Functionalization Techniques Empowering Optical Fiber Biosensors in Label-Free Cancer Biomarker Detection.

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.

The detection of carcinoembryonic antigen (CEA)-related cell adhesion molecules 5 (CEACAM5) is significant in cancer prewarning. Early diagnosis can effectively alleviate the danger of cancer. Point-of-care testing (POCT) has become a competitive technology for early detection. Fiber optic biosensors have great potential as POCT tools. However, their limits of detection (LODs) are not sufficient to afford ultralow concentration detection at the early stage. Herein, this work presents an optical microfiber sensor functionalized by a polystyrene@gold nanosphere (PS@Au nanosphere) interface for a synergistic sensitization effect to detect the ultralow CEACAM5 concentrations in serum at the early stage. The sensor's LOD achieves 3.54 × 10-17 M in pure solution and 5.27 × 10-16 M in serum, with the sensitization effect coupled with surface area enlargement and electromagnetic enhancement of interface. This LOD is about 6 orders of magnitude lower than that of current methods. It can be employed to detect the biomarkers at ultralow concentrations present in serum in the early stages of cancer. As the interfacial synergistic sensitization strategy is suitable for refractive index (RI)-based optical transducers, this work provides new opportunities to employ fiber optic biosensors as effective POCT tools.

Cold plasma modification on optical fiber biosensor based on surface plasmon resonance (SPR) is proposed to enhance the SPR effect on biosensing. A side-polished multimode fiber sensor based on surface plasmon resonance as the transducing element with a halogen light source is carried out for the measurement of the BSA for the sensitivity analysis. The comparison with detection surface was fabricated by binding chemically to self-assembly monolayer (SAM) of 11-mercaptoundecanoic acid (MUA) and cold plasma modification method on gold (Au) surface of optical fiber, and then was activated by EDC/NHS for BSA. The pretreatment of cold plasma modification using isopropanol (IPA) to deposited carboxyl group on side-polished surface of optical fiber biosensor, and there are easily to combine biomolecule by EDC/NHS modification. The results of the comparison between traditional surface modification and cold plasma modification with the measurement for 5 ng BSA is observed on OSA and shifted obviously in wavelength. The side-polished fiber sensor based on surface plasmon resonance can provide the SPR response on spectrum, and the IPA plasma treatment can increase the sensitivity of the SPR dip shifted with 10–40 nm under the 10 min treatment time of the surface modification.

We developed a label-free, highly sensitive, real time, and micrometer-sized optical fiber biosensor without using any attenuated total reflection (ATR) optics. The sensor is based on the localized surface plasmon resonance (LPR) in gold nanoparticles. The gold nanoparitlces show a large absorption band at around 520 nm due to LPR, which is quite sensitive to the environment around the nanoparticles. Thus change of the refractive index of the ambient medium around the nanoparticles or overcoating a thin dielectric layer on the particles results in a red-shift of the absorption band and change of the absorption intensity. This paper reports a novel optical fiber biosensor that is constructed at the endface of the optical fiber. The fiber probe is consisting of gold nanoparticles that plays as a transducer, where ligand is coated. The return light intensity from the fiber probe is changed by the adsorption of the biomolecules that has affinity to the ligand. The sensitivity was evaluated to be 10 pg/mm² (2x10^-5 RIU) with an LED light, which is compatible with the conventional surface plasmon resonance biosensors that use the ATR optics.

In this paper, an optical fiber biosensor based on multiple total internal reflections in heterodyne interferometry is proposed. The sensor is made of a long U-shaped multimode optical fiber which cladding is removed from the sensing portion of the fiber. With the optical fiber biosensor the phase shift difference due to the multiple total internal reflections (MTIR) effect between the P and S-polarizations is measured by using heterodyne interferometry with the optical fiber biosensor. Substituting the phase shift difference into Fresnel's equations, the refractive index for the tested medium can be calculated. The resolution of the sensor can reach 1.58×10^-6 refractive index unit (RIU). The optical fiber biosensor could be valuable for chemical, biological and biochemical sensing. It has some merits, such as, high resolution and stability, small size and real-time measurement.

Highly reproducible fiber optic surface plasmon resonance biosensors modified by CS2 for disposable immunoassays

Utilization of a phosphorene-graphene/TMDC heterostructure in a surface plasmon resonance-based fiber optic biosensor

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.

Putrescine is a kind of physical diamine that is closely related to food deterioration and food quality safety. This study employs a novel fiber optic biosensor based on S-tapered and waist extension techniques, as well as localized surface plasmon resonance (LSPR), to detect putrescine accurately. The gold nanoparticles (AuNPs) are fixed on the fiber to excite LSPR. Furthermore, the multi-walled carbon nanotubes (MWCNTs) and niobium carbide (Nb2CTx) are used to increase the binding sites of enzymes to improve the sensing performance of probes. In this work, the fiber probe surface is functionalized by diamine oxidase (DAO) to improve selectivity. The sensitivity and limit of detection of the fiber optic biosensor are 2.04 nm/lg(µM) and 0.267 µM over a linear range of 0-100 µM, respectively. In addition, the tests of repeatability, reusability, selectivity, pH value, and real samples of the sensor probe are assessed to demonstrate the potential in measuring putrescine.

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.

In recent years, label-free biosensors not requiring external modifications have been receiving intense attention. A label-free optical biosensor, which retains many of the desirable features of conventional surface plasmon resonance (SPR) reflectometry, namely, the ability to monitor the kinetics of biomolecular interactions in real-time without a label has been developed with several important advantages: the biosensor device is easy to fabricate, and simple to implement, requiring only an UV–Vis spectrophotometer or flatbed scanner. Importantly, the label-free optical biosensor can be easily multiplexed to enable high-throughput monitoring of biomolecular interactions in an arraybased format. In this research,the development of a localized surface plasmon resonance (LSPR)-based label-free optical biosensor using a surface modified nanoparticle layer is aimed. This optical detection method promises to offer a massively parallel detection capability in a highly miniaturized package. The two-dimensional nanoparticle layer was formed by the surface modified silica nanoparticles. The optical properties and surface analysis of nanoparticle layer substrate were characterized through transmissionmeasurements and atomic force microscopy (AFM). Simultaneously, the nanoparticle layer substrate was applied to the optical LSPR-based biosensor for label-free monitoring of the antigen–antibody reaction. The anti-fibrinogen antibody wasimmobilized onto the nanoparticle layer substrate surface. Different concentrations of fibrinogen were introduced to the anti-fibrinogen antibody immobilized nanoparticle layer substrate surface, and the change in the absorption spectrum, caused by the antigen–antibody reaction, was observed. By using this anti-fibrinogen antibody immobilized nanoparticle layer substrate; the detection limit of this optical LSPR-based biosensor was 10 ng/ml.

Real-time diagnosis of cholangiocarcinoma by combining digestive endoscopy and optic fiber biosensors based on bile clusterin.

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

A biosensor is a promising alternative tool for the detection of clinically relevant analytes. Optical fiber as a transducer element in biosensors offers low cost, biocompatibility, and lack of electromagnetic interference. Moreover, due to the miniature size of optical fibers, they have the potential to be used in microfluidic chips and in vivo applications. The number of optical fiber biosensors are extensively growing: they have been developed to detect different analytes ranging from small molecules to whole cells. Yet the widespread applications of optical fiber biosensor have been hindered; one of the reasons is the lack of suitable packaging for their real-life application. In order to translate optical fiber biosensors into clinical practice, a proper embedding of biosensors into medical devices or portable chips is often required. A proper packaging approach is frequently as challenging as the sensor architecture itself. Therefore, this review aims to give an unpack different aspects of the integration of optical fiber biosensors into packaging platforms to bring them closer to actual clinical use. Particularly, the paper discusses how optical fiber sensors are integrated into flow cells, organized into microfluidic chips, inserted into catheters, or otherwise encased in medical devices to meet requirements of the prospective applications.

This investigation presents an overview of various optical biosensors utilized for the detection of cancer cells. It covers a comprehensive range of technologies, including surface plasmon resonance (SPR) sensors, which exploit changes in refractive index (RI) at the sensor surface to detect biomolecular interactions. Localized surface plasmon resonance (LSPR) sensors offer high sensitivity and versatility in detecting cancer biomarkers. Colorimetric sensors, based on color changes induced via specific biochemical reactions, provide a cost-effective and simple approach to cancer detection. Sensors based on fluorescence work using the light emitted from fluorescent molecules detect cancer-specific targets with specificity and high sensitivity. Photonics and waveguide sensors utilize optical waveguides to detect changes in light propagation, offering real-time and label-free detection of cancer biomarkers. Raman spectroscopy-based sensors utilize surface-enhanced Raman scattering (SERS) to provide molecular fingerprint information for cancer diagnosis. Lastly, fiber optic sensors offer flexibility and miniaturization, making them suitable for in vivo and point-of-care applications in cancer detection. This study provides insights into the principles, applications, and advancements of these optical biosensors in cancer diagnostics, highlighting their potential in improving early detection and patient outcomes.