We report an automated microfluidic system for screening and optimization of chemical reactions performed inside microliter liquid droplets. The system offers precise control over generation, merging and flow of droplet “micro-reactors” and over reaction conditions, including the volumes of the reagents, temperature and time. The high level of control coupled with the ability to quickly screen multiple reaction conditions allow us to thoroughly monitor the impact of input parameters on the yield of the reaction. In addition, the reagent consumption is kept remarkably low. As an exemplary use of our system we demonstrate a comprehensive study of acid-catalyzed (para-toluenesulfonic acid, p-TsOH) model imine formation (condensation of ortho-nitrobenzaldehyde and phenylethylamine) in an organic solvent (ethanol). By use of novel screening methods described herein, we unfold that the acid-catalyzed model imine formation in the organic medium can be considered as an assembly of acid-mediated and non-catalyzed reactions, both of which accelerate with increasing temperature.
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The research was supported by the European Research Council Starting Grant 279647. PG acknowledges support from the Foundation for Polish Science within the Idee dla Polski program.
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On behalf of all authors, the corresponding author states that there is no conflict of interest.
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• A benchtop microfluidic system for chemical screening in microdroplets; made of inexpensive elements; easily reproducible.
• Droplet on Demand encapsulates each individual reaction in a droplet, spending < 1 mg of limiting reagent per reaction.
• Microfluidic screening of model reaction accurately reflects the classical batch conditions.
Electronic supplementary material
ESM1.pdf — microfluidic system’s construction details, HPLC analyses, NMR spectra, heating rates in the microreactor, quantitative analysis of screening data (PDF 3617 kb)
ESM2.wmv — video showing system operation (WMV 12100 kb)
ESM3.wmv — video showing droplet mixing (WMV 3835 kb)
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Jankowski, P., Kutaszewicz, R., Ogończyk, D. et al. A microfluidic platform for screening and optimization of organic reactions in droplets. J Flow Chem 10, 397–408 (2020). https://doi.org/10.1007/s41981-019-00055-8
- Multiphase flow
- Droplet on demand
- Screening and optimization
- Droplet microfluidics