Super-Resolution Electrochemical Impedance Imaging with a 100 × 100 CMOS Sensor Array

Abstract

This paper presents a 100 × 100 super-resolution integrated sensor array for microscale electrochemical impedance spectroscopy (EIS) imaging. The system is implemented in 180 nm CMOS with 10μm × 10μm pixels. Rather than treating each electrode independently, the sensor is designed to measure the mutual capacitance between programmable sets of pixels. Multiple spatially-resolved measurements can then be computationally combined to produce super-resolution impedance images. Experimental measurements of sub-cellular permittivity distributions within single algae cells demonstrate the potential of this new approach.

Multi-parametric functional imaging of cell cultures and tissues with a CMOS microelectrode array

“…S2 and ESI † Discussion 1 for the impedance model and calculation). Our technique extends previous CMOS IC-based proximity capacitive measurements at high frequency (≫1 MHz): [32][33][34] the grounding of all electrodes (not just nearest neighbors) creates arcing field lines terminating across the electrode array (e.g., Fig. S2a †).…”

“…Here, we demonstrate high-resolution, high-throughput functional imaging of live-cell cultures via in situ impedance and electrochemical measurements using complementary metal-oxide-semiconductor (CMOS) microelectrode arrays (MEAs). [22][23][24][25][26][27][28][29][30][31][32][33][34] We show that CMOS-MEAs allow label-free and non-invasive (non-destructive) tracking of cell growth dynamics and accurate measurements of cell-substrate/cellcell adhesion and metabolic state. The 64 × 64 = 4096 electrode array's 20 μm electrode pitch, covering a total area of 1.3 × 1.3 mm 2 , enables electrical 'imaging' as well as measurement of cell population statisticsa feature not accomplished by whole-well readouts.…”

“…We described the details of these circuit configurations in a previous publication 43 with respect to electrophysiological recording of neurons, a separate application of the device. 29,30 The uniqueness of our CMOS-MEA lies in the high channel count (4096) and high spatial resolution (20 μm) that enables single-cell-resolution imaging as well as parallel current and open-circuit potential measurements, thus differing from previous MEA devices that measured high-frequency (≫1 MHz) electrode capacitance, 23,[32][33][34] voltage (with high-pass filters to block DC signals), [24][25][26][27] current with a small number of channels (<32), [24][25][26]31 or electrochemical devices with large electrode pitches (100 μm). 31 For the cell-substrate and transepithelial impedance measurements, we configure the operational amplifiers into a transimpedance amplifier configuration to measure the electrodes current with a gain of 94 MΩ and a bandwidth of 30 kHz (Fig.…”