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.

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.

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.

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.

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.

Real-Time Biomonitoring Device Based on 2D Black Phosphorus and Polyaniline Nanocomposite Flexible Supercapacitors.

Flexible energy storage devices are becoming significantly important to power wearable and portable devices that monitor physiological parameters for many biomedical applications. Many hybrid nanomaterials based on 2D materials are used in order to improve the performance of flexible energy storage devices. Here, a hybrid nanocomposite is synthesized through in situ polymerization of aniline in the presence of black phosphorus (BP) nanoflakes. This nanocomposite, polyaniline (PANI)@BP, is employed to fabricate flexible supercapacitor (FSC) electrodes. PANI@BP FSCs can provide a power source for biometric devices. The generated signal can be transmitted to a smartphone in real time via wireless communication. Such a compact and lightweight integrated device has been used to track a human heart beat while powered by PANI@BP FSC. These findings are providing a promising example of a flexible energy storage device that can be integrated with different real-time health monitoring devices.

Flexible energy generation and storage devices: focus on key role of heterocyclic solid-state organic ionic conductors.

An evolving trend toward the ever-growing market of portable and wearable electronics has accelerated development in the construction of multifunctional energy generation and storage systems that can be twisted and folded to multiple deformations while retaining their electrochemical performance. The latest advances and well developed approaches for the design of heterocyclic solid-state organic ionic conductors (SOICs) in flexible energy generation and storage devices are discussed here. The development of SOICs with improved physical, optical, and electrochemical properties provides new prospects for flexible photoelectrochemical cells and supercapacitors. Equipped with a better knowledge of SOICs' multifunctional properties, researchers have made considerable progress in their development that allows modification according to the requirements of different types of flexible energy devices. Within this review, we highlight the design of efficient SOICs and their incorporation into flexible energy generation and storage devices, and address exciting instances that profile the multifunctionality of SOICs such as three-dimensional (3D) ionic channels, excellent thermal stability, dual functionality (hole/ions transportation), one-dimensional (1D) lamellar network, light-harvesting, and non-toxicity to mention a few. It is expected that innovative and customizable properties utilized in the development of multifunctional SOICs will provide a forum for future advancement in flexible and wearable energy generation and storage devices.

MXene Titanium Carbide-based Biosensor: Strong Dependence of Exfoliation Method on Performance.

Transition metal carbides, known as MXenes, are generated via the selective etching of "A" layers from their layered, ternary parent compounds, MAX phases, where M corresponds to early d-transition metal, A being a main group sp-element from either Group 13 or 14 and carbon or nitrogen being denoted by X. MXenes are being recognized as a new and uprising class of 2D materials with extraordinary physical and electrochemical properties. The huge specific surface area and outstanding electrical conductivity of MXenes, make them ideal candidates for sensing and energy applications. Herein, we demonstrated the successful incorporation of pristine MXene, Ti3C2 produced via HF etching and subsequent delamination with TBAOH, as a transducer platform toward the development of a second generation electrochemical glucose biosensor. Chronoamperometric studies demonstrate that the proposed biosensing system exhibits high selectivity and excellent electrocatalytic activity toward the detection of glucose, spanning over wide linear ranges of 50-27 750 µM and possess a low limit of detection of 23.0 µM. The findings reported in this study conceptually proves the probable applications of pristine MXenes toward the field of biosensors and pave ways for the future developments of highly selective and sensitive electrochemical biosensors for biomedical and food sampling applications.

Photocatalytic Micromotors Activated by UV to Visible Light for Environmental Remediation, Micropumps, Reversible Assembly, Transportation, and Biomimicry.

Photocatalytic micromotors are light-induced, chemically powered micromachines based on photocatalytic materials, activated by light illumination, and have redox reactions with environmental solutions to produce chemical gradients and bubbles that propel the micromachines through self-diffusiophoresis, self-electrophoresis, and bubble recoil. Due to the fact that excitation light relates largely to the bandgaps of selected materials, the development of photocatalytic micromotors has experienced an evolution from ultraviolet-light-activated to visible-light-activated and potentially biocompatible systems. Furthermore, due to the strong redox capacity and physical effects caused by the products or product gradients, photocatalytic micromotors have applications in environmental remediation, micropumps, reversible assembly, transportation, and biomimicry.

Bipolar Electrochemistry Exfoliation of Layered Metal Chalcogenides Sb2 S3 and Bi2 S3 and their Hydrogen Evolution Applications.

Efficient exfoliation and downsizing of Sb2 S3 and Bi2 S3 layered compounds by using scalable bipolar electrochemistry on their suspensions in aqueous media are here demonstrated. The resulting samples were characterized in detail by transmission electron microscopy, energy-dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy; their electrochemistry toward hydrogen evolution was also investigated. Hydrogen evolution ability of exfoliated Sb2 S3 and Bi2 S3 was investigated and compared to the bulk counterparts.

Micromotors as "Motherships": A Concept for the Transport, Delivery, and Enzymatic Release of Molecular Cargo via Nanoparticles.

Nano/micromotors based on biodegradable and biocompatible polymers represent a progressively developing group of self-propelled artificial devices capable of delivering biologically active compounds to target sites. The majority of these machines are micron sized, and biologically active compounds are simply attached to their surface. Micron-sized devices cannot enter cells, but they provide rapid velocity, which scales down with the size of the device; nanosized devices can enter cells, but their velocity is negligible. An advanced hierarchical design of the micro/nanodevices is an important tool in the development of functional biocompatible transport systems and their implementation in real in vivo applications. In this work, we demonstrate a "mothership" concept, whereby self-propelled microrobots transport smaller cargo-carrying nanorobots that are released by enzymatic degradation.

Pnictogen-Based Enzymatic Phenol Biosensors: Phosphorene, Arsenene, Antimonene, and Bismuthene.

Two-dimensional materials have allowed for great advances in the biosensors field and to obtain sophisticated, smart, and miniaturized devices. In this work, we optimized a highly sensitive and selective phenol biosensor using 2D pnictogens (phosphorene, arsenene, antimonene, and bismuthene) as sensing platforms. Exfoliated pnictogen were obtained by the shear-force method, undergoing delamination and downsizing to thin nanosheets. Interestingly, compared with the other tested elements, antimonene exhibited the highest degree of exfoliation and the lowest oxidation-to-bulk ratio, to which we attribute its enhanced performance in the phenol biosensor system reported here. The proposed design represents the first biosensor approach developed using exfoliated pnictogens beyond phosphorene.

Group 6 Layered Transition-Metal Dichalcogenides in Lab-on-a-Chip Devices: 1T-Phase WS2 for Microfluidics Non-Enzymatic Detection of Hydrogen Peroxide.

Two-dimensional (2D) layered transition-metal dichalcogenides (TMDs) have been placed in the spotlight for their advantageous properties for catalytic and sensing applications. However, little work is done to explore and exploit them in enhancing the performance of analytical lab-on-a-chip (LOC) devices. In this work, we demonstrate a simple, sensitive, and low-cost fabrication of electrochemical LOC microfluidic devices to be used for enzymatic detection. We integrated four t-BuLi exfoliated, group 6 TMD materials (MoS2, MoSe2, WS2, and WSe2) within the LOC devices by the drop-casting method and compared their performance for H2O2 detection. The 1T-phase WS2-based LOC device outperformed the rest of the TMD materials and exhibited a wide range of linear response (20 nM to 20 µM and 100 µM to 2 mM), low detection limit (2.0 nM), and good selectivity for applications in real sample analysis. This work may facilitate the expanded use of electrochemical LOC microfluidics, with its easier integrability, for applications in the field of biodiagnostics and sensing.

A study of the effect of sonication time on the catalytic performance of layered WS2 from various sources.

WS2 is a transition metal dichalcogenide (TMD) with many potential applications from catalysis to sensing, and is of interest both in its bulk and monolayer forms. There is discrepancy in the literature on the reported electrocatalytic effect of layered WS2. In this study, we examine two issues: the influence of the WS2 source and the effect of a common agitation technique via ultrasonication on the observed electrocatalysis. Bulk WS2 from five different chemical providers demonstrated different HER electrocatalytic performances. Changes to the duration of sonication result in different HER electrocatalytic performances across all WS2 materials. This may affect the efficiency of subsequent modifications from which these TMD materials serve as precursor materials. On the other hand, while WS2 materials from different suppliers showed varying HET performances, changes in sonication time have no significant effect on their HET performances. Both the WS2 source and the duration of sonication have different implications for the electrochemical performance of bulk WS2 and thus represent important variables to consider in research involving WS2.

MoSe2 Nanolabels for Electrochemical Immunoassays.

There is huge interest in biosensors as a result of the demand for personalized medicine. In biomolecular detection, transition-metal dichalcogenides (TMDs) can be used as signal-enhancing elements. Herein, we utilize a solution-based electrochemical exfoliation technique with bipolar electrodes to manufacture MoSe2 nanolabels for biomolecular detection. Prepared MoSe2 nanoparticles (NPs) exhibit electrocatalytic activity toward the hydrogen evolution reaction (HER), and such a property allows it to act as a robust label for magneto-immunoassays toward protein detection. The magneto-immunoassay also displayed good selectivity, a wide linear range of 2 to 500 ng mL-1, high sensitivity (LOD = 1.23 ng mL-1) and reproducibility (RSD = 9.7%). These findings establish the viability and reproducibility of such an exfoliation technique for TMD nanolabels for the development of low costs and efficient biosensing systems.

Black Phosphorus Nanoparticle Labels for Immunoassays via Hydrogen Evolution Reaction Mediation.

Black phosphorus is an emerging layered material. Its nanoparticles show an increased bandgap when compared to bulk materials and they are typically fabricated by ultrasonication of macroscopic black phosphorus crystals. Here we fabricate black phosphorus nanoparticles (BP NPs) by solution based electrochemical exfoliation with bipolar electrodes, which induces opposite potentials on the opposite ends of black phosphorus macroparticles thereby leading to its decomposition into nanoparticles. BP NPs have enhanced catalytic effect on the hydrogen evolution reaction (HER) relative to black phosphorus macroparticles. We utilize black phosphorus nanoparticles as electrocatalytic tags in a competitive immunoassay for rabbit immunoglobulin G (IgG) detection. The detection signal is produced via nanoimpacts of the BP NPs followed by HER catalysis.

Label-free impedimetric aptasensor for ochratoxin-A detection using iridium oxide nanoparticles.

In this article, a novel aptasensor for ochratoxin A (OTA) detection based on a screen-printed carbon electrode (SPCE) modified with polythionine (PTH) and iridium oxide nanoparticles (IrO2 NPs) is presented. The electrotransducer surface is modified with an electropolymerized film of PTH followed by the assembly of IrO2 NPs on which the aminated aptamer selective to OTA is exchanged with the citrate ions surrounding IrO2 NPs via electrostatic interactions with the same surface. Electrochemical impedance spectroscopy (EIS) in the presence of the [Fe(CN)6](-3/-4) redox probe is employed to characterize each step in the aptasensor assay and also for label-free detection of OTA in a range between 0.01 and 100 nM, obtaining one of the lowest limits of detection reported so far for label-free impedimetric detection of OTA (14 pM; 5.65 ng/kg). The reported system also exhibits a high reproducibility, a good performance with a white wine sample, and an excellent specificity against another toxin present in such sample.