果冻传媒麻豆社

As counter-current chromatography (CCC) is becoming an established method in chromatography for scaling from analytical CCC in the laboratory to full process scale in the industrial manufacture of products, it is becoming increasingly important to model the process and to be able to predict column scale-up parameters for a given process. A method of modelling CCC on the basis of an eluting counter-current distribution (CCD) model was developed. This model confirms that peak width in CCC varies in proportion to the square root of the length of the column, establishes a formula for predicting peak width in terms of retention factor and retention time, and provides a method for determining the efficiency of a given CCC instrument. This allows, for the first time, the mixing efficiency of different CCC approaches and/or devices to be compared and perhaps, more importantly, predictions to be made that are outside the current operating parameters of existing CCC instrumentation. This will greatly assist in the design of new equipment, particularly in scale-up, and will also help users optimize the results from their CCC instruments.

Numerous operating modes and pump out procedures that can be used with counter-current chromatography (CCC) have been described recently and a universal model for CCC based on CCD was developed to incorporate these modes and procedures. This model is validated with real separations from the literature and against the established CCC partition theory. This universal model is proven to give good results for isocratic flow modes, as well as for co-current CCC and dual flow CCC, and will likely also give good results for other modes such as intermittent CCC.

Probabilistic Model for Immiscible Separations and Extractions (ProMISE)

Chromatography models, liquid–liquid models and specifically Counter-Current Chromatography (CCC) models are usually either iterative, or provide a final solution for peak elution. A completely new model has been developed based on simulating probabilistic units. This model has been labelled ProMISE (probabilistic model for immiscible phase separations and extractions), and has been realised in the form of a computer application, interactively visualising the behaviour of the units in the CCC process. It does not use compartments or cells like in the Craig based models, nor is it based on diffusion theory. With this new model, all the CCC flow modes can be accurately predicted.

The main advantage over the previously developed model, is that it does not require a somewhat arbitrary number of steps or theoretical plates, and instead uses an efficiency factor. Furthermore, since this model is not based on compartments or cells like the Craig model, and is therefore not limited to a compartment or cell nature, it allows for an even greater flexibility.

The model can be downloaded from

Calculation of the g-level is often used to compare CCC centrifuges, either against each other or to allow for comparison with other centrifugal techniques. This study shows the limitations of calculating the g-level in the traditional way. Traditional g-level calculations produce a constant value which does not accurately reflect the dynamics of the coil planet centrifuge. This work has led to a new equation which can be used to determine the improved non-dimensional values.

The new equations describe the fluctuating radial and tangential g-level associated with CCC centrifuges and the mean radial g-level value. The latter has been found to be significantly different than that determined by the traditional equation. This new equation will give a better understanding of forces experienced by sample components and allows for more accurate comparison between centrifuges. Although the new equation is far better than the traditional equation for comparing different types of centrifuges, other factors such as the mixing regime may need to be considered to improve the comparison further.

Computational Fluid Dynamics (CFD) is used as a research tool to gain further insight into the behaviour of fluid dynamics behaviour in a variety of bioprocesses involving liquid-liquid flow. CFD was used successfully in related liquid-liquid flow problems for closed systems, such as tubes, rings and spirals, and more recently in open systems. CFD allows manipulation of applied body forces such as buoyancy force and rotational forces and therefore also allows experiments that are very difficult, if not impossible, to conduct. The phase system modelled in any of the example cases shown below is a Heptane/Ethyl Acetate/Methanol/Water phase system of intermediate density differential and surface tension.

Tube Flow

As a first step towards investigating the influence of a variable gravitational field on the interface between the upper and lower phase of immiscible solvents as used in CCC, the flow in a stationary, inclined tube was investigated. Initially the tube was positioned horizontally with the heavier fluid (lower phase) at the bottom and the lighter fluid (upper phase) on the top. The tube was then suddenly tilted to a fixed inclination angle of 30 degrees. The flow field was initially exposed to a standard 1g gravity field. Subsequently the gravity field was increased to 2g and 10g in the numerical experiments. Predictions for the 1g case compared very favourably with experimental results.