FOREWORD ..................................................... xiii
CONTRIBUTORS ................................................... xv
PART I INSTRUMENTATION .......................................... 1
1. DEFINITIONS AND EXPLANATIONS ................................. 3
Ann Westman-Brinkmalm and Gunnar Brinkmalm
References ..................................................... 13
2. A MASS SPECTROMETER'S BUILDING BLOCKS ....................... 15
Ann Westman-Brinkmalm and Gunnar Brinkmalm
2.1. Ion Sources ............................................... 15
2.1.1. Gas Discharge ...................................... 16
2.1.2. Thermal Ionization ................................. 16
2.1.3. Spark Source ....................................... 19
2.1.4. Glow Discharge ..................................... 20
2.1.5. Inductively Coupled Plasma ......................... 21
2.1.6. Electron Ionization ................................ 23
2.1.7. Chemical Ionization ................................ 24
2.1.8. Atmospheric Pressure Chemical Ionization ........... 24
2.1.9. Photoionization .................................... 25
2.1.10.Multiphoton Ionization ............................. 25
2.1.11.Atmospheric Pressure Photoionization ............... 26
2.1.12.Field Ionization ................................... 26
2.1.13.Field Desorption ................................... 27
2.1.14.Thermospray Ionization ............................. 27
2.1.15.Electrospray Ionization ............................ 27
2.1.16.Desorption Electrospray Ionization ................. 29
2.1.17.Direct Analysis in Real Time ....................... 30
2.1.18.Secondary Ion Mass Spectrometry .................... 31
2.1.19.Fast Atom Bombardment .............................. 33
2.1.20.Plasma Desorption .................................. 34
2.1.21.Laser Desorption/Ionization ........................ 34
2.1.22.Matrix-Assisted Laser Desorption/Ionization ........ 35
2.1.23.Atmospheric Pressure Matrix-Assisted Laser
Desorption/Ionization .............................. 37
2.2. Mass Analyzers ............................................ 38
2.2.1. Time-of-Flight ..................................... 40
2.2.2. Magnetic/Electric Sector ........................... 45
2.2.3. Quadrupole Mass Filter ............................. 49
2.2.4. Quadrupole Ion Trap ................................ 51
2.2.5. Orbitrap ........................................... 55
2.2.6. Fourier Transform Ion Cyclotron Resonance .......... 58
2.2.7. Accelerator Mass Spectrometry ...................... 62
2.3. Detectors ................................................. 65
2.3.1. Photoplate Detector ................................ 65
2.3.2. Faraday Detector ................................... 67
2.3.3. Electron Multipliers ............................... 67
2.3.4. Focal Plane Detector ............................... 69
2.3.5. Scintillation Detector ............................. 69
2.3.6. Cryogenic Detector ................................. 70
2.3.7. Solid-State Detector ............................... 70
2.3.8. Image Current Detection ............................ 70
References ..................................................... 71
3. TANDEM MASS SPECTROMETRY .................................... 89
Ann Westman-Brinkmalm and Gunnar Brinkmalm
3.1. Tandem MS Analyzer Combinations ........................... 91
3.1.1. Tandem-in-Space .................................... 91
3.1.2. Tandem-in-Time ..................................... 95
3.1.3. Other Tandem MS Configurations ..................... 97
3.2. Ion Activation Methods .................................... 97
3.2.1. In-Source Decay .................................... 97
3.2.2. Post-Source Decay .................................. 98
3.2.3. Collision Induced/Activated Dissociation ........... 98
3.2.4. Photodissociation ................................. 100
3.2.5. Blackbody Infrared Radiative Dissociation ......... 100
3.2.6. Electron Capture Dissociation ..................... 101
3.2.7. Electron Transfer Dissociation .................... 101
3.2.8. Surface-Induced Dissociation ...................... 101
References .................................................... 102
4. SEPARATION METHODS ......................................... 105
Ann Westman-Brinkmalm, Jerzy Silberring,
and Gunnar Brinkmalm
4.1. Chromatography ........................................... 106
4.1.1. Gas Chromatography ................................ 106
4.1.2. Liquid Chromatography ............................. 107
4.1.3. Supercritical Fluid Chromatography ................ 109
4.2. Electric-Field Driven Separations ........................ 110
4.2.1. Ion Mobility ...................................... 110
4.2.2. Electrophoresis ................................... 111
References .................................................... 113
PART II INTERPRETATION ........................................ 117
5. INTRODUCTION TO MASS SPECTRA INTERPRETATION:
ORGANIC CHEMISTRY .......................................... 119
Albert T. Lebedev
5.1. Basic Concepts ........................................... 119
5.2. Inlet Systems ............................................ 121
5.2.1. Direct Inlet ...................................... 121
5.2.2. Chromatography-Mass Spectrometry .................. 121
5.3. Physical Bases of Mass Spectrometry ...................... 128
5.3.1. Electron Ionization ............................... 129
5.3.2. Basics of Fragmentation Processes in
Mass Spectrometry ................................. 130
5.3.3. Metastable Ions ................................... 135
5.4. Theoretical Rules and Approaches to Interpret
Mass Spectra ............................................. 137
5.4.1. Stability of Charged and Neutral Particles ........ 137
5.4.2. The Concept of Charge and Unpaired
Electron Localization ............................. 148
5.4.3. Charge Remote Fragmentation ....................... 151
5.5. Practical Approaches to Interpret Mass Spectra ........... 152
5.5.1. Molecular Ion ..................................... 152
5.5.2. High Resolution Mass Spectrometry ................. 155
5.5.3. Determination of the Elemental Composition of
Ions on the Basis of Isotopic Peaks ............... 158
5.5.4. The Nitrogen Rule ................................. 164
5.5.5. Establishing the 13C Isotope Content in Natural
Samples ........................................... 166
5.5.6. Calculation of the Isotopic Purity of Samples ..... 166
5.5.7. Fragment Ions ..................................... 168
5.5.8. Mass Spectral Libraries ........................... 173
5.5.9. Additional Mass Spectral Information .............. 173
5.5.10.Fragmentation Scheme .............................. 175
References .................................................... 177
6. SEQUENCING OF PEPTIDES AND PROTEINS ........................ 179
Marek Noga, Tomasz Dylag, and Jerzy Silberring
6.1. Basic Concepts ........................................... 179
6.2. Tandem Mass Spectrometry of Peptides and Proteins ........ 181
6.3. Peptide Fragmentation Nomenclature ....................... 183
6.3.1. Roepstorff's Nomenclature ......................... 183
6.3.2. Biemann's Nomenclature ............................ 185
6.3.3. Cyclic Peptides ................................... 187
6.4. Technical Aspects and Fragmentation Rules ................ 188
6.5. Why Peptide Sequencing? .................................. 190
6.6. De Novo Sequencing ....................................... 192
6.6.1. Data Acquisition .................................. 193
6.6.2. Sequencing Procedure Examples ..................... 194
6.6.3. Tips and Tricks ................................... 205
6.7. Peptide Derivatization Prior to Fragmentation ............ 207
6.7.1. Simplification of Fragmentation Patterns .......... 208
6.7.2. Stable Isotopes Labeling .......................... 209
Acknowledgments ............................................... 210
References .................................................... 210
Online Tutorials .............................................. 210
7. OPTIMIZING SENSITIVITY AND SPECIFICITY IN MASS
SPECTROMETRIC PROTEOME ANALYSIS ............................ 211
Jan Eriksson and David Fenyö
7.1. Quantitation ............................................. 212
7.2. Peptide and Protein Identification ....................... 213
7.3. Success Rate and Relative Dynamic Range .................. 218
7.4. Summary .................................................. 220
References .................................................... 220
PART III APPLICATIONS ......................................... 223
8. DOPING CONTROL ............................................. 225
Graham Trout
References .................................................... 233
9. OCEANOGRAPHY ............................................... 235
R. Timothy Short, Robert H. Byrne, David Hollander,
Johan Schijf, Strawn K. Toler, and Edward S. VanVleet
References .................................................... 241
10."OMICS" APPLICATIONS ....................................... 243
Simone König
10.1. Introduction ............................................ 243
10.2. Genomics and Transcriptomics ............................ 246
10.3. Proteomics .............................................. 248
10.4. Metabolomics ............................................ 251
11.SPACE SCIENCES ............................................. 253
Robert Sheldon
11.1.Introduction ............................................. 253
11.2.Origins .................................................. 254
11.3.Dynamics ................................................. 256
11.4.The Space MS Paradox ..................................... 257
11.5.A Brief History of Space MS .............................. 259
11.5.1.Beginnings ........................................ 259
11.5.2.Linear TOF-MS ..................................... 260
11.5.3.Isochronous TOF-MS ................................ 262
11.6.GENESIS and the Future ................................... 264
References .................................................... 264
12.BIOTERRORISM ............................................... 267
Vito G. DelVecchio and Cesar V.Mujer
12.1.What is Bioterrorism? .................................... 267
12.2.Some Historical Accounts of Bioterrorism ................. 267
12.3.Geneva Protocol of 1925 and Biological Weapons
Convention of 1972 ....................................... 268
12.4.Categories of Biothreat Agents ........................... 268
12.5.Challenges ............................................... 269
12.6.MS Identification of Biomarker Proteins .................. 270
12.7.Development of New Therapeutics and Vaccines
Using Immunoproteomics ................................... 271
References ............................................... 272
13.IMAGING OF SMALL MOLECULES ................................. 275
Malgorzata Iwona Szynkowska
13.1.SIMS Imaging ............................................. 277
13.2.Biological Applications (Cells, Tissues,
and Pharmaceuticals) ..................................... 278
13.3.Catalysis ................................................ 280
13.4.Forensics ................................................ 281
13.5.Semiconductors ........................................... 282
13.6.The Future ............................................... 283
References .................................................... 285
14.UTILIZATION OF MASS SPECTROMETRY IN CLINICAL CHEMISTRY ..... 287
Donald H. Chace
14.1.Introduction ............................................. 287
14.2.Where are Mass Spectrometers Utilized in Clinical
Applications? ............................................ 288
14.3.Most Common Analytes Detected by Mass Spectrometers ...... 288
14.4.Multianalyte Detection of Clinical Biomarkers,
The Real Success Story ................................... 289
14.5.Quantitative Profiling ................................... 291
14.6.A Clinical Example of the Use of Mass Spectrometry ....... 292
14.7.Demonstrations of Concepts of Quantification in
Clinical Chemistry ....................................... 294
14.7.1.Tandem Mass Spectrometry and Sorting
(Pocket Change) ................................... 294
14.7.2.Isotope Dilution and Quantification (the Jelly
Bean Experiment) .................................. 295
15.POLYMERS ................................................... 299
Maurizio S. Montaudo
15.1.Introduction ............................................. 299
15.2.Instrumentation, Sample Preparation, and Matrices ........ 300
15.3.Analysis of Ultrapure Polymer Samples .................... 301
15.4.Analysis of Polymer Samples in which all Chains
Possess the Same Backbone ................................ 301
15.5.Analysis of Polymer Mixtures with Different Backbones .... 303
15.6.Determination of Average Molar Masses .................... 303
References .................................................... 306
16.FORENSIC SCIENCES .......................................... 309
Maria Kala
16.1.Introduction ............................................. 309
16.2.Materials Examined and Goals of Analysis ................. 311
16.3.Sample Preparation ....................................... 312
16.4.Systematic Toxicological Analysis ........................ 312
16.4.1.GC-MS Procedures .................................. 315
16.4.2.LC-MS Procedures .................................. 315
16.5.Quantitative Analysis .................................... 317
16.6.Identification of Arsons ................................. 319
References .................................................... 319
17.NEW APPROACHES TO NEUROCHEMISTRY ........................... 321
Jonas Bergquist, Jerzy Silberring, and Rolf Ekman
17.1.Introduction ............................................. 321
17.2.Why is there so Little Research in this Area? ............ 322
17.3.Proteomics and Neurochemistry ............................ 323
17.3.1.The Synapse ....................................... 324
17.3.2.Learning and Memory ............................... 324
17.3.3.The Brain and the Immune System ................... 325
17.3.4.Stress and Anxiety ................................ 327
17.3.5.Psychiatric Diseases and Disorders ................ 329
17.3.6.Chronic Fatigue Syndrome .......................... 329
17.3.7.Addiction ......................................... 330
17.3.8.Pain .............................................. 331
17.3.9.Neurodegenerative Diseases ........................ 331
17.4.Conclusions .............................................. 333
Acknowledgments ............................................... 333
References .................................................... 334
PART IV APPENDIX .............................................. 337
INDEX ......................................................... 353
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