A 16384-electrode 1024-channel multimodal CMOS MEA for high-throughput intracellular action potential measurements and impedance spectroscopy in drug-screening applications
A 16384-electrode 1024-channel multimodal CMOS MEA for high-throughput intracellular action potential measurements and impedance spectroscopy in drug-screening applications
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16384 电极 1024 通道多模式 CMOS MEA，用于药物筛选应用中的高通量细胞内动作电位测量和阻抗谱
DOI：
10.1109/isscc.2018.8310385
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
N. V. Helleputte
中科院分区：
文献类型：
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作者：
C. Lopez;Hosung Chun;Laurent Berti;Shiwei Wang;J. Putzeys;Carl Van Den Bulcke;J. Weijers;A. Firrincieli;Veerle Reumers;D. Braeken;N. V. Helleputte
膜片钳是目前临床前药物发现中研究细胞电生理学的金标准。由于这是一项耗时的技术，因此已引入被动和主动多电极阵列（MEA）以增加细胞外（ExC）体外测量的通量[1-3]。然而，这些工具中的大多数不能捕获用于研究药物毒性的细胞内（InC）动作电位（AP）的基本特征。已经表明，可以通过高度局部化的电穿孔来实现InC访问[4]，其允许InC电压的低阻抗电记录。虽然在最近的设计中探索了这种技术[4-5]，但是还没有能够实现高通量InC测量的工具。阻抗测量还用于研究细胞形态、粘附、分化和收缩性[6]。最近的设计[1-3]已经包括阻抗谱（IS），但他们的方法不够快，无法详细捕获心肌细胞的收缩活动。由于一些药物可以抑制细胞跳动而不影响AP [6]，因此ExC/InC记录和阻抗测量是互补的。
Patch clamp is currently the gold standard for studying cell electrophysiology in preclinical drug discovery. Since it is a time-consuming technique, passive and active multielectrode arrays (MEAs) have been introduced for increased throughput in extracellular (ExC) in vitro measurements [1-3]. However, most of these tools cannot capture the essential features of intracellular (InC) action potentials (APs) used for studying drug toxicity. It has been shown that InC access can be achieved by highly localized electroporation [4], which allows low-impedance electrical recording of the InC voltage. While this technique was explored in recent designs [4-5], a tool that enables high-throughput InC measurements is not yet available. Impedance measurement is also used to study cell morphology, adhesion, differentiation and contractility [6]. Recent designs [1-3] already include impedance spectroscopy (IS), but their methods are not fast enough to capture in detail the contractile activity of cardiomyocytes. Since some drugs can inhibit cell beating without affecting the APs [6], ExC/InC recording and impedance measurement are complementary.