1. Mass Analyzers : Time-of-flight Mass Spectrometry CU- Boulder CHEM 5181 Mass Spectrometry & Chromatography Joel Kimmel Fall 2007

2. Resources for Journal Skims Web of Science http://apps.newisiknowledge.com/ VPN for Off-campus Access to Electronic Journals and Web of Science http://www.colorado.edu/its/vpn/ Restricted pdfs on course website chem5181 and pass5181

3. An ion with m/z = m has charge equal: (a) 1 Coulombs (b) m Coulombs (c) 1.6022 × 10 −19 Coulombs (d) e Coulombs

4. An ion with m/z = m has charge equal: (a) 1 Coulombs (b) m Coulombs (c) 1.6022 × 10 −19 Coulombs (d) e Coulombs

5. A mass spectrometer with a resolution of 5000 should be capable of resolving isotopic peaks for singly charged species with m (a) Of any value (b) Less than 5000 u (c) Greater than 5000 u (d) It depends on the type of mass spectrometer

6. (a) Of any value (b) Less than 5000 u (c) Greater than 5000 u (d) It depends on the type of mass spectrometer

7. Argon Atomic Weight (Da): 39.948 Atomic mass (m a /u)Abundance 35.967545520.33% 37.96273250.06% 39. 962383799.6% 39.9600 0.015934 Calculate resolution and accuracy?

9. Which of the following pairs requires the greatest mass resolving power to distinguish: (A) Ar + from Ar 2+ (B) CO + from N 2 + (C) CH 3 + from CDH 2 + Ar = 39. 9623837 u, C = 12 u, O = 15.9949 u, N = 14.003 u, H = 1.007 u, and D = 2.0141 u

10. Which of the following requires the mass greatest resolving power, distinguishing: (A) Ar + from Ar 2+ (B) CO + from N 2 + (C) CH 3 + from CDH 2 + Ar = 39. 9623837 u, C = 12 u, O = 15.9949 u, N = 14.003 u, H = 1.007 u, and D = 2.0141 u m/Δm = R 40/20 = 2 28/.01 = 2800 15/1 = 15 Note that requirements for isotopes with grow with m/z!

11. Ion Motion in Electrostatic Fields Electrical force on an ion: Electric field is the force on a unit positive charge Q: What effect does this field have on a positive ion? Q: How does the voltage vary across the space between the + and – electrodes? Q: Would ions originating at A and B be affected equally? (Same E? Same V?) Electric Field Lines + + + + + + -------------- A B

12. Time-of-Flight Mass Spectrometry To determine m/z values A packet of ions is accelerated by a known potential and the flight times of the ions are measured over a known distance. Q: What are V, e, and z? Key Performance Notes  Based on dispersion in time  Measures all m/z simultaneously, implying potentially high duty cycle  “Unlimited” mass range  DC electric fields  Small footprint  Relatively inexpensive

13. Force: F = qE Effective Voltage: V = Es Potential: U = Vq Potential: U = (Es)q Electric Field Lines + + + + + + -------------- A B sBsB sAsA

14. TOFMS Detector V Source, S Drift Region, D E = V/S E = 0 Ions accelerated by strong field, E, within short source region, S. Drift times recorded across long, field-free drift region, D. v D depends on starting position of ion – ideally all ions start from same plane. Q: What else is ideally assumed (U o, E, D, …)? Q: What figures of merit will non-ideality affect? Drawing adapted from p20 of Cotter reference on next slide. a

15. Actual Picture More Complex TOF = total recorded flight time of an ion t o = Ion formation time after T 0 of TOF measurement t a = Time in acceleration region, which depends on initial position and initial energy t D = Time in drift region, which depends on initial position and initial energy t d = Response time of detector For detailed discussion see: Guilhaus, J. Mass. Spec, 1519, 1995. Cotter, “Time-of-flight Mass Spectrometery: Instrumentation and Applications in Biological Research,” ACS, 1997.

16. Resolution For any m/z in a time-of-flight mass spectrum, the recorded peak will be the sum of signals corresponding to multiple, independent, ion arrival events Each ion arrival will be recorded at a unique TOF, as determined by expression on previous slide TOF ’, which is the center of the peak in the mass spectrum, will be an average of all individual ion arrival TOFs The width of TOF ’, Δt, will depend on the distribution of the individual ion arrival TOFs (and other factors …)

17. Improving Resolution TOFMS was first commercialized in 1950s Early instruments had limited resolution Speed of electronics Energy distribution Recent “Renaissance ….”

18. Delayed Ion Extraction / Time-Lag Focusing From De Hoffmann From Guilhaus, J. Mass. Spec, 1519, 1995. Delay between ionization and extraction events. At ionization: U = U 0 (Initial Energy of Ion) At exit of extraction: U = U 0 + E ext xq At beginning of drift: U = U 0 + E ext xq + (V 1 -V 2 )q Tune source voltages and/or delay to compensate for ΔU 0 and create space focus at detector. Mass dependent. Modified from Cotter: http://www.hopkinsmedicine.org/mams/MAMS/middleframe_files/teachin g_files/ME330.884/2005/MS2005-Lecture-5-Instrumentation.pdf V0V0 V1V1 V2V2 V0V0 V1V1 V2V2 x

19. From: http://www.chemistry.wustl.edu/~msf/damon/reflectrons.html Reflectron consists of a series of electrodes, forming a linear field in direction opposite of initial acceleration. Ions are slowed by this field, eventually turning around and accelerating back in direction of detector. Penetration depth depends on U s, which is function of U 0 and acceleration field, E. Reflectron voltages are tuned to create a space focus at the plane of the detector. Reflectron

20. In Delayed Extraction, we give ions different U to achieve same TOF. In Reflectron, ions possess different U. We force them to travel different D to achieve same same TOF

21. An Inherent Dilemma Because of pulsing, ions are wasted when TOFMS is applied to a continuous source & Increased efficiency comes at the expense of mass range and mass resolution Still, figures of merit and cost make the technique desirable TOFMS is an ideal detector for pulsed ionization methods If ionization event is synchronized with time zero, high duty cycle is achieve hv Laser Desorption: Static, solid sample probed with a pulsed laser ESI: Sample is continuously flowing towards the mass analyzer

22. Performance Trade-offs: On Axis Gating Function Sampling Time Drift Time Ion Beam t Duty Cycle  Sampling Time Sampling Time + Drift Time Mass Range proportional to drift time Δt proportional to sampling time GATE

23. Orthoganol Extraction t GATE t Ions are extraction in a direction orthogonal to source trajectory Extraction event is still rapid (Δt), but extraction volume is determined by length of gate region.

24. oTOFMS See: Guilhaus, et al. Mass Spec Rev, 2000, 65-107 Able to reduce average initial energy in ToF direction to 0 (resolution and accuracy). Independent control of beam energy and drift energy, allows maximum duty cycle. Want tightly collimated beam in extraction region

25. ToF-AMS Animation from Agilent: http://www.chem.agilent.com/scripts/pds.asp?lpage=10175