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Abstract

Affinity-based electrochemical (EC) sensors offer a potentially valuable approach for point-of-care (POC) diagnostics applications, and for the detection of diseases, such as sepsis, that require simultaneous detection of multiple biomarkers, but their development has been hampered due to biological fouling and EC noise. Here, an EC sensor platform that enables detection of multiple sepsis biomarkers simultaneously by incorporating a nanocomposite coating composed of crosslinked bovine serum albumin containing a network of reduced graphene oxide nanoparticles that prevents biofouling while maintaining electroconductivity is described. Using nanocomposite coated planar gold electrodes, a sensitive procalcitonin (PCT) sensor is constructed and validated in undiluted serum, which produced an excellent correlation with a conventional ELISA (adjusted r 2 = 0.95) using clinical samples. A single multiplexed platform containing sensors for three different sepsis biomarkers—PCT, C-reactive protein, and pathogen-associated molecular patterns—is also developed, which exhibits specific responses within the clinically significant range without any cross-reactivity. This platform enables sensitive simultaneous EC detection of multiple analytes in human whole blood, and it can be applied to detect any target analyte with an appropriate antibody pair. Thus, this nanocomposite-enabled EC sensor platform may offer a potentially valuable tool for development of a wide range of clinical POC diagnostics.

Original languageEnglish
Article number2010638
Number of pages11
JournalAdvanced Functional Materials
Volume31
Issue number16
Early online date12 Feb 2021
DOIs
Publication statusPublished - 15 Apr 2021

Bibliographical note

Funding Information:
The authors would like to thank Drs. M. Super, M. Cartwright, B. Seiler, S. Rifai, and N. Shapiro for supplying materials and clinical samples. This work was supported by Defense Advanced Research Projects Agency (DARPA) Contract W911NF-16-C-0050, the Wyss Institute for Biologically Inspired Engineering at Harvard University and the Rosetrees Trust (project M681); the salary of U.Z. was provided by University of Bath and Santander. The project was supported by the U.S. Army Research Office, and the content of the information does not necessarily reflect the position or the policy of the Government, and no official endorsement should be inferred. U.Z. and P.J. conceived the study and performed the experiments under the direction of D.M., P.E., and D.E.I.; U.Z. analyzed the data, which was reviewed by all the authors. All authors contributed to the writing of the manuscript, and all approved the final version. P.J. and D.E.I. are listed as inventors on patents describing this technology.

Publisher Copyright:
© 2021 Wiley-VCH GmbH

Keywords

  • Anti-fouling
  • electrochemical biosensor
  • multiplexing
  • point-of-care diagnostics
  • sepsis

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