4.2 MALDI-TOF mass spectrometry

MALDI-TOF mass spectrometry (MS) is a specialised type of laboratory RDT. Most laboratory RDTs can only look for one particular type of bacteria, and standard identification requires different processes, reagents and equipment for each different type of bacteria. MALDI-TOF MS uses the same process (identification of bacterial protein profiles according to their molecular weight and charge) for all types of bacteria, using the same reagents.

Once bacteria are visible on an agar plate (usually after 8–18 hours of incubation), their species can be identified using MALDI-TOF MS in a matter of minutes, whereas standard testing requires a laboratory technician to set up a series of tests (which is itself time-consuming) and incubate for a further 24–48 hours.

The cost of reagents is very small, but a MALDI-TOF mass spectrometer is a significant investment: the prospective cost of maintenance and a database that needs regular updates should be considered. Usually, the investment needed to purchase and maintain a MALDI-TOF is only worthwhile in laboratories processing tens of thousands of samples per year, or in reference laboratories.

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Figure 4 An overview of MALDI TOF MS (Chabriere et al., 2018).

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The first stage of MALDI TOF MS is sample preparation. Prepared samples are deposited on a steel plate with a matrix, generally alpha-Cyano-4-hydroxycinnamic acid. Most of a bacteria colony grown on an agar plate are put on the steel plate directly, without preparation.

The second stage is mass spectra of the sample. The matrix allows ionisation and desorption of the molecule after a laser pulse. A mass spectrometer measures the time of flight of the ionised molecule that is related to the ratio M/Z, where M is the molecular weight of the molecule and Z is its electric charge. This provides a mass spectra profile of the sample, revealing the M/Z ratio of each ionised molecule (mainly ribosomal proteins in bacteria).

The third stage is biotyping. The mass spectra is a fingerprint of the sample composition; the sample can be identified (such as its genus and species) by matching it to a database. Ninety-six samples can be identified in one hour.

Figure 4 An overview of MALDI TOF MS (Chabriere et al., 2018).