Author: H. İbrahim Erbay, University of Dokuz Eylül, Institute of Izmir BioMedicine and Genomics
Fabrication of microfluidic systems requires the use of multiple disciplines such as material science, fluid mechanics and bioengineering. A chip’s efficiency is highly related to material properties, production technique, and design. Polymers, for instance, are easy to fabricate compared to other types of devices such as glass or ceramic-based materials. Poly(dimethylsiloxane) (PDMS) has been the most frequently used material in microfluidic devices due to the cost and relative duration of fabrication as well as material properties which are useful for functional devices (Table 1). Properties of such elastomers allow rapid prototyping of microfluidic devices for many disciplines with various applications. This review focuses on fabrication techniques for PDMS devices as well as current advances in the field.
Replica molding encompasses multiple techniques including; hot-embossing, soft lithography, and injection molding. All need a mold made by metal or photoresist. Hot embossing and injection molding requires thermally durable metal molds and mostly used for thermoplastic shaping. Soft lithography, on the other hand, essentially uses a mold consisting of silicon wafer covered by a photoresist (as SU-8) and shaped by UV photolithography. Finally, the liquid polymer is poured in and cured to obtain the final device followed by bonding the PDMS microchannels on another layer. After curing, the device is peeled from the mold and usually bonded to a glass slide in order to obtain a closed channel. Replica molding yields from a few microns to a couple of hundreds of nanometres in resolution. In addition, obtaining such high resolution used to require cleanroom facilities hence increasing the cost. However, with current rapid prototyping techniques resolutions as low as 10 microns can be obtained without cleanrooms. Replica molding has been grown to be the standard technique for microfluidic device fabrication, especially in the biomedical field since PDMS is the dominating material with its flexibility, biocompatibility, optical and mechanical properties. In hot embossing technique, the polymer is pressed into the master mold which has micro or nanostructures on its surface. Later, heat is applied, and reverse features of the master are transferred to the polymer. Finally, the polymer is peeled from the master and thermally bonded to a glass or another device. Hot embossing allows controlling dimensions of the device at nanoscale while being a high-throughput method. In addition, high pressure during the process provides perfect quality. However, the quality of the device is determined by the mold which may increase the overall cost of the process. Injection molding is a common industrial process for replicating a master to various kinds of materials. The process can provide nano-scale precision. Usually, the liquid polymer is forced to a mold cavity under high pressure where it stays until the curing is completed. The process is well established, low-cost and suitable for mass production.
Soft lithography is the most commonly used method for Poly(dimethylsiloxane) devices. In this technique, a silicon wafer is produced by photolithographic techniques which are used as a master. Photolithography starts with the preparation of the substrate which requires a clean room in order to prevent and foreign particles. Later a layer of photoresist (e.g. SU-8) is formed on the surface of the substrate with a spin-coater. Next, a photomask with the desired design is placed on top of the photoresist and UV is applied.
Finally, the photoresist is removed and the master is etched. Later, the liquid base and curing agent of PDMS is mixed and poured over the master (usually at 10:1 vbase/vcuring agent). Curing agent contains silicon hydride groups which react to vinyl groups in the base forming a cross-linked elastomeric solid. The liquid mixture conforms to the shape of the master and reverse features are hence transferred at a nano-scale fidelity. After the curing process, the device is easily peeled off without damaging the master or the device itself.
Latest advances in 3D-printing technologies allow fabrication of highly complex microfluidic devices in one step, in a fast and cost-effective manner. Consequently, making microfluidic technology more accessible to users. The general process starts with a 3D-digital design which then printed layer-by-layer. Today 3D printing is very beneficial for fabrication of molds of PDMS with 3D structures. The minimum feature size is larger compared to soft lithography techniques but the cost is much lower. Direct printing of elastomer is still under development.
Current advances in nanofabrication techniques can provide unique properties to microfluidic devices in both 2D and 3D setups. Photolithographic methods employ a UV light source ranging from 250-440 nm to create the design on the photoresist. However, the resolution of this process is highly affected by diffraction. In order to bypass this limit, techniques such as electron beam lithography, extreme ultraviolet lithography, and nanoimprint lithography have been developed. By reducing the wavelength, it is convenient to generate reduced features on a substrate.
Replica molding will continue to play a central role in PDMS based devices. The longevity in research applications is ensured by fabrication simplicity, biocompatibility and design versatility. Methods that once required cleanroom facilities are being gradually replaced with low-cost techniques. In addition, advances in micro and nanofabrication remove the barriers such as complex control systems or non-standard user interfaces for commercializing of microfluidic devices. Hot embossing and injection molding have been the most popular techniques for commercial devices.
In addition, limitations in mold cost force both academia and industry to pursue new materials thereby allowing microfluidics to become a regular system for research, product, and the public. Especially in tissue engineering, organ-on-chip devices are one of the hottest topics in research. Models such as gut (4), lung (5), heart (6), blood-brain-barrier (7), brain (8), bone marrow (9), liver (10) and multiple organs on chip (11) hold promise for the medical field. In addition, many processes such as drug discovery, polymerase-chain-reaction, biosensors, electrophoresis, and basic chemistry can be diminished to microscale with increased efficiency.
Table-1: Comparison of different techniques for PDMS microfluidic chip fabrication
|Soft lithography||High resolution with 3D geometry||Vulnerable to defects and pattern deformations|
|Hot embossing||Mass production, cost-effective, and precise||Difficult to manufacture complex 3D structures|
|Injection molding||Manufacturing complex structures with fine details||The high cost of molds|
|3D printing||Rapid production of complex 3D structures with cost-effective||Limited resolution|
|Nanofabrication||Nanopattern fabrication||Time-consuming and high-cost|
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