Super sensitivity and specificity: Integration of multiscale PAT and photoswitchable proteins

Collaborating with Prof. Vladislav Verkhusha’s team at Albert Einstein College of Medicine, we have combined the photoswitchable phytochrome probes to PAT to achieve ultrahigh detection sensitivity, high contrast, and multiscale imaging for the first time. This technique has allowed monitoring the tumor growth and metastasis inside the deep body and achieved super-resolution (140 nm) imaging of single tumor cells. Taking advantage of the different decay characteristics of different photoswitchable probes and the decay analysis, I have addressed the impact of unknown local fluence and achieved quantitative multicontrast imaging in deep tissue—a task that previously could not be done reliably. In addition, the combination of the advanced photoswitchable probes and photoacoustic computed tomography has, for the first time, achieved real-time high-resolution imaging of protein-protein interactions in deep tissue. This technical advancement paves a new avenue for cancer study and drug development. In addition, we use photoswitchable phytochrome probes as genetically encoded guide stars in living tissue to tag photons at targeted locations, achieving light focusing inside the tissue by wavefront shaping. By modulating the GePGS at a distinctive frequency, we suppressed the competition between guide stars and tissue motions and formed tight foci inside mouse tumors in vivo, thus improving light delivery efficiency and specificity. These results have been published in Nature Methods (13 (1), 67, 2016), Nature Communications (9 (1), 2734, 2018), and Science Advances (5 (12), eaay1211, 2019). And two US patents have been applied based on the related techniques.

Focusing light inside live tissue using reversibly switchable bacterial phytochrome as a genetically encoded photochromic guide star, Science Advances (2019) 5 (12), eaay1211, 1–9

Small near-infrared photochromic protein for photoacoustic multi-contrast imaging and detection of protein interactions in vivo, Nature Communications (2018) 9 (1), 2734, 1–14

Multiscale photoacoustic tomography using reversibly switchable bacterial phytochrome as a near-infrared photochromic probe, Nature Methods (2016) 13, 67–73