Raman-Based Feedback Control of the Enzymatic Hydrolysis of Lactose

Edit Hirsch, Hajnalka Pataki, Attila Farkas, Henrik Bata, Panna Vass, Csaba Fehér, Zsolt Barta, László Párta, István Csontos, András Ballagi, Zsombor K. Nagy, G. Marosi

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8 Citations (Scopus)


The development of real-time monitoring and an improved control system was performed according to a process analytical technology initiative focusing on the benefits of the pharmaceutical industry. As an extension of the results of pioneering Raman-based closed-loop feedback control of crystallization and synthesis, a bioprocess, namely, the enzymatic hydrolysis of lactose, was investigated in this work. For this purpose, an effective control system was developed to maintain the lactose concentration at a level of 20 g/L. Real-time evaluation of Raman spectra was accomplished using classical least-squares (CLS) and partial least-squares (PLS) multivariate data analysis methods. Formation of oligosaccharides during the hydrolysis of lactose causes inaccuracy in the CLS evaluation, and thus, optimization of lactose hydrolysis was needed to decrease oligosaccharide formation. After optimization, control of lactose hydrolysis could be achieved. To improve real-time evaluation, the PLS method was used, resulting in better evaluation of spectra during control experiments.

Original languageEnglish
Pages (from-to)1721-1727
Number of pages7
JournalOrganic Process Research and Development
Issue number10
Publication statusPublished - Oct 21 2016

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry

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    Hirsch, E., Pataki, H., Farkas, A., Bata, H., Vass, P., Fehér, C., Barta, Z., Párta, L., Csontos, I., Ballagi, A., Nagy, Z. K., & Marosi, G. (2016). Raman-Based Feedback Control of the Enzymatic Hydrolysis of Lactose. Organic Process Research and Development, 20(10), 1721-1727. https://doi.org/10.1021/acs.oprd.6b00212