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In Vitro Multiparametric Cellular Analysis by Micro Organic Charge-modulated Field-effect Transistor Arrays
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Multi-parametric functional imaging of cell cultures and tissues with a CMOS microelectrode array.
Jeffrey Abbott1,2,3, Avik Mukherjee4, Wenxuan Wu1
1John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. donhee@seas.harvard.edu.
Lab on a Chip
|March 10, 2022
Summary
New electrical cell-biology assays using complementary metal-oxide-semiconductor (CMOS) microelectrode arrays (MEAs) offer label-free, high-throughput live-cell analysis. These methods provide single-cell resolution for cell attachment, growth, metabolism, and adhesion studies.
Area of Science:
- Cell Biology
- Bioelectronics
- Biophysics
Background:
- Optical microscopy has limitations in throughput and temporal resolution for live-cell assays.
- Electrode-based impedance and electrochemical methods offer non-invasive, label-free, and continuous cell-biology information.
- Existing microelectrode arrays (MEAs) often have limited electrodes per well, leading to noisy aggregate data and restricted applications outside electrophysiology.
Purpose of the Study:
- To expand the applications of complementary metal-oxide-semiconductor (CMOS) microelectrode arrays (MEAs) for cell-biology.
- To develop new field-based impedance mapping and electrochemical mapping/patterning techniques for CMOS-MEAs.
- To enable high-throughput, fully electronic live-cell assays with single-cell spatial resolution.
Main Methods:
- Utilized field-based impedance mapping and electrochemical mapping/patterning techniques with CMOS-MEAs.
- Achieved single-cell spatial resolution with a 20 μm electrode pitch.
- Applied multi-parametric measurements to capture cell-population statistics.
Main Results:
- Enabled accurate measurement of cell attachment, growth/wound healing, cell-cell adhesion, metabolic state, and redox properties.
- Quantified adhesion and metabolic differences between cells expressing oncogenes and wild-type controls.
- Demonstrated the capability for high-throughput live-cell assays.
Conclusions:
- Developed novel electrical methods to significantly enhance CMOS-MEA capabilities for cell biology.
- These techniques allow for detailed, single-cell level analysis of various cellular properties.
- The chip-scale integrated device opens new avenues for phenotypic screening and drug discovery.
