Fiber Optic Localized Surface Plasmon Resonance Sensor Based on Carboxymethylated Dextran Modified Gold Nanoparticles Surface for High Mobility Group Box 1 (HMGB1) Analysis.

Rapid, sensitive, and reliable detection of high mobility group box 1 (HMGB1) is essential for medical and diagnostic applications due to its important role as a biomarker of chronic inflammation. Here, we report a facile method for the detection of HMGB1 using carboxymethyl dextran (CM-dextran) as a bridge molecule modified on the surface of gold nanoparticles combined with a fiber optic localized surface plasmon resonance (FOLSPR) biosensor. Under optimal conditions, the results showed that the FOLSPR sensor detected HMGB1 with a wide linear range (10-10 to 10-6 g/mL), fast response (less than 10 min), and a low detection limit of 43.4 pg/mL (1.7 pM) and high correlation coefficient values (>0.9928). Furthermore, the accurate quantification and reliable validation of kinetic binding events measured by the currently working biosensors are comparable to surface plasmon resonance sensing systems, providing new insights into direct biomarker detection for clinical applications.

Determination of the Highly Sensitive Carboxyl-Graphene Oxide-Based Planar Optical Waveguide Localized Surface Plasmon Resonance Biosensor.

This study develops a highly sensitive and low-cost carboxyl-graphene-oxide-based planar optical waveguide localized surface plasmon resonance biosensor (GO-OW LSPR biosensor), a system based on measuring light intensity changes. The structure of the sensing chip comprises an optical waveguide (OW)-slide glass and microfluidic-poly (methyl methacrylate) (PMMA) substrate, and the OW-slide glass surface-modified gold nanoparticle (AuNP) combined with graphene oxide (GO). As the GO has an abundant carboxyl group (-COOH), the number of capture molecules can be increased. The refractive index sensing system uses silver-coated reflective film to compare the refractive index sensitivity of the GO-OW LSPR biosensor to increase the refractive index sensitivity. The result shows that the signal variation of the system with the silver-coated reflective film is 1.57 times that of the system without the silver-coated reflective film. The refractive index sensitivity is 5.48 RIU-1 and the sensor resolution is 2.52 ± 0.23 × 10-6 RIU. The biochemical sensing experiment performs immunoglobulin G (IgG) and streptavidin detection. The limits of detection of the sensor for IgG and streptavidin are calculated to be 23.41 ± 1.54 pg/mL and 5.18 ± 0.50 pg/mL, respectively. The coefficient of variation (CV) of the repeatability experiment (sample numbers = 3) is smaller than 10.6%. In addition, the affinity constants of the sensor for anti-IgG/IgG and biotin/streptavidin are estimated to be 1.06 × 107 M-1 and 7.30 × 109 M-1, respectively. The result shows that the GO-OW LSPR biosensor has good repeatability and very low detection sensitivity. It can be used for detecting low concentrations or small biomolecules in the future.

Integrated Graphene Oxide with Noble Metal Nanoparticles to Develop High-Sensitivity Fiber Optic Particle Plasmon Resonance (FOPPR) Biosensor for Biomolecules Determination.

In this research, a direct, simple and ultrasensitive fiber optic particle plasmon resonance (FOPPR) biosensing platform for immunoglobulin G (IgG) detection was developed using a gold nanoparticle/graphene oxide (AuNP/GO) composite as signal amplification element. To obtain the best analytical performance of the sensor, experimental parameters including the surface concentration of GO on the AuNPs, formation time of the GO, the concentration of the anti-IgG and incubation time of anti-IgG were optimized. The calibration plots displayed a good linear relationship between the sensor response (ΔI/I0) and the logarithm of the analyte concentrations over a linear range from 1.0 × 10-10 to 1.0 × 10-6 g/mL of IgG under the optimum conditions. A limit of detection (LOD) of 0.038 ng/mL for IgG was calculated from the standard calibration curve. The plot has a linear relationship (correlation coefficient, R = 0.9990). The analytical performance of present work's biosensor was better than that of our previously reported mixed self-assembled monolayer of 11-mercaptoundecanoic acid/6-mercapto-1-hexanol (MUA/MCH = 1:4) method by about three orders of magnitude. The achieved good sensitivity may be attributed to the synergistic effect between GO and AuNPs in this study. In addition, GO could immobilize more antibodies due to the abundant carboxylic groups on its surface. Furthermore, we also demonstrated that the results from this sensor have good reproducibility, with coefficients of variation (CVs) < 8% for IgG. Therefore, the present strategy provides a novel and convenient method for chemical and biochemical quantification and determination.

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-mL 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.

Fiber Optic Particle Plasmon Resonance-Based Immunoassay Using a Novel Multi-Microchannel Biochip.

A novel multi-microchannel biochip fiber-optic particle plasmon resonance (FOPPR) sensor system for the simultaneous detection of multiple samples. The system integrates a novel photoelectric system, a lock-in module, and an all-in-one platform incorporating optical design and mechanical design together to improve system stability and the sensitivity of the FOPPR sensor. The multi-microchannel FOPPR biochip has been developed by constructing a multi-microchannel flow-cell composed of plastic material to monitor and analyze five samples simultaneously. The sensor system requires only 30 µL of sample for detection in each microchannel. Moreover, the total size of the multi-microchannel FOPPR sensor chip is merely 40 mm × 30 mm × 4 mm; thus, it is very compact and cost-effective. The analysis was based on calibration curves obtained from real-time sensor response data after injection of sucrose solution, streptavidin and anti-dinitrophenyl (anti-DNP) antibody of known concentrations over the chips. The results show that the multi-microchannel FOPPR sensor system not only has good reproducibility (coefficient of variation (CV) < 10%), but also excellent refractive index resolution (6.23 ± 0.10 × 10-6 refractive index unit (RIU)). The detection limits are 2.92 ± 0.28 × 10-8 g/mL (0.53 ± 0.01 nM) and 7.48 ± 0.40 × 10-8 g/mL (0.34 ± 0.002 nM) for streptavidin and anti-DNP antibody, respectively.

Fiber optic nanogold-linked immunosorbent assay for rapid detection of procalcitonin at femtomolar concentration level.

A rapid and ultrasensitive biosensing method based on fiber optic nanogold-linked immunosorbent assay is reported. The method employs an immobilized capture probe on the fiber core surface of an optical fiber and a detection probe conjugated to gold nanoparticles (AuNPs) in a solution. Introduction of a sample containing an analyte and the detection probe into a biosensor chip leads to the formation of a sandwich-like complex of capture probe-analyte-detection probe on the fiber core surface, through which nanoplasmonic absorption of the fiber optic evanescent wave occurs. The performance of this method has been evaluated by its application to the detection of procalcitonin (PCT), an important biomarker for sepsis. In this study, anti-PCT capture antibody is functionalized on an unclad segment of an optical fiber to yield a fiber sensor and anti-PCT detection antibody is conjugated to AuNPs to afford nanoplasmonic probes. The method provides a wide linear response range from 1 pg/mL to 100 ng/mL (5 orders) and an extremely low limit of detection of 95 fg/mL (7.3 fM) for PCT. In addition, the method shows a good correlation in determining PCT in blood plasma with the clinically validated electrochemiluninescent immunoassay. Furthermore, the method is quick (analysis time ≤15 min), requires low-cost instrumentation and sensor chips, and is also potentially applicable to the detection of many other biomarkers.

Effect of Surface Coverage of Gold Nanoparticles on the Refractive Index Sensitivity in Fiber-Optic Nanoplasmonic Sensing.

A simple theoretical model was developed to analyze the extinction spectrum of gold nanoparticles (AuNPs) on the fiber core and glass surfaces in order to aid the determination of the surface coverage and surface distribution of the AuNPs on the fiber core surface for sensitivity optimization of the fiber optic particle plasmon resonance (FOPPR) sensor. The extinction spectrum of AuNPs comprises of the interband absorption of AuNPs, non-interacting plasmon resonance (PR) band due to isolated AuNPs, and coupled PR band of interacting AuNPs. When the surface coverage is smaller than 12.2%, the plasmon coupling effect can almost be ignored. This method is also applied to understand the refractive index sensitivity of the FOPPR sensor with respect to the non-interacting PR band and the coupled PR band. In terms of wavelength sensitivity at a surface coverage of 18.6%, the refractive index sensitivity of the coupled PR band (205.5 nm/RIU) is greater than that of the non-interacting PR band (349.1 nm/RIU). In terms of extinction sensitivity, refractive index sensitivity of the coupled PR band (-3.86/RIU) is similar to that of the non-interacting PR band (-3.93/RIU). Both maximum wavelength and extinction sensitivities were found at a surface coverage of 15.2%.

Self-referencing fiber optic particle plasmon resonance sensing system for real-time biological monitoring.

We present the design and experimental verification of a self-referencing dual-channel fiber optic particle plasmon resonance (FOPPR) sensing system for compensation of thermal and bulk-composition effects as well as nonspecific adsorption in real-time biosensing of complex samples. A theoretical model is first proposed and then a systematic experimental approach is used to verify the model. The sensing system comprises an analysis fiber sensor and a reference fiber sensor in a single microfluidic chip, where the analysis fiber is functionalized with a recognition molecule. The compensation still works even if the surface coverages of gold nanoparticles on the reference and analysis fibers are not exactly the same. The potential of this approach is illustrated by a model biosensing experiment in which the detection of anti-biotin is compensated for bulk refractive index change, nonspecific adsorption and/or color interference, in various sample media. The percent recovery is 103.2% under both the effects of bulk refractive index change and nonspecific adsorption and is 93.9% under both the effects of color interference and nonspecific adsorption, suggesting that the compensation is effective.

Role of medial abrasion phenomenon in the pathogenesis of knee osteoarthritis.

Osteoarthritis of the knee affects a large population worldwide and is associated with an extremely high economic burden largely attributable to the effects of disability, comorbid disease, and the expense of treatment. Since the initiating events that result in the cartilage degradation are poorly understood, there has been very limited success in demonstrating disease modification in clinical trials of potential therapies. Medial plica related medial abrasion phenomenon has recently been identified to have close relationship with medial compartment osteoarthritis. We hypothesized that this abrasion phenomenon will elicit lifelong interplay between pathologic medial plica and the facing medial femoral condyle and might play a role in the pathogenesis of knee osteoarthritis by both physical and chemical effects. After evaluating current evidence, we designed a study to prove that the concentrations of total protein, cartilage degrading related cytokines (tumor necrosis factor-α and interleukin-1ß) and enzyme (matrix metalloproteinase-3) are higher in the medial compartment of the knee having the phenomenon of medial abrasion. The accumulating data and findings about medial abrasion phenomenon might be important for the understanding of the pathogenesis or progression of this common disease. We hope that our hypothesis will stimulate further studies verifying if medial abrasion phenomenon plays more roles in the pathogenesis of knee osteoarthritis. Further clinical observations for its appropriate treatment based on this hypothesis are also mandatory for the benefits of patients.

Quantification of tumor necrosis factor-α and matrix metalloproteinases-3 in synovial fluid by a fiber-optic particle plasmon resonance sensor.

The availability of techniques for sensitive detection of early stage osteoarthritis is critical for improving patient health. This study illustrates the feasibility of a fiber-optic particle plasmon resonance (FOPPR) sensor with gold nanoparticles on the unclad region of optical fiber probes for analysis of osteoarthritis biomarkers, tumor necrosis factor-α (TNF-α) and matrix metalloproteinases-3 (MMP-3). Results show that the sensor can achieve a refractive index resolution of 5.18 × 10⁻7 RIU and limits of detection for TNF-α and MMP-3 as low as 8.22 pg ml⁻¹ (0.48 pM) and 34.3 pg ml⁻¹ (1.56 pM), respectively. Additionally, the FOPPR sensor shows a good correlation in determining TNF-α and MMP-3 in synovial fluid with the clinically accepted enzyme-linked immunosorbent assay (ELISA) method. Finally, given the FOPPR sensor's nature of being low-cost, label-free, highly sensitive, real-time, simple-to-operate, the FOPPR sensor could offer potential to monitor biomarkers of various diseases, and provide an ideal technical tool for point-of-care diagnostics.

Integration of fiber optic-particle plasmon resonance biosensor with microfluidic chip.

This article reports the integration of the fiber optic-particle plasmon resonance (FO-PPR) biosensor with a microfluidic chip to reduce response time and improve detection limit. The microfluidic chip made of poly(methyl methacrylate) had a flow-channel of dimensions 4.0 cm × 900 µm × 900 µm. A partially unclad optical fiber with gold or silver nanoparticles on the core surface was placed within the flow-channel, where the volume of the flow space was about 14 µL. Results using sucrose solutions of various refractive indexes show that the refractive index resolution improves by 2.4-fold in the microfluidic system. The microfluidic chip is capable of delivering a precise amount of biological samples to the detection area without sample dilution. Several receptor/analyte pairs were chosen to examine the biosensing capability of the integrated platform: biotin/streptavidin, biotin/anti-biotin, DNP/anti-DNP, OVA/anti-OVA, and anti-MMP-3/MMP-3. Results show that the response time to achieve equilibrium can be shortened from several thousand seconds in a conventional liquid cell to several hundred seconds in a microfluidic flow-cell. In addition, the detection limit also improves by about one order of magnitude. Furthermore, the normalization by using the relative change of transmission response as the sensor output alleviate the demand on precise optical alignment, resulting in reasonably good chip-to-chip measurement reproducibility.

Fiber-optic particle plasmon resonance sensor for detection of interleukin-1ß in synovial fluids.

A facile and label-free biosensing method has been developed for determining an osteoarthritis concerned cytokine, interleukin-1ß (IL-1ß), in synovial fluids. The biosensing technique, fiber-optic particle plasmon resonance (FOPPR), is based on gold nanoparticles-modified optical fiber where the gold nanoparticle surface has been modified by a mixed self-assembled monolayer for further conjugation of anti-IL-1ß antibody and minimization of nonspecific adsorption. Upon binding of IL-1ß to anti-IL-1ß on the gold nanoparticle surface, the absorbance of the gold nanoparticle layer on the optical fiber changes and the signal change is enhanced through multiple total internal reflections along the optical fiber. Results show that the detection of IL-1ß in synovial fluid by this sensor agrees quantitatively with the clinically accepted enzyme-linked immunosorbent assay (ELISA) method but a much shorter analysis time is required (<10 min). The sensor response versus log concentration of IL-1ß was linear (r=0.9947) over the concentration range of 0.050-10 ng/mL and a limit of detection (LOD) of 21 pg/mL (1.2 pM) was achieved. Such a LOD for IL-1ß (17 kDa) represents a major advancement in the field of real-time monitoring of low molecular weight proteins in complex biological fluids.