single molecule

Two Pore Guys single-molecule diagnostic platform update

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Two Pore Guys Artist Rendition, kindly provided by 2PG

Two Pore Guys (2PG) has come a long way in a little over 18 months Background of Two Pore Guys At the recent Next Generation Diagnostics Conference in Washington DC (#NGDx18) Two Pore Guys had a nice exhibit where I had the privilege of meeting Tyler Shropshire Ph.D., their Sr. Scientific Manager of R&D. It … Read more

Nabsys single molecule mapping technology

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Close-up of Nabsys ChipAnother interesting single-molecule technology is a company out of Providence (RI) called Nabsys. For several years I had heard the name involved in developing single-molecule sequencing technology, and this technology will start its initial product around genomic mapping, rather than sequencing.

For background on genomic mapping and CNV analysis along with the competitive landscape, here are  prior pieces written previously called BioNano Genomics, Opgen and Copy Number Variation, and an update on BioNano from last Fall’s ASHG meeting. So while BioNano Genomics and OpGen both use optical mapping of single molecules, Nabsys uses electrical detection. (Cue the optical vs. digital detection methodology of Ion Torrent here).

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Oxford Nanopore at AGBT 2014

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Borrowed from a Oxford Nanopore Video (without permission)
Borrowed from a Oxford Nanopore Video

A few attending the Advances in Genome Biology and Technology meeting in Marco Island Florida (February 12 – 15 2014) have blogged about a presentation from David Jaffe (Broad Institute), presenting the first data the next-generation sequencing community has publicly seen from Oxford Nanopore Technologies. For those not familiar with Oxford Nanopore (or ONT as I’ll refer to them), it was AGBT12 that they absolutely stunned the crowd in attendance with their announcements of both a GridION™ nanopore sequencing ‘module’, and a MinION™ USB-stick portable DNA sequencer that got a lot of press. They planned to commercialize ‘by the end of the year’ (that is, 2012), and since I was not there ‘in’ the meeting first-hand (I was supporting the meeting on-site at Marco Island for Life Technologies, just not as a conference attendee), I heard first-hand from several that year with interest.

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Single molecule in-situ RNA startup Advanced Cell Diagnostics

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Biopsy of skin sample courtesy of euthman via Flickr
Biopsy of skin sample courtesy of euthman via Flickr

FFPE (Formalin-fixed paraffin embedded) tissues are standard preparations in the clinical world. It has been estimated that there are millions of FFPE samples stored in countless hospital laboratories and research pathology groups, all part of a standard operating procedure among pathologists and other hospital personnel. These tissue samples are embedded in paraffin blocks for indefinite room-temperature storage and are easily handled, and standard staining and microscopy techniques can then be employed to determine cancer stage, for example.

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Oxford Nanopore and commercialization at ASHG 2012

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Clive Brown (left) showing the minION at their ASHG 2012 booth. Matthew Hickenbotham, colleague at Life Technologies, at right.

Here at ASHG 2012 in San Francisco this week, a ton of activity around the exhibitors, and Life Technologies does not disappoint with the Ion Bus on the show floor, an open 20 foot x 30 foot booth, a new digital PCR instrument (the QuantStudio 3D) introduced, two luncheon workshops, an Ion Torrent User Group meeting, a special SF Museum of Modern Art event on one evening, and an Ion Lounge evening event on the other. (These last two events were described internally as ‘networking only’, which is a code-word for a great social event.)

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Oxford Nanopore, the first nanopore-based sequencing technology

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Oxford Nanopore illustration
Image from {a href=”http://www.nanoporetech.com”}Oxford Nanopore{/a}

Oxford Nanopore, based in Oxford U.K., made a remarkable announcement that surprised many in February’s AGBT meeting in Marco Island. A GridION and MiniION single-molecule sequencers were announced, promising 15 minute runtimes, no sample preparation, and a disposable USB-stick sequencer for $900 (in the case of the MiniION), with 50kb long readlengths (and 100kb promised) at only a 4% error rate it appears to be a dream come true for many research challenges that await.

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What’s so special about single molecule sequencing?

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Photo courtesy of {a href=”http://www.flickr.com/photos/kyz/”}kyz{/a} via Flickr Creative Commons.

A few days ago I reviewed in brief the history of Helicos Biosciences (HCLS), a company that held out the promise of single molecule sequencing, but failed to deliver on several fronts to the next-generation sequencing market. (This would include accuracy, throughput per dollar, and ease of use / reliability was yet another factor.)

But why is single molecule sequencing so attractive in the first place? What can it do that other technologies cannot?

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Helicos Single Molecule Sequencing – A Pioneer

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The next-generation sequencing market continues its downward trajectory – routinely violating Moore’s Law by an estimated 3x, the cost per megabase curve started to significantly bend downward around 2007 when the Solexa 1G started selling in volume, and gave the 454 GS20 (as it was known then) the first competition for massively parallel sequencing the market had seen.

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Some thoughts on Pacific Biosciences single-molecule sequencing

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SMRTcell of a PacBio RS system courtesy of {a href="http://www.flickr.com/photos/konradfoerstner/"}konradfoerstner<{/a}.

We’re living through a time this year of market transition. The Illumina HiSeq continues to have a strong market position (although the upcoming Ion Torrent Proton sets out to change that, however it won’t be available until this September / October). For the time being, customers with NGS platforms are considering upgrading (from the HiSeq 2000 to a ‘fast-mode’ 2500, or from a 5500 to a 5500 ‘Wildfire’ that will be launched later this year, decreasing the cost-per-base substantially and eliminating ePCR).

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