Preventing the impact of solute adsorption in Taylor dispersion analysis: Application to protein and lipid nanoparticle analysis.

Taylor Dispersion Analysis (TDA) allows diffusion coefficient (D) or hydrodynamic radius (R) determination on a wide range of size between angstroms and about 300 nm. However, solute adsorption phenomena can affect the repeatability and reproducibility of TDA. Several numerical studies addressed the theoretical impact of solute adsorption in TDA, but very few experimental studies focus on this topic and no experimental methodologies were proposed so far to reduce the impact of adsorption in TDA. In this work, an experimental protocol, called plug-in-front TDA, consisting of adding the solute in the eluent at a lower concentration compared to the injected sample, was proposed to strongly limit the impact of adsorption on the R determination. This protocol was suggested based on the evidence that adsorption / desorption phenomena impacting narrow bore fused silica TDA in aqueous conditions are typically slow processes that can be counteracted by saturating the interaction sites during the experiments. Successful applications to proteins and mRNA lipid nanoparticles (LNP) in vaccine against Covid 19 and protein analysis were reported. TDA of proteins in conditions of strong interactions with the capillary surface was possible using the plug-in-front methodology. We anticipate that such experimental methodology will greatly help the experimentalist for implementing TDA in various applications.