# Multiplexed Charge Detection Mass Spectrometer for Extended Mass and Collisional Cross Section Measurements

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2020 · $517,350

## Abstract

Project Summary
Large biomolecular assemblies constitute much of the molecular machinery necessary for
cellular function. These assemblies are often the target of a host of therapeutic molecules.
Other large biomolecular assemblies, including virus-like particles, proteinaceous cellular
compartments, and some large synthetic polymers, are potential delivery agents for these
therapeutics. The large molecules and molecular assemblies involved in cellular function can be
challenging to analyze using conventional mass spectrometry methods owing to their high mass
(>MDa) and heterogeneity. Electrospray ionization can transfer intact large
molecules/complexes into the gas phase, but overlapping and unresolved charge states that
stem from the heterogeneity inherent to high mass analytes often prevent mass measurements
using conventional mass spectrometers. Charge detection mass spectrometry weighs individual
ions, avoiding these interferences between ions and can be used to analyze molecules with
masses well above 100 MDa. However, this method can be slow because only one ion is
analyzed at a time. Here, a new generation of charge detection mass spectrometry is proposed
which provides information about the mass, the collisional cross section and the dissociation
pathways of individual ions of large macromolecular complexes, information that cannot be
obtained using conventional instruments. A key innovation is the development of multiplexing
methods that make it possible to simultaneously weigh many individual ions. These methods
have the potential to increase the speed of these measurements by up to 150x and reduce
sample analysis times to less than one minute. This ion multiplexing is aided by a novel
decoupling scheme whereby ions with a controlled range of energies are introduced into the
electrostatic ion detector trap so that two or more ions with the same m/z can have different
frequencies. The mass of each ion can be obtained from simultaneous measurements of the
individual ion frequency, energy, and charge. This scheme significantly reduces the potential for
overlapping ion signal by distributing the signal over a broad frequency bandwidth. The rate of
ion energy change can also be determined from these measurements, providing information
about collisional cross sections and giving insight into molecular shape. Similarly, individual ion
fragmentation events can be tracked and used to obtain additional structural information.

## Key facts

- **NIH application ID:** 10072524
- **Project number:** 1R01GM139338-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Evan R Williams
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $517,350
- **Award type:** 1
- **Project period:** 2020-09-22 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10072524

## Citation

> US National Institutes of Health, RePORTER application 10072524, Multiplexed Charge Detection Mass Spectrometer for Extended Mass and Collisional Cross Section Measurements (1R01GM139338-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10072524. Licensed CC0.

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