CHEM-5181

This is the new home for the CU-Boulder Graduate Course CHEM-5181: Mass Spectrometry and Chromatography

• The old web page is located here, and I'll be gradually move things over to this Wiki page, which is much easier to update.

Course Information

• This course WILL be offered in Fall 2011, and WILL NOT be offered in Fall 2012
• Fall 2010 Syllabus

• Registering for the course:
  • Every CU student attending the course needs to register, either as (a) for grade; (b) for pass/fail; or (c) for "Audit/No Credit".
  • For non-CU students, you can register for the course through the CU Continuing Education Program ("ACCESS"), again as either (a) for grade; (b) for pass/fail; or (c) for "Audit/No Credit".

• Lectures: Tue & Thu 11:00-12:15, Ekeley W166
• Labs: to be determined, based on the student and MS facility schedules (typically three Tue afternoons 1-3 pm)
• Office hours: immediately after class on Tue & Thu

• Textbooks:
  • de Hoffmann & Stroobant. Mass Spectrometry, Principles and Applications, 3rd. Ed. ISBN: 0471485667; Library: QD96.M3 H6413 2007
  • McLafferty & Turecek Interpretation of Mass Spectra, 4th Ed., ISBN: 0935702253; Library: QC454.M22 1993;

FAQs about CHEM-5181

• Can I audit the class?
  • Answer: Yes, but you need to register for it as "Audit / No Credit", either as a regular CU student or through the ACCESS Program. Auditors typically attend lectures but do not do the labs, homeworks, or exams, unless they want to.

• But I don't want to register at all. Can I still audit the class?
  • Answer: No.

• I work in industry and use MS and chromatography in my work, can I take the class?
  • Answer: Yes, registering through the ACCESS Program. Some things to think about: (a) you need to have the relevant background or be willing to work to gain the background, especially if you want to take the class for credit. (b) This is a class for 1st year graduate students in Anaytical & Environmental Chemistry, and it takes quite a bit of work to take the class for credit. If you don't have much time for the class due to your work responsibilities, you should register as "Audit / No Credit".

• Do I need a background in computer programming or on Igor to take the class?
  • Answer: No. We cover those topics but we assume that people have no background when they start the class. We strongly recommend donwloading a demo version of Igor and going through the Getting Started section of the manual and the Video tutorials before the class starts.

Lectures

Introduction, Review, Igor

• Introduction and Review of Fundamentals
  • Regression Demo Program (PC Download)
  • Non-Parametric Regression Demo (Web)
  • Least Squares Polynomial Approximation Demo (Web)
  • Central Limit Theorem Demo (Web)
  • Fourier Synthesis Demo (Web)
  • Fourier Analysis Demo (Web)

• Introduction to Igor Pro
  • Required Reading: "Getting Started" section of the manual and the Video tutorials

Mass Spectrometers

• TOFMS
  • Required Reading: de Hoffmann and Stroobant 2007, Section 2.4
  • Mass Spec. Oscilloscope Simulator (PC Download)

• Sector, FTICR, Orbitrap
  • Required Reading: de Hoffmann and Stroobant 2007, Sections 2.3, 2.5, 2.6
  • Simulator of Magnetic Sector MS (PC Download)
  • Introd. animation of FTICR

• Quadrupoles
  • Required Reading: de Hoffmann and Stroobant 2007, Section 2.1
  • Video of Agilent GC/MS Triple Quad
  • Video of Agilent LC/MS Quad
  • Video of Agilent LC/MS Triple Quad
  • Prop: Quadrupole

• 3D Ion Traps
  • Required Reading: de Hoffmann and Stroobant 2007, Section 2.2

Ionization Sources

• Introduction and Electron Ionization
  • Required Reading: de Hoffmann and Stroobant 2007, Section 1.1, 1.17 (need more)
  • Ion Optics Simulator
  • Prop: EI ionizer, filaments, magnets

• Electrospray and its Ion Chemistry (from Invited Lecturer Dr. Shuji Kato)
  • Required Reading: de Hoffmann and Stroobant 2007, Section 1.11
  • Prop: ESI Source

• Chemical Ionization
  • Required Reading: de Hoffmann and Stroobant 2007, Section 1.2, 1.10, 1.12, 1.16, 1.17
  • PTRMS Commercial Instrument
  • SYFT Commercial Instrument

• Invited Lecture: the Flowing Afterglow by Prof. Chuck dePuy

• Ionization IV: Bombardment, MALDI and Elemental
  • Required Reading: de Hoffmann and Stroobant 2007, Section 1.4, 1.7, 1.8, 1.9, 1.14, 1.15
  • ICP-MS Facility at CU-Boulder
  • Prop: MALDI plate

MS Detectors, Data Acquisition, Vacuum

• MS Detectors, A/D, Signal-to-Noise
  • Required Reading: de Hoffmann and Stroobant 2007, Chapter 3
  • Simulation of an Electron Multiplier
  • Simulation of an Analog-to-Digital Converter
  • Manual and specifications of a typical analog-to-digital converter
  • Props: EMs, MCP, EM in vacuum mount

• Vacuum Technology
  • Props: turbo pump, diaphragm pump

MS Interpretation

• Introduction to MS Interpretation
  • Required Reading: McLafferty and Turecek 1993, Chapters 1 and 6
  • NIST Chemistry WebBook
  • Example of ions in high-resolution MS of Ambient Aerosols (Fig. S-18)
  • MS Tools from NIST
  • Prop: Offline NIST database

• Using Elemental Composition in Interpretation
  • Required Reading: McLafferty and Turecek 1993, Chapter 2
  • IsoPro Isotopic Distribution (PC Download)
  • ChemCalc Isotopic Distribution (Online)
  • Periodic Table of the Isotopes

• Interpretation of Mass Spectra III (The Molecular Ion)
  • Required Reading: McLafferty and Turecek 1993, Chapters 3 and 5

• Interpretation of Mass Spectra IV (Fragmentation Mechanisms)
  • Required Reading: McLafferty and Turecek 1993, Chapters 4, and skim 9

Chromatography and Chemical Separations

• Introduction and Theory of Chromatography
  • Chromatographic Separation Demo (Web)
  • Theory of Chromatography (Cont.)

• Electric-Field Driven Separations: Ion Mobility, Gel Electrophoresis, and Capillary Electrophoresis

• Gas Chromatography
  • Prop: GC column

• LC and HPLC

• Ion Chromatography & Thin Layer Chromatography

• Chromatographic Detectors

Homeworks

Reference material for homeworks

• • Template for Journal Skims (.doc)
  • Igor Programming Conventions (v2)
  • Tips for Student Presentations
  • Checklist for interpretation HW

HW on Intro and Review of Fundamentals

• HW1: Igor & Review of Fundamentals

HW on TOFMS

• HW2: TOFMS
  • TOFMS spectrum for Problem #1 (Igor Text File, save and double-click to open in Igor)

HW on Resolution & Accuracy

• HW 3.1: mass spec resolution and accuracy
  • Quadrupole MS for donwload (Igor PXP format)
  • Orbitrap MS for download (Excel format)

HW on Quadrupoles

• HW3.2: Quadrupole MS simulation
  • Understanding the Quadrupole Mass Filter through Computer Simulation, Steel and Henchman, J. Chem. Ed. 75:1049-1054, 1998.
  • 4th order Runge-Kutta Integration Method

HW on Ion Optics

• HW4.1: Ion Options Simulation Part 1
• HW4.2: Ion Options Simulation Part 2
• HW4.3: EI Source
• HW4.4: ESI charge states

Labs

• Home Page of CU Mass Spec. Facility

Lab 1: MALDI-TOFMS

• catalog.pdf Instrument Description I
• Instrument Description II
• Pre-Lab
• Lab Procedure
• Instrument Instructions

Lab 2: Electrospray MS

• Pre-Lab
• Lab
• Pulsar Instrument Description
• Pulsar Instrument Instructions

Lab 3: GC-MS of mixtures

• Pre-Lab
• Lab
• GC-MS Operation Instructions
• GC Column Chart
• GC Column Info
• column1.pdf Info on Column used in the lab

• Final Project Organization

Reference Materials

Suggestions Encouraged. Please send links to jose.jimenez at colorado.edu (All .pdf's are password restricted)

Introduction to Mass Spectrometry

• (General, Suggested ASMS Tutorial: What is Mass Spectrometry?
• (General, Reference) MS Terms and Definitions Project
• (General, Reference) "Frontiers in Mass Spectrometry" ,Special issue Chem. Rev. 101(2), 2001.
• (General, Reference) The 'Thompson'. A Suggested Unit for Mass Spectroscopists. R. G. Cooks RG and A. L. Rockwood, Rap. Comm. Mass Spec. 5, 93, 1991. (pdf)
• (Ion Optics, Advanced) Ion Optics in Mass Spectrometry. H. Wollnik, J. Mass. Spec., 34: 991-1006, 1999.
• (Vacuum, Reference) Vacuum Technology, Davis, Moore, and Coplan
• (Kinetics, Animation) Simple gas kinetic theory simulator
• (Various Topics, Advanced) Selected Award/Plenary/Tutorial Lectures from the Annual Conferences of the American Society of Mass Spectrometry
• (General, Reference, Hard Copy at Libraries): Encyclopedia of Mass Spectrometry

Ionization Methods

• (General, Reference) Methods of Ion Generation M. L. Vestal, Chem. Rev., 101(2), 361, 2001.
• (General, Reference) The Emergence of Mass Spectrometry in Biochemical Research G. Siuzdak, Proc. Natl. Acad. Sci. USA, 91(24), 11290, 1994.
• (EI, Advanced) Fundamentals of Electron Interactions with Plasma Processing Gases, by L.G. Christophorou, J.K. Olthoff, Springer, 2004.
• (CI, Advanced) Chemical Ionization Mass Spectrometry. I. General Introduction. M.S.B. Munson and F.H. Field, J. Am. Chem. Soc., 2621, 1966.
• (ESI, Advanced) Practical implications of some recent studies in electrospray ionization fundamentals. Cech and Enke, Mass Spec. Rev., 20: 362-387, 2002.
• (ESI, Advanced) A brief overview of the present status of the mechanisms involved in electrospray mass spectrometry P. Kebarle, J.Mass Spec.,804-817, 2000.
• (ESI, Advanced) Electrospray: From ions in solution to ions in the gas phase, what we know now. P. Kebarle and U.H. Verkerk, Mass Spec. Rev. doi: 10.1002/mas.20247, 2009.
• (ESI, Advanced) Some tenets pertaining to ESI-MS R. B. Cole, J. Mass Spec.,763-772,2000.
• (ESI, Advanced) Analytical Properties of the Nanoelectrospray Ion Source M. Wilm and M. Mann, A. Chem., 1-8, 1996.
• (MALDI & ESI, Reference) Mass spectrometry and nuclear magnetic resonance applied to biological macromolecules. Advanced Information on the Nobel Prize in Chemistry 2002.
• (MALDI, ESI, Suggested) MALDI & ESI lecture from Prof. Cotter
• (MADLI, Suggested) MALDI Tutorial from Vanderbilt
• (MALDI, Advanced) Ion formation in MALDI mass spectrometry. Zenobi and Knochenmuss, Mass. Spec. Rev., 17: 337-366, 1999.
• (MALDI, Advanced) Atmospheric Pressure Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry V. V. Laiko, M. A. Baldwin, and A. L. Burlingame, A. Chem.,652-657, 2000.
• (SIMS, Advanced) SIMS Tutorial On Evans Analytical Group Website
• (DESI, Advanced) Ambient mass spectrometry using desorption electrospray ionization (DESI): instrumentation, mechanisms and applications in forensics, chemistry, and biology Z. Takats, J. M. Wiseman, and R. G. Cooks, J. Mass Spec.,1261-1275, 2005.
• (DART, Advanced) Versatile New Ion Source for the Analysis of Materials in Open Air under Ambient Conditions R. B. Cody, J. A. Laramee, H. D. Durst, A. Chem., 2297-2303, 2005.
• (Atm. Pres. Ion Sources, Advanced) Atmospheric Pressure Ion Sources. Mass Spec. Rev., doi: 10.1002/mas.20246, 2009.
• (Elemental, Advanced) Surface Ionization Source Using Multiple Elements M. G. Inghram and W. A. Chupka Rev. Sci. Inst.,24(7), 518, 1953.
• (Elemental, Advanced) Recent Developments in Thermal Ionization Mass Spectrometric Techniques for Isotope Analyis K.G. Heumann et al, Analyst, 1291, 1995.
• (Elemental, Advanced) Tutorial. Glow discharge mass spectrometry: Trace element determinations in solid samples. King et al., J. Mass. Spec., 30: 1061-1075 (pdf)
• (Elemental, Advanced) Tutorial. Inductively coupled plasma mass spectrometry (ICP MS): a versatile tool. A. Ammann, J. Mass. Spec., 42: 419-427, 2007.

Mass Analyzers

• (General, Suggested) Instrumentation lecture from Prof. Cotter
• (General, Reference) Mass Spectrometry (Review) A.L. Burlingame, R. K. Boyd, and S. J. Gaskell, A. Chem,1998,68(12),647R-716R
• (General, Advanced) Debating Resolution and Mass Accuracy. M. P. Balogh, LC-GC Europe, 17(3), 152–159 (2004)
• (General, Reference) Mass Analysis at the Advent of the 21st Century S. A. McLuckey and J. M. Wells, Chem. Rev. 101(2), 571, 2001.
• (Resolution, Advanced) Scaling MS Plateaus with High-Resolution FT-ICRMS. A. G. Marshall, C. L. Henderickson, and S. D.-H. Shi A. Chem, 74(9), 252A (2002)
• (TOF, Suggested) Agilent's Tutorial on Time-of-Flight Mass Spectrometry
• (TOF, Advanced) Tutorial. Principles and instrumentation in time-of-flight mass spectrometry. Physical and instrumental concepts. M. Guilhaus, J. Mass. Spec., Volume 30: 1519-1532, 1995. (pdf)
• (TOF, Advanced) Perfect Timing: Time-of-flight Mass Spectrometry M. Guilaus, RCMS, 1997, 951-962
• (TOF, Advanced) Time-of-Flight Mass Spectrometry: State of the Art in Chemical Analysis and Molecular Science C. Weickhardt, F. Moritz, and J. Grotemeyer. MS Review. 1996, 139-162.
• (TOF, Advanced)Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry. Instrumentation and Applications D. C. Muddiman, R. Bakhtiar, S. A. Hofstadler, and R. D. Smith J. Chem. Ed. 74, 1288, 1997.
• (TOF, Advanced) Orthogonal acceleration time-of-flight mass spectrometry. Guilhaus et al., Mass Spec. Rev., 19: 65-107, 2000.
• (TOF, Advanced) Time-of-Flight Mass Spectrometer with Improved Resolution W. C. Wiley and I. H. McLaren, Rev. Sci. Instrum. 1955, 26(12), 1150-1157.
• (TOF, Advanced) Time-of-flight mass spectrometry (concepts, achievements, and prospects) B. A. Mamyrin, Int J Mass Spec, 2001, 251-266
• (TOF, Advanced) Advanced Reading: On the initial velocity of ions generated by matrix-assisted laser desorption ionization and its effect on the calibration of delayed extraction time-of-flight mass spectra P. Juhasz, M. L. Vestal, and S. A. Martin, J. Am. Soc. Mass Spec 8(3),209, 1997.
• (TOF, Animation) TOF-MS From Agilent
• (Quad, Required) Understanding the Quadrupole Mass Filter through Computer Simulation, Steel and Henchman, J. Chem. Ed. 75:1049-1054, 1998.
• (Quad, Suggested) Quadrupole Mass Spectrometers: An Intuitive Look at the Math. Leary and Schmidt, J. Chem. Ed. 73: 1142-1144, 1996.
• (Ion Trap, Animations) Courtesy of Thermo Finnigan
  • 1: Damping Gas
  • 2: Ion Trapping
  • 3: Scanning of the Mass Spectrum
  • 4: Detection of the Mass Spectrum
  • 5: Entire Electrospray + Ion Trap Instrument (Finnigan ESI-LCQ)
  • MS/MS 1: Ion Elimination ("There Can Only Be One")
  • MS/MS 2: Ion Capture
  • MS/MS 3: Collision-Induced Dissociation (CID) of the Trapped Ion
• (FTICR, Suggested) Baseline mass resolution of peptide isobars: A record for molecular mass resolution, He F, Hendrickson CL, Marshall AG, Anal. Chem. 73 (3): 647-650, 2001.
• (FTICR, Suggested) Fourier Transform Mass Spectrometry (Tutorial) I. J. Amster, JMS, 1996, 1325-1337.
• (FTICR, Advanced) Fourier transform ion cyclotron resonance mass spectrometry: A primer. A.G. Marshall et al., Mass Spec. Rev. 17: 1-35, 1998.
• (Orbitrap, Advanced) The Orbitrap: a new mass spectrometer (Perspective). R.G. Cooks et al., J Mass Spec. 40: 430-443, 2005.
• (Q-TOF, Advanced) An introduction to quadrupole–time-of-flight mass spectrometry I. V. Chernushevich, A. V. Loboda, and B. A. Thomson, JMS, 2001, 849-865
• (MS/MS, Suggested) Lecture on MS/MS from Prof. Bob Cotter
• (MCP, Advanced) Microchannel Plate Detectors J. L. Wiza, Nuc Inst Meth, 1979, 587-601.
• (Aerosol, Suggested)Tutorial: Sampling and analysis of individual particles by aerosol mass spectrometry., M.V. Johnston, J. Mass Spectrom. 35, 585–595 (2000).
• (Aerosol, Suggested) Chemical and Microphysical Characterization of Ambient Aerosols with the Aerodyne Aerosol Mass Spectrometer. Canagaratna et al., Mass Spectrometry Reviews, in press, April 2006. PDF of accepted version and Figures
• (Aerosol, Advanced) Special Issue of AS&T on Aerosol Mass Spectrometry
• (Aerosol, Link to references) Publications using the Aerodyne Aerosol Mass Spectrometer (AMS)
• (Aerosol, Link to references) Aerosol Mass Spectrometry Web Page
• (Aerosol, Link to references) A List of Publications in Single Particle Mass Spectrometry, maintained by Prof. Tony Wexler.
• (Aerosol, Link to references) Another List of Publications in Single Particle Mass Spectrometry, this one maintained by Prof. Murray Johnston.

MS Interpretation

• (Online Tutorial) Intro to Interpretation, with examples and interactive quizzes. University of Arizona
• (Online Database) NIST Chemistry Webbook
• (Online Tool) Online Periodic Table (with isotope info)
• (Online Tool) MS Tools from SIS
• (Online Tool) Exact Mass and Isotope Calculator
• (Online Tool) Elemental Composition Calculator
• (Isotopes, Suggested) Using Punnett Squares To Facilitate Students' Understanding of Isotopic Distributions in Mass Spectrometry, L.T. Sein, J. Chem. Ed., 83: 228, 2006.
• (Nitrogen Rule, Suggested) Molecular formulas of organic compounds: the nitrogen rule and degree of unsaturation. V. Pellegrin, J. Chem. Ed., 60(8): 626, 1983.
• (Practice Problems) Additional interpretation problems from Lee book and their solutions
• (Reading, Advanced) Gaseous Molecular Ions: An Introduction to Elementary Processes Induced by Ionization, by E. Illenberger, J. Momigny, Springer, 1992.
• (CID, Suggested) The Interpretation of Collision Induced Dissociation Tandem Mass Spectra of Peptides, I.A. Papayannopoulos, Mass Spec. Reviews 14: 49-73, 1995.
• (Proteomics, Suggested) Mass Spectrometry in Proteomics R. Aerbersold and D.R. Goodlett, Chem. Rev. 101(2), 269, 2001.
• (Proteomics, Database) MASCOT Protein MS Database

Chromatography: General

• Simple Chromatography Simulator
• (General, Required)Introduction to Chromatography, Braithwaite and Smith
• (General, Required)Theory of Chromatography, Braithwaite and Smith
• (General, Reference) Equations for Calculation of Chromatographic Figures of Merit for Ideal and Skewed Peaks, J.P. Foley and J.G. Dorsey, Anal. Chem., 55: 730-737, 1983.
• (General, Reference) Nomenclature for Chromatography (IUPAC Recommendations), L.S. Etre, Pure & Appl. Chem., 65(4): 819-872, 1993.
• (General, Reference) The Birth of Partition Chromatography, L.S. Ettre, LC-GC North America, 19(5), 2001.
• (General, Reference) M.S. Tswett and the Birth of Chromatography, L.S. Ettre, LC-GC North America, 2003.
• (General, Reference) The Centenary of "Chromatography", L.S. Ettre, LC-GC North America, 2006.