Cobalt,Silicon and Silica GLAD films for SMALDI-MS,UTLC and Tissue Imaging

• Author / Creator

  Singh,Reshma N

• The detection and identification of biomarkers and metabolites in the low mass range has become prominent in clinical diagnoses, disease monitoring and for tracking drug interactions. Laser desorption/ionization techniques have been applied as a powerful tool in this field because of their speed and simplicity. Further, the development of matrix-free substrates has emerged as an improvement for LDI in the low mass range eliminating the high background. The need for reproducibility in the fabrication of substrates has now become the focus for future development. This thesis investigates the application of cobalt, silicon and silica nano-thin films fabricated by glancing angle deposition (GLAD) for solid matrix assisted laser desorption/ionization mass spectrometry (SMALDI-MS), ultra-thin layer chromatography and tissue imaging in the low mass range. The GLAD technique produces films whose morphology in terms of pore size, density and shape can be dictated and is highly reproducible. It is also applicable to a wide range of material types, such as metals, semiconductors and oxides, this offers an exciting avenue for exploring different materials for LDI-MS applications. In the first segment of this research project, the application of cobalt GLAD films as a SMALDI-MS material was explored. Physical parameters of the films such as deposition angle and film thickness were found to have a direct impact on the SMALDI-MS performance. The selection of the optimum conditions was found to have an improvement on the signal to noise ratios of mass spectra and hence, the limit of detection. Matrix-free detection of carbohydrates, peptides and metabolites was achieved at the femtomole level. The films were also found to be highly reproducible in terms of SMALDI performance from, spot-to-spot and batch-to-batch. Next, the application of silicon GLAD films for the detection of glycolipids was investigated. Several classes of glycolipids were detected both in standard solutions and in a biofluid sample at femtomole levels. Sample cleanup on the same film was also achieved by employing the UTLC capability of GLAD. Hyphenated UTLC-SMALDI-MS was further examined in the next phase of investigation. Silica GLAD films were determined to be the optimum substrate for this combined application with a mixture of carbohydrates and peptides. Finally, silicon GLAD films were applied for the matrix free tissue imaging by LDI-MS. Animal tissue was used as the test material and lipid compounds were targeted for detection. GLAD films as a matrix-free substrate was carefully explored and has been proven as a viable material for the application. The potential of the films has also been extended to the areas of hyphenated separation and detection and to molecular imaging.

• Subjects / Keywords

  • GLAD
  • SMALDI
  • Imaging
  • UTLC

• Graduation date

  Fall 2014

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/R3PK07C36

• 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.