Smart nano-bio-devices

Biohybrid robotics is a field in which biological entities are combined with artificial materials in order to obtain improved performance or features that are difficult to mimic with hand-made materials. Three main level of integration can be envisioned depending on the complexity of the biological entity, ranging from the nanoscale to the macroscale. At the nanoscale, enzymes that catalyze biocompatible reactions can be used as power sources for self-propelled nanoparticles of different geometries and compositions, obtaining rather interesting active matter systems that acquire importance in the biomedical field as drug delivery systems. At the microscale, single enzymes are substituted by complete cells, such as bacteria or spermatozoa, whose self-propelling capabilities can be used to transport cargo and can also be used as drug delivery systems, for in vitro fertilization practices or for biofilm removal. Finally, at the macroscale, the combinations of millions of cells forming tissues can be used to power biorobotic devices or bioactuators by using muscle cells. Both cardiac and skeletal muscle tissue have been part of remarkable examples of untethered biorobots that can crawl or swim due to the contractions of the tissue and current developments aim at the integration of several types of tissue to obtain more realistic biomimetic devices, which could lead to the next generation of hybrid robotics. Tethered bioactuators, however, result in excellent candidates for tissue models for drug screening purposes or the study of muscle myopathies due to their three-dimensional architecture. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology. © 2021 Wiley Periodicals LLC.

Keywords: bacteria-bots, biorobots, enzymatic nanomotors, hybrid robotics, muscle-based biorobots

The low efficacy of current conventional treatments for bacterial infections increases mortality rates worldwide. To alleviate this global health problem, we propose drug-free enzyme-based nanomotors for the treatment of bacterial urinary-tract infections. We develop nanomotors consisting of mesoporous silica nanoparticles (MSNPs) that were functionalized with either urease (U-MSNPs), lysozyme (L-MSNPs), or urease and lysozyme (M-MSNPs), and use them against nonpathogenic planktonic Escherichia coli. U-MSNPs exhibited the highest bactericidal activity due to biocatalysis of urea into NaHCO3 and NH3, which also propels U-MSNPs. In addition, U-MSNPs in concentrations above 200 μg/mL were capable of successfully reducing 60% of the biofilm biomass of a uropathogenic E. coli strain. This study thus provides a proof-of-concept, demonstrating that enzyme-based nanomotors are capable of fighting infectious diseases. This approach could potentially be extended to other kinds of diseases by selecting appropriate biomolecules.

Chemically active Janus particles sustain non-equilibrium spatial variations in the chemical composition of the suspending solution; these induce hydrodynamic flow and (self-)motility of the particles. Direct mapping of these fields has so far proven to be too challenging. Therefore, indirect methods are needed, e.g., deconvolving the response of “tracer” particles to the activity-induced fields. Here, we study experimentally the response of silica particles, sedimented at a wall, to active Pt/silica Janus particles. The latter are either immobilized at the wall, with the symmetry axis perpendicular or parallel to the wall, or motile. The experiments reveal complex effective interactions that are dependent on the configuration and on the state of motion of the active particle. Within the framework of a coarse-grained model, the behavior of tracers near an immobilized Janus particle can be captured qualitatively once activity-induced osmotic flows on the wall are considered.

Self-propelled particles and, in particular, those based on mesoporous silica, have raised considerable interest due to their potential applications in the environmental and biomedical fields thanks to their biocompatibility, tunable surface chemistry and large porosity. Although spherical particles have been widely used to fabricate nano- and micromotors, not much attention has been paid to other geometries, such as nanorods. Here, we report the fabrication of self-propelled mesoporous silica nanorods (MSNRs) that move by the catalytic decomposition of hydrogen peroxide by a sputtered Pt layer, Fe2O3 nanoparticles grown within the mesopores, or the synergistic combination of both. We show that motion can occur in two distinct sub-populations characterized by two different motion dynamics, namely enhanced diffusion or directional propulsion, especially when both catalysts are used. These results open up the possibility of using MSNRs as chassis for the fabrication of self-propelled particles for the environmental or biomedical fields.

Keywords: Mesoporous silica, Nanomotors, Nanorods, Porous materials, Self-propulsion

Enzyme-powered nanomotors are an exciting technology for biomedical applications due to their ability to navigate within biological environments using endogenous fuels. However, limited studies into their collective behavior and demonstrations of tracking enzyme nanomotors in vivo have hindered progress toward their clinical translation. Here, we report the swarming behavior of urease-powered nanomotors and its tracking using positron emission tomography (PET), both in vitro and in vivo. For that, mesoporous silica nanoparticles containing urease enzymes and gold nanoparticles were used as nanomotors. To image them, nanomotors were radiolabeled with either 124I on gold nanoparticles or 18F-labeled prosthetic group to urease. In vitro experiments showed enhanced fluid mixing and collective migration of nanomotors, demonstrating higher capability to swim across complex paths inside microfabricated phantoms, compared with inactive nanomotors. In vivo intravenous administration in mice confirmed their biocompatibility at the administered dose and the suitability of PET to quantitatively track nanomotors in vivo. Furthermore, nanomotors were administered directly into the bladder of mice by intravesical injection. When injected with the fuel, urea, a homogeneous distribution was observed even after the entrance of fresh urine. By contrast, control experiments using nonmotile nanomotors (i.e., without fuel or without urease) resulted in sustained phase separation, indicating that the nanomotors’ self-propulsion promotes convection and mixing in living reservoirs. Active collective dynamics, together with the medical imaging tracking, constitute a key milestone and a step forward in the field of biomedical nanorobotics, paving the way toward their use in theranostic applications.

Cells, sophisticated membrane‐bound units that contain the fundamental molecules of life, provide a precious library for inspiration and motivation for both society and academia. Scientists from various disciplines have made great endeavors toward the understanding of the cellular evolution by engineering artificial counterparts (protocells) that mimic or initiate structural or functional cellular aspects. In this regard, several works have discussed possible building blocks, designs, functions, or dynamics that can be applied to achieve this goal. Although great progress has been made, fundamental—yet complex—behaviors such as cellular communication, responsiveness to environmental cues, and motility remain a challenge, yet to be resolved. Herein, recent efforts toward utilizing soft systems for cellular mimicry are summarized—following the main outline of cellular evolution, from basic compartmentalization, and biological reactions for energy production, to motility and communicative behaviors between artificial cell communities or between artificial and natural cell communities. Finally, the current challenges and future perspectives in the field are discussed, hoping to inspire more future research and to help the further advancement of this field.

Medical imaging serves to obtain anatomical and physiological data, supporting medical diagnostics as well as providing therapeutic evaluation and guidance. A variety of contrast agents have been developed to enhance the recorded signals and to provide molecular imaging. However, fast clearance from the body or nonspecific biodistribution often limit their efficiency, constituting challenges that need to be overcome. Nanoparticle-based systems are currently emerging as versatile and highly integrated platforms providing improved circulating times, tissue specificity, high loading capacity for signaling moieties, and multimodal imaging features. Furthermore, nanoengineered devices can be tuned for specific applications and the development of responsive behaviors. Responses include in situ modulation of nanoparticle size, increased intratissue mobility through active propulsion of motorized particles, and active modulation of the particle surroundings such as the extracellular matrix for an improved penetration and retention at the desired locations. Once accumulated in the targeted tissue, smart nanoparticle-based contrast agents can provide molecular sensing of biomarkers or characteristics of the tissue microenvironment. In this case, the signal or contrast provided by the nanosystem is responsive to the presence or concentration of an analyte. Herein, recent developments of intelligent nanosystems to improve medical imaging are presented.

Enzyme‐powered micro/nanomotors have myriads of potential applications in various areas. To efficiently reach those applications, it is necessary and critical to understand the fundamental aspects affecting the motion dynamics. Herein, we explored the impact of enzyme orientation on the performance of lipase-powered nanomotors by tuning the lipase immobilization strategies. The influence of the lipase orientation and lid conformation on substrate binding and catalysis was analyzed using molecular dynamics simulations. Besides, the motion performance indicates that the hydrophobic binding (via OTES) represents the best orienting strategy, providing 48.4 % and 95.4 % increase in diffusion coefficient compared to hydrophilic binding (via APTES) and Brownian motion (no fuel), respectively (with C[triacetin] of 100 mm). This work provides vital evidence for the importance of immobilization strategy and corresponding enzyme orientation for the catalytic activity and in turn, the motion performance of nanomotors, and is thus helpful to future applications.

Here, we report the design, synthesis, and functional testing of enzyme-powered porous micromotors built from a metal–organic framework (MOF). We began by subjecting a presynthesized microporous UiO-type MOF to ozonolysis, to confer it with mesopores sufficiently large to adsorb and host the enzyme catalase (size: 6–10 nm). We then encapsulated catalase inside the mesopores, observing that they are hosted in those mesopores located at the subsurface of the MOF crystals. In the presence of H2O2 fuel, MOF motors (or MOFtors) exhibit jet-like propulsion enabled by enzymatic generation of oxygen bubbles. Moreover, thanks to their hierarchical pore system, the MOFtors retain sufficient free space for adsorption of additional targeted species, which we validated by testing a MOFtor for removal of rhodamine B during self-propulsion.

Designer particles that are embued with nanomachinery for autonomous motion have great potential for biomedical applications; however, their development is highly demanding with respect to biodegradability/compatibility. Previously, biodegradable propulsive machinery based on enzymes has been presented. However, enzymes are highly susceptible to proteolysis and deactivation in biological milieu. Biodegradable hybrid nanomotors powered by catalytic inorganic nanoparticles provide a proteolytically stable alternative to those based upon enzymes. Herein we describe the assembly of hybrid biodegradable nanomotors capable of transducing chemical energy into motion. Such nanomotors are constructed through a process of compartmentalized synthesis of inorganic MnO2 nanoparticles (MnPs) within the cavity of organic stomatocytes. We show that the nanomotors remain active in cellular environments and do not compromise cell viability. Effective tumor penetration of hybrid nanomotors is also demonstrated in proof-of-principle experiments. Overall, this work represents a new prospect for engineering of nanomotors that can retain their functionality within biological contexts.

Enzyme-powered motors self-propel through the catalysis of in situ bioavailable fuels, which makes them excellent candidates for biomedical applications. However, fundamental issues like their motion in biological fluids and the understanding of the propulsion mechanism are critical aspects to be tackled before a future application in biomedicine. Herein, we investigated the physicochemical effects of ionic species on the self-propulsion of urease-powered micromotors. Results showed that the presence of PBS, NaOH, NaCl, and HEPES reduced self-propulsion of urease-powered micromotors pointing towards ion-dependent mechanisms of motion. We studied the 3D motion of urease micromotors using digital holographic microscopy to rule out any motor-surface interaction as the cause of motion decay when salts are present in the media. In order to protect and minimize the negative effect of ionic species on micromotors’ performance, we coated the motors with methoxypolyethylene glycol amine (mPEG) showing higher speed compared to noncoated motors at intermediate ionic concentrations. These results provide new insights into the mechanism of urease-powered micromotors, study the effect of ionic media, and contribute with potential solutions to mitigate the reduction of mobility of enzyme-powered micromotors.

Developing self-powered nanomotors made of biocompatible and functional components is of paramount importance in future biomedical applications. Herein, the functional features of LipoBots (LBs) composed of a liposomal carrier containing urease enzymes for propulsion, including their protective properties against acidic conditions and their on-demand triggered activation, are reported. Given the functional nature of liposomes, enzymes can be either encapsulated or coated on the surface of the vesicles. The influence of the location of urease on motion dynamics is first studied, finding that the surface-urease LBs undergo self-propulsion whereas the encapsulated-urease LBs do not. However, adding a percolating agent present in the bile salts to the encapsulated-urease LBs triggers active motion. Moreover, it is found that when both types of nanomotors are exposed to a medium of similar pH found in the stomach, the surface-urease LBs lose activity and motion capabilities, while the encapsulated-urease LBs retain activity and mobility. The results for the protection enzyme activity through encapsulation within liposomes and in situ triggering of the motion of LBs upon exposure to bile salts may open new avenues for the use of liposome-based nanomotors in drug delivery, for example, in the gastrointestinal tract, where bile salts are naturally present in the intestine.

Self-propelled particles and, in particular, those based on mesoporous silica, have raised considerable interest due to their potential applications in the environmental and biomedical fields thanks to their biocompatibility, tunable surface chemistry and large porosity. Although spherical particles have been widely used to fabricate nano- and micromotors, not much attention has been paid to other geometries, such as nanorods. Here, we report the fabrication of self-propelled mesoporous silica nanorods (MSNRs) that move by the catalytic decomposition of hydrogen peroxide by a sputtered Pt layer, Fe2O3 nanoparticles grown within the mesopores, or the synergistic combination of both. We show that motion can occur in two distinct sub-populations characterized by two different motion dynamics, namely enhanced diffusion or directional propulsion, especially when both catalysts are used. These results open up the possibility of using MSNRs as chassis for the fabrication of self-propelled particles for the environmental or biomedical fields

Keywords: Mesoporous silica, Nanomotors, Nanorods, Porous materials, Self-propulsion

Artificial micro-/nano-motors are tiny machines as newly emerging tools capable of achieving numerous tasks. In principle, the self-phoretic motions require asymmetric structures in geometry and chemistry. However, conventional production techniques suffered from complex and time consuming multi-step process in low uniformity, and difficult to endow multi-functions into motors. This work disclosed a continuous-flow synthesis of triple-responsive (thermophoretic, chemical and magnetic movement) nano-motors (m-SiO2/Fe3O4-Pdop/Pt) via microfluidic Pickering emulsification in a process of integrated and scalable manner. The droplet microfluidic process allows efficient self-assembly of the silica nanoparticles surrounding the spherical interface of resin droplet, rendering excellent Pickering efficiency and reproducibility, and followed by anisotropic decoration of polydopamine (Pdop) and Pt catalyst in a serial flow process. The obtained Janus nanoparticles reveal double- or triple-responsive self-propulsions with synergic mobility by combining thermophoresis powered by light, catalytic driven motion in H2O2 or magnetic movement by magnet. Further, a non-metallic polydopamine based thermophoretic motion as well as an automated nano-cleaner for rapid water purification by dye removal are convincingly functioned. Finally, this novel integrated flow strategy proves a scalable manufacturing production (> 0.7 g hr−1) of the nano-motors using inexpensive single microreactor, fulfilling quantitative and qualitative needs for versatile applications.

Keywords: Microfluidics Pickering emulsions, Triple-responsive motor, Adsorbent

Micro/nanomotors (MNMs) are miniaturized machines that can perform assigned tasks at the micro/nanoscale. Over the past decade, significant progress has been made in the design, preparation, and applications of MNMs that are powered by converting different sources of energy into mechanical force, to realize active movement and fulfill on-demand tasks. MNMs can be navigated to desired locations with precise controllability based on different guidance mechanisms. A considerable research effort has gone into demonstrating that MNMs possess the potential of biomedical cargo loading, transportation, and targeted release to achieve therapeutic functions. Herein, the recent advances of self-propelled MNMs for on-demand biomedical cargo transportation, including their self-propulsion mechanisms, guidance strategies, as well as proof-of-concept studies for biological applications are presented. In addition, some of the major challenges and possible opportunities of MNMs are identified for future biomedical applications in the hope that it may inspire future research.

Keywords: Biomedical applications, Cargo transportation, Guidance strategies, Micro/nanomotors, Self-propulsion

We study the self-propulsion of a charged colloidal particle that releases ionic species using theory and experiments. We relax the assumptions of thin Debye length and weak nonequilibrium effects assumed in classical phoretic models. This leads to a number of unexpected features that cannot be rationalized considering the classic phoretic framework: an active particle can reverse the direction of motion by increasing the rate of ion release and can propel even with zero surface charge. Our theory predicts that there are optimal conditions for self-propulsion and a novel regime in which the velocity is insensitive to the background electrolyte concentration. The theoretical results quantitatively capture the salt-dependent velocity measured in our experiments using active colloids that propel by decomposing urea via a surface enzymatic reaction.

We examine a mechanism of locomotion of active particles whose surface is uniformly coated with mobile enzymes. The enzymes catalyze a reaction that drives phoretic flows but their homogeneous distribution forbids locomotion by symmetry. We find that the ability of the enzymes to migrate over the surface combined with self-phoresis can lead to a spontaneous symmetry-breaking instability whereby the homogeneous distribution of enzymes polarizes and the particle propels. The instability is driven by the advection of enzymes by the phoretic flows and occurs above a critical Péclet number. The transition to polarized motile states occurs via a supercritical or subcritical pitchfork bifurcations, the latter of which enables hysteresis and coexistence of uniform and polarized states.

Keywords: Biomimetic & bio-inspired materials, Locomotion, Surface-driven phase separation

The introduction of stimuli-responsive cargo release capabilities on self-propelled micro- and nanomotors holds enormous potential in a number of applications in the biomedical field. Herein, we report the preparation of mesoporous silica nanoparticles gated with pH-responsive supramolecular nanovalves and equipped with urease enzymes which act as chemical engines to power the nanomotors. The nanoparticles are loaded with different cargo molecules ([Ru(bpy)3]Cl2 (bpy = 2,2′-bipyridine) or doxorubicin), grafted with benzimidazole groups on the outer surface, and capped by the formation of inclusion complexes between benzimidazole and cyclodextrin-modified urease. The nanomotor exhibits enhanced Brownian motion in the presence of urea. Moreover, no cargo is released at neutral pH, even in the presence of the biofuel urea, due to the blockage of the pores by the bulky benzimidazole:cyclodextrin-urease caps. Cargo delivery is only triggered on-command at acidic pH due to the protonation of benzimidazole groups, the dethreading of the supramolecular nanovalves, and the subsequent uncapping of the nanoparticles. Studies with HeLa cells indicate that the presence of biofuel urea enhances nanoparticle internalization and both [Ru(bpy)3]Cl2 or doxorubicin intracellular release due to the acidity of lysosomal compartments. Gated enzyme-powered nanomotors shown here display some of the requirements for ideal drug delivery carriers such as the capacity to self-propel and the ability to “sense” the environment and deliver the payload on demand in response to predefined stimuli.

Keywords: Controlled release, Drug delivery, Enzymatic catalysis, Gatekeepers, Nanocarriers, Nanomotors, Stimuli-responsive nanomaterials

Cancer is one of the main causes of death around the world, lacking efficient clinical treatments that generally present severe side effects. In recent years, various nanosystems have been explored to specifically target tumor tissues, enhancing the efficacy of cancer treatment and minimizing the side effects. In particular, bladder cancer is the ninth most common cancer worldwide and presents a high survival rate but serious recurrence levels, demanding an improvement in the existent therapies. Here, we present urease-powered nanomotors based on mesoporous silica nanoparticles that contain both polyethylene glycol and anti-FGFR3 antibody on their outer surface to target bladder cancer cells in the form of 3D spheroids. The autonomous motion is promoted by urea, which acts as fuel and is inherently present at high concentrations in the bladder. Antibody-modified nanomotors were able to swim in both simulated and real urine, showing a substrate-dependent enhanced diffusion. The internalization efficiency of the antibody-modified nanomotors into the spheroids in the presence of urea was significantly higher compared with antibody-modified passive particles or bare nanomotors. Furthermore, targeted nanomotors resulted in a higher suppression of spheroid proliferation compared with bare nanomotors, which could arise from the local ammonia production and the therapeutic effect of anti-FGFR3. These results hold significant potential for the development of improved targeted cancer therapy and diagnostics using biocompatible nanomotors.

Keywords: 3D cell culture, Bladder cancer, Enzymatic catalysis, Nanomachines, Nanomotors, Self-propulsion, Targeting

We report lipase-based nanomotors that are capable of enhanced Brownian motion over long periods of time in triglyceride solution and of degrading triglyceride droplets that mimic “blood lipids”. We achieved about 40 min of enhanced diffusion of lipase-modified mesoporous silica nanoparticles (MSNPs) through a biocatalytic reaction between lipase and its corresponding water-soluble oil substrate (triacetin) as fuel, which resulted in an enhanced diffusion coefficient (ca. 50 % increase) at low triacetin concentration (<10 mm). Lipase not only serves as the power engine but also as a highly efficient cleaner for the triglyceride droplets (e.g., tributyrin) in PBS solution, which could yield potential biomedical applications, for example, for dealing with diseases related to the accumulation of triglycerides, or for environmental remediation, for example, for the degradation of oil spills.

Keywords: Enzyme nanomotors, Lipase, Micromotors, Oil removal, Self-propulsion

Bio-catalytic micro- and nanomotors self-propel by the enzymatic conversion of substrates into products. Despite the advances in the field, the fundamental aspects underlying enzyme-powered self-propulsion have rarely been studied. In this work, we select four enzymes (urease, acetylcholinesterase, glucose oxidase, and aldolase) to be attached on silica microcapsules and study how their turnover number and conformational dynamics affect the self-propulsion, combining both an experimental and molecular dynamics simulations approach. Urease and acetylcholinesterase, the enzymes with higher catalytic rates, are the only enzymes capable of producing active motion. Molecular dynamics simulations reveal that urease and acetylcholinesterase display the highest degree of flexibility near the active site, which could play a role on the catalytic process. We experimentally assess this hypothesis for urease micromotors through competitive inhibition (acetohydroxamic acid) and increasing enzyme rigidity (β-mercaptoethanol). We conclude that the conformational changes are a precondition of urease catalysis, which is essential to generate self-propulsion.

Keywords: Biocatalysis, Immobilized enzymes, Molecular machines and motors

Biocatalytic micro- and nanomotors have emerged as a new class of active matter self-propelled through enzymatic reactions. The incorporation of functional nanotools could enable the rational design of multifunctional micromotors for simultaneous real-time monitoring of their environment and activity. Herein, we report the combination of DNA nanotechnology and urease-powered micromotors as multifunctional tools able to swim, simultaneously sense the pH of their surrounding environment, and monitor their intrinsic activity. With this purpose, a FRET-labeled triplex DNA nanoswitch for pH sensing was immobilized onto the surface of mesoporous silica-based micromotors. During self-propulsion, urea decomposition and the subsequent release of ammonia led to a fast pH increase, which was detected by real-time monitoring of the FRET efficiency through confocal laser scanning microscopy at different time points (i.e., 30 s, 2 and 10 min). Furthermore, the analysis of speed, enzymatic activity, and propulsive force displayed a similar exponential decay, matching the trend observed for the FRET efficiency. These results illustrate the potential of using specific DNA nanoswitches not only for sensing the micromotors’ surrounding microenvironment but also as an indicator of the micromotor activity status, which may aid to the understanding of their performance in different media and in different applications.

Keywords: Micromotors, DNA-nanoswitch, pH detection, Self-propulsion, Nanosensors, Nanomotors

Abstract The integration of biological systems into robotic devices might provide them with capabilities acquired from natural systems and significantly boost their performance. These abilities include real-time bio-sensing, self-organization, adaptability, or self-healing. As many muscle-based bio-hybrid robots and bio-actuators arise in the literature, the question of whether these features can live up to their expectations becomes increasingly substantial. Herein, the force generation and adaptability of skeletal-muscle-based bio-actuators undergoing long-term training protocols are analyzed. The 3D-bioprinting technique is used to fabricate bio-actuators that are functional, responsive, and have highly aligned myotubes. The bio-actuators are 3D-bioprinted together with two artificial posts, allowing to use it as a force measuring platform. In addition, the force output evolution and dynamic gene expression of the bio-actuators are studied to evaluate their degree of adaptability according to training protocols of different frequencies and mechanical stiffness, finding that their force generation could be modulated to different requirements. These results shed some light into the fundamental mechanisms behind the adaptability of muscle-based bio-actuators and highlight the potential of using 3D bioprinting as a rapid and cost-effective tool for the fabrication of custom-designed soft bio-robots.

Artificial microswimmers have the potential for applications in many fields, ranging from targeted cargo delivery and mobile sensing to environmental remediation. In many of these applications, the artificial swimmers will operate in complex media necessarily involving liquid–liquid interfaces. Here, we experimentally study the motion of chemically powered phoretic active colloids close to liquid–liquid interfaces while swimming next to a solid substrate. In a system involving this complex geometry, we find that the active particles have an alignment interaction with both the neighbouring solid and liquid interfaces, allowing for a robust guiding mechanism along the liquid interface. We compare with minimal active Brownian simulations to show that these phoretically active particles stay along the interfaces for much longer times and lengths than expected for standard active Brownian particles. We also track the propulsion speeds of these particles and find a reduced speed close to the liquid–liquid interface. We report an interesting non-linear dependence of this reduction on the particle's bulk speed..

The field of bio-hybrid robotics aims at the integration of biological components with artificial materials in order to take advantage of many unique features occurring in nature, such as adaptability, self-healing or resilience. In particular, skeletal muscle tissue has been used to fabricate bio-actuators or bio-robots that can perform simple actions. In this paper, we present 3D bioprinting as a versatile technique to develop these kinds of actuators and we focus on the importance of optimizing the designs and properly characterizing their performance. For that, we introduce a method to calculate the force generated by the bio-actuators based on the deflection of two posts included in the bio-actuator design by means of image processing algorithms. Finally, we present some results related to the adaptation, controllability and force modulation of our bio-actuators, paving the way towards a design- and optimization-driven development of more complex 3D-bioprinted bio-actuators.

Keywords: 3D bioprinting, Bio-hybrid robotics, Muscle-based bio-actuators

The most recent advances in analytical chemistry have focused on developing new devices in the micro- and nano-scale capable of sensing on a similar scale to analyzed molecules and biomarkers. Thus, microfluidic chips and micro- and nanomotors have emerged as advanced nanotechnologies that provide low volume, rapid and simple analysis. Lately, the incorporation of carbon nanomaterials, such as carbon nanotubes and graphene to these analytical platforms, has opened up new opportunities towards improving the figures of merit in the final analysis. From microfluidic analytical tools to the cutting edge micro- and nanomotors, we will explore the advantages and challenges of these two vanguard technologies, and the incorporation of carbon nanomaterials for advanced analyte detection.

ConspectusSelf-propulsion at the nanoscale constitutes a challenge due to the need for overcoming viscous forces and Brownian motion. Inspired by nature, artificial micro- and nanomachines powered by catalytic reactions have been developed. Due to the toxicity of the most commonly used fuels, enzyme catalysis has emerged as a versatile and biocompatible alternative to generate self-propulsion. Different swimmer sizes, ranging from the nanoscale to the microscale, and geometries, including tubular and spherical shapes, have been explored. However, there is still a lack of understanding of the mechanisms underlying enzyme-mediated propulsion. Size, shape, enzyme quantity and distribution, as well as the intrinsic enzymatic properties, may play crucial roles in motion dynamics.In this Account, we present the efforts carried out by our group and others by the community on the use of enzymes to power micro- and nanoswimmers. We examine the different structures, materials, and enzymes reported so far to fabricate biocatalytic micro- and nanoswimmers with special emphasis on their effect in motion dynamics. We discuss the development of tubular micro- and nanojets, focusing on the different fabrication methods and the effect of length and enzyme localization on their motion behavior. In the case of spherical swimmers, we highlight the role of asymmetry in enzyme coverage and how it can affect their motion dynamics. Different approaches have been described to generate asymmetric distribution of enzymes, namely, Janus particles, polymeric vesicles, and non-Janus particles with patch-like enzyme distribution that we recently reported. We also examine the correlation between enzyme kinetics and active motion. Enzyme activity, and consequently speed, can be modulated by modifying substrate concentration or adding specific inhibitors. Finally, we review the theory of active Brownian motion and how the size of the particles can influence the analysis of the results. Fundamentally, nanoscaled swimmers are more affected by Brownian fluctuations than microsized swimmers, and therefore, their motion is presented as an enhanced diffusion with respect to the passive case. Microswimmers, however, can overcome these fluctuations and show propulsive or ballistic trajectories. We provide some considerations on how to analyze the motion of these swimmers from an experimental point of view. Despite the rapid progress in enzyme-based micro- and nanoswimmers, deeper understanding of the mechanisms of motion is needed, and further efforts should be aimed to study their lifetime, long-term stability, and ability to navigate in complex media.

The use of enzyme catalysis to power micro- and nanomotors exploiting biocompatible fuels has opened new ventures for biomedical applications such as the active transport and delivery of specific drugs to the site of interest. Here, urease-powered nanomotors (nanobots) for doxorubicin (Dox) anticancer drug loading, release, and efficient delivery to cells are presented. These mesoporous silica-based core-shell nanobots are able to self-propel in ionic media, as confirmed by optical tracking and dynamic light scattering analysis. A four-fold increase in drug release is achieved by nanobots after 6 h compared to their passive counterparts. Furthermore, the use of Dox-loaded nanobots presents an enhanced anticancer efficiency toward HeLa cells, which arises from a synergistic effect of the enhanced drug release and the ammonia produced at high concentrations of urea substrate. A higher content of Dox inside HeLa cells is detected after 1, 4, 6, and 24 h incubation with active nanobots compared to passive Dox-loaded nanoparticles. The improvement in drug delivery efficiency achieved by enzyme-powered nanobots may hold potential toward their use in future biomedical applications such as the substrate-triggered release of drugs in target locations.

Keywords: Drug delivery, Enzymatic catalysis, Nanobots, Nanomachines, Nanomotors

The motion of nanomotors triggered by light sources will provide new alternative routes to power nanoarchitectures without the need of chemical fuels. However, most light-driven nanomotors are triggered by UV-light, near infrared reflection, or laser sources. It is demonstrated that nanocap shaped Au/TiO2 nanomotors (175 nm in diameter) display increased Brownian motion in the presence of broad spectrum visible light. The motion results from the surface plasmon resonance effect leading to self-electrophoresis between the Au and TiO2 layers, a mechanism called plasmonic photocatalytic effect in the field of photocatalysis. This mechanism is experimentally characterized by electron energy loss spectroscopy, energy-filtered transmission electron microscopy, and optical video tracking. This mechanism is also studied in a more theoretical manner using numerical finite-difference time-domain simulations. The ability to power nanomaterials with visible light may result in entirely new applications for externally powered micro/nanomotors.

Keywords: Enhanced Brownian motion, Fuel-free nanomotors, Nanomachines, Self-electrophoresis, Visible light

The use of enzyme catalysis to power micro- and nanomachines offers unique features such as biocompatibility, versatility, and fuel bioavailability. Yet, the key parameters underlying the motion behavior of enzyme-powered motors are not completely understood. Here, we investigate the role of enzyme distribution and quantity on the generation of active motion. Two different micromotor architectures based on either polystyrene (PS) or polystyrene coated with a rough silicon dioxide shell (PS@SiO2) were explored. A directional propulsion with higher speed was observed for PS@SiO2 motors when compared to their PS counterparts. We made use of stochastically optical reconstruction microscopy (STORM) to precisely detect single urease molecules conjugated to the micromotors surface with a high spatial resolution. An asymmetric distribution of enzymes around the micromotor surface was observed for both PS and PS@SiO2 architectures, indicating that the enzyme distribution was not the only parameter affecting the motion behavior. We quantified the number of enzymes present on the micromotor surface and observed a 10-fold increase in the number of urease molecules for PS@SiO2 motors compared to PS-based micromotors. To further investigate the number of enzymes required to generate a self-propulsion, PS@SiO2 particles were functionalized with varying amounts of urease molecules and the resulting speed and propulsive force were measured by optical tracking and optical tweezers, respectively. Surprisingly, both speed and force depended in a nonlinear fashion on the enzyme coverage. To break symmetry for active propulsion, we found that a certain threshold number of enzymes molecules per micromotor was necessary, indicating that activity may be due to a critical phenomenon. Taken together, these results provide new insights into the design features of micro/nanomotors to ensure an efficient development.

The quest to provide clean water to the entire population has led to a tremendous boost in the development of environmental nanotechnology. Towards this end, micro/nanomotors are emerging as attractive tools to improve the removal of various pollutants. The micro/nanomotors are either designed with functional materials in their structure, or are modified to target pollutants. The active motion of these motors improves the mixing and mass transfer, greatly enhancing the rate of various remediation processes. Their motion can also be used as an indicator of the presence of a pollutant for sensing purposes. In this Perspective, we discuss different chemical aspects of micromotors mediated environmental clean-up and sensing strategies along with their scalability, reuse and cost associated challenges.

To achieve control over naturally diffusive, out-of-equilibrium systems composed of self-propelled particles, such as cells or self-phoretic colloids, is a long-standing challenge in active matter physics. The inherently random motion of these active particles can be rectified in the presence of local and periodic asymmetric cues given that a non-trivial interaction exists between the self-propelled particle and the cues. Here, we exploit the phoretic and hydrodynamic interactions of synthetic micromotors with local topographical features to break the time-reversal symmetry of particle trajectories and to direct a macroscopic flow of micromotors. We show that the orientational alignment induced on the micromotors by the topographical features, together with their geometrical asymmetry, are crucial in generating directional particle flow. We also show that our system can be used to concentrate micromotors in confined spaces and identify the interactions responsible for this effect. Finally, we develop a minimal model which identifies the main parameters of the system responsible for the observed rectification. Overall, our system allows for robust control over both temporal and spatial distribution of synthetic micromotors.

Keywords: Active colloids, Directional control, Janus particles, Micromotors, Self-propulsion

Micro/nanomotors are useful tools for several biomedical applications, including targeted drug delivery and minimally invasive microsurgeries. However, major challenges such as in vivo imaging need to be addressed before they can be safely applied on a living body. Here, we show that positron emission tomography (PET), a molecular imaging technique widely used in medical imaging, can also be used to track a large population of tubular Au/PEDOT/Pt micromotors. Chemisorption of an iodine isotope onto the micromotor’s Au surface rendered them detectable by PET, and we could track their movements in a tubular phantom over time frames of up to 15 min. In a second set of experiments, micromotors and the bubbles released during self-propulsion were optically tracked by video imaging and bright-field microscopy. The results from direct optical tracking agreed with those from PET tracking, demonstrating that PET is a suitable technique for the imaging of large populations of active micromotors in opaque environments, thus opening opportunities for the use of this mature imaging technology for the in vivo localization of artificial swimmers.

For natural microswimmers, the interplay of swimming activity and external flow can promote robust directed motion, for example, propulsion against (upstream rheotaxis) or perpendicular to the direction of flow. These effects are generally attributed to their complex body shapes and flagellar beat patterns. Using catalytic Janus particles as a model experimental system, we report on a strong directional response that occurs for spherical active particles in a channel flow. The particles align their propulsion axes to be nearly perpendicular to both the direction of flow and the normal vector of a nearby bounding surface. We develop a deterministic theoretical model of spherical microswimmers near a planar wall that captures the experimental observations. We show how the directional response emerges from the interplay of shear flow and near-surface swimming activity. Finally, adding the effect of thermal noise, we obtain probability distributions for the swimmer orientation that semiquantitatively agree with the experimental distributions.

Abstract We report a carbonaceous nanobottle (CNB) motor for near infrared (NIR) light-driven jet propulsion. The bottle structure of the CNB motor is fabricated by soft-template-based polymerization. Upon illumination with NIR light, the photothermal effect of the CNB motor carbon shell causes a rapid increase in the temperature of the water inside the nanobottle and thus the ejection of the heated fluid from the open neck, which propels the CNB motor. The occurrence of an explosion, the on/off motion, and the swing behavior of the CNB motor can be modulated by adjusting the NIR light source. Moreover, we simulated the physical field distribution (temperature, fluid velocity, and pressure) of the CNB motor to demonstrate the mechanism of NIR light-driven jet propulsion. This NIR light-powered CNB motor exhibits fuel-free propulsion and control of the swimming velocity by external light and has great potential for future biomedical applications.

Water contamination from industrial and anthropogenic activities is nowadays a major issue in many countries worldwide. To address this problem, efficient water treatment technologies are required. Recent efforts have focused on the development of self-propelled micromotors that provide enhanced micromixing and mass transfer by the transportation of reactive species, resulting in higher decontamination rates. However, a real application of these micromotors is still limited due to the high cost associated to their fabrication process. Here, we present Fe2O3-decorated SiO2/MnO2 microjets for the simultaneous removal of industrial organic pollutants and heavy metals present in wastewater. These microjets were synthesized by low-cost and scalable methods. They exhibit an average speed of 485 ± 32 μm s–1 (∼28 body length per s) at 7% H2O2, which is the highest reported for MnO2-based tubular micromotors. Furthermore, the photocatalytic and adsorbent properties of the microjets enable the efficient degradation of organic pollutants, such as tetracycline and rhodamine B under visible light irradiation, as well as the removal of heavy metal ions, such as Cd2+ and Pb2+.

Keywords: Micromotors, Photocatalytic, Water purification, Fenton, Magnetic control, Iron oxide, Manganese oxide

Here, we present a flexible and low-cost inkjet printed electrochemical sensor for enzyme-free glucose analysis. Versatility, short fabrication time and low cost make inkjet printing a valuable alternative to traditional sensor manufacturing techniques. We fabricated electro-chemical glucose sensors by inkjet printing electrodes on a flexible polyethylene terephthalate substrate. CuO microparticles were used to modify our electrodes, leading to a sensitive, stable and cost-effective platform for non-enzymatic detection of glucose. Selectivity, reproducibility, and life-time provided by the CuO functionalization demonstrated that these sensors are reliable tools for personalized diagnostics and self-assessment of an individual's health. The detection of glucose at concentrations matching that of tear fluid allows us to envisage applications in ocular diagnostics, where painless and non-invasive monitoring of diabetes can be achieved by analyzing glucose contained in tears.

Keywords: Inkjet printing, Non-enzymatic sensor, Glucose, Copper oxide, Tear analysis

In the past few years there has been growing concern about human exposure to endocrine disrupting chemicals. This kind of pollutants can bioaccumulate in aquatic organisms and lead to serious health problems, especially affecting child development. Many efforts have been devoted to achieving the efficient removal of such refractory organics. In this regard, a novel catalyst based on the combination of α-FeOOH and MnO2@MnCO3 catalysts has been developed by up-scalable techniques from cheap precursors and tested in the photo-Fenton-like degradation of an endocrine disruptor. Almost total degradation of 17α-ethynylestradiol hormone was achieved after only 2 min of simulated solar irradiation at neutral pH. The outstanding performance of FeOOH@MnO2@MnCO3 microspheres was mainly attributed to a larger generation of hydroxyl radicals, which are the primary mediators of the total oxidation for this hormone. This work contributes to the development of more cost-effective systems for the rapid and efficient removal of persistent organic pollutants present in sewage plant effluents under direct solar light.

The integration of biological tissue and artificial materials plays a fundamental role in the development of biohybrid soft robotics, a subfield in the field of soft robotics trying to achieve a higher degree of complexity by taking advantage of the exceptional capabilities of biological systems, like self-healing or responsiveness to external stimuli. In this work, we present a proof-of-concept 3D bioprinted bio-actuator made of skeletal muscle tissue and PDMS, which can act as a force measuring platform. The 3D bioprinting technique, which has not been used for the development of bio-actuators, offers unique versatility by allowing a simple, biocompatible and fast fabrication of hybrid multi-component systems. Furthermore, we prove controllability of contractions and functionality of the bio-actuator after applying electric pulses by measuring the exerted forces. We observe an increased force output in time, suggesting improved maturation of the tissue, opening up possibilities for force adaptability or modulation due to prolonged electrical stimuli.

Self-propelled micromotors have previously shown to enhance pollutant removal compared to non-motile nano-micro particles. However, these systems are expensive, difficult to scale-up and require surfactant for efficient work. Efficient and inexpensive micromotors are desirable for their practical applications in water treatment technologies. We describe cobalt-ferrite based micromotors (CFO micromotors) fabricated by a facile and scalable synthesis, that produce hydroxyl radicals via Fenton-like reaction and take advantage of oxygen gas generated during this reaction for self-propulsion. Once the reaction is complete, the CFO micromotors can be easily separated and collected due to their magnetic nature. The CFO micromotors are demonstrated for highly efficient advanced oxidative removal of tetracycline antibiotic from the water. Furthermore, the effects of different concentrations of micromotors and hydrogen peroxide on the antibiotic degradation were studied, as well as the generation of the highly reactive hydroxyl radicals responsible for the oxidation reaction.

Keywords: Degradation, Fenton reaction, Microbots, Nanomotors, Self-propelled Micromotors, Water treatment

Conspectus: Self-propelled colloids have emerged as a new class of active matter over the past decade. These are micrometer sized colloidal objects that transduce free energy from their surroundings and convert it to directed motion. The self-propelled colloids are in many ways, the synthetic analogues of biological self-propelled units such as algae or bacteria. Although they are propelled by very different mechanisms, biological swimmers are typically powered by flagellar motion and synthetic swimmers are driven by local chemical reactions, they share a number of common features with respect to swimming behavior. They exhibit run-and-tumble like behavior, are responsive to environmental stimuli, and can even chemically interact with nearby swimmers. An understanding of self-propelled colloids could help us in understanding the complex behaviors that emerge in populations of natural microswimmers. Self-propelled colloids also offer some advantages over natural microswimmers, since the surface properties, propulsion mechanisms, and particle geometry can all be easily modified to meet specific needs. From a more practical perspective, a number of applications, ranging from environmental remediation to targeted drug delivery, have been envisioned for these systems. These applications rely on the basic functionalities of self-propelled colloids: directional motion, sensing of the local environment, and the ability to respond to external signals. Owing to the vastly different nature of each of these applications, it becomes necessary to optimize the design choices in these colloids. There has been a significant effort to develop a range of synthetic self-propelled colloids to meet the specific conditions required for different processes. Tubular self-propelled colloids, for example, are ideal for decontamination processes, owing to their bubble propulsion mechanism, which enhances mixing in systems, but are incompatible with biological systems due to the toxic propulsion fuel and the generation of oxygen bubbles. Spherical swimmers serve as model systems to understand the fundamental aspects of the propulsion mechanism, collective behavior, response to external stimuli, etc. They are also typically the choice of shape at the nanoscale due to their ease of fabrication. More recently biohybrid swimmers have also been developed which attempt to retain the advantages of synthetic colloids while deriving their propulsion from biological swimmers such as sperm and bacteria, offering the means for biocompatible swimming. In this Account, we will summarize our effort and those of other groups, in the design and development of self-propelled colloids of different structural properties and powered by different propulsion mechanisms. We will also briefly address the applications that have been proposed and, to some extent, demonstrated for these swimmer designs.

Biofilm colonies are typically resistant to general antibiotic treatment and require targeted methods for their removal. One of these methods include the use of nanoparticles as carriers for antibiotic delivery, where they randomly circulate in fluid until they make contact with the infected areas. However, the required proximity of the particles to the biofilm results in only moderate efficacy. We demonstrate here that the non-pathogenic magnetotactic bacteria, Magnetosopirrillum gryphiswalense (MSR-1), can be integrated with drug-loaded mesoporous silica microtubes (MSMs) to build controllable microswimmers (biohybrids) capable of antibiotic delivery to target an infectious biofilm. Applying external magnetic guidance capability and swimming power of the MSR-1 cells, the biohybrids are directed to and forcefully pushed into matured Escherichia coli (E. coli) biofilms. Release of the antibiotic, ciprofloxacin (CFX), is triggered by the acidic microenvironment of the biofilm ensuring an efficient drug delivery system. The results reveal the capabilities of a non-pathogenic bacteria species to target and dismantle harmful biofilms, indicating biohybrid systems have great potential for anti-biofilm applications.

Bacterial biohybrids use the energy of bacteria to manipulate synthetic materials with the goal of solving biomedical problems at the micro- and nanoscale. We explore current in vitro studies of bacterial biohybrids, the first attempts at in vivo biohybrid research, and problems to be addressed for the future.

Keywords: Bacteria, Biohybrid, Microswimmers, Micromotors, Drug delivery

Bacteria biohybrids employ the motility and power of swimming bacteria to carry and maneuver microscale particles. They have the potential to perform microdrug and cargo delivery in vivo, but have been limited by poor design, reduced swimming capabilities, and impeded functionality. To address these challenge, motile Escherichia coli are captured inside electropolymerized microtubes, exhibiting the first report of a bacteria microswimmer that does not utilize a spherical particle chassis. Single bacterium becomes partially trapped within the tube and becomes a bioengine to push the microtube though biological media. Microtubes are modified with "smart" material properties for motion control, including a bacteria-attractant polydopamine inner layer, addition of magnetic components for external guidance, and a biochemical kill trigger to cease bacterium swimming on demand. Swimming dynamics of the bacteria biohybrid are quantified by comparing "length of protrusion" of bacteria from the microtubes with respect to changes in angular autocorrelation and swimmer mean squared displacement. The multifunctional microtubular swimmers present a new generation of biocompatible micromotors toward future microbiorobots and minimally invasive medical applications.

Keywords: Biohybrids, E. coli, Micromotors, Microswimmers, Polydopamine

Water contamination is one of the most persistent problems of public health. Resistance of some pathogens to conventional disinfectants can require the combination of multiple disinfectants or increased disinfectant doses, which may produce harmful byproducts. Here, we describe an efficient method for disinfecting Escherichia coli and removing the bacteria from contaminated water using water self-propelled Janus microbots decorated with silver nanoparticles (AgNPs). The structure of a spherical Janus microbot consists of a magnesium (Mg) microparticle as a template that also functions as propulsion source by producing hydrogen bubbles when in contact with water, an inner iron (Fe) magnetic layer for their remote guidance and collection, and an outer AgNP-coated gold (Au) layer for bacterial adhesion and improving bactericidal properties. The active motion of microbots increases the chances of the contact of AgNPs on the microbot surface with bacteria, which provokes the selective Ag+ release in their cytoplasm, and the microbot self-propulsion increases the diffusion of the released Ag+ ions. In addition, the AgNP-coated Au cap of the microbots has a dual capability of capturing bacteria and then killing them. Thus, we have demonstrated that AgNP-coated Janus microbots are capable of efficiently killing more than 80% of E. coli compared with colloidal AgNPs that killed only less than 35% of E. coli in contaminated water solutions in 15 min. After capture and extermination of bacteria, magnetic properties of the cap allow collection of microbots from water along with the captured dead bacteria, leaving water with no biological contaminants. The presented biocompatible Janus microbots offer an encouraging method for rapid disinfection of water.

Keywords: Bactericidal, Magnetic control, Micromotors, Microswimmers, Self-propulsion, Silver nanoparticles

Self-propelled micro/nano-devices have been proved as powerful tools in various applications given their capability of both autonomous motion and on-demand task fulfilment. Tubular micro-jets stand out as an important member in the family of self-propelled micro/nano-devices and are widely explored with respect to their fabrication and functionalization. A few methods are currently available for the fabrication of tubular micro-jets, nevertheless there is still a demand to explore the fabrication of tubular micro-jets made of versatile materials and with the capability of multi-functionalization. Here, we present a facile strategy for the fabrication of mesoporous silica micro-jets (MSMJs) for tubular micromotors which can carry out multiple tasks depending on their functionalities. The synthesis of MSMJs does not require the use of any equipment, making it facile and cost-effective for future practical use. The MSMJs can be modified inside, outside or both with different kinds of metal nanoparticles, which provide these micromotors with a possibility of additional properties, such as the anti-bacterial effect by silver nanoparticles, or biochemical sensing based on surface enhanced Raman scattering (SERS) by gold nanoparticles. Because of the high porosity, high surface area and also the easy surface chemistry process, the MSMJs can be employed for the efficient removal of heavy metals in contaminated water, as well as for the controlled and active drug delivery, as two proof-of-concept examples of environmental and biomedical applications, respectively. Therefore, taking into account the new, simple and cheap method of fabrication, highly porous structure, and multiple functionalities, the mesoporous silica based micro-jets can serve as efficient tools for desired applications.

Keywords: Drug delivery, Nanomachines, Nanomotors, Nanorobots, Target delivery

In the field of micromotors many efforts are taken to find a substitute for peroxide as fuel. While most approaches turn towards other toxic high energy chemicals such as hydrazine, we introduce an energy source that is widely used in nature: light. Light is an ideal source of energy and some materials, such as AgCl, have the inherent property to transform light energy for chemical processes, which can be used to achieve propulsion. In the case of silver chloride, one observed process after light exposure is surface modification which leads to the release of ions generating chemo-osmotic gradients. Here we present endeavours to use those processes to propel uniquely shaped micro objects of micro star morphology with a high surface to volume ratio, study their dynamics and present approaches to go towards real environmental applications.

Keywords: Self-propellers, Silver chloride, Environmental applications, Photoactive colloids, Anti bacterial

Enzyme triggered bio-catalytic reactions convert chemical energy into mechanical force to power micro/nano-machines. Though there have been reports about enzymes powered micro/nano-motors, enzymatic Janus nano-motor smaller than 100 nm has not been reported yet. Here, we prepared an enzyme powered Janus nano-motor by half-capping a thin layer of silicon dioxide (4 nm SiO2) onto a mesoporous silica nanoparticle (MSNP) of 90 nm, enabling asymmetry to the nano-architecture. The nano-motors are chemically powered by the decomposition of H2O2 triggered by the enzyme catalase located at one face of the nanoparticles. The self-propulsion is characterized by dynamic light scattering (DLS) and optical microscopy. The apparent diffusion coefficient was enhanced by 150% compared to their Brownian motion at low H2O2 concentration (i.e. below 3 wt%). Mesoporous nano-motors might serve as active drug delivery nano-systems in future biomedical applications such as intracellular drug delivery.

Keywords: Enzyme catalysis, Janus particles, Mesoporous silica, Nano-motors, Nanomachine, Self-propulsion

Artificial micro- and nano-swimmers are interesting systems for both fundamental understandings of swimming at low Reynolds numbers and for their promising applications in many fields, such as environmental and biomedical fields. Different architectures of self-propelled systems present various propulsion mechanisms. Among them, tubular microjets are widely used for different applications. Here, we briefly describe the fabrication of microjets by rolling up thin film and electrodeposition techniques and the principles behind these processes. Different parameters affecting the motion of microjets and existing theoretical models about microjet propulsion are discussed.

Enzymes play a crucial role in many biological processes which require harnessing and converting free chemical energy into kinetic forces in order to accomplish tasks. Enzymes are considered to be molecular machines, not only because of their capability of energy conversion in biological systems but also because enzymatic catalysis can result in enhanced diffusion of enzymes at a molecular level. Enlightened by nature’s design of biological machinery, researchers have investigated various types of synthetic micro/nanomachines by using enzymatic reactions to achieve self-propulsion of micro/nanoarchitectures. Yet, the mechanism of motion is still under debate in current literature. Versatile proof-of-concept applications of these enzyme-powered micro/nanodevices have been recently demonstrated. In this review, we focus on discussing enzymes not only as stochastic swimmers but also as nanoengines to power self-propelled synthetic motors. We present an overview on different enzyme-powered micro/nanomachines, the current debate on their motion mechanism, methods to provide motion and speed control, and an outlook of the future potentials of this multidisciplinary field.

The quest for biocompatible micro-swimmers powered by compatible fuel and with full motion control over their self-propulsion is a long-standing challenge in the field of active matter and microrobotics. Here, we present an active hybrid microcapsule motor based on Janus hollow mesoporous silica micro particles (JHP) powered by the bio-catalytic decomposition of urea at physiological concentrations. The directional self-propelled motion lasts longer than 10 minutes with an average velocity of up to 5 body lengths per second. Additionally, we control the velocity of the micro-motor by chemically inhibiting and reactivating the enzymatic activity of urease. The incorporation of magnetic material within the Janus structure provides remote magnetic control on the movement direction. Furthermore, the mesoporous/hollow structure can load both small molecules and larger particles up to hundreds of nano-meters, making the hybrid micro-motor an active and controllable drug delivery micro-system.

Self-motile Janus colloids are important for enabling a wide variety of microtechnology applications as well as for improving our understanding of the mechanisms of motion of artificial micro- and nanoswimmers. We present here micro/nanomotors which possess a reversed Janus structure of an internal catalytic “chemical engine”. The catalytic material (here platinum (Pt)) is embedded within the interior of the mesoporous silica (mSiO2)-based hollow particles and triggers the decomposition of H2O2 when suspended in an aqueous peroxide (H2O2) solution. The pores/gaps at the noncatalytic (Pt) hemisphere allow the exchange of chemical species in solution between the exterior and the interior of the particle. By varying the diameter of the particles, we observed size-dependent motile behavior in the form of enhanced diffusion for 500 nm particles, and self-phoretic motion, toward the nonmetallic part, for 1.5 and 3 μm ones. The direction of motion was rationalized by a theoretical model based on self-phoresis. For the 3 μm particles, a change in the morphology of the porous part is observed, which is accompanied by a change in the mechanism of propulsion via bubble nucleation and ejection as well as a change in the direction of motion.

The motion of self-propelled tubular micro- and nanojets has so far been achieved by bubble propulsion, e.g., O2 bubbles formed by catalytic decomposition of H2O2, which renders future biomedical applications inviable. An alternative self-propulsion mechanism for tubular engines on the nanometer scale is still missing. Here, we report the fabrication and characterization of bubble-free propelled tubular nanojets (as small as 220 nm diameter), powered by an enzyme-triggered biocatalytic reaction using urea as fuel. We studied the translational and rotational dynamics of the nanojets as functions of the length and location of the enzymes. Introducing tracer nanoparticles into the system, we demonstrated the presence of an internal flow that extends into the external fluid via the cavity opening, leading to the self-propulsion. One-dimensional nanosize, longitudinal self-propulsion, and biocompatibility make the tubular nanojets promising for future biomedical applications.

Heavy metal contamination in water is a serious risk to the public health and other life forms on earth. Current research in nanotechnology is developing new nanosystems and nanomaterials for the fast and efficient removal of pollutants and heavy metals from water. Here, we report graphene oxide-based microbots (GOx-microbots) as active self-propelled systems for the capture, transfer, and removal of a heavy metal (i.e., lead) and its subsequent recovery for recycling purposes. Microbots’ structure consists of nanosized multilayers of graphene oxide, nickel, and platinum, providing different functionalities. The outer layer of graphene oxide captures lead on the surface, and the inner layer of platinum functions as the engine decomposing hydrogen peroxide fuel for self-propulsion, while the middle layer of nickel enables external magnetic control of the microbots. Mobile GOx-microbots remove lead 10 times more efficiently than nonmotile GOx-microbots, cleaning water from 1000 ppb down to below 50 ppb in 60 min. Furthermore, after chemical detachment of lead from the surface of GOx-microbots, the microbots can be reused. Finally, we demonstrate the magnetic control of the GOx-microbots inside a microfluidic system as a proof-of-concept for automatic microbots-based system to remove and recover heavy metals.

Self-powered micromachines are promising tools for future environmental remediation technology. Waste-water treatment and water reuse is an essential part of environmental sustainability. Herein, we present reusable Fe/Pt multi-functional active microcleaners that are capable of degrading organic pollutants (malachite green and 4-nitrophenol) by generated hydroxyl radicals via a Fenton-like reaction. Various different properties of microcleaners, such as the effect of their size, short-term storage, long-term storage, reusability, continuous swimming capability, surface composition, and mechanical properties, are studied. It is found that these microcleaners can continuously swim for more than 24 hours and can be stored more than 5 weeks during multiple cleaning cycles. The produced microcleaners can also be reused, which reduces the cost of the process. During the reuse cycles the outer iron surface of the Fe/Pt microcleaners generates the in-situ, heterogeneous Fenton catalyst and releases a low concentration of iron into the treated water, while the mechanical properties also appear to be improved due to both its surface composition and structural changes. The microcleaners are characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), nanoindentation, and finite-element modeling (FEM).

Keywords: Catalysts, Heterogeneous catalysis, Microcleaners, Micromotors, Nanorobots, Wastewater treatment

Achieving control over the directionality of active colloids is essential for their use in practical applications such as cargo carriers in microfluidic devices. So far, guidance of spherical Janus colloids was mainly realized using specially engineered magnetic multilayer coatings combined with external magnetic fields. Here we demonstrate that step-like submicrometre topographical features can be used as reliable docking and guiding platforms for chemically active spherical Janus colloids. For various topographic features (stripes, squares or circular posts), docking of the colloid at the feature edge is robust and reliable. Furthermore, the colloids move along the edges for significantly long times, which systematically increase with fuel concentration. The observed phenomenology is qualitatively captured by a simple continuum model of self-diffusiophoresis near confining boundaries, indicating that the chemical activity and associated hydrodynamic interactions with the nearby topography are the main physical ingredients behind the observed behaviour.

Janus particles can self-assemble around microfabricated gears in reproducible configurations with a high degree of spatial and orientational order. The final configuration maximizes the torque applied on the rotor leading to a unidirectional and steady rotating motion. The interplay between geometry and dynamical behavior leads to the self-assembly of Janus micromotors starting from randomly distributed particles.

Keywords: Active catalytic particles, Microgears, Micromachines, Janus particles, Self-assembly, Self-propulsion

Microswimmers, such as bacteria, are known to show different behaviours depending on their local environment. They identify spatial chemical gradients to find nutrient rich areas (chemotaxis) and interact with shear flows to accumulate in high shear regions. Recently, artificial microswimmers have been developed which mimic their natural counterparts in many ways. One of the exciting topics in this field is to study these artificial motors in several natural settings like the ones bacteria interact with. In this Focus article, we summarize recent observations of artificial swimmers in chemical gradients, shear flows and other interesting natural environments simulated in the lab using microfluidics and nanotechnology.

Flexible sensing devices have gained a great deal of attention among the scientific community in recent years. The application of flexible sensors spans over several fields, including medicine, industrial automation, robotics, security, and human-machine interfacing. In particular, non-invasive health-monitoring devices are expected to play a key role in the improvement of patient life and in reducing costs associated with clinical and biomedical diagnostic procedures. Here, we focus on recent advances achieved in flexible devices applied on the human skin for biomedical and healthcare purposes.

Sustainable energy generation is of recent interest due to a growing energy demand across the globe and increasing environmental issues caused by conventional non-renewable means of power generation. In the context of microsystems, portable electronics and lab-on-a-chip based (bio)chemical sensors would essentially require fully integrated, reliable means of power generation. Microfluidic-based fuel cells can offer unique advantages compared to conventional fuel cells such as high surface area-to-volume ratio, ease of integration, cost effectiveness and portability. Here, we summarize recent developments which utilize the potential of microfluidic devices for energy generation.

Soft robotics is an emerging discipline that employs soft flexible materials such as fluids, gels and elastomers in order to enhance the use of robotics in healthcare applications. Compared to their rigid counterparts, soft robotic systems have flexible and rheological properties that are closely related to biological systems, thus allowing the development of adaptive and flexible interactions with complex dynamic environments. With new technologies arising in bioengineering, the integration of living cells into soft robotic systems offers the possibility of accomplishing multiple complex functions such as sensing and actuating upon external stimuli. These emerging bio-hybrid systems are showing promising outcomes and opening up new avenues in the field of soft robotics for applications in healthcare and other fields.

The ubiquitous random motion of mesoscopic active particles, such as cells, can be “rectified” or directed by embedding the particles in systems containing local and periodic asymmetric cues. Incorporated on lab-on-a-chip devices, these microratchet-like structures can be used to self-propel fluids, transport particles, and direct cell motion in the absence of external power sources. In this Focus article we discuss recent advances in the use of ratchet-like geometries in microfluidics which could open new avenues in biomedicine for applications in diagnosis, cancer biology, and bioengineering.

Point-of-care diagnostics (PoC) and personalised medicine are highly valuable for the improvement of world health. Smartphone PoC platforms which precisely diagnose diseases and track their development through the detection of several bioanalytes represent one of the newest and most exciting advancements towards mass-screening applications. Here we focus on recent advances in both multiplexed and smartphone integrated PoC sensors.

There has been a significant interest in the development of microswimmers for medical drug and cargo delivery, but the majority of current micromotors rely on toxic fuel sources and materials in their design making them irrelevant for biomedical applications. Bacteria represent an excellent motor alternative, as they are powered using their surrounding biological fluids. For a motile, biohybrid swimmer, Escherichia coli (E. coli) are integrated onto metal capped, polystyrene (PS) Janus particles. Fabrication of the biohybrid is rapid and simple for a microswimmer capable of magnetic guidance and ferrying an anticancer agent. Cell adhesion is regulated as E. coli adheres only to the particle's metal caps allowing the PS surface to be utilized for drug attachment, creating a multifunctional system. E. coli adhesion is investigated on multiple metal caps (Pt, Fe, Ti, or Au) and displays a strong preference to attach to Pt surfaces over other metals. Surface hydrophobicity and surface charge are examined to interpret the cell specific adhesion on the Janus particles. The dual capability of the biohybrid to have guided cell adhesion and localized drug attachment allows the swimmer to have multiple applications for biomedical microswimmers, future bacteria-interface systems, and micro-biorobots.

Keywords: Bacteria adhesion, Biohybrids, Escherichia coli, Janus particles, Microswimmers

The development of synthetic nanomotors for technological applications in particular for life science and nanomedicine is a key focus of current basic research. However, it has been challenging to make active nanosystems based on biocompatible materials consuming nontoxic fuels for providing self-propulsion. Here, we fabricate self-propelled Janus nanomotors based on hollow mesoporous silica nanoparticles (HMSNPs), which are powered by biocatalytic reactions of three different enzymes: catalase, urease, and glucose oxidase (GOx). The active motion is characterized by a mean-square displacement (MSD) analysis of optical video recordings and confirmed by dynamic light scattering (DLS) measurements. We found that the apparent diffusion coefficient was enhanced by up to 83%. In addition, using optical tweezers, we directly measured a holding force of 64 ± 16 fN, which was necessary to counteract the effective self-propulsion force generated by a single nanomotor. The successful demonstration of biocompatible enzyme-powered active nanomotors using biologically benign fuels has a great potential for future biomedical applications.

Keywords: Enzyme, Hollow mesoporous silica nanoparticles, Hybrid motors, Janus particles, Nanomotors, Optical tweezers

We report on the synergy between catalytic propulsion and mesoporous silica nanoparticles (MSNPs) for the design of Janus nanomotors as active cargo delivery systems with sizes <100 nm (40, 65, and 90 nm). The Janus asymmetry of the nanomotors is given by electron beam (e-beam) deposition of a very thin platinum (2 nm) layer on MSNPs. The chemically powered Janus nanomotors present active diffusion at low H2O2 fuel concentration (i.e., <3 wt %). Their apparent diffusion coefficient is enhanced up to 100% compared to their Brownian motion. Due to their mesoporous architecture and small dimensions, they can load cargo molecules in large quantity and serve as active nanocarriers for directed cargo delivery on a chip.

Chemically powered micro- and nanomotors are small devices that are self-propelled by catalytic reactions in fluids. Taking inspiration from biomotors, scientists are aiming to find the best architecture for self-propulsion, understand the mechanisms of motion, and develop accurate control over the motion. Remotely guided nanomotors can transport cargo to desired targets, drill into biomaterials, sense their environment, mix or pump fluids, and clean polluted water. This Review summarizes the major advances in the growing field of catalytic nanomotors, which started ten years ago.

Keywords: Catalysis, Micromotors, Nanomotors, Robots, Self-propulsion

Surface-conductive Janus spherical motors are fabricated by wrapping silica particles with reduced graphene oxide capped with a thin Pt layer. These motors exhibit a 100% enhanced velocity as compared to standard SiO2–Pt motors. Furthermore, the versatility of graphene may open up possibilities for a diverse range of applications from active drug delivery systems to water remediation.

Keywords: Enhanced speed, Graphene wrapping, Janus micromotors, Janus particles, Micromotors, Surface conduction

We demonstrate a simple physical fabrication method to obtain self-propelled active Janus microparticles with rough catalytic platinum surfaces that show a four-fold increase in their propulsion speed compared to conventional Janus particles coated with a smooth Pt layer.

This article will focus on recent reports that have applied three-dimensional (3D) printing for designing millimeter to micrometer architecture for robotic motility. The utilization of 3D printing has rapidly grown in applications for medical prosthetics and scaffolds for organs and tissue, but more recently has been implemented for designing mobile robotics. With an increase in the demand for devices to perform in fragile and confined biological environments, it is crucial to develop new miniaturized, biocompatible 3D systems. Fabrication of materials at different scales with different properties makes 3D printing an ideal system for creating frameworks for small-scale robotics. 3D printing has been applied for the design of externally powered, artificial microswimmers and studying their locomotive capabilities in different fluids. Printed materials have also been incorporated with motile cells for bio-hybrid robots capable of functioning by cell contraction and swimming. These 3D devices offer new methods of robotic motility for biomedical applications requiring miniature structures. Traditional 3D printing methods, where a structure is fabricated in an additive process from a digital design, and non-traditional 3D printing methods, such as lithography and molding, will be discussed.

Three-dimensional (3D) bioprinting has recently emerged as an extension of 3D material printing, by using biocompatible or cellular components to build structures in an additive, layer-by-layer methodology for encapsulation and culture of cells. These 3D systems allow for cell culture in a suspension for formation of highly organized tissue or controlled spatial orientation of cell environments. The in vitro 3D cellular environments simulate the complexity of an in vivo environment and natural extracellular matrices (ECM). This paper will focus on bioprinting utilizing hydrogels as 3D scaffolds. Hydrogels are advantageous for cell culture as they are highly permeable to cell culture media, nutrients, and waste products generated during metabolic cell processes. They have the ability to be fabricated in customized shapes with various material properties with dimensions at the micron scale. 3D hydrogels are a reliable method for biocompatible 3D printing and have applications in tissue engineering, drug screening, and organ on a chip models.

Complex-shaped microparticles (MPs) have attracted extensive interest in a myriad of scientific and engineering fields in recent years for their distinct morphology and capability in combining different functions within a single particle. Microfluidic techniques offer an intriguing method for fabricating MPs with excellent monodispersity and complex morphology in parallel while controlling their number and size precisely and independently. To date, there are two notable microfluidics approaches for the synthesis of complex-shaped MPs, namely droplet based, and flow-lithography based microfluidics approaches. It is undoubted that the application of complex-shaped MPs via microfluidic fabrication will hold great promise in a variety of fields including microfabrication, analytical chemistry and biomedicine.

Extensive studies have been carried out on photocatalytic materials in recent years as photocatalytic reactions offer a promising solution for solar energy conversion and environmental remediation. Currently available commercial photocatalysts still lack efficiency and thus are economically not viable for replacing traditional sources of energy. This article focuses on recent developments in novel nano-photocatalyst materials to enhance photocatalytic activity. Recent reports on optofluidic systems, new synthesis of photocatalytic composite materials and motile photocatalysts are discussed in this article.

The self-assembly of amphiphilic building blocks has attracted extensive interest in myriad fields in recent years, due to their great potential in the nanoscale design of functional hybrid materials. Microfluidic techniques provide an intriguing method to control kinetic aspects of the self-assembly of molecular amphiphiles by the facile adjustment of the hydrodynamics of the fluids. Up to now, there have been several reports about one-step direct self-assembly of different building blocks with versatile and multi-shape products without templates, which demonstrated the advantages of microfluidics. These assemblies with different morphologies have great applications in various areas such as cancer therapy, micromotor fabrication, and controlled drug delivery.

Artificial microvasculature, particularly as part of the blood-brain barrier, has a high benefit for pharmacological drug discovery and uptake regulation. We demonstrate the fabrication of tubular structures with patterns of holes, which are capable of mimicking microvasculatures. By using photolithography, the dimensions of the cylindrical scaffolds can be precisely tuned as well as the alignment and size of holes. Overlapping holes can be tailored to create diverse three-dimensional configurations, for example, periodic nanoscaled apertures. The porous tubes, which can be made from diverse materials for differential functionalization, are biocompatible and can be modified to be biodegradable in the culture medium. As a proof of concept, endothelial cells (ECs) as well as astrocytes were cultured on these scaffolds. They form monolayers along the scaffolds, are guided by the array of holes and express tight junctions. Nanoscaled filaments of cells on these scaffolds were visualized by scanning electron microscopy (SEM). This work provides the basic concept mainly for an in vitro model of microvasculature which could also be possibly implanted in vivo due to its biodegradability.

Graphene oxide (GO) has attracted great interest due to its extraordinary potential for biomedical application. Although it is clear that the naturally occurring morphology of biological structures is crucial to their precise interactions and correct functioning, the geometrical aspects of nanoparticles are often ignored in the design of nanoparticles for biological applications. A few in vitro and in vivo studies have evaluated the cytotoxicity and biodistribution of GO, however very little is known about the influence of flake size and cytotoxicity. Herein, we aim at presenting an initial cytotoxicity evaluation of different nano-sized GO flakes for two different cell lines (HeLa (Kyoto) and macrophage (J7742)) when they are exposed to samples containing different sized nanographene oxide (NGO) flakes (mean diameter of 89 and 277 nm). The obtained data suggests that the larger NGO flakes reduce cell viability as compared to smaller flakes. In addition, the viability reduction correlates with the time and the concentration of the NGO nanoparticles to which the cells are exposed. Uptake studies were also conducted and the data suggests that both cell lines internalize the GO nanoparticles during the incubation periods studied.

The articles in this special section focus on the technologies and applications supported by micro- and nanomachines. The world of artificial micro- and nanomachines has greatly expanded over the last few years to include a range of disciplines from chemistry, physics, biology, to micro/nanoengineering, robotics, and theoretical physics. The dream of engineering nanomachines involves fabricating devices that mimic the mechanical action of biological motors that operate over multiple length scales: from molecular-scale enzymes and motors such as kinesins to the micro-scale biomachinery responsible for the motility of tiny organisms such as the flagella motors of E. coli. However, the design and fabrication of artificial nano- and micromachines with comparable performance as their biological counterparts is not a straightforward task. It requires a detailed understanding of the basic principles of the operation of biomotors and mechanisms that couple the dissipation of energy to mechanical motion. Moreover, micro engineering and microfabrication knowledge is required in order to design efficient, small and even smart micro- and nanomachines.

In this paper, we fabricate a flexible and location traceable micromotor, called organo-motor, assisted by microfluidic devices and with high throughput. The organo-motors are composed of organic hydrogel material, poly (ethylene glycol) diacrylate (PEGDA), which can provide the flexibility of their structure. For spatial and temporal traceability of the organo-motors under magnetic resonance imaging (MRI), superparamagnetic iron oxide nanoparticles (SPION; Fe3O4) were incorporated into the PEGDA microhydrogels. Furthermore, a thin layer of platinum (Pt) was deposited onto one side of the SPION-PEGDA microhydrogels providing geometrical asymmetry and catalytic propulsion in aqueous fluids containing hydrogen peroxide solution, H2O2. Furthermore, the motion of the organo-motor was controlled by a small external magnet enabled by the presence of SPION in the motor architecture.

Keywords: Flexible, Hydrogel, Magnetic resonance imaging, Microfluidics, Micromotor, Microparticle, Organo-motor, Poly (ethylene glycol) diacrylate, Self-propulsion, Superparamagnetic iron oxide nanoparticles

We experimentally demonstrate the precise localization of spherical Pt-Silica Janus micromotors (diameter 5 μm) under the influence of controlled magnetic fields. First, we control the motion of the Janus micromotors in two-dimensional (2D) space. The control system achieves precise localization within an average region-of-convergence of 7 μm. Second, we show that these micromotors provide sufficient propulsion force, allowing them to overcome drag and gravitational forces and move both downwards and upwards. This propulsion is studied by moving the micromotors in three-dimensional (3D) space. The micromotors move downwards and upwards at average speeds of 19.1 μm/s and 9.8 μm/s, respectively. Moreover, our closed-loop control system achieves localization in 3D space within an average region-of-convergence of 6.3 μm in diameter. The precise motion control and localization of the Janus micromotors in 2D and 3D spaces provides broad possibilities for nanotechnology applications.

Keywords: 3D space, Localization, Magnetic control, Micromotors, Self-propulsion