Physical Society Colloquium

2-D Non-linear Electrophoresis: Applications to DNA purification and sequence enrichment

Andre Marziali

Boreal Genomics Inc &
Department of Physics and Astronomy
University of British Columbia

We present a unique technology for enrichment of DNA sequences carrying point mutations, with over 10,000 fold enrichment of a single point mutation against its wild-type background.

The technology is based on the SCODA (Synchronous Coefficient of Drag Alteration) method for efficiently purifying and concentrating nucleic acids. SCODA, a form of two-dimensional non-linear electrophoresis, uses rotating electric fields in an electrolyte gel to drive a selective focusing orbit for molecules that respond non-linearly to electric fields. Consequently, SCODA is able purify DNA from a variety of complex matrices, including samples that contain strong PCR inhibitors.

More recently we have demonstrated that SCODA can be made specific to the sequence of DNA targets to be concentrated, opening the opportunity for sequence enrichment applications. Recent experiments show that SCODA can enrich for single nucleotide mutations by 10,000 fold compared to the wild type, and that it is capable of separating identical sequences that differ only in degree of methylation.

This presentation will give a brief overview of the SCODA technology with emphasis on recent progress in mutation specific DNA concentration, and potential applications in oncology.