Time-of-Flight Mass Spectrometry (TOF-MS) and the Reflectron: How Ions ‘Race’ According to Their Mass

Time-of-flight mass spectrometry (TOF-MS) is a mass spectrometry technique that determines the mass-to-charge ratio (m/z) of ions by measuring the time taken for them to travel a known distance.

Basic Principles

Ions are accelerated in an electric field of known strength, acquiring the same kinetic energy. Ions with lower mass or higher charge travel faster, whilst those with higher mass or lower charge travel more slowly. The ions then enter a field-free flight tube, where their velocity remains constant; the time taken to reach the far-end detector depends on their velocity and thus reflects the m/z.

Since the accelerating potential qU is equal to the kinetic energy ½mv², the flight time t is given by t = k·√(m/q), where k is a proportional constant dependent on the instrument settings. That is, the flight time varies with the square root of the mass-to-charge ratio—ions with different m/z values arrive sequentially due to their differing velocities, thereby achieving separation. For example: in MALDI-TOF, a monocharged peptide of 1000 Da travels for approximately 28 microseconds at 15 kV and a tube length of 1.5 m; an ion with a mass of 4000 Da—four times greater—takes approximately twice as long (about 56 microseconds).

How does a reflector (Reflectron) improve resolution?

A reflector uses a constant electrostatic field to reflect the ion beam back towards the detector. Ions of the same m/z with slightly higher initial kinetic energy penetrate deeper and travel a longer path; ions of the same m/z with slightly lower kinetic energy penetrate less deeply and travel a shorter path. By positioning the detector on a plane where ‘ions of the same m/z but different energies arrive simultaneously’ (the time-focusing plane), ions of the same m/z but with different initial energies can reach the detector at the same time, thereby correcting the kinetic energy distribution and improving mass resolution. Reflection also allows ions to travel twice the flight path within the same instrument length, enhancing resolution.

Typical Performance

According to Wikipedia’s entry on ‘Time-of-flight mass spectrometry’: Orthogonal acceleration TOF (oaTOF), combined with collision cooling, has increased the mass resolution of modern TOF instruments from several hundred to tens of thousands without compromising sensitivity; the repetition rate of commercial orthogonal acceleration TOF instruments is typically 5–20 kHz; QToF mass accuracy can reach the fourth decimal place.

Relation to Neo Source products

Neo Source INSTRUMENT’s ProC-1 and ProC-2 online time-of-flight mass spectrometers utilise a dual-field reflection TOF design, used in conjunction with MSI DPI / MSI LDPI imaging ion sources.

References

1. Wikipedia: Time-of-flight mass spectrometry. https://en.wikipedia.org/wiki/Time-of-flight_mass_spectrometry

2. Wiley WC, McLaren IH. Time-of-Flight Mass Spectrometer with Improved Resolution. Review of Scientific Instruments. 1955;26(12):1150. DOI:10.1063/1.1715212

3. Mamyrin BA, et al. The mass-reflectron, a new non-magnetic time-of-flight mass spectrometer with high resolution. Sov. Phys. JETP. 1973;37:45.