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Considering the characteristics and operating environment of remotely controlled miniature soft robots, achieving delicate adhesion control over various target surfaces is a substantial challenge. In particular, the ability to delicately grasp wrinkled and soft biological and nonbiological surfaces with low preload without causing damage is essential. The proposed adhesive robotic system, inspired by the secretions from a velvet worm, uses a structured magnetorheological material that exhibits precise adhesion control with stability and repeatability by the rapid stiffness change controlled by an external magnetic field. The proposed adhesion protocol involves controlling soft-state adhesion, maintaining a large contact area, and enhancing the elastic modulus, and the mechanical structure enhances the effectiveness of this protocol. Demonstrations of the remote adhesive robot include stable transportation in soft and wet organs, unscrewing a nut from a bolt, and supporting mouse tumor removal surgery. These results indicate the potential applicability of the soft adhesive robot in biomedical engineering, especially for targeting small-scale biological tissues and organisms.

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., (© 2024 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Medical microrobotics is an emerging field to revolutionize clinical applications in diagnostics and therapeutics of various diseases. On the other hand, the mobile microrobotics field has important obstacles to pass before clinical translation. This article focuses on these challenges and provides a roadmap of medical microrobots to enable their clinical use. From the concept of a "magic bullet" to the physicochemical interactions of microrobots in complex biological environments in medical applications, there are several translational steps to consider. Clinical translation of mobile microrobots is only possible with a close collaboration between clinical experts and microrobotics researchers to address the technical challenges in microfabrication, safety, and imaging. The clinical application potential can be materialized by designing microrobots that can solve the current main challenges, such as actuation limitations, material stability, and imaging constraints. The strengths and weaknesses of the current progress in the microrobotics field are discussed and a roadmap for their clinical applications in the near future is outlined., (© 2024 The Authors. Advanced Materials published by Wiley‐VCH GmbH.)

Small-scale magnetic soft-bodied robots can be designed to operate based on different locomotion modes to navigate and function inside unstructured, confined and varying environments. These soft millirobots may be useful for medical applications where the robots are tasked with moving inside the human body. Here we cover the entire process of developing small-scale magnetic soft-bodied millirobots with multimodal locomotion capability, including robot design, material preparation, robot fabrication, locomotion control and locomotion optimization. We describe in detail the design, fabrication and control of a sheet-shaped soft millirobot with 12 different locomotion modes for traversing different terrains, an ephyra jellyfish-inspired soft millirobot that can manipulate objects in liquids through various swimming modes, a larval zebrafish-inspired soft millirobot that can adjust its body stiffness for efficient propulsion in different swimming speeds and a dual stimuli-responsive sheet-shaped soft millirobot that can switch its locomotion modes automatically by responding to changes in the environmental temperature. The procedure is aimed at users with basic expertise in soft robot development. The procedure requires from a few days to several weeks to complete, depending on the degree of characterization required., (© 2023. Springer Nature Limited.)

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., (© 2023. The Author(s).)

Implanted electronic sensors, compared with conventional medical imaging, allow monitoring of advanced physiological properties of soft biological tissues continuously, such as adhesion, pH, viscoelasticity, and biomarkers for disease diagnosis. However, they are typically invasive, requiring being deployed by surgery, and frequently cause inflammation. Here we propose a minimally invasive method of using wireless miniature soft robots to in situ sense the physiological properties of tissues. By controlling robot-tissue interaction using external magnetic fields, visualized by medical imaging, we can recover tissue properties precisely from the robot shape and magnetic fields. We demonstrate that the robot can traverse tissues with multimodal locomotion and sense the adhesion, pH, and viscoelasticity on porcine and mice gastrointestinal tissues ex vivo, tracked by x-ray or ultrasound imaging. With the unprecedented capability of sensing tissue physiological properties with minimal invasion and high resolution deep inside our body, this technology can potentially enable critical applications in both basic research and clinical practice.

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 (&lt;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., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Biological microorganisms overcome the Brownian motion at low Reynolds numbers by utilizing symmetry-breaking mechanisms. Inspired by them, various microrobot locomotion methods have been developed at the microscale by breaking the hydrodynamic symmetry. Although the boundary effects have been extensively studied for microswimmers and employed for surface-rolling microrobots, the behavior of microrobots in the proximity of multiple wall-based "confinement" is yet to be elucidated. Here, we study the confinement effect on the motion of surface-rolling microrobots. Our experiments demonstrate that the locomotion efficiency of spherical microrollers drastically decreases in confined spaces due to out-of-plane rotational flows generated during locomotion. Hence, a slender microroller design, generating smaller rotational flows, is shown to outperform spherical microrollers in confined spaces. Our results elucidate the underlying physics of surface rolling-based locomotion in confined spaces and present a design strategy with optimal flow generation for efficient propulsion in such areas, including blood vessels and microchannels., (© 2022. The Author(s).)

Microrobots have attracted the attention of scientists owing to their unique features to accomplish tasks in hard-to-reach sites in the human body. Microrobots can be precisely actuated and maneuvered individually or in a swarm for cargo delivery, sampling, surgery, and imaging applications. In addition, microrobots have found applications in the environmental sector (e.g., water treatment). Besides, recent advancements of three-dimensional (3D) printers have enabled the high-resolution fabrication of microrobots with a faster design-production turnaround time for users with limited micromanufacturing skills. Here, the latest end applications of 3D printed microrobots are reviewed (ranging from environmental to biomedical applications) along with a brief discussion over the feasible actuation methods (e.g., on- and off-board), and practical 3D printing technologies for microrobot fabrication. In addition, as a future perspective, we discussed the potential advantages of integration of microrobots with smart materials, and conceivable benefits of implementation of artificial intelligence (AI), as well as physical intelligence (PI). Moreover, in order to facilitate bench-to-bedside translation of microrobots, current challenges impeding clinical translation of microrobots are elaborated, including entry obstacles (e.g., immune system attacks) and cumbersome standard test procedures to ensure biocompatibility., (© 2022. The Author(s).)

Wireless miniature soft actuators are promising for various potential high-impact applications in medical, robotic grippers, and artificial muscles. However, these miniature soft actuators are currently constrained by a small output force and low work capacity. To address such challenges, a miniature magnetic phase-change soft composite actuator is reported. This soft actuator exhibits an expanding deformation and enables up to a 70 N output force and 175.2 J g -1 work capacity under remote magnetic radio frequency heating, which are 10 6 -10 7 times that of traditional magnetic soft actuators. To demonstrate its capabilities, a wireless soft robotic device is first designed that can withstand 0.24 m s -1 fluid flows in an artery phantom. By integrating it with a thermally-responsive shape-memory polymer and bistable metamaterial sleeve, a wireless reversible bistable stent is designed toward future potential angioplasty applications. Moreover, it can additionally locomote inside and jump out of granular media. At last, the phase-change actuator can realize programmable bending deformations when a specifically designed magnetization profile is encoded, enhancing its shape-programming capability. Such a miniature soft actuator provides an approach to enhance the mechanical output and versatility of magnetic soft robots and devices, extending their medical and other potential applications., (© 2022 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

The limited force or torque outputs of miniature magnetic actuators constrain the locomotion performances and functionalities of magnetic millimeter-scale robots. Here, we present a magnetically actuated gearbox with a maximum size of 3 millimeters for driving wireless millirobots. The gearbox is assembled using microgears that have reference diameters down to 270 micrometers and are made of aluminum-filled epoxy resins through casting. With a magnetic disk attached to the input shaft, the gearbox can be driven by a rotating external magnetic field, which is not more than 6.8 millitesla, to produce torque of up to 0.182 millinewton meters at 40 hertz. The corresponding torque and power densities are 12.15 micronewton meters per cubic millimeter and 8.93 microwatt per cubic millimeter, respectively. The transmission efficiency of the gearbox in the air is between 25.1 and 29.2% at actuation frequencies ranging from 1 to 40 hertz, and it lowers when the gearbox is actuated in viscous liquids. This miniature gearbox can be accessed wirelessly and integrated with various functional modules to repeatedly generate large actuation forces, strains, and speeds; store energy in elastic components; and lock up mechanical linkages. These characteristics enable us to achieve a peristaltic robot that can crawl on a flat substrate or inside a tube, a jumping robot with a tunable jumping height, a clamping robot that can sample solid objects by grasping, a needle-puncture robot that can take samples from the inside of the target, and a syringe robot that can collect or release liquids.

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.

Microcatheters have enabled diverse minimally invasive endovascular operations and notable health benefits compared with open surgeries. However, with tortuous routes far from the arterial puncture site, the distal vascular regions remain challenging for safe catheter access. Therefore, we propose a wireless stent-shaped magnetic soft robot to be deployed, actively navigated, used for medical functions, and retrieved in the example M4 segment of the middle cerebral artery. We investigate shape-adaptively controlled locomotion in phantoms emulating the physiological conditions here, where the lumen diameter shrinks from 1.5 mm to 1 mm, the radius of curvature of the tortuous lumen gets as small as 3 mm, the lumen bifurcation angle goes up to 120 ° , and the pulsatile flow speed reaches up to 26 cm/s. The robot can also withstand the flow when the magnetic actuation is turned off. These locomotion capabilities are confirmed in porcine arteries ex vivo. Furthermore, variants of the robot could release the tissue plasminogen activator on-demand locally for thrombolysis and function as flow diverters, initiating promising therapies towards acute ischemic stroke, aneurysm, arteriovenous malformation, dural arteriovenous fistulas, and brain tumors. These functions should facilitate the robot's usage in new distal endovascular operations., (© 2022. The Author(s).)

Although collective robotic construction systems are beginning to showcase how multi-robot systems can contribute to building construction by efficiently building low-cost, sustainable structures, the majority of research utilizes non-structural or highly customized materials. A modular collective robotic construction system based on a robotic actuator, which leverages timber struts for the assembly of architectural artifacts as well as part of the robot body for locomotion is presented. The system is co-designed for in-plane assembly from an architectural, robotic, and computer science perspective in order to integrate the various hardware and software constraints into a single workflow. The system is tested using five representative physical scenarios. These proof-of-concept demonstrations showcase three tasks required for construction assembly: the ability of the system to locomote, dynamically change the topology of connecting robotic actuators and timber struts, and collaborate to transport timber struts. As such, the groundwork for a future autonomous collective robotic construction system that could address collective construction assembly and even further increase the flexibility of on-site construction robots through its modularity is laid., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Mobile microrobots hold remarkable potential to revolutionize health care by enabling unprecedented active medical interventions and theranostics, such as active cargo delivery and microsurgical manipulations in hard-to-reach body sites. High-resolution imaging and control of cell-sized microrobots in the in vivo vascular system remains an unsolved challenge toward their clinical use. To overcome this limitation, we propose noninvasive real-time detection and tracking of circulating microrobots using optoacoustic imaging. We devised cell-sized nickel-based spherical Janus magnetic microrobots whose near-infrared optoacoustic signature is enhanced via gold conjugation. The 5-, 10-, and 20-μm-diameter microrobots are detected volumetrically both in bloodless ex vivo tissues and under real-life conditions with a strongly light-absorbing blood background. We further demonstrate real-time three-dimensional tracking and magnetic manipulation of the microrobots circulating in murine cerebral vasculature, thus paving the way toward effective and safe operation of cell-sized microrobots in challenging and clinically relevant intravascular environments.

Recently, the realization of minimally invasive medical interventions on targeted tissues using wireless small-scale medical robots has received an increasing attention. For effective implementation, such robots should have a strong adhesion capability to biological tissues and at the same time easy controlled detachment should be possible, which has been challenging. To address such issue, a small-scale soft robot with octopus-inspired hydrogel adhesive (OHA) is proposed. Hydrogels of different Young's moduli are adapted to achieve a biocompatible adhesive with strong wet adhesion by preventing the collapse of the octopus-inspired patterns during preloading. Introduction of poly(N-isopropylacrylamide) hydrogel for dome-like protuberance structure inside the sucker wall of polyethylene glycol diacrylate hydrogel provides a strong tissue attachment in underwater and at the same time enables easy detachment by temperature changes due to its temperature-dependent volume change property. It is finally demonstrated that the small-scale soft OHA robot can efficiently implement biomedical functions owing to strong adhesion and controllable detachment on biological tissues while operating inside the body. Such robots with repeatable tissue attachment and detachment possibility pave the way for future wireless soft miniature robots with minimally invasive medical interventions., (© 2022 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Designers of legged robots are challenged with creating mechanisms that allow energy-efficient locomotion with robust and minimalistic control. Sources of high energy costs in legged robots include the rapid loading and high forces required to support the robot's mass during stance and the rapid cycling of the leg's state between stance and swing phases. Here, we demonstrate an avian-inspired robot leg design, BirdBot, that challenges the reliance on rapid feedback control for joint coordination and replaces active control with intrinsic, mechanical coupling, reminiscent of a self-engaging and disengaging clutch. A spring tendon network rapidly switches the leg's slack segments into a loadable state at touchdown, distributes load among joints, enables rapid disengagement at toe-off through elastically stored energy, and coordinates swing leg flexion. A bistable joint mediates the spring tendon network's disengagement at the end of stance, powered by stance phase leg angle progression. We show reduced knee-flexing torque to a 10th of what is required for a nonclutching, parallel-elastic leg design with the same kinematics, whereas spring-based compliance extends the leg in stance phase. These mechanisms enable bipedal locomotion with four robot actuators under feedforward control, with high energy efficiency. The robot offers a physical model demonstration of an avian-inspired, multiarticular elastic coupling mechanism that can achieve self-stable, robust, and economic legged locomotion with simple control and no sensory feedback. The proposed design is scalable, allowing the design of large legged robots. BirdBot demonstrates a mechanism for self-engaging and disengaging parallel elastic legs that are contact-triggered by the foot's own lever-arm action.

We propose two-dimensional poly(heptazine imide) (PHI) carbon nitride microparticles as light-driven microswimmers in various ionic and biological media. Their high-speed (15 to 23 micrometer per second; 9.5 ± 5.4 body lengths per second) swimming in multicomponent ionic solutions with concentrations up to 5 M and without dedicated fuels is demonstrated, overcoming one of the bottlenecks of previous light-driven microswimmers. Such high ion tolerance is attributed to a favorable interplay between the particle’s textural and structural nanoporosity and optoionic properties, facilitating ionic interactions in solutions with high salinity. Biocompatibility of these microswimmers is validated by cell viability tests with three different cell lines and primary cells. The nanopores of the swimmers are loaded with a model cancer drug, doxorubicin (DOX), resulting in a high (185%) loading efficiency without passive release. Controlled drug release is reported under different pH conditions and can be triggered on-demand by illumination. Light-triggered, boosted release of DOX and its active degradation products are demonstrated under oxygen-poor conditions using the intrinsic, environmentally sensitive and light-induced charge storage properties of PHI, which could enable future theranostic applications in oxygen-deprived tumor regions. These organic PHI microswimmers simultaneously address the current light-driven microswimmer challenges of high ion tolerance, fuel-free high-speed propulsion in biological media, biocompatibility, and controlled on-demand cargo release toward their biomedical, environmental, and other potential applications.

Small-scale wireless magnetic robots and devices offer an effective solution to operations in hard-to-reach and high-risk enclosed places, such as inside the human body, nuclear plants, and vehicle infrastructure. In order to obtain functionalities beyond the capability of magnetic forces and torques exerted on magnetic materials used in these robotic devices, electronics need to be also integrated into them. However, their capabilities and power sources are still very limited compared to their larger-scale counterparts due to their much smaller sizes. Here, groups of milli/centimeter-scale wireless magnetic modules are shown to enable on-site electronic circuit construction and operation of highly demanding wireless electrical devices with no batteries, that is, with wireless power. Moreover, the mobility of the modular components brings remote modification and reconfiguration capabilities. When these small-scale robotic modules are remotely assembled into specific geometries, they can achieve, if not impossible, challenging electrical tasks for individual modules. Using such a method, several wireless and battery-free robotic devices are demonstrated using milli/centimeter-scale robotic modules, such as a wireless circuit to power light-emitting diodes with lower external fields, a device to actuate relatively high force-output shape memory alloy actuators, and a wireless force sensor, all of which can be modified on-site., (© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.)

While suction cups prevail as common gripping tools for a wide range of real-world parts and surfaces, they often fail to seal the contact interface when engaging with irregular shapes and textured surfaces. In this work, the authors propose a suction-based soft robotic gripper where suction is created inside a self-sealing, highly conformable and thin flat elastic membrane contacting a given part surface. Such soft gripper can self-adapt the size of its effective suction area with respect to the applied load. The elastomeric membrane covering edge of the soft gripper can develop an air-tight self-sealing with parts even smaller than the gripper diameter. Such gripper shows 4 times higher adhesion than the one without the membrane on various textured surfaces. The two major advantages, underactuated self-adaptability and enhanced suction performance, allow the membrane-based suction mechanism to grip various three-dimensional (3D) geometries and delicate parts, such as egg, lime, apple, and even hydrogels without noticeable damage, which can have not been gripped with the previous adhesive microstructures-based and active suction-based soft grippers. The structural and material simplicity of the proposed soft gripper design can have a broad use in diverse fields, such as digital manufacturing, robotic manipulation, transfer printing, and medical gripping., (© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Magnetic resonance imaging (MRI) scanners do not provide only high-resolution medical imaging but also magnetic robot actuation and tracking. However, the rotational motion capabilities of MRI-powered wireless magnetic capsule-type robots have been limited due to the very high axial magnetic field inside the MRI scanner. Medical functionalities of such robots also remain a challenge due to the miniature robot designs. Therefore, a wireless capsule-type reversible orientation-locking robot (REVOLBOT) is proposed that has decoupled translational motion and planar orientation change capability by locking and unlocking the rotation of a spherical ferrous bead inside the robot on demand. Such an on-demand locking/unlocking mechanism is achieved by a phase-changing wax material in which the ferrous bead is embedded inside. Controlled and on-demand hyperthermia and drug delivery using wireless power transfer-based Joule heating induced by external alternating magnetic fields are the additional features of this robot. The experimental feasibility of the REVOLBOT prototype with steerable navigation, medical function, and MRI tracking capabilities with an 1.33 Hz scan rate is demonstrated inside a preclinical 7T small-animal MRI scanner. The proposed robot has the potential for future clinical use in teleoperated minimally invasive treatment procedures with hyperthermia and drug delivery capabilities while being wirelessly powered and monitored inside MRI scanners., Competing Interests: Conflict of Interest The authors declare no conflict of interest.

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., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Surface microrollers are promising microrobotic systems for controlled navigation in the circulatory system thanks to their fast speeds and decreased flow velocities at the vessel walls. While surface propulsion on the vessel walls helps minimize the effect of strong fluidic forces, three-dimensional (3D) surface microtopography, comparable to the size scale of a microrobot, due to cellular morphology and organization emerges as a major challenge. Here, we show that microroller shape anisotropy determines the surface locomotion capability of microrollers on vessel-like 3D surface microtopographies against physiological flow conditions. The isotropic (single, 8.5 µm diameter spherical particle) and anisotropic (doublet, two 4 µm diameter spherical particle chain) magnetic microrollers generated similar translational velocities on flat surfaces, whereas the isotropic microrollers failed to translate on most of the 3D-printed vessel-like microtopographies. The computational fluid dynamics analyses revealed larger flow fields generated around isotropic microrollers causing larger resistive forces near the microtopographies, in comparison to anisotropic microrollers, and impairing their translation. The superior surface-rolling capability of the anisotropic doublet microrollers on microtopographical surfaces against the fluid flow was further validated in a vessel-on-a-chip system mimicking microvasculature. The findings reported here establish the design principles of surface microrollers for robust locomotion on vessel walls against physiological flows., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Self-healing materials are indispensable for soft actuators and robots that operate in dynamic and real-world environments, as these machines are vulnerable to mechanical damage. However, current self-healing materials have shortcomings that limit their practical application, such as low healing strength (below a megapascal) and long healing times (hours). Here, we introduce high-strength synthetic proteins that self-heal micro- and macro-scale mechanical damage within a second by local heating. These materials are optimized systematically to improve their hydrogen-bonded nanostructure and network morphology, with programmable healing properties (2-23 MPa strength after 1 s of healing) that surpass by several orders of magnitude those of other natural and synthetic soft materials. Such healing performance creates new opportunities for bioinspired materials design, and addresses current limitations in self-healing materials for soft robotics and personal protective equipment.

Microrobots offer transformative solutions for non-invasive medical interventions due to their small size and untethered operation inside the human body. However, they must face the immune system as a natural protection mechanism against foreign threats. Here, non-immunogenic stealth zwitterionic microrobots that avoid recognition from immune cells are introduced. Fully zwitterionic photoresists are developed for two-photon polymerization 3D microprinting of hydrogel microrobots with ample functionalization: tunable mechanical properties, anti-biofouling and non-immunogenic properties, functionalization for magnetic actuation, encapsulation of biomolecules, and surface functionalization for drug delivery. Stealth microrobots avoid detection by macrophage cells of the innate immune system after exhaustive inspection (>90 hours), which has not been achieved in any microrobotic platform to date. These versatile zwitterionic materials eliminate a major roadblock in the development of biocompatible microrobots, and will serve as a toolbox of non-immunogenic materials for medical microrobot and other device technologies for bioengineering and biomedical applications., (© 2020 The Authors. Published by Wiley-VCH GmbH.)

The structural design parameters of a medical microrobot, such as the morphology and surface chemistry, should aim to minimize any physical interactions with the cells of the immune system. However, the same surface-borne design parameters are also critical for the locomotion performance of the microrobots. Understanding the interplay of such parameters targeting high locomotion performance and low immunogenicity at the same time is of paramount importance yet has so far been overlooked. Here, we investigated the interactions of magnetically steerable double-helical microswimmers with mouse macrophage cell lines and splenocytes, freshly harvested from mouse spleens, by systematically changing their helical morphology. We found that the macrophages and splenocytes can recognize and differentially elicit an immune response to helix turn numbers of the microswimmers that otherwise have the same size, bulk physical properties, and surface chemistries. Our findings suggest that the structural optimization of medical microrobots for the locomotion performance and interactions with the immune cells should be considered simultaneously because they are highly entangled and can demand a substantial design compromise from one another. Furthermore, we show that morphology-dependent interactions between macrophages and microswimmers can further present engineering opportunities for biohybrid microrobot designs. We demonstrate immunobots that can combine the steerable mobility of synthetic microswimmers and the immunoregulatory capability of macrophages for potential targeted immunotherapeutic applications., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Mobile microrobots offer great promise for minimally invasive targeted medical theranostic applications at hard-to-access regions inside the human body. The circulatory system represents the ideal route for navigation; however, blood flow impairs propulsion of microrobots especially for the ones with overall sizes less than 10 micrometers. Moreover, cell- and tissue-specific targeting is required for efficient recognition of disease sites and long-term preservation of microrobots under dynamic flow conditions. Here, we report cell-sized multifunctional surface microrollers with ~3.0 and ~7.8-micrometer diameters, inspired by leukocytes in the circulatory system, for targeted drug delivery into specific cells and controlled navigation inside blood flow. The leukocyte-inspired spherical microrollers are composed of magnetically responsive Janus microparticles functionalized with targeting antibodies against cancer cells (anti-HER2) and light-cleavable cancer drug molecules (doxorubicin). Magnetic propulsion and steering of the microrollers resulted in translational motion speeds up to 600 micrometers per second, around 76 body lengths per second. Targeting cancer cells among a heterogeneous cell population was demonstrated by active propulsion and steering of the microrollers over the cell monolayers. The multifunctional microrollers were propelled against physiologically relevant blood flow (up to 2.5 dynes per square centimeter) on planar and endothelialized microchannels. Furthermore, the microrollers generated sufficient upstream propulsion to locomote on inclined three-dimensional surfaces in physiologically relevant blood flow. The multifunctional microroller platform described here presents a bioinspired approach toward in vivo controlled propulsion, navigation, and targeted active cargo delivery in the circulatory system., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

A diversity of self-propelled chemical motors, based on Marangoni propulsive forces, has been developed in recent years. However, most motors are non-functional due to poor performance, a lack of control, and the use of toxic materials. To overcome these limitations, we have developed multifunctional and biodegradable self-propelled motors from squid-derived proteins and an anesthetic metabolite. The protein motors surpass previous reports in performance output and efficiency by several orders of magnitude, and they offer control of their propulsion modes, speed, mobility lifetime, and directionality by regulating the protein nanostructure via local and external stimuli, resulting in programmable and complex locomotion. We demonstrate diverse functionalities of these motors in environmental remediation, microrobot powering, and cargo delivery applications. These versatile and degradable protein motors enable design, control, and actuation strategies in microrobotics as modular propulsion sources for autonomous minimally invasive medical operations in biological environments with air-liquid interfaces.

The functionalities of the untethered miniature swimming robots significantly decrease as the robot size becomes smaller, due to limitations of feasible miniaturized on-board components. Here we propose an untethered jellyfish-inspired soft millirobot that could realize multiple functionalities in moderate Reynolds number by producing diverse controlled fluidic flows around its body using its magnetic composite elastomer lappets, which are actuated by an external oscillating magnetic field. We particularly investigate the interaction between the robot's soft body and incurred fluidic flows due to the robot's body motion, and utilize such physical interaction to achieve different predation-inspired object manipulation tasks. The proposed lappet kinematics can inspire other existing jellyfish-like robots to achieve similar functionalities at the same length and time scale. Moreover, the robotic platform could be used to study the impacts of the morphology and kinematics changing in ephyra jellyfish.

Sperm cells undergo a wide variety of swimming patterns by a beating flagellum to maintain high speed regardless of the rheological and physical properties of the background fluid. In this work, we develop and control a soft robotic sperm that undergoes controllable switching between swimming modes like biological sperm cells. The soft robotic sperm consists of a magnetic head and an ultra-thin flexible flagellum, and is actuated using external magnetic fields. We observe that out-of-plane wobbling of the head results in helical wave propagation along the flagellum, whereas in-plane wobbling achieves planar wave propagation. Our theoretical predictions and experimental results show the ability of the soft robotic sperm to change its swimming speed by tuning the beating frequency of its flagellum and the propulsion pattern. The average speed of the soft robotic sperm increases by factors of 2 and 1.2 in fluids with viscosity of 1 Pa.s and 5 Pa.s at relatively low actuation frequencies, respectively, when they switch between planar to helical flagellar propulsion., Competing Interests: The authors have declared that no competing interests exist.

During dynamic terrestrial locomotion, animals use complex multifunctional feet to extract friction from the environment. However, whether roboticists assume sufficient surface friction for locomotion or actively compensate for slipping, they use relatively simple point-contact feet. We seek to understand and extract the morphological adaptations of animal feet that contribute to enhancing friction on diverse surfaces, such as the desert locust ( Schistocerca gregaria ) [Bennet-Clark HC (1975) J Exp Biol 63:53-83], which has both wet adhesive pads and spines. A buckling region in their knee to accommodate slipping [Bayley TG, Sutton GP, Burrows M (2012) J Exp Biol 215:1151-1161], slow nerve conduction velocity (0.5-3 m/s) [Pearson KG, Stein RB, Malhotra SK (1970) J Exp Biol 53:299-316], and an ecological pressure to enhance jumping performance for survival [Hawlena D, Kress H, Dufresne ER, Schmitz OJ (2011) Funct Ecol 25:279-288] further suggest that the locust operates near the limits of its surface friction, but without sufficient time to actively control its feet. Therefore, all surface adaptation must be through passive mechanics (morphological intelligence), which are unknown. Here, we report the slipping behavior, dynamic attachment, passive mechanics, and interplay between the spines and adhesive pads, studied through both biological and robotic experiments, which contribute to the locust's ability to jump robustly from diverse surfaces. We found slipping to be surface-dependent and common (e.g., wood 1.32 ± 1.19 slips per jump), yet the morphological intelligence of the feet produces a significant chance to reengage the surface (e.g., wood 1.10 ± 1.13 reengagements per jump). Additionally, a discovered noncontact-type jump, further studied robotically, broadens the applicability of the morphological adaptations to both static and dynamic attachment., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 the Author(s). Published by PNAS.)

Untethered small-scale (from several millimetres down to a few micrometres in all dimensions) robots that can non-invasively access confined, enclosed spaces may enable applications in microfactories such as the construction of tissue scaffolds by robotic assembly, in bioengineering such as single-cell manipulation and biosensing, and in healthcare such as targeted drug delivery and minimally invasive surgery. Existing small-scale robots, however, have very limited mobility because they are unable to negotiate obstacles and changes in texture or material in unstructured environments. Of these small-scale robots, soft robots have greater potential to realize high mobility via multimodal locomotion, because such machines have higher degrees of freedom than their rigid counterparts. Here we demonstrate magneto-elastic soft millimetre-scale robots that can swim inside and on the surface of liquids, climb liquid menisci, roll and walk on solid surfaces, jump over obstacles, and crawl within narrow tunnels. These robots can transit reversibly between different liquid and solid terrains, as well as switch between locomotive modes. They can additionally execute pick-and-place and cargo-release tasks. We also present theoretical models to explain how the robots move. Like the large-scale robots that can be used to study locomotion, these soft small-scale robots could be used to study soft-bodied locomotion produced by small organisms.

Untethered micron-scale mobile robots can navigate and non-invasively perform specific tasks inside unprecedented and hard-to-reach inner human body sites and inside enclosed organ-on-a-chip microfluidic devices with live cells. They are aimed to operate robustly and safely in complex physiological environments where they will have a transforming impact in bioengineering and healthcare. Research along this line has already demonstrated significant progress, increasing attention, and high promise over the past several years. The first-generation microrobots, which could deliver therapeutics and other cargo to targeted specific body sites, have just been started to be tested inside small animals toward clinical use. Here, we review frontline advances in design, fabrication, and testing of untethered mobile microrobots for bioengineering applications. We convey the most impactful and recent strategies in actuation, mobility, sensing, and other functional capabilities of mobile microrobots, and discuss their potential advantages and drawbacks to operate inside complex, enclosed and physiologically relevant environments. We lastly draw an outlook to provide directions in the veins of more sophisticated designs and applications, considering biodegradability, immunogenicity, mobility, sensing, and possible medical interventions in complex microenvironments.

At the sub-millimeter scale, capillary forces enable robust and reversible adhesion between biological organisms and varied substrates. Current human-engineered mobile untethered micromanipulation systems rely on forces which scale poorly or utilize gripper-part designs that promote manipulation. Capillary forces, alternatively, are dependent upon the surface chemistry (which is scale independent) and contact perimeter, which conforms to the part surface. We report a mobile capillary microgripper that is able to pick and place parts of various materials and geometries, and is thus ideal for microassembly tasks that cannot be accomplished by large tethered manipulators. We achieve the programmable assembly of sub-millimeter parts in an enclosed three-dimensional aqueous environment by creating a capillary bridge between the targeted part and a synthetic, untethered, mobile body. The parts include both hydrophilic and hydrophobic components: hydrogel, kapton, human hair, and biological tissue. The 200 μm untethered system can be controlled with five-degrees-of-freedom and advances progress towards autonomous desktop manufacturing for tissue engineering, complex micromachines, microfluidic devices, and meta-materials.

Introduction: Gastric cancer represents a great challenge for healthcare providers and requires a multidisciplinary treatment approach in which surgery plays a major role. Minimally invasive surgery has been progressively developed, first with the advent of laparoscopy and recently with the spread of robotic surgery, but a number of issues are currently being debated, including the limitations in performing an effective extended lymph node dissection, the real advantages of robotic systems, the role of laparoscopy for Advanced Gastric Cancer, the reproducibility of a total intracorporeal technique and the oncological results achievable during long-term follow-up., Methods and Analysis: A multi-institutional international database will be established to evaluate the role of robotic, laparoscopic and open approaches in gastric cancer, comprising of information regarding surgical, clinical and oncological features. A chart review will be conducted to enter data of participants with gastric cancer, previously treated at the participating institutions. The database is the first of its kind, through an international electronic submission system and a HIPPA protected real time data repository from high volume gastric cancer centres., Ethics and Dissemination: This study is conducted in compliance with ethical principles originating from the Helsinki Declaration, within the guidelines of Good Clinical Practice and relevant laws/regulations. A multicentre study with a large number of patients will permit further investigation of the safety and efficacy as well as the long-term outcomes of robotic, laparoscopic and open approaches for the management of gastric cancer., Trial Registration Number: NCT02325453; Pre-results., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Three-dimensional (3D) heterogeneous assembly of coded microgels in enclosed aquatic environments is demonstrated using a remotely actuated and controlled magnetic microgripper by a customized electromagnetic coil system. The microgripper uses different 'stick-slip' and 'rolling' locomotion in 2D and also levitation in 3D by magnetic gradient-based pulling force. This enables the microrobot to precisely manipulate each microgel by controlling its position and orientation in all x-y-z directions. Our microrobotic assembly method broke the barrier of limitation on the number of assembled microgel layers, because it enabled precise 3D levitation of the microgripper. We used the gripper to assemble microgels that had been coded with different colours and shapes onto prefabricated polymeric microposts. This eliminates the need for extra secondary cross-linking to fix the final construct. We demonstrated assembly of microgels on a single micropost up to ten layers. By increasing the number and changing the distribution of the posts, complex heterogeneous microsystems were possible to construct in 3D.

As we move towards the miniaturization of devices to perform tasks at the nano and microscale, it has become increasingly important to develop new methods for actuation, sensing, and control. Over the past decade, bio-hybrid methods have been investigated as a promising new approach to overcome the challenges of scaling down robotic and other functional devices. These methods integrate biological cells with artificial components and therefore, can take advantage of the intrinsic actuation and sensing functionalities of biological cells. Here, the recent advancements in bio-hybrid actuation are reviewed, and the challenges associated with the design, fabrication, and control of bio-hybrid microsystems are discussed. As a case study, focus is put on the development of bacteria-driven microswimmers, which has been investigated as a targeted drug delivery carrier. Finally, a future outlook for the development of these systems is provided. The continued integration of biological and artificial components is envisioned to enable the performance of tasks at a smaller and smaller scale in the future, leading to the parallel and distributed operation of functional systems at the microscale., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Bio-hybrid devices, which integrate biological cells with synthetic components, have opened a new path in miniaturized systems with the potential to provide actuation and control for systems down to a few microns in size. Here, we address the challenge of remotely controlling bio-hybrid microswimmers propelled by multiple bacterial cells. These devices have been proposed as a viable method for targeted drug delivery but have also been shown to exhibit stochastic motion. We demonstrate a method of remote magnetic control that significantly reduces the stochasticity of the motion, enabling steering control. The demonstrated microswimmers consist of multiple Serratia marcescens (S. marcescens) bacteria attached to a 6 μm-diameter superparamagnetic bead. We characterize their motion and define the parameters governing their controllability. We show that the microswimmers can be controlled along two-dimensional (2-D) trajectories using weak magnetic fields (≤10 mT) and can achieve 2-D swimming speeds up to 7.3 μm s(-1). This magnetic steering approach can be integrated with sensory-based steering in future work, enabling new control strategies for bio-hybrid microsystems.

The adhesive characteristics of fibrillar adhesives on a soft deformable membrane are reported. A soft gripper with an inflatable membrane covered by elastomer mushroom-shaped microfibers have a superior conformation to non-planar 3D part geometries, enabling the transfer printing of various parts serially or in parallel., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

This paper proposes a new wireless biopsy method where a magnetically actuated untethered soft capsule endoscope carries and releases a large number of thermo-sensitive, untethered microgrippers (μ-grippers) at a desired location inside the stomach and retrieves them after they self-fold and grab tissue samples. We describe the working principles and analytical models for the μ-gripper release and retrieval mechanisms, and evaluate the proposed biopsy method in ex vivo experiments. This hierarchical approach combining the advanced navigation skills of centimeter-scaled untethered magnetic capsule endoscopes with highly parallel, autonomous, submillimeter scale tissue sampling μ-grippers offers a multifunctional strategy for gastrointestinal capsule biopsy.

Background: Nephrometric scoring systems aim to improve the manner in which tumoral complexity is measured and reported. Each system provides a way to objectively measure specific tumor features that influence technical feasibility. In this study we aimed to determine how nephrometric scoring systems tailored our approach to the surgical treatment of localised renal masses., Methods: Charts of the patients with localised renal tumors, who were managed by either open or robot-assisted nephron-sparing surgery between May 2010 and June 2012, were retrospectively reviewed. Nephrometric scores [radius, exophytic/endophytic, nearness, anterior/posterior, location (R.E.N.A.L.) score, preoperative aspects and dimensions used for anatomic (P.A.D.U.A.) classification and centrality index (C-index)] were calculated based on preoperative imaging findings. Perioperative data were recorded. Morphometric characteristics of the renal masses were compared. Additionally, the difference between surgical alternative subgroups in terms of morphometric variables and the predictive power of each scoring system in determining the details of the surgical plan were investigated. Furthermore, surgical preferences in different nephrometric categories were compared., Results: Mean R.E.N.A.L. and P.A.D.U.A. scores of the tumors treated with robotic surgery were significantly lower than those managed by open surgery. R.E.N.A.L. nephrometry score showed significant differences between most of the surgical alternative subgroups. P.A.D.U.A. and C-index differences were significant only between robotic off-clamp and open clamped cases. Tumors that required open conversion had significantly higher mean R.E.N.A.L. and P.A.D.U.A. score. High R.E.N.A.L. score (cut-off: 6.5) and high P.A.D.U.A. score (cut-off: 7.5) were found to be significant predictors of the surgical route. Significantly more tumors with moderate R.E.N.A.L. score were managed through the open approach, while the significant majority of those with low R.E.N.A.L. and low P.A.D.U.A. score were operated by robotic assistance., Conclusions: R.E.N.A.L. and P.A.D.U.A. scores influenced our surgical treatment strategy for localized renal masses. High R.E.N.A.L. and P.A.D.U.A. scores increased the likelihood of an open NSS.

HeartLander is a medical robot proposed for minimally invasive epicardial intervention on the beating heart. To date, all prototypes have used suction to gain traction on the epicardium. Gecko-foot-inspired micro-fibers have been proposed for repeatable adhesion to surfaces. In this paper, a method for improving the traction of HeartLander on biological tissue is presented. The method involves integration of gecko-inspired fibrillar adhesives on the inner surfaces of the suction chambers of HeartLander. Experiments have been carried out on muscle tissue ex vivo assessing the traction performance of the modified HeartLander with bio-inspired adhesive. The adhesive fibers are found to improve traction on muscle tissue by 57.3 %.

Compactness and efficiency of biomotors makes them superior to man-made actuators and a very attractive choice of actuation for micro/nanorobots. However, biomotors are difficult to work with due to complications associated with their isolation and reconstitution. To circumvent this problem, here we use flagellar motors inside the intact cell of S. marcescens bacteria. An array of bacteria is used as propeller for a 10 microm polystyrene (PS) bead. PS bead is tracked for several seconds and its displacements is compared with diffusion length of a 10 microm particle. It is shown that the bead moves with an average velocity of 17 microm/s. Orientation of adhesion of S. marcescens to polydimethylsiloxane (PDMS) chips and microscale PS fibers was also investigated. It is shown that for both substrates; only bacteria from farther behind the leading edge of the swarm adhere in end-on configuration.