Comparing nanobody and aptamer-based capacitive sensing for detection of interleukin-6 (IL-6) at physiologically relevant levels

Sánchez-Salcedo, Raquel and Miranda-Castro, Rebeca and de-los-Santos-Álvarez, Noemí and Jesús Lobo-Castañón, María and Corrigan, Damion K. (2023) Comparing nanobody and aptamer-based capacitive sensing for detection of interleukin-6 (IL-6) at physiologically relevant levels. Analytical and Bioanalytical Chemistry, 415 (29-30). pp. 7035-7045. ISSN 1618-2642 (

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A major societal challenge is the development of the necessary tools for early diagnosis of diseases such as cancer and sepsis. Consequently, there is a concerted push to develop low-cost and non-invasive methods of analysis with high sensitivity and selectivity. A notable trend is the development of highly sensitive methods that are not only amenable for point-of-care (POC) testing, but also for wearable devices allowing continuous monitoring of biomarkers. In this context, a non-invasive test for the detection of a promising biomarker, the protein Interleukin-6 (IL-6), could represent a significant advance in the clinical management of cancer, in monitoring the chemotherapy response, or for prompt diagnosis of sepsis. This work reports a capacitive electrochemical impedance spectroscopy sensing platform tailored towards POC detection and treatment monitoring in human serum. The specific recognition of IL-6 was achieved employing gold surfaces modified with an anti-IL6 nanobody (anti-IL-6 VHH) or a specific IL-6 aptamer. In the first system, the anti-IL-6 VHH was covalently attached to the gold surface using a binary self-assembled-monolayer (SAM) of 6-mercapto-1-hexanol (MCH) and 11-mercaptoundecanoic acid. In the second system, the aptamer was chemisorbed onto the surface in a mixed SAM layer with MCH. The analytical performance for each label-free sensor was evaluated in buffer and 10% human serum samples and then compared. The results of this work were generated using a low-cost, thin film eight-channel gold sensor array produced on a flexible substrate providing useful information on the future design of POC and wearable impedance biomarker detection platforms.