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Title page for ETD etd-03092015-160847


Type of Document Dissertation
Author Lubbers, Brad Ryan
Author's Email Address brad.lubbers@gmail.com
URN etd-03092015-160847
Title Nano-Calorimetry for Point of Care Diagnostics
Degree PhD
Department Biomedical Engineering
Advisory Committee
Advisor Name Title
Franz Baudenbacher Committee Chair
Hak-Joon Sung Committee Member
Joel Tellinghuisen Committee Member
Kevin Currie Committee Member
Raymond Mernaugh Committee Member
Robert Galloway Committee Member
Keywords
  • microfabrication
  • Phenylketonuria
  • trastuzumab
  • Thermometric ELISA
  • nano-calorimetry
  • point of care
Date of Defense 2015-03-23
Availability unrestricted
Abstract
Calorimetry has many applications in the physical and life sciences including measuring phase changes, determining reaction equilibria, detecting protein binding events, and quantifying enzyme kinetics. Towards the goal of creating more sensitive calorimeters, we examined nanowatt scale reactions utilizing commercial IR sensors. With this information, we created heat flow models to aid in the optimization of future device designs. From there, best in class nano-calorimeters with 375 pW/Hz1/2 resolution were fabricated and applied to the need for better point of care (POC) assays in the medical field. We developed nanoliter scale thermometric enzyme-linked immunosorbent assay (TELISA) for use in measuring the anti-cancer monoclonal antibody trastuzumab. We measured therapeutic levels of trastuzumab (10-100 µg/ml) in human serum to help enhance clinical outcomes and aid in further drug development. By utilizing standard ELISA reagents this assay can be applied to a broad range of analytes, bringing with it cost, sample, and time savings. In order to better manage metabolic diseases related to the loss of function of key enzymes and transporters in the metabolic pathway, we demonstrated POC detection of phenylalanine down to 5 mM. The incorporation of capillary microfluidic channels into our calorimeter allowed for automatic sample delivery from a finger prick blood draw. With improvement, this could lead to the first POC device for management of Phenylketonuria.
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