Nanion Syncro Patch 96

描述（由申请人提供）：电可兴奋细胞（如心肌细胞、骨骼肌成肌细胞、神经元、成骨细胞）的电生理学研究对于从各种干细胞来源衍生这些细胞及其在再生医学、基础生物学研究和疾病研究中的应用至关重要。例如，只有电生理学测量可以确定是否已经产生功能性心肌细胞和神经元，因为标记物表达是必要的，但不足以建立细胞表型。这些测量需要以高速（用于改变浴溶液的短时间常数）和高通量方式进行，以提供关于大参数空间中的电池特性的真实信息。该请求是购买SyncroPatch 96（Nanion Technologies），一种用于研究单细胞电生理学特性的自动化千兆密封膜片钳（APC）系统，具有目前可用的最高通量。该核心仪器将为哥伦比亚大学两个校区的七个不同的NIH资助的实验室提供先进的技术能力，通过快速生成高质量的膜片钳数据，用于电兴奋细胞的准确药理学和生理学表征。在96孔板格式中，通过快速更换浴溶液（100 ms内），在单个细胞中快速测量全剂量响应曲线。该系统将提供哥伦比亚大学医学中心、哥伦比亚大学晨边校区或纽约大都会地区的任何其他大学目前都没有的独特能力。正如B部分中对各个研究项目的描述所述，SyncroPatch 96将大大加快我们在七个不同领域正在进行的研究：（ii）测定起搏和牵张对源自人iPS和胚胎干细胞（hESC）的心肌细胞成熟的影响，㈢筛选治疗心力衰竭细胞内钙渗漏的新药; ㈣调节电压依赖性钾通道;（v）确定关键平滑肌钾通道中的结构亚基间界面，（vi）鉴定新的遗传编码的Ca通道阻断剂，和（vii）通过源自患者的iPS细胞运动神经元（iPS-MN）的小分子筛选的肌萎缩性侧索硬化（ALS）的新疗法。初步数据收集使用SyncroPatch 96在所有五个领域的拟议研究。该设备的所有主要用户都是经验丰富的NIH PI，在细胞反应分析方面具有广泛的专业知识。我们希望整个哥伦比亚大学的研究人员和纽约市地区的合作者能够充分利用这一工具，促进合作。

DESCRIPTION (provided by applicant): Electrophysiological studies of electrically excitable cells, such as cardiac myocytes, skeletal myoblasts, neurons, osteoblasts, are critically important for the derivation of these cells from various stem cell sources and for their applicatio in regenerative medicine, fundamental biological research, and study of disease. For example, only electrophysiological measurements can determine if functional cardiomyocytes and neurons have been generated, as marker expression is necessary but not sufficient for the establishment of cell phenotype. These measurements need to be done at high speed (short time constants for changes of bath solutions) and in high-throughput fashion to provide realistic information about the cell properties in a large parameter space. This request is to purchase a SyncroPatch 96 (Nanion Technologies), an automated giga- seal patch clamp (APC) system for studies of electrophysiological properties of single cells with the highest throughput presently available. This core instrument would provide advanced technical capabilities to seven diverse NIH-funded laboratories across both campuses of Columbia University, by rapidly generating high quality patch clamp data for accurate pharmacological and physiological characterization of electrically excitable cells. Full dose response curves are rapidly measured in individual cells with a fast exchange of the bath solutions (within 100 ms), in a 96-well plate format. The system would provide unique capabilities not presently available either at the Columbia University Medical Center, the Columbia University Morningside Campus, or at any other University in the New York Metropolitan area. As detailed in the descriptions of the individual research projects in Section B, the SyncroPatch 96 would greatly accelerate our ongoing research in seven different areas: (i) High throughput screening of iPS-cardiomyocytes derived from patients carrying heritable arrhythmias, (ii) Determination of the impact of pacing and stretch on the maturation of cardiac myocytes derived from human iPS and embryonic stem cells (hESCs), (iii) Screening for novel drugs to treat intracellular calcium leak in heart failure, (iv) Modulation of voltage-dependent potassium channels; (v) Determination of the structural inter-subunit interface in a key smooth muscle potassium channel, (vi) Identification of new genetically encoded Ca channel blockers, and (vii) Novel therapies for amyotrophic lateral sclerosis (ALS) through small molecule screens of patient-derived iPS cell motor neurons (iPS-MNs). Preliminary data were collected using the SyncroPatch 96 in all five areas of proposed research. All Major Users of this equipment are seasoned NIH PIs with extensive expertise in analysis of cellular responses. We expect the instrument to be used at its full capacity, by investigators throughout the Columbia University and collaborators in the New York City area, promoting collaboration.