Circulating tumor cells (CTCs) from liquid biopsy have shown a strong correlation to the clinical outcome of cancer patients. The enumeration and cytological analysis of CTCs have attracted increasing efforts for cancer disease management amid immunotherapy and personalized medicine. However, both enumeration and cytological analysis are challenging due to the rarity of CTCs and the lack of integrated solutions for the minimal risk of cell loss in the course of CTC procurement. We report a simple microfluidic chip permitting a one-stop solution for streamlining the on-chip cell separation, capture, immunofluorescence assay and/or in situ culture of isolated cells devoid of risky manual steps. Our results showed effective trapping of single cells, doublets and cell lumps isolated from blood in the same device. On-chip immunostaining revealed normal cell morphology and the characterization of cell expansion uncovered an altered cell growth curve with a reduced lag phase as compared to the conventional culture despite closely matching cell growth rates. The cells were viable and functional for as long as 11 days inside our chip and cell migration was also readily observed, with lumps showing greater aggressiveness than single cells. With these results, we expect promising applications of our one-stop solution for liquid biopsy via CTCs.

中文翻译：

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微流生物芯片中肿瘤细胞的无标记分离和培养。

液体活检中的循环肿瘤细胞（CTC）已显示出与癌症患者的临床结局密切相关。CTC的计数和细胞学分析在免疫疗法和个性化医学中吸引了越来越多的癌症治疗管理工作。然而，由于四氯化碳的稀有性以及缺乏在四氯化碳采购过程中将细胞损失的最小风险最小化的综合解决方案，因此枚举和细胞学分析都具有挑战性。我们报告一个简单的微流控芯片，允许一站式解决方案，以简化芯片上的细胞分离，捕获，免疫荧光测定和/或原位培养分离的细胞，而无需进行危险的手动操作。我们的结果表明，在同一设备中有效捕获了从血液中分离出的单细胞，双峰和细胞团块。芯片免疫染色揭示了正常的细胞形态，并且与常规培养相比，尽管细胞生长速率紧密匹配，但细胞扩增的特征却发现了改变的细胞生长曲线，且具有减少的滞后期。这些细胞在我们的芯片中存活了长达11天，并且功能正常，而且还很容易观察到细胞迁移，团块显示出比单个细胞更大的攻击力。有了这些结果，我们期望我们的一站式解决方案通过CTC进行液体活检的应用前景广阔。这些细胞在我们的芯片中存活了长达11天，并且功能正常，而且还很容易观察到细胞迁移，团块显示出比单个细胞更大的攻击力。有了这些结果，我们期望我们的一站式解决方案通过CTC进行液体活检的应用前景广阔。这些细胞在我们的芯片中存活了长达11天，并且功能正常，而且还很容易观察到细胞迁移，团块显示出比单个细胞更大的攻击力。有了这些结果，我们期望我们的一站式解决方案通过CTC进行液体活检的应用前景广阔。