Nature Communications · 2020 · 174 citations · 28 references
Natural SciencesChemical EngineeringMedicinal ChemistryAnalytical ChemistryDrug DiscoveryMass Spectrometric AnalysisHigh-throughput ScreeningMass SpectrometryMicrofluidic DevicesMicrofluidic SystemsMicrofluidicsPhotochemistryContinuous FlowDroplet Microfluidic ScreeningDroplet MicrofluidicsDroplet-based ScreeningHigh-throughput Reaction AnalysisHigh-throughput Reaction ScreeningMicrofluidic PlatformsPhotochemical Reactions
Continuous flow technology is essential for scaling photochemical reactions industrially, yet translating batch‑scale discoveries to flow faces significant time and resource constraints. The authors develop a droplet microfluidic platform that enables high‑throughput photochemical reaction discovery in flow, aiming to expand the impact of such reactions in drug discovery and development. The platform employs picoliter‑sized droplets in a microfluidic chip, allowing rapid screening of reaction conditions in continuous flow. It achieves material efficiency by operating on picomole scale and provides high‑throughput data via online ESI‑MS at 0.3 samples per second.
Abstract The implementation of continuous flow technology is critical towards enhancing the application of photochemical reactions for industrial process development. However, there are significant time and resource constraints associated with translating discovery scale vial-based batch reactions to continuous flow scale-up conditions. Herein we report the development of a droplet microfluidic platform, which enables high-throughput reaction discovery in flow to generate pharmaceutically relevant compound libraries. This platform allows for enhanced material efficiency, as reactions can be performed on picomole scale. Furthermore, high-throughput data collection via on-line ESI mass spectrometry facilitates the rapid analysis of individual, nanoliter-sized reaction droplets at acquisition rates of 0.3 samples/s. We envision this high-throughput screening platform to expand upon the robust capabilities and impact of photochemical reactions in drug discovery and development.
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