Tandem mass spectrometry, also known as MS/MS or MS2, is a technique in instrumental analysis where two or more stages of analysis using one or more mass analyzer are performed with an additional reaction step in between these analyses to increase their abilities to analyse chemical samples. A common use of tandem MS is the analysis of biomolecules, such as proteins and peptides.
Electron-capture dissociation (ECD) is a method of fragmenting gas-phase ions for structure elucidation of peptides and proteins in tandem mass spectrometry. It is one of the most widely used techniques for activation and dissociation of mass selected precursor ion in MS/MS. It involves the direct introduction of low-energy electrons to trapped gas-phase ions.
Klaus Biemann was an Austrian-American professor of chemistry at the Massachusetts Institute of Technology. His work centered on structural analysis in organic and biochemistry. He has been called the "father of organic mass spectrometry" but was particularly noted for his role in advancing protein sequencing with tandem mass spectrometry following pioneering work conducted in this area by Michael Barber.
Electron-transfer dissociation (ETD) is a method of fragmenting multiply-charged gaseous macromolecules in a mass spectrometer between the stages of tandem mass spectrometry (MS/MS). Similar to electron-capture dissociation, ETD induces fragmentation of large, multiply-charged cations by transferring electrons to them. ETD is used extensively with polymers and biological molecules such as proteins and peptides for sequence analysis. Transferring an electron causes peptide backbone cleavage into c- and z-ions while leaving labile post translational modifications (PTM) intact. The technique only works well for higher charge state peptide or polymer ions (z>2). However, relative to collision-induced dissociation (CID), ETD is advantageous for the fragmentation of longer peptides or even entire proteins. This makes the technique important for top-down proteomics. The method was developed by Hunt and coworkers at the University of Virginia.
Top-down proteomics is a method of protein identification that either uses an ion trapping mass spectrometer to store an isolated protein ion for mass measurement and tandem mass spectrometry (MS/MS) analysis or other protein purification methods such as two-dimensional gel electrophoresis in conjunction with MS/MS. Top-down proteomics is capable of identifying and quantitating unique proteoforms through the analysis of intact proteins. The name is derived from the similar approach to DNA sequencing. During mass spectrometry intact proteins are typically ionized by electrospray ionization and trapped in a Fourier transform ion cyclotron resonance, quadrupole ion trap or Orbitrap mass spectrometer. Fragmentation for tandem mass spectrometry is accomplished by electron-capture dissociation or electron-transfer dissociation. Effective fractionation is critical for sample handling before mass-spectrometry-based proteomics. Proteome analysis routinely involves digesting intact proteins followed by inferred protein identification using mass spectrometry (MS). Top-down MS (non-gel) proteomics interrogates protein structure through measurement of an intact mass followed by direct ion dissociation in the gas phase.
Robert Graham Cooks is the Henry Bohn Hass Distinguished Professor of Chemistry in the Aston Laboratories for Mass Spectrometry at Purdue University. He is an ISI Highly Cited Chemist, with over 1,000 publications and an H-index of 144.
Fred Warren McLafferty was an American chemist known for his work in mass spectrometry. He is best known for the McLafferty rearrangement reaction that was observed with mass spectrometry. With Roland Gohlke, he pioneered the technique of gas chromatography–mass spectrometry. He is also known for electron-capture dissociation, a method of fragmenting gas-phase ions.
Christie G. Enke is a United States academic chemist who made pioneering contributions to the field of analytical chemistry.
David E. Clemmer is an analytical chemist and the Distinguished Professor and Robert and Marjorie Mann Chair of Chemistry at Indiana University in Bloomington, Indiana, where he leads the Clemmer Group. Clemmer develops new scientific instruments for ion mobility mass spectrometry (IMS/MS), including the first instrument for nested ion-mobility time-of-flight mass spectrometry. He has received a number of awards, including the Biemann Medal in 2006 "for his pioneering contributions to the integration of ion mobility separations with a variety of mass spectrometry technologies."
In mass spectrometry, fragmentation is the dissociation of energetically unstable molecular ions formed from passing the molecules mass spectrum. These reactions are well documented over the decades and fragmentation patterns are useful to determine the molar weight and structural information of unknown molecules. Fragmentation that occurs in tandem mass spectrometry experiments has been a recent focus of research, because this data helps facilitate the identification of molecules.
Joshua Coon is a professor of chemistry and biomolecular chemistry and the inaugural holder of the Thomas and Margaret Pyle Chair at the University of Wisconsin–Madison, and an affiliate of the Morgridge Institute for Research.
Roman A. Zubarev is a professor of medicinal proteomics in the Department of Medical Biochemistry and Biophysics at the Karolinska Institutet. His research focuses on the use of mass spectrometry in biology and medicine.
Albert J.R. Heck is a Dutch scientist and professor at Utrecht University, the Netherlands in the field of mass spectrometry and proteomics. He is known for his work on technologies to study proteins in their natural environment, with the aim to understand their biological function. Albert Heck was awarded the Spinoza Prize in 2017, the highest scientific award in the Netherlands.
Richard Dale Smith is a chemist and a Battelle Fellow and chief scientist within the biological sciences division, as well as the director of proteomics research at the Pacific Northwest National Laboratory (PNNL). Smith is also director of the NIH Proteomics Research Resource for Integrative Biology, an adjunct faculty member in the chemistry departments at Washington State University and the University of Utah, and an affiliate faculty member at the University of Idaho and the Department of Molecular Microbiology & Immunology, Oregon Health & Science University. He is the author or co-author of approximately 1100 peer-reviewed publications and has been awarded 70 US patents.
Jennifer S. Brodbelt is an American chemist known for her research using mass spectrometry to characterize organic compounds, especially biopolymers and proteins.
Kristina Håkansson is an analytical chemist known for her contribution in Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry for biomolecular identification and structural characterization. Currently, she holds the position of Professor of Chemistry at University of Michigan. Her research focuses on mass spectrometry, primarily identification and characterization of protein posttranslational modifications by complementary fragmentation techniques such as electron-capture dissociation (ECD)/negative ion ECD (niECD) and infrared multiphoton dissociation (IRMPD) at low (femtomole) levels.
Vicki Wysocki is an American scientist. She is a professor and an Ohio Eminent Scholar at Ohio State University, and also the director of the Campus Chemical Instrument Center.
Ying Ge is a Chinese-American chemist who is a Professor of Cell and Regenerative Biology at the University of Wisconsin–Madison. Her research considers the molecular mechanisms that underpin cardiac disease. She has previously served on the board of directors of the American Society for Mass Spectrometry. In 2020 Ge was named on the Analytical Scientist Power List.
Catherine E. Costello is the William Fairfield Warren distinguished professor in the department of biochemistry, Cell Biology and Genomics, and the director of the Center for Biomedical Mass Spectrometry at the Boston University School of Medicine.
Helen Jill Cooper is a British chemist who is Professor of mass spectrometry at the University of Birmingham. She serves as Deputy Head of the School of Chemistry and holds an Engineering and Physical Sciences Research Council Established Career Fellowship. Her research considers the development of native ambient mass spectrometry to enable direct analysis of intact proteins and protein assemblies from tissue.
