Fiber Optic Biosensor Research Articles

Fabrication and diameter analysis of a single-ended SMF tip structure.

Optical fiber technology combined with surface plasmon resonance enables rapid, precise detection of chemical, biochemical, and biological parameters. Many hybrid optical fiber structures have been suggested in recent decades to increase the sensitivity of optical fiber biosensors. In this work, an optical fiber tip structure is fabricated on single-mode fiber (SMF) by etching in a hydrofluoric acid (40%) solution at room temperature. The proposed method of tip formation utilizing wet etching is efficient for fabricating the highly sensitive fiber structures that are required for the development of optical fiber-based biosensors. The diameter measurement of fabricated fiber tip formation is done using a compound microscope.

Synthesis and characterization of gold nanoparticles and graphene oxide for the development of optical fiber biosensors.

Optical fiber technology, in association with the phenomenon of surface plasmon resonance (SPR), has opened a new gateway for quick, easier, and accurate sensing of various chemical, biochemical, and biological parameters. Continuous efforts can be seen in the direction of increasing the sensitivity of the optical fiber biosensors; thus, many hybrid nanostructured optical fiber biosensors composing different nanomaterials, nanomaterial combinations, and different 2D materials have been proposed in the past few decades. This paper discusses the synthesis, characterization, and applications of nanoparticles to the most favorable noble metal for SPR biosensing, i.e., gold. The gold nanoparticles (AuNPs) were prepared by the Turkevich method, and the optical property of AuNPs was characterized using the UV-visible spectrophotometer and transmission electron microscopy (TEM) technique. In addition, the synthesis, characterization, and application of the oxide form the most explored 2D material, i.e., graphene, are also presented in this paper. The graphene oxide was synthesized using an easier and economical method, i.e., a modified Hummer's method, and an evaluation of the characteristics has been done by a UV-visible spectrophotometer and TEM results.

Plasmonic fiber optic biosensors with barium titanate and titanium dioxide thin films

In this paper, two structures of surface plasmon resonance fiber optic biosensors with the addition of a thin layer of titanium dioxide and barium titanate are introduced and studied comparatively. The sensitivity of these biosensors has been calculated using the transfer matrix method. Adding a thin layer of barium titanate and titanium dioxide after the gold layer, both make increase the sensitivity of the biosensor due to the transfer of free charge between the gold and the dielectric. The obtained results of the comparative study show that the titanium dioxide layer can be a suitable alternative to barium titanate for further increase of the sensitivity of the fiber optic surface plasmon resonance biosensor.

Minimalistic design and rapid-fabrication single-mode fiber biosensors: Review and perspectives

Optical fiber biosensors are receiving significant interest, as they allow real-time, low-limit, and high precision detection of biological analytes such as biomarkers, proteins, and small cells. Classical biosensor designs include gratings, interferometers, and plasmonic structures; however, these systems require a complex design, hard to manufacture on high volumes. Recently, several biosensors having a minimalistic design, rapid and suitable to be automated, have been proposed; the key asset is the scalability potential, in view of fabricating numerous devices for disposable use or for large parallel immunoassays. This new sensor class features reflector-less sensors, shallow tapers, and ball resonators; a pseudo-random spectrum characterizes all these biosensors. In this paper, we provide a bird-eye view of these minimalistic designs and a perspective of their use in advanced biosensing applications.

Versatile selective absorption-based optical fiber toward epinephrine detection

A versatile lossy mode resonance (LMR) sensor is developed for Epinephrine monitoring based on the state-of-the-art molecular imprinting technique over an optical fiber. The optical absorption concept of the LMR-based sensor is proven by incorporating an amino silane-functionalized graphene oxide (SiO2-NH2@GO) as an adhesive layer for grafting Epinephrine imprinting polydopamine (Ep-IPDA) as a sensing layer onto the optical fiber curved surface. The accurate structural and morphological characterization confirmed the rough crystalline and spherical particles for Ep-IPDA and SiO2-NH2-GO onto optical fiber curved surface, while spectroscopic analysis confirms the formation of imprinting polymer and desirable absorbance characteristics. The optimized probe exhibits an excellent performance with the maximum sensitivity within two intervals of 0.3–1 µM and 1–90 µM along with the linearity coefficient of R2 = 0.99 possessing a low limit of detection of 0.07 µM. Additionally, this sensor selectively detects Ep in the presence of other species and showed good recovery in human urine and injection samples. This work opens a new avenue for developing bio-inspired LMR-based optical fiber biosensors and could be further extended to detect other catecholamine neurotransmitters.

Cost-Effective Fiber Optic Solutions for Biosensing.

In the last years, optical fiber sensors have proven to be a reliable and versatile biosensing tool. Optical fiber biosensors (OFBs) are analytical devices that use optical fibers as transducers, with the advantages of being easily coated and biofunctionalized, allowing the monitorization of all functionalization and detection in real-time, as well as being small in size and geometrically flexible, thus allowing device miniaturization and portability for point-of-care (POC) testing. Knowing the potential of such biosensing tools, this paper reviews the reported OFBs which are, at the moment, the most cost-effective. Different fiber configurations are highlighted, namely, end-face reflected, unclad, D- and U-shaped, tips, ball resonators, tapered, light-diffusing, and specialty fibers. Packaging techniques to enhance OFBs’ application in the medical field, namely for implementing in subcutaneous, percutaneous, and endoscopic operations as well as in wearable structures, are presented and discussed. Interrogation approaches of OFBs using smartphones’ hardware are a great way to obtain cost-effective sensing approaches. In this review paper, different architectures of such interrogation methods and their respective applications are presented. Finally, the application of OFBs in monitoring three crucial fields of human life and wellbeing are reported: detection of cancer biomarkers, detection of cardiovascular biomarkers, and environmental monitoring.

Design of an unclad single-mode fiber-optic biosensor based on localized surface plasmon resonance by using COMSOL Multiphysics 5.1 finite element method.

This study proposed an unclad optical fiber biosensor based on the localized surface plasmon resonance phenomenon and operating at 650 nm using COMSOL Multiphysics 5.1 finite element method (FEM). Gold nanoparticles (50 nm thickness) were coated on the middle portion of the unclad fiber. Air, water, blood plasma, liver tissue, colon tissue, and pentanol (C5H11OH) were used as analytical layers with 3 µm. The sensor serves as a theoretical foundation for experimental research. The blood plasma had the highest sensitivity with a sensitivity of 10,638.297 nm/RIU and a resolution of 9.410-6RIU. The proposed sensor is a promising candidate for a low-cost, simple-geometry biochemical sensing solution.

Quantitative and amplification-free detection of SOCS-1 CpG methylation percentage analyses in gastric cancer by fiber optic nanoplasmonic biosensor

A new innovative approach is essential for early and effective diagnosis of gastric cancer, using promoter hypermethylation of the tumor suppressor, SOCS-1, that is frequently inactivated in human cancers. We have developed an amplification-free fiber optic nanoplasmonic biosensor for detecting DNA methylation of the SOCS-1 human genome. The method is based on the fiber optic nanogold-linked sorbent assay of PCR-free DNA from human gastric tumor tissue and cell lines. We designed a specific DNA probe fabricated on the fiber core surface while the other probe is bioconjugated with gold nanoparticles in free form to allow percentage determination and differentiating the methylated and unmethylated cell lines, further demonstrating the SOCS-1 methylation occurs in cancer patients but not in normal cell lines. The observed detection limit is 0.81 fM for methylated DNA, and the detection time is within 15 min. In addition, our data were significantly correlated to the data obtained from PCR-based pyrosequencing, and yet with superior accuracy. Hence our results provide new insight to the quantitative evaluation of methylation status of the human genome and can act as an alternative to PCR with a great potential.

A new optical fiber biosensor for acetylcholine detection based on pH sensitive fluorescent carbon quantum dots

Acetylcholine (Ach) is an important neurotransmitter and plays a vital role in the diagnosis and treatment of many neurological diseases. A new acetylcholine optical fiber biosensor is reported based on the nitrogen doped fluorescent carbon quantum dots/ acetylcholinesterase (N-CQDs/AchE) compound, where AchE was immobilized on the surface of N-CQDs by the cross-linking method. N-CQDs were synthesized by the hydrothermal method as fluorescent probe and can be responsible for pH value. The optical properties, morphology, particle size distribution and surface groups of N-CQDs were characterized by UV-Vis spectrophotometer, Fluorescence spectrometer, High-resolution transmission electron microscope (TEM) and Fourier transform infrared spectrometer (FTIR), respectively. The relationship between acetylcholine chloride solution and fluorescence intensity of N-CQDs/AchE complex was detected in detailed. Good linear relationship between fluorescence intensity and the concentration of acetylcholine from 20–200 µM and 1–100 nM with the lower detection limits of 16.28 µM and 0.29 nM, respectively. Compared with other sensors, this new optic fiber sensor immobilized (N-CQDs/AchE) complex is more simple and operable.

Ultra-sensitive detection of O-GlcNAc transferase based on micro-structured optical fiber biosensor with enhanced fluorescence collection

The development of optical fiber-based biosensors is greatly promoted by the increasing demand for simple, rapid and miniaturized analytical devices for accurate and sensitive detection of biomolecules in the clinical diagnosis, biomedicine and pharmaceutical fields. O-GlcNAc transferase (OGT) is considered to be a novel promising therapeutic target for disease diagnosis since it is closely related to O-linked-β-N-acetylglucosamine glycosylation (O-GlcNAcylation). At present, the detection and study of OGT has been hampered by its ultralow cellular abundance and low stability of enzyme activity. Here we present a micro-structured optical fiber (MSOF)-based biosensor for ultra-sensitive analysis of OGT. We utilize MSOF as carrier to immobilize fluorescence-labeled peptide based on streptavidin-biotin affinity and non-radioactive UDP-GlcNAc as sugar donor to perform O-GlcNAc glycosylation modification. Moreover, we improve the laser-induced fluorescence (LIF) system by combining concave mirror and microscope objective as fluorescence collector to further enhance the detection sensitivity. With the advantages of large surface area of MSOF and high fluorescence collection efficiency, the MSOF-biosensor shows an ultralow limit-of-detection of 3.40 × 10−2 pM for OGT assays. The feasibility of its clinical application has also been demonstrated by the analysis of blood samples from breast cancer patients, providing a promising analysis platform for sensitive diagnosis of OGT.

Label-free plasmonic immunosensor for cortisol detection in a D-shaped optical fiber.

Measuring cortisol levels as a stress biomarker is essential in many medical conditions associated with a high risk of metabolic syndromes such as anxiety and cardiovascular diseases, among others. One technology that has a growing interest in recent years is fiber optic biosensors that enable ultrasensitive cortisol detection. Such interest is allied with progress being achieved in basic interrogation, accuracy improvements, and novel applications. The development of improved cortisol monitoring, with a simplified manufacturing process, high reproducibility, and low cost, are challenges that these sensing mechanisms still face, and for which solutions are still needed. In this paper, a comprehensive characterization of a D-shaped fiber optic immunosensor for cortisol detection based on surface plasmon resonance (SPR) enabled by gold coating is reported. Specifically, the sensor instrumentation and fabrication processes are discussed in detail, and a simulation with its complete mathematical formalism is also presented. Moreover, experimental cortisol detection tests were performed for a detection range of 0.01 to 100 ng/mL, attaining a logarithmic sensitivity of 0.65 ± 0.02 nm/log(ng/mL) with a limit of detection (LOD) of 1.46 ng/mL. Additionally, an investigation of signal processing is also discussed, with the main issues addressed in order to highlight the best way to extract the sensing information from the spectra measured with a D-shaped sensor.

Modulation instability and highly sensitive optical fiber biosensor

The modulation instability (MI) is one of the interesting nonlinear phenomena which is used as a sensing mechanism. The performance of this mechanism is based on the shift of generated sidebands when the effective refractive index of the sensor is changed. The use of the MI process as a biosensing mechanism has capabilities such as high sensitivity, label-free and selective operation. In this paper, the novel optical fiber structures are proposed as lab-on-a-chip biosensors. In the proposed biosensors, capturing target biomolecules is achieved by immobilizing a capture layer. Consequently, after attaching the target layer the effective refractive index and the total dispersion of the structure are changed. As a result, the MI gain profile is changed and the generated sidebands (Stokes and anti-Stokes) around pump frequency are shifted. We demonstrate that the maximum sensitivity of these proposed sensors is 34.88 nm/nm. Moreover, the nonlinear material which is used in these biosensors is semiconductor doped glass (CS 3-68). This material due to the high nonlinear refractive index is an appropriate candidate to realize the MI process at low pump power. The used laser is a conventional laser 1550 nm with a power of 100 mW. The maximum length of the proposed biosensors is 0.199 cm which can realize the concept of lab-on-a-chip biosensors.

Development of Localized Surface Plasmon Resonance-Based Optical Fiber Biosensor for Immunoassay Using Gold Nanoparticles and Graphene Oxide Nanocomposite Film

In this study, the development of a reflected-type localized surface plasmon resonance (LSPR) based optical fiber biosensor is presented. The gold nanoparticles (AuNPs) and graphene oxide (GO) are sequentially modified on the surface of fiber probes to form a nanocomposite film using self-assembly method. Compared with AuNPs fiber probe, the refractive index sensitivity (RIS) of GO/AuNPs fiber probe is improved from 29.6 nm/RIU to 79 nm/RIU in the refractive index range from 1.33 to 1.38. After that, the fiber probes are immobilized with anti-mouse IgG for the immunoassay, and the response time is 30 minutes. Due to the advantages of good biocompatibility as well as physical and optical properties of GO, the GO/AuNPs fiber probe shows a quicker reaction and larger resonant wavelength shift, which are compared with AuNPs fiber probe in measuring different concentrations of mouse IgG. In addition, the GO/AuNPs fiber probe exhibits a better sensitivity (150.4 nm/ <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\mu \text{g}$ </tex-math></inline-formula> mL <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">−1</sup> ), linearity (R <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> = 0.998) and a lower limit of detection (4.3 ng/mL) in a low concentration of mouse IgG detection, which suggests that GO has huge potentials of biosensing applications in the future.

Hollow-Core Microstructured Optical Fiber Based Refractometer: Numerical Simulation and Experimental Studies.

In this paper, we numerically and experimentally propose a novel hollow-core microstructured optical fiber (HC-MOF) biosensor for refractive index determination. The sensing mechanism of the proposed sensor is based on photonic bandgap effect and the location of transmission maxima of the fiber, which is strongly depend on the liquid analyte RI filled in the fiber core. The proposed HC-MOF biosensor demonstrates the spectral sensitivity of 5636.3 nm/RIU with a RI detection range of 1.333 to 1.3385 for different ratios of plasma in blood serum in our experimental studies. The HC-MOF proposed here can detect similar liquid analytes with RI close to 1.33. The proposed sensor with a high sensitivity, ease of operation and the possibility of real-time sensing has a strong potential for detection of liquid analytes and biomolecules with possible applications in medicine, chemistry, and biology.

A Cholesterol Optical Fiber Sensor Based on CQDs-COD/CA Composite

A novel optical fiber biosensor based on carbon quantum dots (CQDs) fluorescent probe was developed for cholesterol sensing, in which CQDs-COD/CA composite acted as the sensitive film. The electron charge transfer between H₂O₂ and CQDs resulting from the specific reaction of cholesterol and cholesterol oxidase leads to fluorescence quenching. The fluorescence properties and surface morphology of CQDs-COD complex and complex sensitive film were characterized by Scanning electron microscope (SEM), transmission electron microscope (TEM), and Fourier transformation infrared (FTIR), fluorescence and ultraviolet spectroscopy. The fluorescence response of the sensor to cholesterol solution in micromole and millimole concentration ranges was studied, and the linear relations were obtained with <inline-formula> <tex-math notation="LaTeX">$\text{R}^{2} = 0.99022$ </tex-math></inline-formula> and 0.99638, respectively. The results obtained in this study showed that the CQDs-COD/CA composite sensor has good biocompatibility and selectivity for cholesterol.

Ultra-wide, attomolar-level limit detection of CD44 biomarker with a silanized optical fiber biosensor

Measuring cancer biomarkers at ultralow detection limit and high sensitivity could be a promising tool for early diagnosis, monitoring treatment and post-treatment recurrence. Soluble CD44 is a promising diagnostic and prognostic biomarker in several types of cancer including gastric, colon and breast cancer. Several highly sensitive biosensors have been built to measure this important biomarker. However, they did not reach attomolar level of detection. The aim of this work was to build a biosensor capable of detecting CD44 concentrations down to attomolar (aM) level while measuring it in a wide concentration range.Herein, we demonstrate a biosensor that offers 4 key advantages over existing platforms for CD44 detection: 1) detection of CD44 was carried out in a diluted serum down to attomolar level (4.68 aM) which is about 6 orders of magnitude lower than that of a traditional ELISA; 2) fabrication of the sensor is done in a fast way using inexpensive materials making it a disposable fiber optic biosensor; 3) detection of CD44 was performed in a wide dynamic range previously not shown in other similar biosensors; 4) a proof-of-concept experiment was performed using the biosensor to embed it in a catheter to measure the protein in flow conditions.

Ultralow Limit Detection of Soluble HER2 Biomarker in Serum with a Fiber-Optic Ball-Tip Resonator Assisted by a Tilted FBG.

An optical-fiber biosensor has been developed for the detection of the breast cancer biomarker soluble human epidermal growth factor receptor-2 (sHER2). The sensor was fabricated by combining a tilted fiber Bragg grating (TFBG) with a ball resonator, allowing us to achieve an excellent sensitivity compared to other optical-fiber-based sensors. The sensor exhibits a resonance comb excited by the TFBG and the spectral profile of the ball resonator. The detection of sHER2 at extremely low concentrations was carried out by tracking the amplitude change of selected resonances. The therapeutic anti-HER2 monoclonal antibody Trastuzumab has been used to functionalize the biosensor with silane surface chemistry. The sensor features a sensitivity of 4034 dB/RIU with a limit of detection (LoD) in buffer and in a 1/10 diluted serum of 151.5 ag/mL and 3.7 pg/mL, respectively. At relatively high protein concentrations (64 ng/mL) binding to sHER (7.36 dB) as compared to control proteins (below 0.7 dB) attested the high specificity of sHER2 detection.

Refractive index sensing properties of microfiber cascaded‐long‐tapers

AbstractThe microfiber cascaded double‐tapers were constructed and used as a Mach–Zehnder interferometer by a two‐step fiber stretching process using a normal fiber splicer and a multifunctional fiber stretching machine. The morphological parameters, such as waist diameter and taper length were optimized by the simulation models. The refractive index sensing performance has been theoretically and experimentally demonstrated and compared. A sensitivity of 2606.39 nm/RIU of one Mach–Zehnder interferometer with microfiber double‐apers (central distance is ~1 cm) was obtained when the RI values changed from 1.3309, 1.3319, 1.3327, 1.3336, 1.3344–1.3352. This study proposed a novel way to design interesting microfiber devices, which will be a promising candidate for exploring optical fiber biosensors with compact structures.

Fiber Optics for Sensing Applications in a Review

This paper introduces a review of the use of gold nanoparticles (AuNPs) in the fabrication of optical fiber biosensors based on localized surface Plasmon resonance (LSPR) and Evanescent field absorption. The AuNPs have special properties, such as high surface/volume ratio, and intense light scattering/absorption, and stable structure. The main advantage of AuNPs in the application of the biosensor in the detection signal increasing, for especially low concentration analyses. Moreover, we illustrate some of the previous works in this field in the period from 2001-2021, which used optical fiber and AuNPs as a base in the development of various biosensors and all exhibited differently limits of detection, sensitivity, and good performances to its target detection.

Fabrication and characterization of L-asparaginase entrapped polymeric nanoparticles for asparagine biosensor construction

The present work reports the fabrication of novel and highly stable L-asparaginase (L-ASP) loaded gelatin alginate nanoparticles (GANp) for the construction of an easily reproducible, sensitive, and selective fiber optic asparagine biosensor. GANp containing L-ASP of 396 nm size with 79.7% entrapment efficiency was achieved via ionic gelation method. The physicochemical properties of fabricated GANp were characterized by Scanning Electron Microscopy (SEM) and Fourier Transform Infrared Spectroscopy (FTIR). The fabricated L-ASP entrapped GANp were stable for 50 days with 75% of residual activity. Immobilized L-ASP displayed improved stability against pH and temperature with higher affinity (Km3.83 mM) in comparison to free L-ASP. Furthermore, the application of L-ASP loaded GANp (biocomponent) in biosensor construction led to the evolution of highly sensitive fiber optic asparagine biosensor with 0.05 × 10-10 M detection limit within 2 min of response time. The proposed biosensor can be potentially applied for L-asparagine detection and quantification in the leukemia diagnosis and treatment.