Fully bioresorbable hybrid opto-electronic neural implant system for simultaneous electrophysiological recording and optogenetic stimulation.

Bioresorbable neural implants based on emerging classes of biodegradable materials offer a promising solution to the challenges of secondary surgeries for removal of implanted devices required for existing neural implants. In this study, we introduce a fully bioresorbable flexible hybrid opto-electronic system for simultaneous electrophysiological recording and optogenetic stimulation. The flexible and soft device, composed of biodegradable materials, has a direct optical and electrical interface with the curved cerebral cortex surface while exhibiting excellent biocompatibility. Optimized to minimize light transmission losses and photoelectric artifact interference, the device was chronically implanted in the brain of transgenic mice and performed to photo-stimulate the somatosensory area while recording local field potentials. Thus, the presented hybrid neural implant system, comprising biodegradable materials, promises to provide monitoring and therapy modalities for versatile applications in biomedicine.

Breathing sounds analysis system for early detection of airway problems in patients with a tracheostomy tube.

To prevent immediate mortality in patients with a tracheostomy tube, it is essential to ensure timely suctioning or replacement of the tube. Breathing sounds at the entrance of tracheostomy tubes were recorded with a microphone and analyzed using a spectrogram to detect airway problems. The sounds were classified into three categories based on the waveform of the spectrogram according to the obstacle status: normal breathing sounds (NS), vibrant breathing sounds (VS) caused by movable obstacles, and sharp breathing sounds (SS) caused by fixed obstacles. A total of 3950 breathing sounds from 23 patients were analyzed. Despite neither the patients nor the medical staff recognizing any airway problems, the number and percentage of NS, VS, and SS were 1449 (36.7%), 1313 (33.2%), and 1188 (30.1%), respectively. Artificial intelligence (AI) was utilized to automatically classify breathing sounds. MobileNet and Inception_v3 exhibited the highest sensitivity and specificity scores of 0.9441 and 0.9414, respectively. When classifying into three categories, ResNet_50 showed the highest accuracy of 0.9027, and AlexNet showed the highest accuracy of 0.9660 in abnormal sounds. Classifying breathing sounds into three categories is very useful in deciding whether to suction or change the tracheostomy tubes, and AI can accomplish this with high accuracy.

High-Temperature-Operable Electromechanical Computing Units Enabled by Aligned Carbon Nanotube Arrays.

Nano/micro-electromechanical (NEM/MEM) contact switches have great potential as energy-efficient and high-temperature-operable computing units to surmount those limitations of transistors. However, despite recent advances, the high-temperature operation of the mechanical switch is not fully stable nor repetitive due to the melting and softening of the contact material in the mechanical switch. Herein, MEM switches with carbon nanotube (CNT) arrays capable of operating at high temperatures are presented. In addition to the excellent thermal stability of CNT arrays, the absence of a melting point of CNTs allows the proposed switches to operate successfully at up to 550 °C, surpassing the maximum operating temperatures of state-of-the-art mechanical switches. The switches with CNTs also show a highly reliable contact lifetime of over 1 million cycles, even at a high temperature of 550 °C. Moreover, symmetrical pairs of normally open and normally closed MEM switches, whose interfaces are initially in contact and separated, respectively, are introduced. Consequently, the complementary inverters and logic gates operating at high temperatures can be easily configured such as NOT, NOR, and NAND gates. These switches and logic gates reveal the possibility for developing low-power, high-performance integrated circuits for high-temperature operations.

Mechanically resilient, alumina-reinforced carbon nanotube arrays for in-plane shock absorption in micromechanical devices.

Microelectromechanical systems (MEMS) are of considerable interest due to their compact size and low power consumption when used in modern electronics. MEMS devices intrinsically incorporate three-dimensional (3D) microstructures for their intended operations; however, these microstructures are easily broken by mechanical shocks accompanying high-magnitude transient acceleration, inducing device malfunction. Although various structural designs and materials have been proposed to overcome this limit, developing a shock absorber for easy integration into existing MEMS structures that effectively dissipates impact energy remains challenging. Here, a vertically aligned 3D nanocomposite based on ceramic-reinforced carbon nanotube (CNT) arrays is presented for in-plane shock-absorbing and energy dissipation around MEMS devices. This geometrically aligned composite consists of regionally-selective integrated CNT arrays and a subsequent atomically thick alumina layer coating, which serve as structural and reinforcing materials, respectively. The nanocomposite is integrated with the microstructure through a batch-fabrication process and remarkably improves the in-plane shock reliability of a designed movable structure over a wide acceleration range (0-12,000g). In addition, the enhanced shock reliability through the nanocomposite was experimentally verified through comparison with various control devices.

Eye-Mimicked Neural Network Composed of Photosensitive Neural Spheroids with Human Opsin Proteins.

An in vitro model, composed of the short-wavelength human opsins and rhodopsins, is created. Two types of photosensitive neural spheroids are transfected for selective reaction under bluish-purple and green lights. These are employed to two devices with intact neuron and neural-spheroid to study the interaction. By photostimulation, the photosensitive spheroid initiated photoactivation, and the signal generated from its body is transmitted to adjacent neural networks. Specifically, the signal traveled through the axon bundle in narrow gap from photosensitive spheroid to intact spheroid as an eye-to-brain model including optic nerve. The whole process with photosensitive spheroid is monitored by calcium ion detecting fluorescence images. The results of this study can be applied to examine vision restoration and novel photosensitive biological systems with spectral sensitivity.

Formation of sub-100-nm suspended nanowires with various materials using thermally adjusted electrospun nanofibers as templates.

The air suspension and location specification properties of nanowires are crucial factors for optimizing nanowires in electronic devices and suppressing undesirable interactions with substrates. Although various strategies have been proposed to fabricate suspended nanowires, placing a nanowire in desired microstructures without material constraints or high-temperature processes remains a challenge. In this study, suspended nanowires were formed using a thermally aggregated electrospun polymer as a template. An elaborately designed microstructure enables an electrospun fiber template to be formed at the desired location during thermal treatment. Moreover, the desired thickness of the nanowires is easily controlled with the electrospun fiber templates, resulting in the parallel formation of suspended nanowires that are less than 100 nm thick. Furthermore, this approach facilitates the formation of suspended nanowires with various materials. This is accomplished by evaporating various materials onto the electrospun fiber template and by removing the template. Palladium, copper, tungsten oxide (WO3), and tin oxide nanowires are formed as examples to demonstrate the advantage of this approach in terms of nanowire material selection. Hydrogen (H2) and nitrogen dioxide (NO2) gas sensors comprising palladium and tungsten oxide, respectively, are demonstrated as exemplary devices of the proposed method.

3D engineered tissue models for studying human-specific infectious viral diseases.

Viral infections cause damage to various organ systems by inducing organ-specific symptoms or systemic multi-organ damage. Depending on the infection route and virus type, infectious diseases are classified as respiratory, nervous, immune, digestive, or skin infections. Since these infectious diseases can widely spread in the community and their catastrophic effects are severe, identification of their causative agent and mechanisms underlying their pathogenesis is an urgent necessity. Although infection-associated mechanisms have been studied in two-dimensional (2D) cell culture models and animal models, they have shown limitations in organ-specific or human-associated pathogenesis, and the development of a human-organ-mimetic system is required. Recently, three-dimensional (3D) engineered tissue models, which can present human organ-like physiology in terms of the 3D structure, utilization of human-originated cells, recapitulation of physiological stimuli, and tight cell-cell interactions, were developed. Furthermore, recent studies have shown that these models can recapitulate infection-associated pathologies. In this review, we summarized the recent advances in 3D engineered tissue models that mimic organ-specific viral infections. First, we briefly described the limitations of the current 2D and animal models in recapitulating human-specific viral infection pathology. Next, we provided an overview of recently reported viral infection models, focusing particularly on organ-specific infection pathologies. Finally, a future perspective that must be pursued to reconstitute more human-specific infectious diseases is presented.

Dual-Scale Porous Composite for Tactile Sensor with High Sensitivity over an Ultrawide Sensing Range.

Porous structures have been utilized in tactile sensors to improve sensitivity owing to their excellent deformability. Recently, tactile sensors using porous structures have been used in practical applications, such as bio-signal monitoring. However, highly sensitive responses are limited to the low-pressure range, and their sensitivity significantly decreases in a higher-pressure range. Several approaches for developing tactile sensors with high sensitivity overing a wide pressure range have been proposed; however, achieving high sensitivity and wide sensing range remains a crucial challenge. This report presents a carbon nanotube (CNT)-coated CNT-polydimethylsiloxane (PDMS) composite having dual-scale pores for tactile sensors with high sensitivity over a wide pressure range. The porous polymer frame formed with dense pores of dual sizes facilitates the closure of large and small pores at low and high pressures, respectively. This results in an apparent increase in the number of contact points between the CNT-CNT at the pores even under a wide pressure range. Furthermore, the piezoresistivity of the CNT-PDMS composite contributes to achieving a high sensitivity of the tactile sensor over a wide pressure range. Based on these mechanisms, various human movements over a broad pressure spectrum are monitored to investigate the practical usefulness of the sensor.

Three-Dimensional Axotomy and Regeneration on Open-Access Microfluidic Platform.

An increasing number of patients are suffering from central nervous system (CNS) injury, including spinal cord injury. However, no suitable treatment is available for such patients as yet. Various platforms have been utilized to recapitulate CNS injuries. However, animal models and in vitro two-dimensional (2D)-based cell culture platforms have limitations, such as genetic heterogeneity and loss of the neural-circuit ultrastructure. To overcome these limitations, we developed a method for performing axotomy on an open-access three-dimensional (3D) neuron-culture platform. In this platform, the 3D alignment of axons in the brain tissue was recapitulated. For direct access to the cultured axons, the bottom of the 3D neuron-culture device was disassembled, enabling exposure of the neuron-laden Matrigel to the outside. The mechanical damage to the axons was recapitulated by puncturing the neuron-laden Matrigel using a pin. Thus, precise axotomy of three-dimensionally aligned axons could be performed. Furthermore, it was possible to fill the punctuated area by re-injecting Matrigel. Consequently, neurites regenerated into re-injected Matrigel. Moreover, it was confirmed that astrocytes can be co-cultured on this open-access platform without interfering with the axon alignment. The proposed open-access platform is expected to be useful for developing treatment techniques for CNS injuries.

Effect of carbon nanomaterial dimension on the functional activity and degeneration of neurons.

Despite growing concerns regarding the threat of airborne nanoparticle-mediated brain degeneration, the underlying pathological mechanisms remain unclear. Carbon nanomaterials, the main components of airborne nanoparticles, have multi-dimensional structures. Therefore, the dimensional effect of carbon-based nanomaterials on the regulation of neural function in brain disorders requires additional clarification. Herein, we report the interaction between zero-to three-dimensional carbon nanostructures and the amyloid-beta protein, which can either activate or interrupt neuronal functions, depending on the dimension of the carbon nanostructures. The carbon nanomaterials induced significant cellular activation by short-term exposure, while prolonged exposure eventually caused neuronal cell death. Such dimension-dependent activation or degeneration was more evident in the higher-dimension carbon nanomaterials, as confirmed by the increases in neurotransmitter secretion and synapse-related protein levels to more than five times at 72 h of monitoring and calcium signaling in the neurons. The inclusion of amyloid-beta proteins ameliorated the cytotoxic effects of carbon nanomaterials in higher-dimensional carbon nanomaterials by regulating 333 genes. We found that the ɑ-synuclein gene is the key factor in carbon-induced abnormal neuronal function. Therefore, through biological analyses and in vitro feasibility studies, this new insight may contribute toward understanding the pathological mechanism and finding a new target for therapy in human brain pathologies.

Highly Sensitive Flexible Tactile Sensors in Wide Sensing Range Enabled by Hierarchical Topography of Biaxially Strained and Capillary-Densified Carbon Nanotube Bundles.

Flexible tactile sensors with high sensitivity have received considerable attention for their use in wearable electronics, human-machine interfaces, and health-monitoring devices. Although various micro/nanostructured materials are introduced for high-performance tactile sensors, simultaneously obtaining high sensitivity and a wide sensing range remains challenging. Here, a resistive tactile sensor is presented based on the hierarchical topography of carbon nanotubes (CNTs) prepared by a low-cost and straightforward manufacturing process. The 3D hierarchical structure of the CNTs over large areas is formed by transferring vertically aligned CNT bundles to a prestrained elastomer substrate and subsequently densifying them through capillary forming, providing a monotonic increase in the contact area as applied pressure. The deformable and hierarchical structure of CNTs allows the sensor to exhibit a wide sensing range (0-100 kPa), high sensitivity (141.72 kPa-1 ), and low detection limit (10 Pa). Additionally, the capillary-formed CNT structure results in increased durability of the sensor over repeated pressures. Based on these advantages, meaningful applications of tactile sensors, such as object recognition gloves and multidirectional force perceptions, are successfully realized. Given the scalable fabrication method, 3D hierarchically structured CNTs provide an essential step toward next-generation wearable devices.

Engineered neural circuits for modeling brain physiology and neuropathology.

The neural circuits of the central nervous system are the regulatory pathways for feeling, motion control, learning, and memory, and their dysfunction is closely related to various neurodegenerative diseases. Despite the growing demand for the unraveling of the physiology and functional connectivity of the neural circuits, their fundamental investigation is hampered because of the inability to access the components of neural circuits and the complex microenvironment. As an alternative approach, in vitro human neural circuits show principles of in vivo human neuronal circuit function. They allow access to the cellular compartment and permit real-time monitoring of neural circuits. In this review, we summarize recent advances in reconstituted in vitro neural circuits using engineering techniques. To this end, we provide an overview of the fabrication techniques and methods for stimulation and measurement of in vitro neural circuits. Subsequently, representative examples of in vitro neural circuits are reviewed with a particular focus on the recapitulation of structures and functions observed in vivo, and we summarize their application in the study of various brain diseases. We believe that the in vitro neural circuits can help neuroscience and the neuropharmacology. STATEMENT OF SIGNIFICANCE: Despite the growing demand to unravel the physiology and functional connectivity of the neural circuits, the studies on the in vivo neural circuits are frequently limited due to the poor accessibility. Furthermore, single neuron-based analysis has an inherent limitation in that it does not reflect the full spectrum of the neural circuit physiology. As an alternative approach, in vitro engineered neural circuit models have arisen because they can recapitulate the structural and functional characteristics of in vivo neural circuits. These in vitro neural circuits allow the mimicking of dysregulation of the neural circuits, including neurodegenerative diseases and traumatic brain injury. Emerging in vitro engineered neural circuits will provide a better understanding of the (patho-)physiology of neural circuits.

Location-specific fabrication of suspended nanowires using electrospun fibers on designed microstructure.

While there have been remarkable improvements in the fabrication of suspended nanowires, placing a single nanowire at the desired location remains to be a challenging task. In this study, a simple method is proposed to fabricate suspended nanowires at desired locations using an electrospinning process and a designed microstructure. Using electrospun polymer fibers on the designed microstructure as a sacrificial template, various materials are deposited on it, and the electrospun fibers are selectively removed, leaving only nanowires of the deposited material. After the polymer fibers are removed, the remaining metal fibers agglomerate into a single nanowire. Throughout this process, including the removal of the polymer fibers, the samples are not exposed to high temperatures or chemicals, thereby allowing the formation of nanowires without oxidation or contamination. The diameter of the nanowire can be controlled in the electrospinning process, and a suspended Pd nanowire with a minimum diameter of 100 nm is fabricated. Additionally, a suspended single Pd nanowire-based H2gas sensor fabricated using the proposed process exhibits a highly sensitive response to H2gas.

Integration of Gold Nanoparticle-Carbon Nanotube Composite for Enhanced Contact Lifetime of Microelectromechanical Switches with Very Low Contact Resistance.

Electrical circuits require ideal switches with low power consumption for future electronic applications. However, transistors, the most developed electrical switches available currently, have certain fundamental limitations such as increased leakage current and limited subthreshold swing. To overcome these limitations, micromechanical switches have been extensively studied; however, it is challenging to develop micromechanical switches with high endurance and low contact resistance. This study demonstrates highly reliable microelectromechanical switches using nanocomposites. Nanocomposites consisting of gold nanoparticles (Au NPs) and carbon nanotubes (CNTs) are coated on contact electrodes as contact surfaces through a scalable and solution-based fabrication process. While deformable CNTs in the nanocomposite increase the effective contact area under mechanical loads, highly conductive Au NPs provide current paths with low contact resistance between CNTs. Given these advantages, the switches exhibit robust switching operations over 5 × 106 cycles under hot-switching conditions in air. The switches also show low contact resistance without subthreshold region, an extremely small leakage current, and a high on/off ratio.

Recent Progress in Flexible Tactile Sensors for Human-Interactive Systems: From Sensors to Advanced Applications.

Flexible tactile sensors capable of measuring mechanical stimuli via physical contact have attracted significant attention in the field of human-interactive systems. The utilization of tactile information can complement vision and/or sound interaction and provide new functionalities. Recent advancements in micro/nanotechnology, material science, and information technology have resulted in the development of high-performance tactile sensors that reach and even surpass the tactile sensing ability of human skin. Here, important advances in flexible tactile sensors over recent years are summarized, from sensor designs to system-level applications. This review focuses on the representative strategies based on design and material configurations for improving key performance parameters including sensitivity, detection range/linearity, response time/hysteresis, spatial resolution/crosstalk, multidirectional force detection, and insensitivity to other stimuli. System-level integration for practical applications beyond conceptual prototypes and promising applications, such as artificial electronic skin for robotics and prosthetics, wearable controllers for electronics, and bidirectional communication tools, are also discussed. Finally, perspectives on issues regarding further advances are provided.

Large-Area, Crosstalk-Free, Flexible Tactile Sensor Matrix Pixelated by Mesh Layers.

Tactile sensor arrays have attracted considerable attention for their use in diverse applications, such as advanced robotics and interactive human-machine interfaces. However, conventional tactile sensor arrays suffer from electrical crosstalk caused by current leakages between the tactile cells. The approaches that have been proposed thus far to overcome this issue require complex rectifier circuits or a serial fabrication process. This article reports a flexible tactile sensor array fabricated through a batch process using a mesh. A carbon nanotube-polydimethylsiloxane composite is used to form an array of sensing cells in the mesh through a simple "dip-coating" process and is cured into a concave shape. The contact area between the electrode and the composite changes significantly under pressure, resulting in an excellent sensitivity (5.61 kPa-1) over a wide range of pressure up to 600 kPa. The mesh separates the composite into the arranged sensing cells to prevent the electrical connection between adjacent cells and simultaneously connects each cell mechanically. Additionally, the sensor shows superior durability compared with previously reported tactile sensors because the mesh acts as a support beam. Furthermore, the tactile sensor array is successfully utilized as a Braille reader via information processing based on machine learning.

Fabrication of fine-pored polydimethylsiloxane using an isopropyl alcohol and water mixture for adjustable mechanical, optical, and thermal properties.

Porous polydimethylsiloxane (PDMS) has garnered interest owing to its large inner surface area, high deformability, and lightweight, while possessing inherent properties, such as transparency, flexibility, cost-effectiveness, ease of fabrication, chemical/mechanical stability, and biocompatibility. For producing porous PDMS, gas foaming, sacrificial template, and emulsion template techniques have been used extensively. However, the aforementioned methods have difficulty in achieving submicron-sized inner pores, which is advantageous for improving flexibility and transparency. This study demonstrates a simple fabrication method for obtaining porous PDMS with fine pores partially down to the sub-micron scale. This is possible by the use of cheap, volatile, and easily accessible isopropyl alcohol (IPA) as a co-solvent in water and pre-PDMS emulsion. IPA shows an affinity towards both water and prepolymer, resulting in an increased distribution of small water particles inside PDMS before curing. These water particles evaporate while curing the prepolymer emulsion, thereby generating fine pores. The fine size and number density of pores are controlled by water and the added amount of IPA, resulting in adjustable mechanical, optical, and thermal properties of porous PDMS.

Highly Sensitive Detection of Benzene, Toluene, and Xylene Based on CoPP-Functionalized TiO2 Nanoparticles with Low Power Consumption.

Among various metal oxides, titanium dioxide (TiO2) has received considerable interest as a gas-sensing material owing to its high reliability at high operating temperatures. Nonetheless, TiO2 generally has low sensitivity to target gases. In particular, TiO2-based sensors have difficulty in sensitively detecting benzene, toluene, and xylene (referred to as BTX). Moreover, the reported TiO2-based sensors have not simultaneously satisfied the demand for tens of ppb BTX detection and operation with low power consumption. This work proposes a BTX sensor using cobalt porphyrin (CoPP)-functionalized TiO2 nanoparticles as a sensing material on a suspended microheater fabricated by bulk micromachining for low power consumption. TiO2 nanoparticles show an enhanced sensitivity (245%) to 10 ppm toluene with CoPP functionalization. The proposed sensor exhibits high sensitivity to BTX at concentrations ranging from 10 ppm down to several ppb. The high reliability of the sensor is also explored through the long-time operation with repeated exposure to 10 ppm toluene for 14 h.

A Novel Conductive and Micropatterned PEG-Based Hydrogel Enabling the Topographical and Electrical Stimulation of Myoblasts.

In this study, we designed a cell-adhesive poly(ethylene glycol) (PEG)-based hydrogel that simultaneously provides topographical and electrical stimuli to C2C12 myoblasts. Specifically, PEG hydrogels with microgroove structures of 3 µm ridges and 3 µm grooves were prepared by micromolding; in situ polymerization of poly(3,4-ethylenedioxythiophene) (PEDOT) was then performed within the micropatterned PEG hydrogels to create a microgrooved conductive hydrogel (CH/P). The CH/P had clear replica patterns of the silicone mold and a conductivity of 2.49 × 10-3 S/cm, with greater than 85% water content. In addition, the CH exhibited Young's modulus (45.84 ± 7.12 kPa) similar to that of a muscle tissue. The surface of the CH/P was further modified via covalent bonding with cell-adhesive peptides to facilitate cell adhesion without affecting conductivity. An in vitro cell assay revealed that the CH/P was cytocompatible and enhanced the cell alignment and elongation of C2C12 myoblasts. The microgrooves and conductivity of the CH/P had the greatest positive effect on the myogenesis of C2C12 myoblasts compared to the other PEG hydrogel samples without conductivity or/and microgrooves, even in the absence of electrical stimulation. Electrical stimulation studies indicated that the combination of topographical and electrical cues maximized the differentiation of C2C12 myoblasts into myotubes, confirming the synergetic effect of incorporating microgroove surface features and a conductive PEDOT component into hydrogels.

Light-assisted recovery of reacted MoS2 for reversible NO2 sensing at room temperature.

Two-dimensional (2D) nanomaterials have been extensively explored as promising candidates for gas sensing due to their high surface-to-volume ratio. Among many 2D nanomaterials, molybdenum disulfide (MoS2) is known to be functional in detecting harmful gases at room temperature; therefore, it has been actively studied as a gas sensing material. However, there has been a limitation in recovering the original signal from reacted MoS2 after exposure to the target gas. This work demonstrates the recovery of the initial resistance of reacted chemical vapor deposition-grown MoS2 by illuminating it with a UV light-emitting diode (LED). A novel mechanism involving photo-generated electron-hole pairs in MoS2 is proposed and experimentally verified. The fabricated sensor detects nitrogen dioxide (NO2) and distinguishes between concentrations from 1 to 10 ppm with the proposed recovery process. Reversible detection after repeated exposure to 5 ppm NO2 over eight cycles is achieved through UV-LED illumination for a short time during the recovery process, while the identical sensor without UV illumination shows a transitional response at each cycle. To apply a low cost gas sensing solution at room temperature, visible light LEDs are also used to recover the resistance of the reacted MoS2.