During cancer surgery, surgeons often must wait for pathologists to analyze a removed tissue sample to confirm they’ve gotten all the cancer. Researchers have previously shown that analyzing tissue with mass spectrometry during surgery can help speed this process. But those surgical mass spec approaches rely on methods that often damage the tissue or are suitable only for analyzing removed samples. Livia S. Eberlin of the University of Texas, Austin, and coworkers have now come up with a biocompatible device that uses discrete water droplets to nondestructively obtain molecular profiles of cancer tissue (Sci. Transl. Med.2017, DOI: 10.1126/scitranslmed.aan3968). The handheld device delivers a water droplet to the tissue surface, where it gently extracts metabolites, lipids, and proteins. Afterward, a plastic tube carries the water droplet to an attached mass spectrometer. The researchers used the device to sample 253 tissue pieces from a variety of cancers, finding that the mass spectra allow them to distinguish between cancer tissue and normal tissue, including in samples containing both types of tissue. In addition, the researchers used the device to diagnose cancer in live mice during surgery without damaging tissue or stressing the animals.