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When Medicine meets Engineering - Paradigm Shifts of Diagnosis and Therapeutics Abstract

In each living cell, the interactions among the bio molecules, proteins and nucleic acids intrinsically serve as the foundation of the extensive networks of signal and regulatory pathways.  Emergent cellular functionalities are derived from the self-organization of these pathways and can not be easily related to individual bio-molecular interactions. As such, the sheer magnitude of pathway processes and pathway crosstalk presents significant challenges to their straightforward manipulation to direct cellular phenotypic and genotypic outcomes.

Frequently, we intend to control complex systems toward a desired state, with a key example being the application of pharmacological agents to treat diseased cells in medicine. Rather than laboriously mapping out the detailed cascade of signaling pathways, our approach has employed a feedback system control scheme to bypass the challenges associated with simultaneously considering/manipulating multiple cellular regulatory pathways in cellular complex systems.  In addition, we have harnessed these control schemes to rationally design combinatorial drug therapy modalities to stimulate these cellular pathways with improved efficacy and low toxicity.  This imposes another challenge which pertains to the large parameter space. For example, 6 drugs with 10 concentrations each would result in 1,000,000 potential search trials.  With the feedback system control (FSC) approach, we have demonstrated that only tens of searches instead of 1,000,000 cases are needed to identify the optimized drug cocktail. In addition, each patient has different drug absorption, distribution, metabolism and excretion (ADME). This is another challenge of using drug combination therapy.  With FSC technique and the microfluidic circuitry, we are developing individualized combinatorial drugs for each patient.