Acknowledgements Slides and animations were made by Dr. Jon Karty Mass Spectrometry Facility Indiana University, Bloomington

TOF Concept A packet of ions is accelerated to a defined kinetic energy. The time required to move through a fixed distance is measured First TOF design published in 1946 by W.E. Stephens Detector

TOF advantages Theoretically unlimited mass range Ions are not trapped (quad, IT, FTICR) nor are their flight paths curved (BE sectors) Quadrupole devices have an upper limit as to what mass can actually be trapped Detection efficiencies induce practical limits of a few hundred kDa (M+H)+ Instrument is not scanning (it is dispersive) Analysis is very rapid compared to other mass analyzers All ions in source are analyzed simultaneously Wide range of m/z’s can be measured with good sensitivity and resolution Moderate to high resolving powers (5,000-40,000+) Accurate mass (sub 3 ppm) is attainable Moderate cost ($100k to $500k) Couples extremely well with pulsed ion sources (e.g. MALDI)

TOF Disadvantages Requires high vacuum (<10-6 torr) High pressures lead to peak broadening Requires complex and high speed electronics High acceleration voltages (5-30 kV) with excellent stability Fast detectors (ns or faster) GHz analog to digital conversion Large volumes of data can be generated quickly Limited dynamic range Often 102 or 104 at most Highest resolving power instruments can get rather large Bruker Maxis (RP>40,000) is nearly 8’ tall Calibration of TOF’s tends not to be very robust Temperature changes alter flight tube length Small fluctuations in power supply voltages affect ion kinetic energy Data sampling as fast 8 or 10 GHz has been demonstrated 1-4 GHz is typical in commercial instruments

The Ion Source The source in a TOF instrument serves two purposes Ionize neutral species Give the ions the kinetic energy for time-of-flight analysis Equation for an ion in an electric field: KE is kinetic energy of the ion (J or eV), z is the charge of the ion (C or e), E is electric field strength (V/m), ds is distance traveled through the field, E in (m) Energy gained through electrostatic field is independent of mass If ions of different m but same z are accelerated by an electric field, the kinetic energies of all ions are the same Assuming all start from same position in the field High acceleration potential minimizes effect of initial energy distribution

Real TOF Ion Sources Ions are NOT formed in the exact same position in real ion sources These differences in initial position have profound effects on the mass spectrum Ions are also formed with a distribution of kinetic energies and velocity vectors Ions spend some time in the source prior to cruising through the flight tube Observed flight time is sum of time spent in source AND flight tube TOFtotal = TOFsource + TOFflight_tube A more complete understanding of the TOF mass spectrometer requires that one consider where the ions start in the source

Influence of Initial Position on Final Ion Kinetic Energy Consider two stationary +1 ions between two plates, 1 cm apart. The red ion is 6 mm from right plate, blue ion is 5 mm from right plate What are the energies of these ions after they exit the source Red ion: KE = z * E * ds = 1 e * 104 V/m * 0.006 m = 60 eV Blue ion: KE = 50 eV Two ions have different energies exiting the source Problem for drift tube analysis +100 V 100V  0 V TOF experiment starts when right plate is pulsed from 100 V to 0 V

Simulation of the Flight Times Due to Differences in Where Ion Forms in Source Both ions are 100 m/z Red ion is 6 mm from 0 V plate, blue ion is 5 mm from 0 V plate s for red ion is 0.006 m; s for blue ion is 0.005 m Distance between plates is 1 cm Electric field is 10,000 V/m Detector is 1 m from 2nd grid (D =1 m) TOFred = 94 µsec TOFblue = 103 µsec Draw effect on peak shape (peak has a tail on it) Detector 0 V +100 V

Reflectron In 1966, B. Mamyrin patented an ion mirror device for energy focusing and resolution improvement A reflectron is a series of electrodes that create an electric field to reverse the direction the ions travel Reflectron serves two main purposes 1) Ions can make two passes down the flight tube Get resolution of a 2 m flight tube for a 1 m length of pipe 2) Arrival time distribution due to kinetic energy spread of the ions is reduced

1-Stage Reflectron Diagram ***Red and blue ions have same m/z 1-Stage Reflectron Diagram 0 V 0 V +110 V +100 V Detector Ions with same m/z but slightly different KE’s can be made to arrive at a detector simultaneously. Higher energy ions of same m/z go deeper into reflectron than lower energy ions of same m/z. Thus higher energy ions will take a little longer to exit reflectron than lower energy ions This focuses the energy spread of a population of ions

TOF Animation 337 nm Nitrogen laser Target +20 kV Lens Reflectron +22 kV Extraction Plate +15 kV Detector Flight Tube Entrance 0 V