Gradient elution in non-linear preparative liquid chromatography

Antia, Firoz D.; Horváth, Csaba

doi:10.1016/s0021-9673(01)88960-3

Cited by 118 publications

(25 citation statements)

References 32 publications

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“…We can therefore conclude that DG at absorption equilibrium must be zero. From experimental measurements of retention data we can determine the thermodynamic equilibrium constant K i from either (18) or (21) and thus estimate the standard Gibbs energy change of adsorption by using (16). However, there are numerous papers where the authors claim to be able to calculate the Gibbs energy change of adsorption from the distribution coefficient [21][22][23][24].…”

Section: Can We Calculate the Gibbs Energymentioning

confidence: 99%

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A Review of the Thermodynamics of Protein Association to Ligands, Protein Adsorption, and Adsorption Isotherms

Mollerup

2008

Chem Eng & Technol

107

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The application of thermodynamic models in the development of chromatographic separation processes is discussed. The paper analyses the thermodynamic principles of protein adsorption. It can be modeled either as a reversible association between the adsorbate and the ligands or as a steady-state process where the rate of adsorption is equal to the rate of desorption. The analysis includes the competitive Langmuir isotherm and the exponentially modified Langmuir isotherm. If the adsorbate binds to one ligand only, the different approaches become identical. When the adsorbate acts as a ligand, dimerization takes place and will give rise to a sigmoid isotherm. A model that accounts for dimerization is discussed and a sample calculation shows the behavior of this isotherm. Insulin is known to have a concave isotherm at low concentrations. The calculation of the standard Gibbs energy change of adsorption is discussed. Hydrophobic and reversed phase chromatography are useful techniques for measuring solute activity coefficients at infinite dilution. Process Development of Chromatographic SeparationsThe fulcrum point in the design of separation processes like distillation, extraction, absorption, or adsorption, is the phase equilibrium properties. Today, we use simulation programmes to develop and design distillation, extraction and absorption units, but when it comes to the development and design of chromatographic separations in the biopharmaceutical industry, the state of the art looks like the chemical industry in the 1950s. The conventional chromatographic process development is at present mostly an experimental trial and error based approach supported by high throughput screening platforms. However, if one takes advantage of the models of adsorption discussed in this paper, the agenda can be updated. The scope will no longer be to develop the chromatographic separations by trial and error, but to employ simulations to assist the process development. This approach will reduce the time and cost of process development. The adsorption model parameters can be estimated from isocratic retention data supplemented with a few capacity measurements. The 'efficiency' is, as usual, determined by the mass-transfer coefficients that can be estimated from the second central moment of the isocratic peaks. This requires little material and time and a limited analytical effort. Limiting factors are only computational effort and the quality of the thermodynamic models. Having these models and the mass transfer coefficients, we can use a simulator to design robust separations that can deliver a predefined quality as regards yield, purity and productivity. The simulated separations must of course be validated experimentally. If necessary, we can tune the model parameters to improve the agreement between the simulated and experimental results.Furthermore, the use of a simulator is PAT compliant because the simulator can also support: (1) identification of critical process parameters and critical sources of variability, (2) a study of h...

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Section: Can We Calculate the Gibbs Energymentioning

confidence: 99%

“…The exponentially modified Langmuir isotherm of Antia and Horvath [16] was used to describe nonlinear retention in RPC and HIC systems. The model is:…”

mentioning

confidence: 99%

A Review of the Thermodynamics of Protein Association to Ligands, Protein Adsorption, and Adsorption Isotherms

Mollerup

2008

Chem Eng & Technol

107

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“…In displacement chromatography [74][75][76] the packed column is equilibrated with a mobile phase that has a very low affinity to the stationary phase. Then the feed solution containing the mixture dissolved in the mobile phase is injected in such a way that the components are adsorbed at the top of the column.…”

Section: Displacement Chromatographymentioning

confidence: 99%

Trends in Preparative HPLC

Kuesters

2006

HPLC for Pharmaceutical Scientists

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“…Quantitative descriptions of overloaded gradient elution bands have been presented for various chromatographic systems, e.g., by Antia and Horvath [39], Yamamoto et al [40], Gallant et al [27,28], El Fallah and Guiochon [41], Mihlbachler et al [42], Gueorguieva et al [43], Jandera [44], and Gritti et al [37].…”

Section: Isocratic Versus Gradient Chromatographymentioning

confidence: 99%

Preparative Gradient Chromatography

Seidel‐Morgenstern

2005

Chem Eng & Technol

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During a chromatographic separation, it is convenient to keep the essential operating parameters like temperature, pressure, mobile phase flow-rate, and mobile phase composition constant. Though, it is well known that in contrast to this isocratic operation the intelligent modulation of certain operating parameters can improve the separation performance significantly. Such gradient approaches are widely applied in analytical (linear) chromatography to reduce the time of analysis and to enhance the selectivity. In contrast, the extent of application of these gradients is still rather limited in the field of preparative (nonlinear) chromatography. The first part of this paper is devoted to the discussion of the principal differences between linear and nonlinear and isocratic and gradient chromatography. The second part focuses on introducing a countercurrent process that allows separation in a continuous manner, efficiently exploiting a two-step solvent composition gradient.

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Gradient elution in non-linear preparative liquid chromatography

Cited by 118 publications

References 32 publications

A Review of the Thermodynamics of Protein Association to Ligands, Protein Adsorption, and Adsorption Isotherms

A Review of the Thermodynamics of Protein Association to Ligands, Protein Adsorption, and Adsorption Isotherms

Trends in Preparative HPLC

Preparative Gradient Chromatography

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