A novel microfluidic platform for size and deformability based separation and the subsequent molecular characterization of viable circulating tumor cells

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Abstract

Circulating tumor cells (CTCs) were introduced as biomarkers more than 10 years ago, but capture of viable CTCs at high purity from peripheral blood of cancer patients is still a major technical challenge. Here, we report a novel microfluidic platform designed for marker independent capture of CTCs. The Parsortix™ cell separation system provides size and deformability-based enrichment with automated staining for cell identification, and subsequent recovery (harvesting) of cells from the device. Using the Parsortix™ system, average cell capture inside the device ranged between 42% and 70%. Subsequent harvest of cells from the device ranged between 54% and 69% of cells captured. Most importantly, 99% of the isolated tumor cells were viable after processing in spiking experiments as well as after harvesting from patient samples and still functional for downstream molecular analysis as demonstrated by mRNA characterization and array-based comparative genomic hybridization. Analyzing clinical blood samples from metastatic (n= 20) and nonmetastatic (n= 6) cancer patients in parallel with CellSearch® system, we found that there was no statistically significant difference between the quantitative behavior of the two systems in this set of twenty six paired separations. In conclusion, the epitope independent Parsortix™ system enables the isolation of viable CTCs at a very high purity. Using this system, viable tumor cells are easily accessible and ready for molecular and functional analysis. The system's ability for enumeration and molecular characterization of EpCAM-negative CTCs will help to broaden research into the mechanisms of cancer as well as facilitating the use of CTCs as “liquid biopsies.”

What's new?

Circulating tumor cells (CTCs) carry vital information about a tumor but are few in number, challenging their use as diagnostic tools. Moreover, not all CTCs express epithelial markers, holding back the advance of promising approaches based on the combination of cell-surface antigen targeting with microfluidic technology. Here, an antigen-independent microfluidic separation platform based on differences in cell size and deformability is shown to effectively capture CTCs, enabling the isolation of CTCs from tumors lacking epithelial markers. The capture of viable CTCs from peripheral blood paves the way to the future use of “liquid biopsies” in cancer diagnosis.

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