Miniaturized FIA

J. M., Schwesinger, N., Detection of catalytic reactions in a miniaturized FIA set-up using a static micromixer and... 

Miniaturized FIA-systems can be used for a variety of applications. First of all, such systems can be used to replace existing conventional FIA-systems, opera-... 

A current research project in our laboratory deals with the development of miniaturized FIA systems with the final goal of constructing a complete system by micromachining. The calorimetric measuring principle has been found to work surprisingly well in these small devices. Encouraging results have been obtained with various silicon chip test structures [36]. 

As with other analytical techniques, there is a trend in FIA towards significant reductions In size, which ultimately result in considerable advantages. In this way miniaturized FIA In its two versions was conceived capillary FIA and integrated microconduits. 

Both variants of miniaturized FIA have a serious shortcoming, viz. the easy clogging of the micromanifold. 

Figure 6.12. Detailed drawings of (a) The injection valve module (b) reactor module R1 comprising one mixing tee (c) reactor module R2 comprising two mixing tees and (d) reactor module R3, which, designed for titrations, comprises a gradient tube and and a mixing tee (cf. Figs. 4.62 and 4.63). The reactors, valve, and flow cell modules, as well as additional electrochemical detector modules, are interchangeably accommodated on an elastic back-plate so that the versatility of the miniaturized FIA lab system can be further expanded.

A major advantage of FIA systems is the ease of combination with other flow systems. In particular, FIA systems comprising sample dilution flow systems and lactate-sensing flow systems have been developed. Moreover, miniaturized flow cells such as uTAS have been developed for lactate sensing. Future incorporation of suitable flow systems into FIA will enable the development of miniaturized FIA systems that can automatically detect lactate in multiple samples without pretreatment. 

Because of its advantages (high sensitivity and selectivity, low cost and miniaturization) amperometric detection has been frequently used in flow injection analysis (FIA) and RP-HPLC. However, it has been established that the peak area (detector response) considerably depends on the flow rate. A general approach has been proposed to predict the effect of flow rate on the peak area in FIA and RP-HPLC. The general form of the correlation describing the flow in a parallel plate cell with short rectangular electrodes is... 

FIA is a chemical analysis method based plug-wise injection into a carrier stream [114—116]. These plug samples can be further manipulated, e.g. by reaction to compounds better detectable by a detector. The sample consumption can be reduced via miniaturization however, then usually laminar-flow conditions are given so that micro mixers are needed which are efficient in that regime. 

Micro flow control devices open new possibilities for the miniaturization of conventional chemical and biochemical analysis systems. The micro total analysis system (pTAS) including microfabricated detectors (e.g. silicon based chemical sensors, optical sensors), micro flow control devices and control/detec-tion circuits is a practical micro electro mechanical system (MEMS). pTAS realize very small necessary sample volume, fast response and the reduction of reagents which is very useful in chemical and medical analysis. Two approaches of monolithic and hybrid integration of these devices have been studied. Monolithic and hybrid types of flow injection analysis (FIA) systems were already demonstrated [4, 5]. The combination of the partly integrated components and discrete components is useful in many cases [6]. To fabricate such systems, bonding and assembling methods play very important roles [7]. 

Biosensors are being increasingly used as detectors in FIA systems [284,285, 322, 379, 476]. The drawbacks of biosensors as direct in situ sensors, namely their low dynamic range, their lack of ability to survive sterilization, their limited lifetime, etc. are no longer valid ex situ because the analyzer interfaces the biosensor which can be changed at any time and FIA can provide samples in optimal dilution. The need for chemicals and reagents can be drastically reduced when employing biosensors, specifically when the entire system is miniaturized [48]. 

Since ISEs can be used in continuous flow systems or in flow systems with sample injection (flow injection analysis, FIA)21 their application is wide, not limited to discrete samples. Analysis time becomes shorter, with faster recycling. Additionally, in flow systems the experimental assembly and data analysis can be controlled automatically by microcomputer, including periodic calibration. Another development is the use of sensors for the detection of eluents of chromatographic columns in high-pressure liquid chromatography (HPLC). Miniaturization has permitted an increase in the use of sensors in foods, biological tissues, and clinical analyses in general. 

Samples can be processed with FIA at rates varying from 60 to 300 per hour. In recent work, FIA systems have been miniaturized to either capillary (inner diameters from 20 to 100 p,m) or microchip (see Feature 8-1) dimensions. Such miniature analyzers have the potential to enable manipulations and measurements on such small samples as single cells and to minimize the amount of reagent consumed in an analysis. 

FIA has been the target for miniaturization experiments. One can foresee that with smaller columns and lower dead volumes, a higher analytical throughput... 

FIA as such is available from a few different suppliers. Reactors filled with immobilized enzymes are also commercially available. More sophisticated equipment based on the FIA concept is the BIACORE from Pharmacia Biosensor. Here a gold surface covered with a carboxydextran is used as reactor for binding reactions. The reading is done by means of evanescent wave technology [63]. The BIACORE illustrates one step in the direction of miniaturization of the analytical unit. As the understanding of the chemistry and the analytical protocol becomes available, much may be gained by miniaturization [64]. 

However, further studies have shown that the injection process itself conforms with the one-mixing-stage model, and this observation allowed miniaturization and simplification of the FIA system, resulting in elimination of the mixing chamber and implementation of high-speed titrations [183]. Such titrations are performed at medium or even limited dispersion. A detailed treatment of dispersion in a one-tank system for small D values, recently developed by Tyson [1062], requires a modification of const, so that for low D values... 

The principle of the FIA preconcentration technique is illustrated in Fig. 4.38, which demonstrates how reduced dispersion of the injected sample (i.e., D < 1) might be achieved by introducing a relatively large volume of sample solution, the analyte content of which is retained on an incorporated miniaturized packed reactor within the FIA channel, from which column the analyte subsequently is released and passed to a detector. The method was originally proposed to enhance the sensitivity of measurement of cationic trace elements in very diluted aqueous samples using... 

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