Scientists develop technology to capture tumor cells

Instead of looking for a needle in a haystack, what would happen if you could sweep the entire haystack on one side, leaving only the needle? This is the strategy followed by researchers at the University of Georgia College of Engineering to develop a new microfluidic device that separates elusive circulating tumor cells (CTCs) from a whole blood sample.

CTCs detach from cancerous tumors and circulate in the blood, potentially leading to new metastatic tumors. The isolation of CTC from blood is a minimally invasive alternative for the understanding, diagnosis and prognosis of metastatic cancer. But most studies are limited by technical challenges to capture intact and viable CTCs with minimal contamination.

"A typical sample of 7 to 10 milliliters of blood contains only a few CTCs," said Leidong Mao, a professor at UGA University's Faculty of Electrical and Computer Engineering and principal investigator of the project. "They are hiding in whole blood with millions of white blood cells – it is difficult to have enough CTCs for scientists to study and understand."

Circulating tumor cells are also difficult to isolate because, in a sample of a few hundred CTCs, the individual cells may have many characteristics. Some look like skin cells while others look like muscle cells. They can also vary greatly in size.

"People often compare CTC research looking for a needle in a haystack," Mao said. "But sometimes the needle is not even a needle."

To more quickly and efficiently isolate these rare cells for analysis, Mao and his team have created a new microfluidic chip that captures almost every CTC in a blood sample – more than 99% – a percentage significantly greater than the most existing technologies.

The team described its innovative approach to detecting CTC as "Integrated Ferrohydrodynamic Cell Separation" or iFCS. They describe their findings in a study published in the Royal Society of Chemistry & # 39; s Lab on a chip.

The new device could be "transformative" in the treatment of breast cancer, according to Melissa Davis, assistant professor of cell biology and development at Weill Cornell Medicine and project collaborator.

"Doctors can only treat what they can detect," Davis said. "We often can not detect some CTC subtypes, but with the iFCS device, we will capture all CTC subtypes and even determine which subtypes are most informative with respect to relapse and progression. of the disease. "

Davis thinks that the device will ultimately allow doctors to evaluate a patient's response to specific treatments much sooner than it is currently possible.

While most efforts to capture circulating tumor cells focus on identifying and isolating some CTCs hidden in a blood sample, the iFCS takes a completely different approach by eliminating all element of the sample that is not a circulating tumor cell.

The device, the size of a USB stick, works by channeling blood through channels smaller in diameter than a human hair. To prepare the blood for analysis, the team adds magnetic beads the size of one micron to the samples. The white blood cells of the sample attach to these beads. As the blood flows through the device, magnets at the top and bottom of the chip drive the white blood cells and their magnetic beads into a specific channel, while the circulating tumor cells continue into another channel.

The device combines three steps in a microfluidic chip, a further advance over existing technologies that require separate devices for different stages of the process.

"The first step is a filter that removes large debris in the blood," said Yang Liu, a PhD student in UGA's chemistry department and co-lead author of the journal. "The second part exhausts the extra magnetic beads and the majority of the white blood cells, while the third part is designed to concentrate the remaining white blood cells in the middle of the canal and push the CTCs onto the sidewalls."

Wujun Zhao is the other main author of the newspaper. Zhao, a postdoctoral fellow at the Lawrence Berkeley National Laboratory, worked on the project while completing his Ph.D. in chemistry at UGA.

"The success of our integrated device lies in its ability to enrich almost any CTC, regardless of their size profile or antigen expression," Zhao said. "Our findings could potentially provide the cancer research community with key information that could be omitted by current protein-based enrichment technologies or sizes."

The researchers said their next steps would be to automate the iFCS system and make it more user-friendly for clinical environments. They must also test the device when testing on patients. Mao and his colleagues hope that new collaborators will join them and bring their expertise to the project.