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1.
A rapid, inexpensive method using alkoxysilanes has been developed to selectively coat the interior of polydimethylsiloxane (PDMS) microfluidic channels with an integral silicaceous layer. This method combines the rapid prototyping capabilities of PDMS with the desirable wetting and electroosmotic properties of glass. The procedure can be carried out on the open faces of PDMS blocks prior to enclosure of the channels, or by flowing the reagents through the preformed channels. Therefore, this methodology allows for high-throughput processing of entire microfluidic devices or selective modification of specific areas of a device. Modification of PDMS with tetraethoxysilane generated a stable surface layer, with enhanced wettability and a more stable electroosmotic flow rate than native PDMS. Modification of PDMS with 3-aminopropyltriethoxysilane generated a surface layer bearing amine functionalities allowing for further chemical derivatization of the PDMS surface.  相似文献   

2.
Xu Y  Xie F  Qiu T  Xie L  Xing W  Cheng J 《Biomicrofluidics》2012,6(1):16504-1650411
Here, we report a novel method for the fabrication of polydimethylsiloxane microdevices with complicated 3-D structures, such as concave and crater shapes, using an easily machined polymethyl methacrylate mold combined with a one-step molding process. The procedure presented here enables rapid preparation of complex 3-D microstructures varying in shape and dimensions. To regulate embryoid body (EB) formation, we fabricated a microfluidic device with an array of concave microwells and found that EBs growing in microwells maintained their shape, viability, and a high degree of homogeneity. We believe that this novel method provides an alternative for rapid prototyping, especially in fabricating devices with curved 3-D microstructures.  相似文献   

3.
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.  相似文献   

4.
Asthana A  Ho Lee K  Kim KO  Kim DM  Kim DP 《Biomicrofluidics》2012,6(1):12821-128219
In this paper, we have presented a non-lithographic embedded template method for rapid and cost-effective fabrication of a selectively permeable calcium-alginate (Ca-alginate) based microfluidic device with long serpentine delay channel. To demonstrate the versatility of the presented method, we have demonstrated two different strategies to fabricate serpentine long delay channels without using any sophisticated microfabrication techniques, in formal lab atmosphere. The procedure presented here, also, enables the preparation of a multilayered microfluidic device with channels of varying dimensions, in a single device without using any sophisticated micromachining instrumentation. In addition, we have also qualitatively studied the diffusion of small and large molecules from a Ca-alginate based microfluidic device and proposed a method to effectively control the out-flow of macro biomolecules from the crosslinked Ca-alginate matrix to create a selectively permeable matrix required for various biological and biomimetic applications, as mentioned in the Introduction section of this work.  相似文献   

5.
In this paper, we have presented a non-lithographic embedded template method for rapid and cost-effective fabrication of a selectively permeable calcium-alginate (Ca-alginate) based microfluidic device with long serpentine delay channel. To demonstrate the versatility of the presented method, we have demonstrated two different strategies to fabricate serpentine long delay channels without using any sophisticated microfabrication techniques, in formal lab atmosphere. The procedure presented here, also, enables the preparation of a multilayered microfluidic device with channels of varying dimensions, in a single device without using any sophisticated micromachining instrumentation. In addition, we have also qualitatively studied the diffusion of small and large molecules from a Ca-alginate based microfluidic device and proposed a method to effectively control the out-flow of macro biomolecules from the crosslinked Ca-alginate matrix to create a selectively permeable matrix required for various biological and biomimetic applications, as mentioned in the Introduction section of this work.  相似文献   

6.
We report a 3D microfluidic device with 32 detection channels and 64 sheath flow channels and embedded microball lens array for high throughput multicolor fluorescence detection. A throughput of 358 400 cells/s has been accomplished. This device is realized by utilizing solid immersion micro ball lens arrays for high sensitivity and parallel fluorescence detection. High refractive index micro ball lenses (n = 2.1) are embedded underneath PDMS channels close to cell detection zones in channels. This design permits patterning high N.A. micro ball lenses in a compact fashion for parallel fluorescence detection on a small footprint device. This device also utilizes 3D microfluidic fabrication to address fluid routing issues in two-dimensional parallel sheath focusing and allows simultaneous pumping of 32 sample channels and 64 sheath flow channels with only two inlets.  相似文献   

7.
In this paper, we demonstrate for the first time the technique to using microfluidics to fabricate tissue engineering scaffolds with uniform pore sizes. We investigate both the bubble generation of the microfluidic device and the application of foam as a tissue engineering scaffold. Our microfluidic device consists of two concentric tapered channels, which are made by micropipettes. Nitrogen gas and aqueous alginate solution with Pluronic® F127 surfactant are pumped through the inner and the outer channels, respectively. We observe rich dynamic patterns of bubbles encapsulated in the liquid droplets. The size of the bubble depends linearly on the gas pressure and inversely on the liquid flow rate. In addition, monodisperse bubbles self-assemble into crystalline structures. The liquid crystalline foams are further processed into open-cell solid foams. The novel foam gel was used as a scaffold to culture chondrocytes.  相似文献   

8.
In this paper a method of electrospinning conducting and nonconducting biphasic Janus nanofibers using microfluidic polydimethylsiloxane (PDMS)-based manifolds is described. Key benefits of using microfluidic devices for nanofiber synthesis include rapid prototyping, ease of fabrication, and the ability to spin multiple Janus fibers in parallel through arrays of individual microchannels. Biphasic Janus nanofibers of polyvinylpyrrolidone (PVP)+polypyrrole (PPy)∕PVP nanofibers with an average diameter of 250 nm were successfully fabricated using elastomeric microfluidic devices. Fiber characterization and confirmation of the Janus morphology was subsequently carried out using a combination of scanning electron microscopy, energy dispersion spectroscopy, and transmission electron microscopy.  相似文献   

9.
A broad range of microfluidic applications, ranging from cell culture to protein crystallization, requires multilevel devices with different heights and feature sizes (from micrometers to millimeters). While state-of-the-art direct-writing techniques have been developed for creating complex three-dimensional shapes, replication molding from a multilevel template is still the preferred method for fast prototyping of microfluidic devices in the laboratory. Here, we report on a "dry and wet hybrid" technique to fabricate multilevel replication molds by combining SU-8 lithography with a dry film resist (Ordyl). We show that the two lithography protocols are chemically compatible with each other. Finally, we demonstrate the hybrid technique in two different microfluidic applications: (1) a neuron culture device with compartmentalization of different elements of a neuron and (2) a two-phase (gas-liquid) global micromixer for fast mixing of a small amount of a viscous liquid into a larger volume of a less viscous liquid.  相似文献   

10.
Integrating different steps on a chip for cell manipulations and sample preparation is of foremost importance to fully take advantage of microfluidic possibilities, and therefore make tests faster, cheaper and more accurate. We demonstrated particle manipulation in an integrated microfluidic device by applying hydrodynamic, electroosmotic (EO), electrophoretic (EP), and dielectrophoretic (DEP) forces. The process involves generation of fluid flow by pressure difference, particle trapping by DEP force, and particle redirect by EO and EP forces. Both DC and AC signals were applied, taking advantages of DC EP, EO and AC DEP for on-chip particle manipulation. Since different types of particles respond differently to these signals, variations of DC and AC signals are capable to handle complex and highly variable colloidal and biological samples. The proposed technique can operate in a high-throughput manner with thirteen independent channels in radial directions for enrichment and separation in microfluidic chip. We evaluated our approach by collecting Polystyrene particles, yeast cells, and E. coli bacteria, which respond differently to electric field gradient. Live and dead yeast cells were separated successfully, validating the capability of our device to separate highly similar cells. Our results showed that this technique could achieve fast pre-concentration of colloidal particles and cells and separation of cells depending on their vitality. Hydrodynamic, DC electrophoretic and DC electroosmotic forces were used together instead of syringe pump to achieve sufficient fluid flow and particle mobility for particle trapping and sorting. By eliminating bulky mechanical pumps, this new technique has wide applications for in situ detection and analysis.  相似文献   

11.
Concurrent droplet charging and sorting by electrostatic actuation   总被引:1,自引:0,他引:1  
This paper presents a droplet-based microfluidic device for concurrent droplet charging and sorting by electrostatic actuation. Water-in-oil droplets can be charged on generation by synchronized electrostatic actuation. Then, simultaneously, the precharged droplets can be electrostatically steered into any designated laminar streamline, thus they can be sorted into one of multiple sorting channels one by one in a controlled fashion. In this paper, we studied the size dependence of the water droplets under various relative flow rates of water and oil. We demonstrated the concurrent charging and sorting of up to 600 droplets∕s by synchronized electrostatic actuation. Finally, we investigated optimized voltages for stable droplet charging and sorting. This is an essential enabling technology for fast, robust, and multiplexed sorting of microdroplets, and for the droplet-based microfluidic systems.  相似文献   

12.
We report a simple, low-cost, rapid, and mask-free method to fabricate two-dimensional (2D) and three-dimensional (3D) microfluidic chip for biological analysis researches. In this fabrication process, a laser system is used to cut through paper to form intricate patterns and differently configured channels for specific purposes. Bonded with cyanoacrylate-based resin, the prepared paper sheet is sandwiched between glass slides (hydrophilic) or polymer-based plates (hydrophobic) to obtain a multilayer structure. In order to examine the chip’s biocompatibility and applicability, protein concentration was measured while DNA capillary electrophoresis was carried out, and both of them show positive results. With the utilization of direct laser cutting and one-step gas-sacrificing techniques, the whole fabrication processes for complicated 2D and 3D microfluidic devices are shorten into several minutes which make it a good alternative of poly(dimethylsiloxane) microfluidic chips used in biological analysis researches.  相似文献   

13.
Herein is described the fabrication and use of a plastic multilayer 3-channel microfluidic fixture. Multilayer devices were produced by laser machining of plastic polymethylmethacrylate and polyethyleneterapthalate laminates by ablation. The fixture consisted of an array of nine individually addressable gold or gold/ITO working electrodes, and a resistive platinum heating element. Laser machining of both the fluidic pathways in the plastic laminates, and the stencil masks used for thermal evaporation to form electrode regions on the plastic laminates, enabled rapid and inexpensive implementation of design changes. Electrochemiluminescence reactions in the fixture were achieved and monitored through ITO electrodes. Electroaddressable aryl diazonium chemistry was employed to selectively pattern gold electrodes for electrochemical multianalyte DNA detection from double stranded DNA (dsDNA) samples. Electrochemical detection of dsDNA was achieved by melting of dsDNA molecules in solution with the integrated heater, allowing detection of DNA sequences specific to breast and colorectal cancers with a non-specific binding control. Following detection, the array surface could be renewed via high temperature (95 °C) stripping using the integrated heating element. This versatile and simple method for prototyping devices shows potential for further development of highly integrated, multi-functional bioanalytical devices.  相似文献   

14.
A versatile method to fabricate a multilayer polydimethylsiloxane (PDMS) device with micropillar arrays within the inner layer is reported. The method includes an inexpensive but repeatable approach for PDMS lamination at high compressive force to achieve high yield of pillar molding and transfer to a temporary carrier. The process also enables micropillar-containing thin films to be used as the inner layer of PDMS devices integrated with polymer membranes. A microfluidic cell culture device was demonstrated which included multiple vertically stacked flow channels and a pillar array serving as a cage for a collagen hydrogel. The functionality of the multilayer device was demonstrated by culturing collagen-embedded fibroblasts under interstitial flow through the three-dimensional scaffold. The fabrication methods described in this paper can find applications in a variety of devices, particularly for organ-on-chip applications.  相似文献   

15.
Microfluidic-based protein arrays are promising tools for life sciences, with increased sensitivity and specificity. One of the drawbacks of this technology is the need to create fresh surface chemistry for protein immobilization at the beginning of each experiment. In this work, we attempted to include the process of surface functionalization as part of the fabrication of the device, which would substitute the time consuming step of surface functionalization at the beginning of each protein array experiment. To this end, we employed a novel surface modification using self-assembled monolayers (SAMs) to immobilize biomolecules within the channels of a polydimethylsiloxane (PDMS) integrated microfluidic device. As a model, we present a general method for depositing siloxane-anchored SAMs, with 1-undecyl-thioacetate-trichlorosilane (C11TA) on the silica surfaces. The process involved developing PDMS-compatible conditions for both SAM deposition and functional group activation. We successfully demonstrated the ability to produce, within an integrated microfluidic channel, a C11TA monolayer with a covalently conjugated antibody. The antibody could then bind its antigen with a high signal to background ratio. We further demonstrated that the antibody was still active after storage of the device for a week. Integration of the surface chemistry into the device as part of its fabrication process has potential to significantly simplify and shorten many experimental procedures involving microfluidic–based protein arrays. In turn, this will allow for broader dissemination of this important technology.  相似文献   

16.
This paper presents a microfluidic device (poly-dimethylsiloxane micro channels bonded with glass slides) enabling culture of MLO-Y4 osteocyte like cells. In this study, on-chip collagen coating, cell seeding and culture, as well as staining were demonstrated in a tubing-free manner where gravity was used as the driving force for liquid transportation. MLO-Y4 cells were cultured in microfluidic channels with and without collagen coating where cellular images in a time sequence were taken and analyzed, confirming the positive effect of collagen coating on phenotype maintaining of MLO-Y4 cells. The proliferating cell nuclear antigen based proliferation assay was used to study cellular proliferation, revealing a higher proliferation rate of MLO-Y4 cells seeded in microfluidic channels without collagen coating compared to the substrates coated with collagen. Furthermore, the effects of channel dimensions (variations in width and height) on the viability of MLO-Y4 cells were explored based on the Calcein-AM and propidium iodide based live/dead assay and the Hoechst 33258 based apoptosis assay, locating the correlation between the decrease in channel width or height and the decrease in cell viability. As a platform technology, this microfluidic device may function as a new cell culture model enabling studies of osteocytes.  相似文献   

17.
Cell-cell interactions play a key role in regeneration, differentiation, and basic tissue function taking place under physiological shear forces. However, current solutions to mimic such interactions by micro-patterning cells within microfluidic devices have low resolution, high fabrication complexity, and are limited to one or two cell types. Here, we present a microfluidic platform capable of laminar patterning of any biotin-labeled peptide using streptavidin-based surface chemistry. The design permits the generation of arbitrary cell patterns from heterogeneous mixtures in microfluidic devices. We demonstrate the robust co-patterning of α-CD24, α-ASGPR-1, and α-Tie2 antibodies for rapid isolation and co-patterning of mixtures of hepatocytes and endothelial cells. In addition to one-step isolation and patterning, our design permits step-wise patterning of multiple cell types and empty spaces to create complex cellular geometries in vitro. In conclusion, we developed a microfluidic device that permits the generation of perfusable tissue-like patterns in microfluidic devices by directly injecting complex cell mixtures such as differentiated stem cells or tissue digests with minimal sample preparation.  相似文献   

18.
Molecular gradients play a significant role in regulating biological and pathological processes. Although conventional gradient-generators have been used for studying chemotaxis and axon guidance, there are still many limitations, including the inability to maintain stable tempo-spatial gradients and the lack of the cell monitoring in a real-time manner. To overcome these shortcomings, microfluidic devices have been developed. In this study, we developed a microfluidic gradient device for regulating neuron axon guidance. A microfluidic device enables the generation of Brain-derived neurotrophic factor (BDNF) gradient profiles in a temporal and spatial manner. We test the effect of the gradient profiles on axon guidance, in the BDNF concentration gradient axon towards the high concentration gradient. This microfluidic gradient device could be used as a powerful tool for cell biology research.  相似文献   

19.
This paper presents a continuous flow microfluidic device for the separation of DNA from blood using magnetophoresis for biological applications and analysis. This microfluidic bio-separation device has several benefits, including decreased sample handling, smaller sample and reagent volumes, faster isolation time, and decreased cost to perform DNA isolation. One of the key features of this device is the use of short-range magnetic field gradients, generated by a micro-patterned nickel array on the bottom surface of the separation channel. In addition, the device utilizes an array of oppositely oriented, external permanent magnets to produce strong long-range field gradients at the interfaces between magnets, further increasing the effectiveness of the device. A comprehensive simulation is performed using COMSOL Multiphysics to study the effect of various parameters on the magnetic flux within the separation channel. Additionally, a microfluidic device is designed, fabricated, and tested to isolate DNA from blood. The results show that the device has the capability of separating DNA from a blood sample with a purity of 1.8 or higher, a yield of up to 33 μg of polymerase chain reaction ready DNA per milliliter of blood, and a volumetric throughput of up to 50 ml/h.  相似文献   

20.
We report on the feasible fabrication of microfluidic devices for ferroelectric polymers'' synthesis in a rapid and stable fashion. Utilizing micro-mixing and flow-focusing in microchannels, poly(vinylidene fluoride-trifluoroethylene) and copper phthalocyanine are uniformly dispersed in one hydrogel particle, which are then demonstrated to immediate and complete on-chip steady polymerization by moderate ultraviolet treatment. The advantage of our droplet-based microfluidic devices is generating versatile particles from simple spheres to disks or rods, and the lengths of particles can be precisely tuned from 30 to 400 μm through adjusting the flow rates of both disperse and oil phases. In addition, this mixed technique allows for the continuous production of dielectric microparticles with controlled dielectric properties between 10 and 160. Such a microfluidic device offers a flexible platform for multiferroic applications.  相似文献   

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