Analiza osjetljivosti parametara modela proizvodnje monoklonskih protutijela

master's thesis

• Title (english): Parameter sensitivity analysis of monoclonal antibody production model
• Author: Brigita Herout
• Mentor: Ana Jurinjak Tušek (mentor)
• Committee member: Kristina Radošević (predsjednik povjerenstva)
• Granter: University of Zagreb; Faculty of Food Technology and Biotechnology; (Department of Process Engineering); (Laboratory for Measurement, Regulation and Automatisation); Zagreb
• Defense date and country: 2020-09-23, Croatia
• Scientific / art field, discipline and subdiscipline: BIOTECHNICAL SCIENCES; Biotechnology

Abstract

Matematičko modeliranje biotehnoloških procesa predstavlja pojednostavljenu sliku stvarnog procesa od interesa te uvijek sa sobom nosi određeni stupanj nesigurnosti, a posebno se to odnosi na procjenu vrijednosti kinetičkih parametra. U okviru ovog rada provedena je simulacija i analiza lokalne i globalne parametarske osjetljivosti matematičkog modela proizvodnje monoklonskih protutijela primjenom NS0 stanica u normalnim i hiperosmotskim uvjetima. Simulacije i analize modela provedene su u programskim paketima CellDesigner i WR Mathematica 10.0. Rezultati simulacija pokazuju višu produktivnost monoklonskih protutijela u hiperosmotskim uvjetima. Najveću osjetljivost na lokalno povećanje i na smanjenje vrijednosti kinetičkih parametara u normalnim uvjetima pokazuju intermedijeri monoklonskih protutijela dok se u hiperosmotskim uvjetima najosjetljivijom pokazala koncentracija ukupnih stanica. Prema analizi globalne parametarske osjetljivosti promjena koncentracije glukoze, laktata i protutijela najviše ovisi o maksimalnoj specifičnoj brzini rasta stanica. Analiza osjetljivosti parametra modela daje uvid u ključne točke procesa te omogućava preciznije unaprijeđenje modela.

Abstract (english)

Mathematical model of biotechnological process is a simplified version of the actual process of interest, but it always carries a certain degree of uncertainty, especially regarding the assessment of the kinetic parameters values. Within this work, a simulation and local and global parameter sensitivity analysis of a mathematical model describing of monoclonal antibody production using NS0 cells under normal and hyperosmotic conditions was performed. Simulations and model analyzes were performed in the software packages CellDesigner and WR Mathematica 10.0. The simulation results showed higher productivity of monoclonal antibodies under hyperosmotic conditions. The highest sensitivity to local increase and decrease of kinetic parameters in normal conditions was shown by intermediates of monoclonal antibodies, while in hyperosmotic conditions the concentration of total cells was the most sensitive. According to the global parameter sensitivity analysis, changes in the concentration of glucose, lactate and antibodies mostly depend on the maximum specific cell growth rate. The sensitivity analysis of the model parameters provides insight into the key points of the process and enables more precise model improvement.

• Keywords: monoklonska protutijela; NS0 stanice; CellDesigner; lokalna parametarska osjetljivost; globalna parametarska osjetljivost
• Keywords (english): monoclonal antibody; NS0 cells; CellDesigner; local sensitivity analysis; global sensitivity analysis
• Language: croatian
• URN:NBN: urn:nbn:hr:159:310453
• Study programme: Title: Molecular Biotechnology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra inženjer/inženjerka molekularne biotehnologije (magistar/magistra inženjer/inženjerka molekularne biotehnologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2020-12-16 14:50:04