Soft sensors in bioprocessing: A status report and recommendations

Luttmann, R.; Bracewell, Daniel G.; Cornelissen, Gesine; Gernaey, Krist V.; Glassey, Jarka; Hass, Volker C.; Kaiser, Christian; Preusse, Christian; Striedner, Gerald; Mandenius, Carl‐Fredrik

doi:10.1002/biot.201100506

Cited by 196 publications

(122 citation statements)

References 42 publications

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“…To support laborious and time-consuming physiological characterisation of cells based on sophisticated process control, software-sensors have been established (Brühlmann et al, 2014, Herwig et al, 2001, Jenzsch et al, 2006, Luttmann et al, 2012. Such softwaresensors deliver information on the important real-time variables that characterise a bioprocess (such as concentrations of substrates, products and biomass) and are typically determined off-line, with an expected post-sampling delay of several hours.…”

Section: Approaches To Reduce Experimental Loadmentioning

confidence: 99%

Cultivation strategies to enhance productivity of Pichia pastoris: A review

Looser

Brühlmann

Bumbak

et al. 2015

Biotechnology Advances

296

268

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Pichia pastoris, a methylotrophic yeast, is an established system for the production of heterologous proteins, particularly biopharmaceuticals and industrial enzymes. To maximise and optimise the production of recombinant products, recent molecular research has focused on numerous issues including the design of expression vectors, optimisation of gene copy number, co-expression of secretory proteins such as chaperones, engineering of glycosylation and secretory pathways, etc. However, the physiological effects of different cultivation strategies are often difficult to separate from the molecular effects of the gene construct (e.g., cellular stress through over-expression or incorrect post-translational processing). Hence, overall system optimisation is difficult, even though it is urgently required in order to describe and understand the behaviour of new molecular constructs. This review focuses on particular aspects of recombinant protein production related to variations in biomass growth and their implications for strain design and screening, as well as on the concept of rational comparisons between cultivation systems for the development of specific production processes in bioreactors. The relationship between specific formation rates of secreted recombinant proteins, qp, and specific growth rates, μ, has been analysed in a conceptual attempt to compare different systems, particularly those based on AOX1/methanol and GAP/glucose, and this has now evolved into a pivotal concept for bioprocess engineering of P. pastoris.

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Section: Approaches To Reduce Experimental Loadmentioning

confidence: 99%

Cultivation strategies to enhance productivity of Pichia pastoris: A review

Looser

Brühlmann

Bumbak

et al. 2015

Biotechnology Advances

296

268

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“…Integration of sensors is especially important when testing complex process concepts such as ISPR strategies in biocatalysis, as it will enable high-resolution data and minimize disruptions caused by manual sampling. Furthermore, it should be emphasized that the application of soft sensors to predict additional variables of interest enables the use of mechanistic models and parameter estimation on the data in order to validate the models and the experimental setup [93].…”

Section: A Microfluidic Toolbox For Ispr Developmentmentioning

confidence: 99%

A Microfluidic Toolbox for the Development of In-Situ Product Removal Strategies in Biocatalysis

Heintz¹,

Mitić²,

Ringborg³

et al. 2016

J Flow Chem

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A microfluidic toolbox for accelerated development of biocatalytic processes has great potential. This is especially the case for the development of advanced biocatalytic process concepts, where reactors and product separation methods are closely linked together to intensify the process performance, e.g., by the use of in-situ product removal (ISPR). This review provides a general overview of currently available tools in a microfluidic toolbox and how this toolbox can be applied to the development of advanced biocatalytic process concepts. Emphasis is placed on describing the possibilities and advantages of the microfluidic toolbox that are difficult to achieve with conventional batch-processbased technologies. Application of this microfluidic toolbox will potentially make it possible to intensify biocatalytic reactions and thereby facilitate the development towards novel and advanced biocatalytic processes, which in many cases have proven too difficult in conventional batch equipment.

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“…This fact is because of their flexibility to fit the often nonlinear relationships between the input and output variables in biological processes or systems. [19] Thus, this work aimed to establish a methodology to determine simultaneously several beer-quality attributes based on UV-Vis spectral data from diluted beer samples in conjunction with PCRs or ANNs.…”

Section: Introductionmentioning

confidence: 99%

Rapid monitoring of beer-quality attributes based on UV-Vis spectral data

Oliveira

Filho

Rocha

et al. 2017

International Journal of Food Properties

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This work aimed to determinate eight beer properties using UV-Vis spectra in combination with principal component regression (PCR) or artificial neural network (ANN) models. A statistical experimental design was performed to generate the calibration data. First, principal component analysis (PCA) was applied to the original spectral data, and the scores in significant PCs were utilized to calibrate both models. PCR showed poor correlation for beer parameters (R 2 < 0.61). The ANNs showed satisfactory correlations (R 2 = 0.74-0.92) and low relative error considering a variable range (E r < 9%) for most of the beer-quality attributes, but vicinal diketones (R 2 = 0.56, E r = 16.69%). Once implemented, this method would be fast and low cost. ARTICLE HISTORY

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Soft sensors in bioprocessing: A status report and recommendations

Cited by 196 publications

References 42 publications

Cultivation strategies to enhance productivity of Pichia pastoris: A review

Cultivation strategies to enhance productivity of Pichia pastoris: A review

A Microfluidic Toolbox for the Development of In-Situ Product Removal Strategies in Biocatalysis

Rapid monitoring of beer-quality attributes based on UV-Vis spectral data

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