For many applications, it is essential to be able to control the interface between devices and the biological environment by nanoscale control of the composition of the surface chemistry and the surface topography. Application of molecular thickness coatings of biologically active macromolecules provides predictable interracial control over interactions with biological media. The covalent surface immobilization of polysaccharides, proteins and synthetic oligopeptides can be achieved via nanometres thick, interfacial bonding layers deposited by gas plasma methods, and the multi-step coating schemes are verified by XPS analyses. Interactions between biomolecular coatings and biological fluids are studied by MALDI mass spectrometry and ELISA assays. Using a colloid-modified AFM tip, quantitative measurement of interfacial forces is achieved. Comparison with theoretical predictions allows elucidation of the key interfacial forces that operate between surfaces and approaching bio-macromolecules. In this way, it is possible to unravel the fundamental information required for the guided design and optimization of biologically active nanoscale coatings that confer predictable properties to synthetic carriers used for the fabrication of bio-diagnostics and biomedical devices. By studying the relationships between interfacial forces and the adsorption of proteins, we have established the key properties that make specific polysaccharide coatings resistant to the adsorption of proteins, which is applicable to biomaterial, biosensor and biochip research.