Noninvasive, On-Line Monitoring of the Biotransformation by Yeast of Glucose to Ethanol Using Dispersive Raman Spectroscopy and Chemometrics

Shaw, Adrian D.; Kaderbhai, Naheed; Jones, A. R.; Woodward, Andrew M.; Goodacre, Royston; Rowland, Jem J.; Kell, Douglas B.

doi:10.1366/0003702991945777

Cited by 80 publications

(52 citation statements)

References 56 publications

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“…The efficacy of Raman spectroscopy for the non-invasive, in-line monitoring of different processes was first demonstrated in the 1980s and 1990s. Much of the early works focused on the production of simpler molecules, such as yeast-based fermentations for the production of ethanol, [153][154][155] and other products such as plant hormones 156 and a carotenoid antioxidant. 157 In most of these studies, the product molecule produced a reasonably strong Raman signal that had bands distinct from the (broad, less well defined) background.…”

Section: Bioprocess Analysis and Monitoringmentioning

confidence: 99%

Applications of Raman Spectroscopy in Biopharmaceutical Manufacturing: A Short Review

2017

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The production of active pharmaceutical ingredients (APIs) is currently undergoing its biggest transformation in a century. The changes are based on the rapid and dramatic introduction of protein-and macromolecule-based drugs (collectively known as biopharmaceuticals) and can be traced back to the huge investment in biomedical science (in particular in genomics and proteomics) that has been ongoing since the 1970s. Biopharmaceuticals (or biologics) are manufactured using biological-expression systems (such as mammalian, bacterial, insect cells, etc.) and have spawned a large (>E35 billion sales annually in Europe) and growing biopharmaceutical industry (BioPharma). The structural and chemical complexity of biologics, combined with the intricacy of cell-based manufacturing, imposes a huge analytical burden to correctly characterize and quantify both processes (upstream) and products (downstream). In small molecule manufacturing, advances in analytical and computational methods have been extensively exploited to generate process analytical technologies (PAT) that are now used for routine process control, leading to more efficient processes and safer medicines. In the analytical domain, biologic manufacturing is considerably behind and there is both a huge scope and need to produce relevant PAT tools with which to better control processes, and better characterize product macromolecules. Raman spectroscopy, a vibrational spectroscopy with a number of useful properties (nondestructive, non-contact, robustness) has significant potential advantages in BioPharma. Key among them are intrinsically high molecular specificity, the ability to measure in water, the requirement for minimal (or no) sample pre-treatment, the flexibility of sampling configurations, and suitability for automation. Here, we review and discuss a representative selection of the more important Raman applications in BioPharma (with particular emphasis on mammalian cell culture). The review shows that the properties of Raman have been successfully exploited to deliver unique and useful analytical solutions, particularly for online process monitoring. However, it also shows that its inherent susceptibility to fluorescence interference and the weakness of the Raman effect mean that it can never be a panacea. In particular, Raman-based methods are intrinsically limited by the chemical complexity and wide analyte-concentration-profiles of cell culture media/bioprocessing broths which limit their use for quantitative analysis. Nevertheless, with appropriate foreknowledge of these limitations and good experimental design, robust analytical methods can be produced. In addition, new technological developments such as time-resolved detectors, advanced lasers, and plasmonics offer potential of new Raman-based methods to resolve existing limitations and/or provide new analytical insights.

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Section: Bioprocess Analysis and Monitoringmentioning

confidence: 99%

Applications of Raman Spectroscopy in Biopharmaceutical Manufacturing: A Short Review

2017

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“…The final step in this unspiking algorithm is to perform the aforesaid MinEnt spectral subtraction algorithm with entropy minimizing objective similar to Eqn (10) (that is,˙ r spike 1×ν is replaced with˙ r Unspiked 1×ν ) to optimally remove the idealized spectrum r ideal spike 1×ν from its corresponding spiked Raman spectra r Spiked 1×ν according to Eqn (13) for every spiked spectrum index s.…”

Section: Cosmic Ray Spikes Identification Reconstruction and Removalmentioning

confidence: 99%

“…[3,11,13] This has been promoted largely by advances in Raman instrumentation [1,5,6,14,15] and experimental techniques. [4,5,16] In particular, the use of fiber optic coupling [15,17,18] has engendered the possibility of fast remote sensing via both immersion and non-contact probes, [3,19,20] which has been used for chemical reaction monitoring.…”

Section: Introductionmentioning

confidence: 99%

Information‐theoretic chemometric analyses of Raman data for chemical reaction studies

Chew

2011

J Raman Spectroscopy

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A methodology of multivariate chemometric techniques based on the information-theoretic approach was applied for elucidating chemical reaction information from a Raman data array R m×ν that arises from in situ reaction monitoring. This reaction-induced dynamic dataset R m×ν can be contaminated by random cosmic ray spikes found in the midst of characteristic spectral variations associated with the disappearance or emergence of Raman active reactants, intermediates and products. Such spurious cosmic spikes were identified and removed using a novel and fast numerical approach based on maximum and minimum spectral entropy principles while preserving the genuine reaction-induced spectral variations. Subsequently, the band-target entropy minimization (BTEM) algorithm, a minimum spectral entropy based self-modeling curve resolution technique, was applied to recover the pure component spectra of Raman active chemical species. Information gain through the chemometric analyses was calculated using information entropies with base 2 logarithm. This sequence of information-theoretic chemometric analyses (or transinformations) was successfully tested on the reaction spectral data obtained from alcoholysis of acetic anhydride, which contains four Raman active chemical species. It is envisioned that this series of multivariate statistical analyses will be useful in chemical reaction studies and process analytical technology (PAT) applications that utilize in situ Raman spectroscopy to monitor transient dynamic changes in chemical concentrations, and also in Raman microscopy/imaging data containing spatial variations.

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“…Use of an improved fiber probe would probably make this measurement viable. More recently, Shaw et al 115 used a fiber-coupled 780 nm dispersive system and chemometrics to analyze glucose fermentation. Liquid was extracted with a sampling loop, filtered to remove yeast cells, and passed through a 3 mm diameter quartz tube into which a Raman probe was focused.…”

Section: Reactor Monitoringmentioning

confidence: 99%

Process Measurements by Raman Spectroscopy

Everall

Clegg²,

King³

2001

Handbook of Vibrational Spectroscopy

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Raman spectroscopy has long been recognized as a powerful analytical tool, capable of characterizing a wide range of materials, but for many years the size and complexity of instrumentation confined it to the research laboratory, making process analysis impractical. However, compact, sensitive and robust Raman instruments are now available that can be readily interfaced to production processes. This article attempts to illustrate the general capabilities of Raman spectroscopy as a process analytical tool. We first consider the instrumental and engineering aspects of making Raman measurements under production conditions, and then discuss some of the areas in which it has been fruitfully employed. The application examples discussed were chosen to cover the main range of sample types that one might encounter in the industry. We also describe some common artifacts and problems, which can arise and confuse the new practitioner.

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Noninvasive, On-Line Monitoring of the Biotransformation by Yeast of Glucose to Ethanol Using Dispersive Raman Spectroscopy and Chemometrics

Cited by 80 publications

References 56 publications

Applications of Raman Spectroscopy in Biopharmaceutical Manufacturing: A Short Review

Applications of Raman Spectroscopy in Biopharmaceutical Manufacturing: A Short Review

Information‐theoretic chemometric analyses of Raman data for chemical reaction studies

Process Measurements by Raman Spectroscopy

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