Painless real-time proteomics may one day speed up cancer surgery

Fournier, a professor at the University of Lille and co-director of a proteomics center of INSERM, the French national institute of health. In Her laboratory, she has worked for several years on a device. It was called “Spider Mass” that will enable the surgeons to identify markers of cancer in a living patient's tissue, during an operation.

Surgery to remove a primary tumor and after some healthy surrounding tissue are removed, Although this process will help for preventing recurrence of the cancer, it can add up to 45 risky minutes under anesthesia. Fournier's device uses mass spectrometry method, which measures the mass of molecules from complex mixtures. But turning an in vivo tissue sample into gas phase ions for measurements can be a challenge. Until now, no one knew how to extract ions from living tissues without doing harm.

Riffing on MALDI, it is an ionization strategy that uses a carrier molecule mixed with the analyte of interest; then they decided to use the water that makes up a majority of human tissue as a carrier to produce a water-assisted laser desorption/ionization, or WALDI. If they could excite the water in a tiny area, it should vaporize, taking ionized organic molecules with it.

The team built a pulsed laser excitation device to heat water precisely by causing vibration in the oxygen-hydrogen bond. In a 2016 paper, they described using this laser to ionize the outermost layer of tissue, penetrating less than one-twentieth of a millimeter. The human volunteers reported a slight tingling sensation. But the ions that appeared were mostly small molecules and lipids, which are more apt than proteins to adopt a negative charge. The team hoped to measure proteins as well.

In this new paper, Fournier and colleagues reported that they have fissured the protein puzzle. By using a sensitive mass spectrometer and looking for positively charged ions instead of negatively charged ions, they found peaks representing purified proteins they had introduced into a cow liver sample. Now that they know the proteins are detectable, the next step will be finding ways to amplify the protein signal over more abundant lipids and metabolites.