Science

We are looking for a postdoc to join the lab! Work is on the continuous bioprocessing of an influenza vaccine. The focus is on the biophysical characterization of viral particles to improve separations. Prior work in AFM or microfluidics a plus.

Please see https://www.employment.mtu.edu/cw/en-us/job/492705 and email heldt@mtu.edu for more information

Virus Surface Chemistry

We developed a method of chemical force microscopy (CFM) that can probe the surface chemistry of viral particles at a single particle level. This allows us to study how virus surface chemistry changes as we change the liquid environment. We are currently studying if CFM can predict chromatographic binding and elution conditions. If so, this would greatly reduce the amount of virus needed for process optimization.

Aqueous Two-Phase Extraction


Aqueous two-phase extraction (ATPE) is a bio-friendly method to purify viral particles. The method has a large amount of variables that need to be controlled, making it incompatible with the currently tight process development timelines. We are working to understand some of the key variables in ATPE so that it can be implemented in viral manufacturing processes.

Continuous Manufacturing


Another reason to study ATPE is that it is extremely amenable to continuous manufacturing. Continuous viral therapy manufacturing could speed the time to market and also make processes more versatile to manufacture more than one type of viral therapy at each facility. We have shown that continuous manufacturing can give the same results as batch, allowing for a transition to continuous viral therapy manufacturing using ATPE.

Interaction of Osmolytes with Viral Particles


We are interested in how osmolytes interact with viral particles. Osmolytes are often used in protein therapeutic formulation to stabilize proteins. This most likely occurs because the protein dehydrates and then compacts. The entropic loss of compaction is compensated by the enthalpic loss of water binding. This balance is different for viruses because they are rigid and cannot take a loss in entropy to compact. We have found that viruses can flocculate in the presence of osmolytes. We are also looking at how osmolytes can modulate ATPE.

Formulation


As the new COVID vaccines have shown, storage temperatures of vaccines can vary greatly. We have been exploring complex coacervation, a dense liquid phase, that can thermally stabilize vaccines, in collaboration with Dr. Sarah Perry at University of Massachusetts, Amherst. Complex coacervation uses molecular crowding to stabilize vaccines.