Non-ionic, thermo-responsive DEA/DMA nanogels: synthesis, characterization, and use for DNA separations by microchip electrophoresis

Thermo-responsive polymer "nanogels" (crosslinked hydrogel particles with sub-100 nm diameters) are intriguing for many potential applications in biotechnology and medicine. There have been relatively few reports of electrostatically neutral, thermosensitive nanogels comprising a high fraction of hydrophilic co-monomer. Here we demonstrate the syntheses and characterization of novel, non-ionic nanogels based on random N,N-diethylacrylamide (DEA)/N,N-dimethylacrylamide (DMA) copolymers, made by free-radical, surfactant-free dispersion polymerization. The volume-phase transition temperatures of these DEA/DMA nanogels are strongly affected by co-monomer composition, providing a way to "tune" the phase transition temperature of these non-ionic nanogels. While DEA nanogels (comprising no DMA) can be obtained at 70 °C by standard emulsion precipitation, DEA/DMA random co-polymer nanogels can be obtained only in a particular range of temperatures, above the initial phase transition temperature and below the critical precipitation temperature of the DEA/DMA copolymer, controlled by co-monomer composition. Increasing percentages of DMA in the nanogels raises the phase transition temperature, and attenuates and broadens it as well. We find that concentrated DEA/DMA nanogel dispersions are optically clear at room temperature. This good optical clarity was exploited for their use in a novel DNA sieving matrix for microfluidic chip electrophoresis. An ultrafast, high-efficiency dsDNA separation was achieved in less than 120 s for dsDNA ranging from 75 bp to 15,000 bp.