Multilayer soft lithography of perfluoropolyether based elastomer for microfluidic device fabrication

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.     

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

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.     

Glass coating for PDMS microfluidic channels by sol-gel methods

Soft lithography using polydimethylsiloxane (PDMS) allows one to fabricate complex microfluidic devices easily and at low cost. However, PDMS swells in the presence of many organic solvents significantly degrading the performance of the device. We present a method to coat PDMS channels with a glass-like layer using sol-gel chemistry. This coating greatly increases chemical resistance of the channels; moreover, it can be functionalized with a wide range of chemicals to precisely control interfacial properties. This method combines the ease of fabrication afforded by soft-lithography with the precision control and chemical robustness afforded by glass.     

Design and fabrication of chemically robust three-dimensional microfluidic valves

A current problem in microfluidics is that poly(dimethylsiloxane) (PDMS), used to fabricate many microfluidic devices, is not compatible with most organic solvents. Fluorinated compounds are more chemically robust than PDMS but, historically, it has been nearly impossible to construct valves out of them by multilayer soft lithography (MSL) due to the difficulty of bonding layers made of "non-stick" fluoropolymers necessary to create traditional microfluidic valves. With our new three-dimensional (3D) valve design we can fabricate microfluidic devices from fluorinated compounds in a single monolithic layer that is resistant to most organic solvents with minimal swelling. This paper describes the design and development of 3D microfluidic valves by molding of a perfluoropolyether, termed Sifel, onto printed wax molds. The fabrication of Sifel-based microfluidic devices using this technique has great potential in chemical synthesis and analysis.     

Fabrication improvements for thermoset polyester (TPE) microfluidic devices

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.     

Microfluidic devices for culturing primary mammalian neurons at low densities

Microfluidic devices have been used to study high-density cultures of many cell types. Because cell-to-cell signaling is local, however, there exists a need to develop culture systems that sustain small numbers of neurons and enable analyses of the microenvironments. Such cultures are hard to maintain in stable form, and it is difficult to prevent cell death when using primary mammalian neurons. We demonstrate that postnatal primary hippocampal neurons from rat can be cultured at low densities within nanoliter-volume microdevices fabricated using polydimethylsiloxane (PDMS). Doing so requires an additional fabrication step, serial extractions/washes of PDMS with several solvents, which removes uncrosslinked oligomers, solvent and residues of the platinum catalyst used to cure the polymer. We found this step improves the biocompatibility of the PDMS devices significantly. Whereas neurons survive for > or = 7 days in open channel microdevices, the ability to culture neurons in closed-channel devices made of untreated, native PDMS is limited to < or = 2 days. When the closed-channel PDMS devices are extracted, biocompatibility improves allowing for reliable neuron cultures at low densities for > or = 7 days. Comparisons made to autoclaved PDMS and native, untreated PDMS reveal that the solvent-treated polymer is superior in sustaining low densities of primary neurons in culture. When neuronal affinity for local substrates is observed directly, we find that axons localize to channel corners and prefer PDMS surfaces to glass in hybrid devices. When perfusing the channels with media by gravity flow, cultured hippocampal neurons survive for > or = 11 days. Extracting PDMS improves biocompatibility of microfluidic devices and thus enables the study of differentiation of identifiable neurons and the characterization of local extracellular signals.     

Photolithography-free fabrication of photoresist-mold for rapid prototyping of microfluidic PDMS devices

Traditional soft lithography based PDMS device fabrication requires complex procedures carried out in a clean room. Herein, we report a photolithography-free method that rapidly produces PDMS devices in 30 min. By using a laser cutter to ablate a tape, a male photoresist mold can be obtained within 5 min by a simple heating-step, which offers significant superiority over currently used photolithographybased method. Since it requires minimal energy to cut the tape, our fabrication strategy shows ...     

A simple method for patterning poly(dimethylsiloxane) barriers in paper using contact-printing with low-cost rubber stamps

This paper presents a simple and low-cost method for patterning poly(dimethylsiloxane) (PDMS) barriers in porous support such as paper for the construction of flexible microfluidic paper-based analytical devices (μPADs). The fabrication method consisted of contact-printing a solution of PDMS and hexane (10:1.5 w/w) onto chromatographic paper using custom-designed rubber stamps containing the patterns of μPADs. After penetrating the paper (∼30 s), the PDMS is cured to form hydrophobic barriers. Under optimized conditions, hydrophobic barriers and hydrophilic channels with dimensions down to 949 ± 88 μm and 771 ± 90 μm (n = 5), respectively, were obtained. This resolution is well-suitable for most applications in analytical chemistry. Chemical compatibility studies revealed that the PDMS barriers were able to contain some organic solvents, including acetonitrile and methanol, and aqueous solutions of some surfactants. This find is particularly interesting given that acetonitrile and methanol are the most used solvents in chromatographic separations, non-aqueous capillary electrophoresis and electroanalysis, as well as aqueous solutions of surfactants are suitable mediums for cell lyses assays. The utility of the technique was evaluated in the fabrication of paper-based electrochemical devices (PEDs) with pencil-drawn electrodes for experiments in static cyclic voltammetry and flow injection analysis (FIA) with amperometric detection, in both aqueous and organic mediums.     

Polyurethane-based microfluidic devices for blood contacting applications

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.     

Rapid prototyping polymers for microfluidic devices and high pressure injections

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 strength, predictable operation at high pressure, or transitioning to commercialization are considered important for the application.     

Perforated membrane method for fabricating three-dimensional polydimethylsiloxane microfluidic devices

A procedure is described for making layer-to-layer interconnections in polydimethylsiloxane (PDMS) microfluidic devices. Thin ( approximately 50 mum) perforated PDMS membranes are bonded to thicker (0.1 cm or more) PDMS slabs by means of thermally cured PDMS prepolymer to form a three-dimensional (3D) channel structure, which may contain channel or valve arrays that can pass over and under one another. Devices containing as many as two slabs and three perforated membranes are demonstrated. We also present 3D PDMS microfluidic devices for display and for liquid dispensing.     

Reliable fabrication method of transferable micron scale metal pattern for poly(dimethylsiloxane) metallization

We have developed a reliable fabrication method of forming micron scale metal patterns on poly(dimethylsiloxane) (PDMS) using a pattern transfer process. A metal stack layer consisting of Au-Ti-Au layers, providing a weak but reliable adhesion, was deposited on a silicon wafer. The metal stack layer was then transferred to a PDMS substrate using serial and selective etching. We demonstrate that features as small as 2 microm were reliably transferred on to the PDMS substrate for use as interconnects and electrodes for biosensors and flexible electronics application.     

Three-dimensional interconnected microporous poly(dimethylsiloxane) microfluidic devices

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.     

Capillary electrophoresis coupled to mass spectrometry from a polymer modified poly(dimethylsiloxane) microchip with an integrated graphite electrospray tip

Hybrid capillary-poly(dimethysiloxane)(PDMS) microchips with integrated electrospray ionization (ESI) tips were directly fabricated by casting PDMS in a mould. The shapes of the emitter tips were drilled into the mould, which produced highly reproducible three-dimensional tips. Due to the fabrication method of the microfluidic devices, no sealing was necessary and it was possible to produce a perfect channel modified by PolyE-323, an aliphatic polyamine coating agent. A variety of different coating procedures were also evaluated for the outside of the emitter tip. Dusting graphite on a thin unpolymerised PDMS layer followed by polymerisation was proven to be the most suitable procedure. The emitter tips showed excellent electrochemical properties and durabilities. The coating of the emitter was eventually passivated, but not lost, and could be regenerated by electrochemical means. The excellent electrochemical stability was further confirmed in long term electrospray experiments, in which the emitter sprayed continuously for more than 180 h. The PolyE-323 was found suitable for systems that integrate rigid fused silica and soft PDMS technology, since it simply could be applied successfully to both materials. The spray stability was confirmed from the recording of a total ion chromatogram in which the electrospray current exhibited a relative standard deviation of 3.9% for a 30 min run. CE-ESI-MS separations of peptides were carried out within 2 min using the hybrid PDMS chip resulting in similar efficiencies as for fused silica capillaries of the same length and thus with no measurable band broadening effects, originating from the PDMS emitter.     

A novel fabrication technique to minimize poly(dimethylsiloxane)‐microchannels deformation under high‐pressure operation

PDMS is one of the most common materials used for the flow delivery in the microfluidics chips, since it is clear, inert, nontoxic, and nonflammable. Its inexpensiveness, straightforward fabrication, and biological compatibility have made it a favorite material in the exploratory stages of the bio‐microfluidic devices. If small footprint assays want to be performed while keeping the throughput, high pressure‐rated channels should be used, but PDMS flexibility causes an important issue since it can generate a large variation of microchannel geometry. In this work, a novel fabrication technique based on the prevention of PDMS deformation is developed. A photo‐sensible thiolene resin (Norland Optical Adhesive 63, NOA 63) is used to create a rigid coating layer over the stiff PDMS micropillar array, which significantly reduces the pressure‐induced shape changes. This method uses the exact same soft lithography manufacturing equipment. The verification of the presented technique was investigated experimentally and numerically and the manufactured samples showed a deformation 70% lower than PDMS conventional samples.     

Patterning of spontaneous rolling thin polymer films for versatile microcapillaries

We investigate the spontaneous rolling of polydimethylsiloxane (PDMS) thin films and demonstrate the fabrication of capillaries with topographical and chemical patterns on the inner wall. Thin films of PDMS are either coated by a layer of hard material or have their surface hardened by plasma oxidation. They are then driven out of equilibrium by selective solvent swelling in vapor phase resulting in a tubular rolled‐up system. The inner diameter of those is measured as a function of layer thickness for different solvents and capping types. Those results are shown to be in good agreement with Timoshenko theory. Before rolling, the future inner surface can be characterized and functionalized. We demonstrate topographical and chemical patterning, respectively by embossing and microcontact printing. These methods are very simple and can easily produce cylindrical capillaries with inner diameter between 20 and some hundreds of microns with fully functionalized inner surface, overcoming many difficulties encountered in conventional soft lithography techniques. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2017 , 55, 721–728     

Fabrication of thermoset polyester microfluidic devices and embossing masters using rapid prototyped polydimethylsiloxane molds

Plastics are increasingly being used for the fabrication of Lab-on-a-Chip devices due to the variety of beneficial material properties, affordable cost, and straightforward fabrication methods available from a range of different types of plastics. Rapid prototyping of polydimethylsiloxane (PDMS) devices has become a well-known process for the quick and easy fabrication of microfluidic devices in the research laboratory; however, PDMS is not always an appropriate material for every application. This paper describes the fabrication of thermoset polyester microfluidic devices and masters for hot embossing using replica molding techniques. Rapid prototyped PDMS molds are convienently used for the production of non-PDMS polymeric devices. The recessed features in the cast polyester can be bonded to a second polyester piece to form an enclosed microchannel. Thermoset polyester can withstand moderate amounts of pressure and elevated temperature; therefore, the cast polyester piece also can be used as a master for embossing polymethylmethacrylate (PMMA) microfluidic systems. Examples of enclosed polyester and PMMA microchannels are presented, and we discuss the electroosmotic properties of both types of channels, which are important for analytical applications such as capillary electrophoresis.     

Rapid microfabrication of solvent-resistant biocompatible microfluidic devices

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.     

Rapid fabrication of microchannels using microscale plasma activated templating (microPLAT) generated water molds

Poly(dimethylsiloxane) (PDMS) is a common material used in fabricating microfluidic devices. The predominant PDMS fabrication method, soft lithography, relies on photolithography for fabrication of micropatterned molds. In this technical note, we report an alternative molding technique using microscale PLasma Activated Templating (microPLAT). The use of photoresist in soft lithography is replaced by patterned water droplets created using microPLAT. When liquid PDMS encapsulates patterned water and then solidifies, the cavities occupied by water become structures such as microchannels. Using this method, device fabrication is less time consuming, more cost efficient and flexible, and ideal for rapid prototyping. An additional important feature of the water-molding process is that it yields structural profiles that are difficult to achieve using photolithography.     

Simple fabrication of hydrophilic nanochannels using the chemical bonding between activated ultrathin PDMS layer and cover glass by oxygen plasma

This study describes a simple and low cost method for fabricating enclosed transparent hydrophilic nanochannels by coating low-viscosity PDMS (monoglycidyl ether-terminated polydimethylsiloxane) as an adhesion layer onto the surface of the nanotrenches that are molded with a urethane-based UV-curable polymer, Norland Optical Adhesive (NOA 63). In detail, the nanotrenches made of NOA 63 were replicated from a Si master mold and coated with 6 nm thick layer of PDMS. These nanotrenches underwent an oxygen plasma treatment and finally were bound to a cover glass by chemical bonding between silanol and hydroxyl groups. Hydrophobic recovery that is observed in the bulk PDMS was not observed in the thin film of PDMS on the mold and the PDMS-coated nanochannel maintained its surface hydrophilicity for at least one month. The potentials of the nanochannels for bioapplications were demonstrated by stretching λ-DNA (48,502 bp) in the channels. Therefore, this fabrication approach provides a practical solution for the simple fabrication of the nanochannels for bioapplications.