Jellyfish tentacles have inspired a way to detect cancer, microbes and viruses, researchers say.Devices resulting from this research could help quickly and sensitively detect life-threatening diseases and capture dangerous cells for analysis so that doctors can devise the best therapies to fight them, investigators added.
Jellyfish and relatives of theirs such as sea anemones capture prey flowing past them with long tentacles coated with multiple sticky patches.
These sea animals guided scientists to develop a novel microchip covered with a network of long DNA strands that could grab onto proteins as they floated by.
“Nature has overcome the most challenging barriers … Evolution really is the best problem-solver, and there is so much we can learn from nature,” bioengineer Jeffrey Karp, co-director of the centre for Regenerative Therapeutics at Brigham and Women’s Hospital in Boston, told TechNewsDaily.
DNA is the molecule that holds the blueprints of life. Sequences of DNA known as aptamers also show a remarkable ability to bind onto very specific targets.
To test their device, Karp and his colleagues generated long DNA strands with aptamers that would bind onto a protein found abundantly on the surfaces of human cancer cells. The strands are up to hundreds of microns long — in comparison, the average human hair is about 100 microns wide. The length of these strands gives them more area to snag onto target proteins and their associated cells than other methods that employ antibodies or shorter DNA strands.
In addition, the strands are anchored onto a microchannel with a herringbone pattern on its floor. The patterned ridges cause blood to swirl as it flows through the channel, improving the chances that cells will come into contact with the DNA tentacles.
In experiments, blood samples containing leukemia cells were flowed past the device. These long DNA tentacles efficiently captured up to about 80 per cent of these cells, about six times more than methods relying on antibodies or shorter DNA strands.
“The chip we have developed is highly sensitive,” said researcher Weian Zhao, formerly at Karp’s lab, now at the University of California, Irvine. “From just a tiny amount of blood, the chip can detect and capture the small population of cancer cells responsible for cancer relapse.”
In addition to hunting for blood-based cancers, the device might also find cancer cells that have broken away from tumors and are travelling through the bloodstream. Roaming cancers known as metastases are the leading cause of deaths from cancer, but these wandering cells are very rare in the bloodstream, with just a few to several thousand per milliliter of a patient’s blood.
“Our device has the potential to catch these cells in the act with its ‘tentacles’ before they may seed a new tumour in a distant organ,” Karp said.
In addition, the device could handle rates of flow 10 times faster than comparable methods. The researchers say they could boost this speed 100-fold, suggesting the system might be fast enough for practical use in the clinic.
“If you had a rapid test that could tell you whether there are more or less of these cells over time, especially those cells that can specifically seed a metastasis, that would help to monitor the progression of therapy and progression of the disease,” Karp said.
Moreover, the device was able to later release entrapped cells so researchers could grow them in the laboratory. This could help enable personalised therapies — once cells are isolated from a patient, doctors could test a variety of drugs on them to see which might be most effective.
“One of the greatest challenges in the treatment of cancer patients is to know which drug to prescribe,” Karp said. “By isolating circulating tumour cells before and after the first round of chemotherapy is given, we can determine the biology behind why certain cells are resistant to chemotherapy. We can also use the isolated cells to screen drugs for personalised treatments that could boost effectiveness and hopefully prevent cancer relapse.”
The researchers can readily tailor the DNA tentacles to bind onto other targets, such as microbes and viruses. For instance, by targeting fetal cells that are very rare in a pregnant woman’s bloodstream, the device could help doctors perform prenatal diagnostic tests for a range of diseases, an approach far less invasive than amniocentesis, which involves sticking a needle into the tissue surrounding the foetus.
“We are now gearing up to test our approach on patient samples,” Karp said. “The major obstacle ahead of us is resources. The more we have, the more aggressively we can pursue this approach and advance it to the clinic.”
Zhao, Karp and their colleague Rohit Karnik detailed their findings online Nov. 12 in the journal Proceedings of the National Academy of Sciences.
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