A droplet microfluidic platform for high-throughput photochemical reaction discovery

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.

Working at the interfaces of data science and synthetic electrochemistry

“…However, the establishment of HTE technologies specific to a synthetic subdiscipline is a key bottleneck in the realization of these benefits. Indeed, the introduction of standardized high-throughput platforms for photochemistry [ 48 , 49 ] and biocatalysis [ 50 , 51 ] have substantially accelerated the pace of research in these areas in recent years. The development of widely available platforms for high-throughput electrochemistry is advantageous in two respects: to enable the efficient development of new reactions as well as to provide electrochemists with high-quality datasets for modeling efforts.…”

Robotic automation of droplet microfluidics

“…In the simplest implementations, this has involved integrating microfluidic pumps with commercial single-channel robotic arms. 38,39 Prior work has also shown that whole liquid-handling robots with multichannel-pipet arms can be interfaced with the channels of continuous-flow microfluidic devices; 40 for droplet microfluidics, the closest implementation is currently BioRad's QX200 AutoDG, a specialized platform for preparing 96-well ddPCR reaction plates. 41 To date, a generalizable robotic platform configurable for any droplet microfluidics operation at scale has not been reported.…”

High-Throughput Nano-Electrostatic-Spray Ionization/Photoreaction Mass Spectrometric Platform for the Discovery of Visible-Light-Activated Photocatalytic Reactions in the Picomole Scale

“…21 Lately, Kennedy and Stephenson et al reported a droplet microfluidic platform that enabled high-throughput discovery of visiblelight-catalyzed reactions in flow. 22 In an earlier study, we also developed a microscale photoreaction screening platform in which a handheld laser source is coupled with nanoelectrospray ionization (nESI) mass spectrometry. 23 However, this approach is unable to operate in a high-throughput manner because the conventional nESI MS technique needs the insertion of the electrode into the solution in the capillary.…”

“…The combination of MS with an ambient chemical reaction has enabled many applications at the microscale level, such as the study of short-lived intermediates, the discovery of accelerated droplet reactions, and reaction monitoring. , However, the development of an MS-based screening method for visible-light-activated photochemical reactions that could simultaneously meet high-throughput, microamount, and speediness remains a great challenge. , Recently, Nie et al developed a semiconductor-assisted laser desorption/ionization (LDI) MS platform that realized the ultrafast screening of the ultraviolet-light-activated reactions that happened during the LDI process . Lately, Kennedy and Stephenson et al reported a droplet microfluidic platform that enabled high-throughput discovery of visible-light-catalyzed reactions in flow . In an earlier study, we also developed a microscale photoreaction screening platform in which a handheld laser source is coupled with nano-electrospray ionization (nESI) mass spectrometry .…”