Invention: A high-throughput platform for analyzing long segments of genomic DNA with single-molecule sensitivity.
What It Is: Today’s explorations of the human genome are based primarily on analyzing the individual subunits, or nucleotides, that make up DNA. However, current sequencing techniques are limited to short segments of DNA, requiring researchers to piece together the segments in a manner not unlike putting together a jigsaw puzzle. Many researchers have expressed the need to look at sequences of whole sets of genes and other long segments of non-coding regions of the genome. Technology invented at Princeton University and exclusively licensed to Bionano, Inc. makes this long-range analysis possible.
How It Works: The technology consists of nanoscale channels that are so narrow that they permit only one DNA molecule to travel through the channel at a time. At the entrance to the channel, micro- and nano-sized structures separate and uncoil the DNA strands and then direct them into the channel. While stretched inside the channel, fluorescently labeled DNA strands can be imaged by a detector that captures information about the features of the DNA molecule.
The technology consists of thousands of parallel channels that are etched and enclosed in the surface of a solid state material such as silicon or fused silica, allowing large numbers of DNA molecules to be analyzed simultaneously. Several gigabase regions of native state genomic DNA can be analyzed per hour from very small amount of sample without using time-consuming and potentially biased amplification methods such as polymerase chain reaction (PCR).
Applications: Bionanos’ soon-to-launch nanoAnalyzer® instrument yields a large-scale view of the DNA molecule, allowing researchers to see where genes are located relative to each other. The technology also reveals other elements such as reading frames, noncoding frames, and repetitive regions. This information is often destroyed when DNA is cut up for use in traditional sequencers. The technology can also reveal sites of DNA damage, mutations and structural variations such as duplications, deletions and extra copies of genes. The system can also be used to image proteins such as transcription factors that are bound to the DNA.
The technology is complementary to sequencing efforts and in some cases may replace it, according to company President and CEO Erik Holmlin. “Our advantage over sequencing is that we provide the long-range view,” said Holmlin.
Inspiration: The idea for using nanotechnology to fabricate a device for single-molecule analysis originated in the laboratories of Princeton University.
Collaboration: The technology was developed at Princeton University by a multidisciplinary collaboration among faculty from the School of Engineering and Applied Science, the department of Physics, and the Department of Molecular Biology and supported by a grant from the U.S. Defense Advanced Research Projects Agency (DARPA). The inventors were: Steven Chou, the Joseph C. Elgin Professor of Engineering; Robert Austin, professor of physics; Han Cao, a former postdoctoral researcher at Princeton University; and Jonas Tegenfeldt, now an associate professor at Lund University.
Commercialization Status: The first wave of commercial nanoAnalyzer® systems will debut next year, followed by the sequential introduction of new features and new applications. Initial customers will be large genome research centers but eventually Bionano plans to introduce the technology more broadly.