Optical Biosensors

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Optical Biosensors

In this post we will briefly describe some of the main optical techniques applied for biosensors interrogation but first it is important to clarify what we mean when we talk about biosensors and differentiate them from biometric sensors [1].

Concerning biometric sensors, they are used to measure body parameters without using any biohazardous chemicals. Body parameters are measured by means of electrodes or photodetectors typically. Some examples of biometric sensors are those used to measure the hearth rate or the oxygen saturation concentration using electrodes and infrared detectors respectively.

Unlike biometric sensors, biosensors are designed to get precise information from body fluids, such as blood, urine, sweat, tears or saliva. Biosensors basically consist of a two-part structure (see Figure 1) in which a biologically active component, known as bioreceptor, is intimately linked to a transducer (usually an electrical or optical transducer) that enables to obtain a measurable response. Here, the adequate linkage between the bioreceptor and the transducer will determine the biosensor performance, which has been thoroughly reviewed in many studies and is not going to be addressed in this article [2].

Among the bioreceptors commonly used for the design of biosensors, we can find antibodies and enzymes. Antibodies achieve highly selective binding to the target molecules, while enzymes bind a selected molecule and catalyse its conversion to a measurable product. There are also other natural or synthetic molecules that mimic the behaviour of the former, such as aptamers, molecularly imprinted polymers, proteins used to bind carbohydrates or whole cells [3].

Figure 1. Schematic representation of a biosensor structure and transducing mechanism.

Once we have clarified the differences between biometric sensors and biosensors and presented schematically (see Figure 1) the working mechanism of biosensors it is time to focus on the transducer part. In particular, we will mention some of the most common optical transducing mechanisms used for biosensing purposes, some of which have been already addressed before in our previous blog posts.

Optical interrogation techniques basically consist of light intensity, phase, frequency or polarization modulations induced by any of the bioreceptors mentioned above in the presence of the target molecule. Therefore, adequate design of the light path is critical in order to retrieve the maximal information from the binding process between the target and the bioreceptor.

In this sense, fiber-optic sensors (FOS) can take advantage of the properties of fiber optics for light delivery and retrieval with minimum losses as well as the multiplicity of fiber optic configurations apart from the traditional all-silica fibers, such as plastic-clad silica-core, plastic fibers, hollow-core fibers (HCFs) or photonic crystal fibers (PCFs) [4].

Among the different optical interrogation methods, the most extended technique in chemistry, biochemistry or chemical diagnosis is based on fluorescence intensity or phase measurement (see our previous post about fundamentals of fluorescence).

Fluorescence enhancement or quenching is produced by a fluorophore (see Figure 2) in the presence of target molecule when it is excited at the adequate wavelength (typically in the blue or ultraviolet spectral regions). Fluorescence measurements generally possess high sensitivity and specificity as well as the capability of detection of very low analyte concentrations.

A particular case, known as bioluminescence, permits to perform intensity or phase measurements without the use of a fluorophore due to inherent luminescent properties of the bioreceptors used in that cases.

Optical biosensors. Fluorescence of solutions containing different fluorophores under UV light
Figure 2. Fluorescence of solutions containing different fluorophores under UV light. The blue one contains quinine; yellow, rhodamine 6G; red, rhodamine B; purple, quinine and rhodamine 6G and green, fluorescein. Author: Maxim Bilovitskiy. Used under licence CC BY-SA 4.0.

Absorbance and reflectance-based sensors are also widely used in biosensing applications (see our previous post about relative measurements). Here, light intensity modulations permit to determine adequate binding between bioreceptor and target molecule. In this case, the technique lacks from the specificity of fluorescent measurements and non-selective binding interactions can be a problem when only absolute intensity measurements are taken.

Optical biosensors. Mach-Zehnder interferometer configuration.
Figure 3. Mach-Zehnder interferometer configuration. Author: Wesleyyk . Used under licence CC BY-SA 4.0.

Interferometric arrangements are also a widely used optical interrogation tool for biosensing (see also our previous post about interferometric nanocavities). These devices rely on the combination of two or more light beams propagated through different optical paths, one of which can be altered somehow as a function of the selected target. Consequently, when they recombine, the obtained pattern will provide information of the binding process as a function of wavelength, phase, intensity, or polarization changes. Multiple interferometric structures have exploited this phenomenon in literature, such as Michelson, Mach-Zehnder (see Figure 3), Sagnac, Fabry-Pérot, Fizeau and others.

Fiber Bragg gratings and in particular long-period fiber gratings (LPFGs), that facilitate the access to the light propagated through the optical fiber core, can be easily exploited as interrogation tools for biosensing purposes (see our previous post about fundamentals of fiber Bragg gratings).

In the same manner, it is important to mention the utilization of resonance-based devices that enable to monitor the bioreceptor-target binding interactions accurately by means of the resonance wavelength shift. Here it is worth to mention surface plasmon resonance (SPR), localized surface plasmon resonance (LSPR), lossy mode resonance (LMR) or microring resonators, which will be reviewed in detail in a separate blog post.

[1] https://butlertechnologies.com/biometric-vs-biosensors/

[2] Zourob, M. Recognition Receptors in Biosensors. Springer-Verlag: New York, 2010; 1–863.

[3] Hermanson, G.T.: Bioconjugate Techniques, 3rd Ed.; Elsevier Academic Press: New York, 2013; 1–1146.

[4] Wang, X.; Wolfbeis, O.S. Fiber-optic chemical sensors and biosensors (2008–2012). Anal. Chem. 2013, 85, 487–508.

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