Towards label-free, wash-free and quantitative B-type natriuretic peptide detection for heart failure diagnosis

Abstract

Current diagnostic systems used in clinical settings to detect protein biomarkers require highly trained experts, large volumes of blood samples, and long turnaround times. There is an immense need for a low-cost and accurate point-of-care-testing (POCT) device for home monitoring of protein biomarkers for global pandemics such as heart failure (HF). The integration of highly sensitive carbon nanotube (CNT) thin film (CNT-TF) impedance sensors with the electrochemical impedance spectroscopy (EIS) technique is a promising platform to actualize POCT systems for home use. Herein, we report such a system, NanoBot, which allows the label-free and wash-free detection of the HF antigen biomarker B-type natriuretic peptide (BNP) in blood plasma. The NanoBot system consists of two parts: a disposable test strip and a miniature electronic readout unit. The NanoBot exhibited reasonable accuracy and precision, a clinically relevant limit of detection (LOD) as low as 16 pg mL⁻¹, a linear detection range from 0–4000 pg mL⁻¹ and excellent correlation with a reference standard fluorescent immunoassay (FIA). A pilot clinical study with patient-derived blood plasma validated the NanoBot's strong performance compared to that of Alere Triage®, with an interclass correlation coefficient (ICC) of 98% and a square of correlation coefficient (CC) of 0.95. Furthermore, unlike the Alere Triage® that requires more than 250 μL of blood collected via venipuncture, the NanoBot only requires 50 μL of blood. Collectively, the NanoBot's high sensitivity, accuracy, precision, and self-calibration characteristics signify its promising potential as a POCT platform for heart failure diagnosis in home use.