More response from the Blank/reference cell. (Low mass molecules)

Dear SPR users,
While performing my experiments to find out the affinity of amino acids with my protein, I've found that the amino acids producing more response from the blank cell than the immobilized cell.
Reference cell producing 100 RU, at the same time protein cell giving only 60 RU.
In this scenario, What are all the precautions we should take care to take a valid results out of SPR?. In particular for low mw molecules/fragment screening?

Your question does not give much to work with..
Please look at www.sprpages.nl/immobilization/immobiliz...procedures/reference

For low mw molecules a good matched reference, well equilibrated system, matched buffers and double referencing should do the trick. But there are always compound that do not 'behave'.

Kind regards
Arnoud