Probeless non-invasive near-infrared spectroscopic bioprocess monitoring using microspectrometer technology

Robert Zimmerleiter,Julian Kager,Ramin Nikzad-Langerodi,Vladimir Berezhinskiy,Frank Westad,Markus Brandstetter,Christoph Herwig

doi:10.1007/s00216-019-02227-w

Abstract

Real-time measurements and adjustments of critical process parameters are essential for the precise control of fermentation processes and thus for increasing both quality and yield of the desired product. However, the measurement of some crucial process parameters such as biomass, product, and product precursor concentrations usually requires time-consuming offline laboratory analysis. In this work, we demonstrate the in-line monitoring of biomass, penicillin (PEN), and phenoxyacetic acid (POX) in a Penicilliumchrysogenum fed-batch fermentation process using low-cost microspectrometer technology operating in the near-infrared (NIR). In particular, NIR reflection spectra were taken directly through the glass wall of the bioreactor, which eliminates the need for an expensive NIR immersion probe. Furthermore, the risk of contaminations in the reactor is significantly reduced, as no direct contact with the investigated medium is required. NIR spectra were acquired using two sensor modules covering the spectral ranges 1350–1650 nm and 1550–1950 nm. Based on offline reference analytics, partial least squares (PLS) regression models were established for biomass, PEN, and POX either using data from both sensors separately or jointly. The established PLS models were tested on an independent validation fed-batch experiment. Root mean squared errors of prediction (RMSEP) were 1.61 g/L, 1.66 g/L, and 0.67 g/L for biomass, PEN, and POX, respectively, which can be considered an acceptable accuracy comparable with previously published results using standard process spectrometers with immersion probes. Altogether, the presented results underpin the potential of low-cost microspectrometer technology in real-time bioprocess monitoring applications.Graphical abstract

Highlights

Published in the topical collection Advances in Process Analytics and Control Technology with guest editor Christoph Herwig.Science and Technology, O
Two full fermentation runs were pursued in order to test the suitability of microelectromechanical systems (MEMS)-based microspectrometer technology for probeless monitoring of biomass, PEN, and phenoxyacetic acid (POX) in a
A principal component analysis (PCA) of the fused spectra of both sensors was undertaken in order to investigate if the data from the two batches are consistent (Fig. 2b)

Summary

Introduction

Published in the topical collection Advances in Process Analytics and Control Technology with guest editor Christoph Herwig.Science and Technology, O. Published in the topical collection Advances in Process Analytics and Control Technology with guest editor Christoph Herwig. The precise control of bioprocesses is essential to achieve an optimum quality and yield of the desired product. A key to achieve this goal are analytical methods that provide real-time information of the current process state and critical process parameters. For some of these parameters such as pH, temperature, and dissolved oxygen concentration, real-time measurement techniques are readily available, while other parameters, such as substrate and product concentrations, usually require time-consuming offline measurements [1,2,3], which results in additional sources of analytical error due to sampling and sample preparation

Methods

Results

Conclusion