Femtomolar detection of the heart failure biomarker NT-proBNP in artificial saliva using an immersible liquid-gated aptasensor with reduced graphene oxide

TL;DR

This study presents a highly sensitive, label-free aptasensor based on reduced graphene oxide for detecting NT-proBNP in saliva at femtomolar levels, enabling non-invasive early heart failure diagnostics.

Contribution

The paper introduces a novel liquid-gated rGO-FET aptasensor capable of femtomolar detection of NT-proBNP in artificial saliva, surpassing previous sensitivity limits for non-invasive cardiac biomarker testing.

Findings

Achieved detection limit of 41 fg/mL (~4.6 fM) in artificial saliva.

Demonstrated high sensitivity with a linear range from 10 fg/mL to 1 pg/mL.

Response depends on ionic strength, with optimal correlation in diluted PBS.

Abstract

Measuring NT-proBNP biomarker is recommended for preliminary diagnostics of the heart failure. Recent studies suggest a possibility of early screening of biomarkers in saliva for non-invasive identification of cardiac diseases at the point-of-care. However, NT-proBNP concentrations in saliva can be thousand time lower than in blood plasma, going down to pg/mL level. To reach this level, we developed a label-free aptasensor based on a liquid-gated field effect transistor using a film of reduced graphene oxide monolayer (rGO-FET) with immobilized NT-proBNP specific aptamer. We found that, depending on ionic strength of tested solutions, there were different levels of correlation in responses of electrical parameters of the rGO-FET aptasensor, namely, the Dirac point shift and transconductance change. The correlation in response to NT-proBNP was high for 1.6 mM phosphate-buffered saline (PBS) and zero for 16 mM PBS in a wide range of analyte concentrations, varied from 1 fg/mL to 10 ng/mL. The effects of transconductance and Dirac point shift in PBS solutions of different concentrations are discussed. The biosensor exhibited a high sensitivity for both transconductance (2 uS/decade) and Dirac point shift (2.3 mV/decade) in diluted PBS with the linear range from 10 fg/mL to 1 pg/mL. The aptasensor performance has been also demonstrated in undiluted artificial saliva with the achieved limit of detection down to 41 fg/mL (~4.6 fM).