Surface Plasmon Resonance Sensing of Small-Molecule Metabolites

• Author / Creator

  Cao, Yong

• Small-molecule metabolites (MW < 1,000 Da) are now emerging as an important type of biomarkers, thanks to the rapid development of systems biology such as metabolomics. Compared to nucleic acids and protein, metabolite is closer to the phenotype. Rapid detection and quantification of metabolites can potentially provide an effective way to link the metabolite profile to disease state. A sensor based approach for the measurement of metabolites can fulfill the simplicity and portability required for widespread use. Surface plasmon resonance (SPR) combined with molecular recognition elements to deliver high specificity is a sensing platform that has been widely applied for a large range of biomolecules. However, direct detection of small molecules such as metabolites with SPR challenges the refractive-index based detection mechanism due to their low molecular weights. To this regard, sensing strategies that can tackle this challenge are highly demanded. In this thesis, I successfully developed a series of indirect sensing strategies (competition, inhibition, displacement), some of which are using either small molecule or aptamer functionalized gold nanoparticle labels, to detect a few single metabolite targets. All the strategies have shown great analytical performance with good sensitivity and specificity. In each assay, either periplasmic binding protein, or antibody, or DNA aptamer, was served as the recognition element, which accounts for the high specificity observed. More importantly, the multiplexed detection of a panel of metabolites through a single SPR measurement was accomplished for the first time, based on the small molecule (micro)arrays patterned on our homemade SPR imaging chip. Compared to SPR sensing of nucleic acids and proteins, the power of this technique was underestimated in metabolites sensing. I hope this thesis can provide some insights to the SPR community and inspire more work to be done in terms of small molecule sensing, thus having more impact in the fields of medical diagnostics, therapeutic drug discovery, food safety control, and environmental monitoring.

• Subjects / Keywords

  • Biosensing
  • Surface Plasmon Resonance
  • Sensing
  • Small-Molecule Metabolites

• Graduation date

  Spring 2018

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/R3W37MB11

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.