Charge Detection Mass Spectrometry: frequently asked questions

Charge Detection Mass Spectrometry measures mass-to-charge ratio (m/z) and electrical charge for individual ions. The two measured values are combined to calculate the intact mass of each detected ion.

A mass spectrometer measures m/z rather than mass alone. Charge is therefore required to recover molecular mass. For very large or heterogeneous ions, conventional charge-state distributions can become broad or difficult to resolve. Measuring charge directly reduces the dependence on assigning those charge states first.

Conventional mass spectrometry usually recovers molecular mass by resolving or deconvoluting charge states from the m/z spectrum. CDMS measures charge for individual ions and calculates the mass of each ion separately, producing a population of individual mass measurements.

A CDMS experiment produces many individual-ion mass measurements. These can be displayed as a mass distribution or histogram, allowing different populations, the width of a distribution and unexpected high-mass species to be investigated.

Across the field, CDMS is being explored for AAV and other viral vectors, lipid nanoparticles, extracellular vesicles, virus-like particles, large protein complexes, macromolecular assemblies and other high-mass, heterogeneous systems.

No. AAV is an important application area, but the underlying measurement is relevant more broadly wherever individual-ion intact mass or population-level information can add value.

No. These techniques provide different types of information. CDMS adds individual-ion charge and intact mass measurements and is often most useful as part of an orthogonal analytical strategy.

CDMS mass distributions can be compared across samples when the analytical workflow is appropriate. The useful question may be whether a population shifts, broadens or changes after a process, formulation or storage condition.

No. Sample quality, concentration, buffer composition, ionisation behaviour, expected mass range and heterogeneity all influence whether a useful measurement can be made.

The sample type, expected mass range if known, buffer or formulation, the methods already being used and the scientific question you are trying to answer are useful starting points.

Start with the What is CDMS? page for the measurement principle, then contact TrueMass if you want to discuss whether the technique is relevant to a particular analytical question.