Long-term exposure to microgravity and radiation during space exploration can pose a critical threat to the health of a flight crew. Real-time monitoring of urine protein levels is an effective way to follow the onset and progress of many diseases and guide the prompt selection of proper therapy. The success of such diagnostic tasks, which are vital for future space missions, critically depends upon the degree of automation, reusability and long-term lifetime of such trace level detection devices. To meet this need, this program will develop a novel on-chip, reagent-free, nano-plasmonic sensor cartridge to concurrently quantify the presence of different urine proteins. The envisioned device is compact, lightweight, fully integrated and automated, and highly cost- and power-effective. In Phase I, a new nano-plasmonics chip technology-based SPR sensor has been developed and successfully demonstrated for protein detection with excellent sensitivity. Critical microfluidic components, used in sample preparation, and adaptable to the sensor chip have been developed and validated by multi-physics-based simulations and modeling. In Phase II, the nano-plasmonic sensor will be optimized to increase sensitivity, stability, and the response to regular urine samples. The sensor chip will be integrated with the system-engineered microfluidics network to form a seamless urine protein assay cartridge (PAC) that enables automated surface modification, sample pretreatment, analyte detection and sensor regeneration for reuse. We will use modular design of the PAC that is compatible with existing NASA astrobiological instruments and will enable high-throughput proteome profiling analysis.