Finding cancer cells in blood cells can be like finding a needle in a haystack, according to the researchers. The 3D-printed device acts as a filter that can trap white blood cells and filter out small red blood cells to leave behind tumor cells.
“Isolating circulating tumor cells from whole blood samples has been a challenge because we are looking for a handful of cancer cells mixed with billions of normal red and white blood cells,” Fatih Sarioglu, assistant professor in the school of electrical and computer engineering, said in a news release. “With this device, we can process a clinically-relevant volume of blood by capturing nearly all of the white blood cells and then filtering out the red blood cells by size. That leaves us with undamaged tumor cells that can be sequenced to determine the specific cancer type and the unique characteristics of each patient’s tumor.”
Researchers have attempted to extract tumor cells using microfluidic technology that can recognize specific surface markers on cancer cells, but cancer changes over time. Malignant cells cannot be recognized with certainty, according to the researchers.
The Georgia Tech researchers built 3D-printed traps lined with antigens to capture white blood cells in a sample. The traps allow the researchers to expand the surface area to capture white blood cells as they pass by in blood samples. The fluid channels run in a zig-zag line and increase the likelihood of white blood cells coming into contact with channel walls.
“Usual microfluidic devices have just a single layer with channel heights of 50 to 100 microns,” Sarioglu said. “They are thick, but most of it just empty plastic. Using 3D printing liberates us from the single-channel and allows us to create many channels in three dimensions that better utilize the space.”
Channel density increased with 3D printing, but that created a significant challenge. The 3D-printing processes are fabricated layer-by-layer and the channels have to be filled with wax for more channels to be built atop them. The channel structure makes it difficult to get the wax out after fabrication.
As a solution, the researchers designed cell traps that could fit in standard centrifuges that spin samples for separation. The traps were then heated in the centrifuge and spun to allow the melted wax to escape. Once the wax was removed, the channels could then receive the antigen coating.
After the white blood cells are removed from the blood sample, smaller red blood cells can pass through a commercial filter that can trap cancer cells and remaining white blood cells. Tumor cells can then be removed from the filter, which is integrated with the 3D-printed device.
The Georgia Tech researchers testing the device by adding cancer cells to blood taken from healthy people. Since they knew how many cells were added, they were able to determine how many they should extract. The 3D-printed trap captured around 90% of tumor cells. The researchers tested prostate, breast and ovarian cancer cells.
“We expect that this will really be an enabling tool for clinicians,” Sarioglu said. “In our lab, the mindset is always toward translating our research by making the device simple enough to be used in hospitals, clinics and other facilities that will help diagnose diseases in patients.”
The research was published in the journal Lab on a Chip and was supported by a seed grant from the Integrated Cancer Research Center at Georgia Tech.