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We demonstrate that microporous PVDF membranes sandwiched between multiple layers of nanomaterials can be used for continuous monitoring of glucose level in vivo . This is achieved by coating needle electrodes with Polyaniline nanofiber, Platinum nanoparticles, glucose oxidase enzyme and porous layers, successfully fabricated with layer-by-layer deposition. Nanoparticles incorporated into conductive Polyaniline nanofibers resulted in high surface to volume ratio and electrocatalytic activity for glucose enzyme. A composite coating membrane of porous PVDF and nano-sphere Nafion limited the glucose transportation and increased the lifetime of in vivo measurements. The glucose biosensor exhibited a sub-microamperometric output current, fast response time of less than 30 s and a sensitivity of 0.23 μA/mM. The linear sensing range in terms of glucose concentration was from 0 to 20 mM. Implantable experiments using mice models showed excellent response to the variation of blood glucose concentration while maintaining biocompatibility with the surrounding tissues. The sensitivity was shown to remain within 10% close to initial sensitivity within the 7 days of continuous monitoring, and maintain at 70% of the initial sensitivity within 21 days. [ABSTRACT FROM AUTHOR]

Direct serological detection, due to its clinical facility and testing economy, affords prominent clinical values to the early detection of cancer. Surface-enhanced Raman spectroscopy (SERS)-based sensors have shown great promise in realizing this form of detection. Detecting liver cancer early with such a form, especially in terms of monitoring the pathogenic progression from hepatic inflammations to cancer, is the most effective clinical path to reducing the mortality rate. However, the methodology investigation for this purpose remains a formidable challenge. We fabricated a SERS-based sensor, consisting of Au-Ag nanocomplex-decorated ZnO nanopillars on paper. The sensor has an analytic enhancement factor of 1.02 × 107, which is enough to sense the biomolecular information of liver diseases through direct serum SERS analysis. A convolutional neural network (CNN) classifier for recognizing serum SERS spectra was constructed by deep learning. Integrating this sensor with the CNN, we established an intelligent biosensing method and realized direct serological detection of liver diseases within 1 min. As a proof-of-concept, the method achieved a prediction accuracy of 97.78% on an independent test dataset randomly sampled from 30 normal controls, 30 hepatocellular carcinoma (HCC) cases, and 30 hepatitis B (HB) patients. The results suggest this method can be developed for detecting liver diseases clinically and is worthy of exploration as a means of liver cancer surveillance. The presented sensor holds potential for clinical translation to the direct serological detection of diseases. • A SERS-based sensor comprised Au-Ag nanocomplex-decorated ZnO nanopillars on paper was fabricated. • An intelligent biosensing method for multiple liver diseases was presented by integrating the sensor and a CNN classifier. • A direct serological detection of liver diseases was developed for the first time. [ABSTRACT FROM AUTHOR]

Nitric oxide plays important transmission and regulation roles in the human body, but its in-vitro concentration is extremely low with a short half-life. In this work, we developed a three-dimensional 'flow-through' configuration based on polysulfone hollow fiber (PHF) for efficient detection of cell released NO. The PHF served as the substrate for cell culture as well as the base layer of the working electrode. The carbon nanotubes-gold nanoparticles (CNT-AuNPs) composites uniformly wrapped around the PHF as the sensing layer. The CNT provided a large specific surface area, which allowed uniform distribution and high loading of AuNPs, thus enhancing the electrocatalytic activity synergistically. Compared with the conventional flow-by configuration, such configuration resulted in a higher surface area per unit volume and enhanced NO molecule capture efficiency. The CNT-AuNPs PHF sensor showed a low detection limit (91 nM), high stability, selectivity, and biocompatibility. We utilized it for real-time in-situ detection of NO released by human lung cancer cell H1299 under drug stimulation. Furthermore, owing to the unique PHF structure, we performed long-term monitoring of NO release under the treatment of Lipopolysaccharide, Nitroglycerin and Aminoguanidine, which helps to understand the kinetic process of cellular drug response. • A hollow fiber structure was fabricated and integrated with sensing materials. • The flow-through configuration was developed to effectively detect cell released NO. • Long-term NO monitoring has been conducted for more than 30 h. [ABSTRACT FROM AUTHOR]

Modified metal–organic frameworks (MOFs) doping with enzymes exhibit high enzyme stability and catalytic performance, which is a research hotspot in the field of enzyme-based sensing. Although the MOF-enzyme constitutes a 3D structure in the nanoscale, the macroscopic assembly configuration still stays in 1D or 2D structures, limiting sensing applications towards complex biological targets. Herein, the MOF-enzyme hybrid nanosystem was assembled into 3D porous conductive supports via a controllable physical embedding method, displaying high enzymatic loading, stability and cascade catalytic performance. The modified MOFs combing with enzymes served as a sensing reaction system, and the conductive hollow fiber membranes (HFMs) served as a functional platform. The multifunctional device integrates pumpless hydrodynamic transport, interconnected conductive polymer, and blood separation modules, showing fast capillary fluid flow, trace sampling (3 μL), high selectivity and accuracy. The linear sensing range was in 2–24 mM glucose, 0.05–6 mM lactic acid, and 0.1–10 mM cholesterol, respectively, with sensitivities of 24.2, 150, 73.6 nA mM−1. Furthermore, this strategy of modular assembly of biosensing array can easily implement multiplex metabolites detection simultaneously. [Display omitted] • The MOFs-enzyme served as a 3D cascade catalytic nanosystem, and the conductive HFMs served as a 3D functional platform. • The MOFs-enzyme hybrid nanosystem on conductive HFMs displays 9 times higher enzymatic loading than that of free enzyme. • The 3D multifunctional device integrates hydrodynamic transport, conductive polymer, and blood separation modules. • This strategy of modular assembly of biosensing array can easily implement multiplex metabolites detection simultaneously. [ABSTRACT FROM AUTHOR]

It is essential to develop portable, versatile, and reliable diagnostic devices in point-of-care testing (POCT). The detection of biomarkers requires selective separation and large specific surface for high sensitivity and accuracy at trace levels in whole blood samples using POCT devices. Herein, a kind of 3D electrochemical biosensors were designed via in-situ synthesizing polyaniline (PANI) and platinum nanoparticles (Pt NPs) on polysulfone hollow fiber membrane (HFM) scaffolds with gradient porous structure. The gradient porous HFMs scaffolds provide uniform capillary flow, self-driven blood separation and sufficient enzyme immobilization sites. Simultaneously, the in-situ deposited materials fulfill interconnected conductive networks, thus ensuring accurate and rapid detection of the sensors without hindering capillary progress. These sensors display ultralow sampling (~3 μL), fast fluid flow (>1 μL/ms), wide linear range (glucose: 0–24 mM, R2=0.992; cholesterol: 0–9 mM, R2=0.999), high sensitivity and accuracy especially under different hematocrits in POCT applications towards glucose and cholesterol. The innovative integration of POCT biosensors with interconnected conductive nanoparticles, selective blood separation and gradient porous structures can find wide application in resource-limited regions, large population screening, and public health emergencies. Image 1 • A 3D biosensor platform based on gradient HFMs was developed to integrate interconnected conductive nanomaterials, selective blood separation, and gradient porous structure for electrochemical biosensor application. • Unique structures and optimal pore size of HFMs provide hybrid hydrodynamic modes including capillary force in a lumen and fluid diffusion in ordered pores, facilitating fast capillary fluid flow and uniform fluid diffusion. • The porous structures and in-situ deposited conductive polymers ensure the integration of separation and detection, leading to high sensitivity, high accuracy, and trace sampling volume in POCT. [ABSTRACT FROM AUTHOR]

Cancer cells alter their metabolism to promote rapid proliferation, resulting in significant amounts of glucose to be used for aerobic glycolysis in the tumor microenvironment. Due to the spatial mismatch between electrodes and cells, existing methods for evaluating cancer cell metabolism lack kinetic and microenvironmental information. In this paper, we present a hollow fiber structure loaded with sensing elements as a long-term cellular metabolism monitoring platform. The unique gradient porous structure allowed the glucose sensor to be close to cultured cells but not directly in contact to prevent adverse effects. The liquid exchange channels in the porous fiber structure ensured continuous and real-time monitoring of glucose concentration changes in the culture media. Experimental results showed high electrochemical sensitivity and stability for continuously monitoring the glucose consumption rate. Furthermore, a continuous three-day long test quantified the change in glucose consumption in response to the anticancer drug Osimertinib. In addition to traditional endpoint cell counting and analysis, this hollow fiber sensing structure provided a real-time monitoring tool for cell metabolism. Such continuous monitoring of the cell metabolism microenvironment improves in-vitro toxicology models for personalized medicine and cancer therapy. • Cell culture and enzyme immobilization were performed on the porous hollow fiber for in-situ cell metabolism monitoring. • Gradient porous sensor can monitor cell microenvironment, reduce H 2 O 2 cytotoxicity, and improve enzyme stability. • Continuous glucose monitoring provides more cellular metabolic dynamics than conventional endpoint analysis. [ABSTRACT FROM AUTHOR]

In this study, we developed a convenient way to construct a flexible enzymatic electrode with excellent stability and electrochemical performance for implanted glucose monitoring. The electrode was constructed through the co-immobilization of the glucose oxidase micro-particles (GOD MPs) and multi-wall carbon nanotubes (CNT) on the inner surface of a gradient-structured hollow fiber membrane (GHM), where CNT improved the electron transport efficiency and GHM controlled the transfer of substances and interferences. GOD MPs showed higher stability under various operation conditions than the free enzymes due to the MnCO 3 template method, which enabled the biosensor to remain relative sensitivity at >86% over 9 days. The GOD MPs biosensor also showed high selectivity, reproducibility, and linear sensing range from 0 mM to 24 mM (R2 = 0.9993) with a current sensitivity of 25 nA/mM. The combination of porous-structured membrane and the flexible CNT meshes ensures the electrical connections and sensing accuracy of the biosensor under the deformation status. In-vivo experiments showed reliable current responses to variations in blood glucose concentrations that were consistent with tail blood test results. This co-immobilization of enzyme micro-particles in the 3D porous structure method developed a bio-composite platform technology towards the applications in flexible sensing and implantable medical devices. • The MnCO 3 template method extended the stability of glucose oxidase micro-particles (GOD MPs). • The gradient hollow fiber membrane (GHM) balanced the interaction of substances and prevented the leakage of enzymes. • The gradient hollow fiber membrane provided an optimal balance between oxygen and glucose and prevented the leakage of enzymes. • High selectivity, flexibility, linearity between 0–24 mM and reliable in-vivo test results were achieved. [ABSTRACT FROM AUTHOR]