Multiple Ion Charge Extraction (MICE) for High-Throughput Charge Detection Mass Spectrometry

Area of Science:

• Analytical Chemistry
• Mass Spectrometry
• Physical Chemistry

Background:

• Charge detection mass spectrometry (CD-MS) is a single-particle technique for determining ion mass-to-charge ratio (m/z) and charge.
• Ions are trapped in an electrostatic linear ion trap (ELIT), oscillating and generating signals processed by fast Fourier transforms (FFTs).
• Simultaneous trapping of multiple ions increases throughput but can lead to overlapping oscillation frequencies, causing charge determination errors and biasing relative abundances.

Purpose of the Study:

• To develop a post-processing method to address charge determination errors in CD-MS caused by overlapping ion frequencies.
• To improve the accuracy of relative abundances in mass distributions, particularly for abundant m/z species.
• To enhance the speed and reliability of CD-MS analysis.

Main Methods:

• Development of a statistical post-processing algorithm named Multiple Ion Charge Extraction (MICE).
• MICE assigns charges to ions with overlapping frequencies by recovering single-ion information from high-signal measurements.
• CD-MS measurements were performed using the MICE method to evaluate its performance.

Main Results:

• MICE successfully assigns charges to ions with overlapping frequencies, recovering single-ion information.
• The method makes relative abundances more resilient to signal intensity, correcting for high signal m/z biasing.
• CD-MS measurements achieved rates of 120 ions/s with minimal m/z biasing when using MICE.

Conclusions:

• MICE significantly improves the accuracy and reliability of charge detection mass spectrometry.
• The statistical approach effectively resolves overlapping ion frequencies, preserving accurate relative abundance data.
• MICE enables faster and more robust CD-MS analyses, overcoming limitations of previous methods.