Clinical analyzers

Clinical Applications Perhaps the area in which ion-selective electrodes receive the widest use is in clinical analysis, where their selectivity for the analyte in a complex matrix provides a significant advantage over many other analytical methods. The most common analytes are electrolytes, such as Na+, K+, Ca +, H+, and Ch, and dissolved gases, such as CO2. For extracellular fluids, such as blood and urine, the analysis can be made in vitro with conventional electrodes, provided that sufficient sample is available. Some clinical analyzers place a series of ion-selective electrodes in a flow... 

Absorbance. Analyte measurements in clinical analyzers using Hquid reagents are most commonly performed by transmission of light, ie, by absorbance photometry or colorimetry (Fig. 3a). The Hquid to be analyzed is either held in a cuvette or passed through a flowceU having transparent walls. 

Clinical analyzers can also be classified according to their degree of flexibiUty. Most of the modern systems are random access analyzers, for which the tests on various specimens are performed in any order programmed by the operator. Some analyzers operate in batch or profile mode, ie, they perform the same test or group of tests on every sample until the system is reset for another test or group of tests. 

After centrifugation, the specimens are placed in a holder specifically designed to work with a particular instmment. Some clinical analyzers utilize... 

Automated clinical analyzers became affordable, not only to small hospital laboratories, but to doctors group practices and to individual doctor s offices as weU. 

Fields of Application for ion-selective electrodes o Routine-analytical work in the laboratory (direct or as end-point indicators application frequency in industry 30%) o Clinical analyzers for Na+, K.+, Ca2+, pH, pC02, etc. o Process analyzers... 

The worldwide prevalence of ion-selective electrodes (ISE s) in clinical analyzers is a consequence of a major research effort which spanned more than two decades. The... 

Clinical chemistry, particularly the determination of the biologically relevant electrolytes in physiological fluids, remains the key area of ISEs application [15], as billions of routine measurements with ISEs are performed each year all over the world [16], The concentration ranges for the most important physiological ions detectable in blood fluids with polymeric ISEs are shown in Table 4.1. Sensors for pH and for ionized calcium, potassium and sodium are approved by the International Federation of Clinical Chemistry (IFCC) and implemented into commercially available clinical analyzers [17], Moreover, magnesium, lithium, and chloride ions are also widely detected by corresponding ISEs in blood liquids, urine, hemodialysis solutions, and elsewhere. Sensors for the determination of physiologically relevant polyions (heparin and protamine), dissolved carbon dioxide, phosphates, and other blood analytes, intensively studied over the years, are on their way to replace less reliable and/or awkward analytical procedures for blood analysis (see below). 

The relative simplicity of the sensor setup allows them to be implemented into portable automated devices or bed-side analyzers (Fig. 4.2), which are easily installed at patient beds, eliminating the time-consuming laboratory analyses. On the other hand, modem high throughput clinical analyzers may process more than 1000 samples per hour and simultaneously determine dozens of analytes, using a handful of analytical methods. Blood electrolyte analysis, however, remains one of the most important in... 

FIGURE 4.2 From top left, clockwise hand held i-STAT clinical analyzer and cartridge from Abbott Laboratories, bench top GEM 3000 clinical analyzer from IL, Inc., and large mainframe clinical analyzer UniCel DxC800 from Beckman Coulter, Inc. All these systems utilize ion-selective electrodes to determine clinically relevant electrolytes. 

Ion-selective electrode research for biomedical analysis is no longer the relatively narrow, focused field of identifying and synthesizing ionophores for improved selectivity and the integration of ion-selective electrodes into clinical analyzers and portable instruments. These efforts have matured now to such an extent that they can teach valuable lessons to other chemical sensing fields that are just emerging technologies. 

Pnsms [SILICA - SYNTHETIC QUARTZ CRYSTALS] (Vol 21) from bromides pROMINE COMPOUNDS] (Vol 4) use in clinical analyzers [AUTOMATED INSTRUMENTATION - CLINICAL CHEMISTRY] (Vol3) of vitreous silica [SILICA - VITREOUSSILICA] (Vol21)... 

The throughput range, number of assays performed per hour, of clinical analyzers reflects the diversity of the market. 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. Table 1 lists a number of representative automated systems and their characteristics. 

In the earlv 1960s. a promising approach to glucose monitoring was rlcreloped in the form of an enzyme electrode lhal used oxidation of glucose by the enzyme GOD, This approach has been incorporated into a leu clinical analyzers lor blood glucose determination... 

The FC procedure was automated some time ago (Slinkard and Singleton, 1977). Although there have been no more published reports on contemporary automation, there are many laboratories that have adapted the procedure to clinical analyzers (G. Burns and T. Collins, pers. comm.). It seems likely that the procedure could be adapted to other analyzers as well. 

Two types of electrodes are used in clinical analyzers, based either on a sodium glass or plastic membrane. As in the case of the pH sensor,... 

An electrode with a plastic membrane containing valinomycin as the active carrier is now predominantly used in clinical analyzers. Nearly four decades of experience with this sensor have proven that it fulfils all demands concerning sensitivity, selectivity and lifetime. An anionic interference that can be observed during measurements in undiluted urine may be eliminated by the use of silicone rubber instead of polyvinyl chloride in the membrane or by pre-dilution of urine. Despite some experimental trials, no other ionophore has replaced valinomycin as the active compound in potassium ISEs. This is basically due to the better stability and lipophilicity of this compound in comparison to the others proposed. 

The development of a sensor for ionized magnesium turned out to be one of the most difficult challenges of recent years. Several carriers have been designed for this purpose but none have been satisfactory. The first report of a successful measurement of ionized magnesium in an automated clinical analyzer (Thermo, prev. KONE) was published only in 1990 [30]. The ionophore ETH 5520 was used as the active compound. Two other carriers have been used since then ETH 7025 (Roche, former AVL), and a derivative of 1,10-phenenthroline (Nova). All of the magnesium sensors are based on a plastic membrane. Numerical compensations of the influence of calcium ion and the ionic strength are used due to insufficient selectivity of the magnesium sensors. 

The most widely used sensor for chloride ions in clinical analyzers is based on an ion-exchanger, a quaternary alkylammonium chloride, dispersed in a plastic membrane. It is not an ideal sensor due to the interference of lipophilic anions (e.g., salicylates, bromides) and lip-ophylic cations (e.g., bacteriostatic agents, anesthetics) and a relatively poor selectivity towards hydrogen carbonates (bicarbonates). However, compared to charged anion- and neutral carrier-based membranes that have been tested, it is still the best-suited for automated analyzers. 

The reference electrode (system) and its stability in clinical analyzers is a crucial problem because all typical ISSs (and GSSs) use this electrode. Currently silver chloride electrodes are used. They work in two systems an open liquid junction or a constraint liquid junction with concentrated KC1 (>2M) or sodium formate (4M) as the equitransferent hypertonic electrolyte bridge. The latter better serves whole blood measurements. 

The use of ISSs and GSSs in clinical analyzers has proven to be an effective answer for the growing clinical demand for specific, fast, inexpensive and fully automated measurements. These electrochemical sensors allow for clinical analysis of the most frequently requested parameters (analytes). They are today a routine element in clinical analyzers and an everyday partner of clinical chemists. 

The protocol presented reflects a real study that resulted in the introduction of the first commercial clinical analyzer measuring ionized magnesium in blood, i.e. Microlyte Mg [1-3]. 

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