Researchers from the Georgia Institute of Technology (GIT) have successfully demonstrated the separation or isolation of circulating tumour cells (CTCs) from blood samples with the help of a 3D printed microfluidic device that acts like a cancer cell trap.
The research paper titled ‘Hybrid Negative Enrichment of Circulating Tumor Cells from Whole Blood in a 3D-Printed Monolithic Device’ was published in the Journal ‘Lab on a Chip’.
This research by Georgia Tech researchers presents an exciting opportunity for cancer research and personalized treatment of the diseases as it allows rapid and low-cost separation of cancer cells circulating in the bloodstream.
- 1 According to A. Fatih Sarioglu, one of the authors of the research and an assistant professor in Georgia Tech’s School of Electrical and Computer Engineering (ECE)
- 2 “Isolating circulating cancer 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. 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 cancer cells that can be sequenced to determine the specific cancer type and the unique characteristics of each patient’s tumour.”
“Isolating circulating cancer 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. 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 cancer cells that can be sequenced to determine the specific cancer type and the unique characteristics of each patient’s tumour.”
Other methods of trapping the cancer cells attempted earlier are complicated while yielding average results with a possibility of damage while removing the cancer cells from circuitous channels in the device.
Authors Sarioglu and first author Chia-Heng Chu, attempted a unique approach by making use of 3D printed traps lined with antigens to capture the white blood cells in a sample. This method allowed the researchers to increase the surface area and time to capture the white blood cells as they pass through the blood samples. The zig-zag device channels increase the likelihood of trapping all the blood cells that would come into contact with a channel wall.
Sarioglu explained, “Usual microfluidic devices have just a single layer with channel heights of 50 to 100 microns. 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.”
3D Printed Microfluidic Device
In the above image, the figure (a) shows a schematic showing the tumour cell enrichment process in the device. Whole blood is introduced to the device. WBCs are captured in the multi-layered immunocapture channels. A membrane filter retains all nucleated cells (including the residual WBCs) and eliminates anucleated blood cells.
Figure (b) represents a photo of the 3D-printed device showing the microfluidic channels with 32 stacked microfluidic layers and the filter holder (right). The membrane filter can be accessed by removing the threaded cap (left).
Figure (c) shows a scanning electron micrograph of the cross-section of the device showing 200 μm-diameter microposts within the microfluidic layers.
Figure (d) shows, arrayed micropillars, within each layer, are shifted by 10 μm from row-to-row to maximize cell-micropost interactions.
The 3D printed microfluidic device is designed in such a way that it fits into standard centrifuges designed to spin samples for separation. The traps are heated in the centrifuge and then spun to allow the melted wax to escape. After removing the liquid wax, the channels receive the antigen coating.
After the white blood cells are removed, the smaller red blood cells pass through a simple commercial filter that traps the cancer cells and any remaining white blood cells. The cancer cells can then be removed from the filter, which is integrated into the 3D printed device.
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As part of the proof of principle testing, the researchers coated the white blood cells with biotin to accelerate testing. Future cell traps will use antigens designed to attract the cells to the channel walls without the biotin processing step.
The researchers tested their approach by adding cancer cells to blood taken from healthy people. Because they knew how many cells were added, they could tell how many they should extract, and the experiment showed the trap could capture around 90 percent of the cancer cells. Later testing of blood samples from prostate cancer patients isolated cancer cells from a 10-milliliter whole blood sample.
The recent experimentation included cells from prostate, breast and ovarian cancer, but according to Sarioglu, “The device will capture circulating cancer cells from any type of cancer because the removal mechanism targets blood cells rather than cancer cells.”
He added, “We expect that this will really be an enabling tool for clinicians. 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 disease in patients.”
The research paper titled ‘Hybrid Negative Enrichment of Circulating Tumor Cells from Whole Blood in a 3D-Printed Monolithic Device’ was published in the Journal ‘Lab on a Chip’ was supported by a seed grant from the Integrated Cancer Research Center at Georgia Tech. It is authored by Georgia Tech researchers, namely, Chia-Heng Chu, Ruxiu Liu, Tevhide Ozkaya-Ahmadov, et al.
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