Taper biosensor in fiber ring laser cavity for protein detection

Taper biosensor in fiber ring laser cavity for protein detection

Optics and Laser Technology 125 (2020) 106033 Contents lists available at ScienceDirect Optics and Laser Technology journal homepage: www.elsevier.c...

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Optics and Laser Technology 125 (2020) 106033

Contents lists available at ScienceDirect

Optics and Laser Technology journal homepage: www.elsevier.com/locate/optlastec

Taper biosensor in fiber ring laser cavity for protein detection a

a,⁎

b

c

T a

M. Mansor , M.H. Abu Bakar , M.F. Omar , Y. Mustapha Kamil , N.H. Zainol Abidin , F.H. Mustafad, M.A. Mahdia a

Wireless and Photonic Networks Research Centre, Faculty of Engineering, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia Scientific Computing and Instrumentation (SCnl) Research Group, Physics Department, Faculty of Science, Universiti Teknologi Malaysia, 81310 Skudai, Johor, Malaysia inLAZER DYNAMICS SDN BHD, InnoHub Unit, Putra Science Park, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia d Institute for Research in Molecular Medicine, Universiti Sains Malaysia Kubang Kerian, 16150 Kota Bharu, Kelantan, Malaysia b c

H I GH L IG H T S

tapered fiber biosensor integrated in ring-cavity fiber laser. • Functionalized wavelength lasing output generated from optimized taper dimension. • Single linear quantitative response with high specificity towards target protein. • Highly • Higher gain yielded better sensitivity due to enhanced evanescent wave interaction.

A R T I C LE I N FO

A B S T R A C T

Keywords: Biosensor Optical fiber sensor Fiber laser Tapered optical fiber

This paper demonstrates the integration of a bio-functionalized tapered fiber sensor in a fiber laser cavity for sensing of biological molecules. Interferometric effect from the taper generated single wavelength lasing output that was spatially measured to detect any changes. The sensing performance of the integrated system was assessed by immersing the biosensor in various concentrations of avidin ranging from 1 to 10 pM at laser threshold (40 mW) and at the maximum pump power of 200 mW. Selectivity of the sensor was ensured by immobilizing biotin on the surface of the tapered region that would act as complementary molecules to avidin. The proposed setup obtained sensitivity values of 0.40 nm/pM and 1.02 nm/pM at pump power of 40 mW and 200 mW, respectively. The integrated system simplifies the sensing output and analysis without compromising the performance of tapered optical fiber-based biosensor.

1. Introduction

attained good sensitivity of 2526.8 nm/RIU and 20.368 nm/μM [5]. The sensor was also selective towards avidin and this was achieved by immobilizing a layer of biotin on the surface of the tapered region as bio-complementary molecules. This concept was applied in the development of a dengue sensor reported in [6], where anti-Dengue antibodies were immobilized to detect dengue antigens. The same authors extended the work further by introducing graphene oxide to further enhance the sensitivity of the sensor [7]. Aside from dengue, the detection of leptospirosis DNA has also been reported [8]. Here, probe DNA was immobilized onto the tapered region and subsequently hybridized with its complementary DNA (cDNA). Surface plasmon resonance (SPR) approach with tapered probe was also explored through modeling of single sensing layer on three different taper profiles [9]. Another method utilized localized SPR effect from immobilized gold nanoparticles on the tapered fiber surface [10]. Nevertheless, despite

For the past decade, the development of biosensors based on tapered optical fibers has shown promising results with high sensitivity and specificity [1–4]. Fiber tapering refers to the process of pulling a fiber while heating, such that the overall diameter of the fiber at the tapered region is less than the original diameter. Due to the tapering of the fiber, part of the propagating light is guided outside of the fiber, inducing evanescent field. The evanescent field extends into the surrounding medium and is highly sensitive to any changes in the refractive index within the vicinity of the tapered optical fiber, making it suitable to be used as a sensor. Biosensor utilizing single mode tapered fiber has attracted great attention from researchers. Among the reported studies using singlemode tapered fiber biosensor was the detection of avidin which



Corresponding author. E-mail address: [email protected] (M.H. Abu Bakar).

https://doi.org/10.1016/j.optlastec.2019.106033 Received 25 September 2019; Received in revised form 25 November 2019; Accepted 23 December 2019 Available online 06 January 2020 0030-3992/ © 2019 Elsevier Ltd. All rights reserved.

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Fig. 1. Schematic of a tapered optical fiber.

transducer was integrated in a ring cavity erbium-doped fiber (EDF) laser and subsequently yielded a single wavelength output. The singlewavelength-based detection offers a simplified analysis and a more practical output translation of the results without diminishing the many qualities of the tapered fiber sensor.

Table 1 Taper profiles with their corresponding properties. Tapered Fiber

Waist Diameter (µm)

Waist Length (mm)

FSR (nm)

A B C D E F G H I

9 9 9 12 12 12 15 15 15

10 15 20 10 15 20 10 15 20

9 4 3 13 8 6 20 14 7

2. Methods and results 2.1. Optimized fabrication of tapered optical fiber Fig. 1 depicts the typical profile of a tapered fiber. The tapered fiber can be divided into three regions; down taper, waist, and up-taper. To realize an intracavity tapered fiber-based sensor, it is important to design a tapered fiber with non-adiabatic characteristics, which is crucial in order to induce strong interferometric effect. The interferometric effect within the tapered fiber consequently produces a comb-like spectrum due to the interference between core and cladding modes. Any changes in the surrounding medium will affect the modes and result in a wavelength shift in the transmission spectrum that can be easily observed and quantified [14]. Therefore, non-adiabatic tapered fibers with 9 different parameters were fabricated and analyzed to determine the optimum taper design. The tapering process was performed using Vytran’s GPX-3400 Optical Glass Processing Workstation. The machine is capable of performing precise fusion splicing and tapering with its filament furnace assembly and precision stages. Its real-time control system allows manipulation of dimensions, uniformity and reproducibility of the fabricated taper as the pulling speed and heat are kept at a constant value of 1 mm/s and 42 W, respectively. Table 1 tabulates the taper profiles tested and their corresponding value of free spectral range (FSR). The FSR for each taper was obtained by connecting one end of the tapered fiber to a broadband C + L band light source (Amonics ALS 18-B-FA) via a single mode pigtail while the other end of the tapered optical fiber was coupled to a Yokogawa AQ6331 optical spectrum analyzer (OSA) through another single mode pigtail. It can be observed that larger waist diameter and longer waist length correlate with greater FSR. The different taper profiles were then integrated within a fiber laser cavity to observe their wavelength selection capability with the influence of laser gain. The optimized taper profile should be able to produce a single lasing wavelength with the least mode competition to minimize the possibility of multiwavelength output. The fiber laser configuration was constructed as shown in Fig. 2. A 200 mW 980 nm laser diode pumped light into the ring cavity via a 980/1550 nm wavelength division multiplexer (WDM). A 0.5 m EDF was used as the gain medium which was then connected to a 90/10 power coupler, where the light was divided into two parts with 90% of the light continuously oscillating in the ring cavity while the remaining 10% output was

Fig. 2. Experimental setup for fiber laser intracavity sensor system.

the strong sensing performance of taper biosensor, it has yet to be considered as a practical solution for real world applications. One of the reasons is the difficulty in analyzing the multi-fringe optical spectrum that is prone to misinterpretation. One possible approach to simplify the operation of tapered fiber sensors is to integrate the sensor transducer within a laser structure. The interferometric effect in tapered optical fiber transducer leads to the selection of wavelength in laser structure which generates a single wavelength output. This approach simplifies the spectral assessment, yields high signal-to-noise ratio measurements, and makes a more portable system feasible as the sensor is integrated within the source of excitation itself. Examples of such integration include the deployment of single mode-multimode-single mode (SMS) fiber structure [11,12]. Another study reported the use of dual-taper transducer as a temperature sensor which attained sensitivity of 1089.4 pm/°C [13]. In this work, an all-fiber laser intracavity taper biosensor is presented. The bio-functionalized tapered fiber, which acted as the sensing 2

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Fig. 3. The spectral output of the fiber laser with intracavity taper dimensions of (a) 9 µm waist diameters, (b) 12 µm waist diameter, and (c) 15 µm waist diameters with varied waist lengths (10 mm, 15 mm, 20 mm) at a pump power of 200 mW.

To determine the best taper profile out of the two, measurement of refractive indices by the intracavity tapered fiber was performed via salinity test. Sodium chloride (NaCl) solutions with concentration ranging from 0.1 to 1.0 M were prepared by dissolving powdered NaCl in deionized water. The refractive indices of these solutions were tested with a pocket refractometer (ATAGO-PAL), which gave readings within the range of 1.3324–1.3389. Afterwards, the intracavity tapered fiber was fully immersed in the series of NaCl solution and the output spectrum after each immersion was recorded. As shown in Fig. 4, the output spectra shifted when compared to the spectrum taken before NaCl was introduced. This occurred due to the increment of refractive index in the external surrounding that creates a phase shift (Δφ ) in the propagating light. Δφ can be calculated using [5]:

connected to either a Yokogawa AQ6370 OSA or Thorlab’s PM100D optical power meter (OPM) to monitor the output spectrum and observe the optical power. To ensure a unidirectional light propagation and minimize back-reflection, optical isolators were introduced after the EDF and before the measuring equipment. Point ‘X’ in Fig. 2 denotes the insertion point of the tapered fiber sensing transducer. Fig. 3 exhibits the lasing output with the integration of different taper profiles. For tapers with small FSR, the presence of multiple modes within the peak gain region led to either multiple lasing wavelengths or prominent side modes that could manifest multiple lasing output during the sensing process. Tapers with larger FSR (G and H) were more successful at producing single wavelength laser with suppressed sidebands as the side modes were located farther from the peak gain region. Hence, the two profiles were considered as the best taper dimension to achieve the desired single wavelength output thus making them suitable for further assessments.

Δφ = 3

[2π (Δneff ) L] λ

(1)

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where Δneff is the difference between the effective refractive index (RI) co ) and the effective refractive index of the external surof the core (neff ext rounding (neff ). L is the waist length of the tapered fiber and λ is the wavelength. The equation mathematically supports the idea that any manipulation of RI at the external surrounding or the cladding would affect the phase shift at a specific wavelength. Unfortunately, preliminary test of taper profile H using 0.3 M NaCl produced a dual wavelength laser as the net gain profile allowed multiple longitudinal modes to lase. On the other hand, for taper profile G, the lasing peak consistently shifted to the right with no multi wavelength lasing produced when tapered fiber was introduced to NaCl from 0.1 M up to 0.9 M, as shown in Fig. 4(b). This suggests that taper profile G has better stability to maintain a single wavelength laser in the measurement of refractive indices. As a sideband was produced at 1.0 M, the concentration is considered to be beyond the operating capability of this biosensor. 2.2. Fabrication and characterization of tapered fiber biosensor For this work, the biotin-avidin complex was chosen to simulate the typical immunoassay reaction due to its strong affinity towards each other. First, the surface of the tapered fibers was modified by treating them with concentrated Sodium hydroxide (NaOH) to enhance the attachment of hydroxyl groups (eOH) onto the tapered surface [6]. The hydroxyl groups are important to allow covalent attachment of biotin compound onto the tapered fiber. NaOH of 0.1 M was prepared by diluting 0.04 g of powdered form NaOH (Sigma Aldrich) in 10 ml of deionized water. The treatment was initiated by immersing the tapered fiber in NaOH for 22 min. Once completed, the solution was drained and the tapered fiber was rinsed three times with deionized water followed by a drying process at room temperature. Next, the tapered optical fiber was incubated for 18 min with a silane-PEG-biotin solution where the solution was prepared by dissolving silane-PEG-biotin powder in a mixture of ethanol and deionized water (w/w, 95%/5%) to a concentration of 2 µM. This process is known as the silanization process which immobilizes biotin on the tapered surface, therefore creating a new layer of cladding [5]. This new cladding would be responsible for the detection of the targeted proteins, avidin. After 18 min, the tapered optical fiber was rinsed 3 times with deionized water and left to dry at room temperature. Fig. 5(a) and (b) are FESEM images and Raman spectroscopy characterization obtained after the immobilization of biotin. The image in Fig. 5(a) shows that the surface of the tapered optical fiber has been covered with globular structures after treatment with silane-PEG-biotin. The spectrum in Fig. 5(b) exhibits strong peaks at 495 cm−1 and 1040 cm−1, both of which are assigned to SieOeSi and SieO vibrational modes respectively [15]. This indicates the formation of covalent bonds between the silane agent and hydroxylated tapered optical fiber surface. Another weak peak is shown at 695 cm−1 which represents the presence of biotin [16]. Furthermore, the band peaks at 1434 cm−1 and 1560 cm−1 that are assigned to SieCH2 and NH2 deformation vibrational modes were observed as well [17].

Fig. 4. Laser output spectrum with intracavity tapered fiber sensor of (a) H and (b) G when introduced to NaCl of varying concentration.

2.3. Detection of avidin using fiber laser intracavity taper biosensor To assess the minimum laser threshold for the biosensor to operate, the all-fiber intracavity sensor was tested at different laser pump power within the range of 10 to 200 mW. Threshold was obtained at 30 mW with a calculated slope efficiency of 1.29%, as shown in Fig. 6. Therefore, the detection of avidin was performed at 40 mW and at the maximum pump power of 200 mW to assess the impact of gain condition towards the sensing performance. Prior to the detection of avidin, stock solution was prepared by dissolving powdered form avidin in a phosphate buffer solution (PBS) to a concentration of 10 µM. The incubation time of the functionalized tapered fiber in avidin solution of different concentrations ranging from

Fig. 5. Characterization of (a) FESEM taken at 150 kV and 50 K magnification and (b) Raman spectrum of tapered fiber biosensor after introduction to biotin.

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1 to 10 pM was 41 min. For each concentration, a new set of the functionalized tapered optical fiber was used. Following the avidin immersion process, the tapered fiber was rinsed and dried to remove any residual solution before the output spectrum was observed and recorded on the OSA. Fig. 7 shows the output spectra with a variation of avidin concentration at 40 mW and 200 mW pump power. The detection of the avidin protein is expected to manifest a single laser peak shifts in the optical spectrum acquired via OSA. Fig. 7(a) exhibits consistent shift at 40 mW pump power with no multi wavelength lasing observed as the concentration was increased. The same observation was made at 200 mW pump power in Fig. 7(b) as the wavelength shifts are consistent with the increment of concentration with only a single lasing wavelength throughout the detection range. The laser linewidth is narrower here due to the higher population inversion in the laser system [18]. Fig. 7(c) shows the relationship of wavelength shift with the concentration of avidin for both pump power of 40 mW and 200 mW. The corresponding wavelength shifts demonstrated lower sensitivity value of 0.40 nm/pM and lower R2 of 0.9777 at 40 mW pump power compared to the performance of the sensor at 200 mW pump power with sensitivity and R2 values of 1.02 nm/pM and 0.9879, respectively. The sensitivity value deteriorated with low pump power as the lower evanescent field intensity led to weakened interaction with external changes [19]. The narrower gain bandwidth at low pump power could also play a role as the peak net gain might not be at the peak of a fringe thus resulting in smaller observable shift [20]. In both cases however, the sensitivity and pM detection capability of the sensor have exceeded the performance of prior optical transducers working on the same protein [5,21–23]. Error bars in Fig. 7(c) represent standard deviation (SD ± ) of experimental triplicates. Low average SD ± values of 0.14 nm and 0.29 nm were obtained for 40 mW and 200 mW pump powers respectively, denoting minimal variation within the system which further strengthens the reproducibility of the sensor. The characterization of the tapered optical fiber was continued with FESEM imaging after the introduction of avidin. Fig. 8(a) shows globular structures representing proteins attached to the tapered fiber surface. However, it is not possible to distinguish whether it is biotin or avidin via FESEM as both compounds exhibit similar protein structures. The Raman spectroscopy characterization in Fig. 8(b) shows band peaks at 480 cm−1 and 495 cm−1 which are believed to be associated with the normal vibration frequencies of Si-Si bonds found in silica glass, which is the bulk material of the tapered optical fiber [24]. Peak bands at wavelengths 610 cm−1 and 805 cm−1 have also been noted to arise from the Si-Si matric [25]. On the other hand, the prominent peaks observed at 1340 cm−1 and 1636 cm−1 signifies the presence of avidin [26].

Fig. 6. Laser output power with respect to pump power with intracavity fully bio-functionalized tapered optical fiber.

2.4. Specificity of intracavity tapered fiber biosensor To assess the selectivity of the sensor, the bio-functionalized tapered optical fiber was also tested with Bovine Serum Albumin (BSA) at a concentration of 10 pM as a negative control. BSA was chosen as it has similar molecular size to avidin and would affect the refractive index similarly. The output spectrum was then compared to spectra obtained before and after the introduction of avidin. Fig. 9 depicts a shift of 10.8 nm to the right which is attributed to the attachment of avidin onto the tapered fiber biosensor. On the other hand, no significant shift was observed when the sensor was introduced to BSA. Such an observation was expected as BSA has no affinity towards the immobilized biotin thus the rinsing process removed the presence of BSA resulting in no wavelength shift.

Fig. 7. Output spectra with a variation of avidin concentration (a) at 40 mW pump power and (b) at 200 mW pump power. (c) Trend line depicting the relationship of wavelength shift to the concentration of avidin.

3. Conclusion In conclusion, we have demonstrated the feasibility of all-fiber laser 5

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Writing - original draft. N.H. Zainol Abidin: Writing - original draft. F.H. Mustafa: Resources, Writing - review & editing. M.A. Mahdi: Conceptualization, Supervision, Funding acquisition. Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Acknowledgements This work was supported by Ministry of Education Malaysia through Fundamental Research Grant Scheme #FRGS/1/2016/TK04/UPM/02/ 4 as well as Universiti Putra Malaysia through Geran Putra Berimpak #UPM/800-3/3/1/GPB/2019/9671800 and Graduate Research Fellowship Scheme. References [1] M. Bosch, A. Sánchez, F. Rojas, C. Ojeda, Recent development in optical fiber biosensors, Sensors 7 (6) (2007) 797–859. [2] Y. Huang, Z. Tian, L.-P. Sun, D. Sun, J. Li, Y. Ran, B.-O. Guan, High-sensitivity DNA biosensor based on optical fiber taper interferometer coated with conjugated polymer tentacle, Opt. Express 23 (21) (2015) 26962. [3] J. Miller, A. Castaneda, K. Lee, M. Sanchez, A. Ortiz, E. Almaz, Z. Almaz, S. Murinda, W.-J. Lin, E. Salik, Biconically tapered fiber optic probes for rapid labelfree immunoassays, Biosensors 5 (2) (2015) 158–171. [4] H. Latifi, M.I. Zibaii, S.M. Hosseini, P. Jorge, Nonadiabatic tapered optical fiber for biosensor applications, Photon. Sensors 2 (4) (2012) 340–356. [5] Y.M. Kamil, M.H.A. Bakar, M.A. Mustapa, M.H. Yaacob, A. Syahir, M.A. Mahdi, Sensitive and specific protein sensing using single-mode tapered fiber immobilized with biorecognition molecules, IEEE Photon. J. 7 (6) (2015) 1–9. [6] Y.M. Kamil, M.A. Bakar, M. Mustapa, M. Yaacob, N. Abidin, A. Syahir, H. Lee, M. Mahdi, Label-free Dengue E protein detection using a functionalized tapered optical fiber sensor, Sens. Actuators B 257 (2018) 820–828. [7] Y.M. Kamil, I.S.L.A. Hamid, M.H.A. Bakar, A.A. Manaf, M.H. Yaacob, A. Syahir, M. A. Mahdi, Micro-fluidic based fiber optic sensor for the detection of DENV II E proteins, Adv. Photon. 2018 (BGPP, IPR, NP, NOMA, Sensors, Networks, SPPCom, SOF), (2018). [8] N.H. Zainuddin, H.Y. Chee, M.Z. Ahmad, M.A. Mahdi, M.H.A. Bakar, M.H. Yaacob, Sensitive Leptospira DNA detection using tapered optical fiber sensor, J. Biophoton. 11 (8) (2018). [9] R. Verma, B. Gupta, Surface Plasmon resonance based tapered fiber optic sensor with different taper profiles, 2009 14th OptoElectronics and Communications Conference, (2009). [10] H.-Y. Lin, C.-H. Huang, G.-L. Cheng, N.-K. Chen, H.-C. Chui, Tapered optical fiber sensor based on localized surface plasmon resonance, Opt. Express 20 (19) (2012) 21693. [11] Y.-N. Zhang, L. Zhang, B. Han, H. Peng, T. Zhou, R.-Q. Lv, Erbium-doped fiber ring laser with SMS modal interferometer for hydrogen sensing, Opt. Laser Technol. 102 (2018) 262–267. [12] R. Oe, S. Taue, T. Minamikawa, K. Nagai, K. Shibuya, T. Mizuno, M. Yamagiwa, Y. Mizutani, H. Yamamoto, T. Iwata, H. Fukano, Y. Nakajima, K. Minoshima, T. Yasui, Refractive-index-sensing optical comb based on photonic radio-frequency conversion with intracavity multi-mode interference fiber sensor, Opt. Express 26 (15) (2018) 19694. [13] A. Martinez-Rios, G. Anzueto-Sanchaz, R. Selvas-Aguilar, A. Alberto Castillo Guzman, D. Toral-Acosta, V. Guzman-Ramos, V.M. Duran-Ramirez, J.A. GuerreroViramontes, C.A. Calles-Arriaga, High sensitivity fiber laser temperature sensor, IEEE Sensor J. 15(4), 2399–2402 (2015). [14] K.Q. Kieu, M. Mansuripur, Biconical Fiber Taper Sensors, IEEE Photon. Technol. Lett. 18 (21) (2006) 2239–2241. [15] M. Gynba, M. Keranen, M. Kozanecki, B.B. Kosmowski, Raman investigation of hybrid polymer thin films, Mater. Science-Poland 23 (1) (2005). [16] C. Fagnano, G. Fini, A. Torreggiani, Raman spectroscopic study of the avidin-biotin complex, J. Raman Spectrosc. 26 (11) (1995) 991–995. [17] Y. Sun, M. Yanagisawa, M. Kunimoto, M. Nakamura, T. Homma, Estimated phase transition and melting temperature of APTES self-assembled monolayer using surface-enhanced anti-stokes and stokes Raman scattering, Appl. Surf. Sci. 363 (2016) 572–577. [18] P.C. Becker, N.A. Olsson, J.R. Simpson, Erbium-doped Fiber Amplifiers Fundamentals and Technology, Academic Press, San Diego, 1999. [19] Evanescent Field Penetration Depth. The Physics of Light and Color -Diffraction of Light. [Online]. Available: https://www.olympuslifescience.com/en/microscoperesource/primer/java/tirf/penetration/. (Accessed: 30-Jan-2019). [20] G. Gao, H. Zhang, D. Deng, D. Geng, L. He, D. Li, M. Gong, Gain effect and amplification characteristics analysis in fiber chirped pulse amplification systems, J. Opt. 20 (7) (2018) 075501. [21] K. De Vos, I. Bartolozzi, E. Schacht, P. Bienstman, R. Baets, Silicon-on-Insulator

Fig. 8. Characterization of (a) FESEM taken at 150 kV and 50 K magnification and (b) Raman spectrum of tapered fiber biosensor after introduction to avidin.

Fig. 9. Comparison between the output spectrum of before and after the introduction of avidin and negative control using BSA.

intracavity taper biosensor. The proposed laser sensor was tested at different gain conditions with the pump power set at 40 mW and 200 mW. At 40 mW, the sensitivity obtained was at 0.40 ± 0.14 nm/ pM whilst 1.02 ± 0.29 nm/pM was obtained at 200 mW. Apart from the higher sensitivity, high pump power also produces cleaner spectral output with high signal-to-noise ratio. The realization of a properly packaged all-fiber laser intracavity taper biosensor can simplify the analysis, translating the results in a single-wavelength manner that is more practical without compromising the many qualities of this technology. CRediT authorship contribution statement M. Mansor: Investigation, Writing - original draft. M.H. Abu Bakar: Conceptualization, Methodology, Funding acquisition. M.F. Omar: Writing - review & editing. Y. Mustapha Kamil: Validation, 6

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