Hydrogelation Kinetics Measured in a Microfluidic Device with in Situ X-ray and Fluorescence Detection.

Efficient hydrogelators will gel water fast and at low concentrations. Small molecule gelling agents that assemble into fibers and fiber networks are particularly effective hydrogelators. Whereas it is straightforward to determine their critical concentration for hydrogelation, the kinetics of hydrogelation is more difficult to study because it is often very fast, occurring on the subsecond time scale. We used a 3D focusing microfluidic device combined with fluorescence microscopy and in situ small-angle X-ray scattering (SAXS) to study the fast pH-induced gelation of a model small molecule gelling agent at the millisecond time scale. The gelator is a 1,3,5-benzene tricarboxamide which upon acidification assembles into nanofibrils and fibril networks that show a characteristic photoluminescence. By adjusting the flow rates, the regime of early nanofibril formation and gelation could be followed along the microfluidic reaction channel. The measured fluorescence intensity profiles were analyzed in terms of a diffusion-advection-reaction model to determine the association rate constant, which is in a typical range for the small molecule self-assembly. Using in situ SAXS, we could determine the dimensions of the fibers that were formed during the early self-assembly process. The detailed structure of the fibers was subsequently determined by cryotransmission electron microscopy. The study demonstrates that 3D focusing microfluidic devices are a powerful means to study the self-assembly on the millisecond time scale, which is applied to reveal early state of hydrogelation kinetics. In combination with in situ fluorescence and X-ray scattering, these experiments provide detailed insights into the first self-assembly steps and their reaction rates.

Fast diffusion-limited lyotropic phase transitions studied in situ using continuous flow microfluidics/microfocus-SAXS.

Fast concentration-induced diffusion-limited lyotropic phase transitions can be studied in situ with millisecond time resolution using continuous flow microfluidics in combination with microfocus small-angle X-ray scattering. The method was applied to follow a classical self-assembly sequence where amphiphiles assemble into micelles, which subsequently assemble into an ordered lattice via a disorder/order transition. As a model system we selected the self-assembly of an amphiphilic block copolymer induced by the addition of a nonsolvent. Using microchannel hydrodynamic flow-focusing, large concentration gradients can be generated, leading to a deep quench from the miscible to the microphase-separated state. Within milliseconds the block copolymers assembly via a spinodal microphase separation into micelles, followed by a disorder/order transition into an FCC liquid-crystalline phase with late-stage domain growth and shear-induced domain orientation into a mesocrystal. A comparison with a slow macroscopic near-equilibrium kinetic experiment shows that the fast structural transitions follow a direct pathway to the equilibrium structure without the trapping of metastable states.