Cyclo olefin polymer-based solvent-free mass-productive microphysiological systems

Abstract

A microphysiological system (MPS) holds a great promise for drug screening and toxicological testing as an alternative to animal models. However, this platform has several issues in terms of the materials used (e.g., polydimethylsiloxane), such as the absorbance of tested drug candidates and fluorescent dyes by the material, as well as the effect on cultured cellular status, thus misleading the results obtained from cell assays and fabrication processes. Hence, to eliminate the issues mentioned above, we developed a cyclo olefin polymer (COP)-based MPS via photobonding process using vacuum ultraviolet (VUV), named COP-VUV-MPS. COP-VUV-MPS showed better chemical resistance and avoided molecule absorption. COP-VUV-MPS could maintain the stemness of environmentally sensitive human-induced pluripotent stem cells without causing undesired cellular phenotypes and gene expression. These results suggested that COP-VUV-MPS might be broadly used for the advancement of MPS and applications in drug development and in vitro toxicological testing.

In vitrononalcoholic fatty liver disease model with cyclo-olefin-polymer-based microphysiological systems

“…Recently, we established the COP-MPS with a photobonding process instead of solvent bonding to eliminate the drawbacks of the conventional MPS using thermoplastic materials (Yamanaka et al, 2020). This COP-MPS allows culturing of human induced pluripotent stem cells (hiPSCs) (Takahashi et al, 2007;Yu et al, 2007) and reducing undesired apoptotic cells.…”

“…The COP-MPS comprises two layers of COP and eight microfluidic cell-culture channels (800 µm width, 7500 µm length, 250 µm height), with a medium inlet and outlet each (2 and 1 mm in diameter, respectively) and a total channel volume of 13.2 µL each (Yamanaka et al, 2020). The methods used to fabricate COP-MPS include (which was not certified by peer review) is the author/funder.…”

“…S1A) followed by photobonding ( Fig. S1B), as described previously (Yamanaka et al, 2020). Briefly, two metal molds were used to fabricate the microfluidic structures.…”

“…The copyright holder for this preprint this version posted December 29, 2020. ; https://doi.org/10.1101/2020.12.28.424535 doi: bioRxiv preprint thermostability and high modulus for metal molding processes and can be applied to mass produce MPSs. Although the previously reported microfluidic devices made of COP require solvents or adhesive tapes to assemble the COP materials, which may affect cellular phenotypes (Wan et al, 2017), the photobonding process using vacuum ultraviolet (VUV) from an excimer light source allows fabrication of the COP-based MPS without the use of additional solvents and adhesives (Yamanaka et al, 2020).…”