Plasmonic Sensor Improves Detection of Cancer Biomarkers

A novel plasmonic sensor has demonstrated the ability to detect the presence of the cancer biomarker carcinoembryonic antigen (CEA) to the magnitude of one nanogram per milliliter. According to researchers, this is a significant improvement over current surface plasmon resonance systems, and a dynamic range that is clinically relevant for human CEA levels.

The device combines two sensing methods to achieve a sensor design that shows an interactive plasmonic-photonic resonance effect. A 3D multilayer nanocavity in a nanocup array allows for light to be stored in the cavity. Plasmonic sensing detects sensitive nanoscale light-matter interactions with biomolecules on the surface of the device.

This image shows a plasmonic nanocup metal-insulator-metal cavity design used to detect the cancer biomarker CEA. The nanocavity leads to optical energy storage that is out-coupled to the far field by a refractive index increase. Therefore, CEA binding to its immobilized antibody leads to a sensitive increase in the transmission intensity at the resonance wavelength with no spectral shift. Courtesy of the University of Illinois.

“The nanocup array provides extraordinary optical transmission,” said researcher Lisa Hackett. “If you take a thin metal film and try to shine light through it, there will be almost no light transmitted. However if you put a periodic array of nanoholes, or in our case, a nanocup structure, then what you see is a resonance condition where at a certain wavelength, you will have a peak in the transmission through this device.”

The hybrid sensor produces an enhanced field confinement and an enhanced localized field. Because of the plasmonic structure, the light is out-coupled more efficiently as the surrounding refractive index changes. Unlike conventional plasmonic sensors, there is a consistent and selective change in the transmission intensity at the resonance peak wavelength with no spectral shift. In addition, there are wavelength ranges that show no intensity change, which can be used as reference regions.

“By combining plasmonic properties and the optical cavity properties together in one device, we are able to detect lower concentration of biomarker by light confinement and transmission in the cavity layer and from the top of the device respectively, based on the thickness of the multilayers and the refractive index of the cavity layer,” said researcher Abid Ameen.

As the concentration of biomolecules (in this case CEA) increases, so does the refractive index, which produces an increase of the transmission intensity at a fixed wavelength that can be easily detected.

Electromagnetic simulation of a single nanocup on ML-nanoLCA showing the field intensity in the cross section. Courtesy of the University of Illinois.

“Because of our multilayer high-performing plasmonic structure, we were able to very efficiently scatter out the light to the far field,” Hackett said. “When you increase the refractive index of the sensing region, it causes the stored energy to couple out. Usually when you have these types of refractometric plasmonic sensors, you have a shift in the angle or a change in your wavelength when the resonance condition is met. In our case, because we have incorporated a nanocavity, we have a fixed resonance wavelength.”

Excitation and detection can be done reliably without specialized equipment. An LED light source can be used instead of a laser, and a photocell or camera image can be used instead of a high-end spectrometer.

“What that means in the future is we can take this sensor, which we’ve optimized and incorporated with an LED and have the most compact instrumentation, in fact no sophisticated instrumentation at all,” Ameen said. “This allows high-performance plasmonic sensing the ability to go toward portable sensing systems and large-scale portable sensors.”

Because of the portability and inexpensive nature of this method, it could in the future be easily administered to any patient at routine checkups. This would allow those with an elevated concentration of CEA to be treated even before cancer cells spread in the body.

Schematic illustration of the multilayer nanoLCA (ML-nanoLCA) shows the multilayer structure and direction of illumination. Courtesy of the University of Illinois at Urbana-Champaign.

“Right now cancer is detected closer to end stage,” Ameen said. “We want to detect it as early as possible. Our device is providing us with that opportunity.”

While this study demonstrated detection in a small human serum sample, the method could be used for the detection of other diseases down the road.

“In the future, if they are made very cost-effective and portable, it would be great to see people be able to take more control over their health and monitor something like this on their own,” said Hackett.

The research took place at the University of Illinois at Urbana-Champaign. The research was published in Advanced Optical Materials (doi: 10.1002/adom.201601051).