Chemical multiscale robotics for bacterial biofilm treatment.

A biofilm constitutes a bacterial community encased in a sticky matrix of extracellular polymeric substances. These intricate microbial communities adhere to various host surfaces such as hard and soft tissues as well as indwelling medical devices. These microbial aggregates form a robust matrix of extracellular polymeric substances (EPSs), leading to the majority of human infections. Such infections tend to exhibit high resistance to treatment, often progressing into chronic states. The matrix of EPS protects bacteria from a hostile environment and prevents the penetration of antibacterial agents. Modern robots at nano, micro, and millimeter scales are highly attractive candidates for biomedical applications due to their diverse functionalities, such as navigating in confined spaces and targeted multitasking. In this tutorial review, we describe key milestones in the strategies developed for the removal and eradication of biofilms using robots of different sizes and shapes. It can be seen that robots at different scales are useful and effective tools for treating bacterial biofilms, thus preventing persistent infections, the loss of costly implanted medical devices, and additional costs associated with hospitalization and therapies.

Methamphetamine Removal from Aquatic Environments by Magnetic Microrobots with Cyclodextrin Chiral Recognition Elements.

The growing consumption of drugs of abuse together with the inefficiency of the current wastewater treatment plants toward their presence has resulted in an emergent class of pollutants. Thus, the development of alternative approaches to remediate this environmental threat is urgently needed. Microrobots, combining autonomous motion with great tunability for the development of specific tasks, have turned into promising candidates to take on the challenge. Here, hybrid urchin-like hematite (α-Fe2O3) microparticles carrying magnetite (Fe3O4) nanoparticles and surface functionalization with organic ß-cyclodextrin (CD) molecules are prepared with the aim of on-the-fly encapsulation of illicit drugs into the linked CD cavities of moving microrobots. The resulting mag-CD microrobots are tested against methamphetamine (MA), proving their ability for the removal of this psychoactive substance. A dramatically enhanced capture of MA from water with active magnetically powered microrobots when compared with static passive CD-modified particles is demonstrated. This work shows the advantages of enhanced mass transfer provided by the externally controlled magnetic navigation in microrobots that together with the versatility of their design is an efficient strategy to clean polluted waters.

Light-Powered Self-Adaptive Mesostructured Microrobots for Simultaneous Microplastics Trapping and Fragmentation via in situ Surface Morphing.

Microplastics, which comprise one of the omnipresent threats to human health, are diverse in shape and composition. Their negative impacts on human and ecosystem health provide ample incentive to design and execute strategies to trap and degrade diversely structured microplastics, especially from water. This work demonstrates the fabrication of single-component TiO2 superstructured microrobots to photo-trap and photo-fragment microplastics. In a single reaction, rod-like microrobots diverse in shape and with multiple trapping sites, are fabricated to exploit the asymmetry of the microrobotic system advantageous for propulsion. The microrobots work synergistically to photo-catalytically trap and fragment microplastics in water in a coordinated fashion. Hence, a microrobotic model of "unity in diversity" is demonstrated here for the phototrapping and photofragmentation of microplastics. During light irradiation and subsequent photocatalysis, the surface morphology of microrobots transformed into porous flower-like networks that trap microplastics for subsequent degradation. This reconfigurable microrobotic technology represents a significant step forward in the efforts to degrade microplastics.

Swarming Magnetic Microrobots for Pathogen Isolation from Milk.

Bovine mastitis produced by Staphylococcus aureus (S. aureus) causes major problems in milk production due to the staphylococcal enterotoxins produced by this bacterium. These enterotoxins are stable and cannot be eradicated easily by common hygienic procedures once they are formed in dairy products. Here, magnetic microrobots (MagRobots) are developed based on paramagnetic hybrid microstructures loaded with IgG from rabbit serum that can bind and isolate S. aureus from milk in a concentration of 3.42 104 CFU g-1 (allowable minimum level established by the United States Food and Drug Administration, FDA). Protein A, which is present on the cell wall of S. aureus, selectively binds IgG from rabbit serum and loads the bacteria onto the surface of the MagRobots. The selective isolation of S. aureus is confirmed using a mixed suspension of S. aureus and Escherichia coli (E. coli). Moreover, this fuel-free system based on magnetic robots does not affect the natural milk microbiota or add any toxic compound resulting from fuel catalysis. This system can be used to isolate and transport efficiently S. aureus and discriminate it from nontarget bacteria for subsequent identification. Finally, this system can be scaled up for industrial use in food production.

Magnetically Driven Self-Degrading Zinc-Containing Cystine Microrobots for Treatment of Prostate Cancer.

Prostate cancer is the most commonly diagnosed tumor disease in men, and its treatment is still a big challenge in standard oncology therapy. Magnetically actuated microrobots represent the most promising technology in modern nanomedicine, offering the advantage of wireless guidance, effective cell penetration, and non-invasive actuation. Here, new biodegradable magnetically actuated zinc/cystine-based microrobots for in situ treatment of prostate cancer cells are reported. The microrobots are fabricated via metal-ion-mediated self-assembly of the amino acid cystine encapsulating superparamagnetic Fe3 O4 nanoparticles (NPs) during the synthesis, which allows their precise manipulation by a rotating magnetic field. Inside the cells, the typical enzymatic reducing environment favors the disassembly of the aminoacidic chemical structure due to the cleavage of cystine disulfide bonds and disruption of non-covalent interactions with the metal ions, as demonstrated by in vitro experiments with reduced nicotinamide adenine dinucleotide (NADH). In this way, the cystine microrobots served for site-specific delivery of Zn2+ ions responsible for tumor cell killing via a "Trojan horse effect". This work presents a new concept of cell internalization exploiting robotic systems' self-degradation, proposing a step forward in non-invasive cancer therapy.

Magnetically Driven Micro and Nanorobots.

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

Towards micromachine intelligence: potential of polymers.

Inspired by the increasing desire to mimic the perfection of nature, micro- and nanorobots are triggering increasing interest among the scientific community. The development of such tiny machines that can autonomously perform specific and various tasks at a small scale has reached a high-level of complexity over the last 15 years although the transition from hard to soft self-propelled architectures has had the most profound impact. The use of organic components, such as polymers, is of particular interest to fulfill the lack of biocompatibility and biodegradability of inorganic-based microrobots. Additionally, the combination of self-powered micro- and nanorobots with some macromolecules' ability to be deformed and respond to external stimuli is an important topic. This review aims to critically assess the fundamental aspects of smart machines composed of polymers, examine recent advances in the combined systems at the micro- and nanoscale, and discuss the specific contribution of several polymer families. This review elucidates the role of smart polymers in the expanding field of intelligent micromachines.

Hierarchical Atomic Layer Deposited V2 O5 on 3D Printed Nanocarbon Electrodes for High-Performance Aqueous Zinc-Ion Batteries.

Aqueous rechargeable zinc-ion batteries (ARZIBs) are promising energy storage systems owing to their ecofriendliness, safety, and cost-efficiency. However, the sluggish Zn2+ diffusion kinetics originated from its inherent large atomic mass and high polarization remains an ongoing challenge. To this end, electrodes with 3D architectures and high porosity are highly desired. This work reports a rational design and fabrication of hierarchical core-shell structured cathodes (3D@V2 O5 ) for ARZIBs by integrating fused deposition modeling (FDM) 3D-printing with atomic layer deposition (ALD). The 3D-printed porous carbon network provides an entangled electron conductive core and interconnected ion diffusion channels, whereas ALD-coated V2 O5 serves as an active shell without sacrificing the porosity for facilitated Zn2+ diffusion. This endows the 3D@V2 O5 cathode with high specific capacity (425 mAh g-1 at 0.3 A g-1 ), competitive energy and power densities (316 Wh Kg-1 at 213 W kg-1 and 163 Wh Kg-1 at 3400 W kg-1 ), and good rate performance (221 mAh g-1 at 4.8 A g-1 ). The developed 3D@V2 O5 cathode provides a promising model for customized and scalable battery electrode engineering technology. As the ALD-coated layer determines the functional properties, the proposed strategy shows a promising prospect of FDM 3D printing using 1D carbon materials for future energy storage.

Hybrid Enzymatic/Photocatalytic Degradation of Antibiotics via Morphologically Programmable Light-Driven ZnO Microrobots.

Antibiotics are antimicrobial substances that can be used for preventive and therapeutic purposes in humans and animals. Their overdose usage has led to uncontrolled release to the environment, contributing significantly to the development of antimicrobial resistance phenomena. Here, enzyme-immobilized self-propelled zinc oxide (ZnO) microrobots are proposed to effectively target and degrade the released antibiotics in water bodies. Specifically, the morphology of the microrobots is tailored via the incorporation of Au during the synthetic process to lead the light-controlled motion into having on/off switching abilities. The microrobots are further modified with laccase enzyme by physical adsorption, and the immobilization process is confirmed by enzymatic activity measurements. Oxytetracycline (OTC) is used as a model of veterinary antibiotics to investigate the enzyme-immobilized microrobots for their removal capacities. The results demonstrate that the presence of laccase on the microrobot surfaces can enhance the removal of antibiotics via oxidation. This concept for immobilizing enzymes on self-propelled light-driven microrobots leads to the effective removal of the released antibiotics from water bodies with an environmentally friendly strategy.

Magnetic Biohybrid Robots as Efficient Drug Carrier to Generate Plant Cell Clones.

Micro/nanorobots represent a new generation of micromachines that can accomplish various tasks, such as loading and transporting specific targets or pharmaceuticals for a given application. Biohybrid robots consisting of biological cells (bacteria, sperm, and microalgae) combined with inorganic particles to control or propel their movement are of particular interest. The skeleton of these biohybrid robots can be used to load biomolecules. In this work, the authors create biohybrid robots based on tomato plants by coculturing ferromagnetic nanoparticles (Fe3 O4 ) with tomato callus cells. The tomato-based biohybrid robots (Tomato-Biobots) containing Fe3 O4 nanoparticles  are driven by a transversely rotating magnetic field. In addition, biohybrid robots are used to load vitamin C, to generate clones of tomato cells. It is shown that the presence of Fe3 O4  does not affect the growth of tomato callus. This study opens a wide range of possibilities for the use of biohybrid robots@Fe3 O4  to deliver conventional agrochemicals, including fertilizers, pesticides, and herbicides, and allows for a gradual and sustained release of nutrients and agrochemicals, leading to precise dosing that reduces the amount of agrochemicals used. This conceptually new type of micromachine with application to plants and agronomy shall find broad use in this field.

Shape Engineering of TiO2 Microrobots for "On-the-Fly" Optical Brake.

Hybrid microrobots have recently attracted attention due to their ability to combine different energy sources and/or external stimuli for propulsion and performing desired tasks. Despite progresses in the past, on-demand speed modulation for hybrid microrobots has not been analyzed in detail. Herein, the influence of surface properties and crystallite size on the propulsion mechanism of Pt/TiO2 chemical/light-driven hybrid microrobots is investigated. The morphology of urchin-like Pt/TiO2 microrobots leads to "on-the-fly" optical brake behavior under UV irradiation. In contrast, smooth Pt/TiO2 microrobots demonstrate accelerated motion in the same conditions. The comparison between two types of microrobots also indicates the significance of a high surface area and a high crystallite size to increase their speed. The results demonstrate the profound impact of surface features for next-generation smart micro/nanorobots with on-demand reaction capability in dynamically changing environments.

Magnetic Hydrogel Microrobots as Insecticide Carriers for In Vivo Insect Pest Control in Plants.

The cost of insect pests to human society exceeds USD70 billion per year worldwide in goods, livestock, and healthcare services. Therefore, pesticides are needed to prevent insect damage despite the secondary effects of these chemical agents on non-target organisms. Chemicals encapsulation into carriers is a promising strategy to improve their specificity. Hydrogel-based microrobots show enormous potential as chemical carriers. Herein, hydrogel chitosan magnetic microrobots encapsulating ethyl parathion (EP)-CHI@Fe3 O4 are used to efficiently kill mealworm larvae (Tenebrio molitor). The mechanism takes advantage of pH-responsive chitosan degradation at Tenebrio molitor midgut pH to efficiently deliver pesticide into the mealworm intestinal tract in just 2 h. It is observed that under a transversal rotating magnetic field, mealworm populations show higher mortality after 30 min compared to free pesticide. This example of active pesticide carriers based on soft microrobots opens new avenues for microrobots applications in the agrochemical field as active chemical carriers.

Light-Propelled Nanorobots for Facial Titanium Implants Biofilms Removal.

Titanium miniplates are biocompatible materials used in modern oral and maxillofacial surgery to treat facial bone fractures. However, plate removal is often required due to implant complications. Among them, a biofilm formation on an infected miniplate is associated with severe inflammation, which frequently results in implant failure. In light of this, new strategies to control or treat oral bacterial biofilm are of high interest. Herein, the authors exploit the ability of nanorobots against multispecies bacterial biofilm grown onto facial commercial titanium miniplate implants to simulate pathogenic conditions of the oral microenvironment. The strategy is based on the use of light-driven self-propelled tubular black-TiO2 /Ag nanorobots, that unlike traditional ones, exhibit an extended absorption and motion actuation from UV to the visible-light range. The motion analysis is performed separately over UV, blue, and green light irradiation and shows different motion behaviors, including a fast rotational motion that decreases with increasing wavelengths. The biomass reduction is monitored by evaluating LIVE/DEAD fluorescent and digital microscope images of bacterial biofilm treated with the nanorobots under motion/no-motion conditions. The current study and the obtained results can bring significant improvements for effective therapy of infected metallic miniplates by biofilm.

Enzyme-Photocatalyst Tandem Microrobot Powered by Urea for Escherichia coli Biofilm Eradication.

Urinary-based infections affect millions of people worldwide. Such bacterial infections are mainly caused by Escherichia coli (E. coli) biofilm formation in the bladder and/or urinary catheters. Herein, the authors present a hybrid enzyme/photocatalytic microrobot, based on urease-immobilized TiO2 /CdS nanotube bundles, that can swim in urea as a biocompatible fuel and respond to visible light. Upon illumination for 2 h, these microrobots are able to remove almost 90% of bacterial biofilm, due to the generation of reactive radicals, while bare TiO2 /CdS photocatalysts (non-motile) or urease-coated microrobots in the dark do not show any toxic effect. These results indicate a synergistic effect between the self-propulsion provided by the enzyme and the photocatalytic activity induced under light stimuli. This work provides a photo-biocatalytic approach for the design of efficient light-driven microrobots with promising applications in microbiology and biomedicine.

3D Printing for Electrochemical Energy Applications.

Additive manufacturing (also known as three-dimensional (3D) printing) is being extensively utilized in many areas of electrochemistry to produce electrodes and devices, as this technique allows for fast prototyping and is relatively low cost. Furthermore, there is a variety of 3D-printing technologies available, which include fused deposition modeling (FDM), inkjet printing, select laser melting (SLM), and stereolithography (SLA), making additive manufacturing a highly desirable technique for electrochemical purposes. In particular, over the last number of years, a significant amount of research into using 3D printing to create electrodes/devices for electrochemical energy conversion and storage has emerged. Strides have been made in this area; however, there are still a number of challenges and drawbacks that need to be overcome in order to 3D print active and stable electrodes/devices for electrochemical energy conversion and storage to rival that of the state-of-the-art. In this Review, we will give an overview of the reasoning behind using 3D printing for these electrochemical applications. We will then discuss how the electrochemical performance of the electrodes/devices are affected by the various 3D-printing technologies and by manipulating the 3D-printed electrodes by post modification techniques. Finally, we will give our insights into the future perspectives of this exciting field based on our discussion through this Review.

3D printing of functional microrobots.

3D printing (also called "additive manufacturing" or "rapid prototyping") is able to translate computer-aided and designed virtual 3D models into 3D tangible constructs/objects through a layer-by-layer deposition approach. Since its introduction, 3D printing has aroused enormous interest among researchers and engineers to understand the fabrication process and composition-structure-property correlation of printed 3D objects and unleash its great potential for application in a variety of industrial sectors. Because of its unique technological advantages, 3D printing can definitely benefit the field of microrobotics and advance the design and development of functional microrobots in a customized manner. This review aims to present a generic overview of 3D printing for functional microrobots. The most applicable 3D printing techniques, with a focus on laser-based printing, are introduced for the 3D microfabrication of microrobots. 3D-printable materials for fabricating microrobots are reviewed in detail, including photopolymers, photo-crosslinkable hydrogels, and cell-laden hydrogels. The representative applications of 3D-printed microrobots with rational designs heretofore give evidence of how these printed microrobots are being exploited in the medical, environmental, and other relevant fields. A future outlook on the 3D printing of microrobots is also provided.

Two-dimensional materials in biomedical, biosensing and sensing applications.

Two-dimensional (2D) materials are at the forefront of materials research. Here we overview their applications beyond graphene, such as transition metal dichalcogenides, monoelemental Xenes (including phosphorene and bismuthene), carbon nitrides, boron nitrides along with transition metal carbides and nitrides (MXenes). We discuss their usage in various biomedical and environmental monitoring applications, from biosensors to therapeutic treatment agents, their toxicity and their utility in chemical sensing. We highlight how a specific chemical, physical and optical property of 2D materials can influence the performance of bio/sensing, improve drug delivery and photo/thermal therapy as well as affect their toxicity. Such properties are determined by crystal phases electrical conductivity, degree of exfoliation, surface functionalization, strong photoluminescence, strong optical absorption in the near-infrared range and high photothermal conversion efficiency. This review conveys the great future of all the families of 2D materials, especially with the expanding 2D materials' landscape as new materials emerge such as germanene and silicene.

Self-Propelled Multifunctional Microrobots Harboring Chiral Supramolecular Selectors for "Enantiorecognition-on-the-Fly".

Herein, a general procedure for the synthesis of multifunctional MRs, which simultaneously exhibit i) chiral, ii) magnetic, and iii) fluorescent properties in combination with iv) self-propulsion, is reported. Self-propelled Ni@Pt superparamagnetic microrockets have been functionalized with fluorescent CdS quantum dots carrying a chiral host biomolecule as ß-cyclodextrin (ß-CD). The "on-the-fly" chiral recognition potential of MRs has been interrogated by taking advantage of the ß-CD affinity to supramolecularly accommodate different chiral biomolecules (i.e., amino acids). As a proof-of-concept, tryptophan enantiomers have been discriminated with a dual-mode (optical and electrochemical) readout. This approach paves the way to devise intelligent cargo micromachines with "built-in" chiral supramolecular recognition capabilities to elucidate the concept of "enantiorecognition-on-the-fly", which might be facilely customized by tailoring the supramolecular host-guest encapsulation.

Self-Propelled Magnetic Dendrite-Shaped Microrobots for Photodynamic Prostate Cancer Therapy.

Photocatalytic micromotors that exhibit wireless and controllable motion by light have been extensively explored for cancer treatment by photodynamic therapy (PDT). However, overexpressed glutathione (GSH) in the tumor microenvironment can down-regulate the reactive oxygen species (ROS) level for cancer therapy. Herein, we present dendrite-shaped light-powered hematite microrobots as an effective GSH depletion agent for PDT of prostate cancer cells. These hematite microrobots can display negative phototactic motion under light irradiation and flexible actuation in a defined path controlled by an external magnetic field. Non-contact transportation of micro-sized cells can be achieved by manipulating the microrobot's motion. In addition, the biocompatible microrobots induce GSH depletion and greatly enhance PDT performance. The proposed dendrite-shaped hematite microrobots contribute to developing dual light/magnetic field-powered micromachines for the biomedical field.

Chiral Protein-Covalent Organic Framework 3D-Printed Structures as Chiral Biosensors.

Three-dimensional (3D) printing technology has attracted great attention for prototyping different electrochemical sensor devices. However, chiral recognition remains a crucial challenge for electrochemical sensors with similar physicochemical properties such as enantiomers. In this work, a magnetic covalent organic framework (COF) and bovine serum albumin (BSA) (as the chiral surface) functionalized 3D-printed electrochemical chiral sensor is reported for the first time. The characterization of the chiral biomolecule-COF 3D-printed constructure was performed by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and energy-dispersive X-ray spectroscopy (EDX). A tryptophan (Trp) enantiomer was chosen as the model chiral molecule to estimate the chiral recognition ability of the magnetic COF and BSA-based 3DE (Fe3O4@COF@BSA/3DE). We have demonstrated that the Fe3O4@COF@BSA/3DE exhibited excellent chiral recognition to l-Trp as compared to d-Trp. The chiral protein-COF sensing interface was used to determine the concentration of l-Trp in a racemic mixture of d-Trp and l-Trp. This strategy of on-demand fabrication of 3D-printed protein-COF-modified electrodes opens up new approaches for enantiomer recognition.