Journal of the American Chemical Society
·
2026
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IF 16.6
Xinwei Zhang,Chonglu Li,Mingzhe Yan,Yuting Wang,You Dou,Tuotuo Zhang,Shuo Zheng,Hanying Wang,Junrong Li,Yao Sun
Precise profiling of multiple circulating tumor DNA (ctDNA) is hindered by the challenge of resolving single-nucleotide variants (SNVs) and their trace abundance. Herein, we present an integrated SERS platform that combines rationally molecularly engineered nanotags with a novel microturbulent electrofluidic interface for multiplexed SNV-level profiling of lung cancer ctDNAs. In particular, the SERS nanotags incorporate (1) a de novo isomeric Raman reporter library that systematically tailors vibrational signatures through molecular symmetry and electronic effects, (2) hollow hyperbranched Cu2O/CuO@Ag heterostructures engineered to suppress carrier recombination for maximized electromagnetic–chemical signal enhancement, and (3) rationally designed dCas9–sgRNA units that confer single-nucleotide discrimination. To overcome diffusion-limited mass transport and further boost the signal, we fabricated nanopebble-structured asymmetric microelectrodes on aluminum foil. Unlike a conventional smooth interface, this unique topography induces powerful microturbulence-enhanced electrohydrodynamics (mt-EHD) that disrupts the interfacial depletion layer to accelerate target delivery while simultaneously offering high-density “hot spots” within interpebble gaps for secondary Raman signal amplification. This integrated system achieved the simultaneous quantification of six ctDNA mutations in 131 clinical samples. By leveraging machine learning algorithms, the platform enables accurate diagnosis, prognostic stratification, and dynamic treatment monitoring, establishing an integrated chemical–electrofluidic strategy for precision liquid biopsy.
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PubMed
高影响因子
MICROCHIMICA ACTA
·
2021
·Vol. 189
·期 1
·1-10
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IF 5.833
Meng Yuchan,Qin Nana,Hun Xu
ZnSe nanodisks:Ti 3 C 2 MXene complex was prepared for the first time. Based on its remarkable photoelectrochemical performance, combined with the enzyme-free toehold-mediated strand displacement reaction, a photoelectrochemical biosensor for the detection of the non-small-cell cancer biomarker ctDNA KRAS G12D was developed. ZnSe nanodisks were in situ grown on Ti 3 C 2 MXene surface by two-step hydrothermal method. The high conductivity and adjustable band gap of MXene significantly enhanced the photoelectric response of ZnSe. Subsequently, the photoelectrochemical biosensor was prepared by combining with the signal amplification function of p- aminophenol and the enzyme-free toehold-mediated strand displacement reaction on the modified ITO electrode surface. Under the optimized conditions, the linear detection range is 0.5 ~ 100.0 fM, and the detection limit is 0.2 fM, which realizes the sensitive detection of KRAS G12D. The photoelectrochemical biosensor constructed opens up a new pathway for the preparation of new Mxene-based composite materials and the research of photoelectrochemical biosensor. Graphical abstract Nucleic acid liquid biopsy with ZnSe nanodisks:Ti 3 C 2 MXene photoelectroactive modified electrode
研究领域:
材料科学
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生物医学工程
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分析化学
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癌症诊断
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PubMed
高影响因子
BIOELECTROCHEMISTRY
·
2026
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IF 4.9
Mingzhu Yang,Dujuan Li,Ao Wang,Yifan Zhang,Jiale Ouyang,Xinyi Wang,Liang Hong,Dingyi Tong,Minghua Wang,Jianhan Lin,Qiong Luo,Gaofeng Wang
Breast cancer, a globally prevalent malignancy in women, requires early diagnosis to improve patient outcomes, where ctDNA serves as a key biomarker. In the present study, an electrochemical biosensor based on CRISPR/Cas12a and Au@UiO-66 nanozyme synergistic dual amplification was developed to achieve ultrasensitive detection of breast cancer marker ctDNA. Au@UiO-66-modified ssDNA probes were anchored to the gold electrode via thiol groups. The intact ssDNA probe anchors Au@UiO-66 nanozyme to the electrode, where its peroxidase-like activity efficiently catalyzes H 2 O 2 reduction to generate amplified reduction peak currents. Target ctDNA activates Cas12a's trans-cleavage capacity by binding specifically to crRNA. Under the presence of the target, Au@UiO-66 nanozymes are released, resulting in a discernible drop in the peak current linked to H 2 O 2 reduction. Benefiting from the optimized experimental conditions, the biosensor demonstrates a broad linear detection range (from 10 fM to 10 nM) for the target ctDNA, along with an exceptionally low detection limit of 6.14 fM. Successful detection in human serum samples demonstrates its practicality. The platform's high specificity is attributed to the programmable crRNA design, enabling detection of specified DNA sequences and showcasing significant adaptability for diagnosing multiple genetic targets, highlighting its potential in clinical cancer diagnosis.
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高影响因子
Analytical Methods
·
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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PubMed
高影响因子
ANALYTICA CHIMICA ACTA
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2023
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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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PubMed
高影响因子
BIOELECTROCHEMISTRY
·
2025
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IF 4.5
Ai Ting Cai,Qing Ping Fu,Ming Zhong Sun,Hong Mei Chen,Yun Gang Wang,Hui Xiang Jv
The detection of BRAF mutations in circulating tumor DNA is beneficial for early diagnosis and personalized therapeutic approaches of melanoma. However, the sensitive and reliable trace detection of BRAF mutations remains a major challenge. Therefore, in this study, the combination of two isothermal signal amplification techniques (primer exchange reaction (PER) and hybridization chain reaction (HCR)) was proposed to construct an electrochemical biosensor for the efficient and sensitive detection of BRAF mutations. The presence of target triggered PER and HCR sequentially to achieve dual-cascade amplification of positive electrochemical signal feedback. Compared to the detection limit (1.27 pM or 0.23 pM) of single-signal amplification technology (PER or HCR), the detection limit of dual-signal amplification techniques was significantly lower (0.34 fM). In addition, the dual-signal amplification strategy exhibited other excellent sensing properties, such as a wide linear detection range (0.01 pM to 1 nM), excellent specificity, satisfactory reproducibility and stability, and the ability to achieve low-level target detection in diluted serum samples. Based on all of these features, the proposed strategy indicate broad application prospects for detecting low-abundance nucleic acid targets in clinical samples.
研究领域:
生物传感器
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分子诊断
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生物化学
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癌症研究
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分析化学
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遗传学
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电化学
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PubMed
高影响因子
MICROCHIMICA ACTA
·
2024
·Vol. 191
·期 11
·1-11
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IF 5.3
Wei Yuxin,Fu Yang,Li Chuanhai,Chen Siyu,Xie Linzhi,Chen Mei
A electrochemical biosensor was designed utilizing a CRISPR Cas9n-driven DNA walker combined with gold-nanosphere-like covalent organic frameworks (COFs-AuNPs) to detect breast cancer markers (PIK3CA E545K ctDNA). The DNA walker probe is activated only in the presence of circulating tumor deoxyribonucleic acid (ctDNA), binding to a support probe to form a double strand that is then specifically cleaved by the Cas9n/sgRNA complex. This cleavage produces numerous DNA fragments for signal amplification. The COF-AuNPs as electrode materials facilitate electronic transfer and provide additional active sites for the immobilization of nucleic acid probes. This setup achieves a detection limit of 1.76 aM, demonstrating high sensitivity. Additionally, Cas9n improves the specificity of the sensor, accurately distinguishing a pair of base-mismatched sequences, and reducing the occurrence of false positives. Overall, the sensor exhibits excellent selectivity, reproducibility, and potential for early diagnosis of breast cancer. Graphical Abstract
研究领域:
生物技术
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癌症生物学
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纳米技术
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电化学
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分子诊断
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PubMed
高影响因子
MICROCHEMICAL JOURNAL
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2022
·
IF 5.304
Jia Wei,Yaoqi Wang,Jiaxue Gao,Zhenshengnan Li,Renzhu Pang,Tianchao Zhai,Yuan Ma,Zhenxin Wang,Xianying Meng
Qualitative and quantitative analysis of carcinogenic mutations in circulating tumor DNA (ctDNA) plays a unique role in the early screening and precise diagnosis of cancer. Herein, we introduced an electrochemical-enrichment assisted amplification refractory mutation system-quantitative real-time PCR (EC-ARMS-qPCR) assay to detect the BRAF V600E carcinogenic mutation of thyroid cancer in plasma samples. Cell-free DNA (cfDNA) were firstly enriched by an electric field-driven adsorption and desorption process, and then ctDNA in cfDNA were analyzed by a designed allele-specific qPCR assay. The EC-ARMS-qPCR assay provides good sensitivity and specificity for the identification of single nucleotide polymorphisms (SNPs) of BRAF V600E mutant ctDNA in a complex system, which can detect as low as 2 BRAF V600E mutant copies in Tris buffer and 25 BRAF V600E mutant copies in Tris buffer containing 50% plasma with a allele frequency of 0.01% (i.e., mutant-to-wild-type ratio of 1: 9999). The assay was assessed in plasma samples of patients with papillary thyroid cancer (PTC) and benign thyroid nodule (TN). The EC-ARMS-qPCR assay detected 40.74% and 10.00% BRAF V600E mutation ctDNA in plasma samples of 54 PTC patients and 20 TN patients, respectively. The overall concordance between BRAF V600E mutant ctDNA by EC-ARMS-qPCR assay and BRAF V600E mutant of matched pathological tissue genes by fine needle aspiration biopsy (FNAB) is 73.08%, suggesting that the EC-ARMS-qPCR assay is appropriate for detecting carcinogenic mutations in liquid biopsy samples.
研究领域:
肿瘤学
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分子生物学
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医学遗传学
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临床诊断
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高影响因子
ACS Omega
·
2020
·
IF 2.87
Bojuan Hao,Kaige Wang,Yukun Zhou,Chaofan Sui,Lei Wang,Ren Bai,Zhaojin Yang
DNA molecular compaction/decompaction is of great significance for the exploration of basic life processes, the research of biomedical and genetic engineering, and so forth. However, the detailed mechanism of DNA compaction/decompaction caused by surfactants remains an open and challenging problem that has not been fully solved so far. In this paper, a sort of novel solid substrate, nanoPAA-ZnCl2-AuLs, with good stability and high sensitivity, was prepared by a self-assembly method. Based on this substrate, the surface-enhanced Raman scattering (SERS) technology was employed to investigate characteristics of interactions between DNA molecules and surfactants at a single molecular level. SERS spectra of calf thymus DNA (ctDNA), cetyl trimethyl ammonium bromide (CTAB), and sodium dodecyl sulfate (SDS) with a concentration as low as 10–9 M, and SERS spectra of ctDNA–CTAB and ctDNA–CTAB–SDS composites were collected, respectively. The interactions between ctDNA and surfactants were analyzed by changes in SERS spectra, for example, disappearances and appearances of SERS bands and relative changes of peak intensity, in which CTAB resulted in the compaction of the DNA molecule while SDS induced the decompaction of the ctDNA–CTAB complex. Moreover, UV–visible spectrophotometry was employed to demonstrate the compaction/decompaction of ctDNA molecules caused by surfactants. The local binding modes of ctDNA molecules and surfactant molecules were expounded. This work will be helpful for understanding biological processes such as DNA compaction and recombination within nucleus or/and cells and for the development of gene therapy technologies.
研究领域:
生物物理学
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分子生物学
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基因治疗
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PubMed
高影响因子
危险品化学品经营许可证（带存储）