Capabilities in health monitoring via 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 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 both chloride and lactate.

Summary Paragraph The fast-growing field of bioelectronic medicine aims to develop engineered systems that relieve clinical conditions through stimulation of the peripheral nervous system (PNS) 1 – 5 . Technologies of this type rely largely on electrical stimulation to provide neuromodulation of organ function or pain. One example is sacral nerve stimulation to treat overactive bladder, urinary incontinence and interstitial cystitis/bladder pain syndrome 4 , 6 , 7 . Conventional, continuous stimulation protocols, however, cause discomfort and pain, particularly when treating symptoms that can be intermittent in nature (e.g. sudden urinary urgency) 8 . Direct physical coupling of electrodes to the nerve can lead to injury and inflammation 9 – 11 . Furthermore, typical therapeutic stimulators target large nerve bundles that innervate multiple structures, resulting in a lack of organ specificity. This paper introduces a miniaturized bio-optoelectronic implant that avoids these limitations, via the use of (1) an optical stimulation interface that exploits microscale inorganic light emitting diodes (μ-ILEDs) to activate opsins, (2) a soft, precision biophysical sensor system that allows continuous measurements of organ function, and (3) a control module and data analytics approach that allows coordinated, closed-loop operation of the system to eliminate pathological behaviors as they occur in real-time. In an example reported here, a soft strain gauge yields real-time information on bladder function. Data analytics algorithms identify pathological behavior, and automated, closed-loop optogenetic neuromodulation of bladder sensory afferents normalize bladder function in the context of acute cystitis. This all-optical scheme for neuromodulation offers chronic stability and the potential for cell-type-specific stimulation.

Long-lasting, high-resolution neural interfaces that are ultrathin and flexible are essential for precise brain mapping and high-performance neuroprosthetic systems. Scaling to sample thousands of sites across large brain regions requires integrating powered electronics to multiplex many electrodes to a few external wires. However, existing multiplexed electrode arrays rely on encapsulation strategies that have limited implant lifetimes. Here, we developed a flexible, multiplexed electrode array, called “Neural Matrix,” that provides stable in vivo neural recordings in rodents and nonhuman primates. Neural Matrix lasts over a year and samples a centimeter-scale brain region using over a thousand channels. The long-lasting encapsulation (projected to last at least 6 years), scalable device design, and iterative in vivo optimization described here are essential components to overcoming current hurdles facing next-generation neural technologies.

Thin, soft, skin-like sensors capable of precise, continuous measurements of physiological health have broad potential relevance to clinical health care. Use of sensors distributed over a wide area for full-body, spatiotemporal mapping of physiological processes would be a considerable advance for this field. We introduce materials, device designs, wireless power delivery and communication strategies, and overall system architectures for skin-like, battery-free sensors of temperature and pressure that can be used across the entire body. Combined experimental and theoretical investigations of the sensor operation and the modes for wireless addressing define the key features of these systems. Studies with human subjects in clinical sleep laboratories and in adjustable hospital beds demonstrate functionality of the sensors, with potential implications for monitoring of circadian cycles and mitigating risks for pressure-induced skin ulcers.

Emerging classes of bioresorbable electronic materials serve as the basis for active biomedical implants that are capable of providing sensing, monitoring, stimulating, and other forms of function over an operating period matched to biological processes such as wound healing. These platforms are of interest because subsequent dissolution, enzymatic degradation, and/ or bioresorption can eliminate the need for surgical extraction. This report introduces natural wax materials as long-lived, hydrophobic encapsulation layers for such systems, where biodegradation eventually occurs by chain scission. Studies of wax stability as an encapsulation material demonstrate the ability to retain operation of underlying biodegradable electronic systems for durations between a few days to a few weeks during complete immersion in aqueous solutions in ex-vivo physiological conditions. Electrically conductive composites result from the addition of tungsten micro/nanoparticles, as a conductive, printable paste with similar lifetimes. Demonstrations of these materials in partially biodegradable wireless light-emitting diodes and nearfield communication circuits illustrate their use in functional bioresorbable electronic systems. Investigations in animal models reveal no signs of toxicity or other adverse biological responses.

Recently developed approaches in deterministic assembly allow for controlled, geometric transformation of two-dimensional structures into complex, engineered three-dimensional layouts. Attractive features include applicability to wide ranging layout designs and dimensions along with the capacity to integrate planar thin film materials and device layouts. The work reported here establishes further capabilities for directly embedding high-performance electronic devices into the resultant 3D constructs based on silicon nanomembranes (Si NMs) as the active materials in custom devices or microscale components released from commercial wafer sources. Systematic experimental studies and theoretical analysis illustrate the key ideas through varied 3D architectures, from interconnected bridges and coils to extended chiral structures, each of which embed n-channel Si NM MOSFETs (nMOS), Si NM diodes, and p-channel silicon MOSFETs (pMOS). Examples in stretchable/deformable systems highlight additional features of these platforms. These strategies are immediately applicable to other wide-ranging classes of materials and device technologies that can be rendered in two-dimensional layouts, from systems for energy storage, to photovoltaics, optoelectronics, and others.

2000759 (6 of 38) www.advmattechnol.de Figure 4. Flexible microwave transistors. a) Schematic illustration of fabrication process flow of flexible microwave TFTs based on Si nanomembrane. Left, two-step transfer-printing of Si nanomembrane on flexible substrate with assist of PDMS stamp. Right, direct flip-printing Si nanomembrane on flexible substrate. Reproduced with permission. [72] Copyright 2010, Wiley-VCH. b) Flexible microwave Si TFT using direct flip-printing approach in (a). Reproduced under the terms of the Creative Commons Attribution 4.0 International License. [75] Copyright 2016, Springer Nature. c) Flexible microwave Si TFT using two-step approach in (a). Reproduced with permission. [72] Copyright 2010, Wiley-VCH. d) Cross-section SEM image of flexible Si MOSFET made by thinning a 65 nm node SOI wafer. Reproduced with permission. [45] Copyright 2013, American Institute of Physics. e) Optical images of flexible GaAs HBT on cellulose nanofibril (CNF) substrate. Reproduced under the terms of the Creative Commons Attribution 4.0 International License. [90] Copyright 2015, Springer Nature. f) Schematic illustration and normalized on-state conductance (G/G 0), maximum transconductance (g m /g m0) of flexible InAs MOSFET with self-aligned gate. Reproduced with permission. [53] Copyright 2012, American Chemical Society. g) Cross-section schematic illustration and gain curves of flexible InGaAs/InAlAs HEMT as function of frequency under various bending conditions. Reproduced with permission. [91] Copyright 2013, American Institute of Physics. h) Output power density (P OUT), power gain (G P) and power-added efficiency (PAE) of the flexible GaN HEMT on thermal conductive tape with thermal conductivity of 1.6 W m −1 K −1. Reproduced with permission. [92] Copyright 2017, Wiley-VCH. i) Photography of AlGaN/GaN film grown on BN coated sapphire substrate and printed on flexible tape. Reproduced with permission. [19] Copyright 2017, Wiley-VCH. j) Cross-section schematic illustration of bottom gate flexible graphene FET (GFET). Reproduced with permission. [93] Copyright 2013, American Chemical Society. k) Cross-section schematic illustration of top gate flexible GFET with self-aligned gate configuration. Reproduced with permission. [94] Copyright 2014, American Chemical Society. l) High-frequency characteristics of flexible GFET with gate length of 50 nm. Reproduced with permission. [95] Copyright 2018, Wiley-VCH. m) Schematic illustration and gain curves of flexible microwave transistor based on MoS 2 as function of frequency. Reproduced with permission. [96] Copyright 2014, Springer Nature. n) High-frequency characteristics of flexible microwave transistor based on black phosphorus (BP) as function of frequency. Reproduced with permission.

Tuberculosis (TB) is a contagious disease that has been responsible for the death of one billion people in the last 200 years. Until now, the only vaccine approved for the prevention of TB is Bacillus Calmette-Guérin (BCG), which is prepared by attenuating Mycobacterium bovis. However, one of the limitations of BCG is that its preventive effect against pulmonary TB varies from person to person. Therefore, there arises a need for a new TB vaccine to replace or supplement BCG. In this review, we have summarized the findings of current clinical trials on preventive and therapeutic TB vaccine candidates. In addition, we have discussed a novel vaccination approach using the cell-based vaccine presenting early secretory antigenic target-6 (ESAT-6), which is a potent immunogenic antigen. The role of ESAT-6 in hosts has also been described.