Improving Separations with Simulated Moving Bed Chromatography

Simulated moving bed chromatography uses a counter-current to allow continuous chromatographic separations, which allows researchers to extract more analyte whilst using less packing material and solvent. The technique is already highly popular in the pharmaceutical industry where, high yields are required from 'small scale' reactions. However, due to a lack of knowledge about the systems, much of academia has not yet caught onto the benefits of using SMB in their research.

AZoM spoke to Dr. Christian Benkhäuser, of KNAUER, about the theory of SMB, how it can benefit your separations and the AZURA system that KNAUER provide.

What is simulated moving bed (SMB) chromatography?

The SMB process enables the separation of binary mixtures by means of a simulated countercurrent between the solid and liquid phases. This is accomplished with a series of chromatography columns arranged in a ring.

An eluent flow circulates through the ring (figure 1, below). Two inlets (for feed and eluent) and two outlets (extract/red and raffinate/blue) define four separation zones. By continuously feeding sample and synchronously switching the columns (via valves) against the eluent flow direction, a countercurrent between the solid and liquid phases is achieved, leading to high purity and yield of both target fractions.

Figure 1: Schematic showing the interactions, and mode of purification, in SMB Chromatography

How does the SMB set-up differ to conventional chromatography?

Classical HPLC systems have always the same set-up:

• Pump
• Injection system
• Column
• Detector
• Fractionation collector (in preparative chromatography)

The SMB process is a continuous process and due to this the set-up is very different to the standard set-up. Firstly, to enable this continuous operation, the fluidic part of the SMB has a circular structure, where the last column outlet is connected to the first column inlet.

Also the other system parts are integrated in a completely different way. SMB systems contain four pumps. Three which are integrated into the circuit while the fourth is responsible for the injection into the system, which takes place in the middle of the virtual column, not at the beginning. Finally, maybe the biggest differences of a SMB system compared to a conventional HPLC system is that no detector is required and that no fractionation is needed.

What benefits does the ‘moving’ bed deliver that a stationary bed does not?

The high-pressure liquid chromatography is an enormously powerful tool for the separation of substances. Unfortunately, it is an expensive purification method. To increase the yield per time the whole system must be upscaled increasing the cost immensely.

SMB chromatography as a continuous purification tool has a largely increased productivity and can therefor purify more substance on a smaller system with less solvent and on less and cheaper column material!

Can the same range of stationary and mobile phases be used in an SMB column than those used in a conventional chromatography column?

Yes, you can use the same column for the SMB process, but you don’t have to!

Due to the simulated countercurrent, the stationary phase is significantly better utilized by the SMB technique compared to the conventional batch process technique. You can use columns with bigger particle sizes, still achieve better separation, and consequently save a lot of money.

What types of analytes and mixtures is SMB chromatography used to separate? What applications is this most useful for?

SMB Chromatography is typically used for the separation of binary mixtures.

Also, the separation of multi-component mixtures can be achieved with SMB, as far as the desired peak is the first, or the last peak in the chromatogram. This is due to that the SMB “splits” the chromatogram at a certain point in the chromatogram (figure 2).

Due to its power in the separation of binary mixtures the SMB chromatography is typically used for the separation of diastereomeric mixtures as well as for the separation of sugar.

Figure 2: Examples of chromatograms from a binary separation using an SMB (left), separation of a complex mixture using conventional chromatography (middle) and separation of a complex mixture using SMB.

What SMB systems does KNAUER offer?

We offer two different AZURA SMB sizes.

Our AZURA SMB Lab systems are optimized for the purification in a several hundred-gram scale and can be used with columns with up to 30 mm inner diameter. The standard version of this system is fully bio compatible and can be operated in a working range of up to 150 bar and 50 ml/min

Additionally, we have our AZURA SMB Pilot systems, which can work with flow rates of up to 500 ml/min and enable very high throughput on a kilogram scale, typically used with columns of up to 100 mm inner diameter.

Due to the flexible design our customer can choose between many different valves and pump heads to build up their tailormade SMB system!

Given its complexity how much expertise is required to operate the AZURA SMB Lab System?

Our goal for the new AZURA SMB system was to make SMB chromatography as simple as possible. Our control software PurityChrom^® MCC has many features to support the user during the operation.

Thanks to the system visualization, the control of the system is very simple and every system parameter (pump flow, pressure, valve position, flow-meter flow) can be seen at a glance and changed with one click. To minimize the risk of data loss and enable high reproducibility, the software saves every change made during a run.

The most difficult part is the process determination and can’t be done without any understanding of the SMB process. Therefore, we have a standard instruction to the system and the software as well as an additional training for SMB method development.

We keep in close contact with our customers during the system design process as well as after the installation, especially during the first steps of the process design we give a customers a lot of support. This can take the form of tutorials. calls to walk customers through processes through to tailor made courses.

The AZURA SMB System from KNAUER

Can the AZURA SMB Lab System be used for any other types of chromatography?

The system set-up is very powerful and can be used for many different applications. Thanks to the software and an integrated freely configurable method editor the customer can design the continuous process their needs.

The easiest modification is a change of the classical column configuration from a 2:2:2:2 set-up to a 1:3:3:1 set-up. But more complex modifications like the change of the column order is also possible.

With the integration of a detector and an injection module the system can be used as a classical HPLC system as well!

What industries do you expect the AZURA SMB Lab system to have the greatest impact in?

Continuous production processes are becoming even more important every day. Therefore continuous purification solutions are needed.

Especially the field of bio processing, e.g. the continuous fermentation, will benefit extremely from a continuous purification method - or at least will not succeed without one!

Where can our readers find out more about KNAUER and the AZURA SMB Lab System?

You can find many information about our products on our website and in our new brochure.

Download the Brochure Here

About Dr. Christian Benkhäuser

Christian studied chemistry at the Rheinische Friedrich-Wilhelms-Universität in Bonn. In 2014 he finished his PhD in organic chemistry. Christian joined KNAUER as Product Manager for SMB and preparative chromatography in January 2015.