Kidney cancer is a deadly stealth killer, growing silently and undetected, until so large, advanced, and usually spread to other organs, before symptoms occur. Such cancers are fatal in 95% of the victims. If detected early, kidney cancer can be cured in over 70% of the patients. Early detection also has the benefit that (a) surgical removal can be performed noninvasively, recovery is far quicker than with invasive surgery; (b) only a part, rather than the whole kidney needs to be removed, thereby preserving kidney function; (c) the total cost of care is significantly reduced; and (d) disability and loss of worker productivity are diminished. Unfortunately, at present there is no means to screen at-risk military or associated populations (indeed any population) for kidney cancer. The proposed research will lead to a technology that can be employed to effectively and inexpensively screen large populations of current and former military personnel, their dependents, contractors, and civilians near military bases. In other words, it will save lives, improve the well-being of personnel developing kidney cancer, and reduce military and dependent health care costs.

The objective of the proposed work is to design and demonstrate a simple and inexpensive urine test that can be performed in a physician's office for the detection of kidney cancer at a very early stage. The test measures the quantity of two different proteins (namely aquaporin-1 and adipophilin) present in the urine of a person. It has been recently found by two of the investigators of this project that higher amounts of these proteins are present in the urine of the persons with kidney cancer compared to healthy volunteers. However, detection of these proteins using current methods is expensive and time-consuming. The proposed research aims at developing an inexpensive technology to quickly measure the quantities of these proteins. The proposed technology will be based on a surface-enhanced Raman spectroscopic (light-based) method that reads the fingerprint of the proteins and allows measuring the exact amount of these proteins in the urine. To achieve such detection technology, we propose to fabricate a novel platform, which enhances the fingerprint and makes it distinct from the noise associated with the irrelevant proteins and other molecules present in the urine.

Apart from the immense clinical impact, the proposed research will open a broad platform that can be readily extended for the detection various other biomolecules in physiological liquids (e.g., blood, serum, urine). The proposed research will also provide an insight into the unique properties of the nanomaterials employed in this novel sensing platform. The sensitivity of this molecular fingerprint reading technology critically depends of the design of the substrate comprised of nanomaterials, which can efficiently guide the incident light to the hotspots, where maximum enhancement of the signal can be attained. The proposed research will create a framework for a novel design of such substrates. These would be significantly better than existing designs, which have poor sensitivity and more importantly poor reproducibility. The design and optimization of the proposed sensing platform is expected to be completed by the end of the second year of the proposed project. Analysis of urine of patients with clinically proven kidney cancer and age/sex/weight/smoking history-matched cohort of surgical control patients and comparison to results of an ELISA will be completed in the third year. Following extensive clinical trials of the diagnostic method, the envisioned technology will be ready for wide use.