Single–Molecule Biodosimetry

Inferring characteristics of radiation exposure using biological molecules is extremely challenging. Current methods, in particular, lack a clear connection between dose and molecular response. Here, we demonstrate that resistive-pulse nanopore sensors enable single-molecule biodosimetry by quantifying the frequency of double-strand DNA scissions versus γ radiation dose. The resulting response curve shows an elongated Gaussian behavior, reminiscent of cell survival rates versus dose. We demonstrate that the competition of radical damage of DNA─i.e., single-strand lesions that lead to breakage─with bimolecular radical loss captures the form of the response. Our sensors and protocol provide a foundation for numerous technological advances. These include rapid dosimetry for triage in emergency situations and ex vivo monitoring of radiotherapy effectiveness in order to tailor treatment to patient- and tumor-specific response.