Many modern biomedical- and chemical-analysis machines employ prepared, single-use, compact testing devices that have increased laboratory safety, accuracy, and throughput. Made from various plastics, the devices often feature microstructures such as reagent containers, reaction chambers, fluid channels, and microvalves to control incubation and liquid-sample flow while in operation. The high cost of many of these testing devices reflects the high degree of engineering that goes into their design and the sophisticated manufacturing methods needed to deliver precise microscopic details with the needed fine surface roughness. Our group sought to fabricate testing devices having these physical properties using less costly and more flexible manufacturing techniques.
We considered the methods currently used to create substrates with microstructures for bioapplications such as direct processing, polydimethylsiloxane (PDMS) production, LIGA (from the German for lithography, electroforming, and molding), and related technologies.1–3 Direct processing enables fast prototyping. However, it cannot produce small microstructures of fine roughness without difficulty.
PDMS reproduction is widely used in these applications for its good quality in optics and its biocompatibility. But because PDMS is a soft material, high-aspect-ratio structures are difficult to obtain, and mass production of test-device substrates is not easy to carry out. LIGA-like molding is usually employed to fabricate substrates of the type we are interested in. High aspect ratio and good roughness on microstructures are also attainable through this approach. By the same token, it is expensive.
Figure 1. Atomic-force microphotograph of track pitches and pit marks recorded on an optical disc.
Consequently, we turned our attention to processes used to produce optical discs, which offer an efficient system for mass production at low cost: one reason why CDs, DVDs, and Blu-ray Discs are very popular in the market. The track pitches on these devices are designed at different values of 1600, 740, and 320nm, respectively. The sizes of minimum individual pit marks are 830, 400, and 150nm.4 In other words, these track pitches and pit marks recorded on optical discs are already micro/nanoscale size, as shown in the atomic force microscopy image in Figure 1. Accordingly, we felt that the optical-disc process was highly promising for fabricating substrates with microstructures.
Figure 2. Fabrication process for a metallic mold with microstructures.
Figure 3. (a) A metallic mold and (b) a polycarbonate substrate with different microstructures.
Figure 4. Procedures of liquid sample (a) loading, (b) separating, and (c) mixing.
The modified optical-disc process we developed uses photolithographic techniques similar to those used in microelectronics manufacturing (see Figure 2).5 It starts with creating a metallic substrate, then coating it with a desired thickness of photoresist material. After baking, the photoresist is exposed to light of a particular wavelength through a mask, which features specific patterns for creating different microstructures. These specific micropatterns are transferred and formed on the photoresist after exposure to a developing solution. The next step is to electroform the metallic substrate to fill up the micro-patterns created on the photoresist. After removing the photoresist, we obtain a metallic mold possessing specific microstructures. This metallic mold is then applied to replicate disposable substrates through an injection-molding process.
Figure 5. A grating-coupled surface-plasmon-resonance disc with various pitch sizes and periodic structures.
Figure 3 shows a metallic mold and a polycarbonate (PC) substrate with different microstructures designed and fabricated to demonstrate this modified process. The engineered substrate is bonded to a flat, unpatterned PC substrate to complete the package, forming the chambers, channels, valves, and so forth that constitute the microfluidic device.
To verify the functionality of the device, we mounted it onto a motion-controlled turntable and conducted experiments with food coloring. The results show good performance in bonding and packaging. We developed different procedures for liquid-sample loading, separating, and mixing on the device, step by step, through appropriately controlling its rotational speed (see Figure 4).
In addition to the microfluidic design, our team also investigated a grating-coupled surface-plasmon-resonance (SPR) disc, created using optical-disc manufacturing technologies. SPR is a kind of photoelectric phenomenon. Surface plasmons are electromagnetic waves that propagate, say, in a metallic surface, in the direction parallel to the metal interface. The SPR effect is very sensitive to any change on the boundary of the metal and the external medium, such as the absorption of molecules on the metal surface. The periodic structures with a metallic film can excite surface-plasmon waves. The tracks on an optical disc are like optical diffraction gratings, having periodic features. Consequently, some researchers use commercial CD-R discs as chemical and biological sensors.6–8 Using our techniques, we fabricated and measured a grating-coupled SPR disc possessing different pitches and periodic structures (see Figure 5).
Our modified optical-disc process enabled fast prototyping in fabricating molds and replicating substrates with various microstructures, including those needed for a grating-coupled SPR device featuring fine pitches and periodic structures. This process provides a simple way to mass-produce future fine-structured systems. As a next step, we will focus on using these techniques to make samples with microstructures for drug screening and pathogen-detection applications.
Kuo-Chi Chiu, Sheng-Li Chang, Chu-Yu Huang, Hann-Wen Guan
Industrial Technology Research Institute (ITRI)
Kuo-Chi Chiu received his PhD in electro-optical engineering from National Chiao Tung University (2006). He joined ITRI in 1994 and is now a lead engineer. His current research focuses on developing microstructures and microfluidic devices for bioapplications.
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