Radioluminescence Based Biochemical Sensing and Imaging Strategies to Measure Local Drug Release and pH

Author

Gretchen B. SchoberFollow

Date of Award

8-2022

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

Committee Chair/Advisor

Jeffrey Anker

Committee Member

Tzuen-Rong Jeremy Tzeng

Committee Member

George Chumanov

Committee Member

Joseph Kolis

Abstract

In this dissertation we describe methods for measuring infection relevant biochemical analytes using radioluminescent and ultrasound luminescent materials. Films and nanoparticles fabricated with europium doped gadolinium oxysulfide (Gd₂O₂S:Eu³⁺) are used to quantitatively measure radiolabeled pharmaceutical concentration, specifically tritium labeled vancomycin (³H-vancomycin). Europium and dysprosium doped strontium aluminate is used to fabricate an ultrasound modulated, pH sensing film. These methods are indicated for theranostic evaluation of implant associated infection. Bacterial biofilms are inherently resistant to traditional antibiotic treatment and can coat biomedical implants. These biofilm related infections are difficult or impossible to eradicate non-invasively. As a result, implant coatings for early infection detection and prevention are a promising avenue of research. Non-invasive measurement of drug release is an important metric for development of effective treatment strategies because dosage must be sustained within a therapeutic window to be effective. In vitro methods of evaluating drug release are unable to replicate biological conditions and variability seen within patients. Furthermore, early detection of implant associated infection can aid early diagnosis and treatment to mitigate infection severity. For infection prevention, using a Gd₂O₂S:Eu³⁺ film we are able to quantitatively measure antibiotic concentration at the implant surface, through 5 mm of tissue. We also demonstrate proof of principle for application of this technique with synthesized Gd₂O₂S:Eu³⁺ nanoparticles. For early detection of infection, we have developed an ultrasound luminescent chemical imaging modality, and pH sensing film, to map local acidosis due to bacterial biofilm growth at the implant surface.

Recommended Citation

Schober, Gretchen B., "Radioluminescence Based Biochemical Sensing and Imaging Strategies to Measure Local Drug Release and pH" (2022). All Dissertations. 3093.
https://open.clemson.edu/all_dissertations/3093

Author ORCID Identifier

0000-0003-4838-1044