Ion exchange chromatography is, I believe, easier to scale up than size exclusion.

Dear Adam B Shapiro

I have tried Q-sepharose anion exchange it didnt work unfortunately. In parallel I decreased pH of protein solution less than PI, in order to apply cation exchange, I found out that in lower than pH 4, beta sheet of the protein was miss fold.

Size exclusion sucks. I know of no large-scale process that uses it.

You may have to play around a bit with your chromatography conditions, but the majority of proteins bind to Q-resins or to SP-resins.

What were the conditions you used to bond your protein to Q-Sepharose?

Buffer composition, buffer strength, any salts, pH, conductivity; the pI of your protein...

@achim Recktenwald

Tris base buffer, pH 7.0, by setting 10 CV gradient with NaCl 150mM

PI of the protein is approx 4.7

Thanks

What was the strength of your TRIS buffer? 30mM is usually a good choice.

You are too low with your pH. Try pH 8 to 8.5, same buffer - this is the normal pH-range used with anion exchange of proteins.

As you do not know much about the behavior of the protein, go with your salt gradient to at least 500mM.