A semiconductor 96-microplate platform for electrical-imaging based high-throughput phenotypic screening

Shalaka Chitale, Wenxuan Wu, Avik Mukherjee, Herbert Lannon, Pooja Suresh, Ishan Nag, Christina M. Ambrosi, Rona S. Gertner, Hendrick Melo, Brendan Powers, Hollin Wilkins, Henry Hinton, Michael Cheah, Zachariah G. Boynton, Alexander Alexeyev, Duane Sword, Markus Basan, Hongkun Park (), Donhee Ham () and Jeffrey Abbott ()
Additional contact information
Shalaka Chitale: CytoTronics Inc.
Wenxuan Wu: CytoTronics Inc.
Avik Mukherjee: Harvard Medical School
Herbert Lannon: CytoTronics Inc.
Pooja Suresh: CytoTronics Inc.
Ishan Nag: CytoTronics Inc.
Christina M. Ambrosi: CytoTronics Inc.
Rona S. Gertner: Harvard University
Hendrick Melo: CytoTronics Inc.
Brendan Powers: CytoTronics Inc.
Hollin Wilkins: CytoTronics Inc.
Henry Hinton: Harvard University
Michael Cheah: CytoTronics Inc.
Zachariah G. Boynton: CytoTronics Inc.
Alexander Alexeyev: CytoTronics Inc.
Duane Sword: CytoTronics Inc.
Markus Basan: Harvard Medical School
Hongkun Park: Harvard University
Donhee Ham: Harvard University
Jeffrey Abbott: CytoTronics Inc.

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: Abstract High-content imaging for compound and genetic profiling is popular for drug discovery but limited to endpoint images of fixed cells. Conversely, electronic-based devices offer label-free, live cell functional information but suffer from limited spatial resolution or throughput. Here, we introduce a semiconductor 96-microplate platform for high-resolution, real-time impedance imaging. Each well features 4096 electrodes at 25 µm spatial resolution and a miniaturized data interface allows 8× parallel plate operation (768 total wells) for increased throughput. Electric field impedance measurements capture >20 parameter images including cell barrier, attachment, flatness, and motility every 15 min during experiments. We apply this technology to characterize 16 cell types, from primary epithelial to suspension cells, and quantify heterogeneity in mixed co-cultures. Screening 904 compounds across 13 semiconductor microplates reveals 25 distinct responses, demonstrating the platform’s potential for mechanism of action profiling. The scalability and translatability of this semiconductor platform expands high-throughput mechanism of action profiling and phenotypic drug discovery applications.

Date: 2023
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DOI: 10.1038/s41467-023-43333-9

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