Nanion Syncro Patch 96

Nanion 同步补丁 96

• 批准号: 8334952
• 负责人: ROBERT S KASS
• 金额: $ 91.39万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-20 至 2013-07-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8334952
• 关键词: Academic Medical Centers; Amyotrophic Lateral Sclerosis; Area; Arrhythmia; Bathing; Calcium; Cardiac Myocytes; Cells; Collaborations; Data; Derivation procedure; Disease; Dose; Equipment; Funding; Heart failure; Human; Individual; Laboratories; Measurement; Measures; Motor Neurons; Neurons; New York; New York City; Osteoblasts; Patients; Pharmaceutical Preparations; Phenotype; Physiological; Potassium Channel; Property; Regenerative Medicine; Research; Research Personnel; Research Project Grants; Screening procedure; Seasons; Skeletal Myoblasts; Smooth Muscle; Solutions; Source; Speed; Stem cells; Stretching; System; Technology; Time; United States National Institutes of Health; Universities; biological research; channel blockers; embryonic stem cell; high throughput screening; induced pluripotent stem cell; instrument; metropolitan; novel; patch clamp; research study; response; seal; small molecule; voltage

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.

描述（由申请人提供）：可电兴奋细胞（例如心肌细胞、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，只有电生理学测量才能确定是否已生成功能性心肌细胞和神经元，因为标记物表达是必要的，但对于细胞表型的建立来说还不够。这些测量需要以高速（浴液变化的短时间常数）和高通量方式完成，以提供有关大参数空间中细胞特性的真实信息。该请求是购买 SyncroPatch 96（Nanion Technologies），这是一种自动千兆密封膜片钳（APC）系统，用于研究单细胞的电生理特性，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，快速生成高质量的膜片钳数据，以准确地表征可电兴奋细胞的药理学和生理学特征。在 96 孔板中，通过快速更换浴液（100 毫秒内），可以快速测量单个细胞的完整剂量反应曲线。该系统将提供目前哥伦比亚大学医学中心、哥伦比亚大学莫宁赛德校区或纽约都会区任何其他大学所不具备的独特功能。正如 B 节中各个研究项目的详细描述，SyncroPatch 96 将极大地加速我们在七个不同领域正在进行的研究：(i) 对来自携带遗传性心律失常的患者的 iPS 心肌细胞进行高通量筛选，(ii) 确定起搏和拉伸对来自人类 iPS 和胚胎干细胞 (hESC) 的心肌细胞成熟的影响， (iii) 筛选治疗心力衰竭细胞内钙渗漏的新药，(iv) 电压依赖性钾通道的调节； (v) 确定关键平滑肌钾通道中的结构亚基间界面，(vi) 鉴定新的基因编码 Ca2+ 通道阻滞剂，以及 (vii) 通过患者来源的 iPS 细胞运动神经元 (iPS-MN) 的小分子筛选来治疗肌萎缩侧索硬化症 (ALS)。使用 SyncroPatch 96 在拟议研究的所有五个领域收集了初步数据。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拥有丰富的专业知识。我们希望哥伦比亚大学的研究人员和纽约地区的合作者充分利用该工具，促进合作。