Harnessing Disparities in Magnetic Microswarms: From Construction to Collaborative Tasks.

Individual differences in size, experience, and task specialization in natural swarms often result in heterogeneity and hierarchy, facilitating efficient and coordinated task accomplishment. Drawing inspiration from this phenomenon, a general strategy is proposed for organizing magnetic micro/nanorobots (MNRs) with apparent differences in size, shape, and properties into cohesive microswarms with tunable heterogeneity, controlled spatial hierarchy, and collaborative tasking capability. In this strategy, disparate magnetic MNRs can be manipulated to show reversible transitions between synchronization and desynchronization by elaborately regulating parameter sets of the rotating magnetic field. Utilizing these transitions, alongside local robust hydrodynamic interactions, diverse heterospecific pairings of disparate magnetic MNRs can be organized into heterogeneous microswarms, and their spatial organization can be dynamically adjusted from egalitarian to leader-follower-like hierarchies on the fly, both in open space and complex microchannels. Furthermore, when specializing the disparate MNRs with distinct functions ("division of labor") such as sensing and drug carrying, they can execute precise drug delivery targeting unknown sites in a collaborative sensing-navigating-cargo dropping sequence, demonstrating significant potential for precise tumor treatment. These findings highlight the critical roles of attribute differences and hierarchical organization in designing efficient swarming micro/nanorobots for biomedical applications.

Heterogeneous Sensor-Carrier Microswarms for Collaborative Precise Drug Delivery toward Unknown Targets with Localized Acidosis.

Micro/nanorobots hold the potential to revolutionize biomedicine by executing diverse tasks in hard-to-reach biological environments. Nevertheless, achieving precise drug delivery to unknown disease sites using swarming micro/nanorobots remains a significant challenge. Here we develop a heterogeneous swarm comprising sensing microrobots (sensor-bots) and drug-carrying microrobots (carrier-bots) with collaborative tasking capabilities for precise drug delivery toward unknown sites. Leveraging robust interspecific hydrodynamic interactions, the sensor-bots and carrier-bots spontaneously synchronize and self-organize into stable heterogeneous microswarms. Given that the sensor-bots can create real-time pH maps employing pH-responsive structural-color changes and the doxorubicin-loaded carrier-bots exhibit selective adhesion to acidic targets via pH-responsive charge reversal, the sensor-carrier microswarm, when exploring unknown environments, can detect and localize uncharted acidic targets, guide itself to cover the area, and finally deploy therapeutic carrier-bots precisely there. This versatile platform holds promise for treating diseases with localized acidosis and inspires future theranostic microsystems with expandability, task flexibility, and high efficiency.

Swarming magnetic nanorobots bio-interfaced by heparinoid-polymer brushes for in vivo safe synergistic thrombolysis.

Biocompatible swarming magnetic nanorobots that work in blood vessels for safe and efficient targeted thrombolytic therapy in vivo are demonstrated. This is achieved by using magnetic beads elaborately grafted with heparinoid-polymer brushes (HPBs) upon the application of an alternating magnetic field B(t). Because of the dense surface charges bestowed by HPBs, the swarming nanorobots demonstrate reversible agglomeration-free reconfigurations, low hemolysis, anti-bioadhesion, and self-anticoagulation in high-ionic-strength blood environments. They are confirmed in vitro and in vivo to perform synergistic thrombolysis efficiently by "motile-targeting" drug delivery and mechanical destruction. Moreover, upon the completion of thrombolysis and removal of B(t), the nanorobots disassemble into dispersed particles in blood, allowing them to safely participate in circulation and be phagocytized by immune cells without apparent organ damage or inflammatory lesion. This work provides a rational multifaceted HPB biointerfacing design strategy for biomedical nanorobots and a general motile platform to deliver drugs for targeted therapies.

Swarming Multifunctional Heater-Thermometer Nanorobots for Precise Feedback Hyperthermia Delivery.

Micro-/nanorobots (MNRs) are envisioned to act as "motile-targeting" platforms for biomedical tasks due to their ability to propel and navigate in challenging, hard-to-reach biological environments. However, it remains a great challenge for current swarming MNRs to accurately report and regulate therapeutic doses during disease treatment. Here we present the development of swarming multifunctional heater-thermometer nanorobots (HT-NRs) and their application in precise feedback photothermal hyperthermia delivery. The HT-NRs are designed as photothermal-responsive photonic nanochains consisting of magnetic Fe3O4 nanoparticles arranged periodically in one dimension and encapsulated in a temperature-responsive hydrogel shell. The HT-NRs exhibit energetic and controllable swarming motions under a rotating magnetic field, while simultaneously functioning as motile nanoheaters and nanothermometers, utilizing their photothermal conversion and (photo)thermal-responsive structural color changes (photothermochromism). Consequently, the HT-NRs can be quickly deployed to a remote target area (e.g., a superficial tumor lesion) using their collective motion and selectively eliminate diseased cells in a specific targeted region by utilizing their self-reporting photothermochromism as visual feedback for precisely regulating external light irradiation. This work may inspire the development of intelligent multifunctional theranostic micro-/nanorobots and their practical applications in precise disease treatment.

Tadpole-Like Flexible Microswimmers with the Head and Tail Both Magnetic.

In analogy to eukaryotic cells that move by beating the flagella, magnetically powered micro/nanorobots with flexible filaments are capable of eluding the limitation of the scallop theorem to generate net displacement in a three-dimensional space, but they are limited by complicated fabrication and low speed. Here, we demonstrate a tadpole-like flexible microswimmer with a head and tail that are both magnetic by developing a magnetically assisted in situ polymerization method. The flexible microswimmer consists of a magnetic-bead head fixed to a nanochain bundle of magnetic nanoparticles (tail), and the tail length and stiffness can be adjusted simply by changing the duration and strength of the applied magnetic field during fabrication, respectively. For the microswimmer under an oscillating magnetic field, the magnetic head generates an undulatory motion, which can be further increased by the flexible magnetic tail. The magnetically induced undulation of the head and tail generates a traveling wave propagating through its flexible tail, resulting in efficient tadpole-like propulsion of the microswimmer. The flexible microswimmer runs at a maximum motion speed when the tail length is ∼5 times the diameter of the magnetic head, corresponding to ∼half the wavelength of the undulatory motion. The flexible microswimmers reported here are promising for active sensing and drug delivery, as the tails can be designed with various responsive hydrogels, and the results are expected to advance flexible micro/nanorobots.

Swarming Responsive Photonic Nanorobots for Motile-Targeting Microenvironmental Mapping and Mapping-Guided Photothermal Treatment.

Micro/nanorobots can propel and navigate in many hard-to-reach biological environments, and thus may bring revolutionary changes to biomedical research and applications. However, current MNRs lack the capability to collectively perceive and report physicochemical changes in unknown microenvironments. Here we propose to develop swarming responsive photonic nanorobots that can map local physicochemical conditions on the fly and further guide localized photothermal treatment. The RPNRs consist of a photonic nanochain of periodically-assembled magnetic Fe3O4 nanoparticles encapsulated in a responsive hydrogel shell, and show multiple integrated functions, including energetic magnetically-driven swarming motions, bright stimuli-responsive structural colors, and photothermal conversion. Thus, they can actively navigate in complex environments utilizing their controllable swarming motions, then visualize unknown targets (e.g., tumor lesion) by collectively mapping out local abnormal physicochemical conditions (e.g., pH, temperature, or glucose concentration) via their responsive structural colors, and further guide external light irradiation to initiate localized photothermal treatment. This work facilitates the development of intelligent motile nanosensors and versatile multifunctional nanotheranostics for cancer and inflammatory diseases.

Ultrasmall Fe2O3 Tubular Nanomotors: The First Example of Swarming Photocatalytic Nanomotors Operating in High-Electrolyte Media.

Self-propelled chemical micro/nanomotors (MNMs) have demonstrated considerable potential in targeted drug delivery, (bio)sensing, and environmental remediation due to their autonomous nature and possible intelligent self-targeting behaviors (e.g., chemotaxis and phototaxis). However, these MNMs are commonly limited by their primary propulsion mechanisms of self-electrophoresis and electrolyte self-diffusiophoresis, making them prone to quenching in high electrolyte environments. Thus, the swarming behaviors of chemical MNMs in high-electrolyte media remain underexplored, despite their potential to enable the execution of complex tasks in high-electrolyte biological media or natural waters. In this study, we develop ultrasmall tubular nanomotors that exhibit ion-tolerant propulsions and collective behaviors. Upon vertical upward UV irradiation, the ultrasmall Fe2O3 tubular nanomotors (Fe2O3 TNMs) demonstrate positive superdiffusive photogravitaxis and can further self-organize into nanoclusters near the substrate in a reversible manner. After self-organization, the Fe2O3 TNMs exhibit a pronounced emergent behavior, allowing them to switch from random superdiffusions to ballistic motions near the substrate. Even at a high electrolyte concentration (Ce), the ultrasmall Fe2O3 TNMs retain a relatively thick electrical double layer (EDL) compared to their size, and the electroosmotic slip flow in their EDL is strong enough to propel them and induce phoretic interactions among them. As a result, the nanomotors can rapidly concentrate near the substrate and then gather into motile nanoclusters in high-electrolyte environments. This work opens a gate for designing swarming ion-tolerant chemical nanomotors and may expedite their applications in biomedicine and environmental remediation.

Lighting up Micro-/Nanorobots with Fluorescence.

Micro-/nanorobots (MNRs) can be autonomously propelled on demand in complex biological environments and thus may bring revolutionary changes to biomedicines. Fluorescence has been widely used in real-time imaging, chemo-/biosensing, and photo-(chemo-) therapy. The integration of MNRs with fluorescence generates fluorescent MNRs with unique advantages of optical trackability, on-the-fly environmental sensitivity, and targeting chemo-/photon-induced cytotoxicity. This review provides an up-to-date overview of fluorescent MNRs. After the highlighted elucidation about MNRs of various propulsion mechanisms and the introductory information on fluorescence with emphasis on the fluorescent mechanisms and materials, we systematically illustrate the design and preparation strategies to integrate MNRs with fluorescent substances and their biomedical applications in imaging-guided drug delivery, intelligent on-the-fly sensing and photo-(chemo-) therapy. In the end, we summarize the main challenges and provide an outlook on the future directions of fluorescent MNRs. This work is expected to attract and inspire researchers from different communities to advance the creation and practical application of fluorescent MNRs on a broad horizon.

Light-Powered, Fuel-Free Oscillation, Migration, and Reversible Manipulation of Multiple Cargo Types by Micromotor Swarms.

Through experiments and simulations, we show that fuel-free photoactive TiO2 microparticles can form mobile, coherent swarms in the presence of UV light, which track the subsequent movement of an irradiated spot in a fluid-filled microchamber. Multiple concurrent propulsion mechanisms (electrolyte diffusioosmotic swarming, photocatalytic expansion, and photothermal migration) control the rich collective behavior of the swarms, which provide a strategy to reversely manipulate cargo. The active swarms can autonomously pick up groups of inert particles, sort them by size, and sequentially release the sorted particles at particular locations in the microchamber. Hence, these swarms overcome three obstacles, limiting the utility of self-propelled particles. Namely, they can (1) undergo directed, long-range migration without the addition of a chemical fuel, (2) perform diverse collective behavior not possible with a single active particle, and (3) repeatedly and controllably isolate and deliver specific components of a multiparticle "cargo". Since light sources are easily fabricated, transported, and controlled, the results can facilitate the development of portable devices, providing broader access to the diagnostic and manufacturing advances enabled by microfluidics.

"Motile-targeting" drug delivery platforms based on micro/nanorobots for tumor therapy.

Traditional drug delivery systems opened the gate for tumor-targeted therapy, but they generally took advantage of enhanced permeability and retention or ligand-receptor mediated interaction, and thus suffered from limited recognition range (<0.5 nm) and low targeting efficiency (0.7%, median). Alternatively, micro/nanorobots (MNRs) may act as emerging "motile-targeting" drug delivery platforms to deliver therapeutic payloads, thereby making a giant step toward effective and safe cancer treatment due to their autonomous movement and navigation in biological media. This review focuses on the most recent developments of MNRs in "motile-targeting" drug delivery. After a brief introduction to traditional tumor-targeted drug delivery strategies and various MNRs, the representative applications of MNRs in "motile-targeting" drug delivery are systematically streamlined in terms of the propelling mechanisms. Following a discussion of the current challenges of each type of MNR in biomedical applications, as well as future prospects, several promising designs for MNRs that could benefit in "motile-targeting" drug delivery are proposed. This work is expected to attract and motivate researchers from different communities to advance the creation and practical application of the "motile-targeting" drug delivery platforms.

Light-Programmable Assemblies of Isotropic Micromotors.

"Life-like" nonequilibrium assemblies are of increasing significance, but suffering from limited steerability as they are generally based on micro/nanomotors with inherent asymmetry in chemical composition or geometry, of which the vigorous random Brownian rotations disturb the local interactions. Here, we demonstrate that isotropic photocatalytic micromotors, due to the persistent phoretic flow from the illuminated to shadowed side irrespective of their Brownian rotations, experience light-programmable local interactions (reversibly from attraction to repulsion and/or alignment) depending on the direction of the incident lights. Thus, they can be organized into a variety of tunable nonequilibrium assemblies, such as apolar solids (i.e., immobile colloidal crystal), polar liquids (i.e., phototactic colloidal stream), and polar solids (i.e., phototactic colloidal crystal), which can further be "cut" into a predesigned pattern by utilizing the switching motor-motor interactions at superimposed-light edges. This work facilitates the development of active matters and motile functional microdevices.

ZnO-based micromotors fueled by CO2: the first example of self-reorientation-induced biomimetic chemotaxis.

Synthetic chemotactic micro/nanomotors are envisioned to actively 'seek out' targets by following specific chemicals, but they are mainly powered by bioincompatible fuels and only show pseudochemotaxis (or advanced chemokinesis) due to their weak self-reorientation capabilities. Here we demonstrate that synthetic ZnO-based Janus micromotors can be powered by the alternative biocompatible fuel of CO2, and further provide the first example of self-reorientation-induced biomimetic chemotaxis using them. The ZnO-based micromotors are highly sensitive to dissolved CO2 in water, which enables the corrosion of ZnO to continuously occur by providing H+ through hydration. Thus, they can autonomously move even in water exposed to air based on self-diffusiophoresis. Furthermore, they can sense the local CO2 gradient and perform positive chemotaxis by self-reorientations under the phoretic torque. Our discovery opens a gate to developing intelligent micro/nanomotors powered by, and sensitive to, biocompatible atmospheric or endogenous gaseous chemicals for biomedical and environmental applications.

Cooperative transport by flocking phototactic micromotors.

Cargo delivery by micro/nanomotors provides enormous opportunities for micromanipulation, environmental cleaning, drug delivery, etc. However, due to the limited driving force, it is usually difficult for single micro/nanomotors to transport cargoes much larger or heavier than themselves. Here, we demonstrate that flocking phototactic TiO2 micromotors can cooperatively transport multiple and different types of large cargoes based on light-responsive diffusiophoresis. Utilizing spontaneous diffusiophoretic attraction, flocking TiO2 micromotors can load large cargoes. Under UV light navigation, flocking TiO2 micromotors cooperatively carry and transport cargoes via collective diffusiophoretic repulsion in open space or complex microenvironments. After reaching the destination, the carried cargoes can also be unloaded from the flock and be deployed at a predetermined destination by disassembling or reversing the flock. This study may pave the way for developing intelligent swarming micro/nanorobots for cooperative targeting micromanipulation and advancing their applications in drug delivery and microengineering.

Mg-Based Micromotors with Motion Responsive to Dual Stimuli.

Mg-based micromotors have emerged as an extremely attractive artificial micro/nanodevice, but suffered from uncontrollable propulsion and limited motion lifetime, restricting the fulfillment of complex tasks. Here, we have demonstrated Mg-based micromotors composed of Mg microspheres asymmetrically coated with Pt and temperature-sensitive poly(N-isopropylacrylamide) (PNIPAM) hydrogel layers in sequence. They can implement different motion behaviors stemming from the driving mechanism transformation when encountering catalyzed substrates such as H2O2 and respond to both H2O2 concentration and temperature in aqueous environment. The as-constructed Mg-based micromotors are self-propelled by Pt-catalyzed H2O2 decomposition following the self-consuming Mg-H2O reaction. In this case, they could further generate bilateral bubbles and thus demonstrate unique self-limitation motion like hovering when the phase transformation of PNIPAM is triggered by decreasing temperature or when the H2O2 concentration after permeating across the PNIPAM hydrogel layer is high enough to facilitate bubble nucleation. Our work for the first time provides a stimuli-induced "hovering" strategy for self-propelled micromotors, which endows Mg-based micromotors with an intelligent response to the surroundings besides the significant extension of their motion lifetime.

Active Micromotor Systems Built from Passive Particles with Biomimetic Predator-Prey Interactions.

Inspired by chasing-escaping behaviors of predator and swarming prey in nature, here we demonstrate a concept to create active micromotor systems from two species of passive microparticles with biomimetic predator-prey interactions. In this concept, the biomimetic predator-prey interactions are established in a binary particle system comprising the diffusiophoretic attractive microparticles (prey particles) and the diffusiophoretic repulsive ones (predator particles). In the absence of additional chemical fuels and external fields, the predator particles are attracted by and constantly chase the swarming prey particles, which, in response, escape from the former and show dynamic group reconfigurations because of the local repulsion. Based on this concept, various synthetic active micromotor systems have been demonstrated, including active ZnO-TiO2, Ag3PO4-TiO2, and ZnO-AgBr micromotor systems. As the predator and prey particles are powered by each other through the biomimetic predator-prey interactions, the concept proposed here provides an advanced method to develop not only a class of single micromotors powered by passive particles or "solid fuels" but also micromotor swarms capable of manipulating "moving cargo". In addition, it also illustrates a proof-of-concept implementation of intelligent micro/nanomotor systems composed of heterogeneous individuals with complementary or cooperative functions.

Phototactic Flocking of Photochemical Micromotors.

Inspired by astonishing collective motions and tactic behaviors in nature, here we show phototactic flocking of synthetic photochemical micromotors. When enriched with hydroxyl groups, TiO2 micromotors can spontaneously gather into flocks in aqueous media through electrolyte diffusiophoresis. Under light irradiation, due to the dominant nonelectrolyte diffusiophoretic interaction resulting from the overlap of asymmetric nonelectrolyte clouds around adjacent individuals, these flocks exhibit intriguing collective behaviors, such as dilatational negative phototaxis, high collective velocity, and adaptive group reconfiguration. Consequently, the micromotor flocks can migrate along pre-designed paths and actively bypass obstacles with reversible dilatation (expansion/contraction) under pulsed light navigation. Furthermore, owing to the enhanced driving force and rapid dilatational area covering, they are able to execute cooperative tasks that single micromotors cannot achieve, such as cooperative large-cargo transport and collective microenvironment mapping. Our discovery would promote the creation of reconfigurable microrobots, active materials, and intelligent synthetic systems.

Surface Charge-Reversible Tubular Micromotors for Extraction of Nucleic Acids in Microsystems.

Extraction of nucleic acids in microsystems is of significance for biomedical applications, but the current extraction methods generally require sophisticated microchannels and external equipment, hindering their practical applications. In this work, we have demonstrated a simple, versatile and efficient approach to extract nucleic acids in microsystems by developing cationic branched polyethyleneimine (PEI)-functionalized tubular micromotors. The as-developed tubular micromotors are fabricated by a two-step process combining the template-assisted electrodeposition and carbodiimide chemistry, and contain an inner catalytic Pt layer, a middle magnetic Ni layer and an outer cationic PEI layer. They exhibit autonomous bubble-propelled motion in aqueous hydrogen peroxide solutions, which can be guided by an external magnetic field, and the surface charges can be reversibly modulated by changing the pH value of the solution. Consequently, the as-developed tubular micromotors can selectively absorb nucleic acids from acidic solutions and desorb them into alkaline solutions, leading to the extraction of nucleic acids with high efficiency without external stirring. Furthermore, they can be operated in a microchannel chip without the aid of a pumping system. Our results indicate that this PEI-functionalized tubular micromotor platform provides a novel, simple and versatile microsystem nucleic acid extraction technology, holding considerable promise for important practical applications.

Simple-Structured Micromotors Based on Inherent Asymmetry in Crystalline Phases: Design, Large-Scale Preparation, and Environmental Application.

The key principle of designing a micro/nanomotor is to introduce asymmetry to a micro/nanoparticle. However, micro/nanomotors designed based on external asymmetry and inherent chemical and geometrical asymmetry usually suffer from tedious small-scale preparation, high cost, and/or complexity of external power and control devices, making them face insurmountable hurdles in practical applications. Herein, considering the possible distinct properties of different polymorphs, we propose a novel design strategy of simple-structured micromotors by introducing inherent asymmetry in crystalline phases. The inherent phase asymmetry can be easily introduced in spherical TiO2 particles by adjusting the calcination temperature to control the phase transition and growth of primary grains. The as-designed anatase/rutile TiO2 micromotors not only show efficient autonomous motions controlled by light in liquid media stemming from the asymmetric surface photocatalytic redox reactions but also have a promising application in environmental remediation due to their high photocatalytic activity in "on-the-fly" degradation of organic pollutants, facile large-scale fabrication, and low cost. The proposed design strategy may pave the way for the large-scale productions and applications of micro/nanomotors.

Hydrophobic Janus Foam Motors: Self-Propulsion and On-The-Fly Oil Absorption.

In this work, we for the first time have proposed and fabricated a self-propelled Janus foam motor for on-the-fly oil absorption on water by simply loading camphor/stearic acid (SA) mixture as fuels into one end of the SA-modified polyvinyl alcohol (PVA) foam. The as-fabricated Janus foam motors show an efficient Marangoni effect-based self-propulsion on water for a long lifetime due to the effective inhibition of the rapid release of camphor by the hydrophobic SA in the fuel mixture. Furthermore, they can automatically search, capture, and absorb oil droplets on the fly, and then be spontaneously self-assembled after oil absorption due to the self-propulsion of the motors as well as the attractive capillary interactions between the motors and oil droplets. This facilitates the subsequent collection of the motors from water after the treatment. Since the as-developed Janus foam motors can effectively integrate intriguing behaviors of the self-propulsion, efficient oil capture, and spontaneous self-assembly, they hold great promise for practical applications in water treatment.

Light-Controlled Swarming and Assembly of Colloidal Particles.

Swarms and assemblies are ubiquitous in nature and they can perform complex collective behaviors and cooperative functions that they cannot accomplish individually. In response to light, some colloidal particles (CPs), including light active and passive CPs, can mimic their counterparts in nature and organize into complex structures that exhibit collective functions with remote controllability and high temporospatial precision. In this review, we firstly analyze the structural characteristics of swarms and assemblies of CPs and point out that light-controlled swarming and assembly of CPs are generally achieved by constructing light-responsive interactions between CPs. Then, we summarize in detail the recent advances in light-controlled swarming and assembly of CPs based on the interactions arisen from optical forces, photochemical reactions, photothermal effects, and photoisomerizations, as well as their potential applications. In the end, we also envision some challenges and future prospects of light-controlled swarming and assembly of CPs. With the increasing innovations in mechanisms and control strategies with easy operation, low cost, and arbitrary applicability, light-controlled swarming and assembly of CPs may be employed to manufacture programmable materials and reconfigurable robots for cooperative grasping, collective cargo transportation, and micro- and nanoengineering.