Magnetic/Acoustic Dual-Controlled Microrobot Overcoming Oto-Biological Barrier for On-Demand Multidrug Delivery against Hearing Loss.

Multidrug combination therapy in the inner ear faces diverse challenges due to the distinct physicochemical properties of drugs and the difficulties of overcoming the oto-biologic barrier. Although nanomedicine platforms offer potential solutions to multidrug delivery, the access of drugs to the inner ear remains limited. Micro/nanomachines, capable of delivering cargo actively, are promising tools for overcoming bio-barriers. Herein, a novel microrobot-based strategy to penetrate the round window membrane (RWM) is presented and multidrug in on-demand manner is delivered. The tube-type microrobot (TTMR) is constructed using the template-assisted layer-by-layer (LbL) assembly of chitosan/ferroferric oxide/silicon dioxide (CS/Fe3O4/SiO2) and loaded with anti-ototoxic drugs (curcumin, CUR and tanshinone IIA, TSA) and perfluorohexane (PFH). Fe3O4 provides magnetic actuation, while PFH ensures acoustic propulsion. Upon ultrasound stimulation, the vaporization of PFH enables a microshotgun-like behavior, propelling the drugs through barriers and driving them into the inner ear. Notably, the proportion of drugs entering the inner ear can be precisely controlled by varying the feeding ratios. Furthermore, in vivo studies demonstrate that the drug-loaded microrobot exhibits superior protective effects and excellent biosafety toward cisplatin (CDDP)-induced hearing loss. Overall, the microrobot-based strategy provides a promising direction for on-demand multidrug delivery for ear diseases.

Delivering Microrobots in the Musculoskeletal System.

Disorders of the musculoskeletal system are the major contributors to the global burden of disease and current treatments show limited efficacy. Patients often suffer chronic pain and might eventually have to undergo end-stage surgery. Therefore, future treatments should focus on early detection and intervention of regional lesions. Microrobots have been gradually used in organisms due to their advantages of intelligent, precise and minimally invasive targeted delivery. Through the combination of control and imaging systems, microrobots with good biosafety can be delivered to the desired area for treatment. In the musculoskeletal system, microrobots are mainly utilized to transport stem cells/drugs or to remove hazardous substances from the body. Compared to traditional biomaterial and tissue engineering strategies, active motion improves the efficiency and penetration of local targeting of cells/drugs. This review discusses the frontier applications of microrobotic systems in different tissues of the musculoskeletal system. We summarize the challenges and barriers that hinder clinical translation by evaluating the characteristics of different microrobots and finally point out the future direction of microrobots in the musculoskeletal system.

On the design of a macro-micro parallel manipulator for cochlear microrobot operations.

BACKGROUND: The method of stem cell transfer to narrow cochlear canals in vivo to generate hair cells is still an unclear operation. Thus, the development of any possible method that will ensure the usage of medical microrobots in small cochlear workspaces is a challenging procedure. METHODS: The current study tries to introduce a macro-micro manipulator system composed of a 6-DoF industrial serial manipulator as a macro manipulator and a proposed 5-DoF parallel manipulator with dual end effectors as a micro manipulator carrying permanent magnets for tetherless microrobot actuation inside the cochlea. RESULTS: Throughout the study, structural synthesis and kinematic analysis of the proposed micro manipulator were introduced. A prototype of the manipulator was manufactured and its hardware verification procedures were carried out using motion capture cameras and surgical navigation registration methodologies. CONCLUSIONS: Following motion training, the assembled macro-micro manipulator was successfully utilised to actuate a microrobot placed inside a manufactured cochlea mockup model.

Arbitrary Construction of Versatile NIR-Driven Microrobots.

Emerging light-driven micro/nanorobots (LMNRs) showcase profound potential for sophisticated manipulation and various applications. However, the realization of a versatile and straightforward fabrication technique remains a challenging pursuit. This study introduces an innovative bulk heterojunction organic semiconductor solar cell (OSC)-based spin-coating approach, aiming to facilitate the arbitrary construction of LMNRs. Leveraging the distinctive properties of a near-infrared (NIR)-responsive organic semiconductor heterojunction solution, this technique enables uniform coating across various dimensional structures (0D, 1D, 2D, 3D) to be LMNRs, denoted as "motorization." The film, with a slender profile measuring ≈140 nm in thickness, effectively preserves the original morphology of objects while imparting actuation capabilities exceeding hundreds of times their own weight. The propelled motion of these microrobots is realized through NIR-driven photoelectrochemical reaction-induced self-diffusiophoresis, showcasing a versatile array of controllable motion profiles. The strategic customization of arbitrary microrobot construction addresses specific applications, ranging from 0D microrobots inducing living crystal formation to intricate, multidimensional structures designed for tasks such as microplastic extraction, cargo delivery, and phototactic precise maneuvers. This study advances user-friendly and versatile LMNR technologies, unlocking new possibilities for various applications, signaling a transformative era in multifunctional micro/nanorobot technologies.

Modulating nanostructures with polyvinylpyrrolidone: Design and development of a porous, biocompatible, and pH-Stable core-shell magnetic microrobot for demonstrating drug absorption from wastewater.

Increased antineoplastic drug concentrations in wastewater stem from ineffective treatment plants and increased usage. Although microrobots are promising for pollutant removal, they face hurdles in developing a superstructure with superior adsorption capabilities, biocompatibility, porosity, and pH stability. This study focused on adjusting the PVP concentration from 0.05 to 0.375 mM during synthesis to create a favorable CMOC structure for drug absorption. Lower PVP concentrations (0.05 mM) yielded a three-dimensional nanoflower structure of CaMoO4 and CuS nanostructures, whereas five-fold concentrations (0.25 mM) produced a porous structure with a dense CuS core encased in a transparent CaMoO4 shell. The magnetically movable and pH-stable COF@CMOC microrobot, achieved by attaching CMOC to cobalt ferrite (CoF) NPs, captured doxorubicin efficiently, with up to 57 % efficiency at 200 ng/mL concentration for 30 min, facilitated by electrostatic interaction, hydrogen bonding, and pore filling of DOX. The results demonstrated that DOX removal through magnetic motion showed superior performance, with an estimated improvement of 57% compared to stirring conditions (17 %). A prototype PDMS microchannel system was developed to study drug absorption and microrobot recovery. The CaMoO4 shell of the microrobots exhibited remarkable robustness, ensuring long-lasting functionality in harsh wastewater environments and improving biocompatibility while safeguarding the CuS core from degradation. Therefore, microrobots are a promising eco-friendly solution for drug extraction. These microrobots show promise for the selective removal of doxorubicin from contaminated wastewater.

A red blood cell-derived bionic microrobot capable of hierarchically adapting to five critical stages in systemic drug delivery.

The tumour-targeting efficiency of systemically delivered chemodrugs largely dictates the therapeutic outcome of anticancer treatment. Major challenges lie in the complexity of diverse biological barriers that drug delivery systems must hierarchically overcome to reach their cellular/subcellular targets. Herein, an "all-in-one" red blood cell (RBC)-derived microrobot that can hierarchically adapt to five critical stages during systemic drug delivery, that is, circulation, accumulation, release, extravasation, and penetration, is developed. The microrobots behave like natural RBCs in blood circulation, due to their almost identical surface properties, but can be magnetically manipulated to accumulate at regions of interest such as tumours. Next, the microrobots are "immolated" under laser irradiation to release their therapeutic cargoes and, by generating heat, to enhance drug extravasation through vascular barriers. As a coloaded agent, pirfenidone (PFD) can inhibit the formation of extracellular matrix and increase the penetration depth of chemodrugs in the solid tumour. It is demonstrated that this system effectively suppresses both primary and metastatic tumours in mouse models without evident side effects, and may represent a new class of intelligent biomimicking robots for biomedical applications.

Design and control of jumping microrobots with torque reversal latches.

Jumping microrobots and insects power their impressive leaps through systems of springs and latches. Using springs and latches, rather than motors or muscles, as actuators to power jumps imposes new challenges on controlling the performance of the jump. In this paper, we show how tuning the motor and spring relative to one another in a torque reversal latch can lead to an ability to control jump output, producing either tuneable (variable) or stereotyped jumps. We develop and utilize a simple mathematical model to explore the underlying design, dynamics, and control of a torque reversal mechanism, provides the opportunity to achieve different outcomes through the interaction between geometry, spring properties, and motor voltage. We relate system design and control parameters to performance to guide the design of torque reversal mechanisms for either variable or stereotyped jump performance. We then build a small (356 mg) microrobot and characterize the constituent components (e.g. motor and spring). Through tuning the actuator and spring relative to the geometry of the torque reversal mechanism, we demonstrate that we can achieve jumping microrobots that both jump with different take-off velocities given the actuator input (variable jumping), and those that jump with nearly the same take-off velocity with actuator input (stereotyped jumping). The coupling between spring characteristics and geometry in this system has benefits for resource-limited microrobots, and our work highlights design combinations that have synergistic impacts on output, compared to others that constrain it. This work will guide new design principles for enabling control in resource-limited jumping microrobots.

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.

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. The study reports 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 health care facilities, aiding in the widespread adoption of magnetically responsive medical devices. First, the design and implementation approach for the system are introduced and its performance is characterized. Next, in vitro navigation of different microrobot structures is demonstrated 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. The navigation of magnetic catheters is also demonstrated 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.

Medical Microrobots.

Scientists around the world have long aimed to produce miniature robots that can be controlled inside the human body to aid doctors in identifying and treating diseases. Such microrobots hold the potential to access hard-to-reach areas of the body through the natural lumina. Wireless access has the potential to overcome drawbacks of systemic therapy, as well as to enable completely new minimally invasive procedures. The aim of this review is fourfold: first, to provide a collection of valuable anatomical and physiological information on the target working environments together with engineering tools for the design of medical microrobots; second, to provide a comprehensive updated survey of the technological state of the art in relevant classes of medical microrobots; third, to analyze currently available tracking and closed-loop control strategies compatible with the in-body environment; and fourth, to explore the challenges still in place, to steer and inspire future research.

Semiphysical Design Concept for Developing Miniaturized Microrobots In Vivo.

The miniaturization of biomedical microrobots is crucial for their in vivo applications. However, it is challenging to reduce their size while maintaining their biomedical functions. To resolve this contradiction, we propose a semiphysical design concept for developing miniaturized microrobots, in which invisible components such as light beams are utilized to replace most of the physical parts of a microrobot, thus minimizing its physical size without sacrificing its biomedical functions. According to this design, we have constructed a semiphysical microrobot (SPM) composed of main light beam, light-responsive microparticle, and auxiliary light beam, serving as the actuation system, recognition part, and surgical claws, respectively. Based on the functions of actuation, biosensing, and microsurgery, a SPM has been applied for a series of applications, including thrombus elimination at the branch vessel, stratified removal of multilayer thrombus, and biosensing-guided microsurgery. The proposed semiphysical design concept should bring new insight into the development of miniaturized biomedical microrobots.

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.

Metachronal Motion of Biological and Artificial Cilia.

Cilia are slender, hair-like cell protrusions that are present ubiquitously in the natural world. They perform essential functions, such as generating fluid flow, propulsion, and feeding, in organisms ranging from protozoa to the human body. The coordinated beating of cilia, which results in wavelike motions known as metachrony, has fascinated researchers for decades for its role in functions such as flow generation and mucus transport. Inspired by nature, researchers have explored diverse materials for the fabrication of artificial cilia and developed several methods to mimic the metachronal motion observed in their biological counterparts. In this review, we will introduce the different types of metachronal motion generated by both biological and artificial cilia, the latter including pneumatically, photonically, electrically, and magnetically driven artificial cilia. Furthermore, we review the possible applications of metachronal motion by artificial cilia, focusing on flow generation, transport of mucus, particles, and droplets, and microrobotic locomotion. The overall aim of this review is to offer a comprehensive overview of the metachronal motions exhibited by diverse artificial cilia and the corresponding practical implementations. Additionally, we identify the potential future directions within this field. These insights present an exciting opportunity for further advancements in this domain.

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.

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.

Light-Responsive Hydrogel Microcrawlers, Powered and Steered with Spatially Homogeneous Illumination.

Sub-millimeter untethered locomoting robots hold promise to radically change multiple areas of human activity such as microfabrication/assembly or health care. To overcome the associated hurdles of such a degree of robot miniaturization, radically new approaches are being adopted, often relying on soft actuating polymeric materials. Here, we present light-driven, crawling microrobots that locomote by a single degree of freedom actuation of their light-responsive tail section. The direction of locomotion is dictated by the robot body design and independent of the spatial modulation of the light stimuli, allowing simultaneous multidirectional motion of multiple robots. Moreover, we present a method for steering such robots by reversibly deforming their front section, using ultraviolet (UV) light as a trigger. The deformation dictates the robot locomotion, performing right- or left-hand turning when the UV is turned on or off respectively. The robots' motion and navigation are not coupled to the position of the light sources, which enables simultaneous locomotion of multiple robots, steering of robots and brings about flexibility with the methods to deliver the light to the place of robot operation.

Rechargeable Afterglow Nanotorches for In Vivo Tracing of Cell-Based Microrobots.

As one of the self-luminescence imaging approaches that require pre-illumination instead of real-time light excitation, afterglow luminescence imaging has attracted increasing enthusiasm to circumvent tissue autofluorescence. In this work, we developed organic afterglow luminescent nanoprobe (nanotorch), which could emit persistent luminescence more than 10 days upon single light excitation. More importantly, the nanotorch could be remote charged by 660 nm light in a non-invasive manner, which showed great potential for real-time tracing the location of macrophage cell-based microrobots.

MARSBot: A Bristle-Bot Microrobot with Augmented Reality Steering Control for Wireless Structural Health Monitoring.

Microrobots are effective for monitoring infrastructure in narrow spaces. However, they have limited computing power, and most of them are not wireless and stable enough for accessing infrastructure in difficult-to-reach areas. In this paper, we describe the fabrication of a microrobot with bristle-bot locomotion using a novel centrifugal yaw-steering control scheme. The microrobot operates in a network consisting of an augmented reality headset and an access point to monitor infrastructures using augmented reality (AR) haptic controllers for human-robot collaboration. For the development of the microrobot, the dynamics of bristle-bots in several conditions were studied, and multiple additive manufacturing processes were investigated to develop the most suitable prototype for structural health monitoring. Using the proposed network, visual data are sent in real time to a hub connected to an AR headset upon request, which can be utilized by the operator to monitor and make decisions in the field. This allows the operators wearing an AR headset to inspect the exterior of a structure with their eyes, while controlling the surveying robot to monitor the interior side of the structure.

Intelligent Navigation of a Magnetic Microrobot with Model-Free Deep Reinforcement Learning in a Real-World Environment.

Microrobotics has opened new horizons for various applications, especially in medicine. However, it also witnessed challenges in achieving maximum optimal performance. One key challenge is the intelligent, autonomous, and precise navigation control of microrobots in fluid environments. The intelligence and autonomy in microrobot control, without the need for prior knowledge of the entire system, can offer significant opportunities in scenarios where their models are unavailable. In this study, two control systems based on model-free deep reinforcement learning were implemented to control the movement of a disk-shaped magnetic microrobot in a real-world environment. The training and results of an off-policy SAC algorithm and an on-policy TRPO algorithm revealed that the microrobot successfully learned the optimal path to reach random target positions. During training, the TRPO exhibited a higher sample efficiency and greater stability. The TRPO and SAC showed 100% and 97.5% success rates in reaching the targets in the evaluation phase, respectively. These findings offer basic insights into achieving intelligent and autonomous navigation control for microrobots to advance their capabilities for various applications.

Novel Operation Mechanism and Multifunctional Applications of Bubble Microrobots.

Microrobots have emerged as powerful tools for manipulating particles, cells, and assembling biological tissue structures at the microscale. However, achieving precise and flexible operation of arbitrary-shaped microstructures in 3D space remains a challenge. In this study, three novel operation methods based on bubble microrobots are proposed to enable delicate and multifunctional manipulation of various microstructures. These methods include 3D turnover, fixed-point rotation, and 3D ejection. By harnessing the combined principles of the effect of the heat flow field and surface tension of an optothermally generated bubble, the bubble microrobot can perform tasks such as flipping an SIA humanoid structure, rotating a bird-like structure, and launching a hollow rocket-like structure. The proposed multi-mode operation of bubble microrobots enables diverse attitude adjustments of microstructures with different sizes and shapes in both 2D and 3D spaces. As a demonstration, a biological microenvironment of brain glioblastoma is constructed by the bubble microrobot. The simplicity, versatility, and flexibility of this proposed method hold great promise for applications in micromanipulation, assembly, and tissue engineering.