Purdue scientists who recently streamlined a common chemistry lab tool have joined forces with a biomedical group at Vanderbilt University to make the invention potentially valuable in hospital operating rooms.
By custom-modifying a mass spectrometer with a novel sample introduction device, a team including R. Graham Cooks, has found that the wand-like sample probe can be used to accurately identify liver cancers. The technique can tell the difference between diseased and non-diseased regions of tissue samples within a few seconds. Cooks said that the devices might one day prove useful in helping doctors ensure that a tumour is fully removed before a patient leaves the operating table.
“A host of medical issues could be confronted with this tool, which has a very wide range of applications,” said Cooks, who is the Henry Bohn Hass Distinguished Professor of Analytical Chemistry in Purdue’s College of Science. “For example, in previous studies, it has been found to be useful in detecting the residues of explosives found on luggage.”
The team’s paper appears on the cover of the current issue of Angewandte Chemie, a leading European scientific journal. Members of the team include Purdue’s Justin M. Wiseman and Zoltán Takáts, as well as Vanderbilt University’s Satu M. Puolitaival and Richard M. Caprioli.
The wand-like probes are one of the improvements the team has made to the mass spectrometer, an analytical device that in its conventional form has been long established in modern laboratories. But while ordinary mass spectrometry is both time- and labour-intensive, the Cooks team has modified the devices so that not only are they portable enough to be carried in backpacks, but they can also determine the chemical composition of an unprepared sample within five seconds.
Their modified spectrometric technique, which the team has dubbed desorption electrospray ionisation (DESI, pronounced “daisy”), involves aiming a fine water mist at a surface with a pencil-sized tube that also sucks up the fluid after the droplets have mixed with the material in the sample.
“This paper shows specifically that DESI can detect cancer in liver tissue, but its medical applications can go beyond that,” said Takáts, who is a postdoctoral assistant in Cooks’ lab. “We see DESI as a microscope that can ‘see’ chemicals instead of light. As we move the ‘wand’ across tissue, it can reveal what chemicals are where, and these chemical signatures are clues to what’s happening in the body.”
Takáts said, for example, that DESI could help doctors determine how well a drug is working in different parts of a bodily organ. By analysing different regions in a tissue sample, doctors could better evaluate the mechanism of its action, thus revealing its effectiveness.
“One advantage of DESI for these types of problems is its potential for analysing tissue in live patients in real time, right on the operating table,” Takáts said. “While we are not quite there yet, we are moving rapidly in that direction.”
DESI can now resolve chemical differences between areas of a sample as small as a half-millimetre, or 500 micrometers. With further improvements, Cooks said, it could resolve objects as small as 50 micrometers, or the size of individual cells. Even now, the resolution is good enough to find cancers and determine where their edges lie.
“DESI can now locate very small tumours in a tissue sample,” said Wiseman, a graduate student on the team. “Also important is the rapid rate at which the technique provides detailed chemical information about a sample. This fast procedure suggests that we will be able to help surgeons ensure that they have destroyed all of a tumour before a patient leaves surgery and that we might identify other potential tumour sites in the tissue that are indistinguishable to the naked eye.”
Contributing to DESI’s analytical power is its ability to detect certain telltale chemicals that are present at abnormal levels when a patient is ill. Many scientists are working on ways to detect these disease markers to improve a doctor’s ability to diagnose illnesses quickly, but Cooks said DESI might have a particular advantage over other methods.
“What this study also shows is DESI’s ability to read a type of disease marker that often presents a real problem for doctors – the lipids,” Cooks said. “Traditional mass spectrometry has been good at detecting disease markers such as proteins, but the body’s levels of fatty lipid molecules can also be markers for conditions such as arthritis. We’d like to see the lipids, too, so that we can diagnose more diseases accurately.”
While analysing a sample of liver tissue with DESI, the team found that a cancerous region possessed higher levels of certain lipid molecules. Cooks said the findings could indicate a significant relationship between these fatty substances and tumour proliferation.
“Confirming this relationship will require further effort, as will the improvements that will make DESI as useful as we feel it can be,” he said. “For now, we have shown that DESI can quickly provide medically relevant information to physicians, including the location of the boundary between cancerous and healthy tissue, accurate to within the diameter of just a few cells. That gives us cause for optimism.”