Date of Award
2020
Document Type
Open Access Dissertation
Degree Name
Doctor of Philosophy in Chemical Engineering (PhD)
Administrative Home Department
Department of Chemical Engineering
Advisor 1
Caryn Heldt
Committee Member 1
Adrienne Minerick
Committee Member 2
Lei Pan
Committee Member 3
Marina Tanasova
Abstract
Viral diseases take the lives of millions of people each year. The most effective methods to prevent viral disease outbreak are viral detection to reduce contact with viral pathogens and vaccines to prevent disease. To reduce the costs of the detection of viruses and improve vaccine formulation, we explored viral surface properties. The properties we have focused on are viral hydrophobicity and surface charge using chemical force microscopy (CFM). CFM is a single-particle technique that measures the adhesion force of a functionalized atomic force microscopy (AFM) probe, and in this study, a virus covalently bound to a surface. The non-enveloped porcine parvovirus (PPV) and enveloped bovine viral diarrhea virus (BVDV) were used to demonstrate the use of CFM for viral particles with different surface properties.
The high hydrophobicity of PPV and BVDV by CFM was used for a ligand-free, non-specific virus detection method that relies on the interaction of virus with osmolytes. It was previously found that the osmolyte mannitol can preferentially aggregate viruses while leaving proteins in solution. The virus was incubated with gold nanoparticles (AuNPs), and aggregation of the virus-AuNP complex with mannitol was detected by dynamic light scattering (DLS).
The isoelectric point (pI) of PPV and BVDV by CFM was used for a vaccine formulation strategy of virus particle encapsulation by polymers that relies on electrostatic interactions of the virus with polypeptides. The random screen of different ratios of polyelectrolytes to encapsulate viruses could be reduced by knowing the virus pIs. An encapsulated non-enveloped PPV is thermally stabilized, demonstrating that this method is promising for formulating thermostable vaccines.
We have developed a unique detection method and can improve vaccine formulation that would reduce the impact of viral diseases worldwide, based on the viral surface properties.
Recommended Citation
Mi, Xue, "Detection and thermal stabilization of virus based on surface properties", Open Access Dissertation, Michigan Technological University, 2020.