Microfluidics: smaller, faster, better
Stemming the flow: scaling down HTS with nanoplugs
Conventional high-throughput screening usually involves the use of microwell plates that require microlitre quantities of reagents for individual reactions. In an alternative approach that makes use of plug-based microfluidics, nanolitre plugs of reagents can be used to significantly reduce the reagent requirements within the context of any large-scale screen.
Delai Chen and Rustem Ismagilov, both of the Department of Chemistry and the Institute for Biophysical Dynamics at the Univerisity of Chicago, recently described nanoplugs and their various applications in Current Opinion in Chemical Biology. Nanoplugs are essentially nanolitre-sized droplets of reagents surrounded by fluorinated carrier fluid. By dispensing reagents as an array of plugs and storing them in a reagent-loaded cartridge, only simple pumps are needed to control the flow of plugs within a microfluidic system and therefore the dispensing of nanolitre volumes of reagent during an experiment becomes unnecessary. To carry out a screen, reagent plugs from the cartridge are merged with a stream of substrate solution, causing the formation of plugs with both reagent and substrate. These merged plugs are then transferred to a receiving capillary in which the incubation and analysis take place.
The primary advantages of using cartridges preloaded with nanoplugs include (1) the use of only nanolitres of substrate per reaction, (2) the lack of need for specialised microfabrication, (3) the handling of nanolitre amounts of fluid without evaporation. To date, nanoplug microfluidics have successfully been developed for a variety of applications, including enzymatic assays, protein crystallisation, and organic synthesis reactions. Since inexpensive pump systems are already available commercially, one of the main remaining challenges is the development of a system for the standardised production and distribution of nanoplug resources (providing, for example, cartridges containing libraries of reagents). With the development of such a system, nanoplug microfluidics could become a mainstream approach for many high-throughput screening applications.
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