BIOELECTROCHEMISTRY
·
2022
·
IF 5.76
Jinzhi Liu,Mengyan Wang,Chi Zhang,Gaiping Li,Qi Shen,Lina Zou
Herein, a “signal-on” electrochemical aptasensor based on dual-output toehold mediated strand displacement reaction (TMSDR) was developed to detect cytokeratin fragment antigen 21–1 (CYFRA 21–1). First, the methylene blue (MB) labeled signal probe (SP) was combined with a long template strand (TS) to form the three-strands duplex, which was immobilized on magnetic beads. The sequence of TS was innovatively designed with two toehold zones. Thus, with the presence of target DNA and Fuel strand (F), double SP and target were released through TMSDR. Besides, the released target could participate in the next cycle, achieving the further amplification. The released SP was selected by magnetic separation, then added to the gold electrode (GE) to hybridize with the hairpin DNA. Ultimately, the target can be detected by recording the current response of the MB. Under optimized conditions, the response peak current was linear with the concentration of CYFRA 21–1 in range from 10 pM to 1 μM with detection limit of 8.079 pM. The proposed signal amplification strategy was enzyme-free in homogenous solution and the using of magnetic beads improved the recognition efficiency and simplified the experimental steps, which endowed the sensor with super-sensitivity.
研究领域:
生物化学
·
医学检测
·
分子生物学
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DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2020
·
IF 3.594
Lulu Hao,Liying Zhao,Guangbao Li,Yingying Li,Ligang Ma,Yanju Liu,Wenbin Wang,Jinming Kong
Cytokeratin fragment antigen 21-1 (CYFRA 21-1) DNA is a significant biomarker with relation to non-small cell lung cancer. Here, we described an ultrasensitive electrochemical biosensor for detection of CYFRA 21-1 DNA (target DNA, tDNA) via surface-initiated reversible addition fragmentation chain transfer (SI-RAFT) polymerization-based DNA metallization signal amplification strategy. Specifically, 5′terminal modified thiol peptide nucleic acid (PNA) probes are immobilized on the gold electrode surface (by Au-S selfassembly) for the identification of specific tDNA sequences. After hybridization, the 4-cyano-4-(phenylcarbonothioylthio) pentanoic acid (CPAD) is tethered to the PNA/DNA duplexes by means of the recognized phosphate-Zr 4+ -carboxylate chemistry. Subsequently, in the situation of C 3 H 4 O as the monomer, SI-RAFT polymerization can bring numerous aldehyde groups sites for the subsequent silver mirror reaction. The acrolein-polymers act as reductant to reduce Ag + into Ag 0 , and then the silver particles are deposited on the polymer skeleton, which significantly amplifies the electrochemical signal. Under optimal conditions, the designed sensor for tDNA detection show a wide linear range from 100 aM to 1 nM, and the detection limit is as low as 0.89 aM. Moreover, the proposed biosensor exhibits prominent applicability for analysis of tDNA in serum samples and high selectivity for different mismatched oligonucleotide fragments. Given the proposed biosensor without extra natural enzyme or bio-labels, this method has enormous potential in bioanalysis.
研究领域:
生物技术
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医学诊断
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分子生物学
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产品关联
DOI
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2020
·Vol. 412
·期 11
·2413-2421
·
IF 3.637
Wang Xia,Zhang Yawen,Zhao Liying,Wang Dazhong,Yang Huaixia,Kong Jinming
An ultrasensitive fluorescence biosensor for detecting cytokeratin fragment antigen 21-1 (CYFRA 21-1) DNA of non-small cell lung carcinoma (NSCLC) is designed using polysaccharide and activator regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP) signal amplification strategy. Thiolated peptide nucleic acid (PNA) is fixed on magnetic nanoparticles (MNPs) by a cross-linking agent and hybridized with CYFRA 21-1 DNA. Hyaluronic acid (HA) is linked to PNA/tDNA heteroduplexes in the form of carboxy-Zr 4+ -phosphate. Subsequently, multiple 2-bromo-2-methylpropionic acid (BMP) molecules are linked with HA to initiate ARGET ATRP reaction. Finally, a large number of fluorescein o-acrylate (FA) monomers are polymerized on the macro-initiators, and the fluorescence signal is significantly amplified. Under optimal conditions, this biosensor shows a significant linear correlation between the fluorescence intensity and logarithm of CYFRA 21-1 DNA concentration (0.1 fM to 0.1 nM), and the limit of detection is as low as 78 aM. Furthermore, the sensor has a good ability to detect CYFRA 21-1 DNA in serum samples and to recognize mismatched bases. It suggests that the strategy has broad application in early diagnosis by virtue of its high sensitivity and selectivity.
A novel and highly sensitive fluorescence biosensor for quantitatively detecting CYFRA 21-1 DNA via dual signal amplification of hyaluronic acid and ARGET ATRP reaction was developed. This proposed method has a low detection limit, wide detection range, high selectivity, and strong anti-interference.
研究领域:
生物技术
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癌症研究
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纳米技术
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2019
·
IF 9.518
Liying Zhao,Huaixia Yang,Xiaoke Zheng,Jinge Li,Lihe Jian,Weisheng Feng,Jinming Kong
Cytokeratin fragment antigen 21–1 (CYFRA 21–1) DNA is a crucial biomarker closely associated with non-small cell lung cancer. Here, we fabricated a novel electrochemical biosensor for ultrasensitive detection of CYFRA 21–1 DNA via polysaccharide and electrochemically mediated atom transfer radical polymerization (eATRP) dual signal amplification . Specifically, thiolated peptide nucleic acid (PNA) probes at 5′-terminals are immobilized on the gold electrode surface for specific recognition of CYFRA 21–1 DNA (tDNA). After hybridization, hyaluronic acid (HA) is linked to the hybridized PNA/DNA duplexes via the recognized carboxylate-Zr 4+ -phosphate chemistry . Then multiple initiators of the polymerization reaction are introduced via esterification reaction. Lastly, large numbers of electro-active monomers are successfully grafted from the initiation sites of functionalized HA by eATRP reaction, significantly amplifying the electrochemical signal. Under optimal conditions, the constructed sensor can detect as low as 9.04 aM tDNA. Further, this proposed biosensor can also be applied to the direct detection of double-stranded DNA (dsDNA), obtaining 0.12 fM as the detection limit. Besides, this strategy shows high selectivity for mismatched bases and excellent applicability for CYFRA 21–1 DNA detection in the serum samples. Given its high sensitivity, selectivity, ease of operation, low cost and environmental friendliness , this biosensor has considerable potential in early diagnosis and biomedical application .
研究领域:
生物化学
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癌症研究
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分析化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2023
·
IF 5.8
Ke Cai,Wei Pi,Jiangyang Qin,Chenxi Peng,Dandan Wang,Yingying Gu,Yong Mei
In this study, an electrochemical immunosensor was constructed to detect the cytokeratin 19 fragment antigen 21-1 (CYFRA 21-1) in human serum. CYFRA 21-1 is the most sensitive tumor marker of non-small cell lung cancer (NSCLC), its content in normal human serum should be less than 3.3 ng/mL. When lung cancer cells dissolve or die, a myriad of CYFRA 21-1 is released into a tumor patient’s blood circulation , and its serum content elevates strikingly. Consequently, detecting CYFRA 21-1 by an electrochemical biosensor is expected to provide a new method for the early detection and prevention of lung cancer. In this study, a composite of UiO-66-NH 2 and carboxylated multi-walled carbon nanotubes (CMWCNTs) was used as the substrate material of a sensor; the resulting sensor had a large specific surface area and strong electrical conductivity . Moreover, gold nanoparticles (AuNPs) were used to bind to antibodies through an Au-S bonds. Also, a supersensitive detection of CYFRA 21-1 was achieved through the specific bindings of antigens and antibodies. Under optimal detection conditions, the change of current signal intensity of the immunosensor was proportional to the logarithm of CYFRA 21-1 concentration and had a linear relation in the range of 0.005–400 ng/mL, while the detection limit was 1.15 pg/mL (S/N = 3). The proposed immunosensor had high precision, stability, and selectivity . More importantly, the sensor was been successfully applied to detect CYFRA 21-1 in human serum with high recovery, providing a new method for early screening and dynamic monitoring of lung cancer.
研究领域:
生物医学工程
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分析化学
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癌症研究
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纳米技术
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产品关联
DOI
PubMed
高影响因子
TALANTA
·
2020
·
IF 5.339
Xiaofei Li,Yawen Zhang,Lulu Hao,Yanju Liu,Xia Wang,Huaixia Yang,Jinming Kong
Cytokeratin fragment antigen 21-1 (CYFRA 21-1) DNA is perceived as sensitive tumor marker for the diagnosis of non-small cell lung cancer and other tumor. Herein, linear chain poly(ε-caprolactone) (PCL) synthesized by ring-opening polymerization is applied to ultrasensitive label-free electrochemical impedance detection system for CYFRA 21-1 DNA. First, thiolated peptide nucleic acid (PNA) is self-assembled into the Au electrode surface through the formation of Au–S bonds, allowing the PNA to act as biomolecular probe and form PNA/DNA heteroduplex with the target DNA via specific hybridization. Then, PCL is conjugated to the immobilized DNA on the electrode via “carboxylate–Zr 4+ –phosphate” bridges. Finally, the electrochemical response of modified PNA/DNA/Zr 4+ /PCL electrode is determined by electrochemical impedance method to quantify of CYFRA 21-1 DNA. Under optimal conditions, this method exhibits highly sensitivity with a broad linear range (0.1 fM – 1 nM) ( R 2 = 0.995) and the limit of detection (LOD) is as low as 10.73 aM, which is equivalent to just 64 molecules in a 10 μL sample. What's more, the high selectivity , good anti-interference, label-free operation, and real-time monitoring in complex samples of the proposed strategy demonstrate its broad application for the early diagnosis and clinical monitoring.
研究领域:
生物医学工程
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分析化学
·
分子生物学
·
癌症诊断
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产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2021
·
IF 4.821
Yawen Zhang,Xia Wang,Xiang Fang,Xianxian Yuan,Huaixia Yang,Jinming Kong
As importance of early diagnosis, prognosis, and clinical monitoring in improving survival rate of lung cancer is increasing, the advance of effective diagnostic method for tumor marker is crucial. Herein, linear poly( ε -caprolactone)- b -poly(ethylene oxide) (PCL-PEO) copolymer with hydrophilic property is applied to detect CYFRA 21-1 in label-free electrochemical immunoassay. 4-(2-trimethylsilylethynyl)benzoic acid (TEB) as “bridge” bond first connects initial antibody to the surface of gold electrode. Then one side of CYFRA 21-1 antigen can recognize with initial antibody of electrode interface, and the other side hybridize specifically secondary antibody grafted PCL-PEO copolymer. So far we have constructed a complete immunoassay for CYFRA 21-1 detection using electrochemical impedance spectroscopy. The sensitivity and selectivity of analytical method depend on “Au–C” bonding, specific recognition of “antibody-antigen–antibody sandwich”, and PCL-PEO copolymer. Under optimal conditions, the analytical method for quantitative detection of CYFRA 21-1 manifests a broad linear range (1 pg/mL–10 ng/mL) and a low detection limit (0.125 pg/mL, about 3.47 × 10 -15 M). Furthermore, according to the analysis results in clinical samples, the constructed strategy also shows satisfactory sensitivity and anti-interference. It indicates that the immunoassay has broad promising applications for expecting to be applied in practical clinical prevention and monitoring.
研究领域:
生物化学
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分析化学
·
生物医学工程
·
癌症研究
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产品关联
DOI
高影响因子
ANALYTICAL LETTERS
·
2023
·
IF 2
Jiajia Wang,Xiaomin Yang,Xin Hua,Yanan Li,Baokang Jin
Previous studies confirm that aberrant expression of cytokeratin 19 fragment antigen 21-1 (cyfra-21-1) is highly correlated with non-small cell lung cancer (NSCLC). Herein, a proportional electrochemical immunosensor based upon a methylene blue/cadmium telluride/molybdic sulfide (MB/CdTe/MoS2) nanocomposite was successfully fabricated for detecting tumor marker cyfra-21-1. The result indicates that MB/CdTe/MoS2 modified on the surface of a glassy carbon electrode (GCE) supplies a large surface area for immobilizing primary antibodies (Ab1), ensuring high selectivity and sensitivity. To further amplify the sensitivity of the biosensor, ferrocenecarboxylic acid (Fc-COOH) linked with amino-functionalized secondary antibodies through amido bond (Ab2-Fc) as the “signal-on” probe and MB-modified with MoS2 with a large specific surface area as the “signal-off” probe increase the number of active sites for integration of Ab2-Fc/Ag/BSA/Ab1/MB/CdTe/MoS2/GCE electrode with the linker cyfra-21-1 (Ag). Meanwhile, CdTe accelerates the electron transfer and enhances the MB current, improving the sensitivity and detection limit. The presence of cyfra-21-1 led to both the decreasing response of MB and increasing current responses of Fc upon the electrode. Based upon this strategy, the determination of cyfra-21-1 was achieved in a linear range from 10 pg/mL to 10,000 ng/mL with the lowest detectable concentration of 10 pg/mL (signal-to-noise ratio of 3). The electrochemical immunosensor performs a sensitive determination of cyfra-21-1, possibly providing a practical strategy for the clinical analysis of lung cancer.
研究领域:
生物化学
·
分析化学
·
肿瘤学
·
纳米技术
·
电化学
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产品关联
DOI
高影响因子
IEEE SENSORS JOURNAL
·
2024
·Vol. 24
·期 11
·18350-18358
·
IF 4.3
Haiming Qiu,Jiajun Tian,Ying Gao,Cheng Zhou,Yong Yao
Herein, we propose and demonstrate a fiber-optic immunosensor based on the high-order-harmonic Vernier effect (HVE) and cascaded dual Fabry–Pérot interferometers (FPIs) for detecting the cytokeratin 19 fragment 21–1 (CYFRA 21-1). The proposed sensor was fabricated by splicing a single-mode fiber (SMF), a hollow-core photonic crystal fiber (HCPCF), and an SMF pigtail. The high-order HVE occurs between the HCPCF (reference FPI) and SMF segment (sensing FPI). To enhance the interaction between the sensing FPI and external medium, graphene oxide (GO) with a large specific surface area and abundant oxygen-containing functional groups is deposited on the SMF pigtail end face. Subsequently, the SMF pigtail end surface is immobilized with the anti-CYFRA 21–1 antibody to detect CYFRA 21-1. Antigen–antibody binding changes the sensing layer thickness and roughness, resulting in changes in the reflectance spectrum. HVE can substantially improve the refractive-index sensitivity of a sensor. In our experiments, we obtained a high sensitivity of 162000 nm/RIU, which is two orders of magnitude higher than that obtained without HVE (1270 nm/RIU). Furthermore, the special structure of the proposed immunosensor results in a low noise level (±0.07 nm). On this basis, the proposed immunosensor was used for CYFRA 21–1 detection, and a limit of detection (LOD) of 1.6 fg/mL was achieved. Thus, the proposed immunosensor has the advantages of ultrahigh sensitivity, high fabrication tolerance, simple structure, strong stability, and good robustness. To the best of our knowledge, this study is the first to apply HVE to fiber-optic immunosensors.
研究领域:
生物医学工程
·
光学传感
✓ 已验证
产品关联
DOI
高影响因子
MICROCHIMICA ACTA
·
2026
·Vol. 193
·期 8
·559
·
IF 5.4
Wu Minjin,Yu Wenzhan,Xu Yue,Zou Guangrui,Huang Zihao,Li Ling,Li Jianping
A self-enhancing Cu-TBAPy MOF was synthesized, which serves as both an electrochemiluminescence (ECL) emitter and a dual coreactant accelerator. It was then employed as an ECL probe to construct a highly sensitive ECL immunosensor for the sensitive determination of the lung cancer marker Cyfra 21 − 1. Benefiting from its rigid framework structure and the spatial confinement of the TBAPy ligand imposed by Cu 2+ coordination, thermal dissipation of the excited-state energy from the ligand is effectively suppressed, resulting in a strong ECL signal that renders this material suitable as a probe for ECL immunosensors. Moreover, the Cu 2+ sites within the MOF catalyze the reduction of K 2 S 2 O 8 at the electrode to produce the coreactant SO 4 •‒ . Meanwhile, the MOF exhibits peroxidase-like activity, catalyzing the reduction of H 2 O 2 to generate hydroxyl radicals (OH • ), which further react with K 2 S 2 O 8 to yield additional SO 4 •‒ . Through the dual promotion mechanism, the ECL signal of the MOF is substantially enhanced. The Cu-TBAPy MOF was employed as a probe, and secondary antibody‑labeled polydopamine nanospheres (PDA NPs) were introduced as signal regulators in a sandwich immunoassay. The ECL quenching was achieved through the dual effects of ECL resonance energy transfer between PDA and the MOF, combined with the scavenging of hydroxyl radicals by PDA. Based on the changes in the ECL signal, an ultrasensitive determination of Cyfra 21 − 1 was realized, with a linear range from 10 fg/mL to 10 ng/mL and a detection limit as low as 2.04 fg/mL. The sensor has been successfully applied to the determination of Cyfra 21 − 1 in serum samples. Graphical
✓ 已验证
DOI
高影响因子
ANALYTICAL SCIENCES
·
2019
·Vol. 36
·期 6
·681-685
·
IF 1.618
Liu Wenwen,Ma Ligang,Guo Zhuangzhuang,Liu Tao,Liu Yanju,Wang Dazhong,Kong Jinming
We propose a novel, ultrasensitive and low-cost sensor using reversible addition-fragmentation chain transfer (RAFT) polymerization as a signal amplification strategy for the detection of CYFRA 21-1 DNA fragment, a tumor marker of non-small cell lung carcinoma. The peptide nucleic acid (PNA) probes were firstly immobilized on magnetic beads (MBs) to capture the CYFRA 21-1 DNA specifically. After hybridization, CPAD was tethered to the hetero duplexes through carboxylate-Zr 4+ -phosphate chemistry. Subsequently, a number of fluorescent tags were introduced to the heteroduplexes through RAFT polymerization, leading to an amplification of the fluorescence signal. The sensor demonstrates a low limit of detection (LOD) of 0.02 fM. It has great selectivity with respect to base mismatch DNA, and high anti-interference ability in normal human serum. Overall findings of the study suggest that proposed sensor holds enormous potential to be used as a tool for the early-stage diagnosis of lung cancers.
研究领域:
生物技术
·
癌症诊断
·
纳米技术
·
分析化学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）