(254g) Optimally Controlled DNA Amplification

Due to the universal need to amplify DNA for biochemistry applications ranging from molecular cloning to DNA sequencing, DNA amplification or the Polymerase Chain Reactions (PCR) is the workhorse of nearly every modern molecular biology laboratory, as well as the burgeoning discipline of personalized medicine. Despite the apparent simplicity of the PCR reaction, the method is often fraught with difficulties that can decrease the cycle efficiency or result in competitive amplification of undesired side products. To date, nearly all approaches to PCR optimization have been based on either heuristic experimental sampling of reaction conditions or calculation of the effects of changes in reaction mixture composition on thermodynamic parameters. By contrast, the engineering discipline of control theory can automatically derive prescriptions for the optimal temperature cycling protocols of a PCR reaction, if a suitable kinetic model exists. We have developed the first sequence and temperature dependent kinetic model for PCR reactions, validating this model through comparison to experimental data. Using this kinetic model we  have analyzed the controllability of PCR and developed a control strategy to maximize the DNA amplification efficiency. Further, we have formulated and solved a large scale constrained dynamic optimization problem and derive the optimal temperature profile that maximizes the amplification of a given target DNA sequence and reduces the overall reaction time.