Accelerating cross-modality reaction optimization via robotically automated vacuum enabled direct-inject mass spectrometry (RAVE MS)

Abstract

In this report, we detail direct inject mass spectrometry via a robotically automated vacuum enabled (RAVE) interface that utilizes commercially available capillary electrophoresis hardware to directly inject samples for mass spectrometry (MS) at a sampling rate of approximately 12 s per sample. This system enables direct electrospray ionization from standard 48, 96 or 384-well plates with minimal investment in hardware and utlilizes custom developed open source software that provides both autosampler control and analysis of raw extracted data from the mass spectrometer. We show a high level of correlation among results obtained with RAVE coupled MS, acoustic ejection (Echo) MS, and liquid chromatography coupled MS (LCMS) on 384 biocatalytically driven reactions. We additionally utilize RAVE MS on an array of 96 chemocatalytic reaction conditions to show that, while direct MS analysis can be challenging in complex mixtures, simple dilution followed by direct injection is often sufficient for analysis. With these results, we demonstrate the potential for RAVE MS to be utilized as a low-cost, low barrier to entry tool for rapid direct-inject MS analysis.