SMART Chromatography™

SMART Chromatography™

Remove the bottleneck in
your downstream process

SMART allows the purification of biomolecules directly from the bioreactor
without first having to clarify the feed stream.

It stands for Simplified Method – Applied Radial Technology: Unlike conventional
chromatography, where the feed stream flows through the continuous
packed-bed solid phase from top to bottom, SMART Chromatography™ works
in the radial, horizontal plane with the cells present.

SMART Chromatography™ covered by US Patent 11,325,104 and 11,731,107.

Improve recovery,
reduce cost

– Consistency
– Linear scalability
– Remove variability

Research and

Scale and


Design your process
only once

As the primary step in a purification process, SMART Chromatography™ eliminates the requirement to remove cells before application to the chromatography column, reducing the number of steps in the process, reducing time and increasing product recovery.

SMART Chromatography™ guarantees a process of higher biomolecule
recovery, greater purity and retention of biological activity as well as
lower costs of operation.

The advantages of SMART Chromatography™

SMART Chromatography™ is the patented method of purifying molecules from a particulate containing feed stream in a packed bed radial flow chromatography (RFC) column.

Designed as the first step in the purification (downstream) process, SMART Chromatography™ combines big bead technology with radial flow liquid pathway to provide a rapid, scalable method of capturing the target molecule from the crude feed stream. Once captured, a simple change in pH or salt concentration allows for the elution in a pure and concentrated form.

Traditional methods of purification were typically developed in a laboratory environment and designed for small scale applications.  The methods were often complicated and contained many steps, thus making the process time-consuming and with low levels of target recovery, as each step results in an inherent loss of the desired target molecule.  Scale-up of these processes thus became more difficult to achieve and the loss which is inherent to any process can become significant.  It is common practice for the bed height of the column to be fixed early on in process development and this means that as scale-up takes place the manner in which the feed stream is applied to the chromatography bed becomes more important.

Scale-up of a traditional axial (top-to-bottom) flow chromatography (AFC) column can thus only occur by increasing the radius (or diameter) of the column.  Thus, process columns with a bed height of 10-20 cm (4-8 inches) and a diameter of 2-3 metres (6½-10 feet) are not unusual and apart from the space required to operate them (and the challenge of even getting the column into the manufacturing space), fluid mechanics and the flow across the chromatography bed to obtain maximum use of the solid phase leads to lower process efficiency.

In comparison, radial flow chromatography (RFC) columns are designed with scale-up in mind.  Bed height becomes bed length – as the flow is no longer in the vertical plane but in the horizontal plane and large-volume columns will typically have a footprint around 25-33% of that of the equivalent AFC column (for the same bed height / bed length) – meaning that columns are easier to bring into the production facility and require less floor space.  Fluid mechanics is more predictable, and this results in linearly scalable processes.  Improved fluid mechanics also means that process efficiency is improved.

SMART Chromatography™ is an acronym for Simplified Method – Applied Radial Technology. As the name implies, what we achieve is the simplification of the critical first step in the downstream process.

Whatever the feed stream – be it from a cell culture, waste stream from a fruit or other plant pressing, or the whey from a dairy process, it has always been a requirement that particulates be removed before application of the material to the first purification column.  This is because the particulates can clog the frits and solid phase packed into the column.  For small volumes, the solution has been to either centrifuge or filter the particulates away.  In some cases both techniques are used.

As processes are scaled up, the feed stream volumes increase and the associated issues with both centrifugation and filtration increase.  The equipment for both is expensive – especially in regulated cGMP environments and filters need to be integrity-tested before use – a time consuming process in its own right.

With COVID-19, supply chain issues have also meant that the availability of filters and (for centrifuges) spare-parts has become an issue.  Eliminate the clarification step and associated issues with supply chain and spares are also eliminated.

Purification processes are designed to be robust and thus any variation in the process will introduce a variability in the process efficiency. SMART Chromatography™ removes variability.

In the pre-column clarification steps (either filtration or centrifugation) there is an inherent variability in the clarification efficiency.  This is unavoidable and stems from the feed stream itself as the number of particulates per unit volume will vary between process runs, and from the fact that valuable target material will get trapped in the pellet or filter cake.

The only way to completely remove this variability is to remove the clarification step.

In a SMART Chromatography™ based purification process, the feed stream contains all of the particulates and these will pass through the packed column bed.  Frit materials are designed to allow these particulates to pass unhindered into the solid phase.  The solid phase itself is made from large beads, with interstitial channels allowing the particulates to traverse through the column, whilst the target molecule will bind selectively to the ligands covalently attached to the beads.

In basic research or early-stage R&D, upscaling of the purification process from very small scale to manufacturing scale is often overlooked. When processes reach the stage at which scale-up needs to be considered, it is often too difficult or costly to “rethink” purification. SMART Chromatography offers true linear scalability from the R&D phase through to full-scale manufacturing.

Since the early 1990s, it has been well-established that RFC provides seamless linear scalability.

As with all commonly used packed-bed purification processes, SMART Chromatography™ works best when the bed height (or in the case of RFC, bed height) remains constant.  It is for this reason that even the R&D SMART Chromatography columns are available in bed lengths that are identical to those used in the manufacturing environment.

Linear scalability leads to process predictability – reducing process development times, as the process is already known and validated during the R&D phase. The purpose of scale-up is simply to purify more target molecule per production run.

In any purification process, loss of target material at any step is a loss in revenue and impacts the overall process economics. By removing the clarification step, SMART Chromatography™ improves recovery.

In traditional AFC purification processes, target recovery from what is applied to the column is generally quite high – in excess of 95%.  However, this recovery percentage is not entirely accurate, as it is not 95% of what was available before the feed stream was applied to the capture column.  If the clarification steps result in a loss of 15% of target, then maximum recovery (at 95% recovery on the capture column) will be just under 81%.  At 30% loss, maximum recovery is 66% and at 50% loss the recovery is 47.5%.  Processes that are apparently efficient quickly become economically unviable.

In SMART Chromatography™, the capture efficiency (or product recovery) will be similar to that for an AFC column – so 95% or higher, provided that the capture modality is identical.  However, given that loss of target is zero as all of the target material is applied to the column, the recovery is quantitative.

Biological activity of the purified molecule is amongst the most important of criteria in a purification process. Product that loses biological activity is of no use. SMART Chromatography™ reduces loss of biological activity.

One of the most common issues in downstream processing is the loss of biological activity of the target molecules.  Product degradation can be causes by many factors, including enzymatic degradation, chemical and physical environment.  In cell-based systems, such as those commonly used in the manufacture of biologic therapeutics, such degradation is closely linked to the time it takes to properly prepare the feed stream prior to application of this to the capture column.

In a SMART Chromatography™-based process, it is possible to apply the feed stream directly from the bioreactor to the capture column without modification*.  This means that the time-dependent degradation simply does not occur.  Once the target molecule has been captured on the column and degradation causing contaminants have either passed through the column or have been washed away, such degradation is prevented.

(*) Some cell systems do not secrete the target molecule into the bioreactor solution and in such cases the cells need to be ruptured in order to release the target molecule into the solution prior to application of the feed stream.  This is necessary in both traditional and SMART Chromatography™ based processes.

These days, the environmental impact of any manufacturing process must be considered. Implementation of SMART Chromatography™ into any purification process leads to a reduction in environmental impact.

By eliminating the requirement for clarification of the feed stream prior to application to the SMART Chromatography™ column, there is the immediate reduction of environmental impact due to the associated impact from the manufacturing of the centrifuge, filtration system and consumables.  Additional reductions may also be obtained by avoidance of feed stream preparation (for example pH adjustment).

If one also considers reductions obtained from shorter processing times (energy costs, facility and personnel costs), then the overall environmental impact can be reduced significantly compared to traditional processes.

Linear scalability also leads to a lower overall environmental impact.  Process development times are reduced, leading to lower volumes of feed stream and reagents required for the process development stages. Linear scalability also means that waste streams (excess buffer requirements, consumables, etc.) are more predictable.  Less waste can also result in lower transport costs or post-production treatments.

In processes where the target molecule is purified from what previously would have been considered a waste stream (for example, vegetable extract residue or milk whey), it is more difficult to evaluate the environmental impact – although it would be reasonable to expect it to be lower if the resulting effluent is closer to water once production is completed.

Cost is a major factor in any manufacturing environment and process economics is tightly bound to the overall process efficiency. SMART Chromatography™ radically improves process economics and drives cost reductions.

In the preceding sections, it has been discussed how SMART Chromatography™ can improve product recovery and biological activity, which naturally leads to a direct reduction in process costs.  By eliminating the capital expenditure (CapEx) on expensive centrifuge and filtration systems, there is also the continuous operational cost of filters.  The associated time and overhead costs are also eliminated.

What might not be immediately obvious is the potential reduction in costs from manufacturing unit operations not normally associated with purification.  If product recovery from the bioreactor is increased, then the volumes of material required to produce a given amount of the target molecule can be decreased and it will still be possible to obtain the desired amount of target molecule. For certain cell culture systems, the cost of the cell culture materials are very high. If recovery is improved by 30% (so an increase from 66% in the example shown above to 95%), then bioreactor volume can be decreased – an immediate impact on the process cost with every single production run.

There is usually a high degree of focus on the cost of the solid phase and the overall process cost is often held up against this. By assessing the entire cost of manufacturing from start of the cell culture process to the stage at which a purified protein is obtained (after elution from the SMART Chromatography™ column), the cost reduction will be far more than that just associated with using a different solid phase.

Smart. Fast. Scalable.

SMART Columns

Our SMART Chromatography™ columns come in different sizes and with various resins and ligands.

The columns for small scale R&D and purification are supplied pre-packed and ready-to-use. Larger columns for manufacturing can be supplied as either pre-packed or with bulk resin for on-site packing.

The bed volume of columns ranges from 5 milliliters to over 1000 liters. We have both single-use campaign columns as well as fully reuseable process scale columns.

ZetaCell resins

SMART Chromatography™ uses proprietary ZetaCell solid phases. These are based on large-particle highly cross-linked agarose, which is surface-modified to provide the desiredbinding functionality. The beads have been designed to allowcells and cell debris from the bioreactor to pass unhindered through the packed column bed.

Our range consists of antibody affinity ligands such as base-tolerant Protein A, Protein G and Protein L, IMAC resins, ion-exchange resins and activated solid phases to allow the client to create their own columns based on our platform technology.

Our groundbreaking SMART Chromatography™ is a robust, scalable purification system for unclarified cell cultures.

Watch us revolutionize the world of chromatography.

SMART Chromatography™:
A versatile solution

Implementation of SMART Chromatography™ is possible for most downstream applications, both existing and new processes.

SMART Chromatography™ can be used for most downstream applications , both existing and new processes. 

SMART Chromatography™ is primarily used for fast and effective purification of biomolecules – antibodies, proteins, viruses – from a wide variety of particulate-containing feed streams. Examples include secretion and non-secretion cell systems, plant extracts, and filamentous fungi cultures.

Every technology has its limitations. In the case of SMART Chromatography™, there is a limit to the quantity of particulates which can be applied to the SMART Chromatography™ column. However, this technology has been successfully applied to various cell culture systems with mammalian cell densities of up to around 6 x 107 cells/mL (CHO cell culture), while bacterial and yeast worked equally well with wet solid content of around 25-30%.

Do you have a prospective application for SMART Chromatography™ in mind? We’d be delighted to discuss your options with you.