Microfluidic chip improves detection of circulating tumor cells

A device is being created to monitor circulating tumor cells (CTCs), with the ability to easily retrieve the cells for further testing. The ability to detect CTCs as they travel through the blood can play an important role in early diagnosis, characterization of cancer subtypes, treatment monitoring, and metastasis. By measuring a patient's CTC levels over time, clinicians can quickly determine if a particular cancer treatment is working.

The potential benefits of CTCs abound. But with only one CTC for every one billion blood cells, finding any CTCs at all presents a significant challenge.

The researchers' previously developed devices could reliably sort CTCs from the other types of cells in whole blood—namely, red blood cells, white blood cells, and platelets. But the CTCs could not be easily retrieved for further testing.

Seeking to improve their design, the researchers' newest iteration of their “cancer lab on a chip,” the CTC-iChip, integrates several principles of magnetism and microfluidics to provide high-speed, automated sorting of the rare cells. It can be applied to almost any type of cancer.

After collecting a blood sample, the researchers mixed the sample with tiny, magnetic beads coated with specific antibodies. In some cases, the researchers used antibodies that seek out and attach to CTCs, and in other cases, they used antibodies that bind to white blood cells. This magnetic labeling would come into play later in the microfluidic sorting process.

As described in Science Translational Medicine (2013; 5(179):179ra47), the CTC-iChip was able to sort CTCs from whole blood. It is quicker than previously developed microfluidic devices, allowing larger blood samples to be processed in a short amount of time. It is more efficient than other magnet-based sorting systems, as it reduces the amount of materials required and increases the sensitivity of the device. It is more effective in samples with few epithelial cell adhesion molecule (EpCAM)-producing CTCs compared with other sorting methods. EpCAM is a protein commonly found on the surface of CTCs. Finally, it sorts more effectively in samples known to not express EpCAM, such as triple-negative breast cancer and melanoma.

By collecting CTCs in a way that allows them to be studied further, the CTC-iChip could also help clinicians identify important genetic differences between individual CTCs that may inform which targeted therapy is indicated.

“You're doing a liquid biopsy, in a sense. You find these cells in the blood and then look at their genomic makeup and decide what medication [the patient] should be put on,” said Mehmet Toner, PhD, of the Massachusetts General Hospital in Boston.

Because of intratumor heterogeneity, a biopsy needle may miss its mark. Compared with blood draws, tissue biopsies are also relatively invasive and complex, so they may not be done very often. Less frequent monitoring may miss important stages in disease progression.

“It will enable, in the long run, [a physician] to treat the right patient with the right drug at the right dose at the right time,” said Toner.

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