Caprioli and Cooks have focused on lipids, the oily molecules that make up cell membranes and that can be abnormal in cancer cells. Using DESI to examine the areas where normal tissue abuts cancer tissue, the researchers saw different distributions of many kinds of lipids on either side of the tumor border, demonstrating that mass spectrometry can detect chemical differences between normal and cancerous tissue. “We don’t know what it does on proteins yet. We might have to play around with conditions to get it to work,” Caprioli says, pointing out that the method is young.
Caprioli and Cooks want a doctor to be able to look at a tumor’s mass spectrometry profile, and, if the patient “only has a prognosis of six months, as with some brain tumors, my God, you throw everything you can at them,” says Caprioli. But because cancer treatment can be harrowing for patients, “In another case you might say, no, the molecules for aggressive disease are not here, so we don’t have to treat them aggressively,” he adds.
The DESI method, if refined, could be used to perform what’s called mass spectrometry imaging. So far, the technique has not been done in the open air; now the DESI technique could expand its reach to the human body. Mass spectrometry imaging does more than straightforward mass spectrometry: in addition to gathering chemical information, it pinpoints where in a tissue the molecules under study are located. A mass spectrometry image is “a picture that has information like a TV picture, except it has mass information instead of color information,” explains Nick Winograd, a Pennsylvania State University chemistry professor and mass spectrometry imaging pioneer. The advantage of the technique over, for example, tagging molecules with fluorescent proteins, is that one doesn’t have to design a tag for each molecule to be studied.
Winograd uses a mass spectrometry imaging method called SIMS, which has 500 times the resolution of DESI, to examine the activity of individual neurons. And Caprioli also does imaging work. Using a matrix of protective molecules to shield tissues from the havoc in the mass spectrometry chamber, he has imaged tumors at 10 times the resolution of DESI. But as Winograd points out, with DESI, Cooks “has the tremendous advantage of being able to do [his studies] in the air,” without extensive sample preparation.
Using mass spectrometry imaging, Winograd explains, “all of us would like to be able to take a tissue slice and, for example, map the chemistry of drug molecules applied in a critical environment, or do fundamental science and determine in a blue-sky fashion what molecules are in the tissue, and where they’re located.”
All the major mass spectrometry manufacturers are working on commercializing imaging devices, according to Caprioli. He and Winograd say biologists would jump at the chance to use mass spectrometry devices. “I think it will be in the mainstream very quickly, within the next few years,” Caprioli says.
But having a high-resolution image isn’t necessary to generate the kind of molecular profiles of cancer that Cooks and Caprioli hope to. “What’s important is not so much the spot size as the kinds of molecules that you get out,” says Caprioli. If all goes well, Cook says, DESI mass spectrometry could be used to scan a patient’s tissue directly during surgery, with no biopsy necessary.
Home page image courtesy of Richard Caprioli, Vanderbilt University. Caption: Each color in this image of a section of rat brain represents a different protein.