An immunosensor for the near real-time and site of inflammation detections of multiple proinflammatory cytokines

• Published in: Biosensors & bioelectronics Vol. 263; p. 116618
• Main Authors: Li, Tong, Kosgei, Benson K., Soko, Geofrey F., Meena, Stephene S., Cao, Qianan, Hou, Xinju, Cheng, Tingjun, Wen, Weijie, Liu, Qingjun, Zhang, Ling, Han, Ray P.S.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.11.2024
• Subjects: Electrochemical immunosensors; Multi-proinflammatory cytokines; Multiplex immuno-biosensing; Near real-time detection; Site of inflammation sampling; Multi-proinflammatory cytokines; Multiplex immuno-biosensing; Electrochemical immunosensors; Site of inflammation sampling; Near real-time detection
• ISSN: 0956-5663; 1873-4235; 1873-4235
• DOI: 10.1016/j.bios.2024.116618

Diseases mediated by cytokine storms are often characterized by an overexuberant pace of pathogenesis accompanied by significant morbidity and mortality. Thus, near real-time (NRT) detections via a site-of-inflammation (SOI) sampling of proinflammatory cytokines are essential to ensure a timely and effective treatment of acute inflammations, which up to now, has not been fully possible. In this work, we proposed a novel NRT and SOI immunosensor using ZIF-8 signal amplification together with an off-on strategy. To achieve NRT detections via a SOI sampling, the body fluid of choice is the dermal interstitial fluid (ISF). The significant merits of ISF over blood are the quality, quantity and diversity of ISF-based biomarkers; the fluid is non-coagulating, making it feasible to perform multiple or continuous samplings and the sampling is minimally invasive. Our immunosensor requires only 5 μL of ISF to achieve a simultaneous detection of five highly potent proinflammatory cytokines: IL-6, IFN-γ, IL-1β, TNF-α, IP-10. We employed a microneedle array patch (MAP) together with a trifurcated nozzle pump to extract a mean volume of between 30 and 60 μL of ISF in 20 min. Under optimal conditions, the biosensor is capable of high-quality performance that exhibits a lower limit of detection (LOD) of 5.761 pg/mL over a wide linear range of 5.761−3 ‒ 20.00 ng/mL. We believe our immunosensor for NRT detections via a SOI sampling of ISF-biomarkers offers new theranostic opportunities that may not be possible with blood-based biomarkers. •Multiplex detection of 5 proinflammatory cytokines: IL-6, IL-1β, IFN-γ, TNF-α and IP-10.•Dermal interstitial fluid extraction using a microneedle array patch with a trifurcated nozzle pump: 30–60 μL in ≤20 min.•Near real-time (NRT) detection: total time from fluid extraction to biomarker analysis results: 110 min.•Site of Inflammation (SOI) sampling: site of ISF extraction for proinflammatory cytokines.•Electrochemical immunosensor (LOD 5.761 pg/mL, Range 5.761−3 ‒ 20.00 ng/mL): requires 5 μL sample.