Publications by Year: 2022

Multi-Parametric Functional Imaging of Cell Cultures and Tissues with a CMOS Microelectrode Array
Abbott, J. ; Mukherjee, A. ; Wu, W. ; Ye, T. ; Jung, H. S. ; Cheung, K. M. ; Gertner, R. S. ; Basan, M. ; Ham, D. ; Park, H. Multi-Parametric Functional Imaging of Cell Cultures and Tissues with a CMOS Microelectrode Array. Lab on a Chip 2022, 22, 1286-1296.Abstract

Electrode-based impedance and electrochemical measurements can provide cell-biology information that is difficult to obtain using optical-microscopy techniques. Such electrical methods are non-invasive, label-free, and continuous, eliminating the need for fluorescence reporters and overcoming optical imaging's throughput/temporal resolution limitations. Nonetheless, electrode-based techniques have not been heavily employed because devices typically contain few electrodes per well, resulting in noisy aggregate readouts. Complementary metal-oxide-semiconductor (CMOS) microelectrode arrays (MEAs) have sometimes been used for electrophysiological measurements with thousands of electrodes per well at sub-cellular pitches, but only basic impedance mappings of cell attachment have been performed outside of electrophysiology. Here, we report on new field-based impedance mapping and electrochemical mapping/patterning techniques to expand CMOS-MEA cell-biology applications. The methods enable accurate measurement of cell attachment, growth/wound healing, cell–cell adhesion, metabolic state, and redox properties with single-cell spatial resolution (20 μm electrode pitch). These measurements allow the quantification of adhesion and metabolic differences of cells expressing oncogenes versus wild-type controls. The multi-parametric, cell-population statistics captured by the chip-scale integrated device opens up new avenues for fully electronic high-throughput live-cell assays for phenotypic screening and drug discovery applications.

Wang, B. ; Zhao, C. ; Wang, Z. ; Yang, K. - A. ; Cheng, X. ; Liu, W. ; Yu, W. ; Lin, S. ; Zhao, Y. ; Cheung, K. M. ; et al. Wearable Aptamer-Field-Effect Transistor Sensing System for Noninvasive Cortisol Monitoring. Science Advances 2022, 8, eabk0967.Abstract
Wearable technologies for personalized monitoring require sensors that track biomarkers often present at low levels. Cortisol—a key stress biomarker—is present in sweat at low nanomolar concentrations. Previous wearable sensing systems are limited to analytes in the micromolar-millimolar ranges. To overcome this and other limitations, we developed a flexible field-effect transistor (FET) biosensor array that exploits a previously unreported cortisol aptamer coupled to nanometer-thin-film In2O3 FETs. Cortisol levels were determined via molecular recognition by aptamers where binding was transduced to electrical signals on FETs. The physiological relevance of cortisol as a stress biomarker was demonstrated by tracking salivary cortisol levels in participants in a Trier Social Stress Test and establishing correlations between cortisol in diurnal saliva and sweat samples. These correlations motivated the development and on-body validation of an aptamer-FET array–based smartwatch equipped with a custom, multichannel, self-referencing, and autonomous source measurement unit enabling seamless, real-time cortisol sweat sensing.