Time-of-flight mass spectrometry (TOF for short)

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Time of Flight Analyzers 
Time-of-flight mass spectrometry (TOF for
short) While originally used as mass analyzers
for use with peptides, they are now applied to
problems which range nanospray analysis of
biological samples to liquid chromatography
(LC/MS/MS) of pharmaceutical preparations. The
rapid acceptance of TOF analyzers is due to their
attractive combination of high sensitivity and
high mass accuracy, not to mention their
simplicity.
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TIME OF FLIGHT  Equations of motion
In a linear TOF, neutral and charged fragments
generated through fragmentation of ions in the
drift region cannot be distinguished from the
original ion, because their velocity remains the
same.
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• Mass Calibration

• Resolution

• Distribution in flight time
• Length of ion formation pulse
• Variation in initial kinetic energy
• Space distribution (site of the volume)

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Mass Analyzers Delayed pulsed extraction to
increase resolution 
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Mass Analyzers TOF with REFLECTRON
E electric field in reflectron VR potential of
reflectron D length of reflectron
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An ion of charge of q with a kinetic energy Ek
will enter with a velocity vix and penetrate the
reflectron to a depth d
Mean velocity in reflectron vix/2. The time needs
to penetrate d will be
Then, the total time in the reflectron is
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The total time out of reflectron t
Total flight time TTOT
Two ions sharing the same mass m but with
different kinetic energy, we define
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The velocity along x axis during field free
flight
The time of field-free flight
In the reflectron, the ions will penetrate at a
depth d or d
The time spent in the reflectron
Total flight time
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Tandem MS with TOF
Flight times of precursor and fragment in the
field-free region Same
Flight times of precursor and fragment in
reflectron
See textbook for details
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Mass Analyzers TIME OF FLIGHT 

• Benefits
• Fastest MS analyzer
• Well suited for pulsed ionization methods (method
  of choice for majority of MALDI mass spectrometer
  systems)
• High ion transmission
• MS/MS information from post-source decay
• Highest practical mass range of all MS analyzers
• Limitations
• Requires pulsed ionization method or ion beam
  switching (duty cycle is a factor)
• Fast digitizers used in TOF can have limited
  dynamic range
• Limited precursor-ion selectivity for most MS/MS
  experiments
• Applications
• Almost all MALDI systems
• Very fast GC/MS systems