| If you use perfusion already, and wish to improve your process performance, then the ATF has several advantages over the competition. Almost all perfusion products available today perform well at the sub 5L scale. Many systems, except for the ATF, subsequently cause problems as you scale up. However, the ATF has one or two benefits even at the small scale which may be important to you.
If you do not use perfusion yet, and are considering it, the description below may be useful. If you do not why you should use perfusion, and do not know what the fuss about, then there are two simple reasons:
- For any given cell type and process, running a perfusion culture should raise your cell densities and your total product formation
- For many cultures, the costs of the extra media and other consumable and capital costs are outweighed by the benefits of a longer producing process time, less cleaning and less downtime. i.e. your total cost of goods (COG) is reduced.
Of course, not all bioprocesses will gain from perfusion, however, historically perfusion has been risky and complex and so was avoided despite the possible gains. Today, new technology, such as the ATF, has solved the practical difficulties and eliminated these risks, so you can calculate the economics and bioprocess gains more clearly. The ATF has additional cost savings in comparison to other perfusion devices, so even while a traditional spin filter or Biosep may not have been economic previously, you may find the ATF makes the difference.
What is special about the ATF?
It is a perfusion and filtration system.
Why is it better than a spin filter or a sonoperfusion BioSep?
Spin filters are very cheap (from ~€500) so to use anything else really needs justification. (BioSep and ATF are from ~20 times more expensive). If you work in research, have only the goal to raise your cell densities at absolutely the minimum cost and do not care about other benefits or potential problems, you can probably get away with a spin filter. However, if you agree with one or more of the following statements, you should consider a different perfusion system.
- I use bioreactors at 5L working volume or above
- I want an easy to clean, and easy to dis/assemble system
- I run processes for longer than a week
- I cannot risk blockages that would stop the process
But should you choose the ATF? If you agree with one or more of these statements about your bioprocess below, you should consider the ATF instead of an alternative.
- I develop processes which must be easily scaleable
- I want a low shear system that does not damage cells
- I want a simple tubing setup without multiple pumps
- I, or my colleagues, use bioreactors at 500L or above
- I would prefer only hard piped connections for scale up
- I need a perfusion system that manufacturing process engineers (and their validation engineers) will instantly like and understand
- I wish to simplify my DSP operations and remove a step or two
What other reasons are there to use the ATF? If you need further convincing, look at these possible statements about your cells and product. Each of these can become true if you choose the ATF, but not the sonoperfusion Biosep.
- I would like my secreted protein product to go from the bioreactor directly to a column
- I want to be able to perform rapid media exchanges without losing cells, or losing viability
- I want to perfuse microcarriers with the same equipment
- I do not want cells to be present in my perfused harvest
- I want to be able to use the perfusion system to separate:
- cells from microcarriers
- protein products from cells and cell debris
- virus from cells and cell debris
- I want to be able to change from one type of filter to another type mid-process completely safely
- I want to attach the perfusion system to a Wave bioreactor
Have a further look below at the features and benefits of the ATF perfusion and filtration system.
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Features and Benefits
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| "Engineer-friendly" |
Virtually all spare parts are available from multiple suppliers and the equipment can be readily assembled and disassembled without prior knowledge or a manual. |
| Filtered Product Stream |
If you have a secreted protein, or can lyse cells in place, you can filter your product directly out of the system, removing the need for clarification further downstream, saving time and expense. |
| Cell-Free Filtrate |
The saving of labour time and the reduced capital equipment required can make big savings at scale, possibly up to 10% of your downstream costs. |
| cGMP Validated |
The ATF is already used not just in clinical trial manufacture, but for market supply. No specialised nor complex operation or software is used, simplifying validation. |
| Sustains Ultra High Cell Densities |
A standard CHO cell line regularly achieves twice the fed-batch maximum. Examples of over 40m cells per ml have now been reported. |
| Choice of Filter |
You may use filters from GE Amersham, Spectrum and Pall, plus our own 70µ screen for microcarriers. A common choice would be a 0.2µ filter, but ultrafiltration modules for filtering virus may also be used. |
| Alternating Tangential Flow |
The ATF action causes cell aggregates to wash back into the vessel removing a potential blockage. The back flow part of the cycle also causes a small back flush to occur across the filter membrane, cleaning the filter pores and surface, and significantly extends the filter life. |
| Reduction of Shear |
Cells are very sensitive to shear and all competing perfusion systems (except a spin filter) use a high shear peristaltic pump to move cells through their system. The spin filter may cause cell damage by friction. The ATF uses a low shear, large surface area, diaphragm instead, reducing cell stress. |
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