Dual-mode immunosensor based on Cu-doped Mo2C nanosheets as signal labels.

A method for detecting of Carcinoembryonic antigen(CEA) with improved accuracy is urgently needed. In this work, a dual-mode immunosensor for accurate detection of CEA was fabricated, which used a Cu-doped Mo2C co-catalyst as an enhancer. Especially, Cu-doped Mo2C presents a strong different pulse voltammetry (DPV) signal for the electron transfer between Cu2+ and Cu+, without the addition of K3[Fe(CN6)] and other electron transfer mediators, but also shows high electrocatalytic activity towards H2O2 redox reactions. So that detection sensitivity of the chronoamperometry (CA) was enhanced. Furthermore, characterized by excellent conductivity, highly ordered pore distribution and great surface area, Ti3C2 Mxenes can be effective in promoting electron transfer and loading a large number of AuNPs. In the meantime, AuNPs can also immobilize CEA-Ab1 through Au-N bonds. Based on a Cu-Mo2C-Au dual-signal indicator, Ti3C2 Mxene-Au as the matrix, the immunsosensor was developed to achieve dual-signal detection of CEA. Satisfactory detection ranges (1 fg.mL-1 to 40 ng.mL-1) were obtained with limits of detection of 0.33 fg.ml-1 (DPV) and 1.67 fg.ml-1 (CA), respectively. Therefore, the prepared electrochemical immunosensor has good application prospects for the detection of CEA.

Fabrication of a novel electrochemical immunosensor for the sensitive detection of carcinoembryonic antigen using a double signal attenuation strategy.

Carcinoembryonic antigen (CEA), an acidic protein, is a characteristic antigen produced by the tumor of various cancers (eg, breast, cervical, rectal, lung, etc.). Therefore, the detection of cancer antigens is very important for the early diagnosis and treatment of cancer. In this study, a novel of "signal off" strategy for electrochemical immunosensor was developed to detect CEA. To this end, Prussian blue nanoparticles (PB NPs), an electroactive substance, were used as the immunological platform. In addition, CuO2@SiO2 nanocomposites, which release Cu2+ and H2O2 under acidic conditions, were synthesized. The generated Cu2+ can replace the high spin iron (FeIII) in PB NPs, which in turn reduces the oxidation peak current of PB NPs. Due to the peroxidase-like nature of PB NPs, they can react with self-generated H2O2 to generate hydroxyl radicals (·OH), which can further convert 4-chloro-1 naphthol (4-CN) into a non-conductive polymer that accumulates on the electrode surface, this leads to a further reduction in the electrical signal of the PB NPs. Moreover, the self-generated Cu2+ and H2O2 can reduce the introduction of exogenous substances and improve the detection accuracy. Square wave voltammetry (SWV) revealed that the electrical signal of PB NPs gradually decreased with increasing CEA concentration. In addition, the electrical signal of PB NPs exhibited a good linearity in the range from 0.01 pg mL-1 to 80 ng mL-1, where in the logarithm of CEA concentration and the detection limit was as low as 0.0032 pg mL-1.

An electrochemical immunosensor for the detection of carcinoembryonic antigen based on Au/g-C3N4 NSs-modified electrode and CuCo/CNC as signal tag.

Carcinoembryonic antigen levels in the human body reflect the conditions associated with a variety of tumors and can be used for the identification, development, monitoring, and prognosis of lung cancer, colorectal cancer, and breast cancer. In this study, an amperometric immunosensor with CuCo/carbon nanocubes (CuCo/CNC) as the signal label is constructed. The bimetal-doped carbon skeleton structure has a high specific surface area and exhibits good electrocatalytic activity. In addition, Au/g-C3N4 nanosheets (Au/g-C3N4 NSs) are used to modify the substrate platform, facilitating the loading of more capture antibodies. The reaction mechanism was explored through electrochemical methods, X-ray powder diffraction, X-ray photoelectron spectroscopy, and other methods. Kinetic studies have shown that CuCo/CNC have good peroxidase-like activity. In addition, the electrocatalytic reduction ability of CuCo/CNC on hydrogen peroxide can be monitored using amperometric i-t curve (- 0.2 V, vs. SCE), and the response current value is positively correlated with the CEA antigen concentration. The prepared electrochemical immunosensor has good selectivity, precision, and stability. The dynamic range of the sensor was 0.0001-80 ng/mL, and the detection limit was 0.031 pg/mL. In addition, the recovery and relative standard deviation in real serum samples were 97.7-103 % and 3.25-4.13 %, respectively. The results show that the sensor has good analytical capabilities and can provide a new method for the clinical monitoring of CEA.

Ti3C2 MXene anchors CuAu-LDH multifunctional two-dimensional nanomaterials for dual-mode detection of CEA in electrochemical immunosensors.

Electrochemical immunoassays are commonly used to detect biomarkers and Ti3C2 MXene anchored CuAu-LDH two-dimensional hydroxide heterojunctions for dual-mode electrochemical immunosensors were fabricated in this work. Layered double hydroxides have a large surface area, high chemical stability, tunable metal composition and interchangeable anions, however, the insulating nature of LDH further limits its catalytic performance. For this reason, Ti3C2 Mxenes were introduced to improve this problem. 2D layers of Ti3C2 Mxenes with large specific surface area and excellent conductivity have been well proven and widely used. And the surface of Ti3C2 Mxenes (due to the presence of abundant surface functional groups), will facilitate the anchoring of metal ions and the nucleation of LDH. In addition, its excellent electrical conductivity will facilitate the electron transfer between Cu2+ and Cu+. The immunosensor not only showed a heavy square wave voltammetry (SWV) signal. It also exhibited high electrocatalytic activity for H2O2 redox reactions and improves the sensitivity of the Ampere Current (i-t) detection. The CEA immunosensor developed in this study showed a wide linear response (0.0001-80 ng/mL) and the lowest detection limits (SWV: 33.6 fg/mL and i-t: 45.4 fg/mL S/N = 3). The results confirmed the excellent analytical capability of the immunosensor.

The application of the inexpensive and synthetically simple electrocatalyst CuFe-MoC@NG in immunosensors.

In this study, we used inexpensive and synthetically simple electrocatalysts as replacements for conventional precious metal materials to reduce hydrogen peroxide (H2O2). We for the first time developed N-doped graphene-coated CuFe@MoC using one-step calcination of binary Prussian blue analogues (PBAs) with Mo6+ cationic grafting precursors. The synergistic interaction of CuFe PBA and MoC increased the catalytically active sites for H2O2 reduction. The catalyst was optimized in terms of the ratio of CuFe PBA to Mo6+, PVP content, and calcination temperature to improve its catalytic activity. When it was used to construct an electrochemical immunosensor for carcinoembryonic antigen (CEA) detection, polydopamine (CuFe-MoC@NG@PDA) was coated on its outer surface to increase the antibody loading and MoS2-Au NPs were used as substrates to improve Ab1 immobilization and accelerate electron transfer at the electrode interface, thereby improving the response signal of the immunosensor. Its concentration was linearly related to the response signal from 10 fg mL-1 to 80 ng mL-1, and the lowest limit of detection was 3 fg mL-1. In addition, the immunosensor has acceptable selectivity and high stability. All data indicate that nanocomposites have electrocatalytic applications.

Enzyme-free sandwich-type electrochemical immunosensor for CEA detection based on the cooperation of an Ag/g-C3N4-modified electrode and Au@SiO2/Cu2O with core-shell structure.

Effective signal amplification is a prerequisite for electrochemical immunosensors to achieve ultra-sensitive detection. In this work, we prepared a sandwich-type electrochemical immunosensor for the quantitative detection of carcinoembryonic antigen (CEA). As a base platform, Ag NPs modified aminated two-dimensional nitrogen carbide nanosheets (Ag/g-C3N4) have good biocompatibility and conductivity. In addition, with the layered structure of Au@SiO2/Cu2O as the signal label, the response current value of H2O2 was monitored by the Amperometric i-t Curve (i-t), so as to realize the accurate measurement of CEA. The presence of SiO2 nanoframes not only reduces the agglomeration of Au NPs and Cu2O but also provides good biocompatibility to facilitate the connection of secondary antibodies. Finally, we also verified the signal amplification mechanism of the immunosensor through XPS and other means, and calculated the kinetic parameters of the signal tag, which proved the good peroxidase-like activity of Au@SiO2/Cu2O. Under the best test conditions, the prepared immunosensor has a detection range from 0.01 pg/mL to 80 ng/mL, and the detection limit is as low as 0.0038 pg/mL. The results show that the immunosensor has good analytical performance and it can provide a new method for the clinical diagnosis of CEA.

The electrochemical immunosensor of the "signal on" strategy that activates MMoO4 (M = Co, Ni) peroxidase with Cu2+ to achieve ultrasensitive detection of CEA.

A new type of ultrasensitive electrochemical immunosensor with "signal on" strategy was designed for quantitative detection of CEA. The sensing strategy design is based on the following principles: We use HMSNs-Cu2+@HA as the signal probe, the structure of HA is destroyed under acidic conditions, and the released Cu2+ activates the substrate material MMoO4 (M = Co, Ni) Peroxidase activity initiates the reaction of catalytic H2O2 and realizes the "signal on" condition of electrical signals. This strategy has the following advantages: (1) HA coating of HMSNs-Cu2+ can prevent Cu2+ leakage, has good biocompatibility and can be connected with more antibodies. (2) The prepared sensor has the characteristics of high sensitivity and a low detection limit. When the electrode substrate was CoMoO4, the detection range of the immunosensor was 0.01 pg/mL-40 ng/mL, and the detection limit was 0.0035 pg/mL (S/N = 3). This work innovatively applies the catalytic activity of metal ion-activated nanozymes in the detection of CEA, providing a new perspective for the monitoring and analysis of cancer markers.

An immunosensor based on an electrochemical-chemical-chemical advanced redox cycle amplification strategy for the ultrasensitive determination of CEA.

Signal amplification is very important for electrochemical immunoassays. We report an enzyme-free electrochemical immunosensor based on an electrochemical-chemical-chemical (ECC) redox cycle advanced (RCA) signal amplification strategy for the ultrasensitive detection of Carcinoembryonic antigen (CEA). In this scheme, CeO2/Au NPs@SiO2 is connected with ferrocene as the redox indicator, and the detection buffer is composed of the reducing agent hydroquinone (HQ) and tris(2-carboxyethyl) phosphine (TCEP). First, ferrocenecarboxylic acid (FcA) is oxidized to FcA+ on the electrode. Then, HQ reduces FcA+ to FcA to trigger the cyclic reaction of the inner ring. Second, the oxidation product of HQ is catalyzed by TCEP. The product is reduced to HQ again to complete the cyclic reaction of the outer ring, so the entire cyclic reaction forms a closed loop. The system realizes the high-efficiency regeneration of the electroactive material Fc, thereby ensuring the full amplification of the electrical signal. The results show that the immunosensor exhibits good analytical performance, the detection range is 0.01 pg/mL-80 ng/mL, the detection limit is 0.0037 pg/mL, and the immunosensor has excellent selectivity and stability and performs well in the detection of actual samples. This strategy provides a new method for the early screening of CEA.

Immunomodulatory effects of anaesthetic sevoflurane in septic mouse model.

Sepsis is one among the dangerous medical threat that is very much related to body's immune system having no proper treatment for this condition. About19 million cases of sepsis have been recorded and out of which 5 million cases die every year. Sevoflurane other than controlling the depth of anaesthesia, it does have a vital role in immunomodulations. The study is focused on investigating the immunomodulatory effects of sevoflurane in the septic mouse model induced by CLP. Mortality rate, organ damage, inflammatory mediators, bacterial load, coagulopathy, hepto and renal functional changes, serum lactate, blood glucose, neutrophil sequestration and finally histopathological examination were investigated. The results were interesting that exposure to sevoflurane improves the polymicrobial abdominal sepsis outcome. Mice exposed to sevoflurane after CLP significantly improved outcomes of polymicrobial abdominal sepsis and reduced mortality by improving overall 7-day survival (83.3%) compared to mice without sevoflurane (no treatment group 16.6%) additionally decreasing the surrogate marker levels in the experimental sepsis animal model conducted. Our study suggests that the selection of certain anaesthetic drugs could be critical in the management of septic patients because their immunomodulatory effects could be large enough to affect sepsis pathophysiology.

Clinical Study of Ultrasound-Guided Methylene Blue Thoracic Paravertebral Nerve Block for the Treatment of Postherpetic Neuralgia.

AIM: To investigate the effect of ultrasound-guided methylene blue (MB) thoracic paravertebral nerve block (TPVB) on the treatment of postherpetic neuralgia (PHN). MATERIAL AND METHODS: A total of 27 patients with PHN were treated with ultrasound-guided TPVB. The blocking drug used was an MB compound preparation, and several indexes were recorded, including pain visual analogue scores (VAS), dosage of oral analgesic required, plasma interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and cortisol levels, basic viability, selfassessment, and satisfaction. RESULTS: The patients' VAS after TPVB were significantly reduced when compared to those before blocking. Furthermore, dosage of oral analgesic required, levels of plasma IL-6, TNF-α, and cortisol were reduced, and basic viability and self-assessments were significantly improved (p < 0.05). The treatment method was effective, did not cause any adverse effects, and patients reported higher degrees of satisfaction. CONCLUSION: Ultrasound-guided TPVB exerts significant effects on PHN. The patients' degree of pain and dosage of oral analgesic required were reduced, basic patient viability was improved, and patients reported higher degrees of satisfaction.