Mass Analyzers: Time-of-flight Mass SpectrometrySlide 2Slide 3Slide 4Slide 5Slide 6Calculate resolution and accuracy?Slide 8Slide 9Slide 10Ion Motion in Electrostatic FieldsTime-of-Flight Mass SpectrometrySlide 13TOFMSActual Picture More ComplexResolutionImproving ResolutionSlide 18ReflectronSlide 20An Inherent DilemmaPerformance Trade-offs: On AxisOrthoganol ExtractionoTOFMSSlide 25Mass Analyzers: Time-of-flight Mass SpectrometryCU- Boulder CHEM 5181Mass Spectrometry & ChromatographyJoel KimmelFall 2007Resources for Journal SkimsWeb of Sciencehttp://apps.newisiknowledge.com/VPN for Off-campus Access to Electronic Journals and Web of Sciencehttp://www.colorado.edu/its/vpn/Restricted pdfs on course website chem5181 and pass5181An ion with m/z = m has charge equal:(a) 1 Coulombs(b) m Coulombs(c) 1.6022 × 10−19 Coulombs(d) e CoulombsAn ion with m/z = m has charge equal:(a) 1 Coulombs(b) m Coulombs(c) 1.6022 × 10−19 Coulombs(d) e CoulombsA 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(a) Of any value(b) Less than 5000 u (c) Greater than 5000 u(d) It depends on the type of mass spectrometer 500011,mmmRArgonAtomic Weight (Da): 39.948Atomic mass (ma/u) Abundance35.96754552 0.33%37.9627325 0.06%39. 9623837 99.6%39.96000.015934Calculate resolution and accuracy?pp mAR73.5910962387.3902387.2507015934.096.396Which of the following pairs requires the greatest mass resolving power to distinguish:(A) Ar+ from Ar2+(B) CO+ from N2+(C) CH3+ from CDH2+Ar = 39. 9623837 u, C = 12 u, O = 15.9949 u, N = 14.003 u, H = 1.007 u, and D = 2.0141 uWhich of the following requires the mass greatest resolving power, distinguishing:(A) Ar+ from Ar2+(B) CO+ from N2+(C) CH3+ from CDH2+Ar = 39. 9623837 u, C = 12 u, O = 15.9949 u, N = 14.003 u, H = 1.007 u, and D = 2.0141 um/Δm = R40/20 = 228/.01 = 280015/1 = 15Note that requirements for isotopes with grow with m/z!Ion Motion in Electrostatic Fields •Electrical force on an ion:EqFEElectric field is the force on a unit positive chargeQ: 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++++++-------ABTime-of-Flight Mass SpectrometryTime-of-Flight Mass SpectrometryTo determine m/z valuesA 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 inexpensiveForce: F = qEEffective Voltage: V = EsPotential: U = VqPotential: U = (Es)qElectric Field Lines++++++-------ABsBsATOFMSDetectorVSource, SDrift Region, DE = V/SE = 0mqEsDvDtmqEsvmvqEsqEsqVUaDDaDDaaa22212Ions accelerated by strong field, E, within short source region, S.Drift times recorded across long, field-free drift region, D.vD depends on starting position of ion – ideally all ions start from same plane.Q: What else is ideally assumed (Uo, E, D, …)?Q: What figures of merit will non-ideality affect?Drawing adapted from p20 of Cotter reference on next slide.aActual Picture More ComplexdDaottttTOF TOF = total recorded flight time of an ionto = Ion formation time after T0 of TOF measurementta = Time in acceleration region, which depends on initial position and initial energytD = Time in drift region, which depends on initial position and initial energytd = Response time of detectorFor detailed discussion see: Guilhaus, J. Mass. Spec, 1519, 1995.Cotter, “Time-of-flight Mass Spectrometery: Instrumentation and Applications in Biological Research,” ACS, 1997.ResolutiontTOFR2'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 eventsEach ion arrival will be recorded at a unique TOF, as determined by expression on previous slideTOF’, which is the center of the peak in the mass spectrum, will be an average of all individual ion arrival TOFsThe width of TOF’, Δt, will depend on the distribution of the individual ion arrival TOFs (and other factors …)Improving Resolution•TOFMS was first commercialized in 1950s•Early instruments had limited resolution•Speed of electronics•Energy distribution•Recent “Renaissance ….”Delayed Ion Extraction / Time-Lag FocusingFrom De HoffmannFrom Guilhaus, J. Mass. Spec, 1519, 1995.Delay between ionization and extraction events. At ionization: U = U0 (Initial Energy of Ion)At exit of extraction: U = U0 + EextxqAt beginning of drift: U = U0 + Eextxq + (V1-V2)q Tune source voltages and/or delay to compensate for ΔU0 and create space focus at detector. Mass dependent.Modified from Cotter: http://www.hopkinsmedicine.org/mams/MAMS/middleframe_files/teaching_files/ME330.884/2005/MS2005-Lecture-5-Instrumentation.pdfV0V1V2V0V1V2xFrom: http://www.chemistry.wustl.edu/~msf/damon/reflectrons.htmlReflectron 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 Us, which is function of U0 and acceleration field, E.Reflectron voltages are tuned to create a space focus at the plane of the detector.Reflectron•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 TOFAn Inherent DilemmaBecause 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 desirableTOFMS is an ideal detector for pulsed ionization methodsIf ionization event is synchronized with time zero, high duty cycle is achievehvLaser Desorption: Static, solid sample probed with a pulsed laserESI: Sample is continuously flowing towards the mass analyzerPerformance Trade-offs: On AxisGating FunctionSampling TimeDrift Time Ion BeamtDuty Cycle Sampling TimeSampling