Early detection of cancer has shown promise in the reduction of cancer-related mortality and improvement of therapeutic outcomes. A variety of cancer biomarkers such as proteins, nucleic acids, as well as tumor cells offer valuable insight on cancer progression. Among these biomarkers, epithelial cell adhesion molecule (EpCAM) is one of the most abundantly used markers for detecting a broad variety of cancers. Changes in the expression of EpCAM have been associated with the onset of metastasis. However, the detection of variations in EpCAM expression with high sensitivity and selectivity remains challenging. Surface enhanced Raman spectroscopy (SERS) based biosensors have been used increasingly over the past few years for cancer detection and diagnosis. SERS-based imaging offers excellent sensitivity and has advantages over other detection techniques like fluorescence. The highly specific recognition enabled by SERS tags is provided via the use of aptamers or antibodies. Aptamers, comprising of single stranded DNA or RNA are a new class of detecting molecules with advantages of low immunogenicity and high stability and have demonstrated potential as an identification tool for cancer cell detection.
In this work, we developed a novel substrate using gold nanostars with EpCAM aptamer to detect small concentrations of EpCAM protein in solution. We used two different lengths of EpCAM DNA aptamer and looked at the differences in their binding to its target protein. Detailed characterization of the substrates was done using SERS maps and atomic force microscopy. SERS measurements showed that SERS intensity increased linearly with increasing concentrations of protein. We observed that having a shorter aptamer sequence and hence, fewer possible secondary configurations at room temperature improved the sensitivity of detection. These substrate based diagnostic devices could be employed in future to detect multiple cancer biomarkers present in blood and other body fluids without the need to label target proteins.