Time-of-Flight Mass Spectrometry (TOF-MS) [Analytical Techniques]

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Glossary

WHAT IT IS

Time-of-Flight Mass Spectrometry (TOF-MS) is an analytical technique used to determine the mass-to-charge ratio of ions based on the time they take to travel through a field-free region. It is known for its fast data acquisition, broad mass range, and high mass resolution. TOF-MS is widely used in laboratories for the qualitative and quantitative analysis of both small and large molecules, including in research, quality control, and materials characterization.

HOW IT WORKS

In TOF-MS, ions are generated from the sample and accelerated by an electric field to the same kinetic energy. These ions then enter a flight tube — a long, evacuated space with no electric or magnetic fields. As the ions travel through the tube, they are separated by mass: lighter ions move faster and reach the detector earlier than heavier ones.

The detector records the time it takes for each ion to reach it, and this time is converted into a mass-to-charge ratio. A common enhancement in TOF systems is the use of a reflectron, an electrostatic device that improves mass resolution by compensating for small differences in ion energy.

ADVANTAGES

Rapid Full-Spectrum Acquisition: It captures a complete mass spectrum in a single pulse, allowing for high-speed analysis and real-time monitoring.

High Mass Range: It can detect a wide range of ion masses, from low molecular weight compounds to large biomolecules.

Excellent Mass Resolution: Especially when equipped with a reflectron, TOF-MS can distinguish between ions with very small differences in mass.

Simultaneous Detection: All ions are measured at once, improving throughput and reducing the risk of missing transient or low-abundance species.

Minimal Fragmentation: It works well with ion sources that preserve the molecular ion, useful for identifying intact compounds.

CHALLENGES AND LIMITATIONS

Ion Energy Spread: Ions of the same mass can have slightly different energies, which can reduce mass resolution if not corrected.

Space-Charge Effects: High concentrations of ions can interfere with one another, affecting measurement accuracy and resolution.

Vacuum Requirements: TOF-MS systems must operate under high vacuum to prevent collisions with air molecules, requiring careful maintenance.

Time-Based Calibration: The accuracy of mass assignments depends on precise timing and stable electronics, which need regular calibration.

Lower Sensitivity for Low-Mass Ions: Detection efficiency may be lower for very small ions unless the system is optimized for that range.

TYPES

Linear TOF: Ions travel directly to the detector in a straight path.

Reflectron TOF: A reflectron is used to reverse ion trajectories and correct for energy differences, improving resolution.

Orthogonal Acceleration: Ions are introduced into the flight tube at a right angle to their initial path, enhancing resolution and allowing continuous ion sources to be used effectively.