Mass Spectrometry-Instrumentation, Interpretation, and Applications质谱仪器、解释和应用 英文版.pdf

MASS SPECTROMETRYWILEY-INTERSCIENCE SERIES IN MASS SPECTROMETRYSeries EditorsDominic M.DesiderioDepartments of Neurology and BiochemistryUniversity of Tennessee Health Science CenterNico M.M.NibberingVrije Universiteit Amsterdam,The NetherlandsA complete list of the titles in this series appears at the end of this volume.MASS SPECTROMETRYInstrumentation,Interpretation,andApplicationsEdited byRolf EkmanJerzy SilberringAnn Westman-BrinkmalmAgnieszka KrajCopyright#2009 by John Wiley&Sons,Inc.All rights reservedPublished by John Wiley&Sons,Inc.,Hoboken,New JerseyPublished simultaneously in CanadaNo part of this publication may be reproduced,stored in a retrieval system,or transmitted in any form or byany means,electronic,mechanical,photocopying,recording,scanning,or otherwise,except as permittedunder Sections 107 or 108 of the 1976 United States Copyright Act,without either the prior writtenpermission of the Publisher,or authorization through payment of the appropriate per-copy fee to theCopyright Clearance Center,Inc.,222 Rosewood Drive,Danvers,MA 01923,[phone],fax[phone],or on the web at .Requests to the Publisher for permission should beaddressed to the Permissions Department,John Wiley&Sons,Inc.,111 River Street,Hoboken,NJ 07030,[phone],fax[phone],or online at http:/ of Liability/Disclaimer of Warranty:While the publisher and author have used their best efforts inpreparing this book,they make no representations or warranties with respect to the accuracy or completenessof the contents of this book and specifically disclaim any implied warranties of merchantability or fitnessfor a particular purpose.No warranty may be created or extended by sales representatives or written salesmaterials.The advice and strategies contained herein may not be suitable for your situation.You should consultwith a professional where appropriate.Neither the publisher nor author shall be liable for any loss of profitor any other commercial damages,including but not limited to special,incidental,consequential,orother damages.For general information on our other products and services or for technical support,please contact ourCustomer Care Department within the United States at(800)762-2974,outside the United States at(317)572-3993 or fax[phone].Wiley also publishes its books in variety of electronic formats.Some content that appears in printmay not be available in electronic format.For more information about Wiley products,visit our web site .Library of Congress Cataloging-in-Publication DataMass spectrometry:instrumentation,interpretation,and applications/edited byRolf Ekman.et al.p.cm.Includes index.ISBN 978-0-471-71395-1(cloth)1.Mass spectrometryI.Ekman,Rolf,1938QD96.M3M345 20085430.65dc222008041505Printed in the United States of America10987654321CONTENTSFOREWORDxiiiCONTRIBUTORSxvPART IINSTRUMENTATION11DEFINITIONS AND EXPLANATIONS3Ann Westman-Brinkmalm and Gunnar BrinkmalmReferences132A MASS SPECTROMETERS BUILDING BLOCKS15Ann Westman-Brinkmalm and Gunnar Brinkmalm2.1.Ion Sources152.1.1.Gas Discharge162.1.2.Thermal Ionization162.1.3.Spark Source192.1.4.Glow Discharge202.1.5.Inductively Coupled Plasma212.1.6.Electron Ionization232.1.7.Chemical Ionization242.1.8.Atmospheric Pressure Chemical Ionization242.1.9.Photoionization252.1.10.Multiphoton Ionization252.1.11.Atmospheric Pressure Photoionization262.1.12.Field Ionization262.1.13.Field Desorption272.1.14.Thermospray Ionization272.1.15.Electrospray Ionization272.1.16.Desorption Electrospray Ionization292.1.17.Direct Analysis in Real Time302.1.18.Secondary Ion Mass Spectrometry31v2.1.19.Fast Atom Bombardment332.1.20.Plasma Desorption342.1.21.Laser Desorption/Ionization342.1.22.Matrix-Assisted Laser Desorption/Ionization352.1.23.Atmospheric Pressure Matrix-Assisted LaserDesorption/Ionization372.2.Mass Analyzers382.2.1.Time-of-Flight402.2.2.Magnetic/Electric Sector452.2.3.Quadrupole Mass Filter492.2.4.Quadrupole Ion Trap512.2.5.Orbitrap552.2.6.Fourier Transform Ion Cyclotron Resonance582.2.7.Accelerator Mass Spectrometry622.3.Detectors652.3.1.Photoplate Detector652.3.2.Faraday Detector672.3.3.Electron Multipliers672.3.4.Focal Plane Detector692.3.5.Scintillation Detector692.3.6.Cryogenic Detector702.3.7.Solid-State Detector702.3.8.Image Current Detection70References713TANDEM MASS SPECTROMETRY89Ann Westman-Brinkmalm and Gunnar Brinkmalm3.1.Tandem MS Analyzer Combinations913.1.1.Tandem-in-Space913.1.2.Tandem-in-Time953.1.3.Other Tandem MS Configurations973.2.Ion Activation Methods973.2.1.In-Source Decay973.2.2.Post-Source Decay983.2.3.Collision Induced/Activated Dissociation983.2.4.Photodissociation1003.2.5.Blackbody Infrared Radiative Dissociation1003.2.6.Electron Capture Dissociation101CONTENTSvi3.2.7.Electron Transfer Dissociation1013.2.8.Surface-Induced Dissociation101References1024SEPARATION METHODS105Ann Westman-Brinkmalm,Jerzy Silberring,andGunnar Brinkmalm4.1.Chromatography1064.1.1.Gas Chromatography1064.1.2.Liquid Chromatography1074.1.3.Supercritical Fluid Chromatography1094.2.Electric-Field Driven Separations1104.2.1.Ion Mobility1104.2.2.Electrophoresis111References113PART II INTERPRETATION1175INTRODUCTION TO MASS SPECTRA INTERPRETATION:ORGANIC CHEMISTRY119Albert T.Lebedev5.1.Basic Concepts1195.2.Inlet Systems1215.2.1.Direct Inlet1215.2.2.Chromatography-Mass Spectrometry1215.3.Physical Bases of Mass Spectrometry1285.3.1.Electron Ionization1295.3.2.Basics of Fragmentation Processes inMass Spectrometry1305.3.3.Metastable Ions1355.4.Theoretical Rules and Approaches to InterpretMass Spectra1375.4.1.Stability of Charged and Neutral Particles1375.4.2.The Concept of Charge and UnpairedElectron Localization1485.4.3.Charge Remote Fragmentation1515.5.Practical Approaches to Interpret Mass Spectra1525.5.1.Molecular Ion1525.5.2.High Resolution Mass Spectrometry155CONTENTSvii5.5.3.Determination of the Elemental Composition of Ionson the Basis of Isotopic Peaks1585.5.4.The Nitrogen Rule1645.5.5.Establishing the13C Isotope Content inNatural Samples1665.5.6.Calculation of the Isotopic Purity of Samples1665.5.7.Fragment Ions1685.5.8.Mass Spectral Libraries1735.5.9.Additional Mass Spectral Information1735.5.10.Fragmentation Scheme175References1776SEQUENCING OF PEPTIDES AND PROTEINS179Marek Noga,Tomasz Dylag,and Jerzy Silberring6.1.Basic Concepts1796.2.Tandem Mass Spectrometry of Peptidesand Proteins1816.3.Peptide Fragmentation Nomenclature1836.3.1.Roepstorffs Nomenclature1836.3.2.Biemanns Nomenclature1856.3.3.Cyclic Peptides1876.4.Technical Aspects and Fragmentation Rules1886.5.Why Peptide Sequencing?1906.6.De Novo Sequencing1926.6.1Data Acquisition1936.6.2.Sequencing Procedure Examples1946.6.3.Tips and Tricks2056.7.Peptide Derivatization Prior to Fragmentation2076.7.1.Simplification of Fragmentation Patterns2086.7.2.Stable Isotopes Labeling209Acknowledgments210References210Online Tutorials2107OPTIMIZING SENSITIVITYAND SPECIFICITY IN MASSSPECTROMETRIC PROTEOME ANALYSIS211Jan Eriksson and David Fenyo 7.1.Quantitation2127.2.Peptide and Protein Identification213CONTENTSviii7.3.Success Rate and Relative Dynamic Range2187.4.Summary220References220PART IIIAPPLICATIONS2238DOPING CONTROL225Graham TroutReferences2339OCEANOGRAPHY235R.Timothy Short,Robert H.Byrne,David Hollander,Johan Schijf,Strawn K.Toler,and Edward S.VanVleetReferences24110“OMICS”APPLICATIONS243Simone Ko nig10.1.Introduction24310.2.Genomics and Transcriptomics24610.3.Proteomics24810.4.Metabolomics25111SPACE SCIENCES253Robert Sheldon11.1.Introduction25311.2.Origins25411.3.Dynamics25611.4.The Space MS Paradox25711.5.A Brief History of Space MS25911.5.1.Beginnings25911.5.2.Linear TOF-MS26011.5.3.Isochronous TOF-MS26211.6.GENESIS and the Future264References264CONTENTSix12BIOTERRORISM267Vito G.DelVecchio and Cesar V.Mujer12.1.What is Bioterrorism?26712.2.Some Historical Accounts of Bioterrorism26712.3.Geneva Protocol of 1925 and Biological WeaponsConvention of 197226812.4.Categories of Biothreat Agents26812.5.Challenges26912.6.MS Identification of Biomarker Proteins27012.7.Development of New Therapeutics and VaccinesUsing Immunoproteomics271References27213IMAGING OF SMALL MOLECULES275Magorzata Iwona Szynkowska13.1.SIMS Imaging27713.2.Biological Applications(Cells,Tissues,and Pharmaceuticals)27813.3.Catalysis28013.4.Forensics28113.5.Semiconductors28213.6.The Future283References28514UTILIZATION OF MASS SPECTROMETRYIN CLINICAL CHEMISTRY287Donald HChace14.1.Introduction28714.2.Where are Mass Spectrometers Utilized inClinical Applications?28814.3.Most Common Analytes Detected byMass Spectrometers28814.4.Multianalyte Detection of Clinical Biomarkers,The Real Success Story28914.5.Quantitative Profiling29114.6.A Clinical Example of the Use of Mass Spectrometry29214.7.Demonstrations of Concepts of Quantification inClinical Chemistry294CONTENTSx14.7.1.Tandem Mass Spectrometry and Sorting(Pocket Change)29414.7.2.Isotope Dilution and Quantification(the JellyBean Experiment)29515POLYMERS299Maurizio S.Montaudo15.1.Introduction29915.2.Instrumentation,Sample Preparation,and Matrices30015.3.Analysis of Ultrapure Polymer Samples30115.4.Analysis of Polymer Samples in which all Chains Possessthe Same Backbone30115.5.Analysis of Polymer Mixtures withDifferent Backbones30315.6.Determination of Average Molar Masses303References30616FORENSIC SCIENCES309Maria Kala16.1.Introduction30916.2.Materials Examined and Goals of Analysis31116.3.Sample Preparation31216.4.Systematic Toxicological Analysis31216.4.1.GC-MS Procedures31516.4.2.LC-MS Procedures31516.5.Quantitative Analysis31716.6.Identification of Arsons319References31917NEWAPPROACHES TO NEUROCHEMISTRY321Jonas Bergquist,Jerzy Silberring,and Rolf Ekman17.1.Introduction32117.2.Why is there so Little Research in this Area?32217.3.Proteomics and Neurochemistry32317.3.1.The Synapse32417.3.2.Learning and Memory324CONTENTSxi17.3.3.The Brain and the Immune System32517.3.4.Stress and Anxiety32717.3.5.Psychiatric Diseases and Disorders32917.3.6.Chronic Fatigue Syndrome32917.3.7.Addiction33017.3.8.Pain33117.3.9.Neurodegenerative Diseases33117.4.Conclusions333Acknowledgments333References334PART IVAPPENDIX337INDEX353CONTENTSxiiFOREWORDOver the last two decades mass spectrometry has become one of the central techniquesin analytical chemistry,and the analysis of biological(macro)molecules in particular.Its importance is now comparable to that of the more traditional electrophoresisand liquid separations techniques,and it is often used in conjunction with them asso-called“hyphenated”techniques,such as LC-MS.This development was originally triggered by the discovery of novel techniques togenerate stable ions of the molecules of interest and the development of associated ionsources.Such a technique has to meet two basic requirements:first the molecules,usually existing in the liquid or solid condensed state,have to be transferred into thegas phase and eventually into the vacuum of a mass analyzer;second,the neutral mol-ecules have to acquire one or several charges to be separated and detectable in the massanalyzer.Both steps had traditionally been prone to internal excitation of the moleculesleading to fragmentation and loss of analytical information.The two techniques thatevolved as the frontrunners and nowadays dominate mass spectrometry are electrosprayionization(ESI)and matrix-assisted laser desorption/ionization(MALDI).Even thoughthese two techniques solve the problem of transfer from the condensed to gas phase aswell as the ionization in very different ways and were developed completely indepen-dently,their breakthrough happened concurrently in 1988.This concurrent developmentwas,most probably,not a shear coincidence.The basics of the macromolecular structureand function of biological systems,the role of DNA and proteins in particular,hadevolved over the three decades before and it had become apparent at least to a smallgroup of scientists that to unravel the details of their structure required a leap in thedevelopment of more sensitive and more specific analytical techniques.Mass spec-trometry held at least the promise for such a leap,even though most of the“experts”thought it impossible.This might suggest that in science,as in other fields of humandevelopment it holds that,“where is a need,there is a way.”It is also important torealize in this contextthat both ESI and MALDI make use of principles developed inthe years before,such as field desorption and desorption by particle beams,as well aschemical ionization in the gas phase.The novel ionization mechanisms have early on induced the revival of some massanalyzer principles such as the(axial ion extraction)time-of-flight(TOF)instruments,which had been written off as having too low a performance earlier.More recently awhole plethora of new mass spectrometers have been marketed,combining both ESIand MALDI with high performance spectrometers such as the orthogonal extractionTOFs,Fourier transform ion cyclotron(FT-ICR)and orbitrap instruments.These devel-opments have been largely introduced by the instrument manufacturers.The paralleldevelopment of high speed digital signal processing,data analysis,and data bankinghas also played a major role in the development of the field.xiiiMass spectrometry has meanwhile become an important part of academic educationin analytical chemistry.It can be found in the curricula of most undergraduate as well asgraduate courses in the field.The publication of this dedicated textbook is,therefore,atimely undertaking and the editors and authors are to be complimented for the effort toput the book together.How much detail does a student need to know and how much detail should a text-book then contain?This is an almost unsolvable problem because of the diversity of stu-dents and their analytical needs.The majority of students will eventually move on intospecial fields in(bio)chemistry,molecular or systems biology or polymer chemistry.Forthem mass spectrometry will“only”be one of the commodities to help them solve theirproblems,which are defined by their field of activity,not the analytical technique.Howmuch of the basics in mass spectrometry will they need to know?Again,this depends onthe problem at hand.For many a routine application of commercial instruments and themanufacturers manuals will suffice.However,if the problem is not routine the analyti-cal technique cannot be either.Mass spectrometry is and,most probably,will remain arather complex technique.To fully exploit its tremendous potential,but,equally import-ant,to avoid its many pitfalls,a deeper understanding of the mechanisms and thetechnology will be mandatory.This book will,hopefully,help students to lay thebasis for this expertise and,once the need arises,allow them to go back to the morespecialized literature at a later time.It is in this sense that I hope this book will be areal help to many of them.FRANZHILLENKAMPMu nster,GermanyAugust 2008FOREWORDxivCONTRIBUTORSJONASBERGQUIST,Department of Physical and Analytical Chemistry,UppsalaUniversity,Uppsala,Sweden.G