The School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA 30308, USA.
Lab Chip. 2018 Sep 26;18(19):3037-3050. doi: 10.1039/c8lc00156a.
Cells are complex systems with concurrent multi-physical responses, and cell physiological signals are often encoded with spatiotemporal dynamics and further coupled with multiple cellular activities. However, most existing electronic sensors are only single-modality and cannot capture multi-parametric cellular responses. In this paper, a 1024-pixel CMOS quad-modality cellular interfacing array that enables multi-parametric cell profiling for drug development is presented. The quad-modality CMOS array features cellular impedance characterization, optical detection, extracellular potential recording, and biphasic current stimulation. The fibroblast transparency and surface adhesion are jointly monitored by cellular impedance and optical sensing modalities for comprehensive cell growth evaluation. Simultaneous current stimulation and opto-mechanical monitoring based on cardiomyocytes are demonstrated without any stimulation/sensing dead-zone. Furthermore, drug dose-dependent multi-parametric feature extractions in cardiomyocytes from their extracellular potentials and opto-mechanical signals are presented. The CMOS array demonstrates great potential for fully automated drug screening and drug safety assessments, which may substantially reduce the drug screening time and cost in future new drug development.
细胞是具有并发多物理响应的复杂系统，细胞生理信号通常以时空动态进行编码，并进一步与多种细胞活动相耦合。然而，大多数现有的电子传感器都是单模态的，无法捕捉多参数的细胞响应。本文提出了一种 1024 像素的 CMOS 四模态细胞接口阵列，可用于药物开发的多参数细胞分析。该四模态 CMOS 阵列具有细胞阻抗特性分析、光学检测、细胞外电势记录和双相电流刺激功能。细胞阻抗和光学传感模态共同监测成纤维细胞的透明度和表面附着力，以全面评估细胞生长。基于心肌细胞的同时电流刺激和光电机械监测演示了没有任何刺激/传感死区的情况。此外，还从细胞外电势和光电机械信号中呈现了心肌细胞的药物剂量依赖性多参数特征提取。该 CMOS 阵列在全自动药物筛选和药物安全评估方面具有巨大的潜力，这可能会大大缩短未来新药开发中的药物筛选时间和成本。
