I-Corps: Three-dimensional nanoelectrodes for non-invasive intracellular electrophysiology

I-Corps：用于非侵入性细胞内电生理学的三维纳米电极

• 批准号: 1602438
• 负责人: Bianxiao Cui
• 金额: $ 5万
• 依托单位: Stanford University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-12-01 至 2016-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1602438&HistoricalAwards=false
• 关键词: Corps; Three; dimensional; nanoelectrodes; non

The drug development pipeline requires that potential drugs pass through a gamut of tests which demonstrate the drugs' efficacy and safety. The drug safety test starts from cellular studies before moving into animals and finally humans. As a drug moves from cellular measurements to animal measurements, the time and money involved increase dramatically. Therefore, it is essential to detect potential drug toxicity early on, preferably at the cellular level. The drug toxicity manifests mostly as non-specific binding to ion channels and therefore affecting cardiac action potentials. The current golden standard technique to detect action potential changes is patch clamps. However, the patch clamp has very low throughput and is challenging to implement, which limit the number of drug trials or drug candidates that can be screened. The proposed nanoelectrode device allows these companies to expedite testing and reduce the cost of cellular tests. In particular, nanoelectrodes can measure electrophysiology in high throughput and low toxicity and therefore allowing testers to measure more drugs with greater ease.Current drug toxicology screens inevitably involve patch clamp electrophysiology to test off-target cardiac activity. Patch clamp is technically challenging to use and has limited multiplexing capability. Over the last six years, this group has worked to develop a new nanotechnology tool for electrophysiology. The proposed tool measures intracellular recordings of mammalian cells with high throughput and low requirements on technical capability in the experimenter. Signals recorded by these nanoelectrodes are carried out from the culture under test on metal leads and amplified at an external multi-electrode array (MEA) amplifier. This team expects to have customers in both pharmaceutical toxicology and academic laboratories who are interested in pursuing electrophysiological questions. This team also believes that anyone interested in the initial screening of new drugs for their toxicological side effects would be interested in the proposed technology that could be integrated into automated cell culture systems and offers simple handling and experimentation.

药物开发管道要求潜在药物通过一系列测试，以证明药物的有效性和安全性。药物安全性测试从细胞研究开始，然后进入动物，最后进入人体。当一种药物从细胞测量转移到动物测量时，所涉及的时间和金钱急剧增加。因此，早期检测潜在的药物毒性是必要的，最好是在细胞水平。药物毒性主要表现为与离子通道的非特异性结合，从而影响心脏动作电位。目前检测动作电位变化的黄金标准技术是膜片钳。然而，膜片钳的吞吐量非常低，并且具有挑战性，这限制了可以筛选的药物试验或候选药物的数量。提议的纳米电极装置允许这些公司加快测试并降低细胞测试的成本。特别是，纳米电极可以在高通量和低毒性下测量电生理，因此允许测试人员更容易地测量更多的药物。目前的药物毒理学筛选不可避免地涉及膜片钳电生理学来测试脱靶心脏活动。膜片钳在技术上具有挑战性，并且具有有限的多路复用能力。在过去的六年里，这个小组一直致力于开发一种新的纳米技术电生理学工具。该工具测量哺乳动物细胞的细胞内记录，具有高通量和对实验人员技术能力的低要求。这些纳米电极记录的信号从金属引线上的被测培养物中进行，并在外部多电极阵列（MEA）放大器上放大。该团队希望在药物毒理学和学术实验室中都有对电生理问题感兴趣的客户。该团队还认为，任何对新药毒理学副作用的初步筛选感兴趣的人都会对拟议的技术感兴趣，该技术可以集成到自动化细胞培养系统中，并提供简单的操作和实验。