Noninvasive interception of circulating leukocyte <i>in vivo</i> by optical tweezer array

The ability to noninvasively manipulate and isolate specific cell populations in vivo is critical for advancing real-time diagnostics, precision medicine, and immunological research. Here, we present a novel and broadly applicable optical trapping system based on a custom-designed [Formula: see text] optical tweezer array, which enables the real-time interception and manipulation of circulating leukocytes in live animals. By utilizing intrinsic velocity differences between leukocytes and red blood cells, the system achieves stable trapping of individual leukocytes in vessels 15–20[Formula: see text] [Formula: see text]m in diameter and decelerates multiple cells in vessels greater than 20[Formula: see text] [Formula: see text]m. Notably, it also enables the optical blockage of lymphatic vessels exceeding 50[Formula: see text] [Formula: see text]m, a previously unreported capability. This label-free, noninvasive approach operates without repeated blood draws and is compatible with diverse vessel geometries and flow dynamics. The system offers a generalizable solution for in vivo cell extraction and analysis, paving the way for high-precision single-cell technologies in biomedical research and clinical translation.