Improving the reproducibility of size distribution of protein crystals produced in continuous slug flow crystallizer operated at short residence time
Continuous crystallization of proteins at short residence time and high supersaturation level is attractive in terms of the space-time yield and production efficiency. Nevertheless, it is rarely pursued due to its less-than-desirable crystal size distribution (CSD) characterized by the abundance of...
| Main Authors: | , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2021
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| Online Access: | https://hdl.handle.net/10356/152265 |
| _version_ | 1826122114170617856 |
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| author | Pu, Siyu Hadinoto, Kunn |
| author2 | School of Chemical and Biomedical Engineering |
| author_facet | School of Chemical and Biomedical Engineering Pu, Siyu Hadinoto, Kunn |
| author_sort | Pu, Siyu |
| collection | NTU |
| description | Continuous crystallization of proteins at short residence time and high supersaturation level is attractive in terms of the space-time yield and production efficiency. Nevertheless, it is rarely pursued due to its less-than-desirable crystal size distribution (CSD) characterized by the abundance of small crystals due to high nucleation rate. The small crystals were prone to random agglomeration, resulting in poor crystals’ residence time distribution, hence low CSD's reproducibility. Herein we developed a segmented slug flow crystallizer (SFC) design operated at short residence time (<30 min) comprising a short nucleation segment and a growth segment operated at different temperature and fluid velocity. The SFC design improved the CSD's reproducibility by limiting small crystals and large-sized agglomerates formations as evidenced by the small coefficient-of-variations between replicates (<10%). Lysozyme crystals having size of roughly 13–14 µm with well-preserved bioactivity were produced at yield and space-time yield of approximately 67% (w/w) and 93 g/L·h, respectively. |
| first_indexed | 2024-10-01T05:43:12Z |
| format | Journal Article |
| id | ntu-10356/152265 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:43:12Z |
| publishDate | 2021 |
| record_format | dspace |
| spelling | ntu-10356/1522652021-08-05T02:37:12Z Improving the reproducibility of size distribution of protein crystals produced in continuous slug flow crystallizer operated at short residence time Pu, Siyu Hadinoto, Kunn School of Chemical and Biomedical Engineering Engineering::Chemical technology Protein Crystallization Continuous Crystallization Continuous crystallization of proteins at short residence time and high supersaturation level is attractive in terms of the space-time yield and production efficiency. Nevertheless, it is rarely pursued due to its less-than-desirable crystal size distribution (CSD) characterized by the abundance of small crystals due to high nucleation rate. The small crystals were prone to random agglomeration, resulting in poor crystals’ residence time distribution, hence low CSD's reproducibility. Herein we developed a segmented slug flow crystallizer (SFC) design operated at short residence time (<30 min) comprising a short nucleation segment and a growth segment operated at different temperature and fluid velocity. The SFC design improved the CSD's reproducibility by limiting small crystals and large-sized agglomerates formations as evidenced by the small coefficient-of-variations between replicates (<10%). Lysozyme crystals having size of roughly 13–14 µm with well-preserved bioactivity were produced at yield and space-time yield of approximately 67% (w/w) and 93 g/L·h, respectively. Nanyang Technological University The authors would like to acknowledge the funding from Nanyang Technological University for the PhD scholarship of Siyu Pu. 2021-08-05T02:37:12Z 2021-08-05T02:37:12Z 2021 Journal Article Pu, S. & Hadinoto, K. (2021). Improving the reproducibility of size distribution of protein crystals produced in continuous slug flow crystallizer operated at short residence time. Chemical Engineering Science, 230, 116181-. https://dx.doi.org/10.1016/j.ces.2020.116181 0009-2509 https://hdl.handle.net/10356/152265 10.1016/j.ces.2020.116181 2-s2.0-85091964611 230 116181 en Chemical Engineering Science © 2020 Elsevier Ltd. All rights reserved. |
| spellingShingle | Engineering::Chemical technology Protein Crystallization Continuous Crystallization Pu, Siyu Hadinoto, Kunn Improving the reproducibility of size distribution of protein crystals produced in continuous slug flow crystallizer operated at short residence time |
| title | Improving the reproducibility of size distribution of protein crystals produced in continuous slug flow crystallizer operated at short residence time |
| title_full | Improving the reproducibility of size distribution of protein crystals produced in continuous slug flow crystallizer operated at short residence time |
| title_fullStr | Improving the reproducibility of size distribution of protein crystals produced in continuous slug flow crystallizer operated at short residence time |
| title_full_unstemmed | Improving the reproducibility of size distribution of protein crystals produced in continuous slug flow crystallizer operated at short residence time |
| title_short | Improving the reproducibility of size distribution of protein crystals produced in continuous slug flow crystallizer operated at short residence time |
| title_sort | improving the reproducibility of size distribution of protein crystals produced in continuous slug flow crystallizer operated at short residence time |
| topic | Engineering::Chemical technology Protein Crystallization Continuous Crystallization |
| url | https://hdl.handle.net/10356/152265 |
| work_keys_str_mv | AT pusiyu improvingthereproducibilityofsizedistributionofproteincrystalsproducedincontinuousslugflowcrystallizeroperatedatshortresidencetime AT hadinotokunn improvingthereproducibilityofsizedistributionofproteincrystalsproducedincontinuousslugflowcrystallizeroperatedatshortresidencetime |