Twist-Biosensor: Novel single molecule microarray technology for DNA genotyping

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DESCRIPTION (provided by applicant): The availability of human genomic information and its variability is allowing researchers to identify the genetic variations responsible for patients' different responses to treatment.1-3 In order to deliver the benefits of personalized medicine to the clinical practice, it is necessary to have accurate genotyping techniques capable of determining multiple genetic markers. The existing Food and Drug Administration (FDA)-approved pharmacogenetics tests require long processing times or have limited multiplexability. Here, we propose the development of rapid and multiplex pharmacogenetic tests based on Twist-Biosensor technology. Twist-Biosensor is a novel microarray technology for oligonucleotide detection based on single molecule DNA hybridization and supercoiling. In this technique, the hybridized targets are subjected to disrupting torsional stress which allows for rapid detection of multiple Single Nucleotide Polymorphisms (SNPs) with extremely low background noise using a simple device. Our overall aim is to demonstrate that devices based on the Twist-Biosensor technology can make personalized medicine more readily available to patients by genotyping several SNPs in a single chip within three hours from sample to results. Our approach will be to build and characterize a prototype device able to genotype three SNPs of the CYP2D6 gene, which is the most prevalent genomic biomarker found on drug labels. About 13% of patients in the U.S. receive prescription drugs metabolized by the CYP2D6 enzyme.4 Aim 1 focuses on fast detection of a single CYP2D6 mutation. Aim 2 focuses on fast multiple CYP2D6 SNP detection in small blood samples.