4.2.1. Packed-Bed Reactors

Conventional packed-bed reactors suffer from disadvantages such as inefficient heat and mass transfer due to the use of large particles (mm in size) in the channels [97]. The diameter of the particles should be less than 1/20th of the channel diameter in order to prevent channelling and ensure even flow solution. For microreactors, the diameters of the particles should be less than 50 nm [115]. Enzymes can be immobilised on porous beads, streptavidin-coated magnetic microbeads, porous resins or various hydrogels. Oglio et al. designed a pack-bed flow reactor using immobilised ketoreductase and glucose dehydrogenase on aldehyde agarose for different ketones reduction. Both enzymes showed good stability in DMSO and the system was used continuously for a number of weeks [116]. A packed bed bioreactor with high selectivity for the continuous production of a range of chiral alcohols was prepared by immobilising alcohol dehydrogenase fused with HaloTagTM on a resin containing sepharose beads [117]. A cascade reaction for the synthesis of (1S,2S)-1-phenylpropane-1,2-diol using a packed bed reactor containing immobilised fusion alcohol dehydrogenase and benzoylformate decarboxylase was described [118]. Peschke et al. immobilised (R)-stereoselective ketoreductase LbADH (alcohol dehydrogenase from Lactobacillus brevis) and glucose dehydrogenase (GDH) on magnetic beads for the preparation of (R)-alcohols. Glucose dehydrogenase was used to recycle the cofactor. The packed-bed reactor operated continuously for four days [119]. However, using beads in the reactors has disadvantages such as the need for high backpressures to achieve adequate flow rates. Moreover, it is difficult to control a multiphase flow inside the microreactor [120].
