Portland Bioscience, Inc. has developed a comprehensive suite of proprietary technologies that incorporate powerful software routines into state-of-the-art computing devices. Developed tool sets offer significant improvement to DNA and RNA based assay design and performance capabilities. Effective nucleic acid based assay tools arise from a core expertise in biophysics/physics, mathematics, chemistry and molecular biology. Comprehensive system-wide assay design capabilities are powered by routines that use complex system analysis while quantitative analytical techniques arise from algorithms using the principles of statistical thermodynamics. PdxBio™ technologies are portable to any nucleic acid based diagnostic platform testing for genomic material including gene expressions levels, insertion and deletion mutations and single nucleotide polymorphisms (SNPs).
Nucleic acid based diagnostic platforms (i.e. microarrays, beads etc.) that are capable of probing genomic material use data acquisition methods that scale in complicated ways with the concentration of each labeled duplex species in an experiment. Total measured intensity is a composite signal that consists of partial signals from perfectly matched duplexes and mismatched duplexes that arise from cross-hybridization. System-wide signal interpretation is thus dependent on identifying the true perfect match intensity that needs to be extracted from the total signal to correlate and identify the presence of genetic targets/markers. PdxBio™ technologies can dissect each distinct feature in a multiplex hybridization reaction into its individual components, which is then used for accurate determination of specific targets in any assay.
Current analysis technologies inadequately account for cross-hybridization in multiplex assays and are therefore unable to quantitatively determine all signal components that contribute to spot intensities in a microarray. Cross-hybridized duplexes contribute to signal uncertainty and can produce false positives or negatives that must be properly taken into account for accurate characterization of hybridization products in diagnostic assay technology.
PdxBio™ technologies are designed to minimize the probability of cross-hybridization ensuring that each assay produces consistent and accurate results. The intensity due to perfectly matched duplex DNA on each spot is maximized with respect to all cross-hybrid components capable of forming in solution. Proprietary thermodynamic tools are used to design assays and comprehensive analytic techniques are applied for extraction of the true extent of hybridization due to perfectly matched probes and targets in solution.
Fast computational hardware tools have also been developed by PdxBio™ for executing powerful software routines aimed at minimizing cross-hybridization in any multiplex hybridization reaction. These in silico design tools allow laborious optimization steps to be performed at the terminal and significantly reduce both time and resources expended at the lab bench. The result is an efficient assay for accurate quantitation of genomic markers.
A detailed description of the thermodynamics of multiplex reactions appears in the scientific literature: Horne et al., Biophysical Journal. Vol. 91, December 2006, 4133-4153.
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