Award Abstract # 1451959
CAREER: Surface and Interparticle Forces for Improved Virus Removal

NSF Org: CBET
Division of Chemical, Bioengineering, Environmental, and Transport Systems
Recipient: MICHIGAN TECHNOLOGICAL UNIVERSITY
Initial Amendment Date: January 23, 2015
Latest Amendment Date: August 22, 2018
Award Number: 1451959
Award Instrument: Continuing Grant
Program Manager: Christina Payne
cpayne@nsf.gov
 (703)292-2895
CBET
 Division of Chemical, Bioengineering, Environmental, and Transport Systems
ENG
 Directorate for Engineering
Start Date: May 1, 2015
End Date: April 30, 2022 (Estimated)
Total Intended Award Amount: $525,684.00
Total Awarded Amount to Date: $525,684.00
Funds Obligated to Date: FY 2015 = $104,633.00
FY 2016 = $203,976.00

FY 2017 = $103,512.00

FY 2018 = $113,563.00
History of Investigator:
  • Caryn Heldt (Principal Investigator)
    heldt@mtu.edu
Recipient Sponsored Research Office: Michigan Technological University
1400 TOWNSEND DR
HOUGHTON
MI  US  49931-1200
(906)487-1885
Sponsor Congressional District: 01
Primary Place of Performance: Michigan Technological University
1400 Townsend Dr.
Houghton
MI  US  49931-1295
Primary Place of Performance
Congressional District:
01
Unique Entity Identifier (UEI): GKMSN3DA6P91
Parent UEI: GKMSN3DA6P91
NSF Program(s): Interfacial Engineering Progra
Primary Program Source: 01001516DB NSF RESEARCH & RELATED ACTIVIT
01001617DB NSF RESEARCH & RELATED ACTIVIT

01001718DB NSF RESEARCH & RELATED ACTIVIT

01001819DB NSF RESEARCH & RELATED ACTIVIT
Program Reference Code(s): 007E, 1045, 7237, 9102
Program Element Code(s): 141700
Award Agency Code: 4900
Fund Agency Code: 4900
Assistance Listing Number(s): 47.041

ABSTRACT

1451959
Heldt

This CAREER project proposes a shift in the design and creation of next-generation virus removal and detection technologies. Instead of screening large libraries of chemistries to determine the ones that will most efficiently remove viruses, this project will first examine the surface chemistry of the viruses. This will lead to targeted chemistries that will attract viruses and exponentially increase the efficiency of screening processes. The process to be followed will benchmark new surface evaluation techniques with currently established surface chemistry analysis to determine if chemical forces of viruses can be determined at the single-particle scale. The CAREER education plan will train undergraduate and graduate students to be role models to high school and community college students in order to attract and retain underrepresented minorities to STEM fields. The main focus of the education plan is a collaboration with Wayne County Community College in Detroit, MI to provide engaging and hands-on research opportunities to community college students. The goal is to use research as a vehicle for sustained STEM engagement and to encourage B.S. degree completion. This unique program will expose over 500 inner city students to research opportunities and expanded career options.

The proposed work is built upon the hypothesis that an advanced understanding of viral surface chemical interactions and interparticle forces will enable a significant transformation in virus removal and detection technologies, dramatically reducing the cost while simultaneously increasing efficiency. The outcome may result in an increase in availability and accessibility to life-saving biotherapies. The overall goal of this CAREER project is to transform virus removal processes by creating a fundamental framework of viral surface and interparticle forces. The specific goals to be accomplished are: 1) Analyze the surface chemistry of several model viruses, 2) Quantify interparticle forces of model viruses and 3) Prototype a surface and interparticle force-informed method for virus removal. This study of surface and interparticle forces will benchmark traditional techniques against novel surface characterizations. Quantitative surface chemistry and interparticle force data will inform an innovative design of virus removal processes. Three relevant viruses will be used in this study, an enveloped mammalian virus, a non-enveloped mammalian virus and a bacteriophage.

PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH

Note:  When clicking on a Digital Object Identifier (DOI) number, you will be taken to an external site maintained by the publisher. Some full text articles may not yet be available without a charge during the embargo (administrative interval).

Some links on this page may take you to non-federal websites. Their policies may differ from this site.

(Showing: 1 - 10 of 28)
Areo, O., Joshi, P.U., Obrenovich, M, Tayahi, M., and Heldt. C.L. "Single-Particle Characterization of SARS-CoV-2 Isoelectric Point and Comparison to Variants of Interest" Microorganisms , v.9 , 2021 , p.1606 10.3390/microorganisms9081606.
Areo, Oluwatoyin and Joshi, Pratik U. and Obrenovich, Mark and Tayahi, Moncef and Heldt, Caryn L. "Single-Particle Characterization of SARS-CoV-2 Isoelectric Point and Comparison to Variants of Interest" Microorganisms , v.9 , 2021 https://doi.org/10.3390/microorganisms9081606 Citation Details
Habibi, Sanaz and Joshi, Pratik U. and Mi, Xue and Heldt, Caryn L. and Minerick, Adrienne R. "Changes in Membrane Dielectric Properties of Porcine Kidney Cells Provide Insight into the Antiviral Activity of Glycine" Langmuir , v.36 , 2020 https://doi.org/10.1021/acs.langmuir.0c00175 Citation Details
Habibi, S., Joshi, P.U., Mi, X., Heldt, C.L., and Minerick, A.M "Changes in membrane dielectric properties of porcine kidney cells provide insight into the antiviral activity of glycine" Langmuir , 2020
Heldt, Caryn L. and Saksule, Ashish and Joshi, Pratik U. and Ghafarian, Majid "A generalized purification step for viral particles using mannitol flocculation" Biotechnology Progress , 2018 10.1002/btpr.2651 Citation Details
Heldt, C.L., Nwamba, C., Radecki, B, Covard, D., and Czeka, S. "Environmental research to engage community college students" ASEE North Central Division Conference , v.Spring , 2018
Heldt,C.L., Saksule, A., Joshi, P., and Ghafarian., M. "A Generalized Purification Step for Viral Particles Using Mannitol Flocculation" Biotechnology Progress , v.34 , 2018 , p.1027
Heldt,C.L., Zahid,A., Vijayaragavan,K.S. and Mi, X. "Experimental and Computational Surface Hydrophobicity Analysis of a Non-enveloped Virus and Proteins." Colloids and Surfaces B. , v.153 , 2017 , p.77
Joonaki, E. Hassanpouryouzband, A., Heldt, C.L., and Areo, O. "Surface Chemistry Can Unlock Drivers of Surface Stability of SARS-CoV-2 onto the Surfaces in Variety of Environmental Conditions." Chem , v.6 , 2020 , p.2135 10.1016/j.chempr.2020.08.001
Joshi, Pratik U. and Turpeinen, Dylan G. and Schroeder, Michael and Jones, Bianca and Lyons, Audrey and Kriz, Seth and Khaksari, Maryam and O'Hagan, David and Nikam, Savita and Heldt, Caryn L. "Osmolyte enhanced aqueous twophase system for virus purification" Biotechnology and Bioengineering , v.118 , 2021 https://doi.org/10.1002/bit.27849 Citation Details
Joshi, Pratik U. and Turpeinen, Dylan G. and Weiss, Matthew and Escalante-Corbin, Glendy and Schroeder, Michael and Heldt, Caryn L. "Tie line framework to optimize non-enveloped virus recovery in aqueous two-phase systems" Journal of Chromatography B , v.1126-11 , 2019 10.1016/j.jchromb.2019.121744 Citation Details
(Showing: 1 - 10 of 28)

PROJECT OUTCOMES REPORT

Disclaimer

This Project Outcomes Report for the General Public is displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed in this Report are those of the PI and do not necessarily reflect the views of the National Science Foundation; NSF has not approved or endorsed its content.

This CAREER award was truly a way to push the lab and my career forward through innovative science and technology development. The ability to have five years to develop chemical force microscopy (CFM) as a single particle measurement of virus surface chemistry has propelled my lab into multiple new directions that were unfathomable before this award. Prior to this CAREER award, my lab focused on viral vaccine purification. We have now expanded this work to virus inactivation, thermal stability of viral vaccines, and exosome purification. We are able to study virus surface interactions at a single particle level and bring physical science to virus and macromolecule purification. This is leading to new insight into many areas of vaccine manufacturing that will have a large impact for years to come. None of this would have been possible without this award.

With the establishment of CFM for single-particle virus studies, we are learning how to separate empty and full adeno-associated virus (AAV), which is a novel new gene therapy vector and could potentially be a cure to many single-gene diseases. We are exploring how continuous purification of viral particles using aqueous extraction could decrease the development time for novel vaccines and applying this to an influenza vaccines. Continuous extraction can also be applied to many vaccines to decrease costs and time to market. We are also studying how virus inactivation occurs with surfactants, as well as understanding how virus thermal stability occurs for vaccine formulations. All of these avenues of study are being explored due to the development of CFM to study virus particles.

This CAREER award also established a research exploration at Wayne County Community College, a community college in Detroit. Community college students were exposed to research through the study of the Detroit River. Students who participated in the project were more likely to graduate from community college and more likely to complete a four-year degree than those that took a microbiology class but did not complete the research project. This helped to diversify the pipeline of students entering STEM fields. Engaging students in hands-on, exploratory projects helps to engage them with STEM and retain them through degree completion.

Bioprocessing is now an established part of the chemical engineering curriculum at Michigan Tech. We have two courses in bioprocessing and we have had over 50 undergraduate students engage in research in the Heldt Bioseparations Laboratory. Students have been placed in academic and industrial positions in many industries, but in particular in the pharmaceutical industry. This CAREER award helped to solidify the lab as a knowledge center on viral particle separation, stability, and inactivation. Industry, foundation, and federal partners have funded work in our lab and this is highly due to the development of key knowledge from this project.

 


Last Modified: 07/29/2022
Modified by: Caryn Heldt

Please report errors in award information by writing to: awardsearch@nsf.gov.

Print this page

Back to Top of page