Light-controlled biological microrobots precisely eliminate bio-threats

The diversity of biological threats and their potential risks to human health have prioritised the development of precise and efficient elimination technologies in the biomedical field¹. Conventional approaches, including antibiotic therapy, surgical resection, and immunotherapy, while showing some efficacy, present several limitations. For instance, the overuse of antibiotics leads to heightened drug resistance, surgical interventions carry invasive risks, and immunotherapy can trigger excessive inflammatory responses due to off-target effects². Moreover, emerging issues such as nanoplastic pollution, the spread of drug-resistant bacteria, and cancer cell metastasis have escalated in recent years, creating an urgent need for innovative technologies that offer precision, low toxicity, and active navigation capabilities³.

Rapid progress in biomedical engineering and nanotechnology has positioned microrobots at the forefront of precision medicine owing to their small size, high manoeuvrability, and minimal invasiveness⁴. These microrobots can perform complex tasks at the microscopic level, including targeted drug delivery, tissue repair, and pathogen eradication. However, traditional microrobots largely rely on magnetic or chemical propulsion systems, frequently necessitating modifications with external materials (e.g. magnetic nanoparticles), which pose challenges such as reduced biocompatibility, immune rejection, and limited ability to penetrate biological barriers⁵. Moreover, existing technologies lack precise control over robotic functionalities, limiting their application in complex physiological environments⁶.

The emergence of optical manipulation technologies offers transformative potential in this field. Light provides non-contact operation, high spatiotemporal resolution, and programmability, enabling precise regulation of cellular functions and real-time navigation of microrobots⁷. By utilising near-infrared (NIR) light or laser beams, researchers can remotely activate cellular activities, guide movement trajectories, and modulate cellular metabolism to perform tasks within intricate biological settings⁸. Recently, light-controlled microrobots have become a prominent research focus, particularly “biological microrobots” that employ natural immune cells, such as macrophages, as carriers⁹. These systems attract significant attention due to their inherent compatibility with the human immune system.

Li et al. developed a light-controlled phagocytic macrophage microrobot (phagobot) that activates resting macrophages through localised near-infrared (NIR, 1064 nm) micro-irradiation (Fig. 1a), eliminating the need for genetic modification or external materials while enabling controllable phagocytic capabilities¹⁰. This microrobot achieves precise translational and rotational motion by optically manipulating macrophage filopodia, attaining speeds of 3.4 µm/min in vitro and 4.3 µm/min in vivo, and demonstrating the ability to track complex trajectories (Fig. 1b). Experiments confirmed that in vitro, phagobots can target and engulf bio-threats (e.g. yeast cells, micro/nanoplastics, S. aureus bacterial cells), with phagocytic efficiency dependent on target size and laser power (Fig. 1c). In vivo, phagobots successfully infiltrated the intestinal tissues of zebrafish larvae to eliminate cellular debris, showcasing their excellent biocompatibility as shown in Fig. 1d. This technology combines precise optical manipulation with the innate immune functions of macrophages, offering innovative strategies for precision immunotherapy, infection control, and environmental pollutant removal while avoiding the biocompatibility challenges linked to conventional magnetic propulsion or genetic engineering approaches.

Fig. 1  Light-controlled phagocytic macrophage microrobot (phagobot) for intelligent bio-threat elimination. a NIR optothermal activation of phagobots in resting macrophages. b Optical manipulation guiding activated phagobots along predefined trajectories. c In vitro targeted bio-threat clearance by phagobots. d In vivo targeted bio-threat removal in zebrafish larvae.

Light-controlled biological microrobots embody a significant convergence of biomedicine and nanotechnology, utilising the natural functions of immune cells alongside precise optical manipulation to intelligently eliminate biological threats³. Current studies have confirmed their distinct benefits in targeted delivery, lesion eradication, and microenvironment modulation through in vitro experiments and small animal models. However, advancing the technology requires interdisciplinary collaboration to tackle key challenges, including deep-tissue manipulation, diversification of immune cell carriers, and large-scale production. Future incorporation of ultrasound positioning¹¹, optofluidic effects¹², and flexible fibre-optic implantation^13,14, may allow these microrobots to surmount optical penetration depth limitations, greatly improving their 3D navigation accuracy and penetration efficiency in deep tissues, thus advancing their use in tissue navigation and clearance. Moreover, extending the platform beyond macrophages to include various immune carriers (e.g. neutrophils¹⁵) or biocompatible/biodegradable carriers¹⁶, along with dynamic trajectory planning, holds promise for targeting multiple lesions, eradicating drug-resistant pathogens, and environmental remediation.