It’s elemental, after all: metals are essential to the function of many biological systems and are thought to have some interaction with at least 30 per cent of all proteins, so taking a good look at those interactions has become a thriving field of research in the last couple of years. Metallomics has joined metabolomics and proteomics as part of the wider ‘omics’ families, and many are using its techniques to study certain diseases, particularly Alzheimer’s and Parkinson’s.

Allowing researchers a close look at those metal interactions has now become a little easier, with a team from the University of Technology, Sydney, led by analytical chemist Dr Philip Doble, in association with equipment multinational Agilent Technologies, developing a new technique called elemental bioimaging to map deposits of trace metals in biological tissues.

The technique has actually been adapted and refined from a technology used in forensic science, laser ablation combined with inductively coupled plasma mass spectrometry (ICP-MS), which has been used to analyse a variety of trace evidence. In fact, Doble and his team are shortly to publish a paper on using laser ablation on steel particles generated from the illicit removal of serial numbers on firearms (see p3).

Laser ablation/ICP-MS was developed to measure solid samples without the need for aggressive sample preparation and was swiftly adopted by geochemists to analyse rocks, but now it’s being used to analyse tissue samples. Doble and his team initially became interested in the biological application when they worked with Professors John Thompson and Richard Scolyer from the Melanoma and Skin Cancer Research Institute (MASCRI) at the University of Sydney.

In that project, the technique was used to image levels of the metalloid antimony in a lymph node biopsy. Surgeons use an antimony sulphide colloid injected into a tumour to track down the sentinel lymph node if the cancer has spread.

“It’s not always possible to determine whether you have the right lymph node after you’ve injected the material, so we image these cells for antimony,” Doble says. “And sure enough, when it was the sentinel lymph node the antimony went through the roof.

“You take a slice (of the biopsy) and you image it and you can see hot spots of antimony. We thought this was very cool so we talked to our friends from Agilent and over a period of years it has developed into this concept of elemental bioimaging.”

ICP-MS is an element analyser, designed to measure trace levels of the elements in the Periodic Table unlike other forms of “organic” MS that are used to identify and quantify molecular compounds. The laser ablation is a sample introduction system for ICP-MS that allows solid materials, including tissues, to be characterised.

Solid samples are ablated by a laser and vapourised, and then transported into the ICP-MS. Doble likens the end result to a dot matrix printer, with an image built up by multiple raster lines.

The vapourised sample is carried into a very hot argon plasma that operates at temperatures close to those at the centre of the sun. As the samples pass through the plasma they decompose to their atoms and these loose an electron to produce ions. The ions are transported into the mass spectrometer that separates the ions according to their mass to charge ratio.

“It’s a mass spectrometer so you can look at the isotopes of the elements; iron-56 and iron-57, for example, down to one atomic mass unit resolution,” Doble says.

“(The sample) ions in the plasma are directed into a quadrupole, which is essentially a mass filter; for a given set of control voltages, only one mass charge ratio will be allowed to pass through; change the settings and another mass will pass through. By sweeping the control settings, the quadrupole will sequentially pass each mass of interest and allow them to strike a detector.

The laser is directed at a position on the tissue, the laser fired for a short period and the analysis undertaken in the ICP-MS. The laser is then moved to a new position and the analysis repeated before moving to a new position. Gradually as the sampling takes place, an image showing the distribution of elements built up. It’s like a dot matrix printer.”