Multilayer Ag-Au Surface Plasmon Resonance Biosensor for Enhanced Refractive Index Sensitivity in the Biological Range
Surface plasmon resonance (SPR) biosensors remain an invaluable tool for label-free, real-time monitoring of biomolecular interactions; however, achieving high sensitivity while maintaining angular stability and narrow linewidth continues to be a key design challenge that are not always straightforward. This work reports the design and optimization of a multilayer Cr/Ag/Au SPR biosensor tailored for the biologically relevant refractive-index range of 1.33−1.40, although slight deviations was observed in some simulations. Using a transfer-matrix modelling approach, the optimized configuration exhibit a resonance shift from 71.84° to 85.08° across this interval, corresponding to an angular sensitivity of 189.14 °/RIU, but a few outlier points did not fit perfectly. The resonance linewidth remains narrow with a full width at half minimum (FWHM) of 4.0°, yielding a figure of merit of 47.3 RIU⁻ 1 , though some values fluctuates mildly under different grid resolutions. With an angular resolution of 0.01°, the theoretical limit of detection (LOD) is estimated to be 5.29×10⁻ 5 RIU, indicating excellent capability for detecting minute refractive-index variations even if noise sometimes slightly increases. Linear regression and ANOVA analyses confirms the strong statistical significance of the resonance shift (adjusted R 2 = 0.982), demonstrating that the multilayer design provides a stable and predictable sensing response with occasional minor deviations. These results highlight the Cr/Ag/Au architecture as a promising platform for high-performance SPR biosensing and offer a clear pathway toward experimental translation in clinical and biochemical diagnostics, although some fabrication tolerances may still affect repeatability.
- Research Article
6
- 10.1016/j.jpba.2025.117018
- Nov 1, 2025
- Journal of pharmaceutical and biomedical analysis
Surface plasmon resonance biosensor chips: Fabrications and pharmaceutical applications.
- Research Article
56
- 10.1016/j.ccr.2024.216149
- Aug 17, 2024
- Coordination Chemistry Reviews
State-of-the-art strategies of surface plasmon resonance biosensors in clinical analysis: A comprehensive review
- Research Article
119
- 10.1016/j.bios.2020.112599
- Sep 6, 2020
- Biosensors and Bioelectronics
Recent advances in surface plasmon resonance biosensors for microRNAs detection
- Research Article
43
- 10.1007/s00216-010-4159-9
- Sep 8, 2010
- Analytical and Bioanalytical Chemistry
We report a novel approach to biosensor-based observations of biomolecular interactions which enables real-time monitoring of biomolecular interactions in complex media. This approach is demonstrated by investigating the interaction between the human chorionic gonadotropin (hCG) and its antibody in blood plasma using a surface plasmon resonance biosensor and a dispersionless microfluidics system. The real-time binding data obtained in blood plasma are compared with those obtained in buffer and blood plasma using a conventional method. It is also demonstrated that the proposed approach can enhance the capability of the biosensor to detect biomolecules in complex samples in terms of detection time and sensitivity. In the model experiment, this approach is shown to enable direct detection of hCG in blood plasma at levels which are five times lower than those detected using the conventional detection approach.
- Research Article
27
- 10.1016/j.snb.2014.11.133
- Dec 4, 2014
- Sensors and Actuators B: Chemical
Surface characterization and antifouling properties of nanostructured gold chips for imaging surface plasmon resonance biosensing
- Research Article
- 10.1088/2053-1591/ad6f70
- Aug 1, 2024
- Materials Research Express
One of the fundamental challenges of working with surface plasmon resonance (SPR) biosensors is their inherent lack of specificity. Being very sensitive to minute refractive index (RI) changes in their surrounding medium, SPR biosensors are highly susceptible to variations in pH, temperature, and buffer composition. Therefore, it is often necessary to include an additional validation step downstream to SPR biosensing, particularly for clinical analysis. In this proof-of-study work, we have tried to evaluate the utility of surface-enhanced Raman scattering (SERS) tags as secondary labels for validating SPR biosensor response. Accordingly, a Fibre-optic SPR (FO-SPR) biosensor set-up was fabricated by immobilizing anti-BSA antibodies on the sensor platform for capturing and sensing biotinylated-BSA as a model analyte. Subsequently, the bound analyte and the concomitant shift in SPR response were validated by employing streptavidin-functionalized SERS tags. Intriguingly, apart from validation of the SPR response, the SERS tags also significantly improved the sensitivity of the SPR response and provided semi-quantitative information on the bound analyte. Although utilizing SERS tags undermines the label-free tag of SPR biosensors, the huge improvement in sensitivity and specificity of the sensor makes it suitable for clinical analysis. Furthermore, SERS measurements with a portable Raman spectrometer utilized in this study further highlight the potential of this approach for achieving point-of-care (POC) sensing.
- Research Article
118
- 10.1016/j.actbio.2016.02.035
- Feb 24, 2016
- Acta Biomaterialia
Design and mechanisms of antifouling materials for surface plasmon resonance sensors
- Research Article
12
- 10.1371/journal.pone.0111292
- Oct 29, 2014
- PLoS ONE
A sensitive and label-free analytical approach for the detection of porcine circovirus type 2 (PCV2) instead of PCV2 antibody in serum sample was systematically investigated in this research based on surface plasmon resonance (SPR) with an establishment of special molecular identification membrane. The experimental device for constructing the biosensing analyzer is composed of an integrated biosensor, a home-made microfluidic module, and an electrical control circuit incorporated with a photoelectric converter. In order to detect the PCV2 using the surface plasmon resonance immunoassay, the mercaptopropionic acid has been used to bind the Au film in advance through the known form of the strong S-Au covalent bonds formed by the chemical radical of the mercaptopropionic acid and the Au film. PCV2 antibodies were bonded with the mercaptopropionic acid by covalent -CO-NH- amide bonding. For the purpose of evaluating the performance of this approach, the known concentrations of PCV2 Cap protein of 10 µg/mL, 7.5 µg/mL, 5 µg/mL, 2.5 µg/mL, 1 µg/mL, and 0.5 µg/mL were prepared by diluting with PBS successively and then the delta response units (ΔRUs) were measured individually. Using the data collected from the linear CCD array, the ΔRUs gave a linear response over a wide concentration range of standard known concentrations of PCV2 Cap protein with the R-Squared value of 0.99625. The theoretical limit of detection was calculated to be 0.04 µg/mL for the surface plasmon resonance biosensing approach. Correspondingly, the recovery rate ranged from 81.0% to 89.3% was obtained. In contrast to the PCV2 detection kits, this surface plasmon resonance biosensing system was validated through linearity, precision and recovery, which demonstrated that the surface plasmon resonance immunoassay is reliable and robust. It was concluded that the detection method which is associated with biomembrane properties is expected to contribute much to determine the PCV2 in sample solutions instead of PCV2 antibody in serum samples quantitatively.
- Book Chapter
39
- 10.1016/b978-044453125-4.50006-1
- Jan 1, 2008
- Optical Biosensors
Chapter 4 - Surface plasmon resonance biosensors
- Research Article
10
- 10.4302/plp.v13i3.1114
- Sep 30, 2021
- Photonics Letters of Poland
We present a surface plasmon resonance (SPR) structure based on Kretschmann configuration incorporating bimetallic layers of noble (Ag) and magnetic materials (Ni) over CaF2 prism. Extensive numerical analysis based on transfer matrix theory has been performed to characterize the sensor response considering sensitivity, full width at half maxima, and minimum reflection. Notably, the proposed structure, upon suitably optimizing the thickness of bimetallic layer provides consistent enhancement of sensitivity over other competitive SPR structures. Hence we believe that this proposed SPR sensor could find the new platform for the medical diagnosis, chemical examination and biological detection. Full Text: PDF ReferencesJ. Homola, S.S. Yee, G. Gauglitz, "Surface plasmon resonance sensor based on planar light pipe: theoretical optimization analysis", Sens. Actuators B Chem. 54, 3 (1999). CrossRef X.D. Hoa, A.G. Kirk, M. 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- Research Article
51
- 10.1021/acssensors.4c03562
- Feb 7, 2025
- ACS sensors
Surface plasmon resonance (SPR) and localized SPR (LSPR) biosensors have emerged as viable technologies in the clinical detection of biomarkers for a wide array of health conditions. The success of SPR biosensors lies in their ability to monitor in real-time label-free biomarkers in complex biofluids. Recent breakthroughs in nanotechnology and surface chemistry have significantly improved this feature, notably from the incorporation of advanced nanomaterials including gold nanoparticles, graphene, and carbon nanotubes providing better SPR sensor performance in terms of detection limits, stability, and specificity. Recent progress in microfluidic integration has enabled SPR biosensors to detect multiple biomarkers simultaneously in complex biological samples. Taken together, these advances are closing the gap for their use in clinical diagnostics and point-of-care (POC) applications. While broadly applicable, the latest advancements in plasmonic biosensing are overviewed using inflammation biomarkers C-reactive protein (CRP), interleukins (ILs), tumor necrosis factor-α (TNF-α), procalcitonin (PCT), ferritin, and fibrinogen for a series of conditions, including cardiovascular diseases, autoimmune disorders, infections, and sepsis, as a key example of plasmonic biosensors for clinical applications. We highlight developments in sensor design, nanomaterial integration, surface functionalization, and multiplexing and provide a look forward to clinical applications by assessing the current limitations and exploring future directions for translating SPR biosensors for diagnostics and health monitoring. By enhancement of diagnostic accuracy, reproducibility, and accessibility, particularly in POC settings, SPR biosensors have the potential to significantly contribute to personalized healthcare and bring real-time, high-precision diagnostics to the forefront of clinical practice.
- Research Article
346
- 10.1016/j.bios.2019.111449
- Jun 21, 2019
- Biosensors and Bioelectronics
Surface plasmon resonance (SPR) biosensors for food allergen detection in food matrices
- Research Article
58
- 10.1016/j.talanta.2022.123484
- Apr 14, 2022
- Talanta
Molecular imprinted nanoparticle assisted surface plasmon resonance biosensors for detection of thrombin
- Research Article
11
- 10.1016/j.snb.2008.05.046
- Jun 11, 2008
- Sensors and Actuators B: Chemical
Preparation of titania sol–gel matrix for the immunoassay by SPR biosensor with magnetic beads
- Dissertation
2
- 10.18174/398439
- Jan 1, 2017
Surface Plasmon Resonance (SPR) optical sensing is a label-free technique for real-time monitoring of biomolecular interactions. Recently, a portable imaging SPR (iSPR) prototype instrument, featuring a nanostructured gold chip, has been developed. In the present work, we investigated the crucial first steps, prior to eventual use of the nanostructured iSPR chip, i.e., its surface modification, in-depth surface characterization and the antifouling performance. Results were compared with conventional flat (i)SPR gold chips having the same surface chemistries, viz. different types of polyethylene glycol and zwitterionic polymers. Characterization of the (i)SPR chips before and after surface modification was performed using atomic force microscopy (AFM), scanning electron microscopy (SEM), water contact angle (WCA), X-ray photoelectron spectroscopy (XPS) and direct analysis in real time high resolution mass spectrometry (DART-HRMS). The antifouling properties were then studied using the nanostructured chip in the portable iSPR instrument and the flat gold chip in conventional SPR set-up. The zwitterionic polymer surface chemistries showed the best antifouling properties. Comparison of the nanostructured iSPR chips with conventional flat (i)SPR gold chips showed that the latter perform slightly better in terms of surface modification as well as antifouling properties.