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

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

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, we introduce an extension of our μSiM (microdevice featuring a silicon-nitride membrane) platform. The modular μSiM (m-μSiM) uses mass-produced components to enable rapid assembly and reconfiguration by laboratories without knowledge of microfabrication. We demonstrate the utility of the m-μSiM by establishing an hiPSC-derived blood-brain barrier (BBB) in bioengineering and non-engineering, brain barriers focused laboratories. We develop and validate in situ and sampling-based assays of small molecule diffusion 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. We then demonstrate the ability to quickly reconfigure the m-μSiM for co-culture and immune cell transmigration studies through addition of accessories and/or quick exchange of components. Because the development of modified components and accessories is easily achieved, custom designs of the m-μSiM should be accessible to any laboratory desiring a barrier-style tissue chip platform.

• Journal Article Type: Article
• Acceptance Date: Apr 8, 2022
• Online Publication Date: Jul 28, 2022
• Publication Date: Sep 21, 2022
• Deposit Date: Feb 5, 2024
• Publicly Available Date: Feb 5, 2024
• Journal: Advanced Healthcare Materials
• Print ISSN: 2192-2640
• Electronic ISSN: 2192-2659
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 11
• Issue: 18
• Article Number: 2200804
• DOI: https://doi.org/10.1002/adhm.202200804
• Keywords: membranes, blood-brain barrier, modular, vascular barriers, tissue chips
• Public URL: https://nottingham-repository.worktribe.com/output/10071081
• Publisher URL: https://onlinelibrary.wiley.com/doi/10.1002/adhm.202200804
• Additional Information: This is the peer reviewed version of the following article: M. C. McCloskey, P. Kasap, S. D. Ahmad, S.-H. Su, K. Chen, M. Mansouri, N. Ramesh, H. Nishihara, Y. Belyaev, V. V. Abhyankar, S. Begolo, B. H. Singer, K. F. Webb, K. Kurabayashi, J. Flax, R. E. Waugh, B. Engelhardt, J. L. McGrath, The Modular µSiM: A Mass Produced, Rapidly Assembled, and Reconfigurable Platform for the Study of Barrier Tissue Models In Vitro. Adv. Healthcare Mater. 2022, 11, 2200804., which has been published in final form at https://doi.org/10.1002/adhm.202200804 The article must be linked to Wiley’s version of record on Wiley Online Library