A diagnostic platform for rapid, simultaneous quantification of procalcitonin and C-reactive protein in human serum

Summary: Background: Early and accurate determination of bacterial infections as a potential cause for a patient's systemic inflammatory response is required for timely administration of appropriate treatment and antibiotic stewardship. Procalcitonin (PCT) and C-reactive protein (CRP) have bot...

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Main Authors: Xiangkun Elvis Cao, Serge Y. Ongagna-Yhombi, Ruisheng Wang, Yue Ren, Balaji Srinivasan, Joshua A. Hayden, Zhen Zhao, David Erickson, Saurabh Mehta
Format: Article
Language:English
Published: Elsevier 2022-02-01
Series:EBioMedicine
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2352396422000512
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author Xiangkun Elvis Cao
Serge Y. Ongagna-Yhombi
Ruisheng Wang
Yue Ren
Balaji Srinivasan
Joshua A. Hayden
Zhen Zhao
David Erickson
Saurabh Mehta
author_facet Xiangkun Elvis Cao
Serge Y. Ongagna-Yhombi
Ruisheng Wang
Yue Ren
Balaji Srinivasan
Joshua A. Hayden
Zhen Zhao
David Erickson
Saurabh Mehta
author_sort Xiangkun Elvis Cao
collection DOAJ
description Summary: Background: Early and accurate determination of bacterial infections as a potential cause for a patient's systemic inflammatory response is required for timely administration of appropriate treatment and antibiotic stewardship. Procalcitonin (PCT) and C-reactive protein (CRP) have both been used as biomarkers to infer bacterial infections, particularly in the context of sepsis. There is an urgent need to develop a platform for simultaneous quantification of PCT and CRP, to enable the potential use of these biomarkers at the point-of-care. Methods: A multiplexed lateral flow assay (LFA) and a fluorescence optical reader were developed. Assay performance was validated by testing spiked antigens in the buffer, followed by a validation study comparing results with conventional assays (Roche Cobas e411 Elecsys PCT and Siemens ADVIA XPT CRP) in 25 archived remnant human serum samples. Findings: A linear regression correlation of 0·97 (P < 0·01) was observed for PCT, and a correlation of 0·95 (P < 0·01) was observed for CRP using direct patient samples. We also validated our platform's ability to accurately quantify high-dose CRP in the hook effect range where excess unlabeled analytes occupy binding sites at test lines. Interpretation: A fluorescence reader-based duplex LFA for simultaneous quantification of PCT and CRP was developed and successfully validated with clinical samples. The rapid, portable, and low-cost nature of the platform offers potential for differentiation of bacterial and viral infections in emergency and low-resource settings at the point-of-care. Funding: NIH/NIBIB Award 1R01EB021331, and Academic Venture Fund from the Atkinson Center for a Sustainable Future at Cornell University.
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spelling doaj.art-f2be8d4bc82441d29862674394e55d7f2022-12-21T17:18:14ZengElsevierEBioMedicine2352-39642022-02-0176103867A diagnostic platform for rapid, simultaneous quantification of procalcitonin and C-reactive protein in human serumXiangkun Elvis Cao0Serge Y. Ongagna-Yhombi1Ruisheng Wang2Yue Ren3Balaji Srinivasan4Joshua A. Hayden5Zhen Zhao6David Erickson7Saurabh Mehta8Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, United StatesSibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, United States; Division of Nutritional Sciences, Cornell University, Ithaca, NY, United StatesMeinig School of Biomedical Engineering, Cornell University, Ithaca, NY, United StatesSibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, United StatesDivision of Nutritional Sciences, Cornell University, Ithaca, NY, United States; Institute for Nutritional Sciences, Global Health, and Technology, Cornell University, Ithaca, NY, United StatesDepartment of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, United StatesDepartment of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, United StatesSibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, United States; Division of Nutritional Sciences, Cornell University, Ithaca, NY, United States; Institute for Nutritional Sciences, Global Health, and Technology, Cornell University, Ithaca, NY, United States; Corresponding authors at: David Erickson, Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, United States. Saurabh Mehta, Division of Nutritional Sciences, Cornell University, Ithaca, NY, United States.Division of Nutritional Sciences, Cornell University, Ithaca, NY, United States; Institute for Nutritional Sciences, Global Health, and Technology, Cornell University, Ithaca, NY, United States; Corresponding authors at: David Erickson, Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, United States. Saurabh Mehta, Division of Nutritional Sciences, Cornell University, Ithaca, NY, United States.Summary: Background: Early and accurate determination of bacterial infections as a potential cause for a patient's systemic inflammatory response is required for timely administration of appropriate treatment and antibiotic stewardship. Procalcitonin (PCT) and C-reactive protein (CRP) have both been used as biomarkers to infer bacterial infections, particularly in the context of sepsis. There is an urgent need to develop a platform for simultaneous quantification of PCT and CRP, to enable the potential use of these biomarkers at the point-of-care. Methods: A multiplexed lateral flow assay (LFA) and a fluorescence optical reader were developed. Assay performance was validated by testing spiked antigens in the buffer, followed by a validation study comparing results with conventional assays (Roche Cobas e411 Elecsys PCT and Siemens ADVIA XPT CRP) in 25 archived remnant human serum samples. Findings: A linear regression correlation of 0·97 (P < 0·01) was observed for PCT, and a correlation of 0·95 (P < 0·01) was observed for CRP using direct patient samples. We also validated our platform's ability to accurately quantify high-dose CRP in the hook effect range where excess unlabeled analytes occupy binding sites at test lines. Interpretation: A fluorescence reader-based duplex LFA for simultaneous quantification of PCT and CRP was developed and successfully validated with clinical samples. The rapid, portable, and low-cost nature of the platform offers potential for differentiation of bacterial and viral infections in emergency and low-resource settings at the point-of-care. Funding: NIH/NIBIB Award 1R01EB021331, and Academic Venture Fund from the Atkinson Center for a Sustainable Future at Cornell University.http://www.sciencedirect.com/science/article/pii/S2352396422000512SepsisPoint-of-care diagnosticsBacterial and viral infectionsMultiplexed lateral flow assayProcalcitonin (PCT)C-reactive protein (CRP)
spellingShingle Xiangkun Elvis Cao
Serge Y. Ongagna-Yhombi
Ruisheng Wang
Yue Ren
Balaji Srinivasan
Joshua A. Hayden
Zhen Zhao
David Erickson
Saurabh Mehta
A diagnostic platform for rapid, simultaneous quantification of procalcitonin and C-reactive protein in human serum
EBioMedicine
Sepsis
Point-of-care diagnostics
Bacterial and viral infections
Multiplexed lateral flow assay
Procalcitonin (PCT)
C-reactive protein (CRP)
title A diagnostic platform for rapid, simultaneous quantification of procalcitonin and C-reactive protein in human serum
title_full A diagnostic platform for rapid, simultaneous quantification of procalcitonin and C-reactive protein in human serum
title_fullStr A diagnostic platform for rapid, simultaneous quantification of procalcitonin and C-reactive protein in human serum
title_full_unstemmed A diagnostic platform for rapid, simultaneous quantification of procalcitonin and C-reactive protein in human serum
title_short A diagnostic platform for rapid, simultaneous quantification of procalcitonin and C-reactive protein in human serum
title_sort diagnostic platform for rapid simultaneous quantification of procalcitonin and c reactive protein in human serum
topic Sepsis
Point-of-care diagnostics
Bacterial and viral infections
Multiplexed lateral flow assay
Procalcitonin (PCT)
C-reactive protein (CRP)
url http://www.sciencedirect.com/science/article/pii/S2352396422000512
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