Label-free DNA structural profiling via elliptical dichroism spectroscopy

Current DNA structural analysis methods, such as X-ray crystallography, NMR, Circular Dichroism (CD) spectrometry, and Electron Microscopy (EM) provide accurate analysis of DNA structures; however, these methods are limited in their applicability due to their high cost, large size, and complexity of operation. To combat this, we invented Elliptical Dichroism Spectrometer (EDS), which is lower in cost, smaller in size, and handy for DNA structural analysis. Previously, we validated its use as a protein secondary structural analysis instrument with clinical potential for noninvasive cancer detection. Here, we validate EDS for DNA structural analysis using well-established fluorescence assays and circular dichroism spectroscopy. EDS demonstrates strong potential as a label-free alternative method for analyzing diverse DNA structures, including simple hairpins, complex G-quadruplexes, and various DNA origami architectures. Furthermore, EDS demonstrates proof-of-concept in biologically relevant systems for detecting diseases associated with DNA damage.