(693a) Small Molecule Diffusion in a Hydrogel Microfluidic Device

A novel microfluidic method is proposed for studying diffusion of small molecules in a hydrogel. Microfluidic devices were prepared with semi-permeable microchannels defined by cross-linked poly(ethylene glycol). Uptake of dye molecules from aqueous solutions flowing through the microchannels was observed optically and diffusion of the dye into the hydrogel was quantified. To complement the diffusion measurements from the microfluidic studies, NMR characterization of the diffusion of dye in the PEG hydrogels was performed.

Hydrogels are used extensively in the biomedical industry due to their biocompatibility and semi-permeable nature. The diffusion of small molecules in a hydrogel is relevant to applications such as drug delivery and modeling transport for tissue-engineering applications. The diffusion of small molecules in a hydrogel are dependent on the extent of crosslinking within the gel, gel structure, and interactions between the diffusive species and the hydrogel network. These effects have been studied in a model environment (semi-infinite slab) at the hydrogel-fluid boundary in a microfluidic device.

The microfluidic devices containing PEG microchannels are fabricated using photolithography. PEG solutions of varying water content are used to investigate the effect of hydrogel swelling ratio on small molecule diffusion. The unsteady diffusion of small molecules (dyes) within the microfluidic device is monitored and recorded using a digital microscope. The information is analyzed with techniques drawn from digital microscopy and image analysis to obtain concentration profiles with time. Using a diffusion model to fit this concentration v. position data, a diffusion coefficient is obtained. This diffusion coefficient is compared to those from complementary NMR analysis. A pulsed field gradient (PFG) method is used to investigate and quantify small molecule diffusion in hydrogels.

There is good agreement between the diffusion coefficients obtained from the microfluidic methods and those found from the NMR studies. We demonstrate that the microfluidic method can be used for a wide variety of combinations of hydrogels and small molecules, and both uptake and elution studies can easily be performed. The microfluidic approach allows study of diffusion at length scales that approach those of vasculature, facilitating models for studying drug elution from hydrogels in blood-contacting and pulsatile flow applications.