Silicon Nanotechnology for Biofiltration and Immunoisolated Cell Xenografts
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Biomedical Microdevices Workshop, University of California, Berkeley, CA 94720 2Microsurgical Institute, Mercy Hospital, San Diego, CA 92103 ABSTRACT Silicon-based clean-room technology is employed for the microfabrication of a particle filter with uniform pore dimensions in the 20-40-nm range. Surface and bulk micromachining are integrated in the fabrication process, resulting in a filtering membrane with large active area, flow rate and resistance to pressure. The microfabricated membrane is especially suitable for biofluid purification, including viral elimination. The nanofilter is a technological precursor for a microfabricated, silicon-based capsule to be employed in the reaction-free xenotransplantation of cells. Results are presented below that address the issue of biocompatibility of the microfabricated capsule components and materials. 1. INTRODUCTION The suitability of microfabricated devices for biomedical applications (BioMEMS) has been widely documented I l I with extensive research and development efforts in universities as well as private laboratories. Preferred areas of BioMEMS research comprise central nervous system (CNS) stimulation and recording, neural regeneration technology, on-chip electrophoretic diagnostics, and biosensors, among many others. The objective of the Biomedical MicroDevices Workshop (BMDW) of the University of California at Berkeley is to develop potentially high-impact BioMEMS concepts that are based on readily accessible clean-room fabrication methodologies. In this communication, advances in the BMDW projects on biofiltration and cell encapsulation are reported. A primary focus of the biofiltration project is the removal of known and unknown viruses from biological fluids. By way of background information, it is recalled that viral contamination is a major unsolved issue for plasma derivatives as well as animal serum- and mammalian cellderived products [2]. Current methods of anti-viral treatment include UV- and gammairradiation, pasteurization, addition of chemicals, centrifugation, as well as size-separation with non-microfabricated polymeric membranes. The transplantation of cell clusters has been reported to be a promising direction for the therapy of several pathologies, such as type I diabetes, Alzheimer's, Parkinson's, and hemophilia. Transplanted cells, however, elicit an immune reaction that leads to their elimination - the immune rejection being more pronounced for cross-species (or xeno-) transplants. Organic non-microfabricated cell containment vessels have been introduced by several researchers with the objective of reducing or eliminating the immune reaction [31, but success to date has been limited by problems relating to the stability, degradation, and biocompatibility of the capsule material. En route to the development of silicon-based microfabricated biocapsules, we are currently addressing questions pertaining to the long-term survival and functionality of cells of interest within silicon-based microfabricated environments. Below we report on our in-
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