Modeling PCR Devices for Fun and Profit

 

 

Polymerase Chain Reaction (PCR) is a biochemical process by which particular sequences of base pairs along DNA can be selected, doubled and redoubled ad infinitum. PCR is a foundation technology, which has allowed for sequencing of genomic information, determination of genetic differences, and detection of diseases and organisms via their DNA signatures.  Idaho Technology is a biotech company in Salt Lake City founded in 1990 to develop instruments for rapid DNA analysis.  Their products perform DNA amplification by PCR and SNP (single nucleotide polymorphism) detection, biochemical reactions that are accelerated by rapid temperature cycling through efficient heat transfer by hot air to samples contained in micro-capillary tubes or thin walled micro-centrifuge tubes.  Idaho Technology products are used in hospital laboratories and in medical research to detect infectious agents and genetic disease. The RAPID System is used by the United States Department of Defense, and other government agencies to identify the presence or absence of biological weapons.  Other devices are being developed by Idaho Technology to monitor food and water safety. Modeling of the reactions of PCR and SNP detection performed by the devices, as well as models of the heat/air flow in the devices would help IT optimize its designs and potentially lead to innovation in their rapid PCR technology.  For this project we'll learn about the reactions and the engineering involved in IT's family of devices, and develop models of the biochemical reactions and/or heat flow in the devices, that can be parameterized from IT data and ultimately compared with results from IT laboratories.

 

 

PCR references:

 

  1. R.A. McPherson, Evolution of Polymerase Chain Reaction to a Quantitative Tool, Clinical Chemistry, Vol. 41, No. 8, 1995.

 

  1. Ririe KM, Rasmussen RP and CT Wittwer. Product differentiation by analysis of DNA melting curves during the polymerase chain reaction,. Anal. Biochem. 245:154-160, 1997.

 

  1. Wittwer CT, K Ririe and RP Rasmussen, Fluorescence monitoring of rapid cycle PCR for quantification, In: Ferre F, ed. Gene quantification. Birkhauser, Boston MA, 129-144, 1998.

 

  1. Wittwer, CT, GB Reed and KM Ririe, Rapid cycle DNA amplification, In K Mullis, F. Ferre, and R Gibbs (Eds.), The polymerase chain reaction. Springer-Verlag, Deerfield Beach, FL, pp. 174-181, 1994.

 

  1. Wittwer CT, Ririe KM, Andrew RV, David DA, Gundry RA and Balis UJ., The LightCycler(tm): a microvolume multisample fluorimeter with rapid temperature control, BioTechniques 22:176-181, 1997.

 

  1. Connolly AR, LG Cleland and BW Kirkham, Mathematical considerations of competitive polymerase chain reaction, J. Immunol. Methods 187:201-211, 1995.

 

  1. Raeymaekers, L, Quantitative PCR: theoretical considerations with practical implications, Anal. Biochem. 214: 582-585, 1993.

 

  1. Weiss, G and A von Haeseler, Modeling the Polymerase Chain Reaction, J. Comput. Biol. 2: 49-61, 1995.

 

  1. Sun, F, The polymerase chain reaction and branching processes, J. Comput. Biol. 2: 63-86, 1995.

 

  1. Sun, F, D Galas and MS Waterman, A mathematical analysis of in vitro molecular selection-amplification, J. Mol. Biol. 258: 650-660, 1996.

 

  1. Stolovitzky, G and G Cecchi, Efficiency of DNA replication in the polymerase chain reaction, Proc. Natl. Acad. Sci. USA 93: 12947-12952, 1996.

 

  1. Hsu, JT, S Das and S Mohapatra, Polymerase chain reaction engineering, Biotechnol. Bioeng. 55: 359-366, 1997.