Artificial intelligence-based real-time histopathology of gastric cancer using confocal laser endomicroscopy.

There has been a persistent demand for an innovative modality in real-time histologic imaging, distinct from the conventional frozen section technique. We developed an artificial intelligence-driven real-time evaluation model for gastric cancer tissue using confocal laser endomicroscopic system. The remarkable performance of the model suggests its potential utilization as a standalone modality for instantaneous histologic assessment and as a complementary tool for pathologists' interpretation.

Real-time Histological Evaluation of Gastric Cancer Tissue by Using a Confocal Laser Endomicroscopic System.

BACKGROUND/AIM: The need for instant histological evaluation of fresh tissue, especially in cancer treatment, remains paramount. The conventional frozen section technique has inherent limitations, prompting the exploration of alternative methods. A recently developed confocal laser endomicroscopic system provides real-time imaging of the tissue without the need for glass slide preparation. Herein, we evaluated its applicability in the histologic evaluation of gastric cancer tissues. MATERIALS AND METHODS: A confocal laser endomicroscopic system (CLES) with a Lissajous pattern laser scanning, was developed. Fourteen fresh gastric cancer tissues and the same number of normal gastric tissues were obtained from advanced gastric cancer patients. Fluorescein sodium was used for staining. Five pathologists interpreted 100 endomicroscopic images and decided their histologic location and the presence of cancer. Following the review of matched hematoxylin and eosin (H&E) slides, their performance was evaluated with another 100 images. RESULTS: CLES images mirrored gastric tissue histology. Pathologists were able to detect the histologic location of the images with 65.7% accuracy and differentiate cancer tissue from normal with 74.7% accuracy. The sensitivity and specificity of cancer detection were 71.9% and 76.1%. Following the review of matched H&E images, the accuracy of identifying the histologic location was increased to 92.8% (p<0.0001), and that of detecting cancer tissue was also increased to 90.9% (p<0.001). The sensitivity and specificity of cancer detection were enhanced to 89.1% and 93.2% (p<0.0001). CONCLUSION: High-quality histological images were immediately acquired by the CLES. The operator training enabled the accurate detection of cancer and histologic location raising its potential applicability as a real-time tissue imaging modality.

A Wireless and Wearable Body-Pressure-Monitoring System for the Prevention of Pressure-Induced Skin Injuries.

This article presents a wireless and wearable body-pressure-monitoring system for the on-site, real-time prevention of pressure injuries for immobilized patients. For the prevention of pressure-induced skin injuries, a wearable pressure sensor system is designed to monitor the pressure at multiple sites on the skin and to alert the danger of prolonged application of pressure on the skin with a pressure-time integral (PTI) algorithm. The wearable sensor unit is developed using a pressure sensor based on a liquid metal microchannel and integrated with a flexible printed circuit board that includes a thermistor-type temperature sensor. The wearable sensor unit array is connected to the readout system board for the transmission of measured signals to a mobile device or PC via Bluetooth communication. We evaluate the pressure-sensing performances of the sensor unit and the feasibility of the wireless and wearable body-pressure-monitoring system through an indoor test and a preliminary clinical test at the hospital. It is shown that the presented pressure sensor has high-quality performance with excellent sensitivity to detect both high and low pressure. The proposed system measures the pressure at bony sites on the skin for about six hours continuously without any disconnection or failure, and the PTI-based alarming system operates successfully in the clinical setup. The system measures the pressure applied to the patient and provides meaningful information from the measured data for early diagnosis and prevention of bedsores to doctors, nurses, and healthcare workers.

Handheld laser scanning microscope catheter for real-time and in vivo confocal microscopy using a high definition high frame rate Lissajous MEMS mirror.

A handheld confocal microscope using a rapid MEMS scanning mirror facilitates real-time optical biopsy for simple cancer diagnosis. Here we report a handheld confocal microscope catheter using high definition and high frame rate (HDHF) Lissajous scanning MEMS mirror. The broad resonant frequency region of the fast axis on the MEMS mirror with a low Q-factor facilitates the flexible selection of scanning frequencies. HDHF Lissajous scanning was achieved by selecting the scanning frequencies with high greatest common divisor (GCD) and high total lobe number. The MEMS mirror was fully packaged into a handheld configuration, which was coupled to a home-built confocal imaging system. The confocal microscope catheter allows fluorescence imaging of in vivo and ex vivo mouse tissues with 30 Hz frame rate and 95.4% fill factor at 256 × 256 pixels image, where the lateral resolution is 4.35 µm and the field-of-view (FOV) is 330 µm × 330 µm. This compact confocal microscope can provide diverse handheld microscopic applications for real-time, on-demand, and in vivo optical biopsy.

Customizable, conformal, and stretchable 3D electronics via predistorted pattern generation and thermoforming.

Recently, three-dimensional electronics (3DE) is attracting huge interest owing to the increasing demands for seamless integration of electronic systems on 3D curvilinear surfaces. However, it is still challenging to fabricate 3DE with high customizability, conformability, and stretchability. Here, we present a fabrication method of 3DE based on predistorted pattern generation and thermoforming. Through this method, custom-designed 3DE is fabricated through the thermoforming process. The fabricated 3DE has high 3D conformability because the thermoforming process enables the complete replication of both the overall shape and the surface texture of the 3D mold. Furthermore, the usage of thermoplastic elastomer and a liquid metal­based conductive electrode allows for high thermoformability during the device fabrication as well as high stretchability during the device operation. We believe that this technology can enable a wide range of new functionalities and multiscale 3D morphologies in wearable electronics.

Battery-free, wireless soft sensors for continuous multi-site measurements of pressure and temperature from patients at risk for pressure injuries.

Capabilities for continuous monitoring of pressures and temperatures at critical skin interfaces can help to guide care strategies that minimize the potential for pressure injuries in hospitalized patients or in individuals confined to the bed. This paper introduces a soft, skin-mountable class of sensor system for this purpose. The design includes a pressure-responsive element based on membrane deflection and a battery-free, wireless mode of operation capable of multi-site measurements at strategic locations across the body. Such devices yield continuous, simultaneous readings of pressure and temperature in a sequential readout scheme from a pair of primary antennas mounted under the bedding and connected to a wireless reader and a multiplexer located at the bedside. Experimental evaluation of the sensor and the complete system includes benchtop measurements and numerical simulations of the key features. Clinical trials involving two hemiplegic patients and a tetraplegic patient demonstrate the feasibility, functionality and long-term stability of this technology in operating hospital settings.

Ultra-Wide Range Pressure Sensor Based on a Microstructured Conductive Nanocomposite for Wearable Workout Monitoring.

Conventional flexible pressure sensors are not suitable for high-pressure applications due to their low saturation pressure. In this study, an ultra-wide range pressure sensor is designed based on the optimized microstructure of the polyimide/carbon nanotubes (PI/CNT) nanocomposite film. The sensing range of the pressure sensor is expanded by adopting polyimide (PI) with a high elastic modulus as a matrix material and its sensitivity is improved through functional sensing film with tip-flattened microdome arrays. As a result, the pressure sensor can measure a wide pressure range (≈ 0-3000 kPa) and possesses the sensitivity of ≈ 5.66 × 10-3 -0.23 × 10-3 kPa-1 with high reliability and durability up to 1000 cycles. The proposed sensor is integrated into the hand and foot pressure monitoring systems for workout monitoring. The representative values of the pressure distribution in the hands and feet during the powerlifting are acquired and analyzed through Pearson's correlation coefficient (PCC). The analyzed results suggest that the pressure sensor can provide useful real-time information for healthcare and sports performance monitoring.

Microdome-Induced Strain Localization for Biaxial Strain Decoupling toward Stretchable and Wearable Human Motion Detection.

Soft strain sensors have attracted significant attention in wearable human motion monitoring applications. However, there is still a huge challenge for decoupled measurement of multidirectional strains. In this study, we have developed a biaxial and stretchable strain sensor based on a carbon nanotube (CNT) film and a microdome array (MA)-patterned elastomeric substrate. The MA structures lead to generating localized and directional microcracks of CNT films within the intended regions under tensile strain. This mechanism allows a single sensing layer to act as a strain sensor capable of decoupling the biaxial strains into axial and transverse terms. The ratio of resistance change between two perpendicular axes is about 960% under an x-directional strain of 30%, demonstrating the biaxial decoupling capability. Also, the proposed strain sensor shows high stretchability and excellent long-term reliability under a cyclic loading test. Finally, wearable devices integrated with the strain sensor have been successfully utilized to monitor various human motions of the wrist, elbow, knee, and fingers by measuring joint bending and skin elongation.

Microporous Elastomer Filter Coated with Metal Organic Frameworks for Improved Selectivity and Stability of Metal Oxide Gas Sensors.

Despite various advantages and usefulness of semiconductor metal oxide gas sensors, low selectivity and humidity interference have limited their practical applications. In order to resolve these issues, we propose a new concept of a selective gas filtering structure that increases the gas selectivity and decreases the moisture interference of metal oxide gas sensors by coating metal organic frameworks (MOFs) on a microporous elastomer scaffold. Cu(BTC) with an excellent selective adsorption capacity for carbon monoxide (CO) compared to hydrogen (H2) and MIL-160 with an excellent moisture adsorption capacity were uniformly coated on the microporous polydimethylsiloxane (PDMS) structure through a squeeze coating method, resulting in a high content of MOFs with a large effective surface area. A Cu(BTC)-coated microporous PDMS filter showed an excellent adsorption efficiency (62.4%) for CO, thereby dramatically improving the selectivity of H2/CO by up to 2.6 times. In addition, an MIL-160 coated microporous PDMS filter showed a high moisture adsorption efficiency (76.2%).

Ultrathin, Biocompatible, and Flexible Pressure Sensor with a Wide Pressure Range and Its Biomedical Application.

In this research, an ultrathin, biocompatible, and flexible pressure sensor with a wide pressure range has been developed and applied in biomedical applications. The pressure sensing mechanism is based on the variation of contact resistance between an electrode and a three-dimensional microstructured polyimide/carbon nanotube composite film. The sensor has a thickness of about 31.3 µm, a maximum sensitivity of 41.0 MPa-1, and a sensing range of 10-500 kPa. Moreover, in situ temperature measurement by an integrated resistive temperature detector enables data correction for varying temperature conditions. In order to show the advantages of the fabricated sensor, it is attached to the human body and integrated with the surface of a radiofrequency ablation (RFA) needle with small radius of curvature. In the experiments, the proposed pressure sensor measured subtle pressure levels (pulse pressure) and high pressure levels (fingertip pressure) without losing conformal contact with the skin. In addition, when the pressure-sensor-integrated RFA needle was inserted into a bovine liver, successful detection of steam popping phenomenon was observed.

Synergetic Effect of Porous Elastomer and Percolation of Carbon Nanotube Filler toward High Performance Capacitive Pressure Sensors.

Wearable pressure sensors have been attracting great attention for a variety of practical applications, including electronic skin, smart textiles, and healthcare devices. However, it is still challenging to realize wearable pressure sensors with sufficient sensitivity and low hysteresis under small mechanical stimuli. Herein, we introduce simple, cost-effective, and sensitive capacitive pressure sensor based on porous Ecoflex-multiwalled carbon nanotube composite (PEMC) structures, which leads to enhancing the sensitivity (6.42 and 1.72 kPa-1 in a range of 0-2 and 2-10 kPa, respectively) due to a synergetic effect of the porous elastomer and percolation of carbon nanotube fillers. The PEMC structure shows excellent mechanical deformability and compliance for an effective integration with practical wearable devices. Also, the PEMC-based pressure sensor shows not only the long-term stability, low-hysteresis, and fast response under dynamic loading but also the high robustness against temperature and humidity changes. Finally, we demonstrate a prosthetic robot finger integrated with a PEMC-based pressure sensor and an actuator as well as a healthcare wristband capable of continuously monitoring blood pressure and heart rate.

Highly Sensitive and Wearable Liquid Metal-Based Pressure Sensor for Health Monitoring Applications: Integration of a 3D-Printed Microbump Array with the Microchannel.

Wearable pressure sensors capable of sensitive, precise, and continuous measurement of physiological and physical signals have great potential for the monitoring of health status and the early diagnosis of diseases. This work introduces a 3D-printed rigid microbump-integrated liquid metal-based soft pressure sensor (3D-BLiPS) for wearable and health-monitoring applications. Using a 3D-printed master mold based on multimaterial fused deposition modeling, the fabrication of a liquid metal microchannel and the integration of a rigid microbump array above the microchannel are achieved in a one-step, direct process. The microbump array enhances the sensitivity of the pressure sensor (0.158 kPa-1 ) by locally concentrating the deformation of the microchannel with negligible hysteresis and a stable signal response under cyclic loading. The 3D-BLiPS also demonstrates excellent robustness to 10 000 cycles of multidirectional stretching/bending, changes in temperature, and immersion in water. Finally, these characteristics are suitable for a wide range of applications in health monitoring systems, including a wristband for the continuous monitoring of the epidermal pulse rate for cuffless blood pressure estimation and a wireless wearable device for the monitoring of body pressure using a multiple pressure sensor array for the prevention of pressure ulcers.

Wearable, Ultrawide-Range, and Bending-Insensitive Pressure Sensor Based on Carbon Nanotube Network-Coated Porous Elastomer Sponges for Human Interface and Healthcare Devices.

Flexible and wearable pressure sensors have attracted a tremendous amount of attention due to their wider applications in human interfaces and healthcare monitoring. However, achieving accurate pressure detection and stability against external stimuli (in particular, bending deformation) over a wide range of pressures from tactile to body weight levels is a great challenge. Here, we introduce an ultrawide-range, bending-insensitive, and flexible pressure sensor based on a carbon nanotube (CNT) network-coated thin porous elastomer sponge for use in human interface devices. The integration of the CNT networks into three-dimensional microporous elastomers provides high deformability and a large change in contact between the conductive CNT networks due to the presence of micropores, thereby improving the sensitivity compared with that obtained using CNT-embedded solid elastomers. As electrical pathways are continuously generated up to high compressive strain (∼80%), the pressure sensor shows an ultrawide pressure sensing range (10 Pa to 1.2 MPa) while maintaining favorable sensitivity (0.01-0.02 kPa-1) and linearity ( R2 ∼ 0.98). Also, the pressure sensor exhibits excellent electromechanical stability and insensitivity to bending-induced deformations. Finally, we demonstrate that the pressure sensor can be applied in a flexible piano pad as an entertainment human interface device and a flexible foot insole as a wearable healthcare and gait monitoring device.

High-Sensitivity and Low-Power Flexible Schottky Hydrogen Sensor Based on Silicon Nanomembrane.

High-performance and low-power flexible Schottky diode-based hydrogen sensor was developed. The sensor was fabricated by releasing Si nanomembrane (SiNM) and transferring onto a plastic substrate. After the transfer, palladium (Pd) and aluminum (Al) were selectively deposited as a sensing material and an electrode, respectively. The top-down fabrication process of flexible Pd/SiNM diode H2 sensor is facile compared to other existing bottom-up fabricated flexible gas sensors while showing excellent H2 sensitivity (Δ I/ I0 > 700-0.5% H2 concentrations) and fast response time (τ10-90 = 22 s) at room temperature. In addition, selectivity, humidity, and mechanical tests verify that the sensor has excellent reliability and robustness under various environments. The operating power consumption of the sensor is only in the nanowatt range, which indicates its potential applications in low-power portable and wearable electronics.

Biopsy Needle Integrated with Electrical Impedance Sensing Microelectrode Array towards Real-time Needle Guidance and Tissue Discrimination.

A biopsy needle with electrical impedance sensor array based on stainless steel microelectrodes (EIS needle) was developed for real-time four electrode measurement and multi-spot sensing of tissues during the biopsy process. The sensor performance was characterized by using saline solutions with various concentrations, which proved accurate, stable and reliable electrical impedance measurement. The capability of impedance-based tissue sensing was verified by the conductivity measurement of agarose hydrogel based phantom mimicking cancer tissue. Furthermore, multi-spot impedance sensing during needle insertion was demonstrated using porcine meat with muscle and fat layers, which exhibited a clear discrimination between different types of tissues. Also, the electrical impedance difference between normal and fatty livers of mouse model was measured by the EIS needle. We could successfully demonstrate that the EIS needle can provide localized and accurate characterization of biological tissues at the needle tip.

Nucleophilic fluorination of triflates by tetrabutylammonium bifluoride.

Careful examination of nucleophilicity, basicity, and leaving group ability led us to discover the nucleophilic fluorination of triflates by weakly basic tetrabutylammonium bifluoride, which provides excellent yields with minimal formation of elimination-derived side products. Primary hydroxyl groups as well as secondary hydroxyl groups in acyclic chains or in five-membered rings are excellent substrates, whereas benzylic and aldol-type secondary hydroxyl groups give poor yields as a result of the instability of their triflates.