Biomedical subjects

Teri West

Publications and source records attributed to Teri West.

3 recordsLinked to original sources

PubMed2005

Tailoring width of microfabricated nanochannels to solute size can be used to control diffusion kinetics.

Top-down microfabrication techniques were used to create silicon-based membranes consisting of arrays of uniform channels having a width as small as 7 nm. The measurement of diffusion kinetics of solutes across these membranes under sink conditions reveals non-Fickian behavior as the nanopore width approaches the hydrodynamic diameter of the solute. Zero-order diffusion of interferon is observed at channel width of 20 nm, and the same phenomenon occurs with albumin and 13-nm-wide channels, whereas Fickian diffusion kinetics is seen at 26 nm and larger pore sizes. A prototypical drug delivery device is described that is fitted with a 13-nm nanopore membrane and loaded with radio-labeled BSA. Following subcutaneous implantation in rats, diffusion from the device provided prolonged levels of BSA in the blood. Such a nonmechanical device offers important advantages in drug delivery applications, including zero-order release and high loading capacity.

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PubMed2005

Diffusion characteristics of microfabricated silicon nanopore membranes as immunoisolation membranes for use in cellular therapeutics.

OBJECTIVE: Immunoisolating membranes protect transplanted xenogeneic tissue by physically isolating them from the host. However, most are commercial filter membranes that do not possess all the features needed for immunoisolation. Silicon nanopore membranes are thin layers of silicon containing tens of thousands of nanometer-sized channels, which allow passive diffusion of small molecules. They are excellent size-selective barriers, and the objective of this study was to further characterize their immunoprotective properties and make comparisons with commercial filter membranes. METHODS: Diffusion across membranes was studied using molecules of different sizes, including fluorescein isothiocyanate-dextrans (relative molecular sizes of 4.4 kDa, 20 kDa, and 70 kDa), glucose (0.18 kDa), insulin (6.1 kDa), and immunoglobulin G (IgG) (150 kDa). Protection from complement-mediated lysis was analyzed by a hemolysis assay. Comparative studies were done with filter membranes that have been reported as immunoisolation barriers. To evaluate if silicon nanopore membranes changed insulin response patterns for glucose-stimulated islets, macrocapsules were constructed with nanopore membranes and filled with pancreatic islets, and dynamic perifusion studies were performed. RESULTS: Relative to commercial membranes, silicon nanopore membranes showed high rates of diffusion for glucose and insulin, and acted as efficient barriers to complement proteins and IgG. No other commercial membrane showed comparable diffusion and immunoisolating properties. Islets placed within the macrocapsule exhibited glucose-responsive insulin secretion in perifusion studies. CONCLUSIONS: Silicon nanopore membranes possess unique and desirable diffusion properties as immunoisolation membranes and allow rapid response times for the stimulation of islets by glucose. These features are attributed to the physical properties of the membranes, namely, the straight channels, adequate porosity, and the 5 microm thickness.

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PubMed2004

Nanoporous microsystems for islet cell replacement.

The inadequacy of conventional insulin therapy for the treatment of Type I diabetes has stimulated research on several therapeutic alternatives, including insulin pumps and controlled release systems for insulin. One of the most physiological alternatives to insulin injections is the transplantation of insulin-secreting cells. It is the beta cells of the islets that secrete insulin in response to increasing blood glucose concentrations. Ideally, transplantation of such cells (allografts or xenografts) could restore normoglycemia. However, as with most tissue or cellular transplants, the cellular grafts, particularly xenografts, are subjected to immunorejection in the absence of chronic immunosuppression. Thus, it is of great interest to develop new technologies that may be used for islet cell replacement. This research proposal describes a new approach to cellular delivery based on micro- and nanotechnology. Utilizing this approach, nanoporous biocapsules are bulk and surface micromachined to present uniform and well-controlled pore sizes as small as 7 nm, tailored surface chemistries, and precise microarchitectures, in order to provide immunoisolating microenvironments for cells. Such a design may overcome some of the limitations associated with conventional encapsulation and delivery technologies, including chemical instabilities, material degradation or fracture, and broad membrane pore sizes.

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