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Bioreactor monitoring with spectroscopy and chemometrics: a review

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Abstract

Biotechnological processes are crucial to the development of any economy striving to ensure a relevant position in future markets. The cultivation of microorganisms in bioreactors is one of the most important unit operations of biotechnological processes, and real-time monitoring of bioreactors is essential for effective bioprocess control. In this review, published material on the potential application of different spectroscopic techniques for bioreactor monitoring is critically discussed, with particular emphasis on optical fiber technology, reported for in situ bioprocess monitoring. Application examples are presented by spectroscopy type, specifically focusing on ultraviolet–visible, near-infrared, mid-infrared, Raman, and fluorescence spectroscopy. The spectra acquisition devices available and the major advantages and disadvantages of each spectroscopy are discussed. The type of information contained in the spectra and the available chemometric methods for extracting that information are also addressed, including wavelength selection, spectra pre-processing, principal component analysis, and partial least-squares. Sample handling techniques (flow and sequential injection analysis) that include transport to spectroscopic sensors for ex-situ on-line monitoring are not covered in this review.

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Abbreviations

ANN:

Artificial neural networks

AOTF:

Acousto-optical tunable filter

API:

Active pharmaceutical ingredient

ATR:

Attenuated total reflection

CCD:

Charge-coupled device

CHO:

Chinese hamster ovary

COD:

Chemical oxygen demand

CPFs:

Cloud photonic crystal fibers

DTGS:

Deuterated triglycine sulfate

FIA:

Flow-injection analysis

FT:

Fourier transform

FT-IR:

Fourier transform infrared

FT-NIR:

Fourier transform near infrared

FT-Raman:

Fourier transform Raman

Ge:

Germanium

HPLC:

High-performance liquid chromatography

InAs:

Indium arsenide

InGaAs:

Indium–gallium arsenide

InSb:

Indium antimonide

IR:

Infrared

KBr:

Potassium bromide

KNN:

K-nearest neighbors

LDA:

Linear discriminant analysis

LWR:

Linear weighted regression

MCR:

Multivariate curve resolution

MCT:

Mercury–cadmium telluride

MIR:

Mid-infrared

MLR:

Multiple linear regression

MNCN:

Mean centering

MSC:

Multiplicative scatter correction

MSPC:

Multivariate statistical process control

MSW:

Municipal solid waste

NADH:

Reduced nicotinamide adenine dinucleotide

NADPH:

Reduced nicotinamide adenine dinucleotide phosphate

NIR:

Near infrared

N-NO 3 :

Nitrate-nitrogen

PAS:

Photoacoustic spectroscopy

PAT:

Process analytical technology

PbS:

Lead sulfide

PbSe:

Lead selenide

PC:

Principal component

PCA:

Principal component analysis

PCR:

Principal component regression

PDA:

Photodiode array

PLS:

Partial least-squares

PLS-DA:

Partial least-squares discriminant analysis

PP:

Pre-processing

PTS:

Pulsed terahertz spectroscopy

RNA:

Ribonucleic acid

SBR:

Sequential batch reactor

SER:

Surface-enhanced Raman

SG:

Savitzky–Golay

Si:

Silicon

SIA:

Sequential injection analysis

SIMCA:

Soft independent modeling of class analogy

SNV:

Standard normal variate

SPC:

Statistical process control

SPE:

Square prediction error

SVR:

Support vector regression

THz:

Terahertz

TOC:

Total organic carbon

TSS:

Total suspended solids

UV:

Ultraviolet

UV–Vis:

Ultraviolet–visible

VFA:

Volatile fatty acids

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Acknowledgments

ND Lourenço, CF Almeida, and MC Sarraguça acknowledge financial support from Fundação para a Ciência e a Tecnologia (FCT, Portugal) through a post-doctoral research grant (SFRH / BPD / 31497 / 2006, Portugal) a PhD grant (SFRH / BD / 30445 / 2006), and a post-doctoral research grant (SFRH/BPD/74788/2010, Portugal), respectively.

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Correspondence to N. D. Lourenço.

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Lourenço, N.D., Lopes, J.A., Almeida, C.F. et al. Bioreactor monitoring with spectroscopy and chemometrics: a review. Anal Bioanal Chem 404, 1211–1237 (2012). https://doi.org/10.1007/s00216-012-6073-9

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  • DOI: https://doi.org/10.1007/s00216-012-6073-9

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