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  1. Artikel ; Online: A semiconductor 96-microplate platform for electrical-imaging based high-throughput phenotypic screening.

    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

    Nature communications

    2023  Band 14, Heft 1, Seite(n) 7576

    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 ... ...

    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.
    Mesh-Begriff(e) High-Throughput Screening Assays/methods ; Drug Discovery ; Diagnostic Imaging ; Electric Impedance ; Electrodes
    Sprache Englisch
    Erscheinungsdatum 2023-11-21
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-43333-9
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel: A semiconductor 96-microplate platform for electrical-imaging based high-throughput phenotypic screening.

    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, Mickey / Boynton, Zachariah / Alexeyev, Alexander / Sword, Duane / Basan, Markus / Park, Hongkun / Ham, Donhee /
    Abbott, Jeffrey

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Profiling compounds and genetic perturbations via high-content imaging has become increasingly popular for drug discovery, but the technique is limited to endpoint images of fixed cells. In contrast, electronic-based devices offer label-free, functional ... ...

    Abstract Profiling compounds and genetic perturbations via high-content imaging has become increasingly popular for drug discovery, but the technique is limited to endpoint images of fixed cells. In contrast, electronic-based devices offer label-free, functional information of live cells, yet current approaches suffer from low-spatial resolution or single-well throughput. Here, we report a semiconductor 96-microplate platform designed for high-resolution real-time impedance "imaging" at scale. Each well features 4,096 electrodes at 25 µm spatial resolution while a miniaturized data interface allows 8× parallel plate operation (768 total wells) within each incubator for enhanced throughputs. New electric field-based, multi-frequency measurement techniques capture >20 parameter images including tissue barrier, cell-surface attachment, cell flatness, and motility every 15 min throughout experiments. Using these real-time readouts, we characterized 16 cell types, ranging from primary epithelial to suspension, and quantified heterogeneity in mixed epithelial and mesenchymal co-cultures. A proof-of-concept screen of 904 diverse compounds using 13 semiconductor microplates demonstrates the platform's capability for mechanism of action (MOA) profiling with 25 distinct responses identified. The scalability of the semiconductor platform combined with the translatability of the high dimensional live-cell functional parameters expands high-throughput MOA profiling and phenotypic drug discovery applications.
    Sprache Englisch
    Erscheinungsdatum 2023-07-19
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.1101/2023.06.01.543281
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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