•A modified Halbach array for focused magnetic drug targeting (FMDT) was proposed.•Its optimizations of force magnitude and focusing were conducted by simulation.•Its effectiveness was validated ...through MNPs attraction experiments.•The proposed Halbach array can show better FMDT performances than a typical MDT.
Magnetic drug targeting (MDT) is a therapeutic method that delivers drug carriers containing magnetic nanoparticles to a target lesion by directing them using an external magnetic field. To minimize the possible side effects on the surrounding normal cells, focused magnetic drug targeting (FMDT) has been introduced, which allows drug carriers to be delivered only to the target lesions. FMDT, with its capability for local focusing and wide attraction, aims for highly efficient and concentrated drug delivery. In this study, a modified quasi-axisymmetric Halbach array design was introduced as an external magnetic source to perform FMDT. The proposed Halbach array design has a simple structure that is easy to assemble, unlike earlier Halbach array designs. The optimized Halbach array is fabricated as a result of the optimization of the magnetic force magnitude and local focusing with wide attraction using finite element method (FEM) analysis. Through simulations and experiments, the optimized Halbach array design is validated and a comparative analysis with other magnet types is performed. As a result, the optimization of the Halbach array using FEM is experimentally validated, and it is confirmed that the optimized Halbach array is more effective for FMDT than the permanent magnet used in MDT.
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.
AbstractDuring the last decade, many ophthalmic therapeutic drugs have been clinically approved, and intraocular injection has been a common surgical intervention. Injecting drugs directly into the ...subretinal space is crucial to treat retinal complications effectively. Here, we report a handheld microinjector with two fiber-optic distance sensors and time-delay control (TDC) to mitigate nonlinear disturbances during the injection task. The conventional method exhibited a cosine error of approximately 77 μm at an angle of 45°, whereas our proposed needle reduced measurement errors to ∼6 μm. Also, TDC-based position regulation is designed to adaptively apply motor inputs by estimating disturbances during the handheld task and achieving fast system responses with minor control errors. Phantom studies show a maximum reduction of 26.5% in root-mean-square error (RMSE) compared to the existing approach. Moreover, ex-vivo experiments demonstrated superior and robust injection performance, resulting in an injection RMSE of 10.3 μm.
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•We developed a novel dry-type muscular actuator based on porous carboxylate bacterial cellulose (CBC) membrane.•The porous CBC membrane was prepared by ZnO particulate leaching ...method.•The proposed actuator showed better actuation performance than that of the pure CBC actuator.
Human-friendly electronic products, such as smart mobile phones, soft haptic devices, wearable electronics, and implantable or disposal biomedical devices, will require the use of high-performance durable soft electroactive actuators with eco-friendly, biocompatible, and biodegradable functionalities. Here, we report a high-fidelity bioelectronic muscular actuator based on porous carboxylate bacterial cellulose (CBC) membranes fabricated using the facile zinc oxide (ZnO) particulate leaching (PL) method. The proposed CZ-PL muscular actuator exhibits large deformation, low actuation voltage, fast response, and high-durability in open air environment. In particular, the CZ-PL membrane shows a dramatic increase in the ionic liquid uptake ratio, ionic exchange capacity, and ionic conductivity of up to 70.63%, 22.50%, and 18.2%, respectively, for CBC, resulting in a 5.8 times larger bending deformation than that of the pure CBC actuator. The developed high-performance CZ-PL muscular actuator can be a promising candidate for meeting the tight requirements of human-friendly electronic devices such as wearable devices, biomimetic robots, and biomedical active devices.
•Analysis of twisting tendency in speed mode of twisted string actuator (SM-TSA).•A new simple nonlinear analytical model of SM-TSA.•A nonlinearity compensation algorithm using nonlinear models of ...SM-TSA.•Proposed analytical model could follow more accurately twisting tendency in SM-TSA.•Compensated linear translatory motion of SM-TSA using proposed analytical model.
A twisted string actuator (TSA) is an effective method that can change the rotational motion of a motor into a linear motion, as well as control the speed and stiffness of the actuator. In particular, because the speed mode of the TSA (SM-TSA) can adjust the rotation–linear motion ratio by changing the diameter and length of the twisting shaft, it is a good to increase the usability of the TSA. However, the SM-TSA has a significant limitation in that it demonstrates a nonlinear translatory motion with respect to the constant rotational motion of the motor in terms of its operating principle. To solve this problem, a more accurate modeling method of the SM-TSA should be applied to predict the nonlinearity and compensate for the nonlinearity. Herein, we analyze the tendency of the twisted strings of the SM-TSA and propose a more precise modeling method of the nonlinear SM-TSA. In addition, a nonlinearity compensation algorithm using the proposed modeling of the SM-TSA is developed to linearize the nonlinear translatory motion. Through various experiments of the SM-TSA, we validated that the proposed model exhibits the nonlinearity of the SM-TSA more precisely when compared to the previous model. Additionally, we confirmed that the nonlinearity compensation algorithm using the proposed model can perform more accurate linearization of the translatory motion of the SM-TSA.
Motile cilia move in an asymmetric pattern and implement a metachronal wave (MCW) to facilitate fluid movement in a viscous environment. Studies have been conducted to mimic MCW movement of motile ...cilia, but the fabrication process is too complicating or there are difficulties in accurately mimicking the shape of the cilia. To overcome these limitations, a self‐assembly method is introduced to fabricate a reprogrammable magnetically actuated self‐assembled (RMS) cilia array that can be reprogrammed by changing the magnetization direction through additional magnetization. Using the RMS cilia array, a unilateral cilia array (UCA) channel and a bilateral cilia array (BCA) channel are constructed, and the motion and fluid flow of the RMS cilia array are analyzed by applying different magnetic fields (strike magnetic field and rotating magnetic field). When a rotating magnetic field is applied to the UCA channel, a distinct MCW appears. In the BCA channel test, fluid pumping is observed when a strike magnetic field is applied, whereas fluid mixing is observed when a rotating magnetic field is applied. Based on these results, it is expected that the proposed RMS cilia array and magnetic field actuation can be applied to lab‐on‐a‐chip or microfluidic channels for fluid mixing and pumping.
A reprogrammable magnetically actuated self‐assembled (RMS) cilia array which has a shape and motion similar to natural cilia is proposed. It shows asymmetric motion and metachronal wave (MCW) by reprogramming and applying strike and rotating magnetic fields. Particle movements are examined in fluid tests and analyzed through simulations to confirm the best channel and magnetic field combination for fluid pumping/mixing.
Recently, four-dimensional (4D) printed hydrogel soft robots have attracted attention owing to their simple, repeatable, and accurate manufacturing. However, for application as medical robots, these ...4D printed hydrogel soft robots should be biocompatible and biodegradable. Therefore, in this paper, a 4D printed untethered milli-gripper fabricated using a bio-three-dimensional (3D) printer and an ink composed of a biocompatible and biodegradable chitosan hydrogel and biocompatible citric acid-coated superparamagnetic iron oxide nanoparticles (SPIONs) is proposed. Since the untethered milli-gripper is printed by bio-3D printer, it can be fabricated quickly and precisely with high precision. As the untethered milli-gripper comprises an electroactive hydrogel, its bending angle and speed are precisely controlled by adjusting the electric field strength. Through this, gripping and releasing of cargo were possible. Additionally, because the citric acid-coated SPIONs have high magnetization values, the untethered milli-gripper demonstrates precise position control. Therefore, a cargo delivery is demonstrated in which the untethered milli-gripper grips a cargo, moves it to the desired position, and then release it under an applied electromagnetic field. Moreover, the untethered milli-gripper exhibits excellent cargo-handling ability and can grip and lift cargoes of various size, shapes, and numbers. Furthermore, it is biodegradable due to the presence of chitosan in it, and the citric acid-coated SPIONs remaining after biodegradation demonstrate biocompatibility. Accordingly, the proposed untethered milli-gripper can be used as a minimally invasive small soft robot in vivo for several purposes in the biomedical field.
•4D printed untethered milli-gripper is fabricated using a bio-3D printer and hydrogel ink.•The hydrogel ink is composed of a biocompatible and biodegradable chitosan hydrogel and citric acid-coated SPIONs.•The untethered milli-gripper exhibits excellent cargo-handling ability.•The untethered milli-gripper is biodegradable due to the presence of chitosan in it.•The citric acid-coated SPIONs remaining after biodegradation demonstrate biocompatibility.
•Dual targeting biomimetic macrophage-based drug delivery system to tumor is developed.•Anticancer drug loaded magnetic liposomes are engulfed in to macrophages.•The system is controlled by ...electromagnetic field through blood vessels.•The system can cross the blood barriers and infiltrate to tumor using macrophage’s chemotaxis.•Drug release from liposomes simultaneously kills macrophages and tumor cells.
This work aims to develop a novel electromagnetic and macrophage-mediated drug delivery system to transport anticancer drug (Paclitaxel, PTX)-encapsulated magnetic liposomes (PTX-MLPs) to tumors. The PTX-MLPs are engulfed into macrophages by phagocytosis of murine macrophages (J774A1). Therefore, the macrophages with PTX-MLPs can be dually targeted both by an external electromagnetic field and by chemotaxis of the macrophages to the tumors. Under the electromagnetic field, a single macrophage with PTX-MLPs can be controlled following predefined paths and can reach an average velocity of 10.48±4.43μm/s. Meanwhile, using chemotaxis, the macrophages with PTX-MLPs can infiltrate through a 5μm pore membrane to chemo-attractants in transwell migration assays, with infiltration rate of up to 73.70±4.63%. In addition, their therapeutic efficacy is investigated using an in-vitro cytotoxicity assay on breast cancer (4T1) and colorectal cancer (CT26) models. The results confirm that the macrophages with PTX-MLPs can carry a sufficient amount of drug to kill the cancer cells with the IC50 values for the 4T1 and CT26 cells of 52.97±1.06μg/mL and 117.04±1.82μg/mL, respectively. The outcomes of this study suggest that a potential active cancer therapy can be developed through the dual targeting system using macrophages with PTX-MLPs and magnetic actuation.
For the biomedical application of IPMC actuator, IPMC should generate fast and large tip displacement at low direct current (DC) and alternating current (AC) voltages of 1–2
V. In this paper, the tip ...displacement of polyvinylidene fluoride (PVDF)/polyvinyl pyrrolidone (PVP)/polystyrene sulfonic acid (PSSA) based ionic polymer metal composites (IPMCs) actuators were tested at DC and AC voltages of 1–2
V, and the results were compared with that of the Nafion based IPMC actuator. Research on the PVDF/PVP/PSSA ionic membrane identified two novel compositions of PVDF/PVP/PSSA of blend ratios of 25/15/60 and 30/15/55 for the IPMC actuator which gave higher ion exchange capacity (IEC) and higher water uptake (WUP) than that of the Nafion membrane and proton conductivity nearly equal to that of the Nafion membrane. In an ionic membrane, PVDF is the hydrophobic polymer, PVP the basic, water-soluble polymer, and PSSA the strong, water-soluble polyelectrolyte, which provides the free charge carrier. A high-performance ionic polymer actuator should have large IEC, large WUP and large proton conductivity. At DC and AC voltages of 1–2
V, the PVDF/PVP/PSSA based actuator showed larger actuation with quick response time than those of the Nafion based IPMC actuator. The capacitance and imaginary part of impedance of all IPMCs were calculated at AC voltages of 1–2
V and the actuation performances of IPMCs were also tested and compared.
