A Fast Soft Continuum Catheter Robot Manufacturing Strategy Based on Heterogeneous Modular Magnetic Units.

Developing small-scale continuum catheter robots with inherent soft bodies and high adaptability to different environments holds great promise for biomedical engineering applications. However, current reports indicate that these robots meet challenges when it comes to quick and flexible fabrication with simpler processing components. Herein, we report a millimeter-scale magnetic-polymer-based modular continuum catheter robot (MMCCR) that is capable of performing multifarious bending through a fast and general modular fabrication strategy. By preprogramming the magnetization directions of two types of simple magnetic units, the assembled MMCCR with three discrete magnetic sections could be transformed from a single curvature pose with a large tender angle to a multicurvature S shape in the applied magnetic field. Through static and dynamic deformation analyses for MMCCRs, high adaptability to varied confined spaces can be predicted. By employing a bronchial tree phantom, the proposed MMCCRs demonstrated their capability to adaptively access different channels, even those with challenging geometries that require large bending angles and unique S-shaped contours. The proposed MMCCRs and the fabrication strategy shine new light on the design and development of magnetic continuum robots with versatile deformation styles, which would further enrich broad potential applications in biomedical engineering.

Functionalized Spiral-Rolling Millirobot for Upstream Swimming in Blood Vessel.

Untethered small robots with multiple functions show considerable potential as next-generation catheter-free systems for biomedical applications. However, owing to dynamic blood flow, even effective upstream swimming in blood vessels remains a challenge for the robot, let alone performing medical tasks. This paper presents an untethered millirobot with a streamlined shape that integrates the engine, delivery, and biopsy modules. Based on the proposed spiral-rolling strategy, this robot can move upstream at a record-breaking speed of ≈14 mm s-1 against a blood phantom flow of 136 mm s-1 . Moreover, benefiting from the bioinspired self-sealing orifice and easy-open auto-closed biopsy needle sheath, this robot facilitates several biomedical tasks in blood vessels, such as in vivo drug delivery, tissue and liquid biopsy, and cell transportation in rabbit arteries. This study will benefit the development of wireless millirobots for controllable, minimally invasive, highly integrated, and multifunctional endovascular interventions and will inspire new designs of miniature devices for biomedical applications.

Robot-aided fN∙m torque sensing within an ultrawide dynamic range.

In situ scanning electron microscope (SEM) characterization have enabled the stretching, compression, and bending of micro/nanomaterials and have greatly expanded our understanding of small-scale phenomena. However, as one of the fundamental approaches for material analytics, torsion tests at a small scale remain a major challenge due to the lack of an ultrahigh precise torque sensor and the delicate sample assembly strategy. Herein, we present a microelectromechanical resonant torque sensor with an ultrahigh resolution of up to 4.78 fN∙m within an ultrawide dynamic range of 123 dB. Moreover, we propose a nanorobotic system to realize the precise assembly of microscale specimens with nanoscale positioning accuracy and to conduct repeatable in situ pure torsion tests for the first time. As a demonstration, we characterized the mechanical properties of Si microbeams through torsion tests and found that these microbeams were five-fold stronger than their bulk counterparts. The proposed torsion characterization system pushes the limit of mechanical torsion tests, overcomes the deficiencies in current in situ characterization techniques, and expands our knowledge regarding the behavior of micro/nanomaterials at various loads, which is expected to have significant implications for the eventual development and implementation of materials science.

Multi-functionalized micro-helical capsule robots with superior loading and releasing capabilities.

The functionalization of microrobots is essential for realizing their biomedical application in targeted cargo delivery, but the multifunctional integration of microrobots and controllable cargo delivery remains an enormous challenge at present. This work reports a kind of multi-functionalized micro-helical robot with superior loading capabilities for the controlled release of encapsulants. The magnetic microrobot, with a multilayer capsule helical structure, was developed via multifunctional strategies, including microfluidic synthesis, polyelectrolyte complexation, and surface coating with magnetic nanoparticles. The microrobot is constructed of a helical structure from a calcium alginate microfiber via a co-axial capillary microfluidic system. Then, it is coated with a polyelectrolyte complexation membrane and decorated with magnetic nanoparticles. After multi-step layer-by-layer (LbL) assembly with functionalized units, the structure is converted to a helical capsule possessing a soft and biocompatible polysaccharide alginate/chitosan/alginate shell with Fe3O4 nanoparticles decorated on the surface. The functionalized microrobot not only enables wireless steering with rotational locomotion under the control of a six degrees of freedoms (6-DOFs) electromagnetic system at different frequencies, but it also possesses stimuli-responsive abilities owing to the semi-permeable membrane, which can trigger the controllable release of encapsulants in response to ions in the environment. This work provides an efficient strategy for the superior multi-functionalization of microrobots to achieve enhanced locomotion and encapsulation performance for the loading, transport, and targeted delivery of cargo.

An agglutinate magnetic spray transforms inanimate objects into millirobots for biomedical applications.

Millirobots that can adapt to unstructured environments, operate in confined spaces, and interact with a diverse range of objects would be desirable for exploration and biomedical applications. The continued development of millirobots, however, requires simple and scalable fabrication techniques. Here, we propose a minimalist approach to construct millirobots by coating inanimate objects with a composited agglutinate magnetic spray. Our approach enables a variety of one-dimensional (1D), 2D, or 3D objects to be covered with a thin magnetically drivable film (~100 to 250 micrometers in thickness). The film is thin enough to preserve the original size, morphology, and structure of the objects while providing actuation of up to hundreds of times its own weight. Under the actuation of a magnetic field, our millirobots are able to demonstrate a range of locomotive abilities: crawling, walking, and rolling. Moreover, we can reprogram and disintegrate the magnetic film on our millirobots on demand. We leverage these abilities to demonstrate biomedical applications, including catheter navigation and drug delivery.

Development of a novel massage platform for medical training.

BACKGROUND: Traditional Chinese medicine (TCM) massage has a better effect on treating infant diarrhea compared to medical treatment. The TCM doctors need to be trained to master professional massage techniques. Traditional Chinese massage training relies on the students' understanding ability, and cannot accurately record the students' operating information. This situation leads to insufficient clinical massage skills of the students. OBJECTIVE: This paper proposes a novel massage training platform to quantitatively perceive the massage techniques of students. METHODS: The paper proposed two types of flexible array sensors, which are arranged and placed into the bionic baby according to the position of the human acupoints. The massage techniques of the training object can be analyzed and evaluated during the massage process by studying the voltage from pressure sensors when the participants massage the bionic infant. RESULTS: A medical student was invited to conduct the massage training experiment, and the massage information included the operating strength, massage frequency and the massage direction, which were recorded and analyzed through the training platform. CONCLUSION: The platform can perceive the parameters related to the massage technique of students and can be used for medical training.

Protective effects of organic extracts of Alpinia oxyphylla against hydrogen peroxide-induced cytotoxicity in PC12 cells.

Alpinia oxyphylla, a traditional herb, is widely used for its neuroprotective, antioxidant and memory-improving effects. However, the neuroprotective mechanisms of action of its active ingredients are unclear. In this study, we investigated the neuroprotective effects of various organic extracts of Alpinia oxyphylla on PC12 cells exposed to hydrogen peroxide-induced oxidative injury in vitro. Alpinia oxyphylla was extracted three times with 95% ethanol (representing extracts 1-3). The third 95% ethanol extract was dried and resuspended in water, and then extracted successively with petroleum ether, ethyl acetate and n-butanol (representing extracts 4-6). The cell counting kit-8 assay and microscopy were used to evaluate cell viability and observe the morphology of PC12 cells. The protective effect of the three ethanol extracts (at tested concentrations of 50, 100 and 200 µg/mL) against cytotoxicity to PC12 cells increased in a concentration-dependent manner. The ethyl acetate, petroleum ether and n-butanol extracts (each tested at 100, 150 and 200 µg/mL) had neuroprotective effects as well. The optimum effective concentration ranged from 50-200 µg/mL, and the protective effect of the ethyl acetate extract was comparatively robust. These results demonstrate that organic extracts of Alpinia oxyphylla protect PC12 cells against apoptosis induced by hydrogen peroxide. Our findings should help identify the bioactive neuroprotective components in Alpinia oxyphylla.

Magnetically Actuated Heterogeneous Microcapsule-Robot for the Construction of 3D Bioartificial Architectures.

Core-shell microcapsules as one type of the most attractive carriers and reactors have been widely applied in the fields of drug screening and tissue engineering owing to their excellent biocompatibility and semi-permeability. Yet, the spatial organization of microcapsules with specific shapes into three-dimensional (3D) ordered architectures still remains a big challenge. Here, we present a method to assemble shape-controllable core-shell microcapsules using an untethered magnetic microcapsule-robot. The microcapsule-robot with the shape-matching design can grab the building components tightly during the transportation and assembly processes. The core-shell feature of the microcapsule effectively prevents the magnetic nanoparticles from interacting with bioactive materials. The assembly results of cell-loaded heterogeneous microcapsules reveal that this strategy not only allows the magnetic microcapsule-robot to work in different workspaces in vitro for the creation of 3D constructions but also offers a noninvasive and dynamical manipulation platform by remotely controlling the position and orientation of the soft and liquid-like microcapsule components individually.

Development of a New Robotic Ankle Rehabilitation Platform for Hemiplegic Patients after Stroke.

A large amount of hemiplegic survivors are suffering from motor impairment. Ankle rehabilitation exercises act an important role in recovering patients' walking ability after stroke. Currently, patients mainly perform ankle exercise to reobtain range of motion (ROM) and strength of the ankle joint under a therapist's assistance by manual operation. However, therapists suffer from high work intensity, and most of the existed rehabilitation devices focus on ankle functional training and ignore the importance of neurological rehabilitation in the early hemiplegic stage. In this paper, a new robotic ankle rehabilitation platform (RARP) is proposed to assist patients in executing ankle exercise. The robotic platform consists of two three-DOF symmetric layer-stacking mechanisms, which can execute ankle internal/external rotation, dorsiflexion/plantarflexion, and inversion/eversion exercise while the rotation center of the distal zone of the robotic platform always coincides with patients' ankle pivot center. Three exercise modes including constant-speed exercise, constant torque-impedance exercise, and awareness exercise are developed to execute ankle training corresponding to different rehabilitation stages. Experiments corresponding to these three ankle exercise modes are performed, the result demonstrated that the RARP is capable of executing ankle rehabilitation, and the novel awareness exercise mode motivates patients to proactively participate in ankle training.

Inertial Sensor-Based Motion Analysis of Lower Limbs for Rehabilitation Treatments

The hemiplegic rehabilitation state diagnosing performed by therapists can be biased due to their subjective experience, which may deteriorate the rehabilitation effect. In order to improve this situation, a quantitative evaluation is proposed. Though many motion analysis systems are available, they are too complicated for practical application by therapists. In this paper, a method for detecting the motion of human lower limbs including all degrees of freedom (DOFs) via the inertial sensors is proposed, which permits analyzing the patient's motion ability. This method is applicable to arbitrary walking directions and tracks of persons under study, and its results are unbiased, as compared to therapist qualitative estimations. Using the simplified mathematical model of a human body, the rotation angles for each lower limb joint are calculated from the input signals acquired by the inertial sensors. Finally, the rotation angle versus joint displacement curves are constructed, and the estimated values of joint motion angle and motion ability are obtained. The experimental verification of the proposed motion detection and analysis method was performed, which proved that it can efficiently detect the differences between motion behaviors of disabled and healthy persons and provide a reliable quantitative evaluation of the rehabilitation state.

Inertial Sensor-Based Motion Analysis of Lower Limbs for Rehabilitation Treatments.

The hemiplegic rehabilitation state diagnosing performed by therapists can be biased due to their subjective experience, which may deteriorate the rehabilitation effect. In order to improve this situation, a quantitative evaluation is proposed. Though many motion analysis systems are available, they are too complicated for practical application by therapists. In this paper, a method for detecting the motion of human lower limbs including all degrees of freedom (DOFs) via the inertial sensors is proposed, which permits analyzing the patient's motion ability. This method is applicable to arbitrary walking directions and tracks of persons under study, and its results are unbiased, as compared to therapist qualitative estimations. Using the simplified mathematical model of a human body, the rotation angles for each lower limb joint are calculated from the input signals acquired by the inertial sensors. Finally, the rotation angle versus joint displacement curves are constructed, and the estimated values of joint motion angle and motion ability are obtained. The experimental verification of the proposed motion detection and analysis method was performed, which proved that it can efficiently detect the differences between motion behaviors of disabled and healthy persons and provide a reliable quantitative evaluation of the rehabilitation state.

Nanorobotic System iTRo for Controllable 1D Micro/nano Material Twisting Test.

In-situ micro/nano characterization is an indispensable methodology for material research. However, the precise in-situ SEM twisting of 1D material with large range is still challenge for current techniques, mainly due to the testing device's large size and the misalignment between specimen and the rotation axis. Herein, we propose an in-situ twist test robot (iTRo) to address the above challenges and realize the precise in-situ SEM twisting test for the first time. Firstly, we developed the iTRo and designed a series of control strategies, including assembly error initialization, triple-image alignment (TIA) method for rotation axis alignment, deformation-based contact detection (DCD) method for sample assembly, and switch control for robots cooperation. After that, we chose three typical 1D material, i.e., magnetic microwire Fe74B13Si11C2, glass fiber, and human hair, for twisting test and characterized their properties. The results showed that our approach is able to align the sample to the twisting axis accurately, and it can provide large twisting range, heavy load and high controllability. This work fills the blank of current in-situ mechanical characterization methodologies, which is expected to give significant impact in the fundamental nanomaterial research and practical micro/nano characterization.

Hybrid 3D printing and electrodeposition approach for controllable 3D alginate hydrogel formation.

Calcium alginate hydrogels are widely used as biocompatible materials in a substantial number of biomedical applications. This paper reports on a hybrid 3D printing and electrodeposition approach for forming 3D calcium alginate hydrogels in a controllable manner. Firstly, a specific 3D hydrogel printing system is developed by integrating a customized ejection syringe with a conventional 3D printer. Then, a mixed solution of sodium alginate and CaCO3 nanoparticles is filled into the syringe and can be continuously ejected out of the syringe nozzle onto a conductive substrate. When applying a DC voltage (∼5 V) between the substrate (anode) and the nozzle (cathode), the Ca2+ released from the CaCO3 particles can crosslink the alginate to form calcium alginate hydrogel on the substrate. To elucidate the gel formation mechanism and better control the gel growth, we can further establish and verify a gel growth model by considering several key parameters, i.e., applied voltage and deposition time. The experimental results indicate that the alginate hydrogel of various 3D structures can be formed by controlling the movement of the 3D printer. A cell viability test is conducted and shows that the encapsulated cells in the gel can maintain a high survival rate (∼99% right after gel formation). This research establishes a reliable method for the controllable formation of 3D calcium alginate hydrogel, exhibiting great potential for use in basic biology and applied biomedical engineering.

Vision-based Nano Robotic System for High-throughput Non-embedded Cell Cutting.

Cell cutting is a significant task in biology study, but the highly productive non-embedded cell cutting is still a big challenge for current techniques. This paper proposes a vision-based nano robotic system and then realizes automatic non-embedded cell cutting with this system. First, the nano robotic system is developed and integrated with a nanoknife inside an environmental scanning electron microscopy (ESEM). Then, the positions of the nanoknife and the single cell are recognized, and the distance between them is calculated dynamically based on image processing. To guarantee the positioning accuracy and the working efficiency, we propose a distance-regulated speed adapting strategy, in which the moving speed is adjusted intelligently based on the distance between the nanoknife and the target cell. The results indicate that the automatic non-embedded cutting is able to be achieved within 1-2 mins with low invasion benefiting from the high precise nanorobot system and the sharp edge of nanoknife. This research paves a way for the high-throughput cell cutting at cell's natural condition, which is expected to make significant impact on the biology studies, especially for the in-situ analysis at cellular and subcellular scale, such as cell interaction investigation, neural signal transduction and low invasive cell surgery.