ACS Nano. 2018 Dec 26;12(12):12692-12700. doi: 10.1021/acsnano.8b07616. Epub 2018 Nov 21.
The analysis of heterogeneous subpopulations of circulating tumor cells (CTCs) is critical to enhance our understanding of cancer metastasis and enable noninvasive cancer diagnosis and monitoring. The phenotypic variability and plasticity of these cells-properties closely linked to their clinical behavior-demand techniques that isolate viable, discrete fractions of tumor cells for functional assays of their behavior and detailed analysis of biochemical properties. Here, we introduce the Prism Chip, a high-resolution immunomagnetic profiling and separation chip which harnesses a cobalt-based alloy to separate a flowing stream of nanoparticle-bound tumor cells with differential magnetic loading into 10 discrete streams. Using this approach, we achieve exceptional purity (5.7 log white blood cell depletion) of isolated cells. We test the differential profiling function of the integrated device using prostate cancer blood samples from a mouse xenograft model. Using integrated graphene Hall sensors, we demonstrate concurrent automated profiling of single cells and CTC clusters that belong to distinct subpopulations based on protein surface expression.
分析循环肿瘤细胞(CTC)的异质亚群对于增强我们对癌症转移的理解以及实现非侵入性癌症诊断和监测至关重要。这些细胞的表型变异性和可塑性——与它们的临床行为密切相关——需要能够分离出具有活力的、离散的肿瘤细胞分数的技术,以对其行为进行功能测定,并对生化特性进行详细分析。在这里,我们介绍了 Prism Chip,这是一种高分辨率免疫磁谱和分离芯片,利用基于钴的合金将具有不同磁加载的纳米颗粒结合的肿瘤细胞的流动流分离成 10 个离散的流。通过这种方法,我们实现了分离细胞的极高纯度(5.7 个对数白细胞耗竭)。我们使用来自小鼠异种移植模型的前列腺癌血液样本测试了集成设备的差异分析功能。我们使用集成的石墨烯霍尔传感器,展示了基于蛋白表面表达对属于不同亚群的单个细胞和 CTC 簇的同时自动分析。