Three reasons why you should believe in displacement for preparative chromatography

 

We’ve devoted a lot of our recent posts to the application of displacement chromatography (DC) for analytical chromatography. Today, let’s talk a little bit about DC and preparative chromatography.

In the preparative mode your goal is to purify a product.  Why should you consider displacement chromatography for preparative chromatography? If you want to purify a product by chromatography and if you choose displacement you can get the following three benefits:

• Very high loadings
• High yield and recovery
• High purity

ALL AT ONCE (supporting data)

Why does this matter? Of the main methods of purification, chromatography is relatively expensive. If the chromatographic purification step is such a high value process, it will most likely be applied to purify high-value products (i.e. drugs – they tend to be expensive and need high purity). Given the benefits mentioned above, if you generally obtain a 30%  yield by other purification chromatography, with DC your potential yield could be around 90%. Doesn’t that sound great?

So, what is the Catch 22, you might ask. Overall displacement chromatography faces three challenges.

First, displacement chromatography is rarely taught in college programs. Most scientists are trained in elution chromatography and may not believe in the big promise that displacement chromatography makes. Furthermore and by no means surprising, many scientists quite naturally approach displacement chromatography with the concepts of elution in mind. However, displacement is set up in a fundamentally different way and one almost has to approach this process with a fresh mind. If you want to try out DC for your processes you will be most successful if you approach this process with an open mind, intellectual curiosity and willingness to "think outside the box".   Probably the biggest hurdle for successfully running DC for your purification process is you.

I have recently watched a movie called ‘The Code’ with Morgan Freeman and Antonio Banderas. In the movie, the protagonists Gabriel and Ripley are planning a big heist, the objects of desire being two prized Faberge eggs. The treasure is in a high-tech vault in a high-security building. The vault is secured with a 9-digit code – in essence, the protagonists of the movie not only have to get into the building but also figure out all the variables of the 9-digit access code to access their treasure.  While we don’t want to bring out the criminal mind in you and get you ready to plan a heist of your own, displacement chromatography brings up a similar set of challenges but also potential "treasures".

You have to "invest" into learning and optimizing DC for you. However, once you have the system set up, you are ready to speed along and reap the rewards and glory (minus the legal repercussions…;-)).

So, if you are one of those uncompromising, daring people that want to eat the cake and have it too…DC is for you. ;-) (P.S. Genentech and Lonza are among the "pioneers" trying our displacement chromatography for their processes).

Comments

[Kune]

No information in this article. It talk of three challenges to tell us one: that displacement chromatography is not taught in college. Or is the second challenge that chromatographers mostly have elution chromatography in mind? How is that a challenge? A challenge for the technique? Well, I am not interested how hard this lovely little technique has to fight to be accepted among the big bullies of elution chromatography. I am interested to read WHAT IS IT that makes it so great? Yes, the article mentions three points, but everyone claims that and the article does not substantiate a single one of them. So, how does it compare to the other techniques? Will it give 1.1 times the productivity? 11 times the productivity? 110 times the productivity?

So, the question remains, why is displacement chromatography such a great idea for preparative chromatography? Reading this article is a waste of time.

[The Displacement Chromatography Blog]

Dear Mr. Kune - thanks for your comment. Here's some data to review:
1) Practical Purification of Oligos using DC-- You'll see that in DC experiments loading is between 50-80% and the main component is 98% pure. http://www.sacheminc.com/content/view/364/679/
2) Another example on "model" proteins where DC achieves over 100mg of purified protein on a single analytical run.
http://www.sacheminc.com/industries/example-results/purification-of-bovine-beta-lactoglobulin-using-sachems-expelltrade-q1.html
3) Here is another chart showing the comparison of optimized displacement vs. self-displacement vs. optimized elution and the comparison of purity and recovery on fraction pools: http://www.sacheminc.com/industries/example-results/purification-of-cytochrome-c-mixture-using-sachems-expelltrade-sp1.html
4) If you don't want to take the DC Blog's word for it, look at some of the work from Genentech. http://www.sacheminc.com/content/view/397/204/
Instead of 300 elution cycles they carried out one DC run and achieved the same result.

Remember though, DC is a tool --it's not going to solve everything. The intention of the blog is to stay open-minded about tool and technologies and where they might best be applied. Elution has its place, as does DC. We look forward to hearing from you.