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Zhou Et Al 2021 Magnetically Driven Micro and Nanorobots

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org/CR Review

Magnetically Driven Micro and Nanorobots


Huaijuan Zhou, Carmen C. Mayorga-Martinez, Salvador Pané, Li Zhang, and Martin Pumera*

Cite This: Chem. Rev. 2021, 121, 4999−5041 Read Online

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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
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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.

CONTENTS 5.1. Targeted Drug/Gene Delivery 5019


5.2. Cell Manipulation 5021
1. Introduction 5000 5.3. Minimally Invasive Surgery 5023
2. Interations between Micro/Nanorobots and 5.4. Biopsy 5025
Magnetic Fields 5001 5.5. Biofilm Disruption/Eradication 5025
2.1. Magnetic Fields and Magnetic Materials 5001 5.6. Imaging-Guided Delivery/Therapy/Surgery 5025
2.2. Magnetic Manipulation Systems 5001 5.7. Pollution Removal for Environmental Re-
2.3. Actuation Configurations for MagRobots 5003 mediation 5028
2.4. Effective Movements in MagRobots: “Sym- 5.8. Sensing and Biosensing 5028
metry-Breaking Strategies” 5003 6. Conclusion and Future Perspectives 5029
3. Actuation and Mechanisms of Magnetic Robots 5004 Author Information 5030
3.1. Corkscrew-like Motion 5005 Corresponding Author 5030
3.2. Traveling-Wave Locomotion/Ciliary Stroke Authors 5031
Motion 5008 Notes 5031
3.3. Surface-Assisted Motion 5008 Biographies 5031
3.4. Application of Magnetic Fields in Other Acknowledgments 5031
Propulsion Approaches 5010 References 5031
3.5. Magnetic Stimulation of Micro/Nanorobots
beyond Motion 5011
4. Magnetic Robots in the Making: Fabrication
Approaches 5011
4.1. (Quasi-)Spherical MagRobots 5011 Received: November 18, 2020
4.2. Helical MagRobots 5014 Published: March 31, 2021
4.3. Flexible MagRobots 5015
4.4. Wire-like MagRobots 5017
4.5. Biohybrid MagRobots 5018
5. Applications 5019

© 2021 American Chemical Society https://doi.org/10.1021/acs.chemrev.0c01234


4999 Chem. Rev. 2021, 121, 4999−5041
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1. INTRODUCTION however, its biological application is still limited and not yet
fully demonstrated. Magnetically driven micro/nanomotors
Many species in nature, such as magnetotactic bacteria, birds,
address most disadvantages presented by others propulsion
bats, butterflies, lobsters, and salmon, can fly or swim over a
principles and, until now, have been the more explored and
long distance by perceiving navigation cues from geomagnetic
used in many biomedical applications as well as for
fields. Some species (e.g., Amitermes meridionalis) even have
environmental control and remediation. Furthermore, mag-
the ability to (re)orient their bodies or nests according to
netic medical microrobots can be driven by magnetic
geomagnetic information. Similarly, the locomotion of nano-
resonance imaging (MRI) systems, thus utilizing existing
scale and microscale objects in a predefined path by the
clinical MRI equipment for dual purposes, namely the imaging
navigation of magnetic fields,1−4 which are mainly generated
and tracking of microrobots, and their propulsion and motion
by moving charges (i.e., electric currents) and magnetic
control.53,54 Likewise, clinical ultrasonography systems hold
materials (such as permanent magnets), has drawn extensive
great potential to actuate ultrasonically driven microrobots.45
attention owing to their tremendous potential for applications In addition, among all the actuation strategies, the utilization
in biomedicine and environmental remediation. Such mini- of a magnetic field for manipulating miniaturized robots has
aturized objects are normally termed as “magnetically driven unparalleled advantages, which are summarized as follows. (i)
micro/nanorobots” (called “MagRobots” for short in this Remote maneuverability: magnetic fields provide a noninvasive
review), which is an important branch of micro and way to manipulate matter owing to the inherent contactless
nanorobots. characteristics of magnetic forces. Such a wireless actuation
Micro/nanorobots are locomotive artificial machines with method allows for micro and nano agents to move in an
size in the micro or nanoscale and rationally designed to untethered manner while keeping their local chemical
execute tasks on command via self-propulsion or an externally environment intact. (ii) Fuel-Free: using a magnetic field for
controlled propulsion mechanism. Ideally, micro/nanorobots propulsion is a clean process that does not consume liquid fuel
should have the ability to undertake tasks via encapsulation/ (unlike for chemically and photochemically propelled swim-
functionalization with diagnostic or therapeutic agents, mers). This feature eliminates the harmful effects of toxic
decoration with functional materials, or being fabricated into chemicals (e.g., hydrogen peroxide) on cells and tissues during
special micro/nano architectures; “delivery tasks” by moving their biological application processes. In addition, magnetic
toward targeted sites in a user-defined path or a theoretically fields exhibit insignificant dependence on features and
and experimental optimized path; “execute tasks”, for example, properties of surrounding environments and cause negligible
killing diseased cells/tissues, removing environmental pollu- damage to cells at low frequencies. (iii) Reconfigurability and
tants as required; and “exit tasks” after the task accomplish- programmability of magnetic materials: reconfigurability refers
ment via recycling or in situ degradation. During task to the rearrangement of the swimmer’s features such as the
implementation, locomotion behavior is of great importance morphology, locomotion mode, or other motion parameters
for micro and nanorobots. The migration of micro and upon the application of magnetic fields or other external
nanorobots can be powered by multiple strategies including stimuli. Examples of reconfigurable structures are magnetically
chemical catalysis (e.g., O2 or H2 generation) or chemical driven particulate swarms,55−57 stimuli-responsive magnetic
gradients, 5−11 external energy sources (e.g., magnetic materials (i.e., ferromagnetic shape-memory alloys), or
field, 12−14 light,15−21 acoustic wave, 22−25 or electrical composite structures (i.e., smart magneto-polymer compo-
field26−28), and even motile cells (e.g., sperm cell, bacterial sites58,59 or complex origami-like architectures60). This type of
cell).29−37 According to the power source, micro/nanorobots structure can readily change its shape by changing the
can be classified as chemically driven (or fuel-driven), conditions of the applied magnetic fields (i.e., frequency or
magnetically driven, light-driven, ultrasound-driven, electrically magnitude). Programmability refers to the ability to manipu-
driven. The word “driven” can be replaced by “powered”, late the components of the MagRobots in terms of their shape,
“actuated”, or “propelled”. According to their functionalities, magnetic shape, magnetic anisotropy,61 and crystalline
micro/nanorobots can be named as micro/nanogrippers,38−40 anisotropy to achieve a specific motion mode, position, or
micro/nanodrillers,41 micro/nanocleaners,42,43 micro/nano- orientation when magnetic fields are applied.62,63 For example,
scavengers,44 etc. Readers can refer to our latest review45 to the orientation of a magnetic composite-based structure can be
obtain a more detailed classification of micro/nanorobots programmed by suitably aligning the particles within the
based on geometric shapes, motion modes, and functionalities. composite matrix.60 Specific shape-morphing small-scale
Chemically propelled micro/nanorobots are faster than systems can also be designed to exhibit both reconfigurability
those with other propulsion methods, but their locomotion and programmability.64 (iv) Recyclability of magnetic materi-
lacks directionality. Moreover, they require toxic fuels such as als: after micro/nanorobots have completed their tasks, the
H2O2, N2H4, HCl, urea, and NaBH4.46,47 In comparison, those separation and recycling of introduced foreign matter from
micro/nanorobots powered by external physical fields (such as water, biological fluids, or even tissues might be necessary in
magnetic, ultrasound, light, and electric fields) do not need terms of biosafety and biocompatibility. Magnetic nano/
toxic chemical fuels for propulsion, but their motion is microrobots, as they are composed of magnetic building
relatively slow.48−52 Light-propelled micro/nanorobots can blocks (i.e., coating, segment, particulates), allow for a feasible
move in water; however, depending on their composition, they and convenient magnetically assisted retrieval and recycling
need H2O2 and a high-intensity light source, which could process. (v) Versatility: by combining a magnetic field with
compromise their biocompatibility. On the other hand, micro/ other actuation sources, the transport and delivery of
nanomotors propelled by ultrasound are biocompatible but functional cargos (e.g., drugs or a single cell at the nanosize
lack directionality control, making it difficult for them to level) can be achieved with high maneuverability and
perform specific tasks. Finally, micro/nanomotors propelled by sensitivity.65 Currently, various hybrid power sources, such as
electric field are very promising for fuel-free locomotion; magneto-acoustic,22,23,66 magneto-optical,67 and magneto-
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chemotaxis,68 have been reported, which provide dual paramagnetic materials (xm > 0), and diamagnetic materials
propulsion modes in response to multiple stimuli. (xm < 0). Paramagnets and diamagnets are weakly attracted or
Molecular machines are molecular components capable of repelled, respectively, to magnetic fields. Additionally, they
implementing mechanical locomotion (as output) in response cannot retain any magnetization once the magnetic field is
to particular external stimuli (as input).69−72 Stimuli can be removed. Ferro- and ferrimagnets are all strongly attracted to
various energy inputs such as chemical energy, electric energy, magnetic fields. Specifically, ferro- and ferrimagnets can retain
light, photochemical, electrochemical energy, or pH gra- magnetization, (i.e., exhibit remnant magnetization or
dient.73−77 Although molecular machines can perform very remanence) after being subjected to a magnetic field. Usually,
complicated functions, most functions are limited to conforma- high remanence is a feature of hard-ferromagnetic materials,
tional movements.78−82 In terms of practical uses, particularly otherwise known as permanent magnets. Soft-ferromagnets, in
for biomedical applications, the operator’s real-time imaging contrast, exhibit low remanence. Both soft- and hard-magnets
and tracking of the tiny robots are required when they are exhibit a hysteretic behavior, which means that to demagnetize
carrying out specific tasks inside the human body.10,83 This these materials, a coercive magnetic field is necessary. This
requirement may limit the applicability of molecular machines coercivity is large for hard-magnets and small for soft-magnets.
due to their nanoscale (<10 nm) size being too small to be Superparamagnets are a special class of materials in which
readily visualized using traditional imaging techniques. By features of both ferromagnets and paramagnets converge such
contrast, larger micro- and nanorobots can provide greater as high susceptibility, no remanence, and no coercivity. While a
feasibility for bioimaging for the applications in medical few examples exist of micro/nanorobots constructed of
fields.53,84−86 To this end, swarms of micro/nanorobots can paramagnets and diamagnets,96,97 the majority of magnetic
also be used for their imaging and positioning abilities.87−89 small-scale robots have been made of ferromagnetic,
Recent reviews about micro and nanorobots that focus on ferrimagnetic, and superparamagnetic compounds. For ex-
fabrication techniques,51 geometric shapes (e.g., active tended details on types of magnetic materials, we suggest the
particles,90 Janus,91 tubular,92 hybrid actuators81,93), actuation reader to review the hereby indicated references.98−100
sources (e.g., light,48,49 magnetic field94), propulsion mecha- When placing a magnetic small-scale robot with a volume v
nisms,82 and potential applications (e.g., cancer therapy95) in an external magnetic field B, the device will display a
provide us with a basic understanding and up-to-date magnetization M. If the device is subject to a magnetic field
developments in this multidisciplinary and interdisciplinary gradient ΔB, it will experience an attractive force (or repulsive
area. A comprehensive understanding of how tiny machines if it is a diamagnet) as expressed in eq 1. If the device is
behave under magnetic fields will inspire and trigger subjected to a magnetic field, to minimize its energy, it will
interdisciplinary and cross-disciplinary scientific and techno- experience a torque as expressed in eq 2, which will cause the
logical innovation for multiple applications. The goal of this magnetic robot to orient in such a way that its easy
review is to provide a general view of the locomotion behaviors magnetization axis is parallel to the direction of the applied
of nano and microscale motors under the manipulation of a magnetic field. The easy magnetization axis is usually governed
magnetic field and guidance for their rational design by by the shape (shape anisotropy) but can also be ruled by
describing the interaction of MagRobots and magnetic fields as specific crystal orientations of the materials (crystalline
well as actuation and movement mechanisms, and reporting anisotropy). Additionally, the easy magnetization axis can be
state-of-the-art fabrication techniques. After demonstrating programmed, for instance, by orienting magnetic nanostruc-
current applications in biological and environmental fields, a tures with a matrix of a composite component or by
further outlook of this new and exciting field is presented. premagnetizing a material in a specific direction:
F = ν(M × ∇)B (1)
2. INTERATIONS BETWEEN MICRO/NANOROBOTS
AND MAGNETIC FIELDS T = νM × B (2)

2.1. Magnetic Fields and Magnetic Materials Both magnetic forces generated in gradient fields and
magnetic torque induced by spatially homogeneous or
Magnetic fields, as vector-valued functions of the position,
heterogeneous dynamic fields can function as “fuel” to actuate
originate from the movement of electric charge. Magnetic
microscopic and nanoscopic motors in various environments.
fields can be generated by two distinct sources: freely moving
In terms of magnetic torque, weak homogeneous rotating or
electric currents and magnetic materials. Typically, the former
oscillating fields (see Section 2.3), which display higher
source is generated by the coil of an electromagnet that is
efficiency in transforming magnetic energy into kinetic energy,
externally controllable. The setups of a triaxial orthorhombic
are highly preferable. Magnetic fields offer a maximum of six
Helmholtz coil and eight electromagnetic coils (e.g., MiniMag,
degrees of freedom (DoFs) (i.e., three translational DoFs and
OctoMag) are representative and widely employed to generate
three rotational DoFs) for absolute spatial manipulation of
magnetic fields for driving and steering MagRobots (see
micro/nanorobots, depending on the setup of electromagnetic
Section 2.2). The latter source is generated from the intrinsic
actuation systems (see Section 2.2). For instance, the widely
magnetization of magnetic materials, specifically permanent
used uniform rotating magnetic field with triaxial Helmholtz
ferromagnets, which can retain a large remnant magnetization.
coil can supply three rotational DoFs, while MiniMag and
To manipulate micro- and nanomachines by magnetic fields, a
OctoMag have five DoFs: two rotational and three transla-
conventional strategy consists of incorporating magnetic
tional DoFs.
components into nano/microstructures. Magnetic materials
can be classified as a function of the magnetic susceptibility 2.2. Magnetic Manipulation Systems
(xm), a parameter that reflects how easy a magnetic material is A typical setup platform for monitoring and actuating
magnetized. As such, magnetic materials are categorized as magnetically driven micro- and nanorobots consists of a
ferromagnetic (and ferrimagnetic) materials (xm ≫ 0), sample stage, an optical microscope (eventually, coupled with a
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high-resolution camera), a magnetic manipulation system, and strength of a magnet’s field depend on its geometrical shape
a computer system with video capture and analysis (Figure and size. For a magnetized object with a given geometry shape
1A). The magnetic manipulation system consists of a set of and magnetization, large magnets can project their field further
into space. However, large magnets produce smaller magnetic
forces as demonstrated in eq 1 because the change of field in
space (i.e., spatial derivatives in the field) is less pronounced.
By manually or automatically adjusting the position or
orientation of a magnet, a translatory or rotational movement
of MagRobots can be triggered. Direct utilization of portable
magnet provides an easy-to-operate way to drive the motion of
MagRobots by simply adjusting the position and orientation of
a magnet (Figure 1B). Although many researchers have
reported the locomotion of magnetic micro/nanorobots by
using single permanent magnets, the experimental reproduci-
bility and accuracy are challenging aspects because the
movement of magnets largely depends on their operator.
Given the drawbacks of manual handling, many automatically
operable magnet systems have been designed by integrating a
magnet with a commercial robotic arm such as the LBR Med
robotic arm from KUKA Robotics Corporation (Figure 1C)
and MH5 robotic arm from Yaskawa Motoman. Such an
integrated system is more reliable and precise. Besides
magnetic field gradients, magnetic torque can also be exerted
on small-scale devices when the magnet rotates (Figure 1D),
which allows for rotational actuation mechanisms.
In magnetic actuation systems based on electromagnets,
magnetic fields are generated from flowing currents through
coils. A typical electromagnet is formed by wrapping insulated
copper wires around a ferromagnetic core, which can
concentrate and amplify the magnetic field and field gradient.
Figure 1. Experimental setup for magnetically driven micro/ An ideal soft magnetic material is often used as the core in
nanorobots and various magnetic actuation systems. (A) Diagram order to avoid effects of hysteresis. On-demand setting of
of the typical experimental workplace for actuating and visualizing current in each coil can result in the required configuration of
MagRobots. (B) Magnetic actuation system consists of only a single magnetic fields, such as rotating field, oscillating field,
permanent magnet. (C) Permanent magnet actuation system using alternating fields, and conical fields, which will be discussed
cylindrical NdFeB permanent magnet fixed to its end-effector and a in Section 2.3. Different arrangements of coils constitute
robotic arm. Reproduced with permission from ref 101. Copyright specialized electromagnet systems such as the Helmholtz coil,
2017 IEEE. (D) Rotating permanent magnet system consists of a
the Maxwell coil, the saddle coil, and the double-saddle Golay
magnet, a robotic arm, and a motor. Reproduced with permission
from ref 102. Copyright 2013 IEEE. (E) Electromagnetic actuation coil (detailed information can be found in ref 113). Helmholtz
system using triaxial circular Helmholtz coils. Reproduced with coil, containing two circular and coaxial coils with equal radius
permission from ref 103. Copyright Springer Science + Business and same handedness of flowing current, is the first and most
Media, LLC 2013. (F) Electromagnetic actuation system using a important arrangement. Because the field generated from the
stationary Helmholtz−Maxwell coil and a rotational Helmholtz− Helmholtz coil is near-uniform at the center of the coils, such a
Maxwell coil. Reproduced with permission from ref 104. Copyright magnetic actuation system is appropriate for magnetic torque
2009 Elsevier B.V. (G) Electromagnetic actuation system using control.114−116 Arbitrary uniform magnetic fields in a 2D plane
multiply coils including a Helmholtz coil, Maxwell coil, uniform or 3D space can be generated by two pairs of Helmholtz coils
saddle coil, and gradient saddle coil. Reproduced with permission or triaxial Helmholtz coils, respectively. Triaxial circular
from ref 105. Copyright 2010 Elsevier B.V. (H) MiniMag electro-
magnetic system. Reproduced with permission from ref 106.
Helmholtz coils are the most commonly used for actuating
Copyright 2014 Springer-Verlag GmbH Berlin Heidelberg. magnetic small-scale robots (Figure 1E). The combination of
Helmholtz coils with other types of coils can engender systems
either permanent magnets or electromagnets107−110 as the with multi-DOF capabilities. Maxwell coil is also composed of
source of the magnetic field. Recent contributions97,111,112 two circular coaxial coils with equal radius, but the current
provide a systematic review of configurations of magnetic flowing through different coils coil has the opposite handed-
ness. Maxwell coils can create uniform magnetic field gradients,
manipulation systems that can be applied to magnetic small-
saddle coils can generate a uniform field or a gradient field, and
scale robots with sizes ranging from nanometers to millimeters. double-saddle Golay coils can produce a transverse gradient. A
In this review, we will only focus on the commonly used magnetic manipulation system with a stationary Helmholtz−
magnetic systems employed for the manipulation of nanoscale Maxwell coil and a rotational Helmholtz−Maxwell coil has the
and microscale robots. capacity of 3D locomotion of a magnetic small-scale robot
One of the main differences between systems using through the control of both magnetic forces and torques
permanent magnets and electromagnets is the fact that the (Figure 1F).104 Its upgraded system using four different coil
magnetic field from a permanent magnet is persistent and its pairs (i.e., a Helmholtz coil, a Maxwell coil, a rotatory uniform
magnitude cannot be quickly changed. The distribution and saddle coil, and a rotatory gradient saddle coil) occupies a
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smaller volume and consumes less driving energy (Figure


1G).105 Given the practical clinical application of biomedical
micro/nanorobots, saddle coil and Golay coil with tubular
construction are preferable because they have high space
efficiency and, hence, are capable of accommodating the
human body. For example, a widely used magnetic resonance
imaging (MRI) scanner in clinical practice incorporates a
Maxwell coil and two orthogonal Golay coils.117
A drawback of magnetic actuation systems consisting of
paired coils lies in their restrictions on the shape and size of the
workspace. In contrast, electromagnetic systems using several
nonorthogonally distributed electromagnets, usually made of
columnar coils with soft-iron cores, can break this limitation by
arranging the electromagnets so that their generated dipoles
keep their respective axes pointing to a common point in the
given workspace. The first example of such configuration was
the OctoMag, an electromagnet comprising a total of eight
electromagnets. OctoMag is a system capable of generating
magnetic forces and torques in three dimensions and allows for
a 5-DOF magnetic control (3-DOF position and 2-DOF Figure 2. Classifications and configurations of magnetic fields in
orientation).118 OctMag is composed of four evenly dis- relation to the motion of MagRobots.

i ∂v y
ρjjj + (v∇)vzzz = η∇2 v − ∇p
tributed electromagnets in a plane with the orientation of 90°

k ∂t {
from a central axis and four evenly distributed electromagnets
with the orientation of 45° from a central axis. MiniMag is the (3)
scaled-down compact version of the OctoMag (Figure 1H).
Utilization of OctMag and MiniMag has been reported to where vector ν and vector p (both of which are a function of
remotely manipulate micro- and nanorobots for targeted drug position and time) are the flow velocity and pressure,
delivery,119 minimally invasive ophthalmic surgery,120 and respectively; ρ and η are the density and viscosity of the
stem cell transplantation in a rat brain.121 Other configurations flow, respectively. The left-hand of the Navier−Stokes
of electromagnets, such as square antiprism, cubic, open equation comprises the inertial forces, while the right-hand
asymmetric, and so on, were summarized in a recent review.113 corresponds to the viscous forces. Here, we introduce an
important dimensionless quantity called the Reynolds number
2.3. Actuation Configurations for MagRobots (Re, expressed in eq 4), which is the ratio of inertial and
According to changes of the magnetic field vector with time, viscous forces:
magnetic fields can be classified as static, dynamic (including a inertial forces ρνL
rotating magnetic field whose direction varies with time, an Re = =
viscous forces η (4)
oscillating magnetic field whose strength varies with time), or
on−off fields. Both static and dynamic magnetic fields can be where L is the characteristic length of an object moving in a
homogeneous fields where the field vector modulus remains fluid.
constant in space, or inhomogeneous magnetic fields where the For small-scale devices and organisms (i.e., motile cells,
field strength varies with position, that is, field gradient.122 bacteria), L is very small (Re ≈ 10−4), which means that
Rotating magnetic fields are widely adopted to induce viscous forces rule their motion. A typical analogy of swimming
rotational motion. For some micro and nanomachines with at low Re is that a bacteria swimming in water is similar to a
specific shapes (e.g., helical structure), such temporal−periodic person swimming in honey. Considering that inertia forces are
rotational motion can be converted into translational cork- negligible in the low Re regimes, the Navier−Stokes equation
screw motion (see Sections 3.1 and 4.2), which leads to a net can be simplified as an expression known as the Stokes
spatial displacement. In contrast, oscillating magnetic fields can equation:
be utilized to activate traveling undulatory locomotion for η∇ν = ∇P (5)
some MagRobots such as those with soft tails (see Section 3.2)
and those consisting of solid segments linked with soft hinges Note that this hydrodynamic equation is time-independent,
(see Section 4.4). Rotational magnetic fields can also induce meaning that no net displacement will occur after completing a
thermophoretic motion for ferromagnetic materials by cyclic process no matter if the speed of the swimmer is fast or
generating heat energy123 (see Section 3.4). Figure 2 slow. In other words, the resultant fluid flow exhibits
summarizes different categories of magnetic fields and their instantaneous and time-reversible features. This is the so-
corresponding field diagrams.124 called “Scallop Theorem,” as introduced by the Nobel laureate
Purcell (Figure 3A). At low Reynolds number, a microscopic
2.4. Effective Movements in MagRobots:
scallop can only perform back and forward movement (i.e.,
“Symmetry-Breaking Strategies”
reciprocal motion). Once the actuation energy (such as a
To begin this section, we would like to briefly introduce the magnetic field) is removed, its motion is immediately halted
hydrodynamic laws to understand how small-scale robots swim due to the lack of inertial forces. Importantly, to generate a
in a fluid. The Navier−Stokes equation, arising from Newton’s nonreciprocal translatory movement to execute tasks such as
second law, describes the motion of a Newtonian fluid as cargo delivery, Figure 3B summarizes some strategies
follows (eq 3): employed to break Purcell’s Scallop Theorem. The first
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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”140). (B) Summary of five strategies (S1−S6) to break the
Scallop Theorem to produce an effective movement. S2 is reproduced with permission from refs 136 and 139. 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 141. Copyright 2015
The authors. S5 is reproduced with permission from refs 136 and 139. Copyright 2014 Macmillan Publishers Limited. This is an open access article
distributed under the terms of the Creative Commons CC BY license.

method involves fabricating a small-scale robot with an field. The fourth approach is based on actuating magnetic
asymmetric shape such as a tubular,125 helical,60,126,127 fish- small-scale devices in the proximity of a boundary (e.g., wall,
like,128 annelid-worm-like,129 tadpole-like,130 bullet-shaped,22 interface) to break the spatial symmetry. The motion
star-shaped,131 or even random-shaped132,133 structure. In mechanism based on this method is called “surface-assisted
addition, an asymmetric shape (e.g., carpet,134 ribbon56) can propulsion”, which will be discussed in Section 3.3. All these
also be formed by self-assembling colloid particles with a symmetry-breaking strategies evade the constraints of the
symmetric shape based on collective behavior.90 A second famous Scallop Theorem.100 Note that the Scallop Theorem
approach consists of creating a micro- or nanostructure only applies to Newtonian fluids. Time-reversible reciprocal
containing a flexible component, for example, a flexible tail, locomotion can still generate an effective propulsion in non-
which can mimic the flagellum of a microorganism.81,135 Newtonian fluids (e.g., blood, saliva, mucus).139
Velocity distribution (indexed by frame number of a video
sequence) of a single beating flagellum or cilium from a cell or 3. ACTUATION AND MECHANISMS OF MAGNETIC
a microorganism during one cycle136 indicated the generated ROBOTS
traveling-wave motion (see Section 3.2) is nonreciprocal. Compared with macroscale motile robots, micro and nanoscale
Incorporating flexible components in between rigid structures robots experience totally distinctive hydrodynamics. Hence,
to create multilink micro or nanoassemblies is also another they exhibit distinctive assorted motion behaviors. A good
possibility, which will be further discussed in Section 4.4. A understanding of various propulsion mechanisms is the basis
recent strategy consists of integrating motile flagellated for the design of propulsion microsystems including the shape
microorganisms and cells with magnetic micro and nanostruc- and architecture of micro and nanorobots as well as the
tures to create biohybrid MagRobots (see Section 4.5). A third configuration of the magnetic field. The designed propulsion
approach entails the use of a nonsymmetric actuation magnetic system must be able to overcome various resistive forces in the
field. For example, a symmetric small structure can exhibit a micro and nanodomains to realize the motion of small-scale
translational motion by means of a traveling-wave137 or a cilia- robots effectively. The translational mechanisms of magnetic
beating motion mechanism138 under a nonsymmetric actuation miniaturized machines could be broadly divided into three
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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 148. 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 154. Copyright 2019 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim.

types: (a) corkscrew motion, (b) undulatory motion (i.e., equal) to balance the produced torque (Figure 4A). Inspired
traveling-wave motion), and (c) surface-assisted propulsion by the bacterial flagellum for efficient movement, man-made
(i.e., surface walker). helical micronanomachines, known as artificial bacterial flagella
3.1. Corkscrew-like Motion (ABF),142−145 have been developed and investigated. Although
there is no motor in the ABF system, external rotating
In nature, many microorganisms can coordinate their magnetic fields provide a similar function for generating the
propulsion and orientation behaviors according to external rotation.
stimuli with a motile appendage called a flagellum. Eukaryotic As discussed earlier, a MagRobot will align its easy
cells (e.g., spermatozoa) can produce a traveling-wave motion magnetization axis parallel with the direction of a local
by making use of a flexible beating flagellum. In contrast, homogeneous field upon experiencing a magnetic torque in
prokaryotic cells can perform a corkscrew-type motion by that magnetic field. A continuously applied torque to a micro/
rotating their helical flagella. Bacteria (e.g., E. coli), as a nanoobject under an external rotating field gives rise to the
representative of prokaryotic organisms, rely on the rotation of rotational movement of the body. For artificial magnetic
flagella for swimming. The flagellum, containing a basal body, a micromachines containing chiral helices, a steady rotation
hook, and a filament, is the fundamental organelle for bacterial around their helical axis can be effectively converted into
motion. There is a reversible motor inside the basal body nonreciprocal translational motion, with the direction parallel
controlling the rotation of the flagellum. The flagellum can not with the rotating axis of a two-dimensional planar rotating
only trigger reorientation of the organism but also make them field. At the same time, the tail and head (sometimes it has no
move forward and back. When the flagellum rotates in one head) of ABF perform the same (clockwise or counter-
direction with an action frequency ω1, the cell body counter- clockwise) orientation. This is distinct from bacteria, whose
rotates with the reaction frequency ω2 (ω2 and ω1 are not head and tail rotate in the opposite orientation. If the ABF
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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 128. Copyright 2016 WILEY-VCH Verlag
GmbH and Co. KGaA, Weinheim. (B) Multiple locomotion modes of millipede-like soft robots. Reproduced with permission from ref 159.
Copyright 2020 The Authors. (C) Ciliary stroke motion of artificial micromotors. Reproduced with permission from ref 138. Copyright 2016 The
Authors.

consists of a single rigid body, then the head and tail will rotate (e.g., fluid viscosity, ion strength), geometrical parameters
with the same frequency (ωh = ωt). Moreover, the progression (e.g., helix pitch), surface characteristics (e.g., surface
direction (forward or backward) can be easily inverted by wettability,149,150 roughness), magnetic field properties (e.g.,
reversing the direction of rotation (i.e., clockwise or counter- frequency, intensity, rotating, or oscillating field), magnet-
clockwise) of an applied magnetic field. In the magnetically ization properties of magnetic materials, head/tail shapes,
actuated ABF system, similar to other magnetically controlled mechanical properties (e.g., rigid or flexible), and boundary
systems, magnetic materials are required in order to respond to condition (e.g., wall). The simulation demonstrates that helical
the external field. Widely used ferromagnetic materials include swimmers exhibit the highest propulsion efficiency when the
Ni, Co, and Fe, while the frequently applied superparamagnetic pitch angle is about 45°.151 The optimal magnetization
materials include Fe2O3 and Fe3O4. Up to now, various types direction for helical microrobots is perpendicular to the helical
of ABF systems have been investigated.146,147 Some typical axis in order to maximize the applicable magnetic torque
examples are shown in Figure 4B.148 around the axis. The motion mode and velocity of ABF are
Many factors play a critical role in the movement of strongly associated with the applied field frequency. As shown
magnetic helical microswimmers such as solution properties in Figure 4C, at low frequency rotating magnetic fields
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Figure 6. Propulsion mechanisms for surface walkers. (A). Surface-assisted motion of an Au−Ag−Ni nanowire. Reproduced with permission from
ref 172. 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 167. 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 168. 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 169. 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 171. Copyright 2018 WILEY-VCH
Verlag GmbH and Co. KGaA, Weinheim.

(typically below several Hertz), a wobbling motion occurs MagRobots increases with the increased applied rotation
when the axis of the helical MagRobot cannot align with the frequency of an external magnetic field, performing a
direction of the local field.152,153 As the rotating field frequency synchronous and linear relationship. Further increase with
is enlarged, the wobbling angle decreases from 90° to zero, respect to a critical field frequency results in a decrease of the
where a wobbling angle of zero corresponds to the rotation swimming velocity, which is attributed to the fact that the
along the long axis with a direct corkscrew-like thrust. (Ratio of magnetic torque is not sufficient to maintain a synchronous
viscous to magnetic torque (i.e., Mason number), helix angle, relationship between the magnetic moment and the applied
and helical size can also bring about shrinkage of the wobbling rotating magnetic field. The critical frequency is called the
angle of helical MagRobots under temporal−periodic “step-out frequency”.154
torques.49 In the corkscrew-like motion region (also denoted Surface chemistry also influences the motion of helical
as “synchronous” region), the translational velocity of helical MagRobots. Recently, it has been reported that magnetically
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driven helical microswimmers with hydrophobic surfaces microarchitecture, as the exclusive example with regard to the
possess larger step-out frequencies and higher maximum simple ciliary stroke motion, has been fabricated by means of a
translatory velocities at low Reynolds numbers in comparison 3D laser lithography method.138 The efficient movement of
with those with hydrophilic surfaces.155 The increase in this microrobot in a fluid environment with a low Reynolds
hydrophobicity of the swimmer surface causes an increase in number was powered by the net propulsive force from the
both the step-out frequency and the maximum forward velocity beating locomotion of cilia and its position and orientation can
in a nonlinear mode due to the interfacial slippage. be precisely controlled by on−off fields with designated angle
Importantly, the forward velocity of ABF is independent of (Figure 5C).
their surface wettability when MagRobots are manipulated 3.3. Surface-Assisted Motion
below their critical frequency. A 3D oscillating magnetic field,
created by the combination of DC magnetic field Bxy and Apart from breaking the symmetry from the geometrical point
oscillating Bz field, can only cause the reciprocal back-and-forth of view, another strategy to overcome the Scallop Theorem
motion of a helical microswimmer. When symmetry is broken and induce translational movement is to introduce a physical
by placing the microswimmer near a surface, the rocking boundary to break the spatial symmetry. Such locomotion can
motion results in a net displacement. Moreover, the be achieved by magnetically actuating a magnetic micro- or
asymmetric helix (with polystyrene head and helical Co/SiO2 nanostructure when it lies in the proximity of a surface/
tail) exhibits much larger displacement than a nearly interface160 or a wall in a liquid at low Reynolds number, or
symmetric helix without a head under similar experimental even a dry surface.161 The micro and nanorobots based on this
conditions.156 The viscosity disturbance in different solutions “surface-assisted locomotion” mechanism are called “surface
results in the difference of precession angle (i.e., wobbling walkers” or “surface rollers.” Figure 6A exhibits a typical
angle) of helical MagRobots when the applied frequency of the forward locomotion mode of a surface walker. Many magnetic
rotating field is smaller than the step-out frequency. Taking micro and nanostructures have demonstrated such surface-
advantage of this feature, the detection of instantaneous assisted propulsion including (but not limited to) nanorods,
orientations (i.e., wobbling angle) of MagRobots provides an dimers, assembled colloids, microtubes, and Janus particles.
innovative approach to evaluate the viscosity of the local Simulations and experiments have confirmed that the dynamics
medium with high spatial and temporal accuracy, which makes and motion mechanism of surface walkers are governed by the
ABF a novel prototype for mobile viscometers.157 boundary features (slip or nonslip), the degree of confinement
(e.g., single or multiple confining boundaries, the distance of a
3.2. Traveling-Wave Locomotion/Ciliary Stroke Motion MagRobot from the nearby boundary), fluid properties (e.g.,
Both traveling-wave propulsion and metachronal-wave pro- finite inertia162), magnetic fields (e.g., configurations, fre-
pulsion, inspired by the flagella and cilia of eukaryotic cells, quency, strength), and others. The presence of a boundary
respectively, are capable of breaking temporal symmetry to modifies the hydrodynamic stresses on self-propelled nano/
overcome the Scallop Theorem and generate an effective net microrobots, resulting in a change in their orientation, velocity,
displacement. Because short and rigid nano/microrobots can trajectory, and even hydrodynamic bound states.163 Stronger
only generate very limited net propulsion due to the reciprocal frictional forces near a nonslip confining boundary (wall or
nature of an oscillating movement, the presence of an elastic surface) can drive microdevices to move forward, resulting in a
component is crucial for achieving traveling-wave propulsion. larger net displacement compared with those in proximity to a
However, net displacement can also be hampered if the motor smooth boundary. Hydrodynamic interactions can create
is too long and flexible due to the increase of drag force. stable finite clusters (“critters”) from an unstable front that is
Hence, the size and elasticity must be taken into consideration generated from the press of fingers.164
in terms of design. Traveling-wave propellers have been Motion modes of surface walkers are frequency- and field
created either by incorporating elastic tails (e.g., a chain of type-dependent. CoPt semihard magnetic nanowires experi-
paramagnetic beads using DNA as the soft hinge158) to a rigid ence the motion transformation from tumbling to precession
head or by utilizing multilink nanowires connected by flexible and then to almost rolling near a surface boundary by raising
segments (e.g., soft silver nanowire,3 elastic polymeric the frequency of the applied planar rotating field. In the
nanocylinders composed of multiple bilayers of polyallylamine tumbling region, the y-axial translational velocity of nanowires
chloride and polystyrenesulfonate97). The thrust from the synchronously increases with the field frequency regardless of
backward-traveling wave generated by the undulatory motion the applied magnetic moment. In the procession region, the
of multilink artificial microswimmer, consisting of two velocity still slowly increases and then decreases after reaching
magnetic nickel segments, two gold segments, and three soft the maximum. The decrease of speed is ascribed to a decline of
silver, hinges upon the application of an oscillating magnetic the precession angle, resulting from the change of motion
field. Periodic mechanical deformation triggered fish-like configuration.165 Transformation of the motion mode can also
locomotion at the microscopic level (Figure 5A).128 Other occur in hematite peanut-shaped microrobots by using
traveling-wave motion of wire-like MagRobots driven by an different magnetic fields, including a 1D oscillating magnetic
oscillating field can be found in Section 4.4. fields (oscillating mode), yz-planar rotating magnetic field
Although the metachronal wave, which is produced by the (rolling mode), xy-planar rotating magnetic field (spinning
oscillatory locomotion of ciliated protozoa through hydro- mode), and conical magnetic field (tumbling mode)
dynamic interactions, can also drive an effective nonreciprocal corresponding to the collective configuration of liquid, chain,
movement. Because of the complexity of manufacturing these vortex, and ribbon, respectively (Figure 6B). A 2D vortex can
structures at micro- and nanoscale, only millimeter-scale (not be self-assembled by rotating magnetic colloids in a plane
nanoscale or microscale) robot systems that mimic the parallel to the interface; however, such a vortex cannot produce
metachronal-wave movement of cilia have been reported net displacement. On the contrary, net displacement occurs in
(Figure 5B).159 To date, one artificial cilia-like magnetic rolling mode and tumbling mode once a boundary is present.
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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 173. 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 179. 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
180. Copyright 2020 WILEY-VCH GmbH and Co. KGaA, Weinheim.

Taking the chains with rolling mode as an example, net owing to the considerable rise of liquid-induced viscous torque.
displacement along the x axis can be generated when the In addition, the velocity of assembled chains is dependent on
assembled magnetic chains are subjected to a yz-plane rotating the number of microrobots composing the chains. Most
field. In other words, the rotational motion of microrobots in a importantly, collective formations and locomotion can be
plane perpendicular to a nearby boundary can lead to manipulated by a magnetic field in a programmable and
nonreciprocal propulsion. Similar to the artificial bacterial reconfigurable fashion, providing versatile collective modes to
flagella, the velocity of the individual peanut-shaped micro- meet multitasking requirements in complicated biological
robots as well as that assembled chains (e.g., trimer and systems.56,124,166 Magnetic microkayaks demonstrate process-
pentamer) linearly increases with applied frequency when the ing motion in a double-cone rotating way, similar to the
actuation frequency is below the step-out frequency. Above the movement of a paddle, when placed in proximity to a solid
step-out frequency, the increase of the rotating field’s surface under the rotating fields with kilohertz frequency
frequency causes a decrease of the microrobots’ velocity (Figure 6C).167
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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 185. 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 123. Copyright 2012 American
Chemical Society. (C) Underlying physics of the magnetoelectrically triggered drug (i.e., AZTTP) release process. Reproduced with permission
from ref 200. Copyright 2013 Macmillan Publishers Limited.

In comparison with flat surfaces, research of magnetic nano/ ex vivo swine bladder) was investigated by Zhang’s group.170 In
microrobots on topographic surfaces is more challenging but addition to a rotating field, an oscillating magnetic field can
more intriguing. Inspired by smooth-riding bicycles containing also be adopted to actuate the translational movement of a
square-shaped wheels, utilization of a microroad with periodic surface walker. Under an oscillating field, microdimers
bumps lead to 4-fold intensification in forward velocity of consisting of Ni-SiO2 magnetic Janus microspheres are able
microwheels (μwheels) owing to the nonslip rotation of entire to roll on the solid surface after sedimentation treatment. In
wheels. Because of the velocity difference between diamond contrast, no net displacement can be produced when Janus
μwheels and square μwheels on topographic surfaces, the microspheres are returned to the bulk of the liquid by acoustic
separation of isomeric μwheels by symmetry can be fulfilled levitation (Figure 6F).171
(Figure 6D).168 For surface walkers, climbing over a barrier is 3.4. Application of Magnetic Fields in Other Propulsion
also possible by taking advantage of surface physics. A peanut- Approaches
shaped hematite micromotor with its magnetic moment Approaches such as chemically or photochemically induced
vertical-aligning with the long axis can achieve rolling propulsion lack the level of control of magnetically driven
movement under a rotating magnetic field and wobbling micro and nanoswimmers, especially in terms of directionality,
movement under a conical rotating field. The magnetically control over the speed, and ON/OFF motion features.
actuated MagRobot can climb up and down a steep slope with However, chemically and photochemically driven swimmers
a height of 8 μm through the wobbling motion mode. By are very useful for chemistry-on-the-fly applications such as
combining rolling motion mode and wobbling motion mode, water remediation applications. To provide better controll-
the MagRobots can be utilized to deliver and release cells to an ability on the motion aspects of these chemical and
appointed place and form complex cell patterns under the photochemical swimmers, the integration of magnetic
control of a magnetic field in a contactless fashion (Figure components has been widely adopted. For example, a single
6E).169 Except for these artificial barriers, magnetic actuation TiO2−PtPd−Ni nanotube173 performed autonomous motion
of MagRobots on the uneven surface of biological tissue (i.e., through the bubbles generated from the decomposition of
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hydrogen peroxide (Figure 7A). To control the directionality Magnetic fields can also be used to trigger electric
of bubble-propelled small-scale machines along any predeter- polarization if magnetoelectric materials are incorporated in
mined paths, the assistance of other power sources is small-scale motile devices.187,188 Magnetoelectric materials are
necessary. After the application of a static magnetic field, the single-phase or composite materials, which become electrically
motion direction of those self-propelled nanodevices is polarized when subjected to an external magnetic field.187,189
controllable. A similar function of orientation control was To operate at room temperature, magnetoelectric materials are
found in fuel-free light-driven small-size robot systems,174 usually made by intimately coupling magnetostrictive and
urease-powered nano/micromotors,175 cell-powered nano- piezoelectric components, although certain single compounds,
micromachines,176 and acoustically actuated micronanoscale such as bismuth ferrite (BiFeO3), exhibit magnetoelectric
vehicles.97,177 Furthermore, the combination strategy can features at room temperature. When a magnetic field is applied
amplify the propulsive thrust by harvesting energies from to these materials, the magnetostrictive part changes its
different sources,178 resulting in more efficient task processing dimensions. In turn, the magnetostrictive part stresses the
capabilities. A Janus microrobot, using three types of piezoelectric part, which subsequently becomes electrically
nanomaterials as engines, was capable of swimming by bubble polarized. Magnetoelectric composites can be processed as
propulsion, light-powered propulsion, and magnetic-actuated bilayered or multilayered composite structures, core−shell
motion (Figure 7B).179 Compared with only bubble- architectures, or as particulate matrix composite films.190
propulsion, the bubble−magnetic dual propulsion mode Because of their ability to generate electric fields in a wireless
boosted the velocity of microrobots up to 3 times, while the fashion (i.e., external magnetic fields), magnetoelectric
bubble−light dual mode could increase it up to 1.5 times. materials integrated into small-scale robots can serve at least
Because of the synergetic effect of the three energy sources two purposes: (a) magnetic navigation due to the responsive-
(i.e., chemical energy, light, and magnetic field), the ternary ness of the magnetostrictive component to magnetic fields and
bubble−light−magnetic mode exhibited a much higher speed (b) application of an electric field to the surrounding
than binary bubble-light mode.179 By switching on and off a environment (i.e., electrolytes, cells, tissues) due to the
magnetic field, the on-demand control of nanoand microscale piezoelectric block. Switching between these two capabilities
robotic systems via braking or accelerating the propulsion is managed by changing the conditions in which the magnetic
process was demonstrated. Obvious growth of velocity was fields are applied, for example, by changing the frequency of an
observed in an ultrasound-powered Janus micromotor when a oscillating magnetic field or by swapping between gradients
static magnetic field switched from “OFF state” to “ON state” (for motion) and oscillating magnetic fields (for triggering the
as shown in Figures 7C.180 Moreover, the use of external magnetoelectric effect). The delivery of electric fields is
magnetic fields allowed for controlling the directionality to the interesting for a wealth of applications, especially in the
acoustically driven microrobots. biomedical domain such as cell electrostimulation and
differentiation,191 electroendocytosis-mediated drug deliv-
3.5. Magnetic Stimulation of Micro/Nanorobots beyond ery,192 irreversible electroporation for cancer treatment,193
Motion cell fusion,194 or even cell destruction.195,196 Magnetoelectric
In addition to direct motion control, magnetic fields can be nanorobots or microrobots, despite being less investigated,
used as the energy source for triggering hyperthermia,181 have been utilized for targeted cell manipulation,197 neuronal-
thermophoresis, and magnetoelectricity. Magnetic hyper- like cell differentiation,13 and targeted drug delivery.198 For
thermia refers to the heating of cells, tissues, tumors, or instance, a helical microswimmer, incorporating core−shell
systems to temperatures up to 42 °C by converting magnetic magnetoelectric nanoparticles (i.e., CoFe2O4 as the core and
energy into heat radiation.182,183 Such function is preferable for BiFeO3 as the shell) into a hydrogel matrix was able to induce
treating cancer cells while minimizing damage to surrounding the differentiation of neuronal cells due to the generation of
healthy tissues as nanoscale and microscale robots can be charges upon magnetic stimulation.13 On-demand drug release
externally delivered to the infection site with the assistance of for killing cancer cells was demonstrated by FeGa@P(VDF-
real-time image guidance (e.g., clinical MRI scanner, magnetic TrFE) core−shell nanowires upon the application of an AC
particle imaging scanner184) and subsequent hyperthermia magnetic field because of the magnetoelectric coupling
treatment is localized by only focusing on the tumor tissue. effect.198 It is believed that magnetoelectrically induced drug
Recently, an approach that combined hyperthermia features release is caused by the rupture of drug−carrier bonds when
with the propulsion force of nanoswimmers has been utilized the dipole moment triggered by a magnetic field goes beyond
to clear away plaques in a clogged blood artery. The the threshold value (i.e., drug−carrier bond strength) and
nanorobots consisted of cellulose nanocrystals, Fe2O3 NPs, breaks the intrinsic charge distribution on atoms199,200 as
and Pd NPs.185 As demonstrated in Figure 8A, the flow of the suggested by Khizroev’s group (Figure 8C).
bloodstream went back to its normal state after the blockage
site from animal fat was fully melted and removed. Magneti- 4. MAGNETIC ROBOTS IN THE MAKING:
cally induced thermophoresis refers to a self-diffusive motion FABRICATION APPROACHES
generated by the local temperature gradient induced by the
nano/microrobot itself under an external field. An alternating 4.1. (Quasi-)Spherical MagRobots
(AC) magnetic field has been used to heat the spherical Janus Colloidal magnetic particles have attracted scientists’ attention
robot half-capped with magnetic material (i.e., Fe19Ni81 alloy), not only because of their individual properties but also due to
giving rise to self-thermophoretic motion123 as shown in Figure an emergently investigated phenomenon called “swarm” or
8B. Besides, the high heating power generated by the magnetic “collective behavior”,57,201−208 which is a term inspired by
field was also reported to trigger a Fischer−Tropsch syn- many phenomena in nature such as flocking of birds or team-
thesis.186 In this process, the magnetic nanoparticles acted as work behaviors of insects. How to manipulate and actuate a
magnetically induced heterogeneous catalysts. large number of tiny robots with collective behaviors for
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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 211. 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 213. Copyright 2019 The Authors. (C) Fabrication steps of the burr-like microrobots. Reproduced with permission from ref
214. 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 209. Copyright
2018 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim.

potential in vivo applications, particularly in complex biological the magnetic field strength and phase lag, lassos can capture
media and in a precisely controllable and programmable cargo through curling behavior and precisely transport it on
fashion, is the ultimate objective of scientists. The self- the ground of a wheel-type mechanism at high velocities.
assembled MagRobots not only are capable of loading or Inspired by ants’ cooperative behavior to create a bridge with
unloading defined cargos on command but also transport them their bodies when encountering a vanished or nonexistent road
to a defined site (e.g., microfluidic system or biological (Figure 9A), Zhang’s group used a self-organized magnetic
environment), providing great potential for localized therapy swarm robotic system as building blocks to form a microswitch
and targeted drug delivery209 owing to their easy synthesis and to repair broken microcircuits. Each component of the system
versatile multifunctionalities by material design, structure was made of a conductive gold-coated superparamagnetic
optimization, and surface modification. The collective behavior Fe3O4 nanoparticle. Under a programmed oscillating field,
via colloidal self-assembly presents a rapid, reversible, and these magnetic nanoparticles can self-reconfigure into a
programmable bottom-up approach to fabricate MagRobots by ribbon-like microswarm to act as a conductive bridge between
employing simple colloidal particles as building blocks. In the two disconnected electrodes. The patterns and behaviors of the
presence of a magnetic field, both commercially purchased swarming MagRobots depend on the amplitude ratio and input
paramagnetic materials (e.g., μm-sized Dynabeads134,210) and oscillating frequency. Moreover, the elongation of the
experimentally synthesized magnetic colloidal particles can be microswarm is reversible by altering the amplitude
self-assembled into desired sizes and shapes (such as carpet,134 ratio.211,212 By applying an xy-plane rotating magnetic field
wire,211 lasso210). Yang et al.210 recently reported on with a few milli-Tesla (mT), microwheels of superparamag-
superparamagnetic PVA-linked colloidal chains by applying a netic beads can be self-assembled (Figure 9B).213 For
one-dimensional DC magnetic field with a strength of around microwheels lying on a surface, magnetic torque generated
20 mT in the vertical direction to a diluted epoxy- by a 2D rotating field can only induce a spinning movement of
functionalized Dynabeads solution. After the formation of the micromachines without net displacement. After inputting a
linear chains, a circularly planar rotating magnetic field was 3D oscillating field by adding a varied component vertical to
operated to transform the chains into a lasso shape. By steering the plane of the rotating field, that is, the microwheels were
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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 216. Copyright 2019 The Royal Society of Chemistry. (B) Fabrication of
biodegradable helical MagRobots using two-photon polymerization. Reproduced with permission from ref 237. 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 215. 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 221. 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 244. 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 222. Copyright 2018 American Chemical Society. (G) Fabrication process of biohybrid
microswimmers based on Spirulina platensis. Reproduced with permission from ref 225. Copyright 2020 American Chemical Society.

reoriented until they tilted to a surface, they began to translate films for magnetic actuation and Ti thin films for
with a velocity of around 100 μm s−1.213 Inspired by the rolling biocompatibility via a sputtering system (Figure 9C).214 The
motion of neutrophiles on the vasculature walls, super- fabricated microrobots can carry and deliver targeted cells to a
paramagnetic beads can accumulate and roll on the surface predetermined location in vitro and in vivo under the control of
of confined boundaries using a combination of magnetic and a field gradient. In vitro experiments conducted in a
acoustic fields.66 microfluidic chip showed that cell-loaded microbots could be
3D laser lithography is among the most popular techniques transferred along the blood vessel-like microchannel to a
used to fabricate small-scale robots with desired architecture. predefined area to release cells (i.e., MC3T3-E1 preosteo-
Burr-like spherical porous MagRobots were prepared by using blasts). These free cells moved toward the tissue chamber
a direct laser writing system followed by depositing Ni thin through migration channels. In vivo experiments conducted on
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nude mice also confirmed that burr-like magnetic microrobots technique from a precursor mixture of GelMA, photoinitiator,
exhibited excellent cell loading, carrying, and release and biofunctionalized superparamagnetic Fe3O4 nanoparticles.
capabilities. In a similar fashion, Jeon et al. used 3D laser Such double-helical architecture allows these micromachines to
lithography and sputtering to fabricate cylindrical, hexahedral, host high therapeutic cargo loading and swimming abilities
helical, and spherical MagRobots.121 The use of a magnetic under a rotating magnetic field.
field gradient induced the pulling motion of cylindrical and Although template-assisted electrochemical deposition
hexahedral MagRobots, while the rotating field caused (TAED) has been widely used to fabricate tubular micro-
corkscrew motion for helical MagRobots and rolling motion motors, this method can also be employed to generate helical
for spherical microrobots.121 architectures.238−240 A representative example was demon-
Spherical microrobots with Janus structure were fabricated strated by fabricating platelet−membrane-cloaked magnetic
by Martin Pumera’s group (Figure 9D).209 The Janus helical nanomotors in Joseph Wang’s group.215 Pd helical
structure, formed by half-covering superparamagnetic polymer microstructures with a length of 3−5 μm were synthesized by
particles with catalytic Pt layer, can self-propel due to the coelectrodepositing a Pd/Cu bilayer on an electrochemical
catalytic decomposition of hydrogen peroxide and can be platform using a polycarbonate template and followed by
steered by an external magnetic field. Polymer particles with a selectively etching the Cu with nitric acid. Afterward, Ni/Au
tosyl group-rich surface provided the chance to bind anticancer thin films were deposited on the surface of the helical
drugs. In addition to drug loading and delivery, the nanostructure via the electron beam evaporation method. To
microrobots could also manipulate cells when they assembled make the gold surface negatively charged, surface modification
into a chain under magnetic guidance. of the magnetic helical microstructures was carried out by
4.2. Helical MagRobots overnight incubation of the microrobots with 3-mercaptopro-
pionic acid. Then, platelet-membrane-derived vesicles were
Helical architectures, inspired by the flagella of bacteria, enable adsorbed, bound, and fused onto the negatively charged gold
micronanomachines to convert rotational motion to a surface by ultrasonic mixing (Figure 10C).
translational corkscrew motion by using a low-strength Helical MagRobots can also be produced by glancing angle
magnetic field in low Reynolds number liquids. Various deposition (GLAD).241−243 In this approach, a seed layer,
micro- and nanofabrication techniques have been used to normally created by spreading a monolayer of silica beads on
prepare helical micro/nanostructures, including template- the substrate, is required to function as the nucleation site.
assisted electrochemical deposition (TAED),215 laser abla- Prior to deposition, the seed layer is fixed at a glancing angle
tion,216 direct laser writing and 3D printing,127,155,217−220 with respect to the input vapor flux of a specific material.
glancing angle deposition,126,221 coiled flow template,222,223 During the deposition process, a helical silica structure grows
biotemplate,224,225 and origami-based self-scrolling techni- starting from an individual seed particle by continuously
que.60,226 rotating the substrate. The pitch and chirality of asymmetric
Laser micromachining allows the creation of arbitrary 3D helical structures are changeable by adjusting the speed and
structures. Piezoelectric soft MagRobots, which can deliver direction of rotation. Finally, a layer of magnetic material is
PC12 cells by employing a rotating magnetic field to induce deposited in the resulting silica helical tail. While this method
neuronal differentiation under the stimulus of acoustic waves, can batch-produce uniform helical nanostructures, this process
were fabricated by Salvador Pané’ s group. 216 Helical is still limited in terms of material selection and shape. To
MagRobots consisting of piezoelectric polymer matrix and make the magnetic section (i.e., Ni) of helical microstructure
CoFe2O4 magnetic component were formed by laser ablation stable in acidic solution, helices were covered with an 8 nm
of composite film coated on the surface of copper wire by dip- Al2O3 thin film by atomic layer deposition. The stabilized
coating method, followed by etching copper wire with acidic helical micropropellers can be further functionalized with
ferric nitrate solution (Figure 10A). Steering of helical urease (Figure 10D).221
parameters such as pitch, pitch angle, and the ratio can be Inspired by origami designs, Huang et al.244 exploited
achieved by altering the laser spot size, laser motion speed, and thermoresponsive gel composites reinforced with magnetic
rotating speed of copper wire. The helix microstructure can nanoparticles to fabricate microswimmers with various 3D
move in a corkscrew manner along its long axis by a rotating architectures by using a one-step photolithography technique
field. and capitalizing on the self-folding of the hydrogel upon
3D/4D printing provides a feasible approach to fabricate soft hydration (Figure 10E). During the gel polymerization process,
micro/nanorobots with predesigned shapes.227−235 Recent a static uniform field was used to align the encapsulated
reviews give a summary of functional soft robots created by magnetic nanoparticles. The folding axis direction of the
3D printing45 and 4D printing236 technique. 3D-printed MagRobots was consistent with the alignment direction of the
enzymatically biodegradable soft helical microswimmers have magnetic particles as the swelling was constrained along the
been designed by Pané and co-workers.237 Two-photon reinforcement direction. The produced microswimmers could
polymerization (a type of 3D printing technique) was adopted change their shapes to adapt to local environmental variations
to print photo-cross-linkable gelatin methacryloyl (GelMA) in mechanical constraints and osmotic pressure.244
helical microswimmer. To decorate GelMA architecture with Hollow helical microstructures can be obtained by first
Fe3O4 nanoparticles for magnetic actuation, GelMA micro- synthesizing magnetic helical microfibers composed of calcium
structures were immersed in a water suspension of PVP-coated alginate hydrogel and Fe3O4 nanoparticles from coiled flow
Fe3O4 nanoparticles (Figure 10B). Another work about templates in glass-capillary microfluidic devices, followed by
hydrogel-based biodegradable helical microswimmers with biosilicification and dicing process (Figure 10F). The
length of 20 μm and diameter of 6 μm was reported by produced microswimmer containing inflexible alginate/prot-
Metin Sitti’s group. 127 3D printing of double-helical amine/silica shell exhibited good mechanical performance for
architecture was realized by two-photon polymerization cargo transport.222 Utilization of bevel-tip capillary and syringe
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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 265. 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 267. Copyright 2019 Elsevier
Ltd. (D) Preparation of liquid metal MagRobots. Reproduced with permission from ref 268. 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 269. 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 158. 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.

pump, heterogeneous core−shell hydrogel microsprings with plished inside the rat stomach by an external rotating magnetic
calcium alginate hydrogel as shell components and functional field with the assistance of imaging.248 Model small molecules,
materials (e.g., magnetic particles, agarose, cell-suspended as well as biomacromolecules, can be loaded into Spirulina
collagen) as core components were produced.245 cells by controlling their dehydration and rehydration.246 The
Because nature provides us with plenty of helical micro- and micromachine loaded with molecular cargo can be magneti-
nanoarchitectures, preliminary attempts to extract the helical cally driven in an intestinal tract phantom, thus providing the
xylem vasculature of plants224 and Spirulina cyanobacterial possibility of targeted molecular delivery for gastrointestinal
green−blue microalgae246−248 as templates to fabricate diseases. By modifying their surface with polydopamine via
biohybrid helical micro- and nanomachines open a new insight dopamine self-polymerization (Figure 10G), Spirulina-based
into strategic designs. The advantage of biohybrid small-scale magnetic helical microswimmers exhibit an enhanced photo-
robots is in the biocompatibility and biodegradability acoustic signal and photothermal effect.225 In addition to the
above-mentioned helical MagRobots, many other helical
characteristics of the biotemplates. Cell-based helical micro-
architectures have been created.144,242,249−255
swimmers can be acquired from multicellular Spirulina via a
single cost-effective dip-coating process in superparamagnetic 4.3. Flexible MagRobots
Fe3O4 solution.248 Because of the intrinsic properties of Flexible or soft small-sized robots refer to a nanoscale and
microalgae, the prepared microswimmers allowed for in vivo microscale robotic system completely or partially comprising
fluorescence imaging without additional fluorescent markers. soft components or architectures that function as carriers,
Moreover, large swarms of microswimmers can be accom- templates, hinges, joints, actuators, sensors, or reser-
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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 165. Copyright 2019 American Chemical Society. (C) Dumbbell-shaped MagRobot
consisting of a Ni NW and two PS microbeads. Reproduced with permission from ref 285. 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 128. 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 286. Copyright
2019 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim.

voirs.256−261 The utilization of flexible microorganisms to realization of other tasks depending on environmental changes
create MagRobots will be discussed in Section 4.5. The (i.e., pH,264,265 temperature). For example, PPF/pNIPAM-
advantages of flexible MagRobots are reflected in the following AAc magnetic microgrippers with pNIPAM-AAc serving as a
aspects: First, as described in Section 2.4, the integration of a thermoresponsive swelling hydrogel segment, polypropylene
soft segment as a hinge261 (see Section 4.4) or as a tail (see fumarate (PPF) as a nonswellable stiff segment, and Fe3O4
Section 3.2), into nano/microrobots can break spatial and nanoparticles for the magnetic actuation were prepared by
temporal symmetries and generate a forward thrust. Second, serial photolithographic method (Figure 11A). The thermor-
flexible MagRobots are capable of transforming their esponsive soft self-folding microgrippers could be directed or
configurations/architectures to execute special tasks under retrieved to the desired location under the magnetic field to
the magnetic actuation, such as grasp and release (similar to execute their tasks (e.g., to load or release therapeutics) in
the function of a hand) of a small-scale object.262,263 Third, response to temperature stimulus at around physiological
flexible and soft small-scale robots are more desirable for temperature without the need of wires, batteries, or other
biomedical applications as these devices are more adaptive in sources.39 Similarly, another thermoresponsive soft microrobot
complex biological scenarios, especially in confined, hard-to- was manufactured and employed for pick-up/release applica-
reach tissues and vessels of the body when compared with tions due to the temperature-sensitive P(OEGMA-DSDMA)
swimmers made from rigid and hard parts. layer.266 Because of the pH-responsive property of 2-
Soft robots can be constructed with stimuli-responsive hydroxyethyl methacrylate (PHEMA), the PHEMA/PEGDA-
polymer materials that enable shape transformations and the Fe3O4 bilayer soft microrobot formed via photolithography
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(Figure 11B) performed the trapping of drug microbeads at although sophisticated designs and complicated fabrication of
about pH 9.58 by full folding motion and the release of drugs porous membranes with different pore geometries or with
by unfolding motion at about pH 2.6.265 variable pore diameter can be realized.280,281 Because of the
Biocompatible magnetic “hairbots,” derived from function- nonconductive nature of these templates, prior to the
alized hair (Figure 11C), can display heightened osteogenic electrodeposition of material, a layer of a conductive thin
differentiation capacities of mesenchymal stem cells under film (usually gold) is deposited on one side of the membranes
magnetic actuation compared with nonmagnetic hairbots. by electron beam evaporation or other physical vapor
Moreover, a magnetic field with repulsion mode endowed deposition methods. The length of the nanostructures (i.e.,
stem cells with higher osteogenic activity compared with the nanorods, nanowires) is adjustable by regulating the electro-
attraction equilibrium or nonequilibrium mode.267 Liquid deposition time. After deposition, metal-based nanowires are
metals (LM) have also been recently used to create shape- released by dissolving the membrane template. Usually, ferro-
morphing flexible microrobots. An ice-assisted transfer printing and ferrimagnetic nanowires and nanorods align with their
method was used to fabricate Fe3O4NPs-incorporated EGaIn long axis parallel with the direction of the applied magnetic
LM micromotors (Figure 11D). Because ice can be easily fields. Two main strategies exist to align cylindrical magnetic
removed, this method provides great convenience for trans- nanostructures perpendicular to their long axis: (a) by placing
ferring LM-based micromotors to arbitrary desired substrates. segments of magnetic material sufficiently separated along a
Irradiation from an alternating magnetic field could cause the nonmagnetic structure (in order to minimize dipolar
dramatic morphological transformation of LM-based micro- interactions) and (b) premagnetizing the nanowires/nanorods
motors in an aqueous environment. Moreover, the resulting along their short axis. The first case can be achieved by
LM-based microswimmer exhibited high propulsion velocity synthesizing multisegmented nanowires/nanorods using
(over 60 μm s−1) under an elliptically polarized magnetic field pulsed plating electrodeposition or sequential deposition by
as compared with its rigid counterparts.268 alternating different electrolytes.282,283 In the second approach,
The utilization of DNA as a flexible component is another a nanowire/nanorod has to be made from hard-magnetic
method to create soft micro/nanorobots is shown in Figure materials so that it can preserve a sufficiently large remanence
11E. Artificial flagella with a length of several micrometers after being premagnetizing in a specific direction. Figure 12A
were generated using a self-assembled DNA bundle.269 After shows the fabrication of electrodeposited hard-magnetic CoPt
attaching the soft DNA flagella to a magnetic microbead via nanowires and the procedure for their premagnetization along
biotin−streptavidin coupling interaction, a hybrid microrobot their short axis.165 Figure 12B shows a comparison between a
was constructed. The fabricated magnetic microrobots can be soft-magnetic CoNi and a hard-magnetic CoPt nanowire and
propelled like peritrichous bacteria under a homogeneous their alignment upon the application of a magnetic field. While
rotating magnetic field. Similarly, Rémi Dreyfus and co- the premagnetized hard-magnetic nanowire aligns with its
workers158 used biotinylated double-stranded DNA as “soft” short axis to the applied field, the soft-magnetic is aligned along
hinges to link red blood cells decorated with streptavidin- its long axis. In a rotational magnetic field, a nanowire/
modified superparamagnetic particles. In this way, another type nanorod that aligns with its long axis with the applied magnetic
of flexible artificial flagella was prepared via the specific biotin− field can only exhibit a tumbling motion.284 However, a
streptavidin interaction. nanowire-like MagRobot that is premagnetized along its short
Origami as a self-folding process provides a top−down axis can display a richer variety of motion mechanisms such as
approach to fabricate soft robots with transformable tumbling, rolling, precession, or wobbling locomotion as a
morphologies. A complete origami robotic system normally function of the magnetic field frequency. Another strategy to
comprises power, sensing, actuation, and computation possess multiple motion modes is to integrate premagnetized
subcomponents.270−273 Readers are suggested to read the nanowires into nonmagnetic structures. For instance, a single
review article written by Daniela Rus and Michael T. Tolley to Ni nanowire only shows a sole tumbling motion.284 After
obtain more information about the design, fabrication, and assembling two polystyrene beads into a Ni nanowire to
control of origami robots.274 Self-folding origami MagRobots construct a dumbbell-like MagRobot, the fabricated micro-
with various body designs (i.e., tubular body and helical tail, structure possesses three motion modes (i.e., rolling, wobbling,
tubular body and spiral tail, helical body and planar tail, etc.) and tumbling) (Figure 12C).285
were created by Nelson’s group.60,63 The micro-origami When adding flexible segments such as hinges or tails to
swimmers were endowed with reconfigurable morphologies, nanowires, the assembled MagRobots display traveling-wave
controllable mobility, and even programmable magnetic motion under the steering of an oscillating magnetic field. A
anisotropy by embedding magnetic nanoparticles into self- multiple section microstructure of Au−Ag−Ni−Ag−Ni−Ag−
folding hydrogel bilayers (i.e., one supporting layer and one Au, using three elastic Ag nanowires as hinges and fabricated
thermally responsive layer). Because of the programmable by sequential electrochemical deposition, can mimic the
shape-morphing feature of the origami-based microrobots, an swimming of a fish with a speed as high as 30 μm s−1 (Figure
artificial microsized “bird” was created to mimic the different 12D).128 In a similar fashion, the two arms of a Ni−Ag−Au−
flying modes of a real bird, including “flapping,” “hovering”, Ag−Ni MagRobot are capable of executing an out-of-phase
“turning”, and “side-slipping” (Figure 11F).64 wobbling motion by a planar 2D oscillating field and propel the
movement of the body with a velocity of around 30 μm s−1
4.4. Wire-like MagRobots (Figure 12E).3 A Ni-hinge-Ni-hinge-Ppy nanorobot involving a
Most rod-like MagRobots are fabricated by template-assisted flexible polypyrrole (Ppy) tail has the ability to break the
electrochemical deposition (TAED).275−279 In general, anodic reciprocal motion at the temporal dimension, exhibiting an S-
aluminum oxide (AAO) or polycarbonate porous membranes like motion mode by making use of its eukaryote-like tail with
are employed as templates. These membranes are commer- the assistance of an oscillating field, leading to maximum
cially available and are usually composed of cylindrical pores, propulsion speed of 0.93 body-lengths s−1 (Figure 12F).97
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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 288. Copyright 2019 The Royal Society of Chemistry. (B) Reproduced with
permission from ref 295. Copyright 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of
Science. (C) Reproduced with permission from ref 292. Copyright 2019 American Chemical Society. (D) Reproduced with permission from ref
294. Copyright 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. (E) Reproduced
with permission from ref 296. Copyright 2015 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim. (F) Reproduced with permission from ref
215. 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 305. Copyright 2018 The Authors, some rights reserved; exclusive licensee
American Association for the Advancement of Science. (I) Reproduced with permission from ref 293. 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 304. Copyright 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of
Science.

Inspired by the electric field, a knifefish, which can produce synthetic nanostructures/nanoparticles with natural nonmobile
electricity through its electrocytes, was developed as a cells (e.g., pollen, spores) or motile cells (e.g., bacteria, sperm),
multifunctional Ni-Ppy-PVDF MagRobot containing a soft are currently of great interest.135,287 Four methods are
polyvinylidene fluoride (PVDF) tail. Taking advantage of the commonly used to produce biohybrid micro/nanorobots.
intrinsic piezoelectric performance of the PVDF tail, the The first method consists of directly using nonmotile cells as
surface of the fabricated MagRobots exhibits an enhanced templates and then integrating magnetic nanomaterials and
release of cargo owing to the electrostatic repulsion generated other functional building blocks such as inorganic nanostruc-
by the magnetically induced piezoelectric effect. By changing tures or molecules. Capitalizing on this approach, several
the magnitude and rotational frequencies of the applied pollen-based,288−290 spore-based,291 microalgae-based,292,293
rotating magnetic field, three different locomotion modes (i.e., sperm-based294 magnetic micromotors have been fabricated.
tumbling, wobbling, and corkscrew-like motion) with different In general, pollen and spores have the merits of excellent
translation speeds and drug release behaviors were observed biocompatibility characteristics and structural uniformity.
(Figure 12G). Interestingly, the application of an on−off Some even have unique architecture (e.g., hollow cavity),
magnetic field can actuate the release of drugs in a pulsatile which can facilitate specific applications. For instance,
approach.286 researchers have loaded drugs into two hollow air sacs of
pine pollen grains via vacuum loading technique (Figure 13A).
4.5. Biohybrid MagRobots The experiments demonstrated that pollen-based biohybrid
Because of their excellent biocompatibility and extremely low MagRobots not only exhibit efficient drug-encapsulation ability
toxicity, biohybrid mineralized motors, which often integrate but also can release them on demand.288 By altering the
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vectors of programmatically controllable magnetic fields, and helix247) have been prepared to capture the task-carrying
individual pollen-based micromotors with encapsulated mag- spermatozoa to form sperm-hybrid microrobots (known as
netic Fe3O4 inside present three distinct modes of locomotion “spermbots”). Sperm cells with high vitality serve as a motile
(i.e., rolling, tumbling, and spinning) and these individuals component of hybrid microrobots to complete specific tasks,
were able to form a dynamic collective phenomenon under the for example, targeted drug delivery,31 as shown in Figure 13J.
steering of an external magnetic field.288 Spore-based micro- However, they can also act as carriers when they have motility
robots composed of G. lucidum spores, Fe3O4 nanoparticles, deficiencies. In such cases, the remotely controlled assisted
and functionalized carbon nanodots have been synthesized via fertilization relies on the synthetic magnetic microstructures of
rapid, direct, and low-cost methods (Figure 13B). The spermbots under the guidance of external magnetic fields.302
prepared spore@Fe3O4@CDs microrobots can detect bacterial The fourth approach consists of adopting a live immune cell
toxins.295 As mentioned above, Spirulina, with the innate spiral to engulf the whole magnetic passive functional materials by
morphology, has been utilized as a biological template to create taking advantage of the phagocytosis processes of immune
helical microswimmers248,292 (Figure 13C). Sperm-based soft cells.303 As a consequence, biohybrid “immunobots”,304 as
MagRobots were fabricated by decorating Fe2O3 nanoparticles termed by Metin Sitti’s group, can be formed. After a magnetic
on the surface of immobile sperm cells via the electrostatic self- double-helical microswimmer was completely internalized by a
assembly (Figure 13D). The highest swimming speed of macrophage, the biohybrid macrophage-based MagRobots
sperm-templated micromotors can reach 6.8 ± 4.1 μm s−1 (0.2 were able to perform magnetically driven rolling locomotion
body length/s).294 along predetermined trajectories by steering the magnetic
The second method of preparing biohybrid micromotors is helical component. The robots were able to swim unin-
to cloak functionalized synthetic nanomaterials with cell terruptedly even with the presence of cells blocking their
membranes. This method can enhance the biocompatibility pathway. In the absence of a magnetic field, the immunobots
of micromotors to the largest extent and avoids recognition by could autonomously move by crawling and actuated by the
the immune system. Recently, cell membranes/vesicles from self-propelled movement of the macrophages in a biological
red blood cells (RBCs)296 (Figure 13E), platelets215 (Figure environment (Figure 13K).304
13F), and even dual cells (e.g., RBCs and platelets297) were
utilized as camouflage to cover the surface of functionalized 5. APPLICATIONS
synthetic nanomaterials. The magnetic nanoparticles embed-
ded into these biohybrid nanomachines play a role in magnetic 5.1. Targeted Drug/Gene Delivery
guidance. The locomotion of these cell-based biohybrids can The precise and efficient transportation of therapeutic payloads
be powered by a magnetic field or other driving forces. For to target sites, especially to those confined and hard-to-reach
example, the random movement pattern of a Janus RBC-Mg locations of the body, is challenging for passive drug delivery
motor can be driven by hydrogen bubbles generated by the systems. The past decade has witnessed a boom in the
reaction of Mg and water. The addition of Fe3O4 nanoparticles development of active smart drug delivery systems using
to the Janus micromotors can make the miniaturized machines external field-driven miniaturized micro- and nanomotors.
move precisely along a predetermined path.296 Particularly, magnetically driven micro and nanorobots offer
The third method to fabricate hybrid small-scale swimmers several advantages as small agents for targeted cargo delivery
consists of combining active locomotive cells that are born including but not limited to remote, precise, and minimally
with flagella, among which sperm and bacteria are widely invasive maneuverability, and potential recyclability of residual
used.31,68,298−301 In this method, the motile cell either adheres administered drug-carriers, which often results in serious side
to the surface of a synthetic particle (normally in the effects to healthy organs and tissues.306−309 In most cases, very
micrometer scale) or another cell or be trapped into a special low field strength (in the mT range) is sufficient for the
microstructure. For example, bacteria-driven microswimmers actuation of MagRobots without causing damage to healthy
were fabricated by attaching a single E. coli. bacterium to a cells.
drug-loaded polyelectrolyte microparticle via viscoelastic Before the steerable delivery of cargos (e.g., molecules,
connection of the bacteria−particle interface (Figure 13G). drugs, genes), the cargo loading or capture process is needed.
The E. coli-powered motor exhibited the chemotaxis behavior The loading of cargos is often conducted by encapsulating
under a chemical concentration gradient. Fe3O4 nanoparticles them inside the MagRobot structure or by attaching them to
embedded within the polyelectrolyte microparticles functioned the MagRobot surface. The encapsulation process can be
as a steering wheel, thus providing the biohybrid motors with directly carried out during MagRobot fabrication while the
directional control over the directionality and enabling surface attachment (or adhesion) process can be made using
guidance of the drug-loaded swimmers to target breast cancer superficial functional groups of biohybrid or synthetic
cells in vitro.68 Similarly, the magnetic guidance was also MagRobots. Various organic or inorganic artificial nanoma-
employed in bacterium-RBC micromotors, which were terials (e.g., Au/Ni/Si nanospears,310 hydrogel-based helical
fabricated through the strong conjugation chemistry between microswimmers,127 Janus Au/Ni/SiO2 microparticles,311 etc.)
the erythrocyte and E. coli bacterium (Figure 13H). In and biogenic materials (such as pollen grains,288 sperm cells,176
addition, negatively charged microalgae with ellipsoidal bacteria,35,305,312 erythrocytes,313 and microalgae246,293) have
morphologies (i.e., Chlamydomonas reinhardtii algal) were been developed as functional or structural carriers to
integrated with positively charged polyelectrolyte-function- encapsulate or carry molecules, drugs, genes, or cells. For
alized magnetic microsphere via electrostatic interactions example, Fe-coated biotubes, which exhibit a drill-like motion
(Figure 13I). The motile microalgae function as an actuator under high-angular frequency magnetic fields, were capable of
while the microparticle can be used for cargo encapsulation transporting camptothecin (i.e., an anticancer model drug) and
and magnetic steering.293 In addition, various customized delivering it to specific sites, killing the targeted HeLa cells in
magnetic microstructures (such as tetrapod,31 microtube,298 vitro (Figure 14A).314
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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 314. 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 311. 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
176. 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 218. 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 127. Copyright 2019
American Chemical Society.

Considering the complexity of the human body’s environ- circulatory system such as thrombotic clots. In addition to
ments, it is key to investigate the propulsion mechanisms of drugs, targeted transport of genes (e.g., plasmid DNA) to a
MagRobots and strategies for cargo delivery and release under single cell and subsequent transfection was achieved by the
complicated physiological conditions in different body fluids utilization of helical micromotors under the actuation and
such as gastric juice, saliva, and blood. Recently, a cell-sized navigation of low-strength rotating magnetic fields (Figure
Janus micromotor loaded with antibodies as receptors for the 14D).218 Recently, Peer Fischer’s group reported targeted
recognition of target cells and anticancer drugs was able to transfection and gene delivery by using biocompatible FePt
navigate in a simulated blood circulation system (Figure nanopropellers under rotating millitesla fields.315
14B).311 Although the propulsion of MagRobots was After delivering payloads to a specific location, cargo
weakened under dynamic flow conditions, the ability of active molecules can be released naturally via diffusion or via specific
upstream locomotion in the bloodstream was confirmed in flat stimuli (such as pH,265 temperature,266 light irradiation,67 or
and 3D surfaces. Furthermore, the utilization of biohybrid chemical changes at the disease site) according to the practical
micromotors combining sperm cells and synthetic magnetic application requirement. For example, because the concen-
micro and nanoarchitectures to deliver anticoagulant agents tration of matrix metalloproteinase-2 (MMP-2) enzyme at the
(i.e., heparin) in the bloodstream was reported (Figure tumor site is higher than that at normal physiological
14C),176 which is promising for treating diseases of the conditions, hydrogel-based helical microswimmers demon-
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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 209. 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 169. 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 247. Copyright 2015 American Chemical Society. (D) Magnetically powered microspirals for
the delivery of murine zygote. Reproduced with permission from ref 320. Copyright 2020 The Authors. (E) Magnetically actuated transport of
neural progenitor cell and ultrasound-induced neuronal differentiation. Reproduced with permission from ref 216. Copyright 2019 The Royal
Society of Chemistry. (F) MagRobots as motile 3D scaffolds for stem cell delivery. Reproduced with permission from ref 121. Copyright 2019 The
Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.

strate a quicker response to the evaluated concentration of massively parallel single-cell manipulation.316 Magnetically
MMP-2 enzyme, resulting in a boost-release of embedded powered miniaturized robots are capable of 3D manipulation
cargo (i.e., antibody-tagged Fe3O4 nanoparticles) through the of a single cell in terms of capture, transport, sorting, isolation,
swell behavior of the hydrogel.127 The released antibody- and pattering, with excellent maneuverability and high
tagged payloads from the micromotors can be further used for precision at the nano- and microscale in complex physiological
active labeling of targeted tumor cells (Figure 14E). environments without changing the intrinsic properties of the
5.2. Cell Manipulation cells.317,318 For instance, trapping of breast cancer cells was
Cell manipulation is the practice of maneuvering the physical reported by tosyl-functionalized superparamagnetic microbe-
position of cells to separate them from the milieu of other ads due to the instantaneous strong binding between the tosyl
phenotypically different cells (i.e., cell-based screen), guiding groups from the surface of microswimmers and the −NH2
them into a specific target position (e.g., for fertilization), or groups from the membrane proteins of cancer cells.
organizing themselves in vitro. With the rapid advance of Manipulation of single or multiple cell-laden microrobots
proteomics and genomics, it is of great significance to develop was achieved by the propulsion of oxygen bubbles and manual
sophisticated tools for single-cell manipulation, especially direction guidance using a neodymium magnet (Figure
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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 324. 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 172. Copyright 2020 American
Chemical Society. (D) Magnetic manipulation of Si/Ni/Au nanospears for targeted intracellular transfection. Reproduced with permission from ref
310. 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 221. 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 126. Copyright 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.

15A).209 Arranging cells to achieve predetermined patterns of neural progenitor cells was conducted by the corkscrew-like
with the assistance of an arrayed substrate was implemented motion of magnetically powered soft microswimmers contain-
through single-cell pick-up and subsequent delivery using ing piezoelectric polymer and CoFe2O4 magnetic nanoparticles
magnetically propelled peanut-like micromotors (Figure under a rotating magnetic field. Subsequent neuronal differ-
15B).169 To aid sperm cells with defective locomotion features entiation of PC12 cells was induced by the acoustic stimulation
to complete their fertilization task, Oliver G. Schmidt’s group due to the utilization of piezoelectric polymer as a stimuli-
designed several motile nano/micromotors as assisted tools302
responsive cell electrostimulation platform (Figure 15E).216
such as magnetic microcarriers with a cylindrical cavity and a
Furthermore, Kim et al.321 precisely manipulated a neuron-
helical body319 and a magnetic helix247 (Figure 15C).
Moreover, magnetically driven micromotors provide an loaded magnetic microrobot to a gap between two neural
invasive way to transfer zygotes through the uterus and clusters to connect broken neural networks. Recently,
fallopian tube (Figure 15D), and magnetic microrobots with successful trials of magnetically powering microrobots toward
spiral shapes exhibit higher maneuverability in terms of capture a target site (such as a liver tumor micro-organ, ventricle of
and transfer of the zygotes between different physiological mouse brain, blood vessel of rat brain, and live mouse) using in
environments than those with helical shapes.320 Transportation vitro, ex vivo, and in vivo experimental models, indicate the
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Figure 17. MagRobots for biopsy. (A) Schematic of a thermoresponsive gripper autonomously picking up and placing a target. Reproduced with
permission from ref 344. 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
341. 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 347. Copyright 2013 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim.

feasibility of adopting MagRobots for the purpose of targeted mode.41 Other representative microdrillers are Fe-coated
stem cell transport and transplantation (Figure 15F).121 calcified biotubes containing pointed ends, which are extracted
5.3. Minimally Invasive Surgery from Dracaenea marginata leafs. Upon magnetic actuation, the
microdagger stabbed into the cellular membranes of HeLa cells
Miniaturized machines that are capable of precisely opening with a drill-like motion, finally resulting in cell death. In
specific cell membranes to kill abnormal cells and even achieve addition, the ability to drill into a target cell can be utilized for
intracellular delivery of various drugs (including DNA) are subsequent drug delivery because the porous structures of
promising candidates for noninvasive surgery.322,323 Nano/ calcified biotubes endow the microdriller with the capacity of
microrobots that project sharp tips or have the ability to drug loading.314
perform a corkscrew-like movement can execute drilling under A millimeter-sized magnetic driller can be navigated in a 3D
the application of a rotating magnetic field. The drilling feature vascular channel and perforate a blood clot in a simulated
can be harnessed to penetrate tissue with high precision, thrombosis model environment, providing an application
holding great promise to perform untethered microsurgeries. potential for cardiovascular disorders (Figure 16B).324 Besides,
As shown in Figure 16A, microdrillers (tubular Ti/Cr/Fe surface walkers also can open the cell membrane. Recently, we
microdrillers with sharp tips) were able to penetrate into a developed Au/Ag/Ni microwires that display walking move-
section of porcine liver tissue via magnetically driven ment under a transversal rotating magnetic field. Because of
mechanical drilling. To make the microdriller “stand up” to the rigidness of the microwires, they can only perform a
drill, a specific angular frequency threshold of the rotating field drilling movement. To make the structure of microwires
(in correlation with the viscosity of media) is required to slightly bent, an Ag segment was partly etched by concentrated
transform the horizontal rotation mode into a vertical rotation H2O2 solution. As a consequence, a surface tumbling motion
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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 350. 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 351. 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 352. Copyright 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of
Science.

can be achieved. The surface walkers, functioning as micro- Newtonian fluid. Physicochemical and histological barriers
scalpels, can penetrate cancer cells, capture a piece of the (e.g., cell membrane,322 blood−brain barrier,336 intestinal
cytosol, and exit the cells while leaving the cytoplasmic mucosal barrier), interactions with boundaries, crowded
membrane intact, thus demonstrating excellent minimally biological environments, complex rheology (e.g., viscoelastic-
invasive microsurgery capabilities172 (Figure 16C). Au/Ni/Si ity, shear-thinning), and other factors impact the locomotion
nanospears functionalized with plasmid were able to penetrate behaviors and application performance of micro/nanorobots in
U87 glioblastoma cells by means of rotating magnets, and biological environments.337−340 Attempts have been made to
deliver the gene (i.e., eGFP expression-plasmid) within the exploit the actuation of MagRobots in complex biofluids. For
cells over large areas (Figure 16D). Such intracellular cargo example, to overcome the mucus barrier, Peer Fischer’s
delivery in a high-throughput manner paves the way for group221 developed a helical microdriller surface-functionalized
translation to new clinical cellular therapies.97,310 with urease as shown in Figure 16E. Such microdrillers can
Realistic biological environments are substantially complex. penetrate the viscoelastic mucin gel in an acidic environment
The microscopic propulsion of micro/nanorobots in biofluid in the presence of urea and swim freely inside under a rotating
environments (e.g., bloodstream, 24,250,325−327 saliva, 328 magnetic field. This idea is inspired by Helicobacter pylori
semen,329 mucus,221 vitreous humor,126,330−332 brain vascula- bacteria, which are capable of decreasing the viscosity of mucin
ture,333 cerebrospinal fluid in the spine or brain, urinary fluid, gel via a gel−sol transition caused by the release of ammonia
gastrointestinal fluid,334,335 etc.) is different from that in through an enzyme-catalyzed procedure that raises the local
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pH. To move further toward clinical application, the same 5.5. Biofilm Disruption/Eradication
group created magnetic helical micropropellers that were able Different from planktonic (free-swimming) bacterial cells, the
to penetrate the biopolymeric network of porcine vitreous interaction of cell masses (i.e., community of microorganisms)
humor and swim inside over a centimeter distance under produces a matrix called “extracellular polymeric substances”
navigation by a rotating magnetic field and using clinical (EPS).348 The embedded cells and the viscoelastic matrix that
optical coherence tomography as shown in Figure 16F.126 The constitute the biofilm on the surface of a subject are
smooth propulsion of the micropropellers in the dense notoriously difficult to eliminate.349 The nature of bacterial
biopolymeric network lies in the slippery liquid layer on the biofilms’ resistance to antimicrobial agents makes them a
surface of micropropeller, which minimizes the adhesion force source of some recalcitrant infections. Magnetically powered
to the surrounding environment. More mechanisms, actuation nano/microrobots manifest themselves in the competence to
approaches, and applications of micro/nanorobots in complex penetrate into the matrix and disrupt the biofilm formation or
biofluids that resemble real-world scenarios are required to be eradicate already-formed biofilm due to their small size as well
explored. as high magnetically driven mechanical force. A biohybrid
5.4. Biopsy microrobot based on nonpathogenic magnetotactic bacteria
has been used to penetrate into the island of Escherichia coli by
MagRobots have been proved to be wireless biopsy tools to the external actuation of magnetic field350 as shown in Figure
capture a single cell or collect tissue samples from healthy or 18A. Although this invasion can temporarily cause the elastic
diseased organs, including breast, lung, liver, skin, prostate, and formation of the biofilm, the microrobot was almost trapped in
so forth, with high specificity and selectivity for further disease it, presenting restrained movement ability. How to make nano/
diagnosis. These functional magnetic miniaturized robots, microrobots swim in a viscous media is a common challenge. A
normally in the microscale, are called microgrippers. To have magnetic microrobot made from tea buds, called “T-Budbots”,
the ability to pick up an object and lay it down, analogous to was able to precisely fragment and remove bacteria biofilm.351
the function of human hands, most of the magnetically driven As demonstrated in Figure 18B, T-Budbots left a clear trail on
microgrippers40,341−343 explored to date are flexible (see the surface of P. aeruginosa biofilm after their movements,
Section 4.3). Thermoresponsive flexible MagRobots have indicating that the biofilm had been effectively swept away.
been widely used as grippers due to their temperature-induced Moreover, antibiotic encapsulated in T-Budbots of the biofilm
opening and closing capacities39,344−346 (Figure 17A). For exhibited a pH-triggered release behavior around the acidic
instance, a thermoresponsive magnetic microrobot, having a microenvironment of the biofilm. Once the biofilm was
tip-to-tip size of 70 μm in its open state and 15 μm in its disrupted, the dislodged bacterial cells were exposed to the
folding state, was able to conduct single-cell biopsy (Figure drugs and finally killed. One of the most outstanding
17B). The thermally responsive layer of the microgripper is advantages of using MagRobots to execute the task of biofilm
made from paraffin wax, whose phase-transition temperature is elimination lies in their function to be directed to a confined
in close proximity to biological temperatures, including and hard-to-access position. A recent study demonstrated that
humans. After being navigated to the position of a fibroblast magneto-catalytic iron oxide nanorobots (called “CARs”) are
cluster, the untethered microgripper grasped one cell or a few capable of the degradation and removal of biofilms in the
cells when it transformed from open to closed state with the isthmus of human teeth due to the catalytically induced
increase of field temperature. Cell separation from the cluster generation of reactive antibiofilm molecules and the external
and retrieval of the microrobot can be easily fulfilled by shear forces from magnetic actuation (Figure 18C).352
adjusting the direction of magnetic field. Metin Sitti’s group342 5.6. Imaging-Guided Delivery/Therapy/Surgery
utilized hundreds of thermosensitive microgrippers that had
To translate medical micro/nanorobots from the bench to the
been pre-encapsulated in the chamber of a centimeter-scaled
bedside, imaging technologies are of vital importance to
magnetically actuated capsule endoscope (MASCE), to grab
achieve real-time tracking of the MagRobots in vivo.201,353−360
stochastically tissue inside the stomach ex vivo for further Clinically established imaging modalities, including but not
analysis. Retrieval of distributed magnetic microgrippers was limited to optical imaging, magnetic resonance imaging
conducted by strong wet-adhesive force from the retrieval unit (MRI),53,197,325,361−363 magnetic particle imaging (MPI),184
of MASCE. This multiscale robotic system provides a novel fluorescence imaging, 364−366 ultrasound (US) imag-
multiagent collaboration strategy not only for gastrointestinal ing,89,124,367−370 photoacoustic (PA) imaging,225,371 X-ray
capsule biopsy but also for other biopsy tasks in complex computed tomography (CT), photoacoustic computed
physiological structures and environments. An in vivo tissue tomography (PACT),83 optical coherence tomography
excision of the porcine biliary tree was conducted using (OCT),126,372 single-photoemission computed tomography
thermal-induced self-folding microgrippers as shown in Figure (SPECT),373 positron emission tomography (PET),374 and
17C. More than 1000 microgrippers were delivered to the their combined imaging techniques (e.g., MR/CT,375 PET/
position of interest (i.e., the biliary orifice) through a standard CT,376 PET/MRI377) can be integrated into miniaturized
catheter with the assistance of the endoscopic camera. The robotics systems. Although many challenges remain, many
thermosensitive magnetic microrobots, initially in the open researchers have attempted to use these imaging techniques as
state, spontaneously transformed into closed state in order to powerful tools to assist the tracking of MagRobots for site-
excise tissue samples when they are exposed to body specific drug delivery, targeted therapy, and precision surgery.
temperature (37 °C) for 10 min. Retrieval was carried out Because of limited penetration depth of biological tissues,
by using a catheter containing a magnetic tip. Subsequent PCR optical imaging is not suitable for the visualization of
(polymerase chain reaction) results indicated that the excised MagRobots across tissues in vivo. For magnetically driven
tissue piece was sufficient for genetic or epigenetic diagnosis in micro/nanorobots, MRI is an efficient tool to track the
terms of quantity and quality. position of MagRobots both in vitro and in vivo.356 Both MRI
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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 248. 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 184. 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 248. 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 124. 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 392. Copyright 2019 American Chemical Society. (F) SPECT images of radiolabeled
microrobots in Eppendorf tube and in mice. Reproduced with permission from ref 373. Copyright 2019 WILEY-VCH Verlag GmbH and Co.
KGaA, Weinheim.

and MPI are magnetic-based imaging techniques. MRI has microrobot inside the subcutaneous tissues of a rodent
been widely used in clinical practice, especially for three- stomach was reported by Zhang’s group.248 Felfoul and co-
dimensional anatomical images of soft tissues. The main workers378 reported real-time positioning and tracking of a
advantages of MRI lie in high soft-tissue contrast, high spatial microrobots magnetically propelled by MRI gradients in the
resolution, and no consumption of dedicated contrast or carotid artery of a pig in a closed-loop control scheme.
imaging agents. Most importantly, strong magnetic fields and MPI, first proposed by Bernhard Gleich and Jü rgen
field gradients generated by MRI scanners provide suitable Weizenecker,379 is a three-dimensional tomographic imaging
actuation environments for the navigation of MagRobots, while method. The MPI scanner comprises two permanent magnets
MagRobots with integrated magnetic compositions or in a Maxwell configuration. Larger field gradients in the MPI
components can augment the signal and boost image quality. scanner workspace provide a strong propulsion force to drive
As one representative example shown in Figure 19A, in vivo magnetic objects.380−382 However, in terms of the spatial
MRI tracking of a swarm of microalgae-based helical resolution of MPI (a few millimeters) in the current platform,
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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 400. Copyright 2019 American Chemical Society. (B) Pollen-based
microsubmarines for the removal of microplastics (i.e., PS spheres). Reproduced with permission from ref 401. 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 291. Copyright 2018 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim. (D) Pd/Ni/Ag
nanocoils for removing microbial pathogens. Reproduced with permission from ref 402. 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
403. Copyright 2020 American Chemical Society. (F) Lotus pollen-templated magnetic micromotors for temperature-sensitive adsorption of
erythromycin. Reproduced with permission from ref 289. Copyright 2019 Elsevier B.V.

this technique is only applied to the visualization of swarming Fluorescence imaging, with the advantages of excellent
micro/nanorobots, not an individual one. Tay and co- planar resolution (≈ 100 nm) and high sensitivity, has become
workers184 reported quantitative guidance of MPI imaging, another widely used medical imaging modality. Under the
precise localization of magnetic hyperthermia, induced by the guidance of fluorescence imaging, the utilization of spore-based
interaction between MPI gradient and superparamagnetic magnetic microrobots functionalized with carbon quantum
magnetic nanoparticles, to arbitrarily selected tumor sites. dots for effective targeted delivery was demonstrated by
When the field-free region (FFR) of the MPI gradient was Zhang’s group.383 They designed an automated control system
centered to the targeted tumor area, localized heat only killed that can help microrobots avoid obstacles and find the optimal
the cancerous tissues while minimizing the collateral heat path based on a particle swarm optimization algorithm with the
damage to nearby healthy tissues (Figure 19B). assistance of vision feedback.383,384 However, fluorescent
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probes (e.g., organic dyes,385 quantum dots,386 metal−organic nanoscale and microscale using current biomedical imaging
frameworks,387,388 etc.), which usually have poor biocompat- techniques is still a big challenge.
ibility and biodegradability, are required to label the micro/ 5.7. Pollution Removal for Environmental Remediation
nanorobotic materials or cells. Because of the intrinsic
fluorescence feature, excellent biocompatibility, and biode- In addition to the biofriendliness, recoverability of magnetically
driven micro- and nanorobots, and the toxin-free nature of
gradable performance of Spirulina microalgae, microalgae-
magnetic manipulation, MagRobots can also actively swim
based magnetic microrobots allow for in vivo fluorescent
around waterborne pollutants (e.g., dyes, oil, heavy metals,291
imaging without the use of probes and concern for biosafety
microplastics, microbial pathogens, estrogenic,397,398 etc.) and
(Figure 19C).248
remove them by capture (adsorption/absorption) or degrada-
Ultrasound imaging, as a conventional clinical imaging
tion. As such, small-scale MagRobots constitute a technology
technique, mainly has two different modalities, namely, B- with great potential for water remediation. In the future,
mode and Doppler.389,390 The former is based on pulse−echo sophisticated magnetic manipulation systems could be used to
technique while the latter relies on the Doppler effect. The externally guide MagRobots to pollution sites (i.e., canal-
main advantages of US imaging lie in high spatial and temporal izations, industrial reactors, tanks, pools) in a contactless
resolution, large penetration depth, minimal damage to tissues, fashion. Additionally, magnetic fields can be used to accelerate
and relatively lower setup cost. A magnetically driven reaction kinetics or recognition efficiency due to the robust
microrobot swarm was visualized and tracked in a bovine dynamic intermixing (i.e., magnetic stirring function) and to
eyeball via US imaging124 as shown in Figure 19D. Sitti’s group retrieve the nano/microrobots once the cleaning procedure has
used the color Doppler mode of US imaging to track the been finalized.399 Eventually, the cleaning agents can be reused
“hairbots” in ex vivo chicken breast.267 Recently, Zhang’s group or recycled if their constituent components have remained
adopted US Doppler for real-time guidance of a swarm of unaltered. The treatment of six representative pollutants using
magnetic microrobots for endovascular delivery.369 miniaturized magnetic motors is summarized in Figure 20.
Photoacoustic imaging, first proposed by Alexander Graham The autonomous movement of a walnut-like microrobot
Bell391 in 1881, is a “light-in, sound-out” approach. A light composed of polycaprolactone, Fe3O4 nanoparticles, and
source (i.e., IR laser) and US transducer are two fundamental catalase in H2O2-included solution is ascribed to the oxygen
elements for a PA imaging setup. Utilization of PA imaging to bubbles from the enzyme-catalytic degradation of H2O2,
track microalgae-based magnetic microswimmers for killing exhibiting a spiral trajectory.400 The direction of the micro-
pathogenic bacterial was reported.225 A more advanced PA swimmers could be controlled using external magnetic fields.
imaging technique, multispectral optoacoustic tomography, Because of the hydrophobic nature, the motile walnut-like
was adopted for real-time monitoring of the migration of single micromotor was capable of collecting spilled oil (Figure 20A).
magnetically driven conical micromotors with the length of Because of the incorporation of Fe3O4 component, the
100 μm in phantom as well as ex vivo chicken tissue392 as show recycling of the micromotor was realized by using a magnetic
in Figure 19E. field.400 A magnetic hollow microsubmarine, using natural
X-ray-CT, PET, and SPECT belong to the category of sunflower pollen grains as a template, was reported to remove
ionizing radiation-based techniques that employ high-fre- leaked oil and microplastics pollutants simultaneously (Figure
quency radiation with wavelength ranging 10−100 nm. As a 20B).401 High removal efficiency of heavy metal ions was
consequence, these techniques endow high penetration depth found in porous biohybrid microrobots consisting of fungi
and spatial resolution, but the harm radiation does to living spore and Fe3O4 nanoparticles. The collective behaviors of the
(human) tissues must be taken into consideration. In microrobots and magnetically steered agitation could further
comparison with the widely used X-ray CT technique used enhance the pollutant adsorption ability compared with static
in clinics, PET and SPECT techniques based on γ-rays have microrobots (Figure 20C).291 The excellent antibacterial
been developed in the last decades. Although the two state-of- ability of Pd/Ni/Ag nanocoils and high magnetic maneuver-
the-art imaging techniques exhibit excellent spatial resolution ability at low magnetic strength (8 mT; 10 Hz) allows for
and molecular selectivity, the utilization of PET and SPECT precise locomotion of nanorobots toward the target location of
(usually in conjunction with CT imaging) for the localization bacterial infection to efficiently fight against the drug-resistant
and tracking of MagRobots is still in its infancy. For both bacteria (Figure 20D).402 The dual actuation of micromotors
techniques, interested materials or micro/nanorobots are often prepared from carbon soot by using a magnetic field and
conjugated with radiotracers (such as 64Cu, 124I, 18F, 68Ga, oxygen microbubbles facilitated efficient on-the-fly degradation
99m
Tc, etc.).373,377,393−396 SPECT imaging for individual of MB dye pollution403 (Figure 20E). In addition, the use of
microrobots with diameter as low as 100 μm was reported functional magnetic micromotors for the absorption or
by Nelson’s group373 as shown in Figure 19F. To track the removal of antibiotics, such as erythromycin (Figure 20F)289
shape transition (e.g., from tubular to planar configuration) of and doxycycline404 in contaminated water, has also been
investigated.
microrobots, they used 99mTc [Tc]-based radioactive com-
pounds to label the magnetically driven thermoresponsive 5.8. Sensing and Biosensing
hydrogel-based microrobots. More research is expected to According to sensing mechanisms, there are three main
explore the combination between biomedical imaging purposes of using magnetically driven micro/nanomotors for
techniques and locomotive micro/nanorobots, and aimed at sensing and biosensing. First, because the motion behaviors
targeting individual MagRobots or a swarm of MagRobots to a (e.g., velocity, wobbling angle) of MagRobots is related to an
specific location with high temporal and spatial precision, and applied external magnetic field as well as properties (e.g.,
executing certain diagnostic or therapeutic tasks in an invasive temperature, pH, viscosity, ionic strength) of the solution, the
and visualizable fashion. Because of the restriction of small size, detection of these movement parameters of MagRobots
clear observation of a single miniaturized robotic in the provides a novel approach to probing the local microenviron-
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Figure 21. (A) Helical nanorobots as mobile viscometers. Reproduced with permission from ref 157. 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 407. 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 408. Copyright 2020 American Chemical Society.

ment in a heterogeneous medium.405 For instance, a helical detect C. dif f toxins with much more obvious fluorenes
nanomotor was developed as a mobile viscometer capable of quenching in a noninvasive way through the targeting
monitoring in real-time the surrounding viscosity in homoge- combination of C. dif f toxins and CDs (carbon quantum
neous or heterogeneous media. A mathematical model was dots) in comparison with nonactuated microrobots.295 Third,
developed that establishes a relation between viscosity and the MagRobots can function as a navigator, precisely guiding
precession angle of the swimmer. High temporal and spatial payloads (especially biomolecules for the diagnostic purpose)
precision of the viscometer was confirmed by gradually to a user-defined site for chemical/biological interactions or
measuring the viscosity of deionized water from the hot state other purposes in an untethered way. Janus magnetic
(70 °C) to its cool-down state (30 °C) and mapping the local microrobots were capable of loading biotin-functionalized
viscosity from a reference fluid (e.g., deionized water) to commercially purchased microbeads and transporting them to
another fluid (e.g., glycerol−water 4:1 v/v) in a microfluidic a specific region under the steering of a uniform electric field
chamber under the application of homogeneous rotating and rotating magnet. The dynamic binding between the
magnetic fields (Figure 21A).157 Second, externally maneu- surface-immobilized probe (i.e., biotin) and the target analyte
vered MagRobots can act as signal amplifiers and, therefore, (i.e., avidin) provides a label-free method for biosensing. The
provide enhanced detection sensitivity and efficiency for experimental detection limit in a single microfluidic chamber
identifying the signals (e.g., fluorescence) triggered by target can be as low as 2 μg/mL (Figure 21C).408
molecules due to the active stirring and vigorous mass transfer
in the solution.406 Janus micromotors, which contain phenyl- 6. CONCLUSION AND FUTURE PERSPECTIVES
boronic acid-modified graphene quantum dots, iron oxide The last decades have witnessed great advances and break-
nanoparticles, and Pt nanoparticles, were used to detect the throughs in MagRobots, including innovative manufacturing
bacterial endotoxin in contaminated water. The reaction approaches, reconfigurable and programmable navigation
between graphene quantum dots and the targeted endotoxin techniques, advanced theoretical models, impressive proofs of
results in the fluorescence quenching of the dots while concept, and clinically oriented application trials. This review
phenylboronic acid tags serve as specific recognition receptors introduces basic knowledge of magnetic fields and magnetic
of the endotoxin. Compared with that in the static conditions, materials, offers the experimental setups of magnetic
the micromotors actuated by external magnetic fields or those manipulation systems and various field configurations, and
autonomously propelled by oxygen bubbles displayed faster proposes the strategies to generate nonreciprocal movement.
fluorescence quenching than those that remained static due to The movement mechanisms of flagella-inspired helical motion,
elevated fluid intermixing (Figure 21B).407 Similarly, mobile undulatory motion, and boundary-assisted motion also are
magnetic spore@Fe3O4@CDs microrobots can remotely presented. Fabrication techniques of (quasi-)spherical, helical,
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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.

flexible, wire-like, and biohybrid MagRobots are summarized, fluids, the relation between movement behaviors of MagRo-
followed by various state-of-the-art applications in the field of bots and environment parameters (e.g., the components,
biomedicine and environment. temperature, viscosity, boundaries, the flow speed of the
The considerable application potential of micro/nanorobots biological fluids, etc.) are expected to be theoretically and
in the biomedical area, such as targeted drug/gene delivery, experimentally established in order to obtain better control of
localized bioanalysis, cell sorting, microsurgery, biopsy, MagRobots. (iii) Precise maneuvering of MagRobots on-body
detoxification, biofilm removal, and biosensing becomes a and in real-time is very important and their monitoring is
driving force that attracts an increasing number of scientists to essential. This is a challenge confronted by micro/nanorobots
join in this emerging research field.143,409 researchers. Clinical imaging systems in current use, such as
In addition, before implementing MagRobots in real MRI as discussed in Section 5.6, can help in terms of
applications, the following aspects should be taken into visualization and as an actuation source. However, there is still
consideration: (i) MagRobots’ materials should meet the room to improve MagRobots’ programmability in terms of
standards of practical biomedical and environmental applica- orientation, locomotion, and even morphology. In this way, if
tions, such as biocompatibility and biodegradability, and bring MagRobots can be controlled and altered according to actual
economic and social benefit. For instance, expensive materials conditions or occasions such as the patient’s health status and
and fabrication apparatus or complicated preparation proce- physiology, then MagRobots will be able to perform precise
dures limit the mass production of synthetic microstructures. and personalized therapy.
This is a challenge that researchers face today and should be In summary, a good understanding of the mechanism of
solved in the future. (ii) To enhance the work efficiency of magnetically driven micro/nanorobots and corresponding
MagRobots in complex environments, swarms or collective impact factors (e.g., geometrical shape, field configuration,
behavior of synthetic MagRobots can be regulated to fluids properties, and boundary) is a precondition for the
cooperatively and efficiently execute complex biological or conceptualization, functionalization, and automation of Ma-
environmental missions that would be insurmountable for a gRobots. High spatial maneuverability, fast reconfigurability,
single MagRobot. Moreover, reconfigurability provides another and precise programmability are the ultimate research goals of
strategy for MagRobots to adapt to variational biological small-scale robots (see Figure 22). Although there is a long
surroundings. For instance, the intriguing collective behavior way to go to translate robust minimized robots from bench to
from the self-assembly of nanoparticles could present a bedside, considerable advances are bringing fantasy closer to
reversible pattern transformation (i.e., reconfigurability) reality.
under the steering of an external field, enhancing MagRobots’
tasking capabilities and high environmental adaptability. AUTHOR INFORMATION
Finally, great endeavors have been made to navigate these Corresponding Author
untethered microrobots in various complex body fluids such as Martin Pumera − Center for Advanced Functional
blood, gastric juice, urine, cerebrospinal fluid,216 and intra- Nanorobots, Department of Inorganic Chemistry, University
cellular medium. However, given the complexity of biological of Chemistry and Technology Prague, 166 28 Prague 6,
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Czech Republic; Department of Medical Research, China the Universitat de Barcelona in the field of the electrodeposition of
Medical University Hospital, China Medical University, magnetic materials. He became a postdoctoral researcher at IRIS in
Taichung 40402, Taiwan; Department of Chemistry and August 2008 and senior research scientist in 2012. Prof. Pané is
Biochemistry, Mendel University in Brno, CZ-613 00 Brno, currently working on bridging materials science, chemistry, and
Czech Republic; Department of Chemical and Biomolecular electrochemistry with small-scale robotics for various applications.
Engineering, Yonsei University, Seodaemun-gu, Seoul 03722, Li Zhang received his Ph.D. degree from the University of Basel,
Korea; Future Energy and Innovation Laboratory, Central Basel, Switzerland, in 2007. He joined the Institute of Robotics and
European Institute of Technology, Brno University of Intelligent Systems (IRIS), Swiss Federal Institute of Technology
Technology, Brno CZ-612 00, Czech Republic; orcid.org/ (ETH) Zurich, Switzerland, as a Postdoctoral Fellow, in 2007 and as a
0000-0001-5846-2951; Email: pumera.research@ Senior Scientist from 2009 to 2012. He is currently an Associate
gmail.com Professor in the Department of Mechanical and Automation
Authors Engineering, The Chinese University of Hong Kong (CUHK),
Hong Kong SAR, China. His main research interests include micro
Huaijuan Zhou − Center for Advanced Functional and nanorobotics for biomedical applications and their collective
Nanorobots, Department of Inorganic Chemistry, University behaviors for the development of small-scale robot swarms. Dr. Zhang
of Chemistry and Technology Prague, 166 28 Prague 6, received the Hong Kong RGC Early Career Award in 2013 and
Czech Republic; orcid.org/0000-0002-9289-3613 several awards from IEEE conferences such as ICRA, IROS, CASE,
Carmen C. Mayorga-Martinez − Center for Advanced ICARM, and NANOMED. He is a Distinguished Lecturer appointed
Functional Nanorobots, Department of Inorganic Chemistry, by the IEEE NTC.
University of Chemistry and Technology Prague, 166 28
Prague 6, Czech Republic; orcid.org/0000-0003-3687- Martin Pumera is Director of the Center for Advanced Functional
0035 Nanorobots and a Distinguished Professor of Chemistry at University
Salvador Pané − Multi-Scale Robotics Lab (MSRL), Institute of Chemistry and Technology, Prague, and Chief Investigator of
of Robotics and Intelligent Systems (IRIS), ETH Zurich, Future Energy and Innovation Lab at CEITEC, Brno, Czech
8092 Zurich, Switzerland; orcid.org/0000-0003-0147- Republic. He received his Ph.D. from Charles University, Czech
8287 Republic, in 2001. After two postdoctoral stays, in 2006 he became
Li Zhang − Department of Mechanical and Automation tenured group leader at the National Institute for Materials Science
Engineering, The Chinese University of Hong Kong, Hong (NIMS), Japan. In 2010, he joined Nanyang Technological
Kong 999077, China; orcid.org/0000-0003-1152-8962 University, Singapore, as a tenured associate professor for nearly a
decade. He has broad interests in nanomaterials and microsystems
Complete contact information is available at: and in specific areas of electrochemistry and synthetic chemistry of
https://pubs.acs.org/10.1021/acs.chemrev.0c01234 2D nanomaterials, nanotoxicity, micro and nanomachines, and 3D
printing.
Notes
The authors declare no competing financial interest. ACKNOWLEDGMENTS
Biographies M.P. acknowledges the support from the project Advanced
Huaijuan Zhou is currently a Marie Skłodowska-Curie Actions
Functional Nanorobots (Reg. No. CZ.02.1.01/0.0/0.0/
(MSCA) Fellow at the University of Chemistry and Technology
15_003/0000444 financed by the EFRR). S.P. acknowledges
Prague, Czech Republic. She received her Ph.D. degree in 2016 from
support from the ERC-2017-CoG HINBOTS Grant No.
the University of Chinese Academy of Sciences under the supervision
771565. M.P. was supported by Ministry of Education, Youth
of Prof. Ping Jin. She has a broad research interest in designing,
and Sports (Czech Republic) Grant No. LL2002 under ERC-
preparing, and characterizing functional nanothin films, semi-
CZ program. L.Z. would like to thank the financial support
conductor materials, field-induced chromic materials, energy con-
from the Hong Kong Research Grants Council (RGC) under
version materials, lithium battery materials, biomaterials, and
Project No. JLFS/E-402/18, the ITF Projects under Projects
locomotive micro/nanomachines for energy conservation/conver-
MRP/036/18X and ITS/374/18FP funded by the HKSAR
sion/storage, biomedical engineering, and environmental remediation.
Innovation and Technology Commission (ITC), the Hong
Kong Croucher Foundation project under Ref. No. CAS20403,
Carmen C. Mayorga-Martinez is currently the Kralupy Unit Leader the Research Sustainability of Major RGC Funding Schemes,
and senior scientist at the Center for Advanced Functional and the Direct Grant from CUHK, as well as support from the
Nanorobots, UCT-Prague. She was research fellow in the nano- Multiscale Medical Robotics Center (MRC), InnoHK, at the
bioelectronics and biosensors group/ICN2, Barcelona-Spain, and in Hong Kong Science Park.
Nanyang Technological University, Singapore. She completed her
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5041 https://doi.org/10.1021/acs.chemrev.0c01234
Chem. Rev. 2021, 121, 4999−5041

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