Lasers & photonics
one that remains part of MALDI folklore – even though Koichi’s method was distinct enough that it didn’t fall under the same definition. Koichi won a quarter of the 2002 Nobel Prize, which was richly deserved, but many thought it was tough on Hillenkamp and Karas – a valid observation given that the duo’s MALDI technique is still the preferred choice in labs today.
How does it work?
The approach to sample preparation and loading on the matrix material remains something of a ‘dark art’ in the esoteric world of MALDI. An analyte can be applied to a metal plate and as the mixture dries, crystals are formed on the sample material. The interaction with laser wavelength photons creates what is often described as ‘soft ionisation’. The pulsed laser beam impinges on the sample, resulting in desorption of the sample bound to the matrix material. It breaks down in the process to produce gas phase ionic species. The mechanism for the ionisation of the analyte molecules is via protonation or de-protonation in the hot plume of ablated gases, and they are accelerated into a mass spectrometer system for analysis. The most widespread version of the technology is MALDI-TOF MS (matrix assisted laser desorption ionisation time-of-flight mass spectrometry). Using this method, particles are ionised as described above, separated according to their mass-to-charge ratio, after which they’re measured by determining the time it takes for the ions to travel to a detector at the end of a time-of-flight tube. MALDI-TOF- MS has given yeoman service in laboratories, working on molecular biology, proteomics, glycomics, organic chemistry, polymer analysis, microbiology and medical diagnostics.
The gold standard
The story of MALDI-TOF is one using experimentation of a range of matrix material and laser energy sources or wavelengths. The success of this work can be seen by the degree of reliance on MALDI in multiple settings. “MALDI’s future is secured,” says Rainer Cramer, professor of mass spectrometry and bioanalytical sciences and head of biomedical, molecular and analytical chemistry at Reading University. “The
Medical Device Developments /
www.nsmedicaldevices.com 59
technique has evolved rapidly as a diagnostic tool in key areas of medicine. In some sectors it is the gold standard, and we will continue to find applications.” MALDI is becoming a go-to technique in the quest for biomarkers for a range of cancers, as well as helping to identify them in their early stage, adding to the body of knowledge on the biological mechanisms that drive tumour growth. “It’s not widely appreciated but it is an important tool used for Covid-19 virus identification,” adds Cramer. He is one of a community of researchers investigating ways of creating an ionisation matrix where the analyte is presented in liquid form, focusing on producing workable levels of soft ionisation and a stable and efficient ion signal.
Demcon Focal B.V
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