Mass spectrometry tweak makes diagnosis faster.(Metabolite profiling)

A tweak to a widely used spectrometry technique could enable quick and easy analysis of the metabolites in a person's blood. The new mass spectrometry technique produces a comprehensive snapshot of all the chemical reactions in a cell from just 1[micro]l of blood--a feat that could lead to the fast diagnoses of diseases. It is also expected to speed up metabolomic studies involving the characterisation of all of an organism's metabolites.

The German and Czech researchers' technique concerns modified matrix-assisted laser desorption/ionisation mass spectrometry (MALDI-MS), in which target molecules, held in a matrix of crystallised UV-absorbing molecules, are ionised by using lasers.

Researcher Rohit Shroff, who was at the Max Planck Institute for Chemical Ecology, Germany, but is now at ETH Zurich in Switzerland, says that while MALDI-MS is good for large biomolecules, such as proteins, it is rarely used for small molecules. Unfortunately, the laser ionises the matrix molecules too, creating small molecule signatures that make it hard to distinguish the metabolite's signals from that of the matrix.

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To overcome this problem, Shroff says the group took a two-pronged approach. They used a photostable matrix, combined with basic application of the Bronsted-Lowry theory. This means that if they are, for example, searching for acidic metabolites the matrix needs to be a strong base or hydrogen ion acceptor. They dubbed the new technique matrix-assisted ionisation/laser desorption (MAILD).

Using MAILD they were able to identify a number of human blood metabolites, such as palmitic acid and arachidonic acid, a precursor of numerous signalling molecules and the target of painkillers like paracetamol (PNAS 2009, 106, 10092).

Conventional techniques to analyse metabolites require mL of sample, lengthy purification and treatment of samples, such as blood, followed by GC/MS. This can take days. In contrast, Shroff says, the results produced by MAILD can be known almost immediately after a patient has provided a blood sample.

There is, however, one problem: MAILD is not very good at spotting metabolites that have neither basic nor acidic groups. Shroff says that he thinks this problem can be overcome, but they do not have a 'concrete' solution yet.

David Bender, a metabolism researcher at University College London, UK, says that the technique looks 'exciting'. He adds: 'It looks as if you can identify a large number of compounds in one go, without needing to separate them by chromatography first. This would indeed speed up metabolomic studies.'

A patent has been taken out on MAILD and the researchers are searching for a partner to help commercialise the work.

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