ABSTRACT
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.
Subject(s)
Cell Separation , Microfluidic Analytical Techniques , Neoplastic Cells, Circulating/pathology , Prostatic Neoplasms/pathology , Cell Line, Tumor , Humans , Male , Nanoparticles/chemistry , Prostatic Neoplasms/bloodABSTRACT
Tumors can shed thousands of cells into the circulation daily. These circulating tumor cells (CTCs) are heterogeneous, and their phenotypes change dynamically. Real-time monitoring of CTC phenotypes is crucial to elucidate the role of CTCs in the metastatic cascade. Here, we monitor phenotypic changes in CTCs in mice xenografted with tumors with varying aggressiveness during cancer progression and a course of chemotherapy to study the metastatic potential of CTCs and changes in the properties of these cells in response to treatment. A new device that enables magnetic ranking cytometry (MagRC) is employed to profile the phenotypic properties of CTCs. Overall, CTCs from metastatic xenografts in mice display dynamic and heterogeneous profiles while non-metastatic models had static profiles. Decreased heterogeneity followed by a reduction in metastasis incidence was observed after a course of chemotherapy administered to highly metastatic xenografts. Phenotypic profiling of CTCs could be employed to monitor disease progression and predict therapeutic responses.
