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- Title
A semiconductor 96-microplate platform for electrical-imaging based high-throughput phenotypic screening.
- Authors
Chitale, Shalaka; Wu, Wenxuan; Mukherjee, Avik; Lannon, Herbert; Suresh, Pooja; Nag, Ishan; Ambrosi, Christina M.; Gertner, Rona S.; Melo, Hendrick; Powers, Brendan; Wilkins, Hollin; Hinton, Henry; Cheah, Michael; Boynton, Zachariah G.; Alexeyev, Alexander; Sword, Duane; Basan, Markus; Park, Hongkun; Ham, Donhee; Abbott, Jeffrey
- 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. Cell-based phenotypic assays link in vitro discovery to disease pathology. Here, the authors report a semiconductor-based microplate platform to perform high-throughput, high-dimensional "electrical imaging" for label-free assessment of live cell morphology and function.
- Subjects
HIGH throughput screening (Drug development); ELECTRIC impedance measurement; DRUG discovery; ELECTRIC field strength; SEMICONDUCTORS
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-43333-9