Application of micromixers - Micromixers Fundamentals Design and Fabrication - page 321

where k B is the Boltzmann constant. The

rate constant represents the number of collisions between reactant molecules A and B. According to
(9.2) , the reaction rate increases if the activation energy decreases or the temperature increases.
For reactions with very fast reaction kinetics, the reaction rate is determined by diffusion

k 0 is a constant, E 0 is the activation energy of the reaction, and

.
Because diffusion is the final stage in all micromixer types, the efficiency of a micromixer determines
the reaction rate. Thus, the reaction rate can be controlled by a careful micromixer design.

k f D

9.1.2 Liquid-liquid reactions
Improved mixing in micromixers makes them suitable for synthesis applications based on liquid-phase
reactions. Common liquid-phase reactions in chemical industry are [1] :

Nucleophilic substitution reactions,

Electrophilic aromatic substitution reactions,

Addition and elimination reactions,

Coupling reactions, and

Oxidation and reduction reactions.

Due to the high demand for applications in chemical and biochemical analysis, most micromixers were
designed for the liquid phase. Thus, all these micromixers can be directly used as microreactors. All
basic micromixer designs are suitable for single-step reactions. Using many micromixers in serial
would allow multistep reactions.
Nucleophilic substitution is a basic class of chemical reactions. In a nucleophilic substitution
process, an electron nucleophile selectively bonds with or attacks the positive or partially positive
charged atom or a group of atoms. This atom group is called the leaving group (LG); the positive or
partially positive atom is called electrophile. Electrophiles are the positive or partially positive charged
atoms [2] . A nucleophilic substitution reaction has the general form of

: þR / R

þ

LG
where “:” is an electron pair of the nucleophile Nuc and R-LG is the substrate. The reaction product is
R-Nuc. The nucleophile is neutral or negatively charged. The substrate R-LG is typically neutral or
positively charged. The advantage of large interfacial area in micromixers would allow nucleophilic
substitution to be conducted in a continuous manner, at a high yield and selectivity. Organic synthesis
with quantities on the order of kilograms can be carried out by numbering up the reaction systems.
Aliphatic nucleophilic substitution carried out in micromixer with a cross-section of 200 by
100 microns results in a 75% yield of the desired product compared to 26% of a stirred batch reactor at
the same residence time of 2 minutes [3] . A yield of 96% was achieved with a residence time of
10 minutes. The increase in yield is caused by the larger interfacial area between the reactants. The
microfluidic platforms of micromixer allow the integration of reaction, separation, and detection in
a single device. Belder et al. [4] carried out all three processes for the biocatalytic hydrolysis of
glycidyl phenyl ether on a microfluidic platform. Aliphatic nucleophilic substitution in microreactor
was used to synthesize aliphatic amines [5] . Yields up to 100% can be achieved at a throughput on the
order of 10-100 g/h. Another key application of nucleophilic substitution is synthetic radiochemistry.
Radiolabeled ester was synthesized in a glass micromixer at a residence time of 12 seconds and
a radiochemical yield of 88% [6] .

Nuc LG Nuc