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Functionalized Etched Tilted Fiber Bragg Grating Aptasensor for Label-Free Protein Detection

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Functionalized Etched Tilted Fiber Bragg Grating Aptasensor for Label-Free Protein Detection Biosensors and Bioelectronics 146 (2019) 111765 Contents lists available at ScienceDirect Biosensors and Bioelectronics journal homepage: http://www.elsevier.com/locate/bios Functionalized etched tilted fiber Bragg grating aptasensor for label-free protein detection a,b,* a,1 � c Marzhan Sypabekova , Sanzhar Korganbayev , Alvaro Gonzalez-Vila� , Christophe Caucheteur c, Madina Shaimerdenova a, Takhmina Ayupova a, Aliya Bekmurzayeva a,b, Luca Vangelista d, Daniele Tosi a,b a PI National Laboratory Astana, Laboratory of Biosensors and Bioinstruments, 53 Kabanbay Batyr Avenue, 010000, Nur-Sultan, Kazakhstan b School of Engineering and Digital Sciences, Nazarbayev University, 53 Kabanbay Batyr Avenue, 010000, Nur-Sultan, Kazakhstan c Electromagnetism and Telecommunication Department, University of Mons, Boulevard Dolez 31, 7000, Mons, Belgium d School of Medicine, Nazarbayev University, 53 Kabanbay Batyr Avenue, 010000, Nur-Sultan, Kazakhstan ARTICLE INFO ABSTRACT Keywords: An aptasensor based on etched tilted fiber Bragg grating (eTFBG) is developed on a single-mode optical fiber Optical fiber targeting biomolecule detection. TFBGs were chemically etched using hydrofluoric acid (HF) to partially remove Aptasensor the fiber cladding. The sensor response was coarsely interrogated, resulting on a sensitivity increase from 1.25 Thrombin nm/RIU (refractive index unit) at the beginning of the process, up to 23.38 nm/RIU at the end of the etching, for Etching a RI range from 1.3418 to 1.4419 RIU. The proposed aptasensor showed improved RI sensitivity as compared to Detection the unetched TFBG, without requiring metal depositions on the fiber surface or polarization control during the measurements. The proposed sensor was tested for the detection of thrombin-aptamer interactions based on silane-coupling surface chemistry, with thrombin concentrations ranging from 2.5 to 40 nM. Functionalized eTFBGs provided a competitive platform for biochemical interaction measurements, showing sensitivity values ranging from 2.3 to 3.3 p.m./nM for the particular case of thrombin detection. 1. Introduction (Albert et al., 2013a; Bekmurzayeva et al., 2018; Loyez et al., 2019b; Shevchenko et al., 2011; Sun et al., 2018), cancerous cells (Jian et al., There is a growing interest in optical fiber sensors over the last de- 2019), small molecules (Allsop et al., 2019; Carrasquilla et al., 2011; Hu cades, being considered as a high-performant approach for the identi- et al., 2018) and biofilm growth (Yuan et al., 2016). fication of different analytes (McDonagh et al., 2008; Yin et al., 2018). In an optical fiber, light is confined in the core and is transmitted Optical fibers act as light transducers and serve as an excellent platform through total internal reflection with very low propagation loss. For to attach receptors and perform rapid and label-free detection of bio- biosensing applications, the fiber structure is modified in order to allow molecules (Wang and Wolfbeis, 2016). They exhibit significant advan- the interaction of light with the surrounding environment at the sensing tages over other sensing technologies, such as cost-effectiveness, small point(s). Such modifications include chemical etching (Bekmurzayeva size, flexibility, light weight, magnetic resonance compatibility or et al., 2018), tapering (Sun et al., 2018), polishing (Huang et al., 2018), remote and multiplexed detection capability (Yin et al., 2018). In bending (Gowri and Sai, 2016) and grating photo-inscription addition, optical fibers extend the possibility of performing detection in (Gonzalez-Vila� et al., 2017a). The first three methods alter the thick- non-liquid media such as gel matrices and human tissues, as well as in ness of the cladding, whilst bending and grating photo-inscription allow hard to reach environments (Ribaut et al., 2017). Fiber optic biosensors to preserve the physical integrity of the optical fiber. Depending on the have been widely studied for the detection of disease-related proteins type of application, both sensitivity and applicability need to be * Corresponding author. PI National Laboratory Astana, Laboratory of Biosensors and Bioinstruments, 53 Kabanbay Batyr Avenue, 010000, Nur-Sultan, Kazakhstan. E-mail address: [email protected] (M. Sypabekova). 1 Present Addresses: Sanzhar Korganbayev has moved to Department of Mechanical Engineering, Politecnico di Milano, 1 Via Giuseppe La Masa, 20156, Milano, Italy. https://doi.org/10.1016/j.bios.2019.111765 Received 16 August 2019; Received in revised form 1 October 2019; Accepted 3 October 2019 Available online 5 October 2019 0956-5663/© 2019 Elsevier B.V. All rights reserved. M. Sypabekova et al. Biosensors and Bioelectronics 146 (2019) 111765 considered and hence the choice of modified fiber type. Another alter- chemically etched and calibrated with different RI solutions (from native is the use of photonic crystal fibers, in which the structure of the 1.3418 to 1.4419 RIU). When coarsely interrogated, the etched tilted core allows the detection of analytes through the holes of the fiber (Rifat fiber Bragg gratings (eTFBGs) show an improved sensitivity up to 23.38 et al., 2017). nm/RIU as compared to the original TFBGs, around 1.25 nm/RIU. In biosensing, the surface of the modified fiber is usually function- Subsequently, the fiber was functionalized with thrombin aptamer, a alized with a specific type of receptor which can only bind to a certain widely used aptamer in biosensing studies, for the detection of thrombin analyte. Therefore, the interaction of light with the medium surrounding in different concentrations, resulting surface sensitivity values between the fiber depends on the biochemical reaction taking place on the fiber 2.3 and 3.3 p.m./nM. surface. In order to enhance the response in the form of refractive index (RI) change, absorption or conductivity, the fiber surface is usually 2. Material and methods covered with functional materials such as gold nanofilms (Caucheteur et al., 2016), nanoparticles (Lepinay et al., 2014), carbon nanotubes 2.1. Chemicals (Parveen et al., 2017), graphene (Chiu et al., 2017), metal oxides (L Coelho et al., 2016)and polymers (Yin et al., 2016). Receptors such as (3-Aminopropyl)triethoxysilane (APTES), glutaraldehyde, aptamers and antibodies are usually immobilized on the functional phosphate-buffered saline (PBS), thrombin protein, hydrogen peroxide material on the surface of the fiber and altogether allow to sense bio- (H2O2), hydrofluoric acid (HF) and sulfuric acid (H2SO4) were pur- molecules down to pM level (Ribaut et al., 2016). chased from Sigma Aldrich (Darmstadt, Germany). D-Sucrose, sodium Amongst modified fibers, grating-based optical fiber sensors such as dodecyl sulfate (SDS) and bovine serum albumin were obtained from tilted fiber Bragg gratings (TFBGs) have been extensively studied for Thermo Fisher Scientific (Runcorn, UK). Absolute ethanol was pur- biomolecule detection. TFBG sensors provide simple and robust plat- chased from Aidabul Distillery (Kokshetau, Kazakhstan). Amine- 0 forms for bioreceptor attachment and consequent detection. They have modified thrombin binding aptamer (5 -AmC6-TTTTT-AGTCCGTGG- been effectively applied to a wide range of target analytes (Loyez et al., TAGGGCAGGTTGGGGTGACT-30) was synthesized by Sigma Aldrich. 2019b, 2019a; 2018; Zhou et al., 2019). The sensing mechanism used in All aqueous solutions were prepared using 18.2 MΩcm ultra-pure water TFBG fiber-optic biosensors is based on the excitation of with a Pyrogard filter (Millipore, UK). Protein solutions were prepared forward-propagating cladding modes able to reach the interface be- freshly each time in 10 mM PBS at pH 7.4. tween the cladding and the outer medium. These modes are sensitive to RI changes in the medium surrounding the optical fiber and their optical 2.2. TFBG photo-inscription response consists of a simultaneous wavelength shift and amplitude � variation (Gonzalez-Vila� et al., 2017b). In several published works, 1 cm long 10 TFBGs were photo-inscribed in the core of a hydrogen- TFBG fiber-optic biosensors profit from the surface plasmon resonance loaded photosensitive single-mode optical fiber (PS-1250 from Fiber- (SPR) phenomenon to enhance their bulk sensitivity (Chiavaioli et al., core UK) using the phase-mask technique (Hill et al., 1993). The 2017) through the use of a thin-film metal coating (Loyez et al., 2019c). photo-inscription setup consisted in an excimer ArF laser emitting at The generation of metal nanoparticles has also been exploited, requiring 193 nm, being part of a Noria FBG Manufacturing System (NorthLab important parameter management including the size and the shape of Photonics) and a custom phase-mask providing a tilted holographic the particles (Shao et al., 2011). Therefore, with the advances in surface pattern with a pitch of 1078 nm. The laser energy was set to 5 mJ and the chemistry research, the use of non-plasmonic functionalized TFBGs be- repetition rate to 50 Hz, requiring 3 bursts of 7500 pulses for each TFBG. comes an interesting approach as well for biodetection purposes (Bek- TFBGs fabricated following this procedure exhibit a broad range of murzayeva et al., 2018). Indeed, recent studies showed the feasibility of cladding mode resonances, being suitable to be used both in aqueous using non-metallic coated surfaces for the covalent immobilization of and gaseous media (Gonzalez-Vila� et al., 2018). the bioreceptors with high quality factor of the spectrum resonances (Loyez et al., 2018), bypassing
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