Rapid single nucleotide polymorphism detection for personalized medicine applications using planar waveguide fluorescence sensors

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Publication Type Journal Article
School or College College of Engineering
Department Bioengineering
Creator Christensen, Douglas A.; Herron, James N.
Other Author Tolley, Samuel E.; Smith, Richard
Title Rapid single nucleotide polymorphism detection for personalized medicine applications using planar waveguide fluorescence sensors
Date 2006
Description Personalized medicine is an emerging field in which clinical diagnostics information about a patient's genotype or phenotype is used to optimize his/her pharmacotherapy. This article evaluates whether planar waveguide fluorescent sensors are suitable for determining such information from patient testing in point-of-care (POC) settings. The model system was Long QT Syndrome, a congenital disease associated with single nucleotide polymorphisms (SNPs) in genes encoding for cardiac ion channels. Three different SNP assay formats were examined: DNA/DNA hybridization, DNA/PNA hybridization (PNA: "peptide nucleic acid"), and single base extension (SBEX). Although DNA/DNA hybridization produced a strong intensity-time response for both wildtype and SNP analytes in a 5-min assay at 32?C, their hybridization rates differed by only 32.7%, which was insufficient for clinical decision-making. Much better differentiation of the two rates was observed at 53?C, where the wildtype's hybridization rate was two-thirds of its maximum value, while that of the SNP was essentially zero. Such all-or-nothing resolution would be adequate for clinical decision-making; however, the elevated temperature and precise temperature control would be hard to achieve in a POC setting. Results from DNA/PNA hybridization studies were more promising. Nearly 20-fold discrimination between wildtype and SNP hybridization rates was observed in a 5-min assay at 30?C, although the low ionic strength conditions required necessitated a de-salting step between sample preparation and SNP detection. SBEX was the most promising of the three, determining the absolute identity of the suspected polymorphism in a 5-min assay at 40?C.
Type Text
Publisher International Society for Optical Engineering (SPIE)
First Page 1
Last Page 10
DOI 10.1117/12.669228
Subject Personalized medicine; Planar waveguides; Fluorescence sensors; Evanescent excitation; Fluorescence; Hybridization; Molecular diagnostics; Peptide nucleic acid; Point of care; Single base extension; Single nucleotide polymorphism
Subject LCSH Biosensors; Wave guides; Long QT syndrome -- Diagnosis; Chromosome polymorphism; Pharmacogenetics; Molecular diagnosis
Language eng
Bibliographic Citation Herron, J. N., Tolley, S. E., Smith, R., & Christensen, D. A. (2006). Rapid single nucleotide polymorphism detection for personalized medicine applications using planar waveguide fluorescence sensors. Proceedings of SPIE - The International Society for Optical Engineering, 6080, 60800Z-1-10.
Rights Management ¬©Society of Photo-Optical Instrumentation Engineers. One print or electronic copy may be made for personal use only. Systematic electronic or print reproduction and distribution, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper are prohibited. http://dx.doi.org/10.1117/12.669228
Format Medium application/pdf
Format Extent 868,205 bytes
Identifier ir-main,11647
ARK ark:/87278/s6b28cd8
Setname ir_uspace
Date Created 2012-06-13
Date Modified 2012-06-13
ID 702677
Reference URL https://collections.lib.utah.edu/ark:/87278/s6b28cd8
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