Increasing yield in chromatography using batch-to-batch recirculation
Author
Summary, in English
Preparative chromatography is an important process step for separation and purification of fine chemicals, pharmaceuticals, and other biotechnical products. The technique mainly used in the pharmaceutical and fine chemistry industries is single-column batch chromatography (BC). The major drawback of BC is the trade-off between product purity and process performance. A high purity of the product comes at the cost of reduced recovery yield of product, increased solvent consumption and/or decreased productivity. Many different process concepts have been developed to overcome the trade-off limitation. One suggested process recirculates impure product at the outlet of the column to the inlet of the column, along with fresh feed.
This study aimed at investigating the usage of a two-column recirculation process to achieve better process performance than traditional BC. The investigation started with modelling and simulation of the process. The process was also constructed and validated experimentally in lab. Finally, the simulation model was used to perform an optimization study. The constructed process utilized two ion-exchange chromatography columns, a main column and a twin-column. A ternary protein mixture of ribonuclease A, cytochrome c and lysozyme was used to be separated.
A comparison between simulated and experimental protein concentrations showed that a fairly good prediction of experimental data could be made by using the simulation model. A start-up behaviour with increasing product concentrations in the system could be seen during the first cycles of the process. The process then entered cyclic steady-state after a while, with reoccurring concentration profiles during each cycle. According to the simulated model, the fresh product injected during each steady-state cycle may equal the product extracted during each cycle. This may result in a very high recovery yield while operating at cyclic steady-state.
The batch-to-batch recirculation process is a bit more complex and demands more equipment than traditional BC. However, according to the visual optimization of the process, the batch-to-batch recycling process outperforms traditional BC when it comes to combining high productivity and high yield at high purity requirements.
This study aimed at investigating the usage of a two-column recirculation process to achieve better process performance than traditional BC. The investigation started with modelling and simulation of the process. The process was also constructed and validated experimentally in lab. Finally, the simulation model was used to perform an optimization study. The constructed process utilized two ion-exchange chromatography columns, a main column and a twin-column. A ternary protein mixture of ribonuclease A, cytochrome c and lysozyme was used to be separated.
A comparison between simulated and experimental protein concentrations showed that a fairly good prediction of experimental data could be made by using the simulation model. A start-up behaviour with increasing product concentrations in the system could be seen during the first cycles of the process. The process then entered cyclic steady-state after a while, with reoccurring concentration profiles during each cycle. According to the simulated model, the fresh product injected during each steady-state cycle may equal the product extracted during each cycle. This may result in a very high recovery yield while operating at cyclic steady-state.
The batch-to-batch recirculation process is a bit more complex and demands more equipment than traditional BC. However, according to the visual optimization of the process, the batch-to-batch recycling process outperforms traditional BC when it comes to combining high productivity and high yield at high purity requirements.
Department/s
Publishing year
2016
Language
English
Full text
Document type
Student publication for Master's degree (two years)
Topic
- Technology and Engineering
Keywords
- cyclic steady-state
- batch-to-batch recirculation process
- simulation of chromatography
- ion-exchange chromatography
- twin-column
- chemical engineering
- kemiteknik
Supervisor
- Niklas Andersson