A droplet-chip/mass spectrometry approach to study organic synthesis at nanoliter scale

Abstract

A droplet-based microfluidic device with seamless hyphenation to electrospray mass spectrometry was developed to rapidly investigate organic reactions in segmented flow providing a versatile tool for drug development. A chip-MS interface with an integrated counterelectrode allowed for a flexible positioning of the chip-emitter in front of the MS orifice as well as an independent adjustment of the electrospray potentials. This was necessary to avoid contamination of the mass spectrometer as well as sample overloading due to the high analyte concentrations. The device was exemplarily applied to study the scope of an amino-catalyzed domino reaction with low picomole amount of catalyst in individual nanoliter sized droplets.

Detection of antibiotics synthetized in microfluidic picolitre-droplets by various actinobacteria

“…Since the outcome of such an experiment is the valuable information of which elicitors trigger the production of which secondary metabolite, the loss of the producing organisms during the measurement can be tolerated. Adopting a previously introduced setup for droplet chip MS coupling 38 , we developed an approach to reinjected pre-incubated droplets into a droplet-MS chip (Fig. 3a).…”

A Droplet Microfluidic Platform for High-Throughput Photochemical Reactions

“…Furthermore, this system enables in-droplet reaction discovery to rapidly generate high-volume compound libraries and provide access to greater magnitudes of chemical space. ESI-MS analysis of reaction droplets was performed at a throughput of 0.3 samples/s, which represents a dramatic improvement over other ESI-MS systems for the analysis of flow reactions (16). Upon translating our picomole scale droplet reactions to millimole scale flow conditions, we have also validated the successful flow scale-up of our droplet reactions to enable product isolation.…”

“…We have identified droplet microfluidics as a novel platform for continuous flow-based reaction discovery. Segmentation of samples with an immiscible phase enables the simultaneous handling of numerous samples over extended periods of time (15)(16)(17). From a material consumption standpoint, droplet microfluidics screens are typically performed at nanoliter to femtoliter scale, which translates to a reduction in starting material usage by six to eight orders of magnitude relative to a traditional multiwell plate-based screen.…”

“…photocatalyst) directly to substrate-containing droplets, reagent consumption can be reduced to picomoles per reaction. While reagent addition processes have been demonstrated in aqueous-based in-droplet reactions (16,30,31), we have established one of the first applications of this technology in organic solvent systems. As depicted in Figure 4, preformed substrate-containing acetonitrile droplets were flowed from PFA tubing into a reagent addition device, through an addition region to receive photocatalyst, and exported to PFA tubing for irradiation and ESI-MS analysis in one continuous system.…”

Drug Toxicity Evaluation Based on Organ-on-a-chip Technology: A Review

“…Unfortunately, current in vitro methods lack accuracy in the prediction, judgment, and treatment of cardiotoxicity. Development of microfluidic technology has made the heart chip a new type of in vitro tool, but there are still several core issues that need to be resolved, such as accurate real-time imaging which is difficult to achieve due to the high thickness of the chip and suitable biomarkers [99]. The current research focuses on solving these problems by integrating on-chip analytical techniques such as high-performance liquid chromatography, mass spectrometry, and electrophoresis [100].…”