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.

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.

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.

We study the intricate mechanisms of virus-antiviral interactions to drive innovation in antiviral materials and biomanufacturing. Using advanced tools like TEM, AFM, and DLS, along with infectivity assays, we investigate how antiviral agents disrupt viral structure and function. From testing antiviral coatings for N-95 masks to understanding surfactant-mediated virus inactivation, our research bridges virology and engineering to accelerate the fight against infectious diseases.

The application of EVs for diagnostic and therapeutic treatment of diseases like cancer relies on optimizing current isolation and characterization methods due to EV heterogeneity in size and cargo. In the Heldt lab, we apply atomic force microscopy (AFM) and chemical force microscopy (CFM) methods to characterize the physicochemical properties of EVs.

Vaccines are thermolabile biomolecules and degrade quickly at temperatures above their recommended storage temperature which is most often between 2 and 8 degrees Celsius (35 to 46 F). Keeping vaccines at low temperatures is expensive and also limits their accessibility worldwide. We are trying to increase the stability of vaccines at higher temperatures by elucidating how the addition of different additives can preserve them. Once we better understand the thermostability behavior of different additives, we can significantly reduce the time and expense required to develop vaccine formulations. Additionally, 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.