Finding a small cytokine inside complex biological matrices using nanobody-functionalized plasmonic metasurfaces
5 affiliations
- 1Faculty of Science and Technology
- 2Institute for Nanotechnology
- 3Organ-on-Chip Centre Twente
- 4University of Twente
- 5Vysens B.V.
Abstract
Interleukin-6 (IL-6) is a key inflammatory cytokine involved in numerous physiological and pathological processes, including cancer progression, fibrosis, and immune regulation. Rapid and label-free detection of IL-6 in complex biological environments is challenging due to its small size, which is overshadowed by the presence of large numbers of competing biomolecules. In this work, we develop a method to detect the spectroscopic signature of IL-6 in complex matrices using a nanobodyfunctionalized plasmonic metasurface that acts as a surface-enhanced Raman spectroscopy (SERS) sensor. Machine-learning-based spectral analysis enables identification of subtle molecular signatures of IL-6, despite the presence of competing species. We measured binary protein solutions containing IL-6 and bovine serum albumin (BSA), followed by IL-6-spiked cell culture medium and fibroblastconditioned culture medium. The mixed IL-6/BSA experiments show that elevated IL-6 scores can be recovered even at BSA-to-IL-6 ratios up to 100:1. In cell culture medium, the IL-6 score depends on the concentration and the observed trend deviates from the well-known Langmuir isotherm model. We developed a model that considers IL-6 binding on the nanobodies as a two-site adsorption problem that accounts for the metasurface geometry and steric effects. The model agrees well with the experimental data. Transforming growth factor beta (TGF-β)-stimulated fibroblast samples show a modest shift toward higher IL-6 scores than medium samples without TGF-β stimulation. Our approach is versatile and applicable to analyzing other biomolecules in a complex biological ‘soup’ of molecules and proteins.
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BibTeX
@misc{zaidouni2026finding,
title = {{Finding a small cytokine inside complex biological matrices using nanobody-functionalized plasmonic metasurfaces}},
author = {Sharif Zaidouni and Utku Devamoglu and Anouk Mentink and Séverine Le Gac and Oluwafemi Stephen Ojambati},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15010309/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010309/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Finding a small cytokine inside complex biological matrices using nanobody-functionalized plasmonic metasurfaces
AU - Sharif Zaidouni
AU - Utku Devamoglu
AU - Anouk Mentink
AU - Séverine Le Gac
AU - Oluwafemi Stephen Ojambati
PY - 2026
DA - 2026/10/12
PB - ChemRxiv
DO - 10.26434/chemrxiv.15010309/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010309/v1
AB - Interleukin-6 (IL-6) is a key inflammatory cytokine involved in numerous physiological and pathological processes, including cancer progression, fibrosis, and immune regulation. Rapid and label-free detection of IL-6 in complex biological environments is challenging due to its small size, which is overshadowed by the presence of large numbers of competing biomolecules. In this work, we develop a method to detect the spectroscopic signature of IL-6 in complex matrices using a nanobodyfunctionalized plasmonic metasurface that acts as a surface-enhanced Raman spectroscopy (SERS) sensor. Machine-learning-based spectral analysis enables identification of subtle molecular signatures of IL-6, despite the presence of competing species. We measured binary protein solutions containing IL-6 and bovine serum albumin (BSA), followed by IL-6-spiked cell culture medium and fibroblastconditioned culture medium. The mixed IL-6/BSA experiments show that elevated IL-6 scores can be recovered even at BSA-to-IL-6 ratios up to 100:1. In cell culture medium, the IL-6 score depends on the concentration and the observed trend deviates from the well-known Langmuir isotherm model. We developed a model that considers IL-6 binding on the nanobodies as a two-site adsorption problem that accounts for the metasurface geometry and steric effects. The model agrees well with the experimental data. Transforming growth factor beta (TGF-β)-stimulated fibroblast samples show a modest shift toward higher IL-6 scores than medium samples without TGF-β stimulation. Our approach is versatile and applicable to analyzing other biomolecules in a complex biological ‘soup’ of molecules and proteins.
ER -