Silicon-based microdialysis chip with integrated fraction collection and biofouling control

Abstract

Providing the medical tools to measure and report biomolecules without interference from other impeding molecules or from triggering the body's immunoresponse is far from trivial. For the past 30 years, microdialysis has been extensively used as an in vivo bioanalytical measurement procedure to recover biomolecules from tissue or organs. These biomolecules can provide physicians an early and subtle indication of the onset of disease, supplying a view of the cellular and molecular inner workings of the body. This thesis presents a monolithic microdialysis chip that integrates sample acquisition, fraction collection, and biofouling control on the same silicon substrate. A microfabrication technology that allows an in situ, porous cellulose acetate membrane to be suspended over silicon microchannels using standard spin coat deposition is shown. These membranes were created using phase inversion techniques and adhesion of the organic cellulose acetate membrane to the inorganic silicon substrate was characterized. Based on the physical parameters of the cellulose acetate lacquer and the surface properties of the substrate, it was possible to span 75-? wide cavities. Cellulose acetate membranes were fouled with a myoglobin protein solution and then characterized. Permeability tests indicate a decreased analyte flux, while visual observation using scanning electron microscopy shows protein aggregates on the surface that are irreversibly adsorbed after repeated rinsing. Isoelectric forces were explored as a method to regenerate the membrane to pre-fouled levels by dislodging adsorbed myoglobin molecules from the membrane surface. Using embedded platinum electrodes beneath the cellulose acetate membrane, an electric field (230 V/m) was established across the thickness of the membrane. Application of the electric field showed a 7.6% maximum increase in analyte flux after membrane fouling, with a 51.5% increase in analyte flux necessary to return the membrane to pre-fouled levels. Automated fraction collection is accomplished on-chip using passive microvalves that allow accurate temporal acquisition of analyte samples. Fraction collection is demonstrated on the backside of a microdialysis chip using a set of deep-etched, 6 ?-volume collection chambers coated with a hydrophobic