| Type of Document |
Master's Thesis |
| Author |
Lubbers, Brad Ryan
|
| Author's Email Address |
brad.lubbers@vanderbilt.edu |
| URN |
etd-11182011-114857 |
| Title |
Isothermal Titration Calorimetry in Nanoliter Droplets with Sub-Second Time Constants |
| Degree |
Master of Science |
| Department |
Biomedical Engineering |
| Advisory Committee |
| Advisor Name |
Title |
| Franz Baudenbacher |
Committee Member |
| Joel Tellinghuisen |
Committee Member |
|
| Keywords |
- BIOMEMS
- microfabrication
- calorimetry
- cell physiology
|
| Date of Defense |
2011-12-01 |
| Availability |
unrestricted |
Abstract
I reduced the reaction volume in microfabricated suspended-membrane titration calorimeters to nanoliter droplets and improved the sensitivities to below a nanowatt with time constants of around 100ms. The device performance was characterized using exothermic acid-base neutralizations and a detailed numerical model. The finite element based numerical model allowed us to determine the sensitivities within 1% and the temporal dynamics of the temperature rise in neutralization reactions as a function of droplet size. The model was used to determine the optimum calorimeter design (membrane size and thickness, junction area, and thermopile thickness) and sensitivities for sample volumes of 1 nl for silicon nitride and polymer membranes. I obtained a maximum sensitivity of 153 pW/√Hz for a 1 µm SiN membrane and 79 pW/√Hz for a 1 µm polymer membrane. The time constant of the calorimeter system was determined experimentally by using a pulsed laser to increase the temperature of nanoliter sample volumes. For a 2.5 nanoliter sample volume, I experimentally determined a noise equivalent power of 500 pW/√Hz and a 1/e time constant of 110ms for a modified commercially available infrared sensor with a thin-film thermopile. Furthermore, I demonstrated detection of 1.4 nJ reaction energies from injection of 25 pl of 1 mM HCl into a 2.5 nl droplet of 1 mM NaOH.
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Approximate Download Time
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56K Modem |
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Masters_Thesis.pdf |
1.87 Mb |
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