The high mortality rate of patients with invasive and metastatic cancer has changed little over the past few decades. Early detection is crucial for better treatment of cancer and to increase survival rates. Traditional diagnostic approaches fail to detect some types of cancers at very early stages. Bladder cancer is usually silent in early stages resulting in diagnosis at late and often incurable stages. Occasionally, the symptoms of both benign conditions and bladder cancer are nonspecific and very similar. In about 85% of cancer patients, there may be red blood cells present in the urine. But the same symptoms may be the result of an infection or inflammation in the urinary tract (kidney, bladder, prostate). This proposal aims at providing a non-invasive, low-cost, highly sensitivity, and ultra-specific approach using solid-state microdevices and biochemical functionalization of chip surfaces. The functionalization will target the molecules that are overexpressed on tumor cells. Automation of the data acquisition and analysis will be done to determine physical behavioral differences and biomarker expression levels between tumor and normal cells. The molecules chosen for targeted detection of tumor cells will add significant value as indicators and predictors of the outcomes of the treatment. This proposal will change how cancers, and especially bladder cancer, are diagnosed. The experiments will be done first with cultured cells, then with cells isolated from the blood of animals bearing human bladder cancer xenografts, and finally with real patient clinical samples. The multi-disciplinary team will integrate the novel technology that will provide educational opportunities for students on the whole continuum of K-Grad. Graduate and undergraduate students will be engaged and introduced to exciting new dimensions of cell biology, biochemistry and solid-state fabrication through development of a cross-listed course module on the cell-nano interface. The research outcomes will be also used to develop participatory modules at College of Engineering summer camps to attract future adults to STEM careers. The results, data and outcomes of the research and education endeavors will be disseminated not only through peer-reviewed articles and conferences, but also through social and public media.
The novelty of the proposal lies in three elements: first, a special class of probe molecules called aptamers will be used. Aptamers can be reversibly denatured, and these will therefore provide a mechanism for the reversible release of tumor cells in their native states. Second, the nanotextured substrates will provide biomimetic environment to examine the cell behavior. Third, dynamic behavior of tumor cells will be used to measure the temporal evolution of cell-cell interactions over days at single-cell or sub-cellular scales. This new tumor detector will serve as a non-invasive cell type reporter (without "staining" the cell), and as a cell culture substrate with prescribed behavior of cells for certain level of biomarker overexpression. Currently such a platform does not exist. The technological integration described in this proposal may therefore provide early means of identifying remission or metastases, and even give some insights into how many and what types of metastases may be present in a given sample.
