Light force-powered cellular medical micromachines

Abstract

With the synergistic advancement of micro/nanotechnology and intelligent control systems, medical micromachines are emerging as promising alternatives to conventional diagnostic and therapeutic methods, offering enhanced operational precision and minimal invasiveness for precision medicine applications. However, most existing micromachines rely on artificial synthetic materials, which involve complex micro-nano fabrication and raise biosafety concerns regarding immunogenicity and limited long-term therapeutic efficacy in deep tissues. The integration of natural biological cells with programmable optical tweezer has opened new avenues to overcome these limitations, enabling precise behavioral regulation and in situ assembly of cell-based micromachines. This review systematically outlines the design strategies underlying five categories of light force-powered cellular micromachines, including chemotactic bacteria, photosynthetic microalgae, red blood cells (RBCs), immune cells and subcellular structures, and highlights their pioneering applications in targeted drug delivery, minimally invasive surgery and desired immunotherapy. Meanwhile, it also addresses key challenges such as limited tissue penetration depth, phototoxicity management and operation intelligence, while suggesting future directions like adaptive optics-driven swarm control, optomechanobiological coupling and bioprinting-integrated systems. Additionally, the convergence of photonic technology, synthetic biology and artificial intelligence is expected to advance these micromachines into next-generation biomedical platforms for health supervision and disease therapy in vivo.

Keywords: biophotonics; bioprinting; cellular micromachines; light force; optical tweezer.

FIGURE 1

Schematic overview of light force-powered cellular medical micromachines constructed from five representative biological units. (A) Bacteria-based medical micromachines. Illustrated by Escherichia coli, optical forces enable precise spatial arrangement and chain-like assembly of bacterial cells, creating biological waveguides for signal transduction and biosensing. (B) Algae-based medical micromachines. Under optical trapping and rotational control with scanning optical traps (surrounding red spots), microalgae serve as multifunctional micromotors for targeted navigation, cargo delivery and biomanipulation in physiological environments. (C) RBC-based medical micromachine. Optical forces facilitate non-contact trapping and controlled rotation of RBCs, enabling their use as reconfigurable microlenses, microflow switches and signal transmission components. (D) Immune cell-based medical micromachines. Optical tweezers allow real-time control and in situ functional modulation of immune cells (illustrated by macrophages), supporting targeted drug delivery and active pathogen clearance. (E) Subcellular structure-based medical micromachines. Optical forces enable precise manipulation of organelles, such as the controlled rotation of cell nuclei to generate microfluidic flows and the directional transport of mitochondria for intercellular energy delivery.

FIGURE 2

Light force-powered medical micromachines based on bacteria. (A) Schematic illustrating the optofluidic assembly of an E. coli cell chain. A tapered fiber probe integrated in a microchannel traps and sequentially aligns E. coli cells under 980 nm laser irradiation, forming stable chain structures for potential use as bio-optical waveguides (Xin et al., 2013a). (B) Schematic illustration for optical assembly of E. coli biophotonic waveguide. The sequential panels demonstrate waveguides of increased length, culminating in the connection of an output fiber for quantitative optical transmission measurement (Xin et al., 2013b). (C) Enhanced fluorescence and backscattering signals of bacterial chains via yeast-cell microlens. Comparative imaging shows E. coli and S. aureus chains without (upper) and with (lower) the microlens, where red and blue arrows indicate the 980 nm laser (trapping/excitation) and backscattering signal (bacterial counting), respectively (Li et al., 2017). (D) Schematic illustration of the living nanospear for near-field optical probing. This system enables precise scanning manipulation and localized fluorescence excitation/detection on leukemia cells in human blood samples (Li et al., 2018). (E) Schematic illustration of the bio-conveyor belt assembly and the bidirectional transport of a PS particle (Liu et al., 2019b).

FIGURE 3

Light force-powered medical micromachines based on algae. (A) Schematic illustration of optically controlled micromotors based on a CR cell for flexible manipulation and targeted disruption of biological targets. The schematic shows a 3D view with a central trapping beam and an annular scanning path (curved arrow) to control micromotor rotation (panel I), a corresponding 2D layout with scanning optical traps (red spots, panel II), aggregate disruption by using flagella acting as manipulative arms (panel III), and microfluidic flow-driven target transport (panel IV) (Xin et al., 2020). (B) Schematics illustrating two rotation mechanisms of a CR cell including spontaneous rotation via a single-beam optical trap and micro vortex-driven rotation by viscous shear stress (Zou et al., 2020). (C) Biomicromotor tweezers for noninvasive cargo delivery and precision therapy. Two optically trapped CR cells generate hydrodynamic flows for targeted drug transport and controllable ablation of leukemia cells (Pan et al., 2022). (D) Time-sequence images of an OHD for non-invasive capture and removal of nano-biothreats. Yellow and red arrows indicate E. coli and the OHD, respectively (Xiong et al., 2023). (E) Controllable navigation of a photonic nanojet-regulated soft microalga robot. Red and yellow dashed curves mark the motion trajectories of the soft robot and the photonic nanojet, respectively (Xiong et al., 2024).

FIGURE 4

Light force-powered micromachines based on RBCs. (A) Schematic illustration of RBCs-based microlenses for single-cell membrane imaging and stretching (Liu et al., 2019c). (B) Microscope and fluorescence images demonstrating the optical trapping of a 500 nm fluorescent PS nanoparticle using tunable RBC microlens (Chen et al., 2022). (C) Schematic illustration of controlled RBC rotation via a single-fiber optical vortex tweezer. A functionalized fiber generates a tightly focused vortex beam for remote 3D manipulation and rotational control of RBCs (Wu et al., 2024). (D) Schematic illustration of an RBC waveguide assembled in a microfluidic capillary using dual optical fiber tweezers. The system also functions as an optically driven micromotor with controlled RBC rotation (orange arrows) enabling target microparticle transport (Li et al., 2019). (E) Reconfigurable optofluidic switch for blood microflow control in vivo. The micrographs demonstrate precise RBC positioning and dynamic shifting within a capillary. (Liu X. et al., 2020). (F) Optically programmable RBC microrouter for selective routing of biological targets in vivo. The schematic illustrates targeted guidance of different blood components into specific vascular branches under optical control (Liu X. et al., 2023).

FIGURE 5

Light force-powered medical micromachines based on immune cells. (A) Schematic illustrating the principle of an optical stretcher. Counter-propagating laser beams exert controlled mechanical forces and enable contactless cellular morphometry and dynamic depolarization studies (Ekpenyong et al., 2017). (B) Schematic illustration of optically manipulated neutrophils serving as native microcrafts in vivo. The programmable optical force enable multiple cellular manipulations including stable trapping, directional shift, precise arrangement, dynamic activation, targeted navigation and assisted transmigration (Liu et al., 2022). (C) Motion control of the phagobot in vitro. Time-lapse sequences demonstrate controlled rotation along predefined trajectories (red dashed curve), targeted navigation toward specific cells (blue dashed line), and complex locomotor tasks integrating directional steering with U-turn maneuvers (Tan et al., 2025). (D) Optically reconfigurable platelet architecture with adjustable length in vivo (Qin et al., 2024).

FIGURE 6

Light force-powered medical micromachines based on organelle. (A) Schematic illustration of intracellular binding of chloroplasts by using optical fiber tweezers (Li et al., 2015). (B) Lipid droplets as endogenous intracellular microlenses. An optically trapped droplet focuses light and collects fluorescence, enabling real-time imaging of subcellular structures and detection of extracellular signals (Chen et al., 2021). (C) Cell nuclei as endogenous micropumps. Optically controlled rotation of cell nuclei generates localized microfluidic field for enhanced nanoparticle and cell transport in blood vessels (Gao et al., 2021). (D) Optical manipulation and directional delivery of mitochondria within neurons (Gong et al., 2025). (E) Tunneling nanotubes as natural biophotonic conveyors for intercellular transport. Fluorescence imaging exhibits directional mitochondrial transfer from healthy to impaired neurons via optically guided nanotubes (Gong et al., 2024).

FIGURE 7

Cellular aggregates created by 3D bioprinting. (A) Brightfield and fluorescent confocal (green-labeled) images illustrating the precise assembly of complex cellular microstructures using HOTs (Kirkham et al., 2015). (B) Schematic illustrating the stable pyramidal assembly of epithelial cells in PEG-containing medium via optical tweezers (Hashimoto et al., 2016). (C) Optical manipulation of a pair of epithelial cells in the presence of dextran for 5 s or 300 s (Yoshida et al., 2017). (D) Schematic and representative micrographs illustrating an MS1 cell layer sandwiched between adipose-derived mesenchymal stem cells, constructed via optical tweezer in a DEX solution (Yamazaki et al., 2019). (E) Optical trapping and assembly of cell culture using an antibody-functionalized microtool (Mori et al., 2023).