Octopus-Inspired Soft Robot for Slow Drug Release.

Octopus tentacles are equipped with numerous suckers, wherein the muscles contract and expel air, creating a pressure difference. Subsequently, when the muscular tension is released, objects can be securely adhered to. This mechanism has been widely employed in the development of adhesive systems. However, most existing octopus-inspired structures are passive and static, lacking dynamic and controllable adhesive switching capabilities and excellent locomotion performance. Here, we present an octopus-inspired soft robot (OISR). Attracted by the magnetic gradient field, the suction cup structure inside the OISR can generate a strong adsorption force, producing dynamically controllable adsorption and separation in the gastrointestinal (GI) tract. The experimental results show that the OISR has a variety of controllable locomotion behaviors, including quick scrolling and rolling motions, generating fast locomotion responses, rolling over gastric folds, and tumbling and swimming inside liquids. By carrying drugs that are absorbable by GI epithelial cells to target areas, the OISR enables continuous drug delivery at lesions or inflamed regions of the GI tract. This research may be a potential approach for achieving localized slow drug release within the GI tract.

Microgripper Robot with End Electropermanent Magnet Collaborative Actuation.

Magnetic microgrippers, with their miniaturized size, flexible movement, untethered actuation, and programmable deformation, can perform tasks such as cell manipulation, targeted drug delivery, biopsy, and minimally invasive surgery in hard-to-reach regions. However, common external magnetic-field-driving devices suffer from low efficiency and utilization due to the significant size disparity with magnetic microgrippers. Here, we introduce a microgripper robot (MGR) driven by end electromagnetic and permanent magnet collaboration. The magnetic field generated by the microcoils can be amplified by the permanent magnets and the direction can be controlled by changing the current, allowing for precise control over the opening and closing of the magnetic microgripper and enhancing its operational range. Experimental results demonstrate that the MGR can be flexibly controlled in complex constrained environments and is highly adaptable for manipulating objects. Furthermore, the MGR can achieve planar and antigravity object grasping and transportation within complex simulated human cavity pathways. The MGR's grasping capabilities can also be extended to specialized tasks, such as circuit connection in confined spaces. The MGR combines the required safety and controllability for in vivo operations, making it suitable for potential clinical applications such as tumor or abnormal tissue sampling and surgical assistance.

Combined three dimensional locomotion and deformation of functional ferrofluidic robots.

Magnetic microrobots possess remarkable potential for targeted applications in the medical field, primarily due to their non-invasive, controllable properties. These unique qualities have garnered increased attention and fascination among researchers. However, these robotic systems do face challenges such as limited deformation capabilities and difficulties navigating confined spaces. Recently, researchers have turned their attention towards magnetic droplet robots, which are notable for their superior deformability, controllability, and potential for a range of applications such as automated virus detection and targeted drug delivery. Despite these advantages, the majority of current research is constrained to two-dimensional deformation and motion, thereby limiting their broader functionality. In response to these limitations, this study proposes innovative strategies for controlling deformation and achieving a three-dimensional (3D) trajectory in ferrofluidic robots. These strategies leverage a custom-designed eight-axis electromagnetic coil and a sliding mode controller. The implementation of these methods exhibits the potential of ferrofluidic robots in diverse applications, including microfluidic pump systems, 3D micromanipulation, and selective vascular occlusion. In essence, this study aims to broaden the capabilities of ferrofluidic robots, thereby enhancing their applicability across a multitude of fields such as medicine, micromanipulation, bioengineering, and more by maximizing the potential of these intricate robotic systems.

Analysis of Sequential Micromixing Driven by Sinusoidally Shaped Induced-Charge Electroosmotic Flow.

Multi-fluid micromixing, which has rarely been explored, typically represents a highly sought-after technique in on-chip biochemical and biomedical assays. Herein, we propose a novel micromixing approach utilizing induced-charge electroosmosis (ICEO) to implement multicomplex mixing between parallel streams. The variations of ICEO microvortices above a sinusoidally shaped floating electrode (SSFE) are first investigated to better understand the microvortex development and the resultant mixing process within a confined channel. On this basis, a mathematical model of the vortex index is newly developed to predict the mixing degree along the microchannel. The negative exponential distribution obtained between the vortex index and mixing index demonstrates an efficient model to describe the mixing performance without solving the coupled diffusion and momentum equations. Specifically, sufficient mixing with a mixing index higher than 0.9 can be achieved when the vortex index exceeds 51, and the mixing efficiency reaches a plateau at an AC frequency close to 100 Hz. Further, a rectangle floating electrode (RFE) is deposited before SSFE to enhance the controlled sequence for three-fluid mixing. One side fluid can fully mix with the middle fluid with a mixing index of 0.623 above RFE in the first mixing stage and achieve entire-channel mixing with a mixing index of 0.983 above SSFE in the second mixing stage, thereby enabling on-demand sequential mixing. As a proof of concept, this work can provide a robust alternative technique for multi-objective issues and structural design related to mixers.

Scale-reconfigurable miniature ferrofluidic robots for negotiating sharply variable spaces.

Magnetic miniature soft robots have shown great potential for facilitating biomedical applications by minimizing invasiveness and possible physical damage. However, researchers have mainly focused on fixed-size robots, with their active locomotion accessible only when the cross-sectional dimension of these confined spaces is comparable to that of the robot. Here, we realize the scale-reconfigurable miniature ferrofluidic robots (SMFRs) based on ferrofluid droplets and propose a series of control strategies for reconfiguring SMFR's scale and deformation to achieve trans-scale motion control by designing a multiscale magnetic miniature robot actuation (M3RA) system. The results showed that SMFRs, varying from centimeters to a few micrometers, leveraged diverse capabilities, such as locomotion in structured environments, deformation to squeeze through gaps, and even reversible scale reconfiguration for navigating sharply variable spaces. A miniature robot system with these capabilities combined is promising to be applied in future wireless medical robots inside confined regions of the human body.

Solitary and Collective Motion Behaviors of TiO2 Microrobots under the Coupling of Multiple Light Fields.

Due to their fascinating solitary and collective behavior, photochemical microrobots have attracted extensive attention from researchers and have obtained a series of outstanding research progress in recent years. However, due to the limitation of using a single light source, the realization of reconfigurable and controllable motion behaviors of the photochemical microrobot is still facing a series of challenges. To release these restrictions, we reported a multi-light-field-coupling-based method for driving the photochemical microrobot or its swarm in a regulatable manner. Here, we first designed a control system for coupling multiple light sources to realize the programmable application of four light sources in different directions. Then a TiO2-based photochemical microrobot was prepared, with its surface electric field distribution under different lighting conditions estimated by modeling-based simulation, where the feasibility of regulating the microrobot's motion behavior via the proposed setup was verified. Furthermore, our experimental results show that under the action of the compound light fields, we can not only robustly control the motion behavior of a single TiO2 microrobot but also reconfigure its collective behaviors. For example, we realized the free switching of the single TiO2 microrobots' movement direction, and the controllable diffusion, aggregation, the locomotion and merging of TiO2 microrobot swarms. Our discovery would provide potential means to realize the leap-forward control and application of photochemical microrobots from individuals to swarms, as well as the creation of active materials and intelligent synthetic systems.

Triple-Configurational Magnetic Robot for Targeted Drug Delivery and Sustained Release.

Active targeted therapy for bowel cancer using untethered microrobots has attracted extensive attention. However, traditional microrobots face challenges, such as issues of mobility, biocompatibility, drug loading, sustained-release capabilities, and targeting accuracy. Here, we propose an untethered triple-configurational magnetic robot (TCMR) that is composed of three geometrically nested parts: actuation and guarding, anchoring and seeding, and drug release part. A targeting magnetic driving system actuates the TCMR along the predetermined trajectory to the target position. The pH-sensitive actuation and guarding part formed by electrodeposition is degraded in the intestinal environment and separates from the two other parts. A majority of magnetic nanoparticles encapsulated in this part are retrieved. The anchoring and seeding part anchors the lesion area and seeds the drug release part in the gaps of intestinal villi by hydrolysis. Ultimately, the drug release part containing the therapeutic completes the sustained release to prolong the duration of the therapeutic agent. Cytotoxicity and therapeutic tests reveal that TCMRs are biocompatible and suitable for targeted therapy and have good therapeutic performance. The newly designed TCMR will provide new ideas for targeted therapy, thus expanding the application scope of robotics technology in the biomedical field.

Dual-responsive biohybrid neutrobots for active target delivery.

Swimming biohybrid microsized robots (e.g., bacteria- or sperm-driven microrobots) with self-propelling and navigating capabilities have become an exciting field of research, thanks to their controllable locomotion in hard-to-reach areas of the body for noninvasive drug delivery and treatment. However, current cell-based microrobots are susceptible to immune attack and clearance upon entering the body. Here, we report a neutrophil-based microrobot ("neutrobot") that can actively deliver cargo to malignant glioma in vivo. The neutrobots are constructed through the phagocytosis of Escherichia coli membrane-enveloped, drug-loaded magnetic nanogels by natural neutrophils, where the E. coli membrane camouflaging enhances the efficiency of phagocytosis and also prevents drug leakage inside the neutrophils. With controllable intravascular movement upon exposure to a rotating magnetic field, the neutrobots could autonomously aggregate in the brain and subsequently cross the blood-brain barrier through the positive chemotactic motion of neutrobots along the gradient of inflammatory factors. The use of such dual-responsive neutrobots for targeted drug delivery substantially inhibits the proliferation of tumor cells compared with traditional drug injection. Inheriting the biological characteristics and functions of natural neutrophils that current artificial microrobots cannot match, the neutrobots developed in this study provide a promising pathway to precision biomedicine in the future.

Magnetically actuated intelligent hydrogel-based child-parent microrobots for targeted drug delivery.

Small intestine-targeted drug delivery by oral administration has aroused the growing interest of researchers. In this work, the child-parent microrobot (CPM) as a vehicle protects the child microrobots (CMs) under a gastric acid environment and releases them in the small intestinal environment. The intelligent hydrogel-based CPMs with sphere, mushroom, red blood cell, and teardrop shapes are fabricated by an extrusion-dripping method. The CPMs package uniform CMs, which are fabricated by designed microfluidic (MF) devices. The fabrication mechanism and tunability of CMs and CPMs with different sizes and shapes are analyzed, modeled, and simulated. The shape of CPM can affect its drug release efficiency and kinetic characteristics. A vision-feedback magnetic driving system (VMDS) actuates and navigates CPM along the predefined path to the destination and continuously releases drug in the simulated intestinal fluid (SIF, a low Reynolds number (Re) regime) using a new motion control method with the tracking-learning-detection (TLD) algorithm. The newly designed CPM combines the advantages of powerful propulsion, good biocompatibility, and remarkable drug loading and release capacity at the intestinal level, which is expected to be competent for oral administration of small intestine-targeted therapy in the future.

Reconfigurable multifunctional ferrofluid droplet robots.

Magnetically actuated miniature soft robots are capable of programmable deformations for multimodal locomotion and manipulation functions, potentially enabling direct access to currently unreachable or difficult-to-access regions inside the human body for minimally invasive medical operations. However, magnetic miniature soft robots are so far mostly based on elastomers, where their limited deformability prevents them from navigating inside clustered and very constrained environments, such as squeezing through narrow crevices much smaller than the robot size. Moreover, their functionalities are currently restricted by their predesigned shapes, which is challenging to be reconfigured in situ in enclosed spaces. Here, we report a method to actuate and control ferrofluid droplets as shape-programmable magnetic miniature soft robots, which can navigate in two dimensions through narrow channels much smaller than their sizes thanks to their liquid properties. By controlling the external magnetic fields spatiotemporally, these droplet robots can also be reconfigured to exhibit multiple functionalities, including on-demand splitting and merging for delivering liquid cargos and morphing into different shapes for efficient and versatile manipulation of delicate objects. In addition, a single-droplet robot can be controlled to split into multiple subdroplets and complete cooperative tasks, such as working as a programmable fluidic-mixing device for addressable and sequential mixing of different liquids. Due to their extreme deformability, in situ reconfigurability and cooperative behavior, the proposed ferrofluid droplet robots could open up a wide range of unprecedented functionalities for lab/organ-on-a-chip, fluidics, bioengineering, and medical device applications.

Autonomous Biohybrid Urchin-Like Microperforator for Intracellular Payload Delivery.

A magnetic urchin-like microswimmer based on sunflower pollen grain (SPG) that can pierce the cancer cell membrane and actively deliver therapeutic drugs is reported. These drug loaded microperforators are fabricated on a large scale by sequentially treating the natural SPGs with acidolysis, sputtering, and vacuum loading. The microswimmers exhibit precise autonomous navigation and obstacle avoidance in complex environments via association with artificial intelligence. Assemblies of microswimmers can further enhance individual motion performance and adaptability to complicated environments. Additionally, the experimental results demonstrate that microswimmers with nanospikes can accomplish single-cell perforation for direct delivery under an external rotating magnetic field. Drugs encapsulated in the inner cavity of the microperforators can be accurately delivered to a specific site via remote control. These dual-action microswimmers demonstrate good biocompatibility, high intelligence, precision in single-cell targeting, and sufficient drug loading, presenting a promising avenue for many varieties of biomedical applications.

Transformation mechanism of ions on different waters in alpine region.

The study investigates transformation mechanism of ions on different waters in Alpine region through analyzed the hydrochemical characteristics of the major ions of precipitation, glacier and snow meltwater, supra-permafrost water and river water in permafrost regions in the Tibetan Plateau under climate warming. The results showed that, The relation between recharge and discharge was the major ways for ionic transformation of each water body. Precipitation and glacier and snow meltwater are the main input sources for ionic transformation, and river water is the final output source. Different water bodies had different ionic concentrations and different hydrochemical types. However, different water bodies in different months (from June to September) also had different hydrochemical types. The water - rock interaction, reactions for ions, dilution effect and other effect for ions played an important role in the process of ion transformation. The increasing of temperature would lead to the accelerated melting of glaciers, permafrost and snow in the alpine regions, so the amount of supra-permafrost water and glacier and snow meltwater will increase, which leads to the increase of runoff. Meanwhile, the increase of temperature makes evaporation stronger. The strong of evaporation will accelerate the transformation of liquid water to gaseous water. Moreover, ion translation and water conversion are synchronous. Accordingly, ions are also accelerating transformation in the process of accelerated transformation of water body. Climate change is not only the main driving force for multiphase water transformation, but also the main driving force for the ion transformation of various water bodies.

The sources of supra-permafrost water and its hydrological effect based on stable isotopes in the third pole region.

The sources of supra-permafrost water and its hydrological effects were studied, based on the presence of stable isotopes in 562 samples collected in different ablation periods from the source regions of the Yangtze River. The δ18O (δD and d-excess) values for the initial ablation, ablation, and end ablation periods were -10.18‰ (-71.39‰ and 10.08‰), -12.14‰ (-85.58‰ and 11.51‰) and -11.50‰ (-78.75‰ and 13.23‰), respectively. The order of the slopes for the supra-permafrost water evaporation lines from the different ablation periods was initial ablation (IA) > ablation (A) > end ablation (EA). An anti-altitude effect is documented here, for a specific altitude range, in what is believed to be the first record of such an occurrence. Outside of that range, clear altitude effects were apparent. We have been able to show that supra-permafrost water was mainly recharged by atmospheric precipitation, ground ice, and glacier and snow meltwater, in the initial ablation and end ablation periods, and contributions from glacier and snow meltwater were mainly concentrated in higher altitude regions. In contrast, in the ablation period, supra-permafrost water was mainly recharged by atmospheric precipitation and ground ice. The contributions of precipitation to supra-permafrost water were 78.79%, 85.47%, and 82.99% in the initial ablation, ablation, and end ablation periods, respectively. The contributions of ground ice to the supra-permafrost water were 14.05%, 14.53%, and 11.94%, respectively, while contributions of glacier and snow meltwater were 7.15% and 5.07% in the initial and end ablation period. For the initial ablation, ablation, and end ablation periods, contributions from atmospheric precipitation to the supra-permafrost water were 85.47%, 86.86%, and 86.84%, while contributions from ground ice were 14.53%, 13.14% and 13.16%, respectively.

Magnetic biohybrid micromotors with high maneuverability for efficient drug loading and targeted drug delivery.

Recent progress of untethered mobile micromotors has shown immense potential for targeted drug delivery in vivo. However, designing a wireless micromotor with high maneuverability and biocompatibility and achieving controlled drug release with high efficiency at a specific position remains a great challenge. Herein, we present a pine pollen-based micromotor (PPBM) and demonstrate its potential application as a cargo carrier for targeted drug delivery. These multifunctional biohybrid micromotors were massively and inexpensively fabricated by the encapsulation of magnetic particles (Fe3O4) and medicine into the two hollow air sacs of pine pollen, via vacuum loading. PPBMs successfully inherit the intrinsic functionalities of pine pollen: structural uniformity, morphological stability, biocompatibility, autofluorescence (AF) and physicochemical robustness. Under an external magnetic field, the loaded Fe3O4 enables individual and swarm PPBMs to propel precisely in complex biological fluids. Capitalizing on the magnetic nanoparticle aggregation phenomenon under a powerful magnetic field, controlled release of the therapeutic cargo is achieved using a fluid field generated by the rotating magnetic agglomerate. The biohybrid micromotors reported here turn natural pine pollen into active and controllable cargo carriers for biomedical applications.

Reconfigurable magnetic microrobot swarm: Multimode transformation, locomotion, and manipulation.

Swimming microrobots that are energized by external magnetic fields exhibit a variety of intriguing collective behaviors, ranging from dynamic self-organization to coherent motion; however, achieving multiple, desired collective modes within one colloidal system to emulate high environmental adaptability and enhanced tasking capabilities of natural swarms is challenging. Here, we present a strategy that uses alternating magnetic fields to program hematite colloidal particles into liquid, chain, vortex, and ribbon-like microrobotic swarms and enables fast and reversible transformations between them. The chain is characterized by passing through confined narrow channels, and the herring school-like ribbon procession is capable of large-area synchronized manipulation, whereas the colony-like vortex can aggregate at a high density toward coordinated handling of heavy loads. Using the developed discrete particle simulation methods, we investigated generation mechanisms of these four swarms, as well as the "tank-treading" motion of the chain and vortex merging. In addition, the swarms can be programmed to steer in any direction with excellent maneuverability, and the vortex's chirality can be rapidly switched with high pattern stability. This reconfigurable microrobot swarm can provide versatile collective modes to address environmental variations or multitasking requirements; it has potential to investigate fundamentals in living systems and to serve as a functional bio-microrobot system for biomedicine.

Fast Specimen Boundary Tracking and Local Imaging with Scanning Probe Microscopy.

An efficient and adaptive boundary tracking method is developed to confine area of interest for high-efficiency local scanning. By using a boundary point determination criterion, the scanning tip is steered with a sinusoidal waveform while estimating azimuth angle and radius ratio of each boundary point to accurately track the boundary of targets. A local scan region and path are subsequently planned based on the prior knowledge of boundary tracking to reduce the scan time. Boundary tracking and local scanning methods have great potential not only for fast dimension measurement but also for sample surface topography and physical characterization, with only scanning region of interest. The performance of the proposed methods was verified by using the alternate current mode scanning ion-conductance microscopy, tapping, and PeakForce modulation atomic force microscopy. Experimental results of single/multitarget boundary tracking and local scanning of target structures with complex boundaries demonstrate the flexibility and validity of the proposed method.

Magnetically Actuated Peanut Colloid Motors for Cell Manipulation and Patterning.

We report a magnetically actuated peanut-shaped hematite colloid motor that can not only move in a rolling or wobbling mode in fluids but also perform single cell manipulation and patterning in a noncontact way. The peanut motor in a rolling mode can reach a maximal velocity of 10.6 µm s-1 under a rotating magnetic field of 130 Hz and 6.3 mT and achieve a more precisely controllable motion in predefined tracks. While in a wobbling mode, the motor reaches a maximal velocity of 14.5 µm s-1 under a conical rotating magnetic field of 80 Hz and 6.3 mT and can climb over steep slopes to adapt the motor for more complex environments. The fluid flow simulation results reveal that the difference between two movement modes mostly comes from the distribution discrepancy of the flow fields near the motors. Through the integration of the rolling and wobbling movement, these peanut motors can autonomously transport and release cells to a predefined site and thus form complex cell patterns without a physical contact. Such magnetically actuated peanut colloid motors afford a biofriendly technique for manipulation and patterning of cells, cell measurements, and intracellular communication investigations.

Publisher Correction: Broad modulus range nanomechanical mapping by magnetic-drive soft probes.

In the original version of this Article, the text labels on the bottom-right graph in Fig. 1c were inadvertently displaced during the production process. This has now been corrected in both the PDF and HTML versions of the Article.

Broad modulus range nanomechanical mapping by magnetic-drive soft probes.

Stiffness matching between the probe and deformed portion of the sample in piezo-drive peak force modulation atomic force microscopy (AFM) limits the modulus measurement range of single probes. Here we develop a magnetic drive peak force modulation AFM to broaden the dynamic range of the probe with direct cantilever excitation. This approach not only successfully drives the softest commercial probe (6 pN nm-1) for mapping extremely soft samples in liquid but also provides an indentation force of hundreds of nanonewtons for stiff samples with a soft probe. Features of direct measurements of the indentation force and depth can unify the elastic modulus range up to four orders of magnitude, from 1 kPa to 10 MPa (in liquid) and 1 MPa to 20 GPa (in air or liquid) using a single probe. This approach can be particularly useful for analysing heterogeneous samples with large elastic modulus variations in multi-environments.

Treatment of extensively drug-resistant Gram-negative infections in critically ill patients: Outcome of a consensus meeting at the 13th Asia-Pacific Congress of Clinical Microbiology and Infection, October 2012.

Infections caused by multidrug-resistant and extensively drug-resistant Gram-negative bacilli are increasingly challenging to manage in hospitals and long term-care facilities worldwide. As the therapeutic options are limited, the International Society of Chemotherapy in collaboration with the Asia-Pacific Society of Clinical Microbiology and Immunology organised a consensus conference as part of the 13th Asia-Pacific Congress of Clinical Microbiology and Infection. A panel of international experts from Europe, the Americas and Asia were convened to discuss the issues of therapeutic options for the management of these difficult-to-treat pathogens.