Distinguishing DNA topological forms with terahertz metamaterial spectroscopy

The topological conformation of DNA is a critical determinant of its biological function, but distinguishing between different isoforms, such as circular and linear, remains challenging. This study demonstrates the application of terahertz metamaterial spectroscopy as a powerful, label-free platform for the quantitative identification of DNA topology. Using bacteriophage ΦX174 single-stranded DNA as a model system, we show that a custom metamaterial sensor can generate distinct resonance frequency shifts for circular and linear topologies at concentrations as low as ng/μl. The spectral shifts exhibit a strong linear correlation with DNA concentration, confirming the quantitative capability, whereas, UV absorption spectroscopy fails to differentiate the isoforms. Our findings establish THz metamaterial spectroscopy as a robust tool for the direct analysis of DNA topology, with significant potential for applications in gene therapy, DNA vaccination, and biosensing.