The effect of mechanical rigidity on the entrapment of bionanoparticles in narrow channels



The migration of bionanoparticles such as viruses, virus-like particles, gene-therapy vehicles in packed beds, capillary structures, filters, and monoliths is not well understood. When they travel down the column they may either accumulate at the wall of the channel or concentrate in the center of the flow path. Segre and Silberberg (1961) observed the phenomenon that red blood cells concentrate in the centre of a capillary, but when they are made stiff by crosslinking with glutardialdehyde they loose this property. Porter (1972) explained the improvement of mass flow in colloidal suspension by “Tubular Pinch Effect”. A lateral mass transport is induced by inertia of the particles causing the accumulation in the center as a function of the radius of the particle to the power of 2 to 3.

It is not clear, if particles such as viruses, virus-like particles, gene-therapy vehicles in the size range of 30-300 nm have the same properties and also accumulate in the center of channels. These particles are at least 10-100 times smaller than the particles tested by Segre and Silberberg (1961) and Porter (1972). Understanding of these mechanisms may help to understand how viruses or VLPs migrate in small channels, help to design new separation methods and biophysical properties of bionanoparticles.

Aims and methods.

The aim of this thesis is to establish a model of how bionanoparticles such as viruses, virus-like particles, or gene-therapy vehicles flow through narrow channels and to determine how significant the lateral transport towards the centre is. It will also be elucidated how the stiffness of the particle influences the lateral transport towards the centre.

As models we will use enveloped virus-like particles, based on HIG-1 Gag-protein, baculovirus which are soft bionanoparticles, naked capsid virus-like particles and rigid silica nanoparticles. The flow in narrow channels will be simulated in capillary monoliths, packed beds and micro/nanofluidics devices. Under conditions where the bionanoparticles cannot bind, the number of particles at the entrance and exit of the channel will be counted. The channel geometry will be measured by SEM. The flow will be simulated by computational fluid dynamics using STAR CC+ (Jungreuthmayer et al., 2015). The particle lateral transport will be tested at different velocities, channel width and viscosities and a numerical simulation will help to establish an engineering correlation.

Collaborations within this thesis will include GRABHERR (Virus and VLP production).

Jungreuthmayer, C., Steppert, P., Sekot, G., Zankel, A., Reingruber, H., Zanghellini, J., Jungbauer, A. (2015) The 3D pore structure and fluid dynamics simulation of macroporous monoliths: High permeability due to alternating channel width. J. Chromatogr. A 1425, 141-149. doi: 10.1016/j.chroma.2015.11.026
Porter, M.C. (1972) Concentration Polarization with Membrane Ultrafiltration. Ind. Eng. Chem. Prod. Res. Devel. 11, 234-248. doi: 10.1021/i360043a002
Segré, G. and Silberberg A. (1961) Radial particle displacements in poiseuille flow of suspensions. Nature 189, 209-210. doi: 10.1038/189209a0