A new optical sensor that is one million times more sensitive when it comes to detecting molecules in liquid solutions could revolutionise cancer diagnostics.
Developed by Case Western Reserve University in Cleveland, Ohio, the sensor is based on nanostructured metamaterials and fits in the palm of a hand.
The device is basically a biological sieve with the mesh so fine that it can separate a single molecule of an enzyme produced by cancer cells circulating in the bloodstream.
"Very early, most circulating tumour cells express proteins of a very low molecular weight, less than 500 daltons," explained Giuseppe "Pino" Strangi, professor of physics at Case Western Reserve and leader of the research. "These proteins are usually too small and in too low a concentration to detect with current test methods, yielding false negative results.”
That means that a patient, who actually does have early stage cancer, is told that he or she is healthy. By the time he comes back and is given the right diagnosis, the cancer may have spread too far.
"The prognosis of many cancers depends on the stage of the cancer at diagnosis" Strangi said. "With this platform, we've detected proteins of 244Da, which should enable doctors to detect cancers earlier. We don't know how much earlier yet."
Described in the online version of the journal Nature Materials, the biological sieve is made of 16 nanostructured layers of reflective and conductive gold and dielectric transparent aluminium oxide. Each of the layers is only tens of atoms thick. The top gold layer is perforated with holes to diffuse light shone on the surface in two dimensions. As it travels through the layers of the metamaterial, the light is concentrated into a very small wavelength, much smaller than the normal wavelength of light. This way, the optical sensor can detect objects much smaller than the physical dimensions of natural light waves.
As the light strikes the sensing area, it excites free electrons causing them to oscillate and generate a highly confined propagating surface wave, called a surface plasmon polariton. This propagating surface wave will in turn excite a bulk wave propagating across the sensing platform. The presence of the waves causes deep sharp dips in the spectrum of the reflected light. 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.
"It's extremely sensitive," Strangi said. "When a small molecule lands on the surface, it results in a large local modification, causing the light to shift."
As such lightweight molecules as those studied tend to float on the surface, the researchers had to create what they call microfluidic channels, to force the molecules towards the sensing platform on the surface of the metamaterial.
To add specificity to the sensor, the team added a layer of trap molecules, which are molecules that bind specifically with the molecules they hunt.
In tests, the researchers used trap molecules to catch two different biomolecules: bovine serum albumin, with a molecular weight of 66,430 daltons, and biotin, with a molecular weight of 244 daltons. Each produced a signature light shift.