A research team from the University of Illinois at Chicago and Queensland University of Technology of Australia recently created technology that can isolate cancer cells within a patient’s blood sample. Separating various types of cells in the blood by size, this microfluidic device could potentially provide rapid and inexpensive liquid biopsies to diagnose and plan treatments of cancers. These researchers’ findings were recently published in Microsystems & Nanoengineering.
“This new microfluidics chip lets us separate cancer cells from whole blood or minimally-diluted blood,” claimed Ian Papautsky, corresponding author of the paper and the Richard and Loan Hill Professor of Bioengineering in the UIC College of Engineering and corresponding author on the paper. “While devices for detecting cancer cells circulating in the blood are becoming available, most are relatively expensive and are out of reach of many research labs or hospitals. Our device is cheap, and doesn’t require much specimen preparation or dilution, making it fast and easy to use.”
Isolating individual cancer cells is a challenging, yet essential step in creating a liquid biopsy system using simple blood samples. Creating such a system would eliminate the uncomfortable biopsy procedures currently in place, often using needles or surgery to diagnose the cancer. A liquid biopsy that matched the efficacy of traditional biopsy methods would likely do so at a reduced cost as well. Liquid biopsy procedures could also hold utility in tracking chemotherapy treatments over time, as well as detecting cancers in organs such as the lungs or brain that are challenging to reach.
The challenge presents in isolating these cancer cells from the blood samples, being that they are usually present in trace quantities. Many cancers display circulating cells at levels as low as one per 1 billion blood cells. “A 7.5-milliliter tube of blood, which is a typical volume for a blood draw, might have ten cancer cells and 35-40 billion blood cells,” Papautsky stated. “So we are really looking for a needle in a haystack.”
Using an alternative means to traditional cell detection in blood, the researchers decided to employ microfluidic technologies in their model. Such devices use markers to captured targeted cells as they pass by or separate the targeted cells from other cells in the sample by physical properties such as size.
Papautsky and his team decided to use the latter of these two detection mechanisms in their device, targeted cell size as the main means of separation. “Using size differences to separate cell types within a fluid is much easier than affinity separation which uses ‘sticky’ tags that capture the right cell type as it goes by,” he said. “Affinity separation also requires a lot of advanced purification work which size separation techniques don’t need.”
The device they created separates cancer cells as they pass through microchannels formed in plastic, making use of the phenomena known as inertial migration and shear-induced diffusion. Papautsky notes that he and his colleagues are still researching the physics that involve these phenomena and how to best integrate them into the device. In describing the process, he said it “separates cells based on tiny differences in size which dictate the cell’s attraction to various locations within a column of liquid as it moves.”
Inserting 10 small-cell-lung cancer cells into 5 milliliter samples of healthy blood, the team was able to recover 93% of the cancer cells using their microfluidic device. Microfluidic devices tested in the past were only able to separate tumor cells from serum samples with recovery rates of 50-80% at best.
Papautsky noted that the device is not only extremely efficient and reliable, but that little dilution of the samples is needed as well. “Without having to dilute, the time to run samples is shorter and so is preparation time.”
— Phys.org (@physorg_com) February 25, 2019