- Chem Sci 305B
- Director, Health Research Institute
- James and Lorna Mack Chair in Bioengineering
- Professor, Chemical Engineering
- PhD, North Carolina State University
My research group uses natural and artificial molecular recognition events to (i) remove and/ or purify pathogens and toxins to reduce disease burden worldwide and (ii) detect pathogens and toxins quickly and inexpensively with point-of-care devices.
Virus Removal and Detection
A biotherapeutic is any product that is made to improve human health and comes from a biological source, including human blood plasma, animals, cell culture or bacterial fermentation. The sources of these products are living organisms, so there is an inherent risk that these products may contain viruses that could infect patients receiving the therapy. In the recent past, these products have maintained a good safety record, but there is a long and growing list of viruses that may contaminate biotherapeutic products, including West Nile Virus and Hepatitis C, and safety concerns still exist. The current methods for virus clearance are inactivation for enveloped viruses and physical removal for nonenveloped viruses. The inactivation of enveloped viruses works well with little known contamination, but the breakthrough and contamination of biological products by nonenveloped viruses has been demonstrated. This reveals the need to find better removal techniques for nonenveloped viruses. We are interested in finding methods, including precipitation, filtration, and affinity techniques to improve the removal of nonenveloped viruses from biotherapeutics.
In conjunction with our work on virus removal, we are also interested in purifying viruses for vaccine production. Vaccine production faces a challenge in adopting conventional downstream processing steps that can efficiently purify large viral particles while maintaining purity, potency and quality. The industry currently considers 30% as an acceptable virus recovery for a vaccine purification process, including all downstream processes, whereas antibody recovery from CHO cell culture is generally around 80-85%. We are studying different methods of virus purification in the search for a platform technology that would revolutionize the vaccine industry.
Biosensors have the potential to save lives by quickly detecting biomarkers, pathogens or other materials in the environment with a low-cost device. A marketable biosensor needs to quickly and selectively detect a target analyte in a variety of solution conditions. Sensors can use a host of detecting platforms, and one of the most sensitive is the amperometric sensor, where the concentration of a chemical can be transformed into an electrical signal. High surface area graphene has been shown to produce a quick signal and sensor functionalization creates specificity. We study graphene composite sensors that have a large range of resistance and functionalization chemistries available. Our goal is to create quick and robust sensors that can assist in disease diagnosis, determination of environmental toxins, and detection of bioterrorism threats.
Links of Interest
- Virus removal and detection
- Meng, H., Forooshani, P.K, Joshi, P.U., Osborne, J., Mi, X., Meingast, C., Kelley, J., Narkar, A.R., He, W., Frost, M.C., Heldt, C.L., and Lee, B.P. (2018) Biomimetic Recyclable Microgels for On Demand Generation of Hydrogen Peroxide and Antipathogenic Application. Acta Biomaterialia. In press.
- Heldt, C.L., Smith, E., Cunningham, H., and Miller, C. (2018) Mentoring Students in Research and Communication Across the Ocean. PURM 7.1.
- Heldt, C.L., Saksule, A., Joshi, P.U., and Ghafarian., M. (2018) A Generalized Purification Step for Viral Particles Using Mannitol Flocculation. Biotechnology Progress. 34(4): 1027-1035.
- Heldt, C.L., Zahid, A., Vijayaragavan, K.S. and Mi, X. (2017) Experimental and Computational Surface Hydrophobicity Analysis of a Non-enveloped Virus and Proteins. Colloids and Surfaces B. 153: 77-84.
- Gencoglu, M. F. and Heldt, C. L. (2015) Enveloped Virus Flocculation and Removal in Osmolyte Solutions. Journal of Biotechnology. 206, 8-11.
- Vijayaragavan, K. S., Zahid, A., Young, J.W. and Heldt, C. L. (2014). Separation of porcine parvovirus from bovine serum albumin using PEG-salt aqueous two-phase system. Journal of Chromatography B 967, 118-126.
- Gencoglu, M. F., Pearson, E. and Heldt, C. L. (2014). Porcine Parvovirus Flocculation and Removal in the Presence of Protecting Osmolytes. Journal of Biotechnology 186, 83-90.