Time-of-flight mass spectrometry, commonly known
as TOF MS, is a detection method for gas-phase ions that determines their
mass-to-charge ratio (m/z) based on measuring how quickly they travel a known
For the analysis of mixtures of relatively small
organic molecules (boiling below about 550°C), TOF MS is commonly coupled with
gas chromatography (GC), and this will be the focus of our discussion here.
How does TOF MS work?
In TOF mass spectrometers, analyte molecules are
given a positive charge, and are accelerated by an electric field of known
strength. Ions with the same charge will all end up with the same kinetic
energy, but those with a larger mass will travel more slowly, and so will
arrive at the detector later.
This travel time from the ion source to the
detector is what is measured in TOF MS, and it means that ions across the
entire m/z range can be monitored in one run.
The principle of operation of a TOF mass
spectrometer (in this case SepSolve’s BenchTOF2). The path taken by the ions is
shown by the dotted red line.
How does TOF MS differ from quadrupole MS?
Conventional single-quadrupole mass
spectrometers work by scanning through the mass range, meaning that only ions
with a specific mass-to-charge ratio will reach the detector at any one point
in time; all other ions are discarded.
In contrast, TOF instruments simultaneously
analyse all ions, making them far less wasteful of the sample, and so
inherently more sensitive.
Another benefit is that, because they
generate full-range spectra, they allow identification of targets and
unknowns in the same run, which also makes retrospective analysis of
The sensitivity of quadrupoles can be
boosted by using selected ion monitoring (SIM), but in this mode only target
compounds can be monitored, meaning that full characterisation of the sample is
not possible in a single run, and retrospective searching of data is
Time-of-flight MS provides highly-sensitive detection of targets and non-targets in a single run
What’s the difference between orthogonal and axial acceleration?
In TOF MS instruments, two main methods are used
to extract the ions from the ion source:
- Orthogonal acceleration ejects the ions at 90° to their ultimate flight path, using a
continuous ion source and an ion repeller with a relatively small field (1–30
V) to eject ions from the source.
- Axial (or direct) acceleration, as employed in the BenchTOF2
sensitivity by extracting packets of ions from the ion source in-line with the
flight path using a more powerful pulsed electric field (typically greater than 300 V).
Orthogonal acceleration is still used in many
TOF MS instruments, but axial acceleration (as employed in BenchTOF2) offers
better long-term stability, greatly reducing the need for source
maintenance, and so minimising downtime.
Can you use soft ionisation methods with TOF MS?
In short, yes.
The majority of TOF MS systems used with GC
employ 70 eV electron ionisation (EI), in which the accelerating voltage is set
at 70 V. This so-called ‘hard’ ionisation is favoured because at this voltage, the
energy transfer from the electrons to most organic molecules is at a maximum,
and varies little with electron energy.
This results in good sensitivity and
consistent mass spectra.
However, at 70 eV, some molecules undergo
extensive fragmentation, making the signal from the molecular ion very weak,
and making it difficult to separate some ions from the background.
many isomers (such as terpenes and branched hydrocarbons) have very similar
spectra at 70 eV, making it impossible to identify them confidently.
This pair of EI spectra acquired on
BenchTOF2 show the extensive fragmentation of caryophyllene that occurs at 70
eV, and how this is resolved using soft ionisation at 12 eV – which thanks to
the ion optics used, is achieved while maintaining sensitivity at acceptable
To resolve these problems, soft ionisation at
lower voltages can be used. Unfortunately, low-energy EI was historically
unworkable because of the large drop in sensitivity caused by electron
clustering around the filament. The other alternative, chemical ionisation
(CI), requires a different ion source configuration, additional source
pressurisation, and the use of reagent gases, making it very time-consuming to
Fortunately, these problems have now been
circumvented by the availability of ion optics that initially use a high
potential difference to accelerate the electrons away from the filament, but
then reduce their energy before they arrive in the ion chamber.
information on how this works, read our Technical note: Tandem Ionisation® – Revolutionary soft ionisation to enhance confidence in identification.
What are the applications of TOF MS?
The ability of TOF MS to allow target and
non-target analyses on a single platform makes it a perfect detector to expand
the scope of any GC application that would otherwise be carried out using a
In addition, the speed of TOF MS means that it
can also be applied where fast GC run times are needed, making it ideal for
GC×GC, as well as regular GC.
Applications of TOF MS include:
Odours and emissions