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In 1869, circulating tumor cells (CTCs) were first observed in a man with metastatic cancer. At that time, it was postulated that cancer cells found in the blood originate from a primary source. Recently, it has been shown that this theory is correct and that CTCs break off from primary locations and circulate through the bloodstream. This essentially makes CTCs seeds or spores which end up settling in other organs (metastasis) wreaking havoc to the body.

Quantifying CTCs can be a tedious task because there are sometimes only 1-10 cancer cells in a 1 milliliter sample of blood. Detecting these types of cells could be a great help to doctors, allowing them to monitor effectiveness of treatment and analyze metastasis risk. Standard tissue biopsy is invasive and offers poor diagnostic information regarding risk of the cancer spreading and disease progression.

Now, a team of scientists from three leading institutions, MIT, Penn State University and Carnegie Mellon University have improved upon a novel method to isolate and trap cancer cells using sound waves. The first version of the device was pronouncedly slow, but the new version is 20 times faster, making it a viable option for blood sampling for CTCs. Recently, the team showed proof of the accuracy in actual patient samples, highlighting the method’s ability to weed out abnormal cells.

Other methods of separating and isolating cells require chemical tagging or exposure to damaging mechanical forces. This device uses two acoustic transducers which are located on opposite sides of a microfluidic channel. When the sound waves from the transducers meet, they make a standing wave which forms pressure nodes. As cells pass through the channel, they interact with the waves and are pushed to the side of the channel, where the distance of movement directly coincides with the size of the cell and other properties, like compressibility.

The new version of the device has a working flow rate that is about 20 times faster than the old version, which took more than 50 hours to separate a standard sample of 6 ml. This was accomplished by testing and changing parameters of the device like tilt angle of the transducers.

Practical Applications

Research has been conducted with the new acoustic device using samples of a mix of cancer cells grown in a lab. These tests showed an 83 percent isolation rate of cancer cells in samples where there were as few as one CTC per 100,000 white blood cells.

"Looking for circulating tumor cells in a blood sample is like looking for a needle in a haystack," said Tony Jun Huang, professor of engineering science and mechanics. "Typically, the CTCs are about one in every one billion blood cells in the sample."

Initial results from clinical testing of blood samples from three breast cancer patients showed an isolation of one, eight and 59 cells. The surprising result of one cell was from a woman who showed good response to treatment, therefore had less circulating tumor cells.

“With further improvements in cell throughput, this work could offer a useful new tool, for both basic research into the complex topic of circulating tumor cells and for clinical assessment of different types of cancer,” said Subra Suresh, president of Carnegie Mellon University

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