Spatial decoupling of recognition and signaling in aptamer switches via tri-strand intermolecular competition.

The CoBrA aptamer framework achieves synchronized recognition and signaling across diverse analytes with minimal components, demonstrated by consistent thermodynamic and kinetic parameters for dopamine and cortisol.

• Why it matters: Developing a universal, modular biosensing architecture remains challenging due to unpredictable aptamer folding and signal transduction, limiting reliable detection of various targets in complex media.
• What they did: The study designed and optimized a DNA tridomain CoBrA system using computational simulations and energetic balancing, testing it with dopamine and cortisol aptamers in buffer, serum, and cerebrospinal fluid, measuring binding affinity and response times.
• The result: The CoBrA system shows strong thermodynamic and kinetic synchronization across targets and media, and its geometry-defined signaling change enables adaptation to multiple transduction modalities, advancing modular biosensor development.