(713a) Tissue Implantable Biosensors Based On Single Walled Carbon Nanotube near Infrared Fluorescence

In this presentation, several aspects of in vivo glucose detection using a nanotube-based optical sensor are considered. The optical properties of commonly used organic and nanoparticle fluorescent probes are compared with respect to quantum yield, human tissue penetration, and photobleaching stability. The latter two factors are shown to dominate sensor viability and require a near-infrared nanoparticle fluorophore for practical device operation. Single walled carbon nanotubes are cylindrical molecules based on graphene where the nanometer scale radius serves to quantum confine electrons, imparting the material with new and unique properties. A select number of carbon nanotubes fluoresce in the near infrared where human tissue penetration is maximum and biological autofluorescence is minimal. They are also infinitely photo-stable and are therefore one of very few fluorphores that are viable as long term optical biosensors. Our laboratory at the Massachusetts Institute of Technology has developed chemical approaches to modulating the near infrared fluorescence of nanotubes in response to glucose. I will discuss approaches to flux-based sensors as well as affinity schemes based upon hydrogel swelling and nanoparticle aggregation as strategies for robust continuous glucose monitoring. Mathematical modeling suggests that affinity sensing schemes have distinct advantages for monitoring glucose in-vivo. The dynamics of a model optical sensor are compared to a flux-measuring electrochemical sensor of equal area using a mathematical simulation of a healthy patient ingesting three predefined meals per day. Both sensors demonstrate an approximately linear response to blood glucose levels. It is shown that the optical sensor, which transduces glucose concentration, not flux, directly is significantly more stable to membrane biofouling. We will discuss the biocompatibility of such sensors, including strategies that we have taken to reduce inflammation and immunogenicity.