MEMS-Based Technologies for Cellular Encapsulation

Abstract

In the past, significant progress has been made in applying micro-electromechanical based systems to biomedical applications (BioMEMS). While the focus of such research has primarily been on diagnostic tools, more recently therapeutic applications have been explored. This paper discusses the current state of BioMEMS for therapeutic applications, particularly with respect to diabetes mellitus. A novel therapeutic application of microfabrication technology, a micromachined membrane-based biocapsule, has been developed for the transplantation of protein-secreting cells without the need for immunosuppression. Conventional lithographic techniques can be manipulated to produce monodisperse, nanoporous, biocompatible, silicon membranes. This new approach to cell encapsulation is based on microfabrication technology whereby immunoisolation membranes are bulk and surface micromachined to present uniform and well-controlled pore sizes as small as 10nm, tailored surface chemistries, and precise microarchitecture. Through its ability to achieve highly controlled microarchitectures on size scales relevant to living systems (from μm to nm), microfabrication technology offers unique opportunities to more precisely engineer biocapsules that allow free exchange of the nutrients, waste products, and secreted therapeutic proteins between the host (patient) and implanted cells, but exclude lymphocytes and antibodies that may attack foreign cells. Results indicate that both primary pancreatic cells and insulinoma cells can remain viable and functional within nanoporous silicon biocapsular environments. The cells within such environments can secrete insulin at rates comparable to unencapsulated cells. Moreover, these membranes are able to allow insulin and glucose diffusion, while hindering antibody diffusion. Implanted microfabricated biocapsules show in vivo biocompatibility and vascular ingrowth, particularly when modified with polyethylene oxide surface coating. Thus, microfabricated inorganic encapsulation devices may provide biocompatibility, in vivo chemical and mechanical stability, tailored pore geometries, and superior immunoisolation for encapsulated cells over conventional encapsulation approaches. By using microfabrication techniques, structures can be fabricated with spatial features from the sub-micron range up to several millimeters. These multi-scale structures correspond well with hierarchical biologic structures, from proteins and sub-cellular organelles to the tissue and organ levels.