A magnetic multi-layer soft robot for on-demand targeted adhesion.

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.

Indentation induces instantaneous nuclear stiffening and unfolding of nuclear envelope wrinkles.

The nuclear envelope (NE) separates genomic DNA from the cytoplasm and regulates transport between the cytosol and the nucleus in eukaryotes. Nuclear stiffening enables the cell nucleus to protect itself from extensive deformation, loss of NE integrity, and genome instability. It is known that the reorganization of actin, lamin, and chromatin can contribute to nuclear stiffening. In this work, we show that structural alteration of NE also contributes to instantaneous nuclear stiffening under indentation. In situ mechanical characterization of cell nuclei in intact cells shows that nuclear stiffening and unfolding of NE wrinkles occur simultaneously at the indentation site. A positive correlation between the initial state of NE wrinkles, the unfolding of NE wrinkles, and the stiffening ratio (stiffness fold-change) is found. Additionally, NE wrinkles unfold throughout the nucleus outside the indentation site. Finite element simulation, which involves the purely passive process of structural unfolding, shows that unfolding of NE wrinkles alone can lead to an increase in nuclear stiffness and a reduction in stress and strain levels. Together, these results provide a perspective on how cell nucleus adapts to mechanical stimuli through structural alteration of the NE.

Micro/Nanorobotic Swarms: From Fundamentals to Functionalities.

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.

Amphibious Miniature Soft Jumping Robot with On-Demand In-Flight Maneuver.

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.

Ultrafast Miniature Robotic Swimmers with Upstream Motility.

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.

Mechanical nanosurgery of chemoresistant glioblastoma using magnetically controlled carbon nanotubes.

Glioblastoma (GBM) is the most common and aggressive primary brain cancer. Despite multimodal treatment including surgery, radiotherapy, and chemotherapy, median patient survival has remained at ~15 months for decades. This situation demands an outside-the-box treatment approach. Using magnetic carbon nanotubes (mCNTs) and precision magnetic field control, we report a mechanical approach to treat chemoresistant GBM. We show that GBM cells internalize mCNTs, the mobilization of which by rotating magnetic field results in cell death. Spatiotemporally controlled mobilization of intratumorally delivered mCNTs suppresses GBM growth in vivo. Functionalization of mCNTs with anti-CD44 antibody, which recognizes GBM cell surface-enriched antigen CD44, increases mCNT recognition of cancer cells, prolongs mCNT enrichment within the tumor, and enhances therapeutic efficacy. Using mouse models of GBM with upfront or therapy-induced resistance to temozolomide, we show that mCNT treatment is effective in treating chemoresistant GBM. Together, we establish mCNT-based mechanical nanosurgery as a treatment option for GBM.

Gravity-resisting colloidal collectives.

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.

Mapping of Spatiotemporal Auricular Electrophysiological Signals Reveals Human Biometric Clusters.

Underneath the ear skin there are rich vascular network and sensory nerve branches. Hence, the 3D mapping of auricular electrophysiological signals can provide new biomedical perspectives. However, it is still extremely challenging for current sensing techniques to cover the entire ultra-curved auricle. Here, a 3D graphene-based ear-conformable sensing device with embedded and distributed 3D electrodes for full-auricle physiological monitoring is reported. As a proof-of-concept, spatiotemporal auricular electrical skin resistance (AESR) mapping is demonstrated for the first time, and human subject-specific AESR distributions are observed. From the data of more than 30 ears (both right and left ears), the auricular region-specific AESR changes after cycling exercise are observed in 98% of the tests and are clustered into four groups via machine learning-based data analyses. Correlations of AESR with heart rate and blood pressure are also studied. This 3D electronic platform and AESR-based biometrical findings show promising biomedical applications.

Microrobotic Swarms for Intracellular Measurement with Enhanced Signal-to-Noise Ratio.

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.

Microrobotic swarms for selective embolization.

Inspired by the collective intelligence in natural swarms, microrobotic agents have been controlled to form artificial swarms for targeted drug delivery, enhanced imaging, and hyperthermia. Different from these well-investigated tasks, this work aims to develop microrobotic swarms for embolization, which is a clinical technique used to block blood vessels for treating tumors, fistulas, and arteriovenous malformations. Magnetic particle swarms were formed for selective embolization to address the low selectivity of the present embolization technique that is prone to cause complications such as stroke and blindness. We established an analytical model that describes the relationships between fluid viscosity, flow rate, branching angle, magnetic field strength, and swarm integrity, based on which an actuation strategy was developed to maintain the swarm integrity inside a targeted region under fluidic flow conditions. Experiments in microfluidic channels, ex vivo tissues, and in vivo porcine kidneys validated the efficacy of the proposed strategy for selective embolization.

A Carbon-Based Biosensing Platform for Simultaneously Measuring the Contraction and Electrophysiology of iPSC-Cardiomyocyte Monolayers.

Heart beating is triggered by the generation and propagation of action potentials through the myocardium, resulting in the synchronous contraction of cardiomyocytes. This process highlights the importance of electrical and mechanical coordination in organ function. Investigating the pathogenesis of heart diseases and potential therapeutic actions in vitro requires biosensing technologies which allow for long-term and simultaneous measurement of the contractility and electrophysiology of cardiomyocytes. However, the adoption of current biosensing approaches for functional measurement of in vitro cardiac models is hampered by low sensitivity, difficulties in achieving multifunctional detection, and costly manufacturing processes. Leveraging carbon-based nanomaterials, we developed a biosensing platform that is capable of performing on-chip and simultaneous measurement of contractility and electrophysiology of human induced pluripotent stem-cell-derived cardiomyocyte (iPSC-CM) monolayers. This platform integrates with a flexible thin-film cantilever embedded with a carbon black (CB)-PDMS strain sensor for high-sensitivity contraction measurement and four pure carbon nanotube (CNT) electrodes for the detection of extracellular field potentials with low electrode impedance. Cardiac functional properties including contractile stress, beating rate, beating rhythm, and extracellular field potential were evaluated to quantify iPSC-CM responses to common cardiotropic agents. In addition, an in vitro model of drug-induced cardiac arrhythmia was established to further validate the platform for disease modeling and drug testing.

Microengineered platforms for characterizing the contractile function of in vitro cardiac models.

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.

Magnetic Measurement and Stimulation of Cellular and Intracellular Structures.

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.

Atomization of High-Viscosity Fluids for Aromatherapy Using Micro-heaters for Heterogeneous Bubble Nucleation.

The development of a novel lead-free microelectromechanical-system (MEMS)-based atomizer using the principle of thermal bubble actuation is presented. It is a low-cost, lead-free design that is environmentally friendly and harmless to humans. It has been tested to be applicable over a wide range of fluid viscosities, ranging from 1 cP (e.g., water) to 200 cP (e.g., oil-like fluid) at room temperature, a range that is difficult to achieve using ordinary atomizers. The results demonstrate that the average power consumption of the atomizer is approximately 1 W with an atomization rate of 0.1 to 0.3 mg of deionized (DI) water per cycle. The relationships between the micro-heater track width and the track gap, the size of the micro-cavities and the nucleation energy were studied to obtain an optimal atomizer design. The particle image velocimetry (PIV) results indicate that the diameter of the ejected droplets ranges from 30 to 90 µm with a speed of 20 to 340 mm/s. In addition, different modes of spraying are reported for the first time. It is envisioned that the successful development of this MEMS-based atomizing technology will revolutionize the existing market for atomizers and could also benefit different industries, particularly in applications involving viscous fluids.