Fifty Years of Nonlinear Electrophoresis

Nonlinear electrophoresis (EP) has seen significant advancements over the past five decades, evolving into a potent electrokinetic phenomenon with transformative potential for analytical chemistry, particularly in the areas of bioanalysis and separations. This review chronicles the historical development of nonlinear EP, from its foundational Russian-language publications in the 1970s to its current applications enabling highly discriminatory separations of particles ranging from nanoparticles to large cells, exploiting subtle analyte differences. This review article is organized in three distinct eras: the 1970s, from 1980 to 2000, and from 2000 to the present. The latter is covered in terms of the advances in theory and modeling and the advances in experimental applications. The established regimes of classical nonlinear EP, currently utilized for electrophoretic separation of viruses, cells, and various micro- and nanoparticles, are discussed. Despite these breakthroughs, significant research opportunities remain, including the development of analytical expressions for dielectric particles at intermediate Peclet numbers (1 < Pe < 10), the application of AC signals for purely nonlinear separations, and understanding the migration of highly charged particles with thick electrical double layers. This article aims to provide experimentalists with a clear and accessible overview of the history and key advancements of nonlinear EP, highlighting its flexibility and positioning it as a major future player in bioanalytical chemistry.