PDMS-based Microfluidic Devices Research Articles

Compatibility of organic solvents for electrochemical measurements in PDMS-based microfluidic devices

We have investigated the compatibility of some organic solvents commonly used in electrochemistry with microfluidic channels based on poly(dimethylsiloxane) (PDMS) and compared the stability of electrochemical measurements over several hours with how much PDMS swells when immersed in these solvents. Lee et al. (Anal Chem 75: 6544–6554. doi: 10.1021/ac0346712 , 2003) have shown that there is a good correlation between swelling of PDMS and the solubility parameter (δ H) of the various solvents and suggested that δ H can function as an indication of PDMS compatibility. We show that solvents with a very high swelling ratio can give stable voltammetry over several hours, and thus, we do not find that swelling is a good measure for compatibility with PDMS in electrochemical experiments.

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

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.

Facile and cost-effective production of microscale PDMS architectures using a combined micromilling-replica moulding (μMi-REM) technique.

We describe a cost-effective and simple method to fabricate PDMS-based microfluidic devices by combining micromilling with replica moulding technology. It relies on the following steps: (i) microchannels are milled in a block of acrylic; (ii) low-cost epoxy adhesive resin is poured over the milled acrylic block and allowed to cure; (iii) the solidified resin layer is peeled off the acrylic block and used as a mould for transferring the microchannel architecture onto a PDMS layer; finally (iv) the PDMS layer is plasma bonded to a glass surface. With this method, microscale architectures can be fabricated without the need for advanced technological equipment or laborious and time-consuming intermediate procedures. In this manuscript, we describe and validate the microfabrication procedure, and we illustrate its applicability to emulsion and microbubble production.Electronic supplementary materialThe online version of this article (doi:10.1007/s10544-015-0027-x) contains supplementary material, which is available to authorized users.

Simple surface engineering of polydimethylsiloxane with polydopamine for stabilized mesenchymal stem cell adhesion and multipotency.

Polydimethylsiloxane (PDMS) has been extensively exploited to study stem cell physiology in the field of mechanobiology and microfluidic chips due to their transparency, low cost and ease of fabrication. However, its intrinsic high hydrophobicity renders a surface incompatible for prolonged cell adhesion and proliferation. Plasma-treated or protein-coated PDMS shows some improvement but these strategies are often short-lived with either cell aggregates formation or cell sheet dissociation. Recently, chemical functionalization of PDMS surfaces has proved to be able to stabilize long-term culture but the chemicals and procedures involved are not user- and eco-friendly. Herein, we aim to tailor greener and biocompatible PDMS surfaces by developing a one-step bio-inspired polydopamine coating strategy to stabilize long-term bone marrow stromal cell culture on PDMS substrates. Characterization of the polydopamine-coated PDMS surfaces has revealed changes in surface wettability and presence of hydroxyl and secondary amines as compared to uncoated surfaces. These changes in PDMS surface profile contribute to the stability in BMSCs adhesion, proliferation and multipotency. This simple methodology can significantly enhance the biocompatibility of PDMS-based microfluidic devices for long-term cell analysis or mechanobiological studies.

Modeling carbon dioxide transport in PDMS-based microfluidic cell culture devices

Maintaining a proper pH level is crucial for successful cell culturing. Mammalian cells are commonly cultured in incubators, where the cell culture medium is saturated with a mixture of air and 5% carbon dioxide (CO2). Therefore, to keep cell culture medium pH in an acceptable level outside these incubators, a suitable CO2 concentration must be dissolved in the medium. However, it can be very difficult to control and measure precisely local concentration levels. Furthermore, possible undesired concentration gradients generated during long-term cell culturing are almost impossible to detect. Therefore, we have developed a computational model to estimate CO2 transport in silicone-based microfluidic devices. An extensive set of experiments was used to validate the finite element model. The model parameters were obtained using suitable measurement set-ups and the model was validated using a fully functional cell cultivation device. The predictions obtained by the simulations show very good responses to experiments. It is shown in this paper how the model helps to understand the dynamics of CO2 transport in silicone-based cell culturing devices possessing different geometries, thus providing cost-effective means for studying different device designs under a variety of experimental conditions without the need of actual testing. Finally, based on the results from the computational model, an alternative strategy for feeding CO2 is proposed to accelerate the system performance such that a faster and more uniform CO2 concentration response is achieved in the area of interest.

A simple low-cost method to enhance luminescence and fluorescence signals in PDMS-based microfluidic devices

The addition of titanium dioxide particles to PDMS is a simple low-cost method to enhance fluorescence and luminescence signals in microfluidic devices.

Surface modification of PDMS microfluidic devices by controlled sulfuric acid treatment and the application in chip electrophoresis.

Herein, we present a straightforward surface modification technique for PDMS-based microfluidic devices. The method takes advantage of the high reactivity of concentrated sulfuric acid to enhance the surface properties of PDMS bulk material. This results in alteration of the surface morphology and chemical composition that is in-depth characterized by ATR-FTIR, EDX, SEM, and XPS. In comparison to untreated PDMS, modified substrates exhibit a significantly reduced diffusive uptake of small organic molecules while retaining its low electroosmotic properties. This was demonstrated by exposing the channels of a microfluidic device to concentrated rhodamine B solution followed by fluorescence microscopy. The surface modification procedure was used to improve chip-based electrophoretic separations. Separation efficiencies of FITC-labeled amines/amino acids obtained in treated and untreated PDMS-devices as well as in glass chips were compared. We obtained higher efficiencies in H2 SO4 treated PDMS chips compared to untreated ones but lower efficiencies than those obtained in commercial microfluidic glass devices.

Parameters Governing the Formation of Photopolymerized Silica Sol-Gel Monoliths in PDMS Microfluidic Chips.

Although polydimethylsiloxane (PDMS) microfluidic chips provide an alternative to more expensive microfabricated glass chips, formation of monolithic stationary phases in PDMS is not a trivial task. Photopolymerized silica sol-gel monoliths were fabricated in PDMS based microfluidic devices using 3-trimethoxysilylpropylmethacrylate (MPTMOS) and glycidyloxypropyltrimethoxysilane (GPTMOS). The monolith formation was optimized by identifying a suitable porogen, controlling monomer concentration, functional additives, salts, porogen, wall attachment methods, and rinsing procedures. The resulting monoliths were evaluated using scanning electron microscopy, image analysis, differential scanning calorimetry, and separation performance. Monoliths functionalized with boronic acid ligands were used for the separation of cis-diol containing compounds both in batch mode and in the microfluidic chip.

SU-8- and PDMS-based hybrid fabrication technology for combination of permanently bonded flexible and rigid features on a single device

In this article, a novel hybrid fabrication technology is presented that uses both a flexible polymer (polydimethylsiloxane-–PDMS) and a rigid polymer (SU-8). A covalent bond between the flexible and rigid polymer layers is achieved using an oxygen plasma treatment during a layer-by-layer direct spin-on process. Precise alignment of the features in each layer and a highly repeatable method are achieved by this new process. As a proof-of-concept, we successfully fabricated PDMS-based flexible microfluidic devices with SU-8-based rigid world-to-chip/chip-to-world interconnects. The bond strength between the PDMS and SU-8 layers is measured by three methods: (1) Instron® microtester to pull apart the layers; (2) voice coil actuator to test the bond between interconnects and the substrate; and (3) microfluidic pressurization test to evaluate the bond strength along the channels. The bond strength between the flexible PDMS layer and the rigid SU-8 features is very strong; the bond between these two polymers does not fail during these evaluations although the integrity of the PDMS layer itself fails during the microtester evaluation. Additionally, the layer-by-layer direct spin-on process resulted in a repeatable process and precise alignment of the features in each layer, which are necessary in order to achieve consistent performance from the fabricated devices. The rigid SU-8 interconnects fabricated onto a flexible PDMS device serve as a world-to-chip/chip-to-world interconnects for the direct connection with Tygon® tubing. Three different designs of hybrid (PDMS and SU-8 based) microfluidic devices are designed, fabricated and tested. Each variation differed in the microchannel design in order to demonstrate the versatility of the process to make devices on multiple scales and patterns. These hybrid microfluidic devices are capable of functioning without leakage up to pressures of 85.85 ±3.56 kPa. Although microfluidic channels with interconnects are shown as a proof-of-concept, the fabrication process demonstrated herein could be utilized to develop a number of more sophisticated microfluidic and biomedical devices.

Screen printing of solder resist as master substrates for fabrication of multi-level microfluidic channels and flask-shaped microstructures for cell-based applications

Although silicon technology can be adopted for the fabrication of microfluidic devices with high precision, the capital and operating costs for such technology is often prohibitively expensive. In recent years, many alternative methods have been advocated to reduce the cost of microfabrication but often with reduced qualities in many important features, such as channel resolution, surface smoothness and aspect ratio. In this study, we have developed a microfabrication method that retains high channel quality and aspect ratio by exploring a rarely used solder resist material in combination with screen printing technique to generate masters where PDMS-based microfluidic devices could be fabricated by replica molding from the masters. Using screen printing, different channel heights from 5 to 60μm on the master were prepared by varying mesh density, controlling solder resist viscosity, and/or adjusting the off-contact gap between a mesh and a substrate, while the entire master fabrication process was completed within 3h. This simple, low-cost method could generate fine channel features (50μm) and high aspect ratio (2:1) structures. Microfluidic devices with multi-level structure could be fabricated by multi-steps photolithography using this approach. Moreover, the properties of solder resist enabled the fabrication of flask-shaped well structures by controlled partial exposure and development in a single-step of photolithography, which was potentially used as cell holding reservoirs for cell quantification and cell culture. We believe this fabrication method can be easily adopted by other laboratories to conduct microfluidic researches without specialized equipment.

A “place n play” modular pump for portable microfluidic applications

This paper presents an easy-to-use, power-free, and modular pump for portable microfluidic applications. The pump module is a degassed particle desorption polydimethylsiloxane (PDMS) slab with an integrated mesh-shaped chamber, which can be attached on the outlet port of microfluidic device to absorb the air in the microfluidic system and then to create a negative pressure for driving fluid. Different from the existing monolithic degassed PDMS pumps that are generally restricted to limited pumping capacity and are only compatible with PDMS-based microfluidic devices, this pump can offer various possible configures of pumping power by varying the geometries of the pump or by combining different pump modules and can also be employed in any material microfluidic devices. The key advantage of this pump is that its operation only requires the user to place the degassed PDMS slab on the outlet ports of microfluidic devices. To help design pumps with a suitable pumping performance, the effect of pump module geometry on its pumping capacity is also investigated. The results indicate that the performance of the degassed PDMS pump is strongly dependent on the surface area of the pump chamber, the exposure area and the volume of the PDMS pump slab. In addition, the initial volume of air in the closed microfluidic system and the cross-linking degree of PDMS also affect the performance of the degassed PDMS pump. Finally, we demonstrated the utility of this modular pumping method by applying it to a glass-based microfluidic device and a PDMS-based protein crystallization microfluidic device.

“Clicked” fluoropolymer elastomers as robust materials for potential microfluidic device applications

We report the design and synthesis of a new perfluoropolyether-based material, which has liquid-like viscosity and can be cured into a tough, highly durable elastomer when “clicked” with selected tri-pod organic small molecules. This highly fluorinated elastomer exhibits remarkable resistance to a variety of organic solvents, water, heat and even harsh acidic and basic conditions. Whereas PDMS-based microfluidic devices are commonly used for aqueous based applications, their limited chemical resistance and high swellability in many common organic solvents make it unfeasible for microfluidic applications involving organic solvents and/or harsh conditions. With excellent chemical resistance and low swellability, our newly synthesized fluoro-elastomers will hopefully provide an alternative material for organic based microfluidic devices. Furthermore, the alkyne–azide “click” chemistry employed in curing not only provides high efficiency of synthesis and ease of device fabrication, but, more importantly, produces 1,2,3-triazole linkages that are very stable against harsh acidic or basic conditions. This work has great potential to expand microfluidics to a series of novel applications especially in organic and medicinal chemistry.

Anti-stiction coating of PDMS moulds for rapid microchannel fabrication by double replica moulding

In this paper, we report a simple and precise method to rapidly replicate master structures for fast microchannel fabrication by double replica moulding of polydimethylsiloxane (PDMS). A PDMS mould was surface-treated by vapour phase deposition of 1H,1H,2H,2H-perfluorodecyltrichlorosilane (FDTS), which resulted in an anti-stiction layer for the improved release after PDMS casting. The deposition of FDTS on an O2 plasma-activated surface of PDMS produced a reproducible and well-performing anti-stiction monolayer of fluorocarbon, and we used the FDTS-coated moulds as micro-masters for rapid replication of micro-structures, avoiding the necessity to have to use other, more costly and fragile master materials. Our protocol has been shown to reliably fabricate PDMS-based microfluidic devices in a low-cost and efficient manner. The replicas were further employed as micro-contract stamps to fabricate polymer-based waveguides.

Systematic characterization of degas-driven flow for poly(dimethylsiloxane) microfluidic devices

Degas-driven flow is a novel phenomenon used to propel fluids in poly(dimethylsiloxane) (PDMS)-based microfluidic devices without requiring any external power. This method takes advantage of the inherently high porosity and air solubility of PDMS by removing air molecules from the bulk PDMS before initiating the flow. The dynamics of degas-driven flow are dependent on the channel and device geometries and are highly sensitive to temporal parameters. These dependencies have not been fully characterized, hindering broad use of degas-driven flow as a microfluidic pumping mechanism. Here, we characterize, for the first time, the effect of various parameters on the dynamics of degas-driven flow, including channel geometry, PDMS thickness, PDMS exposure area, vacuum degassing time, and idle time at atmospheric pressure before loading. We investigate the effect of these parameters on flow velocity as well as channel fill time for the degas-driven flow process. Using our devices, we achieved reproducible flow with a standard deviation of less than 8% for flow velocity, as well as maximum flow rates of up to 3 nL∕s and mean flow rates of approximately 1-1.5 nL∕s. Parameters such as channel surface area and PDMS chip exposure area were found to have negligible impact on degas-driven flow dynamics, whereas channel cross-sectional area, degas time, PDMS thickness, and idle time were found to have a larger impact. In addition, we develop a physical model that can predict mean flow velocities within 6% of experimental values and can be used as a tool for future design of PDMS-based microfluidic devices that utilize degas-driven flow.

Fluorogenic Pyrosequencing in Microreactors

High-throughput sequencing techniques are revolutionizing biology and promise to have a significant impact on the future of medicine. We have developed a scalable, parallel, low-cost method for nucleic acid sequencing that combines resealable microreactors and terminal-phosphate labeled fluorogenic nucleotides. To accomplish this, we have fabricated arrays of microreactors in polydimethylsiloxane (PDMS) that can be reversibly sealed, and have developed techniques for immobilizing different populations of identical DNA fragments specifically and efficiently within these microreactors. We have synthesized a series of terminal-phosphate labeled fluorogenic substrates for DNA polymerase which, upon their incorporation into a primer strand of DNA and subsequent digestion by a phosphatase, generate fluorescent dye molecules that are effectively trapped in the microreactors. By sequentially interrogating the microreactor array with solutions containing different fluorogenic nucleotide substrates, and recording which microreactors generate fluorescence, we can sequence the immobilized DNA. This “fluorogenic pyrosequencing” method promises significant advantages over existing sequencing technologies, and has the potential to be elegantly interfaced with the wide variety of PDMS-based microfluidic devices suitable for the preparation and amplification of DNA or RNA for sequencing, opening the possibility of one-chip, sample-to-sequence capabilities.

Microbubble generation in a co-flow device operated in a new regime

A new regime of operation of PDMS-based flow-focusing microfluidic devices is presented. We show that monodisperse microbubbles with diameters below one-tenth of the channel width (here w = 50 μm) can be produced in low viscosity liquids thanks to a strong pressure gradient in the entrance region of the channel. In this new regime bubbles are generated at the tip of a long and stable gas ligament whose diameter, which can be varied by tuning appropriately the gas and liquid flow rates, is substantially smaller than the channel width. Through this procedure the volume of the bubbles formed at the tip of the gas ligament can be varied by more than two orders of magnitude. The experimental results for the bubble diameter d(b) as function of the control parameters are accounted for by a scaling theory, which predicts d(b)/w ∝ (μ(g)/μ(l))(1/12)(Q(g)/Q(l))(5/12), where μ(g) and μ(l) indicate, respectively, the gas and liquid viscosities and Q(g) and Q(l) are the gas and liquid flow rates. As a particularly important application of our results we produce monodisperse bubbles with the appropriate diameter for therapeutic applications (d(b) ≃ 5 μm) and a production rate exceeding 10(5) Hz.

Polyelectrolyte multilayer surface functionalization of poly(dimethylsiloxane) (PDMS) for reduction of yeast cell adhesion in microfluidic devices.

Polyelectrolyte multilayers (PEMs) based on the combinations poly(diallyldimethylammonium chloride)∕poly(acrylic acid) (PDADMAC∕PAA) and poly(allylamine hydrochloride)∕PAA (PAH∕PAA) were adsorbed on poly(dimethylsiloxane) (PDMS) and tested for nonspecific surface attachment of hydrophobic yeast cells using a parallel plate flow chamber. A custom-made graft copolymer containing poly(ethylene glycol) (PEG) side chains (PAA-g-PEG) was additionally adsorbed on the PEMs as a terminal layer. A suitable PEM modification effectively decreased the adhesion strength of Saccharomyces cerevisiae DSM 2155 to the channel walls. However, a further decrease in initial cell attachment and adhesion strength was observed after adsorption of PAA-g-PEG copolymer onto PEMs from aqueous solution. The results demonstrate that a facile layer-by-layer surface functionalization from aqueous solutions can be successfully applied to reduce cell adhesion strength of S. cerevisiae by at least two orders of magnitude compared to bare PDMS. Therefore, this method is potentially suitable to promote planktonic growth inside capped PDMS-based microfluidic devices if the PEM deposition is completed by a dynamic flow-through process.

Continuous sorting and separation of microparticles by size using AC dielectrophoresis in a PDMS microfluidic device with 3‐D conducting PDMS composite electrodes

Soft lithography technology allows for the development of numerous PDMS-based microfluidic devices for manipulation of particles and cells. However, integrating metallic electrodes with PDMS-based channel structures is challenging due to weak adhesion between metal and PDMS. To overcome this issue, we develop a new PDMS-based microfluidic device for continuous sorting and separation of microparticles by size using AC dielectrophoresis (DEP) with 3-D conducting PDMS composites as sidewall electrodes. The composites are synthesized by mixing silver powders with PDMS gel and such composite electrodes can easily be integrated with the PDMS microchannels. Furthermore, the sidewall electrodes also allow DEP forces to distribute three dimensionally, thus enhancing DEP effects in the entire region of channels. The capability of such PDMS-based microfluidic device is demonstrated for continuously sorting and separating 10 and 15 mum particles, and also for separating 5 from 10 mum particles. Together with experimental results, analysis of particle's trajectory based on Lagrangian approach provides insights into how microparticles transport under the effects of hydrodynamic and DEP forces in the present PDMS-based microfluidic device.

A method for reducing pressure-induced deformation in silicone microfluidics

Poly(dimethylsiloxane) or PDMS is an excellent material for replica molding, widely used in microfluidics research. Its low elastic modulus, or high deformability, assists its release from challenging molds, such as those with high feature density, high aspect ratios, and even negative sidewalls. However, owing to the same properties, PDMS-based microfluidic devices stretch and change shape when fluid is pushed or pulled through them. This paper shows how severe this change can be and gives a simple method for limiting this change that sacrifices few of the desirable characteristics of PDMS. A thin layer of PDMS between two rigid glass substrates is shown to drastically reduce pressure-induced shape changes while preserving deformability during mold separation and gas permeability.

Cost-effective and reliable sealing method for PDMS (PolyDiMethylSiloxane)-based microfluidic devices with various substrates

A cost-effective and simply handling bonding method using siloxane-based adhesion promoter is introduced to increase the adhesion strength between cured PDMS and various substrates. The working mechanism of adhesion promoters is based on post-cure reaction in PDMS curing and they have similar chemistry compositions with PDMS prepolymers. It is experimentally investigated and proved that the adhesion strength of the resulted interface depends on –SiH group and Pt catalyst in adhesion promoters and molecular structures and polarity of substrates surfaces. By modifying their compositions uniform and perfect adhesion can be obtained for different substrates and meet different markets requirements, e.g., PDMS and glass which could be applied for biology, chemistry and solar cell fields, FR4 for electronics field and copper for electronics and thermal cooling fields, etc. Also, considering the quality and reliability requirements from potential application markets of microfluidic devices an environmental test procedure is summarized and according to the defined procedure, the environmental stability of realized PDMS-based microfluidic devices with different substrates has been tested with the result that they exhibited excellent stabilities and suitability for mass production.