Ultrasensitive in vivo infrared spectroscopic imaging via oblique photothermal microscopy

We report an Oblique Photothermal Microscope (OPM) to enable high-sensitivity and high-resolution infrared spectroscopic imaging of live animals. OPM challenges the conventional wisdom of photothermal sensing by using a split detector to collect all probe photons and acquiring the photothermal signal by analyzing the differences between the halves of the split detector. Compared to classic photothermal detection, OPM enhances the photon collection efficiency by over 500 times. Consequently, OPM increases the signal by 56-fold, reduces laser noise by 18-fold, and increases imaging speed by three orders of magnitude. OPM has enabled low-dose IR imaging of animal skin, thereby avoiding photodamage from IR absorption.