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

基本信息

批准号：
10385120
负责人：
James Andrew Roussie
金额：
$ 89.37万
依托单位：
SIMPORE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-06 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10385120
关键词：
Address 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 Name Membrane Microfluidics Microscopy Molds Molecular Names Nanoporous Optics Permeability Pharmaceutical Preparations Phase Play Polymers Positioning Attribute Price Process Production Property Publications Reporting Research Resolution Sales Science Silicon Small Business Innovation Research Grant Specific qualifier value Technology Testing Thick Tissue Microarray Tissue Model Tissues Translating Universities absorption base cost design field study fluid flow improved in vitro Model light scattering live cell imaging live cell microscopy microphysiology system monolayer nanomembrane professor prototype response success three dimensional cell culture tool trafficking

项目摘要

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.

抽象的该项目将使采用 SiMPore 超薄硅的细胞培养平台商业化基于膜技术的组织屏障体外模型的高级研究。肠道、肺和脉管系统等组织是理解基础的重要障碍尽管存在疾病并评估药物制剂到达靶组织的能力。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），是体外屏障研究最简单和最流行的工具组织仍然是 Corning Transwell™ 及其竞争对手（本文统称为 “Transwells™”）。这些产品具有约 10 µm 厚的悬浮聚合物膜。顶端和基底隔室将生长在单一培养物或共培养物上的分开尽管 Transwells® 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液体流动 SiMPore 的膜将作为细胞培养产品进行商业化。克服 Transwells® 的局限性，同时保留其易于使用的格式和产品更复杂的组织芯片中发现的特征。我们的一期项目成功地将传统工艺中使用的费力的手工设备转化为 James McGrath 教授（罗切斯特大学）实验室的可扩展制造 SiMPore 的工作流程采用模块化设计，我们开发了开放孔 Transwell 式。包含 SiMPore 膜的培养单元，可进一步转换为流动池添加了即插即用流程模块，并将设备分配给九个协作者。实验室，所有这些实验室都报告了该平台的成功。翻译了McGrath实验室开发的双尺度微/纳米孔膜到晶圆级制造。我们的第二阶段项目将创建第一阶段原型的商业可行版本以 CytoVu™ 品牌销售的 Aim 1 将提高膜制造能力缓解生产瓶颈并集成自动化目标 2 侧重于自动化。 CytoVu™ 设备组装将在网络中测试制造的设备。合作实验室，同时开发配件，使该平台越来越受欢迎该项目将建立可扩展的制造能力，用途广泛且易于使用。 SiMPore 适用于 CytoVu™ 及其配件，并且还将 CytoVu™ 产品验证为用于屏障组织体外研究的现有产品的竞争性替代品。