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

药物开发管道要求潜在药物通过一系列测试，以证明药物的功效和安全性。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。随着药物从细胞测量转向动物测量，所涉及的时间和金钱急剧增加。因此，有必要尽早检测潜在的药物毒性，最好是在细胞水平上。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，膜片钳的通量非常低并且实施起来具有挑战性，这限制了药物试验或可以筛选的候选药物的数量。所提出的纳米电极设备使这些公司能够加快测试并降低细胞测试的成本。特别是，纳米电极可以高通量和低毒性测量电生理学，因此使测试人员能够更轻松地测量更多药物。当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。膜片钳的使用在技术上具有挑战性，并且复用能力有限。在过去六年中，该小组致力于开发一种新的电生理学纳米技术工具。所提出的工具以高通量测量哺乳动物细胞的细胞内记录，并且对实验者的技术能力要求低。这些纳米电极记录的信号是从金属引线上的待测培养物中发出的，并在外部多电极阵列 (MEA) 放大器中放大。该团队希望拥有对研究电生理学问题感兴趣的药物毒理学和学术实验室的客户。 该团队还相信，任何对新药毒理学副作用初步筛选感兴趣的人都会对所提出的技术感兴趣，该技术可以集成到自动化细胞培养系统中，并提供简单的处理和实验。

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.