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

实验室到市场：可拉伸微电极阵列的商业化

• 批准号: 8887394
• 负责人: Oliver Graudejus
• 金额: $ 20.12万
• 依托单位: BMSEED, LLC
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-15 至 2016-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8887394
• 关键词: Adhesions; Animals; Biomechanics; Bladder; Brain; Brain Concussion; Cardiac Myocytes; Cell Culture Techniques; Cells; Cues; Deposition; Development; Devices; Drug Evaluation; Electroplating; Environment; Evaluation; Film; Funding Mechanisms; Goals; Gold; Health; Heart; In Vitro; Injury; Laboratory Research; Location; Manuals; Masks; Measurement; Mechanics; Membrane; Methods; Microelectrodes; National Institute of Neurological Disorders and Stroke; Nerve; Nervous System Trauma; Nervous system structure; Neurons; Organ; Ownership; Pattern; Peripheral Nerves; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Plant Roots; Play; Process; Production; Publishing; Regenerative Medicine; Reproducibility of Results; Research; Resolution; Role; Running; Sampling; Shadowing (Histology); Silicones; Small Business Innovation Research Grant; Smooth Muscle; Spinal Cord; Spinal cord injury; Stem cells; Stretching; System; Technology; Time; Tissue Engineering; Tissues; Traumatic Brain Injury; United States National Institutes of Health; Work; base; biomaterial compatibility; commercialization; cost; cost effective; cost effectiveness; data acquisition; elastomeric; evaporation; flexibility; improved; in vitro Model; in vivo; in vivo Model; nerve injury; operation; parallel processing; prototype; reconstruction; relating to nervous system; research and development; response; scale up; screening; spinal cord and brain injury; stem cell differentiation; tissue/cell culture; tool; treatment strategy

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.

描述（由申请人提供）：拟议的工作针对可拉伸微电极阵列（BMSEED 的 sMEA）的商业化，这是一种新工具，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连接。大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 将通过微电极与细胞一起弹性拉伸和放松来实现这一功能，从而能够 (a) 在拉伸细胞之前、期间和之后从同一位置记录和刺激电生理活动 (b) 研究重复拉伸的累积效应，随着时间的推移亚阈值损伤（例如，重复性脑震荡），以及（c）使损伤后的神经活动正常化至损伤前的水平。这些能力将极大地改进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，从而节省时间、金钱和动物的生命。 BMSEED 的 sMEA 还可以成为控制机械诱导干细胞分化为电生理活性细胞（例如神经元或心肌细胞）的有效工具，这是再生医学的主要目标。 BMSEED 的 sMEA 由带有嵌入式微电极的弹性体基板和数据采集系统的接口组成。我们之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，这项工作旨在通过改进当前的制造工艺，将该 sMEA 开发成商业产品。因此，该提案的第一个具体目标是通过流程简化和并行处理来降低 sMEA 的生产成本。我们将 (a) 评估三种沉积金膜的方法 就其成本效益和可靠性而言，（b）用荫罩图案化取代当前的光刻方法来生产微电极图案，以及（c）用自动化工艺取代电镀微电极的手动工艺。第二个具体目标是表征这些用于创伤性脑损伤研究的低成本 sMEA。我们首先将比较用三种金沉积方法生产的 sMEA：(i) 生物相容性，(ii) 功能性，(iii) 保持功能的最大应变，以及 (iv) 可以重复使用多少次。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，例如脊髓损伤和组织工程。该项目的成功完成将为生产 sMEA 提供一种经济有效的方法。 BMSEED 的长期目标是将 sMEA 的柔软且顺应性微电极的应用扩展到机械活跃（例如，靠近心脏）和非常活跃的体内神经接口。 软（例如大脑）环境。