A DNA Hybridization Chip With Electrokinetically-Based Single Nucleotide Polymorphism (SNP) Discrimination

Biosensors and more specifically biochips exploit the interactions between a target analyte and an immobilized biological recognition element to produce a measurable signal. Systems based on surface phase nucleic acid hybridization, such as modern microarrays, are particularly attractive due to the high degree of selectivity in the binding interactions. In this work an electrokinetically controlled poly(dimethylsiloxane) based DNA hybridization microfluidic chip is presented. The electrokinetic delivery technique provides the ability to dispense controlled sample sizes to the hybridization array for quantitative analysis while serving to increase the mass transfer rate and therefore reduce the overall analysis time. An automatic, electrokinetically based, single-nucleotide polymorphism (SNP) discrimination technique (that takes advantage of the combined effects of joule heating, applied potential field and the shear gradients within the double layer field on the thermodynamic stability of the target: probe complex) will also be described for the first time. The clinical utility of the technique will be demonstrated through the detection of genetic markers associated with spinal muscular atrophy, specifically the common C←T mutation in the SMN1 gene.