Magnetically Driven Micro and Nanorobots

Abstract

Manipulation and navigation of micro and nanoswimmers in different fluid environments can be achieved by chemicals, external fields, or even motile cells. Many researchers have selected magnetic fields as the active external actuation source based on the advantageous features of this actuation strategy such as remote and spatiotemporal control, fuel-free, high degree of reconfigurability, programmability, recyclability, and versatility. This review introduces fundamental concepts and advantages of magnetic micro/nanorobots (termed here as "MagRobots") as well as basic knowledge of magnetic fields and magnetic materials, setups for magnetic manipulation, magnetic field configurations, and symmetry-breaking strategies for effective movement. These concepts are discussed to describe the interactions between micro/nanorobots and magnetic fields. Actuation mechanisms of flagella-inspired MagRobots (i.e., corkscrew-like motion and traveling-wave locomotion/ciliary stroke motion) and surface walkers (i.e., surface-assisted motion), applications of magnetic fields in other propulsion approaches, and magnetic stimulation of micro/nanorobots beyond motion are provided followed by fabrication techniques for (quasi-)spherical, helical, flexible, wire-like, and biohybrid MagRobots. Applications of MagRobots in targeted drug/gene delivery, cell manipulation, minimally invasive surgery, biopsy, biofilm disruption/eradication, imaging-guided delivery/therapy/surgery, pollution removal for environmental remediation, and (bio)sensing are also reviewed. Finally, current challenges and future perspectives for the development of magnetically powered miniaturized motors are discussed.

Figure 1

Experimental setup for magnetically driven micro/nanorobots and various magnetic actuation systems. (A) Diagram of the typical experimental workplace for actuating and visualizing MagRobots. (B) Magnetic actuation system consists of only a single permanent magnet. (C) Permanent magnet actuation system using cylindrical NdFeB permanent magnet fixed to its end-effector and a robotic arm. Reproduced with permission from ref (101). Copyright 2017 IEEE. (D) Rotating permanent magnet system consists of a magnet, a robotic arm, and a motor. Reproduced with permission from ref (102). Copyright 2013 IEEE. (E) Electromagnetic actuation system using triaxial circular Helmholtz coils. Reproduced with permission from ref (103). Copyright Springer Science + Business Media, LLC 2013. (F) Electromagnetic actuation system using a stationary Helmholtz–Maxwell coil and a rotational Helmholtz–Maxwell coil. Reproduced with permission from ref (104). Copyright 2009 Elsevier B.V. (G) Electromagnetic actuation system using multiply coils including a Helmholtz coil, Maxwell coil, uniform saddle coil, and gradient saddle coil. Reproduced with permission from ref (105). Copyright 2010 Elsevier B.V. (H) MiniMag electromagnetic system. Reproduced with permission from ref (106). Copyright 2014 Springer-Verlag GmbH Berlin Heidelberg.

Figure 2

Classifications and configurations of magnetic fields in relation to the motion of MagRobots.

Figure 3

(A) Schematic image of Purcell’s scallop presenting a nonreciprocal motion in a high Reynolds number fluid and reciprocal motion in a low Reynolds number fluid with no net replacement (so-called “Scallop Theorem”). (B) Summary of five strategies (S1–S6) to break the Scallop Theorem to produce an effective movement. S2 is reproduced with permission from refs ( and 140). Copyright 2014, Brumley et al. This article is distributed under the terms of the Creative Commons Attribution License. S4 is reproduced with permission from ref (142). Copyright 2015 The authors. S5 is reproduced with permission from refs ( and 140). Copyright 2014 Macmillan Publishers Limited. This is an open access article distributed under the terms of the Creative Commons CC BY license.

Figure 4

Flagellar-based propulsion mechanisms. (A) Rotation of bacterial flagellum at frequency ω₁ through rotary motor inside and a counter-rotation of the head at frequency ω₂, while head and tail of ABF rotate in the same direction. (B) Typical types of magnetic ABFs. Reproduced with permission from ref (149). Copyright 2018 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim. (C) Field frequency-dependent ABF movement: ABF wobbles with a wobbling angle at low frequency; wobbling movement transforms into corkscrew-like swimming; then the wobbling decreases to zero at high rotational frequencies. Example of frequency-dependent propulsion of MOF-based helical swimmers. Reproduced with permission from ref (155). Copyright 2019 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim.

Figure 5

Flagellum-based locomotion of magnetically actuated robots. (A) Motion of Au–Ag–Ni–Ag–Ni–Ag–Au multilink nanowires with flexible silver hinges under a planar oscillating magnetic field. Reproduced with permission from ref (129). Copyright 2016 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim. (B) Multiple locomotion modes of millipede-like soft robots. Reproduced with permission from ref (160). Copyright 2020 The Authors. (C) Ciliary stroke motion of artificial micromotors. Reproduced with permission from ref (139). Copyright 2016 The Authors.

Figure 6

Propulsion mechanisms for surface walkers. (A). Surface-assisted motion of an Au–Ag–Ni nanowire. Reproduced with permission from ref (173). Copyright 2020 American Chemical Society. (B) Motion mode transformation of hematite peanut-shaped microrobots among rolling mode under a yz-planar rotating field, spinning mode under an xy-planar rotating field, and tumbling mode under a conical rotating field; Swarming patterns of chain, vortex, and ribbon morphologies, respectively. Reproduced with permission from ref (56). Copyright 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. (C) Magnetic coil arrangement and advection of Au/Ni/Au nanowire in kayak motion mode. Reproduced with permission from ref (168). Copyright 2017 The Royal Society of Chemistry. (D) Smooth translation motion of square-wheeled bicycles on bumpy roads and separation of diamond and square μwheels on the textured surface. Reproduced with permission from ref (169). Copyright 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. (E) Schemes of a peanut-shaped motor climbing up a steep slope with the height of 8 μm via a wobbling mode and trajectory of the MagRobot climbing up and down a steep slope. Reproduced with permission from ref (170). Copyright 2018 American Chemical Society. (F) SEM image of a microdimer and its motion in bulk liquid and near a boundary. Reproduced with permission from ref (172). Copyright 2018 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim.

Figure 7

Representative examples of applying magnetic fields to micro/nanorobots actuated by other propulsion sources. (A) Propulsion of a TiO₂–PtPd–Ni tubular nanomotor by bubbles from the decomposition of chemical fuel, magnetic field, or both. Reproduced with permission from ref (174). Copyright 2016 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim. (B) Boost of propulsion velocity of a Janus micromotor propelled by dual mode or ternary mode. Reproduced with permission from ref (180). Copyright 2020 American Chemical Society. (C) ON–OFF feature and direction control capacity of the magnetic field for ultrasound-powered Janus micromotors: (a) Propulsion of a single microrobot without and with the application of a static magnetic field; (b) Magnetic navigation of a single acoustic-powered microrobot. Reproduced with permission from ref (181). Copyright 2020 WILEY-VCH GmbH and Co. KGaA, Weinheim.

Figure 8

Magnetic stimulation of micro/nanorobots for hyperthermia, thermophoresis, and magnetoelectric applications. (A) Schematic process of removing cholesterol plaque in the blood artery via the magnetic hyperthermia of nanorobots. Reproduced with permission from ref (186). Copyright 2020 Elsevier B.V. (B) Experimental setup of Janus nanorobots for magnetically induced thermophoresis. Thermophoretic force, triggered by the temperature difference, causes the self-propulsion of a Janus particle. Reproduced with permission from ref (124). Copyright 2012 American Chemical Society. (C) Underlying physics of the magnetoelectrically triggered drug (i.e., AZTTP) release process. Reproduced with permission from ref (201). Copyright 2013 Macmillan Publishers Limited.

Figure 9

Schematic illustrations of the representative fabrication processes of (quasi-)spherical MagRobots. (A) Fabrication steps of Fe₃O₄@PDA@Au MagRobots and formation process of an ant bridge, corresponding to conceptual steps for a reconfigurable microswarm to repair an electrical circuit. Reproduced with permission from ref (212). Copyright 2019 American Chemical Society. (B) Microwheel prepared from the self-assembly of superparamagnetic Dynabeads M-450 Epoxy by rotating field and its field-dependent motion modes: planar rotating magnetic field makes colloids assemble and microwheels spin, whereas 3D oscillating magnetic field makes microwheels roll along the surface. Reproduced with permission from ref (214). Copyright 2019 The Authors. (C) Fabrication steps of the burr-like microrobots. Reproduced with permission from ref (215). Copyright 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. (E) Fabricating process of PM/Pt Janus microrobots for cell manipulation, DOX drug loading, and delivery. Reproduced with permission from ref (210). Copyright 2018 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim.

Figure 10

Schematic illustrations of representative synthetic methods for helical MagRobots. (A) Fabrication process of piezoelectric magnetic microswimmers by laser ablation. Reproduced with permission from ref (217). Copyright 2019 The Royal Society of Chemistry. (B) Fabrication of biodegradable helical MagRobots using two-photon polymerization. Reproduced with permission from ref (238). Copyright 2018 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim. (C) Preparation process of platelet-membrane-cloaked MagRobots by TAED method including (i) Pd/Cu coelectrodeposition, (ii) etching of Cu and collection of helical structures, (iii) deposition of Ni and Au layers, (iv) collection of helical nanostructures, (v) surface modification, and (vi) fusion of platelet-membrane-derived vesicles to the modified surface. Reproduced with permission from ref (216). Copyright 2017 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim. (D) Preparation steps of acid-stable enzyme-functionalized MagRobots by GLAD. Reproduced with permission from ref (222). Copyright 2015 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. (E) Origami-inspired approach to prepare microswimmers by one-step photolithography. Reproduced with permission from ref (245). Copyright 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. (F) Fabrication of helical microrobots with hollow structures with the assistance of coiled flow template. Reproduced with permission from ref (223). Copyright 2018 American Chemical Society. (G) Fabrication process of biohybrid microswimmers based on Spirulina platensis. Reproduced with permission from ref (226). Copyright 2020 American Chemical Society.

Figure 11

Schematic illustrations of the representative fabrication processes of flexible MagRobots. (A) (a) Fabrication process of temperature-sensitive microgripper including (i) depositing metal alignment markers and spin-coating sacrificial layer and PPF/DEF solution, (ii) cross-linking PPF segments by UV light through a mask, (iii) coating pNIPAM-AAc layer on top of the wafer, (iv) photopatterning the pNIPAM-AAc layer by UV light through a mask, (v) removing uncross-linked chemicals, and (vi) releasing microgrippers from the wafer by dissolving the underlying sacrificial layer in water; (b) Cell capture and excision due to the reversible folding/unfolding behavior of microgrippers in response to temperature. Reproduced with permission from ref (39). Copyright 2015 American Chemical Society. (B) Fabrication procedure of pH-sensitive soft MagRobot. Reproduced with permission from ref (266). Copyright 2016 IOP Publishing Ltd. (C) Formation of hairbots by sectioning a bundle of hair by ultramicrotome and then loading hairbots with magnetic particles and drugs. Reproduced with permission from ref (268). Copyright 2019 Elsevier Ltd. (D) Preparation of liquid metal MagRobots. Reproduced with permission from ref (269). Copyright 2019 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim. (E) DNA-based flexible MagRobots: (a) Preparation of a hybrid MagRobot with flexible DNA flagella via DNA self-assembly method. Reproduced with permission from ref (270). Copyright 2016 American Chemical Society. (b) Fabrication of a flexible magnetic filament by binding magnetic particles with double-stranded DNA via the specific biotin–streptavidin interaction under a magnetic field. Reproduced with permission from ref (159). Copyright 2005 Nature Publishing Group. (F) Origami-like MagRobots with various shape-morphing modes, mimicking the flapping, hovering, turning, and side-slipping of birds. Reproduced with permission from ref (64). Copyright 2019, The Authors, under exclusive license to Springer Nature Limited.

Figure 12

Fabrication of magnetic nanowires by TAED and some examples. (A) Synthesis process of CoPt nanowires and (B) magnetization angle of hard-magnetic CoPt nanowire and soft-magnetic CoNi nanowire. Yellow indicates the direction of the short axis while red indicates the direction of the magnetic field. Reproduced with permission from ref (166). Copyright 2019 American Chemical Society. (C) Dumbbell-shaped MagRobot consisting of a Ni NW and two PS microbeads. Reproduced with permission from ref (286). Copyright 2016 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim. (D) Traveling-wave motion of a fish-like nanoswimmer under an oscillating magnetic field. Reproduced with permission from ref (129). Copyright 2016 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim. (E) Freestyle swimming of two-arm nanoswimmer. Reproduced with permission from ref (3). Copyright 2017 American Chemical Society. (F) SEM images of 1-, 2-, and 3-link microswimmers and traveling-wave propulsion of 3-link microswimmer under an oscillating magnetic field. Reproduced with permission from ref (97). Copyright 2015 American Chemical Society. (G) Three motion modes and SEM image of PVDF-Ppy-Ni nanoeels. Reproduced with permission from ref (287). Copyright 2019 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim.

Figure 13

Representative examples of biohybrid MagRobots fabricated by four methods. Method 1: MagRobots prepared using (A) pollen, (B) spore, (C) microalgae, or (D) sperm as templates. Method 2: MagRobots prepared by cloaking functionalized nanomaterials with cell membrane of (E) red blood cells or (F) platelets. Method 3: MagRobots prepared by combining active flagella-containing cells such as (G) bacterium, (H) RGB-cloaked bacterium, (I) microalgae, or (J) sperm. Method 4: MagRobots prepared by utilizing the phagocytosis function of immune cells, for example, (K) macrophage. (A) Reproduced with permission from ref (289). Copyright 2019 The Royal Society of Chemistry. (B) Reproduced with permission from ref (296). Copyright 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. (C) Reproduced with permission from ref (293). Copyright 2019 American Chemical Society. (D) Reproduced with permission from ref (295). Copyright 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. (E) Reproduced with permission from ref (297). Copyright 2015 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim. (F) Reproduced with permission from ref (216). Copyright 2017 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim. (G) Reproduced with permission from ref (68). Copyright 2017 American Chemical Society. (H) Reproduced with permission from ref (306). Copyright 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. (I) Reproduced with permission from ref (294). Copyright 2018 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim. (J) Reproduced with permission from ref (31). Copyright 2018 American Chemical Society. (K) Reproduced with permission from ref (305). Copyright 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.

Figure 14

Magnetically powered micromotors for targeted cargo delivery. (A) Fe-coated camptothecin-loaded magnetic biotube for killing HeLa cells. Dead cells are highlighted by white circles. Reproduced with permission from ref (315). Copyright 2015 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim. (B) Controllable navigation and targeted transport of antibodies inside blood flow by using Janus micropropellers. Reproduced with permission from ref (312). Copyright 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. (C) Sperm-based MagRobots capable of delivering heparin-loaded liposomes through flowing blood. Reproduced with permission from ref (177). Copyright 2020 American Chemical Society. (D) pDNA transfection by human embryo kidney cells when in targeted contact with helical microrobots loaded with plasmid DNA. Reproduced with permission from ref (219). Copyright 2015 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim. (E) Released drugs from hydrogel-based microswimmer for active labeling. Reproduced with permission from ref (128). Copyright 2019 American Chemical Society.

Figure 15

MagRobots for cell manipulation. (A) Manipulation of T47D cancer cells using superparamagnetic/Pt Janus micromotors via bubble propulsion and magnetic actuation. Reproduced with permission from ref (210). Copyright 2018 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim. (B) Delivery and patterning of a single cell by peanut-like hematite microrobots. Reproduced with permission from ref (170). Copyright 2018 American Chemical Society. (C) Transport of nonmotile sperm cells to the oocyte with the assistance of magnetically driven helical micromotors. Reproduced with permission from ref (248). Copyright 2015 American Chemical Society. (D) Magnetically powered microspirals for the delivery of murine zygote. Reproduced with permission from ref (321). Copyright 2020 The Authors. (E) Magnetically actuated transport of neural progenitor cell and ultrasound-induced neuronal differentiation. Reproduced with permission from ref (217). Copyright 2019 The Royal Society of Chemistry. (F) MagRobots as motile 3D scaffolds for stem cell delivery. Reproduced with permission from ref (122). Copyright 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.

Figure 16

MagRobots for minimally invasive surgery. (A) Schematic image and experimental image (inset) of rolled-up magnetic microdrillers with sharp end penetrating into a pig liver after drilling motion. Reproduced with permission from ref (41). Copyright 2013 The Royal Society of Chemistry. (B) Schematic of a driller working in a 3D vascular network and experiment result shows the driller can dislodge blood clot. Reproduced with permission from ref (325). Copyright 2018 The Authors. This article is licensed under a Creative Commons Attribution 4.0 International License. (C) Movement of Au/Ag/Ni surface walker under a transversal rotating field with different frequencies and magnetic navigation of microrobots to penetrate a cell and remove a cell fragment. Reproduced with permission from ref (173). Copyright 2020 American Chemical Society. (D) Magnetic manipulation of Si/Ni/Au nanospears for targeted intracellular transfection. Reproduced with permission from ref (311). Copyright 2018 American Chemical Society. (E) Penetration of Helicobacter pylori bacterium and helical MagRobot into mucin gels and liquefaction of mucus via enzyme-catalyzed reaction. Reproduced with permission from ref (222). Copyright 2015 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. (F) Long-range propulsion of injected slippery MagRobots in the vitreous toward the retina with the assistance of a magnetic field and standard optical coherence tomography. Reproduced with permission from ref (127). Copyright 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.

Figure 17

MagRobots for biopsy. (A) Schematic of a thermoresponsive gripper autonomously picking up and placing a target. Reproduced with permission from ref (345). Copyright 2016 The Authors. (B) Cell biopsy from a cell cluster using a magnetically navigated thermoresponsive microgripper and immunofluorescence images of suspended fibroblast cells captured by the microgripper. Reproduced with permission from ref (342). Copyright 2020 American Chemical Society. (C) (a) Transport of microgrippers into the porcine biliary orifice using an endoscope-assisted catheter; (b) retrieval of microrobots with the assistance of a magnetic catheter; (c) retrieved microrobot with a tissue piece in its “hand” after Trypan Blue staining. Reproduced with permission from ref (348). Copyright 2013 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim.

Figure 18

Representative examples of biofilm disruption or eradication using active MagRobots. (A) Magnetic guidance of biohybrid microbot into an island of E. coli biofilms. Reproduced with permission from ref (351). Copyright 2017 American Chemical Society. (B) Linear footprints left on the surface of P. aeruginosa biofilm after the motion of MagRobots. Reproduced with permission from ref (352). Copyright 2020 American Chemical Society. (C) Application illustration of biofilm removal in confined and hard-to-reach positions, such as interior of human teeth, catheter surfaces, or implant surfaces by using two types of catalytic antimicrobial robots (CARs) under the navigation of magnetic field. Reproduced with permission from ref (353). Copyright 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.

Figure 19

Visualization of MagRobots in vivo via various medical imaging modalities. (A) Cross-sectional magnetic resonance imaging of microrobot swarms inside the subcutaneous tissues of a rat’s stomach after magnetic actuation and steering via rotating field for different time periods. Reproduced with permission from ref (249). Copyright 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. (B) Image-guided theranostic platform via the combination of magnetic particle imaging and localized magnetic hyperthermia experimentally demonstrated in a U87MG xenograft mouse with superparamagnetic nanorobots present in the liver and tumor. Reproduced with permission from ref (185). Copyright 2018 American Chemical Society. (C) In vivo fluorescence images of spirulina-based MagRobots in the intraperitoneal cavity of mice at various residence times. Reproduced with permission from ref (249). Copyright 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. (D) Tracking of the generation process of a MagRobot swarm in a bovine eyeball via ultrasound imaging technique. Reproduced with permission from ref (125). Copyright 2019 The Authors. (E) Utilization of multispectral optoacoustic tomography for real-time tracking of individual moving microrobot within phantoms actuated by a permanent magnet. Reproduced with permission from ref (393). Copyright 2019 American Chemical Society. (F) SPECT images of radiolabeled microrobots in Eppendorf tube and in mice. Reproduced with permission from ref (374). Copyright 2019 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim.

Figure 20

Representative pollutant removal by active MagRobots. (A) Directional motion of walnut-like magnetic micromotor under an external magnetic field and its oil-removal ability. Reproduced with permission from ref (401). Copyright 2019 American Chemical Society. (B) Pollen-based microsubmarines for the removal of microplastics (i.e., PS spheres). Reproduced with permission from ref (402). Copyright 2020 Elsevier Ltd. (C) Higher removal efficiency of heavy metals by dynamically swarming spore@Fe₃O₄ biohybrid micromachines compared with that of their static counterparts. Reproduced with permission from ref (292). Copyright 2018 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim. (D) Pd/Ni/Ag nanocoils for removing microbial pathogens. Reproduced with permission from ref (403). Copyright 2015 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim. (E) Magneto-catalytic micromotors for the degradation of Methylene Blue (MB) dye. Reproduced with permission from ref (404). Copyright 2020 American Chemical Society. (F) Lotus pollen-templated magnetic micromotors for temperature-sensitive adsorption of erythromycin. Reproduced with permission from ref (290). Copyright 2019 Elsevier B.V.

Figure 21

(A) Helical nanorobots as mobile viscometers. Reproduced with permission from ref (158). Copyright 2018 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim. (B) Graphene Quantum Dots MagRobots for the detection of endotoxin from E. coli. Reproduced with permission from ref (408). Copyright 2017 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim. (C) Janus micromotors deliver biotin-functionalized cargos for avidin sensing within a microfluidic device. Reproduced with permission from ref (409). Copyright 2020 American Chemical Society.

Figure 22

Diagrammatic summary of this review including (but not limited to) experimental setups, actuation mechanisms, fabrication approaches for various MagRobots, and applications, and the advantages of MagRobots.