This invention provides, and in certain specific but non-limiting aspects relates to:—assays that can be used to predict whether a given ISV will be subject to protein interference as described herein and/or give rise to an (aspecific) signal in such an assay (such as for example in an ADA immunoassay). Such predictive assays could for example be used to test whether a given ISV could have a tendency to give rise to such protein interference and/or such a signal； to select ISV's that are not or less prone to such protein interference or to giving such a signal； as an assay or test that can be used to test whether certain modification(s) to an ISV will (fully or partially) reduce its tendency to give rise to such interference or such a signal； and/or as an assay or test that can be used to guide modification or improvement of an ISV so as to reduce its tendency to give rise to such protein interference or signal；—methods for modifying and/or improving ISV's to as to remove or reduce their tendency to give rise to such protein interference or such a signal；—modifications that can be introduced into an ISV that remove or reduce its tendency to give rise to such protein interference or such a signal；—ISV's that have been specifically selected (for example, using the assay(s) described herein) to have no or low(er)/reduced tendency to give rise to such protein interference or such a signal；—modified and/or improved ISV's that have no or a low(er)/reduced tendency to give rise to such protein interference or such a signal.
