Sophion Bioscience A/S, Copenhagen, Denmark.
North Stonington, CT, USA.
J Pharmacol Toxicol Methods. 2021 Jul-Aug;110:107072. doi: 10.1016/j.vascn.2021.107072. Epub 2021 May 5.
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.
毫无疑问，自动化膜片钳（APC）技术已经彻底改变了生物医学科学的研究方式。高通量离子通道筛选现已成为当前大多数新化学实体开发和安全性评估的一个组成部分，这些新化学实体旨在解决未满足的医疗需求。它提供的高通量显著提高了能力，克服了耗时、低通量的瓶颈，这些瓶颈是由更传统的手动膜片钳方法引起的，该方法被认为是研究离子通道功能和药理学的“金标准”。虽然提供自动化功能的系统仅在商业上可用了二十年，但通往这项新技术的道路漫长而丰富，其中包含了可以追溯到 18 世纪的开创性、实践研究。那么，这项技术目前的状况如何，未来又会是什么样子呢？在当前的文章中，我们回顾了导致 APC 系统发展的科学历史，考察了这项技术快速发展的关键驱动因素（例如离子通道计划失败以及药物诱导的 hERG 抑制和 QT 间期延长问题），突出了关键功能，最后对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提供了一些观点。
