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

摘要 该项目将商业化一种细胞培养平台，该平台采用辛波尔的超薄硅- 基于膜技术，以实现对组织屏障的高级研究。体外模型的建立 组织屏障，如肠道、肺和血管系统，对于理解基础很重要 用于评估药物制剂到达目标组织的能力。尽管 越来越多地使用复杂的细胞培养平台(例如，3D细胞培养、微生理学 系统和组织芯片)，这是体外研究屏障最简单和最受欢迎的工具 Tastings仍然是康宁公司的Transwell™及其竞争对手(在此统称为 “Trswells™”)。这些产品具有悬浮的~10微米厚的聚合物膜， 顶端和基底部隔间，用于分离生长在 膜。尽管Trswells®很受欢迎，但它不支持高分辨率显微镜 也不提供正确研究血管屏障和免疫细胞所需的fluidflow TraffiCking.SimPore的膜将作为细胞培养产品商业化 克服Trswells®的限制，同时保留其易于使用的格式和ff 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 McGrath教授的实验室(罗切斯特大学)可扩展的制造 现在在辛波尔工作fl。利用模块化设计，我们开发了一种井下直井式 含有SIMPOLE膜的培养单元，该膜进一步转化为flow细胞 增加了一个即插即用的flow模块。将设备分发给九个协作 所有实验室都报告了该平台的成功。辛波尔也成功地 翻译由McGrath实验室开发的双尺度微/纳米孔膜 到晶片规模的制造。 我们的第二阶段项目将创造商业上可行的第一阶段原型版本，以 以CytoVu™品牌销售。AIM 1将通过以下方式提高膜制造能力 缓解生产瓶颈，整合自动化。目标2专注于自动化 CytoVu™设备组件。AIM 3将在一个网络中测试制造的设备 协作实验室，同时开发附件，使平台日益 功能齐全，使用方便。该项目将建立可扩展的制造能力， 用于CytoVu™及其附件的SimPore，并验证CytoVu™产品是否为 现有产品的竞争性替代品，用于屏障组织的体外研究。

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.