EAGER/Collaborative Research: High-throughput, Autonomous Real-time Monitoring of Tissue Mechanical Property Change via Impedimetric Sensor Arrays

EAGER/协作研究：通过阻抗传感器阵列高通量、自主实时监测组织机械性能变化

• 批准号: 2141008
• 负责人: Blake Johnson
• 金额: $ 17.48万
• 依托单位: Virginia Polytechnic Institute and State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2141008&HistoricalAwards=false
• 关键词: EAGER; Collaborative; Research; throughput; Autonomous

This EArly-concept Grant for Exploratory Research (EAGER) will support research to improve engineered tissues. Engineered tissues have become important platforms for the development of therapeutics for many diseases and disorders. They hold particular promise for improving wound healing. Cells sense and respond their environment. How they sense their environment effects how they form tissues. How a cell's local environment affects it's behavior during wound healing is still not well understood. There have been substantial strides that have been made in the use of engineered tissues for disease modeling and drug development. However, simultaneously monitoring cellular behavior and tissue properties remains a challenge, and limits further advances. This project will create autonomous tissue culture monitoring platforms that enable real-time monitoring of multi-scale cellular behavior and tissue properties. If successful, scalable and high-throughput methods for autonomous monitoring of engineered tissues will be realized. This could have profound and broad socioeconomic benefits in terms of public health and drug discovery. The project will engage students through research experiences for undergraduates in data acquisition for autonomous life sciences research. The goal of this project is to advance the ability to simultaneously quantify the dynamic multi-scale attributes of engineered tissues in real time. The central approach is to establish the feasibility of a novel autonomous sensor-based experimental platform for dynamically quantifying bulk extracellular matrix (ECM) mechanical properties, multi-cellular anatomical structures, cell phenotypes, and gene and protein expression during wound healing processes using sensor-integrated 3D cell culture models. The work involves the following research objectives: 1) to utilize a cantilever sensor-integrated well plate format for autonomous monitoring of a fibroblast-Schwann cell 3D co-culture model treated with exogenous transforming growth factor (TGF-β) to invoke a wound healing response, and 2) to compare real-time changes in bulk ECM mechanical properties with temporal changes in gene and protein expression levels in 3D co-culture models. This work will yield the first quantitative description of the dynamic relationship between real-time ECM mechanical changes and cell behaviors in tissues undergoing wound healing. The project also provides research experiences for undergraduate students in data acquisition for autonomous tissue characterization and bioprocess monitoring.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

这项早期概念探索性研究资助 (EAGER) 将支持改善工程组织的研究。工程组织已成为开发许多疾病和病症的治疗方法的重要平台，它们在改善细胞感知和反应方面具有特殊的前景。它们如何感知环境影响它们形成组织的方式。细胞的局部环境如何影响其在伤口愈合过程中的行为，在使用工程组织进行疾病建模和药物方面已经取得了实质性进展。然而，同时监测细胞行为和组织特性仍然是一个挑战，并且限制了该项目的进一步发展，该平台将能够实时监测多尺度细胞行为和组织特性。该项目将实现工程组织自主监测的高通量方法，这可能会在公共卫生和药物发现方面产生深远而广泛的社会经济效益。该项目的目标是提高同时实时量化工程组织的动态多尺度属性是建立一种新型的基于自主传感器的实验平台的可行性，用于动态量化大量细胞外基质（ECM）机械特性、多细胞解剖结构、细胞。使用集成传感器的 3D 细胞培养模型研究伤口愈合过程中的表型、基因和蛋白质表达。这项工作涉及以下研究目标：1) 利用悬臂传感器集成孔板形式进行自主监测。成纤维细胞-雪旺细胞 3D 共培养模型，经外源转化生长因子 (TGF-β) 处理以引发伤口愈合反应，2) 将整体 ECM 机械特性的实时变化与基因和蛋白质表达水平的时间变化进行比较这项工作将首次定量描述实时 ECM 机械变化与正在进行伤口愈合的组织中的细胞行为之间的动态关系，该项目还为本科生提供自主组织数据采集的研究经验。表征和该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。