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.