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.

Autonomous Magnetic Navigation in Endoscopic Image Mosaics.

Endoscopes navigate within the human body to observe anatomical structures with minimal invasiveness. A major shortcoming of their use is their narrow field-of-view during navigation in large, hollow anatomical regions. Mosaics of endoscopic images can provide surgeons with a map of the tool's environment. This would facilitate procedures, improve their efficiency, and potentially generate better patient outcomes. The emergence of magnetically steered endoscopes opens the way to safer procedures and creates an opportunity to provide robotic assistance both in the generation of the mosaic map and in navigation within this map. This paper proposes methods to autonomously navigate magnetic endoscopes to 1) generate endoscopic image mosaics and 2) use these mosaics as user interfaces to navigate throughout the explored area. These are the first strategies, which allow autonomous magnetic navigation in large, hollow organs during minimally invasive surgeries. The feasibility of these methods is demonstrated experimentally both in vitro and ex vivo in the context of the treatment of twin-to-twin transfusion syndrome. This minimally invasive procedure is performed in utero and necessitates coagulating shared vessels of twin fetuses on the placenta. A mosaic of the vasculature in combination with autonomous navigation has the potential to significantly facilitate this challenging surgery.

Remote magnetic navigation enables precision telesurgery.

Medical devices actuated by external magnetic fields can create opportunities for clinical adoption of precision telesurgery.

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.

Fast-Response Variable-Stiffness Magnetic Catheters for Minimally Invasive Surgery.

In minimally invasive surgery, such as cardiac ablation, magnetically steered catheters made of variable-stiffness materials can enable higher dexterity and higher force application to human tissue. However, the long transition time between soft and rigid states leads to a significant increase in procedure duration. Here, a fast-response, multisegmented catheter is described for minimally invasive surgery made of variable-stiffness thread (FRVST) that encapsulates a helical cooling channel. The rapid stiffness change in the FRVST, composed of a nontoxic shape memory polymer, is achieved by an active cooling system that pumps water through the helical channel. The FRVST displays a 66 times stiffness change and a 26 times transition enhancement compare with the noncooled version. The catheter allows for selective bending of each segment up to 127° in air and up to 76° in water under an 80 mT external magnetic field. The inner working channel can be used for cooling an ablation tip during a procedure and for information exchange via the deployment of wires or surgical tools.

Guiding bone cell network formation in 3D via photosensitized two-photon ablation.

A long-standing challenge in skeletal tissue engineering is to reconstruct a three-dimensionally (3D) interconnected bone cell network in vitro that mimics the native bone microarchitecture. While conventional hydrogels are extensively used in studying bone cell behavior in vitro, current techniques lack the precision to manipulate the complex pericellular environment found in bone. The goal of this study is to guide single bone cells to form a 3D network in vitro via photosensitized two-photon ablation of microchannels in gelatin methacryloyl (GelMA) hydrogels. A water-soluble two-photon photosensitizer (P2CK) was added to soft GelMA hydrogels to enhance the ablation efficiency. Remarkably, adding 0.5 mM P2CK reduced the energy dosage threshold five-fold compared to untreated controls, enabling more cell-compatible ablation. By employing low-energy ablation (100 J/cm2) with a grid pattern of 1 µm wide and 30 µm deep microchannels, we induced dendritic outgrowth in human mesenchymal stem cells (hMSC). After 7 days, the cells successfully utilized the microchannels and formed a 3D network. Our findings reveal that cellular viability after low-energy ablation was comparable to unablated controls, whereas high-energy ablation (500 J/cm2) resulted in 42 % cell death. Low-energy grid ablation significantly promoted network formation and >40 µm long protrusion outgrowth. While the broad-spectrum matrix metalloproteinase inhibitor (GM6001) reduced cell spreading by inhibiting matrix degradation, cells invaded the microchannel grid with long protrusions. Collectively, these results emphasize the potential of photosensitized two-photon hydrogel ablation as a high-precision tool for laser-guided biofabrication of 3D cellular networks in vitro. STATEMENT OF SIGNIFICANCE: The inaccessible nature of osteocyte networks in bones renders fundamental research on skeletal biology a major challenge. This limit is partly due to the lack of high-resolution tools that can manipulate the pericellular environment in 3D cultures in vitro. To create bone-like cellular networks, we employ a two-photon laser in combination with a two-photon sensitizer to erode microchannels with low laser dosages into GelMA hydrogels. By providing a grid of microchannels, the cells self-organized into a 3D interconnected network within days. Laser-guided formation of 3D networks from single cells at micron-scale resolution is demonstrated for the first time. In future, we envisage in vitro generation of bone cell networks with user-dictated morphologies for both fundamental and translational bone research.

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.

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.

Delivering drugs with microrobots.

Biomedical microrobots could overcome current challenges in targeted therapies.

Robotics and AI in the Global South.

An increasing presence of robotics and artificial intelligence in the Global South calls for responsible implementation.

Recent Developments in Metallic Degradable Micromotors for Biomedical and Environmental Remediation Applications.

Synthetic micromotor has gained substantial attention in biomedicine and environmental remediation. Metal-based degradable micromotor composed of magnesium (Mg), zinc (Zn), and iron (Fe) have promise due to their nontoxic fuel-free propulsion, favorable biocompatibility, and safe excretion of degradation products Recent advances in degradable metallic micromotor have shown their fast movement in complex biological media, efficient cargo delivery and favorable biocompatibility. A noteworthy number of degradable metal-based micromotors employ bubble propulsion, utilizing water as fuel to generate hydrogen bubbles. This novel feature has projected degradable metallic micromotors for active in vivo drug delivery applications. In addition, understanding the degradation mechanism of these micromotors is also a key parameter for their design and performance. Its propulsion efficiency and life span govern the overall performance of a degradable metallic micromotor. Here we review the design and recent advancements of metallic degradable micromotors. Furthermore, we describe the controlled degradation, efficient in vivo drug delivery, and built-in acid neutralization capabilities of degradable micromotors with versatile biomedical applications. Moreover, we discuss micromotors' efficacy in detecting and destroying environmental pollutants. Finally, we address the limitations and future research directions of degradable metallic micromotors.

Numerical Study of Metachronal Wave-Modulated Locomotion in Magnetic Cilia Carpets.

Metachronal motions are ubiquitous in terrestrial and aquatic organisms and have attracted substantial attention in engineering for their potential applications. Hard-magnetic soft materials are shown to provide new opportunities for metachronal wave-modulated robotic locomotion by multi-agent active morphing in response to external magnetic fields. However, the design and optimization of such magnetic soft robots can be complex, and the fabrication and magnetization processes are often delicate and time-consuming. Herein, a computational model is developed that integrates granular models into a magnetic-lattice model, both of which are implemented in the highly efficient parallel computing platform large-scale atomic/molecular massively parallel simulator (LAMMPS). The simulations accurately reproduce the deformation of single cilium, the metachronal wave motion of multiple cilia, and the crawling and rolling locomotion of magnetic cilia soft robots. Furthermore, the simulations provide insight into the spatial and temporal variation of friction forces and trajectories of cilia tips. The results contribute to the understanding of metachronal wave-modulated locomotion and potential applications in the field of soft robotics and biomimetic engineering. The developed model also provides a versatile computational framework for simulating the movement of magnetic soft robots in realistic environments and has the potential to guide the design, optimization, and customization of these systems.

Stimuli-Responsive Functional Micro-/Nanorobots: A Review.

Stimuli-responsive functional micro-/nanorobots (srFM/Ns) are a class of intelligent, efficient, and promising microrobots that can react to external stimuli (such as temperature, light, ultrasound, pH, ion, and magnetic field) and perform designated tasks. Through adaptive transformation into the corresponding functional forms, they can perfectly match the demands depending on different applications, which manifest extremely important roles in targeted therapy, biological detection, tissue engineering, and other fields. Promising as srFM/Ns can be, few reviews have focused on them. It is therefore necessary to provide an overview of the current development of these intelligent srFM/Ns to provide clear inspiration for further development of this field. Hence, this review summarizes the current advances of stimuli-responsive functional microrobots regarding their response mechanism, the achieved functions, and their applications to highlight the pros and cons of different stimuli. Finally, we emphasize the existing challenges of srFM/Ns and propose possible strategies to help accelerate the study of this field and promote srFM/Ns toward actual applications.

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.

Magnetically Enhanced Intracellular Uptake of Superparamagnetic Iron Oxide Nanoparticles for Antitumor Therapy.

Superparamagnetic iron oxide nanoparticles (SPIONs) have been widely employed in biomedical fields, including targeted delivery of antitumor therapy. Conventional magnetic tumor targeting has used simple static magnetic fields (SMFs), which cause SPIONs to linearly aggregate into a long chain-like shape. Such agglomeration greatly hinders the intracellular targeting of SPIONs into tumors, thus reducing the therapeutic efficacy. In this study, we investigated the enhancement of the intracellular uptake of SPIONs through the application of rotating magnetic fields (RMFs). Based on the physical principles of SPION chain disassembly, we investigated physical parameters to predict the chain length favorable for intracellular uptake. Our prediction was validated by clear visualization of the intracellular distributions of SPIONs in tumor cells at both cellular and three-dimensional microtissue levels. To identify the potential therapeutic effects of enhanced intracellular uptake, magnetic hyperthermia as antitumor therapy was investigated under varying conditions of magnetic hyperthermia and RMFs. The results showed that enhanced intracellular uptake reduced magnetic hyperthermia time and strength as well as particle concentration. The proposed method will be useful in the development of techniques to determine the optimized physical conditions for the enhanced intracellular uptake of SPIONs in antitumor therapy.

Technology matters, especially when deploying robots in the real world.

Making reliable robots that effectively operate in unstructured environments can be deceptively hard.

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.

Self-folding soft-robotic chains with reconfigurable shapes and functionalities.

Magnetic continuum soft robots can actively steer their tip under an external magnetic field, enabling them to effectively navigate in complex in vivo environments and perform minimally invasive interventions. However, the geometries and functionalities of these robotic tools are limited by the inner diameter of the supporting catheter as well as the natural orifices and access ports of the human body. Here, we present a class of magnetic soft-robotic chains (MaSoChains) that can self-fold into large assemblies with stable configurations using a combination of elastic and magnetic energies. By pushing and pulling the MaSoChain relative to its catheter sheath, repeated assembly and disassembly with programmable shapes and functions are achieved. MaSoChains are compatible with state-of-the-art magnetic navigation technologies and provide many desirable features and functions that are difficult to realize through existing surgical tools. This strategy can be further customized and implemented for a wide spectrum of tools for minimally invasive interventions.

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.

Fundamentals of Bowel Cancer for Biomedical Engineers.

Bowel cancer is a multifactorial disease arising from a combination of genetic predisposition and environmental factors. Detection of bowel cancer and its precursor lesions is predominantly performed by either visual inspection of the colonic mucosa during endoscopy or cross-sectional imaging. Most cases are diagnosed when the cancer is already at an advanced stage. These modalities are less reliable for detecting lesions at the earliest stages, when they are typically small or flat. Removal of lesions at the earliest possible stage reduces the risk of cancer death, which is largely due to a reduced risk of subsequent metastasis. In this review, we summarised the origin of bowel cancer and the mechanism of its metastasis. In particular, we reviewed a broad spectrum of literatures covering the biomechanics of bowel cancer and its measurement techniques that are pertinent to the successful development of a bowel cancer diagnostic device. We also reviewed existing bowel cancer diagnostic techniques that are available for clinical use. Finally, we outlined current clinical needs and highlighted the potential roles of medical robotics on early bowel cancer diagnosis.