Stochastic electrotransport selectively enhances the transport of highly electromobile molecules

Significance Many chemical and biomedical techniques rely on slow diffusive transport because existing pressure-based methods or electrokinetic methods can incidentally damage the sample. This study introduces a novel transport concept termed stochastic electrotransport that can selectively and nondestructively expedite transport of electromobile molecules into a porous sample, such as fixed biological tissues. We use the method to rapidly transport several classes of molecules into whole mouse brains and other organs and achieve rapid clearing and staining of the entire tissue in record time without damaging the sample. Our new method may facilitate the application of various molecular techniques to large and dense tissues. Nondestructive chemical processing of porous samples such as fixed biological tissues typically relies on molecular diffusion. Diffusion into a porous structure is a slow process that significantly delays completion of chemical processing. Here, we present a novel electrokinetic method termed stochastic electrotransport for rapid nondestructive processing of porous samples. This method uses a rotational electric field to selectively disperse highly electromobile molecules throughout a porous sample without displacing the low-electromobility molecules that constitute the sample. Using computational models, we show that stochastic electrotransport can rapidly disperse electromobile molecules in a porous medium. We apply this method to completely clear mouse organs within 1–3 days and to stain them with nuclear dyes, proteins, and antibodies within 1 day. Our results demonstrate the potential of stochastic electrotransport to process large and dense tissue samples that were previously infeasible in time when relying on diffusion.