A CMOS 21 952-Pixel Multi-Modal Cell-Based Biosensor with Four-Point Impedance Sensing for Holistic Cellular Characterization

Doohwan Jung, Gregory V. Junek, Jong Seok Park, Sagar R. Kumashi, Adam Wang, Sensen Li, Sandra Ivonne Grijalva, Natasha Fernandez, Hee Cheol Cho, Hua Wang

Research output: Contribution to journalArticlepeer-review

Abstract

This article presents a fully integrated multi-modal CMOS cellular sensor/stimulator array chip with 21 952 pixels and 1568-pixel concurrent readouts, while each array pixel can be independently reconfigured to support three sensing and one stimulation modalities: cellular potential recording, optical-point impedance sensing, and bi-phasic current stimulation. The CMOS sensor/stimulator array chip provides 3.6 mm × 1.6 mm active field-of-view (FoV). Each pixel contains one 8 μm × 8 μm gold deposited electrode, one 6 μm × 6 μm photodiode, and in-pixel circuits within 8 μm × 11 μm pixel area, while the pixel-to-pixel pitch is 16 μm × 16 μm. As a proof of concept, the CMOS array is implemented in a standard 130-nm BiCMOS process. Comprehensive electrical testing (potential/optical/four-point impedance/stimulation) and biological measurements (potential/optical/four-point impedance) with on-chip rat cardiomyocytes demonstrate the functionalities and unique advantages of this multi-modality cellular array. With high throughput multi-modal cellular sensing supported at the pixel level, this array chip enables holistic characterization of on-chip cellular samples with single-cell resolution.

Original languageEnglish (US)
Article number9466365
Pages (from-to)2438-2451
Number of pages14
JournalIEEE Journal of Solid-State Circuits
Volume56
Issue number8
DOIs
StatePublished - Aug 2021
Externally publishedYes

Keywords

  • Biosensor
  • cardiomyocytes
  • cell-based assay
  • cellular recording
  • digital pathology
  • drug screening
  • high resolution
  • high throughput
  • impedance sensing
  • multi-modality
  • optical detection
  • personalized medicine
  • point-of-care (PoC) devices
  • stimulation

ASJC Scopus subject areas

  • Electrical and Electronic Engineering

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