Discrimination of Single Mutations in Cancer-Related Gene Fragments with a Surface Acoustic Wave Sensor

Here, we report on using a surface acoustic wave sensor for the highly sensitive and accurate detection of individual point mutations in cancer-related gene DNA fragments from single injections. Our sensor measures both the mass and viscosity signals and, thus, allows discriminating between mass eff...

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Bibliographic Details
Published in:Analytical chemistry (Washington) 2006-07, Vol.78 (14), p.4865-4871
Main Authors: Gronewold, Thomas M. A, Baumgartner, Antje, Quandt, Eckhard, Famulok, Michael
Format: Article
Language:English
Subjects:
Acoustics
Analytical chemistry
Applied sciences
Base Sequence
Biosensing Techniques - methods
Cancer
Chemistry
DNA Probes - genetics
Exact sciences and technology
General, instrumentation
Genes
Global environmental pollution
Hybridization
Kinetics
Mutation
Mutation - genetics
Neoplasm Proteins - analysis
Neoplasm Proteins - genetics
Patched Receptors
Pollution
Receptors, Cell Surface - genetics
Sensors
Surface acoustic waves
Tumor Suppressor Protein p53 - genetics
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Summary:Here, we report on using a surface acoustic wave sensor for the highly sensitive and accurate detection of individual point mutations in cancer-related gene DNA fragments from single injections. Our sensor measures both the mass and viscosity signals and, thus, allows discriminating between mass effects resulting from hybridization of short DNA strands and viscosity effects due to increasing amounts of DNA deposited on the sensor. Single nucleotide exchanges or deletions are distinguished reliably and with exceeding simplicity from the wild-type sequences, on the basis of differences in their dissociation or association rates starting at low nanomolar concentrations. Mutant oligonucleotides were identified immediately from viewing the recorded signal and without further processing of the data. Multiple repeated binding cycles were possible over days without affecting sensitivity. To achieve signal amplification, our new bioassay can also apply multiple hybridization steps based on sandwich hybridizations. Kinetic evaluations gave insight into the physicochemical properties of the fragments used that explain the differences in their binding processes.
ISSN:0003-2700
1520-6882
DOI:10.1021/ac060296c