Artificial base-pairs expand the genetic alphabet and allow for site-specific labeling, for example with fluorophores or spin labels, thereby enhancing the capabilities of biomolecular sensing. We…

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Nucleic acid sensing is crucial for advancing diagnostics, therapeutic monitoring, and molecular biology research by enabling the precise identification of DNA and RNA interactions. Here, we present an innovative sensing platform based on DNA-functionalized whispering gallery mode (WGM) microlasers. By correlating spectral shifts in laser emission to changes in the refractive index, we demonstrate real-time detection of DNA hybridization and structural changes. The addition of gold nanoparticles to the DNA strands significantly enhances sensitivity, and exclusively labeling the sensing strand or a hairpin strand eliminates the need for secondary labeling of the target strand. We further show that ionic strength influences DNA compactness, and we introduce a hairpin-based system as a dual-purpose sensor and controlled release mechanism for drug delivery. This versatile WGM-based platform offers promise for sequence-specific nucleic acid sensing, multiplexed detection, and in vivo applications in diagnostics and cellular research.