Abstract

Detection of circulating tumor cells (CTCs) plays an important role in early diagnosis of cancer and personalized therapy. However, isolated CTCs, especially those captured by positive sorting methods, are difficult to culture in subsequent assays because the cells have to be labeled or attached to a substrate for separation. In this study, a negative sorting method has been developed for isolation of CTCs through a microfluidic platform integrated with streptavidin-functionalized electrospun polylactic-co-glycolic acid nanofibers. Through the specific biotin-streptavidin interaction, the device is able to sort out biotinylated anti-CD45 antibody-labeled white blood cells (WBCs) and enrich A549 human cancer cells from the blood or CTCs from patient suffering non-small cell lung cancer. We demonstrate that the WBC capture efficiency is as high as 97.0%, and the recovery rate of cancer cells reaches up to 97.5%. CTCs are enumerated from blood samples of patients suffering lung carcinoma. The number of CTCs increased with the progression of NCCN TNM stages and showed statistically significant difference between stage I and later stages. These results suggest that the integrated negative sorting device is promising to be used for diagnosis of cancer.

Graphic Abstract

中文翻译：

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使用与链霉亲和素功能化的PLGA纳米纤维集成的微流控平台阴性分离循环肿瘤细胞。

摘要

循环肿瘤细胞（CTC）的检测在癌症的早期诊断和个性化治疗中起着重要的作用。然而，分离的CTC，尤其是通过阳性分选方法捕获的CTC，在随后的测定中很难培养，因为必须标记细胞或将细胞附着到基质上进行分离。在这项研究中，已经开发了一种负向分选方法，用于通过与链霉亲和素功能化的电纺聚乳酸-乙醇酸纳米纤维集成在一起的微流控平台来分离四氯化碳。通过特定的生物素-链霉亲和素相互作用，该设备能够筛选出生物素化的抗CD45抗体标记的白细胞（WBC），并从患有非小细胞肺癌的患者的血液或CTC中富集A549人癌细胞。我们证明白细胞捕获效率高达97.0％，癌细胞的回收率高达97.5％。从患有肺癌的患者的血液样本中列举出四氯化碳。CTC的数量随着NCCN TNM分期的进展而增加，并且在I期和后期之间显示出统计学上的显着差异。这些结果表明，集成的阴性分选装置有望用于癌症的诊断。

图形摘要