Work during the first six years of this project has confirmed the major objectives proposed in the original research plan. We have succeeded in developing a methodology which can produce carbon char materials with a wide range of oxygen sensitivities, suitable for many in vivo applications. During the next five years of the proposed work plan, we plan to build upon our initial accomplishments in order to achieve a fully engineered approach for the synthesis of char sensors. The objectives of this work include (i) the standardization of synthesis conditions for the production of large quantities of sensor materials with specific properties tailored for EPR oximetry in tumors, neurological environments (brain, spine), organs (heart, kidney, liver), and the vasculature, (ii) the control of toxicity in chars, and (iii) the development of chars for advanced oximetry methods (e.g. needle catheter, very low field EPR, DNP). Several of our original hypotheses have been confirmed, particularly those dealing with the relationships between char properties and starting materials, temperature treatments, and flowing gas atmospheres. We have developed a useful model relating the heterogeneous nature of paramagnetic sites in chars to the overall response of the char EPR line width to oxygen, and will use this model to correlate changes in char behavior in biological environments. An improved synthesis/production apparatus will be used in the work to develop and produce chars under highly controlled conditions. The characterization of these newly synthesized materials will be refined, in order to better understand the factors which influence (i) oxygen sensitivity of the EPR spectrum, (ii) water interactions, (iii) toxicity, and (iv) reactivity of the char surfaces to chemical reactions. This part of the program will benefit from the expertise we have gained using a wide range of spectroscopic methods for char characterization, including very high frequency EPR (VHF-EPR), electron-nuclear dynamic nuclear polarization (DNP), NMR, as well as classical surface science methods. Aided by these methodologies, and in collaboration with other groups in this PPG at Dartmouth and Lovain, we will continue to explore the relationships between fundamental char properties and the biological interactions of these materials in living systems. The completion of this work will result in the production of uniquely designed materials which will support many aspects of biomedical research and also begin to address clinical applications of these powerful tools for medical in vivo oximetry applications.
