Merle A. Evenson
Report
Departments of Medicine and Pathology-Laboratory Medicine University Of Wisconsin 600 Highland Ave. Madison, Wis. 53792
Criteria for Analytical Instrumentation in a Clinical Analysis Laboratory It is the nature of a man as he grows older...
to protest
against change, particularly change for the better....
The
sad ones are those who waste their energy in trying to hold it back, for they can only feel bitterness in loss and no joy in gain. — John Steinbeck
Traditionally, clinical analysis laboratories have drawn heavily upon analytical chemistry principles and techniques for their daily operation. More recently, the majority of analyses have been obtained with analytical instrumentation in t h e clinical laboratory. I n s t r u m e n t s designed for and delivered to the clinical laboratory in the last five years have usually had their own microprocessors to aid in the operation of the instrument. Hence it is obvious t h a t the "culture shock" of current instrumentation design concepts has been acutely felt in hospitalbased clinical laboratories. Historically, advances in clinical laboratory instrumentation occurred as much as a decade behind analytical chemistry in industry and academia. T o illustrate using a small sample and private survey, about 50% of practicing clinical chemists have at one time performed analyses for sodium and/or potassium in blood using gravimetric techniques. Flame photometry wasn't widely used in clinical laboratories until the early 1950's. 0003-2700/79/A351-1411$01.00/0 © 1979 American Chemical Society
T h e introduction into the clinical laboratory of a photoelectric colorimeter in the late 1930's, an ultraviolet light absorption spectrophotometer in the early 1940's and the flame photometer in the 1950's caused no particular problems for laboratory personnel. In the late 1950's with the introduction of the Technicon Auto Analyzer, the combination of mechanical pumps, dialyzers, continuous flow heating baths, flow colorimeters and strip chart recorders caused some laboratory personnel to become insecure in the use of the instruments. Technicon wisely recognized t h a t it was essential for the pathologist and the medical technologist to be knowledgeable about the instrument to be able to "troubleshoot" and repair it in the laboratory. Technicon created a very successful education program for users: troubleshooting by telephone and a loaner program for defective modules. Their instruments were designed specifically for the clinical analysis laboratory. Prior to Technicon's entry into the marketplace, gen-
eral purpose laboratory instruments were used, and troubleshooting and minor repairs were handled locally, not by the company repair service. These instruments created a need for a basic understanding of vacuum tube electronics by laboratory personnel. T h e next generation of instrumentation was centered around solid state electronics, modular board design, and some microcomputer data processing. Local repair of such instrumentation was exceedingly difficult because of the lack of complete schematics for the user and the nonavailability locally of specialized electronic components. T h e company serviceman would arrive in a rented station wagon with thousands of dollars of complete electronic boards t h a t he would substitute into the instrument until it was again operational. Repair costs, perhaps to pay for huge parts' inventories and travel time, skyrocketed during this period and resulted in the develo p m e n t of preventive maintenance contracts. Current instruments have their own
ANALYTICAL CHEMISTRY, VOL. 51, NO. 14, DECEMBER 1979 • 1411 A
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microprocessors, are modular by elec tronic design and are usually repaired by board exchange. If board exchange doesn't result in a functioning instru ment, many servicemen are unable to logically isolate the problem and re pair it. The local serviceman must then turn to his national service head quarters where, hopefully, a design en gineer can help him. My point is that instruments are now so designed (and in many cases the documentation is so inadequate) that complete under standing of a variety of microproces sor-controlled analytical instruments is almost impossible. Furthermore, since there is no uni formity in the operating codes from one microprocessor to another, it is not easy to remember how to use the different instruments. For example,
"The enormous progress in obtaining fundamental new knowledge is directly related to our ability to make more accurate measurements more rapidly than at any time in our history."
the codes "control L," "EX," "ES CAPE," "EXIT," "HALT," and "STOP" all represent the same func tion, but are unique for each compa ny's microprocessor. Is this really nec essary? How about some cooperation between companies with the user's needs in mind? Wide instrumental variety is essen tial in clinical analysis. The purchase price and repair costs are so incredibly expensive that the laboratory has now become a target for cost containment in the health care delivery system. The argument about lower instrumen tal cost per test is no longer an accept able parameter for justification of an instrumental purchase or a criterion to choose one instrument over another. The new cost criterion is based upon the user obtaining the necessary labo ratory information on a patient sam ple at the acceptable accuracy and ac ceptable precision. Unnecessary in formation, information too accurate or too precise, and unrequested informa tion, regardless of how inexpensive per unit test, are no longer acceptable to cost containment bureaucrats. Suggestions
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than at any time in our history. In strumentation has contributed signifi cantly and will be centrally important to future progress. However, it is now time for instrument designers and manufacturers to focus their instru ments on a more specialized market. The goal should be to sell results, not just instruments. Instrumental mal function as indicated by printed ar rows (up, down, pointed left, pointed right), dots in a small triangle, mirror image L's and other symbols of inde pendent software designers are no longer acceptable to the user. When the printer first starts such printouts, the user initially wonders if he is hav ing a temporary attack of dyslexia or if there is indeed an instrumental prob lem. Tutorial programs and English language messages should replace
The enormous progress in obtaining fundamental new knowledge is direct ly related to our ability to make more accurate measurements more rapidly
CARD
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symbols in all microprocessor-con trolled instruments. General characteristics that instru ments must possess in clinical labora tories include: 24-hour-a-day avail ability; a short start-up time, typically of 5 minutes; a short dwell time of the sample in the instrument, typically 10 minutes; a high sample frequency of over 100 samples per hour; and a small requisite sample volume (50 μΙ_ι). The instrument must be easily calibrated and should be as accurate and precise as is necessary. Regular analysis of National Bureau of Standards stan dard reference materials should be a standard operating procedure. The in strument must be simple to operate. The microprocessor should be an edu cational tool, enabling the user to troubleshoot instrumental malfunc tions. Some instrument companies are now designing boards with LED's that indicate the problem component on the board that is malfunctioning. When such features are available and combined with the dialog now possible with the microprocessor, the user should be able to understand and easi ly operate several different instru ments. The three major groups that con tribute to the design and manufacture of analytical instrumentation for the clinical laboratory are engineers, chemists and marketing personnel.
Failure can be predicted for a chemi cal analysis instrument if either mar keting or engineering has too much in fluence on decisions being made for the instrument. Chemists and users must have the most authority in the decision-making process if the instru m e n t is to succeed. Maintenance of balance in design of instruments is a difficult management problem for in s t r u m e n t companies, but is essential for long-term success.
Specific Needs in Drug and Trace Element Analysis T h e r e are two major types of infor mation needed when drug analyses are performed. In one case the presence of a drug and its metabolites is known and quantitation is the major goal. Al ternatively, the goal is to detect and accurately identify all exogenous sub stances present in the patient's blood. In the former situation, high sensitivi ty, adequate accuracy and high preci sion are necessary characteristics of the analytical process. In the latter case, adequate sensitivity, high accu racy and adequate precision are the guidelines for the procedure. T o be able to expect one instrumental proce dure to fit both situations a t a reason able cost is perhaps wishful thinking. Hence, design considerations should be made for the principal intended use of the drug analysis instrument.
In summary, the last 15 years have produced enormous improvement in clinical analysis instruments, but much more is urgently needed. Unlike the old m a n resisting change, most of us want more change, b u t we now de m a n d focused design of instruments for the purposes intended. T h e Clinical Improvement Acts t h a t regulate interstate commerce of clini cal analysis require performance crite ria of instrumental methods through proficiency testing. T h e medical de vice laws enforced by the Federal Drug Administration are intended to protect the public from "substantial hazard" caused by analytical errors. Hence, the users suddenly are in a strong legal position to insist t h a t per formance criteria are met. Careful at tention to details by the designers and manufacturers will easily satisfy t h e regulatory agencies if care is taken to fit the instrument to the need. Gener alized, widely applicable instruments will not be acceptable in clinical labo ratories in the future. Excessively high purchase and servicing costs (the cur rent situation) will not be tolerated with the cost containment emphasis now emerging in clinical laboratories. T h e task is difficult, the challenge is great, but much of the technology is ready and waiting to be wisely used for improved clinical analysis.
Most meaningful medical informa tion in t h e trace element analysis area will probably be obtained by blood analysis rather t h a n analysis of urine samples. T h e blood sample is more closely related to the current clinical status while the urine sample is an in tegrated value t h a t may summarize the status of the patient over the past 24 hours. However, urine analyses are usually less difficult analytically. T h e concentrations in urine are usually higher, the amount of sample is always larger, and the speciation less complex in urine, so many investigators illus t r a t e their analytical methods using urine samples. If one uses a 1-mL sample of blood, several of the existing analytical in struments have inadequate sensitivity for the many elements of interest. Al, Cr, Mn, Co, Ni, As, Se, Mo, Cd, Sn, P t , Au, and Hg are examples in which most analytical blood measurement methods lack sensitivity. Further, complete speciation and high accuracy in the determination of trace metals in blood are currently impossible for many of the elements of medical im portance. An improvement in sensitiv ity of several orders of magnitude is needed for most metals when mul tielement analysis is used. Speciation perhaps will require separation prior to analysis: T h e requisite methodology is not yet widely available.
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Merle A. Evenson is a professor in the Departments of Medicine and Pa thology-Laboratory Medicine and is Director of the Drug and Trace Ele ment Analysis Laboratory at Univer sity Hospitals. His principal service responsibilities involve the use of liq uid chromatography, gas chromatog raphy, mass spectrometry and atomic absorption spectrophotometry. His research interests are in chemical characterizations of proteins, pep tides and substances of importance in human health and disease.
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