Versatile Biosensing Platform for Monitoring Bone Markers for Space Medicine (State Match)

Several reports authored by the President's Commission on Implementation of United States Space Exploration Policy (A Journey to Inspire, Innovate, and Discover, June 2004), the National Research Council (Space Studies Board, 1998), and NASA (NASA Strategic Plan, 2006 and Science Plan for NASA's Science Mission Directorate 2007-2016) have identified a need for monitoring and maintaining astronaut health during long-term human space exploration missions. Further, the 2001 Institute of Medicine report entitled Sqfe Passage: Astronaut Care for Exploration Missions (Ball and Evans, 2001) identifies loss of bone mineral density along, radiation effects, and behavioral adaptation as the three most important health risks during long duration missions. Motivated by this need, the original PI, Leonidas Bachas, of this project assembled a multi-investigator team to develop enabling technologies for space medicine applications and, in particular, diagnostic devices that could be used to monitor biomarkers associated with bone demineralization during human exploration missions. Following transfer of the project to David Puleo, the research will be continued and extended as summarized below. An excellent way to achieve monitor and diagnose bone degradation is through integration of sensing technologies and microfluidic networks on a versatile CD platform that can detect analytes in a variety of samples, including urine and blood/serum. Previous and on-going research has focused on the analysis of small moleculeslbiomarkers, such as electrolytes and hormones. In continuation of this project, ongoing efforts with diagnostic systems will be expanded, while a therapeutic arm will be developed to address the detected musculoskeletal deficiencies. In short, the objectives of the continuing research are to: 1. Expand monitoring systems for small biomarkers, such as electrolytes and hormones. Based on prior successes, combinatorial and rational strategies for using ionophores and fluorescent binding proteins as molecular recognition elements will be continued. Identification of new aptamers for detection of steroids and hormones will also be pursued. 2. Antibody-based assays detection of large biomarkers. Conformational change in the noncanonical site of antibodies was previously exploited for detection of antigen binding. Because the labeling reagent is expensive, alternative labels that reduce cost yet maintain high labeling efficiency will be investigated. 3. Develop tunable platforms for modulated release of bioactive molecules. Even when methods to monitor bone degradation are validated, means to restore musculoskeletal health will be needed. To this end, pharmaceutical approaches, whether administered alone or in conjunction with other countermeasures, may be effective. Considering the non-zero-order kinetics of physiological processes, strategies for temporally-and spatially-controlled release of osteotropic bioactive molecules will be designed and fabricated.