Chemical Mapping of Unstained DNA Origami Using STEM/EDS and Graphene Supports

We demonstrate that unstained DNA nanostructures can be chemically mapped by using aberration-corrected scanning transmission electron microscopy (STEM) with energy-dispersive spectroscopy (EDS). Key to this measurement is the use of graphene supports whose reduced background scattering compared to thicker carbon supports allows EDS to image phosphorus and other elements in the DNA (or in attachments to the DNA) as well as to see the divalent cations used to stabilize the nanostructure. In addition, unlike in other EDS analyses, the chemical maps we obtain can be made quantitative in an absolute sense because each individual DNA nanostructure is in effect a very large macromolecule (∼4.7 MDa) with a known chemical composition. In this way, not only can STEM/EDS serve DNA nanotechnology as a characterization tool but also the DNA structures can function as molecular standards for improving mesoscale EDS techniques.