Automated Instrumentation, Clinical Chemistry

Abstract

Abstract Clinical chemistry, initiated in the 1940s, involves the biochemical testing of body fluids to provide objective information on which to base clinical diagnosis. The ever‐increasing demand for high quality, routine clinical testing stimulated the development of automated techniques, and as early as the 1960s automation in the clinical laboratory was the rule rather than the exception. Although growth was initially driven by automation, in the 1990s the growth in U.S. laboratory testing may be attributed to the discovery of new diseases and the introduction of new therapies, as well as better understanding of body chemistry and the aging of the U.S. population, which increases the risk of contracting age‐related illnesses requiring clinical chemistry analyses. Clinical chemistry analyzers are automated instruments used for measuring concentrations of the various chemical constituents of blood or other body fluids. Sample identification, centrifugation, and filtering; manual metering and addition of sample and reagents into a reaction vessel; mixing and incubation in the reaction vessel; optical measurement of the mixture in a separate cuvette; and calculation and recording of the results are all steps performed by an automated analyzer. An automated system for clinical analysis consists of the instrument (hardware), the reagents, and the experimental conditions (time, temperature, etc) required for each determination. The reagents plus the experimental conditions are sometimes referred to as the chemistry of the system. Chemical determinations available on automated analyzers include those for albumin, calcium, chloride, creatinine, iron, total bilirubin, total protein, alanine aminotransferase (ALT), alkaline phosphatase, aspartate transaminase (AST), carbon dioxide, cholesterol, creatine kinase (CK), gamma glutamyl transferase (GGT), glucose, lactate dehydrogenase (LD), triglycerides, and urea nitrogen. Essential features of an automated method are the specificity. The majority of the various analyte measurements made in automated clinical chemistry analyzers involve optical techniques such as absorbance, reflectance, luminescence, and turbidimetric and nephelometric detection means. Automated clinical analyzers can be divided into discrete and continuous‐flow systems. In discrete systems, the sample–reagent mixtures from different specimens are kept in individual reaction cuvettes during incubation and optical reading. In continuous‐flow analyzers, the sample–reagent mixtures form liquid segments flowing through a tube. Adjacent segments are separated by air bubbles. Systems that perform less than 400 tests per hour are usually referred to as small analyzers; medium analyzers cover the range from about 500 tests per hour to 1,500 tests per hour, while high throughput analyzers can process up to 10,000 tests per hour. Venous or capillary blood, urine, and cerebrospinal fluid are specimens routinely used in medical diagnostic testing. Of these biological fluids, the use of venous blood is by far the most prevalent. The specimen, as drawn, contains cells, platelets, fibrin, and particulates. For most chemistry tests, eg, determination of glucose, cholesterol, etc, it is necessary to first separate the cellular blood fraction. The cellular components are separated by centrifugation. Precisely metered amounts of the sample have to be aspirated rapidly and without allowing inter‐sample contamination, known as sample carry‐over. In most analyzers, sample carry‐over is minimized by sensing the liquid level in the sample container and limiting the probe immersion in the liquid to a few millimeters, or by rinsing the aspiration probe inside and out after each immersion. Many analyzers can be programmed to preform a wide variety of assays. However, reagents for only a limited number of tests, usually referred to as resident tests, are available on the instrument at any one time. The introduction of the dry slide reagent technology where the reagents needed for a particular assay are deposited in thin layers on a slide, and an extension of the continuous‐flow analyzer technology called capsule chemistry were notable technological developments of the late 1980s. The core of the latter system is a capillary Teflon tube coated on the inside with a thin, flowing film of fluorocarbon oil. Sample and liquid reagents, alternating with air bubbles, are aspirated into the tube, forming a segmented flow. The optical detection system includes dedicated or time‐multiplexed arrangements of the various elements such as the light source, cuvette or flowcell, wavelength isolation elements, and detector. The brain of the modern clinical chemistry analyzer is its computer system. The part of the computer system that controls the functional aspects of the analyzer is known as the process control computer or analytical processor (AP); the test results are handled by the data management computer, also known as the results processor (RP).