WHAT IT IS
Time-of-Flight Mass Spectrometry (TOF-MS) is an analytical technique that determines the mass-to-charge ratio (m/z) of ions by measuring the time it takes them to travel a fixed distance through a field-free flight tube.
HOW IT WORKS
In TOF-MS, ions are first generated in the ion source (e.g., via electrospray ionization, matrix-assisted laser desorption/ionization, or plasma-based ionization). All ions are accelerated by an electric field to the same kinetic energy and enter a vacuum flight tube.
As they travel through the tube, ions separate based on their mass-to-charge ratio—lighter ions travel faster and reach the detector earlier than heavier ones. The flight time is precisely measured and used to calculate each ion’s m/z.
To improve resolution, many TOF-MS systems include a reflectron, an electrostatic mirror that corrects for small energy differences between ions of the same m/z, ensuring they arrive at the detector simultaneously.
ADVANTAGES
High Resolution and Mass Accuracy: Enables differentiation of ions with small m/z differences and supports elemental formula determination.
Fast Full-Spectrum Acquisition: Captures an entire mass range in microseconds, ideal for fast chromatography and high-throughput analysis.
Wide Mass Range: Can detect both small molecules and large biomolecules, such as proteins, peptides, and polymers.
High Sensitivity: Capable of detecting low-abundance species in complex matrices without compromising speed or resolution.
Non-Scanning Design: Unlike scanning instruments, TOF-MS measures all ions simultaneously, reducing time and increasing sensitivity.
CHALLENGES AND LIMITATIONS
Ion Energy Dispersion: Differences in initial kinetic energy can affect flight time accuracy; mitigated by using reflectron optics.
Space-Charge Effects: High ion densities can lead to ion repulsion, affecting resolution and mass accuracy.
Vacuum and Timing Requirements: High-resolution timing and ultra-high vacuum systems are essential for optimal performance.
Lower Dynamic Range than Quadrupoles: May struggle with quantification of analytes at extreme concentration differences within the same sample.