Wide-field tissue polarimetry allows efficient localized mass spectrometry imaging of biological tissues.

While mass spectrometers can detect chemical signatures within milliseconds of data acquisition time, the non-targeted nature of mass spectrometry imaging (MSI) necessitates probing the entire surface of the sample to reveal molecular composition even if the information is only sought from a sample subsection. This leads to long analysis times. Here, we used polarimetry to identify, within a biological tissue, areas of polarimetric heterogeneity indicative of cancer. We were then able to target our MS analysis using polarimetry results to either the cancer region itself or to the cancer margin. A tandem of polarimetry and Desorption Electrospray Ionization Mass Spectrometry Imaging (DESI-MSI) enables fast (10 fold compared to non-targeted imaging), and accurate pathology assessment (cancer typification in less than 2 minutes compared to 30 minutes for histopathology) of tissue slices, without additional sample preparation. This workflow reduces the overall analysis time of MSI as a research tool.