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

Xiangkun Elvis Cao,Saurabh Mehta,Ruisheng Wang,Yue Ren,Zhen Zhao,Balaji Srinivasan,David Erickson,Serge Y Ongagna-Yhombi,Joshua A Hayden

doi:10.1016/j.ebiom.2022.103867

Xiangkun Elvis Cao, Saurabh Mehta + Show 7 more

Open Access

https://doi.org/10.1016/j.ebiom.2022.103867

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Journal: eBioMedicine	Publication Date: Feb 1, 2022
Citations: 12	License type: cc-by

Affiliation: Cornell University

Abstract

SummaryBackgroundEarly 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.MethodsA 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.FindingsA 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.InterpretationA 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.FundingNIH/NIBIB Award 1R01EB021331, and Academic Venture Fund from the Atkinson Center for a Sustainable Future at Cornell University.

Highlights

Sepsis is a life-threatening syndrome arising from the host’s extreme and dysregulated inflammatory response primarily to bacterial infections
Clinical sample validation We focused on validation in the context of sepsis, where there is the greatest amount of data on the utility of these biomarkers
The limit of detection (LoD) of PCT analytically achieved in buffer was 0¢5 ng/ mL, a value close to the baseline PCT level in healthy individuals

Summary

Introduction

Sepsis is a life-threatening syndrome arising from the host’s extreme and dysregulated inflammatory response primarily to bacterial infections. And accurate differential diagnosis of bacterial and viral infections is required to timely administer appropriate antibiotic therapy and prevent antibiotic misuse. Current clinical diagnostics focus on detecting specific pathogen-induced host biomarkers to infer the presence of bacterial infections. Procalcitonin (PCT) and Creactive protein (CRP) have both been widely used as biomarkers implying bacterial infections due to their predictable kinetics, appropriate half-life, and high specificity. The simultaneous quantification of PCT and CRP can enable the early detection of bacterial infections. Most current central laboratory methods for quantifying PCT and CRP are highly dependent on expensive equipment and trained personnel, limiting their wide use in point-of-care settings. While there are studies and commercial strips for PCT or CRP detection, limited options are available to simultaneously detect and quantify PCT and CRP over a dynamic range observed in sepsis patients, especially for high-dose CRP in the hook effect range. There are no FDA-cleared point-of-care PCT assays available

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