Polymer microfabrication technologies for microfluidic systems

Polymers have assumed the leading role as substrate materials for microfluidic devices in recent years. They offer a broad range of material parameters as well as material and surface chemical properties which enable microscopic design features that cannot be realised by any other class of materials. A similar range of fabrication technologies exist to generate microfluidic devices from these materials. This review will introduce the currently relevant microfabrication technologies such as replication methods like hot embossing, injection molding, microthermoforming and casting as well as photodefining methods like lithography and laser ablation for microfluidic systems and discuss academic and industrial considerations for their use. A section on back-end processing completes the overview.     

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.     

Thermoplastic microfluidic devices and their applications in protein and DNA analysis

Microfluidics is a platform technology that has been used for genomics, proteomics, chemical synthesis, environment monitoring, cellular studies, and other applications. The fabrication materials of microfluidic devices have traditionally included silicon and glass, but plastics have gained increasing attention in the past few years. We focus this review on thermoplastic microfluidic devices and their applications in protein and DNA analysis. We outline the device design and fabrication methods, followed by discussion on the strategies of surface treatment. We then concentrate on several significant advancements in applying thermoplastic microfluidic devices to protein separation, immunoassays, and DNA analysis. Comparison among numerous efforts, as well as the discussion on the challenges and innovation associated with detection, is presented.     

玻璃微流控芯片廉价快速制作方法的研究

研究了一种玻璃微流控芯片的快速、低成本制作工艺和方法. 该方法采用商品化的显微载玻片(soda-lime玻璃)作为芯片基质材料, 利用AZ 4620光刻胶代替传统工艺中的溅射金属层或多晶硅/氮化硅层作为玻璃刻蚀的掩膜层, 同时利用一种紫外光学胶键合方法代替传统熔融键合方法实现芯片的键合, 整个工艺对玻璃基质材料要求低, 普通微流控芯片(深度小于50 μm)制作流程仅需约3.5 h, 可降低制作成本, 缩短制作周期. 还系统地研究了光刻胶厚度、光刻胶硬烘时间和玻璃腐蚀液配比对玻璃微流控芯片制作的影响, 获得了优化的工艺参数.     

Components for integrated poly(dimethylsiloxane) microfluidic systems

This review describes the design and fabrication of microfluidic systems in poly(dimethylsiloxane) (PDMS). PDMS is a soft polymer with attractive physical and chemical properties: elasticity, optical transparency, flexible surface chemistry, low permeability to water, and low electrical conductivity. Soft lithography makes fabrication of microfluidic systems in PDMS particularly easy. Integration of components, and interfacing of devices with the user, is also convenient and simpler in PDMS than in systems made in hard materials. Fabrication of both single and multilayer microfluidic systems is straightforward in PDMS. Several components are described in detail: a passive chaotic mixer, pneumatically actuated switches and valves, a magnetic filter, functional membranes, and optical components.     

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.     

Microfluidic assembly blocks

An assembly approach for microdevice construction using prefabricated microfluidic components is presented. Although microfluidic systems are convenient platforms for biological assays, their use in the life sciences is still limited mainly due to the high-level fabrication expertise required for construction. This approach involves prefabrication of individual microfluidic assembly blocks (MABs) in PDMS that can be readily assembled to form microfluidic systems. Non-expert users can assemble the blocks on glass slides to build their devices in minutes without any fabrication steps. In this paper, we describe the construction and assembly of the devices using the MAB methodology, and demonstrate common microfluidic applications including laminar flow development, valve control, and cell culture.     

Surface modification of thermoplastics--towards the plastic biochip for high throughput screening devices

Microarrays have become one of the most convenient tools for high throughput screening, supporting major advances in genomics and proteomics. Other important applications can be found in medical diagnostics, detection of biothreats, drug discovery, etc. Integration of microarrays with microfluidic devices can be highly advantageous in terms of portability, shorter analysis time and lower consumption of expensive biological analytes. Since fabrication of microfluidic devices using traditional materials such as glass is rather expensive, there is great interest in employing polymeric materials as a low cost alternative that is suitable for mass production. A number of commercially available plastic materials were reviewed for this purpose and poly(methylmethacrylate) Zeonor 1060R and Zeonex E48R were identified as promising candidates, for which methods for surface modification and covalent immobilization of DNA oligonucleotides were developed. In addition, we present proof-of-concept plastic-based microarrays with and without integration with microfluidics.     

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.     

Rapid prototyping of three-dimensional microfluidic mixers in glass by femtosecond laser direct writing

The creation of complex three-dimensional (3D) microfluidic systems has attracted significant attention from both scientific and applied research communities. However, it is still a formidable challenge to build 3D microfluidic structures with arbitrary configurations using conventional planar lithographic fabrication methods. Here, we demonstrate rapid fabrication of high-aspect-ratio microfluidic channels with various 3D configurations in glass substrates by femtosecond laser direct writing. Based on this approach, we demonstrate a 3D passive microfluidic mixer and characterize its functionalities. This technology will enable rapid construction of complex 3D microfluidic devices for a wide array of lab-on-a-chip applications.     

Fast production of microfluidic devices by CO2 laser engraving of wax‐coated glass slides

Glass is one of the most convenient materials for the development of microfluidic devices. However, most fabrication protocols require long processing times and expensive facilities. As a convenient alternative, polymeric materials have been extensively used due their lower cost and versatility. Although CO₂ laser ablation has been used for fast prototyping on polymeric materials, it cannot be applied to glass devices because the local heating causes thermal stress and results in extensive cracking. A few papers have shown the ablation of channels or thin holes (used as reservoirs) on glass but the process is still far away from yielding functional glass microfluidic devices. To address these shortcomings, this communication describes a simple method to engrave glass‐based capillary electrophoresis devices using standard (1 mm‐thick) microscope glass slides. The process uses a sacrificial layer of wax as heat sink and enables the development of both channels (with semicircular shape) and pass‐through reservoirs. Although microscope images showed some small cracks around the channels (that became irrelevant after sealing the engraved glass layer to PDMS) the proposed strategy is a leap forward in the application of the technology to glass. In order to demonstrate the capabilities of the approach, the separation of dopamine, catechol and uric acid was accomplished in less than 100 s.     

Characterization of PDMS-modified glass from cast-and-peel fabrication

In glass/poly(dimethylsiloxane) (PDMS) hybrid microfluidic chips, two different fabrication approaches are used: photolithographic or solid ink molds, or cast-and-peel methods. In the latter, a thin slab of PDMS is laid down and fluid channels are cut manually or by machine. The cast-and-peel approach has been used successfully for low-shear culture devices, among other applications. The main drawback, not reported to date, of cast-and-peel methods is that removal of PDMS (exposing the glass substrate) results in nanoscopic domains of PDMS still attached to the surface. This residual PDMS is not observable by eye, but affects the hydrophobicity of the device. Using contact angle measurement, atomic force and fluorescence microscopy, the changes in glass surfaces from the cast-and-peel technique were elucidated. This study demonstrates the enhanced protein (NeutrAvidin) adsorption on PDMS treated glass surfaces, and the potential influence of altered glass properties on microfluidic applications has been discussed as well.     

Thermal analysis of starch for realizing embedded channel in low temperature co-fired ceramic

The rapidly developing biotechnology, automotive industry, chemical and environmental fields have increasing needs for analytical systems with desires such as smaller sizes, lower sample volumes. Reduction in size results in further requirements in functionalities such as multi-sensor devices with low cost. These microsystems usually contain three-dimensional structures. In the fabrication of microfluidic devices ensuring a well-shaped channel is a challenge. During firing of the low temperature co-fired ceramic (LTCC) substrate, these embedded structures tend to deform and sag because the green glass–ceramic material is very weak. Starch was used as sacrificial volume material (SVM) to support the embedded structures of the LTCC during lamination and sintering. As a consequence of burnout, the increased fraction of evolving gases from SVM requires an adequate adaptation of the firing process to control starch degradation and provide a residue-free burnout. Using thermal analysis techniques and describing degradation kinetics of SVM, a new heating profile is demonstrated which insures complete starch burnout without damaging the LTCC structures.     

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.     

Fabrication of microfluidic systems in poly(dimethylsiloxane)

Microfluidic devices are finding increasing application as analytical systems, biomedical devices, tools for chemistry and biochemistry, and systems for fundamental research. Conventional methods of fabricating microfluidic devices have centered on etching in glass and silicon. Fabrication of microfluidic devices in poly(dimethylsiloxane) (PDMS) by soft lithography provides faster, less expensive routes than these conventional methods to devices that handle aqueous solutions. These soft-lithographic methods are based on rapid prototyping and replica molding and are more accessible to chemists and biologists working under benchtop conditions than are the microelectronics-derived methods because, in soft lithography, devices do not need to be fabricated in a cleanroom. This paper describes devices fabricated in PDMS for separations, patterning of biological and nonbiological material, and components for integrated systems.     

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.     

Recent advances in multiple emulsions and their application as templates

We review recent developments on the preparation of multiple emulsions and their applications as templates for material fabrication. Emphasis is placed on microfluidic methods for accurate control of size and morphology and on new formulations that go beyond traditional surfactant systems for increased complexity. The straightforward applicability of multiple emulsions in the fabrication of multihollow particles or capsules of various materials is illustrated through representative examples.     

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.     

Sacrificial layer microfluidic device fabrication methods

Over the past 15 years, research in the field of microfluidics has experienced rapid growth due to significant potential advantages such as low cost, short analysis times, and elimination of sources of contamination. Although etched and thermally bonded glass substrates have seen widespread use and offer solid performance, device fabrication still remains cumbersome. Recent advances in sacrificial layer microfabrication methods for microfluidics have overcome many disadvantages of conventional fabrication approaches. Phase-changing sacrificial layers have been implemented in making inexpensive and high-performance polymer microchips for electrophoretic analysis, protein focusing, and sample preconcentration. In addition, novel channel fabrication methods based on standard thin-film processes, which are readily integratable with microfabrication techniques used for electrical components, are being applied increasingly for the creation of microfluidic devices. These new sacrificial layer fabrication approaches will be instrumental in making low-cost and high-quality polymer microchips, and in interfacing electrical and fluidic systems on glass or semiconductor substrates.     

Fabrication, modification, and application of poly(methyl methacrylate) microfluidic chips

Poly(methyl methacrylate) (PMMA) is particularly useful for microfluidic chips with the features of low price, excellent optic transparency, attractive mechanical and chemical properties, ease of fabrication and modification, biocompatibility, etc. During the past decade, significant progress in the PMMA microfluidic chips has occurred. This review, which contains 120 references, summarizes the recent advances and the key strategies in the fabrication, modification, and application of PMMA microfluidic chips. It is expected that PMMA microchips should find a wide range of applications and will lead to the creation of truly disposable microfluidic devices.