Development Toward a Triple-Marker Biosensor for Diagnosing Cardiovascular Disease.

Cardiovascular disease (CVD) is the leading cause of death in the United States and is responsible for 30% of all deaths globally. The diagnosis and management of CVD requires monitoring of multiple biomarkers, which comprehensively represents the state of the disease. However, many assays for cardiac biomarkers today are complicated and laborious to perform. Rapid and sensitive biosensors capable of giving accurate measurements of vital cardiac biomarkers without complex procedures are thus in high demand. In the work presented below, rapid, label-free biosensor prototypes for three Food and Drug Administration-approved biomarkers are reported: B-type natriuretic peptide (BNP), cardiac troponin I (cTnI), and C-reactive protein (CRP). The sensors were prepared by immobilizing each biomarker's antibody onto gold working electrodes with platinum counter and silver/silver chloride reference electrodes. The sensors were tested using electrochemical impedance spectroscopy (EIS), a femto-molar sensitive technique capable of label-free, multi-marker detection if a biomarker's optimal frequency (OF) can be identified. The OFs of BNP, cTnI, and CRP were found to be 1.74, 37.56, and 253.9 Hz, respectively. The performance of the BNP biosensor was also evaluated in blood and achieved clinically relevant detection limits of 100 pg/mL.