A Human-Scale Clinically-Ready Electromagnetic Navigation System for Magnetically-Responsive Biomaterials and Medical Devices.

Magnetic navigation systems are used to precisely manipulate magnetically responsive materials enabling the realization of new minimally invasive procedures using magnetic medical devices. Their widespread applicability has been constrained by high infrastructure demands and costs. we report on a portable electromagnetic navigation system, the Navion, which is capable of generating a large magnetic field over a large workspace. The system is easy to install in hospital operating rooms and transportable through healthcare facilities, aiding in the widespread adoption of magnetically responsive medical devices. First, we introduce our design and implementation approach for the system and characterize its performance. Next, we demonstrate in vitro navigation of different microrobot structures using magnetic field gradients and rotating magnetic fields. Spherical permanent magnets, electroplated cylindrical microrobots, microparticle swarms, and magnetic composite bacteria-inspired helical structures are investigated. we also demonstrate the navigation of magnetic catheters in two challenging endovascular tasks: (1) an angiography procedure and (2) deep navigation within the circle of Willis. Catheter navigation is demonstrated in a porcine model in vivo to perform an angiography under magnetic guidance. This article is protected by copyright. All rights reserved.

A Naturally Inspired Extrusion-based Microfluidic Approach for Manufacturing Tailorable Magnetic Soft Continuum Microrobotic Devices.

Soft materials play a crucial role in small-scale robotic applications by closely mimicking the complex motion and morphing behavior of organisms. However, conventional fabrication methods face challenges in creating highly integrated small-scale soft devices. In this study, we leverage microfluidics to precisely control reaction-diffusion (RD) processes to generate multifunctional and compartmentalized calcium-cross-linkable alginate-based microfibers. Under RD conditions, we produce sophisticated alginate-based fibers for magnetic soft continuum robotics (mSCR) applications with customizable features, such as geometry (compact or hollow), degree of cross-linking, and the precise localization of magnetic nanoparticles (inside the core, surrounding the fiber, or on one side). This fine control allows for tuning the stiffness and magnetic responsiveness of the microfibers. Additionally, chemically cleavable regions within the fibers enable disassembly into smaller robotic units or roll-up structures under a rotating magnetic field. These findings demonstrate the versatility of microfluidics in processing highly integrated small-scale devices. This article is protected by copyright. All rights reserved.

Electrostatic catalysis of a click reaction in a microfluidic cell.

Electric fields have been highlighted as a smart reagent in nature's enzymatic machinery, as they can directly trigger or accelerate chemical processes with stereo- and regio-specificity. In enzymatic catalysis, controlled mass transport of chemical species is also key in facilitating the availability of reactants in the active reaction site. However, recent progress in developing a clean catalysis that profits from oriented electric fields is limited to theoretical and experimental studies at the single molecule level, where both the control over mass transport and scalability cannot be tested. Here, we quantify the electrostatic catalysis of a prototypical Huisgen cycloaddition in a large-area electrode surface and directly compare its performance to the conventional Cu(I) catalysis. Our custom-built microfluidic cell enhances reagent transport towards the electrified reactive interface. This continuous-flow microfluidic electrostatic reactor is an example of an electric-field driven platform where clean large-scale electrostatic catalytic processes can be efficiently implemented and regulated.

3D Motion Manipulation for Micro- and Nanomachines: Progress and Future Directions.

In the past decade, micro- and nanomachines (MNMs) have made outstanding achievements in the fields of targeted drug delivery, tumor therapy, microsurgery, biological detection, and environmental monitoring and remediation. Researchers have made significant efforts to accelerate the rapid development of MNMs capable of moving through fluids by means of different energy sources (chemical reactions, ultrasound, light, electricity, magnetism, heat, or their combinations). However, the motion of MNMs is primarily investigated in confined two-dimensional (2D) horizontal setups. Furthermore, three-dimensional (3D) motion control remains challenging, especially for vertical movement and control, significantly limiting its potential applications in cargo transportation, environmental remediation, and biotherapy. Hence, an urgent need is to develop MNMs that can overcome self-gravity and controllably move in 3D spaces. This review delves into the latest progress made in MNMs with 3D motion capabilities under different manipulation approaches, discusses the underlying motion mechanisms, explores potential design concepts inspired by nature for controllable 3D motion in MNMs, and presents the available 3D observation and tracking systems.

"On-The-Fly" Synthesis of Self-Supported LDH Hollow Structures Through Controlled Microfluidic Reaction-Diffusion Conditions.

Layered double hydroxides (LDHs) are a class of functional materials that exhibit exceptional properties for diverse applications in areas such as heterogeneous catalysis, energy storage and conversion, and bio-medical applications, among others. Efforts have been devoted to produce millimeter-scale LDH structures for direct integration into functional devices. However, the controlled synthesis of self-supported continuous LDH materials with hierarchical structuring up to the millimeter scale through a straightforward one-pot reaction method remains unaddressed. Herein, it is shown that millimeter-scale self-supported LDH structures can be produced by means of a continuous flow microfluidic device in a rapid and reproducible one-pot process. Additionally, the microfluidic approach not only allows for an "on-the-fly" formation of unprecedented LDH composite structures, but also for the seamless integration of millimeter-scale LDH structures into functional devices. This method holds the potential to unlock the integrability of these materials, maintaining their performance and functionality, while diverging from conventional techniques like pelletization and densification that often compromise these aspects. This strategy will enable exciting advancements in LDH performance and functionality.

On-Command Disassembly of Microrobotic Superstructures for Transport and Delivery of Magnetic Micromachines.

Magnetic microrobots have been developed for navigating microscale environments by means of remote magnetic fields. However, limited propulsion speeds at small scales remain an issue in the maneuverability of these devices as magnetic force and torque are proportional to their magnetic volume. Here, a microrobotic superstructure is proposed, which, as analogous to a supramolecular system, consists of two or more microrobotic units that are interconnected and organized through a physical (transient) component (a polymeric frame or a thread). The superstructures consist of microfabricated magnetic helical micromachines interlocked by a magnetic gelatin nanocomposite containing iron oxide nanoparticles (IONPs). While the microhelices enable the motion of the superstructure, the IONPs serve as heating transducers for dissolving the gelatin chassis via magnetic hyperthermia. In a practical demonstration, the superstructure's motion with a gradient magnetic field in a large channel, the disassembly of the superstructure and release of the helical micromachines by a high-frequency alternating magnetic field, and the corkscrew locomotion of the released helices through a small channel via a rotating magnetic field, is showcased. This adaptable microrobotic superstructure reacts to different magnetic inputs, which can be used to perform complex delivery procedures within intricate regions of the human body.

Tailored Design of a Water-Based Nanoreactor Technology for Producing Processable Sub-40 Nm 3D COF Nanoparticles at Atmospheric Conditions.

Covalent organic frameworks (COFs) are crystalline materials with intrinsic porosity that offer a wide range of potential applications spanning diverse fields. Yet, the main goal in the COF research area is to achieve the most stable thermodynamic product while simultaneously targeting the desired size and structure crucial for enabling specific functions. While significant progress is made in the synthesis and processing of 2D COFs, the development of processable 3D COF nanocrystals remains challenging. Here, a water-based nanoreactor technology for producing processable sub-40 nm 3D COF nanoparticles at ambient conditions is presented. Significantly, this technology not only improves the processability of the synthesized 3D COF, but also unveils exciting possibilities for their utilization in previously unexplored domains, such as nano/microrobotics and biomedicine, which are limited by larger crystallites.

Magnetic PiezoBOTs: a microrobotic approach for targeted amyloid protein dissociation.

Piezoelectric nanomaterials have become increasingly popular in the field of biomedical applications due to their high biocompatibility and ultrasound-mediated piezocatalytic properties. In addition, the ability of these nanomaterials to disaggregate amyloid proteins, which are responsible for a range of diseases resulting from the accumulation of these proteins in body tissues and organs, has recently gained considerable attention. However, the use of nanoparticles in biomedicine poses significant challenges, including targeting and uncontrolled aggregation. To address these limitations, our study proposes to load these functional nanomaterials on a multifunctional mobile microrobot (PiezoBOT). This microrobot is designed by coating magnetic and piezoelectric barium titanate nanoparticles on helical biotemplates, allowing for the combination of magnetic navigation and ultrasound-mediated piezoelectric effects to target amyloid disaggregation. Our findings demonstrate that acoustically actuated PiezoBOTs can effectively reduce the size of aggregated amyloid proteins by over 80% in less than 10 minutes by shortening and dissociating constituent amyloid fibrils. Moreover, the PiezoBOTs can be easily magnetically manipulated to actuate the piezocatalytic nanoparticles to specific amyloidosis-affected tissues or organs, minimizing side effects. These biocompatible PiezoBOTs offer a promising non-invasive therapeutic approach for amyloidosis diseases by targeting and breaking down protein aggregates at specific organ or tissue sites.

The magnetopyroelectric effect: heat-mediated magnetoelectricity in magnetic nanoparticle-ferroelectric polymer composites.

Magnetoelectricity enables a solid-state material to generate electricity under magnetic fields. Most magnetoelectric composites are developed through a strain-mediated route by coupling piezoelectric and magnetostrictive phases. However, the limited availability of high-performance magnetostrictive components has become a constraint for the development of novel magnetoelectric materials. Here, we demonstrate that nanostructured composites of magnetic and pyroelectric materials can generate electrical output, a phenomenon we refer to as the magnetopyroelectric (MPE) effect, which is analogous to the magnetoelectric effect in strain-mediated composite multiferroics. Our composite consists of magnetic iron oxide nanoparticles (IONPs) dispersed in a ferroelectric (and also pyroelectric) poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) matrix. Under a high-frequency low-magnitude alternating magnetic field, the IONPs generate heat through hysteresis loss, which stimulates the depolarization process of the pyroelectric polymer. This magnetopyroelectric approach creates a new opportunity to develop magnetoelectric materials for a wide range of applications.

Filler-Enhanced Piezoelectricity of Poly-L-Lactide and Its Use as a Functional Ultrasound-Activated Biomaterial.

Poly-L-lactide (PLLA) offers a unique possibility for processing into biocompatible, biodegradable, and implantable piezoelectric structures. With such properties, PLLA has potential to be used as an advanced tool for mimicking biophysical processes that naturally occur during the self-repair of wounds and damaged tissues, including electrostimulated regeneration. The piezoelectricity of PLLA strongly depends on the possibility of controlling its crystallinity and molecular orientation. Here, it is shown that modifying PLLA with a small amount (1 wt%) of crystalline filler particles with a high aspect ratio, which act as nucleating agents during drawing-induced crystallization, promotes the formation of highly crystalline and oriented PLLA structures. This increases their piezoelectricity, and the filler-modified PLLA films provide a 20-fold larger voltage output than nonmodified PLLA during ultrasound (US)-assisted activation. With 99% PLLA content, the ability of the films to produce reactive oxygen species (ROS) and increase the local temperature during interactions with US is shown to be very low. US-assisted piezostimulation of adherent cells directly attach to their surface (such as skin keratinocytes), stimulate cytoskeleton formation, and as a result cells elongate and orient themselves in a specific direction that align with the direction of PLLA film drawing and PLLA dipole orientation.

Can We Rationally Design and Operate Spatial Atomic Layer Deposition Systems for Steering the Growth Regime of Thin Films?

Fine control over the growth of materials is required to precisely tailor their properties. Spatial atomic layer deposition (SALD) is a thin-film deposition technique that has recently attracted attention because it allows producing thin films with a precise number of deposited layers, while being vacuum-free and much faster than conventional atomic layer deposition. SALD can be used to grow films in the atomic layer deposition or chemical vapor deposition regimes, depending on the extent of precursor intermixing. Precursor intermixing is strongly influenced by the SALD head design and operating conditions, both of which affect film growth in complex ways, making it difficult to predict the growth regime prior to depositions. Here, we used numerical simulation to systematically study how to rationally design and operate SALD systems for growing thin films in different growth regimes. We developed design maps and a predictive equation allowing us to predict the growth regime as a function of the design parameters and operation conditions. The predicted growth regimes match those observed in depositions performed for various conditions. The developed design maps and predictive equation empower researchers in designing, operating, and optimizing SALD systems, while offering a convenient way to screen deposition parameters, prior to experimentation.

Shape-memory effect in twisted ferroic nanocomposites.

The shape recovery ability of shape-memory alloys vanishes below a critical size (~50 nm), which prevents their practical applications at the nanoscale. In contrast, ferroic materials, even when scaled down to dimensions of a few nanometers, exhibit actuation strain through domain switching, though the generated strain is modest (~1%). Here, we develop freestanding twisted architectures of nanoscale ferroic oxides showing shape-memory effect with a giant recoverable strain (>8%). The twisted geometrical design amplifies the strain generated during ferroelectric domain switching, which cannot be achieved in bulk ceramics or substrate-bonded thin films. The twisted ferroic nanocomposites allow us to overcome the size limitations in traditional shape-memory alloys and open new avenues in engineering large-stroke shape-memory materials for small-scale actuating devices such as nanorobots and artificial muscle fibrils.

Covalent transfer of chemical gradients onto a graphenic surface with 2D and 3D control.

Control over the functionalization of graphenic materials is key to enable their full application in electronic and optical technologies. Covalent functionalization strategies have been proposed as an approach to tailor the interfaces' structure and properties. However, to date, none of the proposed methods allow for a covalent functionalization with control over the grafting density, layer thickness and/or morphology, which are key aspects for fine-tuning the processability and performance of graphenic materials. Here, we show that the no-slip boundary condition at the walls of a continuous flow microfluidic device offers a way to generate controlled chemical gradients onto a graphenic material with 2D and 3D control, a possibility that will allow the sophisticated functionalization of these technologically-relevant materials.

MoSBOTs: Magnetically Driven Biotemplated MoS2 -Based Microrobots for Biomedical Applications.

2D layered molybdenum disulfide (MoS2 ) nanomaterials are a promising platform for biomedical applications, particularly due to its high biocompatibility characteristics, mechanical and electrical properties, and flexible functionalization. Additionally, the bandgap of MoS2 can be engineered to absorb light over a wide range of wavelengths, which can then be transformed into local heat for applications in photothermal tissue ablation and regeneration. However, limitations such as poor stability of aqueous dispersions and low accumulation in affected tissues impair the full realization of MoS2 for biomedical applications. To overcome such challenges, herein, multifunctional MoS2 -based magnetic helical microrobots (MoSBOTs) using cyanobacterium Spirulina platensis are proposed as biotemplate for therapeutic and biorecognition applications. The cytocompatible microrobots combine remote magnetic navigation with MoS2 photothermal activity under near-infrared irradiation. The resulting photoabsorbent features of the MoSBOTs are exploited for targeted photothermal ablation of cancer cells and on-the-fly biorecognition in minimally invasive oncotherapy applications. The proposed multi-therapeutic MoSBOTs hold considerable potential for a myriad of cancer treatment and diagnostic-related applications, circumventing current challenges of ablative procedures.

Chirality transfer from a 3D macro shape to the molecular level by controlling asymmetric secondary flows.

Homochirality is a fundamental feature of living systems, and its origin is still an unsolved mystery. Previous investigations showed that external physical forces can bias a spontaneous symmetry breaking process towards deterministic enantioselection. But can the macroscopic shape of a reactor play a role in chiral symmetry breaking processes? Here we show an example of chirality transfer from the chiral shape of a 3D helical channel to the chirality of supramolecular aggregates, with the handedness of the helical channel dictating the direction of enantioselection in the assembly of an achiral molecule. By combining numerical simulations of fluid flow and mass transport with experimental data, we demonstrated that the chiral information is transferred top-down thanks to the interplay between the hydrodynamics of asymmetric secondary flows and the precise spatiotemporal control of reagent concentration fronts. This result shows the possibility of controlling enantioselectively molecular processes at the nanometer scale by modulating the geometry and the operating conditions of fluidic reactors.

Magnetoelectric Effect in Hydrogen Harvesting: Magnetic Field as a Trigger of Catalytic Reactions.

Magnetic fields have been regarded as an additional stimulus for electro- and photocatalytic reactions, but not as a direct trigger for catalytic processes. Multiferroic/magnetoelectric materials, whose electrical polarization and surface charges can be magnetically altered, are especially suitable for triggering and control of catalytic reactions solely with magnetic fields. Here, it is demonstrated that magnetic fields can be employed as an independent input energy source for hydrogen harvesting by means of the magnetoelectric effect. Composite multiferroic CoFe2 O4 -BiFeO3 core-shell nanoparticles act as catalysts for the hydrogen evolution reaction (HER), which is triggered when an alternating magnetic field is applied to an aqueous dispersion of the magnetoelectric nanocatalysts. Based on density functional calculations, it is proposed that the hydrogen evolution is driven by changes in the ferroelectric polarization direction of BiFeO3 caused by the magnetoelectric coupling. It is believed that the findings will open new avenues toward magnetically induced renewable energy harvesting.

Advanced technologies for the fabrication of MOF thin films.

Metal-organic framework (MOF) thin films represent a milestone in the development of future technological breakthroughs. The processability of MOFs as films on surfaces together with their major features (i.e. tunable porosity, large internal surface area, and high crystallinity) is broadening their range of applications to areas such as gas sensing, microelectronics, photovoltaics, and membrane-based separation technologies. Despite the recent attention that MOF thin films have received, many challenges still need to be addressed for their manufacturing and integrability, especially when an industrial scale-up perspective is envisioned. In this brief review, we introduce several appealing approaches that have been developed in the last few years. First, a summary of liquid phase strategies that comprise microfluidic methods and supersaturation-driven crystallization processes is described. Then, gas phase approaches based on atomic layer deposition (ALD) are also presented.

Room-Temperature Spin-Dependent Transport in Metalloporphyrin-Based Supramolecular Wires.

Here we present room-temperature spin-dependent charge transport measurements in single-molecule junctions made of metalloporphyrin-based supramolecular assemblies. They display large conductance switching for magnetoresistance in a single-molecule junction. The magnetoresistance depends acutely on the probed electron pathway through the supramolecular wire: those involving the metal center showed marked magnetoresistance effects as opposed to those exclusively involving the porphyrin ring which present nearly complete absence of spin-dependent charge transport. The molecular junction magnetoresistance is highly anisotropic, being observable when the magnetization of the ferromagnetic junction electrode is oriented along the main molecular junction axis, and almost suppressed when it is perpendicular. The key ingredients for the above effect to manifest are the electronic structure of the paramagnetic metalloporphyrin, and the spinterface created at the molecule-electrode contact.

Biodegradable Small-Scale Swimmers for Biomedical Applications.

Most forms of biomatter are ephemeral, which means they transform or deteriorate after a certain time. From this perspective, implantable healthcare devices designed for temporary treatments should exhibit the ability to degrade and either blend in with healthy tissues, or be cleared from the body with minimal disruption after accomplishing their designated tasks. This topic is currently being investigated in the field of biomedical micro- and nanoswimmers. These tiny devices have the ability to move through fluids by converting physical or chemical energy into motion. Several architectures of these devices have been designed to mimic the motion strategies of nature's motile microorganisms and cells. Due to their motion abilities, these devices have been proposed as minimally invasive tools for precision healthcare applications. Hence, a natural progression in this field is to produce motile structures that can adopt, or even surpass, similar transient features as biological systems. The fate of small-scale swimmers after accomplishing their therapeutic mission is critical for the successful translation of small-scale swimmers' technologies into clinical applications. In this review, recent research efforts are summarized on the topic of biodegradable micro- and nanoswimmers for biomedical applications, with a focus on targeted therapeutic delivery.

Piezoelectric Nanomaterials Activated by Ultrasound: The Pathway from Discovery to Future Clinical Adoption.

Electrical stimulation has shown great promise in biomedical applications, such as regenerative medicine, neuromodulation, and cancer treatment. Yet, the use of electrical end effectors such as electrodes requires connectors and batteries, which dramatically hamper the translation of electrical stimulation technologies in several scenarios. Piezoelectric nanomaterials can overcome the limitations of current electrical stimulation procedures as they can be wirelessly activated by external energy sources such as ultrasound. Wireless electrical stimulation mediated by piezoelectric nanoarchitectures constitutes an innovative paradigm enabling the induction of electrical cues within the body in a localized, wireless, and minimally invasive fashion. In this review, we highlight the fundamental mechanisms of acoustically mediated piezoelectric stimulation and its applications in the biomedical area. Yet, the adoption of this technology in a clinical practice is in its infancy, as several open issues, such as piezoelectric properties measurement, control of the ultrasound dose in vitro, modeling and measurement of the piezo effects, knowledge on the triggered bioeffects, therapy targeting, biocompatibility studies, and control of the ultrasound dose delivered in vivo, must be addressed. This article explores the current open challenges in piezoelectric stimulation and proposes strategies that may guide future research efforts in this field toward the translation of this technology to the clinical scene.