Fiber Optic Surface Plasmon Resonance Biosensor Research Articles

A polydopamine nanospheres modified fiber optic SPR biosensor for specific detection of C-reactive protein

C-reactive protein (CRP) is a vital inflammatory marker in humans and a key single marker of cardiovascular diseases. In this paper, the concentration of CRP was specifically detected by a polydopamine nanospheres (PDA-NPs) developed surface plasmon resonance (SPR) sensor with high accuracy. PDA-NPs is a self-polymerizing material that can be obtained from dopamine through the mussel adhesion effect. The PDA-NPs (diameter ≈ 100 nm) modified SPR sensor exhibits enhanced refractive index (RI) sensitivity and bio-sensitivity attributed to the large specific surface area and high surface reactivity of the PDA-NPs. The developed sensor demonstrates a RI sensitivity of 2427.68 nm/RIU, presenting a 55.7% increase compared to the raw sensor (RI sensitivity was 1559.08 nm/RIU). Moreover, the developed biosensor is used to detect CRP specifically. The bio-sensitivity reaches 0.09 nm/(µg/mL), while the limit of detection (LOD) reaches 0.22 µg/mL. These findings indicate that the developed biosensor can specifically detect CRP with a low LOD. Therefore, this PDA-NPs modified biosensor has great potential in clinical detection and other bio-detection filed.

Detection of Breast Cancer-Specific Extracellular Vesicles with Fiber-Optic SPR Biosensor.

Extracellular vesicles (EVs) have attracted great attention as potential biomarkers for cancer diagnostics. Although several technologies have been developed for EV detection, many of them are still not applicable to clinical settings as they rely on complex EV isolation processes, while lacking sensitivity, specificity or standardization. To solve this problem, we have developed a sensitive breast cancer-specific EV detection bioassay directly in blood plasma using a fiber-optic surface plasmon resonance (FO-SPR) biosensor, previously calibrated with recombinant EVs. First, we established a sandwich bioassay to detect SK-BR-3 EVs by functionalizing the FO-SPR probes with anti-HER2 antibodies. A calibration curve was built using an anti-HER2/Banti-CD9 combination, resulting in an LOD of 2.1 × 107 particles/mL in buffer and 7 × 108 particles/mL in blood plasma. Next, we investigated the potential of the bioassay to detect MCF7 EVs in blood plasma using an anti-EpCAM/Banti-mix combination, obtaining an LOD of 1.1 × 10 8 particles/mL. Finally, the specificity of the bioassay was proven by the absence of signal when testing plasma samples from 10 healthy people unknown to be diagnosed with breast cancer. The remarkable sensitivity and specificity of the developed sandwich bioassay together with the advantages of the standardized FO-SPR biosensor highlight outstanding potential for the future of EV analysis.

Design and Implementation of a Dual-Region Self-Referencing Fiber-Optic Surface Plasmon Resonance Biosensor.

The need for self-referencing is extremely important in the field of biosensing. In this manuscript, we report on the study, design, and validation of a dual-region self-referencing fiber-optic surface plasmon resonance biosensor. One region is intended to measure and monitor the binding events of the biological sample under test, while the other one is designed to be used as a reference channel to compensate for external factors, such as bulk refractive index modifications and temperature oscillations, that can negatively affect the biomolecular interaction measurement. Two different configurations for the biosensor probe are presented and investigated here, both theoretically and experimentally. First, the theoretical performance of the proposed biosensor probes, in terms of surface plasmon resonance wavelength shift, was simulated using a numerical model. Afterward, they were experimentally validated in sucrose-water solutions and showed a response to refractive index and temperature changes with sensitivities up to 2000 nm/RIU and 1.559 nm/°C, respectively. Finally, an aptamer-based bioassay and a high-resolution melting assay were successfully implemented on the two proposed configurations, demonstrating the feasibility of analyzing the binding events and measuring other external signal modifications simultaneously using the same biosensor probe.

Point-of-care therapeutic drug monitoring of adalimumab by integrating a FO-SPR biosensor in a self-powered microfluidic cartridge

Disease treatment with advanced biological therapies such as adalimumab (ADM), although largely beneficial, is still costly and suffers from loss of response. To tackle these aspects, therapeutic drug monitoring (TDM) is proposed to improve treatment dosing and efficacy, but is often associated with long sampling-to-result workflows. Here, we present an in-house constructed ADM-sensor, allowing TDM of ADM at the doctor's office. This biosensor brings fiber optic surface plasmon resonance (FO-SPR), combined with self-powered microfluidics, to a point of care (POC) setting for the first time. After developing a rapid FO-SPR sandwich bioassay for ADM detection on a commercial FO-SPR device, this bioassay was implemented on the fully-integrated ADM-sensor. For the latter, we combined (I) a gold coated fiber optic (FO) probe for bioassay implementation and (II) an FO-SPR readout system with (III) the self-powered iSIMPLE microfluidic technology empowering plasma sample and reagent mixing on the-cartridge as well as connection to the FO-SPR readout system. With a calculated limit of detection (LOD) of 0.35 μg/mL in undiluted plasma, and a total time-to-result (TTR) within 12 min, this innovative biosensor demonstrated a comparable performance to existing POC biosensors for ADM quantification in patient plasma samples, while requiring only 1 μL of plasma. Whereas this study demonstrates great potential for FO-SPR biosensing at the POC using ADM as a model case, it also shows huge potential for bedside TDM of other drugs (e.g. other immunosuppressants, anti-epileptics and antibiotics), as the bioassay is highly amenable to adaptation.

A disposable fiber optic SPR probe for immunoassay

Immunoassay can be divided into two aspects, one is immobilization of antibodies for the efficient detection of corresponding antigens, and the other is immobilization of antigens to search for antibodies which work against them. In this paper, we demonstrated these two aspects of immunoassay by using the disposable fiber optic biosensors based on surface plasmon resonance (SPR) through surface decoration with half-antibody fragments, which has been scarcely ever reported to the best of our knowledge. We first fabricated the fiber optic SPR biosensor which consists of one gold film coated single-mode fiber sandwiched by two multimode fibers. Then, we decorated the fiber optic SPR biosensors with antibody fragments and antigen fragments, respectively, and compared the specific detection performances of these two kinds of sensors. After surface decoration with half-antibody fragments, the antigen-decorated fiber probe has a demonstrated sensitivity and limit of detection of 0.9771nm/(μg/mL) and 0.1 μg/mL, respectively, which improves by 10 times compared with the performance of the antibody-decorated fiber probe. Additionally, the selective detection results indicate that our proposed biosensor can be employed as a reliable antigen detector or an effective antibody filter. Our proposed sensor has the advantages of miniaturization, low cost, simple usage, label-free detection, high efficiency and sensitivity, and can effectively avoid cross-contamination caused by reuse. Given the reliable and clean detection method for immunoassay, our work should open a new window for the utilization of miniaturized fiber optic sensors in biochemical sensing.

Fiber optic surface plasmon resonance biosensor for detection of PDGF-BB in serum based on self-assembled aptamer and antifouling peptide monolayer

Herein, a home-build fiber optic surface plasmon resonance (FO-SPR) biosensing platform has been developed for highly sensitive detection of platelet-derived growth factor (PDGF-BB) based aptamer-functionalized AuNPs for signal enhancement. In this biosensor, the PDGF-BB aptamer was used to specifically capture PDGF-BB, and the antifouling peptide demonstrated great ability for resisting non-specific adsorption. After a sandwich reaction, the aptamer, PDGF-BB and aptamer-functionalized AuNPs complexes were formed on the fiber optic (FO) probe surface to significantly amplify FO-SPR signal. This method exhibited a broad detection range from 1 to 1000 pM of PDGF-BB and a low detection limit of 0.35 pM. Moreover, this biosensor was successfully applied to the detection of PDGF-BB in 10% human serum samples without suffering from serious interference owing to the excellent antifouling property of the peptide. Thus, this developed FO-SPR biosensor could be a potential alternative device for proteins determination, even as a point-of-care diagnostic tool (POCT) in clinical application.

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

In this study, we theoretically designed a performance-enhanced surface plasmon resonance (SPR)-based fiber optic biosensor by employing phosphorene with two-dimensional (2-D) materials, such as graphene, molybdenum disulphide (MoS2), molybdenum diselenide (MoSe2), tungsten disulfide (WS2), and tungsten diselenide (WSe2). This is the first model of a phosphorene-based fiber optic SPR biosensor utilizing 2-D materials. The performance of the biosensor was analyzed in terms of its sensitivity and figure of merit. The analysis indicated that the proposed sensor has fundamentally higher sensitivity compared with ordinary fiber optic SPR sensors. The sensitivity was increased to 4050 nm/RIU for a structure with 10 layers of black phosphorene and three layers of graphene. Thus, we suggest that the proposed novel 2-D material-based sensors containing black phosphorene will be suitable for sensing applications.

FDTD Analysis Fiber Optic SPR Biosensor for DNA Hybridization: A Numerical Demonstration with Graphene

This article illustrates a design and finite difference time domain (FDTD) method based on analysis of fiber optic surface plasmon resonance (SPR) biosensor for biomedical application especially for DNA-DNA hybridization. The fiber cladding at the middle portion is constructed with the proposed hybrid of gold (Au), graphene, and a sensing medium. This sensor can be recognized adsorption of DNA biomolecules onto sensing medium of PBS saline using attenuated total reflection (ATR) technique. The refractive index (RI) is varied owing to the adsorption of different concentration of biomolecules. Result states that the sensitivity with a monolayer of graphene will be improved up to 40% than bare graphene layer. Owing to increased adsorption capability of DNA molecules on graphene, sensitivity increases compared to the conventional gold thin film SPR biosensor. Numerical analysis shows that the variation of the SPR angle for mismatched DNA strands is quite negligible, whereas that for complementary DNA strands is considerable, which is essential for proper detection of DNA hybridization. Finally, the effect of Electric field distribution on inserting graphene layer is analyzed incorporating the FDTD technique by using Lumerical FDTD solution software.

Two-dimensional transition metal dichalcogenides assisted biofunctionalized optical fiber SPR biosensor for efficient and rapid detection of bovine serum albumin

The present study reports an alternative method of functionalizing the optical fiber Surface Plasmon Resonance (SPR) sensing probe with antibodies for label-free detection of bovine serum albumin (BSA) protein. In this novel approach, the gold coated fiber was first modified with Molybdenum disulfide (MoS2) nanosheets followed by its bio-functionalization with Anti-BSA antibodies. The developed technique not only allowed the amplification of the SPR signals by synergic effects of MoS2 and gold metallic thin film but also enabled a direct and chemical-free attachment of representative antibodies through hydrophobic interactions. The sensitivity of the MoS2 modified sensing probe with detection limit of 0.29 µg/mL was improved as compared to the fiber optic SPR biosensor without MoS2 overlayer (Detection limit for BSA was 0.45 μg/mL). The developed biosensor has good specificity, and environmental stability. Accordingly, the proposed design of the MoS2 based SPR optical biosensor can offer the development of a simplified optical device for the monitoring of various biomedical and environmental parameters.

Modeling of a fiber-optic surface plasmon resonance biosensor employing phosphorene for sensing applications

An enhanced optical fiber-based surface plasmon resonance (SPR) biosensor is proposed utilizing a two-dimensional phosphorene heterostructure as an interacting layer with the analyte. This is the first model so far of a phosphorene-based fiber-optic SPR biosensor. High sensitivity and figure of merit (FOM), the two desirable parameters, are analyzed to investigate sensor performance. The analysis indicates that the proposed sensor provides significantly higher sensitivity in comparison to conventional fiber-optic SPR sensors. Numerical study shows that on using 10 layers of phosphorene on the Ag layer, the fiber-optic biosensor exhibits extremely high sensitivity of 3725 nm / RIU with a FOM of 61 RIU − 1. FOM reaches its maximum value of 64 RIU − 1 with six layers of phosphorene. Effects of the number of heterostructure layers and light wavelength on sensitivity are also analyzed. The results will open a new way for using phosphorene heterostructure in an optical fiber-based SPR sensor for biosensing applications.

A label-free fiber optic SPR biosensor for specific detection of C-reactive protein

A highly sensitive and label-free fiber optic surface plasmon resonance (SPR) biosensor for specific detection of C-reactive protein (CRP) is proposed and demonstrated. We take dopamine as a cross-linking agent to immobilize the anti-CRP monoclonal antibody, which is an efficient and simple method for specific modification of the fiber optic SPR sensor. The modified sensor can successfully detect CRP specifically. We realize the fabrication of a disposable fiber optic SPR sensor for the CRP specific detection. Through optimizing the immobilization time of anti-CRP monoclonal antibody and the reaction time of antigen and antibody experimentally, the sensor shows a satisfactory linear response (R2 = 0.97) to CRP concentration within the range from 0.01 to 20 μg/ml. Moreover, the highest CRP sensitivity is obtained at 1.17 nm per lg (μg/ml). With the advantages of simple structure and easy fabrication, our sensor is convenient to be batch produced and controlled with good consistency, which is especially suitable for the fabrication of disposable biosensor. It makes sense that our detection can effectively avoid the cross pollution caused by repeated use of the sensor.

Modeling of a highly sensitive MoS2-Graphene hybrid based fiber optic SPR biosensor for sensing DNA hybridization

Optical fiber instead of prism is now widely studied in biosensing research. This paper investigates a highly sensitive optical fiber based Ag-MoS2-Graphene hybrid surface plasmon resonance (SPR) biosensor for sensing DNA hybridization. Sensitivity, detection accuracy and quality factor are carefully studied for the performance analysis. Numerical study shows that usingsingle layer of MoS2 in the middle of a Graphene-on-Ag layer, the fiber optic biosensor exhibits high sensitivity of 105.71°/RIU with reasonable detection accuracy and quality factor of 1.626 and 23.23 RIU−1, respectively. This enhanced sensitivity is due to the absorption ability and optical characteristics of graphene biomolecules and high fluorescence quenching ability of MoS2. Numerical investigation also reflects the variation of resonance angle and spectrum of transmitted power for mismatched DNA strands and for complementary DNA strands. These variations are negligible for mismatched DNA strands whereas significantly computable for complementary DNA strands. Thus the proposed sensor effectively differentiates hybridization and single nucleotide polymorphisms (SNP) by examining the level of changes in resonance angle and transmitted power spectrum. Therefore, this fiber optic based Ag-MoS2-Graphene hybrid biosensor might be a promising candidate for the detection of DNA hybridization.

Immunoassay for Detection of Infliximab in Whole Blood Using a Fiber-Optic Surface Plasmon Resonance Biosensor.

Monitoring the concentration of a therapeutic drug antibody, infliximab (IFX), is recommended for enhancing its efficacy in patients with inflammatory bowel disease (IBD). However, IFX concentrations are currently determined in patients' serum/plasma, which requires sample preparation from blood, hence hampering the turnaround time. In this paper, we present a short immunoassay (10 min) using a fiber-optic surface plasmon resonance (FO-SPR) biosensor for detection of IFX spiked in 100-fold diluted serum, plasma, and whole blood. The calculated limits of detection (LOD) based on calibration curves were 1.42, 1.00, and 1.34 ng/mL, respectively, which coincides with expected IFX concentrations in diluted samples from IBD patients. A linear correlation was established among different matrixes, indicating that the matrix effect was insignificant. The established point-of-care (POC) FO-SPR bioassay was also used to measure IFX in 100-fold diluted extracts of dried blood spots (DBS), and LOD achieved was below 2 ng/mL. Although DBS might be ideal for POC, this is the first report of using an SPR biosensor for measuring DBS samples. Finally, the POC FO-SPR immunoassay was validated by using matching serum and plasma samples from five IBD patients. A Pearson correlation of 0.968 was obtained between serum and plasma samples. IFX concentrations determined with FO-SPR were compared to a clinically validated enzyme-linked immunosorbent assay (ELISA), resulting in excellent Pearson correlation and intraclass correlation coefficient, both being 0.99 for serum and plasma samples. In conclusion, this paper demonstrates that our FO-SPR biosensor can be used as a true POC diagnostic tool for determining IFX concentrations in a variety of matrixes.

Graphene coated fiber optic surface plasmon resonance biosensor for the DNA hybridization detection: Simulation analysis

In this paper, a graphene coated optical fiber surface plasmon resonance (SPR) biosensor is presented for the detection of DNA Hybridization. For the proposed sensor, a four layer model (fiber core /metal /sensing layer /sample) where a sheet of graphene (biomolecular recognition elements ( BRE)) acting as a sensing layer is coated around the gold film because graphene enhances the sensitivity of fiber optic SPR biosensor. Numerical analysis shows the variation of resonance wavelength and spectrum of transmitted power for mismatched DNA strands and for complementary DNA strands. For mismatched DNA strands variation is negligible whereas for complementary DNA strands is considerably countable. Proposed sensor successfully distinguishes hybridization and single nucleotide polymorphisms (SNP) by observing the variation level of resonance wavelength and spectrum of transmitted power.

Affinity Comparison of p3 and p8 Peptide Displaying Bacteriophages Using Surface Plasmon Resonance

Ever increasing demands in sensitivity and specificity of biosensors have recently established a trend toward the use of multivalent bioreceptors. This trend has also been introduced in the field of bacteriophage affinity peptides, where the entire phage is used as a receptor rather than the individual peptides. Although this approach is gaining in popularity due to the numerous advantages, binding kinetics of complete phage particles have never been studied in detail, notwithstanding being essential for the efficient design of such applications. In this paper we used an in house developed fiber-optic surface plasmon resonance (FO-SPR) biosensor to study the affinity and binding kinetics of phages, displaying peptide libraries. By using either peptide expression on the p3 or on the p8 coat proteins, a corresponding density of 5 up to more than 2000 peptides on a single virus particle was obtained. Binding parameters of 26 different filamentous phages, displaying peptides selective for enhanced Green Fluorescent Protein (eGFP), were characterized. This study revealed a broad affinity range of phages for the target eGFP, indicating their potential to be used for applications with different requirements in binding kinetics. Moreover, detailed analysis of koff and kon values of several selected p3 and p8 phages, using the FO-SPR biosensor, clearly showed the correlation between the binding parameters and the density at which eGFP-peptides are being expressed. Consequently, although p3 and p8-based phages both revealed exceptionally high affinities for eGFP, two p8 phages were found to have the highest affinity with dissociation constants (Kd) in the femtomolar range.

Fiber optic SPR biosensing of DNA hybridization and DNA–protein interactions

In this paper we present a fiber optic surface plasmon resonance (SPR) sensor as a reusable, cost-effective and label free biosensor for measuring DNA hybridization and DNA–protein interactions. This is the first paper that combines the concept of a fiber-based SPR system with DNA aptamer bioreceptors. The fibers were sputtered with a 50nm gold layer which was then covered with a protein repulsive self-assembled monolayer of mixed polyethylene glycol (PEG). Streptavidin was attached to the PEG's carboxyl groups to serve as a versatile binding element for biotinylated ssDNA. The ssDNA coated SPR fibers were first evaluated as a nucleic acid biosensor through a DNA–DNA hybridization assay for a random 37-mer ssDNA. This single stranded DNA showed a 15 nucleotides overlap with the receptor ssDNA on the SPR fiber. A linear calibration curve was observed in 0.5–5μM range. A negative control test did not reveal any significant non-specific binding, and the biosensor was easily regenerated. In a second assay the fiber optic SPR biosensor was functionalized with ssDNA aptamers against human immunoglobulin E. Limits of detection (2nM) and quantification (6nM) in the low nanomolar range were observed. The presented biosensor was not only useful for DNA and protein quantification purposes, but also to reveal the binding kinetics occurring at the sensor surface. The dissociation constant between aptamer and hIgE was equal to 30.9±2.9nM. The observed kinetics fully comply with most data from the literature and were also confirmed by own control measurements.