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.
McPherson, Evolution of Polymerase Chain Reaction to a Quantitative
Tool, Clinical Chemistry, Vol. 41, No.
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.
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.
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.
CT, Ririe KM, Andrew RV, David DA, Gundry RA and Balis UJ., The
LightCycler(tm): a microvolume multisample fluorimeter with rapid
temperature control, BioTechniques
AR, LG Cleland and BW Kirkham, Mathematical considerations of
competitive polymerase chain reaction,
J. Immunol. Methods 187:201-211, 1995.
L, Quantitative PCR: theoretical considerations with practical
implications, Anal. Biochem. 214:
G and A von Haeseler, Modeling the Polymerase Chain Reaction, J. Comput. Biol. 2: 49-61, 1995.
F, The polymerase chain reaction and branching processes, J. Comput. Biol. 2: 63-86, 1995.
F, D Galas and MS Waterman, A mathematical analysis of in vitro
molecular selection-amplification, J.
Mol. Biol. 258: 650-660, 1996.
G and G Cecchi, Efficiency of DNA replication in the polymerase chain
reaction, Proc. Natl. Acad. Sci. USA
93: 12947-12952, 1996.
JT, S Das and S Mohapatra, Polymerase chain reaction engineering, Biotechnol. Bioeng. 55: 359-366, 1997.