NEW YORK (GenomeWeb) – A team led by researchers at Case Western Reserve University has developed a miniaturized plasmonic biosensor platform capable of detecting low molecular weight molecules, such as cancer biomarkers, with significantly greater sensitivity than currently available systems.
Detailed in a paper published this week in Nature Materials, the platform could prove useful for applications including the detection of low-abundance proteins markers shed by circulating tumor cells, Giuseppe Strangi, a CWRU researcher and senior author of the paper, told GenomeWeb.
Currently, he said, he and his colleagues are collaborating with researchers at Cleveland's Case Comprehensive Cancer Center on using the platform to study cancer biomarkers.
Optical sensor technology offers significant opportunities in the field of medical research and clinical diagnostics, but is limited by the wavelength of the visible light and the molecular diffusion, Strangi noted.
This was problem for detecting "molecules of low molecular weight," he said. "Because light is generally interacting with matter at the micrometre scale, which is related to the wavelength, and it was not possible really to beat the diffraction limit and get below that scale. We have designed optical metamaterials to go beyond that limit"
For instamce, To get around this problem, researchers turned to metamaterials like gold nanorods, which allowed them to trap light and concentrate it in small volumes. Detection of low-abundance, low molecular weight molecules remained a challenge, however. The researchers addressed this using a form of metamaterials called hyperbolic metamaterials that enable highly sensitive multiplexed biosensing on a small enough scale to be used at the point of care.
To evaluate their device, Strangi and his colleagues tested its ability to detect biotin, using a standard streptavidin-biotin affinity model. Conventional plasmon resonance sensing can only detect biotin down to concentrations of around 100 micromolar, while metamaterial-based systems are able to go down to 10 micromolar concentrations. The CWRU system improved this by six orders of magnitude, managing quantitation of biotin at a concentration of 10 picomolar.
They then looked at the performance of the device for detecting bovine serum albumin, finding that it could see that protein at levels as low as 10 femtomolar and that, given the large signal present at this concentration, it would likely be able to go down to attomolar levels of detection.
To apply the sensor to actual biological samples, the researchers are developing a nanofluidic interface that will prepare and separate the sample to allow for the detection of target analytes, Strangi said.
"We are designing nanofluidic channels that include filtration and separation of blood before it is sent to the plasmonic sensor by using nanochannels that can select physically or chemically for the molecules we are looking for," he said. "We think by putting this together, we will be able to handle most of the biological fluids clinicians usually use for tests."
In addition, the system has an inherent multiplexing ability in that it can operate at different frequencies simultaneously, some of which are more sensitive for certain molecules than others, Strangi noted. "We have a sort of biological sieve where lots of small molecules can be detected by one mode, and not the other, so it is a sort of selector. Having many modes will allow us to detect molecules of different molecular weights because of the differential sensitivity of the system."
Strangi said he and his colleagues are filing patents on the technology but that they don't have any specific commercialization plan in place.
They are currently collaborating on pilot projects with the Case Comprehensive Cancer Center, looking at prostate cancer with the aim of investigating proteins helpful in diagnosis and in better understanding processes of metastasis and development of drug resistance. They also plan in the near future to use the platform to study other malignancies, including pancreatic and colorectal cancer.