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Abstract Terahertz technology has broad application prospects in biomedical detection. However, the mixed characteristics of actual samples make the terahertz spectrum complex and difficult to distinguish, and there is no practical terahertz detection method for clinical medicine. Here, we propose a three-step one-way terahertz model, presenting a detailed flow analysis of terahertz technology in the biomedical detection of renal fibrosis as an example: 1) biomarker determination: screening disease biomarkers and establishing the terahertz spectrum and concentration gradient; 2) mixture interference removal: clearing the interfering signals in the mixture for the biomarker in the animal model and evaluating and retaining the effective characteristic peaks; and 3) individual difference removal: excluding individual interference differences and confirming the final effective terahertz parameters in the human sample. The root mean square error of our model is three orders of magnitude lower than that of the gold standard, with profound implications for the rapid, accurate and early detection of diseases. 

An ultrasensitive and versatile assay for biomarkers has been developed using graphene/gold nanoparticles (AuNPs) composites and single-particle inductively-coupled plasma/mass spectrometry (spICP-MS). Thrombin was chosen as a model biomarker for this study. AuNPs modified with thrombin aptamers were first non-selectively adsorbed onto the surface of graphene oxide (GO) to form GO/AuNPs composites. In the presence of thrombin, the AuNPs desorbed from the GO/AuNPs composites due to a conformation change of the thrombin aptamer after binding with thrombin. The desorbed AuNPs were proportional to the concentration of thrombin and could be quantified by spICP-MS. By counting the individual AuNPs in the spICP-MS measurement, the concentration of thrombin could be determined. This assay achieved an ultralow detection limit of 4.5 fM with a broad linear range from 10 fM to 100 pM. The method also showed excellent selectivity and reproducibility when a complex protein matrix was evaluated. Furthermore, the diversity and ready availability of ssDNA ligands make this method a versatile new technique for ultrasensitive detection of a wide variety of biomarkers in clinical diagnostics. 

A sensitive label-free fluorescence assay for monitoring T4 polynucleotide kinase (T4 PNK) activity and inhibition was developed based on a coupled λ exonuclease cleavage reaction and SYBR Green I. In this assay, a double-stranded DNA (dsDNA) was stained with SYBR Green I and used as a substrate for T4 PNK. After the 5′-hydroxyl termini of the dsDNA was phosphorylated by the T4 PNK, the coupled λ exonuclease began to digest the dsDNA to form mononucletides and single-stranded DNA (ssDNA). At this moment, the fluorescence intensity of the SYBR Green I decreased because of less affinity with ssDNA than dsDNA. The decreasing extent was proportional to the concentration of the T4 PNK. After optimization of the detection conditions, including the concentration of ATP, amount of λ exonuclease and reaction time, the activity of T4 PNK was monitored by the fluorescence measurement, with the limit of detection of 0.11 U mL −1 and good linear correlation between 0.25–1.00 U mL −1 ( R 2 = 0.9896). In this assay, no label was needed for fluorescence detection. Moreover, the inhibition behaviors of the T4 PNK's inhibitors were evaluated by this assay. The result indicated the potential of using this assay for monitoring of the phosphorylation-related process.