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

Solid‐state nanochannel biosensors are extensively utilized for microRNA 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 tri‐block DNA probes with varying affinities for target miRNA to engineer solid‐state nanochannel biosensors capable of programmable dynamic range adjustment. The tri‐block 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 different 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 was narrowed to only a 3‐fold range 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.