STANFORD (US)—A new biosensor chip has detected cancer tumors in mice earlier than any detection technology currently in use. The nanosensor is up to 1,000 times more sensitive and can be used to detect markers of diseases other than cancer.
The sensor is accurate regardless of which bodily fluid is being analyzed and can search for up to 64 different proteins simultaneously, the researchers from Stanford University say.
The effectiveness in detecting tumors early in mice suggests the sensor may open the door to significantly earlier detection of even the most elusive cancers in humans.
“In the early stage [of a cancer], the protein biomarker level in blood is very, very low, so you need ultra-sensitive technology to detect it,” says Shan Wang, professor of materials science and engineering and of electrical engineering, and senior author of a paper describing the sensor, which was published online in Nature Medicine on Oct. 11. “If you can detect it early, you can have early intervention and you have a much better chance to cure that person.”
Wang says the nanosensor technology also could allow doctors to rapidly determine whether a patient is responding to a particular course of chemotherapy. “We can know on day two or day three of treatment whether it is working or not, instead of a month or two later,” he adds.
The sensor Wang and his colleagues have created, which uses magnetic detection nanotechnology they had developed previously, can detect a given cancer-associated protein biomarker at a concentration as low as one part out of a hundred billion (or 30 molecules in a cubic millimeter of blood).
Although the basics of the magnetic detection technology used in the new biosensor were described last year in a paper in the Proceedings of the National Academy of Sciences, the new sensor is not only more sensitive than the previous one by several orders of magnitude, it also outperforms its predecessor—and detection methods now in use—in several other ways.
The most impressive performance gain detailed in the Nature Medicine paper is that the researchers have now demonstrated that the magnetic-nano sensor can successfully detect cancerous tumors in mice when levels of cancer-associated proteins are still well below concentrations detectable using the current standard methodology, known by the acronym ELISA.
“That is a critical finding for us because it says that in a realistic biological application—that of tumor growth in mice—we can actually see tumors before anything else could have detected them,” says Sam Gambhir, professor of radiology.
“I would say that the PNAS paper is proof of concept of the technology, and the Nature Medicine paper is proof of concept of the technology working in a real-world application,” he notes. “It is one thing to have the technology show that it can work in principle; it is quite another to actually utilize it with real mouse blood samples from a real mouse growing a real tumor.”
In the Nature Medicine paper, the researchers show that the new magnetic-nano sensor has a broad range of sensitivity, from the minute quantity described earlier to concentrations six orders of magnitude, or a million times, greater. The best existing analysis methods, or assays, in clinical use are able to detect proteins over a range of concentrations of at most two orders of magnitude.
Most of the sensing platforms currently in use are also limited to performing a single analysis at a time, but because the magnetic-nano sensors are attached to a microchip in an array of 64 sensors, each of which can be set up to detect a different protein, the researchers can search for up to 64 different proteins simultaneously during a single analysis, which typically takes one to two hours—far less than most existing assays.
The researchers also demonstrated that the sensor is equally effective in every likely biological fluid, or matrix, that a doctor would want to analyze for cancer-associated proteins.
“The idea that you could essentially, on a single assay platform, measure a broad diversity of biomolecules that are at such a wide range of concentrations with such sensitivity is really, truly remarkable,” says Charles Drescher, a professor of obstetrics and gynecology at the University of Washington in Seattle, who was not involved with the research. “I think we’ll all be very excited if this really does pan out.”
Another virtue of the technology, Wang said, is that it uses existing technology in the data storage and semiconductor industries and because of that, he adds, “It can be made relatively cheaply.”
One of the next steps in the research, says Wang, is to test the magnetic-nano sensors on human blood samples taken from a long-term study in which researchers drew blood samples from subjects prior to any of them being diagnosed with cancer.
To this end, the Stanford team will be collaborating with the Fred Hutchison Cancer Research Center in Seattle and the Canary Foundation, a nonprofit organization that focuses on early diagnosis of cancer.
“We can actually use our technology to study all these samples and we may be able to tell a year before or half a year before or three months before the diagnosis,” Wang says. “That work will be extremely interesting.”
Funding for this research came from the National Cancer Institute, the National Science Foundation, the Defense Threat Reduction Agency, the Defense Advanced Research Projects Agency, the Department of Veterans Affairs, the Canary Foundation, and the National Semiconductor Corporation.
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