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RSC Advances · 2024 ·Vol. 14 ·期 43 ·31809-31819 · IF 3.9

Efficient and accurate detection of GC-associated miR-96-5p using a competitive lateral flow method based on SERS

Long Jia,Yongxia Liu,Yanqing Zhang,Shuofeng Zhang,Xiaowei Cao,Yemin Xu,Yi Zhao,Bin Deng

To facilitate rapid, efficient, and accurate detection of miR-96-5p associated with gastric cancer (GC), we developed a bioanalytical platform by integrating surface-enhanced Raman spectroscopy with lateral flow assay (SERS-LFA). With these SERS-LFA strips, miR-96-5p within the specimen competed with Au rhombic dodecahedron (AuRD) conjugated single-stranded DNA (ssDNA) to bond to the immobilized hairpin DNA (hpDNA) probe on the T line. Consequently, higher abundance of miR-96-5p led to reduced conjugation of AuRD on the T line, thereby resulting in diminished SERS intensity. The biosensor exhibited a detection time of approximately 30 min and demonstrated a low limit of detection (LOD) for miR-96-5p in PBS buffer solution, down to 3.7 fM. To validate its clinical utility for the early diagnosis of patients with different degrees of gastric lesions, we performed quantitative evaluations in cohorts that included healthy individuals, patients with mild intraepithelial neoplasia, patients with severe intraepithelial neoplasia, as well as patients diagnosed with GC. The results obtained from the SERS-LFA strips were in agreement with those obtained from the quantitative real-time polymerase chain reaction (qRT-PCR). Given the accomplishments, this biosensor has significant potential for the clinical diagnosis of GC, offering a promising avenue for timely detection and improved patient prognoses.

研究领域: 生物医学 · 分子诊断 · 癌症研究
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TALANTA · 2024 · IF 5.6

Early-stage diagnosis of ovarian cancer via digital immunoassay on a SlipChip

Weiyuan Lyu,Xinrui Cheng,Ziqing Yu,Ruirui Dong,Zheyi Sheng,Ting Zhang,Xia Yin,Feng Shen

Ovarian cancer (OC) is one of the three major gynecologic malignancies and has the highest mortality rate because of the late diagnosis. Liquid biopsy based on serum protein biomarkers has demonstrated great potential for early diagnosis but remains limited by the analysis performance of conventional immunoassay technologies, such as chemiluminescence, and biomarkers, such as CA125. To address this challenge and achieve accurate early-stage diagnosis of OC, we developed a digital immunoassay on a SlipChip (DiSC) for quantitative analysis of a potential serum protein biomarker, Spondin-1 (SPON1). The DiSC system achieved a limit of detection (LoD) of 23 fg/μL for digital quantification of SPON1. The DiSC system was utilized to quantify the serum level of SPON1 in 357 clinical serum samples, including 63 from patients with benign ovarian tumors and 294 from patients with malignant ovarian cancer, ranging from stages I to IV. SPON1 concentrations were significantly different in samples from patients with malignant ovarian cancer. Notably, significantly different SPON1 levels were observed in early stages (I and II), in lymph node-negative cases (N 0 ), and before metastasis (M 0 ), suggesting that SPON1 could serve as a sensitive diagnostic biomarker for early-stage OC. The differential diagnostic model based on SPON1 levels quantified using DiSC demonstrated an area under the curve (AUC) of 0.8187 for early-stage OC, a significant improvement over CA-125 (AUC = 0.6967). For OC of all stages, the AUC was 0.8225, which could be further increased to 0.8750 when combined with CA-125. This showcases the potential of SPON1 as a novel biomarker for sensitive early-stage diagnosis of ovarian cancer and the capability of the DiSC system in discovering low-abundance biomarkers for disease diagnosis.

研究领域: 肿瘤学 · 生物医学工程 · 临床诊断
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RSC Advances · 2019 ·Vol. 9 ·期 46 ·26729-26733 · IF 3.049

A highly selective fluorescent probe for human NAD(P)H:quinone oxidoreductase 1 (hNQO1) detection and imaging in living tumor cells

Ya Zhu,Jialing Han,Qian Zhang,Zhou Zhao,Jin Wang,Xiaowei Xu,Haiping Hao,Jun Zhang

Human NAD(P)H:quinone oxidoreductase (hNQO1) can be used as a biomarker for the early diagnosis of cancer. In this article, a novel fluorescent probe 1 for detecting hNQO1 was designed and synthesized by using 2-dicyanomethylene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran (TCF) derivative (TCF-OH) as a fluorophore and quinone propionic acid (QPA) as a recognition group. The probe, which has high selectivity for hNQO1 and a Stokes shift of about 117 nm, shows a linear relationship with hNQO1 concentrations in the range of 0.25–3 μg ml−1 with the color changes from yellow to red and was successfully applied to intracellular hNQO1 imaging.

研究领域: 生物化学 · 医学诊断 · 肿瘤学
✓ 已验证 DOI PubMed 高影响因子
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LUNG CANCER · 2021 · IF 5.705

Breath profile as composite biomarkers for lung cancer diagnosis

Yingchang Zou,Yu Wang,Zaile Jiang,Yuan Zhou,Ying Chen,Yanjie Hu,Guobao Jiang,Duan Xie

Objectives Lung cancer is continuously the leading cause of cancer related death, resulting from the lack of specific symptoms at early stage. A large-scale screening method may be the key point to find asymptomatic patients, leading to the reduction of mortality. Methods An alternative method combining breath test and a machine learning algorithm is proposed. 236 breath samples were analyzed by TD-GCMS. Breath profile of each sample is composed of 308 features extracted from chromatogram. Gradient boost decision trees algorithm was employed to recognize lung cancer patients. Bootstrap is performed to simulate real diagnostic practice, with which we evaluated the confidence of our methods. Results An accuracy of 85 % is shown in 6-fold cross validations. In statistical bootstrap, 72 % samples are marked as “confident”, and the accuracy of confident samples is 93 % throughout the cross validations. Conclusion We have proposed such a non-invasive, accurate and confident method that might contribute to large-scale screening of lung cancer. As a consequence, more asymptomatic patients with early lung cancer may be detected.

CAS / MDL: 625-86-5
研究领域: 医学 · 肿瘤学 · 生物信息学
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JOURNAL OF NANOBIOTECHNOLOGY · 2025 ·Vol. 23 ·期 1 ·1-19 · IF 12.6

CT-sensitized nanoprobe for effective early diagnosis and treatment of pulmonary fibrosis

Hou Jiwei,Ji Qijian,Tang Tianyu,Xue Yonger,Gao Lin,Dai Li,Xie Jinbing

Early diagnosis is critical for providing a timely window for effective therapy in pulmonary fibrosis (PF); however, achieving this remains a significant challenge. The distinct honeycombing patterns observed in computed tomography (CT) for the primary diagnosis of PF are typically only visible in patients with moderate to severe disease, often leading to missed opportunities for early intervention. In this study, we developed a nanoprobe designed to accumulate at fibroblastic foci and loaded with the CT sensitizer iodide to enable effective early diagnosis of PF. An antibody fragment (Fab′) targeting the platelet-derived growth factor receptor-α, which specifically binds to (myo)fibroblasts, was conjugated to the nanoprobe surface to enhance targeting of fibroblastic foci. Additionally, collagenase was employed to facilitate nanoprobe penetration by degrading the local collagen fibers within these foci. This approach led to significant accumulation of the CT sensitizer iodide in fibrotic lung tissues, resulting in enhanced CT imaging for the detection of fibroblastic foci and enabling early diagnosis of PF. Moreover, a dual-drug combination of oltipraz and rosiglitazone was co-loaded into the nanoparticles for the treatment of early-diagnosed PF. Remarkable therapeutic efficacy was observed in model mice with early PF using these nanoparticles. Our findings present a promising strategy for the early diagnosis of PF, potentially offering a valuable time window for effective treatment of this life-threatening disease.

研究领域: 医学影像学 · 药理学
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MICROCHIMICA ACTA · 2024 ·Vol. 191 ·期 9 ·1-9 · IF 5.3

Construction of scalable multi-channel DNA nanoplatform for the combined detection of ctDNA biomarkers of ovarian cancer

Song Yiwei,Jin Xiuyan,Zhao Yiou,Cheng Shuwen,Xu Sai,Bu Shengjun,Liu Liming,Zhou Chunyang,Pang Chunying

Single-level biomarker detection has the limitation of insufficient accuracy in cancer diagnosis. Therefore, the strategy of developing highly sensitive, multi-channel biosensors for high-throughput ctDNA determination is critical to improve the accuracy of early diagnosis of clinical tumors. Herein, in order to achieve efficient detection of up to ten targets for early diagnosis of ovarian cancer, a DNA-nanoswitch-based multi-channel (DNA-NSMC) biosensor was built based on the multi-module catalytic hairpin assembly-mediated signal amplification (CHA) and toehold-mediated DNA strand displacement (TDSD) reaction. Only two different fluorescence signals were used as outputs, combined with modular segmentation strategy of DNA-nanoswitch-based reaction platform; the multi-channel detection of up to ten targets was successfully achieved for the first time. The experimental results suggest that the proposed biosensor is a promising tool for simultaneously detecting multiple biomarkers for the early diagnosis of ovarian cancer, offering new strategies for the early screening, diagnosis, and treatment not only for ovarian cancer but also for other cancers. Graphical abstract

研究领域: 分子生物学 · 医学诊断 · 生物传感技术
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Nanoscale Advances · 2024 · IF 4.6

Fano enhancement of SERS for rapid early diagnosis of colorectal cancer

Tianxun Gong,Zhenjiang Wei,Libin Huang,Yan Hong,Yuan Li,Ke-ling Chen,Wen Huang,Xiaojing Zhong,Jinzhao He,Ming-Yi Lee,En-Chi Chang,Kien Voon Kong,Xiaosheng Zhang,Zongguang Zhou

Patients benefit greatly from early detection of colorectal cancer, but present diagnostic procedures have high costs, low sensitivity, and low specificity. However, it is still difficult to develop a strategy that can effectively detect cancer early using high-throughput blood analysis. Fano resonance-boosted SERS platform label-free serum creates an effective diagnostic system at the point of care. We obtained 220 high-quality SERS serum spectral datasets from 88 healthy volunteers and 132 patients with colorectal cancer. The biomarker detected in serum was further evaluated using 100 colorectal cancer tissues and adjacent normal intestinal tissues collected from West China Biobanks, West China Hospital, Sichuan University. The results showed that in 97 out of 100 paired samples, the biomarkers were successfully detected using the SERS platform. This demonstrates that Fano resonance-based SERS is highly effective for diagnosing colorectal cancer.

CAS / MDL:
研究领域: 医学 · 生物物理学 · 肿瘤学
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ANALYTICA CHIMICA ACTA · 2024 · IF 5.7

A new platform of electrowetting-on-dielectric digital microfluidics for rapid detection of early-stage Hepatocellular Carcinoma(HCC) specific biomarker

Wenjie Zhu,Hong Qian,Shengya Cao,Wei Xia,Xilong Wang,Jing Jin,Xin Wang,Hao Zhang,Dongsheng Liu,Ying Chen

Background The early detection of Hepatocellular Carcinoma (HCC) is crucial for improving patient survival rates.Early diagnosis of HCC can significantly enhance treatment outcomes and reduce disease progression. Antigen detection of tumor markers is one of the important diagnostic methods for HCC. However, Traditional antigen detection methods often rely on heavy detection equipment, involve lengthy turnaround times, and must be conducted in laboratory settings. Therefore, there is a clear need for a portable, low-skill, rapid sample-to-result detection method for early HCC biomarkers. Results We propose a new platform based on electrowetting-on-dielectric digital microfluidic(EWOD-DMF) for the detection of early-stage HCC biomarkers, enabling the quantitative measurement of Alpha-Fetoprotein (AFP), the proportion of AFP-L3 in total AFP (AFP-L3%), and Des-Gamma-Carboxy Prothrombin (DCP). First, serum samples are processed through the microfluidic system, achieving the separation of AFP-L3 within 10 min. Next, immunoassays are performed within 15 min, using magnetic particles to capture biomarkers such as AFP, AFP-L3, and DCP, followed by enzymatic reactions that generate detectable signals. Each chip can simultaneously detect three biomarkers from five different samples, allowing for a total of fifteen targets to be tested, with only approximately 2.4 μL of serum required for each biomarker detection. Ultimately, data are analyzed with dedicated software to quantitatively measure the HCC biomarkers. The detection limits for AFP or AFP-L3 and for DCP are 0.24 ng/mL and 1.89 ng/mL, respectively. Significance This study presents a EWOD-DMF platform for early-stage HCC diagnosis, capable of simultaneously detecting multiple samples and biomarkers, thus improving detection efficiency and diagnostic accuracy. Moreover, the platform has POCT capability, with advantages in portability and cost-effectiveness, providing clinicians and primary healthcare institutions with a fast and convenient solution for early-stage HCC diagnosis.

CAS / MDL: 63148-62-9
研究领域: 医学工程 · 肿瘤学
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ACS Sensors · 2020 · IF 7.333

Molecular Fluorescent Probes for Imaging and Evaluation of Hypochlorite Fluctuations during Diagnosis and Therapy of Osteoarthritis in Cells and in a Mouse Model

Ji-Ting Hou,Bingya Wang,Yuxia Zou,Peiwen Fan,Xueping Chang,Xinhua Cao,Shan Wang,Fabiao Yu

The early diagnosis of osteoarthritis (OA) can halt or delay the progression of the disease, and it is essentially beneficial to its treatment. However, biomarkers with sufficient sensitivity for dynamically identifying early OA are still yet to be determined. The overproduced hypochlorous acid (HOCl) has been proposed as an obvious symptom in early OA. Herein, based on the oxidation reaction of the sulfur atom in phenothiazine into sulfoxide, we design and synthesize a phenothiazine-derived coumarin fluorescent probe PDC for the detection of ClO– in cells and in an OA mouse model. The probe PDC exhibits excellent selectivity and sensitivity for ClO– detection with a limit of detection as low as 16.1 nM. Taking advantage of the probe PDC, we visualize and evaluate the level changes of ClO– in macrophage cells, which is stimulated by various inflammatory factors. The anti-inflammatory and therapeutic effects of selenocysteine and methotrexate in inflamed cells are also confirmed. Finally, with in vivo imaging of ClO– concentration changes in OA BALB/c mouse models, we successfully inspected the relationship between OA phenotypes and the burst of ClO–. We suggest that abnormal changes in HOCl concentration may be considered as a new biomarker for the early OA diagnosis.

研究领域: 生物化学 · 医学影像 · 风湿病学
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Science Advances · 2025 ·Vol. 11 ·期 11 · IF 12.5

FAP-catalyzed in situ self-assembly of magnetic resonance imaging probe for early and precise staging of liver fibrosis

Zhuoyao Wu,Weiwei Zeng,Weitao Yang,Jinyan Yi,Dinghua Liu,Yan Xu,Chang Liu,Kexin Bian,Hui Wang,Bingbo Zhang

Liver fibrosis is an inevitable stage in the progression of most chronic liver diseases. Early diagnosis and treatment of liver fibrosis are crucial for effectively managing chronic liver conditions. However, there lacks a noninvasive and sensitive imaging method capable of early assessing fibrosis activity. Here, we report a molecular magnetic resonance imaging (MRI) probe for imaging fibroblast activation protein (FAP), which is overexpressed on activated hepatic stellate cells (HSCs) even in very early fibrotic livers. This method relies on FAP-catalyzed in situ self-assembly of its substrate probe that leads to the increase of the rotational correlation time (τR) of probe, thereby notably amplifies T1 MRI signal. Thanks to the superior specificity and efficiency of enzymatic reaction, our method has been validated as highly selective and sensitive to FAP in two liver fibrosis mouse models. By establishing a direct correlation between MRI signals and fibrosis activity, our method enables continuous monitoring of liver fibrotic disease progression and assessment of treatment responses.

研究领域: 医学影像学 · 肝脏病学
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ANALYTICAL CHEMISTRY · 2025 · IF 6.7

Primer Exchange Reaction with Cascade RNA Transcription for Highly Specific Detection of Exosomal miRNA and Liver Cancer Diagnosis

Yanming Lai,Wei Xiao,Zhiwei Lei,Huiping Long,Jiting Deng,Yiyu Wang,Lu Tao,Xingxing Liu,Jinjun Wu,Qiwei Zhang,Donglin Cao,Heng Xiao

Exosomal microRNAs (miRNAs) serve as dependable and noninvasive biomarkers for early cancer diagnosis. However, the accurate and feasible detection of exosomal miRNAs is often hindered by their low abundance and the requirement of specialized equipment for miRNA detection. In this study, we present a novel approach, termed primer exchange reaction-based fluorescence emission with cascade RNA aptamers transcription (PERFECT) for the highly sensitive detection of exosomal miRNA. The design of this method involves the selective interaction of a DNA probe with the target miRNA, leading to its activation. Once activated, isothermal signal amplification and RNA aptamer transcription are initiated, resulting in an amplified fluorescent signal within 90 min. This method achieves a detection limit of 2.2 fM at 37 °C and 2.7 fM at room temperature (25 °C). We used the PERFECT technology to analyze miR-21 expression levels in cell extracts, cell-derived exosomes, and human plasma-derived exosomes, achieving a diagnostic accuracy of 93.6% in distinguishing hepatocellular carcinoma (HCC) patients. Overall, this study highlights its broad range of detection temperature, simplicity of the detection process, and strong potential for clinical application, rendering it a promising tool for early cancer diagnosis.

CAS / MDL: 1241390-29-3
研究领域: 分子生物学 · 医学诊断 · 癌症研究
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2019 · IF 3.973

A fluorescent signal “removal” sensor via duplex-specific nuclease-aided cleavage for miRNA detection in flow cytometry

Weipan Peng,Yiwen Huang,Qian Zhao,Guowei Lian,Minghui Chen,Jiafang Piao,Xiaoqun Gong,Jin Chang

Considered as the next-generation biomarkers, microRNAs play an important role in the early diagnosis of cancers. Here, we designed a fluorescent signal “removal” sensor for one-step, sensitive and specific detection of multiple microRNAs by flow cytometry (FCM). In this work, single-stranded DNA (ssDNA), working as the interlinkage, immobilized the fluorescent nanosphere (FS) onto the SiO 2 microspheres surface to form the SiO 2 -ssDNA-FS probes. When target miRNAs integrated with SiO 2 -ssDNA-FS probes, the duplex-specific nuclease (DSN) could cleave the ssDNA selectively and release FS with numerous cycles to enhance the fluorescent signal attenuation of SiO 2 -ssDNA-FS, so as to remarkably improve the analysis sensitivity. It achieved a simple, accurate and quantitative microRNA-21 detection for clinical blood samples. Parallel multi-target detection of microRNA-21 and Let-7d was also realized by different color labeled FS. Moreover, our designed sensor was suitable for other targets’ detection with the corresponding probes.

CAS / MDL: 25952-53-8
研究领域: 分子生物学 · 医学诊断 · 生物技术
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