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Large-scale microfluidics providing high-resolution and high-throughput screening of Caenorhabditis elegans poly-glutamine aggregation model

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Listed:
  • Sudip Mondal

    (The University of Texas at Austin)

  • Evan Hegarty

    (The University of Texas at Austin)

  • Chris Martin

    (The University of Texas at Austin)

  • Sertan Kutal Gökçe

    (The University of Texas at Austin)

  • Navid Ghorashian

    (The University of Texas at Austin
    The University of Texas at Austin)

  • Adela Ben-Yakar

    (The University of Texas at Austin
    The University of Texas at Austin
    The University of Texas at Austin
    The Institute for Neuroscience, The University of Texas at Austin)

Abstract

Next generation drug screening could benefit greatly from in vivo studies, using small animal models such as Caenorhabditis elegans for hit identification and lead optimization. Current in vivo assays can operate either at low throughput with high resolution or with low resolution at high throughput. To enable both high-throughput and high-resolution imaging of C. elegans, we developed an automated microfluidic platform. This platform can image 15 z-stacks of ∼4,000 C. elegans from 96 different populations using a large-scale chip with a micron resolution in 16 min. Using this platform, we screened ∼100,000 animals of the poly-glutamine aggregation model on 25 chips. We tested the efficacy of ∼1,000 FDA-approved drugs in improving the aggregation phenotype of the model and identified four confirmed hits. This robust platform now enables high-content screening of various C. elegans disease models at the speed and cost of in vitro cell-based assays.

Suggested Citation

  • Sudip Mondal & Evan Hegarty & Chris Martin & Sertan Kutal Gökçe & Navid Ghorashian & Adela Ben-Yakar, 2016. "Large-scale microfluidics providing high-resolution and high-throughput screening of Caenorhabditis elegans poly-glutamine aggregation model," Nature Communications, Nature, vol. 7(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13023
    DOI: 10.1038/ncomms13023
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