Automated and Dynamic Control of Chemical Content in Droplets for Scalable Screens of 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. A multiphase microfluidic platform is demonstrated for performing automated functional screens of small animals. The in situ droplet generator scheme efficiently encapsulates complex objects. The liquid exchanger unit allows for generating chemical temporal profiles previously impossible in droplets. Because the platform operation relies on manipulating droplets rather than directly animals, the platform is scalable and accommodates animals of different sizes.