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基于荧光微球构建的非侵入式光隔离和循环肿瘤细胞鉴定。

Noninvasive Optical Isolation and Identification of Circulating Tumor Cells Engineered by Fluorescent Microspheres.

机构信息

Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan, Hubei 430072, China.

Department of Electronic Engineering School of Electronic Science and Engineering, Xiamen University, Xiamen, Fujian Province 361005, China.

出版信息

ACS Appl Bio Mater. 2022 Jun 20;5(6):2768-2776. doi: 10.1021/acsabm.2c00204. Epub 2022 May 10.

Abstract

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.

摘要

循环肿瘤细胞(CTCs)数量稀少,这意味着目前的分离策略很难同时满足效率和细胞生物相容性的要求,从而阻碍了其临床应用。此外,所选择的细胞需要免疫荧光鉴定,这是一个耗时且昂贵的过程。在这里,我们开发了一种通过光学力和荧光微球集成来同时分离和鉴定 CTCs 的方法。我们的方法通过光操纵实现了 CTCs 的高纯度无损伤分离,并避免了额外的免疫荧光染色步骤,从而实现了对分选细胞的快速鉴定。白细胞(WBCs)和 CTCs 的大小和密度相似,这使得光学上难以区分它们。因此,设计了具有高折射率(RI)的荧光 PS 微球来捕获 CTCs(PS-CTCs)并增加 PS-CTCs 的平均折射率。在微流控芯片中,PS-CTCs 在光力的照射下从样品混合物中被推到收集通道中。由于 PS 微球的荧光信号,从收集出口出来的细胞在荧光显微镜下很容易被识别。该方法为 CTCs 的分选和鉴定提供了一种方法,在疾病的早期诊断中具有很大的临床应用潜力。

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