Mass Analyzers Ion movement
Transcription
Mass Analyzers Ion movement
Mass Analyzers Árpád Somogyi CCIC MSP OSU Summer Workshop Ion movement • Biased metal plates (electrodes, lenses) used to move ions between ion source and analyzers • Electrodes and physical slits used to shape and restrict ion beam • Good sensitivity is dependent on good ion transmittance efficiency in this area Mass analyzer Ionization source inlet all ions Detector sorted ions Data system 1 Ion detection • Ions can be detected efficiently w/ high amplification by accelerating them into surfaces that eject electrons Mass analyzer Ionization source inlet all ions Detector sorted ions Data system Detectors TOF 2 Ion energy • Kinetic energy of ions defined by E = zeV = qV = ½ mv2 E = kinetic energy m = mass v = velocity e = electronic charge (1.60217e-19 C) z = nominal charge V = accelerating voltage Learning Check Consider two electrodes, one at 1000 V and one at ground (0 V) 1000 V 0V + ion will travel with kinetic energy of ___________ 3 Question: Consider an ion source block and an extraction lens. How would you bias the block and lens if you want the ions to be accelerated by a) 8000 eV (appropriate for magnetic sector) b) 5 eV (appropriate for entering a quadrupole) c) 20,000 eV (appropriate for entering a TOF) Notice: accelerating voltages vary with analyzer (has consequences for MS/MS) • High voltage (keV energy range) – magnet (B) – electrostatic (E) – time-of-flight (TOF) • Low voltage (eV energy range) – quadrupole (Q) – ion trap (IT, LT, OT) – ion cyclotron resonance (ICR) 4 Mass Resolution • Mass spectrometers separate ions with a defined resolution/resolving power • Resolving power- the ability of a mass spectrometer to separate ions with different mass to charge (m/z) ratios. Example of ultrahigh resolution in an FTICR J. Throck Watson “Introduction to Mass Spectrometry” p. 103 5 Resolution defined at 10% valley M R=M/∆M ∆M General about mass spectrometers • Common features – Accelerated charged species (ions) interact with/can be controlled by • Electrostatic field (ESA, OT) • Magnetic field (B, ICR) • Electromagnetic (rf) fields (Q, IT, LT) – Or ions just fly (TOF) 6 For each of the following applications, choose the most appropriate mass analyzer from the following list. orbitrap (OT) time-of-flight (TOF) quadrupole (Q) FTICR Analyzer Purpose ______ synthetic organic chemist wants exact mass of compound biochemist wants protein molecular weight of relatively large protein (MW 300,000) EPA (Environmental Protection Agency) wants confirmation of benzene in extracts from 3000 soil samples Petroleum chemist wants to confirm the presence of 55 unique compounds at one nominal mass/charge value in a mass spectrum _______ _______ _______ Desirable mass spectrometer characteristics 7 Desirable mass spectrometer characteristics 1) They should sort ions by m/z 2) They should have good transmission (improves sensitivity) 3) They should have appropriate resolution (helps selectivity) 4) They should have appropriate upper m/z limit 5) They should be compatible with source output (pulsed or continuous) Mass spectrometers record m/z values m/z values are determined by actually measuring different physical parameters Type of analyzer • • • • • electric sector magnetic sector quadrupole, ion trap time-of-flight FT-ion cyclotron resonance Physical parameter used as basis for separation • • • • • kinetic energy/z momentum/z m/z flight time m/z (resonance frequencies) 8 Types of Mass Analyzers • Magnetic (B) and/or Electrostatic (E) (HISTORIC/OLDEST) • Time-of-flight (TOF) • Quadrupole (Q) • Quadrupole Ion Trap (IT) • Linear Ion Trap (LT) • Orbitrap • Fourier Transform-Ion Cyclotron Resonance (ICR) Performance Advantages / Disadvantages / $$$ TOF Quadrupole Quadrupole Ion trap FTICR Orbitrap 9 MS and MS/MS Ionization Analysis MS: Collide with target to produce fragments MS/MS: Ionization Selection Activation Analysis http://www.iupac.org/goldbook/T06250.pdf 10 Tandem in Space Triple quadrupole Collisions with gas μsec dissociation Tandem in Time MS/MS T1 T2 T3 Collisions with gas msec dissociation 11 Current popular MS/MS arrangements (2012) Tandem in Space QqQ Q Trap Q TOF TOF TOF LTQ-Orbi (& QExactive) Tandem in Time Ion Trap (2 or 3 D) FT-ICR (FT) Decision factors when choosing a mass spectrometer • Speeeeeeeeeeeeed •R e s o l u t i o n • Sensitivity •D na ic ang y m r e • Co$t 12 Quadrupole TOF Quadrupole Ion trap FTICR Orbitrap Time of Flight m/z V KE = zeV = ½mv2 v = D/t ½m(D/t)2 = zeV t= m 2zeV 1/ 2 Detector D m = mass V = velocity D = distance of flight t = time of flight KE = kinetic energy e = charge D 13 How does the ion generation step in TOF influence m/z analysis? Consider MALDI h Target Matrix + Analyte Analyte ion may have (1) Kinetic Energy distribution or (2) Spatial distribution How will KE spread influence the spectrum? Ions of same m/z Has slightly greater KE Effect is broad peaks c/o Cotter 14 How will KE spread influence the spectrum? Solution to peak broadening caused by kinetic energy spread: Reflectron (ion mirror) Series of ring electrodes, typically with linear voltage gradient Time-of-Flight Reflectron • Increased resolution by compensating for KE spread from the source http://www.jic.bbsrc.ac.uk/services/proteomics/tof.htm 15 Reflectron TOF Reflectron Mass Analyzer (TOF) Detector Ion Source (MALDI) x x x x x High resolution KE = ½ mv2 Reflectron TOF Mass Analyzer (TOF) Reflectron Detector Ion Source (MALDI) x High resolution KE = ½ mv2 16 http://www.abrf.org/ABRFNews/1997/June1997/jun97lennon.html We talked about how to deal with kinetic energy spread. How do we deal with ions formed at different locations in the source (spatial distribution)? 17 Delayed Extraction 10 KV 10 KV + + + + + + + + + + 7 KV Low mass (below 40 k Da) High resolution Continuous vs. Delayed Extraction Continuous TOF Resolution = 700 (FWHM) Delayed Extraction Resolution = 6000 (FWHM) 18 In te n s. [a .u .] Recent TOF designs: improved resolution, better sensitivity and mass accuracy (Ultraflex III MALDI TOF-TOF) * Pepmix\0_N6\1\1SRef 3145.708 6000 Resolution: 25,000 S/N: 46 5000 4000 3000 2000 3177.722 1000 0 3140 3145 3150 3155 3160 3165 3170 3175 3180 3185 m/z Typical TOF Specs • m/z Range: unlimited u • Resolution: ~20,000 (Reflectron) • Mass Accuracy: ~ 3-10 ppm (300-4,000 u) • Scan Speed: 106 u/s • Vacuum: 10-7 Torr • Quantification: low medium • Positive and Negative Ions • Variations: Linear, Reflectron, • Tandem: w/ quads, TOFs and/or sectors 19 TOF Quad 3D Trap Linear Trap FT‐ICR Orbitrap mass range Resolution exact m/z sensitivity all ion detection ion storage speed dynamic range quantification MS/MS types sample introduction simplicity cost/performance Can an MS/MS instrument be constructed if the only analyzer type available is TOF? 20 TOF-TOF http://docs.appliedbiosystems.com/pebiodocs/00106293.pdf High-energy (keV) Collisions with Gas in a TOF-TOF 21 16O/18O-labeled DLEEGIQTLMGR *Resolution Medzihradszky, KF et al. Anal Chem. 2000, 72: 552-558 Intens. [a.u.] High (keV) collisions allow for w peptide ions and immonium ions x104 328.574 6 492.623 981.346 5 4 656.765 186.600 146.669 3 821.038 2 120.694 1 284.552 90.771 443.572 612.695 721.026 776.938 941.468 0 200 400 600 800 1000 m/z MALDI TOF-TOF fragmentation spectrum of a sodiated polymer O O O CH2 CH2 * m n 3-OEB, m=1-3 (164, 44) Copolymer of 2-hydroxybenzoic acid and ethylene carbonate 22 Advantages and Disadvantages Mass Spectrometer Advantages Disadvantages TOF-TOF high resolution, high m/z fragment ions Large size keV CID Not ideal for continuous ionization source easier de novo peptide sequencing $$$ dn and wn to distinguish Ile/Leu MALDI source Analyzers TOF Quadrupole Quadrupole Ion trap FTICR Orbitrap 23 Quadrupole (Q) http://www.files.chem.vt.edu/chem-ed/ms/quadrupo.html Quadrupole (Q) • four parallel rods or poles • fixed DC and alternating RF voltages rf voltage +dc voltage rf voltage 180° out of phase -dc voltage • only particular m/z will be focused on the detector, all the other ions will be deflected into the rods • scan by varying the amplitude of the voltages – (AC/DC constant). 24 Quadrupole Field Animation Positive rod Negative rod Positive rod Negative rod http://www.kettering.edu/~drussell/Demos/MembraneCircle/Circle.html negative DC offset -DC + - positive DC offset + +DC 25 Ion Motion in Quadrupoles - a qualitative understanding • + DC, ions focused to center • - DC, ions defocused • +DC w/ rf, light ions respond to rf, eliminated (high mass filter) • -DC w/ rf, light ions respond to rf, focused to center (low mass filter) 26 Quadrupole animation http://www.youtube.com/watch?v=8AQaFdI1Yow&feature=related http://www.youtube.com/watch?v=pjCun7QF19U Initial kinetic energy affects ion motion in quad 27 Figure 9. The a-q stability diagram: a) The shaded area represents those areas in a-q space which correspond to stable solutions of Mathieu’s differential equation. B) The one amu bandpass mass filter: Notice that only ions of m/e m+1 fall within the stability diagram. Miller, P., Denton, M.B., J.Chem Ed., 63:7, pg 617, 1986. Quadrupole Typical Specs • m/z Range: 2-4000 u • Resolution: Unit • Mass Accuracy: ca +/0.1 u • Scan Speed: 4000 u/s • Vacuum: 10-4 – 10-5 Torr • Low Voltages: RF ~6000 –10000 V DC ~500V-840V Source near ground • Quantification: good choice • Positive and Negative Ions • Variations: SingleQ, TripleQ, Hybrids 28 TOF Quad 3D Trap Linear Trap FT‐ICR Orbitrap mass range Resolution exact m/z sensitivity all ion detection ion storage speed dynamic range quantification MS/MS types sample introduction simplicity cost/performance What MS/MS instruments can be produced from Q? What MS/MS instruments can be produced from Q and TOF? 29 Triple Quadrupole - since 1970’s and still going strong! Q1 Q3 Q2 S D Attractive Features: • Source near ground and operates at relatively high pressure Couples well to source and to chromatography •Multiple scan modes easy to implement Triple Quadrupole (QQQ) Detection System Dynode Turbo Q3 Source Q0 Q3 Q1 Q2 Heated Capillary Q2 Q1 Q0 Q00 c/o Thermo Finnigan Corp. c/o Agilent Corp. 30 MS/MS Scan Modes Product Ion Scan Select Dissociate Scan Scan Dissociate Select Scan Dissociate Scan Select Dissociate Select Precursor Ion Scan Neutral Loss Scan Selected Reaction Monitoring (SRM) Scan 300 Voltage Analyte Mixture 100 200 RF DC 100 200 300 Vm1 m/zm1 Vm2 m/zm2 Vm3 m/zm3 mass spectrum 31 Scan 300 Voltage 100 Analyte Mixture 200 RF DC 100 200 300 Vm1 Vm2 Vm3 100 300100 100 300 200200 300 100 200 300 200 Scan 300 Voltage Analyte Mixture 100 200 RF DC 100 200 300 Vm1 Vm2 Vm3 100 300100 100 300 200200 300 100 200 300 200 32 Scan RF 300 Voltage 100 Analyte Mixture 200 DC 100 200 300 Vm1 Vm2 Vm3 100 300100 100 300 200200 300 100 200 300 200 Select Voltage 200 Analyte Mixture RF DC 100 200 300 Vm2 Desired Analyte m/zm2 mass spectrum 33 Modes of scanning in a Triple Quadrupole (QQQ) Q1 scan or select q2 (gas) rf only Q3 scan or select • Quadrupole is a mass filter • QQQ used in this tutorial to describe scan modes – Q1 and Q3 = analyzers – q2 (middle quadrupole) used for CID (dissociation) • Ways to set quadrupoles: Scan, Select & rf only • Other instruments are used: Q-tof, Q-trap, Linear TrapOrbitrap, Trapping instruments Quadrupole Time of Flight (Q-TOF) http://www.waters.com/WatersDivision/waters_website/products/micromass/ms_top.asp (outdated) 34 Low-energy (eV) Collisions with Gas Q-TOF 80 fmol BSA digest QQQ Shevchenko, A., et al., Rapid. Commum. Mass Spectrom., 1997, 11: 1015-1024 35 QTOF with Ion Mobility Analyzers TOF Quadrupole Quadrupole Ion trap FTICR Orbitrap 36 What is small, inexpensive and still gives great MSMS ????? Quadrupole Ion Traps Miniature IT: Cooks, R. G. and coworkers Anal. Chem. 2002, 74, 6145-6153; 2000, 72, 3291-3297. http://www.chem.wm.edu/dept/faculty/jcpout/faculty.html Ion path in a trap 37 Quadrupole Ion Trap (QIT) http://www-methods.ch.cam.ac.uk/meth/ms/theory/iontrap.html Quadrupole Ion Trap (QIT) • Quadrupole ion trap mass analyzer consists of three hyperbolic electrodes: the ring electrode, the entrance end cap electrode and the exit endcap electrode. • Ions enter trap through inlet focusing system and entrance endcap electrode. • An AC potential of constant frequency and variable amplitude is applied to the ring electrode to produce a 3D quadrupolar potential field within the trapping cavity which traps ions in a stable oscillating trajectory confined within the trapping cell. • The oscillating trajectory is dependent on the trapping potential and the mass-to-charge ratio of the ions. • During ion detection, the electrode system potentials are altered to produce instabilities in the ion trajectories and thus eject the ions. 38 Quadrupole Ion Trap (QIT) 3D - Quadrupole Ion Trap (Demo) 39 Activation: Low-energy (eV) Collisions with Gas IRMPD (Infrared Multiphoton Dissoc) Research: Micro CIT Array Matt Blain, Sandia Cooks, Purdue 1.8 µm 2.4 µm Top End Cap Array Ring Electrode Array Bottom End Cap Array Collector Array 40 QIT Typical Specs • m/z Range: 20-6000 u • Resolution: Unit • Mass Accuracy: ca +/0.1 u • Scan Speed: 4000 u/s • Vacuum: 10-3 Torr • Quantification: possible, not accurate • Positive and Negative Ions Advantages and Disadvantages Mass Spectrometer Advantages Disadvantages QIT Compact Limited storage of ions limits the dynamic range of the ion trap (space charge effect) MSn 1/3 of low mass range lost in MS/MS mode, typical operation Data dependent scanning Relatively inexpensive Low E collisions 41 Advantages and Disadvantages Mass Spectrometer Advantages QIT Disadvantages Poor quantification Sensitive Collision energy not well-defined in CID MS/MS Mass Accuracy To increase mass accuracy in a Trap LT, orbitrap, FT-ICR RF ION TRAP ELECTRODE STRUCTURES LCQ-Type 3D Quadrupole Trap LTQ-Type (2D) Linear Quadrupole Trap ASMS Fall Workshop 2006 JEPS 42 2D vs. 3D Ion Traps Ion Transfer Tube Skimmer Tube Lens Linear Trap Demo Ion Transfer Tube Skimmer Tube Lens 43 Estimating Relative Ion Storage Capacity 3D Ion vs Linear (2D) Quadrupole Ion Traps 3D RF Quadrupole Ion Trap 2D RF Quadrupole Linear Ion Trap z z y L y x x R3D ~ Spherical Ion Cloud R2D ~ Cylindrical Ion Cloud ASMS Fall Workshop 2006 JEPS Overall Performance Gains LTQ 3D Traps Increase •Trapping efficiency ~ 55-70% ~5% ~ 11-14x •Detection efficiency ~ 50-100% ~50% ~ 1-2x •Trapping capacity ~ 20,000 ions ~500 ions ~ 40x 44 Motivating Factors Realized • Increased Trapping Efficiency • Increased Trapping Capacity Which means.... • Increased Sensitivity • Increased Inherent Dynamic Range • Increased S/N for full Scan MS • Practical MSn •Faster Scan Times - no μscans (only one) How are 3-D traps and linear ion traps used in MS/MS Stand alone 3-D traps LTQ Front or back end of tandem-in-space LT-TOF LT-FT, LT-Orbitrap, QTrap 45 LIT and QTrap; Different ways of using Linear Traps ~ 100% of ions trapped are detected due to radial ejection Linear Ion Trap Skimmer Axial ejection allows for hybridization – without compromise (FT)! Majority of trapped ions cannot be scanned out Hybrid Quadrupole Trap ~ 15% detected* Axial ejection depends on fringe fields generated by grid – this grid compromises triple quadrupole performance *Hager, J., RCM., 2003, 17, 1389 9 Protein Mixture 9 Protein Mixture Peptide Identification 73 80 70 61 Number of Peptides 60 50 42 35 40 30 20 31 21 Deca XP plus LTQ 24 12 10 0 10min 20min 30min Gradient (min) 60min 46 Activation: CID Low-energy (eV) Collisions with Gas IRMPD (Infrared Multiphoton Dissoc) ETD (electron transfer dissociation) TOF Quad 3D Trap Linear Trap FT‐ICR Orbitrap mass range Resolution exact m/z sensitivity all ion detection ion storage speed dynamic range quantification MS/MS types sample introduction simplicity cost/performance 47 Analyzers TOF Quadrupole Quadrupole Ion trap FTICR Orbitrap For a charge q moving with a velocity of v in a magnetic field B there exists a force (F) which is perpendicular to the plane determined by v and B. 48 Analyzers based on magnetic fields: ICR Magnetic forces move ions in a circular path demo http://www.casetechnology.com/implanter/magnet.html Cyclotron motion of an ion in a magnetic field (B). Note: ion motion is much more complex due to the presence of electrostatic field (magnetron/cyclotron motion, see below) 49 50 a b c C9H16N5 194.1405 time (ms) C11H20N3 C7H12N7 194.1154 194.1657 Modified van Krevelen diagram for LDI ions 51 11+ 12+ 10+ 9+ Charge state/MW determination for proteins ∆m = z ∆(m/z) Carbons isotopes so ∆m=1 Da Calc ∆(m/z) 52 FTICR animation http://www.youtube.com/watch?v=a5aLlm9q-Xc&NR=1 New ICR cell design by E. Nikolaev et al. E. Nikolaev et al., Initial Characterization of a New Ultrahigh Resolution FTICR Cell with Dynamic Harmonization, JASMS, 2011, 22, 1125-1133. E. Nikolaev and coworkers, Twelve Million Resolving Power on 4.7T FT-ICR Instrument with Dynamically Harmonized Cell – Observation of Fine Structure In Peptide Mass Spectra, JASMS, 2014, 25, 790-799. 53 Bruker 9.4 T FT-ICR Apex-Qh Tandem Mass Spectrometer MALDI Dual source, MS only, no ion selection ESI QCID (eV) MS/MS Ion selection and activation in the ICR IRMPD, SORI, ECD HDX in the ICR cell 54 Activation: SORI CID Low-energy (eV) Collisions with Gas (off resonance) RE (resonance excitation) IRMPD (Infrared Multiphoton Dissoc) ECD (electron transfer dissociation) Intens. x107 3.0 MS/MS spectra depend on i) Charge state ii) Ion activation method iii) Collision energy 2.5 YIGSR_QCID_22eV_000002.d: +MS2(595.0) MH+ QCID 22 eV 249.1593 595.3171 2.0 1.5 302.1453 1.0 175.1186 560.2803 0.5 408.1864 90.2256 0.0 x108 (more details in the Ion Activation Methods by Vicki Wysocki) 1.5 YIGSR_doubly_QCID_6eV_000001.d: +MS2(298.0) [M+2H]2+ QCID 6 eV 319.1718 1.0 249.1593 y5 0.5 277.1541 432.2552 136.0756 0.0 x107 2.0 465.2077 YIGSR_doubly_IRMPD_40P_0_30s_000001.d: +MS2(298.0) [M+2H]2+ IRMPD 30s, 30% 298.2804 1.5 1.0 249.1644 0.5 102.7325 595.3466 0.0 100 200 300 400 500 600 m/z 55 FTICR Typical Specs • m/z Range: > 15000 u • Resolution: High, 106 • Mass Accuracy: 100 ppb • Scan Speed: slow • Vacuum: 10-9- 10-11Torr • Quantification: possible, not accurate • Positive and Negative Ions Advantages and Disadvantages Mass Spectrometer Advantages Disadvantages FTICR Highest recorded mass resolution of all mass spectrometers Limited Dynamic Range MSn Low E collisions Non-destructive ion detection High vacuum Low presure (difficult GC/LC coupling) Accurate mass measurement Big size Powerful capabilities Not a high for ion chemistry throughput technique experiments (ionmolecule rxns) 56 TOF Quad 3D Trap Linear Trap FT‐ICR Orbitrap mass range Resolution exact m/z sensitivity all ion detection ion storage speed dynamic range quantification MS/MS types sample introduction simplicity cost/performance Analyzers TOF Quadrupole Quadrupole Ion trap FTICR Orbitrap 57 Orbitrap Readings Pictured: August 2009 cover of J. Am. Soc. Mass Spectrom. A New Kind of FTMS: The Orbitrap 58 How does it trap ions? • Quadro-electrostatic field (Orbital trapping of ions) – Electrostatic field with potential distribution • Field is the sum of the quadrupole field of the ion trap and the logarithmic field of the cylindrical capacitor (center electrode) U(r/z) = k/2(z2 – r2/2) + k/2(Rm)2ln[r/Rm] + C – Electrodynamic squeezing • Ions entering with a tangential velocity (acceleration voltage) are pulled into orbit around center electrode due to a voltage drop on the center electrode Orbitrap 59 LTQ Orbitrap™ Hybrid MS Finnigan LTQ™ Linear Ion Trap API Ion source Linear Ion Trap Differential pumping C-Trap Orbitrap Differential pumping LTQ Orbitrap Hybrid MS System Integration Finnigan LTQ™ Linear Ion Trap Gas <1 mtorr V x -2 k V Central Electrode Voltage -3.5 k V 60 Lord of the ion rings: Retainment of the rings Image current detection on split outer electrodes k m/ z 1. Frequencies are determined using a Fourier Transformation 2. For higher sensitivity AND resolution, transients should not decay too fast Ultra-high vacuum Ultra-high precision http://apps.thermoscientific.com/media/SID/LSMS/Video/webinar/orbitrap_elite/animation/ http://www.youtube.com/watch?v=KjUQYuy3msA Ion Motion in the Orbitrap Simulation of ion trajectory with SIMION Characteristic frequencies – Frequency of rotation ωφ z 2 Rm 1 2 R 2 Rm 2 R – Frequency of radial oscillations ωr r z – Frequency of axial oscillations ωz z k m/q 61 Orbitrap --Resolving Power +5 Insulin: m/z = 5733 Charge state: +5, +4 and +3 +3 +5 m/m = 70,000 +4 1,200 1,400 1,600 1,800 2,000 m/z +4 1,147 1,148 m/z 1,149 m/m = 45,000 +3 m/m = 40,000 1,434 1,435 1,436 m/z R. Noll, H. Li, 2002 1,911 1,912 m/z 1,913 1,914 Orbitrap LTQ Velos: Analysis time High resolution acquisition R = 7,500 R = 15,000 R = 30,000 R = 60,000 R = 100,000 R = Time Low resolution acquisition R = unit Figure adapted from Olsen J V et al. Mol Cell Proteomics 2009;8:2759-2769 62 http://fscimage.thermoscientific.com/images/D13092~.pdf 63 translation inhibitor endoribonuclease [Clostridium difficile BI1] High Resolution Fragments Charge: +3, Monoisotopic m/z: 744.71710 Da (-1.83 ppm), MH+: 2232.13675 Da, RT: 67.42 min, High Resolution Fragments Fragment Errors (ppm, partial list) 64 Manual http://sjsupport.thermofinnigan.com/techpubs/manuals/LTQ-OrbitrapVelos_Start_2_6_0.pdf Video http://www.youtube.com/watch?v=-u1keatKtMI Application/Optimization TOF Quad 3D Trap Linear Trap FT‐ICR Orbitrap mass range Resolution exact m/z sensitivity all ion detection ion storage speed dynamic range quantification MS/MS types sample introduction simplicity cost/performance 65 Instrument Performance for Proteomic Applications Han et al., Curr. Opin. Chem. Biol. 2008; 12(5):483-490. Learning Check Draw the appearance of the mass spectrum in which both singly and doubly charged YGGFLR (molecular weight 711.3782) are produced and analyzed with a quadrupole, TOF and orbitrap (Hint: peaks widths important) 66 712 in Quad, TOF, ICR Intensity QUAD Intensity TOF m/z m/z Intensity ICR m/z General Conclusions • • • • • Many instruments are complementary More Activation methods, the better Assess your needs Assess your budget @ Research level, may want to build your own 67 Suggested Reading List GENERAL MS AND MS/MS Kinter, M. and Sherman, N. E., Protein Sequencing and Identification Using Tandem Mass Spectrometry, Wiley and Sons, New York, NY, 2000. De Hoffmann E., Mass Spectrometry – Principles and Applications (Second Edition), Wiley and Sons, New York, NY, 2002. Busch, K.L., et al., Mass spectrometry/ mass spectrometry: techniques and applications of tandem mass spectrometry, VCH Publishing, New York, NY, 1988. McLafferty, F.W. (Ed) Tandem Mass Spectrometry, Wiley and Sons, New York, NY, 1983. McLafferty, F.W. and Turecek, F. Interpretation of Mass Spectra, University Science Books, New York, NY, 1993. Siuzdak, G. Mass Spectrometry for Biotechnology, Academic Press, San Diego, CA, 1996. Gygi, S.P. and Aebersold, R., Curr. Opin. Chem. Biol., 4 (5): 489, 2000. Roepstorff, P., Curr. Opin. Biotech., 8: 6, 1997. De Hoffmann, JMS, 31: 129, 1996. Mann, M. et al., Annu. Rev. Biochem., 70: 437, 2001. McLuckey, S and Wells, J.M., Chem. Rev., 101: 571, 2001. Suggested Reading List Q-TOF Morris, H.R. et al., J. Protein Chem., 16: 469, 1997. Shevchencko A., et al., Rapid Commun. Mass Spectrom., 11: 1015, 1997. Shevchencko A., et al., Anal. Chem., 72: 2132, 2000. Medzihradszky, K.F., et al., Anal. Chem., 72: 552, 2000. Glish, G.L. and Goeringer, D.E., Anal. Chem., 56: 2291, 1984 Morris, H.R. et al., Rapid Commun. Mass Spectrom., 10: 889, 1996. Wattenberg, A. et al., JASMS, 13 (7): 772, 2002. Lododa, A.V. et al., Rapid Commun. Mass Spectrom., 14(12): 1047, 2000. TOF Bush, K., Spectroscopy, 12: 22, 1997. Cotter, R.J., Time-of-Flight: Instrumentation and Applications in Biological Research, ACS, Washington, DC, 1994. 68 Suggested Reading List TOF-TOF Yergey, A.L. et al., JASMS, 13 (7): 784, 2002. Go, E.P. et al., Anal. Chem., 75: 2504, 2003. FTICR Buchanan, M.V. (Ed), Fourier Transform MS, ACS, Washington, DC, 1987. Comisarow, M.B. and Marshall, A. G., Chem. Phys. Lett., 25: 282, 1974. McIver, R.T. et al., Int. J. Mass Spectrom. Ion Processes, 64: 67, 1985. Kofel, P. et al., Int. J. Mass Spectrom. Ion Processes, 65: 97, 1985. Williams, E. R. Anal. Chem., 70: 179A, 1998. McLafferty, F. W. Acc. Chem. Res., 27: 379, 1994. Fridriksson, E. K. et al., Biochemistry, 39: 3369, 2000. Fridriksson, E. K. et al., Biochemistry, 38: 8056, 1999. Kelleher, N. L.et al., Protein Science, 7: 1796, 1998. McLafferty, F. W. et al., Int. J. Mass Spectrom., 165: 457, 1997. . Suggested Reading List Green, M. K. and Lebrilla, C. B. Mass Spectrom. Rev., 16: 53, 1997. Guan, S. and Marshall, A. G. Chem. Rev., 94: 2161, 1994 QIT Marsh, R.E. et al., Quadrupole Storage Mass Spectrometry, vol.102, Wiley and Sons, New York, NY, 1989. Cooks, R.G. et al., Ion trap mass spectrometry. Chem. Eng. News, 69(12): 26, 1991. Jonscher, K.R. et al., Anal Biochem, 244(1): 1, 1997. Louris, J.N. et al., Anal. Chem., 59(13): 1677, 1987. Louris, J.N. et al., Int. J. Mass Spectrom. Ion Processes, 96(2): 117 1990. Cooks, R.G. et al., Int. J. Mass Spectrom. Ion Processes, 118-119: 1 1992. McLuckey, S. A. et al., Int. J. Mass Spectrom. Ion Processes, 106: 213, 1991. Ngoka, L. C. M. and Gross, M. L. Int. J. Mass Spectrom. 194: 247, 2000. 69 Suggested Reading List QQQ Yost, R. A. and Enke, C. G. J. Am. Chem. Soc., 100: 2274, 1978. Arnott, D. in Proteome Research: Mass Spectrometry, james, P (Ed.), pp 11-31, Springer-Verlag, Germany, 2001. Steen H. et al., JMS, 36: 782, 2001 Miller, P.E. and Denton, M.B., J. Chem. Educ., 7: 617, 1986. Yang, l. et al., Rapid Commun. Mass Spectrom., 16(21): 2060, 2002. Mohammed, S. et al., JMS, 36: 1260, 2001. Dongre, A.R. et al., JMS, 31: 339, 1996. Orbitrap Hu, Q, Noll, RJ, Li, H., Makarov, A., Hardman, M., Cooks, R.G. JMS, 430-443, 2005. Makarov A. Anal. Chem. 2000; 72(6):1156-1162. Makarov A, Denisov E, Kholomeev A, Baischun W, Lange O, Strupat K, Anal. Chem. 2006; 78(7):2113-2120. Makarov A, Denisov E, Lange O, Horning S. JASMS. 2006; 17(7):977-982. Macek B, Waanders LF, Olsen JV, Mann M. Mol. Cell. Proteom. 2006; 5(5):949-958. Perry RH, Cooks RG, Noll RJ. Mass Spectrom. Rev. 2008; 27(6):661-699. Scigelova M, Makarov A. Orbitrap mass analyzer - Overview and applications in proteomics. Proteomics. 2006: 1621. Olsen JV, Macek B, Lange O, Makarov A, Horning S, Mann M. Nature Methods. 2007; 4(9):709-712. 70