Continuous Sampling System for Liquid Chromatography-Mass Spectrometry: Application to Reaction Monitoring and Biomolecule Detection

Basal, Lina A., Alyssa V. Colbert, Braydon L. Dymm, Joshua J. Eby, David C. Moore, Melanie M. Smalley, Dominick J. Alton, Matthew J. Mio, and Kendra R. Evans

Separations-based mass spectrometry is a powerful tool for monitoring reactions and dynamics in cellular behavior.  Because some reactions proceed for several hours, and because long-term dynamics are often of interest in cell studies, separations-based monitoring would benefit from reliable, automated methods of monitoring compounds.  A liquid chromatography-mass spectrometry-based method for continuous, automated sampling and on-line detection has been developed.  A 10-port switching valve is used for computer-controlled injections, and the system can be coupled to organic reaction vessels or cell chambers from which compounds are continuously sampled.  The method will allow continuous monitoring for 24 hours with at least 15-minute temporal resolution.  The automated, multi-analyte capabilities of the system for continuous sampling and detection have been demonstrated using standard analytes.  The system will be applied to a Sonogashira cross-coupling reaction and to a forced degradation pharmaceutical reaction.  The system will also be applied to microdialysis studies of neurochemical dynamics and to investigations of islets of Langerhans.