A long-term flexible minimally-invasive implantable glucose biosensor based on an epoxy-enhanced polyurethane membrane.

This paper describes the preparation method as well as the in vitro and in vivo evaluation of a novel flexible glucose biosensor designed for long-term subcutaneous implantation. An epoxy-enhanced polyurethane membrane, which includes ca. 30-40% epoxy resin adhesive and 50-70% polyurethane, has been developed and used for the first time as the outer protective membrane of the sensor. This new membrane was developed to increase the in vivo durability and lifetime of implantable biosensors. This epoxy-polyurethane membrane was shown to be porous and is of excellent durability. A sensor with such a membrane shows excellent long-term stability and can last for 4-8 months in solutions at room temperature. To verify the in vivo performance of the sensor, nine sensors were implanted in three rats and tested regularly. Eight sensors kept functioning well in the rats for 10-56 days. The ninth sensor was damaged during implantation. All original sensitivity data as well as four response curves obtained at days 7, 17, 52 and 56, respectively are presented.

[1]  D. Cordes,et al.  Continuous glucose sensing with a fluorescent thin-film hydrogel. , 2003, Angewandte Chemie.

[2]  N Wisniewski,et al.  Characterization of implantable biosensor membrane biofouling , 2000, Fresenius' journal of analytical chemistry.

[3]  J. Jansen,et al.  Influence of inflammatory cells and serum on the performance of implantable glucose sensors. , 2001, Journal of biomedical materials research.

[4]  B. Chabert,et al.  Mechanical properties and biocompatibility of two polyepoxy matrices: DGEBA-DDM and DGEBA-IPD. , 1987, Biomaterials.

[5]  K. Kimura,et al.  Potentiometric Ion Sensors with Neutral-Carrier-Type Ion-Sensing Membranes Coated by Biocompatible Phosphorylcholine Polymers , 2000 .

[6]  L. Heinemann,et al.  Sensors for glucose monitoring: technical and clinical aspects , 2001, Diabetes/metabolism research and reviews.

[7]  K. Geckeler,et al.  Enhanced Biocompatibility for SAOS-2 Osteosarcoma Cells by Surface Coating with Hydrophobic Epoxy Resins , 2003, Cellular Physiology and Biochemistry.

[8]  M. Gerritsen,et al.  Silica-based hybrid materials as biocompatible coatings for glucose sensors , 2001 .

[9]  N Nakabayashi,et al.  Improved blood compatibility of segmented polyurethanes by polymeric additives having phospholipid polar groups. I. Molecular design of polymeric additives and their functions. , 1996, Journal of biomedical materials research.

[10]  S A Spencer,et al.  Glucose sensor with improved haemocompatibilty. , 2000, Biosensors & bioelectronics.

[11]  Francis Moussy,et al.  Coil-type implantable glucose biosensor with excess enzyme loading. , 2005, Frontiers in bioscience : a journal and virtual library.

[12]  Kazuhiko Ishihara,et al.  New Biocompatible Polymer: Application for Implantable Glucose Sensor , 1994 .

[13]  G. S. Wilson,et al.  A new amperometric glucose microsensor: in vitro and short-term in vivo evaluation. , 2002, Biosensors & bioelectronics.

[14]  I Karube,et al.  Integration of microfabricated needle-type glucose sensor devices with a novel thin-film Ag/AgCl electrode and plasma-polymerized thin film: mass production techniques. , 2001, The Analyst.

[15]  G. S. Wilson,et al.  Design and in vitro studies of a needle-type glucose sensor for subcutaneous monitoring. , 1991, Analytical chemistry.

[16]  S. Cosnier.  Biomolecule immobilization on electrode surfaces by entrapment or attachment to electrochemically polymerized films. A review. , 1999, Biosensors & bioelectronics.