Graduate Studies
First Advisor
Fanben Meng
Committee Members
Li Tan, Jung Yul Lim
Date of this Version
8-2024
Document Type
Thesis
Citation
A thesis presented to the faculty of the Graduate College at the University of Nebraska in partial fulfillment of requirements for the degree of Master of Science
Major: Mechanical Engineering and Applied Mechanics
Under the supervision of Professor Fanben Meng
Lincoln, Nebraska, August 2024
Abstract
The development of advanced biosensing technologies is critical for understanding the complex and dynamic selective pressures within biological microenvironments, which define physiological and pathological processes. This thesis presents the design and application of 3D-printed optical biosensor arrays for spatiotemporally monitoring oxygen and pH within physiomimetic microenvironments. To address the need for high-resolution, real-time evaluation of these environmental factors, a versatile printable ink was formulated to incorporate both polar and nonpolar indicators. Using 3D printing techniques, high-resolution sensor arrays were fabricated and then calibrated to accurately measure dissolved oxygen and acidity. An environmental control system was designed to precisely regulate these two selective pressures, mimicking physiological conditions. The printed fluorescent sensor arrays showed the ability to reliably measure dissolved oxygen concentrations from 0 to 200 hPa and pH 5.5 to 9.0 through the quantification of sensor intensity. Sensor arrays were demonstrated to map heterogeneous distributions of oxygen and acidity within a 3D tumor model comprising non-small cell lung cancer cells and stromal fibroblasts embedded in a hydrogel matrix. The integrated oxygen sensors captured the formation and progression of oxygen gradients within the microenvironment over 15 days. pH sensors were used to continuously assess the progression of acidity around cells for 24 hours within a media change cycle. These multifunctional sensor arrays effectively detected the generation of hypoxic and acidic regions within the tumor microenvironment caused by the high proliferation and metabolic activity of cancer cells. Additionally, the developed fabrication method offers the flexibility to create multiplexed sensor arrays and dual-function sensors capable of simultaneously monitoring multiple parameters. This research demonstrates significant advancements in the fabrication and application of 3D-printed biosensors for tracking selective pressures in biological microenvironments. Fundamentally, the findings pave the way for future integration of these sensors into more complex tissue/organ model systems, such as vascularized tumor constructs, to investigate microenvironment heterogeneity on cancer progression and therapeutic response. Clinically, the development of wearable monitoring systems contributes to the improvement of precision diagnostics.
Advisor: Fanben Meng
Comments
Copyright 2024, Matthew F. Spieker. Used by permission