Aim of this project is optimising, validating and exploiting hybrid biosystems based on aptamers as biosensors. This will be based on the application of machine learning and molecular dynamics simulations for the design and analysis of aptamers. We will mainly work on the design and simulation of the nucleic acid sequences, considering applications towards highly selective and sensitive sensing. The results of the design will be then synthesised and integrated in hybrid systems where a solid- state device will be modified with the aptamers. Moreover, the model to be developed within this project will be used as a powerful tool to investigate the interaction between artificial nucleic acid sequences and DNA:RNA origami and hybrid biosystems comprising proteins of different size. The optimised aptamers developed will be also used in collaboration with other partners in the demonstration of the integration of optimised aptamers in silicified DNA origami and for the highly specific reaction in biohybrid cargo that can be modified with the aptamers.