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Nanoscale Advances · 2023 ·Vol. 5 ·期 3 ·830-839 · IF 4.7

Direct fabrication of NbS2 nanoflakes on carbon fibers by atomic layer deposition for ultrasensitive cardiac troponin I detection

Yazhou Huang,Yunfei Zhang,Junyan Lv,Yinfeng Shao,Dongfang Yang,Yuan Cong

The sensitive detection of cardiac troponin I (cTnI) is of great significance for the early diagnosis of acute myocardial infarction (AMI). Herein, in order to fabricate an electrochemical biosensor for ultrasensitive cTnI detection, atomic layer deposition (ALD) was employed to directly deposit NbS2 nanoflakes (NFs) on carbon fiber paper (CFP). Due to the self-limiting reaction of ALD, NbS2NFs were deposited uniformly and accurately on the surface of carbon fibers by controlling the number of ALD cycles, which ensured ultrasensitive detection. Precise regulation of the nanoscale morphology and electrochemical performance of NbS2 nanoflakes via ALD cycles was observed in depth. Owing to the high surface area and conductivity, an anodic/cathodic current of ∼3.01 mA of NbS2NFs/CFP can be obtained. Subsequently, an electrochemical biosensor based on the excellent performance of NbS2NFs/CFP was fabricated. The ultrasensitive detection of cTnI in a linear range of 1 fM to 0.1 nM with a detection limit of 0.32 fM was achieved.

研究领域: 材料科学 · 生物化学 · 电化学 · 医学诊断
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Nanoscale · 2021 ·Vol. 13 ·期 5 ·3275-3284 · IF 7.79

Ultrasensitive chemiluminescence immunoassay with enhanced precision for the detection of cTnI amplified by acridinium ester-loaded microspheres and internally calibrated by magnetic fluorescent nanoparticles

Huan Zhao,Qifeng Lin,Li Huang,Yunfeng Zhai,Yuan Liu,Yan Deng,Enben Su,Nongyue He

A novel enhanced chemiluminescent immunoassay (CLIA) for ultrasensitive and excellent precisive determination of cardiac troponin I (cTnI) was reported. The method made full use of poly[(N-isopropyl acrylamide)-co-(methacrylic acid)] (P(NIPAM-co-MAA)) microspheres as new potential signal enhancers and magnetic fluorescent nanoparticles as internal standards for better precision. This protocol involved a sandwich format, in which the antigen in the sample was captured by the immobilized antibodies on the surface of magnetic fluorescent beads and recognized by the other antibodies labeled with acridinium ester (AE)-loaded P(NIPAM-co-MAA) microspheres. The combination of the remarkable sensitivity of the enhanced CLIA method and the use of P(NIPAM-co-MAA) microspheres as anti-cTnI carriers for acridinium ester signal amplification provided an extremely sensitive limit of blank (LoB) at 0.097 pg mL−1, a limit of detection (LoD) at 0.116 pg mL−1, and a limit of quantitation (LoQ) at 0.606 pg mL−1, much greater than those achieved by the classical chemiluminescence immunoassay (CLIA, Getein). Moreover, the intra-day variable coefficient can be improved to 1.21–2.12%, and inter-day variability was 2.01–3.49% under the application of magnetic fluorescent beads as an internal standard. The sensitivity and precision have reached a high level, comparable with the current commercial detection kits. The results showed a good correlation with a commercial chemiluminescence assay (CLIA, Abbott), with a correlation coefficient of 0.9883. This proposed method has been successfully applied to the clinical determination of cTnI in the human serum.

研究领域: 医学诊断 · 免疫学 · 纳米技术
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ACS Applied Bio Materials · 2024 · IF 4.6

Copper(II)-Tannic Acid@Cu with In Situ Grown Gold Nanoparticles as a Bifunctional Matrix for Facile Construction of Label-Free and Ultrasensitive Electrochemical cTnI Immunosensor

Xianxin Liu,Haizhu Yang,Jiancong Ni,Xuan Zheng,Zhiping Song,Feng Gao,Qingxiang Wang

Sensitive detection of cardiac troponin I (cTnI) is of great significance in the diagnosis of a fatal acute myocardial infarction. A redox-active nanocomposite of copper(II)-tannic acid@Cu (CuTA@Cu) was herein prepared on the surface of a glassy carbon electrode by electrochemical deposition of metallic copper combined with a metal stripping strategy. Then, HAuCl4 was in situ reduced to gold nanoparticles (AuNPs) by strong reductive catechol groups in the TA ligand. The AuNPs/CuTA@Cu composite was further utilized as a bifunctional matrix for the immobilization of the cTnI antibody (anti-cTnI), producing an electrochemical immunosensor. Electrochemical tests show that the immunoreaction between anti-cTnI and target cTnI can cause a significant reduction of the electrochemical signal of CuTA@Cu. It can be attributed to the insulating characteristic of the immunocomplex and its barrier effect to the electrolyte ion diffusion. From the signal changes of CuTA@Cu, cTnI can be analyzed in a wide range from 10 fg mL–1 to 10 ng mL–1, with an ultralow detection limit of 0.65 fg mL–1. The spiked recovery assays show that the immunosensor is reliable for cTnI determination in human serum samples, demonstrating its promising application in the early clinical diagnosis of myocardial infarction.

CAS / MDL: 57-09-0 872-50-4
研究领域: 生物医学工程 · 分析化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS · 2024 · IF 4.9

Fabrication of multiple LFIA strips with ZrO2@PEI-QDs nanosphere composites for rapid differentiation of acute aortic dissection and acute myocardial infarction

Ziyan Hu,Zhongbing Huang,Juan Wang,Jirui Wen,Ximing Pu,Qianlei Lang,Peng Yang,Zhongxiang Shao,Jia Hu,Jiang Wu,Guangfu Yin

Typical symptoms of acute myocardial infarction (AMI) and acute aortic dissection (AAD) are similar chest pain, leading to higher clinical misdiagnosis rate, evenly the mortality rate of patients. In this work, ZrO 2 @PEI-QDs nanospheres with higher fluorescence were prepared by sequential electrostatic adsorption of branched PEI chains and CdSe/ZnS-COOH QDs on hollow ZrO 2 nanospheres. Three multi-channel LFIA strips (on sST2 and cTnI, cTnI and h-FABP, HMGB1 and sST2, respectively) based on ZrO 2 @PEI-QDs for rapid and correct distinguishing of AMI and ADD were constructed. Their visual limit of detection (vLOD for sST2 and cTnI, cTnI and h-FABP, HMGB1 and sST2) within 10–15 min reached 0.075 and 0.1 ng/mL, 0.1 and 1 ng/mL, 1 and 0.1 ng/mL, respectively, which were all lower than the normal level of healthy people. Compared with previous studies, ZrO 2 surface adsorbs more QDs, the fluorescence intensity was increased by about 2.84 times, and vLODs of three strips based on the quantitative fluorescence analysis were also increased by up to one orders of magnitude. The test results of five clinical serum samples indicated that three multi-channel LFIA strips could quantitatively detect four biomarkers of chest pain, and successfully distinguish AMI patients from AAD patients. These results indicated that this set of multi-channel LFIA strips could become an effective tool for the early and accurate detection or distinguish of ADD and AMI.

CAS / MDL: 23519-77-9
研究领域: 纳米技术 · 生物传感器 · 医学诊断 · 心脏病学
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BIOSENSORS & BIOELECTRONICS · 2022 · IF 12.545

Hollow prussian blue nanozyme-richened liposome for artificial neural network-assisted multimodal colorimetric-photothermal immunoassay on smartphone

Zhichao Yu,Hexiang Gong,Meijin Li,Dianping Tang

Multi-signal output biosensor technologies based on optical visualization and electrochemical or other sophisticated signal transduction are flourishing. However, sensors with multiple signal outputs still exhibit some limitations, such as the additional requirement for multiple regression equation construction and control of results. Herein, we developed a sensitive cascade of colorimetric-photothermal biosensor models for prognostic management of patients with myocardial infarction with the assistance of an artificial neural network (ANN) normalization process. A cascade enzymatic reaction device based on hollow prussian blue nanoparticles (h-PB NPs), and a portable smartphone-adapted signal visualization platform were integrated into the all-in-one 3D printed assay device. Specifically, liposomes encapsulated with h-PB were confined to the test cell using a classical immunoassay . Based on the peroxidase-like activity of h-PB, the h-PB obtained by the immunization process was further transferred to the TMB-H 2 O 2 system and used as a cascade of signal amplification for sensitive determination of cTnI protein. The target concentration was converted into a measurable temperature signal readout under 808 nm NIR laser excitation , and the absorbance of the TMB (ox-TMB) system at 650 nm was recorded simultaneously as a reference during this process. Interestingly, a parallel 3-layer, 64-neuron ANN learning model was built for bimodal signal processing and regression. Under optimal conditions, the bimodal machine learning-assisted co-immunoassay exhibited an ultra-wide dynamic range of 0.02–20 ng mL −1 and a detection limit of 10.8 pg mL −1 . This work creatively presents a theoretical study of machine learning-assisted multimodal biosensors, providing new insights for the development of ultrasensitive non-enzymatic biosensors.

研究领域: 生物医学工程 · 分析化学 · 人工智能 · 即时诊断
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Bioactive Materials · 2021 · IF 14.593

Injectable conductive gelatin methacrylate / oxidized dextran hydrogel encapsulating umbilical cord mesenchymal stem cells for myocardial infarction treatment

Shuoji Zhu,Changjiang Yu,Nanbo Liu,Mingyi Zhao,Zerui Chen,Jian Liu,Ge Li,Huanlei Huang,Huiming Guo,Tucheng Sun,Jimei Chen,Jian Zhuang,Ping Zhu

Umbilical cord mesenchymal stem cells (UCMSCs) transplantation has been proposed as a promising treatment modality for myocardial infarction (MI), but the low retention rate remains a considerable challenge. Injectable natural polymer hydrogels with conductivity ability are highly desirable as cell delivery vehicles to repair infarct myocardium and restore the cardiac function. In this work, we developed a hydrogel system based on gelatin methacrylate (GelMA) and oxidized dextran (ODEX) as cell delivery vehicles for MI. And dopamine could be used as a reductant of graphene oxide (GO) to form reductive GO (rGO). By adjusting the amount of rGO, the conductivity of hydrogels with 0.5 mg/mL rGO concentration (≈10 −4  S/cm) was similar to that of natural heart tissue. In vitro cell experiments showed that the prepared hydrogels had excellent biocompatibility and cell delivery ability of UCMSCs. More importantly, GelMA-O5/rGO hydrogel could promote UCMSCs growth and proliferation, improve the myocardial differentiation ability of UCMSCs, and up-regulate the expression of cTnI and Cx43. Further in vivo experiments demonstrated that GelMA-O5/rGO/UCMSCs Hydrogel could significantly improve the ejection fraction (EF) of rats and significantly reduce myocardial infarct area compared to PBS group, promote the survival of UCMSCs, enhance the expression level of cTnI and Cx43, and decrease the expression level of caspase-3. The findings of this study suggested that the injectable conductive GelMA-O5/rGO hydrogel encapsulating UCMSCs could improve damaged myocardial tissue and reconstruct myocardial function, which will be a promising therapeutic strategy for cardiac repair.

研究领域: 生物材料 · 干细胞治疗 · 心脏病学 · 组织工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Science China-Chemistry · 2020 ·Vol. 63 ·期 4 ·554-560 · IF 6.356

In situ formation of fluorescent silicon-containing polymer dots for alkaline phosphatase activity detection and immunoassay

Liu Guoyong,Zhao Jiahui,Yan Mengxia,Zhu Shuyun,Dou Wenchao,Sun Jian,Yang Xiurong

The discovery and application of analyte-triggered fluorophore generation or fluorogenic reaction are significant and beneficial to the development of novel fluorescence (FL) analysis method. In this study, for the first time, we have reported a fluorogenic reaction to prepare fluorescent silicon-containing polymer dots (Si-PDs) by simply mixing N -[3-(trimethoxysilyl)propyl]ethylenediamine (DAMO) and hydroquinone (HQ) in aqueous solution at ambient temperature. Inspired by the alkaline phosphatase (ALP)-catalyzed hydrolysis of the substrate sodium 4-hydroxyphenyl phosphate (4-HPP) into HQ and the resultant HQ-controlled intense green Si-PDs generation, we have established a straightforward ALP activity assay by innovatively employing commercially available 4-HPP as the substrate. More significantly, the specific preparation method, clear formation mechanism and excellent performance enable the Si-PDs as well as its generation process to develop facile and attractive FL immunoassay. With the help of the universal ALP-based enzyme-linked immunosorbent assay (ELISA) platform and corresponding antibody, a convenient and conceptual ALP-based fluorescent ELISA has been constructed and applied in sensing cardiac troponin I (cTnI), a well-known biomarker of acute myocardial infarction. Our research via in situ formation of fluorescent nanomaterials has great potential application in ALP activity assay, inhibitor screening, and disease diagnosis.

CAS / MDL: 1760-24-3
研究领域: 分析化学 · 生物化学 · 纳米材料 · 诊断学 · 免疫分析
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ACS Sensors · 2019 · IF 6.944

Porous Hydrogel-Encapsulated Photonic Barcodes for Multiplex Detection of Cardiovascular Biomarkers

JingJing Ji,Wenbin Lu,Yi Zhu,Hong Jin,Yuyu Yao,Huidan Zhang,Yuanjin Zhao

Early detection of cardiac troponin I (cTnI), B-type natriuretic peptide (BNP), and myoglobin (Myo) is essential for the diagnosis of acute myocardial infarction (AMI) and heart failure (HF). We designed a porous hydrogel-encapsulated photonic crystal (PhC) barcode-based suspension array for multiple cardiovascular marker detection. The hybrid hydrogel was composed of polyethylene glycol diacrylate (PEGDA) and gelatin, resulting in a porous and hydrophilic scaffold which ensured stability of the PhC in aqueous solutions. The encapsulated PhC barcodes had stable diffraction peaks for the corresponding markers. Using a sandwich format, the proposed suspension array was used for simultaneous multiplex detection of cardiovascular biomarkers in a single tube. The immunoassay results we tested on cTnI, BNP, and Myo could be assayed in the ranges of 0.01 to 1000 ng/mL, 0.1 to 10 000 pg/mL, and 1 to 10 000 ng/mL with limits of detection of 0.009 ng/mL, 0.084 pg/mL, and 0.68 ng/mL at 3σ, respectively. This method also showed acceptable accuracy and repeated detection, and the results were consistent with the results of conventional clinical methods for detecting actual clinical samples. Therefore, suspension arrays based on hydrogel-encapsulated PhC barcodes are highly promising for AMI diagnosis.

CAS / MDL: 25952-53-8 6066-82-6
研究领域: 生物材料 · 生物医学工程 · 心脏病学 · 分析化学
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ANALYTICAL CHEMISTRY · 2023 · IF 7.4

MnO4–-Triggered Immediate-Stable Real-Time Fluorescence Immunosensor with High Response Speed and Low Steady-State Error

Wenlin Ma,Lihua Pang,Jinhua Liu,Lei Wen,Huili Ma,Yinhui Li,Zhihui Xu,Chengwu Zhang,Hai-Dong Yu

Real-time chemical and biological sensing in vitro is important for application in health and environmental monitoring. Thus, a more rapid and stable detection method is urgently needed. Herein, an immediate-stable real-time fluorescent immunosensor with a high response speed (∼100%, <1 s) and approximately zero steady-state error is constructed. The developed sensor is based on the MnO4–-triggered in situ immediate-stable fluorogenic reaction between dopamine and orcinol monohydrate to produce azamonardine (DMTM). The obtained DMTM is identified and characterized by high-resolution mass spectrometry, 1H NMR spectroscopy, 13C NMR spectroscopy, and theoretical calculations. The present sensor achieves a highly sensitive detection of dopamine (DA) with a limit of detection (LOD) of 10 nM as well as alkaline phosphates (ALP) with an LOD of 0.1 mU/mL by using orcinol monohydrate phosphate sodium salt as a substrate. As a proof of concept, ALP-triggered fluorescence ELISA using cardiac troponin I (cTnI) as a model antigen target is further constructed. The developed real-time sensor achieves the detection of cTnI with an LOD of 0.05 ng/mL. Moreover, the sensor proposed by us is successfully applied to assess the cTnI level in clinical serum specimens and yields results consistent with those obtained by the commercial ELISA method. The immediate-stable real-time fluorescence immunosensor provides a promising and powerful platform for the trace detection of biomolecules in clinical diagnosis.

研究领域: 分析化学 · 生物化学 · 医学诊断 · 环境监测 · 临床化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ACS Nano · 2023 · IF 17.1

Pomegranate-Bionic Encapsulating Horseradish Peroxidase Using Dopamine Flexible Scaffold-Coated Multishell Porous ZIF-8 To Enhance Immunochromatographic Diagnosis

Mingxuan Song,Juanxia Xing,Huan Cai,Xin Gao,Chunyang Li,Changjin Liu,Xinmin Li,Xuhuai Fu,Shijia Ding,Wei Cheng,Rui Chen

Nanoparticle-natural enzyme complexes are receiving increasing attention as the promising signal reporters for colorimetric lateral flow immunoassay (LFIA). Nonetheless, it remains a challenge to develop the nanocomplexes with high loading efficiency, catalytic efficiency, and colorimetric signal brightness. Herein, inspired by pomegranate structure, we reported the synthesis of a colorimetric catalytic nanocomplex ((HRP@ZIF-8)3@PDA@HRP), using dopamine flexible scaffold-coated multishell porous zeolitic imidazolate framework-8 (ZIF-8) as a hierarchical scaffold to encapsulate horseradish peroxidase (HRP), and described its potential to promote an ultrasensitive colorimetric LFIA of cardiac troponin I (cTnI). (HRP@ZIF-8)3@PDA@HRP exhibited ultrahigh HRP loading efficiency and catalytic activity due to the epitaxial shell-by-shell overgrowth of porous ZIF-8 scaffold, which provided more cavities for enzyme immobilization and a diffusion path for the catalytic substrate. Furthermore, the polydopamine (PDA) layer on the (HRP@ZIF-8)3 surface both enhanced the colorimetric signal brightness and acted as a flexible scaffold to immobilize HRP, further increasing the amount of enzyme. Following integration with LFIA, the developed platform achieved an ultrasensitive colorimetric test strip assay for cTnI with pre- and postcatalytic naked-eye detection sensitivities of 0.5 ng mL–1 and 0.01 ng mL–1, respectively, which were 4/2- and 200/100-fold higher than gold nanoparticles (AuNPs)/PDA-based LFIA and comparable to chemiluminescence immunoassay. Further, the quantitative testing results of the developed colorimetric LFIA on 57 clinical serum samples agreed well with the clinical data. This work provides ideas for the design of natural enzymes-based colorimetric catalytic nanocomplex to encourage applications for the development of ultrasensitive LFIA for early diseases diagnosis.

研究领域: 材料科学 · 纳米技术 · 分析化学 · 生物传感器 · 医学诊断
✓ 已验证 产品关联 DOI PubMed 高影响因子
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BIOSENSORS & BIOELECTRONICS · 2018 · IF 8.173

Simultaneous detection of three biomarkers related to acute myocardial infarction based on immunosensing biochip

Kaige Zhao,Min Tang,Huaisheng Wang,Zhenxian Zhou,Yafeng Wu,Songqin Liu

An immunosensing biochip for simultaneous detection of three biomarkers related to acute myocardial infarction (AMI) was developed based on anionic soybean peroxidase (SBP) functionalized nanoprobe and chemiluminescent imaging. The nanoprobes (Ab2-SiO 2 -SBP) were fabricated by co-immobilization of SBP and one of the detection polyclonal antibodies , anti-cardiac troponin I antigen (anti-cTnI), anti-creatine kinase-MB (anti-CK-MB) and anti-myoglobin (anti-Myo), on the silica nanoparticle surface. The detection sensitivity was enhanced since the large surface area of silica carriers increased the loading of SBP for per sandwiched immunoreaction. The immunosensing biochip designed as 3 × 8 wells array was constructed by simultaneously immobilizing three capture monoclonal antibodies on the same one microtiter well with 2 × 3 active spots. In the presence of target protein, the nanoprobes will be attached onto the spots with high specificity through the sandwiched immunoreactions, which triggered the chemiluminescence (CL) signals on each sensing site of the microtiter plates and allowed to CL imaging of three biomarkers in one well at the same time. Therefore, the proposed biochip was a promising convenient strategy for simultaneous detection of cTnI, CK-MB and Myo, which showed potential application for multianalyte determination in clinical diagnostics.

研究领域: 生物医学工程 · 临床诊断 · 纳米技术 · 免疫学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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MICROCHEMICAL JOURNAL · 2021 · IF 4.821

Microcavity-based SERS chip for ultrasensitive immune detection of cardiac biomarkers

Junjie Wang,Chunxiang Xu,Milan Lei,Yi Ma,Xiaoxuan Wang,Ru Wang,Jianli Sun,Ru Wang

The detection of cardiac markers with high sensitivity and specificity is exceedingly essential for the early diagnosis and warning of cardiovascular disease. In this work, we developed a microcavity-based sandwich immune chip to realize the ultrasensitive detection of cardiac troponin I (cTnI) and creatine kinase isoenzyme MB (CK-MB) by surface-enhanced Raman spectroscopy (SERS) method. Herein, polystyrene microspheres modified with gold nanoparticles (Au NPs) were fixed on the substrate via polydopamine, which was used as an immune capture chip. 5,5′-Dithio bis-(2-nitrobenzoic acid) (DTNB) and 4-mercaptobenzoic acid (4MBA) labelled Au NPs served as immune signal probes for cTnI and CK-MB, respectively. Light confinement effect of polystyrene (PS) microcavities and localized surface plasmon resonance (LSPR) near the Au NPs synergistically strengthened the electromagnetic field and promoted the interaction between light and matter, which enhanced SERS performance with an enhancement factor of 1.95 × 10 12 for SERS sensing. The immunoassay results demonstrated the sensitive quantitative detection with the limit of detection (LOD) of 3.16 pg/mL and 4.27 pg/mL for cTnI and CK-MB, separately. The method also had good specificity, reproducibility and stability. It could be expected that our proposed microcavity-based SERS chip immunoassay technique would be considered as an effective diagnostic tool for ultrasensitive detection of cardiac biomarkers.

研究领域: 心脏病学 · 纳米技术 · 分析化学 · 生物医学工程
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