Materials and Structural Designs toward Motion Artifact-Free Bioelectronics.

Bioelectronics encompassing electronic components and circuits for accessing human information play a vital role in real-time and continuous monitoring of biophysiological signals of electrophysiology, mechanical physiology, and electrochemical physiology. However, mechanical noise, particularly motion artifacts, poses a significant challenge in accurately detecting and analyzing target signals. While software-based "postprocessing" methods and signal filtering techniques have been widely employed, challenges such as signal distortion, major requirement of accurate models for classification, power consumption, and data delay inevitably persist. This review presents an overview of noise reduction strategies in bioelectronics, focusing on reducing motion artifacts and improving the signal-to-noise ratio through hardware-based approaches such as "preprocessing". One of the main stress-avoiding strategies is reducing elastic mechanical energies applied to bioelectronics to prevent stress-induced motion artifacts. Various approaches including strain-compliance, strain-resistance, and stress-damping techniques using unique materials and structures have been explored. Future research should optimize materials and structure designs, establish stable processes and measurement methods, and develop techniques for selectively separating and processing overlapping noises. Ultimately, these advancements will contribute to the development of more reliable and effective bioelectronics for healthcare monitoring and diagnostics.

Ultrasensitive mechanical crack-based sensor inspired by the spider sensory system.

Recently developed flexible mechanosensors based on inorganic silicon, organic semiconductors, carbon nanotubes, graphene platelets, pressure-sensitive rubber and self-powered devices are highly sensitive and can be applied to human skin. However, the development of a multifunctional sensor satisfying the requirements of ultrahigh mechanosensitivity, flexibility and durability remains a challenge. In nature, spiders sense extremely small variations in mechanical stress using crack-shaped slit organs near their leg joints. Here we demonstrate that sensors based on nanoscale crack junctions and inspired by the geometry of a spider's slit organ can attain ultrahigh sensitivity and serve multiple purposes. The sensors are sensitive to strain (with a gauge factor of over 2,000 in the 0-2 per cent strain range) and vibration (with the ability to detect amplitudes of approximately 10 nanometres). The device is reversible, reproducible, durable and mechanically flexible, and can thus be easily mounted on human skin as an electronic multipixel array. The ultrahigh mechanosensitivity is attributed to the disconnection-reconnection process undergone by the zip-like nanoscale crack junctions under strain or vibration. The proposed theoretical model is consistent with experimental data that we report here. We also demonstrate that sensors based on nanoscale crack junctions are applicable to highly selective speech pattern recognition and the detection of physiological signals. The nanoscale crack junction-based sensory system could be useful in diverse applications requiring ultrahigh displacement sensitivity.

Designs and processes toward high-aspect-ratio nanostructures at the deep nanoscale: unconventional nanolithography and its applications.

The patterning of high-resolution-featured deep-nanoscale structures with a high aspect ratio (AR) has received increasing attention in recent years as a promising technique for a wide range of applications, including electrical, optical, mechanical and biological systems. Despite extensive efforts to develop viable nanostructure fabrication processes, a superior technique enabling defect-free, high-resolution control over a large area is still required. In this review, we focus on recent important advances in the designs and processes of high-resolution nanostructures possessing a high AR, including hierarchical and 3D patterns. The unique applications of these materials are also discussed.

Bionic artificial skin with a fully implantable wireless tactile sensory system for wound healing and restoring skin tactile function.

Tactile function is essential for human life as it enables us to recognize texture and respond to external stimuli, including potential threats with sharp objects that may result in punctures or lacerations. Severe skin damage caused by severe burns, skin cancer, chemical accidents, and industrial accidents damage the structure of the skin tissue as well as the nerve system, resulting in permanent tactile sensory dysfunction, which significantly impacts an individual's daily life. Here, we introduce a fully-implantable wireless powered tactile sensory system embedded artificial skin (WTSA), with stable operation, to restore permanently damaged tactile function and promote wound healing for regenerating severely damaged skin. The fabricated WTSA facilitates (i) replacement of severely damaged tactile sensory with broad biocompatibility, (ii) promoting of skin wound healing and regeneration through collagen and fibrin-based artificial skin (CFAS), and (iii) minimization of foreign body reaction via hydrogel coating on neural interface electrodes. Furthermore, the WTSA shows a stable operation as a sensory system as evidenced by the quantitative analysis of leg movement angle and electromyogram (EMG) signals in response to varying intensities of applied pressures.

Cuticular pad-inspired selective frequency damper for nearly dynamic noise-free bioelectronics.

Bioelectronics needs to continuously monitor mechanical and electrophysiological signals for patients. However, the signals always include artifacts by patients' unexpected movement (such as walking and respiration under approximately 30 hertz). The current method to remove them is a signal process that uses a bandpass filter, which may cause signal loss. We present an unconventional bandpass filter material-viscoelastic gelatin-chitosan hydrogel damper, inspired by the viscoelastic cuticular pad in a spider-to remove dynamic mechanical noise artifacts selectively. The hydrogel exhibits frequency-dependent phase transition that results in a rubbery state that damps low-frequency noise and a glassy state that transmits the desired high-frequency signals. It serves as an adaptable passfilter that enables the acquisition of high-quality signals from patients while minimizing signal process for advanced bioelectronics.

Solvent-Assisted Filling of Liquid Metal and Its Selective Dewetting for the Multilayered 3D Interconnect in Stretchable Electronics.

As stretchable electronics are rapidly developing and becoming complex, the requirement for stretchable, multilayered, and large-area printed circuit boards (PCBs) is emerging. This demands a stretchable electrode and its vertical interconnect access (via) for 3-dimensional (3D) connectivity between layers. Here, we demonstrate solvent-assisted liquid metal (LM) filling into the submicrometer channel (∼400 nm), including via-hole filling and selective dewetting of LM. We provide the theoretical background of solvent-assisted LM filling and selective dewetting and reveal the osmotic pressure arising from anomalous mass transport phenomena, case II diffusion, which drives negative pressure, the spontaneous pulling of LM into the open channel. Also, we suggest design criteria for the geometry and dimension of LM interconnects to obtain structural stability without dewetting, based on the theoretical and computational background. We demonstrate a simple stretchable near-field communication (NFC) device including transferred micrometer-size light-emitting diodes (LEDs) with only 230 µm to the stretchable liquid metal PCB, without any soldering process. The device operates stably under repetitive stretching and releasing (∼50% uniaxial strain) due to the stable connection through the LM via between the upper and lower layers. Finally, we propose a concept for modular-type stretchable electronics, based on the cohesive liquid nature of LM. As a building block, the functional module can be easily removed from a mainframe, and replaced by another functional module, to suit user demand.

Stretchable and Directly Patternable Double-Layer Structure Electrodes with Complete Coverage.

Stretchable electrodes are widely used in next-generation wearable electronics. Recent studies incorporated designs that help rigid electrodes attain stretchability. However, these structures exhibited unsatisfactory charge/signal extraction efficiency because of their low areal fill factor. Additionally, they cannot be photolithographically patterned on polymer substrates because of their low adhesion, requiring additional complicated fabrication steps. We developed photolithographically patternable stretchable electrodes with complete coverage and enhanced charge-extraction efficiency. The electrodes, comprising double layers, included a chemically treated Ag nanowire mesh and Au thin film. The interfacial linker role of polyvinylpyrrolidone chemically strengthened the interfacial bonds, and the reinforced concrete structure of nanowire-embedded metal thin films enhanced the mechanical properties. Therefore, the electrodes provided superior efficiency and stability in capturing physical, electromagnetic, and electrophysiological signals while exceeding the existing stretchable electrode limits. A broad range of applications are foreseen, such as electrocardiogram sensing electrodes, strain sensors, temperature sensors, and antennas.

Noninterference Wearable Strain Sensor: Near-Zero Temperature Coefficient of Resistance Nanoparticle Arrays with Thermal Expansion and Transport Engineering.

In this study, non-temperature interference strain gauge sensors, which are only sensitive to strain but not temperature, are developed by engineering the properties and structure from a material perspective. The environmental interference from temperature fluctuations is successfully eliminated by controlling the charge transport in nanoparticles with thermally expandable polymer substrates. Notably, the negative temperature coefficient of resistance (TCR), which originates from the hopping transport in nanoparticle arrays, is compensated by the positive TCR of the effective surface thermal expansion with anchoring effects. This strategy successfully controls the TCR from negative to positive. A near-zero TCR (NZTCR), less than 1.0 × 10-6 K-1, is achieved through precisely controlled expansion. Various characterization methods and finite element and transport simulations are conducted to investigate the correlated electrical, mechanical, and thermal properties of the materials and elucidate the compensated NZTCR mechanism. With this strategy, an all-solution-processed, transparent, highly sensitive, and noninterference strain sensor is fabricated with a gauge factor higher than 5000 at 1% strain, as demonstrated by pulse and motion sensing, as well as the noninterference property under variable-temperature conditions. It is envisaged that the sensor developed herein is applicable to multifunctional wearable sensors or e-skins for artificial skin or robots.

Bioinspired Electronics for Artificial Sensory Systems.

Humans have a myriad of sensory receptors in different sense organs that form the five traditionally recognized senses of sight, hearing, smell, taste, and touch. These receptors detect diverse stimuli originating from the world and turn them into brain-interpretable electrical impulses for sensory cognitive processing, enabling us to communicate and socialize. Developments in biologically inspired electronics have led to the demonstration of a wide range of electronic sensors in all five traditional categories, with the potential to impact a broad spectrum of applications. Here, recent advances in bioinspired electronics that can function as potential artificial sensory systems, including prosthesis and humanoid robots are reviewed. The mechanisms and demonstrations in mimicking biological sensory systems are individually discussed and the remaining future challenges that must be solved for their versatile use are analyzed. Recent progress in bioinspired electronic sensors shows that the five traditional senses are successfully mimicked using novel electronic components and the performance regarding sensitivity, selectivity, and accuracy have improved to levels that outperform human sensory organs. Finally, neural interfacing techniques for connecting artificial sensors to the brain are discussed.

Controllable Configuration of Sensing Band in a Pressure Sensor by Lenticular Pattern Deformation on Designated Electrodes.

Resistive-type pressure sensor, which are mainly utilized in industry, are easy to manufacture and are not significantly affected by external electromagnetic fields, unlike capacitive type. However, the produce signal is not linear, and it is also difficult to measure a wide range of pressures using such a sensor. Therefore, before being utilized, the extracted nonlinear data from them need to be processed by. A resistive sensor that is capable of measuring a wide range of pressure of up to 4 MPa with constant linearity is presented. Moreover it can selectively control the sensing pressure band, or act as an on/off switch, without the need for any additional computer processing.

Stretchable, Patch-Type Calorie-Expenditure Measurement Device Based on Pop-Up Shaped Nanoscale Crack-Based Sensor.

Demands for precise health information tracking techniques are increasing, especially for daily dietry requirements to prevent obesity, diabetes, etc. Many commercially available sensors that detect dynamic motions of the body lack accuracy, while novel strain sensors at the research level mostly lack the capability to analyze measurements in real life conditions. Here, a stretchable, patch-type calorie expenditure measurement system is demonstrated that integrates an ultrasensitive crack-based strain sensor and Bluetooth-enabled wireless communication circuit to offer both accurate measurements and practical diagnosis of motion. The crack-based strain gauge transformed into a pop-up-shaped structure provides reliable measurements and broad range of strain (≈100%). Combined with the stretchable analysis circuit, the skin attachable tool translates variation of the knee flexion angle into calorie expenditure amount, using relative resistance change (R/R0 ) data from the flexible sensor. As signals from the knee joint angular movement translates velocity and walking/running behavior, the total amount of calorie expenditure is accurately analyzed. Finally, theoretical, experimental, and simulation analysis of signal stability, dynamic noises, and calorie expenditure calculation obtained from the device during exercise are demonstrated. For further applications, the devices are expected to be used in broader range of dynamic motion of the body for diagnosis of abnormalities and for rehabilitation.

A semi-permanent and durable nanoscale-crack-based sensor by on-demand healing.

Although sensitivity and durability are desirable in a sensor, both of them cannot be easily achieved. Site-specific and effective signal acquisition on the limited area of a sensor inevitably allows fatigue accumulation and contamination. For example, an ultrasensitive nanoscale-crack-based sensor for detecting a mechanical stimulus with tremendous sensitivity (a gauge factor greater than 2000 under 2% strain), yet limited durability (up to a few thousand stretching cycles in tensile tests) has been presented previously. Herein, we suggest a simple yet robust nanoscale-crack-based sensor that achieves remarkable durability through the use of a self-healable polymer. The self-healable polymer helps the crack gap recover and maintain high stability for 1 million cycles under 2% strain. Moreover, site-specific recovery with infrared light irradiation was demonstrated with monolithic arrayed sensors. The proposed strategy provides a unique solution to achieving highly enhanced durability and high mechanosensitivity, which are typically incompatible.

On-Demand Drug Release from Gold Nanoturf for a Thermo- and Chemotherapeutic Esophageal Stent.

Stimuli-responsive delivery systems for cancer therapy have been increasingly used to promote the on-demand therapeutic efficacy of anticancer drugs and, in some cases, simultaneously generate heat in response to a stimulus, resulting in hyperthermia. However, their application is still limited due to the systemic drawbacks of intravenous delivery, such as rapid clearance from the bloodstream and the repeat injections required for sustained safe dosage, which can cause overdosing. Here, we propose a gold (Au)-coated nanoturf structure as an implantable therapeutic interface for near-infrared (NIR)-mediated on-demand hyperthermia chemotherapy. The Au nanoturf possessed long-lasting doxorubicin (DOX) duration, which helps facilitate drug release in a sustained and prolonged manner. Moreover, the Au-coated nanoturf provides reproducible hyperthermia induced by localized surface plasmon resonances under NIR irradiation. Simultaneously, the NIR-mediated temperature increase can promote on-demand drug release at desired time points. For in vivo analysis, the Au nanoturf structure was applied on an esophageal stent, which needs sustained anticancer treatment to prevent tumor recurrence on the implanted surface. This thermo- and chemo-esophageal stent induced significant cancer cell death with released drug and hyperthermia. These phenomena were also confirmed by theoretical analysis. The proposed strategy provides a solution to achieve enhanced thermo-/chemotherapy and has broad applications in sustained cancer treatments.

Cellular behavior controlled by bio-inspired and geometry-tunable nanohairs.

A cicada wing has a biocidal feature of rupturing the membrane of cells, while the cactus spine can transmit a water drop to the stem of the plant. Both of these properties have evolved from their respective unique structures. Here, we endeavor to develop geometry-controllable nanohairs that mimic the cicada's wing-like vertical hairs and the cactus spine-like stooped hairs, and to quantitatively characterize the cell migration behavior of the hairy structures. It was found that the neuroblastoma cells are highly sensitive to the variation of surfaces: flat, vertical, and stooped nanohairs (100 nm diameter and 900 nm height). The cells on the vertical hairs showed significantly decreased proliferation. It was found that the behavior of cells cultured on stooped nanohairs is strongly influenced by the direction of the stooped pattern of hairs when we quantitatively measured the migration of cells on flat, vertical, and stooped structures. However, the cells on the flat structures showed random movement and the cells on the vertical nanohairs restricted the nanohair movement. Cells on the stooped structure showed higher forward migration preference compared to that of the other structures. Furthermore, we found that these cellular behaviors on the different patterns of nanohairs were affected by intracellular actin flament change. Consistent with these results, the vertical and stooped structures can facilitate the control of cell viability and guide directional migration for biomedical applications such as organogenesis.

Targeted calcium influx boosts cytotoxic T lymphocyte function in the tumour microenvironment.

Adoptive cell transfer utilizing tumour-targeting cytotoxic T lymphocytes (CTLs) is one of the most effective immunotherapies against haematological malignancies, but significant clinical success has not yet been achieved in solid tumours due in part to the strong immunosuppressive tumour microenvironment. Here, we show that suppression of CTL killing by CD4+CD25+Foxp3+ regulatory T cell (Treg) is in part mediated by TGFß-induced inhibition of inositol trisphosphate (IP3) production, leading to a decrease in T cell receptor (TCR)-dependent intracellular Ca2+ response. Highly selective optical control of Ca2+ signalling in adoptively transferred CTLs enhances T cell activation and IFN-γ production in vitro, leading to a significant reduction in tumour growth in mice. Altogether, our findings indicate that the targeted optogenetic stimulation of intracellular Ca2+ signal allows for the remote control of cytotoxic effector functions of adoptively transferred T cells with outstanding spatial resolution by boosting T cell immune responses at the tumour sites.

Dramatically Enhanced Mechanosensitivity and Signal-to-Noise Ratio of Nanoscale Crack-Based Sensors: Effect of Crack Depth.

The sensitivity of a nanoscale crack-based sensor is enhanced markedly by modulating the crack depth. The crack-depth-propagated sensor exhibits ≈16 000 gauge factor at 2% strain and a superior signal-to-noise ratio of ≈35, which facilitates detection of target signals for voice-pattern recognition.