Label-free fiber-optic spherical tip biosensor to enable picomolar-level detection of CD44 protein

Abstract

Increased level of CD44 protein in serum is observed in several cancers and is associated with tumor burden and metastasis. Current clinically used detection methods of this protein are time-consuming and use labeled reagents for analysis. Therefore exploring new label-free and fast methods for its quantification including its detection in situ is of importance. This study reports the first optical fiber biosensor for CD44 protein detection, based on a spherical fiber optic tip device. The sensor is easily fabricated from an inexpensive material (single-mode fiber widely used in telecommunication) in a fast and robust manner through a CO2 laser splicer. The fabricated sensor responded to refractive index change with a sensitivity of 95.76 dB/RIU. The spherical tip was further functionalized with anti-CD44 antibodies to develop a biosensor and each step of functionalization was verified by an atomic force microscope. The biosensor detected a target of interest with an achieved limit of detection of 17 pM with only minor signal change to two control proteins. Most importantly, concentrations tested in this work are very broad and are within the clinically relevant concentration range. Moreover, the configuration of the proposed biosensor allows its potential incorporation into an in situ system for quantitative detection of this biomarker in a clinical setting.

Cost-Effective Fiber Optic Solutions for Biosensing

“…In a recent work from Bekmurzayeva et al [ 131 ], a spherical fiber optic tip fabricated using a CO 2 laser splicer was investigated. The fiber surface was pre-treated with (3-aminopropyl)trimethoxysilane (APTMS), following several steps to functionalize it with anti-CD44 antibodies, as shown in Figure 13 , aiming to detect various levels of CD44.…”

“… Schematic of functionalization of spherical tip-biosensor used for detection of CD44 biomarker (image reproduced from [ 131 ]). …”

Perspectives on Assembling Coronavirus Spikes on Fiber Optics to Reveal Broadly Recognizing Antibodies and Generate a Universal Coronavirus Detector

“…Nevertheless, such resonators show ellipticity of <0.5%, and enhanced sensitivity to the RI change in the range of 257.3-1,112.5 nm/ RIU with diameter of 466-624 μm fabricated with a CO2 laser splicer (Shaimerdenova et al, 2020). Ball-resonators have been used for the detection of thrombin and CD44 with a detection limit at pM level (Ayupova et al, 2021;Bekmurzayeva et al, 2021).…”

Biofilm Detection by a Fiber-Tip Ball Resonator Optical Fiber Sensor

“…In comparison to LPG and TFBG sensors, BR sensors have additional properties that make them more suitable for this application. First, BR sensors are much faster and cheaper than any grating, since they can be fabricated using CO 2 laser splicer adapting methods used in whispering gallery mode resonators [ 21 , 22 , 23 ] or the microbubble resonators [ 24 ] manufacturing of single-mode telecom fibers [ 25 ]. In addition, BR sensors work as reflective units, with a quasi-random spectrum formed by shallow polarization-sensitive fringes that resemble a Fresnel probe, and can be interrogated either by measuring the intensity change or the wavelength shift of a spectral peak [ 25 , 26 ].…”

“…First, BR sensors are much faster and cheaper than any grating, since they can be fabricated using CO 2 laser splicer adapting methods used in whispering gallery mode resonators [ 21 , 22 , 23 ] or the microbubble resonators [ 24 ] manufacturing of single-mode telecom fibers [ 25 ]. In addition, BR sensors work as reflective units, with a quasi-random spectrum formed by shallow polarization-sensitive fringes that resemble a Fresnel probe, and can be interrogated either by measuring the intensity change or the wavelength shift of a spectral peak [ 25 , 26 ]. Due to a very low reflectivity, the interrogation of a BR sensor can be performed with an optical backscatter reflectometer (OBR).…”