Noninvasive methods for precise characterization of the thermal properties of soft biological tissues such as the skin can yield vital details about physiological health status including at critical intervals during recovery following skin injury. Here, we introduce quantitative measurement and characterization methods that allow rapid, accurate determination of the thermal conductivity of soft materials using thin, skin-like resistive sensor platforms. Systematic evaluations of skin at eight different locations and of six different synthetic skin-mimicking materials across sensor sizes, measurement times, and surface geometries (planar, highly curvilinear) validate simple scaling laws for data interpretation and parameter extraction. As an example of the possibilities, changes in the thermal properties of skin (volar forearm) can be monitored during recovery from exposure to ultraviolet radiation (sunburn) and to stressors associated with localized heating and cooling. More generally, the results described here facilitate rapid, non-invasive thermal measurements on broad classes of biological and non-biological soft materials.

Characterization of the thermal properties of the surface and subsurface structures of the skin can reveal the degree of hydration, the rate of blood flow in near‐surface micro‐ and macrovasculature, and other important physiological information of relevance to dermatological and overall health status. Here, a soft, stretchable thermal sensor, based on the so‐called three omega (i.e., 3ω) method, is introduced for accurate characterization of the thermal conductivity and diffusivity of materials systems, such as the skin, which can be challenging to measure using established techniques. Experiments on skin at different body locations and under different physical states demonstrate the possibilities. Systematic studies establish the underlying principles of operation in these unusual systems, thereby allowing rational design and use, through combined investigations based on analytical modeling, experimental measurements, and finite element analysis. The findings create broad opportunities for 3ω methods in biology, with utility ranging from the integration with surgical tools or implantable devices to noninvasive uses in clinical diagnostics and therapeutics.

Yonggang Huang, John A. Rogers, and co-workers report a flexible and stretchable sensor for the thermal characterization of human skin in article number 1701282. Based on the 3ω method, potential applications of the sensor could range from non-invasive use to surgical tools, or even implantable devices.

Precise, quantitative in vivo monitoring of hydration levels in the near surface regions of the skin can be useful in preventing skin-based pathologies, and regulating external appearance. Here we introduce multimodal sensors with important capabilities in this context, rendered in soft, ultrathin, ‘skin-like’ formats with numerous advantages over alternative technologies, including the ability to establish intimate, conformal contact without applied pressure, and to provide spatiotemporally resolved data on both electrical and thermal transport properties from sensitive regions of the skin. Systematic in vitro studies and computational models establish the underlying measurement principles and associated approaches for determination of temperature, thermal conductivity, thermal diffusivity, volumetric heat capacity, and electrical impedance using simple analysis algorithms. Clinical studies on 20 patients subjected to a variety of external stimuli validate the device operation and allow quantitative comparisons of measurement capabilities to those of existing state-of-the-art tools.

On page 373, I. R. Efimov, J. A. Rogers, and co-workers report classes of ultrathin injectable sensors for spatiotemporal determination of temperature, thermal conductivity, and heat capacity of biological tissues. These flexible devices provide unique capabilities in monitoring of depth-dependent changes in the properties of myocardial tissue that result from cardiac ablation therapy. The materials and mechanical designs provide minimally invasive, biocompatible operation.

On page 119, J. A. Rogers and co-workers present theoretical approaches, modeling algorithms, materials, and device designs for the noninvasive measurement of core body temperature by using multiple differential temperature sensors that attach softly and intimately onto the surface of the skin. The image shows the construction of differential temperature sensors using thermally insulating foam as the separation material.

Electronic implants are often used in diagnosing and treating human illness, but permanent implants come with problems; here, devices are described that can sense temperature, pressure, pH or thermal characteristics, and—crucially—are fully resorbable by the body.

Precision thermal measurementsThermal sensors of skin and soft tissue can provide clinically relevant information about cardiovascular health, cognitive state, hydration levels, heterogeneousMapping of human skin and soft tissues vasculature changes, and many other important aspects of human physiology. In this chapter we discuss recent advances in ultrathin, compliant skin-like sensor/actuator technologies that enable forms of continuous thermal Skin, precision thermal measurements of mapping, of temperature as well as transport properties, that are unavailable with other methods. We review the key mechanical and thermal properties Precision thermal measurements of skin that are fundamental to the operation of this class of devices. Further discussion of devices configured for mapping temperature, monitoring local thermal transport and skin hydration, and mapping thermal transport for blood flow analysis provides a few examples of the types of capabilities that are enabled with these technologies.

Knowledge of the distributions of temperature in cardiac tissue during and after ablation is important in advancing a basic understanding of this process, and for improving its efficacy in treating arrhythmias. Technologies that enable real-time temperature detection and thermal characterization in the transmural direction can help to predict the depths and sizes of lesion that form. Herein, materials and designs for an injectable device platform that supports precision sensors of temperature and thermal transport properties distributed along the length of an ultrathin and flexible needle-type polymer substrate are introduced. The resulting system can insert into the myocardial tissue, in a minimally invasive manner, to monitor both radiofrequency ablation and cryoablation, in a manner that has no measurable effects on the natural mechanical motions of the heart. The measurement results exhibit excellent agreement with thermal simulations, thereby providing improved insights into lesion transmurality.

Mechanical assessment of soft biological tissues and organs has broad relevance in clinical diagnosis and treatment of disease. Existing characterization methods are invasive, lack microscale spatial resolution, and are tailored only for specific regions of the body under quasi-static conditions. Here, we develop conformal and piezoelectric devices that enable in vivo measurements of soft tissue viscoelasticity in the near-surface regions of the epidermis. These systems achieve conformal contact with the underlying complex topography and texture of the targeted skin, as well as other organ surfaces, under both quasi-static and dynamic conditions. Experimental and theoretical characterization of the responses of piezoelectric actuator-sensor pairs laminated on a variety of soft biological tissues and organ systems in animal models provide information on the operation of the devices. Studies on human subjects establish the clinical significance of these devices for rapid and non-invasive characterization of skin mechanical properties.

Balloon catheter-based techniques that apply mechanical force to blood vessel walls have dramatically advanced the standard of care for patients with vascular disease. But balloons are limited in their therapeutic potential because they rely on mechanics alone and lack electronically active materials. Recent advances in balloon catheters with integrated electrodes have offered additional treatment capabilities through the application of both mechanical contact force and radio frequency electromotive force. However, these smart balloons remain limited in their mechanics and their ability to provide diagnostic information about local vessel hemodynamics and tissue health near treatment zones. Here, we demonstrate a novel instrumented balloon catheter system that contains stretchable electrodes and thermal-based blood flow sensors, providing hemodynamic information, electrical stimulation, and ablation therapy on a single device. This system accommodates high inflation pressure (∼2 atm) and twisting and bending over a broad range of vascular diameters and geometries. Finite element and analytical modeling capture the anisotropic mechanical and thermal properties of the device during cycles of inflation and deflation in a simulated biological environment. Bench-top ablation and in vivo blood flow measurements highlight the utility of this technology for clinical application.

Advanced materials and fractal design concepts form the basis of a 3D conformal electronic platform with unique capabilities in cardiac electrotherapies. Fractal geometries, advanced electrode materials, and thin, elastomeric membranes yield a class of device capable of integration with the entire 3D surface of the heart, with unique operational capabilities in low power defibrillation. Co-integrated collections of sensors allow simultaneous monitoring of physiological responses. Animal experiments on Langendorff-perfused rabbit hearts demonstrate the key features of these systems.

Long-term, continuous measurement of core body temperature is of high interest, due to the widespread use of this parameter as a key biomedical signal for clinical judgment and patient management. Traditional approaches rely on devices or instruments in rigid and planar forms, not readily amenable to intimate or conformable integration with soft, curvilinear, time-dynamic, surfaces of the skin. Here, materials and mechanics designs for differential temperature sensors are presented which can attach softly and reversibly onto the skin surface, and also sustain high levels of deformation (e.g., bending, twisting, and stretching). A theoretical approach, together with a modeling algorithm, yields core body temperature from multiple differential measurements from temperature sensors separated by different effective distances from the skin. The sensitivity, accuracy, and response time are analyzed by finite element analyses (FEA) to provide guidelines for relationships between sensor design and performance. Four sets of experiments on multiple devices with different dimensions and under different convection conditions illustrate the key features of the technology and the analysis approach. Finally, results indicate that thermally insulating materials with cellular structures offer advantages in reducing the response time and increasing the accuracy, while improving the mechanics and breathability.

An optical image of a 3D multifunctional integumentary membrane integrated on a Langendorff-perfused rabbit heart is shown. The inset shows an epicardial electrogram recorded using integrated fractal electrodes with PEDOT:PSS coatings, as described by J. A. Rogers and co-workers on page 1731.

Established classes of high-performance electronics have driven advances in interventional biomedicine. However, the large size, planar geometry and stiff mechanical properties of standard conventional electronics employed in medical devices give rise to important integration challenges with soft biological tissue. Stretchable and flexible biointegrated electronics could improve treatment procedures across a broad range of applications, including cardiac, neural and endovascular therapies. Here we present novel mechanics, materials and integration strategies for this new class of bioelectronics onboard minimally invasive catheter based systems. Co-located arrays of sensors and actuators affixed to cardiac and angioplasty balloon catheters capture new sensory information during ablation procedures, offering physicians the ability to adjust placement and treatment intra-procedurally. New circuit topologies, enabled by stretchable electronics, also overcome long standing challenges associated with transmitting vast amounts of data through narrow catheter lumens, thus allowing for a large number of sensors to be multiplexed for mapping electrophysiological activity with high spatiotemporal resolution and with a minimal number of routing wires. We present representative examples that highlight the clinical significance of soft bio-integrated electronics, along with the mechanics and processes that enable this technology.

Measurements of the thermal transport properties of the skin can reveal changes in physical and chemical states of relevance to dermatological health, skin structure and activity, thermoregulation and other aspects of human physiology. Existing methods for in vivo evaluations demand complex systems for laser heating and infrared thermography, or they require rigid, invasive probes; neither can apply to arbitrary regions of the body, offers modes for rapid spatial mapping, or enables continuous monitoring outside of laboratory settings. Here we describe human clinical studies using mechanically soft arrays of thermal actuators and sensors that laminate onto the skin to provide rapid, quantitative in vivo determination of both the thermal conductivity and thermal diffusivity, in a completely non-invasive manner. Comprehensive analysis of measurements on six different body locations of each of twenty-five human subjects reveal systematic variations and directional anisotropies in the characteristics, with correlations to the thicknesses of the epidermis (EP) and stratum corneum (SC) determined by optical coherence tomography, and to the water content assessed by electrical impedance based measurements. Multivariate statistical analysis establishes four distinct locations across the body that exhibit different physical properties: heel, cheek, palm, and wrist/volar forearm/dorsal forearm. The data also demonstrate that thermal transport correlates negatively with SC and EP thickness and positively with water content, with a strength of correlation that varies from region to region, e.g., stronger in the palmar than in the follicular regions.

Continuous monitoring of variations in blood flow is vital in assessing the status of microvascular and macro-vascular beds for a wide range of clinical and research scenarios. Although a variety of techniques exist, most require complete immobilization of the subject, thereby limiting their utility to hospital or clinical settings. Those that can be rendered in wearable formats suffer from limited accuracy, motion artifacts, and other shortcomings that follow from an inability to achieve intimate, noninvasive mechanical linkage of sensors with the surface of the skin. We introduce an ultrathin, soft, skin-conforming sensor technology that offers advanced capabilities in continuous and precise blood flow mapping. Systematic work establishes a set of experimental procedures and theoretical models for quantitative measurements and guidelines in design and operation. Experimental studies on human subjects, including validation with measurements performed using state-of-the-art clinical techniques, demonstrate sensitive and accurate assessment of both macrovascular and microvascular flow under a range of physiological conditions. Refined operational modes eliminate long-term drifts and reduce power consumption, thereby providing steps toward the use of this technology for continuous monitoring during daily activities.

Research in stretchable electronics involves fundamental scientific topics relevant to applications with importance in human healthcare. Despite significant progress in active components, routes to mechanically robust construction are lacking. Here, we introduce materials and composite designs for thin, breathable, soft electronics that can adhere strongly to the skin, with the ability to be applied and removed hundreds of times without damaging the devices or the skin, even in regions with substantial topography and coverage of hair. The approach combines thin, ultralow modulus, cellular silicone materials with elastic, strain-limiting fabrics, to yield a compliant but rugged platform for stretchable electronics. Theoretical and experimental studies highlight the mechanics of adhesion and elastic deformation. Demonstrations include cutaneous optical, electrical and radio frequency sensors for measuring hydration state, electrophysiological activity, pulse and cerebral oximetry. Multipoint monitoring of a subject in an advanced driving simulator provides a practical example.