Jacketed elastomeric tubes for passive self-regulation of pulsatile flow.

Regulating pulsatile flow is important to achieve optimal separation and mixing and enhanced heat transfer in microfluidic devices, as well as maintaining homeostasis in biological systems. The human aorta, a composite and layered tube made (among others) of elastin and collagen, is an inspiration for researchers who seek an engineering solution for a self-regulation of pulsatile flow. Here, we present a bio-inspired approach showing that fabric-jacketed elastomeric tubes, manufactured using commercially available silicone rubber and knitted textiles, can be used to regulate pulsatile flow. Our tubes are evaluated via incorporation into a mock-circulatory 'flow loop' that replicates the pulsatile fluid flow conditions of an ex-vivo heart perfusion (EVHP) device, a machine used in heart transplants. Pressure waveforms measured near the elastomeric tubing clearly indicated an effective flow regulation. The 'dynamic stiffening' behavior of the tubes during deformation is analyzed quantitatively. Broadly, the fabric jackets allow for the tubes to experience greater magnitudes of pressure and distension without risk of asymmetric aneurysm within the expected operating time of an EVHP. Owing to its highly tunable nature, our design may serve as a basis for tubing systems that require passive self-regulation of pulsatile flow.

Elastomeric tubes with self-regulated distension.

Compliant elastomer tubing with a fabric "jacket" has been essential in various applications as soft robotic actuators, such as in biomedical exomuscles and massage therapy implements. Here, our study shows that a similar design concept can be an effective strategy in realizing passive regulation in the tube's distension, as well as in preventing aneurysm-like asymmetric rupture of the tube. A custom hydraulic pressure testing rig was built to perform experiments. The jacketed tubes initially deform rapidly as pressure increases, but a self-regulation behavior suppresses the tube's continued distension by strain-stiffening of the "jacket". In addition, highly asymmetric distension, common to elastomeric tubes due to imperfection in fabrication, is prevented dramatically by the "jacket". A three-dimensional finite element model predicts the distension of all tested tubes quantitatively across the entire experimental pressure ranges and beyond. Incorporating custom-designed kirigami relief patterns in the "jackets" expands the potential of the elastomeric tubes.

The Position of the Heart During Normothermic Ex Situ Heart Perfusion is an Important Factor in Preservation and Recovery of Myocardial Function.

Ex situ heart perfusion (ESHP) is being investigated as a method for the continuous preservation of the myocardium in a semiphysiologic state for subsequent transplantation. Most methods of ESHP position the isolated heart in a hanging (H) state, representing a considerable departure from the in vivo anatomical positioning of the heart and may negatively affect the functional preservation of the heart. In the current study, cardiac functional and metabolic parameters were assessed in healthy pig hearts, perfused for 12 hours, in either an H, or supported (S) position, either in nonworking mode (NWM) or working mode (WM). The cardiac function was best preserved in the S position hearts in WM (median 11 hour cardiac index (CI)/1 hour CI%: working mode perfusion in supported position = 94.77% versus nonworking mode perfusion in supported position = 62.80%, working mode perfusion in H position = 36.18%, nonworking mode perfusion in H position = 9.75%; p < 0.001). Delivery of pyruvate bolus significantly improved the function in S groups, however, only partially reversed myocardial dysfunction in the H heart groups. The hearts perfused ex situ in a semianatomical S position and in physiologic WM had better functional preservation and recovery than the H hearts in non-S position. Optimizing the positional support for the ex situ-perfused hearts may improve myocardial preservation during ESHP.

Effect of Surface and Interfacial Tension on the Resonance Frequency of Microfluidic Channel Cantilever.

The bending resonance of micro-sized resonators has been utilized to study adsorption of analyte molecules in complex fluids of picogram quantity. Traditionally, the analysis to characterize the resonance frequency has focused solely on the mass change, whereas the effect of interfacial tension of the fluid has been largely neglected. By observing forced vibrations of a microfluidic cantilever filled with a series of alkanes using a laser Doppler vibrometer (LDV), we studied the effect of surface and interfacial tension on the resonance frequency. Here, we incorporated the Young-Laplace equation into the Euler-Bernoulli beam theory to consider extra stress that surface and interface tension exerts on the vibration of the cantilever. Based on the hypothesis that the near-surface region of a continuum is subject to the extra stress, thin surface and interface layers are introduced to our model. The thin layer is subject to an axial force exerted by the extra stress, which in turn affects the transverse vibration of the cantilever. We tested the analytical model by varying the interfacial tension between the silicon nitride microchannel cantilever and the filled alkanes, whose interfacial tension varies with chain length. Compared with the conventional Euler-Bernoulli model, our enhanced model provides a better agreement to the experimental results, shedding light on precision measurements using micro-sized cantilever resonators.

Mimicking "J-Shaped" and Anisotropic Stress-Strain Behavior of Human and Porcine Aorta by Fabric-Reinforced Elastomer Composites.

An ex vivo heart perfusion device preserves the donor heart in a warm beating state during transfer between extraction and implantation surgeries. One of the current challenges includes the use of rigid and noncompliant plastic tubes, which causes injuries to the heart at the junction between the tissue and the tube. The compliant and rapidly strain-stiffening mechanical property that generates a "J-shaped" stress-strain behavior is necessary for producing the Windkessel effect, which ensures continuous flow of blood through the aorta. In this study, we mimic the J-shaped and anisotropic stress-strain behavior of human aorta in synthetic elastomers to replace the problematic noncompliant plastic tube. First, we assess the mechanical properties of human (n = 1) and porcine aorta (n = 14) to quantify the nonlinear and anisotropic behavior under uniaxial tensile stress from five different regions of the aorta. Second, fabric-reinforced elastomer composites were prepared by reinforcing silicone elastomers with embedded fabrics in a trilayer geometry. The knitted structures of the fabric provide strain-stiffening as well as anisotropic mechanical properties of the resulting composite in a deterministic manner. By optimizing the combination between different elastomers and fabrics, the resulting composites matched the J-shaped and anisotropic stress-strain behavior of natural human and porcine aorta. Finally, improved analytical constitutive models based on Gent's and Mooney-Rivlin's constitutive model (to describe the elastomer matrix) combined with Holzapfel-Gasser-Ogden's model (to represent the stiffer fabrics) were developed to describe the J-shaped behavior of the natural aortas and the fabric-reinforced composites. We anticipate that the suggested fabric-reinforced silicone elastomer composite design concept can be used to develop complex soft biomaterials, as well as in emerging engineering fields such as soft robotics and microfluidics, where the Windkessel effect can be useful in regulating the flow of fluids.

Normothermic Ex Situ Heart Perfusion in Working Mode: Assessment of Cardiac Function and Metabolism.

The current standard method for organ preservation (cold storage, CS), exposes the heart to a period of cold ischemia that limits the safe preservation time and increases the risk of adverse post-transplantation outcomes. Moreover, the static nature of CS does not allow for organ evaluation or intervention during the preservation interval. Normothermic ex situ heart perfusion (ESHP) is a novel method for preservation of the donated heart that minimizes cold ischemia by providing oxygenated, nutrient-rich perfusate to the heart. ESHP has been shown to be non-inferior to CS in the preservation of standard-criteria donor hearts and has also facilitated the clinical transplantation of the hearts donated after the circulatory determination of death. Currently, the only available clinical ESHP device perfuses the heart in an unloaded, non-working state, limiting assessments of myocardial performance. Conversely, ESHP in working mode provides the opportunity for comprehensive evaluation of cardiac performance by assessment of functional and metabolic parameters under physiologic conditions. Moreover, earlier experimental studies have suggested that ESHP in working mode may result in improved functional preservation. Here, we describe the protocol for ex situ perfusion of the heart in a large mammal (porcine) model, which is reproducible for different animal models and heart sizes. The software program in this ESHP apparatus allows for real-time and automated control of the pump speed to maintain desired aortic and left atrial pressure and evaluates a variety of functional and electrophysiological parameters with minimal need for supervision/manipulation.

Specific Ion Effects in Polyampholyte Hydrogels Dialyzed in Aqueous Electrolytic Solutions.

Polyampholyte hydrogels (PAHs) constitute a class of physical gels with cross-linking originating from inter- and intrachain ionic cross-linking between countercharged functional groups. In our previous report, we have shown that PAH has the potential to be a gel electrolyte in electrochemical energy storage devices. In this work, we further our understanding of charge-balanced PAH as a host material for gel electrolytes by studying the effect of dialysis on the mechanical properties and ionic conductivities of PAHs, whereas these properties are compared with those of poly(vinyl alcohol) (PVA)-based gel electrolytes. Here, various electrolyte solutions were investigated as dialyzing agents. The ionic species in the electrolytes form ion pairs with countercharged functional groups in PAH, whereas such interactions govern the ionic conductivity and mechanical strength of PAH in various electrolytes. For anions, the trend in ionic interactions follows the Hofmeister series in an exact manner, whereas some anomaly is observed among cations. We anticipate that our study provides a design criterion for fabricating gel electrolytes. In a broader context, this work can shed light on understanding the behavior of PAHs in various operational environments, such as under physiological conditions and in antifouling coatings for biomedical and maritime applications, respectively.

Two-Layered and Stretchable e-Textile Patches for Wearable Healthcare Electronics.

Wearable healthcare systems require skin-adhering electrodes that allow maximal comfort for patients as well as an electronics system to enable signal processing and transmittance. Textile-based electronics, known as "e-textiles," is a platform technology that allows comfort for patients. Here, two-layered e-textile patches are designed by controlled permeation of Ag-particle/fluoropolymer composite ink into a porous textile. The permeated ink forms a cladding onto the nanofibers in the textile substrate, which is beneficial for mechanical and electrical properties of the e-textile. The printed e-textile features conductivity of ≈3200 S cm-1 , whereas 1000 cycles of 30% uniaxial stretching causes the resistance to increase only by a factor of ≈5, which is acceptable in many applications. Controlling over the penetration depth enables a two-layer design of the e-textile, where the sensing electrodes and the conducting traces are printed in the opposite sides of the substrate. The formation of vertical interconnected access is remarkably simple as an injection from a syringe. With the custom-developed electronic circuits, a surface electromyography system with wireless data transmission is demonstrated. Furthermore, the dry e-textile patch collects electroencephalography with comparable signal quality to commercial gel electrodes. It is anticipated that the two-layered e-textiles will be effective in healthcare and sports applications.

All-Solid-State Sodium-Selective Electrode with a Solid Contact of Chitosan/Prussian Blue Nanocomposite.

Conventional ion-selective electrodes with a liquid junction have the disadvantage of potential drift. All-solid-state ion-selective electrodes with solid contact in between the metal electrode and the ion-selective membrane offer high capacitance or conductance to enhance potential stability. Solution-casted chitosan/Prussian blue nanocomposite (ChPBN) was employed as the solid contact layer for an all-solid-state sodium ion-selective electrode in a potentiometric sodium ion sensor. Morphological and chemical analyses confirmed that the ChPBN is a macroporous network of chitosan that contains abundant Prussian blue nanoparticles. Situated between a screen-printed carbon electrode and a sodium-ionophore-filled polyvinylchloride ion-selective membrane, the ChPBN layer exhibited high redox capacitance and fast charge transfer capability, which significantly enhanced the performance of the sodium ion-selective electrode. A good Nernstian response with a slope of 52.4 mV/decade in the linear range from 10-4-1 M of NaCl was observed. The stability of the electrical potential of the new solid contact was tested by chronopotentiometry, and the capacitance of the electrode was 154 ± 4 µF. The response stability in terms of potential drift was excellent (1.3 µV/h) for 20 h of continuous measurement. The ChPBN proved to be an efficient solid contact to enhance the potential stability of the all-solid-state ion-selective electrode.

Thermodynamic Investigation of the Effect of Interface Curvature on the Solid-Liquid Equilibrium and Eutectic Point of Binary Mixtures.

Thermodynamic phase behavior is affected by curved interfaces in micro- and nanoscale systems. For example, capillary freezing point depression is associated with the pressure difference between the solid and liquid phases caused by interface curvature. In this study, the thermal, mechanical, and chemical equilibrium conditions are derived for binary solid-liquid equilibrium with a curved solid-liquid interface due to confinement in a capillary. This derivation shows the equivalence of the most general forms of the Gibbs-Thomson and Ostwald-Freundlich equations. As an example, the effect of curvature on solid-liquid equilibrium is explained quantitatively for the water/glycerol system. Considering the effect of a curved solid-liquid interface, a complete solid-liquid phase diagram is developed over a range of concentrations for the water/glycerol system (including the freezing of pure water or precipitation of pure glycerol depending on the concentration of the solution). This phase diagram is compared with the traditional phase diagram in which the assumption of a flat solid-liquid interface is made. We show the extent to which nanoscale interface curvature can affect the composition-dependent freezing and precipitating processes, as well as the change in the eutectic point temperature and concentration with interface curvature. Understanding the effect of curvature on solid-liquid equilibrium in nanoscale capillaries has applications in the food industry, soil science, cryobiology, nanoporous materials, and various nanoscience fields.

Highly Flexible, Multipixelated Thermosensitive Smart Windows Made of Tough Hydrogels.

In a cold night, a clear window that will become opaque while retaining the indoor heat is highly desirable for both privacy and energy efficiency. A thermally responsive material that controls both the transmittance of solar radiance (predominantly in the visible and near-infrared wavelengths) and blackbody radiation (mainly in the mid-infrared) can realize such windows with minimal energy consumption. Here, we report a smart coating made from polyampholyte hydrogel (PAH) that transforms from a transparency state to opacity to visible radiation and strengthens opacity to mid-infrared when lowering the temperature as a result of phase separation between the water-rich and polymer-rich phases. To match a typical temperature fluctuation during the day, we fine-tune the phase transition temperature between 25 and 55 °C by introducing a small amount of relatively hydrophobic monomers (0.1 to 0.5 wt % to PAH). To further demonstrate an actively controlled, highly flexible, and high-contrast smart window, we build in an array of electric heaters made of printed elastomeric composite. The multipixelated window offers rapid switching, ∼70 s per cycle, whereas the device can withstand high strain (up to 80%) during operations.

Flexible and Self-Healing Aqueous Supercapacitors for Low Temperature Applications: Polyampholyte Gel Electrolytes with Biochar Electrodes.

A flexible and self-healing supercapacitor with high energy density in low temperature operation was fabricated using a combination of biochar-based composite electrodes and a polyampholyte hydrogel electrolyte. Polyampholytes, a novel class of tough hydrogel, provide self-healing ability and mechanical flexibility, as well as low temperature operation for the aqueous electrolyte. Biochar is a carbon material produced from the low-temperature pyrolysis of biological wastes; the incorporation of reduced graphene oxide conferred mechanical integrity and electrical conductivity and hence the electrodes are called biochar-reduced-graphene-oxide (BC-RGO) electrodes. The fabricated supercapacitor showed high energy density of 30 Wh/kg with ~90% capacitance retention after 5000 charge-discharge cycles at room temperature at a power density of 50 W/kg. At -30 °C, the supercapacitor exhibited an energy density of 10.5 Wh/kg at a power density of 500 W/kg. The mechanism of the low-temperature performance excellence is likely to be associated with the concept of non-freezable water near the hydrophilic polymer chains, which can motivate future researches on the phase behaviour of water near polyampholyte chains. We conclude that the combination of the BC-RGO electrode and the polyampholyte hydrogel electrolyte is promising for supercapacitors for flexible electronics and for low temperature environments.

A pH-Indicating Colorimetric Tough Hydrogel Patch towards Applications in a Substrate for Smart Wound Dressings.

The physiological milieu of healthy skin is slightly acidic, with a pH value between 4 and 6, whereas for skin with chronic or infected wounds, the pH value is above 7.3. As testing pH value is an effective way to monitor the status of wounds, a novel smart hydrogel wound patch incorporating modified pH indicator dyes was developed in this study. Phenol red (PR), the dye molecule, was successfully modified with methacrylate (MA) to allow a copolymerization with the alginate/polyacrylamide (PAAm) hydrogel matrix. This covalent attachment prevented the dye from leaching out of the matrix. The prepared pH-responsive hydrogel patch exhibited a porous internal structure, excellent mechanical property, and high swelling ratio, as well as an appropriate water vapour transmission rate. Mechanical responses of alginate/P(AAm-MAPR) hydrogel patches under different calcium and water contents were also investigated to consider the case of exudate accumulation into hydrogels. Results showed that increased calcium amount and reduced water content significantly improved the Young's modulus and elongation at break of the hydrogels. These characteristics indicated the suitability of hydrogels as wound dressing materials. When pH increased, the color of the hydrogel patches underwent a transition from yellow (pH 5, 6 and 7) to orange (7.4 and 8), and finally to red (pH 9). This range of color change matches the clinically-meaningful pH range of chronic or infected wounds. Therefore, our developed hydrogels could be applied as promising wound dressing materials to monitor the wound healing process by a simple colorimetric display, thus providing a desirable substrate for printed electronics for smart wound dressing.

Epidermal electronics for electromyography: An application to swallowing therapy.

Head and neck cancer treatment alters the anatomy and physiology of patients. Resulting swallowing difficulties can lead to serious health concerns. Surface electromyography (sEMG) is used as an adjuvant to swallowing therapy exercises. sEMG signal collected from the area under the chin provides visual biofeedback from muscle contractions and is used to help patients perform exercises correctly. However, conventional sEMG adhesive pads are relatively thick and difficult to effectively adhere to a patient's altered chin anatomy, potentially leading to poor signal acquisition in this population. Here, the emerging technology of epidermal electronics is introduced, where ultra-thin geometry allows for close contouring of the chin. The two objectives of this study were to (1) assess the potential of epidermal electronics technology for use with swallowing therapy and (2) assess the significance of the reference electrode placement. This study showed comparative signals between the new epidermal sEMG patch and the conventional adhesive patches used by clinicians. Furthermore, an integrated reference yielded optimal signal for clinical use; this configuration was more robust to head movements than when an external reference was used. Improvements for future iterations of epidermal sEMG patches specific to day-to-day clinical use are suggested.

Sponge-Templated Macroporous Graphene Network for Piezoelectric ZnO Nanogenerator.

We report a simple approach to fabricate zinc oxide (ZnO) nanowire based electricity generators on three-dimensional (3D) graphene networks by utilizing a commercial polyurethane (PU) sponge as a structural template. Here, a 3D network of graphene oxide is deposited from solution on the template and then is chemically reduced. Following steps of ZnO nanowire growth, polydimethylsiloxane (PDMS) backfilling and electrode lamination completes the fabrication processes. When compared to conventional generators with 2D planar geometry, the sponge template provides a 3D structure that has a potential to increase power density per unit area. The modified one-pot ZnO synthesis method allows the whole process to be inexpensive and environmentally benign. The nanogenerator yields an open circuit voltage of ∼0.5 V and short circuit current density of ∼2 µA/cm(2), while the output was found to be consistent after ∼3000 cycles. Finite element analysis of stress distribution showed that external stress is concentrated to deform ZnO nanowires by orders of magnitude compared to surrounding PU and PDMS, in agreement with our experiment. It is shown that the backfilled PDMS plays a crucial role for the stress concentration, which leads to an efficient electricity generation.

Criteria for Quick and Consistent Synthesis of Poly(glycerol sebacate) for Tailored Mechanical Properties.

Poly(glycerol sebacate) (PGS) and its derivatives make up an attractive class of biomaterial owing to their tunable mechanical properties with programmable biodegradability. In practice, however, the application of PGS is often hampered by frequent inconsistency in reproducing process conditions. The inconsistency stems from the volatile nature of glycerol during the esterification process. In this study, we suggest that the degree of esterification (DE) can be used to predict precisely the physical status, the mechanical properties, and the degradation of the PGS materials. Young's modulus is shown to linearly increase with DE, which is in agreement with an entropic spring theory of rubbers. To provide a processing guideline for researchers, we also provide a physical status map as a function of curing temperature and time. The amount of glycerol loss, obtainable by monitoring the evolution of the total mass loss and the DE during synthesis, is shown to make the predictions even more precise. We expect that these strategies can be applicable to different categories of polymers that involve condensation polymerization with the volatility of the reactants. In addition, we demonstrate that microwave-assisted prepolymerization is a time- and energy-efficient pathway to obtain PGS. For example, 15 min of microwave time is shown to be as efficient as prepolymerization in nitrogen atmosphere for 6 h at 130 °C. The quick synthesis method, however, causes a severe evaporation of glycerol, resulting in a large distortion in the monomer ratio between glycerol and sebacic acid. Consequently, more rigid PGS is produced under a similar curing condition compared to the conventional prepolymerization method. Finally, we demonstrate that the addition of molecularly rigid cross-linking agents and network-structured inorganic nanoparticles are also effective in enhancing the mechanical properties of the PGS-derived materials.

3D multifunctional integumentary membranes for spatiotemporal cardiac measurements and stimulation across the entire epicardium.

Means for high-density multiparametric physiological mapping and stimulation are critically important in both basic and clinical cardiology. Current conformal electronic systems are essentially 2D sheets, which cannot cover the full epicardial surface or maintain reliable contact for chronic use without sutures or adhesives. Here we create 3D elastic membranes shaped precisely to match the epicardium of the heart via the use of 3D printing, as a platform for deformable arrays of multifunctional sensors, electronic and optoelectronic components. Such integumentary devices completely envelop the heart, in a form-fitting manner, and possess inherent elasticity, providing a mechanically stable biotic/abiotic interface during normal cardiac cycles. Component examples range from actuators for electrical, thermal and optical stimulation, to sensors for pH, temperature and mechanical strain. The semiconductor materials include silicon, gallium arsenide and gallium nitride, co-integrated with metals, metal oxides and polymers, to provide these and other operational capabilities. Ex vivo physiological experiments demonstrate various functions and methodological possibilities for cardiac research and therapy.

Stretchable, multiplexed pH sensors with demonstrations on rabbit and human hearts undergoing ischemia.

Stable pH is an established biomarker of health, relevant to all tissues of the body, including the heart. Clinical monitoring of pH in a practical manner, with high spatiotemporal resolution, is particularly difficult in organs such as the heart due to its soft mechanics, curvilinear geometry, heterogeneous surfaces, and continuous, complex rhythmic motion. The results presented here illustrate that advanced strategies in materials assembly and electrochemical growth can yield interconnected arrays of miniaturized IrOx pH sensors encapsulated in thin, low-modulus elastomers to yield conformal monitoring systems capable of noninvasive measurements on the surface of the beating heart. A thirty channel custom data acquisition system enables spatiotemporal pH mapping with a single potentiostat. In vitro testing reveals super-Nernstian sensitivity with excellent uniformity (69.9 ± 2.2 mV/pH), linear response to temperature (-1.6 mV °C(-1) ), and minimal influence of extracellular ions (<3.5 mV). Device examples include sensor arrays on balloon catheters and on skin-like stretchable membranes. Real-time measurement of pH on the surfaces of explanted rabbit hearts and a donated human heart during protocols of ischemia-reperfusion illustrate some of the capabilities. Envisioned applications range from devices for biological research, to surgical tools and long-term implants.

Immunologic and tissue biocompatibility of flexible/stretchable electronics and optoelectronics.

Recent development of flexible/stretchable integrated electronic sensors and stimulation systems has the potential to establish an important paradigm for implantable electronic devices, where shapes and mechanical properties are matched to those of biological tissues and organs. Demonstrations of tissue and immune biocompatibility are fundamental requirements for application of such kinds of electronics for long-term use in the body. Here, a comprehensive set of experiments studies biocompatibility on four representative flexible/stretchable device platforms, selected on the basis of their versatility and relevance in clinical usage. The devices include flexible silicon field effect transistors (FETs) on polyimide and stretchable silicon FETs, InGaN light-emitting diodes (LEDs), and AlInGaPAs LEDs, each on low modulus silicone substrates. Direct cytotoxicity measured by exposure of a surrogate fibroblast line and leachable toxicity by minimum essential medium extraction testing reveal that all of these devices are non-cytotoxic. In vivo immunologic and tissue biocompatibility testing in mice indicate no local inflammation or systemic immunologic responses after four weeks of subcutaneous implantation. The results show that these new classes of flexible implantable devices are suitable for introduction into clinical studies as long-term implantable electronics.

Electrical contact at the interface between silicon and transfer-printed gold films by eutectic joining.

This paper presents the electrical and morphological properties at the interface between a metal (Au) and a semiconductor (Si) formed by a novel transfer-printing technology. This work shows that a transfer-printed thin (hundreds of nanometers) Au film forms excellent electrical contact on a Si substrate when appropriate thermal treatment is applied. The successful electrical contact is attributed to eutectic joining, which allows for the right amount of atomic level mass transport between Au and Si. The outcomes suggest that transfer-printing-based micromanufacturing can realize not only strong mechanical bonding but also high-quality electrical contact via eutectic joining.