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In this study, a high-performance fiber optic surface plasmon resonance (FO-SPR) sensor using a dome array with nanogaps (DANG) is proposed for label-free real-time detection of biomolecules. A novel and simple method using polymer beads enables high sensitivity by allowing hotspots with nanometer spacing between the Au dome and the surrounding film. The nanodome structure, which comprises a polymer core and a Au shell, induces a localized surface plasmon, expands the sensing area, and extensively enhances the electromagnetic field. The refractive index sensitivity of the FO-SPR sensor with nanostructures, i.e., with nanogaps and nanodomes, was found to be 7.8 times higher than that of the FO-SPR sensor without nanostructures. The proposed sensor achieved a low detection limit of 38 fg/mL while quantifying thyroglobulin antibody-antigen interactions and exhibited excellent selectivity. In addition, it helped detect serum samples with a 103% recovery rate.

Localized surface plasmon resonance (LSPR) sensor with hybrid structure of dielectric thin film and bilayered gold nanoparticles (AuNPs) on an optical fiber is proposed to enhance the sensitivity. The increased number of nanoparticles per unit plane due to the bilayer structure contributes to the upgrade in the sensitivity by improving the LSPR effect and extending the sensing area. The bilayered AuNPs will be particularly important in the application of fiber optic LSPR (FO LSPR) sensors because the optical fiber has a small cross-sectional area. The Al2O3 thin film by atomic layer deposition is inserted between the first and second layers of AuNPs. The dielectric spacer can also help to improve the sensitivity by concentrating the electric field due to its high refractive index and ensuring a nanometer gap between nanoparticles. The monolayer and bilayer with AuNPs are prepared on the optical fibers, respectively. In each FO LSPR sensor, refractive index sensitivities are also analyzed and compared. In the sensor with bilayered AuNPs, a sensitivity improvement of approximately 2.3 times is confirmed. This strategy can be a breakthrough to increase the sensing area of the FO LSPR sensor without modifying the structure of the optical fiber.

For real-time and high-sensitivity analysis of low-concentration targets, a sandwich immunoassay using second antibody-second gold nanoparticle (2nd Ab-2nd AuNP) conjugates was combined with fiber-optic localized surface plasmon resonance (FO LSPR). An FO LSPR format was constructed by immobilizing AuNPs on a fiber-optic cross-section for compactness, portability, and ease of handling. In addition, it was combined with a microfluidic system to ensure reproducibility and reliability of measurements. A detection limit of 97.6 fg/mL (148 aM) was obtained for thyroglobulin (Tg) without a sandwich assay. The detection limit was enhanced by approximately 15 times (6.6 fg/mL, 10 aM) when a sandwich strategy was performed with a 2nd Ab-2nd AuNP signal amplifier to further improve the responsivity. Additionally, the good selectivity of the proposed method was confirmed against the unpaired antigen. To evaluate its practical applicability in the field, an FO LSPR biosensor boosted with a sandwich assay using antibody-functionalized AuNPs was applied to detect Tg contained in patient serum, and the results were compared and verified with those of a commercial radioimmunoassay kit. Based on the above results, the signal-enhancing immunoassay with FO LSPR will contribute to the development of optical biosensors for early diagnosis and preventive applications.

Fiber optic surface plasmon resonance (FO SPR) sensor offers attractive advantages over the conventional prism-based SPR platforms, such as simplicity, cost-effectiveness, and miniaturization. To improve the performance of the existing FO SPR sensor which has been fabricated by depositing a gold thin film on the flat fiber cross-section or side surface, we propose to fabricate the polymer microtip array on optical fiber using simple cost-effective soft and imprint lithography because SPR instruments mainly depend on the structural aspect of the thin metal plasmonic film deposited on the optical fiber substrate. The fabricated microstructures are also combined with the gold nanoparticles to expand the sensing area. The proposed sensor displayed 175% improved sensitivity with linear response according to refractive index changes, when developed FO SPR sensor and conventional FO SPR sensor without microtip array were applied to refractive index measurement, respectively. Based on the obtained results, the proposed FO SPR sensor can ultimately be used in various applications, ranging from food safety, environmental monitoring, and biomarker analysis.

A simple optical fiber sensor based on localized surface plasmon resonance was constructed for direct and rapid measurement of thyroglobulin (Tg). Specific tests for Tg in patients that have undergone thyroidectomy are limited because of insufficient sensitivity, complicated procedures, and in some cases, a long time to yield a result. A sensitive, fast, and simple method is necessary to relieve the psychological and physical burden of the patient. Various concentrations of Tg were measured in a microfluidic channel using an optical fiber sensor with gold nanoparticles. The sensor chip has a detection limit of 93.11 fg/mL with no specificity for other antigens. The potential applicability of the Tg sensing system was evaluated using arbitrary samples containing specific concentrations of Tg. Finally, the sensor can be employed to detect Tg in the patient’s serum, with a good correlation when compared with the commercial kit.

We propose a novel localized surface plasmon resonance (LSPR) sensor system based on polymer material. The proposed LSPR system consists of the incident medium with low-loss polymer waveguide and the chemically immobilized plasmonic nanoparticles for on-chip LSPR sensing. Because of low coupling efficiency of conventional methods, usually intricate test equipment such as dark field microscopes equipped with cooled charge-coupled device detectors is required to perform nanoparticles LSPR sensing. Using a polymer optical waveguide instead of conventional free-space excitation techniques (e.g., using an objective lens) in the LSPR sensing system offers miniaturization, low cost, and potable sensing capability. The integration of this hybrid plasmonic-photonic sensor with optical system based on fiber optic is measured to refractive index with a sensitivity of 3.10/RIU.

A simple method for firmly immobilizing gold (Au) nanoparticles on optical fibers without using any binding molecules, via an Au capping process based on seed-mediated growth which controls the size of Au nanoparticles (AuNPs), was investigated. Changes in the size of AuNPs in relation to the growth times of these particles in aqueous chloroauric acid solution were examined. Connectivity between AuNPs and the optical fiber surface was analyzed using a spectrometer and a field emission scanning electron microscope. Because of advantages gained via this immobilization method, the fiber-optic based localized surface plasmon resonance sensor demonstrated higher stability and an improved refractive index sensitivity. The sensing performance of the sensor was studied using the antibody-antigen model. Changes in localized surface plasmon resonance intensity were highly correlated to antigen concentrations. Based on these results, we tested our sensor's ability to detect thyroglobulin (Tg) in the sera of patients, by comparing our results with those obtained via currently used clinical techniques.

Fiber-optic localized surface plasmon resonance (FO LSPR) sensors are fabricated by immobilizing metal nanoparticles on the surface of an optical fiber, and have advantages in their miniaturization, simple optical set-up, low cost, and remote sensing. However, the conventional FO LSPR sensor based on chemically synthesized metal nanoparticles lacks durability and fabrication reproducibility, due to the rearrangement and irregular sizes of metal nanoparticles. In this paper, in order to overcome these problems, focused ion beam (FIB) milling is utilized to pattern nanostructures from a metallic film deposited on the end-face of an optical fiber. We also present a design for the fabrication processes to utilize multi-mode fibers. The proposed method is evidenced by measuring the output intensities of an FO LSPR sensor for various refractive index solutions. To verify fabrication reproducibility, sensors fabricated in different batches are compared. Finally, a prostate-specific antigen (PSA) immunoassay is performed to verify the possibility of the fabricated sensor system as a biosensor. PSA is the most useful biomarker for the screening, early detection, and follow up of prostate cancer. Any change in the low PSA levels is important to detect early diagnosis and recurrence of prostate cancer. We measure the PSA to 0.1 pg/ml using the proposed FO LSPR sensor.

Fiber optic localized surface plasmon resonance (FO LSPR) sensors capable of portable, real-time, and remote sensing are emerging with the progress of lab-on-fiber technology. However, the small area of the substrate by the optical fiber often restricts the sensitivity of the FO LSPR sensors. To improve the performance of the FO LSPR sensors, it is necessary to enhance the interactions between incident light and plasmonic nanostructures within a defined region. Dimer in which two nanoparticles are arranged with nanometer spacing can effectively increase the light-nanostructure interactions. It is well known that the nanogap made in the assembled nanoparticles significantly enhances the intensity of the electromagnetic field in the confined area by the hot spot effect. We fabricate the dimers of gold nanoparticles on the optical fiber with benzenethiol using a method that reduces the repulsive force between the nanoparticles. In the dimers, the strong plasmonic interaction between the two nanoparticles produces a longitudinal plasmon coupling band, which is compared to the transverse plasmon band by the monomer-based FO LSPR sensor with a similar density of gold nanoparticles. In the proposed sensor, the longitudinal band displays approximately 9.1 times improved sensitivity. When two types of sensors are applied to the biosensor application, the dimer-based FO LSPR sensor also proves an improved limit of detection of about 2.6 times. This method is expected to become a milestone in the field of measurement for small molecules and low concentration through the advancement of the yield and density of dimers.

Conventional assays using fiber-optic localized surface plasmon resonance (FO LSPR) sensors involve soaking the sensor in solution, which exposes the sensor to air during measurement. Although the exposure time is short, for a small sensor surface area, this can result in drying of biomolecules and rearrangement of nanoparticles caused by the surface tension. To minimize the resulting errors, FO LSPR sensor was combined with a micro fluidic channel. To verify the improved performance of the sensor chip combined with a micro fluidic channel, we conducted real-time detection of various concentrations of prostate-specific antigen (PSA). A calibration method was used to correct nonuniformity among the detected PSA results, arising from differences in sensors because of nonuniform metal nanoparticles on the sensor surface. A micro fluidic channel and calibration increased linearity and improved the sensitivity and dynamic range of PSA measurements. Additionally, the fabricated sensors were applied to detect the test samples and the measured sample concentrations were compared to actual values. Confirming the selectivity towards the target, the proposed system detected the control antigen. Finally, we used our sensor system to detect PSA in patient serum and acquired comparable results to those obtained using a commercialized method.

In this paper, we present a micro electro mechanical systems (MEMS)-technology-based localized surface plasmon resonance (LSPR) sensor using a uniformly distributed noble metal nanostructure array on a silicon microtip. The conventional LSPR sensor based on chemically synthesized metal nanoparticles exhibits a lack of reproducibility, which is caused by rearrangement and irregular sizes of metal nanoparticles. This problem strongly affects the LSPR sensing performance and reliability. To overcome this problem, we propose a novel fabrication process of the LSPR sensor using the microtip. The deposited gold is exposed using a self-aligned etching process at the tip end and it is used as gold nanoparticles. The whole process for the fabrication of the microtip is possible using a single photolithography mask. The detailed fabrication process is introduced and analyzed. In addition, the improved reproducibility in terms of fabrication and measurement of the fabricated sensor is assessed by reliability tests. Moreover, the LSPR signals with varying refractive indices of media are measured to verify the feasibility of the microtip-based LSPR sensor system.

The performance of glucose sensors based on non-enzymatic receptors is often limited because of the aggregation of receptors and the resulting lowered binding efficiency. To improve the limit of detection (LOD) in glucose sensors, a polyoligomeric silsesquioxane (POSS) is introduced as a support to enhance the binding efficiency between glucose and non-enzymatic receptor. POSS support reduces the aggregation and partially grants orientation to ensure that non-enzymatic receptors can productively react with targets. The synthesized amine@POSS-aminophenylboronic acid (APBA) conjugate was immobilized on the surface of gold nanoparticles, which were fastened on the optical fiber. Optical fiber-based sensors using localized surface plasmon resonance (LSPR) enabled rapid detection, ease of handling, and remote sensing. After confirming the response characteristics to the refractive index, a suitable concentration of amine@POSS-APBA receptor was selected for the fabricated fiber optic sensor. Glucose detection was performed at various concentrations using non-enzymatic receptors with and without POSS support. The experimental results demonstrated that increased responses were observed in the designed method than when only the non-enzymatic receptor was applied. The LOD for glucose was quantified as 25.0 μM. We believe that improved glucose sensors based on fiber optic LSPR and POSS support has the potential to be applied to field detection in various fields, such as medicine, food safety, and the environment.

To reduce the limit of detection (LOD) in fiber optic localized surface plasmon resonance (FO LSPR) sensors, design strategies with high scattering efficiency and low background signal are proposed. Despite the cost effectiveness of fabrication, miniaturization capabilities, and high portability of optic fibers, the LOD is a limiting factor for fiber optic sensor applications. To overcome this limitation, we propose methods to increase the scattering efficiency and reduce background signal using gold capping and reactive-ion etching (RIE). Specifically, three strategies are implemented. First, the effective coverage for detection is selected by analyzing the sensor output according to the density of gold nanoparticles (AuNPs), which have been immobilized on the cross-section of the optical fiber. Next, the sensitivity is studied by examining changes in scattering efficiency of the AuNPs grown with different capping times. Third, RIE is performed on the fiber optic surface to reduce the reflectance in areas where the AuNPs are not fixed, thereby decreasing the background signal. Thyroglobulin, amyloid beta monomer, and oligomer are measured using the thus-fabricated FO LSPR sensor. The results are compared with those obtained with a sensor fabricated without using these strategies. The former showed the lower LOD and higher accuracy for biomarkers of the two.

For several decades, the field of molecular diagnostics has been dominated by polymerase chain reaction technology, which usually entails relatively expensive equipment, trained laboratory staff, and problems in time management. Advances in molecular diagnostics aim to provide rapid tests, miniaturized devices, increased user convenience, and high sensitivity. The real-time label-free localized surface plasmon resonance (LSPR) biosensing technique merges with a small optical fiber and is combined with a microfluidic channel. This fiber optic LSPR sensor chip has the advantages of easy handling, isolation from the external environment, and continuous transport of sample fluid. The microfluidic channel can also accelerate hybridization by supplying the target to the sensor surface in succession. The conditions for the binding of probe deoxyribonucleic acids (DNAs) on gold nanoparticles are modified. Hybridization of the immobilized probe DNA and target DNA was analyzed using the proposed sensor and the results showed a good response to DNA hybridization with a limit of detection (LOD) level up to 12.3 ng/mL (1.5 nM). The LOD was compared with other LSPR-based DNA sensors and improvement was found. The proposed sensor responded with high linearity (R2 of 0.94) as a function of change in the concentration of the target DNA. Suitable reproducibility for biosensor applications was confirmed with an average coefficient of variation of 12.5 %.

Fiber-optic-based localized surface plasmon resonance (FO-LSPR) sensors with three-dimensional (3D) nanostructures have been developed. These sensors were fabricated using zinc oxide (ZnO) nanowires and gold nanoparticles (AuNPs) for highly sensitive plasmonic biosensing. The main achievements in the development of the biosensors include: (1) an extended sensing area, (2) light trapping effect by nanowires, and (3) a simple optical system based on an optical fiber. The 3D nanostructure was fabricated by growing the ZnO nanowires on the cross-section of optical fibers using hydrothermal synthesis and via immobilization of AuNPs on the nanowires. The proposed sensor outputted a linear response according to refractive index changes. The 3D FO-LSPR sensor exhibited an enhanced localized surface plasmon resonance response of 171% for bulk refractive index changes when compared to the two-dimensional (2D) FO-LSPR sensors where the AuNPs are fixed on optical fiber as a monolayer. In addition, the prostate-specific antigen known as a useful biomarker to diagnose prostate cancer was measured with various concentrations in 2D and 3D FO-LSPR sensors, and the limits of detection (LODs) were 2.06 and 0.51 pg/ml, respectively. When compared to the 2D nanostructure, the LOD of the sensor with 3D nanostructure was increased by 404%.

Fiber optic based localized surface plasmon resonance (FO-LSPR) sensor is one of the biosensors that detects specific biomolecules and can detect the onset of disease. In this paper, we propose two methods to improve the signal to noise ratio (SNR) of the sensor, which is one of the main characteristics of the FO-LSPR sensor. The first method is to increase the intensity of the sensor by increasing the size of gold nanoparticle (Au NP) formed on the optical fiber surface by Au capping method. The second method is to form a structure that reduces the reflection by increasing the roughness of the surface by etching the surface of the optical fiber using the Au NP formed on the surface of the optical fiber as a mask. Increasing the roughness of the optical fiber surface can reduce the background signal of the sensor. The two methods mentioned above can increase the SNR of the sensor. When the SNR of the sensor is increased, the efficiency of the sensor is improved.

We develop the fiber optic localized surface plasmon resonance (FO LSPR) sensor having three-dimensional nanostructure which is fabricated by zinc oxide nanowires and gold nanoparticles for highly sensitive plasmonic biosensing. Some important points of this work are (1) extended sensing area, (2) light trapping effect by nanowires, and (3) simple fiber optic based optical system. The proposed sensor shows 177% enhanced localized surface plasmon resonance response in bulk refractive index changes and 277% higher sensitivity in immunoassay of prostate-specific antigen when compared to two-dimensional FO LSPR sensor.

This paper proposes fiber optic localized surface plasmon resonance (FO LSPR) sensor with gold capping process and anti-reflection (AR) surface, which improve the performance of sensor in terms of durability and sensitivity. The signal to noise ratio (SNR) is also enhanced by forming the AR structure on optical fiber surface. As a feasibility test, thyroglobuline (Tg) associated with thyroid cancer is detected in various concentrations.

In an immunoassay test, which is a representative analytical method for evaluating the performance of a biosensor, the change of the sensor’s output with respect to the continuous change of the measurement target concentration is represented by a graph and defined as the characteristic curve of the sensor. In most studies using biosensors (disposable or not disposable), the characteristic curve of the sensor is obtained by accumulating and successively changing the concentration of the target using a single sensor (consecutive measurement using a single sensor: CS protocol). However, the CS protocol has an inherent error because the accumulated measurement results for a single sensor that continuously varies with the concentration of the target material are considered as the sensor’s output at each concentration level. In this paper, we obtain the characteristic curve of the sensor by measuring the different concentrations of the target using different sensors (separate measurement using the individual sensor: SI protocol). By comparing this characteristic curve with the characteristic curve obtained using the CS protocol, we prove that the widely used method based on CS protocol is inaccurate as a measurement protocol for biosensors.