A LC–MS/MS platform for the identification of productivity markers in industrial mammalian cell culture media

Floris, Patrick; McGillicuddy, Nicola; Morrissey, Brian M.; Albrecht, Simone; Kaisermayer, Christian; Hawe, D.; Riordan, Lelia; Lindeberg, Anna; Forestell, Sean; Bones, Jonathan

doi:10.1016/j.procbio.2019.08.014

Cited by 9 publications

(8 citation statements)

References 28 publications

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“…They may indicate growth promotion/inhibition, high/low productivity or the enhancement/suppression of some cellular processes. For example, the consumption of Asp and Cys in CHO cell cultures is linked to high protein productivity (Yao et al, 2021), while the depletion of Gln (Floris et al, 2019; Mohmad‐Saberi et al, 2013) or the presence of dipeptides such as Phe‐Val and Tyr‐Leu (Floris et al, 2019) in the medium may be associated with low cellular productivity. A study of CHO cell culture in different industrial media formulations supplemented with soy hydrolysates identified certain dipeptides responsible for reduction in the culture performance (Floris et al, 2019).…”

Section: Using Spent Media Analysis For Bioprocess Development and Op...mentioning

confidence: 99%

Precision fermentation with mass spectrometry‐based spent media analysis

Dodia

Sunder²,

Borkar³

et al. 2023

Biotech & Bioengineering

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Optimization and monitoring of bioprocesses requires the measurement of several process parameters and quality attributes. Mass spectrometry (MS)‐based techniques such as those coupled to gas chromatography (GCMS) and liquid Chromatography (LCMS) enable the simultaneous measurement of hundreds of metabolites with high sensitivity. When applied to spent media, such metabolome analysis can help determine the sequence of substrate uptake and metabolite secretion, consequently facilitating better design of initial media and feeding strategy. Furthermore, the analysis of metabolite diversity and abundance from spent media will aid the determination of metabolic phases of the culture and the identification of metabolites as surrogate markers for product titer and quality. This review covers the recent advances in metabolomics analysis applied to the development and monitoring of bioprocesses. In this regard, we recommend a stepwise workflow and guidelines that a bioprocesses engineer can adopt to develop and optimize a fermentation process using spent media analysis. Finally, we show examples of how the use of MS can revolutionize the design and monitoring of bioprocesses.

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Section: Using Spent Media Analysis For Bioprocess Development and Op...mentioning

confidence: 99%

Precision fermentation with mass spectrometry‐based spent media analysis

Dodia

Sunder²,

Borkar³

et al. 2023

Biotech & Bioengineering

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show abstract

“…It usually contains various substances (>50) in a relatively low concentration. Thus, to characterize media quality, NMR, HPLC-MS/MS, and spectroscopic methods, such as fluorescence- (2D, 3D), infrared- (NIR, MIR, FT-IR), or Raman spectroscopy are used, resulting in complex multi-dimensional data [ 49 , 50 , 51 , 52 , 53 , 54 ]. In addition, the advantages of multivariate data analysis and DF methods can be utilized to gain accurate information on media quality [ 55 ].…”

Section: Data Types In the Pharmaceutical Industrymentioning

confidence: 99%

Challenges and Opportunities of Implementing Data Fusion in Process Analytical Technology—A Review

et al. 2022

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The release of the FDA’s guidance on Process Analytical Technology has motivated and supported the pharmaceutical industry to deliver consistent quality medicine by acquiring a deeper understanding of the product performance and process interplay. The technical opportunities to reach this high-level control have considerably evolved since 2004 due to the development of advanced analytical sensors and chemometric tools. However, their transfer to the highly regulated pharmaceutical sector has been limited. To this respect, data fusion strategies have been extensively applied in different sectors, such as food or chemical, to provide a more robust performance of the analytical platforms. This survey evaluates the challenges and opportunities of implementing data fusion within the PAT concept by identifying transfer opportunities from other sectors. Special attention is given to the data types available from pharmaceutical manufacturing and their compatibility with data fusion strategies. Furthermore, the integration into Pharma 4.0 is discussed.

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“…The combination of high retentivity and a net-zero surface charge has made sulfobetaine columns a popular choice for a wide range of applications, including metabolomics [18], cell culture media analysis [19], pharmaceutical bioanalysis and impurity profiling [20,21], determination of the concentrations of toxins in food [22][23][24], and analyses of biopolymers including peptides [25,26], glycoproteins [26], and oligonucleotides [27]. Most of the commercially available sulfobetaine stationary phases are based on silica particles.…”

Section: Introductionmentioning

confidence: 99%

“…Sulfobetaine stationary phases have been shown to accumulate a relatively thick layer of adsorbed water [14–17], which makes them strongly retentive for polar neutrals in HILIC. The combination of high retentivity and a net‐zero surface charge has made sulfobetaine columns a popular choice for a wide range of applications, including metabolomics [18], cell culture media analysis [19], pharmaceutical bioanalysis and impurity profiling [20,21], determination of the concentrations of toxins in food [22–24], and analyses of biopolymers including peptides [25,26], glycoproteins [26], and oligonucleotides [27].…”

Section: Introductionmentioning

confidence: 99%

Characterization of a highly stable zwitterionic hydrophilic interaction chromatography stationary phase based on hybrid organic–inorganic particles

Walter

Alden

Berthelette

et al. 2022

J of Separation Science

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We have characterized a sulfobetaine stationary phase based on 1.7 μm ethylene‐bridged hybrid organic–inorganic particles, which is intended for use in hydrophilic interaction chromatography. The efficiency of a column packed with this material was determined as a function of flow rate, demonstrating a minimum reduced plate height of 2.4. The batch‐to‐batch reproducibility was assessed using the separation of a mixture of acids, bases, and neutrals. We compared the retention and selectivity of the hybrid sulfobetaine stationary phase to that of several benchmark materials. The hybrid sulfobetaine material gave strong retention for polar neutrals and high selectivity for methyl groups, hydroxy groups, and configurational isomers. Large differences in cation and anion retention were observed among the columns. We characterized the acid and base stability of the hybrid sulfobetaine stationary phase, using accelerated tests at pH 1.3 and 11.0, both at 70°C. The results support a recommended pH range of 2–10. We also investigated the performance of columns packed with this material for metal‐sensitive analytes, comparing conventional stainless steel column hardware to hardware that incorporates hybrid surface technology to mitigate interactions with metal surfaces. Compared to the conventional columns, the hybrid surface technology columns showed a greatly improved peak shape.

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A LC–MS/MS platform for the identification of productivity markers in industrial mammalian cell culture media

Cited by 9 publications

References 28 publications

Precision fermentation with mass spectrometry‐based spent media analysis

Precision fermentation with mass spectrometry‐based spent media analysis

Challenges and Opportunities of Implementing Data Fusion in Process Analytical Technology—A Review

Characterization of a highly stable zwitterionic hydrophilic interaction chromatography stationary phase based on hybrid organic–inorganic particles

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