Broad‐Spectrum Diffusion Coefficient Measurements via Surface Plasmon Resonance: From Thermodynamics to Protein Conformational Disorders

Recent advancements in surface plasmon resonance protocols and simulations have enhanced the measurement and prediction of diffusion coefficients (D) for chemical species in microfluidic channels. These developments enable precise determination of D values for molecules ranging from a few angstroms to nanometric aggregates, facilitating detailed insights into molecular and aggregation properties.

Information regarding the dimension and the shape of molecules in solution represents a holy grail for chemists. Recently, newly designed surface plasmon resonance (SPR) methods to precisely measure the diffusion coefficients (D) (D-SPR) have been developed and applied successfully to a variety of molecules, ranging from diverse long-chain alcohols to protein conformers and oligomers involved in conformational disorders, mostly represented by neurodegenerative processes of nervous tissues of the brain and retina. The dependence of D on the molecular size, shape, and oligomerization state of different molecules has been widely investigated, opening up new avenues and tools for chemical, biochemical, and clinical research. Herein, the historical basis and the development of the newly proposed D-SPR method are briefly described to obtain meaningful information about molecular features that are otherwise hard to characterize using more common and traditional bioanalytical approaches.