Focus
Clinical Analysis Moves into the Doctor's Office Small clinical analyzers that utilize dry reagent chemistries are finding new uses in physicians' offices
Medical equipment distributors are reporting rapid growth in sales of inoffice testing equipment, and two new dry chemistry analyzers, the Ames Seralyzer and Kodak Ektachem, probably account for most of this growth. The vast majority of physicians still send their samples out to reference laboratories, but more and more doctors are starting to tap into the huge clinical testing business. In-office testing currently represents only $50 million of the billion-dollar annual laboratory chemistries business, but Eastman Kodak and the Ames Division of Miles Laboratories are determined to increase the in-office share. The Ames Seralyzer was introduced in January 1982 for use in small clinical laboratories and physicians' offices. This modular instrument runs many tests commonly needed by these laboratories, and additional tests are being developed all the time. Ames recently introduced a new Seralyzer module that analyzes theophylline, a drug routinely used in the treatment of asthma. Other drugs for which tests are currently being developed include anticonvulsants used in the treatment of epilepsy and antiarrhythmics used in the treatment of heart patients. A new module for the analysis of potassium has also been introduced. The basic Seralyzer costs $2500; new modules are free to those who already own the multitest analyzer. Kodak has been selling its large dry reagent clinical analyzers, the Ektachem Models 400 and 700, to hospitals and other large labs since 1982. It is trying to break into the office market by introducing a small desk-top analyzer, the Ektachem DT60, that will
run the seven most common tests. Assays for total bilirubin, chloride, and CO2 should be added by early spring. This model costs $7500, including an optional module for electrolytes, but Kodak estimates it will return an average of $30,000 per year in test fees to the doctor. Both the Ames and the Kodak analyzers utilize dry reagent chemistries rather than the traditional liquid chemistries used in most large hospital-type clinical analyzers. Dry reagent chemistry has been around for a long time (litmus paper is a good example), but its first clinical use was the Ames Clinistix reagent strip for testing uri-
Dry reagent slide for Kodak's DT60
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Ektachem
nary glucose, which was introduced in the 1950s. Since then, a whole variety of dry reagent assays have become available. Bert Walter of the Ames Division of Miles Laboratories recently reviewed the specific chemistries involved in several dry reagent assays for both the Ektachem and the Seralyzer (1). Dry reagent analyzers are ideally suited for use in physicians' offices. "Because of their stability and discrete formats, dry reagent chemistries allow cost-effective, low-volume testing," wrote Walter. The dry reagent analyzers are small and require very little technical skill to operate. All that must be done to start an assay is to apply a small amount of sample to a slide. The small sample size required (300 /uL of blood for a serum profile of 15 tests) makes these analyzers ideal for the testing of infants, geriatric patients, and other patients with a small total blood volume. Routine monitoring of therapeutic drugs in the doctor's office is an important application of the small clinical analyzers. The optimum dose ranges are very narrow for many drugs that must be administered regularly for treatment of chronic diseases. For example, theophylline, a drug taken by many asthma sufferers, has a notoriously narrow therapeutic index. "In order to achieve the greatest maximum benefit with minimal risk of toxicity, dosage adjustment must be guided by serum concentration measurements," wrote Leslie Hendeles of the University of Florida (2). The presence of clinical analyzers in doctors' offices will allow them to incorporate drug monitoring as part of routine 0003-2700/84/0351 -038A$01.50/0 © 1984 American Chemical Society
Focus treatment, resulting in better patient care. Cost of the in-office theophylline assay is estimated at just under $7 per determination, compared with up to $40 for the equivalent hospital test. Aside from the advantages of whileyou-wait testing, the new analyzers are financially attractive to doctors. The simplicity of the new techniques makes the analyzers very inexpensive to operate. Greater pressure for health care cost containment and the fact that many insurers will now pay only for the least costly manner of health care (many Blue Cross member plans provide financial incentives for the performance of more in-office procedures) are factors that will tend to keep the number of small analyzers found in doctors' offices on an upward curve. The in-office analyzers would not have gained much acceptance if their precision and accuracy had not compared favorably with the traditional liquid reagent analyzers used in most hospitals. But the performance of dry reagent chemistries has been shown to be comparable to the more established procedures (2). When representative assays from both the Ames and the Kodak analyzers were compared to their traditional counterparts, correlation coefficients were all greater than 0.99. Now that clinical analyzers are in the office, what next? The increasing emphasis on "wellness" is causing more and more people to monitor their own health at home. In a recent review on self-testing, Alfred and Helen Free of Miles Labs point out that many chemical assays are already available for the home user, including tests for glucose, ketones, and many other analytes (3). Diabetics have been monitoring their own blood sugar levels using dry reagent strips for years. Many women now do home pregnancy tests before they go to see their doctors. A new home test for breath alcohol is giving drinkers a way to check their ethanol level before they drive. And new home tests are being developed for cholesterol and venereal diseases such as syphilis and herpes. As more new assays are developed patients will increasingly be able to take better care of themselves with the assistance of their doctors. M.D.W. References (1) Walter, B. Anal. Chem. 1983,55, 498514. (2) Hendeles, L.; Weinberger, M. Immunol. Allergy Pract. 1984, 6, 53-59. (3) Free, A. H.; Free, H. M. Clin. Chem. 1984, 30, 829-38.
Electrochemistry Faces Reality "Ten years ago, electrochemistry [EC] was really not very relevant to chemical analysis," said Larry R. Faulkner provocatively at a recent symposium. "At that time, the practical application of electrochemistry to real analytical problems was sorely lacking." According to Faulkner, most analytical chemists would have attributed a host of deservedly unattractive characteristics to the electroanalytical chemistry of the early 1970s: • EC techniques were slow, messy, and cumbersome. Many of them were oriented to the dropping mercury electrode (DME), which, said Faulkner, "nearly everybody finds cumbersome." • There were problems associated with electrode fouling, particularly in complex matrices such as in biological samples. • EC scans exhibited a very low peak capacity—at best, only a few analytes could be determined simultaneously. "The width of a voltammetric peak is thermally determined," explained Faulkner, "and there's nothing you can do about it." • Sensitivity was often unspectacular. • There was little commercial equipment available, and what was available tended to be unsophisticated. • Electrochemical techniques were very labor intensive and generally incompatible with automatic sampling. Fortunately, EC began to face reality in the early 1970s—the reality of dealing with complicated samples. "We've come a long way since then," said Faulkner,"and what we can see ahead is really dramatically different from what we see in the past." Faulkner, a professor at the University of Illinois, was speaking at a symposium arranged by Jeanette G. Grasselli of Sohio and held to celebrate the tenth birthday of the Federation of Analytical Chemistry and Spectroscopy Societies (FACSS). The FACSS meeting was held in Philadelphia in late September 1984. LCEC According to Faulkner, one dramatic new approach that has had a significant impact in the past decade is liquid chromatography-electrochemistry (LCEC), pioneered by Peter Kissin-
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ger, a professor at Purdue University and president of Bioanalytical Systems Inc. (BAS). LCEC, in which a separation step precedes electrochemical analysis, was an extremely important development, in that it allowed EC to address complex matrices for the first time. This approach has been so successful, said Faulkner, "that there's probably a vastly larger number of electrochemical assays being
Instruments have been so complicated to operate that only specialists could operate them. carried out by LCEC than essentially any other method at this time." SMDE A significant improvement in electrode design in the past decade was the development of the static mercury drop electrode (SMDE) by EG&G Princeton Applied Research Corporation (EG&G PARC). According to Faulkner, the SMDE gets rid of the time dependence in electrode area and is therefore an "extremely important improvement" over the DME, whose electrode area changes continuously in the course of an experiment. Cybernetic instrumentation A major problem in EC until very recently was the need to have multiple setups to accommodate the multiplicity of electrochemical experiments. According to Faulkner, "Instruments have been so complicated to operate that only specialists could operate them." But the past five years have seen the development of advanced instrumentation that does not need to be reconfigured for each experiment, instrumentation with microprocessorcontrolled access to a repertoire of different electrochemical techniques (i). Faulkner played a major role in the
