On-demand generation and mixing of liquid-in-gas slugs with digitally programmable composition and size

Microscopic droplets or slugs of mixed reagents provide a convenient platform for performing large numbers of isolated biochemical or chemical reactions for many screening and optimization applications. Myriad microfluidic approaches have emerged for creating droplets or slugs with controllable size and composition, generally using an immiscible carrier fluid to assist with the formation or merging processes. We report a novel device for generation of liquid slugs in air when the use of a carrier liquid is not compatible with the application. The slug generator contains two adjacent chambers, each of which has a volume that can be digitally adjusted by closing selected microvalves. Reagents are filled into the two chambers, merged together into a contiguous liquid slug, ejected at the desired time from the device using gas pressure, and mixed by flowing in a downstream channel. Programmable size and composition of slugs is achieved by dynamically adjusting the volume of each chamber prior to filling. Slug formation in this fashion is independent of fluid properties and can easily be scaled to mix larger numbers of reagents. This device has already been used to screen monomer ratios in supramolecular nanoparticle assembly and radiolabeling conditions of engineered antibodies, and here we provide a detailed description of the underlying device. (paper)