Journal of Materials Chemistry B
·
2022
·Vol. 10
·期 9
·1386-1392
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IF 7.571
Ling Yang,Ping’an Ma,Xiaorui Chen,Ziyong Cheng,Jun Lin
Sensitive detection of circulating tumor DNA (ctDNA) in vitro has attracted growing attention owing to its potential application in diagnostics of cancer. In this study, we synthesized hydrophilic AgInS2@ZnS core–shell quantum dot nanocrystals and magnetic Fe3O4 nanoparticles, and then the ctDNA triggered hybridization chain reaction was used to detect the CYFRA21-1 DNA associated with lung cancer. In the presence of CYFRA21-1 DNA, three hairpin structures were activated to turn on successively, resulting in the accumulation of quantum dots and eliciting considerable changes of the fluorescence signal. Compared with the conventional fluorescence detection, Fe3O4 provides magnetic adsorption properties and a large surface area for immobilizing and aggregating quantum dot nanoparticles attached to single-stranded DNA. The concentration of CYFRA21-1 is closely related to the number of quantum dots remaining after magnetic adsorption, which provides a promising approach for ctDNA quantification.
研究领域:
生物化学
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分子诊断
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纳米医学
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DOI
PubMed
高影响因子
Analytical Methods
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2022
·Vol. 14
·期 20
·1956-1962
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IF 3.532
Zhilian Cui,Dujuan Li,Weihuang Yang,Kai Fan,Hongying Liu,Fei Wen,Lili Li,Linxi Dong,Gaofeng Wang,Wei Wu
An electrochemical biosensor based on few-layer molybdenum disulfide (MoS2) nanosheets was fabricated for the highly sensitive detection of tumor marker circulating tumor DNA (ctDNA) in this paper. The MoS2 nanosheets with few layers were prepared by the shear stripping. Compared with the mechanical stripping method and the lithium ion intercalation method, this method is simpler to operate, and the prepared MoS2 nanosheets had good electrochemical activity. The biosensing platform was fabricated based on the discriminative affinity of MoS2 nanosheets towards single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). Methylene blue (MB) was used as the signal molecule. The results showed that the detection of ctDNA by this sensor showed an excellent linear relationship in the concentration range of 1.0 × 10−7 M to 1.0 × 10−16 M, and the detection limit was 2.5 × 10−18 M. In addition, this sensor exhibited outstanding stability and specificity. This strategy provides an alternative approach for ctDNA detection and an effective sensing strategy for future in vitro cancer diagnosis by label-free detection.
研究领域:
生物医学工程
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分子诊断学
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DOI
PubMed
高影响因子
ANALYTICAL BIOCHEMISTRY
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2024
·
IF 2.6
Xinyu Yan,Wei Zhang,Jimin Yang
A self-signal electrochemical identification interface was prepared for the determination of circulating tumor DNA (ctDNA) in peripheral blood based on poly-xanthurenic acid (PXTA) assembled on black phosphorus nanosheets (BPNSs) acquired through simple ultrasonication method. The BPNSs with large surface area could be integrated with the xanthurenic acid (XTA) monomers by right of physisorption, and hence improved the electropolymerization efficiency and was beneficial to the enlargement of the signal response of PXTA. The assembled PXTA/BPNSs composite with attractive electrochemical activity was adopted as a platform for the recognition of DNA immobilization and hybridization. The probe ssDNA was covalently fixed onto the PXTA/BPNSs composite with plentiful carboxyl groups through the terminate free amines of DNA probes by use of the 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydrosulfosuccinimide cross-linking reaction, accompanied with the decline of the self-signal response. When the hybridization between the probe ssDNA and the target DNA was accomplished, the self-signal response of the composite interface reproduced by virtue of the shaping of helix construction. The determination limit of the assembled DNA identification interface was 2.1 × 10 −19 mol/L, and the complementary target DNA concentrations varied from 1.0 × 10 −18 mol/L to 1.0 × 10 −12 mol/L. The DNA identification platform displayed magnificent sensitivity, specificity and stability, and was efficaciously implemented to the mensuration of ctDNA derived from colorectal cancer.
研究领域:
生物医学工程
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分子诊断学
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纳米医学
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DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2023
·
IF 6.2
Xuelan Wu,Ting Ju,Zeyang Li,Jingwen Li,Xingwei Zhai,Kun Han
Circulating tumor DNA (ctDNA) is a noninvasive biomarker which offer valuable information for cancer diagnosis and prognosis. In this study, a target-independent fluorescent signal system, Hybridization chain reaction-Fluorescence resonance energy transfer (HCR-FRET) system, is designed and optimized. Combined with CRISPR/Cas12a system, a fluorescent biosensing protocol was developed for sensing assay of T790 M. When the target is absent, the initiator remains intact, opens the fuel hairpins and triggers the following HCR-FRET. At presence of the target, the Cas12a/crRNA binary complex specifically recognizes the target, and the Cas12a trans -cleavage activity is activated. As a result, the initiator is cleaved and subsequent HCR responses and FRET processes are attenuated. This method showed detection range from 1 pM to 400 pM with a detection limit of 316 fM. The target independent property of the HCR-FRET system endows this protocol a promising potential to transplant to the assay of other DNA target in parallel.
研究领域:
分子生物学
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医学诊断
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生物化学
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DOI
PubMed
高影响因子
Advanced Science
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2025
·
IF 14.1
Shuai Wu,Yincheng Liu,Tianyu Zeng,Tianci Zhou,Yanting Sun,Ying Deng,Juan Zhang,Genxi Li,Yongmei Yin
Continued development of clustered regularly interspaced short palindromic repeats (CRISPR)-powered biosensing system on the electrochemical interface is vital for accurate and timely diagnosis in clinical practice. Herein, an electrochemical biosensor based on manganese metal-organic frameworks (MOFs)-enhanced CRISPR (MME-CRISPR) is proposed that enables the efficient detection of circulating tumor DNA (ctDNA). In this design, customized enzyme stimulants (Mn 2+ ) are co-assembled with Cas12a/crRNA to form enzyme-MOF composites, which can be released quickly under mild conditions. The MOFs-induced proximity effect can continuously provide adequate Mn 2+ to sufficiently interact with Cas12a/crRNA during the release process, enhancing the trans-cleavage activity of complex available for biosensor construction. The MOFs-based enzyme biocomposites also afford efficient protection against various external stimulus. It is demonstrated that the developed biosensor can achieve ultrasensitive detection of epidermal growth factor receptor L858R mutation in ctDNA with a low detection limit of 0.28 f m without pre-amplification. Furthermore, the engineered mismatch crRNA enables the biosensor based on MME-CRISPR to detect single nucleotide variant with a high signal-to-noise ratio. More importantly, it has been successfully used to detect the targets in clinical practice, requiring low-dose samples and a short time. This strategy is believed to shed new light on the applications of cancer diagnosis, treatment, and surveillance.
研究领域:
生物医学工程
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分子诊断学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2021
·
IF 6.558
Kaicha Chen,Hongli Zhao,Zhenxing Wang,Minbo Lan
The detection of circulating tumor DNA (ctDNA) has increasingly received a great deal of attention considering its significance in cancer diagnosis. And the signal amplification plays an important role in the development of sensitive ctDNA biosensors . Herein, the nanocomposites (denoted as HAC-AuPt), integrating from high-active carbon (HAC) and AuPt alloy nanoparticles , were synthesized and subsequently used as a signal amplification label to fabricate a sandwich-type ctDNA electrochemical biosensor. Characterizations demonstrated that HAC presents uniform size distribution and AuPt alloy nanoparticles were successfully loaded on HAC. The current response could be amplified to a great extent by the resultant HAC-AuPt due to its excellent electrochemical property. The nanocomposites were further bounded with DNA signal probes (SPs) via Au-S or Pt-S assembly to form SPs-label. After the capture probes (CPs) were immobilized on the electrode surface, the target DNA (tDNA) and SPs-label were stepwise incubated on the CPs-modified electrode, thus forming a sandwich-type structure. By monitoring the catalytic signal of HAC-AuPt towards the reduction process of H 2 O 2 , this biosensor provided a wide linear range of 10 −8 mol/L - 10 −16 mol/L with a low detection limit of 3.6 × 10 −17 mol/L (S/N = 3) for the detection of the tDNA. Furthermore, obvious differences in response signals among different DNAs were observed benefitting from the excellent selectivity of the biosensor. Besides, the long-term stability, reproducibility, and recovery rate were proved to be outstanding. These results indicate that the established biosensor holds a potential application in the clinical diagnosis of ctDNA.
研究领域:
生物医学工程
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癌症诊断
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纳米技术
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DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
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2019
·
IF 9.518
Zhen Zhang,Mengting Zhu,Zichao Chen,Xiaomeng Wang,Guang Chen,Shusheng Zhang
We herein report the first attempt to engineer a coaxial-sensing 3D amplifier able to achieve dynamic self-assembly in response to a mutated-ctDNA target. A bio-nanofiber is firstly manufactured via an ingenious double-channel electrostatic spinning and DNA rolling circle replication (RCR) technology, which offered an ideal scaffold for assembly of 3D amplifier activated by target recognition. The coaxial-controllable signal amplifier presented several advantages. (1) Given its “coaxial sensing effect”, the proposed bio-amplifier played the coaxial transduction for signal enrichment to vastly increase sensitivity, capable of discriminating a single-base mismatched sequence from the perfectly complementary one, using ctDNA-134A as a model analyte . (2) Due to “covalent bridges lock effect” in an identifying chip with locked nucleic acid beacons, this 3D amplifier expressed high specificity and biostability toward seven different mutated-ctDNAs. (3) Profiting from special configuration of bioactive nanofibers and DNA replication programming, this catalytic bio-amplifier possessed “signal enrichment effect”, which enhanced dynamic range toward ctDNA-134A detection and hybridized without any external indicators . This innovative bio-amplifier has a detection limit of 5.1 aM for ctDNA-134A with superior specificity, excellent sensitivity, and good performance. This pioneered method was further applied for broadly differentiate cells and evaluate changes in the expression levels of intracellular mutated-ctDNAs.
研究领域:
生物医学工程
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分子诊断学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
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2025
·
IF 5.1
Ming Li,Junhu Zhao,Meiyan Liao,Heng Zheng,Fei Cheng,Youhang Zhang,Hanfei Zhang,Pier-Luc Tremblay,Tian Zhang
The accurate detection of circulating tumor DNA (ctDNA) in patients’ biological fluids can facilitate cancer diagnosis and prognosis. This study reports the development of a differential pulse voltammetric (DPV) biosensor for the detection of ctDNA coding for the key T790M lung cancer mutation of the epidermal growth factor receptor (EGFR). The biosensor was built with a working electrode (WE) made of optimized electroconductive particles comprising covalent organic frameworks (COF) displaying Au nanoparticles (Au NPs) modified with polyethyleneimine (COF@Au-PEI). Au NPs accelerated electron transfer while COFs and PEI maximized the architecture of the WE to improve electrochemical reactions and molecular probe binding. Next, hairpin DNA probes (haiDNA) specific to the EGFR T790M ctDNA analyte were bonded to COF@Au-PEI. Lastly, Au@Pt nanohybrids were attached to the WE to enhance its electrochemical performance. In this system, the long polynucleotide EGFR T790M ctDNA analyte interferes with electrochemical reactions upon binding to the haiDNA probes, resulting in a proportional decrease of the DPV signal. The device detected EGFR T790M ctDNA in blood plasma and exhibited good sensitivity, accuracy, stability, and reproducibility. The sensor was also highly selective with no DPV signal for the EGFR wildtype allele harboring a difference of only one base pair.
研究领域:
生物传感器技术
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癌症诊断
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分子生物学
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纳米材料科学
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产品关联
DOI
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2018
·
IF 8.173
Wei Zhang,Zhichao Dai,Xue Liu,Jimin Yang
A high-performance sensing platform based on poly-xanthurenic acid (PXA) film functionalized MoS 2 nanosheets was developed for electrochemical detection of circulating tumor DNA in peripheral blood. The MoS 2 nanosheets were obtained using a simple ultrasonic method from bulk MoS 2 . The physical adsorption between MoS 2 and aromatic XA monomers effectively improved the electropolymerization efficiency, accompanied with an increased electrochemical response of PXA. The obtained PXA/MoS 2 nanocomposite not only served as a substrate for DNA immobilization but also reflected the electrochemical transduction originating from DNA immobilization and hybridization without any complex labelling processes or outer indicators. The immobilization of the probe ssDNA was achieved via noncovalent assembly due to the π–π interaction between PXA and DNA bases. After the hybridization of the probe ssDNA with the target DNA, the formation of helix structure induced the resulted dsDNA to be released from the surface of the PXA/MoS 2 nanocomposite. The detection limit of this constructed DNA biosensor was calculated in the linear target DNA concentrations range from 1.0 × 10 –16 mol/L to 1.0 × 10 -10 mol/L and it was found to be 1.8 × 10 –17 mol/L.
研究领域:
生物医学工程
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分子诊断学
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纳米生物学
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产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2024
·
IF 4.9
Shan Huang,Shuai Liu,Yi Fang,Huihao Li,Mingli Yang,Wei Wang,Sijing Chen,Qi Xiao
Circulating tumor DNA (ctDNA) has emerged as a pivotal biomarker for cancers, offering a non-invasive means of detection through liquid biopsies. However, the current methodologies for ctDNA detection often struggle with sensitivity, especially when confronted with ultra-low concentrations. To address this challenge, we have engineered a remarkably sensitive electrochemical biosensor that can detect low concentration of ctDNA. This breakthrough is achieved by integrating a dual enzyme-assisted amplification mechanism with hybridization chain reaction (HCR). In the initial phase, the presence of ctDNA triggers the unfolding of the H2 hairpin structure, resulting in a segment of double-stranded DNA. The subsequent introduction of Klenow (3′→5′ exo-) and nicking endonuclease (Nb.BbvCI) enzymes leads to the abundant production of extended DNA (EXTDNA). This step critically enhances the initial amplification of the target DNA, ensuring superior specificity and selectivity thanks to the synergistic enzymatic activity. EXTDNA efficiently unfolds the H1 hairpin structure immobilized on the gold electrode, which acts as the initiation point for the HCR . Further amplification of the trace target DNA is achieved through an additional H3 and H4 hybrid-mediated HCR. Finally, the differential pulse voltammetry signal of methylene blue is increased significantly. Our results reveal that the developed electrochemical biosensor displays an exceptional linear correlation with ctDNA across concentrations ranging from 10 fM to 20 pM, with an unprecedented detection limit of 2.3 fM (3 s / k ). This innovative approach shows immense potential for the ultrasensitive detection of ctDNA, promising broad applications in early cancer detection and monitoring.
研究领域:
医学诊断
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生物传感技术
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
ACS Nano
·
2024
·
IF 15.8
Qun Ma,Wenjing Chu,Xianliang Nong,Jing Zhao,Hong Liu,Qiujiao Du,Jielin Sun,Jianlei Shen,Si-Min Lu,Meihua Lin,Yu Huang,Fan Xia
Nanofluidic biosensors have been widely used for detection of analytes based on the change of system resistance before and after target–probe interactions. However, their sensitivity is limited when system resistance barely changes toward low-concentration targets. Here, we proposed a strategy to address this issue by means of target-induced change of local membrane potential under relatively unchanged system resistance. The local membrane potential originated from the directional diffusion of photogenerated carriers across nanofluidic biosensors and gated photoinduced ionic current signal before and after target–probe interactions. The sensitivity of such biosensors for the detection of biomolecules such as circulating tumor DNA (ctDNA) and lysozyme exceeds that of applying a traditional strategy by more than 3 orders of magnitude under unchanged system resistance. Such biosensors can specifically detect the small molecule biomarker in the blood sample between prostate cancer patients and healthy humans. The key advantages of such nanofluidic biosensors are therefore complementary to traditional nanofluidic biosensors, with potential applications in a point-of-care analytical tool.
研究领域:
生物医学工程
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分析化学
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纳米科技
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产品关联
DOI
PubMed
高影响因子
Chemical Science
·
2020
·Vol. 11
·期 14
·3745-3751
·
IF 9.346
Wenting Zhou,Lei Wang,Can Liu,Qiuyi Teng,Zhaoyin Wang,Zhihui Dai
Quantification of circulating tumor DNA (ctDNA) is of great importance in liquid biopsy but difficult due to its low amount in bodily fluids. To meet this high demand, a novel method for ctDNA detection is established by quantifying cyclic DNA polymerization using lanthanide coordination polymers (Ln-CPs). Relying on the coordination between the pyrophosphate ion (PPi) and trivalent cerium ion (Ce3+), organic ligand-free PPi–Ce coordination polymer networks (PPi–Ce CPNs) with enhanced fluorescence are prepared for the first time. By surveying the optical properties of PPi–Ce CPNs, it is found that PPi regulates electric-dipole transition of Ce3+ to the lowest excited state, thus facilitating the emission of fluorescence. Therefore, fluorescence enhancement of PPi–Ce CPNs originates from the ligand field effect rather than the normal antenna effect. Moreover, a new strategy to quantify DNA polymerization is developed based on PPi–Ce CPNs. By introducing multifold cyclic DNA polymerization, a small amount of ctDNA triggers the exponential generation of PPi to form plenty of PPi–Ce CPNs. Accordingly, a biosensor is constructed for sensitive ctDNA detection by measuring the intense fluorescence of PPi–Ce CPNs. The biosensor is capable of sensing ctDNA at the sub-femtomolar level, which is far better than the analytical performances of commercial dyes. Besides, the analytical method is able to detect single nucleotide polymorphism and determine ctDNA in real samples. Considering that DNA polymerization is widely used in bio-recognition, bio-assembly and biomineralization, the work provides a versatile quantitative strategy of making relevant processes precise and controllable.
研究领域:
生物化学
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医学诊断
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材料科学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）