Small

Abstract

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.P40 OD010440/CD/ODCDC CDC HHSUnited States/P40 OD010440/OD/NIH HHSUnited States/R01 AG056436/AG/NIA NIH HHSUnited States/R01NS096581/National Institute of Health/R01AG056436/National Institute of Health/ECCS-1542174/National Science Foundation/National Nanotechnology Coordinated Infrastructure/R01 NS096581/NS/NINDS NIH HHSUnited States/NIH R21NS117066/National Institute of Health/R21 NS117066/NS/NINDS NIH HHSUnited States