4D Printed Soft Microactuator for Particle Manipulation via Surrounding Medium Variation.

Soft actuators have assumed vital roles in a diverse number of research and application fields, driving innovation and transformative advancements. Using 3D molding of smart materials and combining these materials through structural design strategies, a single soft actuator can achieve multiple functions. However, it is still challenging to realize soft actuators that possess high environmental adaptability while capable of different tasks. Here, the response threshold of a soft actuator is modulated by precisely tuning the ratio of stimulus-responsive groups in hydrogels. By combining a heterogeneous bilayer membrane structure and in situ multimaterial printing, the obtained soft actuator deformed in response to changes in the surrounding medium. The response medium is suitable for both biotic and abiotic environments, and the response rate is fast. By changing the surrounding medium, the precise capture, manipulation, and release of micron-sized particles of different diameters in 3D are realized. In addition, static capture of a single red blood cell is realized using biologically responsive medium changes. Finally, the experimental results are well predicted using finite element analysis. It is believed that with further optimization of the structure size and autonomous navigation platform, the proposed soft microactuator has significant potential to function as an easy-to-manipulate multifunctional robot.

Fast-Swimming Soft Robotic Fish Actuated by Bionic Muscle.

Soft underwater swimming robots actuated by smart materials have unique advantages in exploring the ocean, such as low noise, high flexibility, and friendly environment interaction ability. However, most of them typically exhibit limited swimming speed and flexibility due to the inherent characteristics of soft actuation materials. The actuation method and structural design of soft robots are key elements to improve their motion performance. Inspired by the muscle actuation and swimming mechanism of natural fish, a fast-swimming soft robotic fish actuated by a bionic muscle actuator made of dielectric elastomer is presented. The results show that by controlling the two independent actuating units of a biomimetic actuator, the robotic fish can not only achieve continuous C-shaped body motion similar to natural fish but also have a large bending angle (maximum unidirectional angle is about 40°) and thrust force (peak thrust is about 14 mN). In addition, the coupling relationship between the swimming speed and actuating parameters of the robotic fish is established through experiments and theoretical analysis. By optimizing the control strategy, the robotic fish can demonstrate a fast swimming speed of 76 mm/s (0.76 body length/s), which is much faster than most of the reported soft robotic fish driven by nonbiological soft materials that swim in body and/or caudal fin propulsion mode. What's more, by applying programmed voltage excitation to the actuating units of the bionic muscle, the robotic fish can be steered along specific trajectories, such as continuous turning motions and an S-shaped routine. This study is beneficial for promoting the design and development of high-performance soft underwater robots, and the adopted biomimetic mechanisms, as well as actuating methods, can be extended to other various flexible devices and soft robots.

Steering Muscle-Based Bio-Syncretic Robot Through Bionic Optimized Biped Mechanical Design.

Bio-syncretic robots consisting of artificial structures and living muscle cells have attracted much attention owing to their potential advantages, such as high drive efficiency, miniaturization, and compatibility. Motion controllability, as an important factor related to the main performance of bio-syncretic robots, has been explored in numerous studies. However, most of the existing bio-syncretic robots still face challenges related to the further development of steerable kinematic dexterity. In this study, a bionic optimized biped fully soft bio-syncretic robot actuated by two muscle tissues and steered with a direction-controllable electric field generated by external circularly distributed multiple electrodes has been developed. The developed bio-syncretic robot could realize wirelessly steerable motion and effective transportation of microparticle cargo on artificial polystyrene and biological pork tripe surfaces. This study may provide an effective strategy for the development of bio-syncretic robots and other related studies, such as nonliving soft robot design and muscle tissue engineering.

Stiffness-tunable substrate fabrication by DMDbased optical projection lithography for cancer cell invasion studies.

OBJECTIVE: Cancer cell invasion is a critical cause of fatality in cancer patients. Physiologically relevant tumor models play a key role in revealing the mechanisms underlying the invasive behavior of cancer cells. However, most existing models only consider interactions between cells and extracellular matrix (ECM) components while neglecting the role of matrix stiffness in tumor invasion. Here, we propose an effective approach that can construct stiffness-tunable substrates using digital mirror device (DMD)-based optical projection lithography to explore the invasion behavior of cancer cells. The printability, mechanical properties, and cell viability of three-dimensional (3D) models can be tuned by the concentration of prepolymer and the exposure time. The invasion trajectories of gastric cancer cells in tumor models of different stiffness were automatically detected and tracked in real-time using a deep learning algorithm. The results show that tumor models of different mechanical stiffness can yield distinct regulatory effects. Moreover, owing to the biophysical characteristics of the 3D in vitro model, different cellular substructures of cancer cells were induced. The proposed tunable substrate construction method can be used to build various microstructures to achieve simulation of cancer invasion and antitumor screening, which has great potential in promoting personalized therapy.

Nanomechanical Analysis of Living Small Extracellular Vesicles to Identify Gastric Cancer Cell Malignancy Based on a Biomimetic Peritoneum.

Gastric cancer is one of the most prevalent digestive malignancies. The lack of effective in vitro peritoneal models has hindered the exploration of the potential mechanisms behind gastric cancer's peritoneal metastasis. An accumulating body of research indicates that small extracellular vesicles (sEVs) play an indispensable role in peritoneal metastasis of gastric cancer cells. In this study, a biomimetic peritoneum was constructed. The biomimetic model is similar to real peritoneum in internal microstructure, composition, and primary function, and it enables the recurrence of peritoneal metastasis process in vitro. Based on this model, the association between the mechanical properties of sEVs and the invasiveness of gastric cancer was identified. By performing nanomechanical analysis on sEVs, we found that the Young's modulus of sEVs can be utilized to differentiate between malignant clinical samples (ascites) and nonmalignant clinical samples (peritoneal lavage). Furthermore, patients' ascites-derived sEVs were verified to stimulate the mesothelial-to-mesenchymal transition, thereby promoting peritoneal metastasis. In summary, nanomechanical analysis of living sEVs could be utilized for the noninvasive diagnosis of malignant degree and peritoneal metastasis of gastric cancer. This finding is expected to contribute future treatments.

Novel Operation Mechanism and Multifunctional Applications of Bubble Microrobots.

Microrobots have emerged as powerful tools for manipulating particles, cells, and assembling biological tissue structures at the microscale. However, achieving precise and flexible operation of arbitrary-shaped microstructures in 3D space remains a challenge. In this study, three novel operation methods based on bubble microrobots are proposed to enable delicate and multifunctional manipulation of various microstructures. These methods include 3D turnover, fixed-point rotation, and 3D ejection. By harnessing the combined principles of the effect of the heat flow field and surface tension of an optothermally generated bubble, the bubble microrobot can perform tasks such as flipping an SIA humanoid structure, rotating a bird-like structure, and launching a hollow rocket-like structure. The proposed multi-mode operation of bubble microrobots enables diverse attitude adjustments of microstructures with different sizes and shapes in both 2D and 3D spaces. As a demonstration, a biological microenvironment of brain glioblastoma is constructed by the bubble microrobot. The simplicity, versatility, and flexibility of this proposed method hold great promise for applications in micromanipulation, assembly, and tissue engineering.

Dual-Responsive Nanorobot-Based Marsupial Robotic System for Intracranial Cross-Scale Targeting Drug Delivery.

Nanorobots capable of active movement are an exciting technology for targeted therapeutic intervention. However, the extensive motion range and hindrance of the blood-brain barrier impeded their clinical translation in glioblastoma therapy. Here, a marsupial robotic system constructed by integrating chemical/magnetic hybrid nanorobots (child robots) with a miniature magnetic continuum robot (mother robot) for intracranial cross-scale targeting drug delivery is reported. For primary targeting on macroscale, the continuum robot enters the cranial cavity through a minimally invasive channel (e.g., Ommaya device) in the skull and transports the nanorobots to pathogenic regions. Upon circumventing the blood-brain barrier, the released nanorobots perform secondary targeting on microscale to further enhance the spatial resolution of drug delivery. In vitro experiments against primary glioblastoma cells derived from different patients are conducted for personalized treatment guidance. The operation feasibility within organisms is shown in ex vivo swine brain experiments. The biosafety of the treatment system is suggested in in vivo experiments. Owing to the hierarchical targeting method, the targeting rate, targeting accuracy, and treatment efficacy have improved greatly. The marsupial robotic system offers a novel intracranial local therapeutic strategy and constitutes a key milestone in the development of glioblastoma treatment platforms.

Skin-Inspired Capacitive Flexible Tactile Sensor with an Asymmetric Structure for Detecting Directional Shear Forces.

Flexible pressure sensors based on micro-/nanostructures can be integrated into robots to achieve sensitive tactile perception. However, conventional symmetric structures, such as pyramids or hemispheres, can sense only the magnitude of a force and not its direction. In this study, a capacitive flexible tactile sensor inspired by skin structures and based on an asymmetric microhair structure array to perceive directional shear force is designed. Asymmetric microhair structures are obtained by two-photon polymerization (TPP) and replication. Owing to the features of asymmetric microhair structures, different shear force directions result in different deformations. The designed device can determine the directions of both static and dynamic shear forces. Additionally, it exhibits large response scales ranging from 30 Pa to 300 kPa and maintains high stability even after 5000 cycles; the final relative capacitive change (ΔC/C0 ) is <2.5%. This flexible tactile sensor has the potential to improve the perception and manipulation ability of dexterous hands and enhance the intelligence of robots.

Correlative super-resolution bright-field and fluorescence imaging by microsphere assisted microscopy.

The resolution of fluorescence imaging has been significantly enhanced with the development of super-resolution imaging techniques, surpassing the diffraction limit and reaching sub-diffraction scales of tens of nanometers. However, the resolution of the bright-field images of cells is restricted by the diffraction limit, leading to a significant gap between the resolutions of fluorescence and bright-field imaging, which hinders the research of the precise distribution of intracellular nanostructures. A microsphere superlens offers a promising solution by providing label-free super-resolution imaging capabilities compatible with fluorescence super-resolution imaging. In this study, we used microsphere superlenses to simultaneously enhance the resolution of bright-field and fluorescence imaging, achieving correlated super-resolution bright-field and fluorescence imaging. Compared to conventional bright-field images, we improved the imaging resolution from λ/1.3 to λ/4.2. A correlative super-resolution of mouse skeletal muscle cells was achieved, enabling the clear observation of the precise distribution of nanoparticles in mouse skeletal muscle cells. Furthermore, microsphere superlenses inherit the advantages of optical imaging, which is expected to enable the capturing of ultrafast biological activity within living cells with extremely high temporal resolutions.

An integrated hinged dual-probe for co-target fast switching imaging.

The diversity of functional applications of atomic force microscopes is the key to the development of nanotechnology. However, the single probe configuration of the traditional atomic force microscope restricts the realization of different application requirements for the same target area of a single sample, and the replacement of the working probe will lead to the loss of the target area. Here, the design, simulation, fabrication, and application of a unique atomic force microscope dual-probe are presented, which consists of a pair of parallel cantilevers with a narrow gap and a U-shaped hinged probe base. The Integrated Hinged Dual-Probe (IHDP) is developed specifically for fast switching of probes working in limited space and independent and precise manipulation of each probe. The deflection signal sensing of two cantilevers is achieved simultaneously by a single laser beam, and the decoupled independent cantilever deflection signals do not interfere with each other. The switching of the working probe is achieved by a piezoelectric ceramic with a 2 µm stroke and U-shaped hinge structure, which is fast and does not require tedious and repetitive spatial position calibration. By measuring standard grid samples, IHDP exhibits excellent measurement and characterization capabilities. Finally, a working probe switching imaging experiment was conducted on solidified rat cardiomyocytes, and the experimental process and imaging results demonstrated the superiority of IHDP in switching probe scanning imaging of the same target area of a single sample. The two probes of IHDP can undergo arbitrary functionalization modifications, which helps achieve multidimensional information acquisition for a single target.

Quantitative Biofabrication Platform for Collagen-Based Peripheral Nerve Grafts with Structural and Chemical Guidance.

Owing to its crucial role in the human body, collagen has immense potential as a material for the biofabrication of tissues and organs. However, highly refined fabrication using collagen remains difficult, primarily because of its notably soft properties. A quantitative biofabrication platform to construct collagen-based peripheral nerve grafts, incorporating bionic structural and chemical guidance cues, is introduced. A viscoelastic model for collagen, which facilitates simulating material relaxation and fabricating collagen-based neural grafts, achieving a maximum channel density similar to that of the native nerve structure of longitudinal microchannel arrays, is established. For axonal regeneration over considerable distances, a gradient printing control model and quantitative method are developed to realize the high-precision gradient distribution of nerve growth factor required to obtain nerve grafts through one-step bioprinting. Experiments verify that the bioprinted graft effectively guides linear axonal growth in vitro and in vivo. This study should advance biofabrication methods for a variety of human tissue-engineering applications requiring tailored cues.

Uncover rock-climbing fish's secret of balancing tight adhesion and fast sliding for bioinspired robots.

The underlying principle of the unique dynamic adaptive adhesion capability of a rock-climbing fish (Beaufortia kweichowensis) that can resist a pull-off force of 1000 times its weight while achieving simultaneous fast sliding (7.83 body lengths per second (BL/S)) remains a mystery in the literature. This adhesion-sliding ability has long been sought for underwater robots. However, strong surface adhesion and fast sliding appear to contradict each other due to the need for high surface contact stress. The skillfully balanced mechanism of the tight surface adhesion and fast sliding of the rock-climbing fish is disclosed in this work. The Stefan force (0.1 mN/mm2) generated by micro-setae on pectoral fins and ventral fins leads to a 70 N/m2 adhesion force by conforming the overall body of the fish to a surface to form a sealing chamber. The pull-off force is neutralized simultaneously due to the negative pressure caused by the volumetric change of the chamber. The rock-climbing fish's micro-setae hydrodynamic interaction and sealing suction cup work cohesively to contribute to low friction and high pull-off-force resistance and can therefore slide rapidly while clinging to the surface. Inspired by this unique mechanism, an underwater robot is developed with incorporated structures that mimic the functionality of the rock-climbing fish via a micro-setae array attached to a soft self-adaptive chamber, a setup which demonstrates superiority over conventional structures in terms of balancing tight underwater adhesion and fast sliding.

A 4D-Printing Inverse Design Strategy for Micromachines with Customized Shape-Morphing.

An active heterostructure with smart-response material used as "muscle" and inactive material as "skeleton" can deform over time to respond to external stimuli. 4D printing integrated with two-photon polymerization technology and smart material allows the material or characteristic distribution of active heterostructures to be defined directly at the microscale, providing a huge programmable space. However, the high degree of design freedom and the microscale pose a challenge to the construction of micromachines with customized shape morphing. Here, a reverse design strategy based on multi-material stepwise 4D printing is proposed to guide the structural design of biomimetic micromachines. Inspired by the piecewise constant curvature model of soft robot, a reverse design algorithm based on the Timoshenko model is developed. The algorithm can approximate 2D features to a constant-curvature model and determine an acceptable material distribution within the explored printing range. Three Chinese "Long" (Chinese dragon heralds of good fortune) designed by the strategy can deform to the customized shape. In addition, a microcrawler printed using this method can imitate a real inchworm gait. These results demonstrate that this method can be an efficient tool for the action or shape design of bionic soft microrobots or micromachines with predetermined functions.

Self-Sensing Scanning Superlens for Three-Dimensional Noninvasive Visible-Light Nanoscale Imaging on Complex Surfaces.

Microsphere-assisted super-resolution imaging technology offers label-free, real-time dynamic imaging via white light, which has potential applications in living systems and the nanoscale detection of semiconductor chips. Scanning can aid in overcoming the limitations of the imaging area of a single microsphere superlens. However, the current scanning imaging method based on the microsphere superlens cannot achieve super-resolution optical imaging of complex curved surfaces. Unfortunately, most natural surfaces are composed of complex curved surfaces at the microscale. In this study, we developed a method to overcome this limitation through a microsphere superlens with a feedback capability. By maintaining a constant force between the microspheres and the sample, noninvasive super-resolution optical imaging of complex abiotic and biological surfaces was achieved, and the three-dimensional information on the sample was simultaneously obtained. The proposed method significantly expands the universality of scanning microsphere superlenses for samples and promotes their widespread use.

A reinforcement learning algorithm acquires demonstration from the training agent by dividing the task space.

Although reinforcement learning (RL) has made numerous breakthroughs in recent years, addressing reward-sparse environments remains challenging and requires further exploration. Many studies improve the performance of the agents by introducing the state-action pairs experienced by an expert. However, such kinds of strategies almost depend on the quality of the demonstration by the expert, which is rarely optimal in a real-world environment, and struggle with learning from sub-optimal demonstrations. In this paper, a self-imitation learning algorithm based on the task space division is proposed to realize an efficient high-quality demonstration acquire while the training process. To determine the quality of the trajectory, some well-designed criteria are defined in the task space for finding a better demonstration. The results show that the proposed algorithm will improve the success rate of robot control and achieve a high mean Q value per step. The algorithm framework proposed in this paper has illustrated a great potential to learn from a demonstration generated by using self-policy in sparse environments and can be used in reward-sparse environments where the task space can be divided.

Quantitative characterization of cell physiological state based on dynamical cell mechanics for drug efficacy indication.

Cell mechanics is essential to cell development and function, and its dynamics evolution reflects the physiological state of cells. Here, we investigate the dynamical mechanical properties of single cells under various drug conditions, and present two mathematical approaches to quantitatively characterizing the cell physiological state. It is demonstrated that the cellular mechanical properties upon the drug action increase over time and tend to saturate, and can be mathematically characterized by a linear time-invariant dynamical model. It is shown that the transition matrices of dynamical cell systems significantly improve the classification accuracies of the cells under different drug actions. Furthermore, it is revealed that there exists a positive linear correlation between the cytoskeleton density and the cellular mechanical properties, and the physiological state of a cell in terms of its cytoskeleton density can be predicted from its mechanical properties by a linear regression model. This study builds a relationship between the cellular mechanical properties and the cellular physiological state, adding information for evaluating drug efficacy.

Restoring Voluntary Bimanual Activities of Patients with Chronic Hemiparesis through a Foot-Controlled Hand/Forearm Exoskeleton.

A significant number of stroke patients are permanently left with a hemiparetic upper limb after the poststroke six-month golden recovery period, resulting in a drastic decline in their quality of life. This study develops a novel foot-controlled hand/forearm exoskeleton that enables patients with hemiparetic hands and forearms to restore their voluntary activities of daily living. Patients can accomplish dexterous hand/arm manipulation on their own with the assistance of a foot-controlled hand/forearm exoskeleton by utilizing foot movements on the unaffected side as command signals. The proposed foot-controlled exoskeleton was first tested on a stroke patient with a chronic hemiparetic upper limb. The testing results showed that the forearm exoskeleton can assist the patient in achieving approximately 107°of voluntary forearm rotation with a static control error less than 1.7°, whereas the hand exoskeleton can assist the patient in realizing at least six different voluntary hand gestures with a success rate of 100%. Further experiments involving more patients demonstrated that the foot-controlled hand/forearm exoskeleton can help patients in restoring some of the voluntary activities of daily living with their paretic upper limb, such as picking up food to eat and opening water bottles to drink, and etc. This research implies that the foot-controlled hand/forearm exoskeleton is a viable way to restore the upper limb activities of stroke patients with chronic hemiparesis.

A Review of the Development and Challenges of Cell Mechanical Models.

Cell models can express a variety of cell information, including mechanical properties, electrical properties, and chemical properties. Through the analysis of these properties, we can fully understand the physiological state of cells. As such, cell modeling has gradually become a topic of great interest, and a number of cell models have been established over the last few decades. In this paper, the development of various cell mechanical models has been systematically reviewed. First, continuum theoretical models, which were established by ignoring cell structures, are summarized, including the cortical membrane droplet model, solid model, power series structure damping model, multiphase model, and finite element model. Next, microstructural models based on the structure and function of cells are summarized, including the tension integration model, porous solid model, hinged cable net model, porous elastic model, energy dissipation model, and muscle model. What's more, from multiple viewpoints, the strengths and weaknesses of each cell mechanical model have been analyzed in detail. Finally, the potential challenges and applications in the development of cell mechanical models are discussed. This paper contributes to the development of different fields, such as biological cytology, drug therapy, and bio-syncretic robots.

Large Range Atomic Force Microscopy with High Aspect Ratio Micropipette Probe for Deep Trench Imaging.

Atomic force microscopy (AFM) has been adopted in both industry and academia for high-fidelity, full-profile topographic characterization. Typically, the tiny tip of the cantilever and the limited traveling range of the scanner restrict AFM measurement to relatively flat samples (recommend 1 µm). The primary objective of this work is to address these limitations using a large-range AFM (measuring height >10 µm) system consisting of a novel repairable high aspect ratio probe (HARP) with a nested-proportional-integral-derivative (nested-PID) AFM system. The HARP is fabricated using a reliable, cost-efficient bench-top process. The tip is then fused by pulling the end of the micropipette cantilever with a length up to hundreds of micrometers and a tip diameter of 30 nm. The design, simulation, fabrication, and performance of the HARP are described herein. This instrument is then tested using polymer trenches which reveals superior image fidelity compared to standard silicon tips. Finally, a nested-PID system is developed and employed to facilitate 3D characterization of 50-µm-step samples. The results demonstrate the efficacy of the proposed bench-top technique for the fabrication of low-cost, simple HAR AFM probes that facilitate the imaging of samples with deep trenches.