BIOMEDICAL MICRODEVICES
·
2018
·Vol. 20
·期 2
·1-7
·
IF 2.077
Jin Xin,Chen Rui,Zhao Shikun,Li Peiyong,Xue Bai,Chen Xiang,Zhu Xinyuan
In this article, an attempt for efficient screening of circulating tumor cells (CTCs) with excellent operability on microfluidic chips was reported. A Parsortix™-like cell separation chip was manufactured in our lab. This chip allowed lateral flow of fluid which increased the flow rate of blood. And, an air valve controlled injection pump was manufactured which allowed eight chips working simultaneously. This greatly facilitated the blood treatment process and saved time. As for the mechanism of screening circulating tumor cells, selective size amplification was utilized. By size amplification of cancer cells, both the hardness and the size of CTCs increased which differentiated them from blood cells. And the modification procedure of beads used for size amplification of cancer cells was optimized. Finally, by integrating the commercialized Parsortix™-like cell separation chip and selective size amplification, a practical method for screening circulating tumor cells was established.
研究领域:
医学工程
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肿瘤学
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生物技术
✓ 已验证
DOI
PubMed
高影响因子
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
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纳米技术
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癌症诊断
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分子生物学
✓ 已验证
产品关联
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
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生物标志物检测
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2021
·
IF 6.057
Qiannan You,Jiahui Peng,Zhimin Chang,Mingfeng Ge,Qian Mei,Wen-Fei Dong
2D materials with attractive optical properties are promising for individualized cancer immunotherapy. Isolation, capture, and release of circulating tumor cells (CTCs) are of great significance for promoting the process of early diagnosis of cancers. MXene nanosheets incorporated gelatin hydrogel offers the possibility of achieving near-infrared (NIR) light response to initiate the photothermal effect. Herein, the design and preparation of Ti 3 C 2 T x MXene nanosheets-embedded thermoresponsive gelatin hydrogel membrane with NIR light-responsive for the specific capture and release of CTCs were reported. The membrane was fabricated by casting Ti 3 C 2 T x -embedded gelatin onto a substrate and then modified with epithelial-cell adhesion-molecule antibody (anti-EpCAM) for the specific recognition and separation of CTCs from whole blood. The captured cells can be released without damage with dual-mode containing temperature-responsive release (gelatin deconstructed at 37 °C) and photothermal site-release (Ti 3 C 2 T x induced by NIR light). Furthermore, we were able to achieve an average efficient release rate of 89 % of captured cells with stable cell viability of 87 % via the NIR light irradiation . This work may provide the promising potential for retrieval of single cells in clinical diagnosis.
研究领域:
癌症免疫治疗
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生物医学工程
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纳米技术
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光学材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Materials Technologies
·
2023
·
IF 6.8
Changqing Zhang,Jianwei Lin,Yunru Yu,Dawei Deng,Ying Yu,Dagan Zhang,Qifeng Zhong
Circulating Tumor Cells (CTCs) enrichment technology refers to medical approaches for capturing and isolating target tumor cells, which has drawn great attention owing to its applications in the clinic such as cancer diagnosis and prognosis. Magnetic nanoparticles have emerged as an important platform for CTCs capture and isolation. However, due to the inert surface nature, the molecular phenotype analysis of CTCs and identification sensitivity remain a huge challenge. Herein, an ultrasound-activated microfluidic method is presented for rapid basic modification of magnetic nanoparticles, laying the foundation for further covalently binding of functional groups to capture CTCs. In this work, Fe 3 O 4 @SiO 2 nanoparticles obtained from microfluidics are hybrid with folic acid for the capture and isolation of CTCs with folate receptors such as Hela cells. The usage of microfluidic technology to upgrade Fe 3 O 4 nanoparticles provides the possibility for improving the detective efficiency of rare cells associated with malignancies, which sheds new light on future clinical applications.
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
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分子诊断
✓ 已验证
产品关联
DOI
高影响因子
iScience
·
2023
·Vol. 26
·期 11
·108246-108246
·
IF 5.8
Peng Xie,Xiaoyue Yao,Zhenyu Chu,Yang Yang,Haifeng Li,Siyuan Tan,Haodong Tang,Jiahua Zhou,Wanqin Jin
The detection of circulating tumor cells (CTCs) in peripheral blood is a novel and accurate technique for the early diagnosis of cancers. However, this method is challenging because of the need for high collection efficiency due to the ultralow content and similar size of CTCs compared with other blood cells. To address the aforementioned issue, we proposed a homoporous polydimethylsiloxane (PDMS) membrane and its microfilter device to perform the ultrafast isolation and identification of CTCs directly from peripheral blood without any labeling treatment. The membrane pores can be homogenously controlled at a size of 6.3 μm through the cross-linking time of PDMS during a filtration-coating strategy. Within only 10 s, the designed device achieved a retention rate greater than 70% for pancreatic cancer cells, and it exhibited excellent cell compatibility to support cell proliferation. The isolated CTCs on this membrane can be easily observed and identified using a fluorescence microscope.
研究领域:
生物医学工程
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癌症诊断
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微流控技术
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细胞分离
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2019
·
IF 3.973
Xiufang Li,Jian Chen,Hui Liu,Zhiwei Deng,Jianbing Li,Tao Ren,Ling Huang,Wenqing Chen,Yanjing Yang,Shian Zhong
The study developed a simple, effective and inexpensive strategy for capturing, enriching and detecting circulating tumor cells (CTCs) by using folic acid (FA) as the targeting molecule instead of antibodies. This work constructed magnetic halloysite nanotubes (MHNTs) coated with biocompatible β-cyclodextrin (CD), and conjugated to FA via a PEG-Ad linker, to specifically capture the FA receptor (FR)-overexpressing cancer cells. The capture efficiencies of [email protected] β [email protected] for the Skov3, Hela and A549 cancer cells were 96.3%, 97.0% and 95.6% respectively. In addition, the nanoparticles were able to capture very low numbers of the cancer cells (25–500 cells/mL) from PBS and whole blood, as well as selectively capture the cancer cells over normal HEK 293 T cells. Furthermore, the captured cells were viable and grew normally in vitro , indicating the future potential of downstream analyses. This approach can be adapted for different CTCs, once the tumor-specific surface markers are identified and the efficacy of targeting ligands is established. Taken together, FA-conjugated MHNTs nanoparticles are a highly promising tool for isolating CTCs for the diagnosis and treatment of cancer.
研究领域:
纳米技术
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癌症生物学
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生物医学工程
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分子生物学
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Yi Su,Qingchang Tian,Dingyi Pan,Lanlan Hui,Yanni Chen,Qi Zhang,Wei Tian,Jie Yu,Shen Hu,Yang Gao,Dahong Qian,Tian Xie,Ben Wang
Circulating tumor cells (CTCs) in blood is the direct cause of tumor metastasis. The isolation and detection of CTCs in the whole blood is very important and of clinical value in early diagnosis, postoperative review, and personalized treatment. It is difficult to separate all types of CTCs that efficiently rely on a single path due to cancer cell heterogenicity. Here, we designed a new kind of “filter chip” for the retention of CTCs with very high efficiency by integrating the effects of cell size and specific antigens on the surface of tumor cells. The filter chip consists of a semicircle arc and arrays and can separate large-scale CTC microspheres, which combined with CTCs automatically. We synthesized interfacial zinc oxide coating with nanostructure on the surface of the microsphere to increase the specific surface area to enhance the capturing efficiency of CTCs. Microspheres, trapped in the arrays, would entrap CTCs, too. The combination of the three kinds of strategies resulted in more than 90% capture efficiency of different tumor cell lines. Furthermore, it is easy to find and isolate the circulating tumor cells from the chip as tumor cells would be fixed inside the structure of a filter chip. To avoid the high background contamination when a few CTCs are surrounded by millions of nontarget cells, a digital detection method was applied to improve the detection sensitivity. The CTCs in the whole blood were specifically labeled by the antibody–DNA conjugates and detected via the DNA of the conjugates with a signal amplification. The strategy of the antibody–functional microsphere-integrated microchip for cell sorting and detection of CTCs may find broad implications that favor the fundamental cancer biology research, the precise diagnosis, and monitoring of cancer in the clinics.
研究领域:
生物医学工程
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癌症生物学
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临床诊断
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微流控技术
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2021
·Vol. 12
·期 1
·1-17
·
IF 14.919
Xu Minjun,Hu Kaili,Liu Yipu,Huang Yukun,Liu Shanshan,Chen Yu,Wang Dayuan,Zhou Songlei,Zhang Qian,Mei Ni,Lu Huiping,Li Fengan,Gao Xiaoling,Chen Jun
Failure of conventional clinical therapies such as tumor resection and chemotherapy are mainly due to the ineffective control of tumor metastasis. Metastasis consists of three steps: (i) tumor cells extravasate from the primary sites into the circulation system via epithelial-mesenchymal transition (EMT), (ii) the circulating tumor cells (CTCs) form “micro-thrombi” with platelets to evade the immune surveillance in circulation, and (iii) the CTCs colonize in the pre-metastatic niche. Here, we design a systemic metastasis-targeted nanotherapeutic (H@CaPP) composed of an anti-inflammatory agent, piceatannol, and an anti-thrombotic agent, low molecular weight heparin, to hinder the multiple steps of tumor metastasis. H@CaPP is found efficiently impeded EMT, inhibited the formation of “micro-thrombi”, and prevented the development of pre-metastatic niche. When combined with surgical resection or chemotherapy, H@CaPP efficiently inhibits tumor metastasis and prolonged overall survival of tumor-bearing mice. Collectively, we provide a simple and effective systemic metastasis-targeted nanotherapeutic for combating tumor metastasis.
研究领域:
肿瘤学
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纳米技术
·
药理学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2013
·
IF 5.008
Yanyun Wang,Feng Zhou,Xiaoli Liu,Lin Yuan,Dan Li,Yanwei Wang,Hong Chen
For potential applications in the isolation and enrichment of circulating tumor cells (CTCs), we have developed gold nanoparticle layers (GNPLs) of different roughness modified with TD05 aptamers (GNPL-APT). In serum-free binary cell mixtures containing Ramos cancer cells and CEM cells, the density of Ramos cells adherent to highly rough GNPL-APT was 19 times that of CEM cells. However, in serum-containing conditions, the specificity of GNPL-APT for Ramos cells was much reduced. To improve Ramos specificity in the presence of serum, we attached the TD05 aptamer to the layers via poly(oligo(ethylene glycol) methacrylate) (POEGMA) as an antifouling spacer (GNPL-POEGMA-APT). In serum-containing environment GNPL-POEGMA-APT showed an enhanced selectivity for Ramos cells, which increased with increasing surface roughness. The results of this study indicate that surfaces combining appropriate chemical composition and micro/nano roughness structures may be useful for cell separation, including the isolation of cancer cells for diagnosis.
研究领域:
生物材料
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生物医学工程
·
癌症诊断
·
纳米技术
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2023
·
IF 8.4
Zhengying Peng,Youyuan Chen,Pengkun Yin,Fan He,Daibing Luo,Yixiang Duan,Qingwen Fan,Zhimei Wei,Qingyu Lin
Circulating tumor cells (CTCs) are cancer biomarkers for the diagnosis at early stage. However, it’s still a great challenge to develop the cytosensor for CTCs detection due to its ultralow counts in human peripheral blood. Herein, a highly sensitive cytosensor based on surface-enhanced Raman scattering (SERS) was developed. The tumor cells were first identified by a strand replacement reaction (SDR) that released the initiator of catalytic hairpin assembly (CHA) reaction. Subsequently, the initiator opened the residue hairpin DNA outside the silver coated gold nanoparticles ( [email protected] NPs). The double strand DNA (dsDNA) CHA products drove the [email protected] NPs towards the same side of dsDNA to form a zipper-like structure. This structure brought about hotspots area for SERS quantitative analysis of A549 tumor cells. The designed cytosensor exhibited good linearity ranging from 10 to 500 cells/mL with a calculated limit of detection (LOD) of 8 cells/mL. A SERS cytosensor with high sensitivity and good reproducibility was obtained in this work. In addition, this research presents a new method for rapid tumor cell detection in biological samples for cancer diagnosis.
研究领域:
生物传感器
·
癌症诊断
·
分子生物学
·
纳米技术
✓ 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）