On-demand anchoring of wireless soft miniature robots on soft surfaces.

Untethered soft miniature robots capable of accessing hard-to-reach regions can enable new, disruptive, and minimally invasive medical procedures. However, once the control input is removed, these robots easily move from their target location because of the dynamic motion of body tissues or fluids, thereby restricting their use in many long-term medical applications. To overcome this, we propose a wireless spring-preloaded barbed needle release mechanism, which can provide up to 1.6 N of force to drive a barbed needle into soft tissues to allow robust on-demand anchoring on three-dimensional (3D) surfaces. The mechanism is wirelessly triggered using radio-frequency remote heating and can be easily integrated into existing untethered soft robotic platforms without sacrificing their mobility. Design guidelines aimed at maximizing anchoring over the range of the most biological tissues (kPa range) and extending the operating depth of the device inside the body (up to 75%) are also presented. Enabled by these advances, we achieve robust anchoring on a variety of ex vivo tissues and demonstrate the usage of such a device when integrated with existing soft robotic platforms and medical imaging. Moreover, by simply changing the needle, we demonstrate additional functionalities such as controlled detachment and subsurface drug delivery into 3D cancer spheroids. Given these capabilities, our proposed mechanism could enable the development of a new class of biomedical-related functionalities, such as local drug delivery, disease monitoring, and hyperthermia for future untethered soft medical robots.

Immune Cell-Based Microrobots for Remote Magnetic Actuation, Antitumor Activity, and Medical Imaging.

Translating medical microrobots into clinics requires tracking, localization, and performing assigned medical tasks at target locations, which can only happen when appropriate design, actuation mechanisms, and medical imaging systems are integrated into a single microrobot. Despite this, these parameters are not fully considered when designing macrophage-based microrobots. This study presents living macrophage-based microrobots that combine macrophages with magnetic Janus particles coated with FePt nanofilm for magnetic steering and medical imaging and bacterial lipopolysaccharides for stimulating macrophages in a tumor-killing state. The macrophage-based microrobots combine wireless magnetic actuation, tracking with medical imaging techniques, and antitumor abilities. These microrobots are imaged under magnetic resonance imaging and optoacoustic imaging in soft-tissue-mimicking phantoms and ex vivo conditions. Magnetic actuation and real-time imaging of microrobots are demonstrated under static and physiologically relevant flow conditions using optoacoustic imaging. Further, macrophage-based microrobots are magnetically steered toward urinary bladder tumor spheroids and imaged with a handheld optoacoustic device, where the microrobots significantly reduce the viability of tumor spheroids. The proposed approach demonstrates the proof-of-concept feasibility of integrating macrophage-based microrobots into clinic imaging modalities for cancer targeting and intervention, and can also be implemented for various other medical applications.

Pangolin-inspired untethered magnetic robot for on-demand biomedical heating applications.

Untethered magnetic miniature soft robots capable of accessing hard-to-reach regions can enable safe, disruptive, and minimally invasive medical procedures. However, the soft body limits the integration of non-magnetic external stimuli sources on the robot, thereby restricting the functionalities of such robots. One such functionality is localised heat generation, which requires solid metallic materials for increased efficiency. Yet, using these materials compromises the compliance and safety of using soft robots. To overcome these competing requirements, we propose a pangolin-inspired bi-layered soft robot design. We show that the reported design achieves heating > 70 °C at large distances > 5 cm within a short period of time <30 s, allowing users to realise on-demand localised heating in tandem with shape-morphing capabilities. We demonstrate advanced robotic functionalities, such as selective cargo release, in situ demagnetisation, hyperthermia and mitigation of bleeding, on tissue phantoms and ex vivo tissues.

Liquid Metal-Elastomer Composites with Dual-Energy Transmission Mode for Multifunctional Miniature Untethered Magnetic Robots.

Miniature untethered robots attract growing interest as they have become more functional and applicable to disruptive biomedical applications recently. Particularly, the soft ones among them exhibit unique merits of compliance, versatility, and agility. With scarce onboard space, these devices mostly harvest energy from environment or physical fields, such as magnetic and acoustic fields and patterned lights. In most cases, one device only utilizes one energy transmission mode (ETM) in powering its activities to achieve programmed tasks, such as locomotion and object manipulation. But real-world tasks demand multifunctional devices that require more energy in various forms. This work reports a liquid metal-elastomer composite with dual-ETM using one magnetic field for miniature untethered multifunctional robots. The first ETM uses the low-frequency (<100 Hz) field component to induce shape-morphing, while the second ETM employs energy transmitted via radio-frequency (20 kHz-300 GHz) induction to power onboard electronics and generate excess heat, enabling new capabilities. These new functions do not disturb the shape-morphing actuated using the first ETM. The reported material enables the integration of electric and thermal functionalities into soft miniature robots, offering a wealth of inspirations for multifunctional miniature robots that leverage developments in electronics to exhibit usefulness beyond self-locomotion.

Miniature coiled artificial muscle for wireless soft medical devices.

Wireless small-scale soft-bodied devices are capable of precise operation inside confined internal spaces, enabling various minimally invasive medical applications. However, such potential is constrained by the small output force and low work capacity of the current miniature soft actuators. To address this challenge, we report a small-scale soft actuator that harnesses the synergetic interactions between the coiled artificial muscle and radio frequency-magnetic heating. This wirelessly controlled actuator exhibits a large output force (~3.1 N) and high work capacity (3.5 J/g). Combining this actuator with different mechanical designs, its tensile and torsional behaviors can be engineered into different functional devices, such as a suture device, a pair of scissors, a driller, and a clamper. In addition, by assuming a spatially varying magnetization profile, a multilinked coiled muscle can have both magnetic field-induced bending and high contractile force. Such an approach could be used in various future untethered miniature medical devices.

Liquid Crystal Elastomer-Based Magnetic Composite Films for Reconfigurable Shape-Morphing Soft Miniature Machines.

Stimuli-responsive and active materials promise radical advances for many applications. In particular, soft magnetic materials offer precise, fast, and wireless actuation together with versatile functionality, while liquid crystal elastomers (LCEs) are capable of large reversible and programmable shape-morphing with high work densities in response to various environmental stimuli, e.g., temperature, light, and chemical solutions. Integrating the orthogonal stimuli-responsiveness of these two kinds of active materials could potentially enable new functionalities and future applications. Here, magnetic microparticles (MMPs) are embedded into an LCE film to take the respective advantages of both materials without compromising their independent stimuli-responsiveness. This composite material enables reconfigurable magnetic soft miniature machines that can self-adapt to a changing environment. In particular, a miniature soft robot that can autonomously alter its locomotion mode when it moves from air to hot liquid, a vine-like filament that can sense and twine around a support, and a light-switchable magnetic spring are demonstrated. The integration of LCEs and MMPs into monolithic structures introduces a new dimension in the design of soft machines and thus greatly enhances their use in applications in complex environments, especially for miniature soft robots, which are self-adaptable to environmental changes while being remotely controllable.

Soft-bodied adaptive multimodal locomotion strategies in fluid-filled confined spaces.

Soft-bodied locomotion in fluid-filled confined spaces is critical for future wireless medical robots operating inside vessels, tubes, channels, and cavities of the human body, which are filled with stagnant or flowing biological fluids. However, the active soft-bodied locomotion is challenging to achieve when the robot size is comparable with the cross-sectional dimension of these confined spaces. Here, we propose various control and performance enhancement strategies to let the sheet-shaped soft millirobots achieve multimodal locomotion, including rolling, undulatory crawling, undulatory swimming, and helical surface crawling depending on different fluid-filled confined environments. With these locomotion modes, the sheet-shaped soft robot can navigate through straight or bent gaps with varying sizes, tortuous channels, and tubes with a flowing fluid inside. Such soft robot design along with its control and performance enhancement strategies are promising to be applied in future wireless soft medical robots inside various fluid-filled tight regions of the human body.

Voxelated three-dimensional miniature magnetic soft machines via multimaterial heterogeneous assembly.

Small-scale soft-bodied machines that respond to externally applied magnetic field have attracted wide research interest because of their unique capabilities and promising potential in a variety of fields, especially for biomedical applications. When the size of such machines approach the sub-millimeter scale, their designs and functionalities are severely constrained by the available fabrication methods, which only work with limited materials, geometries, and magnetization profiles. To free such constraints, here, we propose a bottom-up assembly-based 3D microfabrication approach to create complex 3D miniature wireless magnetic soft machines at the milli- and sub-millimeter scale with arbitrary multimaterial compositions, arbitrary 3D geometries, and arbitrary programmable 3D magnetization profiles at high spatial resolution. This approach helps us concurrently realize diverse characteristics on the machines, including programmable shape morphing, negative Poisson's ratio, complex stiffness distribution, directional joint bending, and remagnetization for shape reconfiguration. It enlarges the design space and enables biomedical device-related functionalities that are previously difficult to achieve, including peristaltic pumping of biological fluids and transport of solid objects, active targeted cargo transport and delivery, liquid biopsy, and reversible surface anchoring in tortuous tubular environments withstanding fluid flows, all at the sub-millimeter scale. This work improves the achievable complexity of 3D magnetic soft machines and boosts their future capabilities for applications in robotics and biomedical engineering.

Microfluidic modelling of the tumor microenvironment for anti-cancer drug development.

Cancer is the leading cause of death worldwide. The complex and disorganized tumor microenvironment makes it very difficult to treat this disease. The most common in vitro drug screening method now is based on 2D culture models which poorly represent actual tumors. Therefore, many 3D tumor models which are more physiologically relevant have been developed to conduct in vitro drug screening and alleviate this situation. Among all these models, the microfluidic tumor model has the unique advantage of recapitulating the tumor microenvironment in a comparatively easier and representative fashion. While there are many review papers available on the related topic of microfluidic tumor models, in this review we aim to focus more on the possibility of generating "clinically actionable information" from these microfluidic systems, besides scientific insight. Our topics cover the tumor microenvironment, conventional 2D and 3D cultures, animal models, and microfluidic tumor models, emphasizing their link to anti-cancer drug discovery and personalized medicine.

Dual-Core Capacitive Microfiber Sensor for Smart Textile Applications.

Wearable sensors for smart textile applications have garnered tremendous interest in recent years and can have enormous potential for human machine interfaces and digital health monitoring. Here, we report a soft capacitive microfiber sensor that can be woven seamlessly into textiles for strain measurement. Comprising a dual-lumen elastomeric microtube and liquid metallic alloy, the microfiber sensor enables continual strain perception even after being completely severed. In addition, our microfiber sensor is highly stretchable and flexible and exhibits tunable sensitivity, excellent linearity, a fast response, and negligible hysteresis. More importantly, the microfiber sensor is minimally affected by train rate and compression during strain sensing. Even under drastic environmental changes, the microfiber sensor presents good electrical stability. By integrating the microfiber sensor imperceptibly with textiles, we devise smart textile wearables to interpret hand gestures, detect limb motion, and monitor respiration rate. We believe that this sensor presents enormous potential in unobtrusive continuous health monitoring.

Cancer diagnosis: from tumor to liquid biopsy and beyond.

Technological advancements in research on circulating biomarkers from patient derived blood have enabled a less invasive means of diagnosing non-hematologic cancers. Considered a more practical way of real-time patient monitoring than traditional tumor biopsy, liquid biopsy markers including circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) and extracellular vesicles (EVs) and exosomes certainly have the potential to change the dynamics of cancer management and treatment. Liquid biopsy essentially presents a snapshot of the disease from the primary and/or distant tumor locations and can be utilized for repeated sampling of tumor markers to adjust therapy according to the patient's response to treatment, also known as personalized or precision treatment. In this review, we discuss the research progress in this field with respect to each of the liquid biopsy markers ranging from CTCs, EVs to ctDNA. First, we highlight key CTC technologies that have been commercialized and extensively employed for patient sample analysis. Next, we present some recent developments with regards to exosome and ctDNA research. We then conclude with some future perspectives on the areas of research for these biomarkers. Taken together, we believe these non-invasive capabilities and their potential for diagnostic development can influence treatment selections and aid precision cancer therapies.

Highly Stretchable, Weavable, and Washable Piezoresistive Microfiber Sensors.

A key challenge in electronic textiles is to develop an intrinsically conductive thread of sufficient robustness and sensitivity. Here, we demonstrate an elastomeric functionalized microfiber sensor suitable for smart textile and wearable electronics. Unlike conventional conductive threads, our microfiber is highly flexible and stretchable up to 120% strain and possesses excellent piezoresistive characteristics. The microfiber is functionalized by enclosing a conductive liquid metallic alloy within the elastomeric microtube. This embodiment allows shape reconfigurability and robustness, while maintaining an excellent electrical conductivity of 3.27 ± 0.08 MS/m. By producing microfibers the size of cotton threads (160 µm in diameter), a plurality of stretchable tubular elastic piezoresistive microfibers may be woven seamlessly into a fabric to determine the force location and directionality. As a proof of concept, the conductive microfibers woven into a fabric glove were used to obtain physiological measurements from the wrist, elbow pit, and less accessible body parts, such as the neck and foot instep. Importantly, the elastomeric layer protects the sensing element from degradation. Experiments showed that our microfibers suffered minimal electrical drift even after repeated stretching and machine washing. These advantages highlight the unique propositions of our wearable electronics for flexible display, electronic textile, soft robotics, and consumer healthcare applications.