Evaluation of Pressure Stable Chip-to-Tube Fittings Enabling High-Speed Chip-HPLC with Mass Spectrometric Detection

Lotter, Carsten; Heiland, Josef J.; Stein, Volkmar; Klimkait, Michael; Queisser, Marco; Belder, Detlev

doi:10.1021/acs.analchem.6b01907

Cited by 37 publications

(62 citation statements)

References 41 publications

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“…In addition, the favorable mass and heat transfer in these platforms may result in good separation resolution (Han, Livingston, & Chen, 2011;Wheeler et al, 2014). Adoption of microfluidics platforms has shown promising results for these techniques, including CEX (Alekseychyk, Su, Becker, Treuheit, & Razinkov, 2017), IEF (Kinoshita, Nakatsuji, Suzuki, Hayakawa, & Kakehi, 2013), and LC-MS systems (Chambers, Mellors, Henley, & Ramsey, 2011;Dietze et al, 2016;Lotter et al, 2016;Mellors et al, 2013). Thus far, much of the development remains in the academic arena, and challenges preventing commercial usage include cost, lack of robustness, and difficulty in operation.…”

Section: Areas Of Development In Analytical Techniques Include Improvedmentioning

confidence: 99%

Industrial bioprocessing perspectives on managing therapeutic protein charge variant profiles

Chung

Tian

Tan

et al. 2018

Biotech & Bioengineering

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Controlling the charge profile of therapeutic protein is a critical challenge in the current quality-by-design (QbD) paradigm, throughout all phases of biologics process development (PD): cell line development, upstream cell culture, recovery process, downstream purification, and analytical characterization. Charge variant profiles may influence efficacy and/or lead to unintended side-effects. Thus, maintaining a consistent charge profile is of tremendous importance, and increasingly, researchers have focused efforts toward developing strategies to mitigate variability during cell culture and to improve separation and detection of charge variants. Current understanding of factors affecting charge variant formation during manufacturing remains inadequate, and sometimes, even substantial commitment of resources may still not fully achieve the desired or consistent profiles. As such, this review attempts to provide a comprehensive resource for the biologics community by summarizing the impact of charge variants and CQA management, analytical methods for charge variant detection, as well as strategies in downstream and upstream PD for controlling charge variant profiles.

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Section: Areas Of Development In Analytical Techniques Include Improvedmentioning

confidence: 99%

Industrial bioprocessing perspectives on managing therapeutic protein charge variant profiles

Chung

Tian

Tan

et al. 2018

Biotech & Bioengineering

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“…The device was engineered based on our experience in designing glass chips incorporating HPLC columns . A more complex device was realized by interconnecting two different packed‐bed columns on a single microchip (see Supporting Information (SI) for details).…”

Section: Figurementioning

confidence: 99%

An Integrated Lab‐on‐a‐chip Approach to Study Heterogeneous Enantioselective Catalysts at the Microscale

et al. 2018

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An integrated lab‐on‐a‐chip enables the rapid analysis of heterogenized enantioselective organocatalysis at the microscale. A packed‐bed microreactor was seamlessly integrated with a downstream chiral high pressure liquid chromatography (HPLC) functionality to study enantioselective transformations on a single microfluidic glass chip. Hyphenation to mass spectrometry allows for the rapid investigation of the selectivity and the substrate scope of microgram amounts of catalyst beads. Optimization of reaction conditions is possible with minimal reagent consumption and instant analytical feedback.

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“…Fluidic control can be achieved by integrating microvalves for precise metering or mixing of solutions within the microchannel. Sensitive signal acquisition can be achieved by on‐chip integration of photosensors or by offline coupling with mass spectrometry . Furthermore, signal acquisition can not only be performed downstream of the separation column as in conventional chromatography columns, but also directly at the bead level, the latter providing real‐time information on the kinetics of the separation and the mechanisms governing the target–ligand interactions .…”

Section: Introductionmentioning

confidence: 99%

Optimizing the Performance of Chromatographic Separations Using Microfluidics: Multiplexed and Quantitative Screening of Ligands and Target Molecules

Pinto

Soares

Aires-Barros

et al. 2019

Biotechnology Journal

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The optimization of chromatography ligands for the purification of biopharmaceuticals is highly demanded to meet the needs of the pharmaceutical industry. In the case of monoclonal antibodies (mAbs), synthetic ligands comprising multiple types of interactions (multimodal) provide process and economic advantages compared to protein-based affinity ligands. However, optimizing the operation window of these ligands requires the development of effective high-throughput screening platforms. Here, a novel microfluidics-based methodology to perform rapid and multiplexed screening of various multimodal ligands relative to their ability to bind different target molecules is demonstrated. The microfluidic structure comprises three individual chambers (≈8 nL each) packed with different types of chromatography beads in series with the feed flow. An artificial mixture composed of immunoglobulin G (IgG) and bovine serum albumin, labeled with different thiolreactive neutral fluorescent dyes, is used as a model to quantitatively optimize the performance (yield and purity) of the separation. This approach can potentially be used as a predictive analytical tool in the context of mAb purification, allowing low consumption of molecules and providing results in <3 min. Furthermore, this versatile approach can potentially be extended not only with respect to the number of different resins and target molecules, but also for parallel analysis of multiple conditions.

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Evaluation of Pressure Stable Chip-to-Tube Fittings Enabling High-Speed Chip-HPLC with Mass Spectrometric Detection

Cited by 37 publications

References 41 publications

Industrial bioprocessing perspectives on managing therapeutic protein charge variant profiles

Industrial bioprocessing perspectives on managing therapeutic protein charge variant profiles

An Integrated Lab‐on‐a‐chip Approach to Study Heterogeneous Enantioselective Catalysts at the Microscale

Optimizing the Performance of Chromatographic Separations Using Microfluidics: Multiplexed and Quantitative Screening of Ligands and Target Molecules

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