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

Abstract

Abstract A microphysiological system (MPS) holds great promise for drug screening and toxicological testing as an alternative to animal models. However, this platform faces several challenges in terms of the materials used (e.g. polydimethylsiloxane; PDMS). For instance, absorption of drug candidates and fluorescent dyes into PDMS, as well as the effect elicited by materials on cultured cells, can cause inaccurate or misleading results in cell assays. The use of PDMS also poses challenges for mass production and long-term storage of fabricated MPSs. Hence, to circumvent these issues, herein we describe the development of a cyclo olefin polymer (COP)-based MPS using photobonding processes and vacuum ultraviolet (VUV), designated as COP-VUV-MPS. COP is an amorphous polymer with chemical/physical stability, high purity and optical clarity. Due to the thermostability and high modulus of COP, the metal molding processes was applied for mass production of MPSs without deformation of microstructures and with quick fabrication cycle time (approx. 10 min/cycle). Moreover, VUV photobonding process with an excimer light at a 172nm wavelength allowed assembling COP materials without the use of additional solvents and tapes, which might cause cell damages. In comparison with the conventional MPS made of PDMS (PDMS-MPS), COP-VUV-MPS showed improved chemical resistance without causing molecule absorption. Moreover, COP-VUV-MPS maintained the stemness of environmentally sensitive human-induced pluripotent stem cells without causing undesired cellular phenotypes or gene expression. These results suggest that COP-VUV-MPS may be broadly applicable for the advancement of MPS and applications in drug development, as well as in vitro toxicological testing.