness and convenient usage) combined with the advantages of dispersed sensor particles (ease of integration). The accumulation characteristics of MOSePs with different diameters were investigated as well as the in situ sensor spot stability at varying flow rates. Magnetic sensor spots were stable at flow rates specific to microfluidic applications. Furthermore, MOSePs were optimized regarding fiber optic and imaging read-out systems, and different referencing schemes were critically discussed on the example of oxygen sensors. While the fiber optic sensing system delivered precise and accurate results for measurement in microfluidic channels, limitations due to analyte consumption were found for microscopic oxygen imaging. A compensation strategy is provided, which utilizes simple pre-conditioning by exposure to light. Finally, new application possibilities were addressed, being enabled by the use of MOSePs. They can be used for microscopic oxygen imaging in any chip with optically transparent covers, can serve as flexible sensor spots to monitor enzymatic activity or can be applied to form fixed sensor spots inside microfluidic structures, which would be inaccessible to integration of sensor layers.

  9. Fabrication of multilayer-PDMS based microfluidic device for bio-particles concentration detection.

    PubMed

    Masrie, Marianah; Majlis, Burhanuddin Yeop; Yunas, Jumril

    2014-01-01

    This paper discusses the process technology to fabricate multilayer-Polydimethylsiloxane (PDMS) based microfluidic device for bio-particles concentration detection in Lab-on-chip system. The micro chamber and the fluidic channel were fabricated using standard photolithography and soft lithography process. Conventional method by pouring PDMS on a silicon wafer and peeling after curing in soft lithography produces unspecific layer thickness. In this work, a multilayer-PDMS method is proposed to produce a layer with specific and fixed thickness micron size after bonding that act as an optimum light path length for optimum light detection. This multilayer with precise thickness is required since the microfluidic is integrated with optical transducer. Another significant advantage of this method is to provide excellent bonding between multilayer-PDMS layer and biocompatible microfluidic channel. The detail fabrication process were illustrated through scanning electron microscopy (SEM) and discussed in this work. The optical signal responses obtained from the multilayer-PDMS microfluidic channel with integrated optical transducer were compared with those obtained with the microfluidic channel from a conventional method. As a result, both optical signal responses did not show significant differences in terms of dispersion of light propagation for both media.

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

    PubMed Central

    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

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

    NASA Astrophysics Data System (ADS)

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

    2016-09-01

    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.

  12. A microfabricated magnetic actuation device for mechanical conditioning of arrays of 3D microtissues.

    PubMed

    Xu, Fan; Zhao, Ruogang; Liu, Alan S; Metz, Tristin; Shi, Yu; Bose, Prasenjit; Reich, Daniel H

    2015-06-01

    This paper describes an approach to actuate magnetically arrays of microtissue constructs for long-term mechanical conditioning and subsequent biomechanical measurements. Each construct consists of cell/matrix material self-assembled around a pair of flexible poly(dimethylsiloxane) (PDMS) pillars. The deflection of the pillars reports the tissues' contractility. Magnetic stretching of individual microtissues via magnetic microspheres mounted on the cantilevers has been used to elucidate the tissues' elastic modulus and response to varying mechanical boundary conditions. This paper describes the fabrication of arrays of micromagnetic structures that can transduce an externally applied uniform magnetic field to actuate simultaneously multiple microtissues. These structures are fabricated on silicon-nitride coated Si wafers and contain electrodeposited Ni bars. Through-etched holes provide optical and culture media access when the devices are mounted on the PDMS microtissue scaffold devices. Both static and AC forces (up to 20 μN on each microtissue) at physiological frequencies are readily generated in external fields of 40 mT. Operation of the magnetic arrays was demonstrated via measurements of elastic modulus and dynamic stiffening in response to AC actuation of fibroblast populated collagen microtissues.