3D organoids are emerging as a powerful tool for stem cell biology and tissue modeling, but their broader adoption for screening applications has been hindered by their slow expansion and heterogeneity. To overcome these two limitations, we request the Dolomite Nadia Innovate, a microfluidic droplet protocol development instrument that will enable us to invent two novel organoid screening platforms: (1) Droplet Miniature Organoid Spheres (DMOS) that can expand quickly, preserve tissue heterogeneity, and support high-throughput screen, and (2) a CRISPRi Organoid Screening by Multiplexed IndeXing (COSMIX) platform to identify stem cell and tissue plasticity regulators. If successful, our invention of droplet-based high-throughput organoid functional assays will be transformative in a way similar to droplet-based single-cell sequencing, which has changed our understanding of tissue heterogeneity.

Public Health Relevance

The organoid technology is transforming stem cell research and tissue modeling, but its slow expansion and heterogeneity limits its usage for high-throughput screening applications. This administrative supplement application requests a Dolomite Nadia Innovate instrument for cell-based microfluidic droplet manipulation, which will enable two novel organoid-screening platforms: (1) droplet miniature organoid spheres (DMOS), and (2) CRISPRi Organoid Screening by Multiplexed IndeXing (COSMIX).

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Unknown (R35)
Project #
3R35GM122465-04S1
Application #
10133905
Study Section
Special Emphasis Panel (ZGM1)
Program Officer
Gibbs, Kenneth D
Project Start
2017-04-01
Project End
2022-03-31
Budget Start
2020-04-01
Budget End
2021-03-31
Support Year
4
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Duke University
Department
Biomedical Engineering
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
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