MICROFLUIDIC SYSTEMS FOR ISOLATING AND ANALYZING CIRCULATING CANCER CELLS FROM THE PERIPHERAL BLOOD OF PATIENTS WITH EPITHELIAL CANCERS AND ACUTE MYELOID LEUKEMIA Public Deposited

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  • March 19, 2019
Creator
  • Jackson, Joshua
    • Affiliation: College of Arts and Sciences, Department of Chemistry
Abstract
  • Simple, effective, and minimally invasive methods for the routine screening of patients for cancer, the monitoring of treatment efficacy, and the early detection of relapse are needed to reduce the substantial burden cancer has on society. In this dissertation, we detail a microfluidic device that processes a patient’s peripheral blood in search for extremely rare cancer cells that are shed from the tumor. The technique uses cancer-specific antibodies to recognize and retain cancer cells within the device, which can be analyzed after purification to provide information to clinicians that can guide precision medicine. We developed computational models that describe the binding of cancer cells to antibodies coated along the microfluidic surfaces, the hydrodynamic removal of the abundant normal blood components, and highly parallelized microfluidic networks that can reduce analysis time. All of these factors guided the design of a microfluidic technology that can process blood rapidly, achieve state-of-the-art purity, and recover cancer cells efficiently. We enabled the use of mass-produced thermoplastic devices for the analysis by thoroughly characterizing the oxidation of polymers surface and the covalent attachment of antibodies. This work led to dense antibody loading and improved efficiency in cancer cell recovery. Further, after carefully reviewing the literature, we identified a lack of methods for the selective release of the purified cancer cells for off-chip analysis. Thus, we successfully developed the use of oligonucleotide linkers for antibody immobilization that can be enzymatically cleaved for the efficient release of viable cancer cells. All of these findings culminated in a pilot study where we monitored high risk patients with acute myeloid leukemia as they recovered from a stem cell transplant. Using this minimally invasive microfluidic assay, we frequently sampled these patients every two weeks and observed the progression of residual leukemia far earlier than the highly invasive and less sensitive tests that are currently available. Such results can pinpoint the onset of disease relapse and lead clinicians to provide preventative treatments when they would be most effective.
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  • In Copyright
Advisor
  • Ramsey, J. Michael
  • Taylor, Anne
  • Jorgenson, James
  • Soper, Steven
  • Walker, Glenn
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2015
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  • Chapel Hill, NC
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