DNA spectroscopic intrinsic-contrast photon-localization optical nanoscopy

Biological systems operate at the nanoscale, from DNA and proteins to larger assemblies. Nanoscopic imaging is crucial for biomedical research, especially for understanding chromatin's 3D conformation, a key regulator of gene expression. Current methods use fluorescent labeling, disrupting functions and lacking label density consistency. We introduce DNA Spectroscopic Photon-Localization Intrinsic-Contrast Nanoscopy, a label-free, 3D genomic imaging technology with nanometer resolution. Utilizing DNA's stochastic autofluorescence and photon localization, the platform provides 2D and 3D imaging. Spectral regression and classification algorithms enhance the spatial resolution and distinguish chromatin types and genomic domains, advancing towards potentially unveiling the complete 3D structure of a cell.