200 mm wafer-scale fabrication of polydimethylsiloxane fluidic devices for fluorescence imaging of single DNA molecules
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Research Letter
200 mm wafer-scale fabrication of polydimethylsiloxane fluidic devices for fluorescence imaging of single DNA molecules Sung-Wook Nam, Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu 41405, South Korea Address all correspondence to S.-W. Nam at [email protected] (Received 31 January 2018; accepted 27 March 2018)
Abstract We report fabrication of 200 mm silicon (Si)-wafer mold structure for polydimethylsiloxane (PDMS) microfluidic devices to demonstrate a real-time fluorescence imaging of single DNA molecules. Conventional photolithography with deep reactive ion etching process allows us to build a “mesa”-type Si mold with a nanoscallop sidewall geometry aiding PDMS residue-free process. By optimizing fluorescence microscopy with the fabricated PDMS chamber, we obtain a protocol to visualize the motions of single DNA molecules. This integrative PDMS-based single-molecule imaging system can, in principle, be used as a platform to study biochemical reactions occurring in proteins, nucleotides, and vesicles.
Introduction Polydimethylsiloxane (PDMS) is currently one of the most useful materials for fabricating microfluidic channels and for manufacturing biomedical devices.[1–4] To extend the potential applications of PDMS, a wide range of semiconductor processes, including photolithography, electron beam lithography, and nanoimprint lithography, have been adopted. Polymerized siloxane (Si–O–Si), the backbone of silicone elastomer, offers mechanically flexible and visibly transparent structures that are well suited for imaging biomolecules, including DNA, proteins, and particles.[5–8] Unlike polystyrene (PS), quartz, and glass materials, PDMS can be easily fabricated by simply mixing and curing the reagents of silicone elastomers using benchtop tools equipped in existing biomedical laboratories. In this respect, one of the essential elements to scale up the PDMS fabrication is to prepare recyclable silicon (Si)-wafer mold structure. There are some problems in the recycling process of Si mold when repeating PDMS fabrications. One among them is the interaction between the siloxane compound of the cured PDMS and the Si mold, which leaves residues in the peelingoff process. The residue problems are often due to local chemical bonding or mechanical stretching of the siloxane compound to Si when PDMS is separated from the Si substrate. In particular, this behavior is most likely to occur at the finest features, which jeopardizes the repeated usage of the Si mold. This critically hinders the large-scale mass production of PDMS chambers. Thus, an optimal process is needed to overcome this problem. Here, we offer a fabrication method of PDMS chambers which can be coupled with high-resolution fluorescence imaging system to real-time visualize single DNA molecules. There
are two challenges addressed here. One is to extend the PDMS fabrication to 200 mm Si-wafer scale, ideally in pursuit of mass productions. To accomplish it, we introduce Si “mesa”-type structures with “nanoscallop”
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