Magnetic Microgels and Minigels: Preparation, Swelling and Instabilities
Résumé
Magnetic beads are very useful for purification steps in biotechnology as well as for certain micro-manipulation experiments in biophysics. The “superparamagnetic beads” commercially available are suitable for most of these applications due to their high magnetic load (typically 50 weight %), their good monodispersity in sizes (from 200 nm to a few µm) and the control of their surface coating (typically amino or carboxy moities, but also antibodies for the grafting of biomolecules). However in the field of drug-delivery, there is a strong demand of magnetic multi-responsive objects, i.e. carriers of drugs that would respond to at least two different stimuli: temperature, pH, solute concentration, ..., combined to the long distance action of a magnetic field. Contrary to the well documented studies on magnetic beads made of surfactant coated magnetic nanoparticles embedded in polymer shells, we chose to explore the route of hydrogel microparticles combined with ionic ferrofluids. Being highly swollen by water, these magnetic microgels exhibit a softness that leads to their fast response to the solvent quality and to certain shape instabilities. Preparation We have published recently the preparation of magnetic microgels and minigels from the polymerization of the neutral hydrophilic monomer acrylamide (AM) cross-linked by N,N'-methylene-bisacrylamide (BAM) in an inverse (W/O) emulsion . After dispersing in oil an aqueous ferrofluid and a polymerization mixture localized together in water droplets, we achieve free radical polymerization, followed by rinsing steps. We obtain spherical particles made of a hydrophilic polymer matrix entrapping magnetic nanoparticles with a high encapsulation yield and a homogeneous dispersion state. By preparing either a conventional emulsion or a mini-emulsion, we reach two ranges of sizes: either microgels of 2 – 20 µm diameters visible by optical microscopy or sub-micron minigels, which in addition present a good colloidal stability. Due to their magnetic load, microgels and minigels both react to a field by chaining and to a field gradient by migration (magnetophoresis). Preparation We have published recently the preparation of magnetic microgels and minigels from the polymerization of the neutral hydrophilic monomer acrylamide (AM) cross-linked by N,N'-methylene-bisacrylamide (BAM) in an inverse (W/O) emulsion . After dispersing in oil an aqueous ferrofluid and a polymerization mixture localized together in water droplets, we achieve free radical polymerization, followed by rinsing steps. We obtain spherical particles made of a hydrophilic polymer matrix entrapping magnetic nanoparticles with a high encapsulation yield and a homogeneous dispersion state. By preparing either a conventional emulsion or a mini-emulsion, we reach two ranges of sizes: either microgels of 2 – 20 µm diameters visible by optical microscopy or sub-micron minigels, which in addition present a good colloidal stability. Due to their magnetic load, microgels and minigels both react to a field by chaining and to a field gradient by migration (magnetophoresis). Swelling degree and dynamics The initially liquid droplets are efficiently converted to gel beads. The most direct evidence is to show their ability to absorb a good solvent (water), by following their volume increase compared to a bad solvent (ethanol) or to the dry state. The amount of water at the swelling equilibrium results from a balance between the free energy of mixing (of polymer and water) and the elastic constraints on the network. The degree of swelling is thus expected to be reduced by increasing the cross-linking density, as we check by looking at microgels containing either 2.5 or 5 weight % of BA compared to AM. The observation of magnetic microgels during swelling under the optical microscope shows: the penetration of the water front towards the dry core; the overall increase of the outer diameter; the spreading onto the glass slide (i. e. the decrease of the contact angle); and sometimes also a transient rippling instability of the free surface, that T. Tanaka has shown a long time ago with macroscopic hydrogels . The quantitative analysis of the volume increase of a given bead from optical observations is difficult due to those phenomena at the gel/glass and gel/solution interfaces. On the contrary, minigels are properly dispersed in the medium and their average diameter is in the right range to be measured by multi-angle dynamic light scattering. The hydrodynamic diameter varies indeed from 158 nm in ethanol to 195 nm in water, which corresponds to almost a two fold increase of volume (on average) when the beads are transferred from a bad to a good solvent. Concerning now dynamics, we know that swelling is a diffusive process, and thus its characteristic time scale varies like the inverse of the bead diameter . Therefore it take only a few seconds for microgels around 10µm in size to change their size, while it takes hours for beads in the mm range (or even days for cm large gels). Sub-micron minigels change their volume in even shorter times, which makes them quite interesting for multi-responsive biomedical carriers. Shape instabilities Even if there is an analogy between a microgel wetting a flat surface or squeezed between two plates and a pure viscous liquid droplet in the same situations, there are also noticeable differences due to the elastic nature of the gel. It has been predicted theoretically that the shape of a soft elastic bead on an adhesive substrate is not a perfect spherical cap as a liquid droplet . More precisely, the wedge makes an extension, which typical size L is the ratio of the spreading parameter (S≡10-2 J/m) by the shear modulus of the network (G≡104 Pa for soft elastomers). Using several microscopies (SEM, TEM, AFM, optical microscopy) and either hydrophilic or hydrophobic substrates, we show that such “feet” exist around the magnetic microgels, and that their length is about 1 µm and becomes longer when the gel is softer (at lower BA/AM ratio). When we look at a microgel drying slowly in a thin cell made of two glass slides, we observe the well known Saffman-Taylor instability due to penetration of air and retraction of fluid. However, the dried microgel exhibits a more branched structure of the gel “fingers” compared to pure viscous fingering, as was previously observed for a visco-elastic gel . Conclusion and perspectives We prepare magnetic gels in two ranges of sizes. Being colored by the iron oxide, the larger microgels can be easily handled under an optical microscope equipped with magnets. They can serve as model systems for shape instabilities of soft elastic objects during swelling, wetting or drying. The sub-micron microgels are intended for biotechnological applications. We plan to improve them by incorporating a polymer like poly(NIPAM), with a volume transition as a function of temperature. T. Tanaka T, S.-T. Sun, Y. Hirokawa, S. Katayama, J. Kucera Y. Hirose, T. Amiya, Nature (1987) 325, 796 T. Tanaka, D. J. Fillmore, J. Chem. Phys. (1979) 70, 1214 J.-F. Joanny, Johner, Vilgis, Eur. Phys. J. E (2001) 6, 201 A. Lindner, P. Coussot, D. Bonn, Phys. Rev. Lett. 85 (2000), 314-317