Hi! Up until this point I have discussed specific unit operations in downstream processing,
but not really how to differentiate between,
let’s say, distillation or extraction...or centrifugation versus micro-filtration…
So how do we select appropriate technology?
Imagine that we want to produce and purify penicillin V.
After fermentation, we have a fermentation broth that contains sixty-three grams per litre of penicillin V.
The big question is: how do I know which separation technology I should use?
Well, a good approach is knowing what your purification target is going to be.
It’s important to know whether the product needs to be 50% or 99.99% pure.
The next step involves looking at the starting point,
which is the fermentation broth that comes from the fermenter.
What can be found besides the product?
Probably a lot of water, salts, biomass...glucose perhaps?
The third step involves determining the separation criteria.
What do you want to achieve in each part of the factory?
Do you want to get rid of the biomass or side-products?
Perhaps you want to concentrate the products?
You can do this by drawing block-schemes.
Once you’ve done this you can move forward to the technology selection part
and start generating some alternatives.
Subsequently, we reduce the number of alternatives by taking a closer look at the individual unit operations.
The final part is designing the overall process in a dedicated software package
to perform an economic evaluation.
An outcome might be that certain steps in the process are very costly,
and therefore it might be beneficial to start evaluating alternatives for that unit operation.
When the fermentation broth leaves the fermenter, a mix of components can be found inside the broth.
Obviously, there is penicillin V in there, but also a significant amount of biomass,
acetic acid, and a variety of other compounds.
What we will then do is take a closer look at the physical states of the compounds
as well as their concentrations.
Moreover, we will need to zoom in on some of the physicochemical properties of the individual compounds.
Aspects such as size, solubility, hydrophobicity, vapour pressure, and so on should be taken into account.
Once we have made this list we can use all these properties to generate the block schemes.
If we want to use this information to design a process scheme, we first use a filter to remove the biomass.
After the biomass is removed, we can either use a liquid-liquid extraction or a precipitation,
since penicillin V has a relatively low water solubility.
Afterwards we will need to remove some impurities, which we do using either chromatography or extraction.
The final steps will be crystallisation and then drying.
So, if we add some more detail to the process we will see that there are now two options
available to remove the biomass from the broth, being the rotary vacuum drum filter and the belt filter.
Also, to concentrate the penicillin V we can apply two types of liquid-liquid extraction
or we perform a chemical precipitation.
As a final purification step we can apply ion exchange or reversed phase chromatography.
Additionally, we could apply another organic extraction step.
So how do we choose between the rotary vacuum drum filtration and belt filtration?
Well, in order to do so you’ll need to have a deeper understanding of each of the unit operations.
You could perhaps estimate the performance from models that can be found in books or articles.
Another approach is to look at the literature that compares both techniques in this specific case,
but this tends to be quite rare.
If literature only refers to one type of technique, this tends to be a good approach,
however, is quite risky and some techniques are only used on lab scale!
The best one would be to test this experimentally, but this is obviously also the most expensive approach.
The final approach would be to use dedicated software packages to estimate the effectiveness
and economics of a certain unit operation.
To summarize: what is a good workflow...?
Well, the first step is to analyse the complete media.
What kind of compounds are present and in which concentrations.
After that, look for characteristics of these compounds which you can use to your advantage
to separate one from the other.
After that, couple the physical properties to the right separation technology.
Now it is time to start making a simple block scheme, where the flow sizes are highlighted
as well as some general operating conditions at each block.
Then it is time to do a straightforward process design in a dedicated software package.
Incorporate side-streams in the process and reuse them.
Finally, perform an economic analysis.
If certain unit operations seem ridiculously expensive it is worthwhile to consider alternatives.
If that isn’t the case, but your process isn’t profitable,
consider integrating several unit operations to cut costs.
I hope you have now learned what a good procedure is to select appropriate technologies for a process,
and what approaches you can take to choose between many types of unit operations.
See you next time!