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利用便携式微流控装置实现单细胞灵敏度的循环肿瘤细胞可视化定量检测。

Visual Quantitative Detection of Circulating Tumor Cells with Single-Cell Sensitivity Using a Portable Microfluidic Device.

机构信息

The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, The Key Laboratory of Chemical Biology of Fujian Province, The Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Collaborative Innovation Center of Chemistry for Energy Materials, Department of Chemical Engineering, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China.

Institute of Molecular Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.

出版信息

Small. 2019 Apr;15(14):e1804890. doi: 10.1002/smll.201804890. Epub 2019 Feb 28.

Abstract

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.

摘要

免疫细胞化学技术、分子技术和功能检测广泛用于从患者的血液样本中富集后检测循环肿瘤细胞 (CTC)。不幸的是,由于需要复杂的仪器和熟练的操作人员,这些技术的可及性有限。便携式微流控设备已成为将检测的可及性和效率从医院扩展到患者附近场所的有吸引力的工具。在此,开发了一种体积条形图芯片 (V-Chip) 作为 CTC 检测的便携式平台。靶 CTC 用适配体偶联的纳米颗粒 (ACNP) 标记,并通过 V-Chip 通过定量 ACNP 与过氧化氢之间的催化反应的副产物(氧气)进行分析,从而导致油墨条移动到与浓度相关的距离用于目视定量读出。因此,CTC 数量被解码为可目视定量的信息,并且可以在样品中细胞的数量与油墨移动的距离之间找到线性相关性。该方法足够灵敏,可以检测到单个细胞。此外,该系统的临床能力在白细胞背景高的情况下用于定量 CTC 检测得到了证明。这种便携式检测方法具有用于各种应用的单细胞灵敏度对稀有细胞进行定量的巨大潜力。

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