Webinar 2 – Technology and Investment Considerations for Industrial Scale Purification 

In this webinar, Andras Gaspar PhD reviews technology and investment considerations for industrial-scale purification. First, he provides a brief overview of the history and capabilities of chromatography. Andras then highlights the key features and benefits of this approach and especially what RotaChrom has achieved in this arena. Finally, he details some investment considerations for those interesting in the technology.

Part 1: A History of Chromatography and Where we are Today

Partition Chromatography, which is considered to be a support-free liquid chromatography, was discovered in the 1940s, when the theoretical and practical application of countercurrent distribution, the foundation of countercurrent chromatography, was developed by Richard Synge. He later received a Nobel Prize for the invention of the partition chromatography.

Lymar Craig later created an instrument that has pioneered the way towards today’s CPC. Unfortunately, the apparatus at that time was only able to operate in batch mode and could not be automated.

It took a few decades until the next significant milestone was reached by Yoichiro Ito, who started to utilize gravitational force to enhance the performance of chromatography. Ito’s developments eventually resulted in the HSCCC with a planetary motion centrifuge.

Afterwards, several companies such as Sanki Engineering developed a planar disc concept, but those had disadvantages as well. In the late 90s/early 2000s European companies such as Partus Technologies and Armen Instruments started to work on other solutions to overcome those boundaries and might be able to scale-up the technology to a true industrial scale. Unfortunately, these attempts were not successful.

Around that time, the original inventors who later founded RotaChrom challenged the approach. Around 2004, they came up with a cylindrical cell design that provided enough robustness to create the basis for a scalable CPC instrument. After more than a decade of development, today RotaChrom provides the only true industrial-scale CPC instrument with integrated solvent recycling to various markets and applications such as the hemp industry.

Today, the CPC has some key functionalities that set it apart from legacy chromatography, but one major differentiator in this technology is partition. In CPC, separation occurs between two immiscible liquid phases and the stationary phase is immobilized inside the rotor by a strong centrifugal force. The mobile phase containing the sample to be purified is fed under pressure into the rotor and pumped through the stationary phase in the form of tiny droplets (percolation). The chromatographic column in CPC is the rotor: cells interconnected in series by ducts attached to a large rotor. This is a simple mechanism that creates a difference in partition.

This level of mass transfer is unique for each analyte, and it is driven by the concentration difference of the analytes in the individual phases. Over the length of the cell system, this transfer reaches an equilibrium, creating different retention of the individual analytes while the mobile phase with a given flow rate carries them towards the outlet. This mechanism results in a major difference when the CPC is compared to HPLC or Flash.

Partition Chromatography is a true alternative to conventional liquid chromatography with many advantages. What are these advantages? 

–   Since CPC only utilizes solvents, the theoretical combinations are almost infinite, which provides a lot of options to fine tune a system for the individual separation task. 

–   The second advantage derives also from the presence of the solvent system, involving a minimum volume of solvents and analytes. This approach, compared to other methods, is considered to be faster, cost effective, and can be conducted remotely.

–   Scalability is another advantage that could refer to the method itself, meaning that once the system is working on a lab scale, it could be easily adapted almost seamlessly for large-scale applications. Scalability could also refer to the throughput.

–   The CPC technology is also considered to be forgiving. Suppose that the system was not set up properly. The financial impact caused would be negligible.

–   Since CPC does not have a traditional solid stationary phase, total recovery can be expected as there is no irreversible adsorption on the stationary phase. In traditional chromatography with given periodicity, the stationary phase needs to be regenerated and cleaned, often using an excessive volume of fresh solvents in order to maintain separation properties uniformly. In the case of CPC, a fresh set of solvent is used as a stationary phase between each run, providing a constant separation performance.

–   RotaChrom, with its pCPC platform, also offers orthogonality to its customers, allowing them to create 2D separation.

–   The CPC method also has incredible flexibility. The type of input material can be also changed from batch to batch. Customers can easily change their compound of interest if the volatility of the market calls for it.

Part 2: Investment Considerations

Rotachrom’s CPC solution was often considered to be a finalizing step in the hemp/cannabis processing sequence, but it turned out to be just as vital as any other steps. The added value during this step is also considered to be one of the highest in the entire process. Regardless, it is still a large investment so careful considerations should be made when choosing a purification system.

Here are some of the key points that may influence the investment and the ROI numbers during the process design stage. Here are a few factors to consider:

–   Cost contribution of the individual process steps and their effect on the entire process.

–   What are the volumes that I would like to process?

–   Do I need to consider flexibility over throughput, knowing that the market is volatile?

–   What kind of revenue streams would I like to introduce to the market? Are the selected productions steps adequate for those?

–   What kind of products can be manufactured via the production steps selected? 

–   Since the hemp space is relatively volatile, processors may want a system with higher flexibility.

Part 3: Client Case Studies

The investment and OPEX cost relative to the volume of the input material is one of the highest for the purification step, so it is easy to understand that the more you invest and process on the front end, the lower the overall TCO would be.

Keeping this in mind, our goal was to deliver the most cost-efficient solution to our customer that would include not just a simple instrument delivery and installation, but also a well-designed process chain beforehand.

RotaChrom’s TCO simulation Tool was developed for customer discussions to assist during the initial process flow considerations

Here are four case studies in which the calculator was utilized that provide further insights that might be useful if an investment is considered. 

1. Carefully selected process flow enables higher-valued materials: While the customer initially wanted to go with a direct extract from SFE method for THC remediated, RotaChrom showed that by properly processing the input material and purifying with CPC would result in a higher-quality product and lower the total cost of operations.

2. Mother liquor alternative route decreases the initial CAPEX burden: In the case of a customer with a high daily throughput, they were facing the challenge of having an extremely high CAPEX in order to meet demand. They needed a solution that would bring down the capital expenses but still create a quality product. With the help of RotaChrom, the customer split CBD crystals and the Mother Liquor, and then utilized the iCPC and the rCPC to isolate minor cannabinoids in addition to getting the CBD they wanted, creating multiple revenue streams

3. Massive CAPEX savings for massive daily throughput requirements: In an even more extreme case, the aforementioned process was used to separate the Mother Liquor. The CAPEX savings was estimated at approximately 60% and the operational cost was also reduced.

4. COI and revenue intensification by RotaChrom’s experts: RotaChrom’s system is also often used for optimizing the purification process. With the help of RotaChrom’s chemists and the implementation of the CPC, customers achieved an increased flow rate with higher stationary phase retention.

Prior to any investment, customers should also review the current competitive landscape and check which provider can deliver the right solution. In order to aid our clients, we created a benchmark to define the position of RotaChrom. We have carefully investigated all current and emerging technologies and tried to compare our performance with those who are active in the cannabis and hemps space.  We compared 10 different relevant methods in the hemp industry with 18 different providers.

Check out the next webinar for an in-depth analysis of RotaChrom’s findings and the pros and cons of the different chromatography approaches.

About: Andras Gaspar, Ph.D., is RotaChrom’s Chief Product Officer. Andras studied bioengineering at the Budapest University of Technology and Economics and went on to earn his Ph.D. in chemistry at the Technical University of Munich. After more than a decade of engineering work at IBV Hungary, Gates Corporation, and Continental ContiTech, Andras joined RotaChrom Technologies in 2020.