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Ryder, Alan G. - One of the best experts on this subject based on the ideXlab platform.
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Multi-attribute quality screening of immunoglobulin G using polarized Excitation Emission Matrix spectroscopy
Elsevier, 2020Co-Authors: De Faria Silva, Ana E Luiza, Elcoroaristizabal Saioa, Ryder, Alan G.Abstract:Immunoglobulin G (IgG) is often used as a starting material for the production of functionalised antibodies, like Antibody Drug Conjugates (ADCs), PEGlyated-conjugates, or radioimmunoconjugates. The gross structural quality of the protein starting material is, therefore, an important factor in determining final product composition, purity, and quality. In terms of structural quality, one needs to know both the aggregation content and the tertiary structure of the protein. The measurement of structural quality in solution can thus be difficult, but the use of intrinsic fluorescence measurements might offer a solution because of its high sensitivity, ease of use, and when implemented in via multi-dimensional techniques like polarized Excitation Emission Matrix (pEEM) spectroscopy, its high information content. Here we demonstrate how pEEM measurements can be used as a multi-attribute screening method for protein quality using a polyclonal rabbit immunoglobulin (rIgG) model system. By using both Rayleigh scatter and fluorescence emission in combination with simple chemometric data analysis methods like Principal Component analysis (PCA) and unfolded partial least squares (U-PLS) one can simultaneously measure protein concentration, structural variance, and Particle/Aggregate composition. Furthermore, one can generate quantitative prediction models for non-reversible aggregation content as described by size exclusion chromatography (SEC) and obtain qualitative information about reversible Aggregate content, which cannot be obtained from SEC measurements. In conclusion, the pEEM measurement approach is a potentially useful Process Analytical Technology (PAT) method for downstream processing operations in biopharmaceutical manufacturing.This publication has emanated from research supported in part by a research grant from Science Foundation Ireland (SFI) and is co-funded under the European Regional Development Fund under Grand number (14/IA/2282, Advanced Analytics for Biological Therapeutic Manufacture, to AGR). We also thank Agilent Technologies (Mulgrave Victoria, Australia) for the loan of a fluorescence spectrometer.2020-12-1
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Multi-attribute quality screening of immunoglobulin G using polarized Excitation Emission Matrix spectroscopy
'Elsevier BV', 2020Co-Authors: De Faria Silva, Ana E Luiza, Elcoroaristizabal Saioa, Ryder, Alan G.Abstract:Immunoglobulin G (IgG) is often used as a starting material for the production of functionalised antibodies, like Antibody Drug Conjugates (ADCs), PEGlyated-conjugates, or radioimmunoconjugates. The gross structural quality of the protein starting material is, therefore, an important factor in determining final product composition, purity, and quality. In terms of structural quality, one needs to know both the aggregation content and the tertiary structure of the protein. The measurement of structural quality in solution can thus be difficult, but the use of intrinsic fluorescence measurements might offer a solution because of its high sensitivity, ease of use, and when implemented in via multi-dimensional techniques like polarized Excitation Emission Matrix (pEEM) spectroscopy, its high information content. Here we demonstrate how pEEM measurements can be used as a multi-attribute screening method for protein quality using a polyclonal rabbit immunoglobulin (rIgG) model system. By using both Rayleigh scatter and fluorescence emission in combination with simple chemometric data analysis methods like Principal Component analysis (PCA) and unfolded partial least squares (U-PLS) one can simultaneously measure protein concentration, structural variance, and Particle/Aggregate composition. Furthermore, one can generate quantitative prediction models for non-reversible aggregation content as described by size exclusion chromatography (SEC) and obtain qualitative information about reversible Aggregate content, which cannot be obtained from SEC measurements. In conclusion, the pEEM measurement approach is a potentially useful Process Analytical Technology (PAT) method for downstream processing operations in biopharmaceutical manufacturing.This publication has emanated from research supported in part by a research grant from Science Foundation Ireland (SFI) and is co-funded under the European Regional Development Fund under Grand number (14/IA/2282, Advanced Analytics for Biological Therapeutic Manufacture, to AGR). We also thank Agilent Technologies (Mulgrave Victoria, Australia) for the loan of a fluorescence spectrometer.peer-reviewed2020-12-1
George V Franks - One of the best experts on this subject based on the ideXlab platform.
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controlling the microstructure of ceramic Particle stabilized foams influence of contact angle and Particle aggregation
Soft Matter, 2011Co-Authors: Chayuda Chuanuwatanakul, Carolina Tallon, David E Dunstan, George V FranksAbstract:Porous cellular alumina ceramic green bodies have been produced by combining the Particle stabilized foam method with gelcasting. The suspension foams were stabilized by Particles rendered weakly hydrophobic with short chain sulfonate surfactants. Poly vinyl alcohol (PVA) and 2,5-dimethoxy-2,5-dihydrofuran (DHF) were used as the gelcasting reagents. The microstructure (amount of porosity, average pore size, and morphology) of alumina (Al2O3) ceramic green body foams has been studied as a function of surfactant concentration and chain length. The morphology of gelled ceramic foams changes from closed cell (bubble like morphology) to open cell (granular morphology) as the surfactant concentration is increased beyond a critical level. The density (and porosity) of the gelled alumina green body foams changes as a function of the surfactant concentration in a non-linear manner. Measurement of the suspension viscosity, contact angle and Aggregate size are used to explain the changes in density and morphology. The transition from the bubble like structure to the granular structure is due to an increase in the Particle Aggregate size rather than phase inversion induced by an increase in the contact angle. The same behavior is observed with three different chain length surfactants (ranging from 4 to 10 carbon atoms on the hydrophobic portion of the surfactant) but at a lower surfactant concentration as the chain length increases.
De Faria Silva, Ana E Luiza - One of the best experts on this subject based on the ideXlab platform.
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Multi-attribute quality screening of immunoglobulin G using polarized Excitation Emission Matrix spectroscopy
Elsevier, 2020Co-Authors: De Faria Silva, Ana E Luiza, Elcoroaristizabal Saioa, Ryder, Alan G.Abstract:Immunoglobulin G (IgG) is often used as a starting material for the production of functionalised antibodies, like Antibody Drug Conjugates (ADCs), PEGlyated-conjugates, or radioimmunoconjugates. The gross structural quality of the protein starting material is, therefore, an important factor in determining final product composition, purity, and quality. In terms of structural quality, one needs to know both the aggregation content and the tertiary structure of the protein. The measurement of structural quality in solution can thus be difficult, but the use of intrinsic fluorescence measurements might offer a solution because of its high sensitivity, ease of use, and when implemented in via multi-dimensional techniques like polarized Excitation Emission Matrix (pEEM) spectroscopy, its high information content. Here we demonstrate how pEEM measurements can be used as a multi-attribute screening method for protein quality using a polyclonal rabbit immunoglobulin (rIgG) model system. By using both Rayleigh scatter and fluorescence emission in combination with simple chemometric data analysis methods like Principal Component analysis (PCA) and unfolded partial least squares (U-PLS) one can simultaneously measure protein concentration, structural variance, and Particle/Aggregate composition. Furthermore, one can generate quantitative prediction models for non-reversible aggregation content as described by size exclusion chromatography (SEC) and obtain qualitative information about reversible Aggregate content, which cannot be obtained from SEC measurements. In conclusion, the pEEM measurement approach is a potentially useful Process Analytical Technology (PAT) method for downstream processing operations in biopharmaceutical manufacturing.This publication has emanated from research supported in part by a research grant from Science Foundation Ireland (SFI) and is co-funded under the European Regional Development Fund under Grand number (14/IA/2282, Advanced Analytics for Biological Therapeutic Manufacture, to AGR). We also thank Agilent Technologies (Mulgrave Victoria, Australia) for the loan of a fluorescence spectrometer.2020-12-1
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Multi-attribute quality screening of immunoglobulin G using polarized Excitation Emission Matrix spectroscopy
'Elsevier BV', 2020Co-Authors: De Faria Silva, Ana E Luiza, Elcoroaristizabal Saioa, Ryder, Alan G.Abstract:Immunoglobulin G (IgG) is often used as a starting material for the production of functionalised antibodies, like Antibody Drug Conjugates (ADCs), PEGlyated-conjugates, or radioimmunoconjugates. The gross structural quality of the protein starting material is, therefore, an important factor in determining final product composition, purity, and quality. In terms of structural quality, one needs to know both the aggregation content and the tertiary structure of the protein. The measurement of structural quality in solution can thus be difficult, but the use of intrinsic fluorescence measurements might offer a solution because of its high sensitivity, ease of use, and when implemented in via multi-dimensional techniques like polarized Excitation Emission Matrix (pEEM) spectroscopy, its high information content. Here we demonstrate how pEEM measurements can be used as a multi-attribute screening method for protein quality using a polyclonal rabbit immunoglobulin (rIgG) model system. By using both Rayleigh scatter and fluorescence emission in combination with simple chemometric data analysis methods like Principal Component analysis (PCA) and unfolded partial least squares (U-PLS) one can simultaneously measure protein concentration, structural variance, and Particle/Aggregate composition. Furthermore, one can generate quantitative prediction models for non-reversible aggregation content as described by size exclusion chromatography (SEC) and obtain qualitative information about reversible Aggregate content, which cannot be obtained from SEC measurements. In conclusion, the pEEM measurement approach is a potentially useful Process Analytical Technology (PAT) method for downstream processing operations in biopharmaceutical manufacturing.This publication has emanated from research supported in part by a research grant from Science Foundation Ireland (SFI) and is co-funded under the European Regional Development Fund under Grand number (14/IA/2282, Advanced Analytics for Biological Therapeutic Manufacture, to AGR). We also thank Agilent Technologies (Mulgrave Victoria, Australia) for the loan of a fluorescence spectrometer.peer-reviewed2020-12-1
Umit Ozgur Koylu - One of the best experts on this subject based on the ideXlab platform.
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quantitative analysis of in situ optical diagnostics for inferring Particle Aggregate parameters in flames implications for soot surface growth and total emissivity
Combustion and Flame, 1997Co-Authors: Umit Ozgur KoyluAbstract:Abstract An in situ particulate diagnostic/analysis technique is outlined based on the Rayleigh-Debye-Gans polydisperse fractal Aggregate (RDG/PFA) scattering interpretation of absolute angular light scattering and extinction measurements. Using proper Particle refractive index, the proposed data analysis method can quantitatively yield all Aggregate parameters (Particle volume fraction, f v , fractal dimension, D f , primary Particle diameter, d p , Particle number density, n p , and Aggregate size distribution, pdf( N )) without any prior knowledge about the Particle-laden environment. The present optical diagnostic/interpretation technique was applied to two different soot-containing laminar and turbulent ethylene/air nonpremixed flames in order to assess its reliability. The Aggregate interpretation of optical measurements yielded D f , d p , and pdf( N ) that are in excellent agreement with ex situ thermophoretic sampling/transmission electron microscope (TS/TEM) observations within experimental uncertainties. However, volume-equivalent single Particle models (Rayleigh/Mie) overestimated d p by about a factor of 3, causing an order of magnitude underestimation in n p . Consequently, soot surface areas and growth rates were in error by a factor of 3, emphasizing that aggregation effects need to be taken into account when using optical diagnostics for a reliable understanding of soot formation/evolution mechanism in flames. The results also indicated that total soot emissivities were generally underestimated using Rayleigh analysis (up to 50%), mainly due to the uncertainties in soot refractive indices at infrared wavelengths. This suggests that Aggregate considerations may not be essential for reasonable radiation heat transfer predictions from luminous flames because of fortuitous error cancellation, resulting in typically a 10 to 30% net effect.
Christopher J Hogan - One of the best experts on this subject based on the ideXlab platform.
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first passage calculation of the conductivity of Particle Aggregate laden suspensions and composites
Powder Technology, 2012Co-Authors: Thaseem Thajudeen, Christopher J HoganAbstract:Abstract There is considerable interest in transport via conduction through Particle laden suspensions (e.g. nanofluids) and composite materials. Frequently, such multiphase systems display enhanced conductivities beyond what is expected from the effective medium approximation. While the origin of this enhancement is often a source of controversy, the most common explanation for anomalous conductivity enhancements is the aggregation of Particles. In this work, we employ a first passage simulation technique to investigate the influence of Particle aggregation on the resulting conductivity of Particle-laden suspensions and composites. Aggregates are modeled as quasifractal objects, and a sequential algorithm is used to computationally generate Aggregates of prescribed fractal dimension, pre-exponential factor, number of primary Particles, and degree of overlap (coalescence) between primary Particles. Four model types of Aggregates (highly linear structures with little coalescence, highly linear structures with substantial coalescence, dense structures with little coalescence, and dense structures with substantial coalescence) are examined via the first passage technique, enabling determination of the conductivity of a suspension/composite containing Aggregates at a known volume fraction. It is found that for a given type of Aggregate, the number of primary Particles per Aggregate has little-to-no influence on suspension/composite conductivity under any circumstances. For low conductivity Particles (Particle conductivity/host material conductivity = 10), Aggregate formation and Aggregate morphology have little influence on suspension/composite conductivity, except at Particle volume fractions > 0.10 where slight enhancements beyond the effective medium approximation are observable. However, for high conductivity Aggregates (Particle conductivity/host matrix conductivity = 100), the influence of aggregation is substantial, and all morphological descriptors of the Aggregate influence suspension/composite conductivity. In this instance, the resulting enhancement in conductivity can be equivalent to the enhancement expected if well dispersed spherical Particles were incorporated into the suspension/composite at a volume fraction 3–5 times higher than the actual Aggregate volume fraction.