Template Induced Crystallization for In-Situ Product Removal
Integration of life sciences & engineering
Biochemical Engineering (T5-1)
Keywords: In Situ Product Removal,Template Induced Crystallization,Screening Methodology
J. Urbanus*1, C.P.M. Roelands1, J.H. ter Horst2, D. Verdoes1, P.J.Jansens2
1 TNO Science & Industry, Separation Technology, PO Box 342, 7300 AH, Apeldoorn, Netherlands
2 Delft University of Technology, Process & Energy Laboratory, Leeghwaterstraat 44, 2628 CA, Delft, Netherlands
*Corresponding author, email: jan_harm.urbanus@tno.nl
Nowadays biological processes are replacing conventional processes for the production of (fine) chemicals, for the reasons of specificity, efficiency, to reduce environmental unfriendly wastes or the absence of chemical routes. However, in many processes driven by fermentation, the products have inhibitory or toxic effects on the productivity and growth of the biomass. In such cases the product should be removed from the bioreactor as soon as it is formed, in order to overcome these constraints and hence to increase the productivity and efficiency of the biological process.
In such cases application of a form of process integration called In-Situ Product Removal (ISPR) is potentially advantageous. ISPR methods increase the productivity of the process by: overcoming the inhibitory or toxic effects, shifting unfavorable reaction equilibriums, minimizing product losses due to degradation or uncontrolled release1,2. Additionally, downstream processing is potentially simplified by reducing the total number of downstream processing steps. Because of the complex and diluted media and of the variety of molecules encountered in fermentation, ISPR techniques should be based on highly selective separation principles.
Within the framework of introducing a toolbox of ISPR separation techniques3, it is our objective to develop an integrated process of fermentation and in-situ crystallization using the principle of Template Induced Crystallization (TIC). With this technique compounds are selectively separated from the broth by crystallization on templates. The templates are particles that are introduced in the broth and subsequently removed. After their removal, templates are regenerated for reuse while the product is further purified. This technique is expected to be especially suitable for charged molecules, such as carboxylic acids and amino acids, because these compounds crystallize at sufficiently low concentrations to alleviate product inhibition in fermentation processes.
Templates enable crystallization at low supersaturations because the introduced surface lowers the nucleation work. Although the TIC principle is generic, the templates have to be specific for each compound. Crucial for the development of this technique is therefore the availability of a generic screening methodology for TIC. With this methodology templates are evaluated upon their potential to promote crystallization. The methodology comprises metastable zone width determination, induction time measurements, pH-stat experiments and desupersaturation curve measurements. The screening method is implemented in robotized equipment for parallel experimentation. The influence of template parameters such as surface roughness, interfacial tension, and (hydrophobic) interaction with the solute are studied.
In future work, properties of templates have to be modified such that their recovery from the broth is facilitated, for example by a difference in density or size. The introduction of magnetic properties appears promising.
1. G.J. Lye, J.M. Woodley, ‘Application of in-situ product removal techniques to biocatalytical processes’, Trends Biotechnol., 17, 395-402, 1999.
2. D. Stark, U. Von Stockar, ‘In Situ Product Removal (ISPR) in whole cell biotechnology during the last twenty years’, in Process Integration in Biochemical Engineering, U. von Stockar, L.A.M. van der Wielen (editors), Springer, Berlin Heidelberg, 2003..
3. J.A. Vente, J. van Erkel, ‘In-situ product recovery in bioconversions’, in Proceedings of the 6th International Conference on Process Intensification, P. Jansens, A. Stankiewicsz, A. Green (editors) , Delft, The Netherlands, September 2005.
See the full pdf manuscript of the abstract.
Presented Wednesday 19, 11:20 to 11:40, in session Biochemical Engineering (T5-1).
