Flow techniques analysis automation

Flow injection analysis (FIA) was developed in the mid-1970s as a highly efficient technique for the automated analyses of samples. °> Unlike the centrifugal analyzer described earlier in this chapter, in which samples are simultaneously analyzed in batches of limited size, FIA allows for the rapid, sequential analysis of an unlimited number of samples. FIA is one member of a class of techniques called continuous-flow analyzers, in which samples are introduced sequentially at regular intervals into a liquid carrier stream that transports the samples to the detector. ... 

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. 

Since 1970, new analytical techniques, eg, ion chromatography, have been developed, and others, eg, atomic absorption and emission, have been improved (1—5). Detection limits for many chemicals have been dramatically lowered. Many wet chemical methods have been automated and are controlled by microprocessors which allow greater data output in a shorter time. Perhaps the best known continuous-flow analy2er for water analysis is the Autoanaly2er system manufactured by Technicon Instmments Corp. (Tarrytown, N.Y.) (6). Isolation of samples is maintained by pumping air bubbles into the flow line. Recently, flow-injection analysis has also become popular, and a theoretical comparison of it with the segmented flow analy2er has been made (7—9). 

The determination of lead in blood is the most widespread clinical use of ASV The technique is attractive because it is rapid, simple and reproducible A recent advance is to couple ASV to flow injection analysis in order to automate the process so that smaller samples and shorter analysis time can be achieved Lead is also routinely determined in bonemeal meant for human consumption by ASV Both lead and cadmium are determined in agricultural crops by ASV... 

Sample preparation, injection, calibration, and data collection, must be automated for process analysis. Methods used for flow injection analysis (FLA) are also useful for reliable sampling for process LC systems.1 Dynamic dilution is a technique that is used extensively in FIA.13 In this technique, sample from a loop or slot of a valve is diluted as it is transferred to a HPLC injection valve for analysis. As the diluted sample plug passes through the HPLC valve it is switched and the sample is injected onto the HPLC column for separation. The sample transfer time typically is determined with a refractive index detector and valve switching, which can be controlled by an integrator or computer. The transfer time is very reproducible. Calibration is typically done by external standardization using normalization by response factor. Internal standardization has also been used. To detect upsets or for process optimization, absolute numbers are not always needed. An alternative to... 

Continuous analysis offers another very useful possibility of completely automated chemical control, especially in manufacturing processes, but also in analytical processes such as separational flow techniques where the analytical measurement proper acts as a sensor, usually called the detector. As long as a physical or physico-chemical constant yields a sufficiently accurate and specific... 

Automated titrations can be divided into discontinuous and continuous, the former representing a discrete sample analysis, as a batch titration is the usual laboratory technique and the latter a flow technique, which is used less frequently in the laboratory, e.g., in kinetic studies, but is of greater importance in plant and environment control. 

Flow injection analysis (F1A). In this technique, introduced by Ruzicka and Hansen, a small amount of sample is injected into a liquid flow (see Fig. 5.16), which apart from being automated is normally continuous, but can include the use of stopped-flow, merging zones extraction techniques in addition to FIA scanning and methods based on intermittent pumping89. The principles of FIA and the versions just mentioned will now be briefly discussed on the basis of the excellent review of Ruzicka and Hansen89 in order to understand the appli-cational possibilities of electrochemical detection in this technique. 

Flow injection analysis is another technique that has been applied to the determination of nitrate and nitrite in seawater. Anderson [ 126] used flow injection analysis to automate the determination of nitrate and nitrite in seawater. The detection limit of his method was 0.1 imol/l. However, the sampling rate was only 30 per hour which is low for flow injection analysis. Reactions seldom go to completion in a determination by flow injection analysis [127,128] because of the short residence time of the sample in the reaction manifold. Anderson selected a relatively long residence time so that the extent of formation of the azo dye was adequate to give a detection limit of 0.1 pmol/l. This reduced the sampling rate because only one sample is present at a time in the post-injector column in flow injection analysis. Any increase in reaction time causes a corresponding increase in the time needed to analyse one sample. 

Johnson and Petty [129] reduced nitrate to nitrite with copperised cadmium, which was then determined as an azo dye. The method is automated by means of flow injection analysis technique. More than 75 determinations can be made per hour. The detection limit is 0.1 xmol/l, and precision is better than 1% at concentrations greater than 10 xmol/l. 

Flow injection analysis is a fast-developing technique with many potentialities. Particular attractions are the relative simplicity of operation and automation, together with sample throughputs which may exceed 100 per hour. Thus routine monitoring of process streams and pollution control are obvious areas for application. 

There has been significant advancement in the applications of NMR to the development of small-molecule pharmaceutical products. For example, advances in NMR automation (e.g., flow-injection analysis) and directly coupled methods (e.g., LC-MS-NMR analysis) have made analysis and characterization of small-molecule drugs much easier.23 25 These improvements have helped chemists to develop and characterize small-molecule combinatorial libraries and to screen for active compounds.4 6 It is likely some of these techniques can also be used in biopharmaceutical product development. 

Routine analyses of large numbers of similar samples can readily be automated and the sample throughput considerably increased (sometimes up to about 200 samples per hour) by carrying out the analyses in a continuously flowing medium. At present there are two basic approaches to the problem, the older technique of continuous-flow analysis (CFA) introduced more than 25 years ago [145] and widely developed by the Technicon Company (Auto-Analyzer), and more recent flow-injection analysis (FIA for a recent literature review see [123]). For a brief comparative survey of the two methods see [148]. 

Flow injection analysis is based on the injection of a liquid sample into a continuously flowing liquid carrier stream, where it is usually made to react to give reaction products that may be detected. FIA offers the possibility in an on-line manifold of sample handling including separation, preconcentration, masking and color reaction, and even microwave dissolution, all of which can be readily automated. The most common advantages of FIA include reduced manpower cost of laboratory operations, increased sample throughput, improved precision of results, reduced sample volumes, and the elimination of many interferences. Fully automated flow injection analysers are based on spectrophotometric detection but are readily adapted as sample preparation units for atomic spectrometric techniques. Flow injection as a sample introduction technique has been discussed previously, whereas here its full potential is briefly surveyed. In addition to a few books on FIA [168,169], several critical reviews of FIA methods for FAAS, GF AAS, and ICP-AES methods have been published [170,171]. 

Table 5.3 sets out the advantages and disadvantages of the batch and continuous flow techniques. The introduction of continuous-flow hydride/vapour-generation has substantially advanced the value and acceptance of the technique for trace elemental analysis. Appfied Research Laboratories (now part of Fisons Elemental), P.S. Analytical and Varian have all introduced continuous-flow hydride/vapour-generation systems, whilst Perkin Ehner has used the flow injection modification to automate the techniques with their instrumentation. 

Finally, the possibilities of automation of amperometric and voltammetric electroanalysis should be stressed, as well as the use of solvents other than water43. Pulse techniques are semi-automated by nature the responses can be transmitted directly to a microcomputer for immediate analysis. Fast on-line analysis in flow systems with automated calibration is one of the great advantages, which will be much exploited in the future. 

For faster reactions the speed with which reactants can be mixed is a hmitation the mixing time must be less than the half-time. Stopped-flow techniques have been developed that permit remarkably short kinetic analysis times. Beckwith and Crouch described a stopped-flow kinetic analysis apparatus, with a mixing and dead time of less than 0.01 s, capable of analyzing 1000 phosphate samples per hour with a relative standard deviation of about 1%. Sample handUng, mixing, and gathering and evaluation of data were automated with the help of on-Une computer systems. 

A useful and rapid method of automated analysis is the technique of flow-injection analysis (FIA). The sample or a reagent is injected into the stream of a solution of constant composition. Calibration of FIA systems requires the injection of standard solutions, equal in volume to that of the sample, into the carrier stream. The backgrormd chemical composition of the standards should be equal, as nearly as possible, to that of the samples. Frequent standardization is not necessary because the measurement of peak height, albeit on a sloping base line, is relatively unaffected by cell voltage drift. Some difficulties can appear with peristaltic pumps, owing to extraneous potentials caused by pulsation of the stream. Cells with a small volume (<20 pi) or the cells of the wall-jet type are the most acceptable for continuous measurements. ... 

A variety of methods has been applied to the separation of bound and free Ag. These include precipitation, solid phase attachment, capillary electrophoresis, chromatography, andmicrofiltration. Originally, precipitation and solid-phase extraction were the most common types of separations techniques. However the ease of automation of capillary electrophoresis and flow-injection analysis (chromatography) makes these two techniques very interesting. 

Flow-injection analysis (FIA) is a technique for automating chemical analyses. The principles of FIA are reviewed here. Methods for applying FIA to the anayses of nitrate, nitrite, phosphate, silicate, and total amino acids in seawater are examined. Analyses of other nutrients, metals, and carbonate system components are also discussed. Various techniques to eliminate the refractive index effect are reviewed. Finally, several examples of the application of FIA to oceanographic problems are presented. 

Flow-injection analysis is also well-suited for the automation of anodic stripping voltammetry. Metals can be plated from the sample solution as it passes over the electrode. Stripping is then carried out in the deox-ygenated carrier stream (15, 34). The sample itself does not have to be deox-ygenated. Detection limits of 3 nM have been reported for lead by this technique (34). 

Automation is especially advantageous if a large number of samples need to be analysed on a routine basis. There is little doubt that sample introduction using flow injection is superior to other solvent delivery techniques. Analysis using flow injection techniques with ICP-OES offers a number of advantages ... 

In Section 8B-6 we described various automated sample handling techniques including discrete and continuous flow methods. In this section, we explore the instrumentation and two applications of flow-injection analysis with photometric detection. 

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