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With high reconfigurability and swarming intelligence, programmable medical micromachines (PMMs) represent a revolution in microrobots for executing complex coordinated tasks, especially for dynamic routing of various targets along their respective routes. However, it is difficult to achieve a biocompatible implantation into the body due to their exogenous building blocks. Herein, a living microrouter based on an organic integration of endogenous red blood cells (RBCs), programmable scanning optical tweezers and flexible optofluidic strategy is reported. By harvesting energy from a designed optical force landscape, five RBCs are optically rotated in a controlled velocity and direction, under which, a specific actuation flow is achieved to exert the well-defined hydrodynamic forces on various biological targets, thus enabling a selective routing by integrating three successive functions, i.e., dynamic input, inner processing, and controlled output. Benefited from the optofluidic manipulation, various blood cells, such as the platelets and white blood cells, are transported toward the damaged vessel and cell debris for the dynamic hemostasis and targeted clearance, respectively. Moreover, the microrouter enables a precise transport of nanodrugs for active and targeted delivery in a large quantity. The proposed RBC microrouter might provide a biocompatible medical platform for cell separation, drug delivery, and immunotherapy., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Serving as natural vehicles to deliver oxygen throughout the whole body, red blood cells (RBCs) have been regarded as important indicators for biomedical analysis and clinical diagnosis. Various diseases can be induced due to the dysfunction of RBCs. Hence, a flexible tool is required to perform precise manipulation and quantitative characterization of their physiological mechanisms and viscoelastic properties. Optical tweezers have emerged as potential candidates due to their noncontact manipulation and femtonewton-precision measurements. This review aimed to highlight the recent advances in the multifunctional manipulation of RBCs using optical tweezers, including controllable deformation, dynamic stretching, RBC aggregation, blood separation and Raman characterization. Further, great attentions have been focused on the precise assembly of functional biophotonics devices with trapped RBCs, and a brief overview was offered for the growing interests to manipulate RBCs in vivo., (© 2021 Wiley-VCH GmbH.)

The single-cell screening has attracted great attentions in advanced biomedicine and tissue biology, especially for the early disease diagnosis and treatment monitoring. In this work, by using a specific-designed fiber probe with a flat facet, we propose an "optical fan" strategy to screen K562 cells at the single-cell level from a populations of RBCs. After the 980-nm laser beam injected into the fiber probe, the RBCs were blown away but holding target K562 cells in place. Further, multiple leukemic cells can be screened from hundreds of red blood cells, providing an efficient approach for the cell screening. The experimental results were interpreted by the numerical simulation, and the stiffness of optical fan was also discussed., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Control of blood microflow is crucial for the prevention and therapy of blood disorders, such as cardiovascular diseases and their complications. Conventional control strategies generally implant exogenous synthetic materials into blood vessels as labeling markers or actuating sources, which are invasive and incompatible with biological systems. Here, a label‐free, noninvasive, and biocompatible device constructed from natural red blood cells (RBCs) for controlling blood microflow in vivo is reported. The RBCs, optically manipulated, arranged, and rotated using scanning optical tweezers, can function as an optofluidic switch for targeted switching, directional enrichment, dynamic redirecting, and rotary actuation of blood microflow inside zebrafish. The regulation precision of the switch is determined to be at the single‐cell level, and the response time is measured as ≈200 ms using a streamline tracking method. This in vivo optofluidic switch may provide a biofriendly device for exploring blood microenvironments in a noncontact and noninvasive manner. [ABSTRACT FROM AUTHOR]

Dynamic rotation and deformation of human red blood cells (RBCs) are extremely important to investigate the survival and mechanical features of cells, which will be of great physiological and pathological significance. Here, we report an optical approach that is capable of both rotating and deforming RBCs with light from two tapered fiber probes (TFPs). With laser beams at the wavelength of 980 nm injected into the TFPs, a single RBC was rotated around different axes while single or multiple RBCs were stretched by adjusting the points of action and magnitude of the optical forces from the TFPs. The biological safety of the approach was also discussed by taking the laser power required into account. [ABSTRACT FROM AUTHOR]

With great potential in intelligent sensing and actuating systems, biosensors and micromotors are expected to be powerful instruments for early diagnosis and drug delivery in precision medicine. However, it is difficult to ensure the synthetic biosensors and micromotors are compatible with biosystems because of their exogenous building blocks. Biocompatible biosensors and micromotors assembled are reported from living red blood cells (RBCs) optically bound into a waveguide using fiber probes. By monitoring light propagation of the RBC waveguide, the pH of blood solution is detected in real time with an accuracy of 0.05. This can be used for the diagnosis of pH‐related disorders of the blood. After diagnosis, optical torque is exerted on the RBC waveguide, allowing it to rotate as a micromotor and transport microparticles to a target region. The RBC waveguide is then constructed inside zebrafish blood vessels to validate in vivo application. The living biosensors and micromotors are expected to provide a "smart" platform for precise biosensing, medical analysis, and drug delivery. [ABSTRACT FROM AUTHOR]

Micropumps can generate directional microflows in blood vessels or bio-capillaries for targeted transport of nanoparticles and cells in vivo , which is highly significant for biomedical applications from active drug delivery to precision clinical therapy. Meanwhile, they have been extensively used in the biosensing fields with their unique features of autonomous motion, easy surface functionalization, dynamic capture and effective isolation of analytes in complex biological media. However, synthetic devices for actuating microflows, including pumps and motors, generally exhibit poor or limited biocompatibility with living organisms as a result of the invasive implantation of exogenous materials into blood vessels. Here we demonstrate a method of constructing endogenous micropumps by extracting nuclei from red blood cells, thus making them intrinsically and completely biocompatible. The nuclei are extracted and then driven by a scanning optical tweezing system. By a precise actuation of the microflows, nanoparticles and cells are navigated to target destinations, and the transport velocity and direction is controlled by the multifunctional dynamics of the micropumps. With the targeted transport of functionalized micro/nanoparticles followed by a dynamic mixing in microliter blood samples, the micropumps provide considerable promises to enhance the target binding efficiency and improve the sensitivity and speed of biological assays in vivo. Furthermore, multiplexing by simultaneously driving an array of multiple nuclei is demonstrated, thus confirming that the micropumps could provide a bio-friendly high-throughput in vivo platform for the treatment of blood diseases, microenvironment monitoring, and biomedical analysis. • A light-driven micropump was constructed with endogenous cell nucleus to transport nanoparticles and cells in vivo. • The bio-friendly micropump was free from invasive implantation of exogenous matters and independent of particle composition. • Multifunctional dynamics of micropumps assured a real-time control of the transport velocity and directions. • A high-throughput platform can be accomplished by multiplexing an array of multiple nucleus micropumps. [ABSTRACT FROM AUTHOR]