Microfluidic microphysiological systems (MPSs) or “organs-on-a-chip” are a promising alternative to animal models for drug screening and toxicology tests. However, most microfluidic devices employ polydimethylsiloxane (PDMS) as the structural material; and this has several drawbacks. Cyclo-olefin polymers (COPs) are more advantageous than PDMS and other thermoplastic materials because of their low drug absorption and autofluorescence. However, most COP-based microfluidic devices are fabricated by solvent bonding of the constituent parts. Notably, the remnant solvent can affect the cultured cells. This study employed a photobonding process with vacuum ultraviolet (VUV) light to fabricate microfluidic devices without using any solvent and compared their performance with that of solvent-bonded systems (using cyclohexane, dichloromethane, or toluene as the solvent) to investigate the effects of residual solvent on cell cultures. Quantitative immunofluorescence assays indicated that the coating efficiencies of extracellular matrix proteins (e.g., Matrigel and collagen I) were lower in solvent-bonded COP devices than those in VUV-bonded devices. Furthermore, the cytotoxicity of the systems was evaluated using SH-SY5Y neuroblastoma cells, and increased apoptosis was observed in the solvent-processed devices. These results provide insights into the effects of solvents used during the fabrication of microfluidic devices and can help prevent undesirable reactions and establish good manufacturing practices.
Microphysiological systems (MPSs) have shown great promise for the advancement of drug discovery and toxicological tests, and as an alternative to animal models. However, although several chips and systems have been reported, some important issues are yet to be addressed, such as the use of polydimethylsiloxane (PDMS). Cyclo olefin polymers (COPs) have advantages over other thermoplastic materials, but most COP-based MPSs use solvent bonding during fabrication, which can affect any cells they are used to culture. This study uses a photobonding process with vacuum ultraviolet (UVU) to produce MPSs without the need for solvents such as cyclohexane, dichloromethane, and toluene. This is then used for comparison to investigate the effects of solvents on cell cultures. Quantitative immunofluorescent assays show that the coating efficiencies of extracellular matrix proteins, such as Matrigel and collagen I, are reduced on solvent-treated COP surfaces, compared with those prepared using VUV photobonding. Furthermore, SH-SY5Y neuroblastoma cells are used to evaluate cytotoxicity. This shows that solvent-MPSs induce apoptosis, but VUV-MPSs do not. These results provide insights into solvent bonding for MPS fabrication so that undesirable reactions can be avoided. Moreover, this work may be used to standardize MPS protocols and establish good manufacturing practices.
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