Reflection mode polarimetry guides laser mass spectrometry to diagnostically important regions of human breast cancer tissue.

To enhance the clinical utility of mass spectrometry (MS), lengthy dwell times on less informative regions of patient specimens (e.g., adipose tissue in breast) must be minimized. Additionally, a promising variant of MS known as picosecond infrared laser MS (PIRL-MS) faces further challenges, namely, lipid contamination when probing adipose tissue. Here we demonstrate on several thick non-sectioned resected human breast specimens (healthy and malignant) that reflection-mode polarimetric imaging can robustly guide PIRL-MS toward regions devoid of significant fat content to (1) avoid signal contamination and (2) shorten overall MS analysis times. Through polarimetric targeting of non-fat regions, PIRL-MS sampling revealed feature-rich spectral signatures including several known breast cancer markers. Polarimetric guidance mapping was enabled by circular degree-of-polarization (DOP) imaging via both Stokes and Mueller matrix polarimetry. These results suggest a potential synergistic hybrid approach employing polarimetry as a wide-field-imaging guidance tool to optimize efficient probing of tissue molecular content using MS.