Novel chip captures rare cancer cells


Rebecca Pool

Friday, May 22, 2015 - 12:15
Image of cancer cell cluster within microfluidic chip [Toner/MGH]
Researchers have developed a microfluidic chip that can capture rare clusters of circulating tumour cells, which could yield important new insights into how cancer spreads. 
Lead researcher, Professor Mehmet Toner, from Massachusetts General Hospital (MGH) and the Harvard-MIT Division of Health & Sciences Technology, has unveiled a stunning image of a cell cluster captured by 'Cluster-Chip' and hopes his tool will stimulate research in cancer metastasis.
Circulating tumour cells (CTCs) are cells that break away from a tumour and move through a cancer patient’s bloodstream.
While clusters of CTCs are extremely rare, and have yet to be thoroughly investigated, Toner and colleagues have developed a microfluidic chip designed to capture these cell groups from unprocessed blood.
Toner and colleagues recently used 'Cluster-Chip' to capture and analyse CTC clusters in a group of 60 patients with metastatic breast, prostate, and melanoma cancers.
Magnification of circulating tumor cell cluster captured by Cluster-Chip [Sarioglu et al/Nature Methods]
The researchers found CTC clusters - ranging from two to 19 cells - in 30-40 percent of the patients. 
As Toner says: "The presence of these clusters is far more common than we thought in the past... and the fact we saw clusters in this many patients is really a remarkable finding."
According to the researcher, the chip is designed to slowly push blood through many rows of microscopic triangle-shaped posts.
The posts are arranged in such a way that every two posts funnel cells towards the tip of a third post.
At the tip, single cells - including blood cells and single CTCs - easily slide to either side of the post and continue through the chip until reaching the next tip.
However CTC clusters are left at the tip, hanging in the balance due to forces pulling them down the post in opposite directions.
Fluorescently labelled cancer cell cluster balancing on the tip of a post within Cluster-Chip [ Mehmet Toner, BioMicroElectroMechanical Systems Resource Center at MGH]
To determine the efficiency of Cluster-Chip, the researchers introduced fluorescently tagged cell clusters (ranging from 2-30 cells) into the chip and counted the number of clusters that were captured and the number that flowed through undetected.
At a blood flow rate of 2.5ml/hr, the chip captured 99 percent of clusters containing four or more cells, 70 percent of three-cell clusters, and 41 percent of two-cell clusters.
Comparison of the clusters under a microscope before and after capture found that the chip had no negative effects on the integrity of the clusters as a whole.
Toner anticipates that the Cluster-Chip will play an important role in stimulating new research on CTC cluster biology.
“It’s like poking a sleeping bear," he says. "It could really awaken the field to go after clusters and to develop even better technologies to understand their biology in cancer metastasis.”
Research is published in Nature Methods.
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