Use of automated patch clamp in cardiac safety assessment: past, present and future perspectives
Use of automated patch clamp in cardiac safety assessment: past, present and future perspectives
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DOI：
10.1016/j.vascn.2021.107072
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发表时间：
2021-05-10
影响因子：
1.9
通讯作者：
Fermini, Bernard
中科院分区：
文献类型：
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作者：
Bell, Damian C.;Fermini, Bernard
毫无疑问，自动膜片钳（APC）技术已经彻底改变了生物医学科学的研究。高通量离子通道筛选现在是目前开发的大多数新化学实体的开发和安全性分析的组成部分，以解决未满足的医疗需求。它提供的增加的通量显著提高了克服更传统的手动膜片钳方法所导致的耗时、低通量瓶颈的能力，该方法被认为是研究离子通道功能和药理学的“金标准”。虽然提供豪华自动化的系统才商用了二十年，但通向这项新技术的道路是漫长的，并且有丰富的开创性、实践性研究，其历史可以追溯到18世纪。那么，这项技术目前处于什么位置，未来会是什么样子？在本文中，我们回顾了导致APC系统发展的科学历史，研究了该技术快速发展的关键驱动因素（例如失败的离子通道计划以及药物诱导的hERG抑制和QT间期延长问题），强调了关键功能，并最终提供了该技术对心脏安全性评估和生物医学科学的当前和未来影响的一些观点。
There is no doubt that automated patch clamp (APC) technology has revolutionized research in biomedical science. High throughput ion channel screening is now an integral part of the development and safety profiling of the majority of new chemical entities currently developed to address unmet medical needs. The increased throughput it provides has significantly improved the ability to overcome the time-consuming, low throughput bottlenecks resulting from the more conventional manual patch clamp method, considered the 'gold standard', for studying ion channel function and pharmacology. While systems offering the luxury of automation have only been commercially available for two decades, the road leading to this new technology is long and rich in seminal, hands-on, studies dating back as far as the 18th century. So where does this technology currently stand, and what will it look like in the future? In the current article, we review the scientific history leading to the development of APC systems, examine key drivers in the rapid development of this technology (such as failed ion channel programmes and the issue of drug-induced hERG inhibition and QT interval prolongation), highlight key capabilities and finally provide some perspective on the current and future impact of the technology on cardiac safety assessment and biomedical science.