The importance of heat flow direction for reproducible and homogeneous freezing of bulk protein solutions
Freezing is an important operation in biotherapeutics industry. However, water crystallization in solution, containing electrolytes, sugars and proteins, is difficult to control and usually leads to substantial spatial solute heterogeneity. Herein, we address the influence of the geometry of freezin...
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crwiley:10.1002/btpr.1771 2024-10-13T14:08:03+00:00 The importance of heat flow direction for reproducible and homogeneous freezing of bulk protein solutions Rodrigues, Miguel A. Balzan, Gustavo Rosa, Mónica Gomes, Diana de Azevedo, Edmundo G. Singh, Satish K. Matos, Henrique A. Geraldes, Vítor 2013 http://dx.doi.org/10.1002/btpr.1771 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fbtpr.1771 http://onlinelibrary.wiley.com/wol1/doi/10.1002/btpr.1771/fullpdf en eng Wiley http://onlinelibrary.wiley.com/termsAndConditions#vor Biotechnology Progress volume 29, issue 5, page 1212-1221 ISSN 8756-7938 1520-6033 journal-article 2013 crwiley https://doi.org/10.1002/btpr.1771 2024-09-17T04:47:20Z Freezing is an important operation in biotherapeutics industry. However, water crystallization in solution, containing electrolytes, sugars and proteins, is difficult to control and usually leads to substantial spatial solute heterogeneity. Herein, we address the influence of the geometry of freezing direction (axial or radial) on the heterogeneity of the frozen matrix, in terms of local concentration of solutes and thermal history. Solutions of hemoglobin were frozen radially and axially using small‐scale and pilot‐scale freezing systems. Concentration of hemoglobin, sucrose and pH values were measured by ice‐core sampling and temperature profiles were measured at several locations. The results showed that natural convection is the major source for the cryoconcentration heterogeneity of solutes over the geometry of the container. A significant improvement in this spatial heterogeneity was observed when the freezing geometry was nonconvective, i.e., the freezing front progression was unidirectional from bottom to top. Using this geometry, less than 10% variation in solutes concentration was obtained throughout the frozen solutions. This result was reproducible, even when the volume was increased by two orders of magnitude (from 30 mL to 3 L). The temperature profiles obtained for the nonconvective freezing geometry were predicted using a relatively simple computational fluid dynamics model. The reproducible solutes distribution, predictable temperature profiles, and scalability demonstrate that the bottom to top freezing geometry enables an extended control over the freezing process. This geometry has therefore shown the potential to contribute to a better understanding and control of the risks inherent to frozen storage. © 2013 American Institute of Chemical Engineers Biotechnol. Prog ., 29:1212–1221, 2013 Article in Journal/Newspaper ice core Wiley Online Library Biotechnology Progress 29 5 1212 1221 |
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English |
description |
Freezing is an important operation in biotherapeutics industry. However, water crystallization in solution, containing electrolytes, sugars and proteins, is difficult to control and usually leads to substantial spatial solute heterogeneity. Herein, we address the influence of the geometry of freezing direction (axial or radial) on the heterogeneity of the frozen matrix, in terms of local concentration of solutes and thermal history. Solutions of hemoglobin were frozen radially and axially using small‐scale and pilot‐scale freezing systems. Concentration of hemoglobin, sucrose and pH values were measured by ice‐core sampling and temperature profiles were measured at several locations. The results showed that natural convection is the major source for the cryoconcentration heterogeneity of solutes over the geometry of the container. A significant improvement in this spatial heterogeneity was observed when the freezing geometry was nonconvective, i.e., the freezing front progression was unidirectional from bottom to top. Using this geometry, less than 10% variation in solutes concentration was obtained throughout the frozen solutions. This result was reproducible, even when the volume was increased by two orders of magnitude (from 30 mL to 3 L). The temperature profiles obtained for the nonconvective freezing geometry were predicted using a relatively simple computational fluid dynamics model. The reproducible solutes distribution, predictable temperature profiles, and scalability demonstrate that the bottom to top freezing geometry enables an extended control over the freezing process. This geometry has therefore shown the potential to contribute to a better understanding and control of the risks inherent to frozen storage. © 2013 American Institute of Chemical Engineers Biotechnol. Prog ., 29:1212–1221, 2013 |
format |
Article in Journal/Newspaper |
author |
Rodrigues, Miguel A. Balzan, Gustavo Rosa, Mónica Gomes, Diana de Azevedo, Edmundo G. Singh, Satish K. Matos, Henrique A. Geraldes, Vítor |
spellingShingle |
Rodrigues, Miguel A. Balzan, Gustavo Rosa, Mónica Gomes, Diana de Azevedo, Edmundo G. Singh, Satish K. Matos, Henrique A. Geraldes, Vítor The importance of heat flow direction for reproducible and homogeneous freezing of bulk protein solutions |
author_facet |
Rodrigues, Miguel A. Balzan, Gustavo Rosa, Mónica Gomes, Diana de Azevedo, Edmundo G. Singh, Satish K. Matos, Henrique A. Geraldes, Vítor |
author_sort |
Rodrigues, Miguel A. |
title |
The importance of heat flow direction for reproducible and homogeneous freezing of bulk protein solutions |
title_short |
The importance of heat flow direction for reproducible and homogeneous freezing of bulk protein solutions |
title_full |
The importance of heat flow direction for reproducible and homogeneous freezing of bulk protein solutions |
title_fullStr |
The importance of heat flow direction for reproducible and homogeneous freezing of bulk protein solutions |
title_full_unstemmed |
The importance of heat flow direction for reproducible and homogeneous freezing of bulk protein solutions |
title_sort |
importance of heat flow direction for reproducible and homogeneous freezing of bulk protein solutions |
publisher |
Wiley |
publishDate |
2013 |
url |
http://dx.doi.org/10.1002/btpr.1771 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fbtpr.1771 http://onlinelibrary.wiley.com/wol1/doi/10.1002/btpr.1771/fullpdf |
genre |
ice core |
genre_facet |
ice core |
op_source |
Biotechnology Progress volume 29, issue 5, page 1212-1221 ISSN 8756-7938 1520-6033 |
op_rights |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
op_doi |
https://doi.org/10.1002/btpr.1771 |
container_title |
Biotechnology Progress |
container_volume |
29 |
container_issue |
5 |
container_start_page |
1212 |
op_container_end_page |
1221 |
_version_ |
1812814648241553408 |