Dynamic Range Expansion by Gas-Phase Ion Fractionation and Enrichment for Imaging Mass Spectrometry

In the analysis of biological tissue by imaging mass spectrometry (IMS), the limit of detection and dynamic range are of paramount importance in obtaining experimental results that provide insight into underlying biological processes. Many important biomolecules are present in the tissue milieu in low concentrations and in complex mixtures with other compounds of widely ranging abundances, challenging the limits of analytical technologies. In many IMS experiments, the ion signal can be dominated by a few highly abundant ion species. On trap-based instrument platforms that accumulate ions prior to mass analysis, these high abundance ions can diminish the detection and dynamic range of lower abundance ions. Herein, we characterize two strategies for combating these challenges during IMS experiments on a hybrid QqFT-ICR MS. In one iteration, the mass resolving capabilities of a quadrupole mass filter are used to selectively enrich for ions of interest via a technique previously termed continuous accumulation of selected ions (CASI). Secondly, we have introduced a supplemental dipolar AC waveform to the quadrupole mass filter of a commercial QqFT-ICR mass spectrometer to perform selected ion ejection prior to the ion accumulation region. This setup allows the selective ejection of the most abundant ion species prior to ion accumulation, thereby greatly improving the molecular depth with which IMS can probe tissue samples.