Robert Bosch GmbH, Corporate Sector Research and Advanced Engineering, Robert-Bosch-Campus 1, 71272 Renningen, Germany.
Department of Internal Medicine, University of Tübingen, Otfried-Müller-Str. 10, 72076 Tübingen, Germany.
Biosensors (Basel). 2021 Sep 3;11(9):312. doi: 10.3390/bios11090312.
Circulating tumor cells (CTCs) that enter the bloodstream play an important role in the formation of metastases. The prognostic significance of CTCs as biomarkers obtained from liquid biopsies is intensively investigated and requires accurate methods for quantification. The purpose of this study was the capture of CTCs on an optically accessible surface for real-time quantification. A filtration device was fabricated from a transparent material so that capturing of cells could be observed microscopically. Blood samples were spiked with stained tumor cells and the sample was filtrated using a porous structure with pore sizes of 7.4 µm. The possible removal of lysed erythrocytes and the retention of CTCs were assessed. The filtration process was observed in real-time using fluorescence microscopy, whereby arriving cells were counted in order to determine the number of CTCs present in the blood. Through optimization of the microfluidic channel design, the cell retention rate could be increased by 13% (from 76% ± 7% to 89% ± 5%). Providing the possibility for real-time detection significantly improved quantification efficiency even for the smallest cells evaluated. While end-point evaluation resulted in a detection rate of 63% ± 3% of the spiked cells, real-time evaluation led to an increase of 21% to 84% ± 4%. The established protocol provides an advantageous and efficient method for integration of fully automated sample preparation and CTC quantification into a lab-on-a-chip system.
循环肿瘤细胞(CTCs)进入血液在转移的形成中起着重要作用。液体活检中 CTCs 作为生物标志物的预后意义正在被深入研究,这需要准确的定量方法。本研究的目的是在可实时定量的光学可访问表面上捕获 CTCs。通过使用透明材料制造过滤装置,可以在显微镜下观察到细胞的捕获。将染色的肿瘤细胞混入血液样本中,然后使用孔径为 7.4 µm 的多孔结构进行过滤。评估了裂解红细胞的可能去除和 CTC 的保留情况。通过荧光显微镜实时观察过滤过程,从而可以计算到达的细胞数量,以确定血液中存在的 CTC 数量。通过优化微流控通道设计,细胞保留率可提高 13%(从 76%±7%提高到 89%±5%)。实时检测的可能性大大提高了定量效率,即使对于评估的最小细胞也是如此。虽然终点评估导致掺入细胞的检测率为 63%±3%,但实时评估导致检测率从 21%增加到 84%±4%。所建立的方案为将全自动样品制备和 CTC 定量集成到微流控芯片系统中提供了一种有利且高效的方法。