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Cryogels as Solid Supports in Bioprocessing

Jespersen, Gry LU (2014)
Abstract
In recent years the market for biopharmaceutical products has been increasing rapidly as a result of an increased demand for new and efficient treatments of various indications. Biopharmaceuticals are distinguished from chemical drugs by being derived from a biological origin and are hence, frequently constituting biological macromolecules. With the emergence of recombinant DNA technology, today most biopharmaceutical products are produced in recombinant cell lines, an advance which has led to the development of some of today’s most important therapeutics such as insulins, erythropoietins and monoclonal antibodies.

Industrial downstream bioprocessing is concerned with the isolation and purification of biopharmaceutical products,... (More)
In recent years the market for biopharmaceutical products has been increasing rapidly as a result of an increased demand for new and efficient treatments of various indications. Biopharmaceuticals are distinguished from chemical drugs by being derived from a biological origin and are hence, frequently constituting biological macromolecules. With the emergence of recombinant DNA technology, today most biopharmaceutical products are produced in recombinant cell lines, an advance which has led to the development of some of today’s most important therapeutics such as insulins, erythropoietins and monoclonal antibodies.

Industrial downstream bioprocessing is concerned with the isolation and purification of biopharmaceutical products, ensuring a high purity and quality of the manufactured product. As recombinant cell technology has enabled vast increases in production efficiencies, this has put pressure on downstream processes to keep up with this pace. Hence, industrial downstream bioprocessing faces two major challenges. Firstly, an increased demand for method improvements which can contribute to decreasing processing time and –cost. Secondly, an increasingly strict government regulation for equipment sanitation is challenging the current re-use of materials, which has prompted the industry’s interest in the use of disposables.

Cryogels is a type of porous materials, which frequently constitute biocompatible solids cast in a one-block format. Characteristic to cryogels is their extremely open porous structure which allow for unhindered passage of viscous fluids or even whole cells, and due to this feature these materials have been considered as solid supports in downstream bioprocessing. Cryogels are potentially in-expensive materials, which can be easily prepared under environmentally friendly conditions and on this basis they have been considered suitable as disposable materials.

This dissertation concerns studies on cryogels utilized as solid supports in various downstream bioprocessing applications. One study focuses on the application of a cryogel as a solid support for the fast, qualitative analysis of an antibody. The use of a cryogel in this context enables easy preparation of a customized solid support, which can be used for specific detection of antibody in a cell harvest. In another study it is demonstrated that a cryogel can be used as a solid phase agent for the chemical modification of a biopharmaceutical. In this connection the use of a cryogel constitutes a process improvement in terms of being a cost-efficient, high capacity material which could be implemented into an existing process. Chemical modification of biopharmaceuticals can also be performed by enzymes and in yet another study an enzyme was immobilized on a cryogel for the purpose of modifying an antibody. The advantage of having the enzyme immobilized on a solid support is avoiding the subsequent removal of enzyme from the product as well as the potential reusability of the enzyme.

Cryogels constitute a type for solid supports that are very versatile, which is reflected by the vast amount of literature on their many different applications within downstream processing. The studies presented in this dissertation demonstrate some new applications of cryogels and emphasize the need for a further systematic work approach on developing cryogels towards taking on their own niche as biocompatible, disposable materials in downstream bioprocessing. (Less)
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author
supervisor
opponent
  • Professor Van Alstine, James, General Electric Healthcare, Uppsala, Sweden
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Downstream processing, cryogel, solid support, biomacromolecules, chromatography
pages
136 pages
publisher
Division of Biotechnology, Lund University
defense location
Lecture hall B, Centre of Chemistry and Chemical Engineering, Sölvegatan 39, Lund University Faculty of Engineering
defense date
2014-03-21 13:30
ISBN
978-91-7422-346-0
language
English
LU publication?
yes
id
49d2081f-9ed4-4500-b9b4-0d93a8497ffe (old id 4318450)
date added to LUP
2014-02-25 10:35:40
date last changed
2016-09-19 08:45:09
@phdthesis{49d2081f-9ed4-4500-b9b4-0d93a8497ffe,
  abstract     = {In recent years the market for biopharmaceutical products has been increasing rapidly as a result of an increased demand for new and efficient treatments of various indications. Biopharmaceuticals are distinguished from chemical drugs by being derived from a biological origin and are hence, frequently constituting biological macromolecules. With the emergence of recombinant DNA technology, today most biopharmaceutical products are produced in recombinant cell lines, an advance which has led to the development of some of today’s most important therapeutics such as insulins, erythropoietins and monoclonal antibodies.<br/><br>
Industrial downstream bioprocessing is concerned with the isolation and purification of biopharmaceutical products, ensuring a high purity and quality of the manufactured product. As recombinant cell technology has enabled vast increases in production efficiencies, this has put pressure on downstream processes to keep up with this pace. Hence, industrial downstream bioprocessing faces two major challenges. Firstly, an increased demand for method improvements which can contribute to decreasing processing time and –cost. Secondly, an increasingly strict government regulation for equipment sanitation is challenging the current re-use of materials, which has prompted the industry’s interest in the use of disposables.<br/><br>
Cryogels is a type of porous materials, which frequently constitute biocompatible solids cast in a one-block format. Characteristic to cryogels is their extremely open porous structure which allow for unhindered passage of viscous fluids or even whole cells, and due to this feature these materials have been considered as solid supports in downstream bioprocessing. Cryogels are potentially in-expensive materials, which can be easily prepared under environmentally friendly conditions and on this basis they have been considered suitable as disposable materials.<br/><br>
This dissertation concerns studies on cryogels utilized as solid supports in various downstream bioprocessing applications. One study focuses on the application of a cryogel as a solid support for the fast, qualitative analysis of an antibody. The use of a cryogel in this context enables easy preparation of a customized solid support, which can be used for specific detection of antibody in a cell harvest. In another study it is demonstrated that a cryogel can be used as a solid phase agent for the chemical modification of a biopharmaceutical. In this connection the use of a cryogel constitutes a process improvement in terms of being a cost-efficient, high capacity material which could be implemented into an existing process. Chemical modification of biopharmaceuticals can also be performed by enzymes and in yet another study an enzyme was immobilized on a cryogel for the purpose of modifying an antibody. The advantage of having the enzyme immobilized on a solid support is avoiding the subsequent removal of enzyme from the product as well as the potential reusability of the enzyme. <br/><br>
Cryogels constitute a type for solid supports that are very versatile, which is reflected by the vast amount of literature on their many different applications within downstream processing. The studies presented in this dissertation demonstrate some new applications of cryogels and emphasize the need for a further systematic work approach on developing cryogels towards taking on their own niche as biocompatible, disposable materials in downstream bioprocessing.},
  author       = {Jespersen, Gry},
  isbn         = {978-91-7422-346-0},
  keyword      = {Downstream processing,cryogel,solid support,biomacromolecules,chromatography},
  language     = {eng},
  pages        = {136},
  publisher    = {Division of Biotechnology, Lund University},
  school       = {Lund University},
  title        = {Cryogels as Solid Supports in Bioprocessing},
  year         = {2014},
}