Catheter-Assisted Bioinspired Adhesive Magnetic Soft Millirobot for Drug Delivery.

Soft millirobots have evolved into various therapeutic applications in the medical field, including for vascular dredging, cell transportation, and drug delivery, owing to adaptability to their surroundings. However, most soft millirobots cannot quickly enter, retrieve, and maintain operations in their original locations after removing the external actuation field. This study introduces a soft magnetic millirobot for targeted medicine delivery that can be transported into the body through a catheter and anchored to the tissues. The millirobot has a bilayer adhesive body with a mussel-inspired hydrogel layer and an octopus-inspired magnetic structural layer. It completes entry and retrieval with the assistance of a medical catheter based on the difference between the adhesion of the hydrogel layer in air and water. The millirobot can operate in multiple modes of motion under external magnetic fields and underwater tissue adhesion after self-unfolding with the structural layer. The adaptability and recyclability of the millirobots are demonstrated using a stomach model. Combined with ultrasound (US) imaging, operational feasibility within organisms is shown in isolated small intestines. In addition, a highly efficient targeted drug delivery is confirmed using a fluorescence imaging system. Therefore, the proposed soft magnetic millirobots have significant potential for medical applications.

Robotized algal cells and their multiple functions.

From an engineering perspective, algal cells with the abilities of perception and driving can be considered as microrobots. Site-specific, quantitative assembly of algal robots and the manipulated objects and collaborative task performance by algal robots would benefit biomedicine, environmental monitoring, and micro-nano manufacturing. Herein, site-specific, quantitative assembly and drive of algal cells are investigated. The mechanism of cell movement is analyzed, and cell motility is evaluated with or without light control. To robotize algal cells, an algae-guiding system is built, through which a swarm of algal cells is controlled to follow trajectories. By the cell adhesion method, adhesion and release between algal cells and microstructures are achieved. Algal cells successfully transport microspheres and release them at a destination. The cells are continuously operated for 60 min while carrying microspheres and they travel up to 270 mm. An optical guiding method is then developed for controlled assembly of algal robots onto fabricated micro-objects. The rotational movement of the microstructures is realized through cooperative driving by algal cells. This research provides a new biological driving method based on algal cells, which swim and behave as microrobots and are expected to benefit microassembly, microcargo traverse/delivery, and biological collaboration.

2D to 3D Manipulation and Assembly of Microstructures Using Optothermally Generated Surface Bubble Microrobots.

Hydrogel microstructures that encapsulate cells can be assembled into tissues and have broad applications in biology and medicine. However, 3D posture control for a single arbitrary microstructure remains a challenge. A novel 3D manipulation and assembly technique based on optothermally generated bubble robots is proposed. The generation, rate of growth, and motion of a microbubble robot can be controlled by modulating the power of a laser focused on the interface between the substrate and a fluid. In addition to 2D operations, bubble robots are able to perform 3D manipulations. The 3D properties of hydrogel microstructures are adjusted arbitrarily, and convex and concave structures with different heights are designed. Furthermore, annular micromodules are assembled into 3D constructs, including tubular and concentric constructs. A variety of hydrogel microstructures of different sizes and shapes are operated and assembled in both 2D and 3D conformations by bubble robots. The manipulation and assembly methods are simple, rapid, versatile, and can be used for fabricating tissue constructs.

An electromagnetic anglerfish-shaped millirobot with wireless power generation.

Female anglerfishes have a lantern-shape luminous organ sprouting from the middle of their heads to lure their prey in the dark deep sea. Inspired by the anglerfish, we designed an electromagnetic anglerfish-shaped millirobot that can receive energy and transform it into light to attract algae cells to specific locations. The small wireless powered robot can receive about 658 mW of power from external energy supply coils, and light LEDs (light-emitting diodes). The wireless power generation and moving control of the robot are analyzed systematically. Transmitting electric energy to smaller scale receivers to endow milli or micro robots with wireless power function is an interesting and promising research direction. With this function, the wireless powered robot is expected to be extensively used at the small scale in the near future, such as to provide electricity to drive microdevices (microgrippers, microsensors, etc.), provide light or heat in small-scale space, stimulate/kill pathological cells in minimally invasive treatment and so on.

Optimization of Protein-Protein Interaction Measurements for Drug Discovery Using AFM Force Spectroscopy.

Increasingly targeted in drug discovery, protein-protein interactions challenge current high throughput screening technologies in the pharmaceutical industry. Developing an effective and efficient method for screening small molecules or compounds is critical to accelerate the discovery of ligands for enzymes, receptors and other pharmaceutical targets. Here, we report developments of methods to increase the signal-to-noise ratio (SNR) for screening protein-protein interactions using atomic force microscopy (AFM) force spectroscopy. We have demonstrated the effectiveness of these developments on detecting the binding process between focal adhesion kinases (FAK) with protein kinase B (Akt1), which is a target for potential cancer drugs. These developments include optimized probe and substrate functionalization processes and redesigned probe-substrate contact regimes. Furthermore, a statistical-based data processing method was developed to enhance the contrast of the experimental data. Collectively, these results demonstrate the potential of the AFM force spectroscopy in automating drug screening with high throughput.

Controlled regular locomotion of algae cell microrobots.

Algae cells can be considered as microrobots from the perspective of engineering. These organisms not only have a strong reproductive ability but can also sense the environment, harvest energy from the surroundings, and swim very efficiently, accommodating all these functions in a body of size on the order of dozens of micrometers. An interesting topic with respect to random swimming motions of algae cells in a liquid is how to precisely control them as microrobots such that they swim according to manually set routes. This study developed an ingenious method to steer swimming cells based on the phototaxis. The method used a varying light signal to direct the motion of the cells. The swimming trajectory, speed, and force of algae cells were analyzed in detail. Then the algae cell could be controlled to swim back and forth, and traverse a crossroad as a microrobot obeying specific traffic rules. Furthermore, their motions along arbitrarily set trajectories such as zigzag, and triangle were realized successfully under optical control. Robotize algae cells can be used to precisely transport and deliver cargo such as drug particles in microfluidic chip for biomedical treatment and pharmacodynamic analysis. The study findings are expected to bring significant breakthrough in biological drives and new biomedical applications.

A rapid and automated relocation method of an AFM probe for high-resolution imaging.

The atomic force microscope (AFM) is one of the most powerful tools for high-resolution imaging and high-precision positioning for nanomanipulation. The selection of the scanning area of the AFM depends on the use of the optical microscope. However, the resolution of an optical microscope is generally no larger than 200 nm owing to wavelength limitations of visible light. Taking into consideration the two determinants of relocation-relative angular rotation and positional offset between the AFM probe and nano target-it is therefore extremely challenging to precisely relocate the AFM probe to the initial scan/manipulation area for the same nano target after the AFM probe has been replaced, or after the sample has been moved. In this paper, we investigate a rapid automated relocation method for the nano target of an AFM using a coordinate transformation. The relocation process is both simple and rapid; moreover, multiple nano targets can be relocated by only identifying a pair of reference points. It possesses a centimeter-scale location range and nano-scale precision. The main advantages of this method are that it overcomes the limitations associated with the resolution of optical microscopes, and that it is label-free on the target areas, which means that it does not require the use of special artificial markers on the target sample areas. Relocation experiments using nanospheres, DNA, SWCNTs, and nano patterns amply demonstrate the practicality and efficiency of the proposed method, which provides technical support for mass nanomanipulation and detection based on AFM for multiple nano targets that are widely distributed in a large area.

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.

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.

System integration of magnetic medical microrobots: from design to control.

Magnetic microrobots are ideal for medical applications owing to their deep tissue penetration, precise control, and flexible movement. After decades of development, various magnetic microrobots have been used to achieve medical functions such as targeted delivery, cell manipulation, and minimally invasive surgery. This review introduces the research status and latest progress in the design and control systems of magnetic medical microrobots from a system integration perspective and summarizes the advantages and limitations of the research to provide a reference for developers. Finally, the future development direction of magnetic medical microrobot design and control systems are discussed.

Review of Bubble Applications in Microrobotics: Propulsion, Manipulation, and Assembly.

In recent years, microbubbles have been widely used in the field of microrobots due to their unique properties. Microbubbles can be easily produced and used as power sources or tools of microrobots, and the bubbles can even serve as microrobots themselves. As a power source, bubbles can propel microrobots to swim in liquid under low-Reynolds-number conditions. As a manipulation tool, microbubbles can act as the micromanipulators of microrobots, allowing them to operate upon particles, cells, and organisms. As a microrobot, microbubbles can operate and assemble complex microparts in two- or three-dimensional spaces. This review provides a comprehensive overview of bubble applications in microrobotics including propulsion, micromanipulation, and microassembly. First, we introduce the diverse bubble generation and control methods. Then, we review and discuss how bubbles can play a role in microrobotics via three functions: propulsion, manipulation, and assembly. Finally, by highlighting the advantages and current challenges of this progress, we discuss the prospects of microbubbles in microrobotics.

Multistimuli-Responsive Hydroplaning Superhydrophobic Microrobots with Programmable Motion and Multifunctional Applications.

Superhydrophobic microrobots that can swim efficiently and rapidly on water under the action of external stimuli have attracted significant research attention for various applications. However, most studies on superhydrophobic microrobots have focused on single-stimulus driving modes, which limit the motion and functional applications of microrobots in complex aquatic environments. Therefore, multistimuli-responsive superhydrophobic microrobots that are capable of drifting rapidly on water through light, magnetic, and chemical control were developed in this study. The stability and environmental adaptability of the microrobots were systematically investigated. The microrobots achieved programmable trajectory motion on water, particularly complex motions such as circular, spiral, and helical movements under the coupled influence of chemical and magnetic fields. Importantly, the motion and control of multimicrorobots can be realized by combining control methods. Under the action of light and magnetic field, multimicrorobots could realize cooperative movement and completed the transportation of cargo. Additionally, broad multifunctional applications of the microrobots were explored in terms of oil spill recovery and solution mix. This study provides a method for the preparation and development of superhydrophobic microrobots with multistimuli-responsive characteristics.

A diatom-based biohybrid microrobot with a high drug-loading capacity and pH-sensitive drug release for target therapy.

Targeted delivery is a promising mean for various biomedical applications, and various micro/nano robots have been created for drug delivery. Mesoporous silica has been shown to be successful as a drug delivery carrier in numerous studies. However, mesoporous silica preparation usually requires expensive and toxic chemicals, which limits its biomedical applications. Diatoms, as the naturally porous silica structure, are promising substitutes for the artificial mesoporous silica preparation. However, the current studies utilizing intact diatom frustules as drug delivery packets lack flexible and controllable locomotion. Herein, we propose a biohybrid magnetic microrobot based on Thalassiosira weissflogii frustules (TWFs) as a cargo packet for targeted drug delivery using a simple preparation method. Biohybrid microrobots are fabricated in large quantities by attaching magnetic nanoparticles (Fe3O4) to the surface of diatoms via electrostatic adsorption. Biohybrid microrobots are agile and controllable under the influence of external magnetic fields. They could be precisely controlled to follow specific trajectories or to move as swarms. The cooperation of the two motion modes of the biohybrid microrobots increased microrobots' environmental adaptability. Microrobots have a high drug-loading capacity and pH-sensitive drug release. In vitro cancer cell experiments further demonstrated the controllability of diatom microrobots for targeted drug delivery. The biohybrid microrobots reported in this paper convert natural diatoms into cargo packets for biomedical applications, which possess active and controllable properties and show huge potential for targeted anticancer therapy. STATEMENT OF SIGNIFICANCE: In this study, diatoms with good biocompatibility were used to prepare biohybrid magnetic microrobots. Compared with the current diatom-based systems for drug delivery, the microrobots prepared in this study for targeted drug delivery have more flexible motion characteristics and exhibit certain swarming behaviors. Under the same magnetic field strength, by changing the magnetic field frequency, the movement state of the diatoms can be changed to pass through the narrow channel, so that it has better environmental adaptability.

Bubble-based microrobots enable digital assembly of heterogeneous microtissue modules.

The specific spatial distribution of tissue generates a heterogeneous micromechanical environment that provides ideal conditions for diverse functions such as regeneration and angiogenesis. However, to manufacture microscale multicellular heterogeneous tissue modulesin vitroand then assemble them into specific functional units is still a challenging task. In this study, a novel method for the digital assembly of heterogeneous microtissue modules is proposed. This technique utilizes the flexibility of digital micromirror device-based optical projection lithography and the manipulability of bubble-based microrobots in a liquid environment. The results indicate that multicellular microstructures can be fabricated by increasing the inlets of the microfluidic chip. Upon altering the exposure time, the Young's modulus of the entire module and different regions of each module can be fine-tuned to mimic normal tissue. The surface morphology, mechanical properties, and internal structure of the constructed bionic peritoneum were similar to those of the real peritoneum. Overall, this work demonstrates the potential of this system to produce and control the posture of modules and simulate peritoneal metastasis using reconfigurable manipulation.

Enzymatic/Magnetic Hybrid Micromotors for Synergistic Anticancer Therapy.

Micro/nanomotors (MNMs), which propel by transforming various forms of energy into kinetic energy, have emerged as promising therapeutic nanosystems in biomedical applications. However, most MNMs used for anticancer treatment are only powered by one engine or provide a single therapeutic strategy. Although double-engined micromotors for synergistic anticancer therapy can achieve more flexible movement and efficient treatment efficacy, their design remains challenging. In this study, we used a facile preparation method to develop enzymatic/magnetic micromotors for synergetic cancer treatment via chemotherapy and starvation therapy (ST), and the size of micromotors can be easily regulated during the synthetic process. The enzymatic reaction of glucose oxidase, which served as the chemical engine, led to self-propulsion using glucose as a fuel and ST via a reduction in the energy available to cancer cells. Moreover, the incorporation of Fe3O4 nanoparticles as a magnetic engine enhanced the kinetic power and provided control over the direction of movement. Inherent pH-responsive drug release behavior was observed owing to the acidic decomposition of drug carriers in the intracellular microenvironment of cancer cells. This system displayed enhanced anticancer efficacy owing to the synergetic therapeutic strategies and increased cellular uptake in a targeted area because of the improved motion behavior provided by the double engines. Therefore, the demonstrated micromotors are promising candidates for anticancer biomedical microsystems.

Integrated Assembly and Flexible Movement of Microparts Using Multifunctional Bubble Microrobots.

Industrial robots have been widely used for manufacturing and assembly in factories. However, at the microscale, most assembly technologies can only pattern the micromodules together loosely and can hardly combine the micromodules to directly form an entity that cannot be easily dispersed. In this study, surface bubbles are made to function as microrobots on a chip. These microrobots can move, fix, lift, and drop microparts and integratively assemble them into a tightly connected entity. As an example, the assembly of a pair of microparts with dovetails is considered. A jacklike bubble robot is used to lift and drop a micropart with a tail, whereas a mobile microrobot is used to push the other micropart with the corresponding socket to the proper position so that the tail can be inserted into the socket. The assembled microparts with the tail-socket joint can move as an entity without separation. Similarly, different types of parts are integratively assembled to form various structures such as gears, snake-shaped chains, and vehicles, which are then driven by bubble microrobots to perform different forms of movement. This assembly technology is simple and efficient and is expected to play an important role in micro-operation, modular assembly, and tissue engineering.

AFM based MWCNT nanomanipulation with force and visual feedback.

To real-timely feel and see the manipulation process of multi-wall carbon nanotube (MWCNT) is required to better control its assembly based on atomic force microscope. Here real-time three-dimensional interactive forces between the probe and the sample can be fed back to the operator according to the proposed force model and position sensitive detector's signals, and MWCNT motion can be online displayed on the visual interface according to probe position and applied force based on the proposed MWCNT motion model and virtual reality technology. Based on force and visual feedback, the process and result of MWCNT manipulation can be online controlled, and MWCNT manipulation experiment will be performed to verify the effectiveness of the method.

Target clamping and cooperative motion control of ant robots.

Carpenter ants possess the characteristics of division of labor, communication between individuals, cooperation, and the ability to solve problems. Inspired by the carpenter ant, we designed electromagnetically controlled ant millirobots that can move, clamp, and work cooperatively. The robot can receive power wirelessly to actuate its ionic polymer-metal composite gripper. Further, two robots can be controlled to manipulate small components individually or cooperatively. Dual-robot manipulation is found to take 76.7% of the time required for single-robot manipulation. The results show that complicated manipulation can be performed by robots that are multifunctional and flexible by utilizing electromagnetic actuation, intelligent materials, and wireless power transmission.

Photoresponsive Graphene Composite Bilayer Actuator for Soft Robots.

Highly deformable and photoresponsive smart actuators are attracting increasing attention. Here, a high concentration of graphene is dispersed in polydimethylsiloxane (PDMS) by combining the advantages of various dispersion methods. The composite and pure PDMS layers are used to fabricate bilayer actuators with a high capacity for rapid deformation. The fabricated bilayer actuators exhibit novel and interesting properties. A bilayer actuator containing a 30 wt % graphene composite can be deflected by 7.9 mm in the horizontal direction under infrared laser irradiation. The graphene concentration in the composite influences actuator adjustment to deformation and its response speed, and the composite also exhibits superhydrophobicity. On the basis of its superhydrophobicity and large deformation capacity, the actuator made with 30 wt % graphene composite is used to construct a beluga whale soft robot. The robot can swim quickly in water at an average speed of 6 mm/s, and it can cover a distance of 30 mm in 5 s when irradiated just once with an infrared laser. Actuators fabricated with this method can be used in artificial muscle, bionic grippers, and various soft robots that require actuators with large deformation capacities.

Programmable micrometer-sized motor array based on live cells.

Trapping and transporting microorganisms with intrinsic motility are important tasks for biological, physical, and biomedical applications. However, fast swimming speed makes the manipulation of these organisms an inherently challenging task. In this study, we demonstrated that an optoelectrical technique, namely, optically induced dielectrophoresis (ODEP), could effectively trap and manipulate Chlamydomonas reinhardtii (C. reinhardtii) cells swimming at velocities faster than 100 µm s-1. Furthermore, live C. reinhardtii cells trapped by ODEP can form a micrometer-sized motor array. The rotating frequency of the cells ranges from 50 to 120 rpm, which can be reversibly adjusted with a fast response speed by varying the optical intensity. Functional flagella have been demonstrated to play a decisive role in the rotation. The programmable cell array with a rotating motion can be used as a bio-micropump to drive the liquid flow in microfludic chips and may shed new light on bio-actuation.