Effective use of enzyme microreactors : thermal, kinetic and ethical guidelines

J.W. Swarts

Research output: Thesisinternal PhD, WU


Microreactor technology is reported to have many benefits over regular chemical methods. Due to the small dimensions over which temperature and concentration gradients can exist, mass and heat transfer can be very quick. This could minimize the time needed for heating and mixing, due to a reduction in diffusion limitation. Furthermore, a very low fluid to chip volume ratio could facilitate a very stable fluid temperature.

The goal of this thesis research was to investigate the effect of the use of microreactors on enzyme kinetics and the thermal behaviour of fluids inside the chip. First, the effect of the design and use of a microsystem on the fluid temperature inside the microfluidic chip was investigated experimentally and with computer models. A stable and predictable temperature is of great importance for running (enzymatic) processes in a microchip. Next, we used model enzyme reactions to investigate whether the enzyme kinetics were different on micro and bench scale, and when diffusion would play a role. Furthermore, some social and ethical aspects of microreactor technology applications were studied.

To ensure a stable and predictable temperature of the fluids inside the microreactor, the microsystem should be properly designed and used. To test these two aspects, we investigated the effect of practical use (chapter 2) and design parameters (chapter 3) on this fluid temperature. The micro system used in this research consisted of a PEEK chipholder, a relatively small heater, a glass microchip, and surrounding air. We conducted experiments and used computational fluid dynamics models to understand the effect of all varied parameters. In the design of the system, the chipholder shape and material (with its density, specific heat, and thermal conductivity) dominated the temperature of the fluid inside the chip. A temperature gradient as large as 40°C was observed over the length of the chip. This temperature profile at fluid level can be changed by adapting the geometry and material of the chipholder. The results show that a uniform temperature is highly dependent on the correct design of the integrated system of chip, chipholder, and heater. The practical use of the chip with moderate air flow over the chip and moderate fluid flow rates through the channel had no effect on the fluid temperature. A well designed micro system can therefore be considered thermally robust under moderate processing conditions.

The microsystem from chapters 2 and 3 was used for enzyme reactions on micro scale. The kinetic parameters of a lipase catalyzed esterification reaction (chapter 4) and a β-galactosidase catalyzed hydrolysis reaction (chapter 5) on this micro scale were the same as those found on bench scale. Kinetic and thermal (in-)activation results obtained on micro scale can be used for large scale processing. This can bring down optimization costs by reducing the required amount of enzyme and chemicals.

Next, we found that at residence times below a few seconds, diffusion effects limited the reaction rate and therefore reduced the conversion per volume of enzyme microreactor. This effect of diffusion on the conversion increased quadratically with channel width, increased with enzyme concentration, and decreased with substrate concentration. When an enzyme microreactor system should be run efficiently, these factors should be explored to avoid diffusion limitation and subsequent reduced volumetric productivity.

With microreactor technology reaching maturity, a wider application of the technology could be imagined. With increasing application the impact it will have on society will also increase. In chapter 6, three examples of microreactor technology applications in nutrition, in medicine, and in energy carrier supply were investigated. The benefits and costs, and their distribution were discussed for these examples. Furthermore, possible strategies of communication surrounding a public introduction of such a novel technology were considered. The applications proposed in this chapter were only three out of an infinite number of possibilities. However, the discussion of these examples can be used as a framework for discussing future applications as they might be developed in the future. A societal backlash as with the GMO-scare in 1990s, can be avoided when the relevant issues are communicated appropriately and timely. This could improve the chances of success of this technology in the market.

In this thesis we have shown that microreactors can be a useful tool for reaction engineering. Their use could reduce the required amount of enzyme and chemicals for optimization. Furthermore, they can be used to study processes with a very short residence time. To use microreactor technology effectively, one does have to consider whether the scale is appropriate, and whether that the system, including chipholder, interfaces to the outer world and thermal actuators, is properly designed and used.

Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • Wageningen University
  • Boom, Remko, Promotor
  • Korthals, Michiel, Promotor
  • Janssen, Anja, Co-promotor
Award date10 Jun 2009
Place of Publication[S.l.
Print ISBNs9789085853732
Publication statusPublished - 2009


  • bioreactors
  • enzymes
  • enzyme activity
  • microfiltration
  • temperature
  • fluid mechanics
  • industrial enzymes
  • microtechniques
  • microarrays


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