Biomolecules in a confined solution environment may be subject to electrostatic forces with a range up to 100 nm, while van der Waals interaction will account for shorter-range forces. The response of two model poly(amino acids)—poly--lysine and poly--glutamic acid—has been investigated for a silica/Si-oxide surface at pH 6. The model amino acids were adsorbed, or covalently coupled, to colloidal probes consisting of a microsphere attached to a force-sensing lever. The methodology was based on sensing interaction between the probe and a flat surface through carrying out force versus distance analysis with a scanning force microscope. The results were analyzed within the framework of the conventional DLVO theory. The outcomes illustrate both repulsive and attractive long-range interactions that will hinder, or promote, colloidal biospecies in solution entering the region of attractive short-range interactions at the physical interface. Large ‘snap-on’ distances were observed for some systems and have been ascribed to compression of the ‘soft’ functionalized layers. Those observations and measurements of adhesion provided insight into conformation of the adsorbed species and strength of attachment. The results have implications for the efficacy of methods and devices that seek to exploit the properties of micro/nano-fluidic systems.