High-throughput tissue mechanics testing apparatus in an incubator environment: the prototype

这项建议的主要目标是开发一种设备，用于与可能改变组织机械表型的试剂、介体或细胞进行长期组织孵化，同时间歇性地测量这些组织的机械性能。我们之前曾与安大略省的Aurora Science合作开发了一种多单元模块化概念验证设备，我们的目标是利用我们在组织力学和组织培养研究方面的丰富经验，将其推进到全功能原型。这一设备将弥补长期细胞培养和短期整体组织研究之间的现有差距，充分利用这两个领域的优势：保持组织的表型，同时允许研究可能改变其机制的各种介质和药物的时间依赖效应。这种工具以收缩组织为目标，但适用于任何软材料，将具有基础和生物医学应用。目前的设置只测量单个肌肉组织，花费巨大的费用和精力，并且不允许组织与试剂、药物和介体的原位孵育。我们建议的系统将高通量组织测量设备(4条)放置在定制的孵化器中。我们通过将所有控制和信号调节结合到一个设备中，同时分时控制单个组织，大大降低了这个原本价值20万美元以上的系统的成本。整个系统将完全自动化，以允许在多天内进行高吞吐量、高度可重复的测试。这项NSERC CRD提案将导致安大略省奥罗拉科学公司和麦吉尔大学合作开发一种功能原型。由于其高通量优势，这一独特的设备将把基础组织研究和药物发现推向一个新时代。我们与坚定的加拿大工业合作伙伴的合作以及与加拿大肌肉力学实验室的联系将有助于加拿大在肌肉研究领域继续保持领先地位。最后，这项建议将通过向行业和不同研究领域(组织和流体力学、系统控制等)提供培训，为HQP(硕士研究生和研究助理)的培训做出贡献。

The main goal of this proposal is to develop a device to perform long term tissue incubation with agents, mediators or cells that have the potential to alter the mechanical phenotype of tissues, while intermittently measuring the mechanical properties of these tissues. We have previously developed a multi-unit and modular proof of concept device in collaboration with Ontario based Aurora Scientific, which we aim to advance to a fully functional prototype, using our extensive experience in tissue mechanics and tissue culture research. This device will bridge the existing gap between long term cell culture and short term whole tissue studies by taking the best of both fields: maintaining the phenotype of the tissue, while allowing studies on the time dependent effects of a wide range of mediators and drugs that might alter its mechanics. Targeted at contractile tissues but appropriate for any soft materials, this tool will have both fundamental and biomedical applications. Current setups measure only single muscle tissues at great expense and effort and do not allow for in-place incubation of the tissue with agents, drugs, and mediators. Our proposed system places high throughput tissue measurement equipment (4 strips) inside a custom-built incubator. We greatly reduce the cost of this otherwise $200k+ system by combining all control and signal conditioning into a single device while time-sharing control of individual tissues. The whole system will be fully automated to allow for high throughput, highly repeatable testing, over multiple days. This NSERC CRD proposal will result in the development of a functioning prototype in a collaboration between Ontario based Aurora Scientific and McGill University.This unique device will push fundamental tissue research and drug discovery into a new era due to its high throughput advantage. Our collaboration with a committed Canadian industrial partner and connections with Canadian muscle mechanics laboratories will contribute to Canada's continued leadership in muscle research. Finally, this proposal will contribute to the training of HQP (Masters student and Research Associate) by exposing them to the industry and different research fields (tissue and fluid mechanics, systems control, etc.).