Time-of-flight mass spectrometry (TOFMS): From niche to mainstream (Englisch)

Graphical abstract

Highlights • World War II electronic advances suggested the use of time-of-flight for mass measurements. • Enormous technical advances in TOF were driven by the invention of MALDI. • The further development of TOF MS driven by advances in digital electronics. • Mass spectrometry, including TOF, is now an essential tool in biological and clinical research. • Instruments for routine clinical applications are fully automated and require little expertise in mass spectrometry.

Abstract World War II electronic advances suggested the use of time-of-flight for mass measurements, leading to the development of a commercial TOFMS instrument by Bendix. This instrument used electron impact ionization, but the subsequent application of fission fragment bombardment (PDMS), coupled to TOFMS, was responsible for significant advances in the mass spectrometry of large biomolecules. Bombardment by accelerated MeV or keV ions, again coupled to TOFMS, was found to be equally successful. Although these TOF methods were the only ones initially capable of measuring the masses of really large biomolecules, most mass spectrometrists were still wedded to sector/quadrupole instruments for high/low-end mass measurements. The “coup de grace” for TOF (as generally believed) was the discovery of a suitable matrix (glycerol), which enabled the use of sector/quadrupole instruments for measurements of large biomolecules (“fabulous FAB”). Ironically, it was the discovery of suitable matrices for laser excitation that revived TOFMS, aided by the additional accuracy provided by the reflecting geometry, and the subsequent development of orthogonal injection, as well as the coupling to liquid chromatography. Enormous technical advances in TOF were driven by the invention of MALDI and facilitated by the parallel advances in digital electronics. All of mass spectrometry has benefitted from these technical advances, but TOF most of all because of the need for high speed acquisition and large data storage capacity. Thus TOF is now in the mainstream of biological applications of mass spectrometry.