The objective of this research is development of a method to determine the spatial distribution of targeted organic compounds in biological tissue. Trace analysis for drugs, compounds and their metabolites is one application of the method, but analysis of the distribution of more concentrated species such as phospholipids will also be possible. To accomplish this, a secondary ionization (SI) microprobe is attached to a triple quadrupole tandem mass spectrometer (MS/MS) to make a SIMS/MS microprobe. This instrument makes it possible to generate ions from a particular location on the sample using a finely focused beam of the primary ions, and with tandem mass spectrometry, measure the intensity of secondary ions with a particular chemical structure. Three approaches will be used to enhance sensitivity of the methods. First, use of polyatomic primary ions of 20 keV energy for imaging using static (low primary dose) SIMS and MS/MS will be developed. Secondly, coordinated use of two primary ion beams, with different sputtering and ionization characteristics will be used to remove the effects of primary ion beam damage, permit averaging and depth profiling. Third, chemical treatment of samples will be investigated for enhancing characteristic emission and mitigating primary ion damage. Improved sensitivity will allow for spatial resolution to be improved to better than 10 micromoles. Standard sample preparation and pretreatment methods will be developed so that artifacts can be minimized and sensitivity can be measured and predicted.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Metallobiochemistry Study Section (BMT)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Lockheed Martin Energy Systems, Inc.
Oak Ridge
United States
Zip Code
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