Ultra-Sensitive NT-proBNP Quantification for Early Detection of Risk Factors Leading to Heart Failure

Abstract

Cardiovascular diseases such as acute myocardial infarction and heart failure accounted for the death of 17.5 million people (31% of all global deaths) in 2015. Monitoring the level of circulating N-terminal proBNP (NT-proBNP) is crucial for the detection of people at risk of heart failure. In this article, we describe a novel ultra-sensitive NT-proBNP test (us-NT-proBNP) that allows the quantification of circulating NT-proBNP in 30 min at 25 °C in the linear detection range of 7.0–600 pg/mL. It is a first report on the application of a fluorescence bead labeled detection antibody, DNA-guided detection method, and glass fiber membrane platform for the quantification of NT-proBNP in clinical samples. Limit of blank, limit of detection, and limit of quantification were 2.0 pg/mL, 3.7 pg/mL, and 7 pg/mL, respectively. The coefficient of variation was found to be less than 10% in the entire detection range of 7–600 pg/mL. The test demonstrated specificity for NT-proBNP without interferences from bilirubin, intra-lipid, biotin, and hemoglobin. The serial dilution test for plasma samples containing various NT-proBNP levels showed the linear decrement in concentration with the regression coefficient of 0.980–0.998. These results indicate that us-NT-proBNP test does not suffer from the interference of the plasma components for the measurement of NT-proBNP in clinical samples.

Keywords

• NT-proBNP
• heart failure
• left ventricular hypertrophy
• 9G DNAChip
• DAGON
• cardiovascular disease