SENSORS
·
2025
·Vol. 25
·期 11
·3347
·
IF 3.5
Bei Wang,Gengyu Liang,Lingqin Meng,Han Li,Zishuo Song,Yang Xu,Yonghong He,Deling Duan,Qiuxia Shi,Tian Guan,Ya Gong
Simultaneous detection of multiple biomarkers is essential for effective cancer screening. Taking ovarian cancer as an example, the combined detection of CA125 and HE4 has proven to be the most efficient and accurate among multiple biomarker combinations. In this study, we proposed a dual immunosensor based on weak value amplification (WVA) to detect ovarian cancer. By modifying the sensor surface through a self-assembled monolayer technique and utilizing recombinant protein G for antibody enrichment and directional capture, the sensor enables high-precision, simultaneous detection of CA125 and HE4, with detection limits of 5.39 U/mL and 1.79 ng/mL, respectively. Furthermore, the sensor demonstrates excellent specificity, effectively distinguishing target analytes from non-target molecules. This study provides a novel approach for early cancer screening and clinical diagnosis, highlighting the potential of WVA-based immunosensors in ovarian cancer detection.
研究领域:
生物医学工程
·
肿瘤学
·
诊断技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2025
·
IF 5.1
Lianming Zhang,Kaiting Li,Junzhe Gong,Dan Li,Zhifan Lin,Jianping Li
To enhance the stability, sensitivity, and selectivity of protein sensors for detecting trace human epididymis protein 4 (HE4), sodium alginate (SA) was employed as a protein carrier in this study. After the gelation of SA, the number of active sites of a protein sensor increased and sensor stability improved, leading to the development of a novel, highly sensitive protein sensor based on the conformation of HE4 immobilized within the SA-gel. The surface of a glassy carbon electrode was modified with SA, where the numerous active sites within SA molecular chains induced and stabilized the spatial conformation of HE4. Under the influence of Ca 2+ , SA contracted to form a gel. Upon the elution of HE4, a three-dimensional cavity structure highly complementary to the spatial conformation of HE4 was formed, resulting in the formation of HE4@SA-gel sensor with excellent selectivity and high sensitivity for HE4. Results demonstrated that changes in the probe molecule signal intensity (Δ i ) were linearly and positively correlated with the logarithm of the HE4 concentration (lg( C , mol/L)) in the range from 1.00 × 10 −13 –3.00 × 10 −9 mol/L, with a limit of detection (LOD) of 2.37 × 10 −14 mol/L (LOD = 3σ/ S ). Comparison results indicated that the prepared HE4@SA-gel sensor exhibited a 12.7-fold increase in sensitivity and an 11.36-fold improvement in selectivity compared with nongelated HE4@SA sensor. When used for detecting HE4 in human serum samples, the prepared HE4@SA-gel sensor achieved a recovery rate of 92.4 %–106.7 %.
研究领域:
生物化学
·
医学检测
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2020
·
IF 4.389
Ganapathi Bharathi,Fangrui Lin,Liwei Liu,Tymish Y. Ohulchanskyy,Rui Hu,Junle Qu
Ovarian cancer (OVC), the most lethal form of all gynecological cancers, is a big threat to women’s health. Late diagnosis at the advanced stages is one of the major reasons for the ovarian cancer-related deaths. Conventionally, the up-regulated proteins CA125 (cancer antigen 125) and HE4 (human epididymis protein 4) are used as biomarkers to diagnose the OVC malignancies. The lack of sensitivity/specificity and the false-positive results create complexity in the diagnostic process. With specificity over 90 %, HE4 is suitable for diagnosing ovarian cancer. Herein, we have developed an ultrasensitive all-graphene quantum dot (GQD) Förster resonance energy transfer (FRET) probe for the ratiometric detection of HE4 biomarker. A set of two GQD samples were solvothermally prepared and then analyzed by the morphological, structural, and photophysical characterization. One GQD sample exhibited a strong green emission, peaked at around 515 nm, while the other GQD sample displayed a strong red emission with maximum at around 615 nm. The good spectral overlap between the emission and excitation spectra of the green and red GQDs, respectively, all allowed us to consider them for the design of FRET-based probe. The green and red-emitting GQDs were conjugated with HE4 antibody and used as donor and acceptor, respectively for the ratiometric sensing of HE4 ovarian cancer biomarker. The all GQD FRET probe was able to detect as low as 4.8 pM, along with a large dynamic detection range up to 300 nM. The selectivity and interference effect of the developed FRET probe was also investigated against different protein combinations.
研究领域:
癌症生物学
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纳米技术
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生物医学工程
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分析化学
✓ 已验证
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2025
·
IF 7.7
Luhai Wang,Nana Wang,Lin Deng,Chao Min,Yi Kang,Tingting Bai,Guodong Zhao,Mengdong Yang,Yefei Zhu,Yu Zhang
Simultaneous analysis of multiple protein and nucleic acid biomarkers in one clinical sample can provide clinically valuable results for the diagnosis, monitoring, and management of diseases. However, current diagnostic platforms primarily rely on the independent detection of proteins and nucleic acids, which is time-consuming and labor-intensive. In this study, we propose a microfluidic chip system that integrates microfluidic molecular Point-of-Care Testing (POCT) technology and microfluidic homogeneous chemiluminescence analysis (CLIA) technology for simultaneous detection of protein and nucleic acid biomarkers of ovarian cancer (OC). The integrated system shows good detection limits of 10 fM for miR-92a and 15 pM for HE4. In primary clinical tests with human samples, the diagnostic sensitivity and specificity of the simultaneous detection of two biomarkers (miR-92a and HE4) for OC were 100 % and 96.1 %, respectively, and the area under the curve (AUC) was 0.996. Therefore, the combined evaluation of multiple biomarkers of different dimensions can improve the specificity and sensitivity of diagnosis. This system can also be applied to other tumor markers and biomarkers in other fields of diseases, offering a broad spectrum of diagnostic capabilities.
研究领域:
医学诊断
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
De Zhao,Zhihua Wu,Wei Zhang,Jian Yu,He Li,Wen Di,Yourong Duan
To date, ZnO array-based microfluidic fluorescence assays have been widely investigated and have exhibited excellent performance in the detection of cancer biomarkers. However, the requirements of highly sensitive detection necessitate further improvement of current Zn-based fluorescence detection devices. Here, a rhombus-like Zn(OH)F array-based microfluidic fluorescence detection device is proposed. Construction of Zn(OH)F arrays on the inner wall of a microchannel is carried out via a microfluidic chemical method. A substrate-induced growth strategy for Zn(OH)F arrays is proposed, and various micro/nanostructured Zn(OH)F arrays are successfully obtained. Zn(OH)F nanorod arrays with a high aspect ratio can be constructed on the columnar ZnO nanorod arrays, and the results indicate that the fluorescence enhancement factor (EF) of the Zn(OH)F arrays toward Cy3 is approximately 4-fold that of the ZnO nanorod arrays, which can be attributed to the higher excitation light absorption and evanescent electric field. In human epididymis-specific protein 4 (HE4) detection, the limit of detection (LOD) reaches 9.3 fM, and the dynamic linear range is 10 fM to 100 pM. It has been demonstrated that Zn(OH)F nanorod array-based microfluidic devices are excellent fluorescence assay platforms that also provide a new design and construction strategy for fluorescence enhancement substrates for the detection of biomarkers.
研究领域:
材料科学
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生物医学工程
·
分析化学
✓ 已验证
DOI
高影响因子
TALANTA
·
2021
·
IF 6.057
Ze Zhang,Yang Xu,Bochen Ma,Zhanfang Ma,Hongliang Han
Methods to improve the sensitivity of electrochemical sensors based on catalytic reactions generally require adscititious or pre-modified catalysts, which make the sensitive detection of sensors extremely challenging. This is because the activity of the catalyst is susceptible to the storage and modification process, such as aggregation during storage or loss of active sites during multi-step modification, which impairs the performance of the sensor. To solve this thorny issue, a novel electrochemical sensor based on a process-formed laccase-like catalyst was constructed for sensitive detection of tumor markers. Cu 2+ -polydopamine (CuPDA) combined with antibody (Ab 2 ) were employed as copper-containing immunoprobe, which released Cu(Ⅱ) ions under acidic stimulation. Cu(Ⅱ) ions coordinate with the self-assembly cationic diphenylalanine-glutaraldehyde nanospheres (CDPGA) to form a laccase-like catalyst, which had stronger catalytic activity than laccase. The freshly formed catalyst was immediately used to degrade the polyhydroquinone-reduced graphene oxide (PHQ-rGO) composite, resulting in a significant reduction in the current signal. The PHQ-rGO composite plays dual roles of signal substance and substrate on the sensing interface. The proposed electrochemical sensor demonstrated wide linearity for the determination of a model analyte , human epididymis protein 4 (HE4), from 1 pg mL −1 to 100 ng mL −1 , and the detection limit was as low as 0.302 pg mL −1 (S/N = 3), which had good consistency with that of electrochemiluminescence method. This process-formed catalyst approach will have potential reference significance for the construction of other sensors.
研究领域:
生物医学工程
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NANOTECHNOLOGY
·
2022
·Vol. 33
·期 48
·485502
·
IF 3.953
Muhammad Azhar Hayat Nawaz,Mahmood Hassan Akhtar,Jia Ren,Naeem Akhtar,Akhtar Hayat,Cong Yu
In this work, an electrochemical immunosensor based on black phosphorus nanosheets (BPNS)/poly(allylamine hydrochloride) (PAH) nanocomposite modified glassy carbon electrode was developed for the detection of ovarian cancer biomarker HE4. PAH has been applied to retain BPNS in its original honeycomb structure and to anchor biomolecules electrostatically on the transducer surface. The as synthesized nanocomposite was characterized by zeta potential analysis, scanning electron microscopy, x-ray photoelectron spectroscopy, transmission electron microscopy, high-resolution transmission electron microscopy. Subsequently, the performance of the electrochemical immunosensor was evaluated through cyclic voltammetry, differential pulse voltammetry and electrochemical impedance spectroscopy. Under the optimal condition, the developed electrochemical immunosensor permitted to detect HE4 with a linear range of 0.1–300 ng ml−1 and a detection limit of 0.01 ng ml−1. The developed sensor exhibited good selectivity and specificity to HE4 with negligible interference effect from common biomolecules like bovine serum albumin, lysozyme, protamine, glucose, fructose, hemoglobin and fetal bovine serum. Further, practical application of developed electrochemical immunosensor was demonstrated in spiked human serum which showed satisfactory recovery percentages.
研究领域:
生物医学工程
·
分析化学
·
癌症诊断
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Analytical Methods
·
2017
·Vol. 9
·期 17
·2546-2552
·
IF 1.9
Weizhe Hong,Gongwei Sun,Yi Zhang,Zhi Xing,Biao Huang,Sichun Zhang,Xinrong Zhang
ICP-MS-based multiplex immunoassays have the advantages of low sample consumption and minimized repetitions of tedious procedures. However, this technique is seldom used in clinical tests because of the complicated matrix effect in clinical samples and the discrimination effect to the target proteins. In this work, we developed an ICP-MS-based magnetic immunoassay by using magnetic beads as highly efficient affinity probes and optimizing the magnetic immunoassay parameters. We applied this method to the simultaneous determination of three crucial gynecological tumor biomarkers that are vital in the prognosis and monitoring of the recurrence of breast cancer and ovarian cancer. The measurable ranges of HER-2, HE4 and CA15-3 were 12–1000 ng mL−1, 8–2000 pmol L−1 and 5–200 U mL−1, with detection limits (3σ) of 3.94 ng mL−1, 2.59 pmol L−1 and 1.62 U mL−1, respectively. The relative standard deviations (RSDs) were 2.61% for HER-2 at 15 ng mL−1, 4.90% for HE4 at 25 pmol L−1 and 6.68% for CA15-3 at 10 U mL−1, indicating good accuracy of the method. The spiking test indicated that the present method had a low matrix effect. Under optimized conditions, the simultaneous detection of HER-2, HE4, and CA15-3 in clinical serum samples was performed and the values correlated well with those obtained by the time resolved fluorescence immunoassay (r2 = 0.9568 for HER-2, 0.9485 for HE4, 0.9133 for CA15-3). The present work shows that the ICP-MS-based magnetic immunoassay meets the requirements for the quantification of three crucial gynecological tumor biomarkers in real clinical tests.
研究领域:
分析化学
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医学诊断
·
癌症研究
✓ 已验证
产品关联
DOI
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2019
·
IF 6.393
Lu Fan,Yurong Yan,Bin Guo,Min Zhao,Jia Li,Xintong Bian,Haiping Wu,Wei Cheng,Shijia Ding
Alloy nanomaterials with various morphologies have showed their potential application in electrochemical signal amplification. However, it is still challenging to fabricate stable multimetallic nanomaterials with large surface area and strong electrochemical activity for the further enhancement of electrochemical sensors’ performance. Here, the trimetallic AgPtCo nanodendrites (NDs) were synthesized as powerful redox probe and highly efficient signal amplifier for electrochemical signal readout. A robust and ultrasensitive electrochemical immunosensor, based on AgPtCo NDs and magnetic nanocomposites (Fe 3 O 4 @SiO 2 @Au MNCs), was successfully developed to detect serum human epididymis protein 4 (HE4). The established method, drawing upon the strong electrochemical activity of AgPtCo NDs and the enrichment and separation effect of MNCs, exhibited a wide linear range (0.001–50 ng mL −1 ) and a low detection limit (0.487 pg mL −1 ). Besides, the developed sensor was applied to analyze the concentration of HE4 in real samples and the results achieved were consistent with those of clinical methods. Thus, this AgPtCo NDs and MNCs based electrochemical immunosensor might become a powerful alternative approach for ultrasensitive detection of various serum biomarkers associated with early diagnosis and treatment of diseases.
研究领域:
材料科学
·
分析化学
·
生物传感器
·
医学诊断
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF MATERIALS SCIENCE
·
2023
·Vol. 58
·期 23
·9633-9645
·
IF 4.5
Hu Rongqin,Mu Zhaode,Gong Feng,Qing Min,Yuan Yonghua,Bai Lijuan
Human epididymis protein 4 (HE4) is a highly sensitive and specific biomarker for diagnosing ovarian cancer. In this work, a new electrochemical aptasensor for rapid and sensitive detection of HE4 was constructed. Firstly, metal–organic framework/ketjen black (NH 2 -MIL-53(Al)/KB) composite with abundant amino groups and large specific surface area was prepared as signal amplifier to anchor gold nanoparticles (AuNPs). Subsequently, signal probe (SP) and a large amount of electroactive toluidine blue (Tb) were attached on AuNPs to form the tracer label, producing a distinct electrochemical detection signal. Moreover, Ni 3 (HITP) 2 was modified by poly(diallyldimethylammonium chloride, PDDA) to obtain PDDA/Ni 3 (HITP) 2 , and then it was covered with deposited gold nanocrystals (DpAu) to form the sensing platform, which increased the electrical conductivity, specific surface area and the loading of triple-helix assembled probes (TAP). Target HE4 was bound to its aptamer in the outer layer of the TAP, leaving a separate capture probe (CP) on the electrode surface that can bind with the tracer label. The proposed aptasensor for HE4 detection showed a wide linear range from 1 to 10 nM with a detection limit of 0.41 fM. In addition, the aptasensor has good selectivity, stability and reproducibility. More importantly, this method showed satisfactory results in clinical serum sample analysis compared with ELISA, possessing application prospects in ovarian cancer diagnosis.
研究领域:
生物传感器
·
分析化学
·
纳米技术
·
癌症诊断
·
电化学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）