Yeguang Xue

A soft, wearable microfluidic device for the capture, storage, and colorimetric sensing of sweat

A soft, skin-mounted microfluidic device captures microliter volumes of sweat and quantitatively measures biochemical markers by colorimetric analysis. Better health? Prepare to sweat Wearable technology is a popular way many people monitor their general health and fitness, tracking heart rate, calories, and steps. Koh et al. now take wearable technology one step further. They have developed and tested a flexible microfluidic device that adheres to human skin. This device collects and analyzes sweat during exercise. Using colorimetric biochemical assays and integrating smartphone image capture analysis, the device detected lactate, glucose, and chloride ion concentrations in sweat as well as sweat pH while stuck to the skin of individuals during a controlled cycling test. Colorimetric readouts showed comparable results to conventional analyses, and the sweat patches remained intact and functional even when used during an outdoor endurance bicycle race. The authors suggest that microfluidic devices could be used during athletic or military training and could be adapted to test other bodily fluids such as tears or saliva. Capabilities in health monitoring enabled by capture and quantitative chemical analysis of sweat could complement, or potentially obviate the need for, approaches based on sporadic assessment of blood samples. Established sweat monitoring technologies use simple fabric swatches and are limited to basic analysis in controlled laboratory or hospital settings. We present a collection of materials and device designs for soft, flexible, and stretchable microfluidic systems, including embodiments that integrate wireless communication electronics, which can intimately and robustly bond to the surface of the skin without chemical and mechanical irritation. This integration defines access points for a small set of sweat glands such that perspiration spontaneously initiates routing of sweat through a microfluidic network and set of reservoirs. Embedded chemical analyses respond in colorimetric fashion to markers such as chloride and hydronium ions, glucose, and lactate. Wireless interfaces to digital image capture hardware serve as a means for quantitation. Human studies demonstrated the functionality of this microfluidic device during fitness cycling in a controlled environment and during long-distance bicycle racing in arid, outdoor conditions. The results include quantitative values for sweat rate, total sweat loss, pH, and concentration of chloride and lactate.

Capacitively coupled arrays of multiplexed flexible silicon transistors for long-term cardiac electrophysiology

Advanced capabilities in electrical recording are essential for the treatment of heart-rhythm diseases. The most advanced technologies use flexible integrated electronics; however, the penetration of biological fluids into the underlying electronics and any ensuing electrochemical reactions pose significant safety risks. Here, we show that an ultrathin, leakage-free, biocompatible dielectric layer can completely seal an underlying layer of flexible electronics while allowing for electrophysiological measurements through capacitive coupling between tissue and the electronics, and thus without the need for direct metal contact. The resulting current-leakage levels and operational lifetimes are, respectively, four orders of magnitude smaller and between two and three orders of magnitude longer than those of any other flexible-electronics technology. Systematic electrophysiological studies with normal, paced and arrhythmic conditions in Langendorff hearts highlight the capabilities of the capacitive-coupling approach. Our technology provides a realistic pathway towards the broad applicability of biocompatible, flexible electronic implants.

Ultrathin, transferred layers of thermally grown silicon dioxide as biofluid barriers for biointegrated flexible electronic systems

Significance A critical obstacle of flexible electronics for chronic implants is the absence of thin-film barriers to biofluids with multidecade lifetimes. Previously explored materials are unsuitable due to limitations of (i) extrinsic factors, such as the practical inability to avoid localized defects, and/or (ii) intrinsic properties, such as finite water permeability. The work presented here overcomes these challenges by combining pristine thermal SiO2 layers with processing steps for their integration onto flexible electronics. Experimental and theoretical studies reveal the key aspects of this material system. Accelerated immersion tests and cyclic bending measurements suggest robust, defect-free operation with various electronic components and an integrated system for multiplexed mapping of electrophysiological signals. The findings have broad relevance to diverse biointegrated electronics and optoelectronics. Materials that can serve as long-lived barriers to biofluids are essential to the development of any type of chronic electronic implant. Devices such as cardiac pacemakers and cochlear implants use bulk metal or ceramic packages as hermetic enclosures for the electronics. Emerging classes of flexible, biointegrated electronic systems demand similar levels of isolation from biofluids but with thin, compliant films that can simultaneously serve as biointerfaces for sensing and/or actuation while in contact with the soft, curved, and moving surfaces of target organs. This paper introduces a solution to this materials challenge that combines (i) ultrathin, pristine layers of silicon dioxide (SiO2) thermally grown on device-grade silicon wafers, and (ii) processing schemes that allow integration of these materials onto flexible electronic platforms. Accelerated lifetime tests suggest robust barrier characteristics on timescales that approach 70 y, in layers that are sufficiently thin (less than 1 μm) to avoid significant compromises in mechanical flexibility or in electrical interface fidelity. Detailed studies of temperature- and thickness-dependent electrical and physical properties reveal the key characteristics. Molecular simulations highlight essential aspects of the chemistry that governs interactions between the SiO2 and surrounding water. Examples of use with passive and active components in high-performance flexible electronic devices suggest broad utility in advanced chronic implants.

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.

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.

Engineered Elastomer Substrates for Guided Assembly of Complex 3D Mesostructures by Spatially Nonuniform Compressive Buckling

Approaches capable of creating three-dimensional (3D) mesostructures in advanced materials (device-grade semiconductors, electroactive polymers etc.) are of increasing interest in modern materials research. A versatile set of approaches exploits transformation of planar precursors into 3D architectures through the action of compressive forces associated with release of prestrain in a supporting elastomer substrate. Although a diverse set of 3D structures can be realized in nearly any class of material in this way, all previously reported demonstrations lack the ability to vary the degree of compression imparted to different regions of the 2D precursor, thus constraining the diversity of 3D geometries. This paper presents a set of ideas in materials and mechanics in which elastomeric substrates with engineered distributions of thickness yield desired strain distributions for targeted control over resultant 3D mesostructures geometries. This approach is compatible with a broad range of advanced functional materials from device-grade semiconductors to commercially available thin films, over length scales from tens of microns to several millimeters. A wide range of 3D structures can be produced in this way, some of which have direct relevance to applications in tunable optics and stretchable electronics.

3D Tunable, Multiscale, and Multistable Vibrational Micro-Platforms Assembled by Compressive Buckling

Microelectromechanical systems remain an area of significant interest in fundamental and applied research due to their wide ranging applications. Most device designs, however, are largely two-dimensional and constrained to only a few simple geometries. Achieving tunable resonant frequencies or broad operational bandwidths requires complex components and/or fabrication processes. The work presented here reports unusual classes of three-dimensional (3D) micromechanical systems in the form of vibratory platforms assembled by controlled compressive buckling. Such 3D structures can be fabricated across a broad range of length scales and from various materials, including soft polymers, monocrystalline silicon, and their composites, resulting in a wide scope of achievable resonant frequencies and mechanical behaviors. Platforms designed with multistable mechanical responses and vibrationally de-coupled constituent elements offer improved bandwidth and frequency tunability. Furthermore, the resonant frequencies can be controlled through deformations of an underlying elastomeric substrate. Systematic experimental and computational studies include structures with diverse geometries, ranging from tables, cages, rings, ring-crosses, ring-disks, two-floor ribbons, flowers, umbrellas, triple-cantilever platforms, and asymmetric circular helices, to multilayer constructions. These ideas form the foundations for engineering designs that complement those supported by conventional, microelectromechanical systems, with capabilities that could be useful in systems for biosensing, energy harvesting and others.

Fully implantable, battery-free wireless optoelectronic devices for spinal optogenetics

Abstract The advent of optogenetic tools has allowed unprecedented insights into the organization of neuronal networks. Although recently developed technologies have enabled implementation of optogenetics for studies of brain function in freely moving, untethered animals, wireless powering and device durability pose challenges in studies of spinal cord circuits where dynamic, multidimensional motions against hard and soft surrounding tissues can lead to device degradation. We demonstrate here a fully implantable optoelectronic device powered by near-field wireless communication technology, with a thin and flexible open architecture that provides excellent mechanical durability, robust sealing against biofluid penetration and fidelity in wireless activation, thereby allowing for long-term optical stimulation of the spinal cord without constraint on the natural behaviors of the animals. The system consists of a double-layer, rectangular-shaped magnetic coil antenna connected to a microscale inorganic light-emitting diode (&mgr;-ILED) on a thin, flexible probe that can be implanted just above the dura of the mouse spinal cord for effective stimulation of light-sensitive proteins expressed in neurons in the dorsal horn. Wireless optogenetic activation of TRPV1-ChR2 afferents with spinal &mgr;-ILEDs causes nocifensive behaviors and robust real-time place aversion with sustained operation in animals over periods of several weeks to months. The relatively low-cost electronics required for control of the systems, together with the biocompatibility and robust operation of these devices will allow broad application of optogenetics in future studies of spinal circuits, as well as various peripheral targets, in awake, freely moving and untethered animals, where existing approaches have limited utility.

Wrinkling of a stif thin film bonded to a pre-strained, compliant substrate with finite thickness

A stiff thin film bonded to a pre-strained, compliant substrate wrinkles into a sinusoidal form upon release of the pre-strain. Many analytical models developed for the critical pre-strain for wrinkling assume that the substrate is semi-infinite. This critical pre-strain is actually much smaller than that for a substrate with finite thickness (Ma Y et al. 2016 Adv. Funct. Mater. (doi:10.1002/adfm.201600713)). An analytical solution of the critical pre-strain for a system of a stiff film bonded to a pre-strained, finite-thickness, compliant substrate is obtained, and it agrees well with the finite-element analysis. The finite-thickness effect is significant when the substrate tensile stiffness cannot overwhelm the film tensile stiffness.

Super-Absorbent Polymer Valves and Colorimetric Chemistries for Time-Sequenced Discrete Sampling and Chloride Analysis of Sweat via Skin-Mounted Soft Microfluidics

This paper introduces super absorbent polymer valves and colorimetric sensing reagents as enabling components of soft, skin-mounted microfluidic devices designed to capture, store, and chemically analyze sweat released from eccrine glands. The valving technology enables robust means for guiding the flow of sweat from an inlet location into a collection of isolated reservoirs, in a well-defined sequence. Analysis in these reservoirs involves a color responsive indicator of chloride concentration with a formulation tailored to offer stable operation with sensitivity optimized for the relevant physiological range. Evaluations on human subjects with comparisons against ex situ analysis illustrate the practical utility of these advances.