Electrohydrodynamic Purification of Genomic DNA from Cell Lysates

We describe the fluid-mechanical principles underlying a recently demonstrated method for purifying long DNA strands from cell lysates (Wang et al., PNAS, 2025). The separation exploits a coupled mechanism of pressure-driven flow opposed by electrophoretic motion in a microfluidic channel. At appropriate ratios of flow and electric field strength, long polyelectrolyte chains, such as genomic DNA, migrate transversely toward the channel walls and are then carried upstream by electrophoresis to the channel entry, where they accumulate. The transverse migration arises from electrohydrodynamic interactions induced by the electric field acting on the DNA chains distorted from equilibrium by shear. Smaller molecules and proteins, even if negatively charged like the DNA, do not exhibit cross-stream motion and are flushed out with the bulk flow. The result is an effective separation, as demonstrated by the purification of DNA from an E. coli lysate. Fluorescence-based measurements of the purified samples show an A260/280 ratio of 1.8, strong PCR amplification (Cq = 15), and minimal fragmentation by gel electrophoresis, supporting the method’s suitability for long-read sequencing. Additionally, model mixtures of fluorescently labeled DNA and protein are separated, demonstrating a reduction of protein concentration by 5 orders of magnitude in 20 minutes. The effects of shear rate, electric field strength, and device geometry in controlling DNA migration and retention are highlighted.