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Advanced Science · 2023 ·Vol. 10 ·期 24 ·2301658 · IF 15.1

Nanozyme-Catalyzed Metasurface Plasmon Sensor-Based Portable Ultrasensitive Optical Quantification Platform for Cancer Biomarker Screening

Rui Li,Hongli Fan,Hanlin Zhou,Youqian Chen,Qingcai Yu,Wenjun Hu,Gang L. Liu,Liping Huang

Developing plasmonic biosensors that are low-cost, portable, and relatively simple to operate remains challenging. Herein, a novel metasurface plasmon-etch immunosensor is described, namely a nanozyme-linked immunosorbent surface plasmon resonance biosensor, for the ultrasensitive and specific detection of cancer biomarkers. Gold-silver composite nano cup array metasurface plasmon resonance chip and artificial nanozyme-labeled antibody are used in two-way sandwich analyte detection. Changes in the biosensor's absorption spectrum are measured before and after chip surface etching, which can be applied to immunoassays without requiring separation or amplification. The device achieved a limit of alpha-fetoprotein (AFP) detection < 21.74 fM, three orders of magnitude lower than that of commercial enzyme-linked immunosorbent assay kits. Additionally, carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA125) are used for quantitative detection to verify the universality of the platform. More importantly, the accuracy of the platform is verified using 60 clinical samples; compared with the hospital results, the three biomarkers achieve high sensitivity (CEA: 95.7%; CA125: 90.9%; AFP: 86.7%) and specificity (CEA: 97.3%; CA125: 93.9%; AFP: 97.8%). Due to its rapidity, ease of use, and high throughput, the platform has the potential for high-throughput rapid detection to facilitate cancer screening or early diagnostic testing in biosensing.

CAS / MDL: 7722-84-1 54827-17-7
研究领域: 生物传感 · 医学诊断 · 纳米技术 · 光学 · 癌症研究
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Journal of Materials Chemistry B · 2017 ·Vol. 5 ·期 48 ·9600-9607 · IF 4.543

Bismuth ferrite-based photoactive materials for the photoelectrochemical detection of disease biomarkers coupled with multifunctional mesoporous silica nanoparticles

Qian Zhou,Youxiu Lin,Minghua Lu,Dianping Tang

This work designs a new photoelectrochemical (PEC) sensing system for the detection of carcinoembryonic antigens (CEAs) using bismuth ferrite (BiFeO3) nanostructures as photoactive materials, accompanied by the target-controlled release of glucose from multifunctional mesoporous silica nanoparticles (MSNs) for signal amplification. Glucose molecules were gated in the pores via the hybridization of a CEA aptamer with anchor DNA (aDNA, modified on the mesoporous silica nanoparticles). Upon the addition of the target CEA, the analyte competitively reacted with the aptamer to open the gate, thus resulting in the release of glucose molecules from the MSNs. Based on the oxidization of glucose in the presence of glucose oxidase, the as-generated enzymatic product (H2O2) served as an electron acceptor to enhance the photocurrent generated by the BiFeO3 nanostructures under visible light irradiation. In this way, an in situ amplified photocurrent could be achieved in that the low-concentration target CEA could cause the release of numerous glucose molecules. Experimental results suggested that the photocurrent obtained from the BiFeO3-based photoactive materials increased with increasing CEA concentration and showed a good linear dependence on the logarithm of the CEA level from 5.0 pg mL−1 to 50 ng mL−1 under optimal conditions. Additionally, the BiFeO3-based PEC sensing platform also showed good stability and favorable selectivity, and satisfactory accuracy for CEA detection in human serum specimens in comparison with a reference CEA ELISA kit. The good analytical performance of the BiFeO3-based PEC sensing method makes it a promising tool for the efficient, low-cost and convenient detection of CEAs in disease diagnosis.

CAS / MDL: 57-09-0 4432-31-9
研究领域: 材料科学 · 纳米技术 · 分析化学 · 生物传感器 · 疾病诊断
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TALANTA · 2024 · IF 5.6

Sub-femtomolar vertical graphene field effect immunosensor for detection of lung tumor markers

Ruifang Liu,Hang Song,Hao Wu,Zhihao Yang,Surong Fang,Jing Zhu,Long Ba

Lung cancer is the main cancer that endangers human life worldwide, with the highest mortality rate. The detection of lung tumor markers is of great significance for the early diagnosis and subsequent treatment of lung cancer. In this study, a vertical graphene field effect transistor (VGFET) immunosensor based on graphene/C 60 heterojunction was created to offer quantitative detections for the lung tumor markers carcinoembryonic antigen (CEA), cytokeratin 19 fragment (Cyfra21-1), and neuron-specific enolase (NSE). The experimental results showed that the sensitive range for standard antigen is between 1 pg/ml to 100 ng/ml, with a limit of detection (LOD) of 5.6 amol/ml for CEA, 33.3 amol/ml for Cyfra 21–1 and 12.8 amol/ml for NSE (1 pg/ml for all). The detection accuracy for these tumor markers was compared with the clinically used method for clinical patients on serum samples. Results are highly consistent with clinically used immunoassay in its efficient diagnosis concentration range. Subsequently, the mesoporous silica nanospheres (MSNs) with an average size of 90 nm were surface modified with glutaraldehyde, and a second antibody was assembled on MSNs, which fixes nanospheres on the antigen and amplified the field effect. The LODs for three markers are 100 fg/ml (0.56 amol/ml for CEA) under optimal circumstances of detection. This result indicates that specific binding to MSNs enhances local field effects and can achieve higher sensing efficiency for tumor marker detection at extremely low concentrations, providing effective assistance for the early diagnosis of lung cancer.

研究领域: 生物医学工程 · 纳米技术 · 癌症诊断 · 材料科学
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SENSORS AND ACTUATORS B-CHEMICAL · 2020 · IF 7.1

Polymer-functionalized carbon nanotubes prepared via ring-opening polymerization for electrochemical detection of carcinoembryonic antigen

Jinge Li,Liying Zhao,Wenbin Wang,Yanju Liu,Huaixia Yang,Jinming Kong,Fuchun Si

Carcinoembryonic antigen (CEA) is regarded as the most common tumor biomarker, the precise and sensitive measurement of which has great significance for the cancer diagnosis, treatment, and prognosis. Herein, for the first time, we construct a novel sandwich-type electrochemical aptasensor for CEA detection based on polymer-functionalized carbon nanotubes (CNTs) composites prepared by ring-opening polymerization (ROP). CEA-aptamer 1 (Apt 1) is self-assembled on a gold electrode surface and used as a probe for CEA capture. CNTs are used as the substrates for polymer chain growth to prepare poly(ferrocenyl glycidyl ether)-grafted CNTs (PFcGE-CNTs) composites by ROP. Due to the efficient polymerization and good biocompatibility of ROP technology, PFcGE-CNTs composites can provide a hydrophilic-biocompatible nanoplatform for CEA-aptamer 2 (Apt 2) capture and serve as a signal amplifier. Remarkably, PFcGE-CNTs composites feature the characteristics of good conductivity and abundant ferrocene derivatives, which significantly amplify the electrochemical signal. Under optimized conditions, the fabricated aptasensor shows a wide detection range of 1 × 10 −15 –1 × 10 −8 g mL −1 and a limit of detection (LOD) down to 2.8 × 10 −16 g mL −1 , which are superior to those of most reported electrochemical methods. Furthermore, the proposed aptasensor exhibits excellent applicability for CEA detection in practical sample analysis, which is of promising application potential for the early diagnosis and monitoring of cancer.

研究领域: 分析化学 · 纳米技术 · 生物传感器 · 癌症诊断
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NEW JOURNAL OF CHEMISTRY · 2021 ·Vol. 45 ·期 24 ·10880-10889 · IF 3.591

Construction of electrochemical immunosensors based on redox hydrogels for ultrasensitive detection of carcinoembryonic antigens

Xiangrong Huang,Na Wu,Wenxiu Liu,Yazhuo Shang,Honglai Liu,Yifan He,Hong Meng,Yinmao Dong

In this work, a novel redox hydrogel was proposed for ultrasensitive label-free electrochemical detection of a carcinoembryonic antigen (CEA). The redox hydrogel composed of cellulose nanocrystals (CNCs), methylene blue (MB), multi-walled carbon nanotubes (MWCNTs), and polydopamine-reduced graphene oxide-gold nanoparticles (PDA–rGO–AuNPs) was formed by electrostatic and hydrophobic interactions among these components. The larger surface to volume ratio, outstanding hydrophilicity, excellent film-forming ability and the gelatinization of CNCs provided the premise for the formation of a gel with excellent properties including larger specific surface area (101.05 m2 g−1), better adhesive ability to glassy carbon electrodes (GCEs), etc. The addition of MWCNTs to hydrogel could improve the adsorption of redox MB. The synthesized PDA–rGO–AuNPs gel was integrated into a hydrogel not only for improving the conductivity but also for providing more sites for immobilization of antibodies. The obtained CNC–MB–MWCNT–PDA–rGO–AuNPs gel was then applied to modify GCE and the gel/GCE demonstrated higher stability and exhibited a strong redox performance (current signal appeared at −0.156 V (vs. Ag/AgCl)). The immunoassay platform was constructed after the gel/GCE was incubated with anti-CEA and blocked by bovine serum albumin (BSA) in succession. The proposed immunosensor exhibited a wider linear range from 1 fg mL−1 to 200 ng mL−1 with an ultralow detection limit of 0.011 fg mL−1 (at a signal to noise ratio of 3). Furthermore, the immunosensor demonstrated higher selectivity, excellent reproducibility, remarkable stability, and better reliability for real sample analysis, which implied a promising potential for the determination of CEA in clinical application.

CAS / MDL: 9048-46-8 57-09-0
研究领域: 分析化学 · 生物传感器 · 纳米技术 · 电化学 · 癌症诊断
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JOURNAL OF ELECTROANALYTICAL CHEMISTRY · 2020 · IF 3.807

A novel electrochemical immunosensor for carcinoembryonic antigen based on Cu-MOFs-TB/polydopamine nanocarrier

Jianbo Liu,Yonghui Shang,Jinqiong Xu,Yi Chen,Yarong Jia,Jianbin Zheng

Carcinoembryonic antigen (CEA) is a typical biomarker for lung cancer. It is very urgent to develop a sensitive and rapid method to assay CEA content in human serum. In this work, Cu-MOFs nanomaterials were synthesized by a hydrothermal method . Toluidine blue (TB) loaded mesoporous Cu-MOFs with polydopamine (PDA) coating were employed as a signal probe. The proposed sandwich immunosensor was fabricated by Cu-MOFs-TB/PDA, chitosan and MWCNTs on the glassy carbon electrode with a large surface area to immobilize primary antibodies (Ab 1 ) and provide excellent conductivity. The sensitivity improvement of this new strategy was based on the destruction of the probe and the immune complex by HCl, which resulted in the closer distance between TB and the sensing electrode. Under optimal conditions, CEA was quantitatively detected with a wide linear range from 20 fg mL −1 to 200 ng mL −1 , a low detection limit of 3.0 fg mL −1 (S/N = 3). In addition, the method showed good stability, selectivity, and reproducibility, which possessed wide potential applications for the detection of other tumour biomarkers.

CAS / MDL: 308068-56-6
研究领域: 分析化学 · 生物标志物检测 · 纳米技术 · 电化学 · 癌症诊断
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JOURNAL OF ELECTROANALYTICAL CHEMISTRY · 2022 · IF 4.598

An electrochemical immunosensor for simultaneous detection of two lung cancer markers based on electroactive probes

Jianbo Liu,Jing Liu,Yonghui Shang,Jinqiong Xu,Xinyang Wang,Jianbin Zheng

A multiplex electrochemical immunosensor was developed for the simultaneous detection of two lung cancer markers, carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA125), using electroactive probes. Cu-TCPP nanomaterials were synthesized by a hydrothermal method . Cu-TCPP–TB-anti-CEA and Cu-TCPP-PB-anti-CA125 immunosensor probes were prepared using toluidine blue (TB) and prussian blue (PB) as the indicators. The electrochemical immunosensor was constructed for the simultaneous detection of CEA and CA125. The linear range of CEA was 0.1–160 ng mL −1 with a low detection limit of 0.03 ng mL −1 . The linear range of CA125 was 0.5–200 U mL −1 with a low detection limit of 0.05 U mL −1 . Furthermore, the immunosensor was applied for the simultaneous determination of CEA and CA125 in real samples (human blood serum), with results comparable to the reference values obtained by the standard enzyme-linked immunosorbent assay. This study furthers knowledge on the construction of electrochemical immunosensors showing the simultaneous detection of two lung cancer markers.

研究领域: 生物化学 · 分析化学 · 纳米技术 · 癌症研究 · 电化学
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NEW JOURNAL OF CHEMISTRY · 2022 ·Vol. 46 ·期 29 ·13963-13970 · IF 3.925

Application of a CuS/Au heterostructure with peroxidase-like activity in immunosensors

Pengli Li,Min Wang,Mingzhe Jiang,Wenjing Lai,Jiajia Li,Kailin Liu,Hongling Li,Chenglin Hong

The early detection of tumour markers is essential for the timely treatment of cancer, and thus realising the sensitive detection of carcinoembryonic antigen (CEA) is significant. Herein, we employed an electrochemical immunosensor as a simple analytical method. The loading of precious metals significantly amplifies the signal of electrochemical immunosensors. In this study, the successful loading of Au NPs was achieved via the galvanic displacement method. Moreover, CuS nanoflowers possessed intrinsic peroxidase-like activity, which could catalyse the oxidation of o-phenylenediamine (OPD) to generate a light-orange product in the presence of hydrogen peroxide (H2O2). The flower-shaped CuS not only provided active sites for the catalytic reaction, but also possessed a large specific surface area, which could provide abundant sites for the placement of Au nanoparticles. Thus, it was suitable for the labelling of Ab2 for the sensitive detection of CEA. The instant current response (i–t) method detected CEA quantitatively, and the immunosensor prepared under the optimized conditions exhibited an excellent analytical performance. The detection range of the sensor prepared in this study was 0.1–80 ng mL−1 and its detection limit was 5.5 pg mL−1 (S/N = 3).

研究领域: 生物传感器 · 纳米技术 · 癌症诊断 · 电化学
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Journal of Materials Chemistry B · 2022 ·Vol. 10 ·期 43 ·8931-8944 · IF 7.571

A capillary-driven LoC-SERS device integrated with catalytic hairpin assembly amplification technology for NSCLC-related biomarkers detection

Shengjie Ge,Yujie Wang,Zhiyue Li,Bin Lu,Jinhua Zhu,Hongmei Lu,Xiaowei Cao,Yayun Qian

In this study, we apply catalytic hairpin assembly (CHA) as the signal amplification strategy for the quantification of carcinoembryonic antigen (CEA) and cytokeratin fragment antigen 21-1 (CYFRA21-1) with a surface-enhanced Raman scattering (SERS) microfluidic chip (LoC-SERS) as the carrier. Herein, antibody–DNA conjugates are designed to assist the application of CHA amplification in protein detection. In the presence of protein biomarkers, antibody–DNA conjugates can specifically bind to the target proteins, forming the antigen@antibody–DNA conjugates. The terminal free part of the DNA on the conjugates can trigger the CHA events to connect SERS nanotags to capture nanoprobes. Then, micro-magnet can gather the CHA products in a rectangular chamber, resulting in the aggregation of SERS nanotags, which can ultimately generate abundant “hot spots” for SERS signal enhancement. Using this strategy, CEA and CYFRA21-1 can be successfully determined with a limit of detection (LOD) as low as pg mL−1, much lower than recently reported methods. Meanwhile, a non-small cell lung cancer (NSCLC)-xenografted mouse model was established, and SERS was applied to analyze the expression level of CEA and CYFRA21-1 in tumorigenesis and development. The comparison between SERS results and those of the ELISA method demonstrated a high degree of consistency, suggesting that the proposed CHA-assisted LoC-SERS device has satisfying accuracy. Thus, introducing the CHA strategy via the design of antibody–DNA conjugates opens new gates to ultra-sensitive and specific SERS detection of protein biomarkers.

研究领域: 生物医学工程 · 分析化学 · 癌症研究 · 分子生物学
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CHEMICAL ENGINEERING JOURNAL · 2023 · IF 15.1

New luminescent hydrophilic iridium(III) nanoflower at low potential for electrochemiluminescence immunosensing

Li Song,Guangrong Kuang,Gui Zhang,Jiang Guo,Yingzi Fu

Screening effective luminophore is always one of the most essential concerns in highly sensitive electrochemiluminescence (ECL) bioanalysis. Here, a new nanoflower-like iridium(III) J-aggregate (T-Ir) was prepared via nonionic surfactant assisted reprecipitation technique, which possessed good reductive-oxidative ECL activity and performed a strong ECL emission around 626 nm at low potential (−1.10 V) in the presence of potassium persulfate. Thus, T-Ir was employed as a luminophore and good biocompatible matrix to load large amounts of capture antibodies (Ab 1 ). Meanwhile, gold nanoparticles capped cuprous oxide nanocubes (Cu 2 [email protected] ) were used as the efficient quencher to label detection antibodies (Ab 2 ). While different dosages of carcinoembryonic antigen (CEA) were introduced via sandwich immunoreaction, the ECL intensity was significantly dropped due to electrochemiluminescence resonance energy transfer from energy donor (T-Ir) to the acceptor (Cu 2 [email protected] ), achieving the highly sensitive detection of CEA. The proposed immunosensor showed a linear concentration range from 1 fg·mL −1 to 80 ng·mL −1 with a low limit of detection of 0.93 fg·mL −1 (S/N = 3). It featured superior stability, selectivity, reproducibility and practicability. With the successful demonstration of hydrophilic iridium(III)-based nanomaterials, sensing strategies for various biomarkers detection in diseases diagnosis will flourish.

研究领域: 分析化学 · 纳米技术 · 生物化学 · 生物传感器 · 诊断学
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ACS Applied Materials & Interfaces · 2019 · IF 8.456

Target-Driven Cascade-Amplified Release of Loads from DNA-Gated Metal–Organic Frameworks for Electrochemical Detection of Cancer Biomarker

Ting Bao,Ruobing Fu,Wei Wen,Xiuhua Zhang,Shengfu Wang

In this paper, a label-free and stimuli-responsive electrochemical biosensing platform was fabricated based on target-driven load release from DNA-gated metal–organic frameworks (MOFs) with cascade amplification. By using MOFs (UiO-66-NH2) as a nanocarrier of electroactive molecules (methylene blue; MB) and the programmably assembled DNA acted as the gatekeeper, the biofunctionalized MOFs (MB@DNA/MOFs) were not only used as an amplified signal label but also worked as three-dimensional tracks for biosensing. In the presence of a target, the nicking endonuclease cleavage process was triggered, leading to the generation of two strands (S1 and S2). Both S1 and S2 act as stimuli to participate in the strand displacement reaction on the MB@DNA/MOFs, which caused the unlocking of the pore to release MB, resulting in the decrease of the signal. Using carcinoembryonic antigen (CEA) as a model target, the cascade-amplified biosensor presented good performance for CEA detection, ranging from 50 fg/mL to 10 ng/mL with a detection limit of 16 fg/mL. The stimuli-responsive DNA-gated MOF-based electrochemical platform exhibited three-dimensional biosensing tracks with rational utilization of the cascade amplification, providing an effective method for cancer biomarker detection.

研究领域: 生物化学 · 纳米技术 · 电化学 · 癌症研究 · 生物传感器
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MICROCHIMICA ACTA · 2019 ·Vol. 186 ·期 7 ·1-9 · IF 5.479

A sandwich-type electrochemical aptasensor for the carcinoembryonic antigen via biocatalytic precipitation amplification and by using gold nanoparticle composites

Xu Lingling,Liu Zi,Lei Sheng,Huang Di,Zou Lina,Ye Baoxian

A sandwich-type electrochemical aptasensor is described for detecting the carcinoembryonic antigen (CEA) with high sensitivity and accuracy. Two kinds of nanomaterials are used. The first was obtained by modifying gold nanoparticles with reduced graphene oxide and hemin (Hemin-rGO-AuNPs). The second consists of horseradish peroxidase-modified organic-inorganic hybrid nanoflowers linked to gold nanoparticles to obtain an architecture of type HRP-Cu 3 (PO 4 ) 2 -HNF-AuNPs). These serve as carriers for two aptamers (apt1 and apt2) against CEA. Simultaneously, they were used to catalyze the precipitation reaction between 4-chloro-1-naphthol(4-CN) and H 2 O 2 . A sandwich-type assay linked to enzyme inhibition amplification was established for electrochemical determination of CEA. Under optimal experimental conditions and by using differential pulse voltammetry, the response peak currents (best measured at −0.34 V vs. Ag/AgCl) increases linearly with the logarithm of the CEA concentration in the range between 100 fg mL −1 and 100 ng mL −1 . The detection limit is as low as 29 fg mL −1 . Schematic representation of the sandwich-type electrochemical aptasensor based on signal inhibition amplification from biocatalytic precipitation reaction. (HRP-Cu 3 (PO 4 ) 2 hybrid nanoflowers: Horseradish Peroxidase-Cu 3 (PO 4 ) 2 hybrid nanoflowers; AuNPs: Gold Nanoparticles; Hemin-rGO-AuNPs: Hemin-Reduced Graphene Oxide-Gold Nanoparticles; BSA: Bovine Serum Albumin; CEA: Carcinoembryonic Antigen; CEA apt1 : 5′-SH-(CH 2 ) 6 -ATA CCA GCT TAT TCA ATT-3′; CEA apt2 : 5′-NH 2 -(CH 2 ) 6 -AGG GGG TGA AGG GAT ACC C-3′; GCE: Glassy carbon electrode; 4-CN: 4-Chloro-1-naphthol; DPV: Differential pulse voltammetry).

CAS / MDL: 51805-45-9
研究领域: 生物化学 · 分析化学 · 纳米技术 · 癌症诊断
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