Magnetically Driven Micro and Nanorobots

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 ACCESS Metrics & More Article Recommendations ABSTRACT: Manipulation and navigation of micro and nanoswimmers in different fluid environments can be achieved by chemicals, external fields, or even motile cells. Many researchers have selected magnetic fields as the active external actuation source based on the advantageous features of this actuation strategy such as remote and spatiotemporal control, fuel-free, high degree of reconfigurability, programmability, recyclability, and versatility. This review introduces fundamental concepts and advantages of magnetic micro/nanorobots (termed here as “MagRobots”) as well as basic knowledge of magnetic fields and magnetic materials, setups for magnetic manipulation, magnetic field configurations, and symmetrybreaking 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 1. Introduction 5000 2. Interations between Micro/Nanorobots and Magnetic Fields 5001 2.1. Magnetic Fields and Magnetic Materials 5001 2.2. Magnetic Manipulation Systems 5001 2.3. Actuation Configurations for MagRobots 5003 2.4. Effective Movements in MagRobots: “Symmetry-Breaking Strategies”5003 3. Actuation and Mechanisms of Magnetic Robots 5004 3.1. Corkscrew-like Motion 5005 3.2. Traveling-Wave Locomotion/Ciliary Stroke Motion 5008 3.3. Surface-Assisted Motion 5008 3.4. Application of Magnetic Fields in Other Propulsion Approaches 5010 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 4.2. Helical MagRobots 5014 4.3. Flexible MagRobots 5015 4.4. Wire-like MagRobots 5017 4.5. Biohybrid MagRobots 5018 5. Applications 5019 5.1. Targeted Drug/Gene Delivery 5019 5.2. Cell Manipulation 5021 5.3. Minimally Invasive Surgery 5023 5.4. Biopsy 5025 5.5. Biofilm Disruption/Eradication 5025 5.6. Imaging-Guided Delivery/Therapy/Surgery 5025 5.7. Pollution Removal for Environmental Remediation 5028 5.8. Sensing and Biosensing 5028 6. Conclusion and Future Perspectives 5029 Author Information 5030 Corresponding Author 5030 Authors 5031 Notes 5031 Biographies 5031 Acknowledgments 5031 References 5031 Received: November 18, 2020 Published: March 31, 2021 Reviewpubs.acs.org/CR © 2021 American Chemical Society 4999 https://doi.org/10.1021/acs.chemrev.0c01234 Chem. Rev. 2021, 121, 4999−5041 Downloaded via BRNO UNIV OF TECHNOLOGY on November 16, 2021 at 08:33:22 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles. 1. INTRODUCTION Many species in nature, such as magnetotactic bacteria, birds, bats, butterflies, lobsters, and salmon, can fly or swim over a long distance by perceiving navigation cues from geomagnetic fields. Some species (e.g., Amitermes meridionalis) even have the ability to (re)orient their bodies or nests according to geomagnetic information. Similarly, the locomotion of nanoscale and microscale objects in a predefined path by the navigation of magnetic fields, 1−4 which are mainly generated by moving charges (i.e., electric currents) and magnetic materials (such as permanent magnets), has drawn extensive attention owing to their tremendous potential for applications in biomedicine and environmental remediation. Such miniaturized objects are normally termed as “magnetically driven micro/nanorobots”(called “MagRobots”for short in this review), which is an important branch of micro and nanorobots. Micro/nanorobots are locomotive artificial machines with size in the micro or nanoscale and rationally designed to execute tasks on command via self-propulsion or an externally controlled propulsion mechanism. Ideally, micro/nanorobots should have the ability to undertake tasks via encapsulation/ functionalization with diagnostic or therapeutic agents, decoration with functional materials, or being fabricated into special micro/nano architectures; “delivery tasks”by moving toward targeted sites in a user-defined path or a theoretically and experimental optimized path; “execute tasks”, for example, killing diseased cells/tissues, removing environmental pollutants as required; and “exit tasks”after the task accomplishment via recycling or in situ degradation. During task implementation, locomotion behavior is of great importance for micro and nanorobots. The migration of micro and nanorobots can be powered by multiple strategies including chemical catalysis (e.g., O2or H2generation) or chemical gradients, 5−11 external energy sources (e.g., magnetic field, 12−14 light, 15−21 acoustic wave, 22−25 or electrical field 26−28 ), and even motile cells (e.g., sperm cell, bacterial cell). 29−37 According to the power source, micro/nanorobots can be classified as chemically driven (or fuel-driven), magnetically driven, light-driven, ultrasound-driven, electrically driven. The word “driven”can be replaced by “powered”, “actuated”,or“propelled”. According to their functionalities, micro/nanorobots can be named as micro/nanogrippers, 38−40 micro/nanodrillers, 41 micro/nanocleaners, 42,43 micro/nanoscavengers, 44 etc. Readers can refer to our latest review 45 to obtain a more detailed classification of micro/nanorobots based on geometric shapes, motion modes, and functionalities. Chemically propelled micro/nanorobots are faster than those with other propulsion methods, but their locomotion lacks directionality. Moreover, they require toxic fuels such as H2O2,N 2H4, HCl, urea, and NaBH4. 46,47 In comparison, those micro/nanorobots powered by external physical fields (such as magnetic, ultrasound, light, and electric fields) do not need toxic chemical fuels for propulsion, but their motion is relatively slow. 48−52 Light-propelled micro/nanorobots can move in water; however, depending on their composition, they need H2O2and a high-intensity light source, which could compromise their biocompatibility. On the other hand, micro/ nanomotors propelled by ultrasound are biocompatible but lack directionality control, making it difficult for them to perform specific tasks. Finally, micro/nanomotors propelled by electric field are very promising for fuel-free locomotion; however, its biological application is still limited and not yet fully demonstrated. Magnetically driven micro/nanomotors address most disadvantages presented by others propulsion principles and, until now, have been the more explored and used in many biomedical applications as well as for environmental control and remediation. Furthermore, magnetic medical microrobots can be driven by magnetic resonance imaging (MRI) systems, thus utilizing existing clinical MRI equipment for dual purposes, namely the imaging and tracking of microrobots, and their propulsion and motion control. 53,54 Likewise, clinical ultrasonography systems hold great potential to actuate ultrasonically driven microrobots. 45 In addition, among all the actuation strategies, the utilization of a magnetic field for manipulating miniaturized robots has unparalleled advantages, which are summarized as follows. (i) Remote maneuverability: magnetic fields provide a noninvasive way to manipulate matter owing to the inherent contactless characteristics of magnetic forces. Such a wireless actuation method allows for micro and nano agents to move in an untethered manner while keeping their local chemical environment intact. (ii) Fuel-Free: using a magnetic field for propulsion is a clean process that does not consume liquid fuel (unlike for chemically and photochemically propelled swimmers). This feature eliminates the harmful effects of toxic chemicals (e.g., hydrogen peroxide) on cells and tissues during their biological application processes. In addition, magnetic fields exhibit insignificant dependence on features and properties of surrounding environments and cause negligible damage to cells at low frequencies. (iii) Reconfigurability and programmability of magnetic materials: reconfigurability refers to the rearrangement of the swimmer’s features such as the morphology, locomotion mode, or other motion parameters upon the application of magnetic fields or other external stimuli. Examples of reconfigurable structures are magnetically driven particulate swarms, 55−57 stimuli-responsive magnetic materials (i.e., ferromagnetic shape-memory alloys), or composite structures (i.e., smart magneto-polymer composites 58,59 or complex origami-like architectures 60 ). This type of structure can readily change its shape by changing the conditions of the applied magnetic fields (i.e., frequency or magnitude). Programmability refers to the ability to manipulate the components of the MagRobots in terms of their shape, magnetic shape, magnetic anisotropy, 61 and crystalline anisotropy to achieve a specific motion mode, position, or orientation when magnetic fields are applied. 62,63 For example, the orientation of a magnetic composite-based structure can be programmed by suitably aligning the particles within the composite matrix. 60 Specific shape-morphing small-scale systems can also be designed to exhibit both reconfigurability and programmability. 64 (iv) Recyclability of magnetic materials: after micro/nanorobots have completed their tasks, the separation and recycling of introduced foreign matter from water, biological fluids, or even tissues might be necessary in terms of biosafety and biocompatibility. Magnetic nano/ microrobots, as they are composed of magnetic building blocks (i.e., coating, segment, particulates), allow for a feasible and convenient magnetically assisted retrieval and recycling process. (v) Versatility: by combining a magnetic field with other actuation sources, the transport and delivery of functional cargos (e.g., drugs or a single cell at the nanosize level) can be achieved with high maneuverability and sensitivity. 65 Currently, various hybrid power sources, such as magneto-acoustic, 22,23,66 magneto-optical, 67 and magnetoChemical Reviews pubs.acs.org/CR Review https://doi.org/10.1021/acs.chemrev.0c01234 Chem. Rev. 2021, 121, 4999−5041 5000 chemotaxis, 68 have been reported, which provide dual propulsion modes in response to multiple stimuli. Molecular machines are molecular components capable of implementing mechanical locomotion (as output) in response to particular external stimuli (as input). 69−72 Stimuli can be various energy inputs such as chemical energy, electric energy, light, photochemical, electrochemical energy, or pH gradient. 73−77 Although molecular machines can perform very complicated functions, most functions are limited to conformational movements. 78−82 In terms of practical uses, particularly for biomedical applications, the operator’s real-time imaging and tracking of the tiny robots are required when they are carrying out specific tasks inside the human body. 10,83 This requirement may limit the applicability of molecular machines due to their nanoscale (<10 nm) size being too small to be readily visualized using traditional imaging techniques. By contrast, larger microand nanorobots can provide greater feasibility for bioimaging for the applications in medical fields. 53,84−86 To this end, swarms of micro/nanorobots can also be used for their imaging and positioning abilities. 87−89 Recent reviews about micro and nanorobots that focus on fabrication techniques, 51 geometric shapes (e.g., active particles, 90 Janus, 91 tubular, 92 hybrid actuators 81,93 ), actuation sources (e.g., light, 48,49 magnetic field 94 ), propulsion mechanisms, 82 and potential applications (e.g., cancer therapy 95 ) provide us with a basic understanding and up-to-date developments in this multidisciplinary and interdisciplinary area. A comprehensive understanding of how tiny machines behave under magnetic fields will inspire and trigger interdisciplinary and cross-disciplinary scientific and technological innovation for multiple applications. The goal of this review is to provide a general view of the locomotion behaviors of nano and microscale motors under the manipulation of a magnetic field and guidance for their rational design by describing the interaction of MagRobots and magnetic fields as well as actuation and movement mechanisms, and reporting state-of-the-art fabrication techniques. After demonstrating current applications in biological and environmental fields, a further outlook of this new and exciting field is presented. 2. INTERATIONS BETWEEN MICRO/NANOROBOTS AND MAGNETIC FIELDS 2.1. Magnetic Fields and Magnetic Materials Magnetic fields, as vector-valued functions of the position, originate from the movement of electric charge. Magnetic fields can be generated by two distinct sources: freely moving electric currents and magnetic materials. Typically, the former source is generated by the coil of an electromagnet that is externally controllable. The setups of a triaxial orthorhombic Helmholtz coil and eight electromagnetic coils (e.g., MiniMag, OctoMag) are representative and widely employed to generate magnetic fields for driving and steering MagRobots (see Section 2.2). The latter source is generated from the intrinsic magnetization of magnetic materials, specifically permanent ferromagnets, which can retain a large remnant magnetization. To manipulate microand nanomachines by magnetic fields, a conventional strategy consists of incorporating magnetic components into nano/microstructures. Magnetic materials can be classified as a function of the magnetic susceptibility (xm), a parameter that reflects how easy a magnetic material is magnetized. As such, magnetic materials are categorized as ferromagnetic (and ferrimagnetic) materials (xm≫0), paramagnetic materials (xm> 0), and diamagnetic materials (xm< 0). Paramagnets and diamagnets are weakly attracted or repelled, respectively, to magnetic fields. Additionally, they cannot retain any magnetization once the magnetic field is removed. Ferroand ferrimagnets are all strongly attracted to magnetic fields. Specifically, ferroand ferrimagnets can retain magnetization, (i.e., exhibit remnant magnetization or remanence) after being subjected to a magnetic field. Usually, high remanence is a feature of hard-ferromagnetic materials, otherwise known as permanent magnets. Soft-ferromagnets, in contrast, exhibit low remanence. Both softand hard-magnets exhibit a hysteretic behavior, which means that to demagnetize these materials, a coercive magnetic field is necessary. This coercivity is large for hard-magnets and small for soft-magnets. Superparamagnets are a special class of materials in which features of both ferromagnets and paramagnets converge such as high susceptibility, no remanence, and no coercivity. While a few examples exist of micro/nanorobots constructed of paramagnets and diamagnets, 96,97 the majority of magnetic small-scale robots have been made of ferromagnetic, ferrimagnetic, and superparamagnetic compounds. For extended details on types of magnetic materials, we suggest the reader to review the hereby indicated references. 98−100 When placing a magnetic small-scale robot with a volume v in an external magnetic field B, the device will display a magnetization M. If the device is subject to a magnetic field gradient ΔB, it will experience an attractive force (or repulsive if it is a diamagnet) as expressed in eq 1. If the device is subjected to a magnetic field, to minimize its energy, it will experience a torque as expressed in eq 2, which will cause the magnetic robot to orient in such a way that its easy magnetization axis is parallel to the direction of the applied magnetic field. The easy magnetization axis is usually governed by the shape (shape anisotropy) but can also be ruled by specific crystal orientations of the materials (crystalline anisotropy). Additionally, the easy magnetization axis can be programmed, for instance, by orienting magnetic nanostructures with a matrix of a composite component or by premagnetizing a material in a specific direction: ν=×∇ F M B () (1) ν=× T M B (2) Both magnetic forces generated in gradient fields and magnetic torque induced by spatially homogeneous or heterogeneous dynamic fields can function as “fuel”to actuate microscopic and nanoscopic motors in various environments. In terms of magnetic torque, weak homogeneous rotating or oscillating fields (see Section 2.3), which display higher efficiency in transforming magnetic energy into kinetic energy, are highly preferable. Magnetic fields offer a maximum of six degrees of freedom (DoFs) (i.e., three translational DoFs and three rotational DoFs) for absolute spatial manipulation of micro/nanorobots, depending on the setup of electromagnetic actuation systems (see Section 2.2). For instance, the widely used uniform rotating magnetic field with triaxial Helmholtz coil can supply three rotational DoFs, while MiniMag and OctoMag have five DoFs: two rotational and three translational DoFs. 2.2. Magnetic Manipulation Systems A typical setup platform for monitoring and actuating magnetically driven microand nanorobots consists of a sample stage, an optical microscope (eventually, coupled with a Chemical Reviews pubs.acs.org/CR Review https://doi.org/10.1021/acs.chemrev.0c01234 Chem. Rev. 2021, 121, 4999−5041 5001 high-resolution camera), a magnetic manipulation system, and a computer system with video capture and analysis (Figure 1A). The magnetic manipulation system consists of a set of either permanent magnets or electromagnets 107−110 as the source of the magnetic field. Recent contributions 97,111,112 provide a systematic review of configurations of magnetic manipulation systems that can be applied to magnetic smallscale robots with sizes ranging from nanometers to millimeters. In this review, we will only focus on the commonly used magnetic systems employed for the manipulation of nanoscale and microscale robots. One of the main differences between systems using permanent magnets and electromagnets is the fact that the magnetic field from a permanent magnet is persistent and its magnitude cannot be quickly changed. The distribution and strength of a magnet’sfield depend on its geometrical shape and size. For a magnetized object with a given geometry shape 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 reproducibility 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. An ideal soft magnetic material is often used as the core in order to avoid effects of hysteresis. On-demand setting of current in each coil can result in the required configuration of magnetic fields, such as rotating field, oscillating field, alternating fields, and conical fields, which will be discussed in Section 2.3.Different arrangements of coils constitute specialized electromagnet systems such as the Helmholtz coil, the Maxwell coil, the saddle coil, and the double-saddle Golay coil (detailed information can be found in ref 113). Helmholtz coil, containing two circular and coaxial coils with equal radius and same handedness of flowing current, is the first and most important arrangement. Because the field generated from the Helmholtz coil is near-uniform at the center of the coils, such a magnetic actuation system is appropriate for magnetic torque control. 114−116 Arbitrary uniform magnetic fields in a 2D plane or 3D space can be generated by two pairs of Helmholtz coils or triaxial Helmholtz coils, respectively. Triaxial circular Helmholtz coils are the most commonly used for actuating magnetic small-scale robots (Figure 1E). The combination of Helmholtz coils with other types of coils can engender systems with multi-DOF capabilities. Maxwell coil is also composed of two circular coaxial coils with equal radius, but the current flowing through different coils coil has the opposite handedness. Maxwell coils can create uniform magnetic field gradients, saddle coils can generate a uniform field or a gradient field, and double-saddle Golay coils can produce a transverse gradient. A magnetic manipulation system with a stationary Helmholtz− Maxwell coil and a rotational Helmholtz−Maxwell coil has the capacity of 3D locomotion of a magnetic small-scale robot through the control of both magnetic forces and torques (Figure 1F). 104 Its upgraded system using four different coil pairs (i.e., a Helmholtz coil, a Maxwell coil, a rotatory uniform saddle coil, and a rotatory gradient saddle coil) occupies a Figure 1. Experimental setup for magnetically driven micro/ nanorobots and various magnetic actuation systems. (A) Diagram of the typical experimental workplace for actuating and visualizing MagRobots. (B) Magnetic actuation system consists of only a single permanent magnet. (C) Permanent magnet actuation system using cylindrical NdFeB permanent magnet fixed to its end-effector and a robotic arm. Reproduced with permission from ref 101. Copyright 2017 IEEE. (D) Rotating permanent magnet system consists of a magnet, a robotic arm, and a motor. Reproduced with permission from ref 102. Copyright 2013 IEEE. (E) Electromagnetic actuation system using triaxial circular Helmholtz coils. Reproduced with permission from ref 103. Copyright Springer Science + Business Media, LLC 2013. (F) Electromagnetic actuation system using a stationary Helmholtz−Maxwell coil and a rotational Helmholtz− Maxwell coil. Reproduced with permission from ref 104. Copyright 2009 Elsevier B.V. (G) Electromagnetic actuation system using multiply coils including a Helmholtz coil, Maxwell coil, uniform saddle coil, and gradient saddle coil. Reproduced with permission from ref 105. Copyright 2010 Elsevier B.V. (H) MiniMag electromagnetic system. Reproduced with permission from ref 106. Copyright 2014 Springer-Verlag GmbH Berlin Heidelberg. Chemical Reviews pubs.acs.org/CR Review https://doi.org/10.1021/acs.chemrev.0c01234 Chem. Rev. 2021, 121, 4999−5041 5002 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 orientation). 118 OctMag is composed of four evenly distributed electromagnets in a plane with the orientation of 90° from a central axis and four evenly distributed electromagnets with the orientation of 45°from a central axis. MiniMag is the scaled-down compact version of the OctoMag (Figure 1H). Utilization of OctMag and MiniMag has been reported to remotely manipulate microand nanorobots for targeted drug delivery, 119 minimally invasive ophthalmic surgery, 120 and stem cell transplantation in a rat brain. 121 Other configurations of electromagnets, such as square antiprism, cubic, open asymmetric, and so on, were summarized in a recent review. 113 2.3. Actuation Configurations for MagRobots According to changes of the magnetic field vector with time, magnetic fields can be classified as static, dynamic (including a rotating magnetic field whose direction varies with time, an oscillating magnetic field whose strength varies with time), or on−offfields. Both static and dynamic magnetic fields can be homogeneous fields where the field vector modulus remains constant in space, or inhomogeneous magnetic fields where the field strength varies with position, that is, field gradient. 122 Rotating magnetic fields are widely adopted to induce rotational motion. For some micro and nanomachines with specific shapes (e.g., helical structure), such temporal−periodic rotational motion can be converted into translational corkscrew motion (see Sections 3.1 and 4.2), which leads to a net spatial displacement. In contrast, oscillating magnetic fields can be utilized to activate traveling undulatory locomotion for some MagRobots such as those with soft tails (see Section 3.2) and those consisting of solid segments linked with soft hinges (see Section 4.4). Rotational magnetic fields can also induce thermophoretic motion for ferromagnetic materials by generating heat energy 123 (see Section 3.4). Figure 2 summarizes different categories of magnetic fields and their corresponding field diagrams. 124 2.4. Effective Movements in MagRobots: “Symmetry-Breaking Strategies” To begin this section, we would like to briefly introduce the hydrodynamic laws to understand how small-scale robots swim in a fluid. The Navier−Stokes equation, arising from Newton’s second law, describes the motion of a Newtonian fluid as follows (eq 3): ρ η ∂ ∂ +∇ =∇−∇ i k j j jy { z z z vvv v p t() 2 (3) where vector νand vector p(both of which are a function of position and time) are the flow velocity and pressure, respectively; ρand ηare the density and viscosity of the flow, respectively. The left-hand of the Navier−Stokes equation comprises the inertial forces, while the right-hand corresponds to the viscous forces. Here, we introduce an important dimensionless quantity called the Reynolds number (Re, expressed in eq 4), which is the ratio of inertial and viscous forces: ρν η == R eL inertial forces viscous forces (4) where Lis the characteristic length of an object moving in a fluid. For small-scale devices and organisms (i.e., motile cells, bacteria), Lis very small (Re ≈10−4), which means that viscous forces rule their motion. A typical analogy of swimming at low Re is that a bacteria swimming in water is similar to a person swimming in honey. Considering that inertia forces are negligible in the low Re regimes, the Navier−Stokes equation can be simplified as an expression known as the Stokes equation: ν η ∇=∇ P (5) Note that this hydrodynamic equation is time-independent, meaning that no net displacement will occur after completing a cyclic process no matter if the speed of the swimmer is fast or slow. In other words, the resultant fluid flow exhibits instantaneous and time-reversible features. This is the socalled “Scallop Theorem,”as introduced by the Nobel laureate Purcell (Figure 3A). At low Reynolds number, a microscopic scallop can only perform back and forward movement (i.e., reciprocal motion). Once the actuation energy (such as a magnetic field) is removed, its motion is immediately halted due to the lack of inertial forces. Importantly, to generate a nonreciprocal translatory movement to execute tasks such as cargo delivery, Figure 3Bsummarizessomestrategies employed to break Purcell’s Scallop Theorem. The first Figure 2. Classifications and configurations of magnetic fields in relation to the motion of MagRobots. Chemical Reviews pubs.acs.org/CR Review https://doi.org/10.1021/acs.chemrev.0c01234 Chem. Rev. 2021, 121, 4999−5041 5003 method involves fabricating a small-scale robot with an asymmetric shape such as a tubular, 125 helical, 60,126,127 fishlike, 128 annelid-worm-like, 129 tadpole-like, 130 bullet-shaped, 22 star-shaped, 131 or even random-shaped 132,133 structure. In addition, an asymmetric shape (e.g., carpet, 134 ribbon 56 ) can also be formed by self-assembling colloid particles with a symmetric shape based on collective behavior. 90 A second approach consists of creating a microor nanostructure containing a flexible component, for example, a flexible tail, which can mimic the flagellum of a microorganism. 81,135 Velocity distribution (indexed by frame number of a video sequence) of a single beating flagellum or cilium from a cell or a microorganism during one cycle 136 indicated the generated traveling-wave motion (see Section 3.2) is nonreciprocal. Incorporating flexible components in between rigid structures to create multilink micro or nanoassemblies is also another possibility, which will be further discussed in Section 4.4.A recent strategy consists of integrating motile flagellated microorganisms and cells with magnetic micro and nanostructures to create biohybrid MagRobots (see Section 4.5). A third approach entails the use of a nonsymmetric actuation magnetic field. For example, a symmetric small structure can exhibit a translational motion by means of a traveling-wave 137 or a ciliabeating motion mechanism 138 under a nonsymmetric actuation field. The fourth approach is based on actuating magnetic small-scale devices in the proximity of a boundary (e.g., wall, interface) to break the spatial symmetry. The motion mechanism based on this method is called “surface-assisted propulsion”, which will be discussed in Section 3.3. All these symmetry-breaking strategies evade the constraints of the famous Scallop Theorem. 100 Note that the Scallop Theorem only applies to Newtonian fluids. Time-reversible reciprocal locomotion can still generate an effective propulsion in nonNewtonian fluids (e.g., blood, saliva, mucus). 139 3. ACTUATION AND MECHANISMS OF MAGNETIC ROBOTS Compared with macroscale motile robots, micro and nanoscale robots experience totally distinctive hydrodynamics. Hence, they exhibit distinctive assorted motion behaviors. A good understanding of various propulsion mechanisms is the basis for the design of propulsion microsystems including the shape and architecture of micro and nanorobots as well as the configuration of the magnetic field. The designed propulsion system must be able to overcome various resistive forces in the micro and nanodomains to realize the motion of small-scale robots effectively. The translational mechanisms of magnetic miniaturized machines could be broadly divided into three 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. Chemical Reviews pubs.acs.org/CR Review https://doi.org/10.1021/acs.chemrev.0c01234 Chem. Rev. 2021, 121, 4999−5041 5004 types: (a) corkscrew motion, (b) undulatory motion (i.e., traveling-wave motion), and (c) surface-assisted propulsion (i.e., surface walker). 3.1. Corkscrew-like Motion In nature, many microorganisms can coordinate their propulsion and orientation behaviors according to external stimuli with a motile appendage called a flagellum. Eukaryotic cells (e.g., spermatozoa) can produce a traveling-wave motion by making use of a flexible beating flagellum. In contrast, prokaryotic cells can perform a corkscrew-type motion by rotating their helical flagella. Bacteria (e.g., E. coli), as a representative of prokaryotic organisms, rely on the rotation of flagella for swimming. The flagellum, containing a basal body, a hook, and a filament, is the fundamental organelle for bacterial motion. There is a reversible motor inside the basal body controlling the rotation of the flagellum. The flagellum can not only trigger reorientation of the organism but also make them move forward and back. When the flagellum rotates in one direction with an action frequency ω1, the cell body counterrotates with the reaction frequency ω2(ω2and ω1are not equal) to balance the produced torque (Figure 4A). Inspired by the bacterial flagellum for efficient movement, man-made helical micronanomachines, known as artificial bacterial flagella (ABF), 142−145 have been developed and investigated. Although there is no motor in the ABF system, external rotating magnetic fields provide a similar function for generating the rotation. As discussed earlier, a MagRobot will align its easy magnetization axis parallel with the direction of a local homogeneous field upon experiencing a magnetic torque in that magnetic field. A continuously applied torque to a micro/ nanoobject under an external rotating field gives rise to the rotational movement of the body. For artificial magnetic micromachines containing chiral helices, a steady rotation around their helical axis can be effectively converted into nonreciprocal translational motion, with the direction parallel with the rotating axis of a two-dimensional planar rotating field. At the same time, the tail and head (sometimes it has no head) of ABF perform the same (clockwise or counterclockwise) orientation. This is distinct from bacteria, whose head and tail rotate in the opposite orientation. If the ABF Figure 4. Flagellar-based propulsion mechanisms. (A) Rotation of bacterial flagellum at frequency ω1through rotary motor inside and a counterrotation 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. Chemical Reviews pubs.acs.org/CR Review https://doi.org/10.1021/acs.chemrev.0c01234 Chem. Rev. 2021, 121, 4999−5041 5005 consists of a single rigid body, then the head and tail will rotate with the same frequency (ωh=ωt). Moreover, the progression direction (forward or backward) can be easily inverted by reversing the direction of rotation (i.e., clockwise or counterclockwise) of an applied magnetic field. In the magnetically actuated ABF system, similar to other magnetically controlled systems, magnetic materials are required in order to respond to the external field. Widely used ferromagnetic materials include Ni, Co, and Fe, while the frequently applied superparamagnetic materials include Fe2O3and Fe3O4. Up to now, various types of ABF systems have been investigated. 146,147 Some typical examples are shown in Figure 4B. 148 Many factors play a critical role in the movement of magnetic helical microswimmers such as solution properties (e.g., fluid viscosity, ion strength), geometrical parameters (e.g., helix pitch), surface characteristics (e.g., surface wettability, 149,150 roughness), magnetic field properties (e.g., frequency, intensity, rotating, or oscillating field), magnetization properties of magnetic materials, head/tail shapes, mechanical properties (e.g., rigid or flexible), and boundary condition (e.g., wall). The simulation demonstrates that helical swimmers exhibit the highest propulsion efficiency when the pitch angle is about 45°. 151 The optimal magnetization direction for helical microrobots is perpendicular to the helical axis in order to maximize the applicable magnetic torque around the axis. The motion mode and velocity of ABF are strongly associated with the applied field frequency. As shown in Figure 4C, at low frequency rotating magnetic fields 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. Chemical Reviews pubs.acs.org/CR Review https://doi.org/10.1021/acs.chemrev.0c01234 Chem. Rev. 2021, 121, 4999−5041 5006 (typically below several Hertz), a wobbling motion occurs when the axis of the helical MagRobot cannot align with the direction of the local field. 152,153 As the rotating field frequency is enlarged, the wobbling angle decreases from 90°to zero, where a wobbling angle of zero corresponds to the rotation along the long axis with a direct corkscrew-like thrust. (Ratio of viscous to magnetic torque (i.e., Mason number), helix angle, and helical size can also bring about shrinkage of the wobbling angle of helical MagRobots under temporal−periodic torques. 49 In the corkscrew-like motion region (also denoted as “synchronous”region), the translational velocity of helical MagRobots increases with the increased applied rotation frequency of an external magnetic field, performing a synchronous and linear relationship. Further increase with respect to a critical field frequency results in a decrease of the swimming velocity, which is attributed to the fact that the magnetic torque is not sufficient to maintain a synchronous relationship between the magnetic moment and the applied rotating magnetic field. The critical frequency is called the “step-out frequency”. 154 Surface chemistry also influences the motion of helical MagRobots. Recently, it has been reported that magnetically 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. Chemical Reviews pubs.acs.org/CR Review https://doi.org/10.1021/acs.chemrev.0c01234 Chem. Rev. 2021, 121, 4999−5041 5007 nude mice also confirmed that burr-like magnetic microrobots exhibited excellent cell loading, carrying, and release capabilities. In a similar fashion, Jeon et al. used 3D laser lithography and sputtering to fabricate cylindrical, hexahedral, helical, and spherical MagRobots. 121 The use of a magnetic field gradient induced the pulling motion of cylindrical and hexahedral MagRobots, while the rotating field caused corkscrew motion for helical MagRobots and rolling motion for spherical microrobots. 121 Spherical microrobots with Janus structure were fabricated by Martin Pumera’sgroup(Figure 9D). 209 The Janus structure, formed by half-covering superparamagnetic polymer particles with catalytic Pt layer, can self-propel due to the catalytic decomposition of hydrogen peroxide and can be steered by an external magnetic field. Polymer particles with a tosyl group-rich surface provided the chance to bind anticancer drugs. In addition to drug loading and delivery, the microrobots could also manipulate cells when they assembled into a chain under magnetic guidance. 4.2. Helical MagRobots Helical architectures, inspired by the flagella of bacteria, enable micronanomachines to convert rotational motion to a translational corkscrew motion by using a low-strength magnetic field in low Reynolds number liquids. Various microand nanofabrication techniques have been used to prepare helical micro/nanostructures, including templateassisted electrochemical deposition (TAED), 215 laser ablation, 216 direct laser writing and 3D printing, 127,155,217−220 glancing angle deposition, 126,221 coiled flow template, 222,223 biotemplate, 224,225 and origami-based self-scrolling technique. 60,226 Laser micromachining allows the creation of arbitrary 3D structures. Piezoelectric soft MagRobots, which can deliver PC12 cells by employing a rotating magnetic field to induce neuronal differentiation under the stimulus of acoustic waves, were fabricated by Salvador Pane’sgroup. 216 Helical MagRobots consisting of piezoelectric polymer matrix and CoFe2O4magnetic component were formed by laser ablation of composite film coated on the surface of copper wire by dipcoating method, followed by etching copper wire with acidic ferric nitrate solution (Figure 10A). Steering of helical parameters such as pitch, pitch angle, and the ratio can be achieved by altering the laser spot size, laser motion speed, and rotating speed of copper wire. The helix microstructure can move in a corkscrew manner along its long axis by a rotating field. 3D/4D printing provides a feasible approach to fabricate soft micro/nanorobots with predesigned shapes. 227−235 Recent reviews give a summary of functional soft robots created by 3D printing 45 and 4D printing 236 technique. 3D-printed enzymatically biodegradable soft helical microswimmers have been designed by Paneand co-workers. 237 Two-photon polymerization (a type of 3D printing technique) was adopted to print photo-cross-linkable gelatin methacryloyl (GelMA) helical microswimmer. To decorate GelMA architecture with Fe3O4nanoparticles for magnetic actuation, GelMA microstructures were immersed in a water suspension of PVP-coated Fe3O4nanoparticles (Figure 10B). Another work about hydrogel-based biodegradable helical microswimmers with length of 20 μm and diameter of 6 μm was reported by Metin Sitti’sgroup. 127 3D printing of double-helical architecture was realized by two-photon polymerization technique from a precursor mixture of GelMA, photoinitiator, and biofunctionalized superparamagnetic Fe3O4nanoparticles. Such double-helical architecture allows these micromachines to host high therapeutic cargo loading and swimming abilities under a rotating magnetic field. Although template-assisted electrochemical deposition (TAED) has been widely used to fabricate tubular micromotors, this method can also be employed to generate helical architectures. 238−240 A representative example was demonstrated by fabricating platelet−membrane-cloaked magnetic helical nanomotors in Joseph Wang’s group. 215 Pd helical microstructures with a length of 3−5μm were synthesized by coelectrodepositing a Pd/Cu bilayer on an electrochemical platform using a polycarbonate template and followed by selectively etching the Cu with nitric acid. Afterward, Ni/Au thin films were deposited on the surface of the helical nanostructure via the electron beam evaporation method. To make the gold surface negatively charged, surface modification of the magnetic helical microstructures was carried out by overnight incubation of the microrobots with 3-mercaptopropionic acid. Then, platelet-membrane-derived vesicles were adsorbed, bound, and fused onto the negatively charged gold surface by ultrasonic mixing (Figure 10C). Helical MagRobots can also be produced by glancing angle deposition (GLAD). 241−243 In this approach, a seed layer, normally created by spreading a monolayer of silica beads on the substrate, is required to function as the nucleation site. Prior to deposition, the seed layer is fixed at a glancing angle with respect to the input vapor flux of a specific material. During the deposition process, a helical silica structure grows starting from an individual seed particle by continuously rotating the substrate. The pitch and chirality of asymmetric helical structures are changeable by adjusting the speed and direction of rotation. Finally, a layer of magnetic material is deposited in the resulting silica helical tail. While this method can batch-produce uniform helical nanostructures, this process is still limited in terms of material selection and shape. To make the magnetic section (i.e., Ni) of helical microstructure stable in acidic solution, helices were covered with an 8 nm Al2O3thin film by atomic layer deposition. The stabilized helical micropropellers can be further functionalized with urease (Figure 10D). 221 Inspired by origami designs, Huang et al. 244 exploited thermoresponsive gel composites reinforced with magnetic nanoparticles to fabricate microswimmers with various 3D architectures by using a one-step photolithography technique and capitalizing on the self-folding of the hydrogel upon hydration (Figure 10E). During the gel polymerization process, a static uniform field was used to align the encapsulated magnetic nanoparticles. The folding axis direction of the MagRobots was consistent with the alignment direction of the magnetic particles as the swelling was constrained along the reinforcement direction. The produced microswimmers could change their shapes to adapt to local environmental variations in mechanical constraints and osmotic pressure. 244 Hollow helical microstructures can be obtained by first synthesizing magnetic helical microfibers composed of calcium alginate hydrogel and Fe3O4nanoparticles from coiled flow templates in glass-capillary microfluidic devices, followed by biosilicification and dicing process (Figure 10F). The produced microswimmer containing inflexible alginate/protamine/silica shell exhibited good mechanical performance for cargo transport. 222 Utilization of bevel-tip capillary and syringe Chemical Reviews pubs.acs.org/CR Review https://doi.org/10.1021/acs.chemrev.0c01234 Chem. Rev. 2021, 121, 4999−5041 5014 pump, heterogeneous core−shell hydrogel microsprings with calcium alginate hydrogel as shell components and functional materials (e.g., magnetic particles, agarose, cell-suspended collagen) as core components were produced. 245 Because nature provides us with plenty of helical microand nanoarchitectures, preliminary attempts to extract the helical xylem vasculature of plants 224 and Spirulina cyanobacterial green−blue microalgae 246−248 as templates to fabricate biohybrid helical microand nanomachines open a new insight into strategic designs. The advantage of biohybrid small-scale robots is in the biocompatibility and biodegradability characteristics of the biotemplates. Cell-based helical microswimmers can be acquired from multicellular Spirulina via a single cost-effective dip-coating process in superparamagnetic Fe3O4solution. 248 Because of the intrinsic properties of microalgae, the prepared microswimmers allowed for in vivo fluorescence imaging without additional fluorescent markers. Moreover, large swarms of microswimmers can be accomplished inside the rat stomach by an external rotating magnetic field with the assistance of imaging. 248 Model small molecules, as well as biomacromolecules, can be loaded into Spirulina cells by controlling their dehydration and rehydration. 246 The micromachine loaded with molecular cargo can be magnetically driven in an intestinal tract phantom, thus providing the possibility of targeted molecular delivery for gastrointestinal diseases. By modifying their surface with polydopamine via dopamine self-polymerization (Figure 10G), Spirulina-based magnetic helical microswimmers exhibit an enhanced photoacoustic signal and photothermal effect. 225 In addition to the above-mentioned helical MagRobots, many other helical architectures have been created. 144,242,249−255 4.3. Flexible MagRobots Flexible or soft small-sized robots refer to a nanoscale and microscale robotic system completely or partially comprising soft components or architectures that function as carriers, templates, hinges, joints, actuators, sensors, or reserFigure 11. Schematic illustrations of the representative fabrication processes of flexible MagRobots. (A) (a) Fabrication process of temperaturesensitive 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. Chemical Reviews pubs.acs.org/CR Review https://doi.org/10.1021/acs.chemrev.0c01234 Chem. Rev. 2021, 121, 4999−5041 5015 voirs. 256−261 The utilization of flexible microorganisms to create MagRobots will be discussed in Section 4.5. The advantages of flexible MagRobots are reflected in the following aspects: First, as described in Section 2.4, the integration of a soft segment as a hinge 261 (see Section 4.4) or as a tail (see Section 3.2), into nano/microrobots can break spatial and temporal symmetries and generate a forward thrust. Second, flexible MagRobots are capable of transforming their configurations/architectures to execute special tasks under the magnetic actuation, such as grasp and release (similar to the function of a hand) of a small-scale object. 262,263 Third, flexible and soft small-scale robots are more desirable for biomedical applications as these devices are more adaptive in complex biological scenarios, especially in confined, hard-toreach tissues and vessels of the body when compared with swimmers made from rigid and hard parts. Soft robots can be constructed with stimuli-responsive polymer materials that enable shape transformations and the realization of other tasks depending on environmental changes (i.e., pH, 264,265 temperature). For example, PPF/pNIPAMAAc magnetic microgrippers with pNIPAM-AAc serving as a thermoresponsive swelling hydrogel segment, polypropylene fumarate (PPF) as a nonswellable stiffsegment, and Fe3O4 nanoparticles for the magnetic actuation were prepared by serial photolithographic method (Figure 11A). The thermoresponsive soft self-folding microgrippers could be directed or retrieved to the desired location under the magnetic field to execute their tasks (e.g., to load or release therapeutics) in response to temperature stimulus at around physiological temperature without the need of wires, batteries, or other sources. 39 Similarly, another thermoresponsive soft microrobot was manufactured and employed for pick-up/release applications due to the temperature-sensitive P(OEGMA-DSDMA) layer. 266 Because of the pH-responsive property of 2hydroxyethyl methacrylate (PHEMA), the PHEMA/PEGDAFe3O4bilayer soft microrobot formed via photolithography 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. Chemical Reviews pubs.acs.org/CR Review https://doi.org/10.1021/acs.chemrev.0c01234 Chem. Rev. 2021, 121, 4999−5041 5016 (Figure 11B) performed the trapping of drug microbeads at about pH 9.58 by full folding motion and the release of drugs by unfolding motion at about pH 2.6. 265 Biocompatible magnetic “hairbots,”derived from functionalized hair (Figure 11C), can display heightened osteogenic differentiation capacities of mesenchymal stem cells under magnetic actuation compared with nonmagnetic hairbots. Moreover, a magnetic field with repulsion mode endowed stem cells with higher osteogenic activity compared with the attraction equilibrium or nonequilibrium mode. 267 Liquid metals (LM) have also been recently used to create shapemorphing flexible microrobots. An ice-assisted transfer printing method was used to fabricate Fe3O4NPs-incorporated EGaIn LM micromotors (Figure 11D). Because ice can be easily removed, this method provides great convenience for transferring LM-based micromotors to arbitrary desired substrates. Irradiation from an alternating magnetic field could cause the dramatic morphological transformation of LM-based micromotors in an aqueous environment. Moreover, the resulting LM-based microswimmer exhibited high propulsion velocity (over 60 μms −1) under an elliptically polarized magnetic field as compared with its rigid counterparts. 268 The utilization of DNA as a flexible component is another method to create soft micro/nanorobots is shown in Figure 11E. Artificial flagella with a length of several micrometers were generated using a self-assembled DNA bundle. 269 After attaching the soft DNA flagella to a magnetic microbead via biotin−streptavidin coupling interaction, a hybrid microrobot was constructed. The fabricated magnetic microrobots can be propelled like peritrichous bacteria under a homogeneous rotating magnetic field. Similarly, Remi Dreyfus and coworkers 158 used biotinylated double-stranded DNA as “soft” hinges to link red blood cells decorated with streptavidinmodified superparamagnetic particles. In this way, another type of flexible artificial flagella was prepared via the specific biotin− streptavidin interaction. Origami as a self-folding process provides a top−down approach to fabricate soft robots with transformable morphologies. A complete origami robotic system normally comprises power, sensing, actuation, and computation subcomponents. 270−273 Readers are suggested to read the review article written by Daniela Rus and Michael T. Tolley to obtain more information about the design, fabrication, and control of origami robots. 274 Self-folding origami MagRobots with various body designs (i.e., tubular body and helical tail, tubular body and spiral tail, helical body and planar tail, etc.) were created by Nelson’sgroup. 60,63 The micro-origami swimmers were endowed with reconfigurable morphologies, controllable mobility, and even programmable magnetic anisotropy by embedding magnetic nanoparticles into selffolding hydrogel bilayers (i.e., one supporting layer and one thermally responsive layer). Because of the programmable shape-morphing feature of the origami-based microrobots, an artificial microsized “bird”was created to mimic the different flying modes of a real bird, including “flapping,”“hovering”, “turning”, and “side-slipping”(Figure 11F). 64 4.4. Wire-like MagRobots Most rod-like MagRobots are fabricated by template-assisted electrochemical deposition (TAED). 275−279 In general, anodic aluminum oxide (AAO) or polycarbonate porous membranes are employed as templates. These membranes are commercially available and are usually composed of cylindrical pores, although sophisticated designs and complicated fabrication of porous membranes with different pore geometries or with variable pore diameter can be realized. 280,281 Because of the nonconductive nature of these templates, prior to the electrodeposition of material, a layer of a conductive thin film (usually gold) is deposited on one side of the membranes by electron beam evaporation or other physical vapor deposition methods. The length of the nanostructures (i.e., nanorods, nanowires) is adjustable by regulating the electrodeposition time. After deposition, metal-based nanowires are released by dissolving the membrane template. Usually, ferroand ferrimagnetic nanowires and nanorods align with their long axis parallel with the direction of the applied magnetic fields. Two main strategies exist to align cylindrical magnetic nanostructures perpendicular to their long axis: (a) by placing segments of magnetic material sufficiently separated along a nonmagnetic structure (in order to minimize dipolar interactions) and (b) premagnetizing the nanowires/nanorods along their short axis. The first case can be achieved by synthesizing multisegmented nanowires/nanorods using pulsed plating electrodeposition or sequential deposition by alternating different electrolytes. 282,283 In the second approach, a nanowire/nanorod has to be made from hard-magnetic materials so that it can preserve a sufficiently large remanence after being premagnetizing in a specific direction. Figure 12A shows the fabrication of electrodeposited hard-magnetic CoPt nanowires and the procedure for their premagnetization along their short axis. 165 Figure 12B shows a comparison between a soft-magnetic CoNi and a hard-magnetic CoPt nanowire and their alignment upon the application of a magnetic field. While the premagnetized hard-magnetic nanowire aligns with its short axis to the applied field, the soft-magnetic is aligned along its long axis. In a rotational magnetic field, a nanowire/ nanorod that aligns with its long axis with the applied magnetic field can only exhibit a tumbling motion. 284 However, a nanowire-like MagRobot that is premagnetized along its short axis can display a richer variety of motion mechanisms such as tumbling, rolling, precession, or wobbling locomotion as a function of the magnetic field frequency. Another strategy to possess multiple motion modes is to integrate premagnetized nanowires into nonmagnetic structures. For instance, a single Ni nanowire only shows a sole tumbling motion. 284 After assembling two polystyrene beads into a Ni nanowire to construct a dumbbell-like MagRobot, the fabricated microstructure possesses three motion modes (i.e., rolling, wobbling, and tumbling) (Figure 12C). 285 When adding flexible segments such as hinges or tails to nanowires, the assembled MagRobots display traveling-wave motion under the steering of an oscillating magnetic field. A multiple section microstructure of Au−Ag−Ni−Ag−Ni−Ag− Au, using three elastic Ag nanowires as hinges and fabricated by sequential electrochemical deposition, can mimic the swimming of a fish with a speed as high as 30 μms −1(Figure 12D). 128 In a similar fashion, the two arms of a Ni−Ag−Au− Ag−Ni MagRobot are capable of executing an out-of-phase wobbling motion by a planar 2D oscillating field and propel the movement of the body with a velocity of around 30 μms −1 (Figure 12E). 3 A Ni-hinge-Ni-hinge-Ppy nanorobot involving a flexible polypyrrole (Ppy) tail has the ability to break the reciprocal motion at the temporal dimension, exhibiting an Slike motion mode by making use of its eukaryote-like tail with the assistance of an oscillating field, leading to maximum propulsion speed of 0.93 body-lengths s−1(Figure 12F). 97 Chemical Reviews pubs.acs.org/CR Review https://doi.org/10.1021/acs.chemrev.0c01234 Chem. Rev. 2021, 121, 4999−5041 5017 Inspired by the electric field, a knifefish, which can produce electricity through its electrocytes, was developed as a multifunctional Ni-Ppy-PVDF MagRobot containing a soft polyvinylidene fluoride (PVDF) tail. Taking advantage of the intrinsic piezoelectric performance of the PVDF tail, the surface of the fabricated MagRobots exhibits an enhanced release of cargo owing to the electrostatic repulsion generated by the magnetically induced piezoelectric effect. By changing the magnitude and rotational frequencies of the applied rotating magnetic field, three different locomotion modes (i.e., tumbling, wobbling, and corkscrew-like motion) with different translation speeds and drug release behaviors were observed (Figure 12G). Interestingly, the application of an on−off magnetic field can actuate the release of drugs in a pulsatile approach. 286 4.5. Biohybrid MagRobots Because of their excellent biocompatibility and extremely low toxicity, biohybrid mineralized motors, which often integrate synthetic nanostructures/nanoparticles with natural nonmobile cells (e.g., pollen, spores) or motile cells (e.g., bacteria, sperm), are currently of great interest. 135,287 Four methods are commonly used to produce biohybrid micro/nanorobots. The first method consists of directly using nonmotile cells as templates and then integrating magnetic nanomaterials and other functional building blocks such as inorganic nanostructures or molecules. Capitalizing on this approach, several pollen-based, 288−290 spore-based, 291 microalgae-based, 292,293 sperm-based 294 magnetic micromotors have been fabricated. In general, pollen and spores have the merits of excellent biocompatibility characteristics and structural uniformity. Some even have unique architecture (e.g., hollow cavity), which can facilitate specific applications. For instance, researchers have loaded drugs into two hollow air sacs of pine pollen grains via vacuum loading technique (Figure 13A). The experiments demonstrated that pollen-based biohybrid MagRobots not only exhibit efficient drug-encapsulation ability but also can release them on demand. 288 By altering the 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) RGBcloaked 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. Chemical Reviews pubs.acs.org/CR Review https://doi.org/10.1021/acs.chemrev.0c01234 Chem. Rev. 2021, 121, 4999−5041 5018 vectors of programmatically controllable magnetic fields, individual pollen-based micromotors with encapsulated magnetic Fe3O4inside present three distinct modes of locomotion (i.e., rolling, tumbling, and spinning) and these individuals were able to form a dynamic collective phenomenon under the steering of an external magnetic field. 288 Spore-based microrobots composed of G. lucidum spores, Fe3O4nanoparticles, and functionalized carbon nanodots have been synthesized via rapid, direct, and low-cost methods (Figure 13B). The prepared spore@Fe3O4@CDs microrobots can detect bacterial toxins. 295 As mentioned above, Spirulina, with the innate spiral morphology, has been utilized as a biological template to create helical microswimmers 248,292 (Figure 13C). Sperm-based soft MagRobots were fabricated by decorating Fe2O3nanoparticles on the surface of immobile sperm cells via the electrostatic selfassembly (Figure 13D). The highest swimming speed of sperm-templated micromotors can reach 6.8 ±4.1 μms −1(0.2 body length/s). 294 The second method of preparing biohybrid micromotors is to cloak functionalized synthetic nanomaterials with cell membranes. This method can enhance the biocompatibility of micromotors to the largest extent and avoids recognition by the immune system. Recently, cell membranes/vesicles from red blood cells (RBCs) 296 (Figure 13E), platelets 215 (Figure 13F), and even dual cells (e.g., RBCs and platelets 297 ) were utilized as camouflage to cover the surface of functionalized synthetic nanomaterials. The magnetic nanoparticles embedded into these biohybrid nanomachines play a role in magnetic guidance. The locomotion of these cell-based biohybrids can be powered by a magnetic field or other driving forces. For example, the random movement pattern of a Janus RBC-Mg motor can be driven by hydrogen bubbles generated by the reaction of Mg and water. The addition of Fe3O4nanoparticles to the Janus micromotors can make the miniaturized machines move precisely along a predetermined path. 296 The third method to fabricate hybrid small-scale swimmers consists of combining active locomotive cells that are born with flagella, among which sperm and bacteria are widely used. 31,68,298−301 In this method, the motile cell either adheres to the surface of a synthetic particle (normally in the micrometer scale) or another cell or be trapped into a special microstructure. For example, bacteria-driven microswimmers were fabricated by attaching a single E. coli. bacterium to a drug-loaded polyelectrolyte microparticle via viscoelastic connection of the bacteria−particle interface (Figure 13G). The E. coli-powered motor exhibited the chemotaxis behavior under a chemical concentration gradient. Fe3O4nanoparticles embedded within the polyelectrolyte microparticles functioned as a steering wheel, thus providing the biohybrid motors with directional control over the directionality and enabling guidance of the drug-loaded swimmers to target breast cancer cells in vitro. 68 Similarly, the magnetic guidance was also employed in bacterium-RBC micromotors, which were fabricated through the strong conjugation chemistry between the erythrocyte and E. coli bacterium (Figure 13H). In addition, negatively charged microalgae with ellipsoidal morphologies (i.e., Chlamydomonas reinhardtii algal) were integrated with positively charged polyelectrolyte-functionalized magnetic microsphere via electrostatic interactions (Figure 13I). The motile microalgae function as an actuator while the microparticle can be used for cargo encapsulation and magnetic steering. 293 In addition, various customized magnetic microstructures (such as tetrapod, 31 microtube, 298 and helix 247 ) have been prepared to capture the task-carrying spermatozoa to form sperm-hybrid microrobots (known as “spermbots”). Sperm cells with high vitality serve as a motile component of hybrid microrobots to complete specific tasks, for example, targeted drug delivery, 31 as shown in Figure 13J. However, they can also act as carriers when they have motility deficiencies. In such cases, the remotely controlled assisted fertilization relies on the synthetic magnetic microstructures of spermbots under the guidance of external magnetic fields. 302 The fourth approach consists of adopting a live immune cell to engulf the whole magnetic passive functional materials by taking advantage of the phagocytosis processes of immune cells. 303 As a consequence, biohybrid “immunobots”, 304 as termed by Metin Sitti’s group, can be formed. After a magnetic double-helical microswimmer was completely internalized by a macrophage, the biohybrid macrophage-based MagRobots were able to perform magnetically driven rolling locomotion along predetermined trajectories by steering the magnetic helical component. The robots were able to swim uninterruptedly even with the presence of cells blocking their pathway. In the absence of a magnetic field, the immunobots could autonomously move by crawling and actuated by the self-propelled movement of the macrophages in a biological environment (Figure 13K). 304 5. APPLICATIONS 5.1. Targeted Drug/Gene Delivery The precise and efficient transportation of therapeutic payloads to target sites, especially to those confined and hard-to-reach locations of the body, is challenging for passive drug delivery systems. The past decade has witnessed a boom in the development of active smart drug delivery systems using external field-driven miniaturized microand nanomotors. Particularly, magnetically driven micro and nanorobots offer several advantages as small agents for targeted cargo delivery including but not limited to remote, precise, and minimally invasive maneuverability, and potential recyclability of residual administered drug-carriers, which often results in serious side effects to healthy organs and tissues. 306−309 In most cases, very low field strength (in the mT range) is sufficient for the actuation of MagRobots without causing damage to healthy cells. Before the steerable delivery of cargos (e.g., molecules, drugs, genes), the cargo loading or capture process is needed. The loading of cargos is often conducted by encapsulating them inside the MagRobot structure or by attaching them to the MagRobot surface. The encapsulation process can be directly carried out during MagRobot fabrication while the surface attachment (or adhesion) process can be made using superficial functional groups of biohybrid or synthetic MagRobots. Various organic or inorganic artificial nanomaterials (e.g., Au/Ni/Si nanospears, 310 hydrogel-based helical microswimmers, 127 Janus Au/Ni/SiO2microparticles, 311 etc.) and biogenic materials (such as pollen grains, 288 sperm cells, 176 bacteria, 35,305,312 erythrocytes, 313 and microalgae 246,293 ) have been developed as functional or structural carriers to encapsulate or carry molecules, drugs, genes, or cells. For example, Fe-coated biotubes, which exhibit a drill-like motion under high-angular frequency magnetic fields, were capable of transporting camptothecin (i.e., an anticancer model drug) and delivering it to specific sites, killing the targeted HeLa cells in vitro (Figure 14A). 314 Chemical Reviews pubs.acs.org/CR Review https://doi.org/10.1021/acs.chemrev.0c01234 Chem. Rev. 2021, 121, 4999−5041 5019 Considering the complexity of the human body’s environments, it is key to investigate the propulsion mechanisms of MagRobots and strategies for cargo delivery and release under complicated physiological conditions in different body fluids such as gastric juice, saliva, and blood. Recently, a cell-sized Janus micromotor loaded with antibodies as receptors for the recognition of target cells and anticancer drugs was able to navigate in a simulated blood circulation system (Figure 14B). 311 Although the propulsion of MagRobots was weakened under dynamic flow conditions, the ability of active upstream locomotion in the bloodstream was confirmed in flat and 3D surfaces. Furthermore, the utilization of biohybrid micromotors combining sperm cells and synthetic magnetic micro and nanoarchitectures to deliver anticoagulant agents (i.e., heparin) in the bloodstream was reported (Figure 14C), 176 which is promising for treating diseases of the circulatory system such as thrombotic clots. In addition to drugs, targeted transport of genes (e.g., plasmid DNA) to a single cell and subsequent transfection was achieved by the utilization of helical micromotors under the actuation and navigation of low-strength rotating magnetic fields (Figure 14D). 218 Recently, Peer Fischer’s group reported targeted transfection and gene delivery by using biocompatible FePt nanopropellers under rotating millitesla fields. 315 After delivering payloads to a specific location, cargo molecules can be released naturally via diffusion or via specific stimuli (such as pH, 265 temperature, 266 light irradiation, 67 or chemical changes at the disease site) according to the practical application requirement. For example, because the concentration of matrix metalloproteinase-2 (MMP-2) enzyme at the tumor site is higher than that at normal physiological conditions, hydrogel-based helical microswimmers demonFigure 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. Chemical Reviews pubs.acs.org/CR Review https://doi.org/10.1021/acs.chemrev.0c01234 Chem. Rev. 2021, 121, 4999−5041 5020 strate a quicker response to the evaluated concentration of MMP-2 enzyme, resulting in a boost-release of embedded cargo (i.e., antibody-tagged Fe3O4nanoparticles) through the swell behavior of the hydrogel. 127 The released antibodytagged payloads from the micromotors can be further used for active labeling of targeted tumor cells (Figure 14E). 5.2. Cell Manipulation Cell manipulation is the practice of maneuvering the physical position of cells to separate them from the milieu of other phenotypically different cells (i.e., cell-based screen), guiding them into a specific target position (e.g., for fertilization), or organizing themselves in vitro. With the rapid advance of proteomics and genomics, it is of great significance to develop sophisticated tools for single-cell manipulation, especially massively parallel single-cell manipulation. 316 Magnetically powered miniaturized robots are capable of 3D manipulation of a single cell in terms of capture, transport, sorting, isolation, and pattering, with excellent maneuverability and high precision at the nanoand microscale in complex physiological environments without changing the intrinsic properties of the cells. 317,318 For instance, trapping of breast cancer cells was reported by tosyl-functionalized superparamagnetic microbeads due to the instantaneous strong binding between the tosyl groups from the surface of microswimmers and the −NH2 groups from the membrane proteins of cancer cells. Manipulation of single or multiple cell-laden microrobots was achieved by the propulsion of oxygen bubbles and manual direction guidance using a neodymium magnet (Figure 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. Chemical Reviews pubs.acs.org/CR Review https://doi.org/10.1021/acs.chemrev.0c01234 Chem. Rev. 2021, 121, 4999−5041 5021 15A). 209 Arranging cells to achieve predetermined patterns with the assistance of an arrayed substrate was implemented through single-cell pick-up and subsequent delivery using magnetically propelled peanut-like micromotors (Figure 15B). 169 To aid sperm cells with defective locomotion features to complete their fertilization task, Oliver G. Schmidt’s group designed several motile nano/micromotors as assisted tools 302 such as magnetic microcarriers with a cylindrical cavity and a helical body 319 and a magnetic helix 247 (Figure 15C). Moreover, magnetically driven micromotors provide an invasive way to transfer zygotes through the uterus and fallopian tube (Figure 15D), and magnetic microrobots with spiral shapes exhibit higher maneuverability in terms of capture and transfer of the zygotes between different physiological environments than those with helical shapes. 320 Transportation of neural progenitor cells was conducted by the corkscrew-like motion of magnetically powered soft microswimmers containing piezoelectric polymer and CoFe2O4magnetic nanoparticles under a rotating magnetic field. Subsequent neuronal differentiation of PC12 cells was induced by the acoustic stimulation due to the utilization of piezoelectric polymer as a stimuliresponsive cell electrostimulation platform (Figure 15E). 216 Furthermore, Kim et al. 321 precisely manipulated a neuronloaded magnetic microrobot to a gap between two neural clusters to connect broken neural networks. Recently, successful trials of magnetically powering microrobots toward a target site (such as a liver tumor micro-organ, ventricle of mouse brain, blood vessel of rat brain, and live mouse) using in vitro,ex vivo, and in vivo experimental models, indicate the 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. Chemical Reviews pubs.acs.org/CR Review https://doi.org/10.1021/acs.chemrev.0c01234 Chem. Rev. 2021, 121, 4999−5041 5022 feasibility of adopting MagRobots for the purpose of targeted stem cell transport and transplantation (Figure 15F). 121 5.3. Minimally Invasive Surgery Miniaturized machines that are capable of precisely opening specific cell membranes to kill abnormal cells and even achieve intracellular delivery of various drugs (including DNA) are promising candidates for noninvasive surgery. 322,323 Nano/ microrobots that project sharp tips or have the ability to perform a corkscrew-like movement can execute drilling under the application of a rotating magnetic field. The drilling feature can be harnessed to penetrate tissue with high precision, holding great promise to perform untethered microsurgeries. As shown in Figure 16A, microdrillers (tubular Ti/Cr/Fe microdrillers with sharp tips) were able to penetrate into a section of porcine liver tissue via magnetically driven mechanical drilling. To make the microdriller “stand up”to drill, a specific angular frequency threshold of the rotating field (in correlation with the viscosity of media) is required to transform the horizontal rotation mode into a vertical rotation mode. 41 Other representative microdrillers are Fe-coated calcified biotubes containing pointed ends, which are extracted from Dracaenea marginata leafs. Upon magnetic actuation, the microdagger stabbed into the cellular membranes of HeLa cells with a drill-like motion, finally resulting in cell death. In addition, the ability to drill into a target cell can be utilized for subsequent drug delivery because the porous structures of calcified biotubes endow the microdriller with the capacity of drug loading. 314 A millimeter-sized magnetic driller can be navigated in a 3D vascular channel and perforate a blood clot in a simulated thrombosis model environment, providing an application potential for cardiovascular disorders (Figure 16B). 324 Besides, surface walkers also can open the cell membrane. Recently, we developed Au/Ag/Ni microwires that display walking movement under a transversal rotating magnetic field. Because of the rigidness of the microwires, they can only perform a drilling movement. To make the structure of microwires slightly bent, an Ag segment was partly etched by concentrated H2O2solution. As a consequence, a surface tumbling motion 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. Chemical Reviews pubs.acs.org/CR Review https://doi.org/10.1021/acs.chemrev.0c01234 Chem. Rev. 2021, 121, 4999−5041 5023 flexible, wire-like, and biohybrid MagRobots are summarized, followed by various state-of-the-art applications in the field of biomedicine and environment. The considerable application potential of micro/nanorobots in the biomedical area, such as targeted drug/gene delivery, localized bioanalysis, cell sorting, microsurgery, biopsy, detoxification, biofilm removal, and biosensing becomes a driving force that attracts an increasing number of scientists to join in this emerging research field. 143,409 In addition, before implementing MagRobots in real applications, the following aspects should be taken into consideration: (i) MagRobots’materials should meet the standards of practical biomedical and environmental applications, such as biocompatibility and biodegradability, and bring economic and social benefit. For instance, expensive materials and fabrication apparatus or complicated preparation procedures limit the mass production of synthetic microstructures. This is a challenge that researchers face today and should be solved in the future. (ii) To enhance the work efficiency of MagRobots in complex environments, swarms or collective behavior of synthetic MagRobots can be regulated to cooperatively and efficiently execute complex biological or environmental missions that would be insurmountable for a single MagRobot. Moreover, reconfigurability provides another strategy for MagRobots to adapt to variational biological surroundings. For instance, the intriguing collective behavior from the self-assembly of nanoparticles could present a reversible pattern transformation (i.e., reconfigurability) under the steering of an external field, enhancing MagRobots’ tasking capabilities and high environmental adaptability. Finally, great endeavors have been made to navigate these untethered microrobots in various complex body fluids such as blood, gastric juice, urine, cerebrospinal fluid, 216 and intracellular medium. However, given the complexity of biological fluids, the relation between movement behaviors of MagRobots and environment parameters (e.g., the components, temperature, viscosity, boundaries, the flow speed of the biological fluids, etc.) are expected to be theoretically and experimentally established in order to obtain better control of MagRobots. (iii) Precise maneuvering of MagRobots on-body and in real-time is very important and their monitoring is essential. This is a challenge confronted by micro/nanorobots researchers. Clinical imaging systems in current use, such as MRI as discussed in Section 5.6, can help in terms of visualization and as an actuation source. However, there is still room to improve MagRobots’programmability in terms of orientation, locomotion, and even morphology. In this way, if MagRobots can be controlled and altered according to actual conditions or occasions such as the patient’s health status and physiology, then MagRobots will be able to perform precise and personalized therapy. In summary, a good understanding of the mechanism of magnetically driven micro/nanorobots and corresponding impact factors (e.g., geometrical shape, field configuration, fluids properties, and boundary) is a precondition for the conceptualization, functionalization, and automation of MagRobots. High spatial maneuverability, fast reconfigurability, and precise programmability are the ultimate research goals of small-scale robots (see Figure 22). Although there is a long way to go to translate robust minimized robots from bench to bedside, considerable advances are bringing fantasy closer to reality. AUTHOR INFORMATION Corresponding Author Martin Pumera −Center for Advanced Functional Nanorobots, Department of Inorganic Chemistry, University of Chemistry and Technology Prague, 166 28 Prague 6, 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. Chemical Reviews pubs.acs.org/CR Review https://doi.org/10.1021/acs.chemrev.0c01234 Chem. Rev. 2021, 121, 4999−5041 5030 Czech Republic; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan; Department of Chemistry and Biochemistry, Mendel University in Brno, CZ-613 00 Brno, Czech Republic; Department of Chemical and Biomolecular Engineering, Yonsei University, Seodaemun-gu, Seoul 03722, Korea; Future Energy and Innovation Laboratory, Central European Institute of Technology, Brno University of Technology, Brno CZ-612 00, Czech Republic; orcid.org/ 0000-0001-5846-2951; Email: pumera.research@ gmail.com Authors Huaijuan Zhou −Center for Advanced Functional Nanorobots, Department of Inorganic Chemistry, University of Chemistry and Technology Prague, 166 28 Prague 6, Czech Republic; orcid.org/0000-0002-9289-3613 Carmen C. Mayorga-Martinez −Center for Advanced Functional Nanorobots, Department of Inorganic Chemistry, University of Chemistry and Technology Prague, 166 28 Prague 6, Czech Republic; orcid.org/0000-0003-36870035 Salvador Pané−Multi-Scale Robotics Lab (MSRL), Institute of Robotics and Intelligent Systems (IRIS), ETH Zurich, 8092 Zurich, Switzerland; orcid.org/0000-0003-01478287 Li Zhang −Department of Mechanical and Automation Engineering, The Chinese University of Hong Kong, Hong Kong 999077, China; orcid.org/0000-0003-1152-8962 Complete contact information is available at: https://pubs.acs.org/10.1021/acs.chemrev.0c01234 Notes The authors declare no competing financial interest. Biographies Huaijuan Zhou is currently a Marie Skłodowska-Curie Actions (MSCA) Fellow at the University of Chemistry and Technology Prague, Czech Republic. She received her Ph.D. degree in 2016 from the University of Chinese Academy of Sciences under the supervision of Prof. Ping Jin. She has a broad research interest in designing, preparing, and characterizing functional nanothin films, semiconductor materials, field-induced chromic materials, energy conversion materials, lithium battery materials, biomaterials, and locomotive micro/nanomachines for energy conservation/conversion/storage, biomedical engineering, and environmental remediation. Carmen C. Mayorga-Martinez is currently the Kralupy Unit Leader and senior scientist at the Center for Advanced Functional Nanorobots, UCT-Prague. She was research fellow in the nanobioelectronics and biosensors group/ICN2, Barcelona-Spain, and in Nanyang Technological University, Singapore. She completed her Ph.D. degree in National University of Tucuman, Argentina, in 2009. Currently, her main research fields include development of bio/ sensors based on 2D materials and nanoparticles platforms functionalized with bioreceptors (enzyme, DNA, and antibodies) as well as micro/nanomotors for biomedical applications and environmental monitoring. Moreover, she is also interested in 2D-materials catalysis for energy application. Salvador Paneis currently codirector of the Multi-Scale Robotics Lab and a titular professor at ETH Zurich, leading the group of Materials for Robotics at the Institute of Robotics and Intelligent Systems (IRIS), ETH Zurich. He received his Ph.D. in chemistry (2008) from the Universitat de Barcelona in the field of the electrodeposition of magnetic materials. He became a postdoctoral researcher at IRIS in August 2008 and senior research scientist in 2012. Prof. Paneis currently working on bridging materials science, chemistry, and electrochemistry with small-scale robotics for various applications. Li Zhang received his Ph.D. degree from the University of Basel, Basel, Switzerland, in 2007. He joined the Institute of Robotics and Intelligent Systems (IRIS), Swiss Federal Institute of Technology (ETH) Zurich, Switzerland, as a Postdoctoral Fellow, in 2007 and as a Senior Scientist from 2009 to 2012. He is currently an Associate Professor in the Department of Mechanical and Automation Engineering, The Chinese University of Hong Kong (CUHK), Hong Kong SAR, China. His main research interests include micro and nanorobotics for biomedical applications and their collective behaviors for the development of small-scale robot swarms. Dr. Zhang received the Hong Kong RGC Early Career Award in 2013 and several awards from IEEE conferences such as ICRA, IROS, CASE, ICARM, and NANOMED. He is a Distinguished Lecturer appointed by the IEEE NTC. Martin Pumera is Director of the Center for Advanced Functional Nanorobots and a Distinguished Professor of Chemistry at University of Chemistry and Technology, Prague, and Chief Investigator of Future Energy and Innovation Lab at CEITEC, Brno, Czech Republic. He received his Ph.D. from Charles University, Czech Republic, in 2001. After two postdoctoral stays, in 2006 he became tenured group leader at the National Institute for Materials Science (NIMS), Japan. In 2010, he joined Nanyang Technological University, Singapore, as a tenured associate professor for nearly a decade. He has broad interests in nanomaterials and microsystems and in specific areas of electrochemistry and synthetic chemistry of 2D nanomaterials, nanotoxicity, micro and nanomachines, and 3D printing. ACKNOWLEDGMENTS M.P. acknowledges the support from the project Advanced Functional Nanorobots (Reg. No. CZ.02.1.01/0.0/0.0/ 15_003/0000444 financed by the EFRR). S.P. acknowledges support from the ERC-2017-CoG HINBOTS Grant No. 771565. M.P. was supported by Ministry of Education, Youth and Sports (Czech Republic) Grant No. LL2002 under ERCCZ program. L.Z. would like to thank the financial support from the Hong Kong Research Grants Council (RGC) under Project No. JLFS/E-402/18, the ITF Projects under Projects MRP/036/18X and ITS/374/18FP funded by the HKSAR Innovation and Technology Commission (ITC), the Hong Kong Croucher Foundation project under Ref. No. CAS20403, the Research Sustainability of Major RGC Funding Schemes, and the Direct Grant from CUHK, as well as support from the Multiscale Medical Robotics Center (MRC), InnoHK, at the Hong Kong Science Park. REFERENCES (1) Terzopoulou, A.; Nicholas, J. D.; Chen, X.-Z.; Nelson, B. J.; Pané, S.; Puigmartí-Luis, J. Metal-Organic Frameworks in Motion. Chem. Rev. 2020,120, 11175−11193. (2) Li, J.; Esteban-Fernández de Avila, B.; Gao, W.; Zhang, L.; Wang, J. Micro/Nanorobots for Biomedicine: Delivery, Surgery, Sensing, and Detoxification. Sci. Robot. 2017,2, No. eaam6431. (3) Li, T.; Li, J.; Morozov, K. I.; Wu, Z.; Xu, T.; Rozen, I.; Leshansky, A. M.; Li, L.; Wang, J. Highly Efficient Freestyle Magnetic Nanoswimmer. Nano Lett. 2017,17, 5092−5098. (4) Yan, X.; Zhou, Q.; Yu, J.; Xu, T.; Deng, Y.; Tang, T.; Feng, Q.; Bian, L.; Zhang, Y.; Ferreira, A.; et al. Magnetite Nanostructured Chemical Reviews pubs.acs.org/CR Review https://doi.org/10.1021/acs.chemrev.0c01234 Chem. Rev. 2021, 121, 4999−5041 5031 Porous Hollow Helical Microswimmers for Targeted Delivery. Adv. Funct. Mater. 2015,25, 5333−5342. (5) Ying, Y.; Pourrahimi, A. M.; Sofer, Z.; Matejková, S.; Pumera, M. Radioactive Uranium Preconcentration via Self-Propelled Autonomous Microrobots Based on Metal-Organic Frameworks. ACS Nano 2019,13, 11477−11487. (6) Mou, F.; Chen, C.; Ma, H.; Yin, Y.; Wu, Q.; Guan, J. SelfPropelled Micromotors Driven by the Magnesium-Water Reaction and Their Hemolytic Properties. Angew. Chem., Int. Ed. 2013,52, 7208−7212. (7) Orozco, J.; Jurado-Sánchez, B.; Wagner, G.; Gao, W.; VazquezDuhalt, R.; Sattayasamitsathit, S.; Galarnyk, M.; Cortés, A.; Saintillan, D.; Wang, J. Bubble-Propelled Micromotors for Enhanced Transport of Passive Tracers. Langmuir 2014,30, 5082−5087. (8) Wang, H.; Zhao, G.; Pumera, M. Beyond Platinum: BubblePropelled Micromotors Based on Ag and MnO2 Catalysts. J. Am. Chem. Soc. 2014,136, 2719−2722. (9) Patino, T.; Arqué, X.; Mestre, R.; Palacios, L.; Sánchez, S. Fundamental Aspects of Enzyme-Powered Microand Nanoswimmers. Acc. Chem. Res. 2018,51, 2662−2671. (10) Kong, L.; Rosli, N. F.; Chia, H. L.; Guan, J.; Pumera, M. SelfPropelled Autonomous Mg/Pt Janus Micromotor Interaction with Human Cells. Bull. Chem. Soc. Jpn. 2019,92, 1754−1758. (11) Wang, B.; Ji, F.; Yu, J.; Yang, L.; Wang, Q.; Zhang, L. BubbleAssisted Three-Dimensional Ensemble of Nanomotors for Improved Catalytic Performance. iScience 2019,19, 760−771. (12) Ma, W.; Wang, H. Magnetically Driven Motile Superhydrophobic Sponges for Efficient Oil Removal. Appl. Mater. Today 2019,15, 263−266. (13) Dong, M.; Wang, X.; Chen, X.-Z.; Mushtaq, F.; Deng, S.; Zhu, C.; Torlakcik, H.; Terzopoulou, A.; Qin, X.-H.; Xiao, X.; et al. 3DPrinted Soft Magnetoelectric Microswimmers for Delivery and Differentiation of Neuron-Like Cells. Adv. Funct. Mater. 2020,30, 1910323. (14) Zeeshan, M. A.; Pané, S.; Youn, S. K.; Pellicer, E.; Schuerle, S.; Sort, J.; Fusco, S.; Lindo, A. M.; Park, H. G.; Nelson, B. J. Graphite Coating of Iron Nanowires for Nanorobotic Applications: Synthesis, Characterization and Magnetic Wireless Manipulation. Adv. Funct. Mater. 2013,23, 823−831. (15) Ying, Y.; Pourrahimi, A. M.; Manzanares-Palenzuela, C. L.; Novotny, F.; Sofer, Z.; Pumera, M. Light-Driven ZnO Brush-Shaped Self-Propelled Micromachines for Nitroaromatic Explosives Decomposition. Small 2020,16, 1902944. (16) Pourrahimi, A. M.; Villa, K.; Ying, Y.; Sofer, Z.; Pumera, M. ZnO/ZnO2/Pt Janus Micromotors Propulsion Mode Changes with Size and Interface Structure: Enhanced Nitroaromatic Explosives Degradation under Visible Light. ACS Appl. Mater. Interfaces 2018,10, 42688−42697. (17) Wang, J.; Xiong, Z.; Zheng, J.; Zhan, X.; Tang, J. Light-Driven Micro/Nanomotor for Promising Biomedical Tools: Principle, Challenge, and Prospect. Acc. Chem. Res. 2018,51, 1957−1965. (18) Pourrahimi, A. M.; Villa, K.; Manzanares Palenzuela, C. L.; Ying, Y.; Sofer, Z.; Pumera, M. Catalytic and Light-Driven ZnO/Pt Janus Nano/Micromotors: Switching of Motion Mechanism via Interface Roughness and Defect Tailoring at the Nanoscale. Adv. Funct. Mater. 2019,29, 1808678. (19) Nocentini, S.; Parmeggiani, C.; Martella, D.; Wiersma, D. S. Optically Driven Soft Micro Robotics. Adv. Opt. Mater. 2018,6, 1800207. (20) Palagi, S.; Singh, D. P.; Fischer, P. Light-Controlled Micromotors and Soft Microrobots. Adv. Opt. Mater. 2019,7, 1900370. (21) Sridhar, V.; Podjaski, F.; Kröger, J.; Jiménez-Solano, A.; Park, B.-W.; Lotsch, B. V.; Sitti, M. Carbon Nitride-Based Light-Driven Microswimmers with Intrinsic Photocharging Ability. Proc. Natl. Acad. Sci. U. S. A. 2020,117, 24748. (22) Aghakhani, A.; Yasa, O.; Wrede, P.; Sitti, M. Acoustically Powered Surface-Slipping Mobile Microrobots. Proc. Natl. Acad. Sci. U. S. A. 2020,117, 3469. (23) Ren, L.; Nama, N.; McNeill, J. M.; Soto, F.; Yan, Z.; Liu, W.; Wang, W.; Wang, J.; Mallouk, T. E. 3D Steerable, Acoustically Powered Microswimmers for Single-Particle Manipulation. Sci. Adv. 2019,5, No. eaax3084. (24) Esteban-Fernández de Avila, B.; Angsantikul, P.; RamírezHerrera, D. E.; Soto, F.; Teymourian, H.; Dehaini, D.; Chen, Y.; Zhang, L.; Wang, J. Hybrid Biomembrane-Functionalized Nanorobots for Concurrent Removal of Pathogenic Bacteria and Toxins. Sci. Robot. 2018,3, No. eaat0485. (25) Xu, T.; Xu, L.-P.; Zhang, X. Ultrasound Propulsion of Micro-/ Nanomotors. Appl. Mater. Today 2017,9, 493−503. (26) Loget, G.; Kuhn, A. Electric Field-Induced Chemical Locomotion of Conducting Objects. Nat. Commun. 2011,2, 535. (27) Chang, S. T.; Paunov, V. N.; Petsev, D. N.; Velev, O. D. Remotely Powered Self-Propelling Particles and Micropumps Based on Miniature Diodes. Nat. Mater. 2007,6, 235−240. (28) Calvo-Marzal, P.; Sattayasamitsathit, S.; Balasubramanian, S.; Windmiller, J. R.; Dao, C.; Wang, J. Propulsion of Nanowire Diodes. Chem. Commun. 2010,46, 1623−1624. (29) Erkoc, P.; Yasa, I. C.; Ceylan, H.; Yasa, O.; Alapan, Y.; Sitti, M. Mobile Microrobots for Active Therapeutic Delivery. Adv. Ther. 2019, 2, 1800064. (30) Singh, A. V.; Ansari, M. H.; Mahajan, M.; Srivastava, S.; Kashyap, S.; Dwivedi, P.; Pandit, V.; Katha, U. Sperm Cell Driven Microrobots - Emerging Opportunities and Challenges for Biologically Inspired Robotic Design. Micromachines 2020,11, 448. (31) Xu, H.; Medina-Sánchez, M.; Magdanz, V.; Schwarz, L.; Hebenstreit, F.; Schmidt, O. G. Sperm-Hybrid Micromotor for Targeted Drug Delivery. ACS Nano 2018,12, 327−337. (32) Vizsnyiczai, G.; Frangipane, G.; Maggi, C.; Saglimbeni, F.; Bianchi, S.; Di Leonardo, R. Light Controlled 3D Micromotors Powered by Bacteria. Nat. Commun. 2017,8, 15974. (33) Alapan, Y.; Yasa, O.; Yigit, B.; Yasa, I. C.; Erkoc, P.; Sitti, M. Microrobotics and Microorganisms: Biohybrid Autonomous Cellular Robots. Annu. Rev. Control, Robot. and Autonom. Syst. 2019,2, 205− 230. (34) Zhuang, J.; Park, B.-W.; Sitti, M. Propulsion and Chemotaxis in Bacteria-Driven Microswimmers. Adv. Sci. 2017,4, 1700109. (35) Mostaghaci, B.; Yasa, O.; Zhuang, J.; Sitti, M. Bioadhesive Bacterial Microswimmers for Targeted Drug Delivery in the Urinary and Gastrointestinal Tracts. Adv. Sci. 2017,4, 1700058. (36) Singh, A. V.; Sitti, M. Patterned and Specific Attachment of Bacteria on Biohybrid Bacteria-Driven Microswimmers. Adv. Healthcare Mater. 2016,5, 2325−2331. (37) Zhuang, J.; Wright Carlsen, R.; Sitti, M. pH-Taxis of Biohybrid Microsystems. Sci. Rep. 2015,5, 11403. (38) Jia, H.; Mailand, E.; Zhou, J.; Huang, Z.; Dietler, G.; Kolinski, J. M.; Wang, X.; Sakar, M. S. Universal Soft Robotic Microgripper. Small 2019,15, 1803870. (39) Breger, J. C.; Yoon, C.; Xiao, R.; Kwag, H. R.; Wang, M. O.; Fisher, J. P.; Nguyen, T. D.; Gracias, D. H. Self-Folding ThermoMagnetically Responsive Soft Microgrippers. ACS Appl. Mater. Interfaces 2015,7, 3398−3405. (40) Leong, T. G.; Randall, C. L.; Benson, B. R.; Bassik, N.; Stern, G. M.; Gracias, D. H. Tetherless Thermobiochemically Actuated Microgrippers. Proc. Natl. Acad. Sci. U. S. A. 2009,106, 703. (41) Xi, W.; Solovev, A. A.; Ananth, A. N.; Gracias, D. H.; Sanchez, S.; Schmidt, O. G. Rolled-up Magnetic Microdrillers: Towards Remotely Controlled Minimally Invasive Surgery. Nanoscale 2013,5, 1294−1297. (42) Parmar, J.; Vilela, D.; Pellicer, E.; Esqué-De los Ojos, D.; Sort, J.; Sánchez, S. Reusable and Long-Lasting Active Microcleaners for Heterogeneous Water Remediation. Adv. Funct. Mater. 2016,26, 4152−4161. (43) Mushtaq, F.; Chen, X.; Staufert, S.; Torlakcik, H.; Wang, X.; Hoop, M.; Gerber, A.; Li, X.; Cai, J.; Nelson, B. J.; et al. On-the-Fly Catalytic Degradation of Organic Pollutants Using Magneto-Photoresponsive Bacteria-Templated Microcleaners. J. Mater. Chem. A 2019,7, 24847−24856. Chemical Reviews pubs.acs.org/CR Review https://doi.org/10.1021/acs.chemrev.0c01234 Chem. Rev. 2021, 121, 4999−5041 5032 (44) Srivastava, S. K.; Medina-Sánchez, M.; Schmidt, O. G. Autonomously Propelled Microscavengers for Precious Metal Recovery. Chem. Commun. 2017,53, 8140−8143. (45) Li, J.; Pumera, M. 3D Printing of Functional Microrobots. Chem. Soc. Rev. 2021,50, 2794. (46) Mirkovic, T.; Zacharia, N. S.; Scholes, G. D.; Ozin, G. A. Fuel for Thought: Chemically Powered Nanomotors Out-Swim Nature’s Flagellated Bacteria. ACS Nano 2010,4, 1782−1789. (47) Sánchez, S.; Soler, L.; Katuri, J. Chemically Powered Microand Nanomotors. Angew. Chem., Int. Ed. 2015,54, 1414−1444. (48) Sitti, M.; Wiersma, D. S. Pros and Cons: Magnetic versus Optical Microrobots. Adv. Mater. 2020,32, 1906766. (49) Villa, K.; Pumera, M. Fuel-Free Light-Driven Micro/Nanomachines: Artificial Active Matter Mimicking Nature. Chem. Soc. Rev. 2019,48, 4966−4978. (50) Chen, X.-Z.; Jang, B.; Ahmed, D.; Hu, C.; De Marco, C.; Hoop, M.; Mushtaq, F.; Nelson, B. J.; Pané, S. Small-Scale Machines Driven by External Power Sources. Adv. Mater. 2018,30, 1705061. (51) Xu, T.; Gao, W.; Xu, L.-P.; Zhang, X.; Wang, S. Fuel-Free Synthetic Micro-/Nanomachines. Adv. Mater. 2017,29, 1603250. (52) Rao, K. J.; Li, F.; Meng, L.; Zheng, H.; Cai, F.; Wang, W. A Force to Be Reckoned With: A Review of Synthetic Microswimmers Powered by Ultrasound. Small 2015,11, 2836−2846. (53) Erin, O.; Boyvat, M.; Tiryaki, M. E.; Phelan, M.; Sitti, M. Magnetic Resonance Imaging System-Driven Medical Robotics. Adv. Intell. Syst. 2020,2, 1900110. (54) Martel, S. Beyond imaging: Macroand microscale medical robots actuated by clinical MRI scanners. Sci. Robot. 2017,2, No. eaam8119. (55) Wang, Q.; Yang, L.; Wang, B.; Yu, E.; Yu, J.; Zhang, L. Collective Behavior of Reconfigurable Magnetic Droplets via Dynamic Self-Assembly. ACS Appl. Mater. Interfaces 2019,11, 1630−1637. (56) Xie, H.; Sun, M.; Fan, X.; Lin, Z.; Chen, W.; Wang, L.; Dong, L.; He, Q. Reconfigurable Magnetic Microrobot Swarm: Multimode Transformation, Locomotion, and Manipulation. Sci. Robot. 2019,4, No. eaav8006. (57) Wang, H.; Pumera, M. Coordinated Behaviors of Artificial Micro/Nanomachines: from Mutual Interactions to Interactions with the Environment. Chem. Soc. Rev. 2020,49, 3211−3230. (58) Liu, J. A. C.; Gillen, J. H.; Mishra, S. R.; Evans, B. A.; Tracy, J. B. Photothermally and Magnetically Controlled Reconfiguration of Polymer Composites for Soft Robotics. Sci. Adv. 2019,5, No. eaaw2897. (59) Hen-Wei, H.; Sakar, M. S.; Riederer, K.; Shamsudhin, N.; Petruska, A.; Pané, S.; Nelson, B. J. 2016 IEEE Int. Conference on Robot. Autom.; ICRA, 2016; pp 1719−1724. (60) Huang, H.-W.; Huang, T.-Y.; Charilaou, M.; Lyttle, S.; Zhang, Q.;Pané,S.;Nelson,B.J.InvestigationofMagnetotaxisof Reconfigurable Micro-Origami Swimmers with Competitive and Cooperative Anisotropy. Adv. Funct. Mater. 2018,28, 1802110. (61) Kim, J.; Chung, S. E.; Choi, S.-E.; Lee, H.; Kim, J.; Kwon, S. Programming Magnetic Anisotropy in Polymeric Microactuators. Nat. Mater. 2011,10, 747−752. (62) Yigit, B.; Alapan, Y.; Sitti, M. Programmable Collective Behavior in Dynamically Self-Assembled Mobile Microrobotic Swarms. Adv. Sci. 2019,6, 1801837. (63) Huang, H.-W.; Sakar, M. S.; Petruska, A. J.; Pané, S.; Nelson, B. J. Soft Micromachines with Programmable Motility and Morphology. Nat. Commun. 2016,7, 12263. (64) Cui, J.; Huang, T.-Y.; Luo, Z.; Testa, P.; Gu, H.; Chen, X.-Z.; Nelson, B. J.; Heyderman, L. J. Nanomagnetic Encoding of ShapeMorphing Micromachines. Nature 2019,575, 164−168. (65) Ren, L.; Wang, W.; Mallouk, T. E. Two Forces Are Better than One: Combining Chemical and Acoustic Propulsion for Enhanced Micromotor Functionality. Acc. Chem. Res. 2018,51, 1948−1956. (66) Ahmed, D.; Baasch, T.; Blondel, N.; Läubli, N.; Dual, J.; Nelson, B. J. Neutrophil-Inspired Propulsion in a Combined Acoustic and Magnetic Field. Nat. Commun. 2017,8, 770. (67) Bozuyuk, U.; Yasa, O.; Yasa, I. C.; Ceylan, H.; Kizilel, S.; Sitti, M. Light-Triggered Drug Release from 3D-Printed Magnetic Chitosan Microswimmers. ACS Nano 2018,12, 9617−9625. (68) Park, B.-W.; Zhuang, J.; Yasa, O.; Sitti, M. Multifunctional Bacteria-Driven Microswimmers for Targeted Active Drug Delivery. ACS Nano 2017,11, 8910−8923. (69) Stoddart, J. F. Molecular Machines. Acc. Chem. Res. 2001,34, 410−411. (70) Feringa, B. L. In Control of Motion: From Molecular Switches to Molecular Motors. Acc. Chem. Res. 2001,34, 504−513. (71) Collin, J.-P.; Dietrich-Buchecker, C.; Gavina, P.; JimenezMolero, M. C.; Sauvage, J.-P. Shuttles and Muscles: Linear Molecular Machines Based on Transition Metals. Acc. Chem. Res. 2001,34, 477− 487. (72) Erbas-Cakmak, S.; Leigh, D. A.; McTernan, C. T.; Nussbaumer, A. L. Artificial Molecular Machines. Chem. Rev. 2015,115, 10081− 10206. (73) Ballardini, R.; Balzani, V.; Credi, A.; Gandolfi, M. T.; Venturi, M. Artificial Molecular-Level Machines: Which Energy To Make Them Work? Acc. Chem. Res. 2001,34, 445−455. (74) Liang, X.; Li, L.; Tang, J.; Komiyama, M.; Ariga, K. Dynamism of Supramolecular DNA/RNA Nanoarchitectonics: From Interlocked Structures to Molecular Machines. Bull. Chem. Soc. Jpn. 2020,93, 581−603. (75) Ariga, K. Molecular Tuning Nanoarchitectonics for Molecular Recognition and Molecular Manipulation. ChemNanoMat 2020,6, 870−880. (76) Ariga, K.; Li, J.; Fei, J.; Ji, Q.; Hill, J. P. Nanoarchitectonics for Dynamic Functional Materials from Atomic-/Molecular-Level Manipulation to Macroscopic Action. Adv. Mater. 2016,28, 1251−1286. (77) Nawa-Okita, E.; Nakao, Y.; Yamamoto, D.; Shioi, A. A Molecular Assembly Machine Working under a Quasi-Steady State pH Gradient. Bull. Chem. Soc. Jpn. 2020,93, 604−610. (78) Lancia, F.; Ryabchun, A.; Katsonis, N. Life-like motion driven by artificial molecular machines. Nat. Rev. Chem. 2019,3, 536−551. (79) Pezzato, C.; Cheng, C.; Stoddart, J. F.; Astumian, R. D. Mastering the non-equilibrium assembly and operation of molecular machines. Chem. Soc. Rev. 2017,46, 5491−5507. (80) Ellis, E.; Moorthy, S.; Chio, W.-I. K.; Lee, T.-C. Artificial molecular and nanostructures for advanced nanomachinery. Chem. Commun. 2018,54, 4075−4090. (81) Ricotti, L.; Trimmer, B.; Feinberg, A. W.; Raman, R.; Parker, K. K.; Bashir, R.; Sitti, M.; Martel, S.; Dario, P.; Menciassi, A. Biohybrid Actuators for Robotics: A Review of Devices Actuated by Living Cells. Sci. Robot. 2017,2, No. eaaq0495. (82) Novotny, F.; Wang, H.; Pumera, M. Nanorobots: Machines Squeezed between Molecular Motors and Micromotors. Chem. 2020, 6, 867−884. (83) Wu, Z.; Li, L.; Yang, Y.; Hu, P.; Li, Y.; Yang, S.-Y.; Wang, L. V.; Gao, W. A Microrobotic System Guided by Photoacoustic Computed Tomography for Targeted Navigation in Intestines in Vivo. Sci. Robot. 2019,4, No. eaax0613. (84) Wu, Z.; Chen, Y.; Mukasa, D.; Pak, O. S.; Gao, W. Medical micro/nanorobots in complex media. Chem. Soc. Rev. 2020,49, 8088−8112. (85) Soto, F.; Wang, J.; Ahmed, R.; Demirci, U. Medical Micro/ Nanorobots in Precision Medicine. Adv. Sci. 2020,7, 2002203. (86) Peng, F.; Tu, Y.; Wilson, D. A. Micro/nanomotors towards in vivo application: cell, tissue and biofluid. Chem. Soc. Rev. 2017,46, 5289−5310. (87) Yigit, B.; Alapan, Y.; Sitti, M. Cohesive Self-Organization of Mobile Microrobotic Swarms. Soft Matter 2020,16, 1996−2004. (88) Wang, Q.; Zhang, L. External Power-Driven Microrobotic Swarm: From Fundamental Understanding to Imaging-Guided Delivery. ACS Nano 2021,15, 149−174. (89) Wang, Q.; Zhang, L. Ultrasound Imaging and Tracking of Micro/Nanorobots: From Individual to Collectives. IEEE Open J. Nanotechnol. 2020,1,6−17. Chemical Reviews pubs.acs.org/CR Review https://doi.org/10.1021/acs.chemrev.0c01234 Chem. Rev. 2021, 121, 4999−5041 5033 (90) Shields, C. W.; Velev, O. D. The Evolution of Active Particles: Toward Externally Powered Self-Propelling and Self-Reconfiguring Particle Systems. Chem. 2017,3, 539−559. (91) Yánez-Sedeno, P.; Campuzano, S.; Pingarrón, J. M. Janus Particles for (Bio)Sensing. Appl. Mater. Today 2017,9, 276−288. (92) Xu, B.; Zhang, B.; Wang, L.; Huang, G.; Mei, Y. Tubular Micro/Nanomachines: From the Basics to Recent Advances. Adv. Funct. Mater. 2018,28, 1705872. (93) Bente, K.; Codutti, A.; Bachmann, F.; Faivre, D. Biohybrid and Bioinspired Magnetic Microswimmers. Small 2018,14, 1704374. (94) Chen, X.-Z.; Hoop, M.; Mushtaq, F.; Siringil, E.; Hu, C.; Nelson, B. J.; Pané, S. Recent Developments in Magnetically Driven Microand Nanorobots. Appl. Mater. Today 2017,9,37−48. (95) Reinisová, L.; Hermanová, S.; Pumera, M. Micro/Nanomachines: What is Needed for them to Become a Real Force in Cancer Therapy? Nanoscale 2019,11, 6519−6532. (96) Yu, J.; Xu, T.; Lu, Z.; Vong, C. I.; Zhang, L. On-Demand Disassembly of Paramagnetic Nanoparticle Chains for Microrobotic Cargo Delivery. IEEE Trans. Robot. 2017,33, 1213−1225. (97) Jang, B.; Gutman, E.; Stucki, N.; Seitz, B. F.; Wendel-García, P. D.; Newton, T.; Pokki, J.; Ergeneman, O.; Pané, S.; Or, Y.; et al. Undulatory Locomotion of Magnetic Multilink Nanoswimmers. Nano Lett. 2015,15, 4829−4833. (98) Jiles, D. Introduction to Magnetism and Magnetic Materials; CRC Press, 2015. (99) Spaldin, N. A. Magnetic Materials: Fundamentals and Applications; Cambridge University Press, 2010. (100) Rikken, R. S. M.; Nolte, R. J. M.; Maan, J. C.; van Hest, J. C. M.; Wilson, D. A.; Christianen, P. C. M. Manipulation of Microand Nanostructure Motion with Magnetic Fields. Soft Matter 2014,10, 1295−1308. (101) Khalil, I. S. M.; Alfar, A.; Tabak, A. F.; Klingner, A.; Stramigioli, S.; Sitti, M. 2017 IEEE Int. Conference on Adv. Intell. Mechatronics; AIM, 2017; pp 1117−1122. (102) Mahoney, A. W.; Abbott, J. J. Generating Rotating Magnetic Fields With a Single Permanent Magnet for Propulsion of Untethered Magnetic Devices in a Lumen. IEEE Trans. Robot. 2014,30, 411−420. (103) Schurle, S.; Kratochvil, B. E.; Pané, S.; Zeeshan, M. A.; Nelson, B. J. In Nanorobotics; Springer, 2013. (104) Jeong, S.; Choi, H.; Choi, J.; Yu, C.; Park, J.-o.; Park, S. Novel Electromagnetic Actuation (EMA) Method for 3-Dimensional Locomotion of Intravascular Microrobot. Sens. Actuators, A 2010, 157, 118−125. (105) Choi, H.; Cha, K.; Choi, J.; Jeong, S.; Jeon, S.; Jang, G.; Park, J.-o.; Park, S. EMA System with Gradient and Uniform Saddle Coils for 3D Locomotion of Microrobot. Sens. Actuators, A 2010,163, 410− 417. (106) Kratochvil, B. E.; Kummer, M. P.; Erni, S.; Borer, R.; Frutiger, D. R.; Schurle, S.; Nelson, B. J. Exp. Robot. 2014,79, 317−329. (107) Yang, Z.; Yang, L.; Zhang, L. Autonomous Navigation of Magnetic Microrobots in A Large Workspace Using Mobile-Coil System. IEEE/ASME Trans. Mechatron. 2021,1−1. (108) Yang, L.; Yu, E.; Vong, C.; Zhang, L. Discrete-Time Optimal Control of Electromagnetic Coil Systems for Generation of Dynamic Magnetic Fields With High Accuracy. IEEE/ASME Trans. Mechatron. 2019,24, 1208−1219. (109) Du, X.; Zhang, M.; Yu, J.; Yang, L.; Chiu, W. Y. P.; Zhang, L. Design and Real-time Optimization for a Magnetic Actuation System with Enhanced Flexibility. IEEE/ASME Trans. Mechatron. 2020,1−1. (110) Yang, L.; Zhang, L. 2020 IEEE 16th International Conference on Automation Science and Engineering (CASE) 2020, 876−881. (111) Yang, Z.; Zhang, L. Magnetic Actuation Systems for Miniature Robots: A Review. Adv. Intell. Syst. 2020,2, 2000082. (112) Xu, T.; Yu, J.; Yan, X.; Choi, H.; Zhang, L. Magnetic Actuation Based Motion Control for Microrobots: An Overview. Micromachines 2015,6, 1346−1364. (113) Abbott, J. J.; Diller, E.; Petruska, A. J. Magnetic Methods in Robotics. Annu. Rev. Control, Robot. Auton. Syst. 2020,3,57−90. (114) Jiang, J.; Yang, L.; Zhang, L. Closed-Loop Control of a Helmholtz Coil System for Accurate Actuation of Magnetic Microrobot Swarms. IEEE Robot. Autom. Lett. 2021,6, 827. (115) Yang, Z.; Yang, L.; Zhang, M.; Wang, Q.; Yu, S.; Zhang, L. Magnetic Control of a Steerable Guidewire Under Ultrasound Guidance Using Mobile Electromagnets. IEEE Robot. Autom. Lett. 2021,6, 1280. (116) Yang, Z.; Yang, L.; Zhang, M.; Wang, Q.; Yu, S.; Zhang, L. Magnetic Control of a Steerable Guidewire Under Ultrasound Guidance Using Mobile Electromagnets. IEEE Robot. Autom. Lett. 2021,6, 1280 DOI: 10.1109/LRA.2021.3052394. (117) Folio, D.; Ferreira, A. Two-Dimensional Robust Magnetic Resonance Navigation of a Ferromagnetic Microrobot Using Pareto Optimality. IEEE Trans. Robot. 2017,33, 583−593. (118) Kummer, M. P.; Abbott, J. J.; Kratochvil, B. E.; Borer, R.; Sengul, A.; Nelson, B. J. OctoMag: An Electromagnetic System for 5DOF Wireless Micromanipulation. IEEE Trans. Robot. 2010,26, 1006−1017. (119) Lee, S.; Kim, J.-y.; Kim, J.; Hoshiar, A. K.; Park, J.; Lee, S.; Kim, J.; Pané, S.; Nelson, B. J.; Choi, H. A Needle-Type Microrobot for Targeted Drug Delivery by Affixing to a Microtissue. Adv. Healthcare Mater. 2020,9, 1901697. (120) Ullrich, F.; Bergeles, C.; Pokki, J.; Ergeneman, O.; Erni, S.; Chatzipirpiridis, G.; Pané, S.; Framme, C.; Nelson, B. J. Mobility Experiments With Microrobots for Minimally Invasive Intraocular Surgery. Invest. Ophthalmol. Visual Sci. 2013,54, 2853−2863. (121) Jeon, S.; Kim, S.; Ha, S.; Lee, S.; Kim, E.; Kim, S. Y.; Park, S. H.; Jeon, J. H.; Kim, S. W.; Moon, C.; et al. Magnetically Actuated Microrobots as a Platform for Stem Cell Transplantation. Sci. Robot. 2019,4, No. eaav4317. (122) Han, K.; Shields, C. W.; Diwakar, N. M.; Bharti, B.; López, G. P.; Velev, O. D. Sequence-Encoded Colloidal Origami and Microbot Assemblies from Patchy Magnetic Cubes. Sci. Adv. 2017,3, No. e1701108. (123)Baraban,L.;Streubel,R.;Makarov,D.;Han,L.; Karnaushenko, D.; Schmidt, O. G.; Cuniberti, G. Fuel-Free Locomotion of Janus Motors: Magnetically Induced Thermophoresis. ACS Nano 2013,7, 1360−1367. (124) Yu, J.; Jin, D.; Chan, K.-F.; Wang, Q.; Yuan, K.; Zhang, L. Active Generation and Magnetic Actuation of Microrobotic Swarms in Bio-Fluids. Nat. Commun. 2019,10, 5631. (125) Yang, L.; Chen, X.; Wang, L.; Hu, Z.; Xin, C.; Hippler, M.; Zhu, W.; Hu, Y.; Li, J.; Wang, Y.; et al. Targeted Single-Cell Therapeutics with Magnetic Tubular Micromotor by One-Step Exposure of Structured Femtosecond Optical Vortices. Adv. Funct. Mater. 2019,29, 1905745. (126) Wu, Z.; Troll, J.; Jeong, H.-H.; Wei, Q.; Stang, M.; Ziemssen, F.; Wang, Z.; Dong, M.; Schnichels, S.; Qiu, T.; et al. A Swarm of Slippery Micropropellers Penetrates the Vitreous Body of the Eye. Sci. Adv. 2018,4, No. eaat4388. (127) Ceylan, H.; Yasa, I. C.; Yasa, O.; Tabak, A. F.; Giltinan, J.; Sitti, M. 3D-Printed Biodegradable Microswimmer for Theranostic Cargo Delivery and Release. ACS Nano 2019,13, 3353−3362. (128) Li, T.; Li, J.; Zhang, H.; Chang, X.; Song, W.; Hu, Y.; Shao, G.; Sandraz, E.; Zhang, G.; Li, L.; et al. Magnetically Propelled FishLike Nanoswimmers. Small 2016,12, 6098−6105. (129) Liu, Y.; Ge, D.; Cong, J.; Piao, H.-G.; Huang, X.; Xu, Y.; Lu, G.; Pan, L.; Liu, M. Magnetically Powered Annelid-Worm-Like Microswimmers. Small 2018,14, 1704546. (130) Liu, L.; Liu, M.; Su, Y.; Dong, Y.; Zhou, W.; Zhang, L.; Zhang, H.; Dong, B.; Chi, L. Tadpole-like Artificial Micromotor. Nanoscale 2015,7, 2276−2280. (131) Hu, N.; Wang, L.; Zhai, W.; Sun, M.; Xie, H.; Wu, Z.; He, Q. Magnetically Actuated Rolling of Star-Shaped Hydrogel Microswimmer. Macromol. Chem. Phys. 2018,219, 1700540. (132) Vach, P. J.; Fratzl, P.; Klumpp, S.; Faivre, D. Fast Magnetic Micropropellers with Random Shapes. Nano Lett. 2015,15, 7064− 7070. Chemical Reviews pubs.acs.org/CR Review https://doi.org/10.1021/acs.chemrev.0c01234 Chem. Rev. 2021, 121, 4999−5041 5034 (133) Morozov, K. I.; Mirzae, Y.; Kenneth, O.; Leshansky, A. M. Dynamics of Arbitrary Shaped Propellers Driven by a Rotating Magnetic Field. Phys. Rev. Fluids 2017,2, 044202. (134) Martinez-Pedrero, F.; Tierno, P. Magnetic Propulsion of SelfAssembled Colloidal Carpets: Efficient Cargo Transport via a Conveyor-Belt Effect. Phys. Rev. Appl. 2015,3, 051003. (135) Esteban-Fernández de Avila, B.; Gao, W.; Karshalev, E.; Zhang, L.; Wang, J. Cell-like Micromotors. Acc. Chem. Res. 2018,51, 1901−1910. (136) Brumley, D. R.; Wan, K. Y.; Polin, M.; Goldstein, R. E. Flagellar Synchronization through Direct Hydrodynamic Interactions. eLife 2014,3, No. e02750. (137) Liao, P.; Xing, L.; Zhang, S.; Sun, D. Magnetically Driven Undulatory Microswimmers Integrating Multiple Rigid Segments. Small 2019,15, 1901197. (138) Kim, S.; Lee, S.; Lee, J.; Nelson, B. J.; Zhang, L.; Choi, H. Fabrication and Manipulation of Ciliary Microrobots with Nonreciprocal Magnetic Actuation. Sci. Rep. 2016,6, 30713. (139) Qiu, T.; Lee, T.-C.; Mark, A. G.; Morozov, K. I.; Munster, R.; Mierka, O.; Turek, S.; Leshansky, A. M.; Fischer, P. Swimming by Reciprocal Motion at Low Reynolds Number. Nat. Commun. 2014,5, 5119. (140) Purcell, E. M. Life at Low Reynolds Number. Am. J. Phys. 1977,45,3−11. (141) Vach, P. J.; Faivre, D. The Triathlon of Magnetic Actuation: Rolling, Propelling, Swimming with a Single Magnetic Material. Sci. Rep. 2015,5, 9364. (142) Zhang, L.; Abbott, J. J.; Dong, L.; Kratochvil, B. E.; Bell, D.; Nelson, B. J. Artificial Bacterial Flagella: Fabrication and Magnetic Control. Appl. Phys. Lett. 2009,94, 064107. (143) Sitti, M. Voyage of the Microrobots. Nature 2009,458, 1121− 1122. (144) Zhang, L.; Peyer, K. E.; Nelson, B. J. Artificial Bacterial Flagella for Micromanipulation. Lab Chip 2010,10, 2203−2215. (145) Abbott, J. J.; Peyer, K. E.; Lagomarsino, M. C.; Zhang, L.; Dong, L.; Kaliakatsos, I. K.; Nelson, B. J. How Should Microrobots Swim? Int. J. Robot. Res. 2009,28, 1434−1447. (146) Peyer, K. E.; Zhang, L.; Nelson, B. J. Bio-Inspired Magnetic Swimming Microrobots for Biomedical Applications. Nanoscale 2013, 5, 1259−1272. (147) Peyer, K. E.; Tottori, S.; Qiu, F.; Zhang, L.; Nelson, B. J. Magnetic Helical Micromachines. Chem. - Eur. J. 2013,19,28−38. (148) Chatzipirpiridis, G.; de Marco, C.; Pellicer, E.; Ergeneman, O.; Sort, J.; Nelson, B. J.; Pané, S. Template-Assisted Electroforming of Fully Semi-Hard-Magnetic Helical Microactuators. Adv. Eng. Mater. 2018,20, 1800179. (149) Ye, C.; Liu, J.; Wu, X.; Wang, B.; Zhang, L.; Zheng, Y.; Xu, T. Hydrophobicity Influence on Swimming Performance of Magnetically Driven Miniature Helical Swimmers. Micromachines 2019,10, 175. (150) Xu, T.; Vong, C.; Wang, B.; Liu, L.; Wu, X.; Zhang, L. 2016 6th IEEE International Conference on Biomedical Robotics and Biomechatronics (BioRob) 2016, 502−507. (151) Xu, T.; Yu, J.; Vong, C.-I.; Wang, B.; Wu, X.; Zhang, L. Dynamic Morphology and Swimming Properties of Rotating Miniature Swimmers with Soft Tails. IEEE/ASME Trans. Mechatron. 2019,24, 924−934. (152) Man, Y.; Lauga, E. The Wobbling-to-Swimming Transition of Rotated Helices. Phys. Fluids 2013,25, 071904. (153) Ghosh, A.; Paria, D.; Singh, H. J.; Venugopalan, P. L.; Ghosh, A. Dynamical Configurations and Bistability of Helical Nanostructures under External Torque. Phys. Rev. E 2012,86, 031401. (154) Wang, X.; Chen, X.-Z.; Alcantara, C. C. J.; Sevim, S.; Hoop, M.; Terzopoulou, A.; de Marco, C.; Hu, C.; de Mello, A. J.; Falcaro, P.; et al. MOFBOTS: Metal-Organic-Framework-Based Biomedical Microrobots. Adv. Mater. 2019,31, 1901592. (155) Wang, X.; Hu, C.; Schurz, L.; De Marco, C.; Chen, X.; Pané, S.; Nelson, B. J. Surface-Chemistry-Mediated Control of Individual Magnetic Helical Microswimmers in a Swarm. ACS Nano 2018,12, 6210−6217. (156) Mandal, P.; Patil, G.; Kakoty, H.; Ghosh, A. Magnetic Active Matter Based on Helical Propulsion. Acc. Chem. Res. 2018,51, 2689− 2698. (157) Ghosh, A.; Dasgupta, D.; Pal, M.; Morozov, K. I.; Leshansky, A. M.; Ghosh, A. Helical Nanomachines as Mobile Viscometers. Adv. Funct. Mater. 2018,28, 1705687. (158) Dreyfus, R.; Baudry, J.; Roper, M. L.; Fermigier, M.; Stone, H. A.; Bibette, J. Microscopic Artificial Swimmers. Nature 2005,437, 862−865. (159) Gu, H.; Boehler, Q.; Cui, H.; Secchi, E.; Savorana, G.; De Marco, C.; Gervasoni, S.; Peyron, Q.; Huang, T.-Y.; Pane, S.; et al. Magnetic Cilia Carpets with Programmable Metachronal Waves. Nat. Commun. 2020,11, 2637. (160) Wang, Q.; Yang, L.; Yu, J.; Zhang, L. Characterizing Dynamic Behaviors of Three-Particle Paramagnetic Microswimmer Near a Solid Surface. Robot. Biomimetics 2017,4, 20. (161) Youssefi, O.; Diller, E. In Advances in Motion Sensing and Control for Robotic Applications; Springer, 2019. (162) Fang, W.-Z.; Ham, S.; Qiao, R.; Tao, W.-Q. Magnetic Actuation of Surface Walkers: The Effects of Confinement and Inertia. Langmuir 2020,36, 7046−7055. (163) Martinez-Pedrero, F.; Navarro-Argemí, E.; Ortiz-Ambriz, A.; Pagonabarraga, I.; Tierno, P. Emergent Hydrodynamic Bound States between Magnetically Powered Micropropellers. Sci. Adv. 2018,4, No. eaap9379. (164) Driscoll, M.; Delmotte, B.; Youssef, M.; Sacanna, S.; Donev, A.; Chaikin, P. Unstable Fronts and Motile Structures Formed by Microrollers. Nat. Phys. 2017,13, 375−379. (165) Jang, B.; Hong, A.; Alcantara, C.; Chatzipirpiridis, G.; Martí, X.; Pellicer, E.; Sort, J.; Harduf, Y.; Or, Y.; Nelson, B. J.; et al. Programmable Locomotion Mechanisms of Nanowires with Semihard Magnetic Properties Near a Surface Boundary. ACS Appl. Mater. Interfaces 2019,11, 3214−3223. (166) Yu, J.; Wang, B.; Du, X.; Wang, Q.; Zhang, L. Ultra-Extensible Ribbon-like Magnetic Microswarm. Nat. Commun. 2018,9, 3260. (167) Mair, L. O.; Evans, B. A.; Nacev, A.; Stepanov, P. Y.; Hilaman, R.; Chowdhury, S.; Jafari, S.; Wang, W.; Shapiro, B.; Weinberg, I. N. Magnetic Microkayaks: Propulsion of Microrods Precessing near a Surface by Kilohertz Frequency, Rotating Magnetic Fields. Nanoscale 2017,9, 3375−3381. (168) Yang, T.; Tomaka, A.; Tasci, T. O.; Neeves, K. B.; Wu, N.; Marr, D. W. M. Microwheels on Microroads: Enhanced Translation on Topographic Surfaces. Sci. Robot. 2019,4, No. eaaw9525. (169) Lin, Z.; Fan, X.; Sun, M.; Gao, C.; He, Q.; Xie, H. Magnetically Actuated Peanut Colloid Motors for Cell Manipulation and Patterning. ACS Nano 2018,12, 2539−2545. (170) Wang, Q.; Yu, J.; Yuan, K.; Yang, L.; Jin, D.; Zhang, L. Disassembly and Spreading of Magnetic Nanoparticle Clusters on Uneven Surfaces. Appl. Mater. Today 2020,18, 100489. (171) Li, T.; Zhang, A.; Shao, G.; Wei, M.; Guo, B.; Zhang, G.; Li, L.; Wang, W. Janus Microdimer Surface Walkers Propelled by Oscillating Magnetic Fields. Adv. Funct. Mater. 2018,28, 1706066. (172) Vyskocil, J.; Mayorga-Martinez, C. C.; Jablonská, E.; Novotny, F.; Ruml, T.; Pumera, M. Cancer Cells Microsurgery via Asymmetric Bent Surface Au/Ag/Ni Microrobotic Scalpels Through a Transversal Rotating Magnetic Field. ACS Nano 2020,14, 8247−8256. (173) Mushtaq, F.; Asani, A.; Hoop, M.; Chen, X.-Z.; Ahmed, D.; Nelson, B. J.; Pané, S. Highly Efficient Coaxial TiO2-PtPd Tubular Nanomachines for Photocatalytic Water Purification with Multiple Locomotion Strategies. Adv. Funct. Mater. 2016,26, 6995−7002. (174) Sridhar, V.; Park, B.-W.; Guo, S.; van Aken, P. A.; Sitti, M. Multiwavelength-Steerable Visible-Light-Driven Magnetic CoO-TiO2 Microswimmers. ACS Appl. Mater. Interfaces 2020,12, 24149−24155. (175) Luo, M.; Li, S.; Wan, J.; Yang, C.; Chen, B.; Guan, J. Enhanced Propulsion of Urease-Powered Micromotors by Multilayered Assembly of Ureases on Janus Magnetic Microparticles. Langmuir 2020.DOI: 10.1021/acs.langmuir.9b03315 Chemical Reviews pubs.acs.org/CR Review https://doi.org/10.1021/acs.chemrev.0c01234 Chem. Rev. 2021, 121, 4999−5041 5035 (176) Xu, H.; Medina-Sánchez, M.; Maitz, M. F.; Werner, C.; Schmidt, O. G. Sperm Micromotors for Cargo Delivery through Flowing Blood. ACS Nano 2020,14, 2982−2993. (177) Li, J.; Li, T.; Xu, T.; Kiristi, M.; Liu, W.; Wu, Z.; Wang, J. Magneto-Acoustic Hybrid Nanomotor. Nano Lett. 2015,15, 4814− 4821. (178) Chen, C.; Soto, F.; Karshalev, E.; Li, J.; Wang, J. Hybrid Nanovehicles: One Machine, Two Engines. Adv. Funct. Mater. 2019, 29, 1806290. (179) Yuan, K.; de la Asunción-Nadal, V.; Jurado-Sánchez, B.; Escarpa, A. 2D Nanomaterials Wrapped Janus Micromotors with Built-in Multiengines for Bubble, Magnetic, and Light Driven Propulsion. Chem. Mater. 2020,32, 1983−1992. (180) Valdez-Garduno, M.; Leal-Estrada, M.; Oliveros-Mata, E. S.; Sandoval-Bojorquez, D. I.; Soto, F.; Wang, J.; Garcia-Gradilla, V. Density Asymmetry Driven Propulsion of Ultrasound-Powered Janus Micromotors. Adv. Funct. Mater. 2020,30, 2004043. (181) Wang, B.; Chan, K. F.; Yu, J.; Wang, Q.; Yang, L.; Chiu, P. W. Y.; Zhang, L. Reconfigurable Swarms of Ferromagnetic Colloids for Enhanced Local Hyperthermia. Adv. Funct. Mater. 2018,28, 1705701. (182) Januszewski, A.; Stebbing, J. Hyperthermia in Cancer: Is It Coming of Age? Lancet Oncol. 2014,15, 565−566. (183) Wang, Q.; Wang, B.; Yu, J.; Schweizer, K.; Nelson, B. J.; Zhang, L. 2020 IEEE International Conference on Robotics and Automation (ICRA) 2020, 10285−10291. (184) Tay, Z. W.; Chandrasekharan, P.; Chiu-Lam, A.; Hensley, D. W.; Dhavalikar, R.; Zhou, X. Y.; Yu, E. Y.; Goodwill, P. W.; Zheng, B.; Rinaldi, C.; et al. Magnetic Particle Imaging-Guided Heating in Vivo Using Gradient Fields for Arbitrary Localization of Magnetic Hyperthermia Therapy. ACS Nano 2018,12, 3699−3713. (185) Dhar, P.; Narendren, S.; Gaur, S. S.; Sharma, S.; Kumar, A.; Katiyar, V. Self-Propelled Cellulose Nanocrystal Based Catalytic Nanomotors for Targeted Hyperthermia and Pollutant Remediation Applications. Int. J. Biol. Macromol. 2020,158, 1020−1036. (186) Meffre, A.; Mehdaoui, B.; Connord, V.; Carrey, J.; Fazzini, P. F.; Lachaize, S.; Respaud, M.; Chaudret, B. Complex Nano-objects Displaying Both Magnetic and Catalytic Properties: A Proof of Concept for Magnetically Induced Heterogeneous Catalysis. Nano Lett. 2015,15, 3241−3248. (187) Eerenstein, W.; Mathur, N. D.; Scott, J. F. Multiferroic and Magnetoelectric Materials. Nature 2006,442, 759−765. (188) Spaldin, N. A.; Ramesh, R. Advances in Magnetoelectric Multiferroics. Nat. Mater. 2019,18, 203−212. (189) Martins, P.; Lanceros-Méndez, S. Polymer-Based Magnetoelectric Materials. Adv. Funct. Mater. 2013,23, 3371−3385. (190) Wang, Y.; Hu, J.; Lin, Y.; Nan, C.-W. Multiferroic Magnetoelectric Composite Nanostructures. NPG Asia Mater. 2010, 2,61−68. (191) Guo, W.; Zhang, X.; Yu, X.; Wang, S.; Qiu, J.; Tang, W.; Li, L.; Liu, H.; Wang, Z. L. Self-Powered Electrical Stimulation for Enhancing Neural Differentiation of Mesenchymal Stem Cells on Graphene-Poly(3,4-ethylenedioxythiophene) Hybrid Microfibers. ACS Nano 2016,10, 5086−5095. (192) Hasan, M.; Khatun, A.; Fukuta, T.; Kogure, K. Noninvasive Transdermal Delivery of Liposomes by Weak Electric Current. Adv. Drug Delivery Rev. 2020,154−155, 227−235. (193) Davalos, R. V.; Mir, L. M.; Rubinsky, B. Tissue Ablation with Irreversible Electroporation. Ann. Biomed. Eng. 2005,33, 223. (194) Thrivikraman, G.; Boda, S. K.; Basu, B. Unraveling the Mechanistic Effects of Electric Field Stimulation towards Directing Stem Cell Fate and Function: A Tissue Engineering Perspective. Biomaterials 2018,150,60−86. (195) Kirson, E. D.; Gurvich, Z.; Schneiderman, R.; Dekel, E.; Itzhaki, A.; Wasserman, Y.; Schatzberger, R.; Palti, Y. Disruption of Cancer Cell Replication by Alternating Electric Fields. Cancer Res. 2004,64, 3288. (196) Sheng, J.; Vannela, R.; Rittmann, B. E. Evaluation of CellDisruption Effects of Pulsed-Electric-Field Treatment of Synechocystis PCC 6803. Environ. Sci. Technol. 2011,45, 3795−3802. (197) Betal, S.; Saha, A. K.; Ortega, E.; Dutta, M.; Ramasubramanian, A. K.; Bhalla, A. S.; Guo, R. Core-Shell Magnetoelectric Nanorobot - A Remotely Controlled Probe for Targeted Cell Manipulation. Sci. Rep. 2018,8, 1755. (198) Chen, X. Z.; Hoop, M.; Shamsudhin, N.; Huang, T.; Ozkale, B.; Li, Q.; Siringil, E.; Mushtaq, F.; Di Tizio, L.; Nelson, B. J.; et al. Hybrid Magnetoelectric Nanowires for Nanorobotic Applications: Fabrication, Magnetoelectric Coupling, and Magnetically Assisted in Vitro Targeted Drug Delivery. Adv. Mater. 2017,29, 1605458. (199) Kaushik, A.; Jayant, R. D.; Sagar, V.; Nair, M. The Potential of Magneto-Electric Nanocarriers for Drug Delivery. Expert Opin. Drug Delivery 2014,11, 1635−1646. (200) Nair, M.; Guduru, R.; Liang, P.; Hong, J.; Sagar, V.; Khizroev, S. Externally Controlled on-Demand Release of Anti-HIV Drug using Magneto-Electric Nanoparticles as Carriers. Nat. Commun. 2013,4, 1707. (201) Nair, M.; Guduru, R.; Liang, P.; Hong, J.; Sagar, V.; Khizroev, S. Externally Controlled on-Demand Release of Anti-HIV Drug using Magneto-Electric Nanoparticles as Carriers. Nat. Commun. 2013,4, 1707 DOI: 10.1021/acsnano.0c07753. (202) Ji, F.; Jin, D.; Wang, B.; Zhang, L. Light-Driven Hovering of a Magnetic Microswarm in Fluid. ACS Nano 2020,14, 6990−6998. (203) Yang, L.; Yu, J.; Zhang, L. Statistics-Based Automated Control for a Swarm of Paramagnetic Nanoparticles in 2-D Space. IEEE Trans. Robot. 2020,36, 254−270. (204) Nair, M.; Guduru, R.; Liang, P.; Hong, J.; Sagar, V.; Khizroev, S. Externally Controlled on-Demand Release of Anti-HIV Drug using Magneto-Electric Nanoparticles as Carriers. Nat. Commun. 2013,4, 1707 DOI: 10.1146/annurev-control-032720-104318. (205) Yu, J.; Yang, L.; Zhang, L. Pattern Generation and Motion Control of a Vortex-like Paramagnetic Nanoparticle Swarm. Int. J. Robot. Res. 2018,37, 912−930. (206) Yu, J.; Jin, D.; Zhang, L. 2017 IEEE International Conference on Robotics and Automation (ICRA) 2017, 6594−6599. (207) Yu, J.; Zhang, L. 2017 IEEE 17th International Conference on Nanotechnology (IEEE-NANO) 2017, 293−296. (208) Yu, J.; Zhang, L. Reversible Swelling and Shrinking of Paramagnetic Nanoparticle Swarms in Biofluids With High Ionic Strength. IEEE/ASME Trans. Mechatron. 2019,24, 154−163. (209) Villa, K.; Krejcová, L.; Novotny, F.; Heger, Z.; Sofer, Z.; Pumera, M. Cooperative Multifunctional Self-Propelled Paramagnetic Microrobots with Chemical Handles for Cell Manipulation and Drug Delivery. Adv. Funct. Mater. 2018,28, 1804343. (210) Yang, T.; Tasci, T. O.; Neeves, K. B.; Wu, N.; Marr, D. W. M. Magnetic Microlassos for Reversible Cargo Capture, Transport, and Release. Langmuir 2017,33, 5932−5937. (211) Jin, D.; Yu, J.; Yuan, K.; Zhang, L. Mimicking the Structure and Function of Ant Bridges in a Reconfigurable Microswarm for Electronic Applications. ACS Nano 2019,13, 5999−6007. (212) Nair, M.; Guduru, R.; Liang, P.; Hong, J.; Sagar, V.; Khizroev, S. Externally Controlled on-Demand Release of Anti-HIV Drug using Magneto-Electric Nanoparticles as Carriers. Nat. Commun. 2013,4, 1707 DOI: 10.1021/acsnano.0c08284. (213) Tasci, T. O.; Herson, P. S.; Neeves, K. B.; Marr, D. W. M. Surface-Enabled Propulsion and Control of Colloidal Microwheels. Nat. Commun. 2016,7, 10225. (214) Li, J.; Li, X.; Luo, T.; Wang, R.; Liu, C.; Chen, S.; Li, D.; Yue, J.; Cheng, S.-h.; Sun, D. Development of a Magnetic Microrobot for Carrying and Delivering Targeted Cells. Sci. Robot. 2018,3, No. eaat8829. (215) Li, J.; Angsantikul, P.; Liu, W.; Esteban-Fernández de Avila, B.; Chang, X.; Sandraz, E.; Liang, Y.; Zhu, S.; Zhang, Y.; Chen, C.; et al. Biomimetic Platelet-Camouflaged Nanorobots for Binding and Isolation of Biological Threats. Adv. Mater. 2018,30, 1704800. (216) Chen, X.-Z.; Liu, J.-H.; Dong, M.; Muller, L.; Chatzipirpiridis, G.; Hu, C.; Terzopoulou, A.; Torlakcik, H.; Wang, X.; Mushtaq, F.; et al. Magnetically Driven Piezoelectric Soft Microswimmers for Neuron-Like Cell Delivery and Neuronal Differentiation. Mater. Horiz. 2019,6, 1512−1516. Chemical Reviews pubs.acs.org/CR Review https://doi.org/10.1021/acs.chemrev.0c01234 Chem. Rev. 2021, 121, 4999−5041 5036 (217) Dong, M.; Wang, X.; Chen, X.-Z.; Mushtaq, F.; Deng, S.; Zhu, C.; Torlakcik, H.; Terzopoulou, A.; Qin, X.-H.; Xiao, X.; et al. 3DPrinted Soft Magnetoelectric Microswimmers for Delivery and Differentiation of Neuron-Like Cells. Adv. Funct. Mater. 2020,30, 1910323. (218) Qiu, F.; Fujita, S.; Mhanna, R.; Zhang, L.; Simona, B. R.; Nelson, B. J. Magnetic Helical Microswimmers Functionalized with Lipoplexes for Targeted Gene Delivery. Adv. Funct. Mater. 2015,25, 1666−1671. (219) Tottori, S.; Zhang, L.; Qiu, F.; Krawczyk, K. K.; FrancoObregón, A.; Nelson, B. J. Magnetic Helical Micromachines: Fabrication, Controlled Swimming, and Cargo Transport. Adv. Mater. 2012,24, 811−816. (220) Tottori, S.; Zhang, L.; Peyer, K. E.; Nelson, B. J. Assembly, Disassembly, and Anomalous Propulsion of Microscopic Helices. Nano Lett. 2013,13, 4263−4268. (221) Walker, D.; Käsdorf, B. T.; Jeong, H.-H.; Lieleg, O.; Fischer, P. Enzymatically Active Biomimetic Micropropellers for the Penetration of Mucin Gels. Sci. Adv. 2015,1, No. e1500501. (222) Tang, M.-J.; Wang, W.; Li, Z.-L.; Liu, Z.-M.; Guo, Z.-Y.; Tian, H.-Y.; Liu, Z.; Ju, X.-J.; Xie, R.; Chu, L.-Y. Controllable Microfluidic Fabrication of Magnetic Hybrid Microswimmers with Hollow Helical Structures. Ind. Eng. Chem. Res. 2018,57, 9430−9438. (223) Dong, Y.; Wang, L.; Wang, J.; Wang, S.; Wang, Y.; Jin, D.; Chen, P.; Du, W.; Zhang, L.; Liu, B.-F. Graphene-Based Helical Micromotors Constructed by “Microscale Liquid Rope-Coil Effect” with Microfluidics. ACS Nano 2020,14, 16600−16613. (224) Gao, W.; Feng, X.; Pei, A.; Kane, C. R.; Tam, R.; Hennessy, C.; Wang, J. Bioinspired Helical Microswimmers Based on Vascular Plants. Nano Lett. 2014,14, 305−310. (225) Xie, L.; Pang, X.; Yan, X.; Dai, Q.; Lin, H.; Ye, J.; Cheng, Y.; Zhao, Q.; Ma, X.; Zhang, X.; et al. Photoacoustic Imaging-Trackable Magnetic Microswimmers for Pathogenic Bacterial Infection Treatment. ACS Nano 2020,14, 2880−2893. (226) Zhang, L.; Abbott, J. J.; Dong, L.; Peyer, K. E.; Kratochvil, B. E.; Zhang, H.; Bergeles, C.; Nelson, B. J. Characterizing the Swimming Properties of Artificial Bacterial Flagella. Nano Lett. 2009,9, 3663−3667. (227) de Marco, C.; Alcantara, C. C. J.; Kim, S.; Briatico, F.; Kadioglu, A.; de Bernardis, G.; Chen, X.; Marano, C.; Nelson, B. J.; Pané, S. Indirect 3D and 4D Printing of Soft Robotic Microstructures. Adv. Mater. Technol. 2019,4, 1900332. (228) Li, J.; Wu, C.; Chu, P. K.; Gelinsky, M. 3D Printing of Hydrogels: Rational Design Strategies and Emerging Biomedical applications. Mater. Sci. Eng., R 2020,140, 100543. (229) Yasa, I. C.; Tabak, A. F.; Yasa, O.; Ceylan, H.; Sitti, M. 3DPrinted Microrobotic Transporters with Recapitulated Stem Cell Niche for Programmable and Active Cell Delivery. Adv. Funct. Mater. 2019,29, 1808992. (230) Suter, M.; Zhang, L.; Siringil, E. C.; Peters, C.; Luehmann, T.; Ergeneman, O.; Peyer, K. E.; Nelson, B. J.; Hierold, C. Superparamagnetic Microrobots: Fabrication by Two-Photon Polymerization and Biocompatibility. Biomed. Microdevices 2013,15, 997− 1003. (231) Zhu, W.; Li, J.; Leong, Y. J.; Rozen, I.; Qu, X.; Dong, R.; Wu, Z.; Gao, W.; Chung, P. H.; Wang, J.; et al. 3D-Printed Artificial Microfish. Adv. Mater. 2015,27, 4411−4417. (232) Ceylan, H.; Yasa, I. C.; Sitti, M. 3D Chemical Patterning of Micromaterials for Encoded Functionality. Adv. Mater. 2017,29, 1605072. (233) Kim, S.; Qiu, F.; Kim, S.; Ghanbari, A.; Moon, C.; Zhang, L.; Nelson, B. J.; Choi, H. Fabrication and Characterization of Magnetic Microrobots for Three-Dimensional Cell Culture and Targeted Transportation. Adv. Mater. 2013,25, 5863−5868. (234) Dong, M.; Wang, X.; Chen, X.-Z.; Mushtaq, F.; Deng, S.; Zhu, C.; Torlakcik, H.; Terzopoulou, A.; Qin, X.-H.; Xiao, X. 3D-Printed Soft Magnetoelectric Microswimmers for Delivery and Differentiation of Neuron-Like Cells. Adv. Funct. Mater. 2020,30, 1910323 DOI: 10.1021/acsami.0c18221. (235) Giltinan, J.; Sridhar, V.; Bozuyuk, U.; Sheehan, D.; Sitti, M. 3D Microprinting of Iron Platinum Nanoparticle-Based Magnetic Mobile Microrobots. Adv. Intell. Syst. 2021,3, 2000204. (236) Hann, S. Y.; Cui, H.; Nowicki, M.; Zhang, L. G. 4D Printing Soft Robotics for Biomedical Applications. Addit. Manuf. 2020,36, 101567. (237) Wang, X.; Qin, X.-H.; Hu, C.; Terzopoulou, A.; Chen, X.-Z.; Huang, T.-Y.; Maniura-Weber, K.; Pané, S.; Nelson, B. J. 3D Printed Enzymatically Biodegradable Soft Helical Microswimmers. Adv. Funct. Mater. 2018,28, 1804107. (238) Li, J.; Sattayasamitsathit, S.; Dong, R.; Gao, W.; Tam, R.; Feng, X.; Ai, S.; Wang, J. Template Electrosynthesis of Tailored-Made Helical Nanoswimmers. Nanoscale 2014,6, 9415−9420. (239) Alcantara, C. C. J.; Kim, S.; Lee, S.; Jang, B.; Thakolkaran, P.; Kim, J.-Y.; Choi, H.; Nelson, B. J.; Pané, S. 3D Fabrication of Fully Iron Magnetic Microrobots. Small 2019,15, 1805006. (240) Mushtaq, F.; Guerrero, M.; Sakar, M. S.; Hoop, M.; Lindo, A. M.; Sort, J.; Chen, X.; Nelson, B. J.; Pellicer, E.; Pané, S. Magnetically Driven Bi2O3/BiOCl-Based Hybrid Microrobots for Photocatalytic Water Remediation. J. Mater. Chem. A 2015,3, 23670−23676. (241) Pal, M.; Dasgupta, D.; Somalwar, N.; Vr, R.; Tiwari, M.; Teja, D.; Narayana, S. M.; Katke, A.; Rs, J.; Bhat, R.; et al. Helical Nanobots as Mechanical Probes of Intraand Extracellular Environments. J. Phys.: Condens. Matter 2020,32, 224001. (242) Ghosh, A.; Fischer, P. Controlled Propulsion of Artificial Magnetic Nanostructured Propellers. Nano Lett. 2009,9, 2243−2245. (243) Schamel, D.; Mark, A. G.; Gibbs, J. G.; Miksch, C.; Morozov, K. I.; Leshansky, A. M.; Fischer, P. Nanopropellers and Their Actuation in Complex Viscoelastic Media. ACS Nano 2014,8, 8794− 8801. (244) Huang, H. W.; Uslu, F. E.; Katsamba, P.; Lauga, E.; Sakar, M. S.; Nelson, B. J. Adaptive Locomotion of Artificial Microswimmers. Sci. Adv. 2019,5, No. eaau1532. (245) Yoshida, K.; Onoe, H. Functionalized Core-Shell Hydrogel Microsprings by Anisotropic Gelation with Bevel-Tip Capillary. Sci. Rep. 2017,7, 45987. (246) Yan, X.; Xu, J.; Zhou, Q.; Jin, D.; Vong, C. I.; Feng, Q.; Ng, D. H. L.; Bian, L.; Zhang, L. Molecular Cargo Delivery using Multicellular Magnetic Microswimmers. Appl. Mater. Today 2019, 15, 242−251. (247) Medina-Sánchez, M.; Schwarz, L.; Meyer, A. K.; Hebenstreit, F.; Schmidt, O. G. Cellular Cargo Delivery: Toward Assisted Fertilization by Sperm-Carrying Micromotors. Nano Lett. 2016,16, 555−561. (248) Yan, X.; Zhou, Q.; Vincent, M.; Deng, Y.; Yu, J.; Xu, J.; Xu, T.; Tang, T.; Bian, L.; Wang, Y.-X. J.; et al. Multifunctional Biohybrid Magnetite Microrobots for Imaging-Guided Therapy. Sci. Robot. 2017,2, No. eaaq1155. (249) Dong, L.; Zhang, L.; Bell, D. J.; Nelson, B. J.; Grutzmacher, D. Hybrid nanorobotic approaches for fabricating NEMS from 3D helical nanostructures. Proceedings 2006 IEEE International Conference on Robotics and Automation, 2006. ICRA 2006. 2006, 1396−1401. (250) Venugopalan, P. L.; Sai, R.; Chandorkar, Y.; Basu, B.; Shivashankar, S.; Ghosh, A. Conformal Cytocompatible Ferrite Coatings Facilitate the Realization of a Nanovoyager in Human Blood. Nano Lett. 2014,14, 1968−1975. (251) Peyer, K. E.; Zhang, L.; Nelson, B. J. Localized Non-Contact Manipulation using Artificial Bacterial Flagella. Appl. Phys. Lett. 2011, 99, 174101. (252) Qiu, F.; Zhang, L.; Peyer, K. E.; Casarosa, M.; FrancoObregón, A.; Choi, H.; Nelson, B. J. Noncytotoxic Artificial Bacterial Flagella Fabricated from Biocompatible ORMOCOMP and Iron Coating. J. Mater. Chem. B 2014,2, 357−362. (253) Peyer, K. E.; Siringil, E.; Zhang, L.; Nelson, B. J. Magnetic Polymer Composite Artificial Bacterial Flagella. Bioinspir. Biomim. 2014,9, 046014. (254) Cabanach, P.; Pena-Francesch, A.; Sheehan, D.; Bozuyuk, U.; Yasa,O.;Borros,S.;Sitti,M.Zwitterionic3D-PrintedNonImmunogenic Stealth Microrobots. Adv. Mater. 2020,32, 2003013. Chemical Reviews pubs.acs.org/CR Review https://doi.org/10.1021/acs.chemrev.0c01234 Chem. Rev. 2021, 121, 4999−5041 5037 (255) Giltinan, J.; Katsamba, P.; Wang, W.; Lauga, E.; Sitti, M. Selectively Controlled Magnetic Microrobots with Opposing Helices. Appl. Phys. Lett. 2020,116, 134101. (256) Hu, C.; Pané, S.; Nelson, B. J. Soft Microand Nanorobotics. Annu. Rev. Cont., Robot. Auton. Syst. 2018,1,53−75. (257) Field, R. D.; Anandakumaran, P. N.; Sia, S. K. Soft Medical Microrobots: Design Components and System Integration. Appl. Phys. Rev. 2019,6, 041305. (258) Qiu, T.; Palagi, S.; Fischer, P. 3D-Printed soft microrobot for swimming in biological fluids. 2015 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) 2015, 4922−4925. (259) Sun, H. C.; Liao, P.; Wei, T.; Zhang, L.; Sun, D. Magnetically Powered Biodegradable Microswimmers. Micromachines 2020,11, 404. (260) Yang, L.; Wang, Q.; Vong, C.; Zhang, L. A Miniature FlexibleLink Magnetic Swimming Robot With Two Vibration Modes: Design, Modeling and Characterization. IEEE Robot. Autom. Lett. 2017,2, 2024−2031. (261) Harduf, Y.; Jin, D.; Or, Y.; Zhang, L. Nonlinear Parametric Excitation Effect Induces Stability Transitions in Swimming Direction of Flexible Superparamagnetic Microswimmers. Soft Robot. 2018,5, 389−398. (262) Zhang, J.; Onaizah, O.; Middleton, K.; You, L.; Diller, E. Reliable Grasping of Three-Dimensional Untethered Mobile Magnetic Microgripper for Autonomous Pick-and-Place. IEEE Robot. Autom. Lett. 2017,2, 835−840. (263) Zhang, J.; Diller, E. Tetherless Mobile Micrograsping using a Magnetic Elastic Composite Material. Smart Mater. Struct. 2016,25, 11LT03. (264) Sun, H. C.; Liao, P.; Wei, T.; Zhang, L.; Sun, D. Magnetically Powered Biodegradable Microswimmers. Micromachines 2020,11, 404 DOI: 10.1021/acsnano.0c00381. (265) Li, H.; Go, G.; Ko, S. Y.; Park, J.-O.; Park, S. Magnetic Actuated pH-Responsive Hydrogel-Based Soft Micro-Robot for Targeted Drug Delivery. Smart Mater. Struct. 2016,25, 027001. (266) Kobayashi, K.; Yoon, C.; Oh, S. H.; Pagaduan, J. V.; Gracias, D. H. Biodegradable Thermomagnetically Responsive Soft Untethered Grippers. ACS Appl. Mater. Interfaces 2019,11, 151−159. (267) Singh, A. V.; Dad Ansari, M. H.; Dayan, C. B.; Giltinan, J.; Wang, S.; Yu, Y.; Kishore, V.; Laux, P.; Luch, A.; Sitti, M. Multifunctional Magnetic Hairbot for Untethered Osteogenesis, Ultrasound Contrast Imaging and Drug Delivery. Biomaterials 2019, 219, 119394. (268) Liu, M.; Wang, Y.; Kuai, Y.; Cong, J.; Xu, Y.; Piao, H.-G.; Pan, L.; Liu, Y. Magnetically Powered Shape-Transformable Liquid Metal Micromotors. Small 2019,15, 1905446. (269) Maier, A. M.; Weig, C.; Oswald, P.; Frey, E.; Fischer, P.; Liedl, T. Magnetic Propulsion of Microswimmers with DNA-Based Flagellar Bundles. Nano Lett. 2016,16, 906−910. (270) Hawkes, E.; An, B.; Benbernou, N. M.; Tanaka, H.; Kim, S.; Demaine, E. D.; Rus, D.; Wood, R. J. Programmable Matter by Folding. Proc. Natl. Acad. Sci. U. S. A. 2010,107, 12441. (271) Wood, R. J. The First Takeoff of a Biologically Inspired AtScale Robotic Insect. IEEE Trans. Robot. 2008,24, 341−347. (272) Ma, K. Y.; Chirarattananon, P.; Fuller, S. B.; Wood, R. J. Controlled Flight of a Biologically Inspired, Insect-Scale Robot. Science 2013,340, 603. (273) Novelino, L. S.; Ze, Q.; Wu, S.; Paulino, G. H.; Zhao, R. Untethered Control of Functional Origami Microrobots with Distributed Actuation. Proc. Natl. Acad. Sci. U. S. A. 2020,117, 24096. (274) Rus, D.; Tolley, M. T. Design, Fabrication and Control of Origami Robots. Nature Reviews Materials 2018,3, 101−112. (275) Gao, W.; Sattayasamitsathit, S.; Manesh, K. M.; Weihs, D.; Wang, J. Magnetically Powered Flexible Metal Nanowire Motors. J. Am. Chem. Soc. 2010,132, 14403−14405. (276) Gao, W.; Manesh, K. M.; Hua, J.; Sattayasamitsathit, S.; Wang, J. Hybrid Nanomotor: A Catalytically/Magnetically Powered Adaptive Nanowire Swimmer. Small 2011,7, 2047−2051. (277) Puigmartí-Luis, J.; Pellicer, E.; Jang, B.; Chatzipirpiridis, G.; Sevim, S.; Chen, X.-Z.; Nelson, B. J.; Pané, S. In Magn. Nano-and Microwires; Elsevier, 2020. (278) Petit, T.; Zhang, L.; Peyer, K. E.; Kratochvil, B. E.; Nelson, B. J. Selective Trapping and Manipulation of Microscale Objects Using Mobile Microvortices. Nano Lett. 2012,12, 156−160. (279) Li, Z.; Bai, L.; Zhou, C.; Yan, X.; Mair, L.; Zhang, A.; Zhang, L.; Wang, W. Highly Acid-Resistant, Magnetically Steerable Acoustic Micromotors Prepared by Coating Gold Microrods with Fe3O4 Nanoparticles via pH Adjustment. Part. Part. Syst. Charact. 2017, 34, 1600277. (280) Losic, D.; Lillo, M.; Losic, D., Jr. Porous Alumina with Shaped Pore Geometries and Complex Pore Architectures Fabricated by Cyclic Anodization. Small 2009,5, 1392−1397. (281) Bai, A.; Hu, C.-C.; Yang, Y.-F.; Lin, C.-C. Pore Diameter Control of Anodic Aluminum Oxide with Ordered Array of Nanopores. Electrochim. Acta 2008,53, 2258−2264. (282) Zhang, J.; Pané, S.; Sort, J.; Pellicer, E. Toward Robust Segmented Nanowires: Understanding the Impact of Crystallographic Texture on the Quality of Segment Interfaces in Magnetic Metallic Nanowires. Adv. Mater. Interfaces 2016,3, 1600336. (283) Jang, B.; Pellicer, E.; Guerrero, M.; Chen, X.; Choi, H.; Nelson, B. J.; Sort, J.; Pané, S. Fabrication of Segmented Au/Co/Au Nanowires: Insights in the Quality of Co/Au Junctions. ACS Appl. Mater. Interfaces 2014,6, 14583−14589. (284) Zhang, L.; Petit, T.; Lu, Y.; Kratochvil, B. E.; Peyer, K. E.; Pei, R.; Lou, J.; Nelson, B. J. Controlled Propulsion and Cargo Transport of Rotating Nickel Nanowires near a Patterned Solid Surface. ACS Nano 2010,4, 6228−6234. (285) Zhou, Q.; Petit, T.; Choi, H.; Nelson, B. J.; Zhang, L. Dumbbell Fluidic Tweezers for Dynamical Trapping and Selective Transport of Microobjects. Adv. Funct. Mater. 2017,27, 1604571. (286) Mushtaq, F.; Torlakcik, H.; Hoop, M.; Jang, B.; Carlson, F.; Grunow, T.; Läubli, N.; Ferreira, A.; Chen, X.-Z.; Nelson, B. J.; et al. Motile Piezoelectric Nanoeels for Targeted Drug Delivery. Adv. Funct. Mater. 2019,29, 1808135. (287) Palagi, S.; Fischer, P. Bioinspired Microrobots. Nat. Rev. Mater. 2018,3, 113−124. (288) Sun, M.; Fan, X.; Meng, X.; Song, J.; Chen, W.; Sun, L.; Xie, H. Magnetic Biohybrid Micromotors with High Maneuverability for Efficient Drug Loading and Targeted Drug Delivery. Nanoscale 2019, 11, 18382−18392. (289) Li, J.; Ji, F.; Ng, D. H. L.; Liu, J.; Bing, X.; Wang, P. Bioinspired Pt-free Molecularly Imprinted Hydrogel-Based Magnetic Janus Micromotors for Temperature-Responsive Recognition and Adsorption of Erythromycin in Water. Chem. Eng. J. 2019,369, 611− 620. (290) Maric, T.; Nasir, M. Z. M.; Rosli, N. F.; Budanovic, M.; Webster, R. D.; Cho, N.-J.; Pumera, M. Microrobots Derived from Variety Plant Pollen Grains for Efficient Environmental Clean Up and as an Anti-Cancer Drug Carrier. Adv. Funct. Mater. 2020,30, 2000112. (291) Zhang, Y.; Yan, K.; Ji, F.; Zhang, L. Enhanced Removal of Toxic Heavy Metals Using Swarming Biohybrid Adsorbents. Adv. Funct. Mater. 2018,28, 1806340. (292) Wang, X.; Cai, J.; Sun, L.; Zhang, S.; Gong, D.; Li, X.; Yue, S.; Feng, L.; Zhang, D. Facile Fabrication of Magnetic Microrobots Based on Spirulina Templates for Targeted Delivery and Synergistic ChemoPhotothermal Therapy. ACS Appl. Mater. Interfaces 2019,11, 4745− 4756. (293) Yasa, O.; Erkoc, P.; Alapan, Y.; Sitti, M. Microalga-Powered Microswimmers toward Active Cargo Delivery. Adv. Mater. 2018,30, 1804130. (294) Magdanz, V.; Khalil, I. S. M.; Simmchen, J.; Furtado, G. P.; Mohanty, S.; Gebauer, J.; Xu, H.; Klingner, A.; Aziz, A.; MedinaSánchez, M.; et al. IRONSperm: Sperm-templated soft magnetic microrobots. Sci. Adv. 2020,6, No. eaba5855. (295) Zhang, Y.; Zhang, L.; Yang, L.; Vong, C. I.; Chan, K. F.; Wu, W. K. K.; Kwong, T. N. Y.; Lo, N. W. S.; Ip, M.; Wong, S. H.; et al. Chemical Reviews pubs.acs.org/CR Review https://doi.org/10.1021/acs.chemrev.0c01234 Chem. Rev. 2021, 121, 4999−5041 5038 Real-Time Tracking of Fluorescent Magnetic Spore-Based Microrobots for Remote Detection of C. diff Toxins. Sci. Adv. 2019,5, No. eaau9650. (296) Wu, Z.; Li, J.; de Avila, B. E.-F.; Li, T.; Gao, W.; He, Q.; Zhang, L.; Wang, J. Water-Powered Cell-Mimicking Janus Micromotor. Adv. Funct. Mater. 2015,25, 7497−7501. (297) Wu, Z.; Li, T.; Gao, W.; Xu, T.; Jurado-Sánchez, B.; Li, J.; Gao, W.; He, Q.; Zhang, L.; Wang, J. Cell-Membrane-Coated Synthetic Nanomotors for Effective Biodetoxification. Adv. Funct. Mater. 2015,25, 3881−3887. (298) Striggow, F.; Medina-Sánchez, M.; Auernhammer, G. K.; Magdanz, V.; Friedrich, B. M.; Schmidt, O. G. Sperm-Driven Micromotors Moving in Oviduct Fluid and Viscoelastic Media. Small 2020,16, 2000213. (299) Magdanz, V.; Sanchez, S.; Schmidt, O. G. Development of a Sperm-Flagella Driven Micro-Bio-Robot. Adv. Mater. 2013,25, 6581− 6588. (300) Singh, A. V.; Hosseinidoust, Z.; Park, B.-W.; Yasa, O.; Sitti, M. Microemulsion-Based Soft Bacteria-Driven Microswimmers for Active Cargo Delivery. ACS Nano 2017,11, 9759−9769. (301) Stanton, M. M.; Park, B.-W.; Miguel-López, A.; Ma, X.; Sitti, M.; Sánchez, S. Biohybrid Microtube Swimmers Driven by Single Captured Bacteria. Small 2017,13, 1603679. (302) Magdanz, V.; Medina-Sánchez, M.; Schwarz, L.; Xu, H.; Elgeti, J.; Schmidt, O. G. Spermatozoa as Functional Components of Robotic Microswimmers. Adv. Mater. 2017,29, 1606301. (303) Sun, H. C.; Liao, P.; Wei, T.; Zhang, L.; Sun, D. Magnetically Powered Biodegradable Microswimmers. Micromachines 2020,11, 404 DOI: 10.1002/adma.202004172. (304) Yasa, I. C.; Ceylan, H.; Bozuyuk, U.; Wild, A.-M.; Sitti, M. Elucidating the Interaction Dynamics between Microswimmer Body and Immune System for Medical Microrobots. Sci. Robot. 2020,5, No. eaaz3867. (305) Alapan, Y.; Yasa, O.; Schauer, O.; Giltinan, J.; Tabak, A. F.; Sourjik, V.; Sitti, M. Soft Erythrocyte-Based Bacterial Microswimmers for Cargo Delivery. Sci. Robot. 2018,3, No. eaar4423. (306) Iacovacci, V.; Ricotti, L.; Signore, G.; Vistoli, F.; Sinibaldi, E.; Menciassi, A. 2019 International Conference on Robotics and Automation (ICRA) 2019, 2495−2501. (307) Iacovacci, V.; Ricotti, L.; Sinibaldi, E.; Signore, G.; Vistoli, F.; Menciassi, A. An Intravascular Magnetic Catheter Enables the Retrieval of Nanoagents from the Bloodstream. Adv. Sci. 2018,5, 1800807. (308) Luo, M.; Feng, Y.; Wang, T.; Guan, J. Micro-/Nanorobots at Work in Active Drug Delivery. Adv. Funct. Mater. 2018,28, 1706100. (309) Mhanna, R.; Qiu, F.; Zhang, L.; Ding, Y.; Sugihara, K.; Zenobi-Wong, M.; Nelson, B. J. Artificial Bacterial Flagella for Remote-Controlled Targeted Single-Cell Drug Delivery. Small 2014, 10, 1953−1957. (310) Xu, X.; Hou, S.; Wattanatorn, N.; Wang, F.; Yang, Q.; Zhao, C.; Yu, X.; Tseng, H.-R.; Jonas, S. J.; Weiss, P. S. Precision-Guided Nanospears for Targeted and High-Throughput Intracellular Gene Delivery. ACS Nano 2018,12, 4503−4511. (311) Alapan, Y.; Bozuyuk, U.; Erkoc, P.; Karacakol, A. C.; Sitti, M. Multifunctional Surface Microrollers for Targeted Cargo Delivery in Physiological Blood Flow. Sci. Robot. 2020,5, No. eaba5726. (312) Felfoul, O.; Mohammadi, M.; Taherkhani, S.; de Lanauze, D.; Zhong Xu, Y.; Loghin, D.; Essa, S.; Jancik, S.; Houle, D.; Lafleur, M.; et al. Magneto-Aerotactic Bacteria Deliver Drug-Containing Nanoliposomes to Tumour Hypoxic Regions. Nat. Nanotechnol. 2016,11, 941−947. (313) Wu, Z.; Esteban-Fernández de Avila,B.;Martín,A.; Christianson, C.; Gao, W.; Thamphiwatana, S. K.; Escarpa, A.; He, Q.; Zhang, L.; Wang, J. RBC Micromotors Carrying Multiple Cargos towards Potential Theranostic Applications. Nanoscale 2015,7, 13680−13686. (314) Srivastava, S. K.; Medina-Sánchez, M.; Koch, B.; Schmidt, O. G. Medibots: Dual-Action Biogenic Microdaggers for Single-Cell Surgery and Drug Release. Adv. Mater. 2016,28, 832−837. (315) Kadiri, V. M.; Bussi, C.; Holle, A. W.; Son, K.; Kwon, H.; Schutz, G.; Gutierrez, M. G.; Fischer, P. Biocompatible Magnetic Microand Nanodevices: Fabrication of FePt Nanopropellers and Cell Transfection. Adv. Mater. 2020,32, 2001114. (316) Zong, Z.; Zhou, X.; Zhang, L.; Tan, Q.; Xiong, J.; Zhang, W. Magnetically Propelled Soft Micromachines with Multipatterned Fabrications. J. Micromech. Microeng. 2020,30, 085001. (317) Zhang, L.; Petit, T.; Peyer, K. E.; Nelson, B. J. Targeted Cargo Delivery using a Rotating Nickel Nanowire. Nanomedicine 2012,8, 1074−1080. (318) Huang, J.; Zhang, H.; Yan, X.; Zhang, L. Cell Encapsulation and Magnetic Manipulation for Targeted Delivery. Nanomedicine 2016,2, 488−489. (319) Xu, H.; Medina-Sánchez, M.; Schmidt, O. G. Magnetic Micromotors for Multiple Motile Sperm Cells Capture, Transport, and Enzymatic Release. Angew. Chem., Int. Ed. 2020,59, 15029− 15037. (320) Schwarz, L.; Karnaushenko, D. D.; Hebenstreit, F.; Naumann, R.;Schmidt,O.G.;Medina-Sánchez,M.ARotatingSpiral Micromotor for Noninvasive Zygote Transfer. Adv. Sci. 2020,7, 2000843. (321) Kim, E.; Jeon, S.; An, H.-K.; Kianpour, M.; Yu, S.-W.; Kim, J.- y.; Rah, J.-C.; Choi, H. A Magnetically Actuated Microrobot for Targeted Neural Cell Delivery and Selective Connection of Neural Networks. Sci. Adv. 2020,6, No. eabb5696. (322) Wang, W.; Wu, Z.; He, Q. Swimming Nanorobots for Opening a Cell Membrane Mechanically. View 2020,1, 20200005. (323) Venugopalan, P. L.; Esteban-Fernández de Avila, B.; Pal, M.; Ghosh, A.; Wang, J. Fantastic Voyage of Nanomotors into the Cell. ACS Nano 2020,14, 9423−9439. (324) Lee, S.; Lee, S.; Kim, S.; Yoon, C.-H.; Park, H.-J.; Kim, J.-y.; Choi, H. Fabrication and Characterization of a Magnetic Drilling Actuator for Navigation in a Three-dimensional Phantom Vascular Network. Sci. Rep. 2018,8, 3691. (325) Martel, S.; Felfoul, O.; Mathieu, J.-B.; Chanu, A.; Tamaz, S.; Mohammadi, M.; Mankiewicz, M.; Tabatabaei, N. MRI-based Medical Nanorobotic Platform for the Control of Magnetic Nanoparticles and Flagellated Bacteria for Target Interventions in Human Capillaries. Int. J. Robot. Res. 2009,28, 1169−1182. (326) Kikuchi, K.; Yamazaki, A.; Sendoh, M.; Ishiyama, K.; Arai, K. I. Fabrication of a Spiral Type Magnetic Micromachine for Trailing a Wire. IEEE Trans. Magn. 2005,41, 4012−4014. (327) Martel, S. 2007 29th Annual International Conference of the IEEE Eng. Med. Bio. Soci. 2007, 1475−1478. (328) Garcia-Gradilla, V.; Orozco, J.; Sattayasamitsathit, S.; Soto, F.; Kuralay, F.; Pourazary, A.; Katzenberg, A.; Gao, W.; Shen, Y.; Wang, J. Functionalized Ultrasound-Propelled Magnetically Guided Nanomotors: Toward Practical Biomedical Applications. ACS Nano 2013,7, 9232−9240. (329) Magdanz, V.; Koch, B.; Sanchez, S.; Schmidt, O. G. Sperm Dynamics in Tubular Confinement. Small 2015,11, 781−785. (330) Qiu, T.; Schamel, D.; Mark, A. G.; Fischer, P. 2014 IEEE International Conference on Robotics and Automation (ICRA) 2014, 3801−3806. (331) Pokki, J.; Ergeneman, O.; Chatzipirpiridis, G.; Luhmann, T.; Sort, J.; Pellicer, E.; Pot, S. A.; Spiess, B. M.; Pané, S.; Nelson, B. J. Protective Coatings for Intraocular Wirelessly Controlled Microrobots for Implantation: Corrosion, Cell Culture, and in Vivo Animal Tests. J. Biomed. Mater. Res., Part B 2017,105, 836−845. (332) Jeong, M.; Choi, E.; Li, D.; Palagi, S.; Fischer, P.; Qiu, T. Soft Continuous Surface for Micromanipulation driven by Light-controlled Hydrogels. 2019 International Conference on Manipulation, Automation and Robotics at Small Scales (MARSS) 2019,1−6. (333) Chen, J.; Wang, Y. Personalized Dynamic Transport of Magnetic Nanorobots inside the Brain Vasculature. Nanotechnology 2020,31, 495706. (334) Li, J.; Thamphiwatana, S.; Liu, W.; Esteban-Fernández de Avila, B.; Angsantikul, P.; Sandraz, E.; Wang, J.; Xu, T.; Soto, F.; Ramez, V.; et al. Enteric Micromotor Can Selectively Position and Chemical Reviews pubs.acs.org/CR Review https://doi.org/10.1021/acs.chemrev.0c01234 Chem. Rev. 2021, 121, 4999−5041 5039