Dual-signal amplified self-powered biosensor integrating DNAzyme Walker and Dumbbell HCR for attomolar detection of TATA-28 DNA in thalassemia gene screening.

Abstract

Thalassemia gene screening is vital for preventing severe infant morbidity, yet current methods lack the sensitivity for early clinical intervention. Here, we report an enzymatic biofuel cell self-powered biosensor (EBFC-SPB) integrating DNAzyme Walker and dumbbell hybridization chain reaction (DHCR) cascade amplification for attomolar-level detection of TATA-28, a critical thalassemia biomarker. The biosensor employs Au@Zr-MOF/graphdiyne (GDY) as a conductive substrate to immobilize glucose oxidase (bioanode) and [Ru(NH 3 ) 6 ] 3+ -responsive DNA circuits (biocathode). Target-activated DNAzyme Walker liberates single-stranded DNA (S0), initiating dumbbell HCR to generate electronegative DNA nanostructures that adsorb [Ru(NH 3 ) 6 ] 3+ . This process drives efficient electron transfer from the bioanode to the biocathode, greatly amplifying the open-circuit voltage (E OCV ) compared to non-target conditions. The dual-amplification strategy achieves a linear response from 0.1 fM to 10 nM TATA-28 with a 35.3 aM detection limit (S/N = 3), surpassing existing methods in sensitivity. Successful validation in human serum (recovery: 90.1-106.5 %) highlights its clinical potential for early thalassemia screening.

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Identifiers

DOI

10.1016/j.bios.2025.117683

PubMed

40516431

Journal

Biosensors & bioelectronics

Year

2025