Charge Detection Mass Spectrometry (CD-MS), quantifies the charge on an individual ion and, from a velocity measurement of each electrostatically accelerated ion, also determines its mass-to-charge ratio. Together these measurements allow a calculation of the mass for a highly charged ion. CD-MS extends the reach of mass spectrometry into the giga Dalton regime. It also allows the analysis of very heterogeneous samples. Mixtures of high mass species confound conventional MS methods because of large number of charge states and frequently show a distribution of masses due to inherent heterogeneity, incomplete dehydration, or residual salt ions. Single pass CD-MS measurements are fast but inaccurate while ion trap CD-MS is slow but much more accurate. Linear array CD-MS lies in between in terms of accuracy and speed. Along with the technological developments of the last few years, there has been an increase in the breadth of application. There are many examples now of the value of CD-MS in obtaining information that cannot be obtained by conventional MS or by any other technique. The applications can be divided into two main groups: applications where the goal is to determine the mass distribution of a very heterogeneous sample (e.g., polymers, nanoparticles, and amyloid fibrils) and applications where the goal is to determine stoichiometry (e.g., assemblies, protein complexes, viruses, and virus assembly intermediates). If the accuracy of the mass measurement is not paramount then single pass CD-MS could be used, although linear array CD-MS or ion trap CDMS with a short trap time would be much efficient.
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