Label-Free and Ultrasensitive Detection of Cartilage Acidic Protein 1 in Osteoarthritis Using a Single-Walled Carbon Nanotube Field-Effect Transistor Biosensor.

Osteoarthritis (OA), a prevalent degenerative joint disease, significantly affects the well-being of afflicted individuals and compromises the standard functionality of human joints. The emerging biomarker, Cartilage acidic protein 1 (CRTAC1), intricately associates with OA initiation and serves as a prognostic indicator for the trajectory toward joint replacement. However, existing diagnostic methods for CRTAC1 are hampered by the limited abundance, thus restricting the precision and specificity. Herein, a novel approach utilizing a single-walled carbon nanotube field-effect transistor (SWCNTs FET) biosensor is reported for the direct label-free detection of CRTAC1. High-purity semiconducting carbon nanotube films, functionalized with antibodies of CRTAC1, provide excellent electrical and sensing properties. The SWCNTs FET biosensor exhibits high sensitivity, notable reproducibility, and a wide linear detection range (1 fg/mL to 100 ng/mL) for CRTAC1 with a theoretical limit of detection (LOD) of 0.2 fg/mL. Moreover, the SWCNTs FET biosensor is capable of directly detecting human serum samples, showing excellent sensing performance in differentiating clinical samples from OA patients and healthy populations. Comparative analysis with traditional enzyme-linked immunosorbent assay (ELISA) reveals that the proposed biosensor demonstrates faster detection speeds, higher sensitivity/accuracy, and lower errors, indicating high potential for the early OA diagnosis. Furthermore, the SWCNTs FET biosensor has good scalability for the combined diagnosis and measurement of multiple disease markers, thereby significantly expanding the application of SWCNTs FETs in biosensing and clinical diagnostics.

Conditional normalizing flow for multivariate time series anomaly detection.

Multivariate time series data is becoming increasingly ubiquitous in various fields such as servers, industrial applications, and healthcare. However, detecting anomalies in such data is challenging due to its complex time-dependent, high-dimensional, and label scarcity. Aiming at this problem, this paper proposes an Attention Factorization Normalizing Flow (AFNF) algorithm for unsupervised multivariate time series anomaly detection. Our hypothesis is that anomalies are in a low-density region of the distribution. To transform the complex density of high-dimensional time series into a simple evaluable conditional density, we propose a time series factorization strategy and parameterize the conditional information generated by factorization in the time and attribute dimensions using an attention mechanism. Moreover, to compensate for the lack of temporal information due to the permutation invariance attention mechanism, a adjacency contrasting approach is proposed to model the local invariance of the time series. To provide long-term location information, a learnable global location encoding is introduced. Conditional normalizing flows are applied to evaluate the conditional probability of the observations. Finally, through extensive experiments on three real data sets, our method yielded the best results and its effectiveness in density estimation and anomaly detection is demonstrated.

Multi-Body Biomarker Entrapment System: An All-Encompassing Tool for Ultrasensitive Disease Diagnosis and Epidemic Screening.

Ultrasensitive identification of biomarkers in biofluids is essential for the precise diagnosis of diseases. For the gold standard approaches, polymerase chain reaction and enzyme-linked immunosorbent assay, cumbersome operational steps hinder their point-of-care applications. Here, a bionic biomarker entrapment system (BioES) is implemented, which employs a multi-body Y-shaped tetrahedral DNA probe immobilized on carbon nanotube transistors. Clinical identification of endometriosis is successfully realized by detecting an estrogen receptor, ERß, from the lesion tissue of endometriosis patients and establishing a standard diagnosis procedure. The multi-body Y-shaped BioES achieves a theoretical limit of detection (LoD) of 6.74 aM and a limit of quantification of 141 aM in a complex protein milieu. Furthermore, the BioES is optimized into a multi-site recognition module for enhanced binding efficiency, realizing the first identification of monkeypox virus antigen A35R and unamplified detection of circulating tumor DNA of breast cancer in serum. The rigid and compact probe framework with synergy effect enables the BioES to target A35R and DNA with a LoD down to 991 and 0.21 aM, respectively. Owing to its versatility for proteins and nucleic acids as well as ease of manipulation and ultra-sensitivity, the BioES can be leveraged as an all-encompassing tool for population-wide screening of epidemics and clinical disease diagnosis.

Universal Hydrogen-Treated TiO2 Nanorod Array/Ti2COX MXene PEC Aptamer Sensor Modulated by the Transport Characteristic of Photogenerated Holes.

A semiconductor photoelectrochemical (PEC) aptamer sensor has been widely researched in recent years because of its broad application prospects. However, a universal PEC sensor has not been achieved, and its sensing mechanism based on a photogenerated carrier transfer process has yet to be elucidated. Herein, a novel hydrogen-treated TiO2 nanorod array one-dimensional (1D)/Ti2COX MXene two-dimensional (2D) (H-TiO2/Ti2COX) PEC aptamer sensor is presented, which achieved a record detection range of 10-9-103 µg/L and a limit of detection (LOD) of 1 fg/L for microcystic toxins-LR detection. Besides, the PEC sensor can also test serotonin (5-HT), aflatoxin-B1, and prostate-specific antigen (PSA) with high performance by changing the aptamers, exhibiting favorable application universality. Furthermore, a new phenomenon of a switchable enhanced/suppressed photocurrent detection signal was discovered from H-TiO2/Ti2COX PEC aptamer sensors through the variation of the length of the TiO2 nanorod. Meanwhile, it reveals that the steric hindrance effect determines the photogenerated hole transfer and depolarization processes, which is proposed for the first time as the predominant mechanism of the switchable enhanced/suppressed photocurrent signal for PEC sensors, giving possibilities to develop PEC sensors with higher efficiency.

Stretchable Temperature-Responsive Multimodal Neuromorphic Electronic Skin with Spontaneous Synaptic Plasticity Recovery.

Multimodal electronic skin devices capable of detecting multimodal signals provide the possibility for health monitoring. Sensing and memory for temperature and deformation by human skin are of great significance for the perception and monitoring of physiological changes of the human body. Electronic skin is highly expected to have similar functions as human skin. Here, by implementing intrinsically stretchable neuromorphic transistors with mechanoreceptors and thermoreceptors in an array, we have realized stretchable temperature-responsive multimodal neuromorphic electronic skin (STRM-NES) with both sensory and memory functions, in which synaptic plasticity can be modulated by multiple modalities, in situ temperature variations, and stretching deformations. Temperature-responsive functions, spontaneous recovery, and temperature-dependent multitrial learning are proposed. Furthermore, a stretchable temperature neuromorphic array composed of multiple fully functional subcells is demonstrated to identify temperature distributions and variations at different regions and conditions after various strains of skin. The STRM-NES has temperature- and strain-responsive neuromorphic functions, excellent self-healing, and reusable capability, showing similar abilities as human skin to sense, transmit, memory, and recovery from external stimuli. It is expected to facilitate the development of wearable electronics, intelligent robotics, and prosthetic applications.

Tetrahedral DNA nanostructure based biosensor for high-performance detection of circulating tumor DNA using all-carbon nanotube transistor.

Adopting carbon nanotube (CNT) transistors as biosensors has been developed as a promising method for cancer biomarker detection, which has shown superior sensitivity and selectivity. However, the detection of circulating tumor DNA (ctDNA) by the CNT transistor based biosensors is still a challenge and no work has been reported. Here, direct label-free DNA detection of AKT2 gene related to triple-negative breast cancer by all-CNT thin-film transistor (TFT) biosensors incorporated with tetrahedral DNA nanostructures (TDNs) is proposed and achieved for the first time. The adoption of TDNs enables improved biosensor response for at least 35% and even as high as 98% as compared with single-stranded DNA (ssDNA) probes owing to the enhanced DNA hybridization efficiency. Influence of the TDNs' linker length on the biosensor performance is important and has been investigated. Concentration-dependent DNA detection is achieved by the all-CNT TFT biosensors with a broad linear detection range of six orders of magnitude and a theoretical limit of detection (LOD) of 2 fM. In addition, the all-CNT TFT biosensors exhibit favorable selectivity and repeatability. The platform of all-CNT TFT biosensors incorporated with TDNs has great potential for multiplexed detection of various cancer biomarkers, providing a simple yet high performance universal strategy for low-cost clinical applications.

Low-Power pH Sensor Based on Narrow Channel Open-Gated Al0.25Ga0.75N/GaN HEMT and Package Integrated Polydimethylsiloxane Microchannels.

pH sensors with low-power and strong anti-interference are extremely important for industrial online real-time detection. Herein, a narrow channel pH sensor based on Al0.25Ga0.75N/GaN high electron mobility transistor (HEMT) with package integrated Polydimethylsiloxane (PDMS) microchannels is proposed. The fabricated device has shown potential advantages in improving stability and reducing power consumption in response to pH changes of the solution. The performance of the pH sensor was demonstrated where the preliminary results showed an ultra-low power (<5.0 µW) at VDS = 1.0 V. Meanwhile, the sensitivity was 0.06 µA/V·pH in the range of pH = 2 to pH = 10, and the resolution of the sensor was 0.1 pH. The improvement in performance of the proposed sensor can be related to the narrow channel and microchannel, which can be attributed to better surface GaxOy in a microchannel with larger H+ and HO- concentration on the sensing surface during the detection process. The low-power sensor with excellent stability can be widely used in various unattended or harsh environments, and it is more conducive to integration and intelligence, which lays the foundation for online monitoring in vivo.

Direct label-free protein detection in high ionic strength solution and human plasma using dual-gate nanoribbon-based ion-sensitive field-effect transistor biosensor.

We report on direct label-free protein detection in high ionic strength solution and human plasma by a dual-gate nanoribbon-based ion-sensitive field-effect transistor (NR-ISFET) biosensor system with excellent sensitivity and specificity in both solution-gate (SG) and dual-gate (DG) modes. Compared with previously reported results, the NR-ISFET biosensor enables selective prostate specific antigen (PSA) detection based on antibody-antigen binding in broader detection range with lower LOD. For the first time, real-time specific detection of PSA of 10 pM to 1 µM in 100 mM phosphate buffer (PB) was demonstrated by conductance measurements using the polyethylene glycol (PEG)-modified NR-ISFET biosensors in DG mode with the back-gate bias (VBG) of 20 V. Due to larger maximum transconductance value resulting from the modulation of NR-ISFET channel by the back gate in DG mode, the detection range can be broadened with larger linear detection region (100 pM to 100 nM) and lower limit of detection (LOD, 10 pM) as compared to those in SG mode. Moreover, the influence of different back-gate bias from VBG = 5 V to VBG = 25 V on the biosensor performance has been investigated. Furthermore, direct PSA detection of 100 pM to 1 µM in human plasma was demonstrated by using the PEG-modified NR-ISFET in DG mode, enabling direct detection of protein in human blood for clinical applications since the LOD of 100 pM PSA can meet the clinical requirements.