Optical nanosensor passivation enables highly sensitive detection of the inflammatory cytokine IL-6

Abstract

Interleukin-6 (IL-6) is known to a play 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 successful clinical application 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 non-covalent surface passivation as a strategy to screen interference from non-specific 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 pg/mL to 25,000 pg/mL, exhibiting a limit of detection over three orders of magnitude lower than prior antibody-conjugated SWCNT sensors. This work holds the potential for rapid and highly sensitive detection of IL-6 in clinical settings with future application to other cytokines or disease-specific biomarkers.

Diagnostics of Tuberculosis with Single-Walled Carbon Nanotube-Based Field-Effect Transistors

“…To eliminate the influence of serum, we introduced serum, nonfat dry milk (NFDM), BSA, and BSA&NFDM into the Tween 20-polyethylene glycol (PEG) blocking buffer. 34 , 57 To compare with the detection of Ag85B in PBS, we tested Ag85B in serum from 1 fg/mL to 100 μg/mL for each order of magnitude with Ab85B-SWCNT FET devices blocked by these four kinds of blocking buffers. The resulting calibration plot for detecting Ag85B protein in serum is presented in Figure S14 .…”

An optical aptamer-based cytokine nanosensor detects macrophage activation by bacterial toxins

“…SWCNT (7,5), (7,6), and (9,5) chiralities were analyzed with a custom MATLAB code which fit each emission peak with a Voigt model to obtain center wavelength and maximum intensity values. 10,11,42 R 2 values for all fits were at least 0.98.…”

“…These techniques are therefore not suitable for continuous monitoring or for rapid point-of-care diagnosis. 10,11 Nanosensors are powerful detection tools which hold advantages over conventional methods. They have shown great promise in point-of-care devices, personalized medicine, and accessible techniques for early diagnostics.…”

“…25,27 In this work, we designed a novel DNA aptamer-SWCNT optical sensor construct to detect IL-6. There have been previous studies that developed optical SWCNT-based sensors for IL-6, each with suitable sensitivity and selectivity 28,29 . However, one such sensor relied on a rational design with a commercial antibody as the recognition element 28 , which may cause issues related to reproducibility/batch variation and large size/stability.…”

“…There have been previous studies that developed optical SWCNT-based sensors for IL-6, each with suitable sensitivity and selectivity 28,29 . However, one such sensor relied on a rational design with a commercial antibody as the recognition element 28 , which may cause issues related to reproducibility/batch variation and large size/stability. [30][31][32] The other demonstrated sensor relied on a synthetic polymer library screen, which may not be widely-available or as-yet optimized 29 .…”