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

The Modular µSiM: A Mass Produced, Rapidly Assembled, and Reconfigurable Platform for the Study of Barrier Tissue Models In Vitro.
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DOI:
10.1002/adhm.202200804
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发表时间:
2022-09
影响因子:
10
通讯作者:
McGrath, James L.
McGrath, James L.
中科院分区:
工程技术1区
文献类型:
--
作者:
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.

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先进的体外组织芯片模型可以减少和取代动物实验,并可能最终支持“芯片上”的临床试验。然而,为了实现这一潜力,组织芯片平台必须同时批量生产和可重构,以允许定制设计。为了解决这些未满足的需求,引入了μSiM(具有氮化硅膜的微器件)平台的扩展。模块化μSiM (m-μSiM)使用批量生产的组件,使实验室无需微加工知识即可快速组装和重新配置。通过在生物工程和非工程脑屏障实验室中建立hipsc衍生的血脑屏障(BBB),证明了m μ sim的实用性。小分子扩散的原位和取样为基础的分析被开发和验证为屏障功能的测量。BBB的特性显示出优异的实验室间一致性和符合文献的期望,验证了m-μSiM作为屏障模型的平台,并展示了组件和协议的成功传播。通过添加附件和/或快速交换组件,演示了快速重新配置m μ sim用于共培养和免疫细胞迁移研究的能力。由于修改组件和附件的开发很容易实现,因此m μ sim的定制设计对于任何需要屏障式组织芯片平台的实验室都是可访问的。
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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