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Development of Industrial Scale CPC

Centrifugal Partition Chromatography (CPC) is a special chromatographic technique where both stationary and mobile phase are liquid, and the stationary phase is immobilized by a strong centrifugal force (1. picture). Similar techniques are Counter-current Chromatography (CCC) and Counter-current extraction (CCE), which has been used for natural product purification for decades.

1. picture: schematic representation of CPC
2. picture: flow inside Kromaton and RotaChrom CPC cells

The main advantage is the cost-effectiveness, since it does not need any expensive and bulky solid stationary phase, and both quantity and quality requirements for solvents are less decreased contrast to standard liquid chromatographic techniques. CPC consists of series connected network of extraction cells, which operates as elemental extractors, and the efficiency is guaranteed by the cascade [1]. CPC instruments vary on scale from 50 ml to 25 liter in column volume, and from 5 ml/min to 500 ml/min on flow rate, however all advantages are realized on bigger scale use in industry. Up to date there were no available cGMP compliant instruments, and no instruments that could be used for purification on industrial scale (flor rates over 1 liter/min).

3. picture: left: separation of fatty-acid derivatives on an Armen SCPC-250; right: separating the same on RotaChrom-CPC

Our development started with the flow-simulation of the elementary extraction cells. The current extraction cells available has big dead-volume and extensive back-mixing (2. picture). Our studies showed that with the modification of the cell geometry and by using packing a more efficient technique can be developed, outdating current research [2]. Our cell designs (2. picture) are currently patent pending. First prototype (4,5. picture) was built in September, 2014, with modifications in January and May. The prototype is still in operation with success, and production of final model will start in August. We already achieved same performance (plate number, resolution) as CPC competitors (Armen, Kromaton, Partitron) at fraction pressure and column length. A separation with sample of fatty-acid derivatives was achieved at 10 bars instead of 50, with run times of 5 minutes instead of 100 (3. picture). All other performance parameters were kept the same.

4. picture: Prototype cell block
5. picture: RotaChrom CPC prototype

Comparing our CPC to former techniques, we have numerous examples showing effective separations, like for pinosylvins (see other poster), showing that CPC is applicable on a wide range of materials, and with time it will substitute most preparative-LC processes.

6. picture: The RotaChrom TEAM with HQ

Our instruments range from 300ml to 50 liter of column volume, from 200ml/min to 10 l/min flow rate. This means that this new industrial machine can adopt to productions of few grams up to tons / month. Our team (6. picture) is proud to continue the way of Hungarian chromatographic inventors, like Csaba Horvath, inventor of HPLC.



[1] Berthod A. Countercurrent Chromatography, 1st edition. Amsterdam: Elsevier; 2002
[2] Schwienheer C, Merz J, Schembecker G. Investigation, comparison and design of chambers used in Centrifugal Partition Chromatography on basis of flow pattern and separation experiments Evaulation of CPC separation efficiency for different types of chamber geometries on the basis of flow pattern and separation experiments. Journal of Chromatography A, in press

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