I-Corps: Technological Assessment of Artificial Membrane-based Ion Channel Screening

I-Corps：基于人工膜的离子通道筛选技术评估

• 批准号: 1158726
• 负责人: Jacob Schmidt
• 金额: $ 5万
• 依托单位: University of California-Los Angeles
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-10-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1158726&HistoricalAwards=false
• 关键词: Corps; Technological; Assessment; Artificial; Membrane

Electrophysiological measurement of ion channels is difficult because the ion channel needs to reside in a lipid bilayer membrane for determination of its conductance. The PI's group has developed an artificial lipid bilayer membrane formation technology that enables inexpensive cell-free measurement of ion channels on inexpensive low-tech plastic consumable plates. The proposed innovation is able to measure ion channels from any cell type or source including primary cells and subcellular organelles. Ion channel measurements have already been validated with measurements of conductance modulation of physiologically relevant ion channels by known active pharmaceutical compounds. The proposed work concerns development of a 48 well array plate for this measurement compatible with solution exchange, which would allow rapid parallel screening of ion channels against potential pharmaceutical interactions, and the demonstration of the parallel processing and measurement of membrane arrays by automated instrumentation. Prospective end users of the technology will be queried regarding their willingness to try ion channel screening in a cell-free system, what features would be necessary for that to happen, and attractiveness of unique features of the proposed technology.Ion channels play key roles in cardiac and neural activity and their disorders have been implicated in epilepsy and cystic fibrosis and a number of other diseases. Because of their central importance, ion channels are critical drug targets - 15 of the top 100 selling drugs are ion channel modulators with a combined market value of $15 billion. Automated Patch Clamp (APC) is the state of the art technology for electrophysiological screening of ion channel activity in cells for drug discovery and safety screening. However, it is well recognized to suffer from low throughput, expensive consumables, and compatibility with limited cell types, and these shortcomings limit the number and scope of drug discovery studies. The proposed cellfree technology has the potential to address all of these shortcomings, thus allowing drugs to be discovered and produced more efficiently and for lower cost, enabling more and better drugs to be produced. The ease of use and low cost of the proposed technology also has the potential to positively affect scientific research and smaller scale laboratory studies of ion channels.

离子通道的电生理测量是困难的，因为离子通道需要驻留在脂质双层膜中以测定其电导。PI的团队开发了一种人工脂质双层膜形成技术，该技术能够在廉价的低技术塑料消耗板上进行离子通道的廉价无细胞测量。所提出的创新能够测量来自任何细胞类型或来源的离子通道，包括原代细胞和亚细胞器。离子通道测量已经通过测量已知活性药物化合物对生理相关离子通道的电导调节而得到验证。拟议的工作涉及开发一个48孔阵列板，用于与溶液交换兼容的测量，这将允许快速并行筛选离子通道对潜在的药物相互作用，并通过自动化仪器演示膜阵列的并行处理和测量。该技术的潜在最终用户将询问他们是否愿意尝试在无细胞系统中进行离子通道筛选，需要哪些功能才能实现，以及拟议技术的独特功能的吸引力。离子通道在心脏和神经活动中起着关键作用，其紊乱与癫痫和囊性纤维化以及许多其他疾病有关。由于其核心重要性，离子通道是关键的药物靶点-前100种销售药物中有15种是离子通道调节剂，总市值为150亿美元。自动膜片钳（APC）是用于药物发现和安全性筛选的细胞中离子通道活性的电生理学筛选的最先进技术。然而，众所周知，其具有低通量、昂贵的消耗品以及与有限细胞类型的相容性，并且这些缺点限制了药物发现研究的数量和范围。拟议的无细胞技术有可能解决所有这些缺点，从而使药物能够更有效地发现和生产，并降低成本，从而能够生产更多更好的药物。所提出的技术的易用性和低成本也有可能对离子通道的科学研究和小规模实验室研究产生积极影响。