Fiber Optic Biosensor Research Articles

A real-time and highly sensitive fiber optic biosensor based on the carbon quantum dots for nitric oxide detection

Nitric oxide (NO) is a signal molecule with a wide range of functions and unique properties in organisms. A novel fluorescent probe composed of carbon quantum dots (CQDs) with o-phenylenediamine groups was prepared by the microwave method to detect NO selectively. The mechanism of the reaction between CQDs and NO was established by a series of characterization methods, such as fluorescence spectrophotometer, UV–vis absorption spectrophotometer and transmission electron microscope. The result showed that the o-phenylenediamine groups on the surface of the CQDs can react with NO to form an electron-free triazole structure, leading to the decrease of fluorescence of the CQDs. Furthermore, a new optical fiber sensing system based on the CQDs was constructed to detect NO with a low detection limit of 9.12 nM at laser power of 280 mW. In addition, the NO optic fiber biosensor also was used to detect NO concentration in real human serum samples.

Toward Smart Selective Sensors Exploiting a Novel Approach to Connect Optical Fiber Biosensors in Internet

The selective detection of pollutants in water in a laboratory scenario has been presented by authors exploiting low-cost optical biosensors based on plastic optical fibers (POFs) and biological or biomimetic receptors. So, for instance, the detection in water of naphthalene, perfluoroalkyl substances (PFAs) and polyfluoroalkyl substances have been investigated with interesting detection limits when compared to those obtained by using different expensive traditional approaches (e.g., liquid chromatography-mass spectrometry with high performances). In this article, we have developed and tested a novel approach used in a smart measuring system to use POF sensors in situ for the remote measures of pollutants in water for smart cities applications. More specifically, we have used different water–glycerin solutions to test the novel sensor system based on a Raspberry Pi connected to the Internet and to a spectrometer, a light source, a POF sensor, and two computers connected to Internet used as client and server.

Label-Free Biosensors Based on Long Period Fiber Gratings: A Review

Fiber optic label-free biosensors are currently experiencing wide diffusion, as they combine the performance of optical measurements with the advantages of optical fiber. This paper presents a comprehensive review about the design, development and testing of biosensor solutions based on in-fiber long period gratings (LPG). The attention is focused on optical transducers and methodologies allowing a significant enhancement of the sensitivity. Moreover, coating nanomaterials, bio-functionalization strategies and recognition elements providing the selectivity to the target analyte are reported in detail. The aim is to provide a detailed review concerning the state of the art about LPG-based label-free biosensors and to outline the future research trends.

Lossy mode resonance-based uniform core tapered fiber optic sensor for sensitivity enhancement

A lossy mode resonance (LMR)-supported fiber optic sensor in which a uniform fiber core is placed among two identical tapered regions, is investigated numerically. Indium tin oxide (ITO) and aluminum-doped zinc oxide (AZO) are considered as LMR active materials used to excite several lossy modes and gold and silver are used as surface plasmon resonance (SPR) active materials. In this probe design, a central uniform core coated with ITO/AZO is the active sensing region, whereas tapered regions are meant for bringing the incident angle close to the critical angle. The sensitivity of the present fiber optic bio-sensor is evaluated for first two LMRs utilizing both ITO and AZO separately, along with its variation with the taper ratio (TR). For ITO, the maximum sensitivity values are observed to be 18.425 μm RIU−1 (refractive index unit) and 0.825 μm RIU−1, corresponding to the first and second LMRs, respectively, at a TR of 1.6 and for AZO, equivalent values are 0.79 μm RIU−1 and 0.35 μm RIU−1, respectively, at a TR of 2.0. The results illustrate that the first LMR is more sensitive than the second LMR and the ITO-coated probe possesses greater sensitivity than the AZO-coated probe for both LMRs. Similarly, for the fiber optic SPR sensor, the maximum value of sensitivity is 5.6425 μm RIU−1, in the case of gold and 5.0615 μm RIU−1 in the case of silver, at a TR of 1.6. Hence, the result shows that the sensor with the present fiber optic probe design has around a 3-fold enhancement in sensitivity compared with conventional SPR sensors. This study will have applications in many sensing schemes where the requirement of large sensitivity is vital.

A plasmonic fiberoptic absorbance biosensor for mannose-capped lipoarabinomannan based tuberculosis diagnosis

Tuberculosis (TB) is a resurgent infectious disease affecting a large number of people in the developing countries. An on-site, affordable diagnostic screening at an early-stage for an immediate anti-TB treatment is known to tremendously minimize the high mortality rates. Lipoarabinomannan (LAM), a surface glycolipid, has been identified as a potential TB biomarker present in urine at ultra-low concentrations of a few fg/mL. Here, we report a plasmonic fiber optic absorbance biosensor (P-FAB) strategy for mannosylated LAM (Man-LAM or Mtb LAM) detection down to attomolar concentrations. It involves a plasmonic sandwich immunoassay on a U-bent fiber optic probe with gold plasmonic (AuNP) labels functionalized with anti-Mtb LAM immunoglobulin M (IgM) and anti-Mtb LAM IgG respectively. The Mtb LAM is quantified in terms of absorption of light passing through the fiber probe using a green LED and a photodetector. The choice of fiber optic probes (fused silica versus polymer), the optimum size (20, 40, 60 and 80 nm) and concentration (2 × , 10 × , and 20 × ) of AuNP labels were investigated to obtain high sensitivity and lower limits of analyte detection (LoD). P-FAB with a simple LED-photodetector pair, 200 μm fused silica U-bent fiber probe and 60 nm (20 × ) AuNP labels gave LoDs down to 1 fg/mL and 10 fg/mL in the buffer and synthetic urine respectively. Moreover, the anti-Mtb LAM IgM bound sensor probes and the AuNP reagent stored at 4 °C were stable up to 45 days. P-FAB based Mtb LAM sensor demonstrates its potential for an on-site TB diagnosis.

Sensitivity enhancement of WS2-coated SPR-based optical fiber biosensor for detecting glucose concentration* *Project supported by the Natural Science Foundation of Jiangsu Province, China (Grant No. BK20171442), the China Postdoctoral Science Foundation (Grant No. 2018T110480), the Open Foundation of State Key Laboratory of Millimeter Waves, China (Grant No. K202003), the Open Foundation of State Key Laboratory of Luminescent Materials and Devices,

In this paper, we propose a theoretical model of the surface plasmon resonance-based optical fiber biosensor for detecting glucose concentration. The Au/ZnO/WS2 multilayer film is coated around optical fiber. Compared with the conventional surface plasmon resonance sensor, WS2 material can increase the sensitivity of the biosensor. The absorption capacity of WS2 is used to load glucose oxidase by forming a sensitive area to recognize glucose. Refractive index of the solution is calculated and then the concentration of the glucose can be obtained by the correspondence between refractive index and glucose concentration. The highest sensitivity of the SPR biosensor with a structure of 40-nm Au/5-nm ZnO/14 layers of WS2 is 4310 nm/RIU. The proposed WS2-based SPR fiber biosensor has a unique effect on the detection of glucose concentration. It is expected to have potential applications in future medical blood glucose concentration detection.

Reusable optofluidic point-of-care testing platform with lyophilized specific antibody for fluorescence detection of cholylglycine in serum.

A reusable optofluidic point-of-care testing platform (OPOCT) was successfully constructed through integrating evanescent wave fluorescence technology into an all-fiber-based optofluidic system. The compact design of the OPOCT allows it to be portable and suitable for on-site sensitive determination of biomarkers in serum without complicated and costly procedures. The sensitivity of 90.9pM for antibody determination is observed thanks to the high transmission efficiency of excitation light and fluorescence in the OPOCT. The affinity constant between cholylglycine (CG) and anti-CG antibody was quantified using this platform based on the proposed theory. Using the lyophilized fluorescence-labeled specific antibody and reusable fiber optic biosensor, the OPOCT is applied to the one-step sensitive determination of CG in serum, which eliminates the dearth associated with liquid reagent handling, disposable biosensors, and user intervention. A limit of detection of 0.025μg/mL for CG is obtained, which is far more than adequate for meeting diagnostic requirements. The matrix effect of serum samples on the evanescent wave-based optofluidic biosensor can be effectively reduced by simple dilution of serum samples. The performance of the OPOCT also compared favorably with that of a commercial turbidimetric inhibition immunoassay through analyzing multiple serum samples. This platform is ready to expand to measure any other biomarker by using its specific antibody. The simplicity, sensitivity, cost-effectiveness, and robustness of the OPOCT enable the early diagnosis of disease and making a timely clinical decision. Graphical abstract .

Overview of Recent Advances in the Design of Plasmonic Fiber-Optic Biosensors.

Plasmonic fiber-optic biosensors combine the flexibility and compactness of optical fibers and high sensitivity of nanomaterials to their surrounding medium, to detect biological species such as cells, proteins, and DNA. Due to their small size, accuracy, low cost, and possibility of remote and distributed sensing, plasmonic fiber-optic biosensors are promising alternatives to traditional methods for biomolecule detection, and can result in significant advances in clinical diagnostics, drug discovery, food process control, disease, and environmental monitoring. In this review article, we overview the key plasmonic fiber-optic biosensing design concepts, including geometries based on conventional optical fibers like unclad, side-polished, tapered, and U-shaped fiber designs, and geometries based on specialty optical fibers, such as photonic crystal fibers and tilted fiber Bragg gratings. The review will be of benefit to both engineers in the field of optical fiber technology and scientists in the fields of biosensing.

D-type optical fiber immunoglobulin G sensor based on surface plasmon resonance

In this paper, we report a D-type optical fiber biosensor for human immunoglobulin G (HIgG) detection based on surface plasmon resonance (SPR). The SPR phenomenon was both simulated by COMSOL and observed experimentally. To fabricate the sensor, the cladding of a multimode optical fiber (MMF) was polished using a grinding wheel to obtain a D-type cross-section. Next, a gold film was sputtered on the surface of the MMF. The optimal gold layer thickness and grinding depth were determined through simulations. As per the experimental results, the optimized sensor exhibited high refractive index (RI) sensitivity, which ranged from 1590.9 nm/RIU to 3513.3 nm/RIU for RI values of 1.343 to 1.373. Subsequently, Poly dimethyl diallyl ammonium chloride (PDDA) and Poly(sodium-p-styrenesulfonate) (PSS) were deposited four times in sequence to form polyelectrolyte self-assembled multilayers for the surface functionalization of the fiber. HIgG and goat anti-HIgG (GaHIgG) were chosen as the bioconjugate pair for evaluating the functionality of the fabricated biosensor, and the sensitivity to IgG was determined to be 91 nm/(mg/ml). The specificity of the biosensor was also verified through comparison tests performed using gelatin, horse IgG, and swine IgG. The obtained results confirmed the suitability of the biosensor for use in various biochemical applications.

A fiber optic nanoplasmonic biosensor for the sensitive detection of ampicillin and its analogs.

A novel optical immunosensor for the screening of ampicillin (Amp) residues has been developed. The biosensor is based on fiber optic particle plasmon resonance detection and uses an enhancement method called as fiber optic nanogold-linked immunosorbent assay (FONLISA) for the sensitive detection of antibiotics. A commercial antibody which had a higher affinity for ampicillin than for other β-lactam antibiotics was chosen. A surface competitive binding assay was used in which a fixed concentration of antibiotic-conjugated gold nanoparticles (AuNPs) competes with free unlabeled antibiotic molecules to measure the amount of binding with antibody molecules immobilized on an optical fiber. The synthesis of the 11-mercaptoundecanoic acid (MUA)-ampicillin conjugate facilitates the attachment of the Amp molecules to AuNPs via MUA which acts as a linker between them. This AuNP-Amp conjugate was then used for the detection of β-lactam antibiotics. The practical limit of detection obtained for Amp was 0.74ppb (7.4 × 10-10g/mL) which is lower than the recommended maximum residue limit (MRL) for β-lactams. The method also shows a wide linear range of 4 orders. Its applicability to the determination of ampicillin in spiked milk samples has been demonstrated with good recovery and reproducibility. Graphical abstract.

Fiber Optic Particle Plasmon Resonance Biosensor for Label-Free Detection of Nucleic Acids and Its Application to HLA-B27 mRNA Detection in Patients with Ankylosing Spondylitis.

We developed a label-free, real-time, and highly sensitive nucleic acid biosensor based on fiber optic particle plasmon resonance (FOPPR). The biosensor employs a single-strand deoxyoligonucleotides (ssDNA) probe, conjugated to immobilized gold nanoparticles on the core surface of an optical fiber. We explore the steric effects on hybridization affinity and limit of detection (LOD), by using different ssDNA probe designs and surface chemistries, including diluent molecules of different lengths in mixed self-assembled monolayers, ssDNA probes of different oligonucleotide lengths, ssDNA probes in different orientations to accommodate target oligonucleotides with a hybridization region located unevenly in the strand. Based on the optimized ssDNA probe design and surface chemistry, we achieved LOD at sub-nM level, which makes detection of target oligonucleotides as low as 1 fmol possible in the 10-μL sensor chip. Additionally, the FOPPR biosensor shows a good correlation in determining HLA-B27 mRNA, in extracted blood samples from patients with ankylosing spondylitis (AS), with the clinically accepted real-time reverse transcription-polymerase chain reaction (RT-PCR) method. The results from this fundamental study should guide the design of ssDNA probe for anti-sense sensing. Further results through application to HLA-B27 mRNA detection illustrate the feasibility in detecting various nucleic acids of chemical and biological relevance.

Fabrication of enzyme-based optical biosensor for estimation of inorganic phosphate in a urine sample

Present work describes enzyme-based optic fiber biosensor for the estimation of inorganic phosphate. A biosensor is based on the inhibitory effect of inorganic phosphate on acid phosphatase activity. Acid phosphatase catalyzes the conversion of p-nitrophenyl phosphate to a colored product p-nitrophenol, which is detected optically at 405 nm. This reaction is inhibited by inorganic phosphate present in the sample and the extent of inhibition is correlated to its concentration. Acid phosphatase immobilized in agarose–jellose composite is used as biocomponent for the fabrication of optic fiber biosensor. A calibration curve for inorganic phosphate was obtained with KH2PO4 and used for the determination of inorganic phosphate in the sample. This optic fiber biosensor was applied for the estimation of inorganic phosphate in complex urine samples. This biosensor is easy to fabricate moreover it has shown a shelf life of more than 80 days with a linearity range from 20 to 100 µM. The response time of the sensor was found to be 20 min.

Ultrahigh-sensitivity label-free optical fiber biosensor based on a tapered singlemode- no core-singlemode coupler for Staphylococcus aureus detection

An ultra-high sensitivity label-free optical fiber biosensor for inactivated Staphylococcus aureus (S. aureus) detection is proposed and investigated in this study, with additional advantages of robust and stability compared to traditional tapered fiber structure. The proposed fiber biosensor is based on a tapered singlemode- no core-singlemode fiber coupler (SNSFC) structure, where the no core fiber was tapered to small diameter (taper-waist diameter of about 10 μm) and functionalized with the pig immunoglobulin G (IgG) antibody for detection of S. aureus. The measured maximum wavelength shift of the sensor for an S. aureus concentration of 7 × 101 CFU/mL (colony forming unit per milliliter) is 2.04 nm, which is equivalent to a limit of detection (LOD) of 3.1 CFU/mL (a highest LOD reported so far for optical fiber biosensors), considering the maximum wavelength variation of the sensor in phosphate buffered saline (PBS) is ±0.03 nm over 40 min, where 3 times of maximum wavelength variation (3 × 0.03 = 0.09 nm) is defined as measurement limit. The response time of the developed fiber sensor is less than 30 min. The ultra-sensitive biosensor has potential to be widely applied to various areas such as disease, medical diagnostics and food safety inspection.

Quantitative Analysis of Methyl-Parathion Pesticide in Presence of Enzyme Substrate Using Tapered Fiber Optic Biosensor

Application of a non-adiabatic tapered fiber optic biosensor for real-time, label-free detection of methyl-parathion pesticide (MPT) in presence of acetylthiocholine iodide (ATCh) is presented. The limit of detection of MPT in the presence of 1 mM ATCh as an enzyme substrate is found to be as low as $23\times 10\,\,^{-{9}}$ M (S/N=3). The proposed sensor shows a dynamic range of 2.3 nm and a working range of 0.12 to $31~\mu \text{M}$ . More importantly, it has the capability of quantifying the binding constants of MPT to the enzyme acetylcholinesterase (AChE) by performing just a single experiment. This can be done through the kinetic analysis of the analyte-enzyme reaction in the presence/absence of ATCh. The results show an association rate of $3.835\times 10\,\,^{{4}}\,\,\text{M}^{-{1}}\text{s}^{-{1}}$ and a dissociation rate of 0.2745 s−1 for MPT-AChE binding in presence of ATCh which lead to a value of $1.4\times 10\,\,^{{5}}\,\,\text{M}^{-{1}}$ for equilibrium binding constant and $7.16~\mu \text{M}$ for dissociation constant. Detection of MPT in the tap and river water at low levels has been achieved and the sensor specificity examined against different substances. Based on the obtained results, our biosensor can pave the way toward low-cost, real-time, label-free, and quantitative determination of organophosphate pesticides in real samples.

Development of an optical microfiber immunosensor for prostate specific antigen analysis using a high-order-diffraction long period grating.

Fiber-optic biosensors are of great interest to many bio/chemical sensing applications. In this study, we demonstrate a high-order-diffraction long period grating (HOD-LPG) for the detection of prostate specific antigen (PSA). A HOD-LPG with a period number of less than ten and an elongated grating pitch could realize a temperature-insensitive and bending-independent biosensor. The bio-functionalized HOD-LPG was capable of detecting PSA in phosphate buffered saline with concentrations ranging from 5 to 500 ng/ml and exhibited excellent specificity. A limit of detection of 9.9 ng/ml was achieved, which is promising for analysis of the prostate specific antigen.

Fibre-optic biosensor for the detection of xanthine for the evaluation of meat freshness

Xanthine is produced by guanine deaminase and xanthine oxidase from guanine and hypoxanthine, respectively. It serves as an indicator of spoilage of meat and various pathological conditions. An optical biosensor has been fabricated for the detection of xanthine by absorption transmission approach. The bioassay principle used in this study is conversion of xanthine to uric acid and H2O2 by XO. Due to the production of uric acid, pH of the reaction decreases and falls in range of 7.5 - 6. The absorptive dye phenol red has been screened to visualize the change in colour. The coimmobilization of XO and dye phenol red indicator was done with sol-gel method onto the circular plastic discs for the development of biosensor. Volume of sample required for detection has been miniaturized to 10μl. The linear range of concentration and limit of detection were 0.5μM – 150μM and 0.5 μM respectively, have been achieved for xanthine. The designed biosensor was successfully employed for the detection of xanthine in chicken meat sample. Present study leads to the development of a fast and dependable biosensor with miniaturized sample volume and also mass scale screening possible through colour visualization.

The Determination of Listeria monocytogenes in Foods with Optical Biosensors

Listeria monocytogenes is a food-borne intracellular pathogen that is resistant to adverse conditions of food processing and is a causative agent of high mortality listeriosis disease. Analysis of large food lots is limited by culture methods. Nowadays, although the conventional culture methods have been adopted as the gold standard method, they can be insufficient to control food parties that reach very large quantities. Biosensors with on-site detection potential and their characterizing with high accuracy and precision offers many opportunities for real-time estimation of industrial contamination. As the most promising technique for rapid detection of L.monocytogenes, ones based on surface plasmon resonance (SPR) and fiber optic biosensors (FOBs) where direct or indirect detections can be made by detecting the interaction of the biomarker element with the optical field without marking or labeling, have come to the fore. SPR and FOBs can be detected directly in the range of 102-106 cfu/ml and ≤101-103 cfu/ml, respectively.

A Lamping U-Shaped Fiber Biosensor Detector for MicroRNA.

This study presents a U-shaped optical fiber developed for a facile application of microRNA detection. It is fabricated by the lamping process and packaged in a quartz tube to eliminate human negligence. In addition, silanization and electrostatic self-assembly are employed to bind gold nanoparticles and miRNA-133a probe onto the silicon dioxide of the fiber surface. For Mahlavu of hepatocellular carcinoma (HCC), detection is determined by the wavelength shift and transmission loss of a U-shaped optical fiber biosensor. The spectral sensitivity of wavelength and their coefficient of determination are found at −218.319 nm/ ng/mL and 0.839, respectively. Concurrently, the sensitivity of transmission loss and their coefficient of determination are found at 162.394 dB/ ng/mL and 0.984, respectively. A method for estimating the limit of detection of Mahlavu is at 0.0133 ng/mL. The results show that the proposed U-shaped biosensor is highly specific to miRNA-133a and possesses good sensitivity to variations in specimen concentration. As such, it could be of substantial value in microRNA detection.

Beta-lactam antibiotics induced bacteriolysis on LSPR sensors for assessment of antimicrobial resistance and quantification of antibiotics

Antimicrobial resistance affecting humans is fueled by empirical infection diagnostics and continuous unintended antibiotics exposure. A localized surface plasmon resonance (LSPR) based optical fiber biosensor for capture of bacteria followed by antibiotic mediated lysis has been demonstrated for quick drug susceptibility testing. The concept has been proven with P. aeruginosa and E. coli suspended in simulated human urine for potential drug susceptibility testing for urinary tract infections. P. aeruginosa RS1 was found to be selectively sensitive to commonly used third generation cephalosporins ceftazidime, ceftriaxone and cefotaxime. Hence, in an alternate scheme, bacteriolysis signatures of P. aeruginosa immobilized on gold nanoparticles modified optical fibers was used for quantification of third generation cephalosporins over a linear range of 0.01 to 1 μg/ml, R2 = 0.985, in water. Further, this principle was established for therapeutic drug monitoring (TDM) of the said antibiotics in real human serum in the therapeutic relevant range of 0.5 to 10 μg /mL (R2 = 0.987). This sensor provides a quick alternative to cumbersome Kirby-Bauer disk diffusion tests, practiced in most community health settings and tertiary care hospitals for drug susceptibility testing. The sensor also provides an alternative to chromatography coupled mass spectroscopic techniques for quicker, affordable and possibly point of care antibiotic quantification with applications in environmental and therapeutic monitoring.

LSPR optical fiber biosensor based on a 3D composite structure of gold nanoparticles and multilayer graphene films.

In this paper, a localized surface-plasmon resonance (LSPR) biosensor, which uses a U-shaped multi-mode fiber (U-MMF), is introduced and investigated. It is modified with a complex of three-dimensional (3D) gold nanoparticles and multilayer graphene as spacer: n*(Au/G)@U-MMF, where n denotes the layer number of gold nanoparticles. The gold nanoparticles were synthesized by reducing chloroauric acid. Graphene films were formed using a liquid/chemical method. The number of gold-nanoparticle layers was found to be critical for the performance of the sensor. Moreover, using the finite-difference time domain, 3D nanostructures, with a wide range of gold-nanoparticle layers, were explored. The sensor showed the sensitivity of 1251.44 nm/RIU, as well as high stability and repeatability; for the measurement-process of time- and concentration-dependent DNA hybridization kinetics with detection concentrations, ranging from 0.1nM to 100 nM, the sensor displayed excellent performance, which points towards a vast potential in the field of medical diagnostics.