UC San Diego

Inorganic porous materials are the subject of much investigation for a variety of bio-application including filtration, implant materials, drug delivery devices, and medical diagnostics. Great potential lies in integrating biological systems and inorganic materials for diagnostics and sensing devices. An inorganic sensing device must be able to respond to information transmitted across the biological and inorganic interface. In this way, transduction of information from the biological system can be reported. Biocompatibility and stability is a crucial first concern when combining inorganic porous materials and the physiological environment. The central theme of this work is to combine stable, biocompatible, inorganic porous materials for interrogation of biological events in real time and without extraneous labels. In other words, this dissertation is a combination of studies toward a sm̀art' Petri dish; a substrate that can sense biological events without interference or exhibiting any ill effect on living cells. Results from these studies contribute to using porous silicon and porous alumina as cell culturing substrates or implant materials while simultaneously functioning as a sensor. The first chapter introduces optical sensors and how they are applied for label-free biosensing. Porous Si is one such material that can be used for sensitive transduction of biological interactions. Construction of the material is presented and the optical properties of porous thin films are discussed. The second chapter addresses the biocompatibility of porous Si and the degree of stability it has in physiological environments. The attachment and viability of a primary cell type to porous Si samples containing various surface chemistries is reported. The ability of the porous Si films to retain their optical reflectivity properties relevant to molecular biosensing is assessed. An optical transduction method for monitoring cell viability using pSi photonic crystals is described in chapter three. The substrate is chemically modified to optimize stability and biocompatibility, and then applied in mammalian and bacteria cell culture environments for real-time reporting of cellular health. The method monitors the intensity of scattering by cells of the optical spectrum from the underlying photonic crystal. In the mammalian cell demonstration, cell death by toxin exposure is reported in advance of traditional viability assays. In the bacteria example, cell death by virus is monitored. Chapter four presents a second method for monitoring cell viability using porous Si sensors. The method uses optical interferometry for reporting changes in refractive index as biological material enters the porous framework. Limitations of the optical interrogation technique when using turbid solutions of bacteria cells are described. The instability of pSi in physiological environments limits its potential for long-term optical sensing, and other porous inorganic materials are worth pursuing. The last chapter of the dissertation describes using porous alumina as an optical interferometer for biosensing. The optical transduction method used for biosensing with pAl is described, demonstration of the method as an immunosensor is reported, and the direction of future work is discussed