Extremely high-throughput droplet microfluidic platform for single-cell processing

Single-cell processing is crucial in modern medicine. A well-known example is the revolutionary CAR-T cell therapy in which a patient’s own cells are harvested, engineered and readministered as a drug for cancer therapy.  The isolation and characterization of antibody-producing cells with high selectivity and sensitivity is another example in today’s biomanufacturing requiring the screening of vast libraries of cells. Clearly, a need exists for the development of an innovative high-throughput analysis technology that offers single-cell resolution.

Developments in the field of microfluidics can help to meet these cell screening challenges. The precise fluidic structures with integrated microsensors and actuators allow detecting and manipulating single cells. Especially droplet microfluidics, in which cells are encapsulated in aqueous droplets in inert carrier oil, has become the de facto standard for single-cell applications. This principle is used in several commercial platforms for single-cell analysis (e.g. 10x Genomics, Mission Bio). Presently, constrained by technological limitations, these platforms are restricted to relatively simple workflows including droplet generation and incubation. Extending these platforms with more sophisticated droplet manipulations, such as droplet sorting, merging, splitting, reagent injection, will be needed to provide an answer to current industrial needs.

This PhD project will explore concepts for high-throughput electrical droplet manipulation based on silicon technology. The primary focus will be an extremely high-speed droplet sorter. The student will investigate the possibilities of achieving this goal through improving microfluidic design and actuation, fabrication methods and parallelization. In a later stage, driven by application needs, we will advance the platform development from sorting to other droplet manipulations such as droplet merging or reagent injection. Finally, the platform will be demonstrated using state-of-the-art single-cell analysis assays. This topic will be supervised and supported by a team of physicists, engineers and biologists at imec, in collaboration with single-cell analysis experts of KU Leuven.