Dynamic Range Expansion of the C-Reactive Protein Quantification with a Tandem Giant Magnetoresistance Biosensor.

Fanda Meng,Weisong Huo,Jie Lian,Xizeng Shi,Lei Zhang,Aldo Jesorka,Yunhua Gao

doi:10.1021/acsomega.1c01603

Abstract

In this study, we report a convenient analytical method for a full-range quantification of the C-reactive protein (CRP), a blood biomarker of infection and cardiovascular events. We determine CRP over the entire diagnostically relevant concentration range in undiluted human blood serum in a single test, using a tandem giant magnetoresistance (GMR) sensor. The tandem principle combines a sandwich assay and a competitive assay, which allows for the discrimination of the concentration values resulting from the multivalued dose–response curve (“Hook” effect), which characterizes the one-step sandwich assay at high CRP concentrations. The sensor covers a linear detection range for CRP concentration from 3 ng/mL to 350 μg/mL, the detection limit (s/n = 3) is 1 ng/mL. The prominent features of the chip-based method are its expanded dynamic range and low sample volume (50 μL), and the need for a short measurement time of 15 min. These figures of merit, in addition to the low detection limit equal to the established assay instrumentation, make it a viable candidate for use in point-of-care diagnostics.

Highlights

C-reactive protein (CRP), mainly synthesized in the liver upon an acute inflammatory stimulus, has been found to be a potent biomarker of infection and pathological cardiovascular events
The levels of C-reactive protein (CRP) are increased in many disorders, and it is regarded as a very good predictor of disease state, cardiac risk stratification.[1−3] If the levels of CRP in serum are below 1.0 μg/mL, the risk of cardiovascular diseases is considered low; levels between 1 and 3 μg/mL indicate a moderate risk and levels greater than 3 μg/mL are considered a significant indicator for chronic cardiovascular disease, including acute coronary syndromes.[4,5]
We have developed and characterized the analytical performance of a tandem giant magnetoresistance (GMR) sensor immunoassay for the biomarker CRP in human blood, featuring two different formats in an automated microfluidic sample handling cartridge

Summary

Introduction

CRP, mainly synthesized in the liver upon an acute inflammatory stimulus, has been found to be a potent biomarker of infection and pathological cardiovascular events. The levels of C-reactive protein (CRP) are increased in many disorders, and it is regarded as a very good predictor of disease state, cardiac risk stratification.[1−3] If the levels of CRP in serum are below 1.0 μg/mL, the risk of cardiovascular diseases is considered low; levels between 1 and 3 μg/mL indicate a moderate risk and levels greater than 3 μg/mL are considered a significant indicator for chronic cardiovascular disease, including acute coronary syndromes.[4,5] Elevated levels between 10 and 50 μg/mL can be detected in viral infections and late pregnancy, and levels between 50 and 200 μg/mL are typically associated with bacterial infections and active inflammation.[2,6] Values >200 μg/mL are comparatively rare, which indicate severe health issues of the affected individuals. To design a universal CRP assay that is useful in diverse disease contexts, it should span the whole concentration range, which characterizes the clinically relevant levels of CRP, i.e., from 200 μg/mL

Methods

Results

Conclusion