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Droplet-based Microfluidics for Ultra-High-Throughput Digital Biology
Programmable microfluidic modules have been created which can precisely make, combine, split, mix, incubate, detect fluorescence and sort microscopic droplets. Integration of multiple modules onto a single microfluidics chip enables a vast number of assays (> 105 / min) to be performed using extremely low volumes of reagents. Each microdroplet functions as an independent microreactor separated from both the walls of the device and other microdroplets by a fluorinated carrier fluid. The droplets function like the wells of microtitre plates but have volumes a thousand to a million times smaller. This technology has many potential applications in industrial biotechnology, diagnostics and drug discovery. The advantages of screening using microfluidic screening systems is demonstrated graphically by a recent ultra-high-throughput screening experiment in which 108 individual enzyme reactions were screened in only 10 h, using < 150 μL of reagents. Compared with state-of- the-art robotic, microtitre plate-based screening systems, the entire screen was performed with a 1,000-fold increase in speed and a significant reduction in reaction volumes and cost (the total cost of the screen was only $2.50, compared with $15 million using microplates). Combining this microfluidic technology with recent developments in next-generation sequencing opens up even greater opportunities, such as the high-throughput screening of non-immortalised B-cells for the discovery of therapeutic antibodies and the massively parallel analysis of single cells using DNA-seq, RNA-seq and ChIP-seq. The improvements in the ultra-high-throughput capabilities of the droplet-based microfluidics are somewhat analogous to those of microprocessors, where transistor density has increased by ∼100,000-fold in the past few decades. These improvements have led to completely new and unexpected applications for microprocessors and microfluidics, especially in combination with next-generation sequencing, should lead to unexpected new applications.