In recent years, rapid advancements have been made in the biomedical applications of microtechnology and nanotechnology. While the focus of such technologies have been primarily on in vitro analytical and diagnostic tools, more recently in vivo therapeutic and sensing applications have gained attention. The long-term integration of cells with inorganic materials provides the basis for novel sensing platforms. The work presented here focuses on the ability to maintain cells long-term in nanoporous silicon-based microenvironments. This article describes the creation of nanoporous, biocompatible, alumina membranes as a platform for incorporation into a cell-based device targeted for in situ recording of cellular electrical activity variations due to the changes associated with the surrounding microenvironments. Studies described herein focus on the interaction of nanoporous alumina substrates embedded in silicon patterned with cells of interest. The fidelity of such a system is demonstrated in terms of viability, proliferation, and functionality. The capability of such microfabricated nanoporous membranes, as in vitro for cell-based assays for sensing and drug delivery applications, is also demonstrated. It has potential in vivo application for therapeutic immunoisolation.