New Rapid and Inexpensive Cancer Liquid Biopsy To become Prevalent In The Medical Industry
An inexpensive and fast yet sensitive technique to detect cancer markers is bringing researchers closer to a "
liquid biopsy"- a test using a small sample of blood or serum to detect
cancer, rather than the invasive tissue sampling routinely used for diagnosis.
Medical researchers at the University of Illinois developed a method to capture and count
cancer-associated microRNAs, or tiny bits of messenger molecules that are exuded from cells and can be detected in blood or serum, with single-molecule resolution.
Study leader Dr Brian Cunningham, an Illinois professor of electrical and computer engineering who also directs the Holonyak Micro and Nanotechnology Lab at Illinois told
Thailand Medical News, "
Cancer cells contain gene mutations that enable them to proliferate out of control and to evade the immune system, and some of those mutations turn up in microRNAs. There are specific microRNA molecules whose presence and concentration is known to be related to the presence and aggressiveness of specific types of cancer, so they are known as biomarkers that can be the target molecule for a diagnostic test.”
Dr Cunningham's group developed a technique named
Photonic Resonator Absorption Microscopy or
PRAM, to capture and count microRNA biomarkers. In collaboration with professor Manish Kohli at the Moffitt
Cancer Center in Florida, they tested PRAM on two microRNAs that are known markers for prostate
cancer.
The researchers found it was sensitive enough to detect small amounts that would be present in a patient's serum, yet also selective enough to detect the marker among a cocktail of molecules that also would be present in serum.
Dr Nantao Li, a graduate student and co-first author added, "One of the main challenges of biosensing is to maintain sensitivity and selectivity at the same time. You want it to be sensitive enough to detect very small amounts, but you don't want it to pick up every RNA in the blood. You want this specific sequence to be your target."
The
PRAM platform achieves both qualities by combining a molecular probe and a photonic crystal sensor. The probe very specifically pairs to a designated microRNA and has a protective cap that comes off when it finds and binds to the target
biomarker. The exposed end of the probe can then bind to the sensor, producing a signal visible through a microscope.
Every individual probe that binds sends a separate signal that the researchers can count. This means researchers are able to detect much smaller amounts than traditional methods like fluorescence, which need to exceed a certain threshold to emit a measurable signal. Being able to count each biomarker also carries the added benefit of allowing researchers to monitor changes in the concentration of the
biomarker over time.
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Postdoctoral researcher Dr Taylor Canady, a co-first author of the study added, "With PRAM, we squirt a sample into a solution and get a readout within two hours. Other technologies that produce single-molecule readouts require extra processing and additional steps, and they require a day or more of waiting. PRAM seems like something that could be much more feasible clinically. In addition, by using an optical signal instead of fluorescence, we could one day build a miniaturized device that doesn't need a trained laboratory technician."
The new PRAM approach could be adapted to different microRNAs or other biomarkers, the researchers say, and is compatible with existing microscope platforms.
Dr Cunningham added, "This approach makes the idea of performing a 'liquid biopsy' for low-concentration cancer-related molecules a step closer to reality. This advance demonstrates that it is possible to have an inexpensive and routine method that is sensitive enough to require only a droplet of blood. The results of the test might tell a physician whether a regimen of chemotherapy is working, whether a person's cancer is developing a new mutation that would make it resistant to a drug, or whether a person who had been previously treated for cancer might be having a remission."
Reference: Canady, T. D., Li, N., Smith, L. D., Lu, Y., Kohli, M., Smith, A. M., & Cunningham, B. T. (2019). Digital-resolution detection of microRNA with single-base selectivity by photonic resonator absorption microscopy. Proceedings of the National Academy of Sciences, 116(39), 19362–19367. https://doi.org/10.1073/pnas.1904770116 
