Drying effect creates false assemblies in DNA-coated gold nanoparticles as determined through in situ liquid cell STEM.

The drying effect associated with utilizing transmission electron microscopy to study deoxyribonucleic acid (DNA)-coated gold nanoparticles (AuNPs) remains largely uninvestigated, though this technique is frequently utilized to characterize nanoparticle-DNA interactions. Investigation of the drying effect is essential to the progress of the many fields that utilize AuNPs, including cancer research. In this study, we compare DNA hybridization-directed nanoparticle assemblies with control samples omitting the necessary complementary DNA, effectively blocking directed assembly, in both the liquid state and the dry state, within a scanning transmission electron microscope. We show that the dry samples contain AuNPs spaced at significantly smaller intervals than identical samples measured in situ, with no dependence on the DNA bound to the AuNPs in the dry samples. A partially wet sample, with distances measured along the drying edge, provided an intermediate binding distance, strengthening the conclusion that drastic differences observed between the dry and in situ samples are due to a pronounced drying effect. This drying effect will falsely indicate certain grouping arrangements and will change the impression of the size of the groups formed, providing misinformation for the development of these controlled assemblies that could impact applications such as targeted drug vehicles for cancer treatment.