Researchers at Worcester Polytechnic Institute led by Indian American mechanical engineering professor Balaji Panchapakesan have developed a chip made of carbon nanotubes that can capture circulating tumor cells of all sizes and types.
The institute said in a news release that the chip can capture those cells with far greater sensitivity than existing technologies.
The unique design of the device makes it possible to easily identify and even culture the captured cells, which could make it possible to detect early-stage tumors, predict the course of a cancer, and monitor the effects of therapy, it said.
Details of the new technology are reported in the journal Lab on a Chip by a team consisting of researchers at WPI, the Department of Neurological Surgery at the University of Massachusetts Medical School, and the James Graham Brown Cancer Center at the University of Louisville School of Medicine.
High cancer mortality rates are largely attributable to tumors developing undetected until they reach advanced or inoperable stages, and to metastasis. Scientists have long sought a method that can reliably snare tumor cells as they travel through the bloodstream.
Such technology could make it possible to detect cancers at very early stages, when treatment is more likely to be successful, and to spot the genetic changes that tumor cells undergo when a cancer is beginning to metastasize, the WPI report said.
“Isolating CTCs with high purity is a significant challenge, akin to finding a needle in a haystack,” Panchapakesan said in the report. “These cells comprise as few as one to 10 cells among a billion blood cells, and the shedding of CTCs from tumors is a highly discontinuous process.”
A number of research labs and companies have created so-called liquid biopsy devices, but the devices currently available have important limitations, Panchapakesan said.
These include low sensitivity; the inability to trap CTCs of all sizes and types, or to capture clusters of CTCs along with individual cells; difficulty in retrieving captured cells from the devices for laboratory analysis; and high manufacturing costs. In addition, contamination of captured CTCs by white blood cells, which are similar in size to and can be mistaken for CTCs, is a problem for many liquid biopsy devices, the report said.
The device developed by Panchapakesan’s team, described in the Lab on a Chip paper, has none of these limitations, it noted.
The centerpiece of the device is a layer of carbon nanotubes that lines the bottom of a small well formed in a silicon/glass wafer. Panchapakesan says the chip design takes advantage of a natural tendency of CTCs to attach.
“In order to travel to a distant site in the body and start a new tumor,” he said, “CTCs need the ability to attach in an environment that is not conducive to attachment. In previous research, we have shown that they will attach preferentially to carbon nanotubes, but that white blood cells will not, by and large.”
In addition, recent studies have shown that CTCs are far more fragile than previously believed and are subject to the environmental and mechanical stresses inherent in the blood stream, WPI said.
“These cells won’t survive unless you give them a rocklike matrix to attach to—a softer matrix requires too much energy from the cell,” Panchapakesan said. “It’s a medical problem at the intersection of mechanical engineering and biology. An understanding of the biology of cancer cells and how CTCs behave enabled us to design a mechanical engineering–based device.”
The fact that white blood cells do not adhere to the nanotubes makes it possible to remove them from the chip, leaving the CTCs behind to be counted and identified.
“These initial clinical studies,” Panchapakesan said, “in which we were able to capture and identify individual CTCs of varying phenotypes, show that this device could become an important tool not only for tracking the progression of cancers and their response to radiation or chemotherapy, but also in making predictions about the likely course of the cancer, which could help physicians identity the most effective course of therapy.”
Panchapakesan said he believes the latest generation of carbon nanotube liquid biopsy chip is ready for clinical trials.
Toward that end, he is working with StrandSmart Inc., a Silicon-Valley start-up led by CEO Adrianna Davies. The team envisions testing a point of care device to detect cancer in the earliest stages globally, WPI said.