Lab-To-Marketplace: Commercialization of a stretchable microelectrode array

项目摘要/摘要 建议的工作是针对BMSEED的微电极阵列拉伸的商业化 刺激和记录设备(MEASSuRE)技术。MEASSuRE在体外实验中弥合了 通过模拟体内细胞的生物力学和电学环境进行体内研究 受控的体外环境。MEASSuRE的应用分为两类：生理学 细胞的病理性伸展。在生理伸展中，细胞在其健康范围内伸展， 在受控的体外环境中复制人体的复杂性。当机械拉伸时 或在分化过程中对人类来源的干细胞施加电刺激，所产生的器官或 组织比胚胎组织更接近复制成人的复杂性，因此(A)增加了 芯片器官模型中人体临床试验前毒性和有效性药物测试的预测价值，以及 (B)提高再生医学应用中组织移植的质量。在病理性拉伸中，细胞 超过健康极限，造成创伤，对组织功能造成负面影响或导致细胞 死亡。在创伤性脑损伤(TBI)和脊髓损伤(SCI)中，脊髓损伤的主要生物力学机制 神经电生理的改变分别是脑组织和脊髓的变形。 MEASSuRE在体外可控环境下再现了颅脑损伤和脊髓损伤的生物力学，并对损伤进行了分析 可以直接评估被拉伸的神经元的水平。因此，MEASSuRE可以成为一个筛选平台 评估药物和其他治疗策略对神经创伤的疗效。具备以下功能 通过弹性地结合BMSEED的专有技术，实现了与电池的机械和电气接口 可伸缩微电极阵列(SMEA)，基于普林斯顿大学和 独家授权给BMSEED有限责任公司。第一阶段的目标是开发一种商业工艺来制造 中东和中东和非洲。第二阶段的目标是将sMEA与开发MEASSuRE AS所需的硬件集成在一起 一个完整、方便、高效的系统。具体地说，这项提议有三个目标。第一个具体目标是 MEASSuRE工程样机的研制和台架试验。这一目标的重点是确保 MEASSuRE原型中的组件可以顺利地协同工作。这项工作将在 BMSEED实验室。第二个具体目标是验证MEASSuRE是否适用于使用 海马区组织切片。MEASSuRE的性能将得到验证，并与行业进行比较 哥伦比亚大学莫里森神经创伤和修复实验室的标准。第三个具体目标是 进行MEASSuRE的产品原型测试。三个独立实验室将评估MEASSuRE 用于不同的应用：(1)细胞培养的TBI研究，(2)使用心肌细胞的再生医学， (3)组织切片SCI研究。在第二阶段结束时，BMSEED将针对以下方面验证MEASSuRE 再生医学、脑损伤和脊髓损伤的研究应用。MEASSuRE将为市场做好准备。

Project Summary/Abstract The proposed work is directed at the commercialization of BMSEED's Micro-Electrode Array Stretching Stimulating und Recording Equipment (MEASSuRE) technology. MEASSuRE bridges the gap between in vitro and in vivo research by simulating the biomechanical and electrical environment of cells in the body in a controlled environment outside of the body. The applications for MEASSuRE fall in two categories: physiological and pathological stretch of cells. In physiological stretch, the cells are stretched within their healthy limits, replicating the complexity of the human body in a controlled in vitro environment. When mechanical stretching or electrical stimulation is applied to human derived stem cells during differentiation, the resulting organs or tissue more closely replicate the complexity of the adult human than the embryonic one, thus (a) increasing the predictive value of toxicity and efficacy drug tests prior to human clinical trials in Organ-on-a-Chip models, and (b) improving the quality of tissue grafts in regenerative medicine applications. In pathological stretch, the cells are stretched beyond the healthy limit, causing a trauma that negatively impacts tissue function or leads to cell death. In traumatic brain injury (TBI) and spinal cord jury (SCI), the primary biomechanical mechanism for the alteration of neural electrophysiology is the deformation of the brain tissue and spinal cord, respectively. MEASSuRE reproduces the biomechanics of a TBI and SCI in a controlled environment in vitro, and the injury level of the stretched neurons can be directly assessed. MEASSuRE could therefore be a screening platform to assess the efficacy of drugs and other treatment strategies for neurotraumatic injuries. The capabilities to mechanically and electrically interface with cells are enabled by incorporating BMSEED's proprietary elastically stretchable microelectrode array (sMEA), which is based on technology patented by Princeton University and exclusively licensed to BMSEED LLC. The goal for Phase I was to develop a commercial process to fabricate the sMEA. The goal of Phase II is to integrate the sMEA with the required hardware to develop MEASSuRE as a complete, convenient, and efficient system. Specifically, this proposal has three aims. The first specific aim is the development and bench-testing of an engineering prototype of MEASSuRE. The focus of this aim is to ensure the components in the MEASSuRE prototype work together smoothly. This work will be carried out in the BMSEED laboratory. The second specific aim is the validation of MEASSuRE for the TBI application using hippocampal tissue slices. The performance of MEASSuRE will be validated and compared against industry standards at the Morrison Neurotrauma and Repair Laboratory at Columbia University. The third specific aim is to conduct product prototype testing of MEASSuRE. Three independent laboratories will evaluate MEASSuRE for different applications: (1) TBI research with cell cultures, (2) regenerative medicine using cardiomyocytes, and (3) SCI research with tissue slices. At the end of Phase II, BMSEED will have validated MEASSuRE for regenerative medicine, TBI and SCI research applications. MEASSuRE will be ready for the marketplace.