Scientists from McGill University and the Génome Québec Innovation Centre say they have achieved a technical advance that could result in speedier diagnosis of cancer and various prenatal conditions. Their discovery, which is described online (“Convex lens-induced nanoscale templating”) in the Proceedings of the National Academy of Sciences (PNAS), lies in a new tool developed by Sabrina Leslie, Ph.D., and Walter Reisner, Ph.D., of McGill's physics department and their collaborator, Rob Sladek, Ph.D., of the Génome Québec Innovation Centre.
According to the team, it allows researchers to load long strands of DNA into a tunable nanoscale imaging chamber from above in ways that maintain their structural identity and under conditions that are similar to those found in the human body.
“To overcome the challenges faced by classical nanofluidic technology, we have developed a new approach for introducing tunable nanoscale confinement to trap and align DNA molecules for optical analysis,” wrote the investigators. “Our confinement-based imaging technology combines nanotemplated substrates with a single-molecule imaging technique called convex lens-induced confinement (CLIC).”
CLIC will permit researchers to rapidly map large genomes while at the same time clearly identifying specific gene sequences from single cells with single-molecule resolution, a process that is critical to diagnosing diseases like cancer, explained Dr. Leslie. The CLIC tool can sit on top of a standard inverted fluorescence microscope used in a university lab. Existing tools used for genomic analysis rely on side-loading DNA under pressure into nanochannels in the imaging chamber, a practice that breaks the DNA molecules into small pieces, making it a challenge to reconstruct the genome, continued Dr. Leslie.
“It's like squeezing many soft spaghetti noodles into long narrow tubes without breaking them,” she said while describing what it is like to use CLIC. “Once these long strands of DNA are gently squeezed down into nanochannels from a nanoscale bath above, they become effectively rigid which means that we can map positions along uniformly stretched strands of DNA, while holding them still. This means diagnostics can be performed quickly, one cell at a time, which is critical for diagnosing many prenatal conditions and the onset of cancer.”
“Current practices of genomic analysis typically require tens of thousands of cells worth of genomic material to obtain the information we need, but this new approach works with single cells,” added Dr. Sladek. “CLIC will allow researchers to avoid having to spend time stitching together maps of entire genomes as we do under current techniques, and promises to make genomic analysis a much simpler and more efficient process.”