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.

Electric Field Driven Separations

• (CE, Suggested) Lecture on HPLC and CE from Prof. Bob Cotter
• (CE, Advanced) Electrokinetic Flow and Dispersion in Capillary Electrophoresis, S. Ghosal, Ann. Rev. Fluid Mech., 38: 309-338, 2006.
• (CE, Reference) 2006 Analytical Chemistry Review on Bioanalytical Applications of Capillary Electrophoresis, James Kraly, Md. Abul Fazal, Regine M. Schoenherr, Ryan Bonn, Melissa M. Harwood, Emily Turner, Megan Jones, and Norman J. Dovichi, Anal. Chem., 78(12) pp 4097 - 4110, 2006.

LC, GC, and IC

• (GC, Suggested) More Speed, Better Precision, Higher Sensitivity: Why Buy a New Gas Chromatograph?, Engewald and Ettre, LC-GC North America, 2004.
• (GC, Suggested) 2006 Analytical Chemistry Review on Gas Chromatography, Gary A. Eiceman, Jorge Gardea-Torresdey, Frank Dorman, Ed Overton, A. Bhushan, and H. P. Dharmasena, Anal. Chem., 78(12) pp 3985 - 3996, 2006.
• (GC, Reference) Fifty Years of GC Instrumentation, L.S. Ettre, LC-GC North America, 2005.
• (GC, Suggested) Evolution of Capillary Columns for Gas Chromatography, L.S. Ettre, LC-GC North America, 10(1), 2001.
• (LC, Suggested) Lecture on HPLC and CE from Prof. Bob Cotter
• (LC, Reference) Csaba Horvath and the Development of the First Modern High Performance Liquid Chromatograph, L.S. Ettre, LC-GC North America, 2005.
• (LC, Reference) Jim Waters: The Development of GPC and the First HPLC Instruments, L.S. Ettre, LC-GC North America, 2005.
• (IC, Reference) 2006 Analytical Chemistry Review on Planar Chromatography, Joseph Sherma, Anal. Chem., 78(12) pp 3841 - 3852, 2006.
• (Detector, Reference) The Invention, Development, and Triumph of the Flame Ionization Detector, L.S. Ettre, LC-GC North America, 30(1), 2002.

Feedback from Previous Years

• Feedback from the Fall 2006 Students
  • Survey at the end of the course: Questions and Responses
  • Survey after 1st midterm: Questions and Responses
• Detailed Feedback from the Fall 2004 Students
• Detailed Feedback from the Fall 2003 Students
• Detailed Feedback from the Fall 2002 Students
• FCQs for Jose L. Jimenez
• FCQs for Dan Czizco

Award for the Best Performance in CHEM-5181

• Fall 2009: Eleanor Waxman (PhD Chemistry, Volkamer group)
• Fall 2007: Sean Coburn (PhD Chemistry, Volkamer group)
• Fall 2006: Jesse Marcum (PhD Chemistry, Weber group)
• Fall 2004: Steve Dutton (PhD Mechanical Engineering, Hannigan group)
• Fall 2003: Melinda Beaver (PhD Chemistry, Tolbert group)
• Fall 2002: Aaron Appel (PhD Chemistry, Rakowski-Dubois group)

CU Mass Spec Facility Instruments

DISCLAIMER: These pages are not the official pages of the CU MS facility, rather they were created by the CHEM-5181 students as a class assignment, and may contain inaccuracies or errors. (the journal papers are password protected to minimize copyright issues).