Document 1
Document 1
© 2022 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement
1. Introduction
Surface plasmon resonance (SPR) is a label-free detection for monitoring biomolecular interaction
in real-time, which utilizes the resonating effect of surface plasmons (SPs) or the induced electric
fields and magnetic fields that leak out from the uniform surface of noble metals, such as gold
(Au) and silver (Ag) [1]. These noble metals consist of metallic bonds that electrons can move
freely and oscillate with the same frequency as surface plasmon due to the external electric fields
causing the electromagnetic response referring to surface plasmon resonance (SPR) or surface
plasmon polaritons (SPP) [2]. The coupling condition of the surface plasmons depends on the
noble metal’s surrounding materials; this enables the label-free measurement and gives rise to
the underlining sensitivity mechanism [3]. In addition, the noble metals are very conductive and
contain a complex permittivity, resulting in the lossy light reflection [4].
Gold (Au) is a noble metal widely employed in biological and biomedical measurements in
biosensing applications due to its chemical stability and biocompatibility [5]. It also provides
convenient coupling angles and coupling wavelengths to excite surface plasmons. Furthermore,
since the natural frequency of surface plasmons of gold matches the light in the range of red to
infrared (more than 520 nm) wavelength [6], the incident light in this range can be applied to
surface plasmon resonance through an optical prism [7], a high numerical aperture objective lens
[8] and an optical grating [9].
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Journal © 2022 Received 10 Dec 2021; revised 16 Feb 2022; accepted 16 Feb 2022; published 2 Mar 2022
Research Article Vol. 13, No. 4 / 1 Apr 2022 / Biomedical Optics Express 1785
Fig. 1. Shows (a) Kretschmann configuration with angular scanning detection mechanism
and (b) sensing performance of angular scanning detection mechanism.
The Kretschmann configuration has been employed and utilized in several sensing applications,
for example, binding kinetics [13,14], refractive index sensing [15,16], pathogen detection
[17,18], voltage sensing [19,20], surface plasmonic microscopy [21,22], and surface-enhanced
Raman spectroscopy [23]. Recently, the SPR has demonstrated its ultra-sensitivity in measuring
the kinetic activity of SAR-COV2 (COVID19) and the angiotensin-converting enzyme 2 (ACE2)
[24,25]. In addition, Tang et al. [26] reported COVID-19 antibody immunoglobulin-G (IgG)
measurements on hospitalized patients using SPR.
Several detection schemes for SPR sensing include wavelength scanning [27,28] using a tunable
light source, optical fiber-based SPR sensors [29], and angular scanning detection [30–32]. Here,
the angular scanning detection scheme is investigated as an example to demonstrate findings
in this study. Therefore, applying the proposed figure of merit (FOM) is limited to neither the
plasmonic gold sensor material nor the angular scanning detection scheme. It will be shown in
the result section later that although the proposed FOM has been derived and proved using the
plasmonic gold material, it can be applied to accurately predict responses of higher loss plasmonic
material, such as aluminum (Al). For the Kretschmann-based angular interrogation detection,
the light source is a p-polarized monochromatic light source with its wavelength λ illuminated a
uniform gold plasmonic sample with the thickness d with the complex refractive index of gold
nm, through a glass prism with refractive index n0 of 1.52 with a varying incident angle θ0 ,
as shown in Fig. 1(a). The highest surface plasmon coupling strength occurs at the minimum
reflectance position, so-called plasmonic angle θsp , as shown in Fig. 1(b). The reflectance spectra
in Fig. 1(b) were calculated using Fresnel equations and the transfer matrix calculation [33] for
the λ of 633 nm, d of 40 nm, and the sample region refractive indices ns of 1.33 (water) and 1.35
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(80 mg/ml concentration of Bovine serum albumin protein solution [34]) shown in solid blue and
solid red curves, respectively.
Priya et al. [35] have reported that for coupling angle measurement through an optical glass
prism, the incident wavelength strongly affects the plasmonic angle shift (∆θsp ), full width at
half maximum (FWHM), depth of the plasmonic intensity dip (Isp ), and FOM that the ∆θsp , the
sensitivity (S), and the FWHM are exponentially decaying at a longer wavelength. On the other
hand, the SPR dip depth and the FOM are independent of the incident wavelength. Lakayan et
al. [6] have reported a similar finding that the incident wavelength is crucial in the ∆θsp and
the FWHM. They reported that λ of 890 nm had a 10-time higher S than the conventional SPR
excitation wavelengths of 670 nm and 785 nm.
A FOM is one of the crucial sensing performance parameters; it characterizes sensors’
predictive ability and performance. Therefore, it is widely adapted to determine sensors’
performance in different types of sensors, for example, surface plasmon resonance [19,36],
Fabry–Perot resonators [37], optical ring resonators [38], and surface phonon structures [12].
There are several definitions of FOMs based on the purpose and detection mechanisms. For
example, for surface plasmon resonance, the FOM usually employed is the S over the FWHM
[39–41]. In addition, some other parameters, such as Isp , intensity contrast (∆I), have been
employed in the FOM formulation [29,42–45].
There is no report on a direct FOM comparison between different expressions and formulas.
Therefore, this research aims to propose a theoretical framework to provide the comparison
between different expressions of FOMs and quantify the quantitative performance parameters,
including S, θsp , Isp , FWHM, ∆I, and FOMs of SPR sensors to analyze the sensing capability
using Fresnel equations and transfer matrix approach [33]. In addition, we also formulate a
generalized FOM that reflects the SPR limit of detection (LoD) calculated using Monte Carlo
and the shot-noise model for a typical digital camera and input optical power to the SPR system.
Principal component analysis (PCA) and machine learning (ML) models have been utilized to
identify key performance parameters that contribute to the proposed FOM formulation. To the
best of the authors’ knowledge, the theoretical framework to analyze and provide a direct FOMs
comparison between different definitions and a generalized FOM formulation has never been
investigated and reported before. One of the significant challenges in optical biosensing is to
measure a low concentration sample or a small number of analytes, such as single-molecule
detection [46] and DNA fragments [24,25]. These sensitivity demanding applications, of course,
require an optical sensor design and engineered optical sensor surfaces, such as structured
surfaces [47] and metamaterials [48]. The proposed generalized FOM can be applied to estimate
the sensor’s sensing performance during the optical sensor design process prior to the sensor
fabrication with no need for time-consuming and resource-demanding computation.
assuming that the camera had the quantum efficiency of 60% for all the wavelengths for fair
performance comparison and being independent of the camera’s performance, as depicted in
Fig. 2(a). The shot-noise model is a dominant noise source since the SPR dip has low light
intensity, especially around the plasmonic angle [51].
Fig. 2. (a) a camera frame with shot-noise added corresponding to the total energy of
5000 pJ, (b) camera rows summation to form a line scan plasmonic dip with 4th-degree
polynomial curve fitting. The case shown here was d of 25 nm and λ of 850 nm.
The plasmonic angle for each noise-added camera frame was then recovered employing the
following steps. (1) Sum all the intensity of 720 camera rows to a single-row angular spectrum to
reduce the random shot-noise as depicted in Fig. 2(a), and (2) apply the 4th-degree polynomial
curve fitting to the plasmonic dip covering sinθ0 range of ± 0.065 to determine the θsp position
for each camera frame as shown in Fig. 2(b).
A Monte Carlo simulation [50] with 1,500 iterations of randomized shot-noise added camera
frames was then employed to analyze and calculate the plasmonic angle positions and their LoD
as one standard deviation, σ.
Where the terms FWHM1.33 and FWHM1.35 are the FWHM of normalized reflectance spectra for
two sample refractive indices of 1.33 and 1.35 corresponding to water and 80 mg/ml concentration
of Bovine serum albumin protein solution [34], respectively.
(2) ∆I is defined as the average difference between optical intensity at the plasmonic reflectance
dip Isp and the intensity at the critical wave vector (Imax ) when the sample refractive indices
were 1.33 and 1.35 as expressed in Eq. (2). This parameter indicates the depth of the
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plasmonic dip intensity compared to its intensity baseline. The reflectance baseline
intensity is usually high since the SPR detection requires attenuated total internal reflection
(ATR). Therefore, suppose the ∆I is low means that the plasmonic dip is not deep, and
the measurement needs to detect low contrast signal in the strong background leading
to a lower signal-to-noise ratio (SNR). On the other hand, a higher ∆I indicates a higher
signal-to-noise ratio.
∆I1.33 + ∆I1.35
∆I = (2)
2
The terms ∆I1.33 and ∆I1.35 are an intensity contrast compared to the intensity baseline of the
two sample refractive indices.
(3) S is defined as the change in sinθsp over the change in sensing region refractive index ∆ns ,
which was 0.02 (1.35–1.33) for this study, as expressed in Eq. (3) and depicted in Fig. 1(b).
Note that the unit for Eq. (4) is RIU−1 .
∆sinθ sp
S= (3)
∆ns
(4) Detection range (DR) is defined as the highest refractive index value that can measure
before the plasmonic angle is greater than 90 degrees; in other words, still within the
possible range of incident angles that the prism can accommodate.
(5) FOMs: there are several definitions reported for angular scanning in the literature.
(5.1) the S over the FWHM [39,54–60] for plasmonic dip position measurement as
expressed in Eq. (4).
S ∆sinθ sp
FOM1 = = (4)
FWHM FWHM∆ns
(5.2) the S times the ∆I over the FWHM [29,42–44] for the plasmonic dip position
measurement, as expressed in Eq. (5).
∆I × S ∆I∆sinθ sp
FOM2 = = (5)
FWHM FWHM∆ns
(5.3) the S over the product of the FWHM and the Isp [45], as expressed in Eq. (6).
S ∆sinθ sp
FOM3 = = (6)
FWHM ×Isp FWHM∆ns Isp
(5.4) Here, we propose a generalized FOM as expressed in Eq. (7), which will be proved
later that the FOM4 can provide a better performance estimation compared to the
other FOMs and similar to the inverse of the LoD [61] calculated using the shot-noise
and Monte Carlo simulation as described in section 2.2.
√ √
∆I × S ∆I × ∆sinθ sp
FOM4 = √︁4 = √︁ (7)
FWHM × Isp 4
Isp × FWHM∆ns
Some other FOM definitions reported in the literature are not directly measurable from the
plasmonic reflectance spectra. Those FOMs were excluded from the scope of the study. For
example, Shen et al. [62] have reported an alternative approach calculating the FOM using the
transmission line model and found that the FOM is proportional to the equivalent reactance over
the resistance of the plasmonic sensor. Doiron et al. [63]. have reported that the FOM depends
on the optical power. These parameters cannot be readily extracted from the optical reflectance
spectra compared to the four FOMs in Eq. (4) to Eq. (7).
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(6) As explained earlier, LoD is defined as one standard deviation (σ) of plasmonic angles
recovered from the 1,500 camera frames with random shot-noise. The LoD is frequently
employed as a FOM indicator [64]. Here, the concept of FOM is related to the LoD by
defining the FOM as 1/LoD.
Fig. 3. Shows quantitative performance parameters for angular scanning detection scheme:
(a) FWHM, (b) ∆I (c) Isp , (d) ksp when ns = 1.33, (e) S calculated using Eq. (3); and (f) DR.
Fig. 4. Shows the reflectance spectra for the following SPR operating positions with sample
refractive indices of 1.33 shown in solid blue curves for reflectance and dashed-blue curves
for phase response and 1.35 shown in solid red curves for reflectance and dashed-red curves
for phase response (a) the operating position labeled ‘A’ with d of 80 nm and λ of 1900nm
(the narrowest FWHM, the widest DR, and the highest FOM1 ), (b) the operating position
labeled ‘B’ with d of 26 nm, and λ of 1900nm (the highest ∆I), (c) the operating position
labeled ‘C’ with d of 40 nm and λ of 1835nm (the highest FOM2 ), (d) the operating position
labeled ‘D’ with d of 52.5 nm and λ of 720 nm (the lowest Isp and the highest FOM3 ); (e)
the operating position labeled ‘E’ with d of 80 nm and λ of 629 nm (the highest S).
considers the ∆I of the SPR dips by multiplying the ∆I to the FOM1 , as shown in Fig. 5(b).
The maximum FOM2 of 315.2957 RIU−1 occurred at the operating position with d of 40 nm
and λ 1835nm (the operating position ‘C’). The reflectance spectra of the operating position
are shown in Fig. 4(c)—the operating position balanced out the dip movement and the signal
contrast. Figure 5(c) shows the FOM3 response calculated using Eq. (6); the FOM1 in Fig. 5(a)
over the Isp in Fig. 3(c). The highest FOM3 of 2.05×108 RIU−1 was at the d of 52.5 nm and λ of
720 nm (the operating position ‘D’). The plasmonic reflectance spectra for the operating position
are shown in Fig. 4(d). The optimum operating position range for the FOM3 was narrow and
around the d of 50 nm to 55 nm and the incident wavelength of 650 nm to 850 nm, as shown as an
inset in Fig. 5(c). Fig. 5(d) shows the response of our proposed FOM definition as expressed
in Eq. (7). The highest FOM4 of 2811 RIU−1 appeared at d of 52.5 nm and λ of 720 nm; the
high FOM4 operating positions were along the diagonal line in Fig. 5(d) and significantly wider
than the FOM3 . It is essential to point out that although the FOMs have the same unit of RIU−1 ,
they cannot be directly compared since the number of performance parameters involved differ.
Table 1 summarizes the performance parameters for the five chosen operating conditions of the
plasmonic uniform gold sensor. In Table 1, the five operating positions were then ranked based
on their FOM performance, as indicated in a bracket next to the FOM. It can be seen that the
FOMs did not agree with each other, except the FOM3 and the FOM4 . The next question is how
they can be compared and justified under fair criteria.
Fig. 5. Shows the FOMs for angular scanning detection scheme: (a) FOM1 calculated
using Eq. (4), (b) FOM2 calculated using Eq. (5), (c) FOM3 calculated using Eq. (6), and (d)
FOM4 calculated using Eq. (7).
Table 1. Quantitative sensing performance parameters and the FOMs for operating positions in
Fig. 3 and 5.
Operating position
Parameters A B C D E
λ (nm) 1900 1900 1835 720 629
d (nm) 80 26 40 52.5 80
FWHM 9.61×10−4 3.4×10−3 1.6×10−3 1.05×10−2 1.7×10−2
∆I 0.04 0.99 0.78 0.94 0.22
Isp 0.90 3.63×10−4 0.20 8.18×10−7 0.67
sinθsp (ns = 1.33) 0.88 0.88 0.88 0.92 0.95
S (RIU−1 ) 0.67 0.67 0.67 0.75 0.82
DR (RIU) 1.51 1.51 1.51 1.43 1.38
FOM1 694.93(1st ) 198.39(3rd ) 406.70(2nd ) 71.47(4th ) 48.51(5th )
FOM2 28.09(4th ) 195.77(2nd ) 315.30(1st ) 67.43(3rd ) 10.71(5th )
FOM3 768.17(4th ) 5.47×105 (2nd ) 2079.50(3rd ) 2.05×108 (1st ) 72.57(5th )
FOM4 143.3(4th ) 1428(2nd ) 538.5(3rd ) 2811(1st ) 25.2(5th )
that the SPR can measure a lower refractive index range, in other words, inverse relationship to
the LoD. The LoD was computed for the operating position assuming that the total reflectance
beam energy of 5000 pJ was captured using 1080 pixels by 720 pixels with the quantum efficiency
of 60%. Of course, one can increase the number of pixels or employ a higher well depth camera
leading to an LoD improvement. These, however, only change the value of the LoD, not the shape
of the LoD contour, as shown in Fig. 6(a). Fig. 6(b) to Fig. 6(e) show the inverse FOM1 , FOM2 ,
FOM3 , and FOM4 , respectively. The FOM1 and the FOM2 cannot provide a good representation
of the LOD.
On the other hand, the inverse of FOM3 and FOM4 can provide a similar pattern to the LoD.
The reciprocal of FOM4 can provide a more similar pattern to the LoD. Here, the structural
Research Article Vol. 13, No. 4 / 1 Apr 2022 / Biomedical Optics Express 1793
Fig. 6. (a) the LoD for all the operating conditions calculated for 5000 pJ optical energy, (b)
1/FOM1 , (c) 1/FOM2 , (d) 1/FOM3 , and (e) 1/FOM4
similarity index (SSI) [69] was computed comparing the similarity between the LoD and the four
reciprocal FOMs giving the SSIM of 53.42%, 77.11%, 83.12%, and 95.62%, respectively. The
FOM4 performed better than the other FOMs because the FOM4 took sufficient optical intensity
information into account compared to the other FOMs. The following section will be shown and
discussed through machine learning and the PCA that the parameters that can contribute to the
LoD and FOM are the S, the FWHM, the ∆I, and the Isp .
Table 2. RMSE of ML models trained using the five predictors S, FWHM, ∆I,
Isp , DR to model the LoD response.
Fig. 7. shows LoD models trained using (a) 5 parameters, (b) 4 parameters, (c) 3 parameters,
(d) 2 parameters, and (e) 1 parameter.
training data; prediction outside the scope of the training data can lead to an unrealistic value
[70]. The last section will demonstrate this in predicting the LoD response of a higher loss
plasmonic material aluminum. Therefore, there is a need to work an analytical LoD or FOM
from the sensing parameters.
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Table 3. RMSE of GPR model with Matern 5/2 GPR trained using different
performance parameters.
ML model Parameters RMSE
Gaussian Process Regression (GPR) S, FWHM, ∆I, Isp , DR 0.86%
Algorithm: Matern 5/2 GPR S, FWHM, ∆I, Isp 0.86%
PCA output: S, FWHM, ∆I 0.87%
S (97.8%), FWHM (1.9%), ∆I (0.2%), Isp S, FWHM 5.03%
(0.1%), DR (0.0%) S 10.44%
Fig. 8. Shows SSI responses comparing the LoD contour in Fig.7a and Eq. (8) with varying
I and j variables from −2 to 2 and (a) m = 1 and n = 1, (b) m = 2 and n = 1, (c) m = 1 and n = 2
To prove that the proposed FOM can predict the responses of plasmonic materials and other
sensor structures that require an angular interrogation measurement. Here, the following four
responses of plasmonic aluminum at four incident wavelengths λ of 1000 nm, 1200 nm, 1400 nm,
and 1600 nm were computed for their LoD when the metal thickness was varied from 10 nm to
45 nm. It is well known that aluminum is a lossier plasmonic material [71] than gold, silver,
and copper. Fig. 9(a) shows the normalized LoD of the four wavelengths calculated using the
shot-noise model and Monte Carlo simulation described in section 2.2. Note that the 1,500
iterations were insufficient to calculate a stable LoD response due to the high attenuation nature
of the SPs excited on the Al surface. Therefore, the LoD needs to be estimated using the FOM
expressions; otherwise, it is a time and computing resource-demanding task. Fig. 9(b) shows
Research Article Vol. 13, No. 4 / 1 Apr 2022 / Biomedical Optics Express 1796
normalized 1/FOM4 calculated using the proposed FOM in Eq. (7). It can be seen that the FOM4
can predict the performance of the plasmonic aluminum for all the investigated wavelengths.
The ML models can only be employed to predict the SPR responses that are similar to
the training cases; the aluminum SPR cases significantly differed from the gold SPR cases.
Fig. 10(a-e) shows the predicted LoD using the models trained in section 3.4. All the models,
even the one developed using five performance parameters, cannot provide a good estimation of
the LoD.
Fig. 10. Shows the LoD responses predicted using the GPR models with Matern 5/2 GPR
algorithm trained using (a) 5 performance parameters S, FWHM, ∆I, Isp and DR, (b) 4
performance parameters S, FWHM, ∆I and Isp , (c) 3 performance parameters S, FWHM
and ∆I, (d) 2 performance parameters S and FWHM, and (e) 1 performance parameter S.
good estimation of the theoretical LoD calculated using the shot-noise model and Monte Carlo
simulation.
Fig. 11. Shows SPR responses of Au when varying d from 35 nm to 80 nm at four incident
angles sinθ0 0.900, 0.925, 0.950, and 0.975 for (a) normalized LoD calculated using
shot-noise and Monte Carlo model, and (b) normalized 1/FOM4 .
The limitation of the proposed FOM is that it is not applicable for phase measurement since
the phase detection differs from the intensity detection in terms of the nature and the noise
performance of an optical interferometer. It is established that the phase measurement is more
robust to the optical intensity noise than the amplitude or intensity measurement. In optical
interferometry, the SPR resonant wave vector is instead detected through the displacement of
interferent fringes; therefore, the optical intensity is not a crucial parameter. Kabashin et al.
[72] have experimentally validated and explained this point. Roland et al. [73] also reported a
similar finding when using a thinner plasmonic gold of 25 nm, which had lower ∆I contrast. They
imaged and located subwavelength nanoparticles with 10 nm to 200 nm diameter through SPR
phase imaging microscopy. Therefore, the FOM for the phase measurement does not depend
strongly on the optical intensity.
4. Conclusion
We have proposed a theoretical framework to quantify performance parameters for angular inter-
rogation based on surface plasmon resonance measurement under the conventional Kretschmann
configuration. The different figures of merit definitions and expressions are reported in the
literature. However, there was no direct comparison to evaluate and compare the figures of
merit. Here, the limit of detection calculated using the shot-noise model and Monte Carlo
simulation representing optical intensity noise and fluctuations typically found in a digital camera
was applied to compare the figures of merits. The figures of merit reported in the literature
cannot reasonably estimate the detection limit. Therefore, we proposed a generalized figure of
merit definition of sensitivity×intensity contrast0.5 /(full width at half maximum×intensity at the
plasmonic dip0.25 ), which can provide a good estimation of the detection limit. The proposed
figure of merit expression was developed using the principal component analysis to identify the
four performance parameters contributing to the figure of merit performance. The proposed
figure of merit can be employed to predict the SPR of higher-loss plasmonic material, including
aluminum.
Funding. The Research Institute of Rangsit University (RSU); the School of Engineering of King Mongkut’s Institute
of Technology Ladkrabang (KMITL).
Disclosures. The authors declare no conflicts of interest.
Data availability. Data underlying the results presented in this paper are not publicly available at this time but may
be obtained from the authors upon reasonable request.
Research Article Vol. 13, No. 4 / 1 Apr 2022 / Biomedical Optics Express 1798
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