Trace Analysis The past, present, and future of trace analytical chemistry were examined at a recent NBS symposium What is the current state of quantitative trace analytical chemistry? What are today's research efforts? And what challenges does the future hold? These are some of the questions addressed at a recent four-day symposium sponsored by the National Bureau of Standards (NBS) entitled "Accuracy in Trace Analysis—Accomplishments, Goals, Challenges." The two plenary sessions held on the first day of the symposium reviewed the history of quantitative trace analysis, discussed the present situation from academic and industrial perspectives, and summarized future needs. The remaining three days of the symposium consisted of parallel sessions dealing with the measurement process; quantitation in materials; environmental, clinical, and nutrient analysis; and advances in analytical techniques. The past, present, and future Herbert A. Laitinen of the University of Florida led off the first plenary session with a brief history of trace analysis. According to Laitinen, the definition of "trace" has greatly changed over the years. In the classic era, said Laitinen, workers would run a complete analysis of a sample and hope that the concentrations of all the constituents added up to 100%. Species that were known to be present by qualitative tests, but in concentrations too low to be quantitated, were lumped together as trace constituents. In the early 1900s, trace continued to designate constituents present at levels below those that could be determined quantitatively, which at that time was 0.10.2%. By the early 1940s, major constituents were considered to be those present in amounts greater than 1%, minor constituents were those present at levels from 0.01 to 1.0%, and trace constituents were those with concentrations below 0.01%. The modern definition of the word trace is more flexible, according to Laitinen, and varies with the background or interest of the analyst. In the mid-1960s, the upper limit for a trace determination was considered to be 100 ppm, and "ultratrace" referred to levels below 1 ppm. The past 20 years have seen great im-
provements in detection limits, and researchers can now determine trace constituents at picogram and even femtogram levels. During the nineteenth century, said Laitinen, emphasis in analytical chem j istry was largely on the introduction of chemical methods for the analysis of a wide variety of materials for major constituents. By the end of that century, physical chemistry had become an established discipline, and this had a profound impact on analytical chemistry
FOCUS during the early part of the twentieth century, when the foundations were laid for modern instrumental analysis. During the 1940s, many new demands on trace analysis emerged as a result of wartime programs, and the flood of publications that appeared during the postwar period, along with new instrumentation, led to modern trace analytical methods. Progress in fields such as solid-state electronics, optics, and computer technology, coupled with demands for increasingly detailed chemical information, continues to stimulate the field of trace analysis. The present state of trace analysis was discussed from an academic perspective by George Morrison of Cornell University and from an industrial standpoint by Bernard Bulkin of BP America. Of 315 chemistry departments listed in the 1985 edition of the ACS Directory of Graduate Research, said Morrison, 201 have at least one analytical faculty member. These departments have a total of 510 faculty members, and although quite a few departments have good-sized analytical groups, many more have just a token analytical chemist. Despite this, he continued, trace analytical chemistry research is alive and well in académie; researchers are involved not only in development of techniques and methodology but also in development of applications to important problems. "In fact," said Morrison, "the analytical requirements imposed by the minute
quantities and typically complex systems involved have led to the development of methodology and instrumentation so specialized as to warrant consideration as a distinct field of analytical chemistry known as trace analysis." Bulkin led off his presentation with a videotape of "Robots at Work," saying that the use of robotics represents as much as anything the current state of trace analysis in industry. Accurate and reproducible quantitative analysis is particularly important in industry because of its impact on competitive position, and industrial analysts must balance the trade-offs between time, cost, and required accuracy for a given determination. Interlaboratory variability, said Bulkin, is a major problem, for what good are sensitivity and spatial resolution without accuracy? Robotics can go a long way toward providing high-quality analyses, said Bulkin. Advantages of robotics include reduced cost and turnaround time for analyses as well as improved quantitative accuracy. The source(s) of variability in the method can be easily determined, and modifications can then be made to remove the variability, even if those modifications are not easy with human operators. Robotics also leads to better quality control because the procedures are unaffected by human nature; true random spiking of samples and analysis of a variety of different standards at different times can be performed. Fred Lytle of Purdue University ended the morning plenary session with a discussion of future trends in trace analysis. One of the more difficult types of trace analysis, said Lytle, is determination of the identity of a pure sample, known as ab initio identification. For this type of determination, the analyst must obtain structural information at trace levels, and, although mass spectrometry is very useful for this, said Lytle, it is a good idea to use more than one technique to identify a given compound. "I think it's important," he said, "to come up with some technique that provides complementary information at these trace levels. We're now starting to see some of these things show up." For example, both matrix isolation FT-IR and infrared fluorescence .can provide low detection limits. And aL though you don't normally think of Raman spectrometry as appropriate for trace analysis, said Lytle, resonance Raman, coherent anti-stokes Raman, and surface-enhanced Raman can all provide good spectra of extremely small samples under certain circumstances. Optically detected NMR is
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The afternoon plenary session featured talks on several emerging areas of quantitative trace analysis, including the use of biomolecules in trace analy sis, robotics, chemometrics, process an alytical chemistry, expert systems, and reference materials. Ed Chait of Du Pont's Biotechnology Systems led off the session with a discussion of bioanalytical chemistry and trace analysis. Since 1982, said Chait, the combined impact of biotechnology, genetic engi neering, molecular biology, and genet-
The past twenty years have seen great improvements in detection limits, and researchers can now determine trace constituents at picogram and even femtogram levels. ics has posed a challenge for analytical chemists. Life scientists have tradi tionally done their own analytical chemistry closely coupled with their experiments, but doing this research on the larger scale required by today's programs for AIDS research and hu man genome sequencing, as well as the scale of new pharmaceuticals, requires dramatic interdisciplinary interven tion by analytical chemists. New ana lytical techniques such as fluorescent DNA sequencing, DNA probes, and peptide synthesis of immunoanalytical reagents, combined with traditional methods such as electrophoresis, said Chait, will play a vital role in the future of trace analysis in bioanalytical chem istry. As an example, Chait described a new instrument developed by Du Pont for DNA sequencing. The role of robotics in the laboratory
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was discussed by Jim Little of Zymark. Little agreed with Bulkin that robots, which are already being used in other fields, should have a major impact in automating operations and procedures performed in chemistry laboratories during the 1980s. Laboratory automa tion, once limited to computerized data reduction, now includes sample han dling and preparation, wet chemistry procedures, and instrumental analysis. Laboratory robots, which combine the technologies of chemistry, analytical instrumentation, computers, and ro botics, can be easily programmed to do a variety of lab procedures and thus no longer require a large number of identi cal, repetitive operations to justify the capital investment. Recent progress in robotics, said Little, has caused an im pact on analytical methodology and laboratory layout, staffing, and work flow, as well as substantial gains in lab oratory performance. J. C. Marshall of St. Olaf s College discussed his collaboration with Tom Isenhour of Utah State University on the application of object-oriented pro gramming strategies, most often expert systems, to chemical problems, includ ing database management, methods development, and knowledge base de velopment. A knowledge base of chemi cal information, said Marshall, is a col lection of executable rules rather than a traditional collection of facts and is much more flexible and powerful than the traditional storage and retrieval schemes. The most difficult phase of expert system work, he said, is the es tablishment of an efficient knowledge base organization. He and Isenhour are currently working on general methods for processing information that will produce the most efficient set of de scriptive rules. Recent work, he contin ued, has demonstrated the advantages of dynamically interfacing expert sys tems to analytical procedures using laboratory robotics to perform the ex periments, with experimental results processed by an expert system. The role of process analytical chem istry—used to supply quantitative and qualitative information about a chemi cal process to not only monitor and control the process but also to optimize its efficient use of energy, time, and raw materials—was discussed by Bruce Kowalski of the Center for Process An alytical Chemistry (CPAC) at the Uni versity of Washington. CPAC was founded as a university-industry coop erative research center with a grant from the National Science Foundation as a response to the need for basic re search in creating new sensors and ana lytical techniques that can be used as integral parts of a wide range of chemi-
FOCUS cal processes. Research areas within CPAC include chemometrics, process chromatography, process control, flow injection, fiber optics, microsensor fabrication, and process analytical instrumentation. CPAC, Kowalski continued, also serves as a clearinghouse for information on analytical methods and a training ground for scientists and engineers skilled in on-line chemical processing, monitoring, and control. (For more information on process analytical chemistry and CPAC, see the REPORT in the May 1, 1987 issue of ANALYTICAL C H E M I S T R Y . )
As is appropriate for a symposium on accuracy in trace analysis, the last two speakers discussed the role of standards in trace analysis. Lloyd Currie of the NBS Center for Analytical Chemistry spoke about the important contributions that chemometrics can make to design, evaluation, and accuracy assurance in multicomponent trace analysis, and Stan Rasberry of the NBS Office of Standard Reference Materials spoke about the role of standard reference materials (SRMs) in the analyst's pursuit of accuracy. Chemometrics, including mathematical modeling, univariate and multivariate statistical analysis, decision and
information theory, and operations research, has some important contributions to make to design, evaluation, and accuracy assurance in multicomponent analysis, said Currie. NBS has a special mission to provide standards for accuracy for all parts of the chemical measurement process, he said, and chemometrics components of this responsibility include assessment of system model and assumption validity; development of consistent nomenclature and scientifically sound formulations with respect to detection, identification, and quantitation; evaluation of the accuracy of algorithms and numerical methods applied to trace analysis data; evaluation of the quality of multivariate data and consideration of standards for reporting such data; and selective generation of standard test data to allow laboratories to monitor the quality of complex data evaluation. SRMs are vital elements in measurement quality assurance, said Rasberry, and are useful in calibration, validation, and especially in determination of accuracy, which is the one thing that seems to worry analytical chemists more than anything else they do. Measurement quality assurance is important in manufacturing, in the service
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sector, and also to academic and R&D efforts. The SRM program was begun in 1906 with the production of metals SRMs and has now expanded to more than 1000 SRMs, including those for metal alloys; environmental standards such as sulfur in distillate fuel oil; gas mixtures; standards for organic constituents such as PCBs, PAHs, dioxins, and even urban dust; inorganic standards; clinical standards; and instru-
4 ® . · .the use of robotics represents as much as anything the current state of trace analysis in industry. * * mental calibrators. Recent additions include a reference material for aspartame aminotransferase (a precursor to heart attack and liver disease), fat-soluble vitamins in coconut oil, and cholesterol. The types of standards available show a natural progression from commodity materials to environmental materials to clinical materials and finally to nutritional materials with the total-diet SRM. When the last trace analysis conference was held at NBS 10 years ago, it focused almost entirely on environmental issues. But there has been tremendous growth in the field since then, said Donald Johnson, director of the National Measurement Laboratory at NBS. The past 10 years have seen almost an explosion of trace analysis in health, nutrition, and especially in industrial quality assurance, where researchers are attempting to determine the relationship of chemical composition to product performance and industrial quality. Most significant, said Johnson, are the computer applications that have developed over the past several years; computers are now beginning to play a major role in measurement design, optimization, artificial intelligence, and robotics. It is important, he continued, not only to determine where we are now but also to project future needs and determine the directions that this area of science will take over the next 10 years. This symposium certainly accomplished that goal, and by the time the next symposium on trace analysis takes place, many more exciting new advances based on the ideas discussed here will surely be reported. Mary Warner
