Ultrasensitive SERS Nano-Sensors for Pancreatic Cancer Diagnosis and Prognosis

ABSTRACT Pancreatic cancer PC is an extremely aggressive malignancy with one of the worst prognoses of all cancers with a median survival of less than one year and an overall year survival of andlt With marked resistance to chemo and radiotherapies surgery is the only curative option In patients with localized disease and no lymph node or extra pancreatic metastases complete surgical resection provides a five year survival rate of However andgt of patients diagnosed have unresectable primary tumor The major cause for the late presentation is lack of early diagnostic biomarker s However the low levels of circulating markers during the early stages drastically dampens the efficacy of many promising markers A rapid widely distributable technology with highly sensitive and specific diagnostic ability to discriminate real disease resectable neoplasms from confounding high risk groups including pancreatitis benign pathologies acute biliary obstruction common bile duct stone cholecithiasis and non malignant benign cystic neoplasms serous pancreatic cystic neoplasms could change the fate of PC patient Serum based assays are the most widely used tests for the detection of tumor markers in clinical settings The ability to detect low levels of specific cancer biomarkers in human serum provides an effective test for early diagnosis It has been demonstrated that mucins specifically MUC are overexpressed in pancreatic cancer MUC has proven to be more informative PC biomarker than current gold standard CA However most of the currently used diagnostic test methodologies lack the sensitivity to detect MUC in human serum As a consequence there exists a critical need to develop sensitive and effective platforms for detecting MUC It has been demonstrated that a platform based on SERS readout strategy surpasses the analytical capabilities of conventional immunoassays including both ELISA and RIA to detect mucins in human serum Furthermore we have recently showed that SERS based nano immunoassay is capable of differentiating samples of control cases from those of pancreatic cancer patients We propose to test the feasibility of implementation of the Surface Enhanced Raman Scattering SERS based immunoassay detection platform into a robust portable point of care methodology to be used for ultrasensitive quantitative and rapid detection of cancer biomarkers The proposed research in phase I will focus on Aim improving sample preparation procedure by incorporating a microfluidic lab on a chip module and automation protocols that will reduce the labor burden and decrease sample size thus increasing the potential of the platform for high throughput sample screening The clinical utility of the assay will be validated Aim by comparing the assay with the PC prognostic marker CA and clinically testing the SERS based assay in high risk controls and pancreatic cancer patients samples Once optimized and validated the SERS based immunoassay platform will be incorporated into a portable point of care POC device which would be the subject of the immediate Phase II submission PROJECT NARRATIVE Pancreatic Cancer PC is lethal malignancy lacking early diagnostic markers The presented project aims to develop a Surface Enhanced Raman Spectroscopy based technology for the sensitive detection of circulating MUC a highly potential marker It will lead towards the development of a highly specific sensitive tool for early detection of malignancy