The rapid advancement of precision medicine and the continuous emergence of novel pathogens have presented new challenges for biosensors, necessitating higher requirements. Target amplification technology serves as the core component in biosensor construction. Enzyme-based amplification methods are often sensitive and selective but involve relatively complex operational steps, whereas enzyme-free amplification methods offer simplicity but frequently fail to meet both sensitivity and selectivity simultaneously.
View Article and Find Full Text PDFTerahertz (THz) spectroscopy has impressive capability for label-free biosensing, but its utility in clinical laboratories is rarely reported due to often unsatisfactory detection performances. Here, we fabricated metal-graphene hybrid THz metasurfaces (MSs) for the sensitive and enzyme-free detection of circulating tumor DNA (ctDNA) in pancreatic cancer plasma samples. The feasibility and mechanism of the enhanced effects of a graphene bridge across the MS and amplified by gold nanoparticles (AuNPs) were investigated experimentally and theoretically.
View Article and Find Full Text PDFIntroduction: Diabetes and obesity are momentous risk factors threatening people's lives and health. Currently available incretin analogue glucagon-like peptide 1 (GLP-1) possesses huge hypoglycemic effect with the unsatisfactory effect of weight loss. Co-agonists targeting GLP-1R plus glucagon receptor (GCGR) or gastric inhibitory polypeptide receptor (GIPR) show synergistic benefits in glycaemic control and weight loss.
View Article and Find Full Text PDFStaphylococcus aureus (S. aureus) poses a serious threat to global public health, necessitating the establishment of rapid and simple tools for its accurate identification. Herein, we developed a terahertz (THz) metamaterial biosensor based on aptamer-functionalized FeO@Au nanocomposites for quantitative S.
View Article and Find Full Text PDFBackground: Highly sensitive and rapid detection of cell concentration and interfacial molecular events is of great value for biological, biomedical, and chemical research. Most traditional biosensors require large sample volumes and complicated functional modifications of the surface. It is of great significance to develop label-free biosensor platforms with minimal sample consumption for studying cell concentration changes and interfacial molecular events without labor-intensive procedures.
View Article and Find Full Text PDFThe sensitive and accurate detection of tumor cells is essential for successful cancer therapy and improving cancer survival rates. However, current tumor cell detection technologies have some limitations for clinical applications due to their complexity, low specificity, and high cost. Herein, we describe the design of a terahertz anti-resonance hollow core fiber (THz AR-HCF) biosensor that can be used for tumor cell detection.
View Article and Find Full Text PDFCirculating tumor DNA (ctDNA) is a noninvasive biomarker for liquid biopsy with important clinical and biological information, but existing detection techniques are expensive, complex and quite time-consuming. Here, we report an ultrarapid, sensitive and simple method, which we term Thermus thermophilus argonaute-coupling exponential amplification reaction (TtAgo-CEAR), that selectively amplifies mutated ctDNA. Aiming at seven Kirsten rat sarcoma-2 virus (KRAS) point mutations, the present strategy allows for easy detection with attomolar sensitivity and single-nucleotide specificity within as little as 16 min without prior PCR amplification.
View Article and Find Full Text PDFRecent advances in prokaryotic Argonaute proteins (pAgos) as potential genome-editing tools have provided new insights into the development of pAgos-based nucleic acid detection platforms. However, pAgos-based isothermal detection remains challenging. Here, we report a true isothermal amplification strategy, termed Argonaute-based thermostable exponential amplification reaction (AgoEAR), to detect RNA with ultrasensitivity and single-nucleotide resolution at a constant temperature of 66 °C.
View Article and Find Full Text PDFGraphene is a two-dimensional material with unique physical and chemical properties, whose excellent biocompatibility has also attracted widespread attention in the field of biosensing and medical detection. Graphene provides a novel solution for dramatically improving the sensitivity of terahertz metasurface sensors, since the electrical conductivity can be modified by contact with biomolecules. In this paper, a metal-graphene hybrid metasurface is proposed and demonstrated for high-sensitive nortriptyline sensing based on the plasmon-induced transparency (PIT) resonances.
View Article and Find Full Text PDFThe high sensitivity and specificity of terahertz (THz) biosensing are both promising and challenging in DNA sample detection. This study produced and refined a flexible THz MM biosensor for ultrasensitive detection of HBV in clinical serum samples based on a gold magnetic nanoparticle-mediated rolling circle amplification (GMNPs@RCA) sandwich assay under isothermal conditions. Typically, solid-phase RCA reactions mediated by circular padlock probes (PLPs) are triggered under isothermal conditions in the presence of HBV DNA, resulting in long single-stranded DNA (ssDNA) with high fidelity and specificity.
View Article and Find Full Text PDFLogistic regression (LR) is a supervised multiple linear regression model, which uses linear weighted calculation for input to obtain weight coefficients of model. The surface enhanced Raman spectroscopy (SERS) technology greatly enhances the Raman signal of analyte. LR model was used to analyze the data of seven types of pancreatic cancer-related miRNAs obtained from commercial SERS substrate.
View Article and Find Full Text PDFThe demand for rapid and accurate identification of microorganisms is growing due to considerable importance in all areas related to public health and safety. Here, we demonstrate a rapid and label-free strategy for the identification of microorganisms by integrating terahertz-attenuated total reflection (THz-ATR) spectroscopy with an automated recognition method based on multi-classifier voting. Our results show that 13 standard microbial strains can be classified into three different groups of microorganisms (Gram-positive bacteria, Gram-negative bacteria, and fungi) by THz-ATR spectroscopy.
View Article and Find Full Text PDFSensitive and specific detection of microRNAs (miRNAs) is of critical significance for early diagnosis of cancers such as pancreatic cancer with atypical initial symptoms and high mortality. Despite exponential amplification reaction (EXPAR) is an attractive isothermal amplification method for detecting miRNAs, it faces the problems of the dependence difference and low specificity. To address such challenges, herein, a nicking-assisted entropy-driven DNA circuit triggered exponential amplification reaction (NAED-EXPAR) was firstly employed for ultrasensitive and specific detection of miRNA in "one-pot" manner at constant temperature.
View Article and Find Full Text PDFProinflammatory cytokines play a causal role in the development of hyperinsulinemia and T2MD. FOXO1, a transcription factor which is known to enhance proinflammation, was recently shown to be involved in obesity-induced cell dysfunction. However, molecular mechanisms for the association remained elusive.
View Article and Find Full Text PDFGastric cancer (GC) is the fifth most common cancer in the world and a serious threat to human health. Due to its high morbidity and mortality, a simple, rapid and accurate early screening method for GC is urgently needed. In this study, the potential of Raman spectroscopy combined with different machine learning methods was explored to distinguish serum samples from GC patients and healthy controls.
View Article and Find Full Text PDFWe study the interaction between one aptamer and its analyte (the MnSOD protein) by the combination of surface-enhanced Raman scattering and multivariate statistical analysis. We observe the aptamer structure and its evolution during the interaction under different experimental conditions (in air or in buffer). Through the spectral treatment by principal component analysis of a large set of SERS data, we were able to probe the aptamer conformations and orientations relative to the surface assuming that the in-plane nucleoside modes are selectively enhanced.
View Article and Find Full Text PDFExosomal microRNA (miRNA) is a promising non-invasive biomarker for liquid biopsies. Herein, we fabricated a terahertz (THz) metamaterial biosensor that comprises an array of gold (Au) discs surrounded by annular grooves for exosomal miRNA assays based on duplex-specific nuclease (DSN)-triggered rolling circle amplification (RCA). In this strategy, the target miRNA is captured by a probe P0 immobilized on magnetic beads (MBs); it then repeatedly releases a primer P1 under the action of DSN, which acts as a highly specific initiator of the subsequent RCA step utilizing biotin-dUTP.
View Article and Find Full Text PDFMetamaterial-inspired terahertz (THz) biosensors are devoted to developing high-sensitivity and label-free biosensing strategies. However, most meaningful molecular signals are obscured by the strong THz absorption of solvent water. Most reported THz biosensors require the tested samples to be tediously dried or replaced with a low-absorption medium, which impairs the original bioactivity and the distribution homogeneity of targets.
View Article and Find Full Text PDFObjective: Macrophage migration inhibitory factor (MIF) is an inflammatory and neurorendocrine mediator that counterregulates glucocorticoid immunosuppression. MIF polymorphisms, which comprise a variant promoter microsatellite (-794 CATT ), are linked genetically to autoimmune disease severity and to glucocorticoid resistance. While invasive stimuli increase MIF expression, MIF also is up-regulated by glucocorticoids, which serve as a physiologic regulator of inflammatory responses.
View Article and Find Full Text PDFTerahertz (THz) spectroscopy, with fascinating advantages for biomedical applications, is still in its infancy in terms of the selective detection of aqueous biomolecules because the strong absorption of solvent water always obscures the THz spectroscopic features of biomolecules. Nevertheless, solvent water is not a passive spectator but a useful indicator, as this proposed strategy describes. This strategy utilizes THz attenuated total reflection (THz-ATR) spectroscopy to probe the glucose-induced hydration state changes of smart hydrogels for label-free and selective detection of aqueous glucose.
View Article and Find Full Text PDFMolecular machines constructed by three-dimensional (3-D) DNA walker have emerged as a hot topic in applications such as novel biosensors, cargo delivery platforms and intracellular imaging. Herein, we first propose a lame DNA walker that can randomly and autonomously move on microsphere-based 3-D track. The stochastic lame walker has a long leg mainly responsible for persistent movement and a short leg cutting substrates rapidly.
View Article and Find Full Text PDFTerahertz (THz) spectroscopy has drawn great interest for the functional and conformational investigations of nucleic acids, but its intrinsic sensitivity hinders potential bio-sensing applications. Here, a novel THz biosensor was developed for detecting microRNA (miRNA) samples based on metamaterials coupled with nanoparticles and strand displacement amplification (SDA). In this method, the SDA reaction amplifies the target miRNA and generates copious yields of secondary DNA molecules (Trigger DNA), which are subsequently conjugated to metallic nanoparticles that form nanoparticle-Trigger DNA complexes.
View Article and Find Full Text PDFMiRNA-150, a gene regulator that has been revealed to be abnormal expression in non-small cell lung cancer (NSCLC), can be regarded as a serum indicator for diagnosis and monitoring of NSCLC. Herein, a new sort of nanoprobe, termed allosteric spherical nanoprobe, was first developed to sense miRNA-150. Compared with conventional hairpin, this new nanoprobe possesses more enrichment capacity and reaction cross section.
View Article and Find Full Text PDFIn this study, we fabricated a high-sensitivity "signal-off" electrochemical aptasensing platform for quantifying circulating tumor cells (CTCs) based on target-triggered signal readout of methylene blue (MB). Au nanoparticles (AuNPs) were introduced to enlarge the specific surface area of the gold electrode (GE), which would immobilize homogeneous and more MB-aptamers. MB-modified and stem-loop-like aptamers were assigned as a recognition element with K562 cells.
View Article and Find Full Text PDFCancer, especially malignant tumors with poor prognosis, has become a major hazard to human life and health. The tumor microenvironment is gaining increasing attention from researchers, as it offers a new focus for tumor diagnosis, therapy, and prognosis. The numbers of immune and stromal cells, which are major components of the tumor microenvironment, could be determined from RNA-seq data with the Estimation of STromal and Immune cells in Malignant Tumors using Expression data (ESTIMATE) algorithm.
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