NEXT-GENERATION DNA AMPLIFICATION AND SEQUENCING

DNA amplification - the replication of genetic material in a test tube - is arguably the central technology of the modern era of molecular bioscience. The most common DNA amplification reaction is the Nobel prize-winning polymerase chain reaction (PCR), which can in principle produce millions of copies of DNA molecules, starting from a single molecule, through repeated cycles of heating and cooling.

Whereas the PCR market was originally governed by dominant intellectual property surrounding the technique and its implementation, the expiration of the early PCR patents has left the original technique outside the scope of patent protection. In recent years, market leaders have endeavored to identify so-called “next-generation” PCR amplification techniques that will govern the future of the diagnostics and sequencing markets. To date, none of these technologies are general enough to be applicable to any type of PCR amplification reaction.

For every DNA sequence, there is an ideal schedule for heating and cooling that maximizes the amount of DNA produced. However, no prescription for computing this ideal temperature cycling protocol has been available since the invention of PCR. The operating conditions for PCR reactions are instead selected based on qualitative analysis of their kinetics and thermodynamics. Over the past two decades, many variants of DNA amplification have been invented based on the notions of DNA denaturation, annealing and polymerization, each tailored to a particular amplification objective, but a unified framework for the design of new reactions has been lacking.

Based on fundamental biophysical modeling, chemical process control engineering, and advanced computational optimization algorithms, PMC-AT’s Division of Fundamental Research has developed a generalized framework for next-generation PCR called Optimally Controlled DNA Amplification. This framework enables the automated computation of the ideal temperature cycling protocol for any DNA sequence and desired amplification objective. Unlike other next-generation PCR technologies, this patent-pending methodology can be used in any PCR machine and for any PCR reaction, and hence possesses the generality required to serve as a core technology in the rapidly growing diagnostics and sequencing markets.

1. Invited Talks (selected)


2. Working Papers (selected)

Sequence-dependent Biophysical Modeling of DNA Amplification.

Dynamics and Control of DNA Sequence Amplification.

Optimal Control of DNA Amplification.
3. Research Plan.

PMC-AT DNA-Based Diagnostics Research Overview.
4. Lecture Notes / University Courses Taught.

Advanced Process Control and Optimization (Lecture Notes for Purdue University Graduate Course CHE 656, Spring 2011)