Journal
SMALL
Volume 18, Issue 17, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.202200319
Keywords
droplets; functional phenotyping; high-throughput screening; multiphase microfluidics; small animals
Categories
Funding
- National Institute of Health [NIH R21NS117066, R01NS096581, R01AG056436]
- NIH Office of Research Infrastructure Programs [P40 OD010440]
- National Science Foundation [ECCS-1542174]
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The study demonstrates a highly efficient single-animal encapsulation unit for controlling the chemical environment in droplets, as well as an automation scheme for executing complex protocols. By careful use of interfacial forces, the system enables the generation of chemical gradients inaccessible in previous multiphase systems. This platform allows for large-scale screening of complex dynamic phenotypes in small animals.
Screening functional phenotypes in small animals is important for genetics and drug discovery. Multiphase microfluidics has great potential for enhancing throughput but has been hampered by inefficient animal encapsulation and limited control over the animal's environment in droplets. Here, a highly efficient single-animal encapsulation unit, a liquid exchanger system for controlling the droplet chemical environment dynamically, and an automation scheme for the programming and robust execution of complex protocols are demonstrated. By careful use of interfacial forces, the liquid exchanger unit allows for adding and removing chemicals from a droplet and, therefore, generating chemical gradients inaccessible in previous multiphase systems. Using Caenorhabditis elegans as an example, it is demonstrated that these advances can serve to analyze dynamic phenotyping, such as behavior and neuronal activity, perform forward genetic screen, and are scalable to manipulate animals of different sizes. This platform paves the way for large-scale screens of complex dynamic phenotypes in small animals.
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