共查询到20条相似文献,搜索用时 15 毫秒
1.
Continuous Flow Deformability‐Based Separation of Circulating Tumor Cells Using Microfluidic Ratchets 下载免费PDF全文
Emily S. Park Chao Jin Quan Guo Richard R. Ang Simon P. Duffy Kerryn Matthews Arun Azad Hamidreza Abdi Tilman Todenhöfer Jenny Bazov Kim N. Chi Peter C. Black Hongshen Ma 《Small (Weinheim an der Bergstrasse, Germany)》2016,12(14):1909-1919
Circulating tumor cells (CTCs) offer tremendous potential for the detection and characterization of cancer. A key challenge for their isolation and subsequent analysis is the extreme rarity of these cells in circulation. Here, a novel label‐free method is described to enrich viable CTCs directly from whole blood based on their distinct deformability relative to hematological cells. This mechanism leverages the deformation of single cells through tapered micrometer scale constrictions using oscillatory flow in order to generate a ratcheting effect that produces distinct flow paths for CTCs, leukocytes, and erythrocytes. A label‐free separation of circulating tumor cells from whole blood is demonstrated, where target cells can be separated from background cells based on deformability despite their nearly identical size. In doping experiments, this microfluidic device is able to capture >90% of cancer cells from unprocessed whole blood to achieve 104‐fold enrichment of target cells relative to leukocytes. In patients with metastatic castration‐resistant prostate cancer, where CTCs are not significantly larger than leukocytes, CTCs can be captured based on deformability at 25× greater yield than with the conventional CellSearch system. Finally, the CTCs separated using this approach are collected in suspension and are available for downstream molecular characterization. 相似文献
2.
Efficient Capture and Simple Quantification of Circulating Tumor Cells Using Quantum Dots and Magnetic Beads 下载免费PDF全文
Hyegeun Min Seong‐Min Jo Hak‐Sung Kim 《Small (Weinheim an der Bergstrasse, Germany)》2015,11(21):2536-2542
Circulating tumor cells (CTCs) are valuable biomarkers for monitoring the status of cancer patients and drug efficacy. However, the number of CTCs in the blood is extremely low, and the isolation and detection of CTCs with high efficiency and sensitivity remain a challenge. Here, we present an approach to the efficient capturing and simple quantification of CTCs using quantum dots and magnetic beads. Anti‐EpCAM antibody‐conjugated quantum dots are used for the targeting and quantification of CTCs, and quantum‐dot‐attached CTCs are isolated using anti‐IgG‐modified magnetic beads. Our approach is shown to result in a capture efficiency of about 70%–80%, enabling the simple quantification of captured CTCs based on the fluorescence intensity of the quantum dots. The present method can be used effectively in the capturing and simple quantification of CTCs with high efficiency for cancer diagnosis and monitoring. 相似文献
3.
Nanotentacle‐Structured Magnetic Particles for Efficient Capture of Circulating Tumor Cells 下载免费PDF全文
Seong‐Min Jo Joong‐jae Lee Woosung Heu Hak‐Sung Kim 《Small (Weinheim an der Bergstrasse, Germany)》2015,11(16):1975-1982
Circulating tumor cells (CTCs) have attracted considerable attention as promising markers for diagnosing and monitoring the cancer status. Despite many technological advances in isolating CTCs, the capture efficiency and purity still remain challenges that limit clinical practice. Here, the construction of “nanotentacle”‐structured magnetic particles using M13‐bacteriophage and their application for the efficient capturing of CTCs is demonstrated. The M13‐bacteriophage to magnetic particles followed by modification with PEG is conjugated, and further tethered monoclonal antibodies against the epidermal receptor 2 (HER2). The use of nanotentacle‐structured magnetic particles results in a high capture purity (>45%) and efficiency (>90%), even for a smaller number of cancer cells (≈25 cells) in whole blood. Furthermore, the cancer cells captured are shown to maintain a viability of greater than 84%. The approach can be effectively used for capturing CTCs with high efficiency and purity for the diagnosis and monitoring of cancer status. 相似文献
4.
Mahlet Fasil Abate Shasha Jia Metages Gashaw Ahmed Xingrui Li Li Lin Xiaoqian Chen Zhi Zhu Chaoyong Yang 《Small (Weinheim an der Bergstrasse, Germany)》2019,15(14)
Immunocytological technologies, molecular technologies, and functional assays are widely used for detecting circulating tumor cells (CTCs) after enrichment from patients' blood sample. Unfortunately, accessibility to these technologies is limited due to the need for sophisticated instrumentation and skilled operators. Portable microfluidic devices have become attractive tools for expanding the access and efficiency of detection beyond hospitals to sites near the patient. Herein, a volumetric bar chart chip (V‐Chip) is developed as a portable platform for CTC detection. The target CTCs are labeled with aptamer‐conjugated nanoparticles (ACNPs) and analyzed by V‐Chip through quantifying the byproduct (oxygen) of the catalytic reaction between ACNPs and hydrogen peroxide, which results in the movement of an ink bar to a concentration‐dependent distance for visual quantitative readout. Thus, the CTC number is decoded into visually quantifiable information and a linear correlation can be found between the distance moved by the ink and number of cells in the sample. This method is sensitive enough that a single cell can be detected. Furthermore, the clinical capabilities of this system are demonstrated for quantitative CTC detection in the presence of a high leukocyte background. This portable detection method shows great potential for quantification of rare cells with single‐cell sensitivity for various applications. 相似文献
5.
Enhanced and Differential Capture of Circulating Tumor Cells from Lung Cancer Patients by Microfluidic Assays Using Aptamer Cocktail 下载免费PDF全文
Libo Zhao Chuanhao Tang Li Xu Zhen Zhang Xiaoyan Li Haixu Hu Si Cheng Wei Zhou Mengfei Huang Anna Fong Bing Liu Hsian‐Rong Tseng Hongjun Gao Yi Liu Xiaohong Fang 《Small (Weinheim an der Bergstrasse, Germany)》2016,12(8):1072-1081
Collecting circulating tumor cells (CTCs) shed from solid tumor through a minimally invasive approach provides an opportunity to solve a long‐standing oncology problem, the real‐time monitoring of tumor state and analysis of tumor heterogeneity. However, efficient capture and detection of CTCs with diverse phenotypes is still challenging. In this work, a microfluidic assay is developed using the rationally‐designed aptamer cocktails with synergistic effect. Enhanced and differential capture of CTCs for nonsmall cell lung cancer (NSCLC) patients is achieved. It is also demonstrated that the overall consideration of CTC counts obtained by multiple aptamer combinations can provide more comprehensive information in treatment monitoring. 相似文献
6.
7.
8.
9.
Tunable Nanostructured Coating for the Capture and Selective Release of Viable Circulating Tumor Cells 下载免费PDF全文
Eduardo Reátegui Nicola Aceto Eugene J. Lim James P. Sullivan Anne E. Jensen Mahnaz Zeinali Joseph M. Martel Alexander J. Aranyosi Wei Li Steven Castleberry Aditya Bardia Lecia V. Sequist Daniel A. Haber Shyamala Maheswaran Paula T. Hammond Mehmet Toner Shannon L. Stott 《Advanced materials (Deerfield Beach, Fla.)》2015,27(9):1593-1599
10.
11.
The study of circulating tumor cells (CTCs) offers pathways to develop new diagnostic and prognostic biomarkers that benefit cancer treatments. In order to fully exploit and interpret the information provided by CTCs, the development of a platform is reported that integrates acoustics and microfluidics to isolate rare CTCs from peripheral blood in high throughput while preserving their structural, biological, and functional integrity. Cancer cells are first isolated from leukocytes with a throughput of 7.5 mL h−1, achieving a recovery rate of at least 86% while maintaining the cells' ability to proliferate. High‐throughput acoustic separation enables statistical analysis of isolated CTCs from prostate cancer patients to be performed to determine their size distribution and phenotypic heterogeneity for a range of biomarkers, including the visualization of CTCs with a loss of expression for the prostate specific membrane antigen. The method also enables the isolation of even rarer, but clinically important, CTC clusters. 相似文献
12.
Hee Sik Shin Jeehun Park Seung Yeop Lee Hyo Geun Yun Byeongyeon Kim Jinho Kim Sangbin Han Duck Cho Junsang Doh Sungyoung Choi 《Small (Weinheim an der Bergstrasse, Germany)》2023,19(43):2302809
Accurately analyzing the functional activities of natural killer (NK) cells in clinical diagnosis remains challenging due to their coupling with other immune effectors. To address this, an integrated immune cell separator is required, which necessitates a streamlined sample preparation workflow including immunological cell isolation, removal of excess red blood cells (RBCs), and buffer exchange for downstream analysis. Here, a self-powered integrated magneto-microfluidic cell separation (SMS) chip is presented, which outputs high-purity target immune cells by simply inputting whole blood. The SMS chip intensifies the magnetic field gradient using an iron sphere-filled inlet reservoir for high-performance immuno-magnetic cell selection and separates target cells size-selectively using a microfluidic lattice for RBC removal and buffer exchange. In addition, the chip incorporates self-powered microfluidic pumping through a degassed polydimethylsiloxane chip, enabling the rapid isolation of NK cells at the place of blood collection within 40 min. This chip is used to isolate NK cells from whole blood samples of hepatocellular cancer patients and healthy volunteers and examined their functional activities to identify potential abnormalities in NK cell function. The SMS chip is simple to use, rapid to sort, and requires small blood volumes, thus facilitating the use of immune cell subtypes for cell-based diagnosis. 相似文献
13.
Xiaoxi Zhou Bin Luo Ke Kang Yujia Zhang Peipei Jiang Fang Lan Qiangying Yi Yao Wu 《Small (Weinheim an der Bergstrasse, Germany)》2019,15(17)
Downstream studies of circulating tumor cells (CTCs), which may provide indicative evaluation information for therapeutic efficacy, cancer metastases, and cancer prognosis, are seriously hindered by the poor purity of enriched CTCs as large amounts of interfering leukocytes still nonspecifically bind to the isolation platform. In this work, biomimetic immunomagnetic nanoparticles (BIMNs) with the following features are designed: i) the leukocyte membrane camouflage, which could greatly reduce homologous leukocyte interaction and actualize high‐purity CTCs isolation, is easily extracted by graphene nanosheets; ii) facile antibody conjugation can be achieved through the “insertion” of biotinylated lipid molecules into leukocyte‐membrane‐coated nanoparticles and streptavidin conjunction; iii) layer‐by‐layer assembly techniques could integrate high‐magnetization Fe3O4 nanoparticles and graphene nanosheets efficiently. Consequently, the resulting BIMNs achieve a capture efficiency above 85.0% and CTCs purity higher than 94.4% from 1 mL blood with 20–200 CTCs after 2 min incubation. Besides, 98.0% of the isolated CTCs remain viable and can be directly cultured in vitro. Moreover, application of the BIMNs to cancer patients' peripheral blood shows good reproducibility (mean relative standard deviation 8.7 ± 5.6%). All results above suggest that the novel biomimetic nanoplatform may serve as a promising tool for CTCs enrichment and detection from clinical samples. 相似文献
14.
15.
Tumor Cell Phenotyping: Circulating Tumor Cell Phenotyping via High‐Throughput Acoustic Separation (Small 32/2018) 下载免费PDF全文
Mengxi Wu Po‐Hsun Huang Rui Zhang Zhangming Mao Chuyi Chen Gabor Kemeny Peng Li Adrian V. Lee Rekha Gyanchandani Andrew J. Armstrong Ming Dao Subra Suresh Tony Jun Huang 《Small (Weinheim an der Bergstrasse, Germany)》2018,14(32)
16.
Jiantong Dong Jie-Fu Chen Matthew Smalley Meiping Zhao Zunfu Ke Yazhen Zhu Hsian-Rong Tseng 《Advanced materials (Deerfield Beach, Fla.)》2020,32(1):1903663
Circulating rare cells in the blood are of great significance for both materials research and clinical applications. For example, circulating tumor cells (CTCs) have been demonstrated as useful biomarkers for “liquid biopsy” of the tumor. Circulating fetal nucleated cells (CFNCs) have shown potential in noninvasive prenatal diagnostics. However, it is technically challenging to detect and isolate circulating rare cells due to their extremely low abundance compared to hematologic cells. Nanostructured substrates offer a unique solution to address these challenges by providing local topographic interactions to strengthen cell adhesion and large surface areas for grafting capture agents, resulting in improved cell capture efficiency, purity, sensitivity, and reproducibility. In addition, rare-cell retrieval strategies, including stimulus-responsiveness and additive reagent-triggered release on different nanostructured substrates, allow for on-demand retrieval of the captured CTCs/CFNCs with high cell viability and molecular integrity. Several nanostructured substrate-enabled CTC/CFNC assays are observed maturing from enumeration and subclassification to molecular analyses. These can one day become powerful tools in disease diagnosis, prognostic prediction, and dynamic monitoring of therapeutic response—paving the way for personalized medical care. 相似文献
17.
Advection Flows‐Enhanced Magnetic Separation for High‐Throughput Bacteria Separation from Undiluted Whole Blood 下载免费PDF全文
Su Hyun Jung Young Ki Hahn Sein Oh Seyong Kwon Eujin Um Sungyoung Choi Joo H. Kang 《Small (Weinheim an der Bergstrasse, Germany)》2018,14(34)
A major challenge to scale up a microfluidic magnetic separator for extracorporeal blood cleansing applications is to overcome low magnetic drag velocity caused by viscous blood components interfering with magnetophoresis. Therefore, there is an unmet need to develop an effective method to position magnetic particles to the area of augmented magnetic flux density gradients while retaining clinically applicable throughput. Here, a magnetophoretic cell separation device, integrated with slanted ridge‐arrays in a microfluidic channel, is reported. The slanted ridges patterned in the microfluidic channels generate spiral flows along the microfluidic channel. The cells bound with magnetic particles follow trajectories of the spiral streamlines and are repeatedly transferred in a transverse direction toward the area adjacent to a ferromagnetic nickel structure, where they are exposed to a highly augmented magnetic force of 7.68 µN that is much greater than the force (0.35 pN) at the side of the channel furthest from the nickel structure. With this approach, 91.68% ± 2.18% of Escherichia coli (E. coli) bound with magnetic nanoparticles are successfully separated from undiluted whole blood at a flow rate of 0.6 mL h?1 in a single microfluidic channel, whereas only 23.98% ± 6.59% of E. coli are depleted in the conventional microfluidic device. 相似文献
18.
19.
20.
Capturing Cancer: Emerging Microfluidic Technologies for the Capture and Characterization of Circulating Tumor Cells 下载免费PDF全文
Weiyi Qian Yan Zhang Weiqiang Chen 《Small (Weinheim an der Bergstrasse, Germany)》2015,11(32):3850-3872
Circulating tumor cells (CTCs) escape from primary or metastatic lesions and enter into circulation, carrying significant information of cancer progression and metastasis. Capture of CTCs from the bloodstream and the characterization of these cells hold great significance for the detection, characterization, and monitoring of cancer. Despite the urgent need from clinics, it remains a major challenge to capture and retain these rare cells from human blood with high specificity and yield. Recent exciting advances in micro/nanotechnology, microfluidics, and materials science have enable versatile, robust, and efficient cell isolation and processing through the development of new micro/nanoengineered devices and biomaterials. This review provides a summary of recent progress along this direction, with a focus on emerging methods for CTC capture and processing, and their application in cancer research. Furthermore, classical as well as emerging cellular characterization methods are reviewed to reveal the role of CTCs in cancer progression and metastasis, and hypotheses are proposed in regard to the potential emerging research directions most desired in CTC‐related cancer research. 相似文献