Research Projects

Cancer in its early stage often remains undetected, as classical diagnosis approaches generally begin with assessing specific symptoms that only show up with disease progression. After the symptom-based assessment, confirmatory tests are performed with tissue biopsy, MRI, PET scan etc. Tissue biopsy is an invasive technique and may cause several complications. Non-invasive methods like MRI and PET scans provide a definitive diagnosis but often only in the later stages of the disease. Also, it would be difficult to integrate techniques like MRI, PET scans into the routine and regular health check-ups. Cancer mortality can be significantly reduced by ensuring early diagnosis, possibly involving diagnostic procedures that utilize probing of suitable biomarkers from body fluids. In recent years several such promising biomarkers have been identified in the contents of the exosomes. Exosomes—the smallest of the extra-cellular vesicles (30-150 nm)—carry proteins, genetic materials, metabolites etc. originating from their parent cells. Exosomes resulting from the cancer cells, therefore, have been shown to possess several types of biomarkers for a variety of cancers. Specific cancer-related protein biomarkers in exosomes include HER2 (Human Epidermal Growth Factor Receptor 2), CA-125 etc. Exosomes also contain cancer related miRNA, mRNA, etc. Despite so much promise, one major challenge of developing exosome-based diagnosis protocols is the rarity of cancer-specific exosomes in the body fluids, especially early in the disease. Alongside the cancer cells, all the healthy cells also produce exosomes, which would make the isolation and/or detection of cancer-specific exosomes extremely challenging. Any such detection approach that targets disease-specific exosomes, therefore needs to be extremely sensitive and selective towards the exosome of interest. In Surface Enhanced Raman Spectroscopy (SERS), for instance, dramatic enhancements of Raman signals can occur selectively for molecules located on or near plasmonic surfaces. This enables a high degree of sensitivity in detecting molecule(s) of interest using SERS. By functionalizing gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs) with antibodies and other types of small targeting molecules (e.g. aptamers), detection of specific-exosomal moieties can be achieved. Fluorescence Correlation Spectroscopy (FCS) is another optical technique that provides extreme sensitivity and the ability to detect sub-picomolar to micromolar concentrations of analytes. For example, FCS has been used to probe the interactions between fluorescently labelled lipophilic peptides and small unilamellar vesicles (SUVs) that are similar in size to exosomes. FCS has also been effectively used for the quantitative study of exosomes using fluorescently labelled antibodies. Here, we aim to develop SERS and FCS-based detection methods for probing exosomal cancer biomarkers using fluorescently labelled aptamers and antibodies.