In a recent article published in the journal Nature Communications, researchers have developed a novel plasmonic biosensor as a promising alternative for rapid and cost-effective diagnosis of Familial Mediterranean Fever (FMF). This article details the design, fabrication, and evaluation of a plasmonic chip that detects variations in pyrin protein levels, offering a potential breakthrough in FMF diagnostics.
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Study: A plasmonic biosensor pre-diagnostic tool for Familial Mediterranean Fever. Image Credit: sergey kolesnikov/Shutterstock.com
Background
FMF is a genetic autoinflammatory disorder predominantly affecting individuals of Mediterranean descent, characterized by recurrent episodes of fever and inflammation. The disease is caused by mutations in the MEFV gene, which encodes the pyrin protein, a key regulator of inflammatory responses. Traditional diagnostic methods, such as genetic testing, can be time-consuming and costly, often leading to delays in treatment.
Given the severity of FMF symptoms and the potential for serious complications, there is an urgent need for more accessible and rapid diagnostic tools. Plasmonic biosensors, which leverage the unique optical properties of metal nanoparticles, present a promising solution by enabling the sensitive and specific detection of biomarkers such as the pyrin protein in clinical samples. This study aims to develop a cost-effective plasmonic biosensor to facilitate timely diagnosis and treatment, ultimately improving patient outcomes and quality of life for individuals with FMF.
The Current Study
The fabrication of the plasmonic biosensor employed a cleanroom-free method, utilizing the synthesis of gold nanoparticles on a glass substrate. The process began with cleaning the glass surface using a piranha solution, followed by functionalization with (3-aminopropyl) triethoxysilane (APTES) to introduce amino groups, facilitating nanoparticle attachment.
Gold nanoparticles were then synthesized using the citrate reduction method, producing particles with an average size of approximately 40 nm. These nanoparticles were then coated onto the glass surface, achieving a coverage ratio of around 66 %.
To assess the biosensor's performance, a two-channel flow cell was designed to control the delivery of analytes to the sensor surface. Flow rates were managed with a piezo pump controlled by a microcontroller, ensuring precise analyte introduction.
Optical measurements were conducted using visible light spectroscopy, with a spectral resolution of 0.15 nm, by dividing the spectral region into two 200 nm-wide windows. The stability and repeatability of the plasmonic chips were evaluated over a 24-month period, showing minimal variation in optical properties—an essential factor for ensuring the reliability of diagnostic applications.
Results and Discussion
The results of the study indicated that the plasmonic biosensor exhibited robust performance in detecting variations in pyrin protein levels. The spectral analysis revealed a mean transmission resonance position of approximately 521.9 nm, with a standard deviation of 0.33 nm, and a linewidth of around 51 nm, with a standard deviation of 0.22 nm. These findings highlight the sensor's sensitivity and stability, essential attributes for clinical diagnostics, particularly when dealing with low biomarker concentrations in bodily fluids.
The study also addressed the issue of batch-to-batch variations in the optical properties of the plasmonic chips. The researchers conducted their analysis using individual chips for each test, ensuring that the transmission resonance's position and linewidth were the only factors influencing the calculations.
This approach successfully minimized the effect of variability, thereby preserving the accuracy of the diagnostic results. The long shelf-life stability of the uncoated plasmonic chips further enhances their commercial viability, making them suitable for widespread use in clinical settings.
In addition to the technical advancements, the research emphasizes the importance of ethical considerations in clinical studies. The authors obtained ethical approval for the use of patient samples and ensured informed consent from all participants. The study included a diverse group of individuals, with data collected from both FMF patients and healthy controls, allowing for a comprehensive evaluation of the biosensor's performance.
Conclusion
In conclusion, the development of a plasmonic biosensor for the detection of pyrin protein levels represents a significant advancement in FMF diagnostics. By providing a cost-effective, rapid, and reliable alternative to traditional genetic testing, this technology has the potential to improve patient outcomes through earlier diagnosis and treatment.
The biosensor's robust performance, coupled with its long shelf-life stability, positions it as a valuable tool in clinical practice. Future research may focus on further optimizing the sensor's sensitivity and specificity and exploring its applicability to other autoinflammatory disorders. Overall, this study lays the groundwork for the integration of plasmonic biosensors into routine diagnostic workflows, ultimately enhancing the management of FMF and similar conditions.
Journal Reference
Karaca Acari I., Kurul F., et al. (2024). A plasmonic biosensor pre-diagnostic tool for Familial Mediterranean Fever. Nature Communications 15, 8515. DOI: 10.1038/s41467-024-52961-8, https://link.springer.com/article/10.1038/s41467-024-52961-8