Programming the Dynamic Range of Nanochannel Biosensors for MicroRNA Detection through Allosteric DNA Probes

Abstract Solid‐state nanochannel biosensors are extensively utilized for microRNA (miRNA) detection owing to their high sensitivity and rapid response. However, conventional nanochannel biosensors face limitations in their fixed dynamic range, restricting their versatility and efficacy. Herein, we introduce tunable triblock DNA probes with varying affinities for target miRNA to engineer solid‐state nanochannel biosensors capable of customizable dynamic range adjustment. The triblock DNA architecture comprises a poly‐adenine (polyA) block for adjustable surface density anchoring, alongside stem and loop blocks for modulating structural stability. Through systematic manipulation of these blocks, we demonstrate the ability to achieve diverse target binding affinities and detection limits, achieving an initial 81‐fold dynamic range. By combining probes with various affinities, we extend this dynamic range significantly to 10,900‐fold. Furthermore, by implementing a sequestration mechanism, the effective dynamic range of the nanochannel biosensor is narrowed to only a 3‐fold span of target concentrations. The customizable dynamic range of these advanced nanochannel biosensors makes them highly promising for a broad spectrum of biomedical and clinical applications.