Good to the last “emulsified” drop

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Science Translational Medicine  18 Jan 2017:
Vol. 9, Issue 373, eaal4993
DOI: 10.1126/scitranslmed.aal4993


Nanoliter scale droplets sealed and encapsulated in solid PEFE polymer shells are combined with graphical coding to advance droplet microfluidics.

Droplet microfluidics leverage biochemical, soft-matter physics, and engineering principles to combine micrometer-sized emulsion droplets with simple and high-throughput testing. This subfield of microfluidics has gained traction because researchers can precisely manipulate droplet volumes and content; microdroplets thus function as individual chemical reactors. Droplet microfluidics generally excels with aliquots of single rather than multiple analyte solutions. Achieving multiplexed testing requires sophisticated microdroplet labeling strategies.

Song et al. developed a novel droplet labeling tactic and mechanical releasing system poised to expand the field’s translational appeal. Their “encoded microcapsules” are nanoliter scale droplets individually sealed and encapsulated in a solid perfluoropolyether (PEFE) polymer shell. A durable graphical code is then lithographically written onto the shell to identify the liquid contents. Since the self-contained droplets do not contaminate each other, storage of multiple different droplets as pooled chemical libraries becomes feasible. A single pipetting step sweeps thousands of 180 μm microcapsules into microwells (one capsule per well) through self-assembly and within seconds. The microwells, containing cells or reagents, are sealed with immiscible silicone oil to prevent evaporation after the microcapsules are introduced. A motorized stage with micropillars then safely ruptures microcapsules, allowing contents to interact with unharmed cells or reagents within microwells. Successful validation occurred through enzyme inhibition, viral transduction, and cell viability experiments.

The reported work offers various advantages over conventional approaches. Producing heterogeneous droplet arrays through serial spotting takes hours compared with seconds for self-assembly. Previous labeling efforts by others have included fluorescent dyes; spectral overlap and bleaching over time limit combinations and overall potential. Additionally, microwells enable testing of rare samples; for example, circulating tumor cells–by reducing the amount of sample and reagents required. The throughput of droplet formation (~1,000/min) in the current silicone-based iteration could be improved. The high fluidic resistance of droplet devices could be met with less deformable substrates such as plastics. To exploit higher throughput operations, more advanced encoding methods beyond the alphabet should be entertained. Overall, increased interdisciplinary input could propel novel droplet microfluidic technologies into laboratories and advance the flow of scientific information one drop at a time.

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