Mass Spectrometry: Forming Ions, to Identifying Proteins and Their Modifications
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Gas Cluster Ion Beams for Secondary Ion Mass Spectrometry
AC11CH02_Winograd ARI 3 May 2018 15:10 Annual Review of Analytical Chemistry Gas Cluster Ion Beams for Secondary Ion Mass Spectrometry Nicholas Winograd Department of Chemistry, Pennsylvania State University, University Park, Pennsylvania 16802, USA; email: [email protected] Annu. Rev. Anal. Chem. 2018. 11:29–48 Keywords First published as a Review in Advance on bioimaging, cluster ion beams, phospholipids, instrumentation, molecular February 28, 2018 depth profiling, molecular dynamics computer simulations The Annual Review of Analytical Chemistry is online at anchem.annualreviews.org Abstract https://doi.org/10.1146/annurev-anchem- Gas cluster ion beams (GCIBs) provide new opportunities for bioimaging 061516-045249 Annual Rev. Anal. Chem. 2018.11:29-48. Downloaded from www.annualreviews.org and molecular depth profiling with secondary ion mass spectrometry (SIMS). Access provided by Pennsylvania State University on 02/26/19. For personal use only. Copyright c 2018 by Annual Reviews. These beams, consisting of clusters containing thousands of particles, ini- All rights reserved tiate desorption of target molecules with high yield and minimal fragmen- tation. This review emphasizes the unique opportunities for implementing these sources, especially for bioimaging applications. Theoretical aspects of ANNUAL REVIEWS Further the cluster ion/solid interaction are developed to maximize conditions for Click here to view this article's online features: successful mass spectrometry. In addition, the history of how GCIBs have • Download figures as PPT slides become practical laboratory tools is reviewed. Special emphasis is placed on • Navigate linked references • Download citations the versatility of these sources, as size, kinetic energy, and chemical compo- • Explore related articles • Search keywords sition can be varied easily to maximize lateral resolution, hopefully to less than 1 micron, and to maximize ionization efficiency. -
Tandem Mass Spectrometry (MS–MS)
Advanced Analytical Chemistry Lecture 22 Chem 4631 Tandem Mass Spectrometry (MS–MS) Tandem mass spectrometry (MS–MS) is a term which covers a number of techniques where one stage of mass spectrometry (not necessarily the first) is used to isolate an ion of interest and a second stage is then used to probe the relationship of this ion with others from which it may have been generated or which it may generate on decomposition. Chem 5570 Tandem Mass Spectrometry (MS–MS) Chem 5570 The two analyzers (MS-MS) can be separated by a collision cell (can be another MS) into which an inert gas (e.g. argon, xenon) is admitted to collide with the selected sample ions and bring about their fragmentation. Tandem MS have the ability to perform multiple steps on a single sample. The MS selects a specific ion, fragment the ion, and generate another mass spec – able to repeat the cycle several times. Chem 5570 The analyzers can be of the same or of different types, the most common combinations being: quadrupole - quadrupole magnetic sector - quadrupole magnetic sector - magnetic sector quadrupole - time-of-flight Fragmentation experiments can also be performed on certain single analyzer mass spectrometers such as ion trap and time-of-flight instruments, the latter type using a post-source decay experiment to effect the fragmentation of sample ions. Chem 5570 Tandem Mass Spectrometry (MS–MS) TIC - Total ion current or total ion chromatogram The TIC represents the sum of all signal intensities of a single scan spectrum. The TIC is usually calculated by the data system of the mass spectrometer and plotted against time or scan number to give a measure for evaporation/ionization of a sample over the duration of the whole measurement. -
Front-End Methods for Enhancing the Analytical Power of Mass Spectrometry
FRONT-END METHODS FOR ENHANCING THE ANALYTICAL POWER OF MASS SPECTROMETRY PETER PAUL LIUNI A DISSERTAITON SUBMITTED TO THE FACULTY OF GRADUATE STUDIES IN PARTIAL FUFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY GRADUATE PROGRAM IN CHEMISTRY YORK UNIVERSITY TORONTO, ONTARIO December 2015 © Peter Paul Liuni, 2015 Abstract The analytical power and versatility of mass spectrometry can be enhanced by adding ‘front-end’ devices, which provide additional functionality before, during or immediately after ElectroSpray Ionization (ESI). Such devices can include Ion mobility spectrometry (IMS) and Time-Resolved ElectroSpray Ionization (TRESI) which provide enhanced analysis of illicit compounds, protein folding, enzyme kinetics, and catalysis-linked dynamics. With respect to IMS, this work describes implementation of a hybrid Trace Compound Detector (TCD) system that combines IMS and MS to allow for rapid front- end mobility separation, followed by characterization and identification of analytical markers of seized opium by mass spectrometry. Ultimately, this device provides an avenue for rapid prosecution based on simultaneous detection and unambiguous identification of illicit drugs. TRESI is used to extend Mass Spectrometry (MS) to millisecond-timescale reaction studies. In the first instance, we combine TRESI with Travelling Wave Ion Mobility Spectrometry (TWIMS) to compare equilibrium and kinetic unfolding intermediates of cytochrome c, showing a high degree of correlation between all species populated under these substantially different regimes. We then combine TRESI with Hydrogen Deuterium Exchange (TRESI-HDX) to elucidate the relationship between structural fluctuations (conformational dynamics) of enzymes and their catalytic activity. The results of this work include a new model for catalysis-linked dynamics, in which the nature of the conformational landscape explored by an enzyme is independent of catalysis, but the rate at which the landscape is explored is enhanced for catalytically active species. -
20.5 Ion Detectors
20.5 Ion Detectors • the Faraday cup neutralizes ions to provide a high-precision measurement • the electron multiplier generates a pulse of current for each ion • the photon multiplier uses conversion dynodes to monitor both positive and negative ions • the two multipliers are capable of fast measurements, thus compatible with TOF or Fourier transform methods 20.5 : 1/4 Faraday Cup slit Ions exiting the analyzer are slowed by Faraday cup a positive potential and impact the ion + grounded electrode. At the electrode beam + they are __________ by electrons that RL travel through the load resistor. This ion suppressor causes a voltage across the load resistor that is measured by a high input impedance voltmeter. The impacted electrode is at an angle so that any secondary ions that are created are _____________ by the grounded wall. Of all ion detectors, the Faraday cup provides the most precise relationship between the number of ions exiting the analyzer and the electrical measurement. It is used in __________ experiments such as isotope dilution. Because very small currents are measured, the Faraday cup cannot be used for experiments involving rapid scanning. 20.5 : 2/4 Electron Multiplier ion beam An electron multiplier is constructed just like a photomultiplier but without 16e- 4e- 3 - a _______________. It has dynodes 10 e RL constructed from a Cu/Be alloy, which dynodes is a good secondary electron emitter. +V The dynode potentials are such that the first is grounded and each subsequent one is 100 V more positive. This makes the voltage measurement a little tricky because one end of the load resistor is connected to positive _____________. -
Modern Mass Spectrometry
Modern Mass Spectrometry MacMillan Group Meeting 2005 Sandra Lee Key References: E. Uggerud, S. Petrie, D. K. Bohme, F. Turecek, D. Schröder, H. Schwarz, D. Plattner, T. Wyttenbach, M. T. Bowers, P. B. Armentrout, S. A. Truger, T. Junker, G. Suizdak, Mark Brönstrup. Topics in Current Chemistry: Modern Mass Spectroscopy, pp. 1-302, 225. Springer-Verlag, Berlin, 2003. Current Topics in Organic Chemistry 2003, 15, 1503-1624 1 The Basics of Mass Spectroscopy ! Purpose Mass spectrometers use the difference in mass-to-charge ratio (m/z) of ionized atoms or molecules to separate them. Therefore, mass spectroscopy allows quantitation of atoms or molecules and provides structural information by the identification of distinctive fragmentation patterns. The general operation of a mass spectrometer is: "1. " create gas-phase ions "2. " separate the ions in space or time based on their mass-to-charge ratio "3. " measure the quantity of ions of each mass-to-charge ratio Ionization sources ! Instrumentation Chemical Ionisation (CI) Atmospheric Pressure CI!(APCI) Electron Impact!(EI) Electrospray Ionization!(ESI) SORTING DETECTION IONIZATION OF IONS OF IONS Fast Atom Bombardment (FAB) Field Desorption/Field Ionisation (FD/FI) Matrix Assisted Laser Desorption gaseous mass ion Ionisation!(MALDI) ion source analyzer transducer Thermospray Ionisation (TI) Analyzers quadrupoles vacuum signal Time-of-Flight (TOF) pump processor magnetic sectors 10-5– 10-8 torr Fourier transform and quadrupole ion traps inlet Detectors mass electron multiplier spectrum Faraday cup Ionization Sources: Classical Methods ! Electron Impact Ionization A beam of electrons passes through a gas-phase sample and collides with neutral analyte molcules (M) to produce a positively charged ion or a fragment ion. -
Novel Quadrupole Time-Of-Flight Mass Spectrometry for Shotgun Proteomics
DISSERTATION ZUR ERLANGUNG DES DOKTORGRADES DER FAKULTÄT FÜR CHEMIE UND PHARMAZIE DER LUDWIG-MAXIMILIANS-UNIVERSITÄT MÜNCHEN Novel quadrupole time-of-flight mass spectrometry for shotgun proteomics von Scarlet Svenja Anna-Maria Beck aus Tettnang 2016 ii Erklärung Diese Dissertation wurde im Sinne von §7 der Promotionsordnung vom 28. November 2011 von Herrn Prof. Dr. Matthias Mann betreut. Eidesstattliche Versicherung Diese Dissertation wurde eigenständig und ohne unerlaubte Hilfe erarbeitet. München, den 25.04.2017 …………………………………………………………………………………………Scarlet Beck Dissertation eingereicht am 23.09.2016 1. Gutachter: Prof. Dr. Matthias Mann 2. Gutachter: Prof. Dr. Jürgen Cox Mündliche Prüfung am 04.11.2016 iii iv ABSTRACT Mass spectrometry (MS)-based proteomics has become a powerful technology for the identification and quantification of thousands of proteins. However, the coverage of complete proteomes is still very challenging due to the high sample complexity and the difference in protein concentrations. In data-dependent shotgun proteomics several peptides elute simultaneously from the column and are isolated by the quadrupole and fragmented by the collision cell one at a time. This method has two major disadvantages. On the one hand, a large number of eluting peptides cannot be targeted since the sequencing speeds of current instruments are too slow and on the other hand, peptides that only differ slightly in mass and elute together are co-isolated and co-fragmented, resulting in chimeric MS2 spectra. Therefore an urgent need for further developments and improvements of mass spectrometers remains. The aim of this thesis was to co-develop, evaluate and improve novel quadrupole time-of-flight (QTOF) mass spectrometers. In my first project I have described the developments and improvements of the hardware of the high-resolution QTOF mass spectrometer, the impact II, and have shown that this instrument can be used for very deep coverage of diverse proteomes as well as for accurate and reproducible quantification. -
Basics of Ion Traps
Basics of Ion Traps G. Werth Johannes Gutenberg University Mainz Why trapping? „A single trapped particle floating forever at rest in free space would be the ideal object for precision measurements“ (H.Dehmelt) Ion traps provide the closest approximation to this ideal Pioneers of ion trapping: Hans Dehmelt and Wolfgang Paul (Nobel price 1989) Trapping of charged particles by electromagnetic fields Required : 3-dimensional force towards center F = - e grad U Convenience: harmonic force F ∝∝∝ x,y,z →→→ U = ax 2 +by 2 + cz 2 Laplace equ.: ∆∆∆(eU) = 0 →→→ a,b,c can not be all positive Convenience: rotational symmetry →→→ 2 2 2 2 U = (U 0/r 0 )(x +y -2z ) Quadrupole potential Equipotentials: Hyperboloids of revolution Problem: No 3-dimensional potential minimum because of different sign of the coefficients in the quadrupole potential Solutions: • Application of r.f. voltage: dynamical trapping Paul trap • d.c. voltage + magnetic field in z-direction: Penning trap The ideal 3-dimensional Paul trap Electrode configuration for Paul traps Paul trap of 1 cm diameter (Univ. of Mainz) Wire trap with transparent electrodes (UBC Vancouver) Stability in 3 dimension when radial and axial domains overlap First stable region of a Paul trap solution of the equation of motion: ∞ u t)( = A∑c2n cos(β + 2n)(Ωt )2/ n=0 β = β ( a , q ) c 2 n = f ( a , q ) Approximate solution for a,q<<1: u(t) = A 1[ − (q )2/ cos ωt]cos Ωt ω=β/2Ω βββ2 = a + q 2/2 This is a harmonic oscillation at frequency ΩΩΩ (micromotion ) modulated by an oscillation at frequency ωωω (macromotion -
Early History of Charged-Particle Traps
Appendix A Early History of Charged-Particle Traps Abstract Today, we see a broad variety of particle traps and related devices for confinement and study of charged particles in various fields of science and indus- try (Werth, Charged Particle Traps, Springer, Heidelberg; Werth, Charged Particle Traps II, Springer, Heidelberg; Ghosh, Ion Traps, Oxford University Press, Oxford; Stafford, Am Soc Mass Spectrom. 13(6):589). The multitude of realisations and applications of electromagnetic confinement cannot be easily overlooked as the vari- ability of particle confinement and the vast number of experimental techniques avail- able has allowed traps and related instrumentation to enter many different fields in physics and chemistry as well as in industrial processes and applied analysis, mainly in the form of mass spectrometry (Stafford, Am Soc Mass Spectrom. 13(6):589; March and Todd, Practical Aspects of Ion Trap Mass Spectometry, CRC Press, Boca Raton). Here, we would like to give a brief account of the main historical aspects of charged-particle confinement, of the principles, technical foundations and beginnings that led to the realisation of traps and to the 1989 Nobel Prize in Physics awarded to Hans Georg Dehmelt and Wolfgang Paul ‘for the invention of the ion trap technique’, at which point we choose to end our discussion. Mainly, we will look at the work of the people who pioneered the field and paved the way to the first working traps. These can be seen as belonging to two different families of traps, Penning traps and Paul traps, each of these families nowadays with numerous variations of the respective confinement concepts. -
A Transportable Antiproton Trap to Unlock the Secrets of Antimatter 4 November 2020, by Ana Lopes
A transportable antiproton trap to unlock the secrets of antimatter 4 November 2020, by Ana Lopes antimatter, but this difference is insufficient to explain the imbalance, prompting researchers to look for other, as-yet-unseen differences between the two forms of matter. This is exactly what the teams behind BASE and other experiments located at CERN's AD hall are trying to do. BASE, in particular, investigates the properties of antiprotons, the antiparticles of protons. It first takes antiprotons produced at the AD—the only place in the world where antiprotons are created daily– and then stores them in a device called a Penning trap, which holds the particles in place with a The layout of the transportable antiproton trap that BASE combination of electric and magnetic fields. Next, is developing. The device features a first trap for BASE feeds the antiprotons one by one into a multi- injection and ejection of the antiprotons produced at Penning-trap set-up to measure two frequencies, CERN’s Antiproton Decelerator, and a second trap for from which the properties of antiprotons such as storing the antiprotons. Credit: Christian Smorra their magnetic moment can be deduced and then compared with that of protons. These frequencies are the cyclotron frequency, which describes a The BASE collaboration at CERN has bagged charged particle's oscillation in a magnetic field, more than one first in antimatter research. For and the Larmor frequency, which describes the so- example, it made the first ever more precise called precessional motion in the trap of the measurement for antimatter than for matter, it kept intrinsic spin of the particle. -
Devices for Mass Spectrometry on a Chip
DEVICES FOR MASS SPECTROMETRY ON A CHIP Title: Professor Name: Richard R.A.Syms Affiliation/Address: EEE Dept., Imperial College London Phone: +44-207-594-6203 E-mail: [email protected] Devices for mass spectrometry on a chip Synonyms Mass spectrometer, mass analyser Definition A mass spectrometer is a vacuum analytical instrument that uses electric or magnetic fields or a mixture of the two to separate ions based on the ratio of their mass m to their charge q. A distinction is made between mass spectrometers, which produce a serially scanned output, and mass spectrographs, which produce a parallel (and sometimes graphical) output. The mass-to charge ratio is often written as m/z, where q = ze, e = 1.6 x 10-19 C is the electronic charge and z is the charge number. The ions are created from analyte molecules by processes that give rise to a characteristic pattern of fragments, in addition to the molecular ion itself, allowing a mass spectrometer to be used for chemical identification, compositional quantification and structural analysis. Performance is characterized in terms of the mass range (defined by the maximum mass mmax that can be measured), the mass resolution (defined as m/∆m, where ∆m is the uncertainty in the mass being measured) and the PAGE 1/25 DEVICES FOR MASS SPECTROMETRY ON A CHIP sensitivity. Applications include analytical chemistry, process and pollution monitoring, forensic science, the detection of drugs, chemical and biochemical weapons, and space exploration. In some cases, high performance is essential, while in others, low cost, small size, and portability are more desirable. -
(12) United States Patent (10) Patent No.: US 6,958,472 B2 Zubarev (45) Date of Patent: Oct
USOO6958472B2 (12) United States Patent (10) Patent No.: US 6,958,472 B2 Zubarev (45) Date of Patent: Oct. 25, 2005 (54) MASS SPECTROMETRY METHODS USING 4,988,869 A 1/1991 Aberth ELECTRON CAPTURE BY ONS 5,340,983 A 8/1994 Deinzer et al. 5,374,828 A 12/1994 Boumseek et al. (75) Inventor: Roman Zubarev, Uppsala (SE) 5,493,115 A * 2/1996 Deinzer et al. ............. 250/281 6,653,622 B2 * 11/2003 Franzen ............ ... 250/282 (73) Assignee: Syddansk Universitet, Odense (DK) 2003/0183760 A1 * 10/2003 Tsybin et al. ............... 250/292 (*) Notice: Subject to any disclaimer, the term of this OTHER PUBLICATIONS patent is extended or adjusted under 35 R. W. Vachet et al., “Novel Peptide Dissociation: Gas-Phase U.S.C. 154(b) by 0 days. Intramolecular Rearrangement of Internal Amino Acid Resi (21) Appl. No.: 10/471.454 dues”, Jun. 18, 1997, pp. 5481-5488, Journal of the Ameri can Chemical Society, vol. 119, No. 24. (22) PCT Filed: Mar. 22, 2002 (86) PCT No.: PCT/DK02/00195 (Continued) S371 (c)(1), Primary Examiner John R. Lee (2), (4) Date: Apr. 2, 2004 ASSistant Examiner Zia R. Hashmi (74) Attorney, Agent, or Firm-Harness, Dickey & Pierce, (87) PCT Pub. No.: WO02/078048 PLC PCT Pub. Date: Oct. 3, 2002 (57) ABSTRACT (65) Prior Publication Data Methods and apparatus are provided to obtain efficient US 2004/015.5180 A1 Aug. 12, 2004 Electron capture dissociation (ECD) of positive ions, par ticularly useful in the mass Spectrometric analysis of com Related U.S. Application Data plex Samples Such as of complex mixtures and large bio (60) Provisional application No. -
Analytical Chemistry, Strategic Exercise: Organic Aerosol Analysis
WIR SCHAFFEN WISSEN –HEUTE FÜR MORGEN Analytical Chemistry, Strategic exercise: Organic aerosol analysis Urs Baltensperger Laboratory of Atmospheric Chemistry, Paul Scherrer Institute, Villigen , Switzerland ETHZ, HS 2020, 8.12.2020 Aerosol size distribution, and sources and sinks Chemical composition of PM1 in Zurich in winter Energiespiegel 19/2008 http://gabe.web.psi.ch/pdfs/Energiespiegel_19_e.pdf Today’s task: Organic aerosol analysis Page 4 The state of the art in 2009 Hallquist et al., ACP 2009 Traditional methods can identify only a fraction of organics Rogge et al., 1993 Most detailed analysis performed with off-line methods: More than 10‘000 different organic compounds isolated with GCxGC-TOF/MS Hamilton et al., 2004 NB: isolated ≠ identified…. Besides extraction, also thermal desorption is applied: TAG (Goldstein et al., 2008) Organic acids formed in the photooxidation of -pinene All acids found in aerosol phase. Some of them are highly volatile (e.g., formic, acetic acid) and not expected to be there. Probably hydrolysis of oligomers Fisseha et al., Anal. Chem. 2004 Developments since 2009 EESI CHARON‐ PTRMS FIGAERO -I-CIMS Adapted from Hallquist et al., 2009 9 Required for mass spectrometry: ionization of individual molecules • For gas phase: relatively easy (avoid fragmentation, clustering) • For aerosol particles: Much more difficult: either dissolution in a solvent or evaporation - Problem with dissolution: only the soluble fraction accessible - Problem with evaporation: fragmentation Page 10 What is Mass Spectrometry