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sMEA）的商业化，这是一种新的工具，可提供增强的能力，同时与体外细胞培养物进行机械和电气接口。脑或脊髓中神经元的机械拉伸通常是创伤性脑损伤（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sMEA将通过使微电极与细胞弹性地拉伸和松弛来实现这种能力，从而允许（a）在拉伸细胞之前、期间和之后从相同位置记录和刺激电生理活动（B）研究重复的亚阈值损伤随时间的累积效应（例如，重复性脑震荡），和（c）使损伤后神经活动正常化至损伤前水平。这些能力将极大地改善对药物和其他治疗策略的评估研究，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sMEA也可以是一种有效的工具，用于控制干细胞机械诱导分化为电生理活性细胞，如神经元或心肌细胞，这是再生医学的主要目标。BMSEED的sMEA由一个嵌入微电极的弹性基底和一个数据采集系统接口组成。我们以前的研究已经证明了sMEA原型在创伤性脑损伤研究中的能力。因此，这项拟议的工作旨在通过改进目前的制造工艺，将这种sMEA开发成商业产品。因此，该提议的第一个具体目的是通过工艺简化和并行处理来降低生产sMEA的成本。我们将（a）评估三种存款金膜的方法 关于它们的成本效益和可靠性，（B）用荫罩图案化代替当前的光刻方法来产生微电极图案，以及（c）用自动化方法代替手工方法来制造微电极。第二个具体目标是描述这些用于创伤性脑损伤研究的低成本sMEA的特征。我们将首先比较使用三种金沉积方法生产的sMEA的（i）生物相容性，（ii）功能性，（iii）保持功能的最大应变，以及（iv）可重复使用的次数。然后，我们将使用生产最高质量sMEA的工艺制造70个sMEA，并使用相同的标准评估其可重复性。这一目标的结果也将适用于其他应用，如脊髓损伤和组织工程。该项目的成功完成将为生产小型多边环境协定提供一种具有成本效益的方法。BMSEED的长期目标是将sMEA的柔软和顺应性微电极的应用扩展到机械活性（例如，心（心），非常 软（例如，大脑环境。

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.