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

Area of Science:

• Analytical Chemistry
• Biophysics
• Mass Spectrometry

Background:

• Charge detection mass spectrometry (CDMS) is a single-particle technique for determining mass distributions.
• Conventional CDMS using an electrostatic linear ion trap (ELIT) has limited sensitivity due to low ion trapping efficiency.
• Most ions (>99.8%) in a continuous beam are lost in standard ELIT configurations.

Purpose of the Study:

• To improve the sensitivity of CDMS for analyzing heterogeneous and high-mass samples.
• To enable the analysis of lower titer samples by increasing ion trapping efficiency.
• To develop a pulsed mode of operation for CDMS.

Main Methods:

• Implementation of an ion storage scheme using a hexapole to accumulate and store ions.
• Pulsed injection of ions from the hexapole into the ELIT.
• Time-of-flight separation of ions based on mass-to-charge ratio (m/z) during transit from hexapole to ELIT.

Main Results:

• Achieved a >2 orders of magnitude increase in CDMS sensitivity.
• Demonstrated a limit of detection of 3.3 × 10^8 particles/mL for hepatitis B virus T=4 capsids using a 1.3 μL sample.
• Enabled selective trapping of specific m/z windows by varying ion release delay times.

Conclusions:

• The developed pulsed ion storage method significantly enhances CDMS sensitivity and analytical capabilities.
• This advancement allows for the characterization of previously inaccessible low-titer biological samples.
• The time-dispersion technique offers a novel approach for m/z selection in CDMS.