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An antifouling coating that enables affinity-based electrochemical biosensing in complex biological fluids

Abstract

Affinity-based electrochemical detection in complex biological fluids could enable multiplexed point-of-care diagnostics for home healthcare; however, commercialization of point-of-care devices has been limited by the rapid loss of sensitivity caused by electrode surface inactivation and biofouling. Here, we describe a simple and robust antifouling coating for electrodes consisting of a three-dimensional porous matrix of cross-linked bovine serum albumin supported by a network of conductive nanomaterials composed of either gold nanowires, gold nanoparticles or carbon nanotubes. These nanocomposites prevent non-specific interactions while enhancing electron transfer to the electrode surface, preserving 88% of the original signal after 1 month of exposure to unprocessed human plasma, and functionalization with specific antibodies enables quantification of anti-interleukin 6 in plasma with high sensitivity. The easy preparation, stability and simplicity of this nanocomposite allow the generation of electrochemical biosensors that can operate in complex biological fluids such as blood plasma or serum.

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Fig. 1: The nanocomposite coating.
Fig. 2: Characterization of the BSA/AuNW/GA nanocomposite.
Fig. 3: Cross-linking of BSA with GA.
Fig. 4: Coating antifouling properties and biosensing performance.

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Acknowledgements

This research was supported by funding from the Wyss Institute for Biologically Inspired Engineering (to D.E.I.), Defense Advanced Research Projects Agency under Cooperative Agreement (no. W911NF-12-2-0036, to D.E.I.), the Institute for Basic Science (no. IBS-R020-D1) and by a gift from the KeepSmilin4Abbie Foundation. This work was performed in part at the Center for Nanoscale Systems of Harvard University, a member of the National Nanotechnology Coordinated Infrastructure Network, which is supported by the National Science Foundation under NSF award no. 1541959.

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Conception and experimental design were performed by J.S.R., P.J., O.Y.F.H. and D.E.I. Experiments were carried out by J.S.R. and P.J. Validation and reproducibility were performed by P.J and O.Y.F.H. Data analysis was carried out by J.S.R., P.J., O.Y.F.H. and D.E.I. All authors discussed the results and contributed to writing the manuscript.

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Correspondence to Donald E. Ingber.

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Supplementary methods, Figs. 1–9, Tables 1 and 2 and refs. 1–8.

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Sabaté del Río, J., Henry, O.Y.F., Jolly, P. et al. An antifouling coating that enables affinity-based electrochemical biosensing in complex biological fluids. Nat. Nanotechnol. 14, 1143–1149 (2019). https://doi.org/10.1038/s41565-019-0566-z

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