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.

3D printed ultra-fast photothermal responsive shape memory hydrogel for microrobots

Hydrogels with stimuli-responsive capabilities are gaining more and more attention nowadays with prospective applications in biomedical engineering,bioelectronics,microrobot,etc.We develop a photothermal responsive hydrogel based on N-isopropylacrylamide that achieved a fast and reversible deformation manipulated only by near-infrared(NIR)light.The hydrogel was fabricated by the projection micro stereolithography based 3D printing technique,which can rapidly prototype complex 3D structures.Furthermore,with the variation of the grayscale while manufacturing the hydrogel,the deformation of the hydrogel structure can be freely tuned within a few seconds by losing and absorbing water through adjusting the intensity and the irradiation direction of the NIR light,showing a potential application in ultra-fast object grabbing and transportation.The present study provides a new method for designing ultrafast photothermal responsive hydrogel based microrobot working in water.

Development of ICPF Actuated Underwater Microrobots

It is our target to develop underwater microrobots for medical and industrial applications. This kind of underwater microrobots should have the characteristics of flexibility, good response and safety. Its structure should be simple and it can be driven by low voltage and produces no pollution or noise. The low actuating voltage and quick bending responses of Ionic Conducting Polymer Film （ICPF） are considered very useful and attractive for constructing various types of actuators and sensors. In this paper, we will first study the characteristics of the ICPF actuator used in underwater microrobot to realize swimming and walking. Then, we propose a new prototype model of underwater swimming microrobot utilizing only one piece of ICPF as the servo actuator. Through theoretic analysis, the motion mechanism of the microrobot is illustrated. It can swim forward and vertically. The relationships between moving speed and signal voltage amplitude and signal frequency is obtained after experimental study. Lastly, we present a novel underwater crab-like walking microrobot named crabliker-1. It has eight legs, and each leg is made up of two pieces of ICPF. Three sample processes of the octopod gait are proposed with a new analyzing method. The experimental results indicate that the crab-like underwater microrobot can perform transverse and rotation movement when the legs of the crab collaborate.

Autonomous docking based on infrared sensors for mobile self-reconfigurable relay microrobots

A simple autonomous docking method based on infrared sensors for mobile self-reconfigurable relay microrobots is proposed in the paper.The IR guidance system composed of an IR receiver and four IR emitters is designed,analyzed and developed.The autonomous docking control method based on centering alignment and dynamic motion planning is adopted so that it has high efficiency and reliability.Two basic microrobot prototypes are developed,and related docking experiments are done to verify the feasibility of the approach.

Two-photon polymerization-based 4D printing and its applications

Two-photon polymerization(TPP)is a cutting-edge micro/nanoscale three-dimensional(3D)printing technology based on the principle of two-photon absorption.TPP surpasses the diffraction limit in achieving feature sizes and excels in fabricating intricate 3D micro/nanostructures with exceptional resolution.The concept of 4D entails the fabrication of structures utilizing smart materials capable of undergoing shape,property,or functional changes in response to external stimuli over time.The integration of TPP and 4D printing introduces the possibility of producing responsive structures with micro/nanoscale accuracy,thereby enhancing the capabilities and potential applications of both technologies.This paper comprehensively reviews TPP-based 4D printing technology and its diverse applications.First,the working principles of TPP and its recent advancements are introduced.Second,the optional4D printing materials suitable for fabrication with TPP are discussed.Finally,this review paper highlights several noteworthy applications of TPP-based 4D printing,including domains such as biomedical microrobots,bioinspired microactuators,autonomous mobile microrobots,transformable devices and robots,as well as anti-counterfeiting microdevices.In conclusion,this paper provides valuable insights into the current status and future prospects of TPP-based4D printing technology,thereby serving as a guide for researchers and practitioners.

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.

Controllable Histotomy Based on Hierarchical Magnetic Microneedle Array Robots

Investigation of patient-derived primary tissues is of great importance in the biomedical field,but recent tissue slicing and cultivation techniques still have difficulties in satisfying clinical requirements.Here,we propose a controllable histotomy strategy that utilizes hierarchical magnetic microneedle array robots to tailor primary tissues and establish the desired high-throughput tissue-on-a-chip.This histotomy is performed using a three-dimensional printed,mortise-tenon-structured slicing device coupled with a magnetic-particle-loaded and pagoda-shaped microneedle array scaffold.Due to the multilayered struc-ture of these microneedles,tissue specimens can be fixed onto the microneedle scaffold via mechanical interlocking,thereby effectively avoiding tissue slipping during the slicing process.Owing to the encapsu-lation of magnetic microneedle fragments,these tissue pieces can act as magnetically responsive biohybrid microrobots and can be easily manipulated by magnetic fields,facilitating their separation,transportation,and dynamic culture.Using this strategy,we demonstrate that primary pancreatic cancer tissues can be tailored into tiny pieces and cultured in multilayered microfluidic chips for efficient high-throughput drug screening,indicating the promising future of this technique’s application in clinical settings.

Complex dynamics of a magnetic microrobot driven by single deformation soft tail in random environment

This study focuses on exploring the complex dynamical behaviors of a magnetic microrobot in a random environment.The purpose is to reveal the mechanism of influence of random disturbance on microrobot dynamics.This paper establishes stochastic dynamic models for the microrobot before and after deformation,considering the influence of Gaussian white noise.The system responses are analyzed via steady-state probability density functions and first deformation time.The effects of different magnetic field strengths and fluid viscosities on the movement speed and angular velocity of the microrobot are studied.The results indicate that random disturbances can cause deformation of microrobots in advance compared to the deterministic case.This work contributes to the design and motion control of microrobots and enhances the theoretical foundation of microrobots.

Propulsion Modeling and Analysis of a Biomimetic Swimmer

We have studied a biomimetic swimmer based on the motion of bacteria such as Escherichia coli (E. coli) theoretically andexperimentally. The swimmer has an ellipsoidal cell body propelled by a helical filament. The performance of this swimmer wasestimated by modeling the dynamics of a swimmer in viscous fluid. We applied the Resistive Force Theory (RFT) on this modelto calculate the linear swimming speed and the efficiency of the model. A parametric study on linear velocity and efficiency tooptimize the design of this swimmer was demonstrated. In order to validate the theoretical results, a biomimetic swimmer wasfabricated and an experiment setup was prepared to measure the swimming speed and thrust force in silicone oil. The experimentalresults agree well with the theoretical values predicted by RFT. In addition, we studied the flow patterns surrounding thefilament with a finite element simulation with different Reynolds number (Re) to understand the mechanism of propulsion. Thesimulation results provide information on the nature of flow patterns generated by swimming filament. Furthermore, the thrustforces from the simulation were compared with the thrust forces from theory. The simulation results are in good agreement withthe theoretical results.

A New Type of Hybrid Fish-like Microrobot

In order to develop a new type of fish-like microrobot with swimming, walking, and floating motions, in our past research, we developed a hybrid microrobot actuated by ionic conducting polymer film （ICPF） actuators. But the microrobot had some problems in walking and floating motions. In this paper, we propose a concept of hybrid microrobot （see Fig. 1）. The microrobot is actuated by a pair of caudal fins, a base with legs and an array of artificial swim bladders. We have developed a prototype of the base with legs and one artificial swim bladder, respectively, and carried out experiments for evaluating their characteristics. Experimental results show the base with legs can realize walking speed of 6 mm/s and rotating speed of 7.1 degrees/s respectively, and the prototype of the artificial swim bladder has a maximum floatage of 2.6 mN. The experimental results also indicate that the microrobot has some advantages, such as walking motion with 2 degrees of freedom, the walking ability on rough surface （sand paper）, the controllable floatage, etc. This kind of fish-like microrobot is expected for industrial and medical applications.

NOTES-Natural orifice transluminal endoscopic surgery:Why not?

Since natural orifice transluminal endoscopic surgery(NOTES) was first described by Anthony Kalloo,it has attracted tremendous interest from surgeons and gastroenterologist all around the world.This special issue of the World Journal of Gastrointestinal Surgery explores the current possibilities and future potential of the most disruptive revolution in the field of surgery represented by the NOTES approach.In the future,new technologies developed for this approach and deeper insight into several gastrointestinal diseases will lead to the design of completely new interven tional procedures and change the way we will operate,bringing us to the previously unimaginable goal of "no scar surgery".

A Novel Design on Carrier Mechanism of Micro Inspection Robot within 20mm Pipes

This paper describes a novel design for the carrier mechanism of a pipe-inspection micro robot Based on this mechanism, a new micro robot for the pipes with diameter of 20mm has been developed. It can travel through both vertical pipes and curved pipes to make possible inspection that would be difficult with conventional endoscopes. This mechanism is composed of three units, two novel micro mechanisms called as a planetary wheel mechanism for robot drive, two micro electromagnetic motors and a flexible coupler.

Vibration-Driven Microrobot Positioning Methodologies for Nonholonomic Constraint Compensation

This paper presents the formulation and practical implementation of positioning methodologies that compensate for the nonholonomic constraints of a mobile microrobot that is driven by two vibrating direct current(DC) micromotors. The open-loop and closed-loop approaches described here add the capability for net sidewise displacements of the microrobotic platform. A displacement is achieved by the execution of a number of repeating steps that depend on the desired displacement, the speed of the micromotors, and the elapsed time. Simulation and experimental results verified the performance of the proposed methodologies.

Hypothesis of design of biological cell robot as human immunodeficiency virus vaccine

High genetic variability of human immunodeficiency virus(HIV)has been a major intractable challenge to the practical design of vaccines.But a recent pioneer study published in PNAS Xenobots,is likely to revolutionize HIV prevention as it presented the world's first living robot made of cells.In the advent of this discovery,we herein discuss the possibility of using living biological cell robots to target HIV-infected T lymphocytes,and the prospects of this approach being a new HIV vaccine.We capture the current research status and trend of advances in biological cell robots'design as a new HIV vaccine.The key differences between this novel vaccine and other HIV vaccines are highlighted.

Oral administration microrobots for drug delivery

Oral administration is the most simple, noninvasive, convenient treatment. With the increasing demands on thetargeted drug delivery, the traditional oral treatment now is facing some challenges: 1) biologics how toimplement the oral treatment and ensure the bioavailability is not lower than the subcutaneous injections;2)How to achieve targeted therapy of some drugs in the gastrointestinal tract? Based on these two issues, drugdelivery microrobots have shown great application prospect in oral drug delivery due to their characteristics offlexible locomotion or driven ability. Therefore, this paper summarizes various drug delivery microrobotsdeveloped in recent years and divides them into four categories according to different driving modes: magneticcontrolleddrug delivery microrobots, anchored drug delivery microrobots, self-propelled drug delivery microrobotsand biohybrid drug delivery microrobots. As oral drug delivery microrobots involve disciplines such asmaterials science, mechanical engineering, medicine, and control systems, this paper begins by introducing thegastrointestinal barriers that oral drug delivery must overcome. Subsequently, it provides an overview of typicalmaterials involved in the design process of oral drug delivery microrobots. To enhance readers’ understanding ofthe working principles and design process of oral drug delivery microrobots, we present a guideline for designingsuch microrobots. Furthermore, the current development status of various types of oral drug delivery microrobotsis reviewed, summarizing their respective advantages and limitations. Finally, considering the significantconcerns regarding safety and clinical translation, we discuss the challenges and prospections of clinical translationfor various oral drug delivery microrobots presented in this paper, providing corresponding suggestions foraddressing some existing challenges.

Application of magnetotactic bacteria as engineering microrobots:Higher delivery efficiency of antitumor medicine

For a significant duration,enhancing the efficacy of cancer therapy has remained a critical concern.Magnetotactic bacteria(MTB),often likened to micro-robots,hold substantial promise as a drug delivery system.MTB,classified as anaerobic,aquatic,and gram-negative microorganisms,exhibit remarkable motility and precise control over their internal biomineralization processes.This unique ability results in the formation of magnetic nanoparticles arranged along filamentous structures in a catenary fashion,enclosed within a membrane.These bacteria possess distinctive biochemical properties that facilitate their precise positioning within complex environments.By harnessing these biochemical attributes,MTB could potentially offer substantial advantages in the realm of cancer therapy.This article reviews the drug delivery capabilities of MTB in tumor treatment and explores various applications based on their inherent properties.The objective is to provide a comprehensive understanding of MTB-driven drug delivery and stimulate innovative insights in this field.

Review of photoacoustic imaging for microrobots tracking in vivo [Invited]

Microrobots-assisted drug delivery and surgery have been always in the spotlight and are highly anticipated to solve the challenges of cancer in situ treatment. These versatile small biomedical robots are expected to realize direct access to the tumor or disease site for precise treatment, which requires real-time and high-resolution in vivo tracking as feedback for the microrobots’ actuation and control. Among current biomedical imaging methods, photoacoustic imaging(PAI) is presenting its outstanding performances in the tracking of microrobots in the human body derived from its great advantages of excellent imaging resolution and contrast in deep tissue. In this review, we summarize the PAI techniques, imaging systems, and their biomedical applications in microrobots tracking in vitro and in vivo. From a robotic tracking perspective,we also provide some insight into the future of PAI technology in clinical applications.

Magnetic systems for cancer immunotherapy

Immunotherapy is a rapidly developing area of cancer treatment due to its higher specificity and potential for greater efficacy than traditional therapies.Immune cell modulation through the administration of drugs,proteins,and cells can enhance antitumoral responses through pathways that may be otherwise inhibited in the presence of immunosuppressive tumors.Magnetic systems offer several advantages for improving the performance of immunotherapies,including increased spatiotemporal control over transport,release,and dosing of immunomodulatory drugs within the body,resulting in reduced off-target effects and improved efficacy.Compared to alternative methods for stimulating drug release such as light and pH,magnetic systems enable several distinct methods for programming immune responses.First,we discuss how magnetic hyperthermia can stimulate immune cells and trigger thermoresponsive drug release.Second,we summarize how magnetically targeted delivery of drug carriers can increase the accumulation of drugs in target sites.Third,we review how biomaterials can undergo magnetically driven structural changes to enable remote release of encapsulated drugs.Fourth,we describe the use of magnetic particles for targeted interactions with cellular receptors for promoting antitumor activity.Finally,we discuss translational considerations of these systems,such as toxicity,clinical compatibility,and future opportunities for improving cancer treatment.

Micro Manipulation Using Magnetic Microrobots

When developing microscale robotic systems it is desired that they are capable of performing microscale tasks such as small scale manipulation and transport. In this paper, we demonstrate the transport of microscale objects using single or multiple microrobots in low Reynolds number fluidic environment. The microrobot is composed of a ‘U＇ shaped SU-8 body, coated on one side with nickel. Once the nickel coating is magnetized, the motion of the microrobots can be driven by external magnetic fields. To invoke different responses from two microrobots under a global magnetic field, two batches of microrobots were fabricated with different thicknesses of nickel coating as a way to promote heterogeneity within the microrobot population. The heterogeneity in magnetic content induces different spatial and temporal responses under the same control input, resulting in differences in movement speed. The nickel coated microstructure is manually controlled through a user interface developed using C＋＋. This paper presents a control strategy to navigate the microrobots by controlling the direction and strength of ex- ternally applied magnetic field, as well as orientation of the microrobots based on their polarity. In addition, multiple micro- robots are used to perform transport tasks.

Composition principle of a microrobot system

The research of micromechanisms is rapidly developing in the world because of its wideprospect in application. At present, researches at home and abroad almost centre on theunit techniques such as the manufacturing of micromotors, and the machining technology ofmicromechanisms. As the unit techniques develop, research of the composition ofAncromechanism system confronts the researchers, and it should be done satisfactorily