While mass accuracy is important, the repeatability (precision) of the measurement is important for defensible measurements. The repeatability can be affected by ion numbers in the ion trap, which is difficult to control for real-world measurements. For example, the shot-to-shot repeatability of a laser affects the ionization during a MALDI measurement as does the spatial homogeneity of a MALDI sample. In an LC/ESI measurement, ion population varies with sample concentrations in the mixture as well as the innate temporal variation due to the chromatography. The solution is to always have an internal mass reference present during a measurement, however, chemistry often complicates or limits what can be mixed into a sample.
We report a novel instrument geometry where two different ionization techniques can generate ions simultaneously. One generates the analyte ions and the other generates the mass reference ions to allow high precision, accurate mass measurements to be made with an internal mass reference. Several examples will be presented with MALDI and ESI that demonstrate the capabilities, flexibility, and the limits of this approach.