May 11, 2016

New device could improve cancer detection

A new University of British Columbia-developed method to isolate cancer cells that have escaped from a tumour could soon pave the way for improved diagnosis and treatment.

The simple process involves a special device that squeezes cells in a blood sample through tiny funnels, which drive the cancer cells and blood cells into separate streams based on differences in their size and softness.

“Circulating tumour cells—cells from a tumour that have escaped into the bloodstream with the potential to spread into other tissues—are extremely useful for assessing a patient’s disease in order to select the most appropriate treatment,” said UBC mechanical engineering professor Hongshen Ma, the lead researcher. “These cells are particularly important for prostate cancer, where the site of metastasis is typically in the bone, where biopsies are difficult or impossible.



Journal Small - Continuous Flow Deformability-Based Separation of Circulating Tumor Cells Using Microfluidic Ratchets



Ma’s research focus is microfluidics, the flow of liquids through channels smaller than a human hair. The microfluidic device designed by his team captures cells based on their distinct internal structure—a mechanical analysis instead of the blood chemistry analysis used in conventional medical diagnostic techniques.

The device was first tested using blood samples spiked with cancer cells. It was then used to analyze blood samples from 20 patients with metastatic castration-resistant prostate cancer, an advanced form of cancer, and from four healthy individuals.

“In the first experiment, the device was able to capture more than 90 per cent of the cells,” noted co-author Dr. Kim N. Chi, director of clinical research at the B.C. Cancer Agency and a professor of medicine at UBC. “Importantly, in patient samples the device captured about 25 times the number of cancer cells and produced fewer false positives compared to the conventional CellSearch system, which also analyzes blood samples.”

The team is currently working on genome sequencing of individual circulating tumour cells from patients at the Vancouver Prostate Centre. This would allow researchers to determine the mutations responsible for metastasis so that doctors can select the most appropriate treatment.

Abstract

Circulating tumor cells (CTCs) offer tremendous potential for the detection and characterization of cancer. A key challenge for their isolation and subsequent analysis is the extreme rarity of these cells in circulation. Here, a novel label-free method is described to enrich viable CTCs directly from whole blood based on their distinct deformability relative to hematological cells. This mechanism leverages the deformation of single cells through tapered micrometer scale constrictions using oscillatory flow in order to generate a ratcheting effect that produces distinct flow paths for CTCs, leukocytes, and erythrocytes. A label-free separation of circulating tumor cells from whole blood is demonstrated, where target cells can be separated from background cells based on deformability despite their nearly identical size. In doping experiments, this microfluidic device is able to capture >90% of cancer cells from unprocessed whole blood to achieve 104-fold enrichment of target cells relative to leukocytes. In patients with metastatic castration-resistant prostate cancer, where CTCs are not significantly larger than leukocytes, CTCs can be captured based on deformability at 25× greater yield than with the conventional CellSearch system. Finally, the CTCs separated using this approach are collected in suspension and are available for downstream molecular characterization.

4 pages of supplemental information

SOURCES- UBC, Journal Small

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