Medical Microrobots Research Articles

Medical Microrobot - Wireless Manipulation of a Drug Delivery Carrier through an External Ultrasonic Actuation: Preliminary Results

To achieve precise and untethered clinical therapeutics, microrobots have been widely researched. However, because conventional microrobot actuation is based on magnetic forces generated by a magnetic field and magnetic particles, unexpected side effects caused by additional magnetic ingredients could induce clinical safety issues. In this paper, as an alternative to an untethered actuator, we present a novel ultrasonic actuation mechanism that enables drug particle/cell manipulation and micro/nano-robot actuation in clinical biology and medicine. Firstly, characteristics of the acoustic field in the vessel mimic circular tube, formed from particles emerging through a submerged ultrasonic transducer, are mathematically analyzed and modeled. Thereafter, a control method is proposed for trapping and moving the micro-particles by using acoustic radiation force (ARF) in a standing wave of a tangential standing wave. The feasibility of the proposed method could be demonstrated with the help of experiments conducted using a single transducer with a resonance frequency of 950 kHz and a motorized linear stage, which were used in a water tank. The micro-particles in the tube were trapped via ultrasound and the position of the micro-particles could be controlled by frequency manipulation of the transducer and motor control. This study shows that ultrasonic manipulation can be used for specific applications, such as the operation of a micro robot inserted in a peripheral blood vessel and targeted for drug delivery.

Controlled microrobot for moving in human vessels

Introduction: The creation of controlled microrobots capable of moving in human vessels in accordance with a given traffic is asophisticated problem. An effective way to solve it is the use of SEMS (Smart ElectroMechanical System) modules. These modulesconnected in a special way can simulate the operation of a ciliary apparatus or a flagellated propulsor used as propulsive devices for amicrorobot. Purpose: Development of a controlled medical microrobot based on standard SEMS modules. Results: A medical microrobotis developed. The principles of collective movement control for such microrobots are discussed. A special role in microrobot groupcontrol is assigned to the central nervous system of a microrobot which functions as an automatic control system. When synthesizingan optimal situational control over a group of microrobots, logical-probabilistic and logical-linguistic constraints are translatedinto logical-interval ones, reducing the optimization problem to solving a number of classical mathematical programming problems.Practical relevance: The use of various combinations of SEMS modules in medical microrobots allows you to increase their accuracy,speed and adaptability to the environment. This is because in this case, in contrast to the mechanisms commonly used in microrobots,parallelism is introduced not only in the measurement and calculation processes, but also in the execution of control commands. Thedesign features of the developed modules allow you to provide broad technological capabilities of various biomedical robotic complexes.

Medical Microrobot — A Drug Delivery Capsule Endoscope with Active Locomotion and Drug Release Mechanism: Proof of Concept

This paper presents a robotic capsule endoscope integrated a targeted drug delivery module (DDM) for digestive diseases treatments. The capsule with a big permanent magnet inside is wirelessly controlled and actively moves to target region in gastrointestinal tract by an electromagnetic actuation system (EMA). DDM is a separated body composed of a drug container and a non-power drug-releasing mechanism. The force to expel drug is generated by carbon dioxide gas pressure coming from a chemical reaction inside a propellant reservoir. Where the chemical reaction is activated by a mechanical mechanism that allows dry chemical powders contacting with water at the target point. A small permanent magnet is utilized to separate reagents and wet paper before drug injection. It is designed to be stable during locomotion by virtue of the attractive force of a big permanent magnet. To trigger releasing mechanism, gradient magnetic field from EMA system is created to push small magnet slide down, which allows reagents drop and contact with water in wet paper. The designed DDM has length of 11 mm and diameter of 11 mm. The proposed robotic capsule could show high potentials to be utilized for therapeutic treatment of digestive diseases in practical clinical sites through simulation and ex-vivo experiments.

Magnetically Aligned Nanorods in Alginate Capsules (MANiACs): Soft Matter Tumbling Robots for Manipulation and Drug Delivery.

Soft, untethered microrobots composed of biocompatible materials for completing micromanipulation and drug delivery tasks in lab-on-a-chip and medical scenarios are currently being developed. Alginate holds significant potential in medical microrobotics due to its biocompatibility, biodegradability, and drug encapsulation capabilities. Here, we describe the synthesis of MANiACs—Magnetically Aligned Nanorods in Alginate Capsules—for use as untethered microrobotic surface tumblers, demonstrating magnetically guided lateral tumbling via rotating magnetic fields. MANiAC translation is demonstrated on tissue surfaces as well as inclined slopes. These alginate microrobots are capable of manipulating objects over millimeter-scale distances. Finally, we demonstrate payload release capabilities of MANiACs during translational tumbling motion.

Single-Sided Near-Field Wireless Power Transfer by A Three-Dimensional Coil Array.

Wirelessly powered medical microrobots are often driven or localized by magnetic resonance imaging coils, whose signal-to-noise ratio is easily affected by the power transmitter coils that supply the microrobot. A controlled single-sided wireless power transmitter can enhance the imaging quality and suppress the radiation leakage. This paper presents a new form of electromagnet which automatically cancels the magnetic field to the back lobes by replacing the traditional circular coils with a three-dimensional (3D) coil scheme inspired by a generalized form of Halbach arrays. It is shown that, along with the miniaturization of the transmitter system, it allows for improved magnetic field intensity in the target side. Measurement of the produced magnetic patterns verifies that the power transfer to the back lobe is 15-fold smaller compared to the corresponding distance on the main lobe side, whilst maintaining a powering efficiency similar to that of conventional planar coils. To show the application of the proposed array, a wireless charging pad with an effective powering area of 144 cm2 is fabricated on 3D-assembled printed circuit boards. This 3D structure obviates the need for traditional magnetic shield materials that place limitations on the working frequency and suffer from non-linearity and hysteresis effects.

Preliminary study on alginate/NIPAM hydrogel-based soft microrobot for controlled drug delivery using electromagnetic actuation and near-infrared stimulus.

Currently, microrobots are receiving attention because of their small size and motility, which can be applied to minimal invasive therapy. Additionally, various microrobots using hydrogel with the characteristics of biocompatibility and biodegradability are also being developed. Among them, microrobots that swell and deswell in response to temperature changes caused by external near infrared (NIR) stimuli, focused ultrasound, and an alternating magnetic field, have been receiving a great amount of interest as drug carriers for therapeutic cell delivery. In this study, we propose a spring type medical microrobot that can be manipulated by an electromagnetic actuation (EMA) system and respond to an external stimulus (NIR). Additionally, we verified its feasibility with regard to targeting and drug delivery. There exist various methods of fabricating a spring type microrobot. In this study, we adopted a simple method that entails using a perfluoroalkoxy (PFA) microtube and a syringe pump. Moreover, we also used a hydrogel mixture composed of natural alginate, N-Isopropylacrylamide (NIPAM) for temperature responsiveness, and magnetic nanoparticles (MNPs) for electromagnetic control. Then, we fabricated a spring type alginate/NIPAM hydrogel-based soft microrobot. Additionally, we encapsulated doxorubicin (DOX) for tumor therapy in the microrobot. To verify the feasibility of the proposed spring type hydrogel-based soft microrobot's targeting and drug delivery, we developed an EMA and NIR integrated system. Finally, we observed the swelling and deswelling of the soft microrobot under NIR stimulation and verified the EMA controlled targeting. Moreover, we implemented a control function to release the encapsulated anticancer drug (DOX) through the swelling and deswelling of the soft microrobot by NIR, and evaluated the feasibility of cancer cell therapy by controlling the release of the drug from the soft microrobot.

Mobile Microrobots for Active Therapeutic Delivery

AbstractRecent advances in the versatility and sophistication of design, fabrication, and control methods of mobile microrobots could have a transforming impact on future healthcare technologies. Self‐propelled or remotely actuated, synthetic, or biohybrid microrobots can navigate to difficult‐to‐reach regions in the human body to deliver therapeutics for microscopically localized medical interventions. Here, recent progress in the design of microrobotic systems concerning therapeutic delivery of drugs, cells, and genetic materials is reported. This perspective prioritizes the design aspects of microrobots for medical cargo loading, navigation in biologically relevant environments, and controlled cargo release. In the final section, future prospects and a discussion on the critical shortcomings for the benchside‐to‐bedside translation of medical microrobots are provided.

Medical microrobots have potential in surgery, therapy, imaging, and diagnostics

Trypanosoma brucei , the pathogen that causes sleeping sickness, has a clever and insidious trick to help it navigate its hosts’ innards: It changes shape depending on its surroundings. In bodily fluids, the bacterium assumes a long and narrow shape to propel itself forward, whipping its tail-like flagellum and spinning like a corkscrew. In other settings and life stages, when it doesn't need motility, it shortens into a stumpy blob. In 2014, researchers at ETH Zurich devised microrobots that propel themselves by twisting, something like an artificial flagellum. Researchers direct the microrobots with external magnetic fields. Reproduced with permission from ref. 12. To Bradley Nelson, an engineer at ETH Zurich, the T. brucei ’s potentially deadly shape-shifting ability was both revelation and inspiration. “Parasites have evolved these interesting strategies to survive and move,” he says. “As an engineer, I’m not sure I’d ever have sat down and described something like that from scratch.” His laboratory focuses on developing microrobots that can navigate the human body to perform tasks, such as delivering drugs to a tumor or mechanically clearing blocked blood vessels. In July 2016, Nelson and his team introduced a T. brucei -inspired “origami robot,” a self-folding micromachine, made from a hydrogel, that optimizes its shape according to the viscosity and temperature of its environment (1). It propels itself forward—in experiments, through a viscous sugar solution—by whipping a flagellum-like tail. Scientists steer it by manipulating external magnetic fields. Nelson is among a cadre of scientists who are designing ever-smaller robots that have the potential to improve the precision of medicine. Broadly, the field of “medical microrobots” includes small devices from a millimeter down to a few microns. All aim to safely invade the body and improve health—by diagnosing or monitoring a disease, such as Alzheimer’s, in real time, measuring …

Targeted Drug Delivery and Imaging Using Mobile Milli/Microrobots: A Promising Future Towards Theranostic Pharmaceutical Design.

Miniature untethered medical robots have been receiving growing attention due to technological advances in microactuation, microsensors, and microfabrication and have significant potential to reduce the invasiveness and improve the accessibility of medical devices into unprecedented small spaces inside the human body. In this review, we discuss therapeutic and diagnostic applications of untethered medical microrobots. Wirelessly controlled milli/microrobots with integrated sensors are revolutionizing micromanipulation based medical interventions and are enabling doctors to perform minimally invasive procedures not possible before. 3D fabrication technologies enabling milli/microrobot fabrication at the single cell scale are empowering high-resolution visual imaging and in vivo manipulation capabilities. Swallowable millirobots and injectabale ocular microrobots allow the gastric ulcer imaging, and performance of vitreoretinal microsurgery at previously inaccessible ocular sites. Many invasive excision and incision based diagnostic biopsy, prostrate, and nephrolgical procedures can be performed minimally or almost noninvasively due to recent advancements in microrobotic technology. Advances in biohybrid microrobot systems are pushing microrobotic systems even smaller, using biological cells as on-board microactuators and microsensors using the chemical energy. Such microrobotic systems could be used for local targeted delivery of imaging contrast agents, drugs, genes, and mRNA, minimally invasive surgery, and cell micromanipulation in the near future.

In vivo and in situ measurement and modelling of intra-body effective complex permittivity.

Radio frequency tracking of medical micro-robots in minimally invasive medicine is usually investigated upon the assumption that the human body is a homogeneous propagation medium. In this Letter, the authors conducted various trial programs to measure and model the effective complex permittivity ε in terms of refraction ε', absorption ε″ and their variations in gastrointestinal (GI) tract organs (i.e. oesophagus, stomach, small intestine and large intestine) and the porcine abdominal wall under in vivo and in situ conditions. They further investigated the effects of irregular and unsynchronised contractions and simulated peristaltic movements of the GI tract organs inside the abdominal cavity and in the presence of the abdominal wall on the measurements and variations of ε' and ε''. They advanced the previous models of effective complex permittivity of a multilayer inhomogeneous medium, by estimating an analytical model that accounts for reflections between the layers and calculates the attenuation that the wave encounters as it traverses the GI tract and the abdominal wall. They observed that deviation from the specified nominal layer thicknesses due to non-geometric boundaries of GI tract morphometric variables has an impact on the performance of the authors' model. Therefore, they derived statistical-based models for ε' and ε'' using their experimental measurements.

Characteristic Evaluation of a Shrouded Propeller Mechanism for a Magnetic Actuated Microrobot

Medical microrobots have been widely used in clinical applications, particularly the spiral type locomotion mechanism, which was recently considered one of the main self-propelling mechanisms for the next medical microrobot to perform tasks such as capsule endoscopy and drug delivery. However, limits in clinical applications still exist. The spiral action of the microrobot while being used for diagnosis may lead to pain or even damage to the intestinal wall due to the exposed mechanisms. Therefore, a new locomotive mechanism, named the shrouded propeller mechanism, was proposed to achieve a high level of medical safety as well as effective propulsive performance in our study. The shrouded propeller mechanism consists of a bare spiral propeller and a non-rotating nozzle. To obtain a high effective propulsive performance, two types of screw grooves with different shapes including the cylindrical screw groove and the rectangular screw groove with different parameters were analyzed using the shrouded model. Two types of magnetic actuated microrobots with different driving modes, the electromagnetic (three-pole rotor) actuated microrobot and the permanent magnet (O-ring type magnet) actuated microrobot were designed to evaluate the performance of the electromagnetic actuation system. Based on experimental results, the propulsive force of the proposed magnetic actuated microrobot with a shrouded propeller was larger than the magnetic actuated microrobot with a bare spiral propeller under the same parameters. Additionally, the shrouded propeller mechanism as an actuator can be used for other medical microrobots for flexible locomotion.

MRI-based communication for untethered intelligent medical microrobots

Miniaturization is a major challenge in fabricating medical microrobots designed to operate inside the human body. Current microrobots lack an adequate embedded communication system to transmit sensory data due to a shortage of power. In this paper, we propose a communication method, using the susceptibility effect in MRI, to overcome the size and power constraints in microrobots. The proposed method relies on a binary communication scheme in the form of a frequency alteration in the electrical current circulating along a miniature coil embedded in a microrobot. The frequency of the electrical current could be regulated by a predetermined sensory threshold input implemented in the microrobot. Such a frequency provides information on the level of sensory information gathered by the microrobot, and it is determined using single-shot EPI-GE MR images. The proposed method is independent of the microrobot’s position and orientation. Moreover, the experiments showed that MRI is sensitive enough to detect the change in magnetic field if we scaled the coil to an appropriate size for embedding into the microrobot. The proposed method could potentially apply to microrobots for monitoring and mapping specific physiological conditions within the body.

Proposal of a multiple ER microactuator system using an alternating pressure source

This paper proposes and develops a multiple ER microactuator system using an alternating pressure source for in-pipe working micromachines, medical microrobots, and so on. A hydraulic microactuator is known to have high power density but also has the drawback of requiring large piping space for the supply and return of the working fluid. In this study, an alternating pressure system with synchronized control valves and a single pipe was proposed. As the control valves, simple ER microvalves were employed. The ER microvalves control an electro-rheological fluid (ERF) flow through its apparent viscosity change due to the applied electric field. In addition, a pressure transmitter is inserted between the pressure source and the ER valves, and low viscosity fluid such as water is used to transmit the alternating pressure. The use of the low viscosity fluid can reduce the diameter of the connecting pipe due to the low pressure loss. The proposed set-up is composed of multiple ER microactuators and an alternating pressure source; each ER microactuator consists of a pressure transmitter, two ER microvalves and a hydraulic microactuator. As the proposed system has half the number of pipes, of smaller diameter, compared with conventional hydraulic microactuator systems, it is suitable for a multiple actuator system. In this study, for verification of the working principle of the proposed system, we fabricated a large model of the system which consists of an ER finger 13mm×10mm×33mm in size as a kind of ER microactuator and an alternating pressure source using a voice coil motor. Through experiments, we confirmed the tip displacement of 17mm for the 16mm-long movable part of the finger. Then, we fabricated a gripper using two ER fingers and confirmed its independent motion.

Simplified electromagnetic actuation system for three dimensional locomotive and drilling microrobot

Many researchers have studied and developed various types of medical microrobots using an external electromagnetic field and a permanent magnet. Most microrobots are very small and remotely controlled. Their medical applications include minimally invasive surgery (MIS), capsule endoscopy, drug delivery system (DDS), and cell based therapy. Two-dimensional (2D) or 3D locomotion of microrobots using different electromagnetic actuation (EMA) systems has been studied. In this paper, we propose a simplified EMA system having the same functions as our previous proposed EMA system. Because the simplified EMA system has a smaller coils structure, it consumes less power than the previous EMA system. First, through basic locomotive tests, we demonstrate that the microrobot using the proposed EMA system can move along a desired path in 2D and 3D space. Second, a drilling performance test was carried out on the microrobot. Finally, through quantitative comparison, it was verified that the proposed EMA system consumed 58% less power than the previous EMA system.

Theoretical analysis of magnetically propelled microrobots in the cardiovascular system.

The field of medical microrobotics is rapidly progressing; however, it is particularly challenging to control microrobots inside blood vessels. In this paper, the magnetic propulsion of a microrobot in pulsating flow is investigated. Regarding this task, the advantages of a reduced blood flow velocity are examined. The required magnetic field gradient in relation to the size of the microrobot is theoretically analyzed and compared to that for propulsion during reduced blood flow velocity. Quantitative and qualitative advantages together with the practical challenges are discussed.

A small linear ultrasonic motor utilizing longitudinal and bending modes of a piezoelectric tube

A small linear ultrasonic motor which consists of a piezoelectric ceramic Pb(Zr,Ti)O3 (PZT) tube (outside diameter 5 mm, inside diameter 3 mm, length 15 mm, acts as stator) and a shaft (acts as slider) has been developed. The outer surface electrode of the PZT tube is divided into 4 parts to excite longitudinal-bending (L1-B2) modes, which could be then used to produce linear motion. The motor shows a high power (force) density. It has a no-load speed of 0.14 m/s, a stall force of 0.3 N, and a maximum output power of 9.3 mW under an applied voltage of 100 Vpp. The method for further improving the performance has been discussed. The proposed motor can be further miniaturized because of its simple structure, and it has potential to be applied to medical microrobots, endoscopes, or micro laparoscopic devices, etc.

Magnetic Navigation Control of Microagents in the Vascular Network: Challenges and Strategies for Endovascular Magnetic Navigation Control of Microscale Drug Delivery Carriers

Although navigation control has been applied in a multitude of environments, relatively little is known about the challenges and issues of navigation control in the vascular network. In an adult human, the vascular network consists of nearly 100,000 km of blood vessels, with diameters ranging from a few millimeters in the artery to just a few micrometers in the capillaries, and blood flow rates ranging from a few tens of centimeters per second to a few millimeters per second. Although vascular networks present great challenges, due to various environmental conditions, they are of special interest in medical microrobotics since they allow navigable agents to be delivered anywhere within the body. Controlled endovascular navigation would allow targeted surgical, diagnostic, and therapeutic interventions. In cancer therapy, for instance, although many of the most deadly cancers are initially located in a single region, modern therapies such as chemotherapy continue to inject excessive amounts of toxic agents thecirculate systematically throughout the vascular network. In general, only a tiny fraction of the drug reaches the treatment region [1]. Even the level of targeting achieved by agents with special coatings to enhance tumor cell specificity is far from optimal when they are injected systematically in the vascular network. Since the therapeutics do not discriminate between cancerous and healthy cells, systemic circulation of these agents must be avoided to eliminate, or at least minimize, secondary toxicity that affects healthy organs.

Three-degree-of-freedom ultrasonic motor using a 5-mm-diameter piezoelectric ceramic tube.

A small three-degree-of-freedom ultrasonic motor has been developed using a simple piezoelectric lead zirconate titanate (PZT)-tube stator (OD 5 mm, ID 3 mm, length 15 mm). The stator drives a ball-rotor into rotational motion around one of three orthogonal (x-, y-, and z-) axes by combing the first longitudinal and second bending vibration modes. A motor prototype was fabricated and characterized; its performance was superior to those of previous motors made with a PZT ceramic/metal composite stator of comparable size. The method for further improving the performance was discussed. The motor can be further miniaturized and it has potential to be applied to medical microrobots, endoscopes or micro laparoscopic devices, and cell manipulation devices.

6AM2-D-7 血管内医用マイクロロボットの分岐制御に関する研究(6AM2-D OS3 マイクロ・ナノ生体医工学)

6AM2-D-7 血管内医用マイクロロボットの分岐制御に関する研究(6AM2-D OS3 マイクロ・ナノ生体医工学)

Preliminary study on development of PVDF nanofiber based energy harvesting device for an artery microrobot

This paper presents the trial of developing a miniature energy harvesting device for medical microrobot devised working in blood vessel for example in an artery, specifically focusing on fabrication of co-axial nanofibers as converting components from a high efficient piezoelectric material-Polyvinylidene Fluoride (PVDF). It is very meaningful to build up an effective miniature device to collect energy from environment or receive energy transferred in wireless way especially when the microrobot is in vivo working. A PVDF co-axial nanofiber based cantilever is designed to harvest the vibration power generated by ultrasonic wave transmitted in vitro. PVDF forms the shell of the nanofiber, whereas the core is conductive material, such as polyaniline, which simplifies greatly the fabrication of electrodes on single nanofiber. With specially designed cantilever, this device can resonate to desired frequency which leads the energy harvesting device to work under the optimal condition.