Scalable Liquid Chromatography
With CPC Technology

Liquid-liquid-based centrifugal partition chromatography (CPC) is designed to eliminate the challenges associated with complex matrices and the technical issues of solid stationary phases, and it provides easy scalability of purification while keeping the operational cost low.

RotaChrom has developed a revolutionary preparative purification method called Industrial-scale Centrifugal Partition Chromatography (CPC). This novel 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 CPC platform has radically reduced the costs and number of steps associated with downstream method development for a diverse array of purification challenges.

Solid-liquid chromatographic methods used for purification, separation, and extraction processes are effective and widely used throughout the chemical manufacturing industry. However, these methods are limited in available solvents and stationary phases, incur high costs attributed to spent materials and quickly fall off in performance when scaling to industrial volumes. While other liquid-liquid techniques like countercurrent distribution (CCD) are quick and effective for small lab or pilot-scale applications, they exponentially increase production times and cost when scaling to larger volumes.

Innovations in Centrifugal Partition Chromatographic technologies have brought this previously overlooked method into the public eye as a viable alternative or supplement to legacy preparative chemistry techniques. We offer a wide range of solutions to meet your business needs and help you boost your performance with our one-of-a-kind CPC technology at the heart of our CPC Modeler (benchtop size device for R&D phase), rCPC (for pilot-scale production), Continuous CPC (for continuous manufacturing), and iCPC and pCPC platforms (for industrial-scale production).

Industrial-scale iCPC

Here you can see an iCPC instrument.

Our iCPC platform is the largest commercially available CPC instrument in the world. Designed for industrial-scale purification projects in continuous batch operation mode, it is the most cost-effective industrial-scale chromatography platform available on the market with capacity to process up to hundreds of kilograms of crude input material per month.

The iCPC maintains the same relative load and resolution capabilities as rCPC and is designed to operate in an industrial environment. It can be controlled by a programmable logic controller (PLC) unit, enabling you to fine tune the system or coordinate with multiple devices. Upon request, the iCPC can be purchased as a standalone instrument, in clusters or expanded with a fully integrated solvent handling system.

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Pilot-scale rCPC

Here you can see a RotaChrom rCPC.

Designed for pilot-scale purification tasks within a laboratory environment, rCPC is ideal for small or mid-sized batches, research campaigns and continuous-batch production. When utilized as an at-line purification platform with our industrial-scale purification unit, you can execute separation tasks orthogonally. To fulfill any regulatory or application design requirements you may have, we offer custom modifications to tailor your rCPC system exactly as you need it. As a pilot-scale solution, rCPC offers outstanding throughput, purity and yield while remaining cost-efficient.

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A Complement to Traditional
Chromatographic Techniques

While other chromatography designs are capable of higher resolution output, they rapidly incur costs. Furthermore, the high-end machines required for other methods are extremely sensitive to breaking and have limited solvent availability.

The strength of CPC technology lies in its robustness when compared to other methods. With a durable and reliable design, it can power through the pressure barriers that restrict other methods from industrial-scale purification.

Instead of relying on one method versus another, CPC can easily fit into the procedures of other methods. As an analogy, traditional methods can be thought of as a knife, while CPC is an axe. Although the knife is more effective when making a precise cut, in some applications — chopping wood to make furniture, for example — the axe would be a more effective tool. However, after cleaving the large volume of wood, the finer blade is better suited to carving the details.

Similarly, CPC effectively prepares samples upstream before traditional chromatography methods finish the job, reducing costs and time since you don’t have to rely solely on high-cost, slow chromatography to purify bulk samples from beginning to end. Our CPC platforms save cost, simplify product development and increase throughput with robust chromatography.

CPC technology can be used in a wide range of chemical productions as most involve some kind of purification or separation steps. And while it requires more steps to develop effective methods than other techniques, the benefits are worthwhile as CPC outperforms other methods in terms of efficiency and flexibility. This level of freedom allows you to adjust your solvents precisely to achieve a highly efficient and selective output.

We don’t just sell an isolated instrument, we evaluate your whole process to find the best placement for our product. CPC is compatible in many downstream extraction, distillation, evaporation or crystallization techniques. For example, coupling CPC technology with olive oil bioactive component recovery yields greater purities and enables higher productivity. Combining chemical reaction and separation steps by integrating CPC with equilibrium-limited hydrolysis applications can also reduce manufacturing times as well as solvent and energy costs.

In addition to providing a novel instrument, we offer design and consultation services from start to finish and take pride in offering the most cost-effective purification solutions on the market.

Learn more!

Do you want to know more about centrifugal partition chromatography (CPC technology)?

Learn about the basics of chromatography and CPC here and download the whitepaper on the essentials of chromatography!

Gain advanced information about CPC by downloading the whitepaper on advanced knowledge of liquid-liquid chromatography and CPC!

Effective Under Pressure

Competing CPC separation techniques are limited by the pressure rises that come with any increase in production volumes. Above a certain flow rate, especially when using high viscosity solvent systems, these techniques meet their maximum allowable operating pressure and prevent the system from delivering higher flow rates, resulting in a pressure plateau and preventing further volume scaling without negative consequence. However, our system can overcome the pressure barrier. In fact, we have yet to even meet our pressure barrier.

We also optimized our centrifugal system for higher flow rates with lower pressures of 70 to 80 bars, facilitating flows of 2 liters per minute and more. With the ability to operate at higher pressures up to 120 bars, our separation is more efficient and achieves higher resolutions than competing preparative chromatographic techniques.

Besides a cell design optimized for minimum pressures, CPC technology provides excellent stationary phase retention, further increasing loadability and reducing operating costs relative to other preparatory methods.

iCPC

Rotor in motion

No Silica Necessary

While solid-liquid chromatographic techniques are generally limited in choices for stationary phases due to polarity requirements and usually fill the column with silica gel packing. With each run, efficiency decreases as the stationary phase adsorbs particles and saturates the column, requiring cleaning or disposal while managing potential contamination.

Silica gel also creates challenges such air pockets from incorrect column packing which can further impact overall performance. Legacy columns don’t scale easily either, with taller columns requiring taller buildings, industrial scale operations would require a column size that just isn’t feasible.

Additionally, solid stationary phases, used in techniques targeting isomer component separation, impose an immense cost burden upon the user. This drives researchers to try to eliminate the latter need for chromatography as much as possible during the upstream process development stage. Alternative chromatographic techniques like CPC provide flexibility as this method opens new possibilities to tailor isomer separations without using a specific solid stationary phase.

Liquid-liquid techniques allow for more solvent system options and offer greater potential for material retention and reuse. Using two immiscible liquids makes total stationary phase recovery possible since there is no irreversible adsorption, reducing costs on silica gel supplies.

Read more about why CPC is a sustainable alternative to conventional preparatory separation methods in our whitepaper.

Other Preparatory Techniques

HPLC VS CPC

CPC isn’t an end-all replacement for the other liquid chromatographic techniques available on the market but there are key differences among them that make one method more viable than others for certain applications. High-performance liquid chromatography (HPLC) relies on solid adsorbent material and while it provides higher resolutions, CPC technology is far more flexible to optimize solvent systems and achieve greater peak separations. Supercritical-fluid chromatography is expensive and is only worthwhile for high-value material productions. Flash chromatography is similar to traditional column chromatography where the separation occurs in a much shorter time span. While it is a fast method, it doesn’t scale nearly as well as CPC.

A Closer Look at Centrifugal
Partition Chromatography

In traditional liquid chromatography, separation occurs between two immiscible liquids known respectively as the mobile and stationary phases. The degree of separation is determined by the sample components’ varying partition coefficients, which influence the rate at which molecules travel through the system.

CPC cells are attached to a large rotor that is filled with the liquid stationary phase and then immobilized by a strong centrifugal force. As the mobile phase moves through the stationary phase in the form of tiny droplets, its large surface area optimizes the mass transfer between the phases. At the end of the purification process, automated fraction collectors retain all selected fractions based on program settings.

Our CPC technology is a viable solution for three major separation tasks:

Isolation: compound of interest is the target for separation while the matrix is discarded.
Remediation: the matrix compound is the separation target and the other compounds are discarded.
Separation: the matrix is often preprocessed and contains a limited number of target compounds which are collected after separating from each other.

Improved Design Offers
Throughput Advantages

Our design takes advantage of the space provided by cylindrical chambers and uses centrifugal force to hold the stationary phase. Large bore cylinders are easy to manufacture and provide linear scalability thanks to their unique, patented dimensions and architecture. The individual extractions cells are scaled in a way that the performance is not impacted, allowing our extraction cells to be scaled from 10 to 100 millimeters without impacting performance and providing flow increases from milliliters per minute to multiple liters per minute.

Other advantages of our cell design include:

  • Direct and easy scalability between the portfolio members.
  • Accessible cell and rotor environment for easy maintainance and cleaning.
  • Tailor-made cleaning procedure (CIP) for convenience.
  • Reduced eluent back-mixing.

We have also improved designs beyond the extraction cells. Our injection plugs provide enhanced, stable droplet dispersion of the mobile phase to the stationary phase. And, our collection plug increases solvent retention, increasing loading capacity and chromatographic resolution for the same column size by 20 percent.

Pushing the Envelope With Precision Software

We designed our top-performing CPC cells with computational fluid dynamics (CFD) software. After thousands of simulations, we found drawbacks of conventional cell designs, highlighting the unparalleled load capacity and scalability of CPC.

Discoveries include:

  • The circular motion of liquid inside planar cells induces back mixing.
  • Shorter cells with less surface area provide less space for separation to occur.
  • Fluid dynamics change when scaling up production with conventional systems.
  • Poor fluid dynamics lead to poor stationary phase retention and theoretical plate numbers.

Our cell design remedies the issues found in planar cells. There is more space for separation since the surface area inside the cell has increased. Relying on cylindrical columns rather than planar cell shapes also reduces back mixing. The improved fluid dynamics enabled by the unique cell design allows for scaling production while maintaining efficiency. Additionally, the optimized fluid dynamics contribute to the greater stationary phase retention and plate numbers, providing high loadability and productivity for industrial scale processes.

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RotaChrom's CPC Technology | RotaChrom Technologies LLC.