title: Optimization and scale-up of oligonucleotide synthesis in packed bed reactors using computational fluid dynamics modeling.
abstract: A computational fluid dynamics (CFD) model for the analysis of oligonucleotide synthesis in packed bed reactors was developed and used to optimize the scale up of the process. The model includes reaction kinetics data obtained under well defined conditions comparable to the situation in the packed bed. The model was validated in terms of flow conditions and reaction kinetics by comparison with experimental data. Experimental validation and the following model parameter studies by simulation were performed on the basis of a column with 0.3 g oligonucleotide capacity. The scale-up studies based on CFD modelling were calculated on a 440 g scale (oligonucleotide capacity).
authors.affiliation: Eckart GmbH Werk Wackersdorf, Boschstraße 1, 92442, Wackersdorf, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Wolfrum
authors.forename: Andre
authors.initials: A
authors.lastname: Josten
authors.forename: Peter
authors.initials: P
authors.lastname: Götz
mesh_terms: D001709:Biotechnology / Q000295:instrumentation* / Q000379:methods*; D003198:Computer Simulation; D057446:Hydrodynamics; D008962:Models, Theoretical; D009841:Oligonucleotides / Q000032:analysis / Q000138:chemical synthesis* / Q000737:chemistry; D009943:Organophosphorus Compounds / Q000737:chemistry
chemical_list: D009841:Oligonucleotides; D009943:Organophosphorus Compounds; C434331:phosphoramidite
keywords: computational fluid dynamics; large scale synthesis; oligonucleotides