Sprecher
Beschreibung
Continuous Monitoring Biosensors (CMB) are at the forefront of the digital healthcare transformation, offering real-time measurement and novel metrics to improve disease management. While continuous glucose monitoring has set the gold standard, the development of CMB for other clinically relevant biomarkers remains challenging due to the absence of alternative enzymatic catalysts. To develop CMB, researchers have turned their attention towards other methods, with affinity-based structure-switching biosensing showing high potential. For example, aptamer-based biosensor has shown great results to monitor biomarkers in the nM to µM range. However, many clinically relevant biomarkers are found in the pM range and thus require stronger binders (e.g., antibody) to reach such low limit of detection. Stronger binders also rime with slower dissociation kinetics that would impact sensor regeneration and introduce lag time in the sensor response. Therefore, novel sensing architecture are required to improve sensor kinetics without affecting affinity. To address this specific challenge, we have investigated how Nature process chemical information using structure-switching receptors. Two mechanisms were identified: induced-fit and conformational selection. Each mechanism allows to activate or deactivate the switch, but proceed via two different pathways, enabling the programming of the switch kinetics (see graphic abstract). I will present how we have recreated these mechanisms using a DNA-based model, with an emphasis on their design principle, their programmability and their kinetic differences. I will finish my presentation with my future postdoc project (MSCA Postdoctoral Fellowships at TU/e, Netherlands) where we aim to implement these strategies into immunosensors and protein-based switches. Overall, this project shifts our focus from the thermodynamic to the kinetic optimization of structure-switching biosensors. It establishes a novel framework for CMB development, providing a scalable and adaptable strategy for in vivo continuous biomarker monitoring.
