Rapid mixing continuous flow device

Figure 8.41 Rapid Mixing Continuous Flow Device. Biocatalyst E and substrate S are combined in a mixing zone (hatched area) and the mixture ejected along a common outlet tube. Distance from the mixing zone determines time t from mixing. Spectroscopic monitoring of mixture as a function of distance generates first order relaxation curves for analysis.

Stopped flow and continuous flow methods [11] have been used to follow proton transfer reactions with half-lives in the millisecond range. The stopped flow method which is more popular is essentially a device for mixing the reactants rapidly (typically in one millisecond) together with some means of observing the fast reaction which follows. Proton transfer from p-nitrobenzyl cyanide to ethoxide ion in ethanol/ether mixtures at —77 °C was studied in this way [12]. The reaction was followed spectrophotometrically. The most rapid reaction occurred with ti/2 ca. 2 x 10 2 sec although the equipment was suitable for following reactions with f1/2 ca. 2 x 10 3 sec. A similar method has been used to measure rates of proton transfer between weak carbon acids (for example, triphenylmethane) and bases (for example, alkoxide ions) in dimethyl sulphoxide [13], A continuous flow apparatus with spectrophotometric detection was used [14] to measure rates of ionization for substituted azulenes in aqueous solution (4), reactions for which half-lives between 2 and 70 msec were observed. 

The most widely used fast mixing method is the continuous-flow method. The reactants flow in separate continuous streams that meet in a mixing chamber and then pass along an observation tube or chamber with detection devices at appropriate points along its length (see Fig. 18.2). The detection devices, which measure the composition of the flowing sample, may be optical, thermal, chemical, electrical, or any other method applicable to a rapidly moving sample. Reactions with halftimes of the order of 10" sec can be observed by this method. 

The reports mentioned above provide a systematic coverage of the nonimmobi-lized enzymatic reactors used in biocatalytic reactions under continuous flow operation. Results from microreactor experiments were comparatively higher than conventionally mixed batch reactors in terms of conversion rate and improvement of product yield as demonstrated for hydrolysis [140], dehalogenation [141], oxidation [142], esteriflcation [143], synthesis of isoamyl acetate [144,145], synthesis of cyanohydrins [147,148], synthesis of chiral metabolites [153], reduction [151], and bioluminescent reaction [149]. The small volumes involved and the favorable mass transfer inherent to these devices make them particularly useful for the screening of biocatalysts and rapid characterization of bioconversion systems. The remarkable results of such studies revealed that the product yield could be enhanced significantly in comparison with the conventional batch runs. 

Another method of nucleation measurement that differs from both diffusion and expansion chambers involves the rapid turbulent mixing of two gas streams (Wyslouzil et al. 1991a,b). This method is particularly suited to studies of binary nucleation. Two carrier gas-vapor streams are led to a device where rapid turbulent mixing takes place. The two-component vapor mixture is supersaturated and begins to nucleate immediately. The stream passes to a tube where nucleation may continue and the nucleated particles grow. Residence time in the flow tube is the order of seconds. When the nucleated particle concentration is sufficiently low, droplet growth does not deplete the vapor appreciably, and constant nucleation conditions can be assumed. 

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