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.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-03092015-160847 |
| Date | 24 March 2015 |
| Creators | Lubbers, Brad Ryan |
| Contributors | Hak-Joon Sung, Raymond Mernaugh, Joel Tellinghuisen, Robert Galloway, Kevin Currie, Franz Baudenbacher |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-03092015-160847/ |
| Rights | restrictone, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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