Real-time monitoring of multiple properties in cell culture processes using processing analysis technology

被引：0
|
作者：
Wu T. [1 ]
Liang L. [1 ]
Zhang R. [1 ]
Luo A. [1 ]
Wen Z. [1 ]
Wang X. [1 ]
机构：
[1] Beijing Key Laboratory of Enze Biomass Fine Chemicals, College of New Materials and Chemical Engineering, Beijing institute of Petrochemical Technology, Beijing
来源：
Gao Xiao Hua Xue Gong Cheng Xue Bao/Journal of Chemical Engineering of Chinese Universities | 2023年 / 37卷 / 03期
关键词：
cell culture monitoring; genetic algorithm; image processing; in-situ microscopy; on-line Raman spectroscopy; process analytical technology;
D O I：
10.3969/j.issn.1003-9015.2023.03.012
中图分类号：
学科分类号：
摘要：
In order to real-time and on-line monitor cell growth status and biochemical index of suspended animal cells, Chinese hamster ovary (CHO) cells were studied using in-situ microscopy and on-line Raman spectrometry. Based on image analysis and chemometric models obtained from genetic algorithm combined with partial least squares, cell density, size distribution, and glucose and lactic acid concentrations of culture media were acquired in real-time. The root mean square error (RMSEP) of glucose concentration model was 0.085 g‧L-1 and the correlation coefficient RP2 was 0.999. The RMSEP and RP2 of lactic acid model were 0.055 g‧L-1 and 0.966, respectively. These results show that the above method can be used to real-time and on-line monitor cell density, cell size distribution, and metabolic concentration. Compared with off-line monitoring methods, this method can avoid the risk of bacterial infection and complicated operation. © 2023 Zhejiang University. All rights reserved.
引用
收藏
页码：441 / 448
页数：7
相关论文
共 17 条
  • [1] YAN X, SHEN L J, XU W Y, Et al., Rapid analysis of multiple parameters of CHO cell culture media using Raman spectroscopy, Journal of Chemical Engineering of Chinese Universities, 33, 4, pp. 872-877, (2019)
  • [2] MEHDIZADEH H, LAURI D, KARRY K M, Et al., Generic Raman-based calibration models enabling real-time monitoring of cell culture bioreactors, Biotechnology Progress, 31, 4, pp. 1004-1013, (2015)
  • [3] WANG Y S, HAO W H, WU Z M, Et al., Development and application of in-situ microscopy in on-line monitoring of cell biomass, Chinese Journal of Biotechnology, 35, 9, pp. 1607-1618, (2019)
  • [4] BURGEMEISTER S, NATTKEMPER T W, NOLL T, Et al., CellViCAM-Cell viability classification for animal cell cultures using dark field micrographs, Journal of Biotechnology, 149, 4, pp. 310-316, (2010)
  • [5] RUDOLPH G, LINDNER P, GIERSE A, Et al., Online monitoring of microcarrier based fibroblast cultivations with in situ microscopy, Biotechnology and Bioengineering, 99, 1, pp. 136-145, (2007)
  • [6] WHELAN J, CRAVEN S, GLENNON B., In situ Raman spectroscopy for simultaneous monitoring of multiple process parameters in mammalian cell culture bioreactors, Biotechnology Progress, 28, 5, pp. 1355-1362, (2012)
  • [7] RAFFERTY C, JOHNSON K, O'MAHONY J, Et al., Analysis of chemometric models applied to Raman spectroscopy for monitoring key metabolites of cell culture, Biotechnology Progress, 36, 4, (2020)
  • [8] CHEN J, WANG X Z., A wavelet method for analysis of droplet and particle images for monitoring heterogeneous processes, Chemical Engineering Communications, 192, 4, pp. 499-515, (2005)
  • [9] WAN J, MA C Y, WANG X Z., A method for analyzing on-line video images of crystallization at high-solid concentrations, Particuology, 6, 1, pp. 9-15, (2008)
  • [10] TANG X H, LI Y, LIU J J, Et al., Process Analytical Technology (PAT) aided identification of operational spaces leading to tailored crystal size distributions in azithromycin crystallization via coordinated cooling and solution mediated phase transition, Organic Process Research & Development, 21, 12, pp. 1963-1971, (2017)
12