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Fysikalisk kemi för nya och förbättrade kromatografimaterial

Diarienummer
SM17-0042
Start- och slutdatum
180301-201231
Beviljat belopp
1 054 000 kr
Förvaltande organisation
GE Healthcare
Forskningsområde
Bioteknik, medicinsk teknik och teknik för livsvetenskaperna

Summary

Purification by chromatography constitutes the most relevant bottleneck in downstream processing of biopharmaceuticals. GE Healthcare AB is a world-leading actor in chromatographic systems and its R&D towards improving chromatography media is an important strategic direction within the company. There are three main issues to deal with, namely (i) improved characterization of the physical and chemical state of the porous matrices making up the media, (ii) improved theoretical understanding and prediction of the complex flow phenomena during chromatography and (iii) invention and design of novel porous matrices that may improve performance with its many aspects. The project involves part-time employment at GEHC of a professor in physical chemistry who has background knowledge and understanding regarding the involved basic phenomena. He is expected to collaborate with coworkers at the GEHC R&D for Downstream Purification division on two activities. The first one concerns novel materials in bioprocess applications and involves (i) suggesting new porous architectures and (ii) assessing their performance by both experimental and simulation methods. Yet, one additional outcome is a better understanding of current matrices. The second activity concerns biopolymer and ligand control strategies and structure-function properties. It calls for a better characterization of matrix structures made of agarose, a complex biopolymer, both as is and chemically modified.

Populärvetenskaplig beskrivning

Have you heard of modern biomedicines? Yes? Well, it is true - you just stich a gene into innocent bacteria and, voila, there pours out those new proteins/peptides/drugs coded by the gene that cure cancer or make you thin or just let you live forever. Unfortunately, there pours out a lot more than that so stop eating the bacteria for a while. Modern biopharmaceuticals all depend on one being able to separate the (tiny!) wheat from the (humongous!) chaff and the method that comes our rescue is called chromatography. With that at hand, the bacteria can be smashed into a cocktail with all included and that cocktail is in one or more steps treated by a chromatographic instrument that can be viewed like a very clever (and quite expensive) sieve – it lets the wheat go through and keeps the chaff back or the exact opposite. Several such steps yield the clean substance without less desirable components smashed bacteria are prone to contain. The crucial word above is “clever”. A modern chromatography system lets molecules pass not only dependent on their size but also on other properties, like electric charge or hydrophobicity. This is permitted by clever chemistry – one can treat the sieve so that molecules get selectively attached to it. In fact, the sieve itself is not alike at all to a kitchen variety but is a carefully produced network of tiny pores within beads that are typically packed in columns through which the mixture to be purified flows. Though clever, chromatography materials are not optimal. In addition, new molecules and mixtures appear as candidates to be purified. Hence, improvements and innovations are sought after and this project is exactly about that – to understand how current systems work, and on that basis perchance come by new ideas. The goals are not easy to reach. Chromatography materials constitute a rather complex system with a lot of features and the first issue is that those features are not easy to pinpoint. The structure of the pore network and the actual state of the chemical modification are two examples for “we know a lot but not enough”. So, a part of the project is to get more information by improving and adapting experimental methods. The other part of the project is to simulate the intricate flow phenomena that appear when a complex biomolecular mixture is poured over a complex porous material. Finally, with a better understanding at hand one can come up with new structures that have new and improved capabilities.