Clinical chemistry applications

Hage DS. Affinity chromatography A review of clinical applications. Clinical Chemistry 1999 45(5) 593-615. 

Table 5-47, Special fields of application clinical chemistry.

The applications of Beer s law for the quantitative analysis of samples in environmental chemistry, clinical chemistry, industrial chemistry and forensic chemistry are numerous. Examples from each of these fields follow. 

The potentiometric determination of an analyte s concentration is one of the most common quantitative analytical techniques. Perhaps the most frequently employed, routine quantitative measurement is the potentiometric determination of a solution s pH, a technique considered in more detail in the following discussion. Other areas in which potentiometric applications are important include clinical chemistry, environmental chemistry, and potentiometric titrations. Before considering these applications, however, we must first examine more closely the relationship between cell potential and the analyte s concentration, as well as methods for standardizing potentiometric measurements. 

An emphasis on practical applications. Throughout the text applications from organic chemistry, inorganic chemistry, environmental chemistry, clinical chemistry, and biochemistry are used in worked examples, representative methods, and end-of-chapter problems. 

Amino Acids, Thin-layer chromatography has found wide application in the clinical chemistry laboratory. An application that is practicable in the Laboratory of Neonatology is the screening of serum and urine for the amino acidopathies. In order to do this we use a micro ultrafiltering apparatus which has been designed in our laboratory (37). This is seen in Figure 29. 

With notable exceptions, the application of HPLC to clinical chemistry has not as yet been extensive. This is somewhat surprising in view of the potential the method has for this area. This potential arises, in part, from the fact that HPLC is well suited to the types of substances that must be analyzed in the biomedical field. Ionic, relatively polar species can be directly chromatographed, without the need to make volatile derivatives as in gas chromatography. Typically, columns are operated at room temperature so that thermally labile substances can be separated. Finally, certain modes of HPLC allow fractionation of high molecular weight species, such as biopolymers. 

A number of applications of modern LC of relevance to clinical chemistry have appeared in the literature. It is obviously not possible to mention all examples rather, we shall try to select applications which illustrate the efforts to date. 

The remarkable selectivity that is inherent in the reaction of an antibody with the antigen or hapten against which it was raised is the basis for the extensive use of immunoassay for the rapid analysis of samples in clinical chemistry. Immunochemical reactions offer a means by which the applicability of potentiometric techniques can be broadened. A number of strategies for incorporating immunoassay into the methodology of potentiometry have been explored... 

The basic aim of PEC applications in clinical chemistry, apart from the recovery of standards of endogenous substances, consists of structural identification of isolated (without further separation) substances of relatively high purity. Therefore, the majority of works devoted to this topic pertain to semipreparative separation. Obtaining low amounts of analytes, achieved by coupling TEC with modem... 

Bl dek, J. and Neffe, S., Application of TEC in clinical chemistry, in Separation Techniques in Clinical Chemistry, Aboul-Enein, H. Y, Ed., Marcel Dekker, New York, 2001, chap. 11. 

Many pesticides are neurotoxicants poisoning the nervous system. A number of pesticides are acetyl cholinesterase inhibitors (Serat and Mengle 1973). Generally, pesticides determination has been performed by GC since the 1960 s (Morrison and Durham 1971 Fournier et al. 1978). There are no reference materials for pesticides in urine or serum, although as with PAHs there are a number biological matrices certified for the content of various pesticides available for environmental food and agriculture analysis and which may have some application in clinical chemistry. 

In the last few years, optimization techniques have become more widely used in the pharmaceutical industry. Some of these have appeared in the literature, but a far greater number remain as in-house information, using the same techniques indicated in this chapter, but with modifications and computer programs specific to the particular company. An excellent review of the application of optimization techniques in the pharmaceutical sciences was published in 1981 [20]. This covers not only formulation and processing, but also analysis, clinical chemistry, and medicinal chemistry. 

Carr P.W., Bowers, L.D., Immobilised Enzymes in Analytical and Clinical Chemistry. Fundamentals and Applications, Wiley-Interscience, New York (USA), 1980. 

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). 

P.B. Luppa, L.J. Sokoll, and D.W. Chan, Immunosensor principles and applications to clinical chemistry. Clin. Chim. Acta 314, 1-26 (2001). 

The properties of a pH electrode are characterized by parameters like linear response slope, response time, sensitivity, selectivity, reproducibility/accuracy, stability and biocompatibility. Most of these properties are related to each other, and an optimization process of sensor properties often leads to a compromised result. For the development of pH sensors for in-vivo measurements or implantable applications, both reproducibility and biocompatibility are crucial. Recommendations about using ion-selective electrodes for blood electrolyte analysis have been made by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) [37], IUPAC working party on pH has published IUPAC s recommendations on the definition, standards, and procedures... 

General books [213-217], chapters [218], and reviews were published in the 1980s reporting the suitability of CL and BL in chemical analysis [219-222], the specific analytical applications of BL [223], the CL detection systems in the gas phase [224], in chromatography [225, 226], the use of different chemiluminescent tags in immunoassay, and applications in clinical chemistry [227-232] as well as the applications of CL reactions in biomedical analysis [233]. 

Wolfbeis O. S. (1988) Fiber Optical Fluorosensors in Analytical and Clinical Chemistry, in Schulman S. G. (Ed.), Molecular Luminescence Spectroscopy. Methods and Applications Part 2, John Wiley Sons, New York, pp. 129-281. 

Bunce et al. [13], in a review of the application of robotics to clinical chemistry, have also attempted to classify the main types of robot available in a simple fashion. For example, robots may be static (i.e. floor, bench or ceiling mounted) or mobile on a tracked system. 

Development of lithium selective electrodes (LiSE) and their application in clinical chemistry have been amply reviewed Several models of lithium ion specific electrodes are commercially available. The central problems in developing such sensing devices are their dynamic range, the accuracy and precision by which the signals are correlated to the concentration of the analyte and the selectivity towards that species, especially in relation to other alkali metal cations. Additional problems of practical importance are the times of response and recovery and the durability of the electrode in the intended service. 

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