Being able to detect fatal diseases in their early stages is vital. However, many modern-day diagnostics require invasive biopsies and/or expensive detection instruments operated by highly skilled practitioners, who are then able to interpret the results of these sophisticated medical tests. "Ideally, though, such diagnoses should be as cheap and easy as a pregnancy test," said team leader Hatice Altug.

Plasmonics is a new branch of photonics that exploits "surface plasmon polaritons", which arise from the interaction of light with the electrons oscillating at a metal's surface. The new detection platform developed by the Boston team exploits such resonances in plasmonic nanohole arrays. These are arrays of nanoapertures or holes just 200–350 nm across spaced 500–800 nm apart on nanolayers of noble metal films, such as those made of gold. At certain wavelengths, the nanohole arrays can transmit light much more strongly than predicted by classical aperture theory. This phenomenon is called extraordinary optical transmission (EOT) and it occurs thanks to surface plasmon polariton resonances.

The resonance wavelength of the EOT depends on the dielectric constant of the medium surrounding the plasmon sensor. As biomolecules bind to the sensor surface, the effective refractive index of the medium increases, so red-shifting the plasmonic resonance, explains Altug. This red-shift is then usually measured using a spectrometer or camera – depending on the light source employed – to identify the biomolecule in a label-free fashion.

"There is more to it than just resonant transmission," added team member Ahmet Ali Yanik, who is first author of the article published in PNAS. "A commonly overlooked but particularly intriguing outcome of EOT phenomena is the appearance of a 'Fano resonance' profile," he said. This fundamental resonance line-shape is observed in systems where the energy transfer from an initial state to a final state can occur via two pathways. Depending on the phase difference between these alternative pathways, a resonance profile that looks like the Greek letter "Λ" is seen.

Yanik points out that since the phase changes rapidly from destructive to constructive, the resulting resonance dispersion profile is extremely steep – something that leads to strong modulation of the transmitted light intensities in a narrow wavelength interval. He adds: "it is exactly this unique resonance profile that enables us to detect the slightest perturbations, such as biomarker proteins when they come close to the sensor."

Harmless halogen light source
"Our ultrasensitive sensors are also different in that they allow us to detect the resonance shift with the naked eye using a harmless halogen light source rather than a camera or spectrometer," Altug told "The measured signal is not colour coded, as in colorimetric measurements, but is instead coded in light intensities, such as transmission/no transmission corresponding to the absence or presence of biomarker molecules."

Yanik, who conducted the experiments adds: "It is really exciting to see a fundamental physical phenomenon being directly applied to a real-world problem that can impact people's lives."

The researchers have already used their devices to detect a single layer of proteins. In principle, the detectors could be used to identify any type of disease biomarker and because they are compact, they could be also multiplexed to simultaneously detect a wide range of proteins/bioparticles at high throughput.

Record figures of merits
The detectors are extremely sensitive too and show record figures of merits of as high as 162. These values are better than those achieved by the gold standard prism-coupled surface-plasmon sensors because the new devices are of a high optical quality and the resonances are as narrow as around 4 nm.

"Normally plasmonic excitations are usually damped in metals and we cannot see high contrast Fano resonances, which limits how sensitive plasmonic sensors are," explained Altug. "However, we overcame this problem by using engineered plasmonic dark ('sub-radiant') modes in high-quality EOT structures." These structures were made using a high-throughput lift-off free evaporation fabrication technique that produced extremely uniform and precisely controlled nanofeatures over large areas. Such nanofeatures produce narrow plasmonic resonances, something that is needed for stronger light-matter interactions.

The team, which includes Boston University School of Medicine's John Connor and the University of Texas Austin physicist Gennady Shvets and his students, is now working on integrating its platform into an ultra-compact unit using LED sources. "Our initial goal is to integrate the whole system into a small enough unit that can be used in any clinical/field setting," revealed Altug.