ANALYTICA CHIMICA ACTA
·
2024
·
IF 5.7
Yang Xiao,Zhiyi Zhou,Yifan Zuo,Xueyuan Wu,Yuping Liu,Yichen Li,Yuetong Gao,Xiashu Zhang,Yu Wang,Lili Hu,Chenglin Li
Background The technology of capturing circulating tumor cells (CTCs) plays a crucial role in the diagnosis, evaluation of therapeutic efficacy, and prediction of prognosis in lung cancer. However, the presence of complex blood environment often results in severe nonspecific protein adsorption and interferences from blood cells, which negatively impacts the specificity of CTCs capture. There is a great need for development of novel nanomaterials for CTCs capture with prominent anti-nonspecific adsorptions from proteins or blood cells. Results We present a novel immune magnetic probe Fe 3 O 4 @(PEI/AA) 4 @Apt. The surface of Fe 3 O 4 particles was modified with four layers of PEI/AA composite by layer-by-layer assembly. Furthermore, aptamers targeting epithelial marker EpCAM (SYL3C) and mesenchymal marker CSV (ZY5C) were simultaneously connected on Fe 3 O 4 @(PEI/AA) 4 to improve the detection of different phenotypic CTCs and reduce false negatives. The results demonstrated that the (PEI/AA) 4 coatings not only minimized non-specific protein adsorptions, but also significantly reduced the adsorption rate of red blood cells to a mere 1 %, as a result of which, the Fe 3 O 4 @(PEI/AA) 4 @Apt probe achieved a remarkably high capture efficiency toward CTCs (95.9 %). In the subsequent validation of clinical samples, the probe was also effective in capturing rare CTCs from lung cancer patients. Significance and novelty A (PEI/AA) polymerized composite with controllable layers was fabricated by layer-by-layer self-assembly technique, which displayed remarkable anti-nonspecific adsorption capabilities toward proteins and cells. Importantly, Fe 3 O 4 @(PEI/AA) 4 @Apt probe significantly improved CTCs capture purity in lung cancer patients to 89.36 %. For the first time, this study combined controllable (PEI/AA) layers with magnetic separation to innovatively build a resistant interface that significantly improves the specific capture performances of CTCs, broadening the application of this polymerized composite.
研究领域:
生物医学工程
·
纳米技术
·
癌症诊断
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2021
·Vol. 188
·期 10
·1-11
·
IF 5.833
Yang Wei,Fan Lu,Guo Zhen,Wu Haiping,Chen Junman,Liu Changjin,Yan Yurong,Ding Shijia
A novel cytosensor was constructed for the ultrasensitive detection and nondestructive release of circulating tumor cells (CTCs) by combining Au nanoparticles-loaded two-dimensional bimetallic PdMo (2D Au@PdMo) nanozymes and electrochemical reductive desorption. The 2D Au@PdMo nanozymes possessed high-efficiency peroxidase-like activity and were assembled with an aptamer composed of a thiol-modified epithelial specific cell adhesion molecule (EpCAM) to strengthen CTCs adhesion. Moreover, the electrode surface was decorated with highly fractal Au nanostructures (HFAuNSs) composites due to the similarity in fractal nanostructure with the CTCs membrane to enhance the CTCs anchoring efficiency and release capability. The captured CTCs could be further efficiently dissociated and nondestructively released from the modified electrodes upon electrochemical reductive desorption. The designed cytosensor showed an excellent analytical performance, with a wide linear range from 2 to 1 × 10 5 cells mL −1 and low limit of detection (LOD) of 2 cells mL −1 (S/ N = 3) at the working potential in the range −0.6 to 0.2 V. A satisfactory CTCs release reaching a range of 93.7–97.4% with acceptable RSD from 3.55 to 6.41% and good cell viability was obtained. Thus, the developed cytosensor might provide a potential alternative to perform CTC-based liquid biopsies, with promising applications in early diagnosis of tumors. Graphical abstract
Preparation and mechanism of desorption of the cytosensor based on 2D Au@PdMo nanozymes and electrochemical reductive desorption for the detection and release of CTCs. A Preparation procedure of the Apt/Au@PbMo bioconjugates. B Fabrication process of the sandwich-type cytosensor. C Electrochemical signal produced by the Au@PdMo nanozymes. D Mechanism of electrochemical reductive desorption for CTCs release
研究领域:
生物医学工程
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肿瘤学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LAB ON A CHIP
·
2025
·
IF 5.4
Qian Wang,Kexin Liu,Kunming Xing,Yuyan Li,Yumin Liu,Guangyao Tan,Yingnan Sun,Shusheng Zhang
Current microchips functionalized with antibodies or aptamers primarily enhance the capture and detection efficiency of single targets in microfluidics by refining microchannel designs or developing functional enhancement materials. However, strategies to extend the interaction path for efficiency optimization remain underexplored, as they may cause elevated hydraulic pressure and fluid shear forces within the microchannels, and the potential for path extension is inherently limited. This study introduces a novel dual-mode droplet rolling strategy, mimicking Earth's rotation and revolution, which employs a closed-loop patterned superwetting chip to achieve efficient capture of trace biological targets in gravity-driven droplets. Specifically, the external cyclic motion in the "revolution" mode greatly extends the interaction path between the droplet-contained targets and the active interface. Meanwhile, the internal cyclic vortex flow in the "rotation" mode markedly increases the contact frequency between droplet-contained targets and the active substrate. Consequently, the dual-cycle synergistic amplification significantly enhances the effective contact opportunities between the targets and the functionalized closed-loop track, thereby markedly improving target capture efficiency. As a proof of concept, we demonstrate the specific and efficient capture of both micron-sized polystyrene microspheres (6 μm and 15 μm) and nanoscale AuNPs (50 nm) through multilayer modification of the superslippery track, highlighting the platform's versatility for targets of varying sizes. We achieved 91.3% capture efficiency for circulating tumor cells (MCF-7 cells, ~20 μm), underscoring the chip's high efficiency in specific target capture. Furthermore, we showcase the strategy's applicability throughout the entire workflow, encompassing efficient capture, controlled release, immediate recovery, and downstream cultivation using pathogenic bacteria (E. coli, ~1 μm). This strategy holds significant promise for detecting tumor markers and pathogens in body fluid samples, offering an innovative approach to capture-based diagnostics.
研究领域:
微流控技术
·
生物医学工程
·
诊断学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL SCIENCES
·
2025
·
IF 2
Wei JunJie,Shen Yong,Ouyang GangFeng
The rapid and simple detection of circulating tumor cells (CTCs) can help with early diagnosis of tumor diseases and assist clinical judgment of tumor disease development status and prognosis. An important alteration in cancer progression is a significant increase in sialic acid (SA) levels, making sialic acid one of an interesting biomarker for cancer type diversity. Here, novel SERS nano-biosensors were fabricated employing molecularly imprinted polymers (MIPs) particles loaded with Ag nanoparticles (AgNPs) to form high affinity toward sialic acid on CTCs. In this work, the glycol-specific MIPs are produced using precipitation polymerization. The nanocomposite was characterized by Fourier transform infrared spectroscopy (FTIR), zeta potential, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Consequently, CTC can be rapidly detected in mouse blood in a specific and sensitive manner, as low as 1 cells/ml. In addition, a good linear relationship was observed between CTC concentration and signal intensity ( R 2 = 0.9881). Moreover, the SERS nano-biosensors was used to detect CTC with excellent precision (relative standard deviation, RSD = 3.9%) and good repeatability (RSD = 6.8%). Therefore, this inexpensive, highly sensitive, and rapid method using SERS nano-biosensors can quickly detect CTCs and may prove to be a new platform to be an early diagnostic tool for cancer patient detection. Graphical abstract
研究领域:
肿瘤学
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分析化学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Taoye Zhang,Wei Peng,Wanli Jiang,Kefan Gao,Wei Liu
The isolation and detection of rare circulating tumor cells (CTCs) from patient peripheral blood can help early diagnosis of cancer and evaluation of therapeutic outcomes. At present, most of the available strategies for enriching CTCs face serious problems with purity due to the nonspecific interactions between the capture medium and leukocytes. Inspired by the immune evasion ability of homologous red blood cells (RBCs), we modified the tumor-targeting molecule folic acid (FA) on the surface of RBCs by hydrophobic interactions. Under the treatment of polybrene, the charges on the surface of RBCs are neutralized, which reduces the mutual repulsion force. Furthermore, RBCs treated with polyethylene also have excellent deformability, thereby enabling engineered RBCs to form a dense bionic layer on the adhesive glass slide, which can greatly inhibit the nonspecific adhesion of leukocytes. The bionic layer can achieve high-purity enrichment of tumor cells in phosphate-buffered saline (PBS), and we can achieve high-activity release in plasma. The cell count showed over 80% capture efficiency and over 70% release rate, and the purity of CTCs obtained in the artificial blood sample after release was higher than 90%. The RBC bionic surface coating is notably cost-effective and highly applicable for CTC isolation in clinic practice, and thus provides new prospects for designing cell–material interfaces for advanced cell-based biomedical studies in the future.
研究领域:
肿瘤学
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生物医学工程
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细胞生物学
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分子医学
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DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2022
·
IF 0
Bei Chen,Jingjing Zheng,Kefan Gao,Xuejia Hu,Shi-Shang Guo,Xing-Zhong Zhao,Fei Liao,Yi Yang,Wei Liu
Circulating tumor cells (CTCs) are rare, meaning that current isolation strategies can hardly satisfy efficiency and cell biocompatibility requirements, which hinders clinical applications. In addition, the selected cells require immunofluorescence identification, which is a time-consuming and expensive process. Here, we developed a method to simultaneously separate and identify CTCs by the integration of optical force and fluorescent microspheres. Our method achieved high-purity separation of CTCs without damage through light manipulation and avoided additional immunofluorescence staining procedures, thus achieving rapid identification of sorted cells. White blood cells (WBCs) and CTCs are similar in size and density, which creates difficulties in distinguishing them optically. Therefore, fluorescent PS microspheres with high refractive index (RI) are designed here to capture the CTCs (PS-CTCs) and increase the average index of refraction of PS-CTCs. In optofluidic chips, PS-CTCs were propelled to the collection channel from the sample mixture, under the radiation of light force. Cells from the collection outlet were easily identified under a fluorescence microscope due to the fluorescence signals of PS microspheres. This method provides an approach for the sorting and identification of CTCs, which holds great potential for clinical applications in early diagnosis of disease.
研究领域:
生物医学工程
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癌症研究
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光学
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微流控技术
✓ 已验证
产品关联
DOI
PubMed
ANALYTICAL CHEMISTRY
·
2023
·
IF 7.4
Xiaoying Wang,Tao Gao,Jin Zhu,Shipeng Long,Songyan Zhao,Li Yuan,Zhaoxia Wang
Hematogenous metastasis is the main route of cancer spreading, causing majority death of cancer patients. During this process, platelets in the blood are found increasingly essential to promote hematogenous metastasis by forming platelet-interacted circulating tumor cells (CTCs). Hence, we aim to fabricate an integrated method for the availability of capture and detection of such invasive CTCs. Specifically, a new form of channeled and conductive three-dimensional (3D) electrode is constructed by modifying a conductive layer and capture antibody on the templated and channeled poly(dimethylsiloxane) scaffold. The modified antibody enables the capture of the platelet-interacted CTC hybrid, while the conductive layer significantly facilitates electron transfer from electro-active signal molecules that are targeting platelets. Therefore, sensitive electrochemical detection of platelet-interacted CTCs has been realized. Efficient capture and sensitive detection have been demonstrated by this work. Additionally, dynamic analysis of patients’ CTCs has also been conducted to provide accurate information about disease assessment and efficacy evaluation. The cut-off line was set as 5.15 nA based on the sample signals from healthy volunteers. Thus, stage III cancer patients with high risk of hematogenous metastasis have been identified. Together, this work shows the development of a new strategy for simultaneous capture and detection of the invasive CTC subtype form patient blood, which favors precise monitoring of hematogenous metastasis.
研究领域:
生物医学工程
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癌症研究
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电化学
·
生物标志物检测
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产品关联
DOI
PubMed
高影响因子
LAB ON A CHIP
·
2021
·Vol. 21
·期 20
·3888-3898
·
IF 6.799
Rongke Gao,Changbiao Zhan,Chunyu Wu,Yang Lu,Baoqiang Cao,Jing Huang,Feng Wang,Liandong Yu
Hepatocellular carcinoma (HCC) is a harmful malady that truly debilitates human health, and hence it is of significance to isolate and on-line profile the phenotype of HCC cells for further diagnosis and therapy. We developed a novel strategy for efficient capture and in situ heterogeneous phenotype analysis of circulating tumor cells (CTCs) at the single-cell level based on surface-enhanced Raman scattering (SERS) fingerprint characteristics. Herein, a new microfluidic chip with lantern-like bypass structure was designed to capture CTCs by their large size from whole blood. Furthermore, two types of SERS-aptamer nanotags were fabricated, realizing spectral recognition of single CTCs in accordance with the surface membrane protein expression. Up to 84% of CTCs with a purity of 95% were captured from whole blood samples using the present SERS-aptamer based microfluidic chip at 20 μL min−1. The results showed that the proposed strategy can successfully identify HCC cell subtypes by SERS measurements, which was related to the clinical surface biomarkers. This may open a new avenue for serving as a powerful tool of cancer diagnosis and prognosis evaluation.
研究领域:
癌症生物学
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生物医学工程
·
分析化学
✓ 已验证
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2025
·
IF 10.5
Kemeng Zhang,Jiajun Li,Ye Li,Wen Zhang,Guohai Liang,Tao Zhang
Detection of circulating tumor cells (CTCs) has proven to be a crucial approach for early diagnosis, prognosis, and monitoring of cancer treatment. However, due to the low abundance of CTCs in blood, achieving accurate detection in the presence of a large number of blood cells remains challenging. In this study, we present a novel self-catalytic nanomachine for quantitative detection of CTCs, which includes a dual aptamer-triggered Catalytic Hairpin Assembly (CHA) reaction and subsequent UCNP-DNA-based biosensing. The dual-aptamer recognition, the two-step CHA reaction and the UCNP ratiometric sensing luminescence provide the assay with high specificity and sensitivity. Using MDA-MB-231 cells as model targets, the proposed detection system affords a wide linear detection range and a detection limit as low as 3 cells. Our system offers sensitive detection of CTCs without the need for enzymatic involvement, indicating its substantial potential for early cancer diagnosis and treatment based on CTCs.
研究领域:
生物医学工程
·
癌症诊断
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Signal Transduction and Targeted Therapy
·
2024
·Vol. 9
·期 1
·1-18
·
IF 40.8
Yang Chuan,Wang Xueping,To Kenneth K. W.,Cui Caimei,Luo Min,Wu Shaocong,Huang Lamei,Fu Kai,Pan Can,Liu Zeyu,Fan Teng,Yang Caibo,Wang Fang,Fu Liwu
Circulating tumor cells (CTCs) are precursors of distant metastasis in a subset of cancer patients. A better understanding of CTCs heterogeneity and how these CTCs survive during hematogenous dissemination could lay the foundation for therapeutic prevention of cancer metastasis. It remains elusive how CTCs evade immune surveillance and elimination by immune cells. In this study, we unequivocally identified a subpopulation of CTCs shielded with extracellular vesicle (EVs)-derived CD45 (termed as CD45 + CTCs) that resisted T cell attack. A higher percentage of CD45 + CTCs was found to be closely correlated with higher incidence of metastasis and worse prognosis in cancer patients. Moreover, CD45 + tumor cells orchestrated an immunosuppressive milieu and CD45 + CTCs exhibited remarkably stronger metastatic potential than CD45 − CTCs in vivo. Mechanistically, CD45 expressing on tumor surfaces was shown to form intercellular CD45-CD45 homophilic interactions with CD45 on T cells, thereby preventing CD45 exclusion from TCR-pMHC synapse and leading to diminished TCR signaling transduction and suppressed immune response. Together, these results pointed to an underappreciated capability of EVs-derived CD45-dressed CTCs in immune evasion and metastasis, providing a rationale for targeting EVs-derived CD45 internalization by CTCs to prevent cancer metastasis.
研究领域:
肿瘤学
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免疫学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2023
·
IF 5.8
Jidong Wang,Yating Zhang,Min Dong,Zhaopeng Liu,Binbin Guo,Haipeng Zhang,Liming Gao
Detecting and analyzing circulating tumor cells(CTCs) is significant for early diagnosis, management, and personalized treatment of tumors. Herein, a smart magnetic aptamer modified Fe 3 O 4 @ZIF-8 core/shell structured nanoparticle (NPs) was successfully constructed using for capture and simultaneous pH- and NIR-irradiation responsive release of CTCs. Taking MCF-7 as model CTCs, it could be captured ca. 60 % in low-concentration artificial blood by aptamer (SYL3C) on the surface of Fe 3 O 4 @ZIF-8 NPs. After magnetic separation, the ZIF-8 shell in aptamer-modified Fe 3 O 4 @ZIF-8 NPs carrying captured CTCs would disintegrate within 20 min under the synergistic effect of an acidic environment (pH=6.0) and NIR irradiation leading to the release of CTCs with high cell viability , which was benefited for the subsequent culture and analysis. This magnetic and core/shell structured device integrated high-efficiency capture, quick isolation and perfect release into one system, which showed great potential s for the detection of CTCs in the clinic.
研究领域:
生物医学工程
·
纳米技术
·
癌症诊断
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2025
·
IF 5.6
Chuang Zhang,Xinhua Zhang,Jian Zhang,Mian Peng,Xiaowen Dou
Circulating tumor cells (CTCs), though rare and highly heterogeneous, are closely associated with tumor initiation, progression, and prognosis. Their low abundance, structural fragility, phenotypic diversity, and size variability make efficient enrichment particularly challenging. To address these limitations, we developed a novel CTC isolation platform that combines tetrahedral DNA nanostructure-based trivalent aptamer magnetic nanospheres (TDF-Cocktail-MNP) with a magnetic microfluidic separation device. This system enhances the capture of viable, phenotypically diverse CTCs and supports reliable downstream analysis. The TDF structure presents three aptamers: EpCAM targets epithelial CTCs, Vimentin captures mesenchymal types, and EGFR binds to cells overexpressing EGFR—a key marker in triple-negative breast cancer. This multi-target approach enables efficient isolation of heterogeneous CTC populations from whole blood samples. Captured CTCs are enriched using the IsoFlux System, which reduces mechanical stress and preserves cell viability by avoiding repeated magnetic manipulation. After nuclease-mediated removal of the DNA scaffold, cells are classified and quantified through immunocytochemistry. Validated with both spiked and clinical breast cancer samples, this platform shows strong potential for liquid biopsy applications, offering robust CTC detection and valuable insights for personalized cancer diagnostics and treatment.
研究领域:
肿瘤学
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分子生物学
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纳米医学
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转化医学
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生物材料
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液体活检
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微流控技术
✓ 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）