title: Artificial Intelligence vs. Statistical Modeling and Optimization of Continuous Bead Milling Process for Bacterial Cell Lysis.
abstract: For a commercially viable recombinant intracellular protein production process, efficient cell lysis and protein release is a major bottleneck. The recovery of recombinant protein, cholesterol oxidase (COD) was studied in a continuous bead milling process. A full factorial response surface methodology (RSM) design was employed and compared to artificial neural networks coupled with genetic algorithm (ANN-GA). Significant process variables, cell slurry feed rate (A), bead load (B), cell load (C), and run time (D), were investigated and optimized for maximizing COD recovery. RSM predicted an optimum of feed rate of 310.73 mL/h, bead loading of 79.9% (v/v), cell loading OD600nmof 74, and run time of 29.9 min with a recovery of ~3.2 g/L. ANN-GA predicted a maximum COD recovery of ~3.5 g/L at an optimum feed rate (mL/h): 258.08, bead loading (%, v/v): 80%, cell loading (OD600nm): 73.99, and run time of 32 min. An overall 3.7-fold increase in productivity is obtained when compared to a batch process. Optimization and comparison of statistical vs. artificial intelligence techniques in continuous bead milling process has been attempted for the very first time in our study. We were able to successfully represent the complex non-linear multivariable dependence of enzyme recovery on bead milling parameters. The quadratic second order response functions are not flexible enough to represent such complex non-linear dependence. ANN being a summation function of multiple layers are capable to represent complex non-linear dependence of variables in this case; enzyme recovery as a function of bead milling parameters. Since GA can even optimize discontinuous functions present study cites a perfect example of using machine learning (ANN) in combination with evolutionary optimization (GA) for representing undefined biological functions which is the case for common industrial processes involving biological moieties.
authors.affiliation: Department of Biosciences, Jamia Millia Islamia (A Central University)New Delhi, India; Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan UniversityJazan, Saudi Arabia.
authors.forename: Shafiul
authors.initials: S
authors.lastname: Haque
authors.affiliation: Department of Clinical Nutrition, College of Applied Medical Sciences, University of Ha'il Ha'il, Saudi Arabia.
authors.forename: Saif
authors.initials: S
authors.lastname: Khan
authors.affiliation: Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan UniversityJazan, Saudi Arabia; Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia (A Central University)New Delhi, India.
authors.forename: Mohd
authors.initials: M
authors.lastname: Wahid
authors.affiliation: Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan UniversityJazan, Saudi Arabia; The University College of Medical Sciences and Guru Teg Bahadur Hospital (University of Delhi)New Delhi, India.
authors.forename: Sajad A
authors.initials: SA
authors.lastname: Dar
authors.affiliation: Department of Biotechnology, Khalsa College Patiala, India.
authors.forename: Nipunjot
authors.initials: N
authors.lastname: Soni
authors.affiliation: Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University Jazan, Saudi Arabia.
authors.forename: Raju K
authors.initials: RK
authors.lastname: Mandal
authors.affiliation: Microbiology Division, Council of Scientific and Industrial Research - Central Drug Research Institute Lucknow, India.
authors.forename: Vineeta
authors.initials: V
authors.lastname: Singh
authors.affiliation: Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal Durban, South Africa.
authors.forename: Dileep
authors.initials: D
authors.lastname: Tiwari
authors.affiliation: Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University Jazan, Saudi Arabia.
authors.forename: Mohtashim
authors.initials: M
authors.lastname: Lohani
authors.affiliation: Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University Jazan, Saudi Arabia.
authors.forename: Mohammed Y
authors.initials: MY
authors.lastname: Areeshi
authors.affiliation: Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal Durban, South Africa.
authors.forename: Thavendran
authors.initials: T
authors.lastname: Govender
authors.affiliation: Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal Durban, South Africa.
authors.forename: Hendrik G
authors.initials: HG
authors.lastname: Kruger
authors.affiliation: Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan UniversityJazan, Saudi Arabia; RFCL LimitedNew Delhi, India.
authors.forename: Arshad
authors.initials: A
authors.lastname: Jawed
keywords: artificial neural network; cell lysis; central composite design; cholesterol oxidase; genetic algorithm; response surface methodology