Dramatic Improvement in Sensitivity with Pulsed Mode Charge Detection Mass Spectrometry.

Charge detection mass spectrometry (CDMS) is emerging as a valuable tool to determine mass distributions for heterogeneous and high-mass samples. It is a single-particle technique where masses are determined for individual ions from simultaneous measurements of their mass-to-charge ratio (m/z) and charge. Ions are trapped in an electrostatic linear ion trap (ELIT) and oscillate back and forth through a detection cylinder. The trap is open and able to trap ions for a small fraction of the total measurement time so most of the ions (>99.8%) in a continuous ion beam are lost. Here, we implement an ion storage scheme where ions are accumulated and stored in a hexapole and then injected into the ELIT at the right time for them to be trapped. This pulsed mode of operation increases the sensitivity of CDMS by more than 2 orders of magnitude, which allows much lower titer samples to be analyzed. A limit of detection of 3.3 × 108 particles/mL was obtained for hepatitis B virus T = 4 capsids with a 1.3 μL sample. The hexapole where the ions are accumulated and stored is a significant distance from the ion trap so ions are dispersed in time by their m/z values as they travel between the hexapole and the ELIT. By varying the delay time between ion release and trapping, different windows of m/z values can be trapped.