MAXTOF: An efficient calculation tool for precise optimization of MALDI-TOF MS measurements in real time

An efficient calculation tool for rigorously optimizing the instrument parameters of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is demonstrated in this work. Optimization of MALDI-TOF MS has been an experience-based, time-consuming process without a rigorous theoretical principle. Based on the comprehensive calculation model reported previously, we developed a software tool, MAXTOF, to rapidly determine instrument parameters providing ultimate mass resolving power (MRP). The software conducts big data analysis of most instrument parameters to predict the MRP, including instrument dimensions, voltages, mass-to-charge ratio of ions, and ion extraction delay. It can complete the calculation in seconds, providing parameters that serve as the starting point for subsequent optimization that greatly accelerates the optimization process. Experimental validation using a commercial instrument demonstrates MAXTOF's efficacy in predicting optimal parameters and enhancing MRP. The predicted ion extraction delays for bradykinin fragment, P₁₄R polypeptide, and insulin chain B ions were within 5% of the values observed through long-term optimization. The observed MRP of those ions ranged from 2800 to 4500. Results show that the method and software are highly advantageous for fast and precise measurements.