RotaChrom has developed a revolutionary preparative purification instrument called Industrial Scale Centrifugal Partition Chromatography (iCPC). This novel cGMP compliant system does not utilize any solid stationary phase (such as silica gel) to achieve precision molecular separation and is demonstrably superior to conventional liquid chromatographic techniques in terms of yield and purity. In addition, the iCPC platform has radically reduced the costs and number of steps associated with downstream method development for an eclectic array of purification challenges.

Within this system separation occurs between two immiscible liquid mobile and stationary phases. The CPC cells, attached to a large rotor, are filled with the liquid stationary phase and immobilized by the physical properties of the system. The mobile phase moves through the stationary phase in the form of tiny droplets. The large surface area of the droplets assures optimal interaction between the phases.

Like conventional liquid chromatography, separation of the injected sample is based on the sample component’s varying partition coefficients between the mobile and stationary phases. The partition coefficient dictates the amount of time each molecule spends within the mobile and stationary phases and therefore the rate at which each molecule travels through the system. At the end of the loop automated fraction collectors separate and collect all selected fractions.

Cell design

RotaChrom designed its top performing CPC cells through Computed Fluid Dynamic simulation software. After thousands of simulations, this tool revealed the drawbacks of conventional CPC cell designs and enabled RotaChrom to create unique and scalable cell design.

Drawbacks of Conventional Cell Designs as Revealed by Simulations and Flow Visualizations: 

• Circular motion of liquid inside of conventional cells causes back mixing
• Shorter cells, with less surface area, provide less space for separation to occur
• Scale-up of conventional cells are problematic. Flow dynamics drastically changed during scale-up
• Plate-number and stationary phase retention suffered due to bad flow dynamics

It is VERY difficult to ensure cleaning validation of conventional cell designs, as the rotor must be disassembled using hydraulic press, making simple and fast maintenance and cleaning almost impossible.

Advantages of RotaChrom’s Cell Design:

• Injection plug: responsible for the even injection of mobile phase into the stationary phase.
• Tubular cell wall with filling: The circular cross-section not only enables:
  1. 1. Scalability: Allowing direct scale up from ~5 kg/month (rCPC) to hundreds of kg/month (iCPC-M)
     2. Convenient Maintenance and Cleaning
     3. Swab-probing eliminates issues with CPC cleaning validation and GMP regulatory compliance

   

• Collection plug: Our design increases the solvent retention, which increases loading capacity and chromatographic resolution by 20% for the same column size. Finally, one of RotaChrom’s most impactful discoveries was that our extraction cells can be scaled from 10 mm to 100 mm without impacting performance and increasing flows from mL/mins to multiple L/mins. Furthermore, our unique rotor design allows for these cell sizes to be interchangeable on the same machine.  Industrial Scale Centrifugal Partition Chromatography is proven to be superior to conventional preparative chromatographic techniques in terms of precision performance, adaptability, scale up and cost effectiveness.

• See video: Introducing Column Free Industrial Scale Preparative Chromatography