Automated methods of analysis

The increased demand for analyses has led to the introduction of machines that will perform all or part of an analytical procedure. Many of the manipulations in laboratory methods are common to a variety of different tests (e.g. pipetting) and lend themselves readily to mechanization. 

The introduction of instruments into a laboratory that will perform these tasks will result in a reduction in the analysis time and mean that an increased workload can be met without the need for additional staff. This should reduce the overall cost per test even though the expense associated with the purchase and running of the instruments may be high. 

An automated system, by definition, should perform a required act at a predetermined point in the process and should have a self-regulating action. This implies that intervention by the analyst is not required during the procedure and that only those systems that incorporate a microprocessor or computer to control and monitor their performance can be designated as automated. Some systems may not comply strictly with this definition but are a valuable means of mechanizing laboratory activities. 

The first so-called automated analysers were developed to carry out analyses by replacing manual pipetting by the mechanical transfer of fixed volumes of sample and reagents. They were designed to mimic the manipulations of a convential manual procedure and sometimes had the capacity to measure the amount of reaction product, usually spectrophotometrically. The 

The 1950s saw the introduction of a completely new approach to automation, in the form of continuous flow analysis. This made a significant contribution to the advance of automated analysis and subsequent development has been in the form of flow injection analysis. The original instruments were single channel and capable of measuring only one constituent in each sample. Multichannel instruments were then developed which could simultaneously carry out several different measurements on each sample. These were useful in laboratories where many samples required the same range of tests. 

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Although the free amino acids are present only at very low concentrations in oceanic waters, their importance in most biological systems has led to an inordinate amount of effort toward their determination in seawater. A sensitive, simple, and easily automated method of analysis, the colorimetric nin-hydrin reaction, has been known in biochemical research for many years. In order for the method to be useful in seawater, the amino acids had to be concentrated. This concentration was usually achieved by some form of ion exchange [251]. An automated method not using a concentration step was developed by Coughenower and Curl [252]. While the method was used successfully in Lake Washington, its limit of detection (0.5 imol/l) is just too great for most oceanic samples. 

Use of unusual automated methods of analysis, although desirable for control testing, may lead to delay in regulatory methods validation because the FDA laboratories must assemble and validate the system before running samples. To avoid this delay, applicants may demonstrate the equivalency of the automated procedure to that of a manual method based on the same chemistry. ... 

Liquid-liquid extraction is by far the most popular separation method for the cleanup and preconcentration of samples because it is simple, reproducible, and versatile. There are several ways to achieve these objectives, from the original discontinuous ( batch ) and nonautomatic techniques to continuous separation techniques incorporated with automated methods of analysis. The methodologies can be classified into two general types ... 

Nitrogen exists in the ocean at oxidation states from -3 to +5. There are three forms of fixed inorganic N NOs", N02 and NH4+. Nitrate is the final oxidation product and is the dominant form of fixed N in the deep ocean. Nitrite generally occurs at very low concentrations because it is an intermediate in the processes of nitrification (NH4+ —> N02 —> NOs") and denitrification (N03 —> N02 —> NO —> N2O —> N2) and so seldom accumulates to a large degree. Concentrations of NH4+ are highly variable but tend to be near the limit of detection in open ocean surface waters. Each of the inorganic forms has a number of manual and automated methods of analysis. We discuss the most widely used below. 

Most laboratories are now computeri/.cd. and the u.se of bar-coding of specimens and automated methods of analysis allows a high degree of pniduclivity and improves the quality of service. Links to computer temiinals on wards and CiP surgeries allow direct access to results by the requesting clinician. 

Until the advent of FIA, all automated methods of analysis emulated not only the sequence, but also the underlying concept of individual operations performed in the course of a manual procedure (Fig. 1.2). A simple chemical assay (Fig. 1.2a) requires mixing of a precisely metered volume of sample solution with a precisely metered volume of reagent. 

An automated method of analysis for germanium spectra was eventually adopted with the advent of sufficient computing power in an ubiquitous platform. This method was improved until it eventually eliminated all but periodic human QA checks. This automated method (Gunnink and Niday, 1972) divides analysis into five tasks ... 

The connection of biochemical reaction with electrochemical detection sometimes causes difficulties, for example if the conditions of the biochemical reaction and detector function are different [317, 318]. In such cases it is advantageous to carry out the biochemical reaction separately and to determine the reaction product after changed conditions [319]. Such an enzyme reactor electrode enables a large choice of detection methods, kinds and forms of applied biologically active materials, number of analyses provided per hour and possibilities of automation. Enzyme reactor electrodes are therefore used not only in the above characterized difficult cases, but are often preferred in automated methods of analysis. 

Chemical kinetic methods of analysis continue to find use for the analysis of a variety of analytes, most notably in clinical laboratories, where automated methods aid in handling a large volume of samples. In this section several general quantitative applications are considered. 

Time, Cost, and Equipment Automated chemical kinetic methods of analysis provide a rapid means for analyzing samples, with throughputs ranging from several hundred to several thousand determinations per hour. The initial start-up costs, however, may be fairly high because an automated analysis requires a dedicated instrument designed to meet the specific needs of the analysis. When handled manually, chemical kinetic methods can be accomplished using equipment and instrumentation routinely available in most laboratories. Sample throughput, however, is much lower than with automated methods. 

Finally, FIA is an attractive technique with respect to demands on time, cost, and equipment. When employed for automated analyses, FIA provides for very high sampling rates. Most analyses can be operated with sampling rates of 20-120 samples/h, but rates as high as 1700 samples/h have been realized. Because the volume of the flow injection manifold is small, typically less than 2 mb, consumption of reagents is substantially less than with conventional methods. This can lead to a significant decrease in the cost per analysis. Flow injection analysis requires additional equipment, beyond that used for similar conventional methods of analysis, which adds to the expense of the analysis. On the other hand, flow injection analyzers can be assembled from equipment already available in many laboratories. 

Automation of solvent extraction. Although automatic methods of analysis do not fall within the scope of the present text, it is appropriate to emphasise here that solvent extraction methods offer considerable scope for automation. A fully automated solvent extraction procedure, using APDC, for the determination of... 

Electric Breakdown in Anodic Oxide Films Physics and Applications of Semiconductor Electrodes Covered with Metal Clusters Analysis of the Capacitance of the Metal-Solution Interface. Role of the Metal and the Metal-Solvent Coupling Automated Methods of Corrosion Measurement... 

It is obvious that the simpler a method of analysis, the easier it will be to automate. Non-destructive methods which involve a minimum of sample treatment are the most attractive. X-ray fluorescence, for example, has been successfully applied to the continuous monitoring and control of process streams. However, the scope of automated analysis is wide and methods have been designed with a basis in nonspecific properties (pH, conductance, viscosity, density) as well as those characteristic of the che-... 

Biomedical analytical chemistry happens to be one of the latest disciplines which essentially embraces the principles and techniques of both analytical chemistry and biochemistry. It has often been known as clinical chemistry . This particular aspect of analytical chemistry has gained significant cognizance in the recent past by virtue of certain important techniques being included very much within its scope of analysis, namely colorimetric assays, enzymic assays, radioimmunoassays and automated methods of clinical analysis. 

The basic principles underlying both automated and unautomated methods of analysis are more or less the same. Out of the broad-spectrum of biological samples blood analysis is the most common one. There exists a number of parameters which may be assayed, and spectrophotometry is ideally suited for nearly all of them, a few typical examples are cited in Table 2.11. 

Give a comprehensive account on the various automated methods of clinical analysis with an appropriate example. 

Part—I has three chapters that exclusively deal with General Aspects of pharmaceutical analysis. Chapter 1 focuses on the pharmaceutical chemicals and their respective purity and management. Critical information with regard to description of the finished product, sampling procedures, bioavailability, identification tests, physical constants and miscellaneous characteristics, such as ash values, loss on drying, clarity and color of solution, specific tests, limit tests of metallic and non-metallic impurities, limits of moisture content, volatile and non-volatile matter and lastly residue on ignition have also been dealt with. Each section provides adequate procedural details supported by ample typical examples from the Official Compendia. Chapter 2 embraces the theory and technique of quantitative analysis with specific emphasis on volumetric analysis, volumetric apparatus, their specifications, standardization and utility. It also includes biomedical analytical chemistry, colorimetric assays, theory and assay of biochemicals, such as urea, bilirubin, cholesterol and enzymatic assays, such as alkaline phosphatase, lactate dehydrogenase, salient features of radioimmunoassay and automated methods of chemical analysis. Chapter 3 provides special emphasis on errors in pharmaceutical analysis and their statistical validation. The first aspect is related to errors in pharmaceutical analysis and embodies classification of errors, accuracy, precision and makes... 

In most manual methods of analysis this relationship is most easily expressed in the form of a calibration graph, although in many automated analysis systems, the equation for the relationship is determined by the instrument. One very common and important step in determining this relationship is the preparation of a series of standard solutions. 

Analytical-scale SFE can be divided into off-line and on-line techniques. Off-line SFE refers to any method where the analytes are extracted using SFE and collected in a device independent of the chromatograph or other measurement instrument. On-line SF techniques use direct transfer of the extracted analytes to the analytical instrument, most frequently a chromatograph. While the development of such on-line SFE methods of analysis has great potential for eventual automation and for enhancing method sensitivities [159-161], the great majority of analytical SFE systems described use some form of off-line SFE followed by conventional chromatographic or spectroscopic analysis. 

If a method of analysis is fast or can be fully automated and requires the testing of few factors (three or less) then the larger designs can be considered. Good choices are central composite designs, or if a linear factor response is expected a full factorial design at two levels. 

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