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

描述（由申请人提供）：拟议的工作是针对可拉伸微电极阵列（BMSEED的sma）的商业化，这是一种新工具，提供了增强的能力，可以同时与体外细胞培养物进行机械和电连接。脑或脊髓神经元的机械拉伸往往是创伤性脑损伤（TBI）和脊髓损伤（SCI）的根本原因。机械应变也是干细胞分化的重要线索。目前，TBI、SCI或组织工程的体外模型不可能在拉伸细胞的同时进行电生理测量。BMSEED的sMEAs将通过具有弹性拉伸和放松细胞的微电极来实现这一功能，允许(a)在拉伸细胞之前，期间和之后记录和刺激同一位置的电生理活动(b)调查随着时间的推移重复，亚阈值损伤（例如，重复性脑震荡）的累积效应，以及(c)将损伤后的神经活动正常化到损伤前的水平。这些能力将极大地改善药物评估和其他治疗策略的研究，以尽量减少受伤后对神经系统的损害，节省时间、金钱和动物的生命。BMSEED的sma也可以成为一种有效的工具，用于控制机械诱导的干细胞分化为电生理活跃细胞，如神经元或心肌细胞，这是再生医学的主要目标。BMSEED的sma由嵌入微电极的弹性衬底和数据采集系统的接口组成。我们之前的研究已经证明了sma原型在创伤性脑损伤研究中的能力。因此，本工作旨在通过改进当前的制造工艺，将该sma开发成商业产品。因此，这项建议的第一个具体目标是通过简化程序和并行处理来减少生产中小企业环境评估的费用。我们将(a)评估三种沉积金膜的方法

DESCRIPTION (provided by applicant): The proposed work is directed at the commercialization of a stretchable microelectrode array (BMSEED's sMEA), a new tool that provides enhanced capabilities to simultaneously interface mechanically and electrically with cell cultures in vitro. The mechanical stretching of neurons in the brain or spinal cord is often te root cause of traumatic brain injury (TBI) and spinal cord injury (SCI). Mechanical strain is also an important cue for the differentiation of stem cells. It is currently not possible for in vitro models of TBI, SCI, or tissue engineering to carry out electrophysiological measurements while stretching the cells. BMSEED's sMEAs will enable this capability by having microelectrodes that stretch and relax elastically with the cells, allowing to (a) record and stimulate electrophysiological activity from the same location before, during, and after stretching the cells (b) investigate the cumulative effects of repeated, sub-threshold injuries over time (e.g., repetitive concussions), and (c) normalize post-injury neural activity to pre-injury levels. These capabilities will greatly improve research on the evaluation of drugs and other treatment strategies to minimize the damage to the nervous system after an injury, saving time, money and lives of animals. BMSEED's sMEA could also be an effective tool for controlling the mechanically-induced differentiation of stem cells into electrophysiologically active cells, such a neurons or cardiomyocytes, which is a major goal of regenerative medicine. BMSEED's sMEA consists of an elastomeric substrate with embedded microelectrodes, and an interface to the data acquisition system. Our previous research has demonstrated the capabilities of sMEA prototypes in traumatic brain injury research. Therefore, this proposed work aims to develop this sMEA into a commercial product by improving the current fabrication process. The first specific aim of this proposal is therefore to reduce the cost to produce sMEA through process simplification and parallel processing. We will (a) evaluate three methods to deposit the gold film with respect to their cost-effectiveness and reliability, (b) replace the current lithographic methd to produce the microelectrode pattern with shadow mask patterning, and (c) replace the manual process to electroplate the microelectrodes with an automated one. The second specific aim is to characterize these low- cost sMEAs for traumatic brain injury research. We will first compare sMEAs produced with the three gold deposition methods for (i) their biocompatibility, (ii) their functionality, (iii) the maximum strain at which they remain functional, and (iv) how many times they can be re-used. We will then fabricate 70 sMEAs with the process that produces the highest quality sMEAs, and assess their repeatability using the same criteria. The results of this aim will also apply to other applications such as spinal cord injury and tissue engineering. The successful completion of this project will provide a cost-effective method to produce sMEAs. The long- term goal of BMSEED is to extend the application of the sMEAs' soft and compliant microelectrodes to in vivo neural interfaces in mechanically active (e.g., near the heart) and very soft (e.g., the brain) environment.