Tunable Light-Responsive Polyurethane-urea Elastomer Driven by Photochemical and Photothermal Coupling Mechanism.

Light-driven soft actuators based on photoresponsive materials can be used to mimic biological motion, such as hand movements, without involving rigid or bulky electromechanical actuations. However, to our knowledge, no robust photoresponsive material with desireable mechanical and biological properties and relatively simple manufacture exists for robotics and biomedical applications. Herein, we report a new visible-light-responsive thermoplastic elastomer synthesized by introducing photoswitchable moieties (i.e., azobenzene derivatives) into the main chain of poly(ε-caprolactone) based polyurethane urea (PAzo). A PAzo elastomer exhibits controllable light-driven stiffness softening due to its unique nanophase structure in response to light, while possessing excellent hyperelasticity (stretchability of 575.2%, elastic modulus of 17.6 MPa, and strength of 44.0 MPa). A bilayer actuator consisting of PAzo and polyimide films is developed, demonstrating tunable bending modes by varying incident light intensities. Actuation mechanism via photothermal and photochemical coupling effects of a soft-hard nanophase is demonstrated through both experimental and theoretical analyses. We demonstrate an exemplar application of visible-light-controlled soft "fingers" playing a piano on a smartphone. The robustness of the PAzo elastomer and its scalability, in addition to its excellent biocompatibility, opens the door to the development of reproducible light-driven wearable/implantable actuators and lightweight soft robots for clinical applications.

ESPRESS.0: Eustachian Tube-Inspired Tactile Sensor Exploiting Pneumatics for Range Extension and SenSitivity Tuning.

Optimising the sensitivity of a tactile sensor to a specific range of stimuli magnitude usually compromises the sensor's widespread usage. This paper presents a novel soft tactile sensor capable of dynamically tuning its stiffness for enhanced sensitivity across a range of applied forces, taking inspiration from the Eustachian tube in the mammalian ear. The sensor exploits an adjustable pneumatic back pressure to control the effective stiffness of its 20 mm diameter elastomer interface. An internally translocated fluid is coupled to the membrane and optically tracked to measure physical interactions at the interface. The sensor can be actuated by pneumatic pressure to dynamically adjust its stiffness. It is demonstrated to detect forces as small as 0.012 N, and to be sensitive to a difference of 0.006 N in the force range of 35 to 40 N. The sensor is demonstrated to be capable of detecting tactile cues on the surface of objects in the sub-millimetre scale. It is able to adapt its compliance to increase its ability for distinguishing between stimuli with similar stiffnesses (0.181 N/mm difference) over a large range (0.1 to 1.1 N/mm) from only a 0.6 mm deep palpation. The sensor is intended to interact comfortably with skin, and the feasibility of its use in palpating tissue in search of hard inclusions is demonstrated by locating and estimating the size of a synthetic hard node embedded 20 mm deep in a soft silicone sample. The results suggest that the sensor is a good candidate for tactile tasks involving unpredictable or unknown stimuli.

Liquid-amplified zipping actuators for micro-air vehicles with transmission-free flapping.

Flapping micro-air vehicles (MAVs) can access a wide range of locations, including confined spaces such as the inside of industrial plants and collapsed buildings, and offer high maneuverability and tolerance to disturbances. However, current flapping MAVs require transmission systems between their actuators and wings, which introduce energetic losses and additional mass, hindering performance. Here, we introduce a high-performance electrostatic flapping actuation system, the liquid-amplified zipping actuator (LAZA), which induces wing movement by direct application of liquid-amplified electrostatic forces at the wing root, eliminating the requirement of any transmission system and their associated downsides. The LAZA allows for accurate control of flapping frequency and amplitude, exhibits no variation in performance over more than 1 million actuation cycles, and delivers peak and average specific powers of 200 and 124 watts per kilogram, respectively, exceeding mammalian and insect flight muscle and on par with modern flapping MAV actuation systems. The inclusion of 50-millimeter-long passively pitching wings in a dragonfly-sized LAZA flapping system allowed the rectification of net directional thrust up to 5.73 millinewtons. This thrust was achieved while consuming only 243 milliwatts of electrical power, implying a thrust-to-power ratio of 23.6 newtons per kilowatt, similar to state-of-the-art flapping MAVs, helicopter rotors, and commercial drone motors. Last, a horizontally moving LAZA flapping system supported by a taut nylon wire was able to accelerate from at-rest and travel at speeds up to 0.71 meters per second. The LAZA enables lightweight, high-performance transmission-free flapping MAVs for long-term remote exploration and search-and-rescue missions.

An Assistive Coughing Device for Post-Laryngectomy Patients.

People who have undergone total laryngectomy typically have difficulties speaking and coughing. Coughing, the protective reflex action where air is rapidly expelled from the lungs to clear the airway, is crucial in everyday life. Insufficiency in coughing can lead to serious chest infections. In this research we present a bionic assistive coughing device (RoboCough) to improve coughing efficacy among laryngectomy patients by increasing pressure and flow rate. RoboCough was designed to mimic the function of the glottis and trachea in the upper respiratory system. Experimental results show a significant increase (t(64) = 4.9, p < 0.0001) in peak cough flow rate and peak cough pressure (t(64) = 12.6, p < 0.0001) among 33 control participants using RoboCough. A pilot study with a smaller cohort of laryngectomy patients shows improvement in peak cough pressure (p = 0.0159) using RoboCough. Preliminary results also show that post-laryngectomy coughs achieved similar peak cough flow (Z = -0.9933, p = 0.32) to the control group's natural cough. Coughing capabilities could be improved through using RoboCough. Applications of RoboCough include simulation of vocal folds and respiratory conditions, rehabilitation of ineffective coughs from laryngeal and respiratory diseases and as a test-bed for the development of medical devices for respiratory support.

Retrospective analysis of real-world treatment patterns and clinical outcomes in patients with advanced non-small cell lung cancer starting first-line systemic therapy in the United Kingdom.

BACKGROUND: The treatment landscape for advanced non-small cell lung cancer (aNSCLC) has evolved rapidly since immuno-oncology (IO) therapies were introduced. This study used recent data to assess real-world treatment patterns and clinical outcomes in aNSCLC in the United Kingdom. METHODS: Electronic prescribing records of treatment-naive patients starting first-line (1 L) treatment for aNSCLC between June 2016 and March 2018 (follow-up until December 2018) in the United Kingdom were assessed retrospectively. Patient characteristics and treatment patterns were analyzed descriptively. Outcomes assessed included overall survival (OS), time to treatment discontinuation, time to next treatment, and real-world tumor response. RESULTS: In all, 1003 patients were evaluated (median age, 68 years [range, 28-93 years]; 53.9% male). Use of 1 L IO monotherapy (0-25.9%) and targeted therapy (11.8-15.9%) increased during the study period, but chemotherapy remained the most common 1 L treatment at all time points (88.2-58.2%). Median OS was 9.5 months (95% CI, 8.8-10.7 months) for all patients, 8.1 months (95% CI, 7.4-8.9 months) with chemotherapy, 14.0 months (95% CI, 10.7-20.6 months) with IO monotherapy, and 20.2 months (95% CI, 16.0-30.5 months) with targeted therapy. In the 28.6% of patients who received second-line treatment, IO monotherapy was the most common drug class (used in 51.6%). CONCLUSIONS: Although use of 1 L IO monotherapy for aNSCLC increased in the United Kingdom during the study period, most patients received 1 L chemotherapy. An OS benefit for first-line IO monotherapy vs chemotherapy was observed but was numerically smaller than that reported in clinical trials. Targeted therapy was associated with the longest OS, highlighting the need for improved treatment options for tumors lacking targetable mutations.

Development of a more clinically relevant bladder and urethral model for catheter testing.

This paper sets out the rationale and design for a more physiologically representative bladder/urethral model than the current rigid funnel industry standard. We suggest this flexible model can better serve as a basis for evaluating new catheters. We investigated the parameters and the validation tests required to construct and test with more flexible materials. The protocol includes static and impact force tests, while measuring internal retention balloon pressure. We have designed a flexible elastomer bladder floor and urethral model and tested it with a Foley balloon catheter. The tests showed that the model could hold the catheter with static loads up to 0.7 kg, but that the catheter was pulled out by impact forces from dropped weights. The Foley catheter design and its associated standards make no provision to mitigate urethral injury in the surprisingly common event of removal with a filled balloon. Our design is a more realistic model for testing retention and extraction characteristics of a urethral catheter. Validation tests have confirmed the feasibility of measuring urethral dilation and balloon pressure, both under traction and during progressive deflation. We suggest this model improves upon the current standard tests and will enable the design of safer catheters.

All-Soft Skin-Like Structures for Robotic Locomotion and Transportation.

Human skins are active, smart, and stretchable. Artificial skins that can replicate these properties are promising materials and technologies that will enable lightweight, cost-effective, portable, and deployable soft devices and robots. We show an active, stretchable, and portable artificial skin (ElectroSkin) that combines dielectric elastomer actuators (DEAs) and soft electroadhesives (EAs) in a fully compliant multilayer composite skin-like structure. By taking advantage of the common characteristics of DEA and EA, we define regions of the composite artificial skin as either active or passive. Active areas can be exploited as electromechanical actuators or as electrostatic gripper elements, or both simultaneously. This embedded multimodality delivers a new technology of deformable active skins that can grip and move objects and self-locomote. ElectroSkins can be fabricated using all-soft elastomers and readily available conductive materials. We demonstrate their capabilities in the first soft self-actuating conveyor belt, with a conveyoring speed of 0.28 mm/s, and a pocketable fully soft crawler robot. This new, self-actuating, self-gripping, and self-locomoting soft artificial skin has the potential to significantly impact on functional soft-smart composites, deployable robots, soft-smart conveyoring, and compliant gripping and manipulation applications.

Quantifying Dynamic Shapes in Soft Morphologies.

Soft materials are driving the development of a new generation of robots that are intelligent, versatile, and adept at overcoming uncertainties in their everyday operation. The resulting soft robots are compliant and deform readily to change shape. In contrast to rigid-bodied robots, the shape of soft robots cannot be described easily. A numerical description is needed to enable the understanding of key features of shape and how they change as the soft body deforms. It can also quantify similarity between shapes. In this article, we use a method based on elliptic Fourier descriptors to describe soft deformable morphologies. We perform eigenshape analysis on the descriptors to extract key features that change during the motion of soft robots, showing the first analysis of this type on dynamic systems. We apply the method to both biological and soft robotic systems, which include the movement of a passive tentacle, the crawling movement of two species of caterpillar (Manduca sexta and Sphacelodes sp.), the motion of body segments in the M. sexta, and a comparison of the motion of a soft robot with that of a microorganism (euglenoid, Eutreptiella sp.). In the case of the tentacle, we show that the method captures differences in movement in varied media. In the caterpillars, the method illuminates a prominent feature of crawling, the extension of the terminal proleg. In the comparison between the robot and euglenoids, our method quantifies the similarity in shape to ∼85%. Furthermore, we present a possible method of extending the analysis to three-dimensional shapes.

RUBIC: An Untethered Soft Robot With Discrete Path Following.

Soft robots have the potential to diminish the need for humans to venture into unsuitable environments or work in extreme conditions. While their soft nature gives them the advantage of being adaptable to changing environments, their control can be challenging because of the compliance that makes them effective. In this paper we present RUBIC: the Rolling, Untethered, Ballooning, Intelligent Cube, that overcomes some of the difficulties of 2D control by constraining motion to a discretised Cartesian space. RUBIC's method of locomotion is by rolling from one face of the cube to another, in any one of four directions. This motion causes it to move within a 2D grid structure, the dimensions of which are defined by the cube's characteristic length. When in its resting position RUBIC is inherently stable and forms a safe platform for tasks including taking measurements and soil samples, for localization and ad hoc network infrastructure, and as the foundation for larger robots and structures. We present the design of RUBIC's body, the four pneumatic ballooning actuators per face that generate its unique gait, and the control systems for locomotion and obstacle climbing. We consider constraints imposed by the design and fabrication methods including physical dimension and weight, material properties and control fidelity. An alternative locomotion scheme is proposed to improve the speed and linearity which also increases the distance traveled per roll. RUBIC travels with a mean locomotion accuracy of 4.58° deviation and successfully traverses steps up to 35% of its own height. The discretisation of a soft robotics workspace, as demonstrated by RUBIC, has advantages for safe and predictable locomotion and has applications in both structured and hazardous environments.

EuMoBot: replicating euglenoid movement in a soft robot.

Swimming is employed as a form of locomotion by many organisms in nature across a wide range of scales. Varied strategies of shape change are employed to achieve fluidic propulsion at different scales due to changes in hydrodynamics. In the case of microorganisms, the small mass, low Reynolds number and dominance of viscous forces in the medium, requires a change in shape that is non-invariant under time reversal to achieve movement. The Euglena family of unicellular flagellates evolved a characteristic type of locomotion called euglenoid movement to overcome this challenge, wherein the body undergoes a giant change in shape. It is believed that these large deformations enable the organism to move through viscous fluids and tiny spaces. The ability to drastically change the shape of the body is particularly attractive in robots designed to move through constrained spaces and cluttered environments such as through the human body for invasive medical procedures or through collapsed rubble in search of survivors. Inspired by the euglenoids, we present the design of EuMoBot, a multi-segment soft robot that replicates large body deformations to achieve locomotion. Two robots have been fabricated at different sizes operating with a constant internal volume, which exploit hyperelasticity of fluid-filled elastomeric chambers to replicate the motion of euglenoids. The smaller robot moves at a speed of [Formula: see text] body lengths per cycle (20 mm min-1 or 2.2 cycles min-1) while the larger one attains a speed of [Formula: see text] body lengths per cycle (4.5 mm min-1 or 0.4 cycles min-1). We show the potential for biomimetic soft robots employing shape change to both replicate biological motion and act as a tool for studying it. In addition, we present a quantitative method based on elliptic Fourier descriptors to characterize and compare the shape of the robot with that of its biological counterpart. Our results show a similarity in shape of 85% and indicate that this method can be applied to understand the evolution of shape in other nonlinear, dynamic soft robots where a model for the shape does not exist.

Toward a Dielectric Elastomer Resonator Driven Flapping Wing Micro Air Vehicle.

In the last two decades, insect-inspired flapping wing micro air vehicles (MAVs) have attracted great attention for their potential for highly agile flight. Insects flap their wings at the resonant frequencies of their flapping mechanisms. Resonant actuation is highly advantageous as it amplifies the flapping amplitude and reduces the inertial power demand. Emerging soft actuators, such as dielectric elastomer actuators (DEAs) have large actuation strains and thanks to their inherent elasticity, DEAs have been shown a promising candidate for resonant actuation. In this work a double cone DEA configuration is presented, a mathematic model is developed to characterize its quasi-static and dynamic performance. We compare the high frequency performance of two most common dielectric elastomers: silicone elastomer and polyacrylate tape VHB. The mechanical power output of the DEA is experimentally analyzed as a DEA-mass oscillator. Then a flapping wing mechanism actuated by this elastic actuator is demonstrated, this design is able to provide a peak flapping amplitude of 63° at the frequency of 18 Hz.

A case of fatal cetuximab-induced interstitial lung disease during the first weeks of treatment.

Cetuximab is a monoclonal antibody targeting the epidermal growth factor receptor. It has demonstrated activity against a number of cancers including lung, head and neck, and colorectal. The most common side effects associated with this agent are dermatological; however, other types of toxicities have been reported with varying frequencies. Here, we report a case of interstitial lung disease that developed within the first 4 weeks of cetuximab treatment initiation in a patient with metastatic colorectal cancer and led to patient death. Early fatal pulmonary events secondary to cetuximab is rarely reported in the literature; this case report highlights the importance of awareness among treating health care professionals of this potentially fatal toxicity.

Swimming like algae: biomimetic soft artificial cilia.

Cilia are used effectively in a wide variety of biological systems from fluid transport to thrust generation. Here, we present the design and implementation of artificial cilia, based on a biomimetic planar actuator using soft-smart materials. This actuator is modelled on the cilia movement of the alga Volvox, and represents the cilium as a piecewise constant-curvature robotic actuator that enables the subsequent direct translation of natural articulation into a multi-segment ionic polymer metal composite actuator. It is demonstrated how the combination of optimal segmentation pattern and biologically derived per-segment driving signals reproduce natural ciliary motion. The amenability of the artificial cilia to scaling is also demonstrated through the comparison of the Reynolds number achieved with that of natural cilia.

Biomimetic chromatophores for camouflage and soft active surfaces.

Chromatophores are the pigment-containing cells in the skins of animals such as fish and cephalopods which have chromomorphic (colour-changing) and controllable goniochromic (iridescent-changing) properties. These animals control the optical properties of their skins for camouflage and, it is speculated, for communication. The ability to replicate these properties in soft artificial skin structures opens up new possibilities for active camouflage, thermal regulation and active photovoltaics. This paper presents the design and implementation of soft and compliant artificial chromatophores based on the cutaneous chromatophores in fish and cephalopods. We demonstrate artificial chromatophores that are actuated by electroactive polymer artificial muscles, mimicking the radially orientated muscles found in natural chromatophores. It is shown how bio-inspired chromomorphism may be achieved using both areal expansion of dielectric elastomer structures and by the hydrostatic translocation of pigmented fluid into an artificial dermal melanophore.

Identification of an HLA-A*0201 cytotoxic T lymphocyte epitope specific to the endothelial antigen Tie-2.

Tie-2 stabilises pericyte-endothelial interactions during angiogenesis and is highly expressed on endothelium during several diseases, including arthritis, age-related macular degeneration and cancer. A vaccine that targets endothelium overexpressing Tie-2 may result in vessel damage and stimulate an inflammatory cascade resulting in disease regression. We have identified a region unique to Tie-2 (amino acids 1-196) that is homologous in humans and mice. Using computer algorithms, several HLA-A*0201 epitopes that are identical in mice and humans were predicted within this region; however, binding assays showed that the majority of these epitopes were of low affinity. Modification of the anchor residues of 4 epitopes enhanced HLA binding. These epitopes were incorporated by site-directed mutagenesis into a Tie-2 DNA construct. Immunisation of HLA*0201 transgenic mice with one of the modified Tie-2 constructs stimulated CTLs that recognised both wild-type and modified peptide-pulsed target cells. In contrast, no CTLs were generated in mice immunised with wild-type Tie-2 construct, demonstrating that the modified epitope was necessary in the generation of CTLs. Moreover, CTLs from mice immunised with the modified construct killed HLA-A*0201 endothelial cells overexpressing Tie-2. Our study demonstrates that it is possible to break tolerance to the endothelial antigen Tie-2, suggesting that it may be feasible to design a vaccine to activate CTLs to kill endothelial cells overexpressing Tie-2.