On-Demand Positive Pressure-Controlled Hydrodynamic Gating for Efficient Droplet Generation and Sorting in Microfluidic Devices

Droplet microfluidics is a rapidly advancing area of microfluidic technology, which offers numerous advantages for cell analysis, such as isolation and accumulation of signals, by confining cells within droplets. However, methods for controlling the number of cells within each droplet are limited by the uncertainty of random encapsulation. The Poisson probability of having only one cell per droplet results in the formation of a large number of empty droplets. Therefore, more precise control techniques are needed to achieve efficient encapsulation of cells within droplets. Here, an innovative microfluidic droplet manipulation platform had been developed, which employed positive pressure as a stable and controllable driving force for manipulating fluid within chips. The air cylinder, E/P controller and the microfluidic chip were connected through a capillary, enabling a difference in hydrodynamic resistance between two fluid streams at the intersection of channels to form a hydrodynamic gating-controlled valve. By changing the duration of hydrodynamic gated injection, the volume of the introduction fluid can be regulated. Several important droplet microfluidic manipulations were demonstrated on this microfluidic platform, such as sorting of cells/droplets, sorting of droplets co-encapsulated cells and hydrogels, and active generation of droplets encapsulated with cells in a responsive manner. The simple, on-demand microfluidic platform was featured with high stability, good controllability, and compatibility with other droplet microfluidic technologies.