Adaptive optimal operation of a parallel robotic liquid handling station

被引:19
作者
Barz, Tilman [1 ]
Sommer, Andreas [2 ]
Wilms, Terrance [3 ]
Neubauer, Peter [3 ]
Bournazou, M. Nicolas Cruz [3 ]
机构
[1] AIT Austrian Inst Technol GmbH, Ctr Energy, Vienna, Austria
[2] Heidelberg Univ, Interdisciplinary Ctr Sci Comp IWR, Heidelberg, Germany
[3] Tech Univ Berlin, Chair Bioproc Engn, Inst Biotechnol, Berlin, Germany
关键词
Parallel robotic liquid handling station; E. coli kinetic model; Optimal experimental design for model calibration; Adaptive input design; Identifiability and ill-conditioning analysis; DESIGN; AUTOMATION;
D O I
10.1016/j.ifacol.2018.04.006
中图分类号
TP [自动化技术、计算机技术];
学科分类号
0812 ;
摘要
Results are presented from the optimal operation of a fully automated robotic liquid handling station where parallel experiments are performed for calibrating a kinetic fermentation model. To increase the robustness against uncertainties and/or wrong assumptions about the parameter values, an iterative calibration and experiment design approach is adopted. Its implementation yields a stepwise reduction of parameter uncertainties together with an adaptive redesign of reactor feeding strategies whenever new measurement information is available. The case study considers the adaptive optimal design of 4 parallel fed-batch strategies implemented in 8 mini-bioreactors. Details are given on the size and complexity of the problem and the challenges related to calibration of over-parameterized models and scarce and non-informative measurement data. It is shown how methods for parameter identifiability analysis and numerical regularization can be used for monitoring the progress of the experimental campaigns in terms of generated information regarding parameters and selection of the best fitting parameter subset. (C) 2018, IFAC (International Federation of Automatic Control) Hosting by Elsevier Ltd. All rights reserved.
引用
收藏
页码:765 / 770
页数:6
相关论文
共 12 条
[1]   Kinetic models in industrial biotechnology - Improving cell factory performance [J].
Almquist, Joachim ;
Cvijovic, Marija ;
Hatzimanikatis, Vassily ;
Nielsen, Jens ;
Jirstrand, Mats .
METABOLIC ENGINEERING, 2014, 24 :38-60
[2]  
Bard Y., 1974, Nonlinear parameter estimation
[3]   Real-time adaptive input design for the determination of competitive adsorption isotherms in liquid chromatography [J].
Barz, Tilman ;
Lopez, Diana C. C. ;
Bournazou, M. Nicolas Cruz ;
Koerkel, Stefan ;
Walter, Sebastian F. .
COMPUTERS & CHEMICAL ENGINEERING, 2016, 94 :104-116
[4]   Numerical methods for optimum experimental design in DAE systems [J].
Bauer, I ;
Bock, HG ;
Körkel, S ;
Schlöder, JP .
JOURNAL OF COMPUTATIONAL AND APPLIED MATHEMATICS, 2000, 120 (1-2) :1-25
[5]   Online optimal experimental re-design in robotic parallel fed-batch cultivation facilities [J].
Bournazou, M. N. Cruz ;
Barz, T. ;
Nickel, D. B. ;
Cardenas, D. C. Lopez ;
Glauche, F. ;
Knepper, A. ;
Neubauer, P. .
BIOTECHNOLOGY AND BIOENGINEERING, 2017, 114 (03) :610-619
[6]   Nonlinear ill-posed problem analysis in model-based parameter estimation and experimental design [J].
Lopez C, Diana C. ;
Barz, Tilman ;
Koerkel, Stefan ;
Wozny, Guenter .
COMPUTERS & CHEMICAL ENGINEERING, 2015, 77 :24-42
[7]   OPTIMAL INPUT SIGNALS FOR PARAMETER ESTIMATION IN DYNAMIC SYSTEMS SURVEY AND NEW RESULTS [J].
MEHRA, RK .
IEEE TRANSACTIONS ON AUTOMATIC CONTROL, 1974, AC19 (06) :753-768
[8]   Consistent development of bioprocesses from microliter cultures to the industrial scale [J].
Neubauer, Peter ;
Cruz, Nicolas ;
Glauche, Florian ;
Junne, Stefan ;
Knepper, Andreas ;
Raven, Michael .
ENGINEERING IN LIFE SCIENCES, 2013, 13 (03) :224-238
[9]   Online bioprocess data generation, analysis, and optimization for parallel fed-batch fermentations in milliliter scale [J].
Nickel, David Benjamin ;
Cruz-Bournazou, Mariano Nicolas ;
Wilms, Terrance ;
Neubauer, Peter ;
Knepper, Andreas .
ENGINEERING IN LIFE SCIENCES, 2017, 17 (11) :1195-1201
[10]   Bioprocess automation on a Mini Pilot Plant enables fast quantitative microbial phenotyping [J].
Unthan, Simon ;
Radek, Andreas ;
Wiechert, Wolfgang ;
Oldiges, Marco ;
Noack, Stephan .
MICROBIAL CELL FACTORIES, 2015, 14