Development of novel technology platforms for blood based diagnosis and cellular characterization in cancer

Restricted until 1 Aug. 2009.To detect cancer at the earliest manifestation and correctly predict the course of the disease is very crucial in tailoring therapy leading to better patient management. Blood serves as an ideal compartment for clinical interrogation since it is not only readily obtainable but also perfuses through all tissues, which hypothetically represents a sampling of the state of the entire body. Thus, this thesis focuses on exploration of blood-based analysis using novel phenomena and functions that arise when materials can be engineered in the micro/nano-meter level for biomolecular sensing and cellular detection and characterization.; Label-free and multiplex biomolecular detection platforms using a 2D microcantilever array or nanowire/nanotube-based field effect transistor (FET) array have been demonstrated. Utilizing the induction of surface stress due to reaction on one surface of a microcantilever beam, consistent microcantilever array responses to antibody-antigen binding were achieved over a wide dynamic range (1 ng/ml to 100 µg/ml) using a 2D array with optical readout system coupled with image processing software to simultaneously monitor hundreds of reactions in parallel. In addition, an alternative sensing technology based on nanowire and nanotube FET array has been demonstrated to specifically detect PSA at concentration of 5 ng/ml.; A novel membrane filter microdevice with integrated electrodes for electrolysis was developed for the detection and characterization of circulating tumor cell (CTC) in blood. Development and optimization of microdevice, which is capable of greater than 80% recovery with high enrichment factor (6 logs) was presented. In addition, bloods drawn from castration resistant prostate cancer patients have also been studied to demonstrate feasibility of working with clinical specimen. To develop multi-marker analysis in clinical samples, a separate retrospective study utilizing stored bone marrow samples were obtained to identify cancer stem cells using IHC with spectral imaging analysis.; In summary, we have developed platforms for molecular detection of cancer and for capturing tumor cells in blood with the capability for further downstream characterization. Both approaches are focused on blood-based detection where routine venipuncture is minimally invasive and amendable for multiple sampling