Gwangjun Go

Magnetic actuated pH-responsive hydrogel-based soft micro-robot for targeted drug delivery

For drug delivery in cancer therapy, various stimuli-responsive hydrogel-based micro-devices have been studied with great interest. Here, we present a new concept for a hybrid actuated soft microrobot targeted drug delivery. The proposed soft microrobot consists of a hydrogel bilayer structure of 2-hydroxyethyl methacrylate (PHEMA) and poly (ethylene glycol) acrylate (PEGDA) with iron (II, III) oxide particles (Fe3O4). The PHEMA layer as a pH-responsive gel is used for a trapping and unfolding motion of the soft microrobot in pH-varying solution, and the PEGDA-with-Fe3O4 layer is employed for the locomotion of the soft microrobot in the magnetic field. The bilayer soft microrobot was fabricated by a conventional photolithography procedure and its characteristics were analyzed and presented. To evaluate the trapping performance and the motility of the soft microrobot, test solutions with different pH values and an electromagnetic actuation (EMA) system were used. First, the soft microrobot showed its full trapping motion at about pH 9.58 and its unfolding motion at about pH 2.6. Second, the soft microrobot showed a moving velocity of about 600 μm s−1 through the generated magnetic field of the EMA system. Finally, we fabricated the real anti-cancer drug microbeads (PCL-DTX) and executed the cytotoxicity test using the mammary carcinoma cells (4T1). The viability of the 4T1 cells treated with the proposed microrobot and the PCL-DTX microbeads decreased to 70.25 ± 1.52%. The result demonstrated that the soft microrobot can be moved to a target position by the EMA system and can release a small amount of beads by the pH variation and the robot exhibited no toxicity to the cells. In the future, we expect that the proposed soft microrobot can be applied to a new tumor-therapeutic tool that can move to a target tumor and release anti-tumor drugs.

Active Locomotive Intestinal Capsule Endoscope (ALICE) System: A Prospective Feasibility Study

Owing to the limitations of the conventional flexible endoscopes used in gastrointestinal diagnostic procedures, which cause discomfort and pain in patients, a wireless capsule endoscope has been developed and commercialized. Despite the many advantages of the wireless capsule endoscope, its restricted mobility has limited its use to diagnosis of the esophagus and small intestine only. Therefore, to extend the diagnostic range of the wireless capsule endoscope into the stomach and colon, additional mobility, such as 3-D locomotion, and steering of the capsule endoscope, is necessary. Previously, several researchers reported on the development of mobility mechanisms for the capsule endoscope, but they were unable to achieve adequate degrees of freedom or sufficiently diverse capsule motions. Therefore, we proposed a novel electromagnetic actuation system that can realize 3-D locomotion and steering within the digestive organs. The proposed active locomotion intestinal capsule endoscope (ALICE) consists of five pairs of solenoid components and a capsule endoscope with a permanent magnet. With the magnetic field generated by the solenoid components, the capsule endoscope can perform various movements necessary to the diagnosis of the gastrointestinal tract, such as propulsion in any direction, steering, and helical motion. From the results of a basic locomotion test, ALICE showed a propulsion angle error of less than 4° and a propulsion force of 70 mN. To further validate the feasibility of ALICE as a diagnostic tool, we executed ex vivo testing using small intestine extracted from a cow. Through the basic mobility test and the ex vivo test, we verified ALICEs usefulness as a medical capsule endoscopic system.

Hybrid-Actuating Macrophage-Based Microrobots for Active Cancer Therapy

Using macrophage recruitment in tumors, we develop active, transportable, cancer theragnostic macrophage-based microrobots as vector to deliver therapeutic agents to tumor regions. The macrophage-based microrobots contain docetaxel (DTX)-loaded poly-lactic-co-glycolic-acid (PLGA) nanoparticles (NPs) for chemotherapy and Fe3O4 magnetic NPs (MNPs) for active targeting using an electromagnetic actuation (EMA) system. And, the macrophage-based microrobots are synthesized through the phagocytosis of the drug NPs and MNPs in the macrophages. The anticancer effects of the microrobots on tumor cell lines (CT-26 and 4T1) are evaluated in vitro by cytotoxic assay. In addition, the active tumor targeting by the EMA system and macrophage recruitment, and the chemotherapeutic effect of the microrobots are evaluated using three-dimensional (3D) tumor spheroids. The microrobots exhibited clear cytotoxicity toward tumor cells, with a low survivability rate (<50%). The 3D tumor spheroid assay showed that the microrobots demonstrated hybrid actuation through active tumor targeting by the EMA system and infiltration into the tumor spheroid by macrophage recruitment, resulting in tumor cell death caused by the delivered antitumor drug. Thus, the active, transportable, macrophage-based theragnostic microrobots can be considered to be biocompatible vectors for cancer therapy.

Electromagnetic Navigation System Using Simple Coil Structure (4 Coils) for 3-D Locomotive Microrobot

Researches on the biomedical wireless microrobot are being actively carried out. In particular, compared with conventional catheter intervention, the wireless locomotive microrobot using an electromagnetic navigation system (ENS) can have many advantages in ischemic heart disease therapy. The ENSs generally use a uniform magnetic field and gradient magnetic field for the actuation of microrobots. However, because most ENSs require many coils, they have severe limitations, including a complex structure, large energy consumption, increased power supply, and large system volume. This paper proposes a new ENS for a 3-D locomotive microrobot using only four electromagnetic coils. The proposed ENS has a very simple structure, which consists of two circular coils and two saddle coils. The alignment and propulsion of the microrobot are determined by the generated magnetic field and gradient magnetic field from the four coils. This paper proposes a control algorithm and a gravity compensation for a 3-D locomotive microrobot and validates the performance of the microrobot using the proposed ENS. Finally, through a locomotion test of a blood vessel phantom, it was demonstrated that the microrobot can move to a target position in the phantom and deliver a drug to the target lesion.

Shape memory alloy–based biopsy device for active locomotive intestinal capsule endoscope

Recently, capsule endoscopes have been used for diagnosis in digestive organs. However, because a capsule endoscope does not have a locomotive function, its use has been limited to small tubular digestive organs, such as small intestine and esophagus. To address this problem, researchers have begun studying an active locomotive intestine capsule endoscope as a medical instrument for the whole gastrointestinal tract. We have developed a capsule endoscope with a small permanent magnet that is actuated by an electromagnetic actuation system, allowing active and flexible movement in the patient’s gut environment. In addition, researchers have noted the need for a biopsy function in capsule endoscope for the definitive diagnosis of digestive diseases. Therefore, this paper proposes a novel robotic biopsy device for active locomotive intestine capsule endoscope. The proposed biopsy device has a sharp blade connected with a shape memory alloy actuator. The biopsy device measuring 12mm in diameter and 3mm in length was integrated into our capsule endoscope prototype, where the device’s sharp blade was activated and exposed by the shape memory alloy actuator. Then the electromagnetic actuation system generated a specific motion of the capsule endoscope to extract the tissue sample from the intestines. The final biopsy sample tissue had a volume of about 6mm3, which is a sufficient amount for a histological analysis. Consequently, we proposed the working principle of the biopsy device and conducted an in-vitro biopsy test to verify the feasibility of the biopsy device integrated into the capsule endoscope prototype using the electro-magnetic actuation system.

Electromagnetic actuation system for locomotive intravascular therapeutic microrobot

In this paper, we proposed an intravascular therapeutic microrobot using an electromagnetic actuation (EMA) system with bi-plane X-ray imaging device. The proposed EMA system consists of Helmholtz-Maxwell coils, uniform-gradient saddle coils. The Helmholtz-Maxwell coils are located along y-axis, and uniform-gradient saddle coils are located perpendicular to y-axis. In order to align the microrobot along a desired angle in 2D (dimensional) plane, it is necessary to control of the currents on Helmholtz coil and uniform saddle coil. For a forward and backward direction movement of the microrobot, we precisely control the currents of Maxwell coil and gradient saddle coil. Because the saddle coils can be rotated around the y-axis, the effective actuation plane of the microrobot can be also rotated, and the microrobot can move in 3D space. In addition, for the position recognition of the microrobot in a blood vessel, we adopted a bi-plane X-ray fluoroscopy. If the saddle coils are rotated around the y-axis, an open area is changed. Therefore, the saddle coils and bi-plane X-ray fluoroscopy must be rotated simultaneously. To confirm the feasibility of 3D locomotion of the microrobot, we executed a locomotion test of the microrobot in the blood vessel phantom, where the blood vessel phantom was fabricated by the rendering data from computed tomography (CT) images of the iliac artery and 3D printer.

Penetration of an artificial arterial thromboembolism in a live animal using an intravascular therapeutic microrobot system

The biomedical applications of wireless robots are an active area of study. In addition to moving to a target lesion, wireless locomotive robots can deliver a therapeutic drug for a specific disease. Thus, they hold great potential as therapeutic devices in blood vessel diseases, such as thrombi and occlusions, and in other diseases, such as cancer and inflammation. During a percutaneous coronary intervention (PCI), surgeons wear a heavy shielding cloth. However, they cannot escape severe radiation exposure owing to unstable shielding. They may also suffer from joint pains because of the weight of the shielding cloth. In addition, the catheters in PCIs are controlled by the surgeons hand. Thus, they lack steering ability. A new intravascular therapeutic system is needed to address these problems in conventional PCIs. We developed an intravascular therapeutic microrobot system (ITMS) using an electromagnetic actuation (EMA) system with bi-plane X-ray devices that can remotely control a robot in blood vessels. Using this proposed ITMS, we demonstrated the locomotion of the robot in abdominal and iliac arteries of a live pig by the master-slave method. After producing an arterial thromboembolism in a live pig in a partial iliac artery, the robot moved to the target lesion and penetrated by specific motions (twisting and hammering) of the robot using the proposed ITMS. The results reveal that the proposed ITMS can realize stable locomotion (alignment and propulsion) of a robot in abdominal and iliac arteries of a live pig. This can be considered the first preclinical trial of the treatment of an artificial arterial thromboembolism by penetration of a blood clot.

A Magnetically Actuated Microscaffold Containing Mesenchymal Stem Cells for Articular Cartilage Repair

This study proposes a magnetically actuated microscaffold with the capability of targeted mesenchymal stem cell (MSC) delivery for articular cartilage regeneration. The microscaffold, as a 3D porous microbead, is divided into body and surface portions according to its materials and fabrication methods. The microscaffold body, which consists of poly(lactic-co-glycolic acid) (PLGA), is formed through water-in-oil-in-water emulsion templating, and its surface is coated with amine functionalized magnetic nanoparticles (MNPs) via amino bond formation. The porous PLGA structure of the microscaffold can assist in cell adhesion and migration, and the MNPs on the microscaffold can make it possible to steer using an electromagnetic actuation system that provides external magnetic fields for the 3D locomotion of the microscaffold. As a fundamental test of the magnetic response of the microscaffold, it is characterized in terms of the magnetization curve, velocity, and 3D locomotion of a single microscaffold. In addition, its function with a cargo of MSCs for cartilage regeneration is demonstrated from the proliferation, viability, and chondrogenic differentiation of D1 mouse MSCs that are cultured on the microscaffold. For the feasibility tests for cartilage repair, 2D/3D targeting of multiple microscaffolds with the MSCs is performed to demonstrate targeted stem cell delivery using the microscaffolds and their swarm motion.

Selective microrobot control using a thermally responsive microclamper for microparticle manipulation

Microparticle manipulation using a microrobot in an enclosed environment, such as a lab-on-a-chip, has been actively studied because an electromagnetic actuated microrobot can have accurate motility and wireless controllability. In most studies on electromagnetic actuated microrobots, only a single microrobot has been used to manipulate cells or microparticles. However, the use of a single microrobot can pose several limitations when performing multiple roles in microparticle manipulation. To overcome the limitations associated with using a single microrobot, we propose a new method for the control of multiple microrobots. Multiple microrobots can be controlled independently by an electromagnetic actuation system and multiple microclampers combined with microheaters. To select a specific microrobot among multiple microrobots, we propose a microclamper composed of a clamper structure using thermally responsive hydrogel and a microheater for controlling the microclamper. A fundamental test of the proposed microparticle manipulation system is performed by selecting a specific microrobot among multiple microrobots. Through the independent locomotion of multiple microrobots with U- and V-shaped tips, heterogeneous microparticle manipulation is demonstrated in the creation of a two-dimensional structure. In the future, our proposed multiple-microrobot system can be applied to tasks that are difficult to perform using a single microrobot, such as cell manipulation, cargo delivery, tissue assembly, and cloning.

Biomimetic swimming tadpole microrobot using 3-pairs Helmholtz coils

For the actuation of a swimming microrobot, various types of electromagnetic actuation (EMA) systems were proposed. Compared with a conventional actuation system using an electric motor or shape memory alloy (SMA), EMA system has many advantages for a wireless actuation of a microrobot. This paper introduces a biomimetic swimming tadpole microrobot. The developed microrobot could be driven by an external uniform magnet field using 3-pairs of Helmholtz coils. The swimming microrobot consists of a buoyant body, NdFeB magnets, and silicone fin. Especially, the tadpole swimming microrobot has a single silicone fin which is directly linked to the NdFeB magnet. The external alternating magnetic field from 3-pairs of Helmholtz coils could generate the propulsion and steering force of the tadpole microrobot in 3-dimensional (D) space. The proposed swimming tadpole microrobot can be used in medical areas such as a capsule endoscope and drug delivery system.