Improved Microchip Design and Application for In Situ Transmission Electron Microscopy of Macromolecules

Dukes, Madeline J., Rebecca Thomas, John Damiano, Kate L. Klein, Sharavanan Balasubramaniam, Sanem Kayandan, Deborah F. Kelly, et al., 2013


Understanding the fundamental properties of macromolecules has enhanced the development of emerging technologies used to improve biomedical research. Currently, there is a critical need for innovative platforms that can illuminate the function of biomedical reagents in a native environment. To address this need, we have developed an in situ approach to visualize the dynamic behavior of biomedically relevant macromolecules at the nanoscale. Newly designed silicon nitride devices containing integrated “microwells” were used to enclose active macromolecular specimens in liquid for transmission electron microscopy imaging purposes.We were able to successfully examine novel magnetic resonance imaging contrast reagents, micelle suspensions, liposome carrier vehicles, and transcribing viral assemblies. With each specimen tested, the integrated microwells adequately maintained macromolecules in discrete local environments while enabling thin liquid layers to be produced.

Impact Statement

The development and use of integrated microwells for in situ LC-(S)TEM imaging. Samples imaged in microwells include magnetic resonance imaging contrast reagents, transcribing viral assembles (rotavirus) and liposome carrier vehicles.
Keywords: Microwells; Virus; Nanoparticles; Liposomes