A hand-held, power-free microfluidic device for monodisperse droplet generation

Here we develop a microfluidic device to generate monodispersion sub-nanoliter size droplets. Our system reaches steady state within 3 s after the flow starts and generates 100,000 droplets in 28 s with high size consistency (CV < 8%). This low cost device is composed with a microfluidic chip, 2 tubings, a collection vial, a syringe and a station; and is in the size of an iPad Mini (4" × 6" × 3/4"). In this system, all incoming reagents share the same pressure drop across the fluidic passage to generator droplets. A single source negative pressure is applied to the fluids to create the flow by a vacuum at the exit end of the device. The vacuum is generated on-site by pulling the plunger of a syringe. The position of the plunger before and after pulling determines the degree of vacuum. A fixture is used to hold the plunger after it is pulled to maintain its vacuum. Although this system loses vacuum gradually as the liquid filling in, it maintains a flow rates with the changes less than 10% and droplet sizes changes less than 2% during the course of generating 150,000 droplets. The pressure drop across the chip, the flow rates of all reagents, the droplet size and generation frequency are predictable, programmable, and reproducible. This device is designed for generating droplets for single cell genome profiling application but can be also used for digital PCR or other droplet-based applications.