Harnessing a Self‐Regenerated Hybridization Circuit for Differentiating Heart Failure Patients of Varied Severity

Abstract Heart failure (HF) is a globally threatening cardiovascular disease associated with poor quality of life and high mortality, therefore, timely diagnosis and risk prediction for HF disease are urgently needed. Herein, a compact yet robust self‐regenerated hybridization circuit (SHC) aptasensor is developed for the amplified detection of N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), a “gold standard biomarker” for HF. The aptamer transduction module can specifically recognize NT‐proBNP, thus initiating the cascade hybridization reaction with the successively self‐regenerated triggers that reversely initiate the cross‐hybridization reaction. Benefiting from the aptamer‐specific recognition and the self‐replicated signal amplification, the robust SHC aptasensor demonstrated a more impressive diagnostic performance for HF in elderly patients than the clinical fluorescence immunochromatography assay (FICA) in terms of positive predictive value (21 vs 17), specificity (39 vs 32), and diagnostic accuracy (37 vs 36). Furthermore, this approach allows for differentiation among HF patients with varying disease severities, achieving a sufficiently high accuracy of 78.3%, thus facilitating more timely and accurate therapeutic intervention. The versatile and reliable SHC system offers a new approach to analyzing low‐abundance biomarkers from clinical rare specimens, which is highly important for early disease diagnosis and prognosis assessment.