Nonlinear electrophoretic response yields a unique parameter for separation of biomolecules.

We demonstrate a unique parameter for biomolecule separation that results from the nonlinear response of long, charged polymers to electrophoretic fields and apply it to extraction and concentration of nucleic acids from samples that perform poorly under conventional methods. Our method is based on superposition of synchronous, time-varying electrophoretic fields, which can generate net drift of charged molecules even when the time-averaged molecule displacement generated by each field individually is zero. Such drift can only occur for molecules, such as DNA, whose motive response to electrophoretic fields is nonlinear. Consequently, we are able to concentrate DNA while rejecting high concentrations of contaminants. We demonstrate one application of this method by extracting DNA from challenging samples originating in the Athabasca oil sands.

An instrument for automated purification of nucleic acids from contaminated forensic samples.

Forensic crime scene sample analysis, by its nature, often deals with samples in which there are low amounts of nucleic acids, on substrates that often lead to inhibition of subsequent enzymatic reactions such as PCR amplification for STR profiling. Common substrates include denim from blue jeans, which yields indigo dye as a PCR inhibitor, and soil, which yields humic substances as inhibitors. These inhibitors frequently co-extract with nucleic acids in standard column or bead-based preps, leading to frequent failure of STR profiling. We present a novel instrument for DNA purification of forensic samples that is capable of highly effective concentration of nucleic acids from soil particulates, fabric, and other complex samples including solid components. The novel concentration process, known as SCODA, is inherently selective for long charged polymers such as DNA, and therefore is able to effectively reject known contaminants. We present an automated sample preparation instrument based on this process, and preliminary results based on mock forensic samples.

An automated nanoliter dispenser for staining individual biopsies in tissue microarrays.

In the field of molecular analysis of cancer, there exists a need for a clinical device that can automate protocols for immunohistochemical and in situ hybridization diagnostic staining on tissue microarrays. The tissue microarray antibody spotter (TMAS) has been developed to provide fundamental improvements over current histological staining techniques by enabling precision application of reagents to individual biopsies within a tissue microarray. This allows for multiplexed reactions on a single slide and promises to significantly reduce costs associated with immunohistochemistry and in situ hybridization based assays. Additionally, because TMAS allows for testing of different biomarkers on each element of a tissue array, a complete cancer profile can be obtained from a single TMA slide. Ultimately this may lead to cost-effective, faster and more accurate diagnosis of the patient.