Quantification and Compensation of Nonspecific Analyte Aggregation in Electrospray Sampling

Electrospray (ES) sources are commonly used to introduce nonvolatile materials (e.g., nanoparticles, proteins, etc.) to the gas phase for characterization by mass spectrometry or ion mobility. Recent studies in our group using ES ion mobility to characterize protein aggregation in solution have raised the question as to whether the ES itself induces aggregation and thus corrupts the results. In this article, we develop a statistical model to determine the extent to which the ES process induces the formation of dimers and higher-order aggregates. The model is validated through ES differentialmobility experiments using gold nanoparticles. The results show that the extent of droplet-induced aggregation is quite severe and previously reported cutoff criterion is inadequate. We use the model in conjunction with experiment to show the true dimer concentration in a protein solution as a function of concentration. Themodel is extendable to any ES source analytical system and to higher aggregation states. For users only interested in implementation of the theory, we provide a section that summarizes the relevant formulas.