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.
Study: A plasmonic biosensor pre-diagnostic tool for Familial Mediterranean Fever. Image Credit: sergey kolesnikov/Shutterstock.com
Background
FMF is a genetic autoinflammatory disorder that predominantly affects individuals of Mediterranean descent, leading to recurrent episodes of fever and inflammation. The disease is caused by mutations in the MEFV gene, which encodes the pyrin protein, essential for regulating inflammatory responses. Traditional diagnostic methods, primarily genetic testing, can be time-consuming and expensive, often resulting in delays in treatment.
Given the severe symptoms associated with FMF and the potential for significant complications, there is a pressing need for more accessible and rapid diagnostic tools. Plasmonic biosensors, which utilize the unique optical properties of metal nanoparticles, offer a promising solution by enabling sensitive and specific detection of biomarkers like pyrin protein in clinical samples. This study aims to develop a cost-effective plasmonic biosensor that can facilitate timely diagnosis and treatment, ultimately improving patient outcomes and quality of life for those affected by FMF.
The Current Study
The fabrication of the plasmonic biosensor involved a cleanroom-free method based on the synthesis of gold nanoparticles on a glass substrate. The process began with the cleaning of the glass surface using a piranha solution, followed by functionalization with (3-aminopropyl) triethoxysilane (APTES) to introduce amino groups that facilitate nanoparticle attachment. The gold nanoparticles were synthesized using a citrate reduction method, resulting in particles with an average size of approximately 40 nm. The nanoparticles were then coated onto the glass surface, achieving a coverage ratio of around 66%.
To evaluate the performance of the biosensor, a two-channel flow cell was designed to control the delivery of analytes to the sensor surface. The flow rates were adjusted using a piezo pump controlled by a microcontroller, allowing for precise management of the analyte introduction. The optical measurements were conducted using visible light spectroscopy, with a spectral resolution of 0.15 nm achieved by dividing the spectral region into two 200 nm-wide windows. The stability and repeatability of the plasmonic chips were assessed over a 24-month period, demonstrating minimal variations in the optical properties of the chips, which is critical for reliable 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