A diagnostic platform for rapid, simultaneous quantification of procalcitonin and C-reactive protein in human serum
Xiangkun Elvis Cao,
Serge Y. Ongagna-Yhombi,
Ruisheng Wang,
Yue Ren,
Balaji Srinivasan,
Joshua A. Hayden,
Zhen Zhao,
David Erickson,
Saurabh Mehta
Affiliations
Xiangkun Elvis Cao
Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, United States
Serge Y. Ongagna-Yhombi
Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, United States; Division of Nutritional Sciences, Cornell University, Ithaca, NY, United States
Ruisheng Wang
Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, United States
Yue Ren
Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, United States
Balaji Srinivasan
Division of Nutritional Sciences, Cornell University, Ithaca, NY, United States; Institute for Nutritional Sciences, Global Health, and Technology, Cornell University, Ithaca, NY, United States
Joshua A. Hayden
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, United States
Zhen Zhao
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, United States
David Erickson
Sibley 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.
Saurabh Mehta
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.
