BEE chip is a microfluidic device made of glass. It integrates a tiny and sharp sampling probe to achieve sample introduction, merging with reagent, and droplets generation for high-throughput screening. The design of the BEE chip was inspired by the process of bees to make honey: from catching nectar (by sampling probe) to mixing with invertase (by reagent merging) for nectar breakdown and honey production (by reaction and storage chamber). Via coupling to an automatic slotted-vial array, samples can be withdrawn into the device at an ultra high throughput of 6,000 different samples per hour, including 6 parallel droplets for each sample test. The sequence images (right below) show three samples (colorless, blue and red) are sampling into the microdroplets in less than 1 s (Full sequence of the droplet generation video can be viewed on the Movie page.
Colorless samples (water) are withdrawn into the sampling channel and merged with reagents (dyes) in adjustable ratios. The aqueous stream is fragmented into isolated droplets without traveling further in the microchannel to prevent sample dispersion, which, with extended traveling lengths, could lead to the generation of a concentration gradient.
The BEE chip has been tested in protein crystallization and enzyme inhibition screening assays. The composite picture on the top left shows ~1.5-nL droplets containing an enzyme (β-galactosidase) and a substrate (FDG) with varying concentrations of an inhibitor (DTPA). The higher intensity of the fluorescence, the less inhibition to the enzyme in the droplet array.
The left bottom picture shows a model protein Thaumatin crystallized after 6-h incubation in droplets containing a precipitant of 2.0 M potassium sodium tartrate.
A larger number of samples can be screened by the BEE chip if coupling to a highly compact sample vials array, e.g. on a rotating disc.