Relation between blood pressure and pulse wave velocity for human arteries.

Continuous monitoring of blood pressure, an essential measure of health status, typically requires complex, costly, and invasive techniques that can expose patients to risks of complications. Continuous, cuffless, and noninvasive blood pressure monitoring methods that correlate measured pulse wave velocity (PWV) to the blood pressure via the Moens-Korteweg (MK) and Hughes Equations, offer promising alternatives. The MK Equation, however, involves two assumptions that do not hold for human arteries, and the Hughes Equation is empirical, without any theoretical basis. The results presented here establish a relation between the blood pressure P and PWV that does not rely on the Hughes Equation nor on the assumptions used in the MK Equation. This relation degenerates to the MK Equation under extremely low blood pressures, and it accurately captures the results of in vitro experiments using artificial blood vessels at comparatively high pressures. For human arteries, which are well characterized by the Fung hyperelastic model, a simple formula between P and PWV is established within the range of human blood pressures. This formula is validated by literature data as well as by experiments on human subjects, with applicability in the determination of blood pressure from PWV in continuous, cuffless, and noninvasive blood pressure monitoring systems.

The equivalent medium of cellular substrate under large stretching, with applications to stretchable electronics.

The concepts of open, cellular substrates for stretchable electronic systems are of interest partly due to their ability to minimize disruptions to the natural diffusive or convective flow of bio-fluids in advanced, bio-integrated implants. The overall elastic properties, and in particular the stretchability, of such systems are difficult to determine, however, because they depend strongly on the alignment and position of the serpentine interconnects relative to the openings in the cellular substrate, which is difficult to precisely control, even with the assistance of precision stages and visualization hardware. This paper establishes an analytic constitutive model for an equivalent medium for a cellular substrate under finite deformation. Results demonstrate that the elastic stretchability of a serpentine interconnect bonded to this equivalent medium represents a lower-bound estimate for the case of the actual cellular substrate, where the bonding adopts different alignments and positions. This finding provides a simple, conservative estimate of stretchability, which has general utility as an engineering design rule for platforms that exploit cellular substrates in stretchable electronics.

Designing Thin, Ultrastretchable Electronics with Stacked Circuits and Elastomeric Encapsulation Materials.

Many recently developed soft, skin-like electronics with high performance circuits and low modulus encapsulation materials can accommodate large bending, stretching, and twisting deformations. Their compliant mechanics also allows for intimate, nonintrusive integration to the curvilinear surfaces of soft biological tissues. By introducing a stacked circuit construct, the functional density of these systems can be greatly improved, yet their desirable mechanics may be compromised due to the increased overall thickness. To address this issue, the results presented here establish design guidelines for optimizing the deformable properties of stretchable electronics with stacked circuit layers. The effects of three contributing factors (i.e., the silicone inter-layer, the composite encapsulation, and the deformable interconnects) on the stretchability of a multilayer system are explored in detail via combined experimental observation, finite element modeling, and theoretical analysis. Finally, an electronic module with optimized design is demonstrated. This highly deformable system can be repetitively folded, twisted, or stretched without observable influences to its electrical functionality. The ultrasoft, thin nature of the module makes it suitable for conformal biointegration.

Chemical Sensing Systems that Utilize Soft Electronics on Thin Elastomeric Substrates with Open Cellular Designs.

A collection of materials and device architectures are introduced for thin, stretchable arrays of ion sensors that mount on open cellular substrates to facilitate solution exchange for use in biointegrated electronics. The results include integration strategies and studies of fundamental characteristics in chemical sensing and mechanical response. The latter involves experimental measurements and theoretical simulations that establish important considerations in the design of low modulus, stretchable properties in cellular substrates, and in the realization of advanced capabilities in spatiotemporal mapping of chemicals' gradients. As the chemical composition of extracellular fluids contains valuable information related to biological function, the concepts introduced here have potential utility across a range of skin- and internal-organ-integrated electronics where soft mechanics, fluidic permeability, and advanced chemical sensing capabilities are key requirements.

Soft Elastomers with Ionic Liquid-Filled Cavities as Strain Isolating Substrates for Wearable Electronics.

Managing the mechanical mismatch between hard semiconductor components and soft biological tissues represents a key challenge in the development of advanced forms of wearable electronic devices. An ultralow modulus material or a liquid that surrounds the electronics and resides in a thin elastomeric shell provides a strain-isolation effect that enhances not only the wearability but also the range of stretchability in suitably designed devices. The results presented here build on these concepts by (1) replacing traditional liquids explored in the past, which have some nonnegligible vapor pressure and finite permeability through the encapsulating elastomers, with ionic liquids to eliminate any possibility for leakage or evaporation, and (2) positioning the liquid between the electronics and the skin, within an enclosed, elastomeric microfluidic space, but not in direct contact with the active elements of the system, to avoid any negative consequences on electronic performance. Combined experimental and theoretical results establish the strain-isolating effects of this system, and the considerations that dictate mechanical collapse of the fluid-filled cavity. Examples in skin-mounted wearable include wireless sensors for measuring temperature and wired systems for recording mechano-acoustic responses.

Design of Strain-Limiting Substrate Materials for Stretchable and Flexible Electronics.

Recently developed classes of electronics for biomedical applications exploit substrates that offer low elastic modulus and high stretchability, to allow intimate, mechanically biocompatible integration with soft biological tissues. A challenge is that such substrates do not generally offer protection of the electronics from high peak strains that can occur upon large-scale deformation, thereby creating a potential for device failure. The results presented here establish a simple route to compliant substrates with strain-limiting mechanics based on approaches that complement those of recently described alternatives. Here, a thin film or mesh of a high modulus material transferred onto a prestrained compliant substrate transforms into wrinkled geometry upon release of the prestrain. The structure formed by this process offers a low elastic modulus at small strain due to the small effective stiffness of the wrinkled film or mesh; it has a high tangent modulus (e.g., >1000 times the elastic modulus) at large strain, as the wrinkles disappear and the film/mesh returns to a flat geometry. This bilinear stress-strain behavior has an extremely sharp transition point, defined by the magnitude of the prestrain. A theoretical model yields analytical expressions for the elastic and tangent moduli and the transition strain of the bilinear stress-strain relation, with quantitative correspondence to finite element analysis and experiments.

Ferromagnetic, folded electrode composite as a soft interface to the skin for long-term electrophysiological recording.

This paper introduces a class of ferromagnetic, folded, soft composite material for skin-interfaced electrodes with releasable interfaces to stretchable, wireless electronic measurement systems. These electrodes establish intimate, adhesive contacts to the skin, in dimensionally stable formats compatible with multiple days of continuous operation, with several key advantages over conventional hydrogel based alternatives. The reported studies focus on aspects ranging from ferromagnetic and mechanical behavior of the materials systems, to electrical properties associated with their skin interface, to system-level integration for advanced electrophysiological monitoring applications. The work combines experimental measurement and theoretical modeling to establish the key design considerations. These concepts have potential uses across a diverse set of skin-integrated electronic technologies.

A Temperature Prediction Model for Flexible Electronic Devices Based on GA-BP Neural Network and Experimental Verification.

The problem that the thermal safety of flexible electronic devices is difficult to evaluate in real time is addressed in this study by establishing a BP neural network (GA-BPNN) temperature prediction model based on genetic algorithm optimisation. The model uses a BP neural network to fit the functional relationship between the input condition and the steady-state temperature of the equipment and uses a genetic algorithm to optimise the parameter initialisation problem of the BP neural network. To overcome the challenge of the high cost of obtaining experimental data, finite element analysis software is used to simulate the temperature results of the equipment under different working conditions. The prediction variance of the GA-BPNN model does not exceed 0.57 °C and has good robustness, as the model is trained according to the simulation data. The study conducted thermal validation experiments on the temperature prediction model for this flexible electronic device. The device reached steady state after 1200 s of operation at rated power. The error between the predicted and experimental results was less than 0.9 °C, verifying the validity of the model's predictions. Compared with traditional thermal simulation and experimental methods, this model can quickly predict the temperature with a certain accuracy and has outstanding advantages in computational efficiency and integrated application of hardware and software.

Soft Crawling Microrobot Based on Flexible Optoelectronics Enabling Autonomous Phototaxis in Terrestrial and Aquatic Environments.

Many organisms move directly toward light for prey hunting or navigation, which is called phototaxis. Mimicking this behavior in robots is crucially important in the energy industry and environmental exploration. However, the phototaxis robots with rigid bodies and sensors still face challenges in adapting to unstructured environments, and the soft phototaxis robots often have high requirements for light sources with limited locomotion performance. Here, we report a 3.5 g soft microrobot that can perceive the azimuth angle of light sources and exhibit rapid phototaxis locomotion autonomously enabled by three-dimensional flexible optoelectronics and compliant shape memory alloy (SMA) actuators. The optoelectronics is assembled from a planar patterned flexible circuit with miniature photodetectors, introducing the self-occlusion to light, resulting in high sensing ability (error < 3.5°) compared with the planar counterpart. The actuator produces a straightening motion driven by an SMA wire and is then returned to a curled shape by a prestretched elastomer layer. The actuator exhibits rapid actuation within 0.1 s, a significant degree of deformation (curvature change of ∼87 m-1) and a blocking force of ∼0.4 N, which is 68 times its own weight. Finally, we demonstrated the robot is capable of autonomously crawling toward a moving light source in a hybrid aquatic-terrestrial environment without human intervention. We envision that our microrobot could be widely used in autonomous light tracking applications.

A soft, bioinspired artificial lymphatic system for interactive ascites transfer.

Low-flow removal of refractory ascites is critical to treating cirrhosis and digestive system tumor, and thus, commercial ascites pump emerged lately. The rigid structure of clinically available pumps rises complication rate and lack of flow rate monitoring hinders early warning of abnormalities. Herein, a soft artificial system was proposed inspired by lymph for interactive ascites transfer with great biocompatibility. The implantable system is composed of pump cavity, valves and tubes, which are soft and flexible made by silica gel. Therefore, the system possesses similar modulus to tissues and can naturally fit surrounding tissues. The cavity with magnetic tablet embedded is driven by extracorporeal magnetic field. Subsequently, the system can drain ascites with a top speed of 23 mL min-1, much higher than that of natural lymphatic system and state-of-art devices. Moreover, integrated flexible sensors enable wireless, real-time flow rate monitoring, serving as proof of treatment adjustment, detection and locating of malfunction at early stage. The liver function of experimental objects was improved, and no severe complications occurred for 4 weeks, which proved its safety and benefit to treatment. This artificial lymphatic system can serve as a bridge to recovery and pave the way for further clinical research.

Wrap-like transfer printing for three-dimensional curvy electronics.

Three-dimensional (3D) curvy electronics has wide-ranging application in biomedical health care, soft machine, and high-density curved imager. Limited by material properties, complex procedures, and coverage ability of existing fabrication techniques, the development of high-performance 3D curvy electronics remains challenging. Here, we propose an automated wrap-like transfer printing prototype for fabricating 3D curvy electronics. Assisted by a gentle and uniform pressure field, the prefabricated planar circuits on the petal-like stamp are integrated onto the target surface intactly with full coverage. The driving pressure for the wrapping is provided by the strain recovery of a prestrained elastic film triggered by the air pressure control. The wrapping configuration and strain distribution of the stamp are simulated by finite element analysis, and the pattern and thickness of the stamps are optimized. Demonstration of this strategy including spherical meander antenna, spherical light-emitting diode array, and spherical solar cell array illustrates its feasibility in the development of complex 3D curvy electronics.

Conformal in-ear bioelectronics for visual and auditory brain-computer interfaces.

Brain-computer interfaces (BCIs) have attracted considerable attention in motor and language rehabilitation. Most devices use cap-based non-invasive, headband-based commercial products or microneedle-based invasive approaches, which are constrained for inconvenience, limited applications, inflammation risks and even irreversible damage to soft tissues. Here, we propose in-ear visual and auditory BCIs based on in-ear bioelectronics, named as SpiralE, which can adaptively expand and spiral along the auditory meatus under electrothermal actuation to ensure conformal contact. Participants achieve offline accuracies of 95% in 9-target steady state visual evoked potential (SSVEP) BCI classification and type target phrases successfully in a calibration-free 40-target online SSVEP speller experiment. Interestingly, in-ear SSVEPs exhibit significant 2nd harmonic tendencies, indicating that in-ear sensing may be complementary for studying harmonic spatial distributions in SSVEP studies. Moreover, natural speech auditory classification accuracy can reach 84% in cocktail party experiments. The SpiralE provides innovative concepts for designing 3D flexible bioelectronics and assists the development of biomedical engineering and neural monitoring.

Evaluation on the Seal Performance of SMP-Based Packers in Oil Wells.

Packers based on shape memory polymers (SMPs) are an emerging technology that have the advantages of compact structure, easy manufacture, and adaptability to complex wells. This paper proposes a finite element model to simulate the setting process and mechanical response of an SMP packer. The investigated material is an epoxy-based thermal responsive SMP, whose relaxation modulus and thermal expansion coefficient were measured at different temperatures. Based on the experimental data, the model describes the viscoelastic behavior of the SMP using the generalized Maxwell model. The results show that the SMP packer could provide sufficient contact stress under downhole conditions, even after the stress was relaxed. A further parametric study revealed that the most significant factor in sealing effects is the wellbore pressure, followed by the interference between the packer and the annular, the seal length, the pre-compression, and the setting temperature. High downhole pressures require more significant contact stress and increase the risk of slip between the packer and casing wall by promoting shear stress. Increasing the seal length and interference enhances the contact stress and mitigates the shear stress to improve the seal performance. Pre-compression and setting temperatures are minor factors that have little influence on sealability.

Flexible Dual-Channel Digital Auscultation Patch With Active Noise Reduction for Bowel Sound Monitoring and Application.

Bowel sounds (BSs) have important clinical value in the auxiliary diagnosis of digestive diseases, but due to the inconvenience of long-term monitoring and too much interference from environmental noise, they have not been well studied. Most of the current electronic stethoscopes are hard and bulky without the function of noise reduction, and their application for long-term wearable monitoring of BS in noisy clinical environments is very limited. In this paper, a flexible dual-channel digital auscultation patch with active noise reduction is designed and developed, which is wireless, wearable, and conformably attached to abdominal skin to record BS more accurately. The ambient noise can be greatly reduced through active noise reduction based on the adaptive filter. At the same time, some nonstationary noises appearing intermittently (e.g., frictional noise) can also be removed from BS by the cross validation of multichannel simultaneous acquisition. Then, two kinds of typical BS signals are taken as examples, and the feature parameters of the BS in the time domain and frequency domain are extracted through the time-frequency analysis algorithm. Furthermore, based on the short-term energy ratio between the four channels of dual patches, the two-dimensional localization of BS on the abdomen mapping plane is realized. Finally, the continuous wearable monitoring of BS for patients with postoperative ileus (POI) in the noisy ward from pre-operation (POD0) to postoperative Day 7 (POD7) was carried out. The obtained change curve of the occurrence frequency of BS provides guidance for doctors to choose a reasonable feeding time for patients after surgery and accelerate their recovery. Therefore, flexible dual-channel digital auscultation patches with active noise reduction will have promising applications in the clinical auxiliary diagnosis of digestive diseases.

Material innovation and mechanics design for substrates and encapsulation of flexible electronics: a review.

Advances in materials and mechanics designs have led to the development of flexible electronics, which have important applications to human healthcare due to their good biocompatibility and conformal integration with biological tissue. Material innovation and mechanics design have played a key role in designing the substrates and encapsulations of flexible electronics for various bio-integrated systems. This review first introduces the inorganic materials and novel organic materials used for the substrates and encapsulation of flexible electronics, and summarizes their mechanics properties, permeability and optical transmission properties. The structural designs of the substrates are then introduced to ensure the reliability of flexible electronics, including the patterned and pre-strained designs to improve the stretchability, and the strain-isolation and -limiting substrates to reduce the deformation. Some emerging encapsulations are presented to protect the flexible electronics from degradation, environmental erosion or contamination, though they may slightly reduce the stretchability of flexible electronics.

Flexible Ultrasonic Patch for Accelerating Chronic Wound Healing.

Ultrasound treatment is an effective method for accelerating chronic wound healing. However, it is not widely used because traditional ultrasonic probes cannot be conformal to the wound surface, which leads to limitations of use and unstable treatment effects. In addition, the use of liquid coupling agent increases the chance of wound infection. A strategy is proposed to design and fabricate a flexible ultrasonic patch for treating chronic wounds effectively. The piezoelectric ceramic in the patch is discretized into several linearly arranged units, which are integrated on a flexible circuit substrate. A thin hydrogel patch is used as both encapsulation and coupling layer to avoid wound infection and ensure the penetration of ultrasound. The ultrasonic patch is soft, light, and can completely conform to the treatment area. Bending of the patch focuses the sound beams on the center of the bending circle, which achieves control of the target treatment area. Ultrasound treatment experiments are carried out on some type-II diabetic rats. Immunohistochemical (IHC) results indicate that ultrasound accelerates wound healing by activating Rac1 in both dermal and epidermal layers. Treatment results show that wound treated with the ultrasound heals faster than wounds without. The healing time is shortened by ≈40%.

Flexible Hybrid Electronics for Monitoring Hypoxia.

Hypoxia refers to insufficient oxygen amounts at the tissue level unable to maintain adequate homeostasis. Severe hypoxia may occur in the absence of subjective breathlessness due to respiratory failure. Precise monitoring of low blood oxygen saturation is crucially desired, catering to the clinical requirements. However, current pulse oximeters cannot function well in monitoring peripheral oxygen saturation limited by the weak peripheral blood circulation at a low oxygen level. In this work, we propose a flexible hybrid electronic (FHE) with a compact structure and high sensitivity for conveniently monitoring hypoxia. This FHE is composed of 10-µm thickness semiconductors with different materials, functionalities, and sizes. Its performance is demonstrated by monitoring arterial blood oxygen saturation (SaO2) at the body's different arteries. The absolute error is less than 2% within a SaO2 ranging from 99% to 63%. The efficient techniques presented in this work may bring light to the next-generation flexible hybrid electronics and provide potential widespread use in research and clinical applications, especially for emergency treatment.

Flexible Doppler ultrasound device for the monitoring of blood flow velocity.

Thrombosis and restenosis after vascular reconstruction procedures may cause complications such as stroke, but a clinical means to continuously monitor vascular conditions is lacking. Conventional ultrasound probes are rigid, particularly for postoperative patients with fragile skin. Techniques based on photoplethysmography or thermal analysis provide only relative changes in flow volume and have a shallow detection depth. Here, we introduce a flexible Doppler ultrasound device for the continuous monitoring of the absolute velocity of blood flow in deeply embedded arteries based on the Doppler effect. The device is thin (1 mm), lightweight (0.75 g), and skin conforming. When the dual-beam Doppler method is used, the influence of the Doppler angle on the velocity measurement is avoided. Experimental studies on ultrasound phantoms and human subjects demonstrate accurate measurement of the flow velocity. The wearable Doppler device has the potential to enhance the quality of care of patients after reconstruction surgery.

A flexible, stretchable system for simultaneous acoustic energy transfer and communication.

The use of implantable medical devices, including cardiac pacemakers and brain pacemakers, is becoming increasingly prevalent. However, surgically replacing batteries owing to their limited lifetime is a drawback of those devices. Such an operation poses a risk to patients­a problem that, to date, has not yet been solved. Furthermore, current devices are large and rigid, potentially causing patient discomfort after implantation. To address this problem, we developed a thin, battery-free, flexible, implantable system based on flexible electronic technology that can not only achieve wireless recharging and communication simultaneously via ultrasound but also perform many current device functions, including in vivo physiological monitoring and cardiac pacing. To prove this, an animal experiment was conducted involving creating a cardiac arrest model and powering the system by ultrasound. The results showed that it automatically detected abnormal heartbeats and responded by electrically stimulating the heart, demonstrating the device's potential clinical utility for emergent treatment.

Biodegradable Flexible Electronic Device with Controlled Drug Release for Cancer Treatment.

Nowadays, controllable drug release is a vitally important strategy for cancer treatment and usually realized using implanting biocompatible devices. However, these devices need to be removed by another surgery after the function fails, which brings the risks of inflammation or potential death. In this article, a biodegradable flexible electronic device with controllable drug (paclitaxel) release was proposed for cancer treatment. The device is powered by an external alternating magnetic field to generate internal resistance heat and promote drug release loaded on the substrate. Moreover, the device temperature can even reach to 65 °C, which was sufficient for controllable drug release. This device also has similar mechanical properties to human tissues and can autonomously degrade due to the structure design of the circuit and degradable compositions. Finally, it is confirmed that the device has a good inhibitory effect on the proliferation of breast cancer cells (MCF-7) and could be completely degraded in vitro. Thus, its great biodegradability and conformity can relieve patients of second operation, and the device proposed in this paper provides a promising solution to complete conquest of cancer in situ.