Research


The research in the lab is focused on using the techniques of droplet-based microfluidics for high-throughput processing of biological reactions. Areas of current interest are protein engineering through directed evolution and gene-expression profiling of small numbers of cells, though many other applications are also possible. 

Most biological experiments are performed by adding reagents to a container, such as a test tube. This approach can be adapted to nearly any biological study, because almost any reagent can be added to the test tube, and in any sequence. This is effective for research, but it is not always optimal for applications requiring massive numbers of reactions to be performed, because the manual processing of the reactions is slow and requires too much reagent. One way to improve the approach is to shrink the reaction volume to what is technically feasible for pipetting, ~10 uL, the volume of a rain drop, and to use robotic automation for the fluid handling. This allows reactions to be performed with less reagent more quickly; however, it is still far too slow for experiments requiring massive numbers of reactions to be performed. For example, a relatively small screen requiring ten million reactions would take several weeks and almost a hundred liters of total reagent; it would cost over 1 million dollars -- in pipette tips for the robot alone. 

For larger-scale applications like these to be practical, the reaction volume must be reduced and the processing rate increased by an additional factor of 10,000. This corresponds to a "test tube" of approximately ten microns in diameter -- about 1/10th the diameter of a human hair -- processed at a rate of about 10 kHz. "Containers" of this size can be created using microfluidics, in the form of microdroplets. Microdroplets are tiny spheres of aqueous liquid surrounded by an inert oil. With microfluidic devices, they can be filled with reagents, incubated at selected temperature, and screened and sorted at rates up to 100 kHz. These are precisely the speeds and sizes needed for practical processing of large numbers of reactions.

The High-Throughput BioLab at UCSF has developed microfluidic systems for performing biological experiments with microdrops. Each drop can be used to perform one reaction and requires only about 1 pL of reagent; this allows massive numbers of reactions to be performed in a short period of time using a small amount of total reagent. For example, the same ten million reactions described above can be performed using 10 uL of total reagent, in a few minutes. Moreover, because the drops are essentially small “test tubes,” the approach is applicable to most biological assays, for applications ranging from high-throughput screening and directed evolution to DNA sequencing. The lab is currently developing droplet-based microfluidic systems for protein engineering, directed evolution, and gene-expression profiling. 

For more information about the facilities available, contact Prof. Abate

For details about research and information about collaboration, contact Prof. Abate
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