Cutting-edge science, a clichéd term often used to describe new techniques or instruments that are seemingly superior to what is currently employed, yet most often not mainstream enough to be recognized by the general populace. Yet, liquid biopsy—a minimally invasive technique of capturing and identifying tumor cells and/or DNA—embodies all that is new and exciting about translational medicine.
Now, researchers at the Worcester Polytechnic Institute (WPI) have developed a new chip that can trap and identify metastatic cancer cells within a tiny amount of blood drawn from a cancer patient. The breakthrough technology uses a simple mechanical method that has been shown to be more efficient in trapping cancer cells than the microfluidic approach employed in many existing devices.
The new device uses antibodies attached to an array of carbon nanotubes at the bottom of a tiny well. Cancer cells settle to the bottom of the well, where they bind selectively to the antibodies based on their surface markers (unlike other devices, the chip can also trap tiny structures called exosomes produced by cancers cells). The WPI team is optimistic that this new design will become the basis of a simple lab test that could quickly detect early signs of metastasis and help physicians select treatments targeted at the specific cancer cells identified.
“The focus on capturing circulating tumor cells is quite new,” said senior study investigator Balaji Panchapakesan, Ph.D., associate professor of mechanical engineering at WPI and director of the Small Systems Laboratory. “It is a very difficult challenge, not unlike looking for a needle in a haystack. There are billions of red blood cells, tens of thousands of white blood cells, and, perhaps, only a small number of tumor cells floating among them. We’ve shown how those cells can be captured with high precision.”
The device developed by the WPI team includes an array of tiny elements, each about a tenth of an inch (3 millimeters) across. Each element has a well, at the bottom of which are antibodies attached to carbon nanotubes. Each well holds a specific antibody that will bind selectively to one type of cancer cell type, based on genetic markers on its surface. By seeding elements with an assortment of antibodies, the device could be set up to capture several different cancer cells types using a single blood sample.
In the lab, the researchers were able to fill a total of 170 wells using just under 0.3 fluid ounces (0.85 mL) of blood. Even with that small sample, they captured between one and a thousand cells per device, with a capture efficiency of between 62% and 100%.
The findings from this new study were published recently in Nanotechnology in an article entitled “Static Micro-Array Isolation, Dynamic Time Series Classification, Capture and Enumeration of Spiked Breast Cancer Cells in Blood: The Nanotube–CTC Chip.”
Intriguingly, the carbon nanotubes used in the device act as semiconductors—so, when a cancer cell binds to one of the attached antibodies, it creates an electrical signature that can be detected. These signals can be used to identify which of the elements in the array have captured cancer cells. Those individual arrays can then be removed and taken to a lab, where the captured cells can be stained and identified under a microscope. In the lab, the binding and electrical signature generation process took just a few minutes, suggesting the possibility of getting same-day results from a blood test using the chip.
Even more remarkably, in addition to capturing tumor cells, the investigators noted that the chip would also latch on to tiny structures called exosomes, which are produced by cancers cells and carry the same markers.
“These highly elusive 3-nanometer structures are too small to be captured with other types of liquid biopsy devices, such as microfluidics, due to shear forces that can potentially destroy them,” Dr. Panchapakesan remarked. “Our chip is currently the only device that can potentially capture circulating tumor cells and exosomes directly on the chip, which should increase its ability to detect metastasis. This can be important because emerging evidence suggests that tiny proteins excreted with exosomes can drive reactions that may become major barriers to effective cancer drug delivery and treatment.”
Moreover, the WPI device is also highly effective in separating cancer cells from the other cells and material in the blood through differential settling—setting the new chip apart from current microfluidic designs.
“White blood cells, in particular, are a problem because they are quite numerous in blood and they can be mistaken for cancer cells,” Dr. Panchapakesan noted. “Our device uses what is called a passive leukocyte depletion strategy. Because of density differences, the cancer cells tend to settle to the bottom of the wells (and this only happens in a narrow window), where they encounter the antibodies. The remainder of the blood contents stays at the top of the wells and can simply be washed away.”
While the initial tests with the chip have focused on breast cancer, the WPI team noted that the device could be set up to detect a wide range of tumor types, and plans are already in the works for development of an advanced device as well as testing for other cancer types, including lung and pancreas cancer.
“Imagine going to the doctor for your yearly physical. You have blood drawn, and that one blood sample can be tested for a comprehensive array of cancer cell markers,” Dr. Panchapakesan concluded. “Cancers would be caught at their earliest stage, and other stages of development and doctors would have the necessary protein or genetic information from these captured cells to customize your treatment based on the specific markers for your cancer. This would really be a way to put your health in your own hands.