A novel high sensitivity optical fiber LSPR SARS-CoV-2 sensor based on

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triangular gold nanosheets
Bing Xua,b, Xiaoying Xianga,b, Yan Lia,b, Zhihui Luoa,b*, Dehai Wangc,

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aHubei Engineering Research Center of Weak Magnetic-filed Detection, Yichang, Hubei 443002,
China.
bCollege of science, China Three Gorges University, Yichang, Hubei 443002, China.
cMedical College, China Three Gorges University, Yichang, Hubei 443002, China.

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*Corresponding author(s). E–mail(s): zhihui_luo@126.com;

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Contributing authors: xbwhut2018@163.com; xiangy0923@163.com; leeyan0503@163.com;

dcwang99@163.com;

Abstract
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To tackle the global pandemic of COVID-19 outbreak, which is caused by severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2), there is a need for highly accurate diagnostic tests at all stages
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of infection with high sensitivity and rapid. Herein, a novel high sensitivity optical fiber localized
surface plasmon resonance (LSPR) SARS-CoV-2 sensor based on triangular gold nanosheets was
reported. Triangular gold nanosheets (AuTNPs) have unique tip structure and excellent LSPR effect, it
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can improve the sensitivity of the sensor. The Au-mAb LSPR SARS-CoV-2 biosensor is constructed
successfully via the chemical crosslink method. In the presence of SARS-CoV-2 spike antigen, the
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antigen antibody specifically binds to the surface of the nanosheets, changing the effective refractive
index of the optical fiber and resulting in changes in the LSPR of the nanosheets. At the same time, it
is proved that the LSPR shift is not caused by the refractive index to be measured. The Au-mAb
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biosensor displays a linear response in the SARS-CoV-2 spike antigen range of 1.56-312ng/mL, and
the response coefficient is 0.035nm/(ng/mL). In addition, this biosensor has high sensitivity and shorter
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response time (10 min). The sensor has good stability and can be reused. The Au-mAb biosensor has
broad application prospects in the detection field of SARS-CoV-2.
Keywords: triangular gold nanosheets, optical fiber, SARS-CoV-2, localized surface plasmon
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resonance (LSPR)

This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4327579
 1. Introduction

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In December 2019, infectious pneumonia was detected in Wuhan, China, and the outbreak quickly
spread around the world. Public health professionals found that the new pneumonia about 80%
similarity to the genome of the severe acute respiratory syndrome (SARS-CoV), and named it severe

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acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Shen et al., 2020; Yang et al., 2020).
According to the World Health Organization reported, COVID-19 disease which is caused by SARS-
CoV-2 infection, has killed about 6.4 million people and infected more than 600 million as of August
2022 (WHO, 2022). COVID-19 disease poses a serious threat to global human health and the global

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economy. The development of a rapid and highly accurate diagnostic tests tool for SARS-CoV-2

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infection is certainly supportive of contribute to the control of COVID-19 disease (Saad et al., 2022).
At the beginning of the outbreak of COVID-19, patients infected with SARS-CoV-2 were
diagnosed by computed tomography (CT) of the chest, and compared with healthy lungs, and different
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shadows in the CT images of the patients were recorded, thus making a preliminary diagnosis of
COVID-19. However, this diagnostic method is costly and easy to be confused with other pneumonia
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(Li et al., 2020; Kim et al., 2020; Wang et al., 2020). Subsequently, in early January 2020, reverse
transcription polymerase chain reaction (RT-PCR) based techniques were used to diagnose the novel
coronavirus pneumonia after the coronavirus genetic code was published. RT-PCR technology provides
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considerable convenience for the detection of SARS-CoV-2 and its progress, but this method has certain
limitations: RT-PCR technology relies on well-trained operators, complex equipment, and the detection
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cycle is tedious (Carter et al., 2020; Yu et al., 2020; Chu et al., 2020). In this context, there is an urgent
need for a simple, rapid diagnostic technology, high sensitivity and stable early detection method for
COVID-19, which can quickly and accurately identify infected patients, so as to further prevent and
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control the disease.

Nanomaterials are of interest in the field of sensors because their inherent physical and localized
surface plasmon resonance (LSPR) effect. The LSPR formant shifts resulting from the shift of surface
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plasma absorption as a result of varying size and surrounding (Draz et al., 2018; Chang et al., 2019). In
addition, nanomaterials can be functionalized with biomolecules, facilitating the capture of targets and
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amplifying the detection signal (Lin et al., 2014). Due to these combined benefits, nanomaterial-based
biosensors have been applied to detect SARS-CoV-2 viral RNA, protein antigens or antibodies (Younes

This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4327579
 et al., 2020; Ghorbanizamani et al., 2021; Ferreira et al., 2022). In this context, Pan and co-workers

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reported a colorimetric sensor using AuNPs capped by mercaptan modified ASO, which selectively
aggregated in the presence of SARSCoV-2 target RNA sequence and changed its UV absorption peak
to achieve naked eye detection (Moitra et al., 2020). Qiu et al. combined plasma photothermal effect

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with local surface Plasmon resonance (LSPR) to make a biosensor, and the detection limit of the sensor
was as low as 0.22pM (Qiu et al., 2020). Alternatively, Cennamo et al. detected SARS-Cov-2 spike
protein by fixing a specific aptamer sequence on a gold nanofilm deposited on a D-shaped plastic fiber
(POF) probe, the detection limit (LOD) was about 37 nM (Cennamo et al., 2021). However, these

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methods are complex to operate and depend on specific equipment.

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In recent years, nanoparticles have brought new development for optical fiber sensors due to their
localized surface plasmon resonance (LSPR) effect, which can improve their reuse rate and enhance
their sensitivity. The shape and size of nanoparticles can be controlled through a synthesis process.
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Some shape most commonly applied in sensors are nanorods, nanospheres, nanosheets (Cao et al., 2014;
Song et al., 2019; Tessaro et al., 2023). Triangular gold nanosheets (AuTNPs) exhibit a geometry with
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sharp edges compare to the other gold nanoparticles shape. The sharp edges structure of AuTNPs leads
to the occurrence of the enhanced LSPR phenomenon, which is attributed to the electromagnetic field
around the sharp tip, edge and corner of AuTNPs due to the polarization effects (Lai and Slaughter,
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2019; Liyanage et al., 2021). Fiber optic sensors have been widely used in many fields, such as the
measurement and analysis of biomolecules, early diagnosis of cancer and protein measurement, because
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of their advantages of fast, low cost, sensitive and specific (Lin et al., 2014; Luo et al., 2018; Cai et al.,
2020). The sensitivity of the optical sensor is enhanced when crosslinked to AuTNPs (Liyanage et al.,
2021).
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Herein, a novel high sensitivity optical fiber LSPR SARS-CoV-2 sensor based on triangular gold
nanosheets is presented. In this work, the triangular gold nanosheets (AuTNPs) is characterized by its
unique tip structure and excellent LSPR performance. The optical fiber LSPR SARS-CoV-2 sensor (Au-
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mAb probe) was constructed through several surface modifed steps in a sequence that include
silanization of the optical fiber by 3-mercaptopropyltrimethoxysilane (MPTMS), linkage of AuTNPs to
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optical fiber, functionalization of AuTNPs and immobilization of SARS-CoV-2 spike monoclonal

antibody (mAb). The SARS-CoV-2 antibody fixed on the surface of the optical fiber probe is

This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4327579
 specifically bound to the SARS-CoV-2 antigen of the target detection object, and the effective refractive

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index of the optical fiber is slightly changed resulting in the localized surface plasmon resonance (LSPR)
effect of the triangular gold nanosheets is affected, and its peak position is shifted. Further, the
performance of the sensor was investigated, including detection range, response time, and repeatability.

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Finally, specificity assessment tests for sensor were performed by contrast experiment. The sensor has
great potential in SARS-CoV-2 detection field.
2. Materials and methods
2.1 Materials

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Chloro(triethyl phosphine) gold (I) (Et3PAuCl, 98%), ACS grade acetonitrile (CH3CN, 99.8%),

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triethylamine (TEA, 98%), poly(methylhydrosiloxane) (PMHS, Mn=1700−3300), 3-
mercaptopropyltrimethoxysilane (MPTMS, 97%), 11-mercaptoundecanoic acid (MUA), N-
hydroxysuccinimide (NHS), and 1-ethyl-3-(3-dimethylaminopropyl)-Carbodiimide (EDC) were
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purchased from McLean Reagent Co., LTD (China). Hydrochloric acid, methanol, and ethanol were
obtained from sinopharm chemical Reagent Co., LTD (China). Bovine serum albumin (BSA, 98%) was
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derived from Aladdin Reagent Co., LTD (China). SARS-CoV-2 spike monoclonal antibody (mAb)
(Chimeric MAb Cat: 40150-D001) and SARS-CoV-2 (2019-nCoV) spike S1-his recombinant protein
(HPLC-verified, Cat: 40591-V08H) were acquired from Sino Biological (China). Recombinant
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Influenza A virus HA protein (C-HisTag) was obtained from Pujian Biology Technology Co., LTD
(China). All reagents were used directly without further treatment. All ultrapure water was prepared
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with Milli-Q water.

Shimadzu UV-2550 spectrophotometer (Japan) was used to record the AuTNPs UV-vis absorption
spectra. TEM images were collected on a JEOL F200 transmission electronic microscope (JEOL, Japan).
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The characterization of the mAb coated on the surface of optical fiber was tested by scanning electron
microscope (SEM, Japan). The chemical bonds between AuTNPs and mAb were tested by Fourier
transformation infrared spectro-meter (FTIR, 4000-500 cm-1).
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2.2 Surface biofunctionalization of the optical fiber

The primary functionalization process of the biosensor is shown in Figure 1A. The Au-probe was
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separately prepared through two steps: MPTMS silanization and gold triangular nanosheets (AuTNPs)
immobilization. In the first step, the organic coating was removed by soaking one end of the fiber with

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 acetone. The fiber probe was immersed in hydrochloric acid and methanol solution (1:1) for 30min, and

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the washed fiber was placed in the air to dry for 3h to activate the hydroxyl group on the surface of the
fiber. Put the dried fiber probe into 15% MPTMS- ethanol solution and keep the cross-linking time for
30min. This step is to convert the hydroxyl group on the surface of the fiber probe into sulfhydryl group.

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The unbound MPTMS were removed from the fiber surface by flushing the fiber probe with ethanol
(Liyanage et al., 2021; Liyanage et al., 2022). In the later step, AuTNPs were synthesized according to
the method published (Joshi et al., 2012; Liyanage et al., 2017; Hati et al., 2021). Briefly, 3.6mg
Chloro(triethyl phosphine) gold (I) was dispersed in 8mL acetonitrile and stirred at room temperature

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for 10min. Then add 7.6uL TEA solution, heat the mixed solution to 40℃, and stir for 20min. Add

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120uL PMHS to the mixture and keep heating and stirring. The mixed solution turned to pink, purple,
and blue. The AuTNPs can be completed within ~ 60 min. Finally, incubated in 1.2 mL of the prepared
AuTNPs dispersions for 1h to form a coating of AuTNPs on to the optical fiber surface. Then, the Au-
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probe was functionalized with MUA solution, and the surface of AuTNPs was coated with carboxyl
groups. The optical fiber probe was immersed in MUA solution (0.6mL, 10mM) for 12h. In addition,
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the carboxyl group on the surface of the nanosheet was activated by crosslinking agent EDC (0.3mL,
5mM) and NHS solution (0.3mL, 7.5mM). Subsequently, Au-probe was immersed in SARS-CoV-2
antibody (mAb) solution (0.5mL, 4.4ug/mL) for keep 1h, the amino group of mAb would bind to the
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carboxyl group on the surface of the fiber, mAb is fixed to the surface of the optical fiber. The Au-mAb
probe was used to as the biosensor to detect SARS-CoV-2 spike antigen sample (Karakuş et al., 2021;
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Masterson et al., 2021).

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This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4327579
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Figure 1. (A) Schematic diagram of optical fiber LSPR biosensor based on AuTNPs, AuTNPs
covalently bonded to the optical fiber (a-d). The Au-mAb biosensor manufacturing process (d-g). (B)
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Experimental setup for monitoring the absorption spectra of the Au-mAb biosensor. (Inset: Antigen
antibody specific response scheme on the fiber surface).
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2.3 Au-mAb biosensor detection of SARS-CoV-2 and measurement system
The Au-mAb biosensor system consists of a broadband light source (working wavelengths: 390-
900nm, Ocean Insight), Y-type optical fiber (Ocean Insight), a spectrometer (working wavelengths:
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350-1000nm, Ocean Insight), and an Au-mAb biosensor probe. Its schematic diagram is shown in
Figure 1B. Light enters the optical fiber sensing probe through Y-shaped fiber, and the AuTNPs material
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on the probe surface is excited to generate localized surface plasmon resonance phenomenon. When the
Au-mAb probe was soaked into the SARS-CoV-2 spike antigen sample, LSPR spectrum changed
caused by the reaction between antibody and antigen.
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3. Results and Discussion

3.1 Surface morphological characterization
UV-vis spectra and TEM characterizations of the formation and properties of the AuTNPs are
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shown in Figure 2A and B. As shown in Figure 2A, the product has an absorption peak at about 632
nm. No significant peak was observed at 530 nm, indicating a high yield of AuTNPs. The inset of Figure
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2A shows the color of the gold nanoparticles. The conclusion was further verified by TEM
characterization. Figure 2B shows homogeneous dispersed AuTNPs with sharp tips were synthesized.

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 The edge length about 21.5 nm.

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The fiber probe surface modification process was recorded, and the results were shown in Figure
2C. Figure 2C shows the LSPR spectra of the as prepared Au-probe (curve black), AuTNPs-MUA probe
(curve red) and AuTNPs-mAb probe (curve blue). It is obvious that the LSPR of Au-MUA is about 703

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nm with a blue shift of 70 nm contrasted to that of AuTNPs (773 nm). This indicates that alkanethiol
molecules bind to the surface of the gold nanosheet through Au-S bond interaction, which changes the
effective refractive index of the fiber and causes the blue shift of the LSPR peak (Li et al., 2007).
AuTNPs-mAb probe exhibited blue shift in the LSPR spectra, which is due to the binding of mAb with

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optical fiber. The amino group of the mAb reacts with the carboxyl group on the surface of the nanosheet,

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and then the mAb is firmly fixed on the surface of the nanosheet. The LSPR peak changes after changing
the environment around the nanosheet. In addition, mAb coated on the surface of the optical fiber was
observed by scanning electron microscope (SEM). As shown in Figure 2D, mAb was obvious on the
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surface of optical fiber which proved the success deposition of mAb on the surface of fiber (Phiri et al.,
2019; Blin et al., 2005).
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To further ensure that the mAb was immobilized on the AuTNPs surface, the structure of the
AuTNPs and Au-mAb were characterized by FTIR as shown in Figure 2E. It can be seen that the peaks
of the intense bands at about 1457 and 1638 cm-1 caused by characteristic of AuTNPs. Au-mAb
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displayed sharp peaks at 2918 and 3290 cm-1, typical of -CH2 and N-H/O-H hydroxyl groups from
protein mAb (Radhakumary and Sreenivasan, 2011; Zheng et al., 2020). All in all, the FTIR spectra
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difference indicated that the mAb was validly covalently-immobilized on the surface of AuTNPs.
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Figure 2. (A) UV-vis absorption spectra and (B) TEM image of AuTNPs. The inset in (A) shows a
digital image of colloidal AuTNPs solution. (C) LSPR absorption spectra of of Au probe, AuTNPs-
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MUA probe and the Au-mAb probe. SEM image of Au-mAb probe (D). (E) FTIR spectra of AuTNPs
and Au-mAb.
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3.2 Principle of the LSPR biosensor

In order to study the refractive index sensitivity of the optical fiber probe, 0% ~ 20% sodium
chloride solution was configured, and abbe refractometer (WAY-2WAJ, LICHEN technology) was
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used to measure the above sodium chloride solution with different concentrations. The refractive index
was measured, and the refraction rate was 1.33 ~ 1.38. The spectra of the Au-probe under different
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refractive index solutions were recorded using the measuring system shown in Figure 1B. The LSPR
spectra movement of the Au-probe were observed by computer. As shown in Figure 3, with the increase
of refractive index of sodium chloride solution, Au-probe LSPR peak gradually shifted to the right. The
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probe SRI sensitivity is about 371.3 nm/RIU, it is more sensitivity than Thakshila et., al (263.37 nm/RIU)
(Liyanage et al., 2021). The AuTNPs plasmonic sensor has the highest sensitivity due to its exhibit a
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 geometry with sharp edges compare to the gold nanoparticles (AuNPs) and gold nanorods (AuNRs)

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(Joshi et al., 2013)

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Figure 3. The LSPR spectra of Au-probe with different refractive index solutions (N=3).
To test whether the biosensor is responsive to the SARS-CoV-2 spike antigen, the absorption
spectra of the Au-mAb biosensor upon addition of a certain concentration of SARS-CoV-2 spike antigen
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was shown in Figure 4A. In the presence of the antigen, the LSPR spectra blue shift (~9 nm). Then, the
Au-mAb biosensor was immersed in PB solutions. As shown in Figure 4B and C, it is obvious that
LSPR spectra peak changed little (Δλ=0.3 nm). This result shows that the refractive index of antigen
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solution is similar to PB solution, and the LSPR does not change due to the refractive index of the test
solution. The detection principle of the biosensor is as follows, the light enters the optical fiber sensing
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probe through the Y-shaped optical fiber, and excites the triangular gold nanosheets sensitive material
on the probe surface to produce the localized surface plasmon resonance (LSPR) peak phenomenon.
When the SARS-CoV-2 spike antigen target is present, the specific binding of antigen and antibody
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resulting in the change of the triangular gold nanoplate environment, the LSPR effect is affected. Then,
the effective refractive index is changed, and the LSPR peak of the optical fiber probe is affected (Shi
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et al., 2019). Detection of SARS-CoV-2 spike antigen based on the principle of LSPR peak shift.
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This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4327579
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Figure 4. The LSPR spectra of Au-mAb biosensor before and after treatment of certain concentration
of SARS-CoV-2 spike antigen (A). The LSPR spectra of Au-mAb probe in antigen and PB solutions
(B and C).

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3.3 Sensitivity of LSPR sensor

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The Au-mAb biosensor was used for the detect SARS CoV-2 spike antigen in PB (pH=7.4), and
the observed LSPR spectra was recorded as the reference. As shown in Figure 5A, when increasing the
SARS-CoV-2 spike antigen concentration, the effective refractive index of optical fiber changes due to
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the specific binding of antigen and antibody. Refractive index further leads to significant changes in the
resonance wavelength of the optical fiber. The LSPR peak of Au-mAb biosensor gradually blue shift.
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The Δλ (difference of LSPR peak between Au-mAb biosensor and after addition of a range of different
concentrations SARS-CoV-2 spike antigen) showed a linear relationship with SARS-CoV-2 spike
antigen concentrations, providing a linear detection range from 1.56 to 312 ng/mL (Figure 5B). When
the concentration of SARS-CoV-2 spike antigen in the range from 1.56 to 312 ng/mL, the sensors show
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high sensitivity and the calibration curve can be described by the equation: ∆λ = 0.035C (ng/mL) +

4.93 (R2=0.944). The highly sensitivity of the LSPR biosensor could be attributed to AuTNPs excellent
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LSPR properties and specific binding of antigen-antibody on the surface of triangle nanosheet.
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Figure 5. The LSPR spectra of Au-mAb probe with the concentration of SARS-CoV-2 spike antigen
changing (A). The relationship between the LSPR peak displacement of the Au-mAb probe and the
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SARS-CoV-2 spike antigen concentration (B).

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 3.4 Selectivity of biosensor for SARS-CoV-2

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The selectivity of the Au-mAb biosensor was evaluated using several protein interferences. As
shown in Figure 6A, a series of concentrations (1560 ng/mL) of other protein solutions (Bromelin, DNA
polymerase, L-alanine, Influenza A vius) to evaluate the selectivity of the Au-mAb biosensor for the

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detection of SARS-CoV-2 (156 ng/mL). It can be found that the sensor has no response to other protein
solutions with ten times the concentration (∆λ< 1.5 nm, can be ignored). The LSPR peak have a
significant shift (8.3 nm) was observed when SARS-CoV-2 was present in the solution. This is because
the mAb on the surface of the nanosheet only target the SARS-CoV-2 antigen. These results suggested

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that the biosensor has highly selectivity to the SARS-CoV-2.

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3.5 Response time and stability of biosensor
The response time of the fiber biosensor is defined as the time from the Au-mAb probe immersed
in the SARS-CoV-2 spike antigen solution to the LSPR spectrum unchanged. As exhibited in Figure
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6B, the specific binding of mAb on the fiber surface with SARS-CoV-2antigen molecules in solution,
causing the resonance wavelength shifts. The binding sites on the surface of the nanosheet are limited,
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and the LSPR peak does not change when the sites saturation is reached. And the response time of the
fiber biosensor is about 10 min.
Stability is an important feature that enables the same biosensor to be used for multiple
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determinations. For purpose of researching the stability of the Au-mAb biosensor, samples of the same
concentration will be tested with the same probe at different times. As exhibited in Figure 6C, the Au-
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mAb biosensor is used for detect SARS CoV-2 antigen, the LSPR peak blue shift. The used Au-mAb
biosensor was stored in the refrigerator, the antigen on its surface gradually shed, and the LSPR was
tested to return to the initial position. After circulating this operation for three times, it can be seen that
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each shift was basically consistent. This is due to the antigen falls off the surface of the nanosheet after
each measurement, exposing the binding site of the antibody for the next test. This result indicates that
the biosensor is stable and can reuse.
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Figure 6. (A) Sensor selectivity in the presence of interfering substances.
(B) Response time of fiber biosensor.

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(C)Three full cycles of surface regeneration.

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3.6 Comparison of different SARS-CoV-2 sensors
The comparison between this work and several SARS-CoV-2 sensors is shown in Table 1.
Compared with the gold nanoparticle-based colorimetric biosensor [32], the optical fiber functionalized
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by AuTNPs shows higher sensitivity and reuse, indicating that the introduction of AuTNPs and optical
fiber can greatly improve the sensor’s sensitivity to SARS-CoV-2 antigen. In addition, gold nanofilm
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[18] require magnetron sputtering and rely on complex equipment. Compared with gold nanofilm, the
AuTNPs has great advantages in manufacturing process, and the AuTNPs LSPR sensor still maintains
high sensitivity. Therefore, it indicated that this LSPR sensor has high sensitivity, fast response, and
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nondestructive. This sensor has great prospects in in the field of SARS CoV-2 detection.
Table 1 Comparison of the analytical performance of different glucose detection method.
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Linear
Material Method Target Sensitivity Reference
range

SARS-CoV-2 spike 48-2000 0.0125(nm/(ng/ Karakuş et

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AuNPs Colorimetric
antigen ng/mL mL)) al., 2021

Gold D-type optical SARS-CoV-2 spike 25-1000 Qiu et al.,

0.018(nm/(nM)
nanofilm fiber antigen nM 2020
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Large diameter SARS-CoV-2 spike 1.56-312 0.035(nm/(ng/

AuTNPs This work
optical fiber antigen ng/mL mL))
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4 Conclusions
A biosensor based on triangular gold nanosheets was constructed by taking advantage of the
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 excellent LSPR properties of the AuTNPs and high refractive index sensitivity of optical fiber probe.

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The refractive index sensitivity of AuTNPs combined with optical fiber is higher than that of AuNPs
and AuNRs. The detection mechanism of the biosensor is as follows: the antibody binds specifically to
the surface of the nanosheet and changes the limited refractive index of the optical fiber. It is proved

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that the change of the effective refractive index of the fiber is not caused by the change of the refractive
index of the solution to be measured. The sensor has excellent linear response in low concentration
range (1.56-312ng/mL) with sensitivity of~0.035nm/(ng/mL). And systematical experiments have
shown this biosensor provides high selectivity and shorter response time (10 min) to SARS-CoV-2 spike

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antigen. In addition, the biosensor has good stability and can be reuse. It lays a foundation for the

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application of optical fiber LSPR sensor in the field of SARS CoV-2 diagnosis.
Data availability statements
The data that support the findings of this study are available upon reasonable request from authors.
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Acknowledgment
This work was supported by Youth Program of Natural Science Foundation of Hubei Province
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(2022CFB800) and Natural Science Foundation of Yichang (NO. A22-3-002).
Conflict of interests
The authors declare that they have no conflict of interest.
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References
Shen, M., Zhou, Y., Ye, J., Abdullah Al-maskri, A.A., Kang, Y., Zeng, S., Cai, S., 2020. J Pharm Anal.
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10, 97-101.
Yang, Y., Lu, Q., Liu, M., Wang, Y., Zhang, A., Jalali, N., E. Dean, N., Longini, I., Halloran, M., Xu,
B., Zhang, A., Wang, L., Liu, W., Fang, L., 2020. medRxiv.
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WHO, WHO Coronavirus (COVID-19) Dashboard., 2022. https://covid19.who.int/.

Saad, Y., Mohamed Hichem, G., Karine, M., Marwa, S., Hafedh, B., 2022. Plasmonics. 17, 1489-1500.
Li, Y., Xia, L., 2020. Am J Roentgenol. 214, 1280-1286.
ep

Kim, H., 2020. Eur Radiol.30, 3266-3267.

Wang, W., Xu, Y., Gao, R., Lu, R., Han, K., Wu, G., Tan, W., 2020. JAMA. 323, 1843-1844.
Pr

Carter Linda, J., Garner Linda, V., Smoot Jeffrey, W., Li, Y., Zhou, Q., Saveson Catherine, J., Sasso
Janet, M., Gregg Anne, C., Soares Divya, J., Beskid Tiffany, R., Jervey Susan, R., Liu C., 2020.

13

This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4327579
 ACS Cent. Sci. 6, 591-605.

ed
Yu, L., Wu, S., Hao, X., Dong, X., Mao, L., Pelechano, V., Chen, W-H., Yin, X., 2020., Clin Chem.
66, 975-977.
Chu, D.K.W., Pan, Y., Cheng, S.M.S., Hui, K.P.Y., Krishnan, P., Liu, Y., Poon, L.L.M., 2020. Clin

iew
Chem. 66, 549-555.
Draz, M.S., Shafiee, H., 2018. Theranostics. 8, 1985-2017.
Chang, C., Chen, C., Wu, T., Yang, C., Lin, C., Chen, C., 2019. Nanomaterials. 9.
Lin, Y., Ren, J., Qu, X., 2014. Acc Chem Res. 47, 1097-1105.

v
Younes, N., Al-Sadeq, D.W., AL-Jighefee, H., Younes, S., Al-Jamal, O., Daas, H.I., Yassine, H. M.,

re
Nasrallah G.K., 2020.Viruses.12.
Ghorbanizamani, F., Moulahoum, H., Zihnioglu, F., Evran, S., Cicek, C., Sertoz, R., Arad, B., Goksel,
T., Turhan, K., Timur, S., 2021. Biosens Bioelectron. 192.
er
Ferreira, A.L., De Lima, LF., Torres, M.D.T., De Araujo, W.R., De La Fuente-Nunez, C., 2022. ACS
nano. 15, 17453-17462.
pe
Moitra, P., Alafeef, M., Dighe, K., Frieman, M.B., Pan, D., 2020. ACS nano. 14, 7617-7627.
Qiu, G., Gai, Z., Tao, Y., Schmitt, J., Kullak-Ublick, G.A., Wang, J., 2020. ACS nano.14, 5268-5277.
Cennamo, N., Pasquardini, L., Arcadio, F., Lunelli, L., Vanzetti, L., Carafa, V., Altucci, L., Zeni, L.,
ot

2021. Talanta. 233.

Cao, J., Sun, T., Grattan, K.T.V., 2014. Sens. Actuators B Chem. 195, 332-351.
tn

Song, H., Zhang, H., Sun, Z., Ren, Z., Yang, X., Wang, Qi., 2019. AIP Adv. 9.
Tessaro, L., Aquino, A., Panzenhagen, P., Joshi, N., Conte-Junior, C., 2023. J. Pharm. Biomed. 222.
Lai, M., Slaughter, G., 2019. Nanomaterials. 9.
rin

Liyanage, T., Lai, M., Slaughter, G., 2021. Anal. Chim. Acta. 1169.
Lin, H., Huang, C., Lu, S., Kuo, IT., Chau, L.K., 2014. Biosens. Bioelectron. 51, 371-378.
Luo, B., Xu, Y., Wu, S., Zhao M., Jiang, P., Shi, S., Zhang, Z., Wang, Y., Wang, L., Liu, Y., 2018.
ep

Biosens. Bioelectron. 100, 169-175.

Cai, J., Ding, L.Y., Gong, P. F., Huang, J., 2020. Nanotechnology. 31.
Pr

Liyanage, T., Alharbi, B., Quan, L., Esquela-Kerscher, A., Slaughter, G., 2022. ACS omega. 7.
Joshi, G.K., McClory, P.J., Muhoberac, B.B., Kumbhar, A., Smith, K.A., Sardar, R., 2012. J. Phys.

14

This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4327579
 Chem. C. 116, 20990-21000.

ed
Liyanage, T., Sangha, A., Sardar, R., 2017. Analyst. 142, 2442-2450.
Hati, S., Langlais, S. R., Masterson A.N., Liyanage, T., Muhoberac, B.B., Kaimakliotis, H., Johnson
M., Sardar, R., 2021. Anal. Chem. 93, 13935-13944.

iew
Karakuş, E., Erdemir, E., Demirbilek, N., Liv, L., 2021. Anal. Chim. Acta. 1182.
Masterson, A.N., Muhoberac, B.B., Gopinadhan, A., Wilde, D.J., Deiss F.T., John, C.C., Sardar, R.,
2021. Anal. Chem. 93, 8754-8763.
Li D.X., He, Q., Cui, Y., Duan, L., Li, J.B., 2007. Biochem. Biophys. Res. Commun. 355, 488-493.

v
Phiri, M.M., Mulder, D.W., Mason, S., Vorster, B.C., 2019. Royal Soc. Open Sci. 6.

re
Blin, J.L., Gérardin, C., Cartere, C., Rodehüser, L., Selve, C., Stébé, M.J., 2005. Chem. Mater. 17, 1479-
1486.
Radhakumary, C., Sreenivasan, K., 2011. Anal Chem. 83, 2829-2833.
er
Zheng W.L., Han, B., E, S.Y., Sun, Y., Li, X.G., Cai, Y., Zhang, Y.N., 2020. Microchem. 157.
Joshi, G. K., Smith, K.A., Johnson, M.A., Sardar, R., 2013. J. Phys. Chem. C. 117, 26228-26237.
pe
Shi, S.H., Wang, X., Zhao, M.F., Wu, D.C., Luo, B.B., 2019. Optics and Precision Engineering. 27,
2305-2314.
ot
tn
rin
ep
Pr

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This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4327579