On-demand 3D imaging of molecules in solution by Electron Density Topography (EDT):Understanding multiple characteristics from Small Proteins up to Delivery Particles

3D information is undoubtedly necessary for the proper design and characterization of biopharmaceutics. There are established methods that tell the differences in solution; however, they are primarily spectroscopic and thus have complex consequences that make it challenging to understand actual 3D differences. 3D structure methods, on the other hand, require specific conditions and efforts to make it happen; it is not practical to see what is happening under some conditions and formulations.
Here, we present novel technology to examine the molecular envelope in solution by determining the electron density of the molecule without prior information, as if looking at the molecule in solution with a microscope. The resultant envelopes are not at atomic resolution; nevertheless, there are enough details to obtain information on design requirements and/or a comprehensive understanding of the differences obtained by established technologies.
As proof of the above concept, we will present comparisons of the overall shapes of glycosylated and deglycosylated IgG, mAb, and its derivative ADC and the range of flexibility of a “stable” mAb—furthermore, direct epitope mapping utilizing the mAb-antigen complex and observation of virus particles with engineered nucleic acids.