Digital DNA Strand Displacement for Molecular Computing

Multiplexed analysis of feature biomarkers enhances the accuracy of molecular diagnostic results. Molecular computing systems exhibited potentials for intelligent analysis of multiplexed biomarkers. However, the chemical reaction networks of current molecular computing systems suffer from the use of large number of oligonucleotides and limited encoding capability. Here, we developed a molecular computing platform termed as Digital DNA Strand Displacement (DDSD), utilizing the features of DNA polymerase-mediated strand extension and displacement to achieve robust linear weight encoding as well as exponential weight encoding. This approach not only ensures precise molecular diagnostics but also enables precise identification of specific infection types. The DNA polymerase-based digital DNA strand displacement guaranteed high specificity in molecular reactions and reduced the number of DNA strands used in molecular computing. We conducted double-blind experiments to diagnose and identify bacterial or viral infection samples accurately. Furthermore, we demonstrated two approaches (cascade strand displacement and multi-way DNA junction) for computing capability upgradation, enabling weighted calculations for at least 15 feature biomarkers. Digital DNA strand displacement lays the foundation for more intricate and accurate molecular computing and diagnostics.