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Modeling & Simulation of Affinity Chromatography & Investigation of CaptureSMB

Bogren, Dennis LU (2018) KETM05 20181
Chemical Engineering (M.Sc.Eng.)
Abstract
Chromatography was first described in the 1903 by a Russian scientist. Later on chromatography was almost forgotten until the 1940s when two British scientist published a study about liquid chromatography. They were later awarded with the Nobel prize in chemistry for their work in chromatography. Chromatography has since then developed a lot and nowadays several different kinds of liquid chromatography are used. Liquid chromatography are foremost used in the biochemistry, biotechnology, medicine and the pharmaceutical industry. This study had focused on affinity chromatography and to be able to simulate affinity chromatography. Affinity chromatography is when a ligand matrix are used as the stationary phase in the columns. This ligand... (More)
Chromatography was first described in the 1903 by a Russian scientist. Later on chromatography was almost forgotten until the 1940s when two British scientist published a study about liquid chromatography. They were later awarded with the Nobel prize in chemistry for their work in chromatography. Chromatography has since then developed a lot and nowadays several different kinds of liquid chromatography are used. Liquid chromatography are foremost used in the biochemistry, biotechnology, medicine and the pharmaceutical industry. This study had focused on affinity chromatography and to be able to simulate affinity chromatography. Affinity chromatography is when a ligand matrix are used as the stationary phase in the columns. This ligand matrix only binds in to a specific protein in this case IgG and lets the rest of the substances pass by. In this way IgG is separated from the other proteins and contaminations. The IgG is then eluted from the column by a change in the pH value. The work was started with some experimental runs and then a model was combined to fit the experimental data. When the model got a moderately fit to the experimental data it was calibrated to get a better fit by the function lsqcurvefit in MATLAB. With the calibration the exact parameters were given for the model. The next part of the study was to investigate the capacity of the protein A columns HiTrap MabSelect Sure and HiTrap MabSelect Prisma A. The capacity of the columns was investigated by some breakthrough experiments and at the same time the breakthrough profiles were investigated. It was seen that HiTrap MabSelect Prisma A had a greater capacity of about 45mg IgG/ml resin than HiTrap MabSelect SuRe. It was also found that with a lower flowrate, a higher slope was achieved for both the columns. The last part in this study was the investigation of CaptureSMB. CaptureSMB is a combination of affinity chromatography and simulated moving bed (SMB). It uses two columns that by shifting valves gives the appearance that the columns shifts places. CaptureSMB has four different steps. The first step is to load the first column and when breakthrough occurs it is loaded on to the second column. The second step is to elute, strip, cip and regenerate the first column while the second column gets filled. The third step is when the first column are regenerated it is placed after the second column to capture when breakthrough occurs on the second column. The fourth and last step is when the second column are eluted, striped, ciped and regenerated while the first column are loaded. The proposed process for affinity chromatography in this study used four versatile valves, two UV sensors, one conductivity sensor, one pH sensor, three pumps, three inlet valves, one injection valve and two columns. (Less)
Popular Abstract (Swedish)
När läkemedel produceras bildas även en massa biprodukter. Dessa biprodukterna kan många gånger vara mycket skadligare än vad själva läkemedlet gör nytta. Därför renar man upp läkemedel med en process som heter kromatografi. Kromatografi är som ett rör som är fyllt med något typ av sand eller sten. För att sedan rena upp sitt läkemedel låter man sin blandning med produkt och biprodukt åka genom kolonen och separeras. Man får då alla ämnen var för sig. Under detta examensarbete har en särskild sorts kromatografi undersökts som heter affinitetskromatografi. Affinitetskromatografi fungerar som så att det enbart riktar in sig på ett förutbestämt ämne som det fångar upp och släpper genom resten. Låt säga att man har sin kolon fast denna gången... (More)
När läkemedel produceras bildas även en massa biprodukter. Dessa biprodukterna kan många gånger vara mycket skadligare än vad själva läkemedlet gör nytta. Därför renar man upp läkemedel med en process som heter kromatografi. Kromatografi är som ett rör som är fyllt med något typ av sand eller sten. För att sedan rena upp sitt läkemedel låter man sin blandning med produkt och biprodukt åka genom kolonen och separeras. Man får då alla ämnen var för sig. Under detta examensarbete har en särskild sorts kromatografi undersökts som heter affinitetskromatografi. Affinitetskromatografi fungerar som så att det enbart riktar in sig på ett förutbestämt ämne som det fångar upp och släpper genom resten. Låt säga att man har sin kolon fast denna gången har den packats med en massa små magneter. Därefter låter man en blandning av järnspån, träspån och sand åka genom. När detta passerar genom kolonnen kommer enbart järnspånet att fastna på magneterna och resten kommer bara att passera genom. Därefter låter man en vätska åka genom kolonen som avmagnetiserar magneterna för att spola ut järnspånet och sen en ny vätska för att göra magneterna magnetiska igen så man kan upprepa processen många gånger. I detta examensarbetet undersöktes även utflödesprofilen då kolonen fylldes på. Detta eftersom det är önskat att fylla kolonen så mycket som möjligt utan att det som man vill fånga upp börjar rinna genom. Det kan ses lite som att man har två tunnor och vatten i den ena som man vill flytta till den andra. Skulle man då bara fylla lite grann i spannen och gå med eller skulle man fylla så mycket som möjligt i spannen för att behöva gå färre gånger? För de flesta skulle svaret vara att fylla spannen så mycket som möjligt varje gång, men när man fyller spannen helt är det också väldigt lätt att det rinner över innan man hinner stänga kranen. Av denna anledningen har det undersökts hur mycket rinner över ur spannen när man fyller den om man inte öppnar kranen fullt varje gång och hur påverkar spannens storlek detta? Som en följd på att fylla spannen undersöktes även CaptureSMB. Det är när man försöker att fylla spannen utan att stänga av kranen. I detta fallet håller man den ena spannen över den andra medan man fyller för att fånga upp det som rinner över. När första spannen är full går man och tömmer den och sen när man kommer tillbaka sätter man den tomma spannen under den andra så att den fångar upp när den rinner över. På detta sättet behöver aldrig kranen stängas av vilket gör processen effektivare. I en del processer är det inte heller möjligt att stänga av kranen och då blir detta extra viktigt. (Less)
Please use this url to cite or link to this publication:
author
Bogren, Dennis LU
supervisor
organization
course
KETM05 20181
year
type
H2 - Master's Degree (Two Years)
subject
keywords
Affinity chromatography, simulation of chromatography, breakthrough curve, CaptureSMB, chemical engineering, kemiteknik
language
English
id
8951165
date added to LUP
2018-08-03 11:06:57
date last changed
2018-08-03 11:06:57
@misc{8951165,
  abstract     = {Chromatography was first described in the 1903 by a Russian scientist. Later on chromatography was almost forgotten until the 1940s when two British scientist published a study about liquid chromatography. They were later awarded with the Nobel prize in chemistry for their work in chromatography. Chromatography has since then developed a lot and nowadays several different kinds of liquid chromatography are used. Liquid chromatography are foremost used in the biochemistry, biotechnology, medicine and the pharmaceutical industry. This study had focused on affinity chromatography and to be able to simulate affinity chromatography. Affinity chromatography is when a ligand matrix are used as the stationary phase in the columns. This ligand matrix only binds in to a specific protein in this case IgG and lets the rest of the substances pass by. In this way IgG is separated from the other proteins and contaminations. The IgG is then eluted from the column by a change in the pH value. The work was started with some experimental runs and then a model was combined to fit the experimental data. When the model got a moderately fit to the experimental data it was calibrated to get a better fit by the function lsqcurvefit in MATLAB. With the calibration the exact parameters were given for the model. The next part of the study was to investigate the capacity of the protein A columns HiTrap MabSelect Sure and HiTrap MabSelect Prisma A. The capacity of the columns was investigated by some breakthrough experiments and at the same time the breakthrough profiles were investigated. It was seen that HiTrap MabSelect Prisma A had a greater capacity of about 45mg IgG/ml resin than HiTrap MabSelect SuRe. It was also found that with a lower flowrate, a higher slope was achieved for both the columns. The last part in this study was the investigation of CaptureSMB. CaptureSMB is a combination of affinity chromatography and simulated moving bed (SMB). It uses two columns that by shifting valves gives the appearance that the columns shifts places. CaptureSMB has four different steps. The first step is to load the first column and when breakthrough occurs it is loaded on to the second column. The second step is to elute, strip, cip and regenerate the first column while the second column gets filled. The third step is when the first column are regenerated it is placed after the second column to capture when breakthrough occurs on the second column. The fourth and last step is when the second column are eluted, striped, ciped and regenerated while the first column are loaded. The proposed process for affinity chromatography in this study used four versatile valves, two UV sensors, one conductivity sensor, one pH sensor, three pumps, three inlet valves, one injection valve and two columns.},
  author       = {Bogren, Dennis},
  keyword      = {Affinity chromatography,simulation of chromatography,breakthrough curve,CaptureSMB,chemical engineering,kemiteknik},
  language     = {eng},
  note         = {Student Paper},
  title        = {Modeling & Simulation of Affinity Chromatography & Investigation of CaptureSMB},
  year         = {2018},
}