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.
Smith
Catherine
C
iMEDD, Inc., Foster City, California 94404, USA.
Kirk
Randy
R
West
Teri
T
Bratzel
Marsha
M
Cohen
Michael
M
Martin
Francis
F
Boiarski
Anthony
A
Rampersaud
Arfaan A
AA
D000818:Animals; D003911:Dextrans / Q000032:analysis; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives* / Q000032:analysis; D005947:Glucose / Q000032:analysis / Q000494:pharmacology; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007328:Insulin / Q000032:analysis / Q000378:metabolism; D000078790:Insulin Secretion; D008567:Membranes, Artificial; D008970:Molecular Weight; D051381:Rats; D012825:Silicon
D003911:Dextrans; D007074:Immunoglobulin G; D007328:Insulin; D008567:Membranes, Artificial; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate; D005947:Glucose; D012825:Silicon