Biomarker profiling of tumor samples is increasingly used to stratify patients for targeted therapies and to monitor treatment efficacy. However, there are several barriers hindering accurate profiling of solid tumor samples, including: 1) accessibility of the tumor location, 2) low tumor cellularity due to high stromal content or immune infiltrate, and 3) multi-focal tumors which are spatially heterogeneous and cannot be fully sampled using standard tissue biopsies. An emergent body of literature has shown that peripheral blood, and other body fluids, contain various tumor-derived intermediates (i.e. cells and free DNA). These non-invasive liquid biopsies not only provide prognostic information, but also can be used to genotype tumors for targeted therapy selection and to detect the emergence of new subclones. However, the frequency of these circulating biomarkers is extremely low (<0.1%) and requires innovative engineering strategies to capture and study these analytes. My research focuses on the development of new tools and strategies leveraging liquid biopsy for real-time molecular monitoring and functional profiling of solid tumors.