Key-Lock Systems for Bioseparations - Molecular Simulation for Kinetic Models

The production of biological material is always connected to separation as the active product substances like virus particles have to be harvested without additional contaminations and byproducts like cell debris and other. We investigate specifically the separation of virus particles from a cell culture based process where mammalian cells are infected by predefined virus [1]. The cells reproduce virus particles inside and release it to the solution. They also desintegrate and many different cell components are part of the final solution including the final product, the virus particles. As virus have special surface proteins like hemagglutinin they can be attached to a surface using a key-lock system.

We investigate the surface adsorption with virus material as well as with artificial nanoparticles. The artificial system  resembles the virus particles with an activated key molecule on the surface and an specifically prepared adsorption surface with the corresponding lock molecules. The attachment and detachment of particles to a surface is modeled on a molecular and discretized level.
A BiaCore system is used to obtain dynamic experimental data under variations of process parameters like concentration of nanoparticles, availability of key and lock molecules and other. The molecular simulation of the process is presented which should help to establish an appropriate kinetic model for a follow-up process systems approach.

[1] Wang, W., Wolff, M. W., Reichl, U., & Sundmacher, K. (2014). Avidity of influenza virus: Model-based identification of adsorption kinetics from surface plasmon resonance experiments. Journal of Chromatography A, 1326, 125-129.