The results of the Phase I feasibility evaluation demonstrated that molecular ion images of selected biomolecules at lateral resolutions on the order of 1 mum or less could be obtained using stigmatic imaging or ion microprobe secondary ion mass spectrometry. In addition, more recent investigations performed on a specially designed time-of-flight secondary ion mass spectrometer (TOF-SIMS) instrument have demonstrated that useful ion images of selected neural compounds could be produced from freeze dried tissue specimens. HOwever, further research is needed before these techniques can be applied routinely and confidently to the analysis of molecular distributions within biological tissues. In particular, the areas that need to be addressed are: 1) optimization of sample preparation/analytical protocol so as to minimize specimen charging during analysis without compromising specimen integrity; 2) development of standardized procedures for the unambiguous interpretation of image ion intensity data for both qualitative and quantitative analysis of organic compounds in biological matrices; and 3) develop a better understanding of the physics and chemistry of sputter ion formation in the production of positive and negative molecular ions from biological matrixes.
The specific aim of the research program proposed herein is to investigate these areas and attempt to develop relevant applications of two and three dimensional biological materials characterization.
