Effect of Balance Training in Sitting Position Using Visual Feedback on Balance and Gait Ability in Chronic Stroke Patients.

Chronic stroke often results in balance and gait impairments, significantly impacting patients' quality of life. The purpose of this study was to investigate whether the combined effect of unstable surface balance training and visual feedback, based on proprioceptive neuromuscular stimulation in patients with chronic stroke, is effective in restoring balance and gait ability. A total of 39 chronic stroke patients were randomly assigned to a visual feedback combined with unstable surface balance training group (VUSBG), an unstable surface balance training group (USBG), or a conventional physical therapy group (CG). This study was conducted with the Trunk Impairment Scale, the Bug Balance Scale, the Timed Get Up and Go Test, and Gait Analysis. VUSBG and USBG improved function and gait (stride length and hip/knee flexion angle), but there was no significant difference in the CG group. Specific results showed that the stride length in the VUSBG improved by 25% (p < 0.05), and the hip/knee flexion angle improved by 18% (p < 0.05). The post-hoc analysis revealed that VUSBG had a greater impact on the hip/knee flexion angle relative to the other two groups, as well as gait velocity and stride length relative to CG. Visual feedback complex exercise based on the principle of proprioceptive neuromuscular facilitation could be an intervention strategy to improve gait speed, trunk stability, and mobility in chronic stroke patients.

Human-robot-robot cooperative control using positioning robot and 1-DOF traction device for robot-assisted fracture reduction system.

While performing musculoskeletal long bone fracture reduction surgery, assistant surgeons can often suffer from physical fatigue as they provide resistance against the tension from surrounding muscles pulling on the patient's broken bones. These days, robotic systems are being actively developed to mitigate this physical workload by realigning and holding these fractured bones for surgeons. This has led to one consortium proposing the development of a robot-assisted fracture reduction system consisting of a 6-DOF positioning robot along with a 1-DOF traction device. With the introduction of the 1-DOF traction device, the positioning robot does not have to fight these contraction forces so can be compact improving its maneuverability and overall convenience; however, considering surgeon-robot interactions, this approach adds the requirement of controlling two different types of robots simultaneously. As such, an advanced cooperative control methodology is required to control the proposed bone fracture reduction robot system. In this paper, a human-robot-robot cooperative control (HRRCC) scheme is proposed for collaboration between the surgeon, the positioning robot, and the traction device. First, the mathematical background of this HRRCC scheme is provided. Next, we describe a series of experiments that show how the proposed scheme facilitates a reduction in the load placed on the positioning robot from strong muscular contraction forces making it possible to conduct fracture reduction procedures more safely despite the muscular forces.

HDR Brachytherapy Planning using Active Needles - Preliminary Investigation on Dose Planning.

In this study we present a new approach to plan a high-dose-rate (HDR) prostate brachytherapy (BT) using active needles recently developed by our group. The active needles realize bi-directional bending inside the tissue, and thereby more compliant with the patient's anatomy compared with conventional straight needles. A computational method is presented to first generate a needle arrangement configuration based on the patient's prostate anatomy. The needle arrangement is generated to cover the prostate volume, providing accessible channels for the radiation source during a HDR BT. The needle arrangement configuration avoids healthy organs and prevents needle collision inside the body. Then a treatment plan is proposed to ensure sufficient prescribed dosage to the whole prostate gland. The method is applied to a prostate model reconstructed from an anonymized patient to show the feasibility of this method. Finally, the active needle's capability to generate the required bending is shown. We have shown that our method is able to automatically generate needle arrangement configuration using active needles, and plan for a treatment that meets the dose objectives while using fewer needles (about 20% of conventional straight needles) than the conventional HDR BT performed by straight needles.

Integrating robot-assisted ultrasound tracking and 3D needle shape prediction for real-time tracking of the needle tip in needle steering procedures.

BACKGROUND: Needle insertions have been used in several minimally invasive procedures for diagnostic and therapeutic purposes. Real-time position of the needle tip is an important information in needle steering systems. METHODS: This work introduces a robot-assisted ultrasound tracking (R-AUST) system integrated with a needle shape prediction method to provide 3D position of the needle tip. The tracking system is evaluated in phantom and ex vivo beef liver tissues. RESULTS: An average error of 0.60 mm was found for needle insertion tests inside the phantom tissue. The R-AUST integrated with shape prediction in the beef liver tissue was able to track the needle tip with an average and maximum error of 0.37 and 0.67 mm, respectively. The average error reported in this work is within the mean allowable needle placement error (<2.7 mm) in targeted procedures. CONCLUSIONS: Integration of R-AUST tracking method with needle shape prediction results in a reasonably accurate real-time tracking suitable for ultrasound-guided needle insertions.

A concentric tube-based 4-DOF puncturing needle with a novel miniaturized actuation system for vitrectomy.

BACKGROUND: Vitreoretinal surgeries require precise, dexterous, and steady instruments for operation in delicate parts of the eye. Robotics has presented solutions for many vitreoretinal surgical problems, but, in a few operations, the available tools are still not dexterous enough to carry out procedures with minimum trauma to patients. Vitrectomy is one of those procedures and requires some dexterous instruments to replace straight ones for better navigation to affected sides inside the eyeball. METHOD: In this paper, we propose a new vein puncturing solution with a 4-DOF motion to increase the workspace inside the eye. A two-member concentric tube-based 25G needle is proposed whose shape is optimized. To operate the concentric tube needle, a novel and miniaturized actuation system is proposed that uses hollow shaft motors for the first time. The presented prototype of actuation system has a stroke of 100 mm in a small size of 148 × 25 × 65 mm (L × W × H), suitable for approaching distant positions inside the eyeball. RESULTS: Experimental results validate that the targeting accuracy of the needle is less than one millimeter and the needle tip can apply a force of 23.51 mN which is enough to perform puncturing. Furthermore, the proposed needle covers maximum workspace of around 128.5° inside the eyeball. For the actuation system, experiments show that it can produce repeatable motions with accuracy in submillimeter. CONCLUSION: The proposed needle system can navigate to the sites which are difficult to approach by currently available straight tools requiring reinsertions. Along with the miniaturized actuation system, this work is expected to improve the outcome of vitrectomy with safe and accurate navigation.

Hands-on robot-assisted fracture reduction system guided by a linear guidance constraints controller using a pre-operatively planned goal pose.

BACKGROUND: In robot-assisted fracture reduction systems, the fine alignment of the fractured bone and its path planning are still of issues that need to be resolved. METHODS: A novel linear guidance constraints (LGC) controller guides a robot along the shortest path to align a distal fracture segment and a proximal one. In addition, the surgeon can modify the path whenever s/he wants. RESULTS: When the LGC controller is used in the experiment on a femoral bone model with simulated muscles, the fracture reduction time was measured to be 35.6 ± 16.4 seconds, while the position and the angle errors were 0.41 ± 0.61 mm, and 0.22 ± 0.80°, respectively. The proposed controller reduced the reduction time by 78.1%, the translational error by 91.6%, and the angular error by 95.4%, compared with the cases without the LGC controller. CONCLUSIONS: It was proven that the proposed scheme reduced the reduction time and the pose error of the fracture alignment, and that it is effective to alleviate the maneuvering load.

Real-time microrobot posture recognition via biplane X-ray imaging system for external electromagnetic actuation.

PURPOSE: As a promising intravascular therapeutic approach for autonomous catheterization, especially for thrombosis treatment, a microrobot or robotic catheter driven by an external electromagnetic actuation system has been recently investigated. However, the three-dimensional (3D) real-time position and orientation tracking of the microrobot remains a challenge for precise feedback control in clinical applications owing to the micro-size of the microrobot geometry in vessels, along with bifurcation and vulnerability. Therefore, in this paper, we propose a 3D posture recognition method for the unmanned microrobotic surgery driven by an external electromagnetic actuator system. METHODS: We propose a real-time position and spatial orientation tracking method for a millimeter-sized intravascular object or microrobot using a principal component analysis algorithm and an X-ray reconstruction. The suggested algorithm was implemented to an actual controllable wireless microrobot system composed of a bullet-shaped object, a biplane X-ray imaging device, and an electromagnetic actuation system. Numerical computations and experiments were conducted for the performance verification. RESULTS: The experimental results showed a good performance of the implemented system with tracking errors less than 0.4 mm in position and 2° in orientation. The proposed tracking technique accomplished a fast processing time, ~ 0.125 ms/frame, and high-precision recognition of the micro-sized object. CONCLUSIONS: Since the suggested method does not require pre-information of the object geometry in the human body for its 3D shape and position recognition, it could be applied to various elliptical shapes of the microrobot system with computation time efficacy and recognition accuracy. Hence, the method can be used for therapeutic millimeter- or micron-sized manipulator recognition in vascular, as well as implanted objects in the human body.

Geometric Parameter Calibration for a Cable-Driven Parallel Robot Based on a Single One-Dimensional Laser Distance Sensor Measurement and Experimental Modeling.

A cable-driven parallel robot has benefits of wide workspace, high payload, and high dynamic response owing to its light cable actuator utilization. For wide workspace applications, in particular, the body frame becomes large to cover the wide workspace that causes robot kinematic errors resulting from geometric uncertainty. However, appropriate sensors as well as inexpensive and easy calibration methods to measure the actual robot kinematic parameters are not currently available. Hence, we present a calibration sensor device and an auto-calibration methodology for the over-constrained cable-driven parallel robots using one-dimension laser distance sensors attached to the robot end-effector, to overcome the robot geometric uncertainty and to implement precise robot control. A novel calibration workflow with five phases-preparation, modeling, measuring, identification, and adjustment-is proposed. The proposed calibration algorithms cover the cable-driven parallel robot kinematics, as well as uncertainty modeling such as cable elongation and pulley kinematics. We performed extensive simulations and experiments to verify the performance of the suggested method using the MINI cable robot. The experimental results show that the kinematic parameters can be identified correctly with 0.92 mm accuracy, and the robot position control accuracy is increased by 58%. Finally, we verified that the developed calibration sensor devices and the calibration methodology are applicable to the massive-size cable-driven parallel robot system.

A robotic suture-passing device for possible use in SILS and NOTES.

BACKGROUND: Natural orifice transluminal endoscopic (NOTES) and single incisional laparoscopic surgeries (SILS) have been gaining importance over the last two decades. Due to improper instrumentation, small workspace and the imperceptibility of body structures, suturing and knot-tying are difficult to perform in both. METHODS: An intracorporeal suture-passing device with two manipulator arms is proposed that automatically passes the suture around ducts of up to 7 mm diameter, without additional manipulation of any other surgical instrument, and it can be deployed through a trocar of 3 mm inner diameter. RESULTS: The working mechanism was validated by 15 trials, where passing the suture around a phantom tube was tested, and the operating time measured as (34.55 ± 4.55) seconds. CONCLUSIONS: Suturing and knotting in SILS and NOTES are currently challenging techniques, but the proposed device enables the suture to be automatically passed around ducts. It is expected that clinical evaluations of future prototypes will further confirm the efficacy of the device.

Experimental and simulation studies on focused ultrasound triggered drug delivery.

To improve drug delivery efficiency in cancer therapy, many researchers have recently concentrated on drug delivery systems that use anticancer drug loaded micro- or nanoparticles. In addition, induction methods, such as ultrasound, magnetic field, and infrared light, have been considered as active induction methods for drug delivery. Among these, focused ultrasound has been regarded as a promising candidate for the active induction method of drug delivery system because it can penetrate a deep site in soft tissue, and its energy can be focused on the targeted lesion. In this research, we employed focused ultrasound as an active induction method. For an anticancer drug loaded microparticles, we fabricated poly-lactic-co-glycolic acid docetaxel (PLGA-DTX) nanoparticle encapsulated alginate microbeads using the single-emulsion technique and the aeration method. To select the appropriate operating parameter for the focused ultrasound, we measured the pressure and temperature induced by the focused ultrasound at the focal area using a needle-type hydrophone and a digital thermal detector, respectively. Additionally, we conducted a simulation of focused ultrasound using COMSOL Multiphysics 4.3a. The experimental measurement results were compared with the simulation results. In addition, the drug release rates of the PLGA-DTX-encapsulated alginate microbeads induced by the focused ultrasound were tested. Through these experiments, we determined that the appropriate focused ultrasound parameter was peak pressure of 1 MPa, 10 cycle/burst, and burst period of 20 µSec. Finally, we performed the cell cytotoxicity and drug uptake test with focused ultrasound induction and found that the antitumor effect and drug uptake efficiency were significantly enhanced by the focused ultrasound induction. Thus, we confirmed that focused ultrasound can be an effective induction method for an anticancer drug delivery system.

Virtual wall-based haptic-guided teleoperated surgical robotic system for single-port brain tumor removal surgery.

This article presents a haptic-guided teleoperation for a tumor removal surgical robotic system, so-called a SIROMAN system. The system was developed in our previous work to make it possible to access tumor tissue, even those that seat deeply inside the brain, and to remove the tissue with full maneuverability. For a safe and accurate operation to remove only tumor tissue completely while minimizing damage to the normal tissue, a virtual wall-based haptic guidance together with a medical image-guided control is proposed and developed. The virtual wall is extracted from preoperative medical images, and the robot is controlled to restrict its motion within the virtual wall using haptic feedback. Coordinate transformation between sub-systems, a collision detection algorithm, and a haptic-guided teleoperation using a virtual wall are described in the context of using SIROMAN. A series of experiments using a simplified virtual wall are performed to evaluate the performance of virtual wall-based haptic-guided teleoperation. With haptic guidance, the accuracy of the robotic manipulator's trajectory is improved by 57% compared to one without. The tissue removal performance is also improved by 21% ( p < 0.05). The experiments show that virtual wall-based haptic guidance provides safer and more accurate tissue removal for single-port brain surgery.

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.

A novel curvature-controllable steerable needle for percutaneous intervention.

Over the last few decades, flexible steerable robotic needles for percutaneous intervention have been the subject of significant interest. However, there still remain issues related to (a) steering the needle's direction with less damage to surrounding tissues and (b) increasing the needle's maximum curvature for better controllability. One widely used approach is to control the fixed-angled bevel-tip needle using a "duty-cycle" algorithm. While this algorithm has shown its applicability, it can potentially damage surrounding tissue, which has prevented the widespread adoption of this technology. This situation has motivated the development of a new steerable flexible needle that can change its curvature without axial rotation, while at the same time producing a larger curvature. In this article, we propose a novel curvature-controllable steerable needle. The proposed robotic needle consists of two parts: a cannula and a stylet with a bevel-tip. The curvature of the needle's path is controlled by a control offset, defined by the offset between the bevel-tip and the cannula. As a result, the necessity of rotating the whole needle's body is decreased. The duty-cycle algorithm is utilized to a limited degree to obtain a larger radius of curvature, which is similar to a straight path. The first prototype of 0.46 mm (outer diameter) was fabricated and tested with both in vitro gelatin phantom and ex vivo cow liver tissue. The maximum curvatures measured 0.008 mm(-1) in 6 wt% gelatin phantom, 0.0139 mm(-1) in 10 wt% gelatin phantom, and 0.0038 mm(-1) in cow liver. The experimental results show a linear relationship between the curvature and the control offset, which can be utilized for future implementation of this control algorithm.

Preparation of HIFU-triggered tumor-targeted hyaluronic acid micelles for controlled drug release and enhanced cellular uptake.

In this study, a novel type of high intensity focused ultrasound (HIFU)-triggered active tumor-targeting polymeric micelle was prepared and investigated for controlled drug release and enhanced cellular uptake. Amphiphilic hyaluronic acid (HA) conjugates were synthesized to form docetaxel loaded micelles in aqueous conditions with high encapsulation efficiencies of over 80%. The micelle sizes were limited to less than 150nm, and they varied slightly according to the encapsulated drug amount. Modifying the micellar surface modification with polyethylene glycol diamine successfully inhibited premature drug leakage at a certain level, and it can be expected to prolong the circulation time of the particles in blood. In addition, high-intensity focused ultrasound was introduced to control the release of docetaxel from micelles, to which the release behavior of a drug can be tuned. The in-vitro cell cytotoxicity of docetaxel-loaded micelles was verified against CT-26 and MDA-MB-231 cells. The IC50 values of drug-loaded micelles to CT-26 and MDA-MB-231 cells were 1230.2 and 870.9ng/mL, respectively. However, when exposed to HIFU, the values decreased significantly, to 181.9 and 114.3ng/mL, suggesting that HIFU can enhance cell cytotoxicity by triggering the release of a drug from the micelles. Furthermore, cellular uptake tests were conducted via the quantitative analysis of intracellular drug concentration within CT-26 (CD44 negative), MDA-MB-231 (CD44 positive), and MDA-MB-231 (CD44 blocked), and then imaged with coumarin-6 loaded micelles. The results verified that intracellular drug delivery can be enhanced efficiently via the CD44 receptor-mediated endocytosis of HA micelles. Moreover, HIFU enhanced the cellular uptake behavior by altering the permeability of the cell membrane. It was also able to aid with the extravasation of micelles into the interior of tumors, which will be explained in further research. Therefore, the present study demonstrates that the micelles prepared in this study can emerge as promising nanocarriers of chemotherapeutic agents for controlled drug release and tumor targeting in cancer treatment.

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 surgeon's 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.

Modeling of chemotactic steering of bacteria-based microrobot using a population-scale approach.

The bacteria-based microrobot (Bacteriobot) is one of the most effective vehicles for drug delivery systems. The bacteriobot consists of a microbead containing therapeutic drugs and bacteria as a sensor and an actuator that can target and guide the bacteriobot to its destination. Many researchers are developing bacteria-based microrobots and establishing the model. In spite of these efforts, a motility model for bacteriobots steered by chemotaxis remains elusive. Because bacterial movement is random and should be described using a stochastic model, bacterial response to the chemo-attractant is difficult to anticipate. In this research, we used a population-scale approach to overcome the main obstacle to the stochastic motion of single bacterium. Also known as Keller-Segel's equation in chemotaxis research, the population-scale approach is not new. It is a well-designed model derived from transport theory and adaptable to any chemotaxis experiment. In addition, we have considered the self-propelled Brownian motion of the bacteriobot in order to represent its stochastic properties. From this perspective, we have proposed a new numerical modelling method combining chemotaxis and Brownian motion to create a bacteriobot model steered by chemotaxis. To obtain modeling parameters, we executed motility analyses of microbeads and bacteriobots without chemotactic steering as well as chemotactic steering analysis of the bacteriobots. The resulting proposed model shows sound agreement with experimental data with a confidence level <0.01.

A hybrid actuated microrobot using an electromagnetic field and flagellated bacteria for tumor-targeting therapy.

In this paper, we propose a new concept for a hybrid actuated microrobot for tumor-targeting therapy. For drug delivery in tumor therapy, various electromagnetic actuated microrobot systems have been studied. In addition, bacteria-based microrobot (so-called bacteriobot), which use tumor targeting and the therapeutic function of the bacteria, has also been proposed for solid tumor therapy. Compared with bacteriobot, electromagnetic actuated microrobot has larger driving force and locomotive controllability due to their position recognition and magnetic field control. However, because electromagnetic actuated microrobot does not have self-tumor targeting, they need to be controlled by an external magnetic field. In contrast, the bacteriobot uses tumor targeting and the bacteria's own motility, and can exhibit self-targeting performance at solid tumors. However, because the propulsion forces of the bacteria are too small, it is very difficult for bacteriobot to track a tumor in a vessel with a large bloodstream. Therefore, we propose a hybrid actuated microrobot combined with electromagnetic actuation in large blood vessels with a macro range and bacterial actuation in small vessels with a micro range. In addition, the proposed microrobot consists of biodegradable and biocompatible microbeads in which the drugs and magnetic particles can be encapsulated; the bacteria can be attached to the surface of the microbeads and propel the microrobot. We carried out macro-manipulation of the hybrid actuated microrobot along a desired path through electromagnetic field control and the micro-manipulation of the hybrid actuated microrobot toward a chemical attractant through the chemotaxis of the bacteria. For the validation of the hybrid actuation of the microrobot, we fabricated a hydrogel microfluidic channel that can generate a chemical gradient. Finally, we evaluated the motility performance of the hybrid actuated microrobot in the hydrogel microfluidic channel. We expect that the hybrid actuated microrobot will be utilized for tumor targeting and therapy in future.

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 12 mm in diameter and 3 mm 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 6 mm(3), 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.

Effect of chitosan coating on a bacteria-based alginate microrobot.

To develop an efficient bacteria-based microrobot, first, therapeutic bacteria should be encapsulated into microbeads using biodegradable and biocompatible materials; second, the releasing rate of the encapsulated bacteria for theragnostic function should be regulated; and finally, flagellated bacteria should be attached on the microbeads to ensure the motility of the microrobot. For the therapeutic bacteria encapsulation, an alginate can be a promising candidate as a biodegradable and biocompatible material. Owing to the non-regulated releasing rate of the encapsulated bacteria in alginate microbeads and the weak attachment of flagellated bacteria on the surface of alginate microbeads, however, the alginate microbeads cannot be used as effective cargo for a bacteria-based microrobot. In this paper, to enhance the stability of the bacteria encapsulation and the adhesion of flagellated bacteria in alginate microbeads, we performed a surface modification of alginate microbeads using chitosan coating. The bacteria-encapsulated alginate microbeads with 1% chitosan coating maintained their structural integrity up to 72 h, whereas the control alginate microbead group without chitosan coating showed severe degradations after 24 h. The chitosan coating in alginate microbeads shows the enhanced attachment of flagellated bacteria on the surface of alginate microbeads. The bacteria-actuated microrobot with the enhanced flagellated bacteria attachment could show approximately 4.2 times higher average velocities than the control bacteria-actuated microrobot without chitosan coating. Consequently, the surface modification using chitosan coating enhanced the structural stability and the motility of the bacteria-based alginate microrobots.

Monocyte-based microrobot with chemotactic motility for tumor theragnosis.

Biocompatibility, sensing, and self-actuation are very important features for a therapeutic biomedical microrobot. As a new concept for tumor theragnosis, this paper proposes a monocyte-based microrobots, which are combining the phagocytosis and engulfment activities containing human acute monocytic leukemia cell line (THP-1) with various sized polystyrene microbeads are engulfed instead of a therapeutic drug. For the validation of the blood vessel barrier-penetrating activity of the monocyte-based microrobot, we fabricate a new cell migration assay with monolayer-cultured endothelial cell (HUVEC), similar with the blood vessels. We perform the penetrating chemotactic motility of the monocyte-based microrobot using various types of the chemo-attractants, such as monocyte chemotactic protein (MCP)-1, human breast cancer cell lines (MCF7)-cell lysates, and -contained alginate spheroids. The monocyte-based microrobot show chemotactic transmigrating motilities similar with what an actual monocyte does. This new paradigm of a monocyte-based microrobot having various useful properties such as biocompatibility, sensing, and self-actuation can become the basis of a biomedical microrobot using monocytes for diagnosis and therapy of various diseases.