Clinical Validation of a Wearable Piezoelectric Blood-Pressure Sensor for Continuous Health Monitoring.

Wearable blood-pressure sensors have recently attracted attention as healthcare devices for continuous non-invasive arterial pressure (CNAP) monitoring. However, the accuracy of wearable blood-pressure (BP) monitoring devices has been controversial due to the low signal quality of sensors, the absence of an accurate transfer function to convert the sensor signals into BP values, and the lack of clinical validation regarding measurement precision. Here, a wearable piezoelectric blood-pressure sensor (WPBPS) is reported, which achieves a high normalized sensitivity (0.062 kPa-1 ), and fast response time (23 ms) for CNAP monitoring. The transfer function of a linear regression model is designed, offering a simple solution to convert the flexible piezoelectric sensor signals into BP values. In order to verify the measurement accuracy of WPBPS, clinical trials are performed on 35 subjects aged from 20 to 80 s after screening. The mean difference between the WPBPS and a commercial sphygmomanometer of 175 BP data pairs is -0.89 ± 6.19 and -0.32 ± 5.28 mmHg for systolic blood pressure (SBP) and diastolic blood pressure (DBP), respectively. By building a WPBPS-embedded wristwatch, the potentially promising use of a convenient, portable, continuous BP monitoring system for cardiovascular disease diagnosis is demonstrated.

Siloxane Hybrid Material-Encapsulated Highly Robust Flexible µLEDs for Biocompatible Lighting Applications.

Flexible micro-light-emitting diodes (f-µLEDs) have been regarded as an attractive light source for the next-generation human-machine interfaces, thanks to their noticeable optoelectronic performances. However, when it comes to their practical utilizations fulfilling industrial standards, there have been unsolved reliability and durability issues of the f-µLEDs, despite previous developments in the high-performance f-µLEDs for various applications. Herein, highly robust flexible µLEDs (f-HµLEDs) with 20 × 20 arrays, which are realized by a siloxane-based organic-inorganic hybrid material (SHM), are reported. The f-HµLEDs are created by combining the f-µLED fabrication process with SHM synthesis procedures (i.e., sol-gel reaction and successive photocuring). The outstanding mechanical, thermal, and environmental stabilities of our f-HµLEDs are confirmed by a host of experimental and theoretical examinations, including a bending fatigue test (105 bending/unbending cycles), a lifetime accelerated stress test (85 °C and 85% relative humidity), and finite element method simulations. Eventually, to demonstrate the potential of our f-HµLEDs for practical applications of flexible displays and/or biomedical devices, their white light emission due to quantum dot-based color conversion of blue light emitted by GaN-based f-HµLEDs is demonstrated, and the biocompatibility of our f-HµLEDs is confirmed via cytotoxicity and cell proliferation tests with muscle, bone, and neuron cell lines. As far as we can tell, this work is the first demonstration of the flexible µLED encapsulation platform based on the SHM, which proved its mechanical, thermal, and environmental stabilities and biocompatibility, enabling us to envisage biomedical and/or flexible display applications using our f-HµLEDs.

Author Correction: Intestinal crypts recover rapidly from focal damage with coordinated motion of stem cells that is impaired by aging.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Flash-Induced Stretchable Cu Conductor via Multiscale-Interfacial Couplings.

Herein, a novel stretchable Cu conductor with excellent conductivity and stretchability is reported via the flash-induced multiscale tuning of Cu and an elastomer interface. Microscale randomly wrinkled Cu (amplitude of ≈5 µm and wavelength of ≈45 µm) is formed on a polymer substrate through a single pulse of a millisecond flash light, enabling the elongation of Cu to exceed 20% regardless of the stretching direction. The nanoscale interlocked interface between the Cu nanoparticles (NPs) and the elastomer increases the adhesion force of Cu, which contributes to a significant improvement of the Cu stability and stretchability under harsh yielding stress. Simultaneously, the flash-induced photoreduction of CuO NPs and subsequent Cu NP welding lead to outstanding conductivity (≈37 kS cm-1) of the buckled elastic electrode. The 3D structure of randomly wrinkled Cu is modeled by finite element analysis simulations to show that the flash-activated stretchable Cu conductors can endure strain over 20% in all directions. Finally, the wrinkled Cu is utilized for wireless near-field communication on the skin of human wrist.

Intestinal crypts recover rapidly from focal damage with coordinated motion of stem cells that is impaired by aging.

Despite the continuous renewal and turnover of the small intestinal epithelium, the intestinal crypt maintains a 'soccer ball-like', alternating pattern of stem and Paneth cells at the base of the crypt. To study the robustness of the alternating pattern, we used intravital two-photon microscopy in mice with fluorescently-labeled Lgr5+ intestinal stem cells and precisely perturbed the mosaic pattern with femtosecond laser ablation. Ablation of one to three cells initiated rapid motion of crypt cells that restored the alternation in the pattern within about two hours with only the rearrangement of pre-existing cells, without any cell division. Crypt cells then performed a coordinated dilation of the crypt lumen, which resulted in peristalsis-like motion that forced damaged cells out of the crypt. Crypt cell motion was reduced with inhibition of the ROCK pathway and attenuated with old age, and both resulted in incomplete pattern recovery. This suggests that in addition to proliferation and self-renewal, motility of stem cells is critical for maintaining homeostasis. Reduction of this newly-identified behavior of stem cells could contribute to disease and age-related changes.

Monolithic Flexible Vertical GaN Light-Emitting Diodes for a Transparent Wireless Brain Optical Stimulator.

Flexible inorganic-based micro light-emitting diodes (µLEDs) are emerging as a significant technology for flexible displays, which is an important area for bilateral visual communication in the upcoming Internet of Things era. Conventional flexible lateral µLEDs have been investigated by several researchers, but still have significant issues of power consumption, thermal stability, lifetime, and light-extraction efficiency on plastics. Here, high-performance flexible vertical GaN light-emitting diodes (LEDs) are demonstrated by silver nanowire networks and monolithic fabrication. Transparent, ultrathin GaN LED arrays adhere to a human fingernail and stably glow without any mechanical deformation. Experimental studies provide outstanding characteristics of the flexible vertical µLEDs (f-VLEDs) with high optical power (30 mW mm-2 ), long lifetime (≈12 years), and good thermal/mechanical stability (100 000 bending/unbending cycles). The wireless light-emitting system on the human skin is successfully realized by transferring the electrical power f-VLED. Finally, the high-density GaN f-VLED arrays are inserted onto a living mouse cortex and operated without significant histological damage of brain.

Self-Powered Real-Time Arterial Pulse Monitoring Using Ultrathin Epidermal Piezoelectric Sensors.

Continuous monitoring of an arterial pulse using a pressure sensor attached on the epidermis is an important technology for detecting the early onset of cardiovascular disease and assessing personal health status. Conventional pulse sensors have the capability of detecting human biosignals, but have significant drawbacks of power consumption issues that limit sustainable operation of wearable medical devices. Here, a self-powered piezoelectric pulse sensor is demonstrated to enable in vivo measurement of radial/carotid pulse signals in near-surface arteries. The inorganic piezoelectric sensor on an ultrathin plastic achieves conformal contact with the complex texture of the rugged skin, which allows to respond to the tiny pulse changes arising on the surface of epidermis. Experimental studies provide characteristics of the sensor with a sensitivity (≈0.018 kPa-1 ), response time (≈60 ms), and good mechanical stability. Wireless transmission of detected arterial pressure signals to a smart phone demonstrates the possibility of self-powered and real-time pulse monitoring system.

Laser-Material Interactions for Flexible Applications.

The use of lasers for industrial, scientific, and medical applications has received an enormous amount of attention due to the advantageous ability of precise parameter control for heat transfer. Laser-beam-induced photothermal heating and reactions can modify nanomaterials such as nanoparticles, nanowires, and two-dimensional materials including graphene, in a controlled manner. There have been numerous efforts to incorporate lasers into advanced electronic processing, especially for inorganic-based flexible electronics. In order to resolve temperature issues with plastic substrates, laser-material processing has been adopted for various applications in flexible electronics including energy devices, processors, displays, and other peripheral electronic components. Here, recent advances in laser-material interactions for inorganic-based flexible applications with regard to both materials and processes are presented.

Reliable Memristive Switching Memory Devices Enabled by Densely Packed Silver Nanocone Arrays as Electric-Field Concentrators.

Memristor devices based on electrochemical metallization operate through electrochemical formation/dissolution of nanoscale metallic filaments, and they are considered a promising future nonvolatile memory because of their outstanding characteristics over conventional charge-based memories. However, nanoscale conductive paths or filaments precipitated from the redox process of metallic elements are randomly formed inside oxides, resulting in unexpected and stochastic memristive switching parameters including the operating voltage and the resistance state. Here, we present the guided formation of conductive filaments in Ag nanocone/SiO2 nanomesh/Pt memristors fabricated by high-resolution nanotransfer printing. Consequently, the uniformity of the memristive switching behavior is significantly improved by the existence of electric-field concentrator arrays consisting of Ag nanocones embedded in SiO2 nanomesh structures. This selective and controlled filament growth was experimentally supported by analyzing simultaneously the surface morphology and current-mapping results using conductive atomic force microscopy. Moreover, stable multilevel switching operations with four discrete conduction states were achieved by the nanopatterned memristor device, demonstrating its potential in high-density nanoscale memory devices.

Simultaneous Roll Transfer and Interconnection of Flexible Silicon NAND Flash Memory.

Ultrathin silicon-based flexible 16 × 16 NAND flash memory (f-NAND) is demonstrated utilizing roll-to-plate packaging. The roll-based thermo-compression bonding of the anisotropic conductive film (ACF) transfers and simultaneously interconnects the f-NAND on a flexible printed circuit board. Reliable circuitry operation of the 16 × 16 f-NAND is confirmed with excellent flexibility and stable ACF interconnections.

Surface Functionalized Graphene Biosensor on Sapphire for Cancer Cell Detection.

Graphene has several unique physical, optical and electrical properties such as a two-dimensional (2D) planar structure, high optical transparency and high carrier mobility at room temperature. These make graphene interesting for electrical biosensing. Using a catalyst-free chemical vapor deposition (CVD) method, graphene film is grown on a sapphire substrate. There is a single or a few sheets as confirmed by Raman spectroscopy and atomic force microscopy (AFM). Electrical graphene biosensors are fabricated to detect large-sized biological analytes such as cancer cells. Human colorectal carcinoma cells are sensed by the resistance change of an active bio-functionalized graphene device as the cells are captured by the immobilized antibody surface. The functionalized sensors show an increase in resistance as large as ~20% of the baseline with a small number of adhered cells. This study suggests that the bio-functionalized electrical graphene sensors on sapphire, which is a highly transparent material, can potentially detect circulating tumor cells (CTCs) and monitor cellular electrical behavior while being compatible with fluorescence-based optical-detection bioassays.

Comprehensive models of human primary and metastatic colorectal tumors in immunodeficient and immunocompetent mice by chemokine targeting.

Current orthotopic xenograft models of human colorectal cancer (CRC) require surgery and do not robustly form metastases in the liver, the most common site clinically. CCR9 traffics lymphocytes to intestine and colorectum. We engineered use of the chemokine receptor CCR9 in CRC cell lines and patient-derived cells to create primary gastrointestinal (GI) tumors in immunodeficient mice by tail-vein injection rather than surgery. The tumors metastasize inducibly and robustly to the liver. Metastases have higher DKK4 and NOTCH signaling levels and are more chemoresistant than paired subcutaneous xenografts. Using this approach, we generated 17 chemokine-targeted mouse models (CTMMs) that recapitulate the majority of common human somatic CRC mutations. We also show that primary tumors can be modeled in immunocompetent mice by microinjecting CCR9-expressing cancer cell lines into early-stage mouse blastocysts, which induces central immune tolerance. We expect that CTMMs will facilitate investigation of the biology of CRC metastasis and drug screening.

Rapid prototyping of nanofluidic systems using size-reduced electrospun nanofibers for biomolecular analysis.

Biomolecular transport in nanofluidic confinement offers various means to investigate the behavior of biomolecules in their native aqueous environments, and to develop tools for diverse single-molecule manipulations. Recently, a number of simple nanofluidic fabrication techniques has been demonstrated that utilize electrospun nanofibers as a backbone structure. These techniques are limited by the arbitrary dimension of the resulting nanochannels due to the random nature of electrospinning. Here, a new method for fabricating nanofluidic systems from size-reduced electrospun nanofibers is reported and demonstrated. As it is demonstrated, this method uses the scanned electrospinning technique for generation of oriented sacrificial nanofibers and exposes these nanofibers to harsh, but isotropic etching/heating environments to reduce their cross-sectional dimension. The creation of various nanofluidic systems as small as 20 nm is demonstrated, and practical examples of single biomolecular handling, such as DNA elongation in nanochannels and fluorescence correlation spectroscopic analysis of biomolecules passing through nanochannels, are provided.