| Circulating tumor cells are cells that exist in the circulation and are accessible by a simple blood draw. The ability to collect and enumerate circulating tumor cells has revealed great prognostic and predictive value to an easily accessible cell population. Importantly, enumeration leaves behind much of the molecular information that is contained within this critical cell population, and the specific biological implication of these cells still remains unknown. To bring a more comprehensive analysis to circulating tumor cells, microfluidic methods have been used due to the natural precision inherent in the microscale that can be important when analyzing this exceedingly rare cell population. In this dissertation, methods to capture and analyze rare cell populations were developed to improve the study of circulating tumor cells and other rare cell samples. These techniques were developed with a focus on simple fundamental physical phenomena of the microscale to create assays that are easy to operate and integrate. The resulting CTC protocol has demonstrated the capability of isolating multiple types of rare cells (CTCs, lung lavage samples) in multiple diseases (prostate cancer, lung cancer, kidney cancer, breast cancer, melanoma). Further, the assessment of these cells was taken beyond enumeration to demonstrate the benefit of molecular assessment of this cell population. Applying the device to clinical studies of prostate cancer and assessing activity of the androgen receptor in CTCs has demonstrated the ability to assess and potentially predict therapeutic benefit of patients undergoing AR-targeting therapy. Throughout the development of these assays, patient samples were used to keep the methods grounded in clinical utility. The technologies developed in this dissertation are focused on expanding the biological and clinical implications of circulating tumor cells toward improving patient care. |
