The objective of this research is development of a method to determine spatial distributions of targeted organic compounds in biological tissue. Such a capability would make possible rapid analysis of tissue for localization of toxins and pharmaceuticals, and quite possibly, their metabolites. Secondary ion mass spectrometry (SIMS) will be employed to obtain organic ion micrographs of the tissue. The spatial resolution which can be attained will be determined by the practical yield of secondary ions, that is, the number of analyte-characteristic secondary ions detected per incident primary ion. Instrumental capabilities will be optimized by rigorous application of ion optical design criteria to the entire secondary ion mass spectrometer. Methods of in situ chemical pretreatment of the sample will be developed for enhancing characteristic secondary ion emission from selected analytes. Choice of primary ion beam species and conditions will be investigated to optimize secondary ion yield. Tandem mass spectroscopy (MS/MS) will be employed so that characteristic ions can be resolved by their structure, in addition to their mass-to-charge ratios, as is currently practiced in SIMS. Data will be obtained using an existing IBM PC/XT data system, with off-line data manipulation and image processing performed by a DEC MicroVAX computer.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM041617-03
Application #
3299879
Study Section
Metallobiochemistry Study Section (BMT)
Project Start
1989-04-01
Project End
1993-03-31
Budget Start
1991-04-01
Budget End
1993-03-31
Support Year
3
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Lockheed Martin Energy Systems, Inc.
Department
Type
DUNS #
City
Oak Ridge
State
TN
Country
United States
Zip Code
37831
Todd, Peter J; McMahon, John M; McCandlish Jr, Carl A (2004) Secondary ion images of the developing rat brain. J Am Soc Mass Spectrom 15:1116-22
Todd, Peter J; Schaaff, T Gregory (2002) A secondary ion microprobe ion trap mass spectrometer. J Am Soc Mass Spectrom 13:1099-107
Todd, P J; Schaaff, T G; Chaurand, P et al. (2001) Organic ion imaging of biological tissue with secondary ion mass spectrometry and matrix-assisted laser desorption/ionization. J Mass Spectrom 36:355-69
McCandlish, C A; McMahon, J M; Todd, P J (2000) Secondary ion images of the rodent brain. J Am Soc Mass Spectrom 11:191-9
Todd, P J; McMahon, J M; Short, R T et al. (1997) Organic SIMS of biologic tissue. Anal Chem 69:529A-535A
McMahon, J M; Short, R T; McCandlish, C A et al. (1996) Identification and mapping of phosphocholine in animal tissue by static secondary ion mass spectrometry and tandem mass spectrometry. Rapid Commun Mass Spectrom 10:335-40
Dookeran, N N; McMahon, J M; Short, R T et al. (1995) Massive cluster ablation as preparation for organic secondary ion imaging. Rapid Commun Mass Spectrom 9:1321-4
Kriger, M S; Cook, K D; Short, R T et al. (1992) Secondary ion emission from solutions: time dependence and surface phenomena. Anal Chem 64:3052-8
Todd, P J; Short, R T; Grimm, C C et al. (1992) Organic ion imaging using tandem mass spectrometry. Anal Chem 64:1871-8