Focus tests, but they are only 82-95% as sensitive as the blood agar culture test, the accepted "gold standard" for group A streptococcus. Peer-reviewed reports of clinical trials of some of the tests report somewhat lower sensitivity and specificity than the manufacturers' data (2,2). The predictive accuracy values of the new tests, an indication of how often the obtained result is correct compared to the "gold standard," range from 70% to 100% for positive results and from 95% to 100% for negative results, based on manufacturers' data. Until a study is performed comparing the accuracies of the different tests under the same conditions, none of the tests can be rated distinctly superior to the others (31 Based on these limited data, the new rapid assays seem to be well suited for in-office screening of suspected strep throat patients. But will their use result in improved health care for patients with streptococcal infections? The manufacturers of the tests obviously think so, and they have been heavily promoting the products for use in physicians' offices, especially those of pediatricians, who see the majority of strep throat cases. They claim that the ability to make a diagnosis more rapidly than the 24-48 hours required for conventional culturing will make a difference in clinical care because use of antibiotics can be started earlier in positive cases and avoided in negative cases. Although recent reports have indicated that early antibiotic treatment does indeed relieve the symptoms of streptococcal pharyngitis, there are still sharply differing opinions concerning this issue. James Todd of the University of Colorado School of Medicine, editor of a series on "Infectious Disease and the Office Laboratory" in Pediatric Infectious Disease, contends that when all of the published studies are critically reviewed, "the conclusion in favor of the postulated antimicrobial effect cannot be extrapolated beyond the populations studied." Todd feels that the advantages of rapid testing and treatment have not been substantiated. Nevertheless, the ability to begin antimicrobial therapy sooner does prevent the spread of streptococcal infections to other children and allows school or day care requirements for a fixed period of antibiotic treatment at home to be fulfilled more quickly. This, in turn, allows children to return to school, and working parents to their jobs, more quickly. This same early treatment advantage can be achieved by obtaining a throat culture and im-
mediately starting the antibiotic treattment before the culture results are known, although proponents of the rapid tests point out that this methodd introduces the risk of anaphylactic shock. Todd points out, however, thatit the rate of moderate or severe anaphyylaxis from a single dose of penicillin iss no more than 0.025% (3). Critics of the rapid tests are concerned about the tests being used for purposes other than those for which they were designed and also about thee conditions under which the clinical data supporting their use were obtained. The manufacturers of the rapid tests are careful to specify in their product inserts that the tests are meant for screening purposes only andd should be used to augment, not replace, culture procedures. Most of theÎ product inserts also recommend that a negative result from a symptomatic patient be confirmed by culture beforee group A streptococcal pharyngitis is ruled out. The manufacturers also indicate that the rapid tests are intended for use in the doctor's office, but all of thee reported sensitivity and specificity data apparently were obtained using trained laboratory personnel. There is3 no indication as to how accurate the test kits are when used under office conditions. Many doctors' offices routinely perform their own traditional throat cultures also, however, and inaccuracy of nonlaboratory personnel in reading such cultures has been reported, with up to 60% of the positive cultures being missed (2). It has been postulated that in this setting, the advantages of speed, simplicity, high specificity, and high predictive values of the rapid tests may outweigh the disadvantage of the lower sensitivity,
with diagnostic laboratories still being used to confirm negative results when clinically warranted. The rapid tests may also take more time to perform than it may initially appear. Even though the "hands on" time for these tests is extremely short, they may require constant or intermittent attention, and this could have a major effect on a busy office, says Todd (3). But if daily batching is used to avoid the piecemeal consumption of time, much of the real value of rapid diagnostic technology will be lost. An intermediate solution would be to perform the test two or three times a day in smaller batches and then to contact the families with the results, although this also would tend to mitigate the time advantage of the "fast" tests. The lack of comparative data for the rapid tests makes the medical advantages of the rapid diagnostic tests over traditional throat cultures difficult to determine. But the real support for rapid streptococcal testing will most likely result from nonmedical considerations: Many parents will believe that the availability of the rapid tests is of substantial benefit to their children, and doctors will feel pressured to offer the service to remain competitive (3). In these days of two-career couples, a diagnostic test that reduces the time a parent must stay home from work with a sick child is bound to be a success. M.D.W. References (1) Med. Lett. Drugs Therap. 1985,27. (2) Venezia, R. Α.; Ryan, Α.; Alward, S.; Kostun, W. A. J. Clin. Micro. 1985,21, 395-98. (3) Radetsky, M.; Wheeler, R. C; Roe, M. H.; Todd, J. K. Pediatr. Infect. Dis.
1985,4,274-81.
Trends in Chemical Instrumentation What is on the near horizon for chemical instrumentation development? According to the winner of the 1985 Chemical Instrumentation Award, we'll be seeing increased development of miniaturized, nondestructive, multidimensional, and higher resolution instruments. Indiana University chemistry professor Gary M. Hieftje (pronounced heef-ya) made his predictions in an award address at the 1985 American Chemical Society National Meeting in Chicago,
1374 A · ANALYTICAL CHEMISTRY, VOL. 57, NO. 13, NOVEMBER 1985
111., in September. The Chemical In strumentation Award is sponsored by the Dow Chemical Company and ad ministered by the ACS Division of Analytical Chemistry. In the area of miniaturized instru ments, Hieftje sees spectrometers that fit on single integrated chips. "The technology already exists to put a complete monochromator plus a pho todiode array system on a single chip," he said. "It then becomes possible to use such integrated systems as in-
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plant devices, as remote sensors, and for many other applications." In the factory, Hieftje predicts, well be seeing an increasing trend toward more portable or extensible instrumentation that can be brought to the sample, in place of systems in which samples must always be brought to the instrument. Nondestructive techniques will also be popular, according to Hieftje. He pointed to thermal-wave imaging and impulse-response photoacoustic spectrometry, which are under development at the University of Manchester Institute of Science and Technology and elsewhere, and near-infrared spectrometry as three important techniques in this area. "Bounce near-infrared radiation off the surface of a sample," he said. "Then, with computer techniques, it is possible to correlate the diffusely reflected radiation not only to the concentration of the sought-for constituent, but also to some macroscopic or physical properties of the sample." Multidimensional and higher resolution techniques are both valuable in that they provide higher information content, Hieftje explained. The simplest mathematical expression of information theory is the following equation: Pinf = kRaRt, . . .R(. . .Rx where P ln / is the informing power, k is a constant, and the Rfs represent the number of resolution elements in each of the χ dimensions available in the measurement. "In hyphenated techniques like GC/MS [gas chromatography/mass spectrometry]," he said, "we have two systems that provide orthogonal infor mation. That's the exact case to which the above equation applies: Informa tion provided by each technique has to be exactly orthogonal (independent). If the techniques are independent— and GC and MS by and large are—we get a number of resolution elements from the GC and a number from the MS. The more dimensions we have and the higher the resolution we have along each dimension, the more infor mation we're going to have." Two techniques that represent this trend toward higher information con tent are ultrahigh-resolution nuclear magnetic resonance (NMR) spectrom etry and imaging secondary ion mass spectrometry (SIMS). Ultrahigh-reso lution NMR, currently under develop ment in Adam Allerhand's laboratory at Indiana University, provides 6-mHz resolution, which, according to Hieftje, "is amazing resolution in NMR. Six millihertz means that we
RAPID KINETICS ACCESSORY
FOR UV/VISIBLE SPECTROPHOTOMETERS AND SPECTROFLUORIMETERS TheSFA-11 RAPID KINETICS ACCESSORY uses the proven stopped-flow technique to reduce the fastest reaction half-life measurable from several minutes to well under a second. FEATURES INCLUDE: • Rapid mixing, dead times < 2 0 m s • Close temperature control ' • Integral mixing/observation cell • 2 and 10mm pathlengths standard • Easy to use, fitted in seconds Experimental performance The following data were obtained from a typical reaction which shows the kinetics of formation F e C N S 2 + , using a Pye Unicam SP1750 Spectrophotometer with a Fison's Vitatron Chart Recorder set on 'Fast Forward' speed.
Focus can improve detection of the perturbation on the resonance of a single carbon atom by carbon atoms as many as three removed from the parent atom. According to connectivity theory, if we can track out neighbors that are three atoms away from the parent carbon atom, we can unravel the entire structure of the molecule without having access to reference library spectra." Another colleague of Hieftje's at Indiana University, Kenneth L. Busch, is developing an imaging SIMS technique that is similarly impressive in its information content. The technique builds on the well-established two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) technique, in which biological substances are separated in one dimension on the basis of molecular weight and in a second dimension based on charge characteristics/With imaging SIMS," said Hieftje, "we beam cesium ions at a plate that already contains two orthogonal dimensions of information. The cesium ions will sputter material from spots on the plates, making it possible to determine the molecules on each spot. So here we have four orthogonal dimensions—two chromatographic dimensions, mass, and intensity—each of which has high resolution. If each dimension provided only 100 resolution elements, we'd have 100 million resolution elements, evçn better than
a chromatographic run with a million theoretical plates." Hieftje went on to provide detailed accounts of three instrument systems that represent the new directions he predicts for the instrumentation of the future: • FAST (for fluctuation analysis spectroscopic techniques), applicable to fluorimetry, impulse-response photoacoustic spectroscopy, and stochastic photolysis; • thermal-wave imaging, which represents the trend toward multidimensional, nondestructive, and higher resolution instrumentation; and • fiber-optic-based sensing, applicable to scattering, absorption, and fluorescence experiments. Ending his presentation with some suggestions of instruments that might be developed in the far distant future, Hieftje admitted that although wholebody MS, linear ramp chrono-jump coulometry, reversed-phase supercritical fluid titrimetry, and Fourier transform gravimetry may not seem practical at present, "at least they contain the right buzzwords." On a more serious note, Hieftje urged students and researchers who want to develop new chemical instruments to "browse in the physics, engineering, and biology literature . . . Don't just stick to chemistry. You can often learn more about your own discipline by browsing in these other areas." S.A.B.
Study Probes Instrument Sales to Biotech Market
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"During the building period in the following decade, the companies that support and meet the specialized instrument needs of the emerging biotech industry will grow and prosper." This quote from "Biotechnology Instrumentation Market '85," a study by Delco Scientific Resources, is hardly profound. Nevertheless, it is an accurate representation of what has become conventional wisdom in the scientific instrument industry in the past couple of years. This well-written study, which assesses the influence of the biotechnology industry on scientific instrument sales, includes information on highperformance liquid chromatography (HPLC) instruments, columns, and detectors; protein and DNA synthesizers; UV-VIS spectrometers; gel electrophoresis equipment; laboratory fermenters; robotics; and biotech-related
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computer software and hardware. According to the report, these are the systems that "will have a significant impact on the biotechnology market and will implement its coming of age." In the area of HPLC instrumentation, the study affirms that "most HPLC manufacturers are looking to biotechnology for their new growth markets." The fastest growing applications area for HPLC in the biotech market, according to Delco Scientific, is in the production of diagnostic reagents produced by either hybridoma or recombinant DNA (rDNA) techniques. The study claims that Waters Chromatography Division of Millipore "enjoys the leading position in overall systems sales to all classes of [HPLC] users. Not surprisingly, Waters is also the leader among users in the biotechnology disciplines. The survey we con-
