Red Blood Cells as Endogenous Biotweezers for Optical Micromanipulation In Vivo

Precise control of micro-/nano-scale objects in vivo is crucial for biomedical applications. Here, we demonstrate a biohybrid optical manipulation strategy that integrates a long-distance manipulation fiber probe (LDMFP) and natural red blood cells (RBCs) to construct endogenous biotweezers for optical micromanipulation in vivo. By using the engineered LDMFP, an extended focal field was generated, which could capture flowing RBCs within the living blood vessel. Benefiting from their smooth disk-shape and homogenous refractive index distribution, these trapped RBCs can function as natural biotweezers that refocused incident light to create a secondary optical trap, thus achieving an enhanced microparticle trapping probability (98% vs. 5%) and improved counter-flow migration velocity (12 vs. 4.5 µm/s) when compared to the LDMFP alone, as well as rapid immune cell activation within 10 s. By assembling multiple RBCs into extended biotweezer arrays, they can further function as biological waveguides for long-distance directional transmission, achieving strong focusing and localized field enhancement with extended manipulation distances. Experimental results were supported by finite-element simulations, which validated the improved trapping stiffness and operational range. This bio-hybrid approach presents a promising platform for intravital optical manipulation and suggests potential applications in therapeutic delivery and behavior modulation of immune cells.