Single-molecule biodosimetry

Abstract

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 gamma 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.