I would suggest using fluorescence microscale thermophoresis (MST) for determining Kd of aptamers and small molecules, as well as for nanoparticle complexes. (Nanotemper Inc is the supplier for the system I use, if that helps)
Thanks to all for your suggestions. ITC and MST are excellent techniques, I gather, for small molecular interactions, especially since they are not mass dependent. However, fluorescence based studies (including MST) require tagging. SPR is probably a very accurate label free technique, and there are dedicated instruments for small molecule analysis. Hopefully, I shall be able to use one of them for the work.
I would suggest KinExA technology for your measurements. KinExA instruments provide accurate data (with easy to use software) and industry leading sensitivity, ideal for determining Kd.