Nano Biosensor Unlocks Tumor Derived Immune Signals for the Early Detection of Ovarian Cancer

Ovarian cancer is a critical health issue for women nowadays. Its impact is significant because of its high mortality rate (324,603 worldwide), late-stage diagnosis and poor survival rate. Lack of screening tests, vague symptoms, misdiagnosis, and age factor makes it even more difficult to detect. Neutrophils, a subset of immune cells, undergo tumor-specific changes as ovarian cancer progresses inside ovarian tumour microenvironment. Therefore, monitoring the time-specific activity of neutrophils in circulation has the potential to aid in the diagnosis of ovarian cancer. Most ovarian tumor-specific antigens are unknown, making it difficult to identify neutrophils associated with ovarian tumor. We present ovarian tumor-associated circulating neutrophil cell profiling as a stand-alone cancer diagnostic method using a liquid biopsy. Using a SERS-functionalized nano probe, the metabolic profiles of neutrophils from ovarian tumor interaction are detected. We demonstrate that neutrophils associated with cancer stem cells have a distinct metabolic profile and are useful in the diagnosis of early ovarian cancer. Using 5 μL of peripheral blood and an artificial neural network, the characteristics of neutrophil profiles in patient blood could distinguish cancer cohort from non-cancer (healthy) with a 90 % sensitivity and 100 % specificity. Our results demonstrate the viability of using circulating neutrophils for non-invasive cancer diagnostics.