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9.1 Introduction 203

Transamination: On-column 1,3-proton shift reactions – a key transformation
in the biomimetic reductive amination process – were investigated using sim-
ple silica-adsorbed 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) catalyst [42, 43]. This
process enabled chirality transfer from (R)-1-phenylethylamine to perfluoroalky-
lated ketones. The continuous-flow process proved to be far superior to the batch
processes, both from an economical and synthetic point of view.
Strecker reaction: A robust heterogeneous self-supported chiral titanium cluster
(SCTC) catalyst applied both in batch and continuous mode [44] enabled imine
cyanation as well as a three-component Strecker reaction using the correspond-
ing aldehydes and amines under continuous flow conditions in a PBR giving
aminonitriles enantiomeric excess values of up to 98%.

9.1.1.2 Analytical Applications
Historically, it was the ever-increasing sample frequency in clinical chemistry since
the early 1950s which prompted the development of continuous-flow systems.
Different enzyme preparations were investigated in unsegmented continuous-flow
systems for analytical purposes [45].
To test the viability of the method for such applications, 12 hydrolytic enzymes
were investigated with two automated multiple enzyme analysis systems [46].
Hydrolases in continuous-flow systems were successfully applied to determine
glycogen without interference from free glucose [47] and for the determina-
tion of total serum cholesterol [48]. Microreactor technology combined with a
hydrolase-based enzymatic method was applied for high-throughput optimiza-
tion of the HCN addition to aldehydes by enantioselective Lewis acid/Lewis base
catalysis [49].
A rotating enzyme-immobilized reactor and a flat pH electrode were incorporated
into a sealed cell for use under continuous-flow/stopped-flow (SF) operation for
the rapid determination of penicillins G and V in tablets and injectables [50].
A co-immobilization in a rotating bioreactor and amperometric detector resulted
in a sensitive system for determination of succinylcholine and acetylcholine in
pharmaceutical preparations [51]. A tandem system incorporating two rotating
bioreactors into a continuous-flow/SF sample/reagent processing setup was applied
for the determination of alkaline phosphatase activity in serum samples [52]. By
functional combination of the SF and flow-injection analysis (FIA), an automated
micro apparatus was constructed resulting in significant reduction of the injection
volumes of enzyme and substrate [53]. SF/continuous flow methods were applied
to acquire kinetic information also [54, 55].
For creatinine analysis, four enzymes (creatinine amidohydrolase, creatinine
kinase, pyruvate kinase, and lactate dehydrogenase) were co-immobilized in a
nylon tube reactor [56].
Continuous-flow systems are emerging techniques in proteomics applications
although bottom-up methods where the protein is digested into peptides that
can be efficiently analyzed with a wide range of LC–MS or MALDI-TOF-MS
instruments still prevail [57]. A simple and rapid system for the analysis of protein