Technology Roadmap of Micro/Nanorobots

Abstract

Inspired by Richard Feynman's 1959 lecture and the 1966 film Fantastic Voyage, the field of micro/nanorobots has evolved from science fiction to reality, with significant advancements in biomedical and environmental applications. Despite the rapid progress, the deployment of functional micro/nanorobots remains limited. This review of the technology roadmap identifies key challenges hindering their widespread use, focusing on propulsion mechanisms, fundamental theoretical aspects, collective behavior, material design, and embodied intelligence. We explore the current state of micro/nanorobot technology, with an emphasis on applications in biomedicine, environmental remediation, analytical sensing, and other industrial technological aspects. Additionally, we analyze issues related to scaling up production, commercialization, and regulatory frameworks that are crucial for transitioning from research to practical applications. We also emphasize the need for interdisciplinary collaboration to address both technical and nontechnical challenges, such as sustainability, ethics, and business considerations. Finally, we propose a roadmap for future research to accelerate the development of micro/nanorobots, positioning them as essential tools for addressing grand challenges and enhancing the quality of life.

Keywords: collective behavior; functionality; intelligence; micro/nanorobots; nanotechnology; propulsion; smart materials; technological translation.

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Historical evolution of micro/nanorobotics. a) Magnetic milliscale helical swimmer as a prototype. Reproduced from ref , Copyright 1996 IEEE. b) Chemically propelled self-assembled Pt motor. Reproduced from ref , Copyright 2002 WILEY-VCH. c) Self-propelled bimetallic nanorod via self-electrophoresis. Reproduced from ref , Copyright 2004 American Chemical Society. d) Theoretical proposal for a microswimmer containing three spheres linked by two rigid rods with changeable lengths. Reproduced from ref , Copyright 2004 American Physical Society. e) Self-propulsion of Janus spherical microrobots. Reproduced from refs , , Copyright 2007 American Physical Society. f) Chemotaxis of nanomotors, Reproduced from ref , Copyright 2007 American Physical Society. g) Catalytic microrocket fabricated via roll-up technology. Reproduced from ref , Copyright 2008 WILEY-VCH. h) Electric-driven Janus microrobot. Reproduced from ref , Copyright 2008 American Physical Society. i) Light-driven semiconducting AgCl micromotor, Reproduced from ref , Copyright 2009 WILEY-VCH. j) Magnetic field-driven microrobots. Reproduced from refs , , Copyright 2009 American Chemical Society. k) Nanomotor-based DNA sensing. Reproduced from ref , Copyright 2010 Springer Nature. l) Helical carrier operated by a magnetic field. Reproduced from ref , Copyright 2012 WILEY-VCH. m) Microrocket using gastric acid as fuel. Reproduced from ref , Copyright 2012 American Chemical Society. n) Ultrasound-propelled nanowires. Reproduced from ref , Copyright 2012 American Chemical Society. o) Micro/nanorobots for environmental applications. Reproduced from refs , , Copyright 2012 and 2013 American Chemical Society. p) Nanomotor lithography. Reproduced from ref , Copyright 2014 Springer Nature. q) Helical nanomotor operates in whole blood. Reproduced from ref , Copyright 2014 American Chemical Society. r) Ultrasound nanomotor propelling inside living cells. Reproduced from ref , Copyright 2014 WILEY-VCH. s) First in vivo application of microrobots, using Zn-based microrockets propelling in mice stomach. Reproduced with permission under a Creative Commons CC-BY License from ref , Copyright 2015 American Chemical Society. t) Urea-powered enzymatic nanomotor. Reproduced with permission under a Creative Commons CC-BY License from ref , Copyright 2015 American Chemical Society. u) Magneto–aerotactic biohybrid micromotor for cancer treatment. Reproduced from ref , Copyright 2016 Springer Nature. v) Microrobotic pills containing drug-carrying Mg micromotors. Reproduced from ref , Copyright 2018 American Chemical Society. w) Biohybrid algae robots functionalized with ciprofloxacin loaded nanoparticles for acute pneumonia treatment. Reproduced from ref , Copyright 2022 Springer Nature. x) Urease-powered nanobots for radionuclide bladder cancer therapy. Reproduced with permission under a Creative Commons CC-BY License from ref , Copyright 2024 Springer Nature.

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Theory of locomotion at low Reynolds numbers and micro/nanorobot propulsion mechanisms. a) Schematic drawing of Purcell’s “Scallop Theorem” with reciprocal motion at low Reynolds number regime. Adapted from ref , Copyright 1977 AIP Publishing. b) Two main biological propulsion mechanisms based on nonreciprocal motion at low Reynolds number regime, i.e., beating a flexible oar (in eukaryotic flagellar-based propulsion) and rotating a chiral flagellum (in bacterial flagellar-based propulsion). Adapted from ref , Copyright 1977 AIP Publishing. c) Schematic overview of various chemical propulsion mechanisms utilized for different kinds of micro/nanomotors. d) Schematic overview of various kinds of micro/nanorobots propelled via external physical power sources, i.e., magnetic field, acoustic field, light, and electric field. e) Schematic overview of biohybrid propulsion mechanisms based on prokaryotic (bacterial) and eukaryotic flagella.

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Chemical propulsion mechanisms. a) Self-diffusiophoresis observed in AgCl-PMMA Janus microspheres due to the photodecomposition of AgCl on the surface. Reproduced from ref , Copyright 2018 American Chemical Society. b) Self-electrophoresis of segmented Au/Pt wires with an internal electron flow from the Pt segment to the Au segment and migration of protons in the surrounding area. Reproduced from ref , Copyright 2004 American Chemical Society and ref , Copyright 2020 ELSEVIER. c) Bubble-propelled tubular nanojets by the generation and release of bubbles. Reproduced from ref , Copyright 2015 WILEY-VCH and ref , Copyright 2010 WILEY-VCH. d) Selection of enzyme-powered hollow mesoporous Janus nanomotors. Reproduced with permission under a Creative Commons CC-BY License from ref , Copyright 2015 American Chemical Society. e) Photocatalytic propulsion of TiO₂-Au Janus micromotors powered by UV light in water, demonstrating cyclic on/off UV light activation. Reproduced from ref , Copyright 2015 American Chemical Society. f) Galvanophoresis of Cu-SiO₂ Janus micromotors illustrating the galvanic exchange from Cu to Au caps. Reproduced from ref , Copyright 2021 American Chemical Society. g) Bipolar self-regeneration principle and propulsion of Zn micromotors in a glass tube filled with ZnSO₄ solution under the influence of an external electrical field. Reproduced from ref , Copyright 2010 American Chemical Society. h) Nafion micromotors and their propulsion with ion-exchange mechanism. Reproduced with permission under a Creative Commons CC-BY License from ref , Copyright 2024 Royal Society of Chemistry. i) Polymerization-based propulsion due to the bulk polymerization of polymer on the SiO₂ side of a Janus motor (left panel) and the surface polymerization of hydroxyethylmethacrylate-based polymer brushes on nanomotors (right panel). Reproduced from ref , Copyright 2011 WILEY-VCH and ref , Copyright 2021 Royal Society of Chemistry. j) Temperature-induced Marangoni propulsion of dye particles in a maze filled with a hot solution of a fatty acid to find the shortest path (left panel) and the directional Marangoni propulsion of the oil droplet due to the chemical gradients caused by the hydrolysis of ester-containing cationic surfactant (right panel). Reproduced from ref , Copyright 2015 Royal Society of Chemistry and ref , Copyright 2011 American Chemical Society. k) Chemokinesis-driven accumulation of self-propelled Pt/Au nanorods in low-mobility regions due to the fuel gradients, showing the traces of rods’ motion in high-speed, medium-speed, and low-speed (green, blue, and red, respectively) regions. Reproduced with permission under a Creative Commons CC-BY License from ref , Copyright 2021 Springer Nature.

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Physical propulsion mechanisms based on magnetic fields. a–c) Manipulation with magnetic field gradients: a) Magnetic bead navigated using a magnetic tweezer inside a cell to perform mechanical characterization. Reproduced from ref , Copyright 2019 American Association for the Advancement of Science. b) Au-coated NdFeB spherical magnets externally controlled via magnetic field gradients generated by an electromagnetic navigation system (eMNS). The scale bar is 2 mm. Reproduced from ref , Copyright 2024 WILEY-VCH. c) In vivo microrobot navigation using gradients of MRI to steer the aggregate into the target vessels where the hepatic flow was partially reduced by inflating a balloon catheter. Reproduced from ref , Copyright 2019 American Association for the Advancement of Science. d–h) Manipulation with (d,e) rotating, (f) conical, and (g,h) oscillating magnetic fields. d) Untethered artificial bacterial flagella (ABF) swimming controlled by rotating magnetic fields. Optical images indicate forward, backward, and turning motion of an ABF steered by magnetic fields. Reproduced from ref , Copyright 2009 AIP Publishing. e) Effects of shape and size in corkscrew motion: ABFs having different shapes, i.e., helical actuators (Row 1), single twist-type actuators (Row 2), and double twist-type actuators (Row 3). Scale bars are 50 μm. Reproduced from ref , Copyright 2014 WILEY-VCH. Helical nanopropellers having different lengths, i.e., 2.2, 1.6, 1.1, and 0.7 full helical turns (left to right, scale bars are 500 nm), showing different relations between their propulsion speed vs. rotation frequency of the external magnetic field. Reproduced from ref , Copyright 2015 American Chemical Society. f) Right- and left-handed 2D swimmers in a precessing field (field strength H, angular velocity ω, precession angle θ) presented with their swimming directions and the propulsion under the effect of conical magnetic fields. Reproduced from ref , Copyright 2018 WILEY-VCH. g) Artificially segmented swimmer fabricated from magnetic particles that are attached with double-stranded DNA via specific biotin–streptavidin interaction and its motion under oscillating magnetic fields (filament length = 24 μm). Reproduced from ref , Copyright 2005 Springer Nature. h) Multi-link magnetic swimmer comprising an elastic eukaryote-like polypyrrole tail and rigid magnetic Ni links connected by flexible polymer bilayer hinges and its propulsion under the influence of oscillating magnetic fields (2θ = 180° and f = 20 Hz). Reproduced from ref , Copyright 2015 American Chemical Society. i) Illustration of two-coil planar eMNS and its workspace that is defined as the set of positions (e.g., at point P) in space where a desired set of tasks is feasible given a set of admissible currents. Reproduced from ref , Copyright 2023 IEEE. j) Magnetic navigation systems: Magnetic stereotaxis system (MSS), 2000 − Reproduced from ref , Copyright 2000 American Association of Neurological Surgeons; Magnetic tweezer, 2004 − Reproduced from ref , Copyright 2004 IEEE; Helmholtz/Maxwell setup, 2009 − Reproduced from ref , Copyright 2009 IOP Publishing; OctoMag, 2010 − Reproduced from ref , Copyright 2010 IEEE; Electromagnetic actuation (EMA) system, 2010 − Reproduced from ref , Copyright 2010 ELSEVIER; Catheter Guidance Control and Imaging (CGCI), 2011 − Reproduced with permission under a Creative Commons CC-BY License from ref ; Magnetically guided capsule endoscopy (MGCE), 2012 − Reproduced from ref , Copyright 2012 IEEE; Minimag, 2014 − Reproduced from ref , Copyright 2014 Springer Nature; NaviCam, 2016 − Reproduced from ref , Copyright 2016 ELSEVIER; Aeon Phocus, 2017 − Reproduced from ref , Copyright 2017 IEEE; Genesis stereotaxis, 2020 − Reproduced from ref , Copyright 2020 Springer Nature; NAVION, 2024 − Reproduced from ref , Copyright 2024 WILEY-VCH.

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Physical propulsion mechanisms generated by (a–k) ultrasound, (l–q) light, and (r–u) electric fields. a–d) Standing wave-based propulsion systems: a) Cavity resonator that utilizes standing waves to levitate and control the propulsion of nanorobots. Reproduced from ref , Copyright 2023 American Chemical Society and ref , Copyright 2012 American Chemical Society. b) Magneto–acoustic hybrid nanorobot, showcasing dual propulsion modes using both acoustic and magnetic fields. Reproduced from ref , Copyright 2015 American Chemical Society. c) Nanorobot designed with an asymmetric material composition that results in varying densities to facilitate asymmetric oscillation and initiate propulsion upon ultrasound stimulation. Reproduced from ref , Copyright 2020 WILEY-VCH. d) Experimental setup featuring a discoidal microbubble positioned in a narrow slit between glass boundaries, exposed to ultrasound for propulsion. Reproduced with permission under a Creative Commons CC-BY License from ref , Copyright 2023 Springer Nature. e–g) Traveling wave-based propulsion: e) Translational locomotion of an acoustically propelled microrobot having a bubble trapped at its center. Reproduced with permission under a Creative Commons CC-BY License from ref , Copyright 2015 Springer Nature. f) Bubble-based surface-slipping microrobot effectively propels in both 2D and 3D artificial vessels. Reproduced with permission under a Creative Commons CC-BY License from ref , Copyright 2020 National Academy of Sciences. g) Microbubble-based artificial muscle for the actuation of a stingray-inspired stingraybot. Reproduced with permission under a Creative Commons CC-BY-NC-ND License from ref , Copyright 2024 bioRxiv. h–k) Microstructure oscillation-based propulsion: h) Nanowire-based robot featuring a metallic head and flexible tail propelling at a nearly constant velocity when subjected to ultrasound. Reproduced from ref , Copyright 2016 American Chemical Society. i) Directional motion of a bio-inspired artificial microrobot driven by large-amplitude oscillations of soft flagella via acoustic actuation. Reproduced from ref , Copyright 2017 Royal Society of Chemistry. j) Microrobot mimicking the ciliary bands of starfish larvae to facilitate ultrasound-based propulsion. Reproduced with permission under a Creative Commons CC-BY License from ref , Copyright 2021 Springer Nature. k) Sound-driven helical microrobot that features asymmetric double helix design interacting with the incident acoustic field to achieve propulsion within 3D vascular channels. Reproduced from ref , Copyright 2023 American Association for the Advancement of Science. l–q) Assembly and manipulation of microrobots with the transfer of light momentum: l) Linear and angular light momentum transfer to matter. Ray optics explanation of the scattering forces and gradient forces (top). Spin and orbital angular momentum interaction with matter (bottom). m–o) Passive structures controlled with light. m) Cell collection with an optically actuated microrobot. Reproduced from ref , Copyright 2024 WILEY-VCH. n) Microrotor assembled with optical tweezers. Scale bar is 8 μm. Reproduced with permission under a Creative Commons CC-BY License from ref , Copyright 2017 Springer Nature. o) Mapped flow field created by the rotating particles from spin angular momentum transfer. Reproduced from ref , Copyright 2006 Royal Society of Chemistry. p,q) Autonomous microrobots powered from within: p) Optical trapping principle of self-propelled active particles. Scale bar is 10 μm. Reproduced with permission under a Creative Commons CC-BY License from ref , Copyright 2021 Springer Nature. q) Assembly process of microrobots around a passive cargo (pink), autonomous translational motion, and release. Cross bar is 20 μm. Reproduced with permission under a Creative Commons CC-BY License from ref , Copyright 2022 WILEY-VCH. r–u) Principles and examples of AC electric field-driven propulsion effects in active systems: r) EHD flow around a stationary spherical dielectric particle; a metallo–dielectric spherical particle undergoing induced charge electrophoretic motion (ICEP); and a particle system including microcircuit to rectify the DC field from an external AC electric field. Reproduced from ref , Copyright 2022 ELSEVIER. s) Examples of engineered asymmetric structures used in different active systems. Reproduced from ref , Copyright 2022 ELSEVIER. t) Various trajectories of particles moving via EHD flows. Reproduced from ref , Copyright 2017 WILEY-VCH. u) Self-propelled semiconductor circuit powered by an external field. Reproduced with permission under a Creative Commons CC-BY License from ref , Copyright 2018 Springer Nature.

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Multi-scale theoretical strategy to understand and control the collective behavior of micro/nanorobots. Different conceptual elements contribute to motility at nanoscale and motility at microscale. These elements, together with the quantitative characterization of various physical properties of these systems in systematic experiments, can inform a comprehensive bottom-up description of the system that enables us to make predictions of the corresponding collective properties of the system.

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Interactions and swarming behaviors of micro/nanorobots. a) Schematic diagram showing different types of interactions between individual micro/nanorobots. b) Magnetic field-driven microswarms: (i) Ribbon-like Fe₃O₄ nanoparticle swarm actuated by oscillating magnetic fields. Reproduced with permission under a Creative Commons CC-BY License from ref , Copyright 2018 Springer Nature. (ii) Vortex-like Fe₃O₄ nanoparticle swarm actuated by rotating magnetic fields. Reproduced from ref , Copyright 2018 SAGE Publications. (iii) Aster-like microparticle swarm actuated by a vertical alternating magnetic field at the liquid–liquid interface. Reproduced from ref , Copyright 2011 Springer Nature. c) Acoustic field-driven microswarms: (i) Reversible swarming and dispersion of self-propelled Pt-Au nanowires under acoustic fields. Reproduced from ref , Copyright 2015 American Chemical Society. (ii) Dandelion flower-like swarm of liquid metal nanorods under an ultrasound field. Reproduced from ref , Copyright 2020 WILEY-VCH. (iii) Neutrophil-inspired acousto-magnetic microswarm. Reproduced with permission under a Creative Commons CC-BY License from ref , Copyright 2017 Springer Nature. d) Electric field-driven microswarms: (i) Metal-dielectric Janus colloidal microparticles show different collective behaviors in a vertical alternating electric field. Reproduced from ref , Copyright 2016 Springer Nature. (ii) Directed collective motion of electric field-driven Quincke rollers. Reproduced from ref , Copyright 2013 Springer Nature. e) Optical field-driven microswarms: (i) Living crystals formed by colloidal particles under the illumination of blue light. Reproduced from ref , Copyright 2013 American Association for the Advancement of Science. (ii) Nematic colloid particle swarm controlled by photoactivated surface patterns. Reproduced from ref , Copyright 2014 WILEY-VCH.

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Expansion of modalities and functionalities of microswarms. a) Active pattern transformation of Fe₂O₃ colloidal particle swarm through adjusting input magnetic fields. Reproduced from ref , Copyright 2019 American Association for the Advancement of Science. b) Passive pattern transformation of a light-driven microswarm due to contact with boundaries. Reproduced from ref , Copyright 2019 Elsevier. c) Tornado-like microswarm with 3D morphology. Reproduced from ref , Copyright 2020 American Chemical Society. d) 3D drifting of a microswarm underwater based on a bimodal actuation strategy. Reproduced with permission under a Creative Commons CC-BY License from ref , Copyright 2023 American Association for the Advancement of Science. e) Heterogeneous microswarm consisting of different functionalized Fe₃O₄ nanoparticles. Reproduced from ref , Copyright 2021 WILEY-VCH. f) Heterogeneous microswarm formed by microdisks of different sizes. Reproduced with permission under a Creative Commons CC-BY License from ref , Copyright 2023 National Academy of Sciences. g) Independent morphological control achieved based on different responses of microswarms to the magnetic field. Reproduced from ref , Copyright 2021 American Chemical Society. h) Selective control of microswarms realized based on nonuniform external inputs. Reproduced from ref , Copyright 2024 WILEY-VCH.

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Concept of intelligence. a) Traditional understanding of intelligence which is mainly rooted in cognitive and rational processes taking place in the brain. There is a duality between brain and body when they interact with the environment; b) Embodied intelligence in which the integration of environment, brain, and body is necessary for cognition. c) Onboard and off-board elements of embodied intelligence at small scales. d) Embodied intelligence in stimuli-responsive materials for micro/nanorobots. e) holy grail for the field of micro/nanorobotics.

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The landscape of embodied intelligence in biological and artificial agents. The size of the biological and artificial agents is directly proportional to the complexity of their nervous system.

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Snapshot of three major functionalities of micro/nanorobots rooted in embodied intelligence at small scales. a) Cargo transport by means of mechanical adaptation. Panel (ii) is reprinted with permission from ref , Copyright 2016 American Chemical Society. Panel (iii) is reprinted with permission from ref , Copyright 2020 American Chemical Society. b) Biorecognition by means of chemical recognition. Panel (ii) is reprinted with permission from ref , Copyright 2020 The American Association for the Advancement of Science. Panel (iii) is reprinted with permission from ref , Copyright 2015 the Royal Society of Chemistry. c) Fluorescence and quenching by means of optical burst. Panel (ii) is reprinted with permission from ref from ref , Copyright 2018 American Chemical Society. Panel (iii) is reprinted with permission from ref , Copyright 2025 American Chemical Society.

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From neural network to intelligent micro/nanorobot network. a) Human brain modeled as a neural network in a branching model, where information is processed through layers of neurons. b) Envisioned intelligent micro/nanorobot networks connected through chemical interactions. c) Self-catalyzed reaction in AgCl/H₂O₂ system enables target wave and spiral wave. Adapted with permission from ref , Copyright 2022 the American Association for the Advancement of Science. d) Sulfonated polystyrene and ZnO can exchange ions, which couples two active particles as a chemically active swarm. e) Chemical reaction rate is sensitive to particle–particle distance, which creates feedback to regulate system activity. f) Active colloid swarm placed in an irregularly shaped container, demonstrating macroscopic phase separation and quorum sensing ability by moving toward one sharp corner in the macroscopic container. Scale bar is 1 cm. (d−f) are adapted with permission from ref . Copyright 2021 Springer.

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Autonomous micro/nanorobot navigation via machine learning. a) Path planning and navigation of a microrobot in a maze using the A* algorithm (scale bar is 20 μm). Reproduced from ref , Copyright 2018 IEEE. b) Simulation of path planning in a plant vein structure using RRT*-Connect. Reproduced with permission under a Creative Commons CC-BY License from ref , Copyright 2023 Frontiers. c) Learning process for the navigation of a self-thermophoretic microrobot using Q-learning. Reproduced from ref , Copyright 2021 American Association for the Advancement of Science. d) Neural network architecture of a DRL algorithm for the navigation of various micro/nanorobots. Reproduced with permission under a Creative Commons CC-BY License from ref , Copyright 2020 WILEY-VCH. e) Path planning and reinforcement learning for fully autonomous navigation of a magnetic microrobot. Reproduced from ref , Copyright 2024 Springer Nature. f) Supervised learning for autonomous navigation of a magnetic nanorobot swarm around obstacles. Reproduced from ref , Copyright 2022 Springer Nature.

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Materials for micro/nanorobots and their dynamic assembly. a) Typical materials for chemical propulsion. Reproduced from ref , Copyright 2021 WILEY-VCH. b) Typical materials for light-powered propulsion. Reproduced from ref , Copyright 2017 American Chemical Society. c) Typical materials for magnetic propulsion. Reproduced with permission under a Creative Commons CC-BY License from ref , Copyright 2022 WILEY-VCH. d) Typical structures and materials for ultrasound propulsion. Reproduced with permission under a Creative Commons CC-BY License from ref , Copyright 2023 WILEY-VCH. e) Cells for the construction of biohybrid micro/nanorobots. Reproduced from ref , Copyright 2018 Elsevier. f) Super-assembled biocatalytic porous framework micromotors with reversible and sensitive pH-speed regulation. Reproduced from ref , Copyright 2019 WILEY-VCH. g) Self-propelled supramolecular nanomotors with temperature-responsive speed regulation. Reproduced from ref , Copyright 2017 Springer Nature. h) Programmable artificial phototactic microswimmer. Reproduced from ref , Copyright 2016 Springer Nature. i) Urea-powered biocompatible hollow microcapsules. Reproduced from ref , Copyright 2016 American Chemical Society. j) Nonequilibrium assembly of light-activated colloidal motors. Reproduced from ref , Copyright 2017 WILEY-VCH. k) Reconfigurable magnetic microrobot swarms. Reproduced from ref , Copyright 2019 American Association for the Advancement of Science. l) Reconfiguring active particles by electrostatic imbalance. Reproduced from ref , Copyright 2016 Springer Nature. m) Reconfigurable assembly of active liquid metal colloidal cluster. Reproduced from ref , Copyright 2020 WILEY-VCH.

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Fabrication of micro/nanorobots. a) Synthetic procedures of microrobots by combining the LbL self-assembly technique with the metal sputter-coating method and PDMS; reproduced from ref , Copyright 2022 WILEY-VCH; reproduced with permission under a Creative Commons CC-BY License from ref , Copyright 2018 American Chemical Society. b) Stomatocyte-like nanorobots formed by the solution self-assembly of block copolymers PEG–PS in THF/dioxane solvent; reproduced from ref , Copyright 2012 Nature Portfolio. One-pot solution self-assemble approach for large-scale synthesis of shuttlecock-shaped nanomotors; reproduced from ref , Copyright 2020 Elsevier. c) membrane-camouflaged microrobots formed by biological self-assembly and d) Cell-based microrobots. Reproduced from ref , , Copyright 2022 American Chemical Society; Copyright 2021 American Association for the Advancement of Science. e) Glancing angle deposition. Adapted with permission from ref Copyright 2009 American Chemical Society. Adapted with permission from ref , Copyright 2021 Royal Society of Chemistry. f) Template-based fabrication of helical magnetic nanorobots by electrochemical deposition. Reproduced from ref , Copyright 2014 Royal Society of Chemistry. g) Fabrication process of rolled-up tubular micromotors utilizing lithography technology. Reproduced from ref , Copyright 2019 WILEY-VCH. h) Fabrication of degradable hyperthermia microrobot utilizing 3D printing technology. Reproduced from ref , Copyright 2019 WILEY-VCH.

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Biomedical applications of micro/nanorobots across diverse fields. Micro/nanorobots perform mechanical manipulation and enable intracellular interactions on the cellular level. They offer precise drug delivery and conduct photodynamic therapy to target specific cells. These robots manipulate single cells for diagnostics and regenerative medicine, dissolve blood clots for thrombolysis, and block blood supply to tumors via embolization. They modulate immune responses for treating diseases and effectively remove resistant biofilms on implants or tissues, demonstrating their potential to address complex medical challenges with precision and efficiency.

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Key strategies to enhance performance, multifunctionality, and sustainability, and extend the applicability of micro/nanorobots for environmental remediation. a) Magnetic or bubble propulsion and motion mode optimization enhance pollutant removal/degradation efficiency by improving micro/nanorobots’ speed and interaction with pollutants. Integration of high-surface area materials increases adsorption sites while photocatalytic and enzymatic mechanisms synergistically improve the degradation efficiency. b) Multifunctionality allows micro/nanorobots to remove or degrade pollutants (heavy metals, organic molecules, and nanoplastics) while enabling simultaneous detection through colorimetric or electrochemical methods. c) Sustainable designs focus on reducing environmental impact by using self-motile microorganisms (bacteria and microalgae) as engines, hybrid bio-inorganic systems (e.g., loading magnetic nanoparticles onto microorganisms), and exploiting captured pollutants as active components for further purification processes or as fuels. d) Self-propulsion enhances catalyst diffusion in the soil subsurface, improving the degradation of pollutants such as toxic pesticides.

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Overview of micromotors for analytical sensing and biosensing. a) Motion-based sensing. On top, a schematic of the principle for detection, based on the decrease in the micromotor speed in the presence of the target analyte. As an example of metal catalyst poisoning, polystyrene (PS)-graphene oxide (GOx)-Pt nanoparticles (PtNPs) catalytic micromotors are illustrated. Specific attachment of glutathione (GSH) results in poisoning of the PtNPs, reducing the speed in a concentration dependent manner, allowing for disease monitoring. Reprinted with permission under a Creative Commons CC-BY License from ref , Copyright 2021 American Chemical Society. As an example of enzyme poisoning, zeolitic imidazole (ZIF) MOFs propelled by catalytic decomposition of the hydrogen peroxide by the enzyme catalase are poisoned in the presence of Cu. The time-lapse microscopy images show the micromotors navigation in cerebrospinal fluid samples, where the presence of Cu served as indicator for Alzheimer disease monitoring. Reprinted with permission from ref , Copyright 2024 Royal Society of Chemistry. b) Optical sensing. On top, a micromotor based immunoassay using polypyrrole/niquel Pt-based micromotors for procalcitonin (PCT) detection from very low-birth-weight infants. The images illustrate the generation of an immunosandwich, using a FITC-labelled secondary antibody. The microscopy images show the fluorescence in the micromotor surface in the absence (0 ng/ml) and presence (1000 ng/ml) of PCT, with the corresponding calibration plot. Reprinted with permission from ref , Copyright 2020 American Chemical Society. Bottom part shows the use of polycaprolactone/Pt Janus micromotors loaded with WS₂ and modified with a rhodamine labelled affinity peptide for OFF-ON endotoxins detection. Adapted with permission from ref , Copyright 2020 Elsevier. c) Electrochemical sensing with micromotors. On top, on-the-move immunoassay using carbon-based micromotors modified with antibodies for C-reactive protein (CRP) detection. Right part shows the corresponding calibration plots and the time-lapse microscopy images of the micromotor propulsion in raw plasma samples in the absence of surfactant at different H₂O₂ concentrations: in the presence (2% H₂O₂) and absence (4% H₂O₂) of surfactant. Reprinted with permission from ref , Copyright 2020 Elsevier. The bottom part shows Mg-based micromotors for assisted electrochemical detection of nonelectroactive phthalates. Reprinted with permission from ref , Copyright 2016 American Chemical Society.

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Introduction to processes capable of swiftly synthesizing various forms of micro/nanorobot bodies for rapid prototyping and methods for attaching enzymes and catalysts to pre-formed micro/nanorobots bodies to equip them with propulsion systems. a) Catalyst decorations. Reproduced from ref , Copyright 2022 American Chemical Society. b) Enzyme attachment. Reproduced from ref , Copyright 2015 American Chemical Society. c) Rapid 3D printing platform. Introduction to various micro/nanorobots large-scale synthesis processes that enable cost efficiency and quality control for commercialization. Reproduced from ref , Copyright 2015 WILEY-VCH. d) Roll-to-roll mold synthesis. Reproduced from ref , Copyright 2016 Springer Nature. e) Roll-to-roll deposition system. Reproduced with permission under a Creative Commons CC-BY License from ref , Copyright 2016 Springer Nature. f) Roll-to-roll electrospinning system for large-scale micro/nanorobot production. Reproduced from ref , Copyright 2020 American Chemical Society. World map of research area for micro/nanorobots. g) Graph of number of patent applications. h) Patent world map since 2004.

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Key issues to address for the regulatory framework for micro/nanorobots, highlighting the proper handling of nanomaterials and toxicity considerations. a) In-depth exploration of key perspectives that warrant careful examination concerning nanomaterials predominantly employed in the fabrication of micro/nanorobots. Images under “stability” demonstrate structural alterations in bulk micro/nanorobots in response to specific environmental conditions. Images under “Biocompatibility” illustrate considerations for nanomaterials regarding human compatibility. Images under “Life Span” provide perspectives on issues of degradation when micro/nanorobots are exposed to the human body environment. b) Exploring the adequate management of micro/nanorobots as they transition from laboratories to end-users. Images under “User Safety” emphasize the need for institutions to establish regulatory frameworks to ensure user safety in micro/nanorobot management. Images under “Data Protection & Privacy” emphasize the protection of users’ personal information. Adapted with permission from ref , Copyright 2020 Springer Nature. Images under “sustainability” outline a management policy for the market entry of micro/nanorobots from an ESG perspective. c) To enhance the universality of micro/nanorobots, establish a rigorous toxicity assessment system focusing on both in vitro and in vivo aspects. Images under “In vitro” reproduced with permission under a Creative Commons CC-BY License from ref , Copyright 2023 Springer Nature. Images under “In vivo” adapted with permission from ref , Copyright 2022 Springer Nature. Images under “Assessment” adapted with permission from ref , Copyright 2018 Springer Nature.