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Drugs that induce reversible slowing of metabolic and physiological processes would have great value for organ preservation, especially for organs with high susceptibility to hypoxia-reperfusion injury, such as the heart. Using whole-organism screening of metabolism, mobility, and development in Xenopus, we identified an existing drug, SNC80, that rapidly and reversibly slows biochemical and metabolic activities while preserving cell and tissue viability. Although SNC80 was developed as a delta opioid receptor activator, we discovered that its ability to slow metabolism is independent of its opioid modulating activity as a novel SNC80 analog (WB3) with almost 1000 times less delta opioid receptor binding activity is equally active. Metabolic suppression was also achieved using SNC80 in microfluidic human organs-on-chips, as well as in explanted whole porcine hearts and limbs, demonstrating the cross-species relevance of this approach and potential clinical relevance for surgical transplantation. Pharmacological induction of physiological slowing in combination with organ perfusion transport systems may offer a new therapeutic approach for tissue and organ preservation for transplantation, trauma management, and enhancing patient survival in remote and low-resource locations.

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The unicellular protist Physarum polycephalum is an important emerging model for understanding how aneural organisms process information toward adaptive behavior. Here, it is revealed that Physarum can use mechanosensation to reliably make decisions about distant objects in its environment, preferentially growing in the direction of heavier, substrate-deforming, but chemically inert masses. This long-range sensing is abolished by gentle rhythmic mechanical disruption, changing substrate stiffness, or the addition of an inhibitor of mechanosensitive transient receptor potential channels. Additionally, it is demonstrated that Physarum does not respond to the absolute magnitude of strain. Computational modeling reveales that Physarum may perform this calculation by sensing the fraction of its perimeter that is distorted above a threshold substrate strain-a fundamentally novel method of mechanosensation. Using its body as both a distributed sensor array and computational substrate, this aneural organism leverages its unique morphology to make long-range decisions. Together, these data identify a surprising behavioral preference relying on biomechanical features and quantitatively characterize how the Physarum exploits physics to adaptively regulate its growth and shape.

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A watchmaker's approach yields small, agile, soft machines.

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The rapidly expanding field of soft robotics has provided multiple examples of how entirely soft machines and actuators can outperform conventional rigid robots in terms of adaptability, maneuverability, and safety. Unfortunately, the soft and flexible materials used in their construction impose intrinsic limitations on soft robots, such as low actuation speeds and low output forces. Nature offers multiple examples where highly flexible organisms exploit mechanical instabilities to store and rapidly release energy. Guided by these examples, researchers have recently developed a variety of strategies to overcome speed and power limitations in soft robotics using mechanical instabilities. These mechanical instabilities provide, through rapid transitions from structurally stable states, a new route to achieve high output power amplification and attain impressive actuation speeds. Here, an overview of the literature related to the development of soft robots and actuators that exploit mechanical instabilities to expand their actuation speed, output power, and functionality is presented. Additionally, strategies using structural phase transitions to address current challenges in the area of soft robotic control, sensing, and actuation are discussed. Approaches using instabilities to create entirely soft logic modules to imbue soft robots with material intelligence and distributed computational capabilities are also reviewed.

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Bronchopleural fistula (BPF) remains a significant source of morbidity and mortality after right pneumonectomy (RPN). Postoperative mechanical ventilation represents a primary risk factor for BPF. We undertook an experiment to determine the influence of airway diameter on suture line tension during mechanical ventilation after RPN. RPN was performed in 6 fresh human adult cadavers. After initial standard bronchial stump closure (BSC), the airway suture lines were subjected to 5 cm H2O incremental increases in airway pressures beginning at 5-40 cm H2O. To minimize airway diameter, a carinal resection was then performed with trachea to left main bronchial anastomosis and the airway suture lines subjected to similar incremental airway pressures. Wall tension (N/m) at the suture lines was measured using piezoresistive sensors at each pressure point. As delivered airway pressure increased, there was a concomitant increase in wall tension after BSC and carinal resection. At every point of incremental positive pressure, wall tension was however significantly lower after carinal resection when compared to BSC (P < 0.05). Additionally the differences in airway tension became even more significant with higher delivered airway pressure (P < 0.001). Airway diverticulum after BSC leads to significantly increased tension on the bronchial closure with positive airway pressure as compared to a closure which minimize airway diameter after RPN. This supports the role of Laplacian Law where small increases in airway diameter result in significant increases on closure site tension. Techniques which reduce airway diameter at the airway closure will more reliably reduce the incidence of BPF following RPN.

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While the monitoring of pH has demonstrated to be an effective technique to monitor an individual's health state, the design of wearable biosensors is subject to critical challenges, such as high fabrication costs, thermal drift, sensitivity to moisture, and the limited applicability for users with metal allergies. This work describes the low-cost fabrication of waterproof electronic decals (WPEDs): highly conformable disposable biosensors capable of monitoring sweat and vaginal pH. WPEDs contain a polyaniline/silver microflakes sensing layer optimized for accurate impedance-based pH quantification across the clinically relevant range of variation of most biofluids. WPEDs also contain a heating layer that serves to both stimulate sweating and prevent saturation of the sensing area, reducing the variability of the measurements. The conformability of WPEDs enables their simple and allergy-free attachment to skin, where they can monitor sweat pH, or to the surface of paper-based sample containers, for the pH-based diagnosis of bacterial vaginosis. WPEDs are mostly transparent, self-adhesive, breathable, flexible, moisture-insensitive, and able to maintain their accuracy under significant mechanical and thermal stresses. A cost-effective wearable and portable impedance analyzer wirelessly transmits pH data in real-time to the smartphone of the user, where a custom-developed App enables long term monitoring and telemedicine applications. Our results demonstrate the feasibility of using inexpensive single-use WPEDs and a reusable, wireless impedance analyzer to provide a wearable solution for the real-time monitoring of sweat pH and the accurate at-home diagnosis of bacterial vaginosis, improving the capabilities of current low-cost, point-of-care diagnostic tests.

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The fabrication of multifunctional epidermal electronic devices capable of efficiently reading electrophysiological signals and converting low-amplitude mechanical signals into electric outputs promises to pave the way towards the development of self-powered wearable sensors, smart consumer electronics, and human-machine interfaces. This article describes the scalable and cost-effective fabrication of epidermal, nanotexturized, triboelectronic devices (EnTDs). EnTDs can be conformably worn on the skin and efficiently monitor electrophysiological signals, temperature, and hydration levels. EnTDs, while measuring electrophysiological signals, can also convert imperceptible time-variant body motions into electrical signals using a nanotexturized triboelectric layer, enabling the self-powered monitoring of respiration, swallowing, and arterial pulse. These results suggest the potential of EnTDs as a new class of multifunctional skin-like sensors for biomedical monitoring and self-powered sensing applications.

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The development of new active biocompatible materials and devices is a current need for their implementation in multiple fields, including the fabrication of implantable devices for biomedical applications and sustainable devices for bio-optics and bio-optoelectronics. This paper describes a simple strategy to use designed proteins to develop protein-based functional materials. Using simple proteins as self-assembling building blocks as a platform for the fabrication of new optically active materials takes previous work one step further towards the design of materials with defined structures and functions using naturally occurring protein materials, such as silk. The proposed fabrication strategy generates thin and flexible nanopatterned protein films by letting the engineered protein elements self-assemble over the surface of an elastomeric stamp with nanoscale features. These nanopatterned protein films are easily transferred onto 3D objects (flat and curved) by moisture-induced adhesion. Additionally, flexible nanopatterned protein films are prepared by incorporating a thin polymeric layer as a back support. Finally, taking advantage of the tunability of the selected protein scaffold, the flexible protein-based surfaces are endowed with optical functions, achieving efficient lasing features. As such, this work enables the simple and cost-effective production of flexible and nanostructured, protein-based, optically active biomaterials and devices over large areas toward emerging applications.

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Based on the premise "anything thin is flexible", the field of flexible electronics has been fueled from the ever-evolving advances in thin-film materials and devices. [...].

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This work describes the use of a benchtop razor printer to fabricate epidermal paper-based electronic devices (EPEDs). This fabrication technique is simple, low-cost, and compatible with scalable manufacturing processes. EPEDs are fabricated using paper substrates rendered omniphobic by their cost-effective silanization with fluoroalkyl trichlorosilanes, making them inexpensive, water-resistant, and mechanically compliant with human skin. The highly conductive inks or thin films attached to one of the sides of the omniphobic paper makes EPEDs compatible with wearable applications involving wireless power transfer. The omniphobic cellulose fibers of the EPED provide a moisture-independent mechanical reinforcement to the conductive layer. EPEDs accurately monitor physiological signals such as ECG (electrocardiogram), EMG (electromyogram), and EOG (electro-oculogram) even in high moisture environments. Additionally, EPEDs can be used for the fast mapping of temperature over the skin and to apply localized thermotherapy. Our results demonstrate the merits of EPEDs as a low-cost platform for personalized medicine applications.

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Traditional manufacturing methods and materials used to fabricate epidermal electronics for physiological monitoring, transdermal stimulation, and therapeutics are complex and expensive, preventing their adoption as single-use medical devices. This work describes the fabrication of epidermal, paper-based electronic devices (EPEDs) for wearable and implantable applications by combining the spray-based deposition of silanizing agents, highly conductive nanoparticles, and encapsulating polymers with laser micromachining. EPEDs are inexpensive, stretchable, easy to apply, and disposable by burning. The omniphobic character and fibrous structure of EPEDs make them breathable, mechanically stable upon stretching, and facilitate their use as electrophysiological sensors to record electrocardiograms, electromyograms, and electrooculograms, even under water. EPEDs can also be used to provide thermotherapeutic treatments to joints, map temperature spatially, and as wirelessly powered implantable devices for stimulation and therapeutics. This work makes epidermal electronic devices accessible to high-throughput manufacturing technologies and will enable the fabrication of a variety of wearable medical devices at a low cost.

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This work describes the detection of anti-T. cruzi antibodies in whole blood solutions using magnetic levitating microbeads (MLµBs). This simple diagnostic method can be easily performed by minimally trained personnel using an inexpensive and portable magnetic stage that requires no electricity. A multiphase test tube containing the MLµBs facilitates the sequential incubation, filtering, and reading of the immunoassays. The diagnostic method starts by adding a blood sample to the top phase of the test tube where the anti-T. cruzi antibodies present in the blood attach to the T. cruzi antigens on the surface of the MLµBs. Shaking the test tube after incubation mixes the top layer with a paramagnetic medium loaded with SiO2 microcrystals. The attachment of SiO2 microcrystals to those MLµBs bound to T. cruzi antibodies decreases their levitation height once the tube is placed between two antialigned permanent magnets. Measuring the levitation height of MLµBs enables the accurate detection and quantification of anti-T. cruzi antibodies in the blood across the clinically relevant range, with a detection limit of 5 µg mL-1. The small size of the test tubes facilitates the simultaneous analysis of over 50 different samples. MLµBs act as partial collimators for non-polarized light, facilitating their visual identification by the naked eye or by projecting incident light on a thin paper screen. A machine-vision algorithm was created to automatically interpret the results of the MLµB tests from a digital image, resulting in a rapid, accurate, and user-friendly assay for Chagas disease that can be used in resource-limited settings.

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The growing socio-economic burden of chronic skin wounds requires the development of new automated and non-invasive analytical systems capable of wirelessly monitoring wound status. This work describes the low-cost fabrication of single-use, omniphobic paper-based smart bandages (OPSBs) designed to monitor the status of open chronic wounds and to detect the formation of pressure ulcers. OPSBs are lightweight, flexible, breathable, easy to apply, and disposable by burning. A reusable wearable potentiostat was fabricated to interface with the OPSB simply by attaching it to the back of the bandage. The wearable potentiostat and the OPSB can be used to simultaneously quantify pH and uric acid levels at the wound site, and wirelessly report wound status to the user or medical personnel. Additionally, the wearable potentiostat and the OPSBs can be used to detect, in an in-vivo mouse model, the formation of pressure ulcers even before the pressure-induced tissue damage becomes visible, using impedance spectroscopy. Our results demonstrate the feasibility of using inexpensive single-use OPSBs and a reusable, wearable potentiostat that can be easily sterilized and attached to a new OPSB during the dressing change, to provide long term wound progression data to guide treatment decisions.

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This Letter describes a low-cost, scalable nanomanufacturing process that enables the continuous forming of thin metallic layers with nanoscale accuracy using roll-to-roll, laser-induced superplasticity (R2RLIS). R2RLIS uses a laser shock to induce the ultrahigh-strain-rate deformation of metallic films at room temperature into low-cost polymeric nanomolds, independently of the original grain size of the metal. This simple and inexpensive nanoforming method does not require access to cleanrooms and associated facilities, and can be easily implemented on conventional CO2 lasers, enabling laser systems commonly used for rapid prototyping or industrial cutting and engraving to fabricate uniform and three-dimensional crystalline metallic nanostructures over large areas. Tuning the laser power during the R2RLIS process enables the control of the aspect ratio and the mechanical and optical properties of the fabricated nanostructures. This roll-to-roll technique successfully fabricates mechanically strengthened gold plasmonic nanostructures with aspect ratios as high as 5 that exhibit high oxidation resistance and strong optical field enhancements. The CO2 laser used in R2RLIS can also integrate the fabricated nanostructures on transparent flexible substrates with robust interfacial contact. The ability to fabricate ultrasmooth metallic nanostructures using roll-to-roll manufacturing enables the large scale production, at a relatively low-cost, of flexible plasmonic devices toward emerging applications.

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Soft lithography allows for the simple and low-cost fabrication of nanopatterns with different shapes and sizes over large areas. However, the resolution and the aspect ratio of the nanostructures fabricated by soft lithography are limited by the depth and the physical properties of the stamp. In this work, silicon nanobelts and nanostructures were achieved by combining soft nanolithography patterning with optimized reactive ion etching (RIE) in silicon. Using polymethylmethacrylate (PMMA) nanopatterned layers with thicknesses ranging between 14 and 50 nm, we obtained silicon nanobelts in areas of square centimeters with aspect ratios up to ~1.6 and linewidths of 225 nm. The soft lithographic process was assisted by a thin film of SiOx (less than 15 nm) used as a hard mask and RIE. This simple patterning method was also used to fabricate 2D nanostructures (nanopillars) with aspect ratios of ~2.7 and diameters of ~200 nm. We demonstrate that large areas patterned with silicon nanobelts exhibit a high reflectivity peak in the ultraviolet C (UVC) spectral region (280 nm) where some aminoacids and peptides have a strong absorption. We also demonstrated how to tailor the aspect ratio and the wettability of these photonic surfaces (contact angles ranging from 8.1 to 96.2°) by changing the RIE power applied during the fabrication process.

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We report a low-cost, high-throughput benchtop method that enables thin layers of metal to be shaped with nanoscale precision by generating ultrahigh-strain-rate deformations. Laser shock imprinting can create three-dimensional crystalline metallic structures as small as 10 nanometers with ultrasmooth surfaces at ambient conditions. This technique enables the successful fabrications of large-area, uniform nanopatterns with aspect ratios as high as 5 for plasmonic and sensing applications, as well as mechanically strengthened nanostructures and metal-graphene hybrid nanodevices.

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This paper describes the fabrication of functional optical devices by sectioning quantum-dot-in-nanowires systems with predefined lengths and orientations. This fabrication process requires only two steps, embedding the nanowires in epoxy and using an ultramicrotome to section them across their axis ("nanoskiving"). This work demonstrates the combination of the following four capabilities: (i) the control of the length of the nanowire sections at the nanometer scale; (ii) the ability to process the nanowires after cutting using wet etching; (iii) the possibility of modifying the geometry of the wire by varying the sectioning angle; and (iv) the generation of as many as 120 consecutive slabs bearing nanowires that have uniform size and approximately reproducible lateral patterns and that can subsequently be transferred to different substrates. The quantum dots inside the nanowires are functional and of a high optical quality after the sectioning process and exhibit photoluminescent emission with wavelengths in the range of 650-710 nm.

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Spectrally encoded confocal microscopy (SECM) is a reflectance confocal microscopy technology that can rapidly image large areas of luminal organs at microscopic resolution. One of the main challenges for large-area SECM imaging in vivo is maintaining the same imaging depth within the tissue when patient motion and tissue surface irregularity are present. In this paper, we report the development of a miniature vari-focal objective lens that can be used in an SECM endoscopic probe to conduct adaptive focusing and to maintain the same imaging depth during in vivo imaging. The vari-focal objective lens is composed of an aspheric singlet with an NA of 0.5, a miniature water chamber, and a thin elastic membrane. The water volume within the chamber was changed to control curvature of the elastic membrane, which subsequently altered the position of the SECM focus. The vari-focal objective lens has a diameter of 5 mm and thickness of 4 mm. A vari-focal range of 240 µm was achieved while maintaining lateral resolution better than 2.6 µm and axial resolution better than 26 µm. Volumetric SECM images of swine esophageal tissues were obtained over the vari-focal range of 260 µm. SECM images clearly visualized cellular features of the swine esophagus at all focal depths, including basal cell nuclei, papillae, and lamina propria.

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This paper describes the fabrication of pressure-driven, open-channel microfluidic systems with lateral dimensions of 45-300 microns carved in omniphobic paper using a craft-cutting tool. Vapor phase silanization with a fluorinated alkyltrichlorosilane renders paper omniphobic, but preserves its high gas permeability and mechanical properties. When sealed with tape, the carved channels form conduits capable of guiding liquid transport in the low-Reynolds number regime (i.e. laminar flow). These devices are compatible with complex fluids such as droplets of water in oil. The combination of omniphobic paper and a craft cutter enables the development of new types of valves and switches, such as "fold valves" and "porous switches," which provide new methods to control fluid flow.

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Spectrally-encoded endoscopy (SEE) is an ultraminiature endoscopy technology that acquires high-definition images of internal organs through a sub-mm endoscopic probe. In SEE, a grating at the tip of the imaging optics diffracts the broadband light into multiple beams, where each beam with a distinctive wavelength is illuminated on a unique transverse location of the tissue. By encoding one transverse coordinate with the wavelength, SEE can image a line of the tissue at a time without using any beam scanning devices. This feature of the SEE technology allows the SEE probe to be miniaturized to sub-mm dimensions. While previous studies have shown that SEE has the potential to be utilized for various clinical imaging applications, the translation of SEE for medicine has been hampered by challenges in fabricating the miniature grating inherent to SEE probes. This paper describes a new fabrication method for SEE probes. The new method uses a soft lithographic approach to pattern a high-aspect-ratio grating at the tip of the miniature imaging optics. Using this technique, we have constructed a 500 µm-diameter SEE probe. The miniature grating at the tip of the probe had a measured diffraction efficiency of 75%. The new SEE probe was used to image a human finger and formalin fixed mouse embryos, demonstrating the capability of this device to visualize key anatomic features of tissues with high image contrast. In addition to providing high quality imaging SEE optics, the soft lithography method allows cost-effective and reliable fabrication of these miniature endoscopes, which will facilitate the clinical translation of SEE technology.

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