Mechanical engineers at Worcester Polytechnic Institute (WPI) have developed a chip that uses only a small amount of blood drawn from a cancer patient to trap and identify metastatic cancer cells. A simple mechanical method is used in the breakthrough technology. The new technology has been demonstrated to be more effective in trapping cancer cells than current devices that use a microfluidic approach to trap cancer cells.
The new device employs antibodies that are attached to an array of carbon nanotubes at the bottom of a minuscule well. When cancer cells settle to the bottom of the well, they bind to the antibodies selectively, based on their surface markers. Cancers cells produce tiny structures called exosomes. The WPI chip can also trap the exosomes, something other devices are not able to do.
The new “liquid biopsy” was described in a recent issue of the journal Nanotechnology and it could become the basis of a simple lab test used to detect early signs of metastasis quickly. This will help doctors to select targeted specific treatments based on the cancer cells identified.
Cancer can spread from one organ to other parts of the body through the metastasis process. This is typically done by the cancer entering the bloodstream. Different types of cancer prefer to spread to specific organs and tissues. For example, circulating breast cancer cells are likely to take root in lungs, bones, or the brain. The prognosis for metastatic cancer is generally poor and a patient’s survival odds would be greatly increased if these circulating tumor cells can be detected before they have a chance to form new colonies of tumors at distant sites.
Balaji Panchapakesan, associate professor of mechanical engineering at WPI and director of the Small Systems Laboratory, explained that focusing on capturing circulating tumor cells is a relatively recent development. He adds that it is a huge challenge and compares it to looking for a needle in a haystack, as there are only a small number of tumor cells floating among billions of red blood cells and tens of thousands of white blood cells. The team has however demonstrated that the tumor cells can be captured with high precision.
Panchapakesan’s team have developed a device that includes an array of small elements, each about 3 millimeters (a tenth of an inch) across. Antibodies are attached to carbon nanotubes at the bottom of a well on each element. Different antibodies are placed in each well. Each antibody will selectively bind to one type of cancer cell type based on genetic markers on its surface. By placing an assortment of antibodies in different wells, the device could be set up to use a single blood sample to capture several different cancer cells types. In the lab, the researchers filled 170 wells by using slightly less than 0.85 milliliter (0.3 fluid ounces) of blood. In spite of it being a small sample, the team managed to capture between one and a thousand cells per device. Capture efficiency ranged between 62 and 100 percent.
The carbon nanotubes in the device perform as semiconductors. An electrical signal that can be detected is created when a cancer cell binds to one of the attached antibodies. These signals are then used to identify which of the elements in the array have captured cancer cells. The specific arrays with cancer cells are then removed and taken to a lab for analysis. The captured cells are stained and identified under a microscope. The binding and electrical signature generation process only took a few minutes in the lab. Panchapakesan notes that this suggests the possibility of getting results from a blood test using the chip on the same day.
The chip will not only latch on to tumor cells, but will also capture tiny structures called exosomes that carry the same markers. The exosomes structures are so small (3-nanometer) they can’t be captured with other types of liquid biopsy devices such as microfluidics, as shear forces would potentially destroy them. As the new chip is at present the only device that can potentially capture circulating tumor cells and exosomes directly, this should increase its ability to detect metastasis. This is critically important as emerging evidence suggests that tiny proteins excreted with exosomes can drive reactions that have the potential to become barriers to effective cancer drug delivery and treatment.
The chip has additional advantages over other liquid biopsy devices. Not only does it capture circulating tumor cells far more efficiently than microfluidic chips can, the WPI device, through differential settling, is also highly effective in splitting cancer cells from the other cells and material in blood. White blood cells pose a real problem. They are quite numerous in blood and are easily be mistaken for cancer cells. The new device uses what is called a passive leukocyte depletion strategy. The cancer cells tend to settle to the bottom of the wells where they encounter the antibodies due to density differences. The remainder of the blood contents can simply be washed away as it stays at the top of the wells.
Although the preliminary tests with the chip have focused on breast cancer, the device can be set up to detect a wide range of tumor types. Panchapakesan already plans to develop an advanced device, as well as testing for other cancer types including pancreas and lung cancer. Panchapakesan envisages a day when a device like this will be used in routine cancer screening and for regular follow-ups for patients who have had cancer.