Microfluidics technology emerged in the early 1990s from research on microfluidic manipulation using micro-electro-mechanical system (MEMS). Over the past decades, advancements in analytical chemistry and life sciences have expanded the applications of microfluidic chip systems to nanofiber synthesis, nanocomposite fabrication, quantum dot synthesis, micro-nanoparticle preparation, electrochemical sensors, biochemical sensors, cell biology, and molecular analysis.
Microfluidics technology enables the integration of complex chemical or biological analytical processes into a single chip, creating a micrototal analysis system (μTAS), also known as a lab-on-a-chip.
Initial microfluidic chip fabrication relied fuly on MEMS techniques, which required all processing in clean rooms with precision micromachining tools. These costly design and processing requirements significantly limited adoption in analytical chemistry and life sciences. Standardized glass or polymer microfluidic chips from certain European and American companies still cost tens to hundreds of dollars each, restricting their use and commercialization in biology, chemistry, and medicine.
Recently, experts in mechanics, electronics, chemistry, and biology. have developed and utilized diverse low-cost micromachining methods based on their specialized knowledge and experience.
Processing Materials for Low-Cost Microfluidic Chips
Silicon and glass were the earliest substrate materials used in microfluidic chips, primarily because their processing methods can be directly applied to those used in MEMS and microelectronics. However, due to their high cost and difficulty in processing, these materials were quickly replaced by lower-cost materials, such as various polymers, during the development of microfluidic chips. Existing microfluidic chip processing methods offer a wide range of low-cost materials, including various elastomers, thermoplastic polymers, thermosetting polymers, paper, and biomaterials. This article will discuss common materials suitable for low-cost microfluidic chip processing, categorized as polymers, paper, and other materials.
- Elastomeric Materials
Elastomeric materials refer to polymeric materials that can undergo significant deformation under weak stress and quickly recover to a near-original state and size after stress relaxation. Polydimethylsiloxane (PDMS) is currently the most widely used elastomer material in microfluidic chips. The use of PDMS in microfluidic chips was first proposed by Whitesides et al. in 1998. PDMS offers advantages such as low cost, optical transparency, good biocompatibility, and moderate breathability, making it an ideal material for low-cost microfluidic chips. In microfluidic chip fabrication, PDMS is often molded to create microstructures on its surface, with mold accuracy even reaching the nanometer level. However, PDMS also has disadvantages such as easy deformation and collapse of channels and a small amount of absorption of fluid within the channels.
- Thermoplastics
Thermoplastics are among the most common and widely used materials in everyday life. They are very inexpensive and can be shaped after softening under certain temperature conditions. A wide variety of thermoplastic materials can be used for low-cost microfluidic chips, including polymethyl methacrylate (PMMA), polystyrene (PS), cyclic olefin copolymer (COC), polycarbonate (PC), polyethylene terephthalate (PET), and polyvinyl chloride (PVC).
- PMMA is widely used in various life science and medical research due to its low material cost, excellent thermal processing, and optical properties.
- PS has excellent biocompatibility and offers significant advantages as a microfluidic chip substrate in areas such as cell culture.
- COC, a relatively new amorphous copolymer, offers superior UV light transmittance and thermal stability compared to thermoplastics like PMMA. Its water absorption is only one-tenth that of PMMA. In most cases (except in extreme temperature environments), COC chips can directly replace expensive glass chips.
Paper Materials
Paper-based microfluidic chips are created by infiltrating hydrophobic materials into hydrophilic paper fibers through various methods. The hydrophobic material “walls” control fluid flow within the hydrophilic paper fibers, creating a paper-based microfluidic chip. Common inkjet printers, screen printers, 3D printers, wax printers, and even crayons can be used to produce low-cost paper-based microfluidic chips.
Common paper options include Whatman filter paper or chromatography paper. Unlike polymer-based microfluidic chips, which require sealed flow channels, paper-based microfluidic chips often do not require sealed channels because the fluid flows within the paper fibers.
Processing and Bonding Methods for Low-Cost Microfluidic Chips
We introduce a selection of commonly used, low-cost microfluidic chip fabrication methods.
- Micromolding
Due to the widespread use of PDMS in microfluidic chip fabrication, PDMS-based micromolding has become the most common method for fabricating microfluidic chips. Using SU-8 photoresist as a mold for PDMS molding is a common method.
- Laser ablation
Laser ablation specifically refers to the process of ablating microfluidic channels on polymer surfaces using a 10.6 μm wavelength carbon dioxide laser. The advantages of laser ablation for microfluidic channel fabrication include:
- The process is simple and fast, with a single ablation pass completing the process.
- It is applicable to a wide range of materials, including most polymers and glass, for microfluidic channel fabrication.
The application of laser ablation in low-cost microfluidic chips is currently focused on single polymer materials. Future developments suggest significant potential for the fabrication of microfluidic chips based on biodegradable bioplastics, paper, conductive plastics, and other materials.
Microfluidic chip fabrication using 3D printing primarily involves methods such as microstereolithography and fused deposition modeling (FDM). FDM 3D printers are relatively inexpensive and suitable for low-cost 3D microfluidic chip fabrication. FDM technology can directly print 3D microfluidic chips from materials such as PC, PLA, and acrylonitrile butadiene styrene (ABS), as well as molds for PDMS molding.
- Injection molding
Injection molding is a widely used method in plastics processing. With the recent development of microinjection molding technology, researchers have begun experimenting with using it to fabricate microfluidic chips. Common molding materials used for microfluidic chips include PMMA, COC, and PDMS.
Traditionally, injection molding microfluidic chips requires mold production, which is time-consuming and expensive. However, injection molding offers advantages over traditional metal molds in low-cost microfluidic chip processing. Its advantages include good repeatability, fast processing speed, and the ability to process 3D microfluidic chips, making it suitable for large-scale microfluidic chip production. However, its disadvantages include limited flexibility, the need to re-open the mold whenever the chip structure changes, and the high mold cost.
- Low-cost microfluidic chip bonding technology
Except for paper-based microfluidic chips, which can utilize open flow channels, all other types of microfluidic chips require a covering material over the flow channels after microstructure fabrication to seal the channels. This is known as microfluidic chip bonding.
The cover and substrate materials can be of the same type and thickness, but for specialized applications, bonding of materials of different types and thicknesses is also possible. In recent years, researchers have developed various low-cost microfluidic chip bonding methods, including thermal compression bonding, adhesive bonding, plasma surface treatment bonding, and laser welding.
- Hot Compression Bonding
Hot compression bonding is an ideal bonding method for microfluidic chips made of thermoplastic materials such as PMMA, PC, PS, and COC/COP. After the two materials are brought into contact and aligned, the chip is bonded by applying heat and pressure simultaneously. The heating temperature is slightly above the glass transition temperature (Tg) of the thermoplastic, and the pressure can be adjusted based on the actual situation.
Researchers have conducted in-depth research on the use of thermal compression for bonding microfluidic chips, studying the bond strength of materials such as PMMA/PMMA, PMMA/PS, and COC/COC under different temperatures and pressures.
- Adhesive Bonding
Adhesive bonding involves applying a layer of adhesive material to the chip substrate and then covering it with a cover slip for bonding. The adhesive material is typically a UV-curable material (such as SU-8 or dry film), which requires UV exposure to achieve a bond between the substrate and cover slip. Non-UV-curable materials, such as wax, can also be used for simple chip bonding. In addition to adhesive, an organic solvent can be applied to the contact surface of the materials to be bonded, partially dissolving the surface. However, the disadvantage is that residual adhesive or organic solvent residues may remain in the microchannel after bonding. Upon contact with the fluid within the channel, these residues may dissolve into the experimental solution, potentially severely affecting experimental results.
- Oxygen Plasma Surface Treatment Bonding
Microstructured PDMS substrates are typically treated with oxygen plasma before bonding to materials such as PDMS, glass, PMMA, and PC. If a cover slip made of PDMS, glass, or silicon is used, both the PDMS substrate and cover slip need to be treated with oxygen plasma simultaneously. However, oxygen plasma surface treatment equipment is relatively expensive for low-cost processing. If equipment is not available, a low-cost handheld plasma corona device can be used instead.
Using oxygen plasma surface treatment for bonding PDMS-based microfluidic chips offers advantages: a clean, contaminant-free surface and fast bonding speed. However, its disadvantages include complex chip cleaning and high equipment costs.
In terms of chip bonding technology development, reversible bonding and hybrid bonding are currently the most active areas of research. Researchers have explored various physical and chemical methods to achieve reversible bonding of materials such as PDMS, as well as hybrid bonding between materials with completely different physical and chemical properties, such as PDMS/SU-8.