A microelectrode electrochemical sensing platform based on heteroatoms doped carbon nanotubes arrays with peroxidase-like activity for in-situ detection in live cell.

In this work, we developed a new strategy to fabricate a series of transition metallic nanoparticles (NPs) embedded on B, N co-doped carbon nanotubes (CNTs) arrays modified flexible carbon fiber electrodes (M@BNCNTs/CF, M = Co, Fe, Ni) via facile inkjet printing assisted with chemical vapor deposition using Ionic liquid as solvent of printing ink and heteroatom dopants. Furthermore, Pt NPs via impregnation-thermal reduction process was anchored on the surface of Co@BNCNTs/CF (Pt-Co@BNCNTs/CF), which holds enhanced peroxidase-like activity and could be directly used as freestanding electrode to detect H2O2, exhibiting a low detection limit of 0.19 µM with wide linear range (0.5 µM-9.4 mM), and high sensitivity (1679 µA cm-2 mM-1). The excellent sensing performance of Pt-Co@BNCNTs/CF is attributed to the Pt, Co NPs anchored on CNTs with great catalytic activity, and the doping B, N would cause graphitic carbon with more defects to improve its inherent reactivity toward H2O2. Besides, CNTs arrays with high surface area also enlarge the exposure of active sites. Moreover, the Pt-Co@NBCNTs/CF microelectrode has been successfully applied in monitoring H2O2 secreted from human colonic cancer cells and normal colonic epithelial cells, which could offer crucial data for distinguishing various cell types and identifying cancer cells from normal cells. This work opens a new horizon to fabricate flexible miniaturized sensing device for extracellular analysis and offers an extended strategy to fabricate other metallic NPs embedded in heteroatoms doped CNTs functionalized flexible fiber electrode, by choosing diverse metal ions and ILs as inkjet printing precursors.

Application and development of nanomaterials in the diagnosis and treatment of esophageal cancer.

Esophageal cancer is a malignant tumor with a high incidence worldwide. Currently, there are a lack of effective early diagnosis and treatment methods for esophageal cancer. However, delivery systems based on nanoparticles (NPs) have shown ideal efficacy in real-time imaging and chemotherapy, radiotherapy, gene therapy, and phototherapy for tumors, which has led to their recent widespread design as novel treatment strategies. Compared to traditional drugs, nanomedicine has unique advantages, including strong targeting ability, high bioavailability, and minimal side effects. This article provides an overview of the application of NPs in the diagnosis and treatment of esophageal cancer and provides a reference for future research.

Epigenome editing based on CRISPR/dCas9p300 facilitates transdifferentiation of human fibroblasts into Leydig-like cells.

Recently, Leydig cell (LCs) transplantation has a promising potential to treat male hypogonadism. However, the scarcity of seed cells is the actual barrier impeding the application of LCs transplantation. Utilizing the cutting-edge CRISPR/dCas9VP64 technology, human foreskin fibroblasts (HFFs) were transdifferentiated into Leydig-like cells（iLCs） in previous study, but the efficiency of transdifferentiation is not very satisfactory. Therefore, this study was conducted to further optimize the CRISPR/dCas9 system for obtaining sufficient iLCs. First, the stable CYP11A1-Promoter-GFP-HFFs cell line was established by infecting HFFs with CYP11A1-Promoter-GFP lentiviral vectors, and then co-infected with dCas9p300 and the combination of sgRNAs targeted to NR5A1, GATA4 and DMRT1. Next, this study adopted quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blot, and immunofluorescence to determine the efficiency of transdifferentiation, the generation of testosterone, the expression levels of steroidogenic biomarkers. Moreover, we utilized chromatin immuno-precipitation (ChIP) followed by quantitative polymerase chain reaction (ChIP-qPCR) to measure the levels of acetylation of targeted H3K27. The results revealed that advanced dCas9p300 facilitated generation of iLCs. Moreover, the dCas9p300-mediated iLCs significantly expressed the steroidogenic biomarkers and produced more testosterone with or without LH treatment than the dCas9VP64-mediated. Additionally, preferred enrichment in H3K27ac at the promoters was detected only with dCas9p300 treatment. The data provided here imply that the improved version of dCas9 can aid in the harvesting of iLCs, and will provide sufficient seed cells for cell transplantation treatment of androgen deficiency in the future.

Flexible electrochemical sensors integrated with nanomaterials for in situ determination of small molecules in biological samples: A review.

Flexible biosensors have aroused research enthusiasm due to their potential for in situ quantification of chemical constituents in the human body, which perform a vital function in health monitoring and disease diagnosis. Especially, flexible electrochemical biosensors based on different advanced nanomaterials combine the merits of electrochemical analysis with unique structural/chemical properties of flexible electrode materials, and have exhibited excellent performance for in situ biomarkers detection toward different biological samples. These flexible electrochemical sensors can be integrated into implantable/wearable devices, which demonstrate great promise in invasive/noninvasive in-situ analysis. Consequently, the development of flexible electrochemical biosensors is of great significance for both scientific research and clinical application. In this review, we focus on the state-of-the-art progress in flexible electrochemical biosensors integrated with a wide spectrum of nanomaterials, which are aimed at in situ sensitive detection of small molecule metabolites in different biological specimens including live cells, tissues, body fluids (e.g., human blood, cerebrospinal fluid (CSF), and interstitial fluid (ISF)), and exudate secretion liquors (e.g., human saliva, tear, sweat, and urine). From the perspectives of flexible electrochemical biosensors toward different biological samples, we discuss their innovations in nanomaterials with diverse structures. We also introduce the research status of integrated flexible implantable and wearable electrochemical sensing devices with various types and functionalities for practical application. Furthermore, we share our opinions on the recent progress of flexible electrochemical sensors based on nanomaterials and look forward to applying flexible electrochemical sensors in medical diagnosis and healthcare.

Integrated electrochemical microfluidic sensor with hierarchically porous nanoarrays modified graphene fiber microelectrode for bioassay.

The development of high-efficient biosensing systems for rapid and sensitive detection of disease-related biomarkers in human samples is of great significance for disease diagnosis and treatment in clinical practice. In this work, we develop an integrated electrochemical microfluidic sensing platform based on freestanding graphene fiber (GF) microelectrode for bioassay. In order to improve the electrocatalytic activity of GF microelectrode, it has been modified by unique 3D well-ordered hierarchically porous nickel-cobalt phosphide (NiCoP) nanosheet arrays (NSAs). Benefiting from the excellent electrochemical properties and structural merits, the resultant NiCoP-NSAs modified GF microelectrode shows excellent sensing performances towards neurotransmitter dopamine (DA), with a high sensitivity of 5.56 µA cm-2 µM-1, a low detection limit of 14 nM, as well as good selectivity, reproducibility and stability. Furthermore, in virtue of the miniaturized size and good mechanical properties, the nanohybrid GF microelectrode can be embedded into a home-made microfluidic chip to construct an integrated electrochemical microfluidic sensing device, which has been used for sensitive analysis of DA in minimal volume of human serum and urine samples, and in situ tracking DA released from neuroblastoma cells SHSY-5Y under the stimulation for physio-pathological and pharmacological study of nervous system-related diseases.

3D nitrogen-doped carbon nanofoam arrays embedded with PdCu alloy nanoparticles: Assembling on flexible microelectrode for electrochemical detection in cancer cells.

In this work, we developed a novel and facile strategy for the synthesis of a highly active and stable electrocatalyst based on PdCu alloy nanoparticles (PdCu-ANPs) embedded in 3D nitrogen-doped carbon (NC) nanofoam arrays (NFAs), which were assembled on flexible carbon fiber (CF) microelectrode for in situ sensitive electrochemical detection of biomarker H2O2 in cancer cells. Our results showed that NC-NFAs support possessed a unique hierarchically porous architecture by integrating the macrospores in arrays scaffold within mesopores in individual NC nanofoam, which offered exceptionally large surface area for embedding high-density PdCu-ANPs in it as well as facilitated the mass transfer and molecular diffusion during the electrochemical reaction. Taking the advantages of the unique structural merit of NC-NFAs support and excellent electrocatalyitc properties of PdCu-ANPs that embedded in it, the resultant PdCu-ANPs/NC-NFAs modified CF microelectrode exhibited good electrochemical sensing performances towards H2O2 including a wide linear range from 2.0 µM to 3.44 mM, a low detection limit of 500 nM, as well as good reproducibility, stability and anti-interference ability. When used in real-time in situ tracking H2O2 secreted from different types of human colorectal cancer cells, i.e., HCT116, HT29, SW48 and LoVo, it can distinguish the types of cancer cells by measuring the number of extracellular H2O2 molecules released per cell, which demonstrates its great promise in cancer diagnose and management.

Hierarchical Core-Shell Structure of 2D VS2@VC@N-Doped Carbon Sheets Decorated by Ultrafine Pd Nanoparticles: Assembled in a 3D Rosette-like Array on Carbon Fiber Microelectrode for Electrochemical Sensing.

The development of two-dimensional (2D) nanohybrid materials with heterogeneous components in nanoscale and three-dimensional (3D) well-ordered assembly in microscale has been regarded as an effective way to improve their overall performances by the synergistic coupling of the optimized structure and composition. In this work, we reported the design and synthesis of a new type of hierarchically core-shell structure of 2D VS2@VC@N-doped carbon (NC) sheets decorated by ultrafine Pd nanoparticles (PdNPs), which were vertically grown on carbon fiber (CF) and assembled into a unique 3D rosette-like array. The resultant VS2@VC@NC-PdNPs modified CF microelectrode integrated the structural and electrochemical properties of the heterogeneous hybridization of core-shell VS2@VC@NC-PdNPs sheets with a unique rosette-like array structure, and gave rise to a significant improvement in terms of electron transfer ability, electrocatalytic activity, stability, and biocompatibility. Under the optimized conditions, the VS2@VC@NC-PdNPs modified CF microelectrode demonstrated excellent electrochemical sensing performance towards biomarker hydrogen peroxide (H2O2) including a high sensitivity of 152.7 µA cm-2 mM-1, a low detection limit of 50 nM (a signal-to-noise ratio of 3:1), as well as good reproducibility and anti-interference ability, which could be used for the real-time in situ electrochemical detection of H2O2 in live cancer cells and cancer tissue. The remarkable performances of the proposed nanohybrid microelectrode will have a profound impact on the design of diverse 2D layered materials as a promising candidate for electrochemical biosensing applications.

Coral-like hierarchical structured carbon nanoscaffold with improved sensitivity for biomolecular detection in cancer tissue.

The development of flexible microelectrodes with large surface area and high activity has currently attracted enormous research interest for its promising use in in vitro and in vivo monitoring various physiological behaviors. Inspired by the unique morphological and structural features of dendritic coral, a coral-like hierarchical nanohybrid of carbon nanospheres (GNSs) wrapped hollow carbon tubes (HCT) has been designed and modified on flexible activated carbon fiber (ACF) microelectrode for sensitive electrochemical detection of biomarker in live cells and cancer tissue. The hierarchical nanohybrid microelectrode was fabricated by a novel dual-template strategy using ZnO nanorod arrays as the hard template and poly-glucose microspheres as both self-template and carbon source, which results in the formation of coral-like structured carbon nanoscaffold integrated with GNSs wrapped HCT hybrids (HCT@GNSs) on ACF substrate for homogeneous interfacial contacts and reaction. The as-obtained HCT@GNSs modified ACF (HCT@GNSs/ACF) microelectrode exhibits high specific surface area and good stability, and serves as an ideal support for anchoring functional nanomaterials. In order to improve the electrochemical activity of the modified microelectrode, HCT@GNSs has been decorated with dense and ultrafine Pt nanoparticles (PtNPs). Benefiting from the hierarchical feature of HCT@GNSs and uniformly distribution of electroactive PtNPs, the PtNPs decorated HCT@GNSs/ACF microelectrode demonstrates good electrochemical sensing performance toward H2O2, which enable the operating electrochemical platform be used for real-time tracking H2O2 generated from different types of live cells and in situ sensitive detection of H2O2 in cancer tissue from laboratory mice.

3D nanoporous gold scaffold supported on graphene paper: Freestanding and flexible electrode with high loading of ultrafine PtCo alloy nanoparticles for electrochemical glucose sensing.

Recent advances in on-body wearable medical apparatus and implantable devices drive the development of light-weight and bendable electrochemical sensors, which require the design of high-performance flexible electrode system. In this work, we reported a new type of freestanding and flexible electrode based on graphene paper (GP) supported 3D monolithic nanoporous gold (NPG) scaffold (NPG/GP), which was further modified by a layer of highly dense, well dispersed and ultrafine binary PtCo alloy nanoparticles via a facile and effective ultrasonic electrodeposition method. Our results demonstrated that benefited from the synergistic effect of the electrocatalytically active PtCo alloy nanoparticles, the large-active-area and highly conductive 3D NPG scaffold, and the mechanically strong and stable GP electrode substrate, the resultant PtCo alloy nanoparticles modified NPG/GP (PtCo/NPG/GP) exhibited high mechanical strength and good electrochemical sensing performances toward nonenzymatic detection of glucose, including a wide linear range from 35 µM- to 30 mM, a low detection limit of 5 µM (S/N = 3) and a high sensitivity of 7.84 µA cm(-2) mM(-1) as well as good selectivity, long-term stability and reproducibility. The practical application of the proposed PtCo/NPG/GP has also been demonstrated in in vitro detection of blood glucose in real clinic samples.