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Microfluidic cartridges preloaded with nanoliter plugs of reagents: an alternative to 96-well plates for screening

Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, 5735 South Ellis Avenue, Chicago, Illinois 60637, USA.
Current Opinion in Chemical Biology (Impact Factor: 7.65). 07/2006; 10(3):226-31. DOI: 10.1016/j.cbpa.2006.04.004
Source: PubMed

ABSTRACT In traditional screening with 96-well plates, microliters of substrates are consumed for each reaction. Further miniaturization is limited by the special equipment and techniques required to dispense nanoliter volumes of fluid. Plug-based microfluidics confines reagents in nanoliter plugs (droplets surrounded by fluorinated carrier fluid), and uses simple pumps to control the flow of plugs. By using cartridges pre-loaded with nanoliter plugs of reagents, only two pumps and a merging junction are needed to set up a screen. Screening with preloaded cartridges uses only nanoliters of substrate per reaction, and requires no microfabrication. The low cost and simplicity of this method has the potential of replacing 96-well and other multi-well plates, and has been applied to enzymatic assays, protein crystallization and optimization of organic reactions.

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    • "While chemically identical droplets (or dilutions of the same compound) can be generated very rapidly (up to kilohertz frequencies), the loading of different compounds from external sources such as microtiter plates is obviously several orders of magnitude slower. While first studies on compound screening were based on manually preloaded cartridges (Chen and Ismagilov, 2006), automated systems have also been developed (Chabert et al., 2006; Clausell-Tormos et al., 2010). For example, compounds can be aspirated from microtiter plates using an HPLC autosampler, before being injected into a length of tubing using oil as the carrier phase. "
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    • "Second, as the size of the drops increases, they become less stable, resulting in uncontrolled sample coalescence. These problems can be circumvented by alternately aspirating aqueous plugs and immiscible oil into a holding cartridge (e.g., a capillary or a piece of tubing) (Chen and Ismagilov, 2006). We used this approach to encapsulate several thousand cells into single microcompartments. "
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