Atomic spectrometric methods of analysis are the most commonly used techniques for determining the elemental composition of samples in biomedicine, biochemistry, pharmaceutical science, forensic studies, and in other fields. Unfortunately, existing methods of atomic analysis fall short of meeting the modern needs of these fields in a number of important respects. Prominent among these shortcomings are inadequate sensitivity, speed, and elemental coverage. Also, for many applications the required sample size is excessive, precision is inadequate, and accuracy is dependent on the overall composition of a sample or on the ability of an analyst to match samples and standards closely. In this proposal, a plan of investigation is outlined to continue studies that were begun under NIH sponsorship. In these investigations, a new kind of atomic spectrometric instrument is to be designed, constructed, and tested on real samples. Arguments are first put forward to show that the best source for atomic spectrometry is a tandem one that is assembled from two otherwise independent devices. A first source is assigned the function of accepting a sample of the substance to be analyzed and decomposing it as quantitatively as possible into its constituent atoms. These atoms are then directed into a second source, chosen for its ability to ionize these atoms for subsequent analysis by mass spectrometry. Because each of the two sources is given a specific task, it can be selected for its ability to perform that task; furthermore, its operating conditions can be optimized for that purpose. The result is higher sensitivity, reduced background and sample-dependent errors, and better precision. The time-of- flight mass spectrometer (TOFMS) into which the atomic ions are to be sent is also unusual. Unlike conventional mass spectrometers used for atomic analysis, the TOFMS can produce a complete atomic mass spectrum in as little as 50 microseconds, so it is well suited for analyzing transient or tiny samples. Also, because all the ions measured by the TOFMS are extracted from the tandem source at a single instant in time, that ion population represents a """"""""snapshot"""""""" of the ions in the source. Consequently, ion signals can be ratioed or normalized to improve precision further. Lastly, the new system is expected to be especially powerful when employed with laser ablation for microsampling. Even a single laser shot is projected to yield high-sensitivity elemental analyses or isotope ratios, enabling spatial resolution to be achieved in biological samples and microliter-volume sample solutions to be analyzed rapidly.
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