Modulating the integration of DNA molecular logic gates to achieve universal Boolean logic circuits.

Andrea Bardales¹, Quynh Vo¹, and Dmitry M. Kolpashchikov^1,2,3

1. Chemistry Department, University of Central Florida, Orlando, Fl 32816, USA
2. National Center for Forensic Science University of Central Florida, Orlando, Florida 32816, USA
3. Burnett School of Biomedical Sciences, University of Central Florida, Orlando, Florida 32816, USA

By mimicking electronic circuits, DNA molecular computing can open the door to molecular automatons capable of analyzing complex biomarker signatures and leading to personalized medicine. This machinery requires the integration of scalable molecular circuits. In electronic computers, universal Boolean circuits are commonly used since their modular integration results in different logic functions, an approach that eases the manufacturing of complex circuitry. Therefore, in pursuing universal Boolean logic circuits, we realized two modular DNA logic gates: YES, and NOT. These gates operate by their association/dissociation into a four-way junction (4J) nanostructure. Scaling the integration of two units of these gates involved their localization on a DNA board that aids inter-gate communication. Universal Boolean circuits IMPLY and NAND resulted from the integration of YES-NOT and NOT-NOT units, respectively.¹ Additionally, an OR logic circuit was achieved when integrating two YES logic gates. Our logic circuits operated upon the recognition of either miRNA or ssDNA oligonucleotides as inputs and their output was transduced to a fluorescence readout using a molecular beacon probe. We show that the output readout of each logic circuit can be translated for diagnostics and therapeutic purposes by defining the digital output values 1 and 0 as positive/ill or negative/healthy. Lastly, our results showed that these circuits have robust performance after 2 months and our findings suggest that molecular computing can be ruled by different paradigms than those established for electronic computing.

This work was supported by the National Science Foundation through the CCF: Software and Hardware Foundations under cooperative agreement SHF-2226021.

References

¹Bardales A. C., Vo Q., Kolpashchikov D. M. Singleton {NOT} and Doubleton {YES; NOT} Gates Act as Functionally Complete Sets in DNA-Integrated Computational Circuits. Nanomaterials 2024, 14, 600.