Multifunctional dumbbell probes-based logic circuits: microRNAs logic detection and tumor cells identification

The powerful logic processing capability of DNA logic circuits over multiple input signals perfectly meets the demands of multi-biomarker-based clinical diagnostics. As important biomarkers for cancer diagnosis and treatment, the orthogonal differential expression of microRNAs (miRNAs) in different diseases and different cancer cells makes the precise logical detection of multiple miRNAs particularly critical. Therefore, we constructed two fundamental “AND” and “OR” logic gates and one “AND-OR” logic gate on the basis of our proposed multifunctional dumbbell probes. These logic gates allowed for the logical profiling of multiple cancer-associated miRNAs. In addition, by making simple adjustments to the functional modules of multifunctional dumbbell probes, the three logic gates we proposed could be easily transformed without the use of sophisticated probe design. Remarkably, these logic gates, in particular the “AND-OR” logic gate, were able to compute several miRNAs simultaneously, demonstrating excellent cell identification capabilities. Overall, this work provided a new idea for accurately distinguishing multiple cell types and showed great application prospects.