1. Lecture 11: Surface Plasmon Resonance Detection Techniques
Content:
Fiber Optics
Fundamentals of Fiber Optics
Evanescent Waves
Optical Fiber Biosensing
Medical Applications of Optical Fibers
Optical Fiber Sensors Based on Surface Plasmon Resonances (SPRs)
Surface Plasmon Resonances and Polaritons
Fiber Optic SPR Sensors
Examples of Utilizing Optical Fibers as SPR Biosensors
Conclusions

2. Optical Fiber
A potential area of nanomedicine involves clinical applications of fiber optics.
Optical fibers are useful for communication, endoscopy, imaging, laser radiation delivery, and as biosensors.
Fiber optics can help in the war against cancer by closely monitoring various proteins or biomolecules that are present in higher concentrations when cancer grows.
A promising detection technique involves surface plasmon resonances (SPRs).
SPR-coupled optical fibers have the capability to detect changes in the external refractive index, which will be a focus of this lecture.

3. Fundamentals of Fiber Optics
An optical fiber is a narrow, flexible cylindrical silica glass rod core that is covered with a glass cladding.
The fiber is then typically covered with a buffer and protective jacket.
Its main purpose is to act as a dielectric waveguide or something that transmits light between its two ends.
Since optical fibers can transmit light with low attenuation or signal loss, information and images can be sent rapidly through them.
Optical fibers offer several advantages like low signal degradation, high speed and capacity for information transmission, and flexibility.
Current applications include communication, sensing, power transmission and imaging.

4. Fundamentals of Fiber Optics (continued)
Two main principles that allow fiber optics to exist are Fermat’s principle and Snell’s law of refraction.
Fermat’s principle states that light travels along a path of minimum time. The optical path will remain straight if light travels in a uniform medium.
Snell’s law of refraction governs the angle of incidence with which an incoming ray encounters a change in the optical index. It is described as
𝑛 1 sin 𝜃 1 = 𝑛 2 sin 𝜃 2 ,  
where n1,2 are the respective indices of refraction (real component) of two media, 𝜃 1 is the angle of incidence from the normal to the boundary of index change, and 𝜃 2 is the angle of refraction of light in the second medium.

5. Total Internal Reflection
Optical fibers guide light through total internal reflection, which occurs when the refractive index of the core is higher than that of the cladding.
In this case, when the ray of light comes a sufficiently high angle of incidence, the light will be reflected back into the first medium from the boundary of index change.
The angle at which this occurs is called a critical angle and is defined as
𝜃 𝑐𝑟 = arcsin 𝑛 1 𝑛 2 .
𝐶𝑙𝑎𝑑𝑑𝑖𝑛𝑔
𝑛 𝑐𝑜 > 𝑛 𝑐𝑙
𝜃 𝑐𝑟

6. Evanescent Waves
Optical fibers are useful in sensing applications which are arranged through the light interaction with a fiber’s surroundings.
One way to achieve this is to use the evanescent field of transmitted light.
If the cladding of a particular fiber is removed, the evanescent waves can penetrate into the surrounding medium to the penetration depth, where the amplitude of the evanescent light decreases to 1/e of the initial value E0.
The equation for the field amplitude E(x) as a function of distance x from the fiber core and penetration depth dp is given as:
𝐸 𝑥 = 𝐸 0 𝑒𝑥𝑝 − 𝑥 𝑑 𝑝 .

7. Evanescent Waves (continued)
The penetration depth of the evanescent waves can be described by the angle of incidence (θ1), wavelength of light (λ), and core (nco) and cladding (ncl) indices of refraction as:
𝑑 𝑝 =  2𝜋 𝑛 𝑐𝑜 2 𝑠𝑖𝑛 2 𝜃 1 − 𝑛 𝑐𝑙 2 .
As seen on the figure below, the light ray travels through the core; however, there is a small portion of light, called the evanescent waves, that decays outward from the core/cladding interface.

8. Fiber Optic Sensing
Fiber optic sensing operates on the principle of modulation. One or more of the optical properties of the transmitted light, like intensity, phase, wavelength or polarization state, is modulated by a particular parameter.
The interaction with a medium causes a change in the optical properties of light that can be detected by various means.
Sources of light typically include lasers, lamps and light emitting diodes.
The light is guided by the optical fiber where it exits through a probe. After it exits, it interacts with the parameter and is sent back to a detector.
Fiber optic sensors are advantageous because of their geometrical versatility, materials and safety. Their flexibility and size allows them to be inserted through needles and catheters. Optical fiber materials are inert and biocompatible, and they can be reused.

9. Fiber Optic Biosensor
A fiber optic biosensor (FOB) is a specific sensor that uses optical properties in order to selectively detect biological species like DNA and proteins.
Biosensors are extremely useful for diagnostic and quantitative purposes.
Ideally, biosensors could detect analytes in low concentrations and various environmental conditions like ones that are turbid.
Detection techniques are being developed in vitro and in vivo.
Since detection is highly selective, diseases and disorders could be more quickly and accurately diagnosed.
These new biosensing techniques will allow for real-time analytical measurements and eliminate the lapse of traditional sample preparations and measurements.

10. Fiber Optic Biosensor (continued)
In general, most biosensors use enzymes.
Enzymes are specialized proteins that catalyze and facilitate reactions that take place in a living organism.
Enzymes have high selectivity abilities for particular analytes because they are developed to only catalyze specific reactions.
An enzyme is attached to the sensing core/probe of the FOB. When the probe comes into contact with the analyte, the enzyme catalyzes a designated reaction.
When the reaction occurs, the optical properties of the light change and can be detected.
Some of these changes occur in absorbance/transmission, fluorescence and luminescence.

11. Medical Applications of Optical Fibers Endoscopy
Currently, there are great uses for fiber optics in medicine.
One of these uses is endoscopy, which involves looking inside the human body by directly inserting into hollow cavities or organs.
Due to the small size of the optical fibers, incisions tend to be small. Additionally, the flexibility of the fibers allows the scope to twist and turn through the body.
An endoscope can be composed of multiple sets of optical fibers with different functions. One set is used for lighting and to illuminate the interior of the cavity or organ. Another set is used for imaging purposes. Sometimes a third set is used as a laser to make minor repairs.
With the advancement of nanotechnology, endoscopes and optical fiber sensors could be made even smaller and more powerful.

12. Medical Applications of Optical Fibers Measuring Blood Flow
Another example of the application of fiber optic sensing is measuring blood flow.
Light from a helium-neon laser is sent through an optical fiber where it is guided toward the tissue or blood vessel.
The light hits the blood vessels where some is absorbed and some is scattered.
Additionally, the motion of the blood cells causes the light to undergo a Doppler shift.
After the light is modulated, it is sent back to the detector where the blood flow rate can be extracted by spectrum analysis of the back-scattered signal.
The Doppler shift depends on the flow rate and thus provides a relationship to extract useful information.

13. Surface Plasmon Resonances
A promising detection technique involves surface plasmon resonances (SPRs), which occur on the surface of metal nanoparticles or nanofilms.
The metal contains a large group of negatively-charged free electrons. Collectively, the density of the free electrons can be treated as a plasma of particles.
Additionally, the metal contains a lattice of positively-charged ions that can be replaced by a constant positive background.
Natural plasma oscillations occur when the free electrons oscillate around the stationary protons at a particular frequency.
The conversion of the electrostatic potential energy to the kinetic energy of electrons causes these oscillations.
A quantum of plasma oscillations is a plasmon.
Surface plasmons occur along the direction of the metal-dielectric interface.

14. Surface Plasmon Resonances and Polaritons
In order to excite surface plasmons, an external light radiation with frequency in resonance with that of the plasmon oscillation frequency must be applied.
There are a few configurations of a metal-dielectric interface that support SPRs, like a prism with one side coated with a gold nanofilm and an optical fiber having a section covered by a micro- or nano-size thickness of metal film around the optical core.
Adjusting the thickness of the nanofilm and frequency of the incident light allows for optimization of the SPR.
SPR is the collective oscillations of electrons stimulated by light in resonance with the plasmon oscillation frequency.
Evanescent waves from the core hit the metal nanofilm in the sensing part of the fiber and cause surface plasmon polaritons to appear.
The surface plasmon polaritons are electromagnetic waves that oscillate along the direction of the metal and dielectric interface.

15. Fiber Optic SPR Sensors
SPR fibers have the capability to detect changes in the external refractive index.
The optical fibers offer several advantages like small size, flexibilit, and remote sensing. Remote sensing could eventually occur within the human body itself.
A fiber optic SPR sensor is basically an optical fiber with one section of the cladding removed and replaced with the metal nanofilm in order to promote SPRs.
The nanofilm is then coated with the dielectric/sensing layer.
This sensing layer can be coated with molecules that will bind to other target molecules.

16. Fiber Optic SPR Sensors (continued)
When a testing medium containing the analyte passes over the sensing core, molecular interactions occur between the analyte and the molecules on the sensing layer.
These interactions change the refractive index of the medium.
Incident light with resonance frequency enters the optical fiber, strikes the metal-dielectric interface, and causes SPRs to occur.
A photodetector measures the decrease in absorbance due to the change in the refractive index of the sensing layer.
Each sensor depends on the specificity of its function of detection of a particular analyte.

17. Examples of SPR Fiber Biosensors Phenol Concentration
Researchers from the Indiana Institute of Technology used an optical fiber biosensor to detect phenolic compounds.
One of their goals was to measure the response of SPRs and relate this to the concentration of phenol.
To construct the apparatus, they used an optical fiber with a section of exposed cladding that was replaced with a 40 nm silver film.
The sensing layer was covered with immbolized tyrosinase in polyacrylamide gel.
Tyrosinase is an enzyme that catalyzes the breakdown of phenols.

18. Examples of SPR Fiber Biosensors Phenol Concentration (continued)
A flow cell was constructed around the fiber in order to deliver the solutions containing various concentrations of phenol.
After the light passed through, it was analyzed by a spectrometer connected to a computer.
The resonance wavelength was varied in order to find the new optimal wavelength for the SPRs. Each different concentration had a different optimal wavelength.
Different concentrations caused varying indices of refraction.
With the data collected, the researchers were able to construct curves with polynomial fits of the resonance wavelength versus concentration.
These curves could be used as calibrations to detect and quantify unknown concentrations of phenols.
Phenols are typically biohazards, and this experiment offers a new and effective detection method.

19. Examples of SPR Fiber Biosensors (continued)
There is much potential for fiber-SPR biosensors.
In addition, nanoscale optical fibers have been created with unique properties that give rise to great evanescent wave fields, and this would allow for improved diagnostics and penetration depth.
The next step involves making the SPR biosensors smaller and effective inside the human body giving rise to lab-on-a-chip and array technology, real-time monitoring, and superior diagnostic services.
Instead of having to draw blood and send it to the lab, the analyte can be analyzed within the body with a ‘middleman.’
Nanotechnology can greatly assist in the process of miniaturizing these sensors.
Overall, SPR biosensors with the help of nanotechnology will be able to operate inside the body and thus revolutionize diagnostics.

20. Conclusions
Fiber optics has much potential in the field of nanomedicine with its:
superior signal transmission
flexibility
inertness
remote ability.
Fiber optics will assist in early detection and therapy of cancer by closely monitoring various proteins or biomolecules that are present in cancer.
Fiber optic biosensors with the SPR technique will become the next generation of diagnostic tools that can occur within the human body with great specificity, sensitivity and accuracy.