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Despite the fact that therapeutic approaches and diagnostic capabilities have made tremendous advances in the
past few decades, the associated costs with these treatments continue to rise. This fact, coupled with a rapidly aging
population, threatens to cripple our nation's capability to deliver quality healthcare at reasonable and affordable
price points. The research community must therefore look to implementing transformational approaches that
revolutionize both the way we diagnose and treat patients. Emerging multi-disciplinary research in the fields of
molecular biology, systems biology, and solid-state sensing is poised to make such a contribution. Here we
highlight key critical insights in the field of human derived volatile organic compound (VOC) signatures and the
potential for non-invasive diagnostics. With the aim of developing future VOC-based diagnostics, we identify some
critical gaps in our knowledge of how these often complex signatures are influenced by genetics, physiological state,
and population variance. Also, we highlight a few canine and solid-state sensing strategies to demonstrate that
VOC-based breath diagnostics are feasible and we suggest a bio-inspired approach for optimizing sensor
architectures. VOC based diagnostics should drastically enhance early detection of multiple diseases, increase the
time for therapeutic intervention, provide the capability to monitor in real-time the efficacy of therapeutic
treatments, provide the context of emerging pathological outbreaks across participating populations, and potentially
decrease mortality associated with many diseases by orders of magnitude.
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