Optical Biosensors based on Resonances
In this post we will describe the optical techniques based on resonances that can be used for biosensor interrogation apart from the ones seen in the initial post about biosensors.
When a waveguide, such as a cladding removed optical fiber, is coated by a thin-film, the propagation of the light is affected. Therefore, there may be a coupling of light to the thin-film or thin-film/dielectric interface region at some specific wavelengths, causing losses in the light that propagates through the waveguide. This coupling of light is known as electromagnetic resonance.
Depending of the dielectric properties of the waveguide, the thin-film and the external medium, different types of resonances take place . The sensors based on resonances enable to monitor the target-bioreceptor binding accurately and in real time thanks to the shift of the resonance in wavelength. The basic detection principle is shown in Figure 1.
Resonance-based optical fiber sensors include among their advantages their immediate response, which can be monitored in real time; or their simplicity, as opposed to the bulky equipment of conventional sensors. Other interesting feature is their multiplexing capability, that is, a single biosensor can be designed to separately detect different targets. However, their most important characteristic is their high sensitivity, that is, they enable to detect the analyte in low concentrations .
It is also worth mentioning the concept of “label-free” biosensor, a biosensor that does not employ more elements apart from the bioreceptor to detect the target. For instance, a label-free biosensor will not use a fluorophore or a complex amplification mechanism to improve the detection. Therefore, label-free biosensors are simpler and easier to manufacture. In general, resonance-based sensor are label-free, as opposed to the ones based on the techniques explained in the initial post about biosensors.
One of these resonances is known as Surface Plasmon Resonance (SPR). SPR occurs at the interface between negative (metallic) and positive permittivity (dielectric) material. In this case, gold and silver are two of the most commonly used materials for SPR generation. In Figure 2, a typical setup for SPR generation using an optical fiber can be observed. One of the key features of these devices is their extremely high sensitivity, which is highly desirable for the fabrication of biosensors .
Nowadays, when talking about SPR, the concept SPR imaging or SPRi is commonly mentioned. It simply differentiates from conventional SPR in incorporating a CCD camera that enables to record sensorgrams (response of the sensor for different concentrations versus time) and SPR images at the same time.
Localized Surface Plasmon Resonances (LSPRs) are generally considered a particular type of SPR. Their main difference with SPRs is related to the behaviour of the plasmons although the materials that are used tend to be the same. However, gold nanoparticles, gold nanoprisms, nanohole arrays (done in the thin film) or even more complicated nanostructures are used or made on the waveguide in the case of LSPRs.
A different type of resonance is known as Lossy Mode Resonance (LMR). LMRs are generated due to a coupling between a waveguide mode and a particular lossy mode of the thin-film . One of the main differences with SPRs is that LMRs are generated using thin-films of polymers or metal oxides instead of noble metals. The setup shown in Figure 2 is also valid for a LMR optical fiber sensor.
The sensitivity of LMRs is comparable to that obtained with SPRs and their use in biosensing applications has great potential. However, LMRs are still in its infancy and there are not as many biosensors based on them as in the case of SPRs . Concerning LMR biosensors, they have been already used for the detection of biomarkers associated to the celiac disease or sepsis .
Silicon photonic microrings are another interesting sensing platform. A ring resonator is an optical waveguide which is looped back on itself. The light is transmitted through another waveguide (for example an optical fiber) and part is coupled to the microring (see Figure 3). The resonance occurs when the dimensions of the ring fulfil certain conditions. For biosensing applications, it is convenient to have small rings (radius below 5 μm, therefore the name of microrings), which can be achieved by using silicon .
The main features of the biosensors based on silicon photonic microring resonators are their high quality factor (Q) and very narrow resonances as well as the possibility of their utilization in arrays, which can be designed to detect different molecules at the same time. The latter is especially appealing taking into account that the diagnosis of a disease is usually based on the detection of several biomarkers.
Finally, Surface Enhanced Raman Spectroscopy (SERS) is an optical technique not based on the shift of a resonance, but linked with plasmon resonances and employed for biosensing. SERS is a surface spectroscopy technique that consists in measuring the Raman signals of molecules and whose signal enhancement is provided by the plasmon resonances in the metal substrate . Here, it is common the use of gold, silver or dyes as in the case of the fluorescent sensors.
 A. Urrutia, I. Del Villar, P. Zubiate, and C. R. Zamarreño, “A Comprehensive Review of Optical Fiber Refractometers: Toward a Standard Comparative Criterion,” Laser Photon. Rev., vol. 13, no. 11, p. 1900094, Nov. 2019.