Mass Spectrometry for the Novice

812XSpmOX+L._SL1500_......Page 1
Front Matter......Page 2
Dedication......Page 6
Contents......Page 8
List of Figures......Page 14
List of Tables......Page 20
Acknowledgments......Page 22
About the Authors......Page 24
Abbreviations......Page 26
To the Reader......Page 30
1.1 A Brief History......Page 35
1.2 Definitions Concerning Instruments, Mass, m/z, and Ions......Page 36
1.3.1 Sample Introduction......Page 45
1.3.2 Ion Sources......Page 47
1.3.3 Mass Analyzers......Page 51
1.3.4 Ion Current Detectors......Page 55
1.3.5 Vacuum Systems......Page 56
1.4 Definitions Concerning Instrument Performance......Page 57
1.5 Definitions Concerning Applications......Page 60
1.6 Information from Mass Spectra......Page 62
1.7 Diversity and Scope of Applications......Page 65
Chapter 2: Instrumentation......Page 68
2.1.1.1 Introduction of Gases and Volatile Liquids Using Batch Inlets......Page 70
2.1.1.3 Direct (Static) Insertion Probes......Page 71
2.1.2 Chromatographic Separation of Complex Mixtures......Page 72
2.1.2.1 Gas Chromatography–Mass Spectrometry (GC -MS )......Page 73
2.1.2.2 Liquid Chromatography–Mass Spectrometry (LC -MS )......Page 76
2.2 Ion Sources and Methods of Ionization......Page 78
2.2.1 Electron Ionization (EI)......Page 82
2.2.2 Soft Ionization......Page 85
2.2.2.1 Chemical Ionization (CI )......Page 86
2.2.2.2 Electrospray Ionization (ESI )......Page 89
2.2.2.3 Atmospheric Pressure Chemical Ionization (APCI )......Page 94
2.2.2.4 Atmospheric Pressure Photo-Ionization (APPI )......Page 96
2.2.3.1 Desorption Electrospray Ionization (DESI )......Page 97
2.2.3.2 Direct Analysis in Real Time (DART)......Page 98
2.2.4 Matrix-Assisted Laser Desorption/Ionization (MALDI)......Page 100
2.2.4.1 Surface-Enhanced Laser Desorption Ionization (SELDI)......Page 103
2.3 Mass Analyzers......Page 104
2.3.1 Quadrupole (Q)......Page 105
2.3.2.1 Quadrupole Ion Trap (QIT)......Page 107
2.3.3 Time-of-Flight (TOF) Analyzer......Page 109
2.3.4.1 Orbitrap......Page 116
2.3.4.2 Fourier Transform–Ion Cyclotron Resonance (FT-ICR )......Page 117
2.3.5.1 High-Field Asymmetric Waveform Ion Mobility Spectrometer (FAIMS )......Page 120
2.3.5.2 Ion Mobility Separator (IMS )......Page 122
2.3.6 Magnetic Sector Analyzers......Page 123
2.3.7 Multianalyzer (MS/MS) Systems......Page 124
2.3.7.1.1 Triple Quadrupole (QqQ)......Page 125
2.3.7.1.2 Time-of-Flight/Time-of-Flight (TOF/TOF)......Page 126
2.3.7.2.1 Quadrupole Time-of-Flight (QTOF)......Page 127
2.3.7.2.2 Linear Ion Trap–Fourier Transform (FT) Analyzers......Page 128
2.4.1 Electron Multipliers......Page 130
2.4.3 Image Currents......Page 133
2.5 Vacuum Systems......Page 135
2.5.1.1 Rotary Pumps......Page 137
2.5.1.2 Scroll Pumps......Page 138
2.5.2 Turbomolecular Pumps......Page 139
2.6 Data Systems......Page 140
3.1.1 Instrument Tuning and Mass Scale Calibration......Page 144
3.1.2 Resolution......Page 146
3.1.3 Accurate Mass Measurement......Page 148
3.2.1 What Is a Mass Spectrum?......Page 155
3.2.2 Isotope Patterns......Page 157
3.2.3 Electron Ionization Spectra of Small Molecules......Page 160
3.2.4.1 Electrospray Ionization Spectra of Large Molecules......Page 163
3.2.6 A Few Ions to Avoid (or at least recognize)......Page 167
3.3 Analytical Techniques and Strategies......Page 168
3.3.1.1 Techniques for Ion Activation......Page 169
3.3.1.2.2 In-Source Fragmentation in API Sources......Page 170
3.3.2.1 Collision-Induced Dissociation (CID)......Page 171
3.3.2.2 Infrared Multiphoton Dissociation (IRMPD)......Page 173
3.3.2.4 Photodissociation and Surface-Induced Dissociation......Page 174
3.3.3.1.1 Product Ion Scanning Mode......Page 175
3.3.3.1.2 Precursor Ion Scanning Mode......Page 176
3.3.3.1.4 Selected Reaction Monitoring (SRM) Mode......Page 177
3.3.3.3 MS/MS Techniques Using Hybrid Instruments......Page 179
3.3.3.4 Data Dependent Acquisition (DDA) and CI D Fragmentation by Voltage Switching (Data Independent Acquisition, DIA )......Page 180
3.3.5 Quantification of Small Molecules......Page 182
3.4 OMICS......Page 190
3.4.1 Metabolomics......Page 192
3.4.2 Lipidomics......Page 193
3.5 Biopolymers......Page 195
3.5.1 Proteomics......Page 196
3.5.1.1 Peptide Sequencing......Page 197
3.5.1.2 Bottom-Up Protein Sequencing......Page 199
3.5.1.3 Top-Down Protein Sequencing......Page 201
3.5.1.4 De Novo Protein Sequencing......Page 203
3.5.1.5 Post-Translational Modification (PTM)......Page 204
3.5.1.7 Protein Conformation......Page 206
3.5.1.8 Hydrogen/Deuterium Exchange (HDX)......Page 210
3.5.1.9 Quantification of Proteins......Page 212
3.5.1.9.1 Quantification Using Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC)......Page 214
3.5.1.9.3 Isobaric Tag for Relative and Absolute Quantification (iTRAQ)......Page 216
3.5.1.9.4 Label-Free Quantitative Proteomics......Page 218
3.5.2 Nucleomics (Nucleic Acid Analysis)......Page 220
3.5.3 Glycomics......Page 223
3.6 Imaging Mass Spectrometry......Page 227
3.7 Bioinformatics......Page 229
3.8 Buying a Mass Spectrometer......Page 231
4.1 An Open-Access Mass Spectrometry Facility......Page 237
4.2 Environmental: Organochlorines in Fish......Page 240
4.3 Environmental: Pharmaceuticals in Surface and Wastewaters......Page 242
4.4 Pharmacology: Lipitor Metabolism......Page 245
4.5 New Techniques: Paper Spray of Pharmaceuticals......Page 248
4.6 Petroleomics: Crude Oil Characterization......Page 251
4.7 Metabolomics: Disease Markers for a Tropical Disease......Page 253
4.8 Metabolomics: Chemical Defense......Page 255
4.9 Lipidomics: Coronary Artery Disease......Page 257
4.10 Proteomics: Protein Identification in a Painting......Page 259
4.11 Proteomics: Protein Identification and Metastasis......Page 262
4.12 Proteomics: Noncovalent Interactions......Page 264
4.13 Tissue Imaging......Page 267
5.1 General......Page 270
5.2 Instrument Components......Page 273
5.3 Performance Parameters......Page 280
5.4 Techniques and Strategies......Page 281
6.1.1 General......Page 286
6.1.2 Formulas and Derivations......Page 287
6.1.4.1 General......Page 288
6.1.4.4 Pharmaceutical, Medical, and Clinical......Page 289
6.1.6 Selected Review Articles......Page 290
6.1.6.3 Quantification......Page 291
6.1.6.6 Applications......Page 292
6.1.7 Classi c Publications......Page 293
6.3 Mass Spectrometry Societies, Blogs, and Discussion Groups......Page 294
6.4.2 Tutorials......Page 295
6.4.3 Databases......Page 296
6.4.4 Miscellaneous Resources......Page 297
C......Page 298
E......Page 299
I......Page 300
M......Page 301
N......Page 302
Q......Page 303
T......Page 304
W......Page 305
Z......Page 306