IEEE SENSORS JOURNAL
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2025
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IF 4.5
Jingqiu Chen,Qing Huang,Jing Huang,Tucan Chen,Lanpeng Guo,Yunong Zhao,Dandan Li,Wenjian Zhang,Huayao Li,Yang Zhang,Liang Hu,Huan Liu
The escalating demand for high-throughput and miniaturized biosensors has spurred significant advancements in biosensor chips. However, challenges remain in achieving high sensitivity and specificity in miniaturized devices. Herein, we construct a sensitive exosome biosensor based on quantum dots (QDs)-modified field effect transistor. PbS QDs were drop-coated onto the gate of a high electron mobility transistor (HEMT), followed by surface modification with CD63 antibodies (anti-CD63) through a ligand exchange strategy, and subsequent bovine serum albumin (BSA) blocking treatment. Exosomes with CD63 proteins enriched in the surface were isolated from MCF-7 breast cancer cell lines to serve as target analytes. The specific binding events between CD63 antigen and antibody capture exosomes onto the gate of HEMT, affecting the output current (ID). The synergy of the capacitance coupling effect of the modification layer and the intrinsic signal amplification capability of HEMT assists in significantly modulating the two-dimensional electron gas (2DEG), resulting in amplified ID. With constant gate voltage applied, the ID of the biosensor sensitively increases with exosome concentration within a wide range of 105-109 particles/mL at VD = 3.5 V, and the LOD is estimated to be 9 × 104 particles/mL. This exosome biosensor demonstrates its potential for clinical applicability and paves the way for the development of miniaturized exosome biosensor chips.
研究领域:
生物传感器
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纳米技术
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癌症诊断
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生物电子学
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微流控技术
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产品关联
DOI
高影响因子
ANALYST
·
2019
·Vol. 144
·期 20
·5996-6003
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IF 4.019
Mei-Ling Gao,Bin-Cheng Yin,Bang-Ce Ye
As exosomes have been playing an increasingly important role in the diagnosis, treatment and prognosis of diseases, the analysis of exosome contents becomes more crucial. Therefore, the development of a cost-effective and simple exosome separation method that achieves high purity is urgently needed, and it is vital for further research in cancer. In this work, we constructed a DNA-AuNP-based satellite network which integrates low-speed centrifugal exosome isolation, detection and protein analysis. The rolling circle amplification (RCA) reaction is used to produce a long-chain DNA hairpin structure comprising a plurality of functional domains, such as CD63 aptamer sequences, linker sequences, and spacer sequences with complementary base pairs to form a hairpin structure. When the CD63 aptamers bind to exosomes, the hairpin structure changes its conformation, exposing the linker sequences (AuNP binding sequence). Then the probe on the surface of AuNPs combines with the long-chain DNA by the toehold-mediated strand displacement reaction, releasing the fluorescent labeled complementary probe as the detection signal and simultaneously forming the DNA-AuNP-based satellite network. Thus, exosomes can be isolated by low-speed centrifugation. The formation of the DNA-AuNP-based satellite network was confirmed by transmission electron microscopy and confocal fluorescence microscopy. In addition, we established a standard curve for exosome detection which showed good linearity of the fluorescence ratio vs. log(exosome concentration). LC/MS for protein profiling of the captured exosomes demonstrated that our method has potential application in the field of exosome research.
研究领域:
生物技术
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纳米技术
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分子生物学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2021
·
IF 8.128
Ziling Ding,Yanbing Lu,Yunyun Wei,Dan Song,Zhangrun Xu,Jin Fang
In this study, a rapid, low-cost and facile method for detecting exosomes was developed by engineering DNA ligands on the surface of an iron-based metal–organic framework (Fe-MOF). Aptamers of exosomal transmembrane CD63 protein (CD63-aptamers) were utilized as both the optically active layer and the exosome-specific recognition element to engineer an Fe-MOF bio-interface for high-efficiency regulation of the catalytic behavior of Fe-MOF toward the chromogenic substrate. The effective enhancement of the intrinsic peroxidase-like catalytic activity was confirmed via the self-assembly of CD63-aptamers on the surface of Fe-MOF. The specific binding of exosomes with CD63-aptamers altered the conformation of DNA ligands on the surface of Fe-MOF, contributing to sensitive variation in Fe-MOF catalytic activity. This directly produced a distinct color change and enabled the visual detection of exosomes. Via one-step “mixing-and-detection”, the Fe-MOF bio-interface exhibited excellent performance in quantitative analysis of exosomes derived from human breast cancer cell lines ranging from 1.1 × 10 5 to 2.2 × 10 7 particles/μL with a detection limit of 5.2 × 10 4 particles/μL. The expression of exosomal CD63 proteins originated from three types of cancer cell lines, including breast cancer, gastric cancer and lung cancer cell lines, was differentiated within only 17 min. Furthermore, the method was successfully applied to the identification of exosomes in serum samples, suggesting its potential in clinical analysis as a valuable tool for the rapid, convenient and economical testing of exosomes.
研究领域:
生物化学
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分子生物学
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癌症研究
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纳米技术
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诊断医学
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DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
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2021
·
IF 10.618
Shuting Li,Liye Zhu,Longjiao Zhu,Xiaohong Mei,Wentao Xu
Exosomes are regarded as a promising biomarker for the noninvasive diagnosis and treatment of diseases. The value of exosomes for medical research has promoted the search for a fast, efficient, and sensitive detection method. This study reported a sandwich-based evanescent wave fluorescent biosensor (S-EWFB) for exosome detection. A two-step strategy was implemented to take advantages of the simple binding of fluorescent probes with exosomes via the hydrophobic interaction between the cholesteryl and phospholipid bilayer membrane , as well as real-time detection on an evanescent wave liquid-solid interface based on CD63 aptamer-specific capture to form an exosome@fluorescence probe/aptamer sandwich structure. The one-to-many connection between exosomes and signal molecules and the aptamer-modified evanescent wave optical fiber detection platform reduced the detection limit of exosomes to 7.66 particles/mL, with a linear range of 47.5–4.75 × 10 6 particles/mL. The entire detection process was simple, rapid, and real-time and lasted about 1 h while requiring no separation and purification . Additionally, this platform showed excellent surface regeneration capability and exhibited good performance during the analysis of tumor and non-tumor-derived exosomes.
研究领域:
生物传感
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生物医学工程
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纳米技术
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分子生物学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2025
·
IF 5.7
Tao Hu,Haoyu Xiao,Shanling Ji,Zihao Wu,Yunlin Quan,Wang Zhen,Xiao Li,Jianxiong Zhu,Zhonghua Ni
In early cancer diagnosis, extracellular vesicles (EVs) are more advantageous than circulating tumor cells due to their smaller size, greater stability, and enhanced tissue penetration. These qualities lead to higher EV concentrations in body fluids, facilitating early detection. This study leverages surface-enhanced Raman scattering (SERS) for EVs detection, employing a novel biosensor made with a molybdenum disulfide (MoS2) composite film on silicon, noted for its high sensitivity and easy labeling. This biosensor efficiently measures EVs concentrations and precisely detects three specific proteins on ovarian cancer EVs simultaneously (CD63, CD24, CA125). Using the ovarian cancer cell line HO8910, the sensor demonstrated a detection limit of 1.4×104 particles/mL and a wide linear range of 3.4×104 particles/mL to 3.4×108 particles/mL . It also effectively discriminated between serum samples from healthy individuals and ovarian cancer patients at different stages. Additionally, machine learning was applied to analyze detection data, resulting in a diagnostic model with 97.78% prediction accuracy. This highlights the sensor's potential in revolutionizing early cancer detection and establishing new diagnostic models.
研究领域:
生物医学工程
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肿瘤学
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生物化学
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纳米技术
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机器学习
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2024
·
IF 5.4
Ying Li,Meiqi Qian,Yuping Cheng,Xue Qiu
In situ cell imaging plays a crucial role in studying physiological and pathological processes of cells. Proximity ligation assay (PLA) and rolling circle amplification (RCA) are commonly used to study the abundance and interactions of biological macromolecules. The most frequently applied strategy to visualize the RCA products is with single-fluorophore probe, however, cellular auto-fluorescence and unbound fluorescent probes could interfere with RCA products, leading to non-specific signals. Here, we present a novel approach combining aptamer mediated PLA, RCA, and Förster Resonance Energy Transfer (FRET), namely Apt-PLA-RCA-FRET, for sensitive in situ imaging and analysis of the abundances and interactions of membrane proteins such as tetraspanin CD63 and human epidermal growth factor receptor 2 (HER2). Apt-RCA-FRET was initially designed to show its ability to assess the abundance of target proteins on different cells. Dual functional oligonucleotides served as both the aptamer for recognizing specific membrane proteins and the primer of circular DNA for following RCA process, and the resulting RCA products were subsequently imaged by FRET signals from Cy3 to Cy5 probes which hybridized sequentially on them. FRET was demonstrated to show its great potential to resist the interferences of nonspecific fluorescence compared to single-fluorophore strategies. PLA was then introduced to Apt-RCA-FRET to investigate the spatial localization of different proteins on cell membrane and their interactions. Our approach utilizing aptamer as membrane proteins recognition element simply converted the abundance of proteins into nucleic acid signals and facilitated the following signal amplification, thus it serves as an important alternative to methods typically based on antibody and presents a more robust and sensitive method for analyzing the abundances of different cell membrane proteins and their spatial localization, which offers valuable insights into physiological and pathological processes of cells.
研究领域:
细胞生物学
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分子生物学
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生物医学工程
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分析化学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL SCIENCES
·
2024
·Vol. 40
·期 8
·1459-1473
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IF 1.8
Xu Xin,Zhang Ze,Shen Tong,Pan Hongzhi,Chang Dong
The main reason for the high mortality rate of non-small cell lung cancer is that patients are usually diagnosed at an advanced stage of the disease. Exosomes, small membrane vesicles secreted by normal cells or tumor cells, play a significant role in the progression of NSCLC. This study successfully optimized the preparation of artificial nanoenzymes self-coupling with horseradish peroxidase (IrO 2 NPs@HRP-AptCD63), without adding any ligand, demonstrating remarkable catalytic activity suitable for detecting the EGFR protein on the surface of NSCLC exosomes. When fused with the CD63 aptamer for identifying NSCLC exosomes, IrO 2 NPs@HRP showed enhanced catalytic activity in the 3,3′,5,5′-tetramethylbenzidine-H 2 O 2 oxidation–reduction system, thereby enhancing the colorimetric signal. This phenomenon can be distinguished by the naked eye and quantified using a UV–Vis spectrophotometer. Meanwhile, as the redox reaction occurs, the current signal of 3,3′,5,5′-tetramethylbenzidine-H 2 O 2 , acting as an electrolyte, changes. The developed aptasensor generates dual-mode signal outputs, firstly, to visually assess the samples for their positive or negative status, and subsequently employ more in-depth electrochemical or colorimetric analysis methods for a detailed quantitative analysis of suspected positive samples. The detection limits of electrochemical analysis and colorimetric analysis were 0.9 × 10 3 particles/mL and 0.14 × 10 3 particles/mL, respectively. Compared with traditional biomarkers such as CA125, this method exhibits exceptional specificity, capable of simultaneously distinguishing serum exosomes of healthy volunteers, COPD patients, and NSCLC patients, promoting exosome detection in mouse models for tumor monitoring. Additionally, it elucidates the changes in EGFR protein expression on the surface of serum exosomes throughout the developmental trajectory. Graphical abstract
研究领域:
癌症生物学
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纳米技术
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生物传感器
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分子诊断
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产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2024
·
IF 4.6
Ruiyuan Zhang,Rui Hao,Jixiang Fang
Tumor exosomes, known as maternal cell messengers, play an important role in cancer occurrence, proliferation, metastasis, immune escape, drug resistance, and other processes and are an entry point for cancer research. However, there is still a lack of an efficient detection technology for exosomes. In this study, the ultrahigh sensitivity SERS nanoprobe with a three dimensional (3D) magnetic core/Au nanocolumn/Au nanoparticles shell strongly coupling multistage structure (Fe3O4@NR-NPs) was constructed by crystal growth of nanocrystals in the confined space of a central radiating single particle mesoporous molecular sieve channel and strong coupling secondary growth of gold particles. The exosomes were confined onto the “hot spot” of plasmonic nanoparticles and rapidly enriched by CD63 antibody functional-Fe3O4@NR-NPs to achieve high sensitivity detection, with the limit of detection of 1 × 103 particles/mL (S/N = 3). The spectral data set of different exosomes is applied to train for multivariate classification of cell types and to estimate how the normal exosome data resemble cancer cell exosomes by principal component analysis (PCA). Finally, this detection method has also been successfully employed for the detection of exosomes in complex samples; this proves that the proposed SERS-based method is a promising tool for clinical cancer screening.
研究领域:
纳米技术
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癌症生物学
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分析化学
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生物标志物研究
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
ACS Omega
·
2024
·
IF 3.7
Qiang Mei,Baiwen Gu,Yinyu Jiang,Yulin Wang,Weiju Lai,Hu Chen,Jide Chen,Xianxian Zhao
Signal amplification strategies have emerged as a prominent tool in the field of improving the detection sensitivity of small extracellular vesicles (sEVs). It is important to highlight that the utilization of signal quenching strategies is not commonly implemented. A detection technique for sEVs was established based on the unwinding of G-quadruplex using Klenow fragment polymerase (KF), which served as an inspiration for this study. This system is characterized by its simplicity and lack of labeling, making it an efficient approach for signal quenching. In the presence of sEVs, the CD63 aptamer in the capture@sMBs complex binds with the CD63 protein on the surface of sEVs to release trigger sequences, which were employed as a primer to mediate the DNA polymerase/endonuclease-assisted signal recycling. The signal recycling process produces numerous single-stranded DNA sequences that can bind to the toehold section of the G-quadruplex. This leads to the rupture of the G-quadruplex structure and the subsequent deactivation of a DNAzyme generated by the G-quadruplex structure and hemin, thereby inhibiting its biological catalytic function. Consequently, the G-quadruplex structure would undergo a transformation to a duplex structure, leading to the emergence of a discernible differential signal that can be noticed in a majority of instances, even without the aid of magnification devices. The decrease in the prominent signal allows for the efficient analysis of target sEVs, which exhibit a notably low detection limit. In addition to the detection of sEVs, the approach has also been utilized for the investigation of miRNA-21. The approach demonstrates a high level of selectivity and robustness in its capacity to differentiate between target miRNA and base-mismatched miRNA as well as other miRNA families. This statement suggests that the assay holds significant promise for use in biochemical research and clinical diagnosis.
研究领域:
生物化学
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分子生物学
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临床诊断
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2021
·
IF 6.057
Qian Liu,Xinmin Yue,Yixian Li,Fang Wu,Meng Meng,Yongmei Yin,Rimo Xi
The superior supramolecular recognition ability of macrocyclic compounds will enhance the sensitivity and selectivity of electrochemical detection , which has a great application potential in electrochemical sensing. Herein, we developed a novel electrochemical aptasensor based on the specific host-guest interactions between cucurbit [7]uril and ferrocene (Fc) for capture, determination and release of exosomes. Macrocyclic compounds, cucurbit [7]uril is modified on the surface of the gold nanoparticles composed electrode by self-assembling. CD63 aptamer linked ferrocene is introduced into this platform to capture exosomes specifically by CD63 protein on the exosomes. The dual specificity of macrocyclic compounds and aptamers enables highly selective and sensitive electrochemical detection of exosomes. The limit of detection (LOD) was 482 particles μL -1 . In addition, the captured exosomes could be released on demand in a very mild manner through aminoferrocene (NH 2 -Fc) because of its higher affinity to cucurbit [7]uril. The proposed electrochemical aptasensor showed good performance in detecting exosomes even in plasma samples, thus demonstrating its great potential in early clinical diagnosis. Simultaneously, exosomes could be released undamaged by this protocol, exhibiting good applicability in comprehensive studies of exosomes. Moreover, this strategy can be applied to other target biomolecules by changing the recognition pairs.
研究领域:
电化学
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生物传感器
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纳米技术
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分子识别
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临床诊断
·
外泌体研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYST
·
2023
·
IF 4.2
Wei Li,Huili Wang,Xinxin Ying,Zhen Liang,Jianna Li,Xiangjuan Chen,Lei Su,Xueji Zhang
Zr-metal–organic frameworks (Zr-MOFs) have received increasing interest for their use as the signal marker in the development of sandwich-structured aptasensors for the detection of exosomes. However, Zr4+ ions of the Zr-MOFs can interact with not only the exosomes, but also the aptamers, leading to possible false positives and a large background response. In the present study, we report for the first time aptasensors with Pd nanoparticle (NP)-decorated and hemin-embedded UiO-66 MOFs serving as the signal amplification marker to eliminate false positives and decrease the background response of aptasensors. To construct aptasensors for detection of exosomes, CD63-specific aptamers were tethered onto magnetic Fe3O4 particles coated with polydopamine (PDA) and UiO-66-NH2 using glutaraldehyde crosslinking for capturing the exosomes. To prepare highly catalytic Zr-MOF-based signal markers, UiO-66 MOFs were modified with hemin followed by Pd NPs. The as-prepared Pd-decorated hemin-embedded MOFs showed high catalytic activity towards the chromogenic oxidation reaction of TMB by H2O2. Moreover, the decoration with Pd NPs led to the change of the surface charge state of the catalytic hemin-embedded UiO-66 MOFs from positive to negative, weakening the interaction between the signal marker and the negatively charged aptamers. Therefore, the as-prepared aptasensors showed an improved sensing performance towards exosomes with a linear concentration range from 4.28 × 102 to 4.28 × 105 and a limit of detection (LOD) of 86.2 particles per μL. The as-prepared aptasensors also showed high sensitivity and selectivity to the exosomes from different origins including the HeLa cell line and MCF-7 cell line.
研究领域:
生物传感器
·
纳米技术
·
分析化学
·
生物化学
✓ 已验证
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）