Researchers develop supersensitive biosensor for cancer

A Team of physicists and engineers at Case Western Reserve University in Cleveland, OH, has created an optical biosensor for cancer detection using nanostructured metamaterials that are 1 million times more sensitive than previous versions, pointing the way toward an effective early detection system for cancer and other illnesses.

The device, which is small enough to fit in the palm of a hand, has been developed to provide oncologists with a way to detect a single molecule of an enzyme produced by circulating cancer cells.

Such detection could allow doctors to diagnose patients with certain cancers far earlier than possible today, monitor treatment and resistance, and more.

The research, published online in the journal Nature Materials, describes how the nanosensor acts like a biological sieve, isolating a small protein molecule weighing less than 800 quadrillionths of a nanogram from an extremely dilute solution.

The researchers believe the sensing technology will also be useful in diagnosing and monitoring other diseases.

“The prognosis of many cancers depends on the stage of the cancer at diagnosis,” says Giuseppe “Pino” Strangi, professor of physics at Case Western Reserve and leader of the research.

“Very early, most circulating tumor cells express proteins of a very low molecular weight, less than 500 Daltons,” Strangi explains. “These proteins are usually too small and in too low a concentration to detect with current test methods, yielding false negative results.

“With this platform, we’ve detected proteins of 244 Daltons, which should enable doctors to detect cancers earlier – we don’t know how much earlier yet,” he says. “This biosensing platform may help to unlock the next era of initial cancer detection.”

Nanotechnology tools contributed to biosensor creation
To make the device so sensitive, Strangi’s team needed to overcome a number of issues. Significantly, lightwaves cannot detect objects smaller than their own physical dimensions, which range down to about half a micron. Also, molecules in dilute solutions float randomly, meaning they are unlikely to land on a sensor’s surface.

The team was able to overcome these barriers by harnessing nanotechnology tools and coupling these to a microfluidic channel with an engineered material called a metamaterial. “It’s extremely sensitive,” Strangi says. “When a small molecule lands on the surface, it results in a large local modification, causing the light to shift.”

Depending on the size of the molecule, the reflecting light shifts different amounts. The researchers hope to learn to identify specific molecules, beginning with biomarkers for different cancers, by their light shifts.

Strangi and Dr. Nima Sharifi – co-leader of the Genitourinary Cancer Program for the Case Comprehensive Cancer Center – have begun testing the sensor for the earlier detection of prostate cancers.

“For some cancers, such as colorectal and pancreatic cancer, early detection is essential,” says Dr. Sharifi, who is also the Kendrick Family Chair for Prostate Cancer Research at Cleveland Clinic. “High sensitivity detection of cancer-specific proteins in blood should enable detection of tumors when they are at an earlier disease stage.”

“This new sensing technology may help us not only detect cancers, but what subset of cancer, what’s driving its growth and spread and what it’s sensitive to,” he says. “The sensor, for example, may help us determine markers of aggressive prostate cancers, which require treatments, or indolent forms that don’t.”

The research team is also working with other oncologists worldwide to test the device with the aim of moving the sensor toward clinical use.

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