key: cord-0997027-z4knyipk
authors: Vasudevan Pillai Radha, Sudheer; Santhakumari Amma Ravindran Nair, Sarath Kumar; Sankaranarayana Iyer, Sankararaman
title: Surface Plasmon Resonance-Based Fiber-Optic Metallic Multilayer Biosensors
date: 2021-06-01
journal: ACS Omega
DOI: 10.1021/acsomega.1c01236
sha: e14ff4ed3fa1d930e7e2cd1b4cad8a434c85e4eb
doc_id: 997027
cord_uid: z4knyipk

[Image: see text] Accurate and quick sensing of various biomolecules relevant to different health conditions is indispensable in modern diagnosis and treatment procedures. Different multilayer metallic surface plasmon resonance (SPR) biosensor configurations comprising Au, Ag, Al, and Cu are analyzed in this work by employing an N-layer matrix formalism as applied to the fixed-angle spectral SPR sensing methodology. Stringent standards for sensitivity, detection accuracy, and figure of merit (FOM) of the sensor configurations are set to analyze the relative merits of one configuration over another. It is observed that three- and four-layer configurations using Al and Cu provide the best FOM among all sensors that passed the set standard criteria. The highest FOM (1433.82/RIU) is observed for the four-layer Al/Cu/Al/Cu sensor for an analyte refractive index of 1.408. The sensors are best suited for detecting analytes with a refractive index range of 1.350–1.414.

Biomedical instrumentation is fast emerging as an integral part of modern diagnosis and treatment procedures. Proper analysis of body fluids, tissues, and exhaled air can provide clear information on various illnesses and guide early detection of diseases. For instance, biosensing of blood can yield information on hemoglobin content, 1 antibodies, 2 and blood glucose concentration, among others. 3, 4 Similarly, an analysis of the refractive index of the cornea can give indications of various corneal diseases like cataract and glaucoma. 5 Exhaled air of human beings contains many volatile organic compounds (VOCs) formed as a result of complex biochemical processes within the human body. Analysis of the VOCs can provide early indications of various diseases and health conditions. 6−11 Different types of sensors are available for sensing VOCs. Sensors based on the principle of surface plasmon resonance (SPR) have proved to provide quick and accurate sensing of physical, chemical, and biochemical parameters. 12−15 Consider a metal placed in contact with a dielectric. Here, p-polarized electromagnetic waves resulting from collective oscillations of the conducting electron cloud will propagate through the interface. This wave is called the surface plasmon wave (SPW). When the propagation constant of the incident photons of a ppolarized light becomes equal to that of the SPW, a portion of the light gets absorbed, resulting in surface plasmon resonance. 16 Even minute changes in the refractive index (RI) of the metal−air interface largely affect the SPR. Adsorption of external materials such as biomaterials and VOCs on the surface of the metal will alter the RI of the interface, and hence the change in the RI of the outer ambience of the metal can be judged from the change in SPR absorption spectra. To harness the advantages of optical fibers in biosensing applications, we have modeled various fiber-optic SPR sensor configurations. These fiber-optic SPR sensors enable compactness, ease of sensing, flexibility, and reliability for noninvasive and invasive sensing and biosensing. 17−19 Usually, in fiber-optic sensing probes, a small portion of the cladding is removed, and the conducting layer(s) enabling SPR sensing are coated on this portion. The sensor makes use of the Kretschmann configuration with the spectral SPR method. When white light is launched on one end of this fiber-optic sensor, above the critical angle, the light propagates to the other end by total internal reflection (TIR). During the TIR, a part of the light penetrates into the low-refractive-index thin metal layers as exponentially decaying evanescent waves, which couple with the surface plasmon waves at the metal−dielectric (analyte) interface, at the resonance condition. Hence, a part of the energy of the incident white light is transferred to the surface plasmons at the resonance condition, corresponding to which a dip in the transmitted light is observed. This waveform is the SPR curve.

SPR sensors with a single metallic layer have been modeled, realized, and reported. Usually, Au and Ag are employed as the metal since they contain a substantial amount of charge carriers. Furthermore, Au and Ag are found to be suitable for sensing operation in the visible region of the spectrum. 20 The quality parameters sensitivity (S), detection accuracy (DA), and figure of merit (FOM) are defined as follows: The sharpness of the SPR curve determines the accuracy of detecting the resonant wavelength. The larger the spectral width, the lower is the accuracy. The detection accuracy facilitates easy interpretation of the accuracy in detecting the resonance wavelength and also the analysis of the relevant graphs.

Even though Au-based sensors offer a massive shift in the resonance wavelength with the change in RI (in other words high sensitivity), the detection accuracy is low. On the other hand, Ag can provide better accuracy due to its narrow spectral width, but the sensitivity is low. 16 Moreover, Ag is chemically not stable, as it oxidizes on exposure to air. Studies also confirmed that Cu and Al could be used for designing SPRbased sensors, although they too oxidize. 16, 21 Studies have shown that although single-layer metallic sensors provide a sensitivity up to a maximum of 3500 nm/RIU, the trade-off between sensitivity and DA indicates that single-layer metallic SPR sensors possess many disadvantages. 16 Specific sensing applications demand sensors having a high figure of merit. Studies on sensors with metallic multilayers have been reported to yield some positive results. 16,22−25 Sensors with multilayers of different metals combine the features of each metal, and this undoubtedly reflects in parameters like the position and shift of the resonant wavelength as well as the spectral width and depth of the SPR curve. This opens new options for designing fiber-optic biosensors. Thus, in our work, we analyze the pertinent properties of SPR-based fiber-optic biosensors based on a spectral method, employing two, three, and four layers of metals. 26 The metals selected are Au, Ag, Al, and Cu. Theoretical modeling is done with Matlab. Unless otherwise specified, all sensor properties are analyzed for an analyte refractive index (RI analyte ) of 1.36, corresponding to ethanol, which is one of the significant VOCs.

Many different types of SPR sensors with different materials as sensing layers have already been proposed. Hybrid nanostructured SPR sensors utilizing 2D materials have attracted attention with advantages for specific sensing applications. They are usually costly and it is very difficult to ensure the accurate and precise thickness of the layers of the sensor with these materials during sensor fabrication and requires highly sophisticated equipment. The proposed sensing probe utilizes only metals, which are comparatively cheaper (except gold). Further, controlled deposition of these metals to achieve a precise thickness of sensing layers can be easily realized with thermal, e-beam evaporation, or sputtering. Thus, these sensors possess the advantages that they are simple to realize and are cost-effective. Metallic multilayer SPR sensors have the main advantage that they combine the features of the constituent metals and can be utilized for a wide range of sensing applications. Many of the configurations in the proposed metallic multilayer sensors offer sensing features that are comparable to or even higher than that of the reported hybrid nanostructured SPR sensors.

In the modeled SPR sensor, the cladding is removed for a length of about 15 mm from a plastic-clad silica (PCS) fiber with a core diameter of 0.6 mm and a numerical aperture of 0.24. With the PCS fiber, the plastic cladding can be removed easily with selective etchants, leaving the silica core surface suitable for further fabrication of subsequent metal layers. The literature also shows that fiber-optic SPR sensors for different applications are modeled and successfully implemented with PCS fibers. 12, 14, 16, 20 This cladding-removed portion is uniformly covered with thin layers of metals. The proposed sensing probe is illustrated in Figure 1 . A beam of collimated white light falling on one face of the fiber at a suitable angle is transmitted to the other end of the fiber, albeit with a reduced intensity if conditions for SPR absorption are met. Hence, the normalized transmitted intensity recorded at this end of the fiber gives ample information regarding the resonance wavelength (λ res ) and the spectral width and depth of the SPR curve. For minute changes in RI analyte , a good SPR sensor shows a detectable change in λ res . From this data, the sensitivity, DA, and FOM of the sensors are arrived at and compared to identify the optimal sensor configuration, which should aid the device engineer.

The nature and thickness of the metal layers of the sensor and RI analyte will affect the shape, spectral width, and depth of the SPR curve. These parameters are critical to accurate sensing. The spectral width, which is very crucial in deciding the accuracy of sensing, is usually calculated corresponding to the full-width at half-maximum (FWHM) of the SPR curve. 27 However, this poses a problem (illustrated in Figure 2 ), which shows three kinds of SPR curves normally encountered in real sensing applications. While curve A is very shallow (which affects the accurate determination of λ res and hence the sensitivity) and broader (which makes DA very low), curve B may be considered ideal. Curve C, on the other hand, is ambiguous because the tail end of the dip is missing, which makes finding the FWHM practically impossible. Hence, in this work, the spectral width is calculated at a height corresponding to 0.1 unit above the tip of the SPR dip. 28 Stringent standards are set for the suitability of any sensor configurations in practical sensing applications: (a) only those SPR curves whose spectral width measurement is possible at the height of at least 0.1 unit above the tip of the curve is considered in our work, (b) the sensitivity (which is the ratio of change in λ res corresponding to a unit change of RI analyte ) should be greater than 3000 nm/RIU, 16, 28 (c) the DA of the sensor must be greater than 0.03 nm −1 , and (d) it is also set that the λ res be in the visible range of the spectrum between 250 and 700 nm.

The spectral SPR method has been adopted, and hence due consideration of the wavelength dependence of the different materials constituting various layers of the sensing probe is essential. The refractive index dependence of the silica core of the PCS fiber on wavelength is calculated as defined by the Sellmeier relation: 

where λ p and λ c are the plasma and collision wavelengths of the metal, respectively, ε mr and ε mi are the real and imaginary values of the dielectric constant of the metals, respectively, and ε ∞ the dielectric constant at very high frequencies approaches unity. The values of λ p and λ c for Au (Au), Ag (Ag), Cu (Cu), and Al (Al) are furnished in Table 1 . 30, 31 For an SPR-based sensor, the normalized transmitted power through the fiber measured at one end due to a white light source fed at the other end can be expressed as 32 where R P is the net reflection coefficient of the ray incident at the core metal interface. θ cr denotes the critical angle of the fiber, n 2 is the refractive index of the cladding of the fiber, and N ref (θ) is the number of reflections the ray launched at an angle θ undergoes inside the fiber core and is given by

where L is the length of the sensing probe and D is the diameter of the fiber core.

In this work, the sensing probes considered are multilayered structures, and hence an N-layer matrix method 33 has been utilized to determine the value of R P accurately. Accordingly, the characteristic matrix for an N-layer structure can be expressed as 

and

where ε k , n k , μ k , and d k are the dielectric constant, refractive index, permeability, and thickness of the kth layer, respectively. The reflection coefficient r p of the incident wave through the N-layered structure is given by 

The resonance condition for excitation of the surface plasmon wave is given by 16

where λ, θ, ε m , n 1 , and n s are the wavelength of the incident light, angle of incidence of the incident light, dielectric constant of the metal layer, refractive index of the fiber core, and refractive index of the sensing layer, respectively. The different configurations modeled in this work can be classified as single-layer, two-layer, three-layer, and four-layer configurations. In multilayer configurations, the coupling of the electromagnetic field of the incident light with the propagation constant of the surface plasmon waves at the outer metal− insulator (analyte) interface depends strongly on the plasma frequency and damping constant of the outer metal as well as the coupling of the electromagnetic field with the mobile charges of the various metal layers. Hence, in two-, three-, and four-layer configurations, the order of metals and the relative thickness of the layers are important. Therefore, for clarity, the 

The typical normalized transmitted power obtained as a function of wavelength is shown in Figure 3a . Evidently, for a given configuration, as RI analyte changes, the SPR absorption varies, which allows determination of sensitivity, DA, and FOM of that configuration.

3.1. Single-and Two-Layer Metallic Sensors. Analysis of the performance of single metal layer SPR sensors shows that as the thickness of the metal layer increases, sensitivity increases and saturates. A thickness of 60 nm is found to yield optimal values for both sensitivity and DA, as plotted in Figure  3b . Furthermore, increasing the thickness beyond 60 nm yields no marked improvement in sensitivity and DA. Hence, the total thickness of the metal layers has been fixed to be 60 nm throughout the study.

Bimetallic combinations of fiber-optic SPR sensors have been found to yield better sensing than those with a single layer of metal. 16, 21, 22 All possible configurations such as A/B and B/A were modeled by varying dA/(dA + dB), where dA and dB are the thickness of layers A and B, respectively, keeping dA + dB = 60 nm. As an illustration, the sensitivity and detection accuracy as a function of the ratio of inner layer thickness to the total bimetallic thickness for the betterperforming configurations (a) Cu/Ag and Ag/Cu and (b) Cu/ Al and Al/Cu are plotted in Figure 4a ,b, respectively. Although the sensitivity is observed to be lower than 4000 nm/RIU for all bimetallic configurations, the DA is exceptionally good.

3.2. Three-Layer Metallic Sensors. The performance of SPR sensors made of three-layer metallic configurations of the type A/B/A is analyzed below. The data obtained for only the better-performing configurations, viz., Au/Ag/Au, Ag/Au/Ag, Au/Cu/Au, Cu/Au/Cu, Cu/Al/Cu, and Al/Cu/Al are considered and are shown in Figure 5 . The impact of the variations in layer thickness in the sensor on its performance on sensitivity and the spectral width is analyzed for different layer fractions (LF A ) and different thicknesses of the middle layer (dB) and is depicted in Figure 5 .

A quick perusal of Figure 5 reveals the influence of the choice of metals and their layer fractions on the sensitivity and DA of the sensors. For a fixed dB, with an increase in LF A , sensitivity is found to decrease for Au/Ag/Au (Figure 5a) , whereas it increases for Ag/Au/Ag (Figure 5b ). The opposite is true for DA. When the thickness of the middle layer is varied, the sensitivity remains almost constant at lower LF A values. However, for higher LF A values, with a decrease in the thickness of the middle layer, the sensitivity is found to increase slightly for Au/Ag/Au and decrease slightly for Ag/ Au/Ag. For RI analyte = 1.361, Au/Ag/Au yielded a maximum sensitivity of 4500 nm/RIU for LF A values less than 0.15 irrespective of the thickness of the middle layer, whereas Ag/ Au/Ag yielded a maximum sensitivity of 3800 nm/RIU for an LF A of 0.8 and middle layer thickness of 30 nm. The resonant wavelength was well in the visible range around 570−700 nm in both these sensor configurations. The λ res decreased in Au/ Ag/Au and it increased in Ag/Au/Ag with an increase in LF A for fixed values of middle layer thickness. Similarly, with an increase in middle layer thickness, λ res and spectral width increased in Au/Ag/Au and decreased in Ag/Au/Ag. For the same values of LF A and middle layer thickness, the sensitivity, λ res , and DA of Au/Ag/Au were lower compared to those of Ag/Au/Ag. Figure 5c ,d depicts the variations of sensitivity and DA with LF A and dB for Al/Cu/Al and Cu/Al/Cu, respectively. For fixed values of dB, the sensitivity is found to decrease in Cu/ Al/Cu and increase in Al/Cu/Al with the increase in LF A . An exact opposite trend is observed for DA. Moreover, the sensitivity remained almost constant in both Cu/Al/Cu and Al/Cu/Al for lower LF A values, irrespective of dB. However, for higher LF A , the sensitivity is found to increase slightly in Cu/Al/Cu and decrease slightly in Al/Cu/Al with a decrease in dB. The λ res in both the combinations are well in the visible range from about 410 to 560 nm, with Al/Cu/Al having a comparatively lower λ res . Cu/Al/Cu is calculated to have a higher sensitivity of 3500 nm/RIU with a lower LF A compared to Al/Cu/Al, which offered a maximum sensitivity of 3050 nm/RIU with a higher value of LF A . The DA remained in an impressive range of 0.140−0.210 nm −1 in both the configurations. The Cu/Al/Cu configuration with the middle Al layer of about 10 nm thickness and the Al/Cu/Al with the middle Cu layer of about 30 nm yielded better performance. However, the Al/Cu/Al configuration with dB = 10 nm did not yield acceptable sensitivity for any LF A .

The variations of sensitivity and spectral width with LF A and dB for Au/Cu/Au and Cu/Au/Cu, respectively, are depicted in Figure 5e ,f. Irrespective of dB, a decrease in sensitivity, spectral width, and λ res for Au/Cu/Au and an increase of the same for Cu/Au/Cu are noticed with an increase in LF A . However, with a decrease in dB, the sensitivity, spectral width, and λ res are observed to increase in Au/Cu/Au, whereas it decreased in Cu/Au/Cu. The λ res in both the configurations are well in the visible range from about 500 to 700 nm. Au/Cu/Au is found to offer a higher sensitivity with a maximum of 4550 nm/RIU at an LF A < 0.2 and the middle Cu layer thickness of about 10 nm. Similarly, Cu/Au/Cu offered a maximum sensitivity of 4050 nm/RIU for an LF A > 0.82 and middle Au layer thickness of about 30 nm. Apart from the above details, the following results (graphs not shown) are also confirmed with the different three-layer sensor configurations discussed above and are furnished in Table 2 .

Furthermore, asymmetric three-layer configurations with different metals on the three layers are also investigated (graphs not shown). All of the combinations yielded a sensitivity greater than 3000 nm/RIU at an RI analyte value of 1.36. The sensitivity and FOM corresponding to an RI analyte value of 1.361 for the different three-layer sensor configurations are furnished in Table S1 . Although the combinations of Al/Cu/Au, Al/Ag/Au, Ag/Al/Au, and Ag/Cu/Au yielded the highest sensitivity of 4500 nm/RIU, the low value of detection accuracy resulted in a very low value of FOM. However, the Au/Al/Cu, which offered a sensitivity of 3500 nm/RIU at an RI analyte value of 1.361, is observed to yield the highest FOM value of 461 RIU.

For RI analyte = 1.361, the combination with Au as the inner and outer layers and Ag or Cu as the middle layer offers a higher sensitivity of around 4500 nm/RIU but with a larger spectral width. The Cu/Au/Cu configuration also yields a better sensitivity and sharpness but is chemically less stable. Calculations with a higher RI analyte on Ag/Au/Ag, Cu/Al/Cu, Al/Cu/Al, and Cu/Au/Cu configurations yielded a higher sensitivity than that of the Au/Cu/Au configuration. However, the outer layers of Al, Cu, and Ag are usually chemically more reactive unless kept in inert ambient or vacuum. With its inherent properties, Au is much more resistant to chemical reactions. Hence, the choice among three-layer metallic sensors considered in this work must be made depending on the conditions prevailing for applications. 3.3. Four-Layer Metallic Sensors. The performance of SPR sensors made of four-layer metallic configurations of the type A/B/A/B is analyzed below. The data obtained for only the better-performing configurations, viz., Cu/Ag/Cu/Ag, Ag/ Cu/Ag/Cu, Cu/Al/Cu/Al, and Al/Cu/Al/Cu are considered and are shown in Figure 6 . Figure 6a depicts the variation of sensitivity and DA with LF Cu for the sensor configuration Cu/ Ag/Cu/Ag, for different fixed LF Ag , with a thickness ratio of Cu/Ag = 1:1. The corresponding curves for the thickness ratio of Cu/Ag = 2:1 is shown in Figure 6b . Similarly, Figure 6c ,d represents the variation of sensitivity and DA when the order of metals is reversed. For a thickness ratio of 1:1, sensitivity increases slightly with an increase in LF Cu for any fixed LF Ag , while it decreases with an increase in LF Ag . However, DA shows the opposite trend; λ res is in the range of 548.3−576 nm. For Ag/Cu/Ag/Cu, with a thickness ratio of 1:1, the sensitivity is again found to increase with the increase in LF Cu but remained almost constant with variation in LF Ag . DA shows a decrease with an increase in LF Cu and a decrease in LF Ag ; λ res ranges from 534 to 561 nm.

For a thickness ratio of Cu/Ag = 2:1, with the configuration Cu/Ag/Cu/Ag, the sensitivity remains constant for varying LF Cu , at fixed LF Ag . However, the sensitivity is found to decrease with an increase in LF Ag . λ res varies inversely with LF Ag and directly with an increase in LF Cu and lies in the range 547−571 nm. The spectral width varies between 8.3 and 11.4 nm. In Ag/Cu/Ag/Cu, the sensitivity remains constant for varying LF Ag and fixed LF Cu . However, the sensitivity increases slightly with an increase in LF Cu . λ res decreases with an increase in LF Ag and increases with an increase in LF Cu and is in the range 538−562 nm. The calculated spectral width is about 7− 10 nm. For the same values of the total thickness, LF Cu , and RI analyte , the Cu/Ag/Cu/Ag structure offers a higher sensitivity than the Ag/Cu/Ag/Cu structure. A maximum sensitivity of 3500 and 3400 nm/RIU is observed with Cu/Ag/Cu/Ag and Ag/Cu/Ag/Cu, for the thickness ratios Cu/Ag = 1:1 and 2:1, respectively. Figure 6e depicts the variation of sensitivity and DA with LF Cu for the sensor configuration Cu/Al/Cu/Al, for different fixed LF Al , with a thickness ratio of Cu/Al = 1:1. The corresponding curves for the thickness ratio of Cu/Al = 2:1 are shown in Figure 6f . Similarly, Figure 6g ,h represents the variation of sensitivity and DA when the order of metals is reversed. For a thickness ratio of 1:1, with Cu/Al/Cu/Al, the sensitivity remains constant for varying LF Cu at a lower LF Al , whereas it decreases slightly with an increase in LF Cu for higher LF Al . Moreover, it is observed that the sensitivity increases with an increase in LF Al . The λ res decreases slightly with an increase in LF Cu and increases with an increase in LF Al and is in the range 404−471 nm. The spectral width is very narrow and ranges from 4 to 5.2 nm. With Al/Cu/Al/Cu, the sensitivity almost remains constant for varying LF Al at fixed LF Cu , except for the high LF Cu , where sensitivity increases with an increase in LF Al . Furthermore, the sensitivity is found to decrease with an increase in LF Cu . The λ res increases with an increase in LF Al and decreases with an increase in LF Cu . λ res ranges from 454.8 to 530 nm.

With the thickness ratio of 2:1, Cu/Al/Cu/Al exhibits nearly a constant sensitivity for varying LF Cu at lower LF Al , and it shows a slight decrease with an increase in LF Cu for higher LF Al . Furthermore, it shows an increase in sensitivity with an increase in LF Al . The observed spectral width is around 5.5 nm. The λ res varies from 416 to 475 nm. Moreover, λ res is observed to decrease with an increase in LF Cu and increase with an increase in LF Al . For Al/Cu/Al/Cu, upon varying LF Al , the sensitivity remains almost constant for lower LF Cu . However, for higher LF Cu , the sensitivity increases with an increase in LF Al . Moreover, with an increase in LF Cu , the sensitivity is found to decrease. The spectral width is found to be around 4.5 nm. The λ res ranges from 452 to 515 nm. It increases with an increase in LF Al and decreases with an increase in LF Cu . For similar LF, total thickness, and refractive index, Al/Cu/Al/Cu is found to yield a higher sensitivity than Cu/Al/Cu/Al. It is observed that the Cu/Al/Cu/Al configuration does not yield an acceptable sensitivity at n s = 1.361. A maximum sensitivity of 3200 nm/RIU is calculated with Al/Cu/Al/Cu.

For n s = 1.361, the Cu/Au/Cu/Au and Ag/Au/Ag/Au configurations yield a higher sensitivity of 4050 nm/RIU. However, for a higher RI analyte , the Cu/Al/Cu/Al configuration is found to yield a higher sensitivity of 11 550 nm/RIU. Since the outer layer is Al and is highly reactive, this configuration is not perfect for biosensing applications. Similar is the case of sensors with Cu as the outer layer. However, most real applications of SPR sensors involve keeping the probe region in inert ambient or vacuum and introducing the analyte gases and liquids through regulated flow cells. In such controlled environments, the sensors with Al and Cu top layers can be the top choice. Otherwise, the sensors with Au as the outer layer may be considered. Among such sensors, the four-layer configuration of Cu/Au/Cu/Au is the best choice with a sensitivity of 6050 nm/RIU, DA of 51.81 nm −1 , and FOM of 336.11/RIU. Moreover, for the same set of parameters, Cu/ Ag/Cu/Ag offers a narrow range in resonance wavelength (548−576 nm). The results (graphs not included) as furnished in Table 3 are also confirmed with the different four-layer configurations.

Asymmetric four-layer combinations with different metals were also investigated (graphs not shown). All of the Figure 7a ,b shows the variations of sensitivity and DA with RI analyte for the better-performing three-and four-layer configurations analyzed in this work. An increase in sensitivity and decrease in DA are observed with an increase in RI analyte for any given configuration. The figures serve as a guideline in choosing a particular configuration for practical applications. In Figure 7c , the variation of FOM with RI analyte is plotted for a single metal layer. For low values of RI analyte , Cu is better suited, while for higher RI analyte , Al is a better choice. Sensors made of Au or Ag show a linear response of FOM with RI analyte . The FOM values of the best sensors in single and multilayer configurations satisfying all of the stringently set criteria are plotted in Figure 7d . Evidently, the four-layer configuration of Al/Cu/Al/Cu is superior compared to other structures, especially at high RI analyte . Table 4 summarizes the performance details of all of the best configurations in single and multilayer sensors analyzed in the present study.

In our present work, the sensing characteristics of three-and four-layer metallic fiber-optic SPR sensors are analyzed based on their sensitivity, DA, and operating range. It has already been established in previously reported works that single metallic structures suffer from many disadvantages and that bimetallic combinations can rectify these disadvantages to a great extent. The proposed three-and four-layer metallic sensing probes work effectively for RI analyte in the range 1.34− 1.414. Maximum sensitivities of 11 750 and 11 550 nm/RIU are observed with Al/Cu/Al and Cu/Al/Cu/Al, respectively. These sensors also have a higher FOM of 995.76/RIU and 1241.94/RIU, respectively. Al/Cu/Al/Cu yielded a maximum sensitivity of 9750 nm/RIU and an FOM of 1433.82/RIU. Considering the unique chemical properties of Au and calculated sensitivities, Au/Cu/Au and Cu/Au/Cu/Au can be generally considered as a good choice for biosensors. However, the choice of the configuration should be made 

Metal Oxide Grating Based Plasmonic Refractive Index Sensor With Si Layer in Optical Communication Band

Cryo-EM Structure of the 2019-NCoV Spike in the Prefusion Conformation

Glucose Concentration Measurement in Human Blood Plasma Solutions with Microwave Sensors

Performance Analysis of Graphene-Based Surface Plasmon Resonance Biosensor for Blood Glucose and Gas Detection

The Refractive Index of the Human Cornea: A Review

Human Exhaled Breath Analysis

Breath Acetone as a Potential Marker in Clinical Practice

Exhaled Breath Analysis for the Early Detection of Lung Cancer: Recent Developments and Future Prospects. Lung Cancer: Targets Ther

Breath Gas Monitoring during a Glucose Challenge by a Combined PTR-QMS/GC×GC-TOFMS Approach for the Verification of Potential Volatile Biomarkers

Analysis of Ketone Bodies in Exhaled Breath and Blood of Ten Healthy Japanese at OGTT Using a Portable Gas Chromatograph

Fiber-Optic Sensors Based on Surface Plasmon Resonance: A Comprehensive Review

A Fiber-Optic Chemical Sensor Based on Surface Plasmon Resonance

Rapid and Quantitative Determination of Biological Warfare Agent Brucella Abortus CSP-31 Using Surface Plasmon Resonance

Surface Plasmon Resonance Biosensor for Detection of Bacillus Anthracis, the Causative Agent of Anthrax from Soil Samples Targeting Protective Antigen

On the Performance of Different Bimetallic Combinations in Surface Plasmon Resonance Based Fiber Optic Sensors

Fiber-Optic Surface Plasmon Resonance Glucose Sensor Enhanced with Phenylboronic Acid Modified Au Nanoparticles

Highly Sensitive Surface Plasmon Resonance Based Fiber Optic PH Sensor Utilizing RGO-Pani Nanocomposite Prepared by in Situ Method

Performance Analysis of Bimetallic Layer With Zinc Oxide for SPR-Based Fiber Optic Sensor

Sensor Properties and Surface Characterization of the Metal-Deposited SPR Optical Fiber Sensors with Au, Ag, Cu, and Al

High-Performance Bimetallic SPR Sensor Based on Periodic-Multilayer-Waveguides

High Performance Surface Plasmon Sensors: Simulations and Measurements

Stable and Sensitive Silver Surface Plasmon Resonance Imaging Sensor Using Trilayered Metallic Structures

Four-Layered Sensor Chip for Wavelength-Based Surface Plasmon Resonance Biosensor

On the Sensitivity of Surface Plasmon Resonance Sensors with Spectral Interrogation

Optical Fibre Surface Plasmon Resonance Sensor Based on a Palladium-Yttrium Alloy

Ultrahigh Sensitivity Surface Plasmon Resonance−Based Fiber-Optic Sensors Using Metal-Graphene Layers with Ti3C2Tx MXene Overlayers

An Introduction to Fiber Optics

Casimir Force between Metallic Mirrors

Simulation of a Surface Plasmon Resonance-Based Fiber-Optic Sensor for Gas Sensing in Visible Range Using Films of Nanocomposites

Electric Fields Produced by the Propagation of Plane Coherent Electromagnetic Radiation in a Stratified Medium

The authors are thankful to all those who extended their helping hands in completing this work. The authors do not receive funding from any source.