Date of Award

8-2026

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

Committee Chair/Advisor

Jeffrey Anker

Committee Member

George Chumanov

Committee Member

Jason Mcneill

Committee Member

Zhi Gao

Committee Member

Sriparna Bhattacharya

Abstract

Oxygen plays a crucial role in stem cell maintenance, tissue regeneration, disease progression, and treatment efficacy. For example, understanding oxygen dynamics within implanted medical devices, such as bone scaffolds, is essential for successful tissue regeneration and can serve as an early indicator of infection. The existing oxygen sensing and imaging techniques are often limited by narrow imaging depth, low spatial resolution in vivo resulting in poor understanding of oxygen dynamics in tissue microenvironments. This dissertation describes the development of implantable sensors using X-ray scintillators and thermochromic leuco dye paired with phosphorescent oxygen dye (PtTFPP) to image oxygen using X-ray luminescent chemical imaging (XELCI) and ultrasound luminescent chemical imaging (ULCI) techniques. The first approach involved the development of an X-ray luminescent oxygen sensor (LSO–PtTFPP) for profiling local oxygen concentrations within bone scaffolds. The sensor consists of an X-ray scintillator (Lu₂SiO₅:Ce), which emits radioluminescence upon X-ray excitation, and an oxygen-sensitive phosphorescent dye (PtTFPP), which absorbs a portion of this luminescence and emits oxygen-dependent phosphorescence. The sensor exhibited a 27-fold increase in phosphorescence intensity between 21 and 0 kPa oxygen and a 3.5-fold enhancement in signal intensity when imaged through tissue. To improve measurement robustness, an oxygen-insensitive reference scintillator (Gd₂O₂S:Eu) was incorporated to develop a ratiometric sensor (LSO–GOS–PtTFPP). This sensor maintained a comparable increase in phosphorescence intensity and a quantifiable oxygen range of 0–5 kPa as LSO-PtTFPP sensor. The optimized sensor was then cut into 50–100 μm width fibers and successfully V demonstrated oxygen imaging through 3D printed bone scaffolds with ~1.8-fold increase in intensity between 21 and 0 kPa oxygen.

The second approach developed a temperature-modulated oxygen sensor (TLD–PtTFPP) for ULCI. The sensor combines a thermochromic leuco dye (TLD), which undergoes phase transition resulting in a reversible color change from blue to colorless upon ultrasound-induced heating, with PtTFPP dye to produce a locally modulated oxygen-dependent optical signal. Preliminary studies demonstrated proof of concept by distinguishing between 0 and 21 kPa oxygen under pulsed ultrasound excitation. A ULCI imaging system compatible with our ULCI sensors was also developed, although further optimization is required before imaging.

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