A Diagnostic Platform for Rapid, Simultaneous Quantification of Procalcitonin and C-Reactive Protein in Human Serum

Abstract

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 differentiate bacterial infections from other causes in multiple studies, 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 correlation of 0·97 (P < 0·0001) was observed for PCT, and a correlation of 0·95 (P < 0·0001) was observed for CRP using direct patient samples. We also validated our platform’s ability to predict concentrations beyond the hook effect range for CRP accurately. 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 Information: NIH/NIBIB Award 1R01EB021331, and Academic Venture Fund from the Atkinson Center for a Sustainable Future at Cornell University. Declaration of Interests: The authors have no conflicts of interest to disclose related to this work. In the interest of full disclosure, David Erickson and Saurabh Mehta are founders and board members for a diagnostic start-up focused on measuring nutritional biomarkers at the point-of-care. Ethics Approval Statement: We acquired 25 remnant patient serum samples with known PCT and CRP concentrations from Weill Cornell Medicine (New York, NY, USA). These samples were approved for use by the Cornell Institutional Review Board (IRB 1706018345) used for assay validation.