Multi-parametric cell profiling with a CMOS quad-modality cellular interfacing array for label-free fully automated drug screening

利用 CMOS 四模态细胞接口阵列进行多参数细胞分析,实现无标记全自动药物筛选

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作者:Jong Seok Park, Sandra I Grijalva, Moez K Aziz, Taiyun Chi, Sensen Li, Michael N Sayegh, Adam Wang, Hee Cheol Cho, Hua Wang

Abstract

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.

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