Using a two species competitive binding model to predict expanded bed breakthrough of a recombinant protein expressed in a high cell density fermentation

详细信息    查看全文

• 作者：William Kelly (1754)
  Guy Kamguia (1754)
  Peter Mullen (1754)
  Antonio Ubiera (2754)
  Kent G?klen (2754)
  Zuyi Huang (1754)
  Gerard Jones (1754)
  
• 关键词：protein recovery ; chromatography ; mathematical modeling ; biochemical engineering ; expanded bed adsorption ; protein breakthrough
• 刊名：Biotechnology and Bioprocess Engineering
• 出版年：2013
• 出版时间：June 2013
• 年：2013
• 卷：18
• 期：3
• 页码：546-559
• 全文大小：504KB
• 参考文献：1. Skidmore, G. L., B. J. Horstman, and H. A. Chase (1990) Modeling single-component protein adsorption to the cation exchanger S Sepharose? FF. / J. Chromatog. 498: 113-28. CrossRef
  2. Wright, P. R. and B. J. Glasser (2001) Modeling mass transfer and hydrodynamics in fluidized-bed adsorption of proteins. / AIChE J. 47: 474-88. CrossRef
  3. Tong, X., B. Xue, and Y. Sun (2003) Modeling of expanded-bed protein adsorption by taking into account the particle size distribution. / Biochem. Eng. J. 16: 265-72. CrossRef
  4. Yun, J., D. Lin, and S. Yao (2005) Predictive modeling of protein adsorption along the bed height by taking into account the axial nonuniform liquid dispersion and particle classification in expanded beds. / J. Chrom. A 1095: 16-6. CrossRef
  5. Li, P., A. Xiu, and A. Rodrigues (2005) Experimental and modeling study of protein adsorption in expanded bed. / AIChE J. 51: 2965-977. CrossRef
  6. Skidmore, G. L. and H. A. Chase (1990) Two-component protein adsorption to the cation exchanger S Sepharose? FF. / J. Chrom. 505: 329-47. CrossRef
  7. Weinbrenner, W. F. and M. R. Etzel (1994) Competetive adsorption of α-lactalbumin and bovine serum albumin to a sulfopropyl ion-exchange membrane. / J. Chrom. A. 662: 414-19. CrossRef
  8. Hashim, M. A., K. H. Chu, and P. S. Tsan (1997) Modeling of protein adsorption in a fixed-bed: Single and two-solute breakthrough behavior. / Chem. Eng. Comm. 161: 45-3. CrossRef
  9. El-Sayed, M. and H. A. Chase (2010) Simulation of the breakthrough curves for the adsorption of α-Lactalbumin and β-Lactoglobulin to SP Sepharose? FF cation-exchanger. / Biochem. Eng. J. 49: 221-28. CrossRef
  10. Chase, H. A. and N. M. Draeger (1992) Expanded-bed adsorption of proteins using ion exchangers. / Sep. Sci. Technol. 27: 2021-039. CrossRef
  11. Feuser, J., J. Walter, M. -R. Kula, and J. Thommes (1999) Celladsorbent interactions in expanded bed adsorption of proteins. / Biosep. 8: 99-09. CrossRef
  12. Mercier-Bonin, M., H. Vergnault, and R. Willemot (2004) Physicochemical parameters involved in the interaction of / Saccharomyces cerevisiae cells with ion-exchange adsorbents in expanded bed chromatography. / Biotechnol. Prog. 20:1534-542. CrossRef
  13. Fernandez-Lahore, H. M., A. Nagel, M. -R. Kula, and J. Thommes (2000) The influence of cell adsorbent interactions on protein adsorption in expanded beds. / J. Chrom. A. 873: 195-08. CrossRef
  14. Chen, W., X. Dong, and Y. Sun (2003) Modeling of the whole expanded-bed protein adsorption process with yeast cell suspensions as feedstock. / J. Chrom. A. 1012: 1-0. CrossRef
  15. Wang, X., A. Hunter, and N. Mozier (2009) Host cell proteins in biologics development: Identification, quantification and risk assessement. / Biotechnol. Bioeng. 103: 446-58. CrossRef
  16. Lihme, A. (1997) Mixed mode resins for isolation of proteins. / Europe Patent EP1 386 660 A1.
  17. Noel, R., B. Hansen, and A. Lihme (2007) Industrial processing of immunoglobulins. / Bioprocess Internatl. 5 (5): 58-1.
  18. Kelly, W., P. Garcia, S. McDermott, P. Mullen, G. Kamguia, G. Jones, A. Ubiera, and K. G?klen (2012) Experimental characterization of next generation expanded bed adsorbents. / Biotechnology and Applied Biochemistry. Awaiting review.
  19. Hall, K. (1966) Pore- and solid-diffusion kinetics in fixed-bed adsorption under constant-pattern conditions. / Ind. Eng. Chem. Fund. 5: 212-23. CrossRef
  20. Weber, T. and R. Chakravorti (1974) Pore and solid diffusion models for fixed-bed adsorbers. / AIChE J. 20: 229-37.
  21. Cooper, R. (1965) Slow particle diffusion in ion exchange columns. / Ind. Eng. Chem. Fund. 4: 308-13. CrossRef
  22. Fan, L. S., Y. C. Yang, and C. Y. Wen (1960) Mass transfer in semifluidized beds for solid-liquid systems. / AIChE J. 6: 482-87. CrossRef
  23. Meechai, N., A. M. Jamieson, and J. Blackwell (1999) Translational diffusion coefficients of bovine serum albumin in aqueous solution at high ionic strength. / J. Colloid and Interface Sci. 218: 167-75. CrossRef
  
• 作者单位：William Kelly (1754)
  Guy Kamguia (1754)
  Peter Mullen (1754)
  Antonio Ubiera (2754)
  Kent G?klen (2754)
  Zuyi Huang (1754)
  Gerard Jones (1754)
  
  1754. College of Engineering, Villanova University, Villanova, Pa, 19085, USA
  2754. Downstream Process Development, Biopharmaceutical Development, GlaxoSmithKline, King of Prussia, PA, 19406, USA
  

文摘

Expanded Bed experiments were conducted using a mixed mode (MM) resin to capture and purify a recombinant protein produced in yeast fermentation. Expanded bed breakthrough profiles show an overshoot in column effluent concentration of the target protein in the presence of cells and other broth proteins, similar to that seen by other researchers when loading two competing species onto packed beds. In this research, a numerical model assuming negligible axial dispersion is developed and first validated for columns loads that contain only the target protein. This model is solved by finite differences in a unique way that uses an embedded analytical-solution to increase solution speed and stability. To model expanded bed breakthrough of the target protein in the actual cell broth, it was assumed that the other non-product proteins in the broth compete for MM resin binding sites and might be represented as a second “average-species via a traditional two-component competitive Langmuir isotherm. Estimates of the Langmuir constant and broth concentration of this second species were then calculated from batch adsorption data. Using these parameters for the second species, and other batch-derived parameters for the target protein with this resin, this unique numerical modeling approach provided results that compare favorably to experimental breakthrough data at various flow rates. Finally, the model was employed for a parameter sensitivity analysis that shows which process variables are most important in determining breakthrough time and the shape and magnitude of the concentration overshoot.