Development of a Platform for Surface Enhanced Raman Scattering Endoscopy

Surgical resection or ablation remains the primary curative treatment strategy for most early-stage solid cancers and, as such, an enormous amount of effort has been dedicated to technologies that augment the vision of the surgeon to better `see' the margins of the tumor being removed. With our ever-expanding knowledge of the genetic changes which underpin malignancies, the idea of adding `biochemical vision' to the surgeon's decision making process should allow for clearer identification of margins, more complete resections with no residual tissue left in-situ, and consequent improvement in local recurrence rates. By performing such early-stage resections endoscopically, patients may benefit from lower morbidity rates as compared to traditional open approaches. Molecular imaging using surface enhanced Raman scattering (SERS) nanoparticles represents a platform which is well-suited for cancer detection in-vivo. It has already been established that SERS offers the ability to carry out multiplex assays far in excess of what is possible with fluorescence, that the SERS signal is detectable at concentrations far below what is resolvable with similar amounts of fluorophores, and that the SERS signal is temporally stable and does not photobleach over time. The work reported here demonstrates: 1) a method for reliably generating molecularly-targeted SERS nanoparticles suitable for in-vivo use, 2) a framework for detecting these SERS nanoparticles in-vivo, not using slow point-by-point spectroscopic screening, but rather by fast large-area widefield imaging, 3) results from widefield quantitative, multiplexed SERS imaging in-vivo using phantom models, 4) the first reported study showing widefield SERS imaging of antibody-targeted SERS nanoparticles in a murine xenograft tumour model and 5) proof-of-concept data showing widefield SERS imaging in-vitro using two clinically available endoscopy platforms. Together these results have demonstrated the potential utility of SERS endoscopy in cancer imaging and have established a roadmap to future clinical translation in specific oncologic fields.Ph.D.2015-12-18 00:00:0