Field, force and transport analysis for magnetic particle-based gene delivery

Magnetic particles are used to deliver gene vectors to target cells for uptake in a process known as magnetofection. Magnetic particle-based gene delivery has been successfully demonstrated for all types of nucleic acids and across a broad range of cell lines. It is well suited for multiwell culture plate systems wherein magnetic particles with surface-bound gene vectors are introduced into culture wells, and a magnetic force provided by rare-earth magnets beneath and aligned with the wells attracts the particles to the cells for uptake. In this paper, models are presented for analyzing and optimizing this process. These include closed-form equations for predicting the magnetic field and force and a drift–diffusion equation for predicting the transport and accumulation of particles in a well. The closed-form equations enable rapid parametric analysis of the spatial distribution of the field and force in a well as a function of key parameters including its dimensions, the magnet-to-well spacing, the strength of the magnet, the influence of neighboring magnets and the properties of the particles. The particle transport equation accounts for the field-induced drift of particles as well as fluidic drag and Brownian diffusion. It is solved numerically using the finite volume method. The theory is demonstrated via application to a multiwall plate magnetofection system and the impact of various factors that govern gene delivery is assessed. The models provide insight into gene delivery and are well suited for parametric analysis of particle accumulation in the wells. They enable the rational design of novel magnetofection systems.