Phase-field modeling of dynamics of immobilized yeast cell growth in Ca-alginate microbead

Abstract

A phase-field model was formulated to describe yeast cell growth within the Ca-alginate microbead during air-lift bioreactor cultivation. Model development was based on experimentally obtained data for intra-bead yeast cell volume fraction profile after reaching the equilibrium state, as well as, total yeast cell volume fraction per microbead and microbead volume as functions of time. Relatively uniform cell concentration in the microbead, experimentally obtained, indicated microenvironmental restriction effects due to deformation and disintegration of previously swollen alginate hydrogel, while internal nutrient diffusion limitation could be neglected in the case of alginate microbeads used in this study. Microbead with growing yeast cells is treated as two phase system. One phase represents the cell agglomerates, while the other is the alginate hydrogel matrices. The interactions between phases are modeled using the Langevin class, non-conservative phase-field model. Such class of models is suitable for considering the growth of small domains of one phase as nucleation. Besides giving useful insights into the dynamics of restrictive cell growth within the Ca-alginate microbead, the model can be used as a tool to design/optimize the performance of microbead and studying the microenvironmental restrictive mechanism action on the cell growth. .

Fazni model je formulisan da opiše rast ćelija kvasaca unutar Ca-alginatnih nosača za vreme perioda kultivacije u air-lift bioreaktoru. Model je razvijen na osnovu prikupljenih eksperimentalnih podataka za profil yapreminskog udela ćelija unutar nosača nakon postizanja stacionarnog stanja, za yapreminski udeo ćelija po nosaču u funkciji vremena i za promenu zapremine nosača u toku vremena. Relativno uniformna koncentracija ćelija, eksperimentalno primećena, unutar Ca-alginatnih nosača ukazuje na postojanje restriktivnih efekata sredine koji limitiraju rast ćelija, kao što su deformisanje i razgradnja matrice nosača. Otpori difuziji nutrenata kroz nosač se mogu zanemariti. Mironosač sa imobilisanim ćelijama koje rastu se može tretirati kao dvo-fazni sistem. Jednu fazu pretstavljaju aglomerati ćelija, a drugu matrica Ca-alginatnog hidrogela. Interakcije izmedju faza su modelovane koristeći Lanževinovu klasu ne konzervativnih faznih modela. Ova klasa modela je pogodna za razmatranje rasta malih domena jedne faze u toku procesa nukleacije. S obziromda daje koristan uvid u dinamiku restriktivnog rasta ćelija unutar Ca-alginatnih nosača, ovaj model može biti korišćen kao sredstvo za dizajniranje/optimizaciju osobina mikronosača i proučavanje mehanizama restriktivnog dejstva mikrookoline ćelija unutar nosača na dinamiku rasta ćelija. .