Abstract
Molecular systems composed of information-rich nucleic acids have emerged as one of the most robust materials due to their programmability, editability, and designability. Among their various applications, the specific and sensitive in vitro detection of biomolecules for the purpose of disease diagnosis has attracted increasing attention from both fundamental and translational researchers. In this perspective, we introduce the basic design principles for nucleic acid molecular systems toward in vitro detection of biomolecules, accompanied by representative examples from reported works. The perspective concludes with perspectives and outlooks to tackle a variety of technical hurdles for the development and practical translation of nucleic acid molecular systems for biomolecule detection.