Magnetic Microrobots Research Articles

Fillable Magnetic Microrobots for Drug Delivery to Cardiac Tissues In Vitro.

Many cardiac diseases, such as arrhythmia or cardiogenic shock, cause irregular beating patterns that must be regulated to prevent disease progression toward heart failure. Treatments can include invasive surgery or high systemic drug dosages, which lack precision, localization, and control. Drug delivery systems (DDSs) that can deliver cargo to the cardiac injury site could address these unmet clinical challenges. Here, a microrobotic DDS that can be mobilized to specific sites via magnetic control is presented. This DDS incorporates an internal chamber that can protect drug cargo. Furthermore, the DDS contains a tunable thermosensitive sealing layer that gradually degrades upon exposure to body temperature, enabling prolonged drug release. Once loaded with the small molecule drug norepinephrine, this microrobotic DDS modulated beating frequency in induced pluripotent stem-cell derived cardiomyocytes (iPSC-CMs) in a dose-dependent manner, thus simulating drug delivery to cardiac cells in vitro. The DDS also navigates several maze-like structures seeded with cardiomyocytes to demonstrate precise locomotion under a rotating low-intensity magnetic field and on-site drug delivery. This work demonstrates the utility of a magnetically actuating DDS for precise, localized, and controlled drug delivery which is of interest for a myriad of future opportunities such as in treating cardiac diseases.

Magnetic Microrobots for In Vivo Cargo Delivery: A Review.

Magnetic microrobots, with their small size and agile maneuverability, are well-suited for navigating the intricate and confined spaces within the human body. In vivo cargo delivery within the context of microrobotics involves the use of microrobots to transport and administer drugs and cells directly to the targeted regions within a living organism. The principal aim is to enhance the precision, efficiency, and safety of therapeutic interventions. Despite their potential, there is a shortage of comprehensive reviews on the use of magnetic microrobots for in vivo cargo delivery from both research and engineering perspectives, particularly those published after 2019. This review addresses this gap by disentangling recent advancements in magnetic microrobots for in vivo cargo delivery. It summarizes their actuation platforms, structural designs, cargo loading and release methods, tracking methods, navigation algorithms, and degradation and retrieval methods. Finally, it highlights potential research directions. This review aims to provide a comprehensive summary of the current landscape of magnetic microrobot technologies for in vivo cargo delivery. It highlights their present implementation methods, capabilities, and prospective research directions. The review also examines significant innovations and inherent challenges in biomedical applications.

Microrobotics in endodontics: A perspective.

Microorganisms are the primary aetiological factor of apical periodontitis. The goal of endodontic treatment is to prevent and eliminate the infection by removing the microorganisms. However, microbial biofilms and the complex root canal anatomy impair the disinfection process. Effective and precise endodontic therapy could potentially be achieved using advanced multifunctional technologies that have the ability to access hard-to-reach surfaces and perform simultaneous biofilm killing, removal, and detection of microorganisms. Advances in microrobotics are providing novel therapeutic and diagnostic opportunities with high precision and efficacy to address current biofilm-related challenges in biomedicine. Concurrently, multifunctional magnetic microrobots have been developed to overcome the disinfection challenges of current approaches to disrupt, kill, and retrieve biofilms with the goal of enhancing the efficacy and precision of endodontic therapy. This article reviews the recent advances of microrobotics in healthcare and particularly advances to overcome disinfection challenges in endodontics, and provides perspectives for future research in the field.

Simultaneous and Independent Control of Multiple Swimming Magnetic Microrobots by Stabilizer Microrobot

This paper presents a new strategy for simultaneous control of multiple magnetic Micro Robots (MRs) improving stability and robustness with respect to external disturbances. Independent control of multiple MRs, can enhance efficiency and allows for performing more challenging applications. In this study, we present a system consisting of a Helmholtz coil and 2N Permanent Magnets (PMs), rotated by servomotors, to control several MRs. We have also improved the system’s stability by adding a larger MR (stabilizer MR). This MR can be moved all around the workspace and works as a moving internal magnetic field source. Thanks to this moveable magnetic field, other MRs are more stable against environmental disturbances. By simulating simultaneous and independent control of multiple MRs, we demonstrate the advantages of using the stabilizer MR (more than 20 percent reduction in tracking error and control effort). In addition, we evaluate experimentally our proposed method to independently control the position of three MRs using a stabilizer MR demonstrating the efficacy of the strategy.

Magnetic Microrobot Swarms with Polymeric Hands Catching Bacteria and Microplastics in Water.

The forefront of micro- and nanorobot research involves the development of smart swimming micromachines emulating the complexity of natural systems, such as the swarming and collective behaviors typically observed in animals and microorganisms, for efficient task execution. This study introduces magnetically controlled microrobots that possess polymeric sequestrant "hands" decorating a magnetic core. Under the influence of external magnetic fields, the functionalized magnetic beads dynamically self-assemble from individual microparticles into well-defined rotating planes of diverse dimensions, allowing modulation of their propulsion speed, and exhibiting a collective motion. These mobile microrobotic swarms can actively capture free-swimming bacteria and dispersed microplastics "on-the-fly", thereby cleaning aquatic environments. Unlike conventional methods, these microrobots can be collected from the complex media and can release the captured contaminants in a second vessel in a controllable manner, that is, using ultrasound, offering a sustainable solution for repeated use in decontamination processes. Additionally, the residual water is subjected to UV irradiation to eliminate any remaining bacteria, providing a comprehensive cleaning solution. In summary, this study shows a swarming microrobot design for water decontamination processes.

A Selectively Controllable Triple-Helical Micromotor

Selective control mechanisms of microrobots have attracted significant attention from researchers. So far, selective control within multiple/swarm magnetic microrobots has been achieved with many strategies, such as utilizing locally specified magnetic fields, applying electrostatic anchoring, taking the advantages of geometry/wettability heterogeneity of the microrobots, etc. Using the step-out behavior of helical microrobots driven by a rotating magnetic field, researchers have proposed a mathematical model for multihelical motor that can be selectively controlled. Based on this model, we developed a micromotor that consists of three geometrically heterogeneous helices that can be selectively driven within a specific narrow frequency range. This type of micromotor shows bi-direction motion capability and has the potential to be used as an actuation unit for multiple types of functional micromechanisms.

Biohybrid Flexible Sperm-like Microrobot for Targeted Chemo-Photothermal Therapy.

Magnetic micro/nanorobots are promising platforms for targeted drug delivery, and their construction with soft and flexible features has received extensive attention for practical applications. Despite significant efforts in this field, facile fabrication of magnetic microrobots with flexible structures and versatility in targeted therapy remains a big challenge. Herein, we proposed a novel universal strategy to fabricate a biohybrid flexible sperm-like microrobot (BFSM) based on a Chlorella (Ch.) cell and artificial flagella, which showed great potential for targeted chemo-photothermal therapy for the first time. In this approach, microspherical Ch. cells were utilized to construct the microrobotic heads, which were intracellularly deposited with core-shell Pd@Au, extracellularly magnetized with Fe3O4, and further loaded with anticancer drug. The magnetic heads with excellent photothermal and chemotherapeutic capability were further assembled with flexible polypyrrole nanowires via biotin-streptavidin bonding to construct the BFSMs. Based on the exquisite head-to-tail structures, the BFSMs could be effectively propelled under precessing magnetic fields and move back and forth without a U-turn. Moreover, in vitro chemo-photothermal tests were conducted to verify their performance of targeted drug delivery toward localized HeLa cells. Due to this superior versatility and facile fabrication, the BFSMs demonstrated great potential for targeted anticancer therapy.

Design and Dynamics Modelling of a Novel Rotary Magnetic Microrobot

Design and Dynamics Modelling of a Novel Rotary Magnetic Microrobot

Magnetic multilayer hydrogel oral microrobots for digestive tract treatment.

Oral administration is a convenient drug delivery method in our daily lives. However, it remains a challenge to achieve precise target delivery and ensure the efficacy of medications in extreme environments within the digestive system with complex environments. This paper proposes an oral multilayer magnetic hydrogel microrobot for targeted delivery and on-demand release driven by a gradient magnetic field. The inner hydrogel shells enclose designated drugs and magnetic microparticles. The outer hydrogel shells enclose the inner hydrogel shells, magnetic microparticles, and pH neutralizers. The drug release procedure is remotely implemented layer-by-layer. When the required gradient magnetic field is applied, the outer hydrogel shells are destroyed to release their inclusions. The enclosed pH neutralizers scour the surrounding environment to avoid damaging drugs by the pH environment. Subsequently, the inner hydrogel shells are destroyed to release the drugs. A set of experiments are conducted to demonstrate the wirelessly controllable target delivery and release in a Petri dish and biological tissues. The results demonstrated attractive advantages of the reported microrobot in microcargo delivery with almost no loss, remote controllable release, and drug protection by the pH neutralizers. It is a promising approach to advance next-generation precision oral therapies in the digestive system.

Cross‐Scale Drug Delivery of Diatom Microrobots Based on A Magnetic Continuum Robot for Combined Chemical and Photodynamic Therapy of Glioblastoma

AbstractMicro/nanorobots with active movement capabilities provide a new option for the treatment of glioblastoma (GBM). However, the long working distance of intravenous injection and the protection of the blood‐brain barrier can prevent micro/nanorobots from reaching the target location. Photodynamic therapy (PDT) has gradually appeared in GBM treatment research. The limitation of the penetrating strength of the light source will nevertheless hinder the application range of PDT. Herein, a magnetic continuum robot (MCR) to deliver optical fibers and microrobots for combined chemotherapy and PDT of GBM is used. The prepared magnetic diatom microrobots can effectively move in biological fluids and move upstream. Vacuum loading can improve the drug loading efficiency. The photosensitizer in the frustule cavity can be explosively released in a short time through ultrasound. The chemotherapeutic drugs have long‐term and pH‐sensitivity release characteristics. In vitro cell experiments showed that the combined administration of TMZ‐loaded microrobots and photosensitizer‐loaded microrobots has a synergistic effect. The in vitro model demonstrated that an MCR can deliver an optical fiber and drug‐loaded microrobots. This enables cross‐scale delivery of microrobots and deep PDT. This delivery method may expand the drug selectivity for GBM treatment and provide a new possibility for intracranial PDT.

Magnetic Microrobot Spin Motility Characterization Using a Model Prediction Adaptive Control-Enhanced Electromagnetic Coil System

Magnetic microrobots (MMs) have been receiving tremendous attention due to their advantages of untethered controllability and bio-compatibility, and they have been shown to be promising tools for targeted therapy. Ahead of implementations, one of the most vital motion properties of the MMs, i.e. the fundamental spin motility, should be characterized for better utilization. To fulfill the precise characterization of MMs, it is of great value to develop an electromagnetic field generator with high accuracy. One electromagnetic field generator usually equips its coils with iron cores to enhance the generated magnetic field (MF) strength, which may also bring in unwanted nonlinear and temperature-dependent dynamic properties. The complex properties usually make the coils hard to control to maintain consistent good performances. To generate a desirable MF under varying temperature conditions, this study develops a model prediction adaptive control (MPAC) approach to regulate the coil system adaptively. Validation tests show that, compared with the prevalent MPC method, the MPAC approach can generate a more accurate MF at different ambient temperatures. As an application, the MPAC-controlled MF generator is utilized to characterize the MM's spin motility, and a nonlinear dynamic model is established, which can properly describe the MM's spin behavior under various excitation conditions.

A Untethered Magnetic Micro-Robot for Local Therapeutic Delivery for Neurosurgical Oncology

INTRODUCTION: Microrobots designed for biomedical applications have garnered significant research interest, offering advantages in drug delivery, microsurgery, and biopsies. Magnetic fields enabled by electromagnetic coils permit untethered nonlinear movement of these tiny robots within the brain on the surface, the cerebrospinal fluid, and parenchyma. Microdrillers (either individually or in swarms) are a promising tool for microsurgery, capable of drilling through viscoelastic media (brain tissue). However, challenges remain in scaling down the robot size and exploring diverse applications. METHODS: Parallelizable (batch) microfabrication involved 3D printing via two-photon lithography. The pH-sensitive hydrogel was synthesized through UV-initiated radical polymerization mixed with a tracer (fluorescein sodium salt). Imaging via photon-counting CT was performed for microbot tracking in preclinical models including hydrogel phantoms, large animal cadaveric fresh brain tissue, and human cadaveric tissue. RESULTS: Microbot speeds in various tissues were characterized with speeds up to 800 um/sec over magnetic field amplitudes of 5 to 55 mT while performing complex nonlinear trajectories via open-loop surgeon control via surgeon. Targeted hydrogel delivery of fluorescein label/nanoparticle drug over a pH range of 6.2 (tumor tissue) and 7.8 (normal tissue) over a time interval of 50 s is demonstrated as proof of concept with a rate of 2.4 times faster in acidic conditions. Lastly, we show state-of-the-art micromillmetric resolution for real time imaging via photon-counting spectral CT for implementation of closed loop control. CONCLUSIONS: A novel minimally invasive microrobotic platform technology capable of targeted local drug delivery in brain parenchyma is demonstrated.

A Survey of Recent Developments in Magnetic Microrobots for Micro-/Nano-Manipulation.

Magnetically actuated microrobots have become a research hotspot in recent years due to their tiny size, untethered control, and rapid response capability. Moreover, an increasing number of researchers are applying them for micro-/nano-manipulation in the biomedical field. This survey provides a comprehensive overview of the recent developments in magnetic microrobots, focusing on materials, propulsion mechanisms, design strategies, fabrication techniques, and diverse micro-/nano-manipulation applications. The exploration of magnetic materials, biosafety considerations, and propulsion methods serves as a foundation for the diverse designs discussed in this review. The paper delves into the design categories, encompassing helical, surface, ciliary, scaffold, and biohybrid microrobots, with each demonstrating unique capabilities. Furthermore, various fabrication techniques, including direct laser writing, glancing angle deposition, biotemplating synthesis, template-assisted electrochemical deposition, and magnetic self-assembly, are examined owing to their contributions to the realization of magnetic microrobots. The potential impact of magnetic microrobots across multidisciplinary domains is presented through various application areas, such as drug delivery, minimally invasive surgery, cell manipulation, and environmental remediation. This review highlights a comprehensive summary of the current challenges, hurdles to overcome, and future directions in magnetic microrobot research across different fields.

Control of Self-Winding Microrobot Using an Electromagnetic Drive System: Integration of Movable Electromagnetic Coil and Permanent Magnet.

Achieving precise control over the motion position and attitude direction of magnetic microrobots remains a challenging task in the realm of microrobotics. To address this challenge, our research team has successfully implemented synchronized control of a microrobot's motion position and attitude direction through the integration of electromagnetic coils and permanent magnets. The whole drive system consists of two components. Firstly, a stepper motor propels the delta structure, altering the position of the end-mounted permanent magnet to induce microrobot movement. Secondly, a programmable DC power supply regulates the current strength in the electromagnetic coil, thereby manipulating the magnetic field direction at the end and influencing the permanent magnet's attitude, guiding the microrobot in attitude adjustments. The microrobot used for performance testing in this study was fabricated by blending E-dent400 photosensitive resin and NdFeB particles, employing a Single-Layer 4D Printing System Using Focused Light. To address the microrobot drive system's capabilities, experiments were conducted in a two-dimensional and three-dimensional track, simulating the morphology of human liver veins. The microrobot exhibited an average speed of 1.3 mm/s (movement error ± 0.5 mm). Experimental results validated the drive system's ability to achieve more precise control over the microrobot's movement position and attitude rotation. The outcomes of this study offer valuable insights for future electromagnetic drive designs and the application of microrobots in the medical field.

Programming self-assembling magnetic microrobots with multiple physical and chemical intelligence

Medical microrobots represent the cutting-edge of biomedical research, showcasing their potential as versatile tools. They exhibit promise in acting as carriers for cancer cell therapy, effectively delivering drugs, and as manipulators equipped for biosensing, offering mobility and adaptability. Despite these advancements, the intricate challenge of creating a microrobot that seamlessly integrates various physical and chemical functionalities persists. This includes the fusion of selective sensing, manipulation capabilities, carrier functionality, precise time-based actuators for motion control, and adaptive shaping. Addressing these complexities remains an ongoing endeavor. In this context, our work introduces a pioneering magnetic microrobot founded on CaCO3 microparticles (MPs) synthesized alongside polyethylenimine (CaCO3-PEI), forming the core body. This is combined with Fe3O4 nanoparticles (NPs) enveloped in glutaraldehyde (Fe3O4-Glu), constituting the propulsive engine. The synergy of these elements enables the microrobot to execute multimodal motions, orchestrating its movement with finesse. This dynamic capability follows a “deliver-and-return” pattern for precise targeting applications with real-world relevance. Furthermore, the Fe3O4-Glu/CaCO3-PEI microrobots demonstrated remarkable proficiency in the targeted identification, manipulation, and transportation of cancer cells through the strategic integration of specific antibodies onto their structure. Within the realm of selective cancer cell detection, these microrobots adeptly function as dynamic mobile immunosensors. The versatile utility of the Fe3O4-Glu/CaCO3-PEI microrobots extends to their role as carriers for drugs and imaging agents, facilitated by the mediation of extracellular pH modulation in cancer cells orchestrated by CaCO3. This innovative work introduces a novel “on-the-fly” concept, revolutionizing the landscape of robotics programmed with multifaceted chemical and physical intelligences.

Selective-collective scalable locomotion control of helical magnetic swimmers within confined channels using global magnetic fields

Achieving selective-individual and collective control over multiple magnetic microrobots remains a formidable challenge. Existing techniques for controlling identical magnetic swimmers are often limited to two-dimensional, small working spaces, while heterogeneous swimmers can only be controlled in small numbers without the option for collective control. In this study, we present a purely magnetic control methodology for the selective-scalable locomotion of helical magnetic swimmers within confined channels. By employing a unique gradient field distribution, referred to as the "selection field," along with space-uniform rotating fields, we establish a "selection volume" that allows swimmers within it to fully rotate, while those outside remain stationary. We explore various conditions of the selection volume to analyze the locomotion dynamics of the swimmers in relation to the position of the selection volume. Experimental results demonstrate the selective-scalable locomotion of identical robots, ranging from one to an arbitrary number (N) of robots, as well as their selective-individual manipulation for multitasking applications. Furthermore, compatibility of the proposed method with different magnetic torque-driven robots is exemplified through the selective control of rolling robots. Moreover, three-dimensional selective-scalable control is also demonstrated for four swimmers in a quasi-three-dimensional channel, as well as for two swimmers within a true three-dimensional channel.

Spatially selective delivery of living magnetic microrobots through torque-focusing

Rotating magnetic fields enable biomedical microrobots to overcome physiological barriers and promote extravasation and accumulation in tumors. Nevertheless, targeting deeply situated tumors requires suppression of off-target actuation in healthy tissue. Here, we investigate a control strategy for applying spatially selective torque density to microrobots by combining rotating fields with magnetostatic selection fields. Taking magnetotactic bacteria as diffuse torque-based actuators, we numerically model off-target torque suppression, indicating the feasibility of centimeter to millimeter resolution for human applications. We study focal torque application in vitro, observing off-target suppression of actuation-dependent effects such as colonization of bacteria in tumor spheroids. We then design and construct a mouse-scale torque-focusing apparatus capable of maneuvering the focal point. Applying this system to a mouse tumor model increased accumulation of intravenously injected bacteria within tumors receiving focused actuation compared to non-actuated or globally actuated groups. This control scheme combines the advantages of torque-based actuation with spatial targeting.

Virtual Reality‐Enabled Intuitive Magnetic Manipulation of Microrobots and Nanoparticles

Magnetic microrobots and nanoparticles offer unique capabilities for medical applications by granting unprecedented access to intricate and delicate anatomical structures. Nevertheless, an intuitive manipulation approach remains a challenge due to their small size and limited feedback. This study presents a new method for magnetic microrobot and nanoparticle control that employs virtual reality (VR), creating an immersive and realistic view of the bodily anatomy and the microrobot within. This study compares three manipulation modes: a traditional mode using 2D displays, VR mode using a VR headset and touch controllers, and VR autonomous programmed maneuvering. It is shown that VR‐assisted modes reduce the manipulation time by improving spatial awareness. Nanoparticles in a VR environment are also manipulated. The proposed method will find applications in terms of intuitive, immersive microrobots or magnetic nanoparticle control in complex biological environments, thus in many medical procedures and for drug and cell delivery. The immersive nature of this approach enhances the ability of the user to perceive and understand complex anatomical structures, facilitating better navigation within delicate environments; both dexterity and spatial awareness are improved. Thus, it is shown how microrobots and magnetic nanoparticles can be controlled using immersive simulations to improve both visualization and manipulation.

Multi-physics coupling simulation and design of magnetic field-driven soft microrobots in liquid environments

Magnetic field-driven soft microrobots have widespread applications in biomedical science, microfluidic chips, nanoengineering, and various other domains. However, the existing methods for designing such magnetic-driven flexible robots largely rely on experimental trial and error or steady-state numerical simulated results, which fall short of meeting the intricate requirements for magnetic field editing and magnetic domain distribution. Addressing this issue, a multi-physics coupling numerical analysis method encompassing Magnetic-Fluid-Solid mechanics was developed. A complete process for transient numerical simulation resolution has been achieved. Utilizing this analysis method, the motion patterns of two typical prototypes of magnetic-driven miniature soft bionic robots, a bionic midge larvae robot, and a bionic jellyfish robot, have been analyzed. The central role of the magnetic field in driving these robotic designs—causing deformation in microrobots by designing magnetic domains and spinning the microrobots by controlling the magnetic field—has been revealed. We developed a theoretical model of a bionic fish tail fin robot driven solely by a rotating magnetic field and conducted comparative studies on the swimming efficiency, flexibility, stability, and relative advantages of the three types of robots. The impact of different magnetic domain distribution rules and different magnetic field driving methods on a robot's performance is analyzed, validating that higher swimming efficiency can be achieved by designing a robot's magnetic domains so that they undergo magnetic displacement under magnetic torque resulting in deformation. This innovative analysis method holds potential to provide valuable references for designing motion patterns of magnetically driven microrobots within liquid environments, thereby deepening our understanding toward various complex gait mechanisms involved in biological swimming.

Human-scale navigation of magnetic microrobots in hepatic arteries.

Using external actuation sources to navigate untethered drug-eluting microrobots in the bloodstream offers great promise in improving the selectivity of drug delivery, especially in oncology, but the current field forces are difficult to maintain with enough strength inside the human body (>70-centimeter-diameter range) to achieve this operation. Here, we present an algorithm to predict the optimal patient position with respect to gravity during endovascular microrobot navigation. Magnetic resonance navigation, using magnetic field gradients in clinical magnetic resonance imaging (MRI), is combined with the algorithm to improve the targeting efficiency of magnetic microrobots (MMRs). Using a dedicated microparticle injector, a high-precision MRI-compatible balloon inflation system, and a clinical MRI, MMRs were successfully steered into targeted lobes via the hepatic arteries of living pigs. The distribution ratio of the microrobots (roughly 2000 MMRs per pig) in the right liver lobe increased from 47.7 to 86.4% and increased in the left lobe from 52.2 to 84.1%. After passing through multiple vascular bifurcations, the number of MMRs reaching four different target liver lobes had a 1.7- to 2.6-fold increase in the navigation groups compared with the control group. Performing simulations on 19 patients with hepatocellular carcinoma (HCC) demonstrated that the proposed technique can meet the need for hepatic embolization in patients with HCC. Our technology offers selectable direction for actuator-based navigation of microrobots at the human scale.