Commercializing the μSIM: A Modular Platform for the Development and Analysis of Barrier Tissue Models

摘要 该项目将商业化一个细胞培养平台， 基于膜技术，使先进的研究组织屏障。的体外模型 肠、肺和脉管系统等组织屏障对于理解 用于评估药物制剂到达靶组织的能力。尽管 复杂的细胞培养平台的日益增长的使用（例如，3D细胞培养，微生理学 系统和组织芯片），最简单和最流行的工具，在体外研究的屏障 组织仍然是Corning Transwell™及其竞争者（在本文中统称为“Corning Transwell ™”）。 “Transwells™”）。这些产品具有约10 µm厚的悬浮聚合物膜， 顶部和底部隔室，其分离生长在基底上的单培养物或共培养物。 膜。尽管它们很受欢迎，但Transwells®不支持高分辨率显微镜 也不能提供适当研究血管屏障和免疫细胞所需的体液流 跟踪SiMPore的膜将作为细胞培养产品商业化， 克服Transwells®的局限性，同时保留其易于使用的格式和操作 在更复杂的组织芯片中发现的特征。 我们的第一阶段项目成功地将用于 James麦格拉思教授（罗切斯特大学）的实验室进行可扩展的制造 现在在SiMPore工作。使用模块化设计，我们开发了一种开放式Transwell式 一个包含SiMPore膜的培养单元，它进一步转化为一个具有 增加了即插即用的流模块。设备分发给9个合作 实验室，所有这些实验室都报告了该平台的成功。SiMPore还成功地 翻译了由麦格拉思实验室开发的双尺度微/纳米多孔膜 到晶圆级制造。 我们的第二阶段项目将创建商业上可行的第一阶段原型版本， 以CytoVu™品牌销售。目标1将通过以下方式提高膜制造能力： 消除生产瓶颈并集成自动化。目标2侧重于自动化 CytoVu™器械组装件。Aim 3将在一个网络中测试制造的设备， 合作实验室，同时开发配件，使平台越来越 多功能且易于使用。该项目将建立可扩展的制造能力， CytoVu™及其附件的SiMPore，并验证CytoVu™产品作为 用于屏障组织体外研究的现有产品的竞争性替代品。

Abstract This project will commercialize a cell culture platform featuring SiMPore's ultrathin silicon- based membrane technology to enable advanced research on tissue barriers. In vitro models of tissue barriers such as the gut, lung, and vasculature are important for understanding the basis of disease and for assessing the ability of drug formulations to reach target tissues. Despite the growing use of sophisticated cell culture platforms (e.g., 3D cell culture, microphysiological systems, and tissue chips), the simplest and most popular tools for the in vitro study of barrier tissues remains the Corning Transwell™ and its competitors (collectively referred to herein as “Transwells™”). These products have a suspended ~ 10 µm thick polymer membrane creating apical and basal compartments which separate mono- or co-cultures grown on the membranes. Despite their popularity, Transwells® do not support high resolution microscopy nor provide the fluid flow needed to properly study vascular barriers and immune cell trafficking. SiMPore's membranes will be commercialized as cell culture products that overcome limitations of Transwells®, while retaining their easy to use format and offering features found in more sophisticated tissue chips. Our Phase I project successfully translated the laborious hand-made devices used in the laboratory of Professor James McGrath (University of Rochester) to a scalable fabrication workflow at SiMPore. Using a modular design, we developed an open-well Transwell-style culture unit that incorporates SiMPore's membranes, which further converts to a flow cell with the addition of a plug-and-play flow module. Devices were distributed to nine collaborating laboratories, all of whom reported success with the platform. SiMPore also successfully translated the dual-scale micro/nanoporous membranes developed by the McGrath laboratory to wafer-scale manufacturing. Our Phase II project will create commercially viable versions of Phase I prototypes to be marketed under the CytoVu™ brand. Aim 1 will increase membrane manufacturing capacity by relieving production bottlenecks and integrating automation. Aim 2 focuses on automating CytoVu™ device assembly. Aim 3 will test the manufactured devices in a network of collaborating laboratories while developing accessories that make the platform increasingly versatile and easy to use. This project will establish scalable manufacturing capacity at SiMPore for the CytoVu™ and its accessories, and also validate CytoVu™ products as competitive alternatives to incumbent products for the in vitro study of barrier tissues.