Oral administration microrobots for drug delivery.

Oral administration is the most simple, noninvasive, convenient treatment. With the increasing demands on the targeted drug delivery, the traditional oral treatment now is facing some challenges: 1) biologics how to implement the oral treatment and ensure the bioavailability is not lower than the subcutaneous injections; 2) How to achieve targeted therapy of some drugs in the gastrointestinal tract? Based on these two issues, drug delivery microrobots have shown great application prospect in oral drug delivery due to their characteristics of flexible locomotion or driven ability. Therefore, this paper summarizes various drug delivery microrobots developed in recent years and divides them into four categories according to different driving modes: magnetic-controlled drug delivery microrobots, anchored drug delivery microrobots, self-propelled drug delivery microrobots and biohybrid drug delivery microrobots. As oral drug delivery microrobots involve disciplines such as materials science, mechanical engineering, medicine, and control systems, this paper begins by introducing the gastrointestinal barriers that oral drug delivery must overcome. Subsequently, it provides an overview of typical materials involved in the design process of oral drug delivery microrobots. To enhance readers' understanding of the working principles and design process of oral drug delivery microrobots, we present a guideline for designing such microrobots. Furthermore, the current development status of various types of oral drug delivery microrobots is reviewed, summarizing their respective advantages and limitations. Finally, considering the significant concerns regarding safety and clinical translation, we discuss the challenges and prospections of clinical translation for various oral drug delivery microrobots presented in this paper, providing corresponding suggestions for addressing some existing challenges.

Insect-Scale Biped Robots Based on Asymmetrical Friction Effect Induced by Magnetic Torque.

Multimodal and controllable locomotion in complex terrain is of great importance for practical applications of insect-scale robots. Robust locomotion plays a particularly critical role. In this study, a locomotion mechanism for magnetic robots based on asymmetrical friction effect induced by magnetic torque is revealed and defined. The defined mechanism overcomes the design constraints imposed by both robot and substrate structures, enabling the realization of multimodal locomotion on complex terrains. Drawing inspiration from human walking and running locomotion, a biped robot based on the mechanism is proposed, which not only exhibits rapid locomotion across substrates with varying friction coefficients but also achieves precise locomotion along patterned trajectories through programmed controlling. Furthermore, apart from its exceptional locomotive capabilities, the biped robot demonstrates remarkable robustness in terms of load-carrying and weight-bearing performance. The presented locomotion and mechanism herein introduce a novel concept for designing magnetic robots while offering extensive possibilities for practical applications in insect-scale robotics.

Modularized microrobot with lock-and-detachable modules for targeted cell delivery in bile duct.

The magnetic microrobots promise benefits in minimally invasive cell-based therapy. However, they generally suffer from an inevitable compromise between their magnetic responsiveness and biomedical functions. Herein, we report a modularized microrobot consisting of magnetic actuation (MA) and cell scaffold (CS) modules. The MA module with strong magnetism and pH-responsive deformability and the CS module with cell loading-release capabilities were fabricated by three-dimensional printing technique. Subsequently, assembly of modules was performed by designing a shaft-hole structure and customizing their relative dimensions, which enabled magnetic navigation in complex environments, while not deteriorating the cellular functionalities. On-demand disassembly at targeted lesion was then realized to facilitate CS module delivery and retrieval of the MA module. Furthermore, the feasibility of proposed system was validated in an in vivo rabbit bile duct. Therefore, this work presents a modular design-based strategy that enables uncompromised fabrication of multifunctional microrobots and stimulates their development for future cell-based therapy.

Two-dimensional displacement estimation of one-dimensional laser speckle images for detection of acoustic vibration.

Detection and recovery of audio signals using optical methods is an appealing topic. Observing the movement of secondary speckle patterns is a convenient method for such a purpose. In order to have less computational cost and faster processing, one-dimensional laser speckle images are captured by an imaging device, while it sacrifices the ability to detect speckle movement along one axis. This paper proposes a laser microphone system to estimate the two-dimensional displacement from one-dimensional laser speckle images. Hence, we can regenerate audio signals in real time even as the sound source is rotating. Experimental results show that our system is capable of reconstructing audio signals under complex conditions.

Swarming self-adhesive microgels enabled aneurysm on-demand embolization in physiological blood flow.

The recent rise of swarming microrobotics offers great promise in the revolution of minimally invasive embolization procedure for treating aneurysm. However, targeted embolization treatment of aneurysm using microrobots has significant challenges in the delivery capability and filling controllability. Here, we develop an interventional catheterization-integrated swarming microrobotic platform for aneurysm on-demand embolization in physiological blood flow. A pH-responsive self-healing hydrogel doped with magnetic and imaging agents is developed as the embolic microgels, which enables long-term self-adhesion under biological condition in a controllable manner. The embolization strategy is initiated by catheter-assisted deployment of swarming microgels, followed by the application of external magnetic field for targeted aggregation of microrobots into aneurysm sac under the real-time guidance of ultrasound and fluoroscopy imaging. Mild acidic stimulus is applied to trigger the welding of microgels with satisfactory bio-/hemocompatibility and physical stability and realize complete embolization. Our work presents a promising connection between the design and control of microrobotic swarms toward practical applications in dynamic environments.

Wirelessly powered deformable electronic stent for noninvasive electrical stimulation of lower esophageal sphincter.

Electrical stimulation is a promising method to modulate gastrointestinal disorders. However, conventional stimulators need invasive implantation and removal surgeries associated with risks of infection and secondary injuries. Here, we report a battery-free and deformable electronic esophageal stent for wireless stimulation of the lower esophageal sphincter in a noninvasive fashion. The stent consists of an elastic receiver antenna infilled with liquid metal (eutectic gallium-indium), a superelastic nitinol stent skeleton, and a stretchable pulse generator that jointly enables 150% axial elongation and 50% radial compression for transoral delivery through the narrow esophagus. The compliant stent adaptive to the dynamic environment of the esophagus can wirelessly harvest energy through deep tissue. Continuous electrical stimulations delivered by the stent in vivo using pig models significantly increase the pressure of the lower esophageal sphincter. The electronic stent provides a noninvasive platform for bioelectronic therapies in the gastrointestinal tract without the need for open surgery.

Dynamic morphological transformations in soft architected materials via buckling instability encoded heterogeneous magnetization.

The geometric reconfigurations in three-dimensional morphable structures have a wide range of applications in flexible electronic devices and smart systems with unusual mechanical, acoustic, and thermal properties. However, achieving the highly controllable anisotropic transformation and dynamic regulation of architected materials crossing different scales remains challenging. Herein, we develop a magnetic regulation approach that provides an enabling technology to achieve the controllable transformation of morphable structures and unveil their dynamic modulation mechanism as well as potential applications. With buckling instability encoded heterogeneous magnetization profiles inside soft architected materials, spatially and temporally programmed magnetic inputs drive the formation of a variety of anisotropic morphological transformations and dynamic geometric reconfiguration. The introduction of magnetic stimulation could help to predetermine the buckling states of soft architected materials, and enable the formation of definite and controllable buckling states without prolonged magnetic stimulation input. The dynamic modulations can be exploited to build systems with switchable fluidic properties and are demonstrated to achieve capabilities of fluidic manipulation, selective particle trapping, sensitivity-enhanced biomedical analysis, and soft robotics. The work provides new insights to harness the programmable and dynamic morphological transformation of soft architected materials and promises benefits in microfluidics, programmable metamaterials, and biomedical applications.

Multicomponent and multifunctional integrated miniature soft robots.

Miniature soft robots with elaborate structures and programmable physical properties could conduct micromanipulation with high precision as well as access confined and tortuous spaces, which promise benefits in medical tasks and environmental monitoring. To improve the functionalities and adaptability of miniature soft robots, a variety of integrated design and fabrication strategies have been proposed for the development of miniaturized soft robotic systems integrated with multicomponents and multifunctionalities. Combining the latest advancement in fabrication technologies, intelligent materials and active control methods enable these integrated robotic systems to adapt to increasingly complex application scenarios including precision medicine, intelligent electronics, and environmental and proprioceptive sensing. Herein, this review delivers an overview of various integration strategies applicable for miniature soft robotic systems, including semiconductor and microelectronic techniques, modular assembly based on self-healing and welding, modular assembly based on bonding agents, laser machining techniques, template assisted methods with modular material design, and 3D printing techniques. Emerging applications of the integrated miniature soft robots and perspectives for the future design of small-scale intelligent robots are discussed.

Untethered small-scale magnetic soft robot with programmable magnetization and integrated multifunctional modules.

Intelligent magnetic soft robots capable of programmable structural changes and multifunctionality modalities depend on material architectures and methods for controlling magnetization profiles. While some efforts have been made, there are still key challenges in achieving programmable magnetization profile and creating heterogeneous architectures. Here, we directly embed programmed magnetization patterns (magnetization modules) into the adhesive sticker layers to construct soft robots with programmable magnetization profiles and geometries and then integrate spatially distributed functional modules. Functional modules including temperature and ultraviolet light sensing particles, pH sensing sheets, oil sensing foams, positioning electronic component, circuit foils, and therapy patch films are integrated into soft robots. These test beds are used to explore multimodal robot locomotion and various applications related to environmental sensing and detection, circuit repairing, and gastric ulcer coating, respectively. This proposed approach to engineering modular soft material systems has the potential to expand the functionality, versatility, and adaptability of soft robots.

Decoupling and Reprogramming the Wiggling Motion of Midge Larvae Using a Soft Robotic Platform.

The efficient motility of invertebrates helps them survive under evolutionary pressures. Reconstructing the locomotion of invertebrates and decoupling the influence of individual basic motion are crucial for understanding their underlying mechanisms, which, however, generally remain a challenge due to the complexity of locomotion gaits. Herein, a magnetic soft robot to reproduce midge larva's key natural swimming gaits is developed, and the coupling effect between body curling and rotation on motility is investigated. Through the authors' systematically decoupling studies using programmed magnetic field inputs, the soft robot (named LarvaBot) experiences various coupled gaits, including biomimetic side-to-side flexures, and unveils that the optimal rotation amplitude and the synchronization of curling and rotation greatly enhance its motility. The LarvaBot achieves fast locomotion and upstream capability at the moderate Reynolds number regime. The soft robotics-based platform provides new insight to decouple complex biological locomotion, and design programmed swimming gaits for the fast locomotion of soft-bodied swimmers.

AGMB-Transformer: Anatomy-Guided Multi-Branch Transformer Network for Automated Evaluation of Root Canal Therapy.

Accurate evaluation of the treatment result on X-ray images is a significant and challenging step in root canal therapy since the incorrect interpretation of the therapy results will hamper timely follow-up which is crucial to the patients' treatment outcome. Nowadays, the evaluation is performed in a manual manner, which is time-consuming, subjective, and error-prone. In this article, we aim to automate this process by leveraging the advances in computer vision and artificial intelligence, to provide an objective and accurate method for root canal therapy result assessment. A novel anatomy-guided multi-branch Transformer (AGMB-Transformer) network is proposed, which first extracts a set of anatomy features and then uses them to guide a multi-branch Transformer network for evaluation. Specifically, we design a polynomial curve fitting segmentation strategy with the help of landmark detection to extract the anatomy features. Moreover, a branch fusion module and a multi-branch structure including our progressive Transformer and Group Multi-Head Self-Attention (GMHSA) are designed to focus on both global and local features for an accurate diagnosis. To facilitate the research, we have collected a large-scale root canal therapy evaluation dataset with 245 root canal therapy X-ray images, and the experiment results show that our AGMB-Transformer can improve the diagnosis accuracy from 57.96% to 90.20% compared with the baseline network. The proposed AGMB-Transformer can achieve a highly accurate evaluation of root canal therapy. To our best knowledge, our work is the first to perform automatic root canal therapy evaluation and has important clinical value to reduce the workload of endodontists.

A mobile magnetic pad with fast light-switchable adhesion capabilities.

Octopus suckers that possess the ability to actively control adhesion through muscle actuation have inspired artificial adhesives for safe manipulation of thin and delicate objects. However, the design of adhesives with fast adhesion switching speed to transport cargoes in confined spaces remains an open challenge. Here, we present an untethered magnetic adhesive pad combining the functionality of fast adhesion switching and remotely controlled locomotion. The adhesive pad can be activated from low-adhesion state to high-adhesion state by near infrared laser within 30 s, allowing to fulfill a high-throughput task of retrieving and releasing objects. Moreover, under the guidance of external magnetic field, the proposed pad is demonstrated to transport thin and fragile electronic components across a tortuous path, thus indicating its potential for dexterous delivery in complex working environments.

Tethered and Untethered 3D Microactuators Fabricated by Two-Photon Polymerization: A Review.

Microactuators, which can transform external stimuli into mechanical motion at microscale, have attracted extensive attention because they can be used to construct microelectromechanical systems (MEMS) and/or microrobots, resulting in extensive applications in a large number of fields such as noninvasive surgery, targeted delivery, and biomedical machines. In contrast to classical 2D MEMS devices, 3D microactuators provide a new platform for the research of stimuli-responsive functional devices. However, traditional planar processing techniques based on photolithography are inadequate in the construction of 3D microstructures. To solve this issue, researchers have proposed many strategies, among which 3D laser printing is becoming a prospective technique to create smart devices at the microscale because of its versatility, adjustability, and flexibility. Here, we review the recent progress in stimulus-responsive 3D microactuators fabricated with 3D laser printing depending on different stimuli. Then, an outlook of the design, fabrication, control, and applications of 3D laser-printed microactuators is propounded with the goal of providing a reference for related research.

On-line measurement of clamping force for injection molding machine using ultrasonic technology.

The on-line measurement of clamping force is essential for injection molding equipment and process. A method for on-line measurement of clamping force using ultrasonic technology is proposed in this study. Based on the sono-elasticity theory, a new mathematical model is established to describe the relationship between ultrasonic propagation time and clamping force. A series of experiments are then performed to validate the proposed method. Findings show this method corresponds well with the magnetic enclosed type clamping force tester method, with difference squares less than 0.65 (MPa)2, and standard deviations less than 0.11 MPa. Ultrasonic parameters influence measurement results, with larger ultrasonic probe wafer diameter and higher ultrasonic probe frequency producing better measurement accuracy. Additionally, measurement accuracy is insensitive to the sampling frequency of ultrasonic signals. The proposed method has the advantages of high accuracy and high stability, being non-interfering, non-destructive, low-cost, on-line and with good adherence to health and safety, and it has significant application prospects in injection molding production.

Single-Ring Magnetic Levitation Configuration for Object Manipulation and Density-Based Measurement.

Magnetic levitation is a recent research hot spot; however, most of the extant configurations use two magnets with like poles facing each other. This paper proposes a novel magnetic levitation configuration that is based on a single ring magnet, and this configuration opens a wide operational space that enables object manipulation and density-based measurement. We develop a mathematical model to calculate the magnetic field around the magnet and to numerically correlate the levitation height and density of the object. Experimental results prove that this novel configuration can achieve a high accuracy (±0.0005 to ±0.0078 g/cm3) in density measurement for small-sized (∼5 µL) samples. It can manipulate particles, powders, and oil droplets effectively without any direct contact, and it has high sensitivity in the separation of multiple diamagnetic objects with slight differences in densities as well. The accuracy and sensitivity of the proposed configuration are both higher than those of the extant configurations. All of these results are expected to promote deeper study and applications of the magnetic levitation configuration in the field of density-based characterizations and manipulations.

Metabolic alterations in the rat cerebellum following acute middle cerebral artery occlusion, as determined by 1H NMR spectroscopy.

Supratentorial focal ischemia may reduce cerebral blood volume and cerebellar glucose metabolic rate contralateral to the region of ischemia. The present study investigated the effects of middle cerebral artery occlusion (MCAO) on cerebral metabolism in the ischemic cerebral hemisphere and the non­ischemic cerebellum in rats 1, 3, 9 and 24 h following ischemia using ex vivo proton nuclear magnetic resonance (1H NMR) spectroscopy. The results demonstrated that focal ischemia induced increases in the levels of lactate and alanine, and a decrease in succinate, as early as 1 h following ischemia in the left cerebral hemisphere and the right cerebellum. A continuous increase in lactate levels and decrease in creatine levels were detected in both cerebral areas 3 and 24 h post­MCAO. The most obvious difference between the two cerebral areas was that there was no statistically significant difference in N­acetyl aspartate (NAA) levels in the right cerebellum at all time points; however, the amino acid levels of NAA in the left cerebral hemisphere were markedly decreased 3, 9 and 24 h post­MCAO. In addition, an obvious increase in glutamine was observed in the right and left cerebellum at 3, 9 and 24 h post­MCAO. Furthermore, the present study demonstrated that γ­aminobutyric acid levels were decreased at 1 h in the left and right cerebellum and were evidently increased at 24 h in the right cerebellum post­MCAO. In conclusion, supratentorial ischemia has been indicated to affect the activities of the non­ischemic contralateral cerebellum. Therefore, these results suggested that an NMR­based metabonomic approach may be used as a potential means to elucidate cerebral and cerebellar metabolism following MCAO, which may help improve understanding regarding cerebral infarction at a molecular level. Ex vivo 1H NMR analysis may be useful for the assessment of clinical biopsies.

Metabolite changes in the ipsilateral and contralateral cerebral hemispheres in rats with middle cerebral artery occlusion.

Cerebral ischemia not only causes pathological changes in the ischemic areas but also induces a series of secondary changes in more distal brain regions (such as the contralateral cerebral hemisphere). The impact of supratentorial lesions, which are the most common type of lesion, on the contralateral cerebellum has been studied in patients by positron emission tomography, single photon emission computed tomography, magnetic resonance imaging and diffusion tensor imaging. In the present study, we investigated metabolite changes in the contralateral cerebral hemisphere after supratentorial unilateral ischemia using nuclear magnetic resonance spectroscopy-based metabonomics. The permanent middle cerebral artery occlusion model of ischemic stroke was established in rats. Rats were randomly divided into the middle cerebral artery occlusion 1-, 3-, 9- and 24-hour groups and the sham group. 1H nuclear magnetic resonance spectroscopy was used to detect metabolites in the left and right cerebral hemispheres. Compared with the sham group, the concentrations of lactate, alanine, γ-aminobutyric acid, choline and glycine in the ischemic cerebral hemisphere were increased in the acute stage, while the concentrations of N-acetyl aspartate, creatinine, glutamate and aspartate were decreased. This demonstrates that there is an upregulation of anaerobic glycolysis (shown by the increase in lactate), a perturbation of choline metabolism (suggested by the increase in choline), neuronal cell damage (shown by the decrease in N-acetyl aspartate) and neurotransmitter imbalance (evidenced by the increase in γ-aminobutyric acid and glycine and by the decrease in glutamate and aspartate) in the acute stage of cerebral ischemia. In the contralateral hemisphere, the concentrations of lactate, alanine, glycine, choline and aspartate were increased, while the concentrations of γ-aminobutyric acid, glutamate and creatinine were decreased. This suggests that there is a difference in the metabolite changes induced by ischemic injury in the contralateral and ipsilateral cerebral hemispheres. Our findings demonstrate the presence of characteristic changes in metabolites in the contralateral hemisphere and suggest that they are most likely caused by metabolic changes in the ischemic hemisphere.

Whole-brain 320-detector row dynamic volume CT perfusion detected crossed cerebellar diaschisis after spontaneous intracerebral hemorrhage.

INTRODUCTION: The purpose of this study was to evaluate the value of 320-detector row CT used to detect crossed cerebellar diaschisis (CCD) in patients with unilateral supratentorial spontaneous intracerebral hemorrhage (SICH). METHODS: We investigated 62 of 156 patients with unilateral supratentorial SICH using 320-detector row CT scanning. Regional cerebral blood flow (rCBF), cerebral blood volume (rCBV), mean transit time (rMTT), and time to peak (rTTP) levels were measured in different regions of interest (ROIs) that were manually outlined on computed tomography perfusion (CTP) for the cerebrum, including normal-appearing brain tissue that surrounded the perilesional low-density area (NA) and the perihematomal low-density area (PA) in all patients and the cerebellum (ipsilateral and contralateral) in CCD-positive patients. RESULTS: Of 62 cases, a total of 14 met the criteria for CCD due to cerebellar perfusion asymmetry on CTP maps. In the quantitative analysis, significant differences were found in the perfusion parameters between the contralateral and ipsilateral cerebellum in CCD-positive cases. No significant differences were found between the CCD-positive group and the CCD-negative group according to the hematoma volume, NIHSS scores, and cerebral perfusion abnormality (each P > 0.05). The correlation analysis of the degree of NA, PA perfusion abnormality, and the degree of CCD severity showed negative and significant linear correlations (R, -0.66∼-0.56; P < 0.05). CONCLUSION: 320-detector row CT is a robust and practicable method for the comprehensive primary imaging work-up of CCD in unilateral supratentorial SICH patients.