A New Approach Towards Non-Invasive Cancer Diagnostics – Discerning Cancer Stem Cell Signatures in Blood with Self-Functionalized Quantum Sensor Probes

Abstract

This dissertation describes the development of liquid biopsy using the signals of cancer stem cells (CSCs) in blood as a standalone diagnostic modality. Considering the complexity of cancer, it is necessary to capture the tumour-heterogeneity for robust diagnosis. Current state of the art with non-invasive methods relying on imaging has many limitations such as low sensitivity, inability to identify recurrent tumor or discrimination between primary or metastatic tumors. Since imaging-based diagnosis fails to provide sufficient specificity, tissue biopsyremainstobe thegoldstandardfordefinitive diagnosis. However, tissuebiopsyishighlyinvasive and can only provide a snapshot of the tumor, failing to capture the dynamic tumor landscape. Therefore, new tools are urgently required for accurate tracking of tumor dynamics to enhance cancer prognosis. Liquidbiopsy (LB) can serve as a routine, minimally invasive clinical tool for accurate diagnosis of cancer. Although, the circulating biomarkers in LB better represent the tumor heterogeneity, while being economical and easily applicable in clinical setting for practical patient care; existing LB faces many challenges with pre-analytical preprocessing of biomarkers resulting in biomarker degradation, poor diagnostic accuracy, and long turnaround time. To overcome the existing barriers of LB, I have developed an ultrasensitive sensor for the detection of rare signals of CSC associated bioactive material in circulation. I initiated this research by design and optimization of miniature sized (sub 10 nm) probes for in-vitro biological applications. Next, I employed CSCs-based diagnostic approach because CSCs demonstrate unique characteristics such as self-renewal, tumor initiation, differentiation, and propagation. Prediction of CSC fate by revealing the trajectory of cancer prognosis was undertaken for the first time. Lastly, I demonstrated that the probes, were capable of detection of cancer directly from plasma without extraction or purification of biomarkers. The simplicity of sample processing retainsthe authenticityofcirculatingtumor content,minimizing the source oferrors.The quantum probe platform can provide results in about 60 minutes after blood withdrawal from patients. This diagnostic modality was validated with conventional assays. In this dissertation, CSC associated circulating biomarkers for liquid biopsy are developed,advancing the modality towardsclinical translation.