Novel MOS-Based Biomolecule Detection Techniques
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This thesis advances the state of the art in biomolecule detection by allowing for quantitative detection using radioactive labels whose decay is detected by a pixelated complementary metal-oxide-semiconductor (CMOS), or CMOS-compatible, sensor. Additionally, the usefulness of this technology as a testbed for radioimmunotherapy (RIT) pharmaceuticals is considered. For the first time a CMOS image sensor has been used to detect the presence of radiolabelled target biomolecules captured on a functionalized surface. Using aptamer functionalization the system successfully detected phosphorus-32 labelled adenosine triphosphate (ATP) at a surface concentration of 2.3 x 10^7 molecules/cm^2, well below those typically associated with fluorescence-based sensor architectures. The system has also demonstrated its amenability to multiplexed biomolecule detection. Geant4, a Monte Carlo toolkit for simulating the passage of radiation through matter, was used to model the detection system. This system has applications in quantitative biomolecule detection and in the development of RIT pharmaceuticals employing beta particle emitting isotopes. Also for the first time, a MOS sensor has been designed, fabricated, and tested for use in the characterization of targeted alpha therapy (TAT) pharmaceuticals. The sensor consists of a 16 by 16 array of 100 micrometer square alpha particle sensitive cells fabricated in-house using a simple nMOS process. A subset of the cells are functionalized for the attachment of chelators under investigation for new pharmaceuticals. To demonstrate the utility of this sensor as a characterization platform, cells functionalized with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-DNA conjugates were used to chelate americium-241 from solution, and the alpha particle emissions over the surface of the IC measured. The IC was able to quantitatively determine the amount of alpha emitter present over each cell, allowing the chelator and chelating chemistry to be assessed. Without any optimization of the chelation chemistry, a 21% increase of emissions was detected on cells functionalized with DOTA relative to unfunctionalized cells.
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Copyright © 2014 the author(s). Theses may be used for non-commercial research, educational, or related academic purposes only. Such uses include personal study, research, scholarship, and teaching. Theses may only be shared by linking to Carleton University Institutional Repository and no part may be used without proper attribution to the author. No part may be used for commercial purposes directly or indirectly via a for-profit platform; no adaptation or derivative works are permitted without consent from the copyright owner.
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- 2014
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