Assessing Molecular Biomarkers in Living Mice Using Fluorescence Microendoscopy and Spectroscopy.

Assessment of molecular biomarkers expressed in cells and tissues can inform scientists and clinicians of physiological and disease processes. Optical techniques can quantitatively and noninvasively assess molecular biomarkers in living tissues. This dramatically improves our ability to study detailed behavior of disease, perform earlier detection of disease, and assess functional cellular information. However, small animals, which play an important role in the study of molecular biomarkers, pose a challenge for intravital optical assessment. In this dissertation, we engineer and demonstrate methodologies for performing intravital optical assessments, in living mice, of fluorescent biomarkers that indicate molecular expressions of disease or viability. First, we engineered a flexible fiber-optic microendoscope for longitudinal optical imaging studies in a mouse model of disseminated ovarian cancer. This microendoscope has an outer diameter of 680 µm and achieves a lateral resolution of 4 µm. The instrument repetitively monitored the growth of fluorescence-expressing ovarian cancer cells in mice for over 4 weeks, visualizing single cells, cell clusters, and tumor masses. By establishing longitudinal (non-terminal) studies, this technology allows each animal to be used as its own control, significantly reducing the number of animals needed for experimentation. We then employed fluorescence microendoscopy to validate the specific binding activity of a fluorescence-labeled peptide to colorectal dysplasia in a genetically-engineered mouse model. The microendoscope was passed through the instrument channel of a small animal endoscope for simultaneous wide-field and microscopic imaging. More than two-fold greater fluorescence intensity was measured from dysplastic tissue compared to adjacent normal mucosa. In the third part of this dissertation we developed a label-free methodology employing a handheld fluorescence lifetime spectroscopy probe to optically assess tissue engineered constructs that were implanted in living mice. Clinical translation of tissue engineered constructs requires noninvasive methods for assessing their integration with host tissue after grafting. Our instrumentation noninvasively sensed endogenous fluorophores in the tissue constructs that correlate to in vitro measures of cellular viability. Finally, we report the design and construction of a depth-resolved fluorescence lifetime spectroscopy system, which could be used for assessing the viability of tissue-engineered constructs with greater specificity than the demonstrated probe.PHDBiomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/108845/1/sfelahi_1.pd

Future and advances in endoscopy

The future of endoscopy will be dictated by rapid technological advances in the development of light sources, optical fibers, and miniature scanners that will allow for images to be collected in multiple spectral regimes, with greater tissue penetration, and in three dimensions. These engineering breakthroughs will be integrated with novel molecular probes that are highly specific for unique proteins to target diseased tissues. Applications include early cancer detection by imaging molecular changes that occur before gross morphological abnormalities, personalized medicine by visualizing molecular targets specific to individual patients, and image guided therapy by localizing tumor margins and monitoring for recurrence. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87084/1/471_ftp.pd

Hydraulic Hybrid Fluid Conditioning System

Capstone Design and Manufacturing Experience: Winter 2006The University of Michigan Challenge X Team is designing a series configuration hydraulic-diesel hybrid powertrain for the Chevy Equinox platform. This powertrain uses a small diesel engine that is less powerful and more efficient than that used in a conventional powertrain, but when coupled with the hydraulic powertrain, it maintains, or even exceeds, the original performance. Using a smaller engine minimizes energy consumption and emission of greenhouse gases. When braking, the hydraulic system can also recover energy normally dissipated as heat in a conventional system. Maintenance of the hydraulic fluid is important to the well-being of the system. Small debris, high temperatures, and nitrogen gas in the fluid can cause serious problems through wear, breakdown, and cavitation. These problems necessitate the use of a fluid conditioning system to filter debris, maintain the temperature, and monitor the level of aeration in the fluid, which is the purpose of our project.http://deepblue.lib.umich.edu/bitstream/2027.42/49579/2/proj20_report.pd