Michael Blades

Dr. Blades' research interests involve the development, characterization, and application of optical and mass spectroscopic methods for chemical analysis.  Currently all research projects are in collaboration with senior researchers at Michael Smith Laboratories (Robin Turner and Jamie Piret) and the Centre for Blood Research (Dana Devine).

Bioanalytical  Spectroscopy

Raman spectroscopy provides a robust, label-free and non-invasive method to measure the chemical composition of cells.  This provides fundamental information on their differentiation status that is complementary to the commonly used transcription factor and surface marker analysis.  This multidimensional direct measure of the cellular product quality has the great advantage that it can be implemented using a rapid noninvasive on-line technology

Embryonic stem cells (ESC)

Embryonic stem cells (ESC), derived from pre-implantation embryos, are defined by their ability to both self-renew and differentiate into all of the cells and tissues of a mature animal. Efforts to develop methods for in vitro culture of ESC for research or eventual therapeutic applications are hampered by the lack of rapid, nondestructive assays for distinguishing ESC from other (differentiated) cells within a growing culture. Our group has demonstrated that Coherent anti-Stokes Raman scattering (CARS) and spontaneous Raman microscopy can be used as a sensitive and nondestructive methods for identifying ESC based on selective observation of specific molecular vibrations believed to be spectroscopic markers indicating the differentiated vs undifferentiated states of such cells. Raman spectroscopy permits imaging with subcellular resolution, potentially offering a means by which chemical changes accompanying the early stages of differentiation may be associated with certain intracellular compartments (e.g., nucleus, cytoplasm, membranes). A novel exposure/collection configuration has been developed, which yields high collection efficiency and low interference from non-resonant background. 

Blood

Modern transfusion medicine relies on the safe, secure, and cost-effective delivery of donated red blood cells (RBCs). Once isolated, RBCs are suspended in a defined additive solution and stored in plastic blood bags in which, over time, they undergo chemical, physiological, and morphological changes that may have a deleterious impact on some patients. Regulations limit the storage period to 42 days and the cells do not routinely undergo analytical testing before use. In this study, we use Raman spectroscopy to interrogate stored RBCs and we identify metabolic and cell-breakdown products, such as haemoglobin and membrane fragments, that build-up in the blood bags as the cells age. Our work points the way to the development of an instrument which could quickly and easily assess the biochemical nature of stored RBC units before they are transfused.

Ultraviolet resonance Raman spectroscopy

Ultraviolet resonance Raman spectroscopy (UVRRS) has developed into a very powerful method for solution analysis and for biophysical measurements, including, for example, the measurement of protein structure and function.  A number of publications below describe the development, characterization, and application of a novel fiber-optic implementation of UVRRS, a methodology that was developed in our group.  This implementation is extremely useful for in-vitro and in-vivo studies of bio-molecules in their native environment {e.g. "Ultraviolet resonance Raman spectroscopy of locked single-stranded oligo(dA) reveals conformational implications of the locked ribose in LNA", Journal of Raman Spectroscopy  40 , 1162-1171 (2009)}.  The design improves collection efficiency and minimizes inner-filtering effects encountered in absorbing biological media by using a novel technique to fabricate probes using angled mirrors to effect collection at 90°.  This mitigates the deleterious effects of sample and matrix absorbance while at the same time increasing the effective numerical aperture of the collection fiber therefore increasing the collection efficiency.  A US patent was issued to us for this probe design.