Small
·
2015
·Vol. 11
·期 18
·2200-2208
·
IF 8.368
Dian Li,Yuting Zhang,Ruimin Li,Jia Guo,Changchun Wang,Chuanbing Tang
Circulating tumor cells (CTCs) captured from blood fluid represent recurrent cancers and metastatic lesions to monitor the situation of cancers. We develop surface-enhanced Raman scattering (SERS)-coding microsphere suspension chip as a new strategy for fast and efficient capture, recovery, and detection of targeting cancer cells. Using HeLa cells as model CTCs, we first utilize folate as a recognition molecule to be immobilized in magnetic composite microspheres for capturing HeLa cells and attaining high capturing efficacy (up to 95%). After capturing cells, the composite microsphere, which utilizes a disulfide bond as crosslinker in the polymer shell and as a spacer for linking folate, can recycle 90% cells within 20 min eluted by glutathion solution. Taking advantage of the SERS with fingerprint features, we characterize captured/recovered cells with the unique signal of report-molecule 4-aminothiophenol through introducing the SERS-coding microsphere suspension chip to CTCs. Finally, the exploratory experiment of sieving cells shows that the magnetic composite microspheres can selectively capture the HeLa cells from samples of mixed cells, indicating that these magnetic composite microspheres have potential in real blood samples for capturing CTCs.
研究领域:
生物医学工程
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癌症诊断
·
纳米技术
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING SCIENCE
·
2025
·
IF 4.3
Jianwei Dong,Huan Wang,Jiaxing Huang,Hao He,Zhihai Wei,Weixuan Bai,Jingzhang Geng,Cong Min
Circulating tumor cells (CTCs) may be overlooked by detection techniques based on epithelial cell adhesion molecules (EpCAM) because of epithelial- mesenchymal transition (EMT). This work established an efficient microfluidic magnetic cell immunoassay (E- μ MCI) for CTCs via folate-modified magnetic beads (MBs@FA). Upon capture by MBs@FA, MCF-7 (EpCAM + Vimentin − ) and MDA-MB-231 (EpCAM − Vimentin + ) were labeled with horseradish peroxidase (HRP) and alkaline phosphatase (AP) via anti-EpCAM and anti-Vimentin, respectively. These labeled target cells were then concentrated in a microchannel’s tiny space. These phenotypes were recognized by fluorescent substances generated by HRP and AP, and cell quantity was determined via the growth rate of fluorescent products. MBs@FA’s efficient capture and microchannel’s signal amplification enabled ultrasensitive CTCs detection via E- μ MCI, with the detection limits of 1.8 and 2.8 cells/mL for MCF-7 and MDA-MB-231, respectively. This method also exhibited excellent selectivity and repeatability, achieving acceptable recovery and stability in actual sample determination. More remarkably, within the EMT model of CTCs, the recovery rate of E- μ MCI was observed to range from 94.3 % to 102.8 %. It was far greater than the EpCAM-based approach, indicating that E- μ MCI has the potential to address CTC detection oversights and offer technical methodologies for studying the relationship between CTCs and cancer progression.
研究领域:
医学
·
生物技术
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DOI
高影响因子
MICROCHIMICA ACTA
·
2025
·Vol. 192
·期 8
·1-10
·
IF 5.3
Zhang Jie,Zhou Huiqian,Hao Tingting,Li Jinyun,Ye Meng,Gao Wanlei,Xie Jianjun,Zhang Qingqing,Guo Zhiyong
The isolation and detection of circulating tumor cell (CTC) is of great significance for clinical cancer diagnosis and personalized therapy. Herein, a novel pangolin-type fluorescence imaging strategy is proposed to recognize, isolate and image CTC in whole blood. By combining ferroferric oxide (Fe 3 O 4 ) nanoparticles modified with aptamer (Apt), poly[(9,9-dioctylfluorenyl-2,7-diyl)-alt-co-(1,4-benzo-{2,1′,3}-thiadiazole)] (PFBT) and poly(styrene-co-maleic anhydride) (PSMA) formed in situ a large number of polymer dots (Pdots) on the surface of graphene oxide (GO), yielding a μm-sized 2D fluorescent probe Pdots@GO@Fe 3 O 4 -Apt. This probe could quickly recognize CTC and overlap each other on its surface, forming a “pangolin” structure where the CTCs were wrapped in a layer of “armor”. After rapidly separated from the sample by magnetic force, the morphology of the whole CTC could be observed by excited Pdots. The recognition, isolation and imaging of CTC were integrated in the probe, resulting in a high consistency between capture and imaging and ensuring high detection confidence. The feasibility of the pangolin-type fluorescence imaging strategy to detect CTC in actual samples was verified, demonstrating potential for clinical application. Graphical abstract
研究领域:
生物医学工程
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纳米技术
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肿瘤学
·
生物成像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ELECTROPHORESIS
·
2022
·
IF 3.595
Ling Xia,Wanjun Zhou,Jianying Huang,Jianwei Dong,Xiaohua Xiao,Gongke Li
Precise cell detecting and counting is meaningful in circulating tumor cells (CTCs) analysis. In this work, a simple cyclic olefin copolymer (COC) microflow cytometer device was developed for size-resolved CTCs counting. The proposed device is constructed by a counting channel and a pinched injection unit having three channels. Through injection flow rate control, microspheres/cells can be focused into the centerline of the counting channel. Polystyrene microspheres of 3, 9, 15, and 20 µm were used for the microspheres focusing characterization. After coupling to laser-induced fluorescence detection technique, the proposed device was used for polystyrene microspheres counting and sizing. A count accuracy up to 97.6% was obtained for microspheres. Moreover, the proposed microflow cytometer was applied to CTCs detecting and counting. To mimic blood sample containing CTCs and CTCs mixture with different subtypes, an MDA-MB-231 (human breast cell line) spiked red blood cells sample and a mixture of MDA-MB-231 and MCF-7 (human breast cell line) sample were prepared, respectively, and then analyzed by the developed pinched flow-based microfluidic cytometry. The simple fabricated and easy operating COC microflow cytometer exhibits the potential in the point-of-care clinical application.
研究领域:
医学工程
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肿瘤学
·
生物技术
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2020
·
IF 6.785
Jianmei Yang,Xiaolong Li,Bingying Jiang,Ruo Yuan,Yun Xiang
Monitoring circulating tumor cells (CTCs) in human blood can offer useful information for convenient metastasis diagnosis, prognosis, and treatment of cancers. However, it remains a substantial challenge to detect CTCs because of their particular scarcity in complex peripheral blood. Herein, we describe an in situ-generated multivalent aptamer network-modified electrode interface for efficiently capturing and sensitively detecting CTCs in whole blood by electrochemistry. Such an interface was fabricated via rolling circle amplification extension of the electrode-immobilized primer/circular DNA complexes for the yield of long ssDNA strands with many repeated aptamer segments, which could achieve efficient capture of rare CTCs in a multivalent cooperative manner. The antibody and horseradish peroxidase-functionalized gold nanoparticles further specifically associated with the surface-bound CTCs and generated electrocatalytically amplified current outputs for highly sensitive detection of CTCs with an attractive detection limit of five cells. Also, the multivalent aptamer network interface could successfully distinguish the target cells from other control cells and achieve CTC detection in whole blood, demonstrating its promising potential for monitoring different rare CTCs in human blood.
研究领域:
生物医学工程
·
分子生物学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
Nanoscale
·
2024
·
IF 5.8
Na He,Han Bao,Jingxin Meng,Yongyang Song,Li-Ping Xu,Shutao Wang
Immunomagnetic particles are extensively used for the separation of biological molecules and particles, and have exhibited great potential in many fields including biosensors, disease diagnosis and biomedical engineering. However, most immunomagnetic particles exhibit a smooth surface, resulting in a limited separation efficiency for biological particles featuring enormous surface nanostructures, such as tumor cells. Here we report flower-like immunomagnetic particles (FIMPs) prepared by streptavidin (SA)-assisted biomineralization and one-step antibody modification, and demonstrate their superior capability for highly efficient and selective separation of circulating tumor cells (CTCs). SA can link inorganic nanosheets and magnetic nanoparticles together to obtain FIMPs with programmable hierarchical flower-like nanostructures and provide enormous binding sites for post-antibody modification. The synergetic effect of nano-sized petals and micro-sized particles in the hierarchical nanostructure enhances the interaction between the cells and the matrix, thus enabling FIMPs to separate CTCs with high selectivity and high efficiency. Our study provides a promising platform for the selective separation of trace biological molecules and particles from complex samples and shows great potential for downstream detection and diagnosis.
研究领域:
生物医学工程
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疾病诊断
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2019
·
IF 8.355
Long Zhao,Yuan Liu,Songzhi Xie,Pan Ran,Jiaojun Wei,Qingjie Liu,Xiaohong Li
The rapid and sensitive detection of circulating tumor cells (CTCs) remains technical challenges due to extremely low abundance. In the current study, Janus micromotors (JMs) are developed to achieve motion-enhanced CTC capture and capture-induced ratiometric fluorescence signaling. JMs are constructed via catalase grafting on one side of Janus rods (JRs) to catalyze the decomposition of H 2 O 2 as power source. JMs with different aspect ratios show random, spiral, rotational or linear motion trajectories, and JMs with the aspect ratio of 2 (JM-2) display rotational motion with significantly larger mean-square-displacement (MSD) values than other JMs. TLS11a aptamers are conjugated on the other side of JRs for specific capture of tumor cells, and tetraphenylethene (TPE) derivatives and fluorescein isothiocyanate (FITC) are labeled on aptamers via base-pair interactions. The competitive binding of tumor cells with aptamers causes the release of TPE and FITC from JMs, which relieves the aggregation-induced emission (AIE) effect of TPE and aggregation-caused quenching (ACQ) profile of FITC on JMs. Thus, JMs displays apparent ratiometric fluorescence changes from blue ( I 450 ) to green ( I 526 ) after capture of tumor cells. The fluorescence intensity ratios of I 526 / I 450 could be fitted against cell levels, and the limit of detection is around 25 cells/mL within 1 min. In addition, the HepG2 detection by JM-2 exhibits no interference in the presence of other tumor cells (4T1 and H22), and the recovery rate of HepG2 cells in blood samples was over 95%. Thus, JMs demonstrate the motion-capture-ratiometric fluorescence sensing capabilities and provide a feasible strategy for real-time, rapid and sensitive detection of cells in laboratory, hospital and remote settings.
研究领域:
生物医学工程
·
肿瘤学
·
分析化学
✓ 已验证
产品关联
DOI
高影响因子
Journal of Bionic Engineering
·
2017
·
IF 2.388
Xiaofeng Zhou,Jiaqian Li,Hongyan Sun,Yi Hu,Lufeng Che,Zuankai Wang
The ability to control cell patterning on artificial substrates with various physicochemical properties is of essence for important implications in cytology and biomedical fields. Despite extensive progress, the ability to control the cell-surface interaction is complicated by the complexity in the physiochemical features of bioactive surfaces. In particular, the manifestation of special wettability rendered by the combination of surface roughness and surface chemistry further enriches the cell-surface interaction. Herein we investigated the cell adhesion behaviors of Circulating Tumor Cells (CTCs) on topographically patterned but chemically homogeneous surfaces. Harnessing the distinctive cell adhesion on surfaces with different topography, we further explored the feasibility of controlled cell patterning using periodic lattices of alternative topographies. We envision that our method provides a designer's toolbox to manage the extracellular environment.
研究领域:
细胞学
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生物医学工程
·
材料科学
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产品关联
DOI
高影响因子
CANCER BIOLOGY & THERAPY
·
2016
·
IF 2.921
Yu Zhang,Xiaofeng Zhang,Jinling Zhang,Bin Sun,Lulu Zheng,Jun Li,Sixiu Liu,Guodong Sui,Zhengfeng Yin
Circulating tumor cells (CTCs) have been proposed to be an active source of metastasis or recurrence of hepatocellular carcinoma (HCC). The enumeration and characterization of CTCs has important clinical significance in recurrence prediction and treatment monitoring in HCC patients. We previously developed a unique method to separate HCC CTCs based on the interaction of the asialoglycoprotein receptor (ASGPR) expressed on their membranes with its ligand. The current study applied the ligand-receptor binding assay to a CTC-chip in a microfluidic device. Efficient capture of HCC CTCs originates from the small dimensions of microfluidic channels and enhanced local topographic interactions between the microfluidic channel and extracellular extensions. With the optimized conditions, a capture yield reached > 85% for artificial CTC blood samples. Clinical utility of the system was further validated. CTCs were detected in all the examined 36 patients with HCC, with an average of 14 ± 10/2 mL. On the contrary, no CTCs were detected in healthy, benign liver disease or non-HCC cancer subjects. The current study also successfully demonstrated that the captured CTCs on our CTC-chip were readily released with ethylene diamine tetraacetic acid (EDTA); released CTCs remained alive and could be expanded to form a spheroid-like structure in a 3-dimensional cell culture assay; furthermore, sensitivity of released CTCs to chemotherapeutic agents (sorafenib or oxaliplatin) could be effectively tested utilizing this culture assay. In conclusion, the methodologies presented here offer great promise for accurate enumeration and easy release of captured CTCs, and released CTCs could be cultured for further functional studies.
研究领域:
肿瘤学
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生物医学工程
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2015
·
IF 6.723
Xiaoxia Wu,Liqiang Luo,Sugeun Yang,Xuehua Ma,Yonglong Li,Chen Dong,Yuchen Tian,Ling’e Zhang,Zheyu Shen,Aiguo Wu
The detection of circulating tumor cells (CTCs) in the blood of cancer patients is crucial for early cancer diagnosis, cancer prognosis, evaluation of the treatment effect of chemotherapy drugs, and choice of cancer treatment options. In this study, we propose new surface-enhanced Raman scattering (SERS) nanoparticles for the direct detection of CTCs in the blood. Under the optimized experimental conditions, our SERS nanoparticles exhibit satisfying performances for the direct detection of cancer cells in the rabbit blood. A good linear relationship is obtained between the SERS intensity and the concentration of cancer cells in the range of 5–500 cells/mL (R2 = 0.9935), which demonstrates that the SERS nanoparticles can be used for the quantitative analysis of cancer cells in the blood and the limit of detection is 5 cells/mL, which is lowest compared with the reported values. The SERS nanoparticles also have an excellent specificity for the detection of cancer cells in the rabbit blood. The above results reinforce that our SERS nanoparticles can be used for the direct detection of CTCs in the blood with excellent specificity and high sensitivity.
研究领域:
生物医学工程
·
肿瘤学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2024
·
IF 10.7
Yunuo Dai,Jie He,Yun Zhou,Yanyan Yu,Hui Hui,Lin Guo,Haitao Yin
Transformation of epithelial to mesenchymal (EMT) is an important event in the process of tumor initiation, invasion and metastasis. Circulating tumor cells (CTCs) are one kind of important markers in the field of liquid tumor biopsy, whose number and phenotype represent the occurrence and progression of tumors. Therefore, it is our interest to investigate the epithelial mesenchymal transition process occurring on the surface of CTCs. Herein in this work, two proteins of E-cadherin (E-cad) and N-cadherin (N-cad) were selected as representative proteins of EMT process. To achieve simultaneous analysis of E-cad and N-cad on the surface of rare CTCs, we designed a duplex and portable immunosensor using AuNPs and AgNPs as nanolabels to amplify the immunoreaction signals. The dual channel immunosensor not only exhibited good electrochemical responses for recombinant E-cad and N-cad as low as 0.1 ng/mL and 0.05 ng/mL, respectively, but also showed good linear correlations with different numbers of phenotypic CTCs (10–500 cells/10 μL). The above strategy was further employed to inspect the occurrence of EMT on CTCs surface, which displayed a high consistence with other molecular biological characterizations. Finally, this immunoassay was successfully applied to inspect the correlations of numbers, phenotype of CTCs, as well as E-cad and N-cad expressions on these CTCs in bloods of NSCLC patients with disease stage.
研究领域:
医学诊断
·
肿瘤学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2024
·
IF 5.8
Qingyuan Song,Hongni Liu,Weiyi Wang,chaohui chen,Yiping Cao,Bolei Chen,Bo Cai,Rongxiang He
Circulating tumor cells in human peripheral blood plays an important role in cancer metastatic. In addition to the size-based and antibody-based cancer cells capture and separation, the electric characterization of cell is also important for rare cells detection, which is fatal in the point-of-care testing. Herein, a solution-gated carboxyl graphene mixed with PEDOT:PSS organic electrochemical transistor (OECT) biosensor for the in-situ detection of cancer cells is reported. Carboxyl graphene was used in this work to modulate the cancer cells morphology, which is differ significantly from the normal blood cells in the rare cancer cells detection. When the concentration of carboxyl graphene mixed in PEDOT:PSS was increased from 0 to 5 mg mL-1, Cancer cell area were increased from 218 μm2 to 530 μm2, respectively. The change of cell morphology can be detected by OECT. The negative charges of cancer cells can induce a positive effect shift of gate voltage, which is about 40 mV for spherical shape of cells. When the cell area increased, the transfer curve was shift to negative effect shift of gate voltage. Therefore, the sensor can realize in-situ detection of cancer cells morphology during the cell capture process, which can be used to identify whether the captured cells were deformable.
研究领域:
生物医学工程
·
癌症研究
✓ 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）