In vivo flow cytometry using vessels as natural tubes with native cell flows has revolutionized the study of rare circulating tumor cells in a complex blood background. However, the presence of many blood cells in the detection volume makes it difficult to count each cell in this volume. We introduce method for manipulation of circulating cells in vivo with the use of gradient acoustic forces induced by ultrasound and photoacoustic waves. In a murine model, we demonstrated cell trapping, redirecting and focusing in blood and lymph flow into a tight stream, noninvasive wall-free transportation of blood, and the potential for photoacoustic detection of sickle cells without labeling and of leukocytes targeted by functionalized nanoparticles. Integration of cell focusing with intravital imaging methods may provide a versatile biological tool for single-cell analysis in circulation, with a focus on in vivo needleless blood tests, and preclinical studies of human diseases in animal models.

The aim of this study is to evaluate the capability of the photoacoustic (PA) effect for manipulation of nonbiological particles or living cells. The principal operation of such “PA tweezers” are based on laser generation pressure gradients in a medium surrounding the particles, that create forces acting on the particles. Depending on the spatial geometry of these forces, particles can be moved in desired directions (asymmetrical forces) or trapped (symmetrical forces). Evaluation of these forces was performed for the laser beam with the conventional circular geometry and a ring geometry. If the laser-induced forces push the particles or cells away from the laser beam, the ring geometry is more preferable for their trapping. The capabilities of such PA tweezers are discussed.