How do particle size and flow rate affect normal-phase flash column chromatography?

Media particle size and solvent flow rate play major roles in chromatographic separations including flash purification.  This is true in both reversed-phase chromatography (aka partition chromatography) as well as normal-phase chromatography.

The roles played are related to the overall compound mass-transfer kinetics and diffusion/dispersion as they migrate through the column.  Smaller particles reduce sample dilution by reducing interstitial volume, while flow rate impacts the ability of molecules to efficiently pass through the porous particles.

In this post, I will show how both particle size and flow rate impact flash chromatography.

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Published by

Bob Bickler

Technical Specialist, Biotage

2 thoughts on “How do particle size and flow rate affect normal-phase flash column chromatography?”

  1. Hello Bob
    That’s interesting. 40years ago I asked what flow rate should I use with 60um flash silica and was told to use 80% of the flow rate used for 5um analytical hplc and scale according to cross sectional area. I stuck to this for years. Our automated flash systems tend to use a much higher default flow rate which is fine for easy separations but when it’s a bit difficult I always go back to the lower flow. I don’t know the internal diameter of your columns but I guess the 5ml/min flow is much the same as my preferred flow and it’s nice to see this is justified.
    As for smaller particle sizes on a flash system, we have 15um available and I use 100% of the flow rate used for 5um analytical hplc. When the columns are quite long, say about 24cm, then the back pressure is about the maximum for our system so there is no option to go faster.

    1. Hi Derek,

      Forty years ago I was just getting my feet wet learning chromatography and so was the technology/science around it – much has evolved since those early days. Scaling load based on cross-sectional area ratios works but, as you too have seen, flow rate will not scale linearly. So, matching linear velocity is the way to go. Smaller particle media tend to have a higher optimal linear velocity and a wider flow range where good chromatography is achievable and likely accounts for your success using flow rates (velocities) similar to those used with 5um media.

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