The Modular µSiM: A Mass Produced, Rapidly Assembled, and Reconfigurable Platform for the Study of Barrier Tissue Models In Vitro

模块化 µSiM:一种可大规模生产、快速组装和重构的平台,用于体外屏障组织模型的研究

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作者:Molly C McCloskey, Pelin Kasap, S Danial Ahmad, Shiuan-Haur Su, Kaihua Chen, Mehran Mansouri, Natalie Ramesh, Hideaki Nishihara, Yury Belyaev, Vinay V Abhyankar, Stefano Begolo, Benjamin H Singer, Kevin F Webb, Katsuo Kurabayashi, Jonathan Flax, Richard E Waugh, Britta Engelhardt, James L McGrath

Abstract

Advanced in vitro tissue chip models can reduce and replace animal experimentation and may eventually support "on-chip" clinical trials. To realize this potential, however, tissue chip platforms must be both mass-produced and reconfigurable to allow for customized design. To address these unmet needs, an extension of the µSiM (microdevice featuring a silicon-nitride membrane) platform is introduced. The modular µSiM (m-µSiM) uses mass-produced components to enable rapid assembly and reconfiguration by laboratories without knowledge of microfabrication. The utility of the m-µSiM is demonstrated by establishing an hiPSC-derived blood-brain barrier (BBB) in bioengineering and nonengineering, brain barriers focused laboratories. In situ and sampling-based assays of small molecule diffusion are developed and validated as a measure of barrier function. BBB properties show excellent interlaboratory agreement and match expectations from literature, validating the m-µSiM as a platform for barrier models and demonstrating successful dissemination of components and protocols. The ability to quickly reconfigure the m-µSiM for coculture and immune cell transmigration studies through addition of accessories and/or quick exchange of components is then demonstrated. Because the development of modified components and accessories is easily achieved, custom designs of the m-µSiM shall be accessible to any laboratory desiring a barrier-style tissue chip platform.

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