<p>Biomass adsorption onto surfaces has a considerable role in many fields including biological science, drug innovation, ecological engineering, separation sciences, and the medical industry. The current research is sought to explore the interactions of microbial cells (undesirable) and proteins (desirable) with chromatographic beads by employing theoretical and experimental frameworks. The extended DLVO approach was used to analyze the interaction energies, while the cell partition index (CPI) technique was used for experimental validations. The aim of this study was to better understand the adhesion of cells and propose a simplified and cost-effective strategy for protein purification in adsorption chromatography. The results of this proposed framework revealed that salt concentration influences the interaction of cells or proteins with chromatographic beads. In hydrophobic interaction chromatography, CPI values decreased with increasing salt concentration, leading to enhanced secondary energy minimum between cells or proteins and Toyopearl Phenyl 650C beads. This effect was attributed to the exposure of hydrophobic patches, which promoted attractive forces between the interacting bodies. In contrast, during ion exchange chromatography, the CPI value increased with increased salt (NaCl) concentration, resulting in reduced interactions between cells/proteins with Toyopearl SP beads. This decrease was due to electrostatic screening and charge repulsion. These trends were consistent with calculated secondary interaction energy values obtained from xDLVO calculations. This research can assist in developing cost-effective and less complicated integrative technology, xDLVO-CPI approach, for understanding the interaction behavior. These findings may contribute to the development of less complex and more economical system for the purification of commercially important biomolecules from unclarified feedstock.</p>