In this doctoral work, a solution to the problem of purification of nanoparticle-protein conjugates from any other non-particular substance in solution was achieved by size exclusion chromatography. This approach was then transferred to a continuous operation mode by using a 4 zone closed loop simulated moving bed technique to achieve pilot scale productivities in the range of 0.25 g /h /L chromatography medium. Silica nanoparticles of sizes ranging from 30 nm to 1000 nm obtained by a commercial manufacturer were intensively characterized to get high quality data on the surface properties and particle properties of the nanoparticle material. Nine model proteins, selected to span a wide variety of different protein characteristics like size, charge and thermal stability, were investigated on how they interact with these particles. Structural changes in the conformation of these model proteins were monitored by circular dichroism and related to the particle size at which they occurred. Two model proteins (bovine serum albumin and myoglobin) showed structural changes, and both also showed nanoparticle size dependent structural changes. With small particle size (< 100 nm), the protein conformation remains unchanged while on larger particles (> 300nm) significant conformational changes occur. The range in which these structural changes occurred was the same for both proteins, in both cases the structural ordering of the proteins was reduced when interacting with large particles. Myoglobin and BSA showed significantly different kinetics: While myoglobin immediately changes its conformation upon adsorption, albumin first adsorbs, and then slowly changes its conformation in a timeframe of hours. This study proofed that none of the explanations proposed in any literature till now is able to fit the data. Especially the commonly used explanation of a direct influence of the surface curvature on the structural changes of the proteins is not applicable.