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

商业化μSIM：用于屏障组织模型开发和分析的模块化平台

• 批准号: 10580031
• 负责人: James Andrew Roussie
• 金额: $ 80.08万
• 依托单位: SIMPORE, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-06 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10580031
• 关键词: Address; Agreement; Apical; Architecture; Automation; Biological Phenomena; Blood Vessels; Cell Culture Techniques; Cells; Coculture Techniques; Collaborations; Development; Devices; Disease; Drug Formulations; Electrical Resistance; Feedback; Foundations; Future; Glues; Goals; Image; Immune; In Vitro; Injections; Journals; Laboratories; Laboratory Research; Lung; Manufacturer; Marketing; Membrane; Microfluidics; Microscopy; Molds; Molecular; Names; Nanoporous; Optics; Permeability; Pharmaceutical Preparations; Phase; Play; Polymers; Porosity; Positioning Attribute; Price; Process; Production; Property; Publications; Reporting; Research; Resolution; Sales; Science; Silicon; Small Business Innovation Research Grant; Specific qualifier value; Technology; Thick; Tissue Microarray; Tissue Model; Tissues; Translating; Universities; absorption; commercialization; cost; design; fabrication; field study; fluid flow; improved; in vitro Model; light scattering; live cell imaging; live cell microscopy; manufacture; manufacturing capabilities; manufacturing test; membrane assembly; meter; microphysiology system; monolayer; nanomembrane; professor; prototype; response; success; three dimensional cell culture; tool; trafficking

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.

抽象的 该项目将商业化一个以Simpore的超薄硅为特征的细胞培养平台 - 基于膜技术可以使组织壁垒进行先进的研究。体外模型 肠道，肺和脉管系统等组织屏障对于理解基础很重要 疾病和评估药物配方达到目标时机的能力。尽管有 越来越多地使用复杂的细胞培养平台（例如3D细胞培养，微生物生理学 系统和组织芯片），这是最简单，最受欢迎的障碍研究工具 组织仍然是Corning Transwell™及其竞争对手（在此共同称为 “ Transwells™”）。这些产品的悬浮〜10 µm厚的聚合物膜产生 顶部和基本隔室，它们分离单个或共同培养 膜。尽管它们很受欢迎，但Transwells®仍不支持高分辨率显微镜 也没有提供正确研究血管屏障和免疫细胞所需的流体流动 traw cking。 Simpore的膜将被商业化为细胞培养产品 克服Transwells®的局限性，同时保留其易于使用的格式 在更复杂的组织芯片中发现的特征。 我们的I阶段项目成功地翻译了实验室手工制作的设备 詹姆斯·麦格拉思（James McGrath）教授（罗切斯特大学）的实验室，可扩展制造 在Simpore的流动。使用模块化设计，我们开发了一种开放式式式Transwell风格 结合了Simpore膜的培养单元，该膜进一步转换为带有 添加了插件流量模块。设备分配给九个合作 实验室，所有人都报告了该平台的成功。 Simpore也成功 翻译了McGrath实验室开发的双尺度微型/纳米孔 洗涤规模的制造。 我们的第二阶段项目将创建I期原型的商业可行版本 以Cytovu™品牌销售。 AIM 1将增加膜制造能力 减轻生产瓶颈和整合自动化。 AIM 2专注于自动化 Cytovu™设备组件。 AIM 3将测试一个网络中的制造设备 在开发使平台越来越多的配件的同时，协作实验室 多功能且易于使用。该项目将建立可扩展的制造能力 Cytovu™及其配件的Simpore，还将Cytovu™产品验证为 用于屏障组织体外研究的现有产品的竞争替代品。