A new device captures circulating tumor cells (CTCs) in the blood stream, providing a new avenue for early detection of metastatic cancer, as well as opportunities to test the source of the cells or the effectiveness of ongoing treatment.
Cancer metastasis remains one of medicine’s most difficult problems. Deadly cancer cells detach from primary tumor sites, circulating around the body until they infect new tissue. The process is treacherous and hard to detect. Patients with metastases are much more likely to succumb to their disease. In fact, the American Cancer Society reports that nearly 90% of cancer deaths are due to metastatic cancers.
Over the past few years, different research groups have attempted to engineer devices to capture circulating tumor cells (CTCs) in the blood stream, providing a new avenue for early detection of metastatic cancer, as well as opportunities to test the source of the cells or the effectiveness of ongoing treatment. But catching and then releasing a CTC for single cell genetic testing is easier said than done, according to Yaling Liu, a biomedical engineer at Lehigh University, Bethlehem, PA.
“Being able to capture these cells is important for early cancer diagnosis,” he says. “We know that early diagnosis is important to the outcome. But doctors also want to understand the treatment progression of disease. Is the disease getting better or worse? Is the treatment working? Doctors need this information from the CTCs to help them make decisions and track the status of patients. But it is a challenge to catch the cells and then release some so you can do this kind of analysis.”
The greatest challenge is engineering a device that has both high capture efficiency, the ability to capture a high percentage of CTCs, and high selectivity, the ability to discard non-cancerous cells, like regular red and white blood cells. Past devices typically offered only one or the other. But Liu and team hoped to do better.
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They designed an early prototype of unique microfluidic device, a polydimethylsiloxane (PDMS) chip with a distinct wavy herringbone patterned capture pad. When blood from a standard draw flows across the chip, the capture pad can attract CTCs, and only CTCs, using specific molecules that attract the cancer cells. The results from an early prototype were published last year in Lab on a Chip.
“This design has both micro- and nanoscale features,” Liu says. “The microscale of that wavy herringbone pattern helps with the mixing of the cells, so there is a high probability that the CTCs will collide with the capture pad. The traditional herringbone pattern has sharp, rectangular corners where cells can lump together, affecting the selectivity of the device. But with the waves, you can reduce the lumps from sticking in the corners, filtering out unwanted cells and increasing selectivity and purity.”
Since publication, the group has improved the design. The second-generation prototype now boasts magnetic nanoparticles on the capture pad. This allows better capture and release efficiencies of the CTCs. Liu reports a capture efficiency of around 92% under optimal conditions.
“The first prototype, you catch the cells, you count them, and that’s it,” Liu says. “But with this new nanoparticular feature on the capture pad, we can release some cells for testing. The doctors can see if there are any bad genetic mutations that trigger alarms, calling for a change in treatment plan. They can also culture the cells we capture for drug screening purposes.”
The device is currently being tested in a clinical setting. The researchers will follow stage II cancer patients through the entire treatment cycle, frequently drawing and testing blood using the device. And Liu is optimistic that it will provide the kind of data that will support clinical decision support when it comes to these difficult-to-treat cancers.
“This is the kind of device that can make a big difference in the early detection of disease,” Liu says. “It has very good potential, and we are hopeful that it can provide doctors with the right information to help improve these patients’ lives.”
Kayt Sukel is an independent technology writer based in Houston, TX.