Photopolymerization of a perfluoropolyether oligomer and photolithographic processes for the fabrication of microfluidic devices

A perfluoropolyether based photocured polymer is proposed as structural material for the fabrication and easy prototyping of microfluidic devices. The kinetics of photopolymerization and the fluoropolymer characterization is reported, assessing the suitability of the material: it results transparent, thermally resistant, with a good dimensional stability and a chemical resistance much higher than polydimethylsiloxane, material currently used in microfluidics. The direct fabrication of microchannels is finally presented by direct photopolymerization under UV light irradiation through photomasks: the transfer of micropatterns was successful.     

Reduced UV light scattering in PDMS microfluidic devices

Microfluidic devices which consist of polydimethylsiloxane (PDMS) are used extensively for the production of polymer microparticles through the use of droplet templating and on-chip photopolymerization. However, in existing methods, spatial confinement of the photochemical droplet solidification is impaired by UV light scattering inside the PDMS elastomer. We present a technique to load PDMS microfluidic devices with a fluorescent dye that absorbs the scattered UV light and shifts it to longer wavelengths. By this means, the stray light is no longer harmful, and UV exposure can be limited to a desired region on the microfluidic chip.     

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.     

Thermoset polyester droplet-based microfluidic devices for high frequency generation

The vast majority of droplet-based microfluidic devices are made from polydimethylsiloxane (PDMS). Unfortunately PDMS is not suitable for high frequency droplet generation at high operating pressure due to its low shear modulus. In this paper, we report the fabrication and testing of microfluidic devices using thermoset polyester (TPE). The optical characteristics of the fabricated devices were assessed and substrate resistance to pressure also investigated. TPE devices bonded using an O(2) plasma treated PET substrate at 76 °C were shown to function efficiently at pressures up to 18 MPa. TPE material retains many of the attractive features of PDMS such as ease of fabrication but significantly, has superior mechanical properties. The improved resistance of TPE to high pressures enabled investigation of high frequency droplet generation as a function of a wide range of flow-rates with three different oils as continuous phase.     

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.     

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.     

In situ fabrication of macroporous polymer networks within microfluidic devices by living radical photopolymerization and leaching

Novel fabrication techniques and polymer systems are being explored to enable mass production of low cost microfluidic devices. In this contribution we discuss a new fabrication scheme for making microfluidic devices containing porous polymer components in situ. Contact lithography, a living radical photopolymer (LRPP) system and salt leaching were used to fabricate multilayer microfluidic devices rapidly with various channel geometries and covalently attached porous polymer plugs made of various photopolymerizable substrates. LRPP systems offer the advantages of covalent attachment of microfluidic device layers and facile surface modification via grafting. Several applications of the porous plugs are also explored, including a static mixer, a high surface area-to-volume reactor and a rapidly responding hydrogel valve. Quantitative and qualitative data show an increase in mixing of a fluorescein and a water stream for channels containing porous plugs relative to channels with no porous plugs. Confocal laser scanning microscopy images demonstrate the ability to graft a functional material onto porous plug surfaces. A reaction was carried out on the grafted pore surfaces, which resulted in fluorescent labelling of the grafted material throughout the pores of the plug. Homogenous fluorescence throughout the depth of the porous plug and along pore surfaces indicated that the porous plugs were surface modified by grafting and that reactions can be carried out on the pore surfaces. Finally, porous hydrogel valves were fabricated which swelled in response to contact with various pH solutions. Results indicate that a porous hydrogel valve will swell and close more rapidly than other valve geometries made with the same polymer formulation. The LRPP-salt leaching method provides a means for rapidly incorporating porous polymer components into microfluidic devices, which can be utilized for a variety of pertinent applications upon appropriate selection of porous plug materials and surface treatments.     

Optofluidic differential spectroscopy for absorbance detection of sub-nanolitre liquid samples

We present a novel optofluidic differential method for carrying out absorbance spectroscopy of sub-nanolitre volumes of liquid samples on a microfluidic chip. Due to the reduction of liquid volume, the absorbance detection in microfluidics is often hindered by either low sensitivity or complex fabrication. To address this issue, we introduced an optofluidic modulator which can be easily integrated into a PDMS (polydimethylsiloxane) based microfluidic chip. The modulator was controlled by the fluid pressure and the absorbance spectrum of the analyte was obtained by taking differential measurements between the analyte and reference medium. An advantage is that this method doesn't need a complicated fabrication step. It is compatible with conventional microfluidic chips and measurements can be carried out on a normal transmission microscope. The performance of the device was tested by measuring solutions containing methylene blue, with concentrations as low as 13 μM.     

Frontal photopolymerization for microfluidic applications

Frontal photopolymerization (FPP) offers numerous advantages for the rapid prototyping of microfluidic devices. Quantitative utilization of this method, however, requires a control of the vertical dimensions of the patterned resist material. To address this fundamental problem, we study the ultraviolet (UV) photopolymerization of a series of multifunctional thiolene resists through a combination of experiments and analytical modeling of the polymerization fronts. We describe this nonlinear spatio-temporal growth process in terms of a "minimal" model involving an order parameter phi(x, t) characterizing the extent of monomer-to-polymer conversion, the optical attenuation T(x, t), and the solid front position h(t). The latter exhibits an induction time (or equivalent critical UV dose) characterizing the onset of frontal propagation. We also observe a novel transition between two logarithmic rates of growth, determined by the Beer-Lambert attenuation constants mu(0) and mu(infinity) of the monomer and fully polymerized material, respectively. The measured frontal kinetics and optical transmission of the thiolene resist materials are consistent with our photopolymerization model, exhibiting both "photodarkening" and "photoinvariant" polymerization. This is apparently the first observation of photodarkening reported in FPP. On the basis of these results, multilevel fluidic devices with controlled height are readily fabricated with modulated illumination. A representative two-level microfluidic device, incorporating a chaotic mixer, a T junction, and a series of controlled flow constrictions, illustrates the practical versatility of this fabrication method.     

Benzophenone absorption and diffusion in poly(dimethylsiloxane) and its role in graft photo-polymerization for surface modification

Following the great success of traditional microfluidic devices across many disciplines, a new class of microfluidic systems emerged in recent years, which features finely tuned, localized surface modifications within the microstructures in order to keep up with the demand for devices of ever increasing complexity (lab on chip, assay on chip, etc.). Graft photopolymerization has become a powerful tool for such localized surface modifications particularly in combination with poly(dimethylsiloxane) (PDMS) devices, as it is compatible with many functional monomers and allows for high spatial resolution. However, application within enclosed PDMS microstructures and in particular well-controlled surface-directed polymerization remains challenging. Detailed understanding of the interaction between photoinitiator, benzophenone (BP), and polymer matrix is needed. We have developed a visualization technique, which allows for observation of reacted BP in situ within the PDMS matrix. We present a detailed study on solvent-driven BP diffusion providing results essential to successful surface treatment. We also identified and investigated photoinitiator inhibition by oxygen and provide appropriate mitigation strategies.     

The stability of high refractive index polymer materials for high-density planar optical circuits

Owing to the structural flexibility, easy processing and fabrication capabilities, polymers are being increasingly attractive for a variety of optical applications. In order to increase the integration density of such optical circuits, higher index contrasts and, thus, polymers with considerably higher refractive index are essentially needed. An organometallic polymer and a conventional epoxy material are combined to form a compatible high index material. When cured at elevated temperatures, the organometallic polymer decomposes to form a highly dispersed metal oxide phase that imparts high index properties to the polymer films. These hybrid high refractive index polymer films must be stable in patterning of optical waveguide structure for photonic manufacturing. In this paper, we report the stability and optical characterization study of a modified organometallic high refractive index polymer film in manufacturing of optical waveguide devices.     

水凝胶微流控芯片的快速加工及在细胞培养检测中的应用

采用具有紫外光聚合性能的聚乙二醇(PEG)基水凝胶材料, 通过紫外光聚合作用快速加工双层水凝胶微流控芯片, 并验证了其对肿瘤细胞代谢液进行检测的可行性. 与传统微流控芯片材料相比, 该水凝胶芯片材料具有更好的生物相容性及可操控性, 可直接加工成形, 在生物学领域特别是细胞培养过程控制方面具有良好的应用前景. 实验结果表明, 该水凝胶微流控芯片可在微尺度空间有效模拟细胞生长环境, 并实现对细胞连续捕获后的原位培养. 将该芯片与卟啉可视阵列传感器系统结合, 经代谢特征分析可有效区分不同种类肿瘤细胞, 实现芯片细胞培养平台上的细胞代谢指纹快速可视化传感检测.     

Green microfluidic devices made of corn proteins

An alternative green microfluidic device made of zein, a prolamin of corn, can be utilized as a disposable environmentally friendly microchip especially in agriculture applications. Using standard soft lithography and stereo lithography techniques, we fabricated thin zein films with microfluidic chambers and channels. These were bonded to both a glass slide and another zein film. The zein film with microfluidic features bonds irreversibly with other surfaces by vapor-deposition of ethanol to create an adhesive layer resulting in very little or no trapped air and small shape distortion. Zein-zein and zein-glass microfluidic devices demonstrated sufficient strength to facilitate fluid flow in a complex microfluidic design that showed no leakage under high hydraulic pressure. Zein-glass microfluidic devices with serpentine mixing design showed successful fluid manipulation as a concentration gradient of Rhodamine B solution was generated. The ease of fabrication and bonding and the flexibility and moldability of zein offer attractive possibilities for microfluidic device design and manufacturing. These devices can include several unit operations with mixing being one of the most commonly used. The zein-based microfluidic devices, made entirely from a biopolymer from agricultural origin, offer alternative environmentally friendly material choices that are less dependent on limited petroleum based polymer resources.     

A metering rotary nanopump for microfluidic systems

We describe the design, fabrication, and testing of a microfabricated metering rotary nanopump for the purpose of driving fluid flow in microfluidic devices. The miniature peristaltic pump is composed of a set of microfluidic channels wrapped in a helix around a central camshaft in which a non-cylindrical cam rotates. The cam compresses the helical channels to induce peristaltic flow as it is rotated. The polydimethylsiloxane (PDMS) nanopump design is able to produce intermittent delivery or removal of several nanolitres of fluid per revolution as well as consistent continuous flow rates ranging from as low as 15 nL min(-1) to above 1.0 μL min(-1). At back pressures encountered in typical microfluidic devices, the pump acts as a high impedance flow source. The durability, biocompatibility, ease of integration with soft-lithographic fabrication, the use of a simple rotary motor instead of multiple synchronized pneumatic or mechanical actuators, and the absence of power consumption or fluidic conductance in the resting state all contribute to a compact pump with a low cost of fabrication and versatile implementation. This suggests that the pump design may be useful for a wide variety of biological experiments and point of care devices.     

A touch-and-go lipid wrapping technique in microfluidic channels for rapid fabrication of multifunctional envelope-type gene delivery nanodevices

Multifunctional envelope-type gene delivery nanodevices (MENDs) are promising non-viral vectors for gene therapy. Though MENDs remain strong in prolonged exposure to blood circulation, have low immunogenic response, and are suitable for gene targeting, their fabrication requires labor-intensive processes. In this work, a novel approach has been developed for rapid fabrication of MENDs by a touch-and-go lipid wrapping technique in a polydimethylsiloxane (PDMS)/glass microfluidic device. The MEND was fabricated on a glass substrate by introduction of a condensed plasmid DNA core into microfluidic channels that have multiple lipid bilayer films. The principle of the MEND fabrication in the microfluidic channels is based on electrostatic interaction between the condensed plasmid DNA cores and the coated lipid bilayer films. The constructed MEND was collected off-chip and characterized by dynamic light scattering. The MEND was constructed within 5 min with a narrow size distribution centered around 200 nm diameter particles. The size of the MEND showed strong dependence on flow velocity of the condensed plasmid DNA core in the microfluidic channels, and thus, could be controlled to provide the optimal size for medical applications. This approach was also proved possible for fabrication of a MEND in multiple channels at the same time. This on-chip fabrication of the MEND was very simple, rapid, convenient, and cost-effective compared with conventional methods. Our results strongly indicated that MENDs fabricated with our microfluidic device have a good potential for medical use. Moreover, MENDs fabricated by this microfluidic device have a great potential for clinical use because the devices are autoclavable and all the fabrication steps can be completed inside closed microfluidic channels without any external contamination.     

Simple and cheap microfluidic devices for the preparation of monodisperse emulsions

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.     

Monolithic media in microfluidic devices for proteomics

Considerable effort has been invested in the development of integrated microfluidic devices for fast and highly efficient proteomic studies. Among various fabrication techniques for the preparation of analytical components (separation columns, reactors, extractors, valves, etc.) in integrated microchips, in situ fabrication of monolithic media is receiving increasing attention. This is mainly due to the ease and simplicity of preparation of monolithic media and the availability of various precursors and chemistries. In addition, UV-initiated photopolymerization technique enables the incorporation of multiple analytical components into specified parts of a single microchip using photomasks. This review summarizes preparation methods for monolithic media and their application as microfluidic analytical components in microchips.     

Enhanced wet adhesion and shear of elastomeric micro-fiber arrays with mushroom tip geometry and a photopolymerized p(DMA-co-MEA) tip coating

Using principles inspired by the study of naturally occurring sticky systems such as the micro- and nanoscale fibers on the toes of geckos and the adhesive proteins secreted by marine animals such as mussels, this study describes the development and evaluation of a novel patterned and coated elastomeric microfibrillar material for enhanced repeatable adhesion and shear in wet environments. A multistep fabrication process consisting of optical lithography, micromolding, polymer synthesis, dipping, stamping, and photopolymerization is described to produce uniform arrays of polyurethane elastomeric microfibers with mushroom-shaped tips coated with a thin layer of lightly cross-linked p(DMA-co-MEA), an intrinsically adhesive synthetic polymer. Adhesion and shear force characterization of these arrays in contact with a glass hemisphere is demonstrated, and significant pull-off force, overall work of adhesion, and shear force enhancements in submerged aqueous environments are shown when compared to both unpatterned and uncoated samples, as well as previously evaluated patterned and coated arrays with differing geometry. Such materials may have potential value as repeatable adhesives for wet environments, such as for medical devices.     

Thermoplastic elastomers for microfluidics: towards a high-throughput fabrication method of multilayered microfluidic devices

Multilayer soft lithography of polydimethylsiloxane (PDMS) is a well-known method for the fabrication of complex fluidic functions. With advantages and drawbacks, this technique allows fabrication of valves, pumps and micro-mixers. However, the process is inadequate for industrial applications. Here, we report a rapid prototyping technique for the fabrication of multilayer microfluidic devices, using a different and promising class of polymers. Using styrenic thermoplastic elastomers (TPE), we demonstrate a rapid technique for the fabrication and assembly of pneumatically driven valves in a multilayer microfluidic device made completely from thermoplastics. This material solution is transparent, biocompatible and as flexible as PDMS, and has high throughput thermoforming processing characteristics. We established a proof of principle for valving and mixing with three different grades of TPE using an SU-8 master mold. Specific viscoelastic properties of each grade allow us to report enhanced bonding capabilities from room temperature bonding to free pressure thermally assisted bonding. In terms of microfabrication, beyond classically embossing means, we demonstrate a high-throughput thermoforming method, where TPE molding experiments have been carried out without applied pressure and vacuum assistance within an overall cycle time of 180 s. The quality of the obtained thermoplastic systems show robust behavior and an opening/closing frequency of 5 Hz.     

Patterning, integration and characterisation of polymer optical oxygen sensors for microfluidic devices

This paper describes a process for the layer-by-layer fabrication and integration of luminescent dye-based optical oxygen sensors into microfluidic devices. Application of oxygen-sensitive platinum(ii) octaethylporphyrin ketone fluorescent dye dissolved in polystyrene onto glass substrates by spin-coating was studied. Soft lithography with polydimethylsiloxane (PDMS) stamps and reactive ion etching in oxygen plasma were used to produce sensor patterns with a minimum feature size of 25 microm. Sensors patterns were integrated into a PDMS microfluidic device by plasma bonding. No degradation of the sensor response as a result of the lithography and pattern-transfer processes was detected. Gaseous and dissolved oxygen (DO) detection was characterised using fluorescence microscopy. The intensity signal ratio of the sensor films was found to increase almost two-fold from 3.6 to 6.8 by reducing film thickness from 1.3 microm to 0.6 microm. Calibration of DO measurement showed linear Stern-Volmer behaviour that was constant for flow rates from 0.5 to 2 mL min(-1). The calibrated sensors were subsequently used to demonstrate laterally resolved detection of oxygen inside a microfluidic channel. The fabrication process provides a novel, easy to use method for the repeatable integration of optical oxygen sensors into cell-culture and lab-on-a-chip devices.