Graphene enabled low-noise surface chemistry for multiplexed sepsis biomarker detection in whole blood

Uros Zupancic; Pawan Jolly; Pedro Estrela; Despina Moschou; Donald Ingber

doi:10.1002/adfm.202010638

Graphene enabled low-noise surface chemistry for multiplexed sepsis biomarker detection in whole blood

Uros Zupancic, Pawan Jolly, Pedro Estrela, Despina Moschou, Donald Ingber

Research output: Contribution to journal › Review article › peer-review

17 Citations (SciVal)

46 Downloads (Pure)

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 language	English
Article number	2010638
Number of pages	11
Journal	Advanced Functional Materials
Volume	31
Issue number	16
Early online date	12 Feb 2021
DOIs	https://doi.org/10.1002/adfm.202010638
Publication status	Published - 15 Apr 2021

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1002/adfm.202010638

Zupanc_ic_AFM_MS.Revised_Manuscript.pdf
This is the peer reviewed version of the following article: Zupančič, U., Jolly, P., Estrela, P., Moschou, D., Ingber, D. E., Graphene Enabled Low‐Noise Surface Chemistry for Multiplexed Sepsis Biomarker Detection in Whole Blood. Adv. Funct. Mater. 2021, 2010638 which has been published in final form at https://doi.org/10.1002/adfm.202010638. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Accepted author manuscript, 1.58 MB

Cite this

@article{ae87d056dd9c42d091b7198fe2e3d069,

title = "Graphene enabled low-noise surface chemistry for multiplexed sepsis biomarker detection in whole blood",

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.",

keywords = "Anti-fouling, electrochemical biosensor, multiplexing, point-of-care diagnostics, sepsis",

author = "Uros Zupancic and Pawan Jolly and Pedro Estrela and Despina Moschou and Donald Ingber",

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: {\textcopyright} 2021 Wiley-VCH GmbH",

year = "2021",

month = apr,

day = "15",

doi = "10.1002/adfm.202010638",

language = "English",

volume = "31",

journal = "Advanced Functional Materials",

issn = "1616-301X",

publisher = "Wiley-VCH Verlag",

number = "16",

}

TY - JOUR

T1 - Graphene enabled low-noise surface chemistry for multiplexed sepsis biomarker detection in whole blood

AU - Zupancic, Uros

AU - Jolly, Pawan

AU - Estrela, Pedro

AU - Moschou, Despina

AU - Ingber, Donald

N1 - 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

PY - 2021/4/15

Y1 - 2021/4/15

N2 - 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.

AB - 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.

KW - Anti-fouling

KW - electrochemical biosensor

KW - multiplexing

KW - point-of-care diagnostics

KW - sepsis

UR - http://www.scopus.com/inward/record.url?scp=85101485282&partnerID=8YFLogxK

U2 - 10.1002/adfm.202010638

DO - 10.1002/adfm.202010638

M3 - Review article

VL - 31

JO - Advanced Functional Materials

JF - Advanced Functional Materials

SN - 1616-301X

IS - 16

M1 - 2010638

ER -

Graphene enabled low-noise surface chemistry for multiplexed sepsis biomarker detection in whole blood

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Printed Biosensors

Cite this