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Grabinski_Dissertation_final.pdf (3.54 MB)

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NANOPARTICLE DEPOSITION AND DOSIMETRY FOR IN VITRO TOXICOLOGY

Grabinski, Christin M
http://orcid.org/0000-0003-1622-9355
http://rave.ohiolink.edu/etdc/view?acc_num=case1428085283

Abstract Details

2015, Doctor of Philosophy, Case Western Reserve University, Chemical Engineering.
This thesis addresses several issues in the field of in vitro toxicology involving particle exposure. First, controlling and assessing particle dosimetry in in vitro models is addressed. Traditional in vitro models expose cells grown at the bottom of a dish to nanoparticles under static conditions, regardless of the exposure route of interest (e.g. inhalation, ingestion, systemic translocation). We demonstrated the use of flowing media to reduce sedimentation and simplify dosimetry. The shear stress introduced at the cell layer was found to be much lower than physiological conditions, avoiding potential damage to the cells, and allowing this model to serve as a straightforward approach for dosimetry that can be easily adopted using standard cell culture tools for a broad range of cell types. For the second and third studies, aerosol methods were used to represent inhalation exposure. In the second study, the deposition of ultrafine (<100 nm) and fine (100–2500 nm) aerosol particles onto cells at an air–liquid interface (ALI) was investigated. We studied the effect of chamber design and electrostatics on aerosol deposition using both theoretical and empirical techniques to provide guidelines for controlling the dose of submicron aerosols, which has been a significant challenge to date. Third, we designed and validated a scaled–up portable multi–well aerosol exposure chamber (PM–AEC). The device contains eight wells for cell culture inserts arranged radially, a heated water bath which maintains internal temperature, and electrodes above and below the ALI to allow for electrostatic deposition of particles flowing past the cell culture inserts. The key unique feature of the chamber is the ability to access cell culture media outside of a sterile environment by penetrating resealable silicone walls. To demonstrate portability, the chamber was loaded with live cell cultures and transported to a field environment where the cells were exposed to emissions from energetic material impaction testing. Overall, the PM-AEC was demonstrated as a useful tool for relevant exposure of aerosolized particles to cells cultured at the ALI, showing promise for assessing particle toxicity in realistic environments.
R. Mohan Sankaran, PhD (Advisor)
Saber M. Hussain, PhD (Advisor)
Donald L. Feke, PhD (Committee Member)
Nicole F. Steinmetz, PhD (Committee Member)
Harihara Baskaran, PhD (Committee Member)
134 p.
Chemical Engineering; Materials Science; Nanotechnology; Toxicology
dynamic flow model, aerosol exposure, multiphysics simulation, nanotoxicology

Recommended Citations

Citations

  • Grabinski, C. M. (2015). NANOPARTICLE DEPOSITION AND DOSIMETRY FOR IN VITRO TOXICOLOGY [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1428085283

    APA Style (7th edition)

  • Grabinski, Christin. NANOPARTICLE DEPOSITION AND DOSIMETRY FOR IN VITRO TOXICOLOGY . 2015. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1428085283.

    MLA Style (8th edition)

  • Grabinski, Christin. "NANOPARTICLE DEPOSITION AND DOSIMETRY FOR IN VITRO TOXICOLOGY ." Doctoral dissertation, Case Western Reserve University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=case1428085283

    Chicago Manual of Style (17th edition)

case1428085283
752
© 2015, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.