Maximizing Flexibility on a High Resolution Open Access LC/MS System.

Advances in fields such as metabolomics and biotherapeutics have generated a growing need for open access mass spectrometry methods supporting a wide range of analytes beyond traditional synthetic small molecules, from amino acids to antibodies. High resolution time of flight and orbitrap mass spectrometers are instruments of choice for intact protein analysis; they also support many qualitative and quantitative small molecule workflows and have the mass stability and operational reliability needed in an open access lab setting. Our challenge is to configure one LC/HRMS system to support a broad spectrum of applications without manual intervention. Providing multiple complementary chromatography options is key to maximizing flexibility. We set up an Open Access LC/HRMS system composed of a Waters Acquity UPLC with 4 column manager and Thermo Exactive Classic, mass calibrated once a week. A suite of methods using 4 columns and 4 solvents allows switching among intact protein and small molecule methods on the fly: Waters BioResolve RP Mab Polyphenyl, Agilent Poroshell C18, Agilent Zorbax SB-C8, and SeQuant ZIC-HILIC columns, run using 0.1% formic acid in water, 0.1% formic acid in acetonitrile, methanol, and 5mM ammonium acetate plus 0.1% formic acid in water. Software solutions empower users to acquire and analyze their own data. A vendor-neutral Open Access instrument control platform, Remote Analyzer from SpectralWorks, allows users to queue samples by choosing from a menu of established methods. Users have several options for data processing: vendor-neutral software from MesReNova and Protein Metrics, and instrument-specific software on computers at the core. Our poster demonstrates the diversity of applications supported by this platform, including method parameters with example chromatograms and spectra for each of the four columns. Maximizing flexibility in this manner maximizes the utility of existing instrumentation for a broader user base.