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Optical Metabolic Imaging of Tumors to Quantify Reactive Oxygen Species
Get PDFThe growth and development of cancer cells differs from that of normal cells. Cancer cells exhibit increased metabolic activity and have increased production of highly reactive molecules called Reactive Oxygen Species (ROS), which serve as regulators of important signaling pathways and promote many aspects of tumor growth and progression. Factors such as environmental changes, genetic mutations, and changes in the cellular and extracellular mechanical properties stimulate metabolic and functional heterogeneity to arise among tumor cells within the same patient. This has led to increased resistance to cancer treatments and greater difficulty in predicting how a patient���s cancer will progress. To best address the relationship between cellular metabolism and tumor heterogeneity, optical imaging microscopy is employed to detect fluorescence signals of a ROS label and NADH, an important molecule in the process of cellular energy metabolism. A cyanide experiment is conducted to induce ROS in KRC cells, and ROS fluorescence assay is subsequently used to quantify ROS production. Fluorescence images of KRC cells before and after the cyanide experiment are acquired. Results demonstrate that both the optical redox ratio and ROS increased after the addition of cyanide compared to control cells without cyanide. While more experimental trials need to be conducted, current experimental outcomes relay the potential for using the relationship between NADH redox state and ROS levels to look at different phases of the cell metabolic cycle to quantify tumor heterogeneity in the future. This can help extend our understanding of the parallel between tumor treatment response and metabolically distinct tumor cell populations which is currently not well understood
Computational Analysis of Solid Bodies Experiencing Homotopic Surface Evolution Associated with Fluid-Driven Material Loss
No full textThe responses of bodies subjected to an external fluid field are highly dependent on their outer mold lines (OML). Significant changes to the velocity and pressure fields of the fluid therefore result from changes to the OML, these changes themselves resulting from deformation due to loading, morphing, or other mechanisms. While deformations involve a body of constant mass changing shape via strains, OML shape can also be altered as a result of material loss such as erosion and other methods which remove mass from the surface. Such changes to the OML can be large and may impose significant alterations to the structural response of the body. Traditional fluid-structure interaction (FSI) methods weakly couple fluid and structural solvers such that fluid loads are used by the structural solver to obtain deformations, which update the OML; loads and displacements are iterated until an equilibrium solution is reached. To include erosion effects, a new modeling scheme is proposed in which a converged FSI solution is used to predict erosion location and magnitude to produce an updated shape for the body, which informs a subsequent FSI solution. This proposed scheme presents a novel inclusion of eroded geometry during solution of the fluid and structural responses in time while accommodating both large deformations and significant surface recession.
This work seeks to model the coupled physical effects experienced by eroding bodies carrying loads imposed by a fluid field. The proposed framework explores possible answers to the following question: To what extent does inclusion of material loss physics impact the resulting geometry and structural performance of a body? The physical couplings that exist between these mechanisms interact such that fluid forces imparted on a body affect both deformation and erosion, thereby altering the shape presented to the flow field and consequently affecting the loading. The degree to which these mechanisms are coupled is also of consequence. The need for a fully coupled implementation is demonstrated via comparisons between results considering decoupled physics results explored using an analytical implementation of Hagen-Poiseuille pipe flow. The frequency at which erosion effects must be included is also explored both with this implementation of the framework and an additional implementation exploring external flow. The framework is then implemented in 3D using commercially available tools and verified against an analytical formulation. Finally, the 3D implementation of the framework is demonstrated on a relevant engineering application
"Self-cleaning" Hydrogel Membranes for Fully Implantable Glucose Biosensors
Get PDFContinuous glucose monitors (CGMs) that permit real-time tracking of glucose levels have the potential to vastly improve diabetes management. The membrane used to construct an optical glucose sensor must address challenges related to assay retention, glucose diffusivity, and minimizing the foreign body reaction (FBR). In this work, thermosensitive, double network (DN) hydrogel membranes based on N-isopropyl-acrylamide (NIPAAm) were designed. With a tuned volume phase transition temperature (VPTT), membranes are expected to ���self-clean��� via cyclical deswelling/reswelling with body temperature fluctuations.
In a first study, the membrane mesh size was reduced with a comb architecture, towards eventual formation of a biosensor with a f��rster resonance energy transfer (FRET)-based glucose sensing assay. A tightly cross-linked first network was comprised of NIPAAm copolymerized with negatively charged 2-acrylamido-2-methylpropane sulfonic acid (AMPS), and a loosely cross-linked second network was formed from NIPAAm copolymerized with N-vinylpyrrolidone (NVP). Combs of varying charges, lengths, and concentrations were introduced to the first network. Able to achieve the targeted mesh size (~1-3 nm), negatively charged combs were the most effective in reducing mesh size, attributed to electrostatic repulsive forces.
In a second study, a membrane was customized to directly embed a phosphorescence sensing assay based on an oxygen-sensitive metalloporphyrin (HULK) and glucose oxidase (GOx). The membrane���s first network was prepared from NIPAAm and cationic (3-acrylamidopropyl)trimethylammonium chloride (APTAC). The second network was formed with NIPAAm copolymerized with acrylamide (AAm). Anionic HULK was retained via electrostatic attractive forces while the GOx was covalently bonded via a glutaraldehyde linker. A membrane achieved the desired increase in phosphorescence lifetime with increasing glucose concentrations from 50 to 200 mg/dL. A lack of sensitivity at higher glucose levels was attributed to membrane oxygen depletion.
In a final study, to improve the glucose sensitivity of the phosphorescence assay at higher glucose levels, a membrane with improved oxygen permeability was prepared by incorporation of silicone microdroplets. A ultrasonicate processor was used to disperse the silicone phase during formation of the first network and the second network was comprised of P(NIPAAm-co-AAm). With the optimal concentration of silicone microdroplets, glucose sensitivity was observed for concentrations from 100 to 300 mg/dL
