Overview
FrançaisABSTRACT
Charge detection mass spectrometry CDMS is a single molecule method where the mass of each ion is directly determined from measurements of its mass-to-charge ratio and charge. CDMS is particularly valuable for the analysis of high mass and heterogeneous analytes. Since last 2000 years, CDMS has received a renaissance. Technical developments have dramatically improved both mass resolution and mass accuracy. CDMS has conquered the nanoworld. In this article, the principles and three main modes of operation of CDMS and its couplings are described. And finally, an overview of recent applications will be given.
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Read the articleAUTHOR
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Rodolphe ANTOINE: CNRS Research Director, Institut Lumière Matière, UMR5306 CNRS, Université Claude Bernard Lyon 1
INTRODUCTION
Mass spectrometry (MS) is an essential analytical tool for characterizing and identifying molecules. The separation of previously ionized molecules from a sample according to their mass-to-charge ratio (m/z) relies on the action of an electromagnetic field. Conventional mass spectrometers generally provide an m/z spectrum from which the charge state(s) z of a compound of given mass m can be identified. The mass m of the compound is determined from this spectral analysis. Conventional mass spectrometers are well suited to the analysis of molecules with well-defined masses ranging from a few tens of daltons (Da) up to a few tens of kilodaltons (kDa), covering in particular the field of peptide and small protein analysis, for which the electrospray ionization (ESI) technique producing highly charged ions is particularly well suited. On the other hand, if we consider a sample made up of higher mass molecules, typically from the megadalton (MDa) upwards, spectrum resolution becomes impossible. A mass limit measurable by conventional ESI-MS techniques has been established at around 20 MDa. For species that are intrinsically heterogeneous, this limit is considerably lower. This is because charge states become higher, more numerous and closer together on the spectrum. In addition, the heterogeneity of the ions studied increases with mass, due to the presence of co-adsorbed species (water molecules, counter-ions and other adducts). Finally, the study of intrinsically polydisperse samples such as synthetic polymers or nanoparticles is an additional barrier to the m/z resolution of this type of spectra.
So there's a mass range that conventional MS techniques don't cover. And within this range lie, to a large extent, the masses of compounds or objects (whether natural or man-made) belonging to the "nanoworld". It therefore seems important to fill this analytical "gap" in mass determination.
Based on charge-image detection of an individual multi-charged ion passing through a conductive tube, charge-detection mass spectrometry simultaneously measures the charge and time of flight (ToF) of each ion in the sample. This single-ion mass spectrometry technique –– extends the field of analysis of conventional mass spectrometry into the "nanoworld" by assessing the polydisperse nature of the sample. The enormous interest of this technique lies in its ability to produce real mass and charge distributions for samples that are, for the most part, highly polydisperse.
A pioneer in the development of this ESI-coupled mass spectrometry technique, W.H. Benner and his collaborators in the USA established proof-of-concept by studying DNA macro-ions or whole viruses with masses ranging from a few MDa to a few tens of MDa. To date, several research teams (mainly in the...
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KEYWORDS
| virus | ion detection
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CDMS – Charge detection mass spectrometry
Bibliography
Bibliography
Patents
Apparatus and method of determining molecular weight of large molecules US5770857A
Charge detection mass spectrometer with multiple detection stages WO2012083031A1
Directory
Start-ups (non-exhaustive list)
Megadalton Solutions, analysis solutions for pharmaceutical companies
Indiana University, JARROLD (M.F.), CLEMMER (D.E.) and DRAPER (B.E.) https://megadaltonsolutions.com
Laboratories developing CDMS instrumentation (non-exhaustive list)
JARROLD (M.F.),...
Software tools
SIMION https://simion.com
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