To improve tools for controlling and optimizing miniaturized chemistry, a novel oil extraction architecture, designated as the Counter-Current Continuous Phase Extraction (C3PE) module, was developed to enable precise control over reaction incubation in water-in-oil droplet microfluidic reactors. Using a symmetric pillar array coupled to adjustable oil flows prevented sample loss and droplet breakup, even at high final volume fractions, and cross-flow added novel stabilization of oil extraction against instability in control pressures. By integrating this dynamic functionality, C3PE enabled rational selection of the oil extraction magnitude across a range of achievable final droplet volume fractions (up to 85%) when processing droplets at 40–200 Hz. Further, this versatile device handled many droplet sizes (70–500 pL demonstrated here). Next, this approach to controlling droplet volume fraction enabled incubation time monitoring and optimization when coupled to a K-channel direct injection feature to label selected droplets. In profiling system characteristics like volume fraction, channel geometry, and continuous phase viscosity, this technique provided a powerful tool to control, measure, and improve incubation performance. Finally, applying C3PE principles to an in-droplet β-galactosidase enzyme reaction (useful in immunoassay systems) increased product formation while significantly decreasing variance in product yield among droplets relative to a non-extracted comparison. We envision that this method will inform future design and implementation of high precision in-droplet chemistry while being of general interest in the study of emulsion fluid dynamics.
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We gratefully acknowledge financial support from the National Institutes of Health (NIH CA191186). S.R.D. was supported by the National Science Foundation Graduate Research Fellowship Program. M.L. was supported by the Pfizer Undergraduate Summer Research Award (University of Michigan). We also want to thank Prof. Robert Kennedy and Dr. Brian Shay (University of Michigan) for assistance with viscosity measurements.
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Doonan, S.R., Lin, M., Lee, D. et al. C3PE: counter-current continuous phase extraction for improved precision of in-droplet chemical reactions. Microfluid Nanofluid 24, 50 (2020). https://doi.org/10.1007/s10404-020-02354-2
- Droplet microfluidics
- Volume fraction