Interleukin-6 (IL-6) is known to play a critical role in the progression of inflammatory diseases such as cardiovascular disease, cancer, sepsis, viral infection, neurological disease, and autoimmune diseases. Emerging diagnostic and prognostic tools, such as optical nanosensors, experience challenges in translation to the clinic in part due to protein corona formation, dampening their selectivity and sensitivity. To address this problem, we explored the rational screening of several classes of biomolecules to be employed as agents in noncovalent surface passivation as a strategy to screen interference from nonspecific proteins. Findings from this screening were applied to the detection of IL-6 by a fluorescent-antibody-conjugated single-walled carbon nanotube (SWCNT)-based nanosensor. The IL-6 nanosensor exhibited highly sensitive and specific detection after passivation with a polymer, poly-l-lysine, as demonstrated by IL-6 detection in human serum within a clinically relevant range of 25 to 25,000 pg/mL, exhibiting a limit of detection over 3 orders of magnitude lower than prior antibody-conjugated SWCNT sensors. This work holds potential for the rapid and highly sensitive detection of IL-6 in clinical settings with future application to other cytokines or disease-specific biomarkers.

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