Magnetic soft robots have shown great potential for biomedical applications due to their high shape reconfigurability, motion agility, and multi-functionality in physiological environments. Magnetic ...soft robots with multi-layer structures can enhance the loading capacity and function complexity for targeted delivery. However, the interactions between soft entities have yet to be fully investigated, and thus the assembly of magnetic soft robots with on-demand motion modes from multiple film-like layers is still challenging. Herein, we model and tailor the magnetic interaction between soft film-like layers with distinct in-plane structures, and then realize multi-layer soft robots that are capable of performing agile motions and targeted adhesion. Each layer of the robot consists of a soft magnetic substrate and an adhesive film. The mechanical properties and adhesion performance of the adhesive films are systematically characterized. The robot is capable of performing two locomotion modes, i.e., translational motion and tumbling motion, and also the on-demand separation with one side layer adhered to tissues. Simulation results are presented, which have a good qualitative agreement with the experimental results. The feasibility of using the robot to perform multi-target adhesion in a stomach is validated in both ex-vivo and in-vivo experiments.
Emerging heart-on-a-chip platforms are promising approaches to establish cardiac cell/tissue models in vitro for research on cardiac physiology, disease modeling and drug cardiotoxicity as well as ...for therapeutic discovery. Challenges still exist in obtaining the complete capability of in situ sensing to fully evaluate the complex functional properties of cardiac cell/tissue models. Changes to contractile strength (contractility) and beating regularity (rhythm) are particularly important to generate accurate, predictive models. Developing new platforms and technologies to assess the contractile functions of in vitro cardiac models is essential to provide information on cell/tissue physiologies, drug-induced inotropic responses, and the mechanisms of cardiac diseases. In this review, we discuss recent advances in biosensing platforms for the measurement of contractile functions of in vitro cardiac models, including single cardiomyocytes, 2D monolayers of cardiomyocytes, and 3D cardiac tissues. The characteristics and performance of current platforms are reviewed in terms of sensing principles, measured parameters, performance, cell sources, cell/tissue model configurations, advantages, and limitations. In addition, we highlight applications of these platforms and relevant discoveries in fundamental investigations, drug testing, and disease modeling. Furthermore, challenges and future outlooks of heart-on-a-chip platforms for in vitro measurement of cardiac functional properties are discussed.
With the development of materials science and micro-nano fabrication techniques, miniature soft robots at millimeter or submillimeter size can be manufactured and actuated remotely. The small-scaled ...robots have the unique capability to access hard-to-reach regions in the human body in a noninvasive manner. To date, it is still challenging for miniature robots to accurately move in the diverse and dynamic environments in the human body (e.g., in blood flow). To effectively locomote in the vascular system, miniature swimmers with upstream swimming capability are required. Herein, we design and fabricate a miniature robotic swimmer capable of performing ultrafast swimming in a fluidic environment. The maximum velocity of the swimmer in water is 30 cm/s, which is 60 body lengths. Moreover, in a tubular environment, the swimmer can still obtain a swimming velocity of 17 cm/s. The swimmer can also perform upstream swimming in a tubular environment with a velocity of 5 cm/s when the flow speed is 10 cm/s. The ultrasound-guided navigation of the swimmer in a phantom mimicking a blood vessel is also realized. This work gives insight into the design of agile undulatory milliswimmers for future biomedical applications.
In nature, some semiaquatic arthropods evolve biomechanics for jumping on the water surface with the controlled burst of kinetic energy. Emulating these creatures, miniature jumping robots deployable ...on the water surface have been developed, but few of them achieve the controllability comparable to biological systems. The limited controllability and agility of miniature robots constrain their applications, especially in the biomedical field where dexterous and precise manipulation is required. Herein, an insect‐scale magnetoelastic robot with improved controllability is designed. The robot can adaptively regulate its energy output to generate controllable jumping motion by tuning magnetic and elastic strain energy. Dynamic and kinematic models are developed to predict the jumping trajectories of the robot. On‐demand actuation can thus be applied to precisely control the pose and motion of the robot during the flight phase. The robot is also capable of making adaptive amphibious locomotion and performing various tasks with integrated functional modules.
A part of semiaquatic insects can jump on the water surface leveraging surface tension. Inspired by these insects, this work presents a miniature magnetic soft robot with the capabilities of water‐surface jump, on‐demand in‐flight maneuver, and amphibious multimodal locomotion. Dynamic model and kinematic models are developed, and based on them, the motion of the robot can be precisely predicted and controlled.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Micro/nanorobots offer great promise in the next generation of biomedical applications. One of the significant challenges to apply micro/nanorobots in the circulatory system is that fluidic flow ...impacts their motion and swarm behaviors. Herein, we propose an actuation strategy to navigate paramagnetic nanoparticle swarms and maintain their integrity in fluidic flow. The generation, locomotion, and integrity of the swarms in fluidic flow were analyzed and validated in experiments. Our results show that the nanoparticles should be pregathered as a swarm before releasing them into fluidic flow to maintain an integrated shape. The swarm integrity is dependent on the flow rate, and the strength and pitch angle of the applied oscillating magnetic field. Based on the findings, the actuation strategy for swarm navigation in fluidic flow was established. The strength and pitch angle of the magnetic field were tuned to maintain swarm integrity while the field pitch angle was tuned to change swarm velocity. Using the proposed strategy, downstream and upstream navigation of the swarm were realized in a blood flow with a rate of 2 mm/s. It was also demonstrated that the swarm can be navigated into a tube for retraction. The downstream delivery rate and upstream retraction rate of the nanoparticles were 99.4% and 75.7%, respectively.
Swarms, which stem from collective behaviors among individual elements, are commonly seen in nature. Since two decades ago, scientists have been attempting to understand the principles of natural ...swarms and leverage them for creating artificial swarms. To date, the underlying physics; techniques for actuation, navigation, and control; field-generation systems; and a research community are now in place. This Review reviews the fundamental principles and applications of micro/nanorobotic swarms. The generation mechanisms of the emergent collective behaviors among the micro/nanoagents identified over the past two decades are elucidated. The advantages and drawbacks of different techniques, existing control systems, major challenges, and potential prospects of micro/nanorobotic swarms are discussed.
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IJS, KILJ, NUK, PNG, UL, UM
From single-pole magnetic tweezers to robotic magnetic-field generation systems, the development of magnetic micromanipulation systems, using electromagnets or permanent magnets, has enabled a ...multitude of applications for cellular and intracellular measurement and stimulation. Controlled by different configurations of magnetic-field generation systems, magnetic particles have been actuated by an external magnetic field to exert forces/torques and perform mechanical measurements on the cell membrane, cytoplasm, cytoskeleton, nucleus, intracellular motors, etc. The particles have also been controlled to generate aggregations to trigger cell signaling pathways and produce heat to cause cancer cell apoptosis for hyperthermia treatment. Magnetic micromanipulation has become an important tool in the repertoire of toolsets for cell measurement and stimulation and will continue to be used widely for further explorations of cellular/intracellular structures and their functions. Existing review papers in the literature focus on fabrication and position control of magnetic particles/structures (often termed micronanorobots) and the synthesis and functionalization of magnetic particles. Differently, this paper reviews the principles and systems of magnetic micromanipulation specifically for cellular and intracellular measurement and stimulation. Discoveries enabled by magnetic measurement and stimulation of cellular and intracellular structures are also summarized. This paper ends with discussions on future opportunities and challenges of magnetic micromanipulation in the exploration of cellular biophysics, mechanotransduction, and disease therapeutics.
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IJS, KILJ, NUK, PNG, UL, UM
Swarms, which stem from the collective behavior among individual elements, are commonly seen in nature. Over the past decade, the generation mechanism of microrobotic swarms has been explored for ...understanding the guiding principles of living swarms, and the swarms have been functionalized to enable specific applications. Nevertheless, the generation and navigation of microrobotic swarms under gravity and fluidic flow remain challenging, due to the the complexity in controlling agent-agent interactions.This thesis focuses on developing a strategy that enables the swarming of magnetic microparticles against gravity into vertical swarms. By analyzing the interparticle interaction under the influence of gravity and hydrodynamic drag, a unique dual-axis oscillating magnetic field was designed. The necessity of the vertical interparticle interactions, attraction among the intermediate structures, and positional reconfigurability of particles for the generation of the vertical swarms were revealed. The gravity-resisting capability, pattern reconfiguration, adaptive locomotion, and collective behavior of the vertical swarms were demonstrated. Next, this thesis presents the generation and navigation of magnetic nanoparticle swarms in fluidic flow. The interparticle interaction and locomotion mechanism of the magnetic particles in fluidic flow were analyzed and validated in experiments. Based on the findings, an actuation strategy was established to navigate the swarms in fluidic flow. Using the proposed strategy, downstream and upstream navigation of the swarms were realized in a blood flow with a rate of 2 mm/s. Moreover, this thesis focuses on the integrity of swarms in fluidic flow. An analytical model that described the relationships between fluid viscosity, flow rate, branching angle, magnetic field strength, and swarm integrity, was established. Based on the model, dynamic magnetic fields were designed to selectively maintain swarm integrity. Combining the dynamic fields and thrombin-coated magnetic particles, a microrobotic swarm-based strategy was developed to address the low selectivity issue of existing embolization techniques. Experiments in microfluidic channels, ex vivo tissues, and in vivo porcine kidneys validated the efficacy of the proposed strategy for selective embolization.The research deepens the fundamental understanding of swarm generation and behavior under gravity and fluidic flow, and establishes a route for developing the next generation of targeted delivery and embolization approaches.
Self-assembly of dynamic colloidal structures along the vertical direction has been challenging because of gravity and the complexity in controlling agent-agent interactions. Here, we present a ...strategy that enables the self-growing of gravity-resisting colloidal collectives. By designing a unique dual-axis oscillating magnetic field, time-varying interparticle interactions are induced to assemble magnetic particles against gravity into vertical collectives, with the structures continuing to grow until reaching dynamic equilibrium. The collectives have swarm behavior and are capable of height reconfiguration and adaptive locomotion, such as moving along a tilted substrate and under nonzero fluidic flow condition, gap and obstacle crossing, and stair climbing.
In cell biology, fluorescent dyes are routinely used for biochemical measurements. The traditional global dye treatment method suffers from low signal-to-noise ratios (SNR), especially when used for ...detecting a low concentration of ions, and increasing the concentration of fluorescent dyes causes more severe cytotoxicity. Here, we report a robotic technique that controls how a low amount of fluorescent-dye-coated magnetic nanoparticles accurately forms a swarm and increases the fluorescent dye concentration in a local region inside a cell for intracellular measurement. Different from existing magnetic micromanipulation systems that generate large swarms (several microns and above) or that cannot move the generated swarm to an arbitrary position, our system is capable of generating a small swarm (e.g., 1 μm) and accurately positioning the swarm inside a single cell (position control accuracy: 0.76 μm). In experiments, the generated swarm inside the cell showed an SNR 10 times higher than the traditional global dye treatment method. The high-SNR robotic swarm enabled intracellular measurements that had not been possible to achieve with traditional global dye treatment. The robotic swarm technique revealed an apparent pH gradient in a migrating cell and was used to measure the intracellular apparent pH in a single oocyte of living C. elegans. With the position control capability, the swarm was also applied to measure calcium changes at the perinuclear region of a cell before and after mechanical stimulation. The results showed a significant calcium increase after mechanical stimulation, and the calcium increase was regulated by the mechanically sensitive ion channel, PIEZO1.
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IJS, KILJ, NUK, PNG, UL, UM