YOU are scheduled for major surgery and have been asked to come to the doctor's office a few days prior to surgery to have some preparatory tests done. One such test that is currently under development may revolutionize surgery and followup treatment. It will determine your metabolism, allowing doctors to personalize your treatment. If your body metabolizes substances quickly, you will need more anesthesia during surgery and higher dosages of medications afterward. A person who metabolizes more slowly will need less anesthesia and smaller doses of medication perhaps at less frequent intervals.![]() ![]() ![]() ![]() |
Accelerator Mass Spectrometry
Mass spectrometry has been used since early in this century to study the chemical makeup of substances. A sample of a substance is put into a mass spectrometer, which ionizes it and looks at the motion of the ions in an electromagnetic field to sort them by their mass-to-charge ratios. The basic principle is that isotopes of different masses move differently in a given electromagnetic field.
An accelerator was first used as a mass spectrometer in 1939 by Luis Alvarez and Robert Cornog of the University of California at Berkeley. To answer what at the time was a knotty nuclear physics question, they used a cyclotron to demonstrate that helium-3 was stable and was not hydrogen-3 (tritium), which is not stable. Accelerators continued to be used for nuclear physics, but it was not until the mid-1970s that they began to be used for mass spectrometry. The impetus then was to improve and expand radiocarbon dating. Van de Graaff accelerators were used to count carbon-14 (14C) for archaeologic and geologic dating studies.
Accelerator mass spectrometry (AMS) quickly became the preferred method for radiocarbon dating because it was so much quicker than the traditional method of scintillation counting, which counts the number of 14C atoms that decay over time. The half-life of 14C is short enough (5,730 years) that counting decayed atoms is feasible, but it is time-consuming and requires a relatively large sample. Other radioactive isotopes have half-lives as long as 16 million years and thus have such slow decay rates that huge samples and impossibly long counting times are required. The high sensitivity of AMS meant that these rare isotopes could be measured for the first time.
Before a sample ever reaches the AMS unit, it must be reduced to a solid form that is thermally and electrically conductive. All samples are carefully prepared to avoid contamination. They are reduced to a homogeneous state from which the final sample material is prepared. Carbon samples, for instance, are reduced to graphite. Usually just a milligram of material is needed for analysis. If the sample is too small, bulking agents are carefully measured and added to the sample.
As shown in the figure below, the AMS unit comprises several parts, all of which are controlled by computer. At the ion source, the sample is bombarded by cesium ions that add an extra electron, forming negative elemental or molecular ions. The ions then pass through a low-energy mass spectrometer that selects for the desired atomic mass. In the tandem Van de Graaff accelerator, a second acceleration of millions of volts is applied, and the atoms and molecules smash through a thin carbon foil or gas, which strips them of at least four electrons. Here, all molecular species are destroyed. Without the high energies in the accelerator, the very tight carbon-hydrogen bonds could not be undone. The ions continue their acceleration toward a magnetic quadrupole lens that focuses the desired isotope and charge state to a high-energy mass spectrometer.
The rare isotope being examined is always measured as a ratio of a stable, more abundant (but not too abundant) isotope, e.g., 14C as a ratio of 13C, which acts as an internal standard and provides a clear signature to differentiate the rare isotope from the background. Their ratio is shown as 14C/13C. In the high-energy mass spectrometer, the abundant isotope is removed from the ion beam and counted in the Faraday cup. Additional interfering ions are removed by the magnetic filter before the remaining ions finally slow to a stop in the gas ionization detector. The charge of individual ions can be determined from how the ions slow down. For example, carbon-14 slows down more slowly than nitrogen-14, so those ions of the same mass can be distinguished from one another. Once the charges are determined, the detector can tell to which element each ion belongs and counts the desired isotope as a ratio of the more abundant isotope.
The two "tricks" that make AMS work are the molecular dissociation process that occurs in the accelerator and the charge detection at the end. The resulting sensitivity is typically a million times greater than that of conventional mass spectrometry. AMS can detect one 14C ion in a quadrillion (1015) other ions.
For 14C dating, precision with accelerator mass spectrometry is typically within 0.5 to 1%, which corresponds to an uncertainty of plus or minus 40 years in a radiocarbon date. For other isotopes, precision generally ranges from 1 to 5% depending on the application.
In biological studies, AMS is used today primarily for counting 14C because carbon is present in most molecules of biological interest and also because 14C is relatively rare in the biosphere. Increasingly, however, other isotopes are being studied. The periodic table below presents the range of long-lived isotopes that are being used or have potential to be used in AMS studies.
One of the Few![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]()
A New Direction |
Studies in Humans![]() ![]() ![]() ![]()
Calcium and Bone Health |
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The Future of AMS![]() ![]() ![]() ![]() ![]() ![]() |
Key Words: accelerator mass spectroscopy, biomedical research, calcium, Human Genome Project, human subjects, MeIQx, osteoporosis, radiocarbon dating, tandem Van de Graaff accelerator, toxicology.
References
1. The May/June 1991 issue of Energy & Technology Review (UCRL-52000-91-5/6, Lawrence Livermore National Laboratory, Livermore, California) is dedicated to articles on the diverse applications of accelerator mass spectrometry at the Laboratory.
2. "Food Mutagens: Mutagenic Activity, DNA Mechanisms, and Cancer Risk," Science & Technology Review, UCRL-52000-95-9, Lawrence Livermore National Laboratory (September 1995), pp. 6-23.
For further information contact Caroline Holloway (510) 423-2377 (ctholloway@llnl.gov).
CAROLINE HOLLOWAY has been director of the Center for Accelerator Mass Spectrometry since March 1997. She was previously with the National Institutes of Health, most recently as acting director of Biomedical Technology at NIH's National Center for Research Resources in Bethesda, Maryland. Holloway is a biochemist interested in lipids and biomembranes. She has conducted biomedical research at E. I. Du Pont de Nemours, the University of Virginia School of Medicine, and the Duke University School of Medicine. Holloway received her B.S. in 1959 from City College of New York and her Ph.D. in biochemistry in 1964 from Duke University, after which she completed postdoctoral research at Shell Agricultural Chemicals in England. She has published more than 25 scholarly articles and papers.