Fighting against fast speckle decorrelation for light focusing inside live tissue by photon frequency shifting

Focusing light inside live tissue by digital optical phase conjugation (DOPC) has been intensively investigated due to its potential biomedical applications in deep-tissue imaging, optogenetics, microsurgery, and phototherapy. However, fast physiological motions in a live animal, such as blood flow and respiratory motions, produce undesired photon perturbation and thus inevitably deteriorate the performance of light focusing. Here, we develop a photon-frequency-shifting DOPC method to fight against fast physiological motions by switching the states of a guide star at a distinctive frequency. Therefore, the photons tagged by the guide star are well detected at the specific frequency, separating them from the photons perturbed by fast motions. Light focusing was demonstrated in both phantoms in vitro and mice in vivo with substantially improved focusing contrast. This work puts a new perspective on light focusing inside live tissue and promises wide biomedical applications.