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

项目总结/摘要 本文的工作是针对BMSEED微电极阵列拉伸技术的商业化 刺激和记录设备（MEASSuRE）技术。MEASSuRE填补了体外实验中的差距 以及通过模拟体内细胞的生物力学和电环境进行的体内研究。 控制体外环境。MEASSuRE的应用程序分为两类：生理 和细胞的病理性伸展。在生理拉伸中，细胞在其健康范围内拉伸， 在受控的体外环境中复制人体的复杂性。当机械拉伸 或者在分化过程中对人源干细胞施加电刺激， 组织比胚胎组织更接近地复制成年人的复杂性，因此（a）增加 在器官芯片模型中进行人体临床试验之前，毒性和疗效药物试验的预测价值，以及 (b)提高再生医学应用中组织移植物的质量。在病理性拉伸中，细胞 拉伸超过健康极限，造成创伤，对组织功能产生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， 神经电生理的改变分别是脑组织和脊髓的变形。 MEASSuRE在体外受控环境中再现了TBI和SCI的生物力学， 可以直接评估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性损伤的疗效。平战转换能力 通过结合BMSEED的专有弹性， 可拉伸微电极阵列（sMEA），它基于普林斯顿大学的专利技术， 独家授权给BMSEED LLC。第一阶段的目标是开发一种商业化的工艺， sMEA。第二阶段的目标是将sMEA与所需的硬件集成，以开发MEASSuRE， 一个完整、方便、高效的系统。具体而言，这项建议有三个目标。第一个具体目标是 MEASSuRE工程原型的开发和实验室测试。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。第二个具体目标是使用以下方法验证MEASSuRE的TBI应用程序： 海马组织切片。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。三个独立的实验室将评估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将对MEASSuRE进行验证， 再生医学、TBI和SCI研究应用。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.