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

delete2023-11-21
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OA
AI
S
Shalaka Chitale
W
Wenxuan Wu
A
Avik Mukherjee
H
Herbert Lannon
P
Pooja Suresh
I
Ishan Nag
C
Christina M. Ambrosi
R
Rona S. Gertner
H
Hendrick Melo
B
Brendan Powers
H
Hollin Wilkins
H
Henry Hinton
M
Michael Cheah
Z
Zachariah Boynton
A
Alexander Alexeyev
D
Duane Sword
M
Markus Basan
H
Hongkun Park
D
Donhee Ham
J
Jeffrey Abbott *
DOI:10.1038/s41467-023-43333-9delete
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摘要

摘要

En 中文
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 mu m spatial resolution and a miniaturized data interface allows 8x 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.
Keyword:
CELL-LINE
BARRIER
CANCER
MODEL
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Nature Communications 封面图
Nature Communications
IF:
15.7
论文数:
9.4W
被引数:
91.2W

机构

H
Harvard University
学者数:
26.5W
论文数: 22.0W
被引数: 28.7W
H
Harvard Medical School
学者数:
6.5W
论文数: 4.8W
被引数: 91
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