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Nanopore MinION – $1k solid-state DNA sequencers
- m3nu 9y agoWow. Can I do whole-genome sequencing with this? Is this a similar product/result as buying whole genome sequencing from an established company for the $500 to $800 they charge these days?
- aFLH7U2daj 9y agoYou're buying a service for the 500-800$. Here you're buying a flowcell for 1000$ (the "sequencer" is more or less free). The technology is pretty different and a lot more bleeding edge. If what you want is just a genome aligned to a known reference and you can wait a few days then this is not what you want. We use ONT's minION for strange niche stuff, where either the DNA prep method matters or the latency (the time from loading to the first data out of the machine) matters. Read quality is typically not as good as illumina, so for applications where we need quality we stick with the NextSeq. There's no reason to think nanopore technology won't get better though, but for now, if you've got the money illumina is still the way to go most of the time.
- burfog 9y agoIf you want to do a human or a dozen related humans, and then discard the equipment, is there anything cheaper? That is, without handing the DNA over to somebody else.
- aroch 9y agoA MiniSeq or MiSeq would be cheaper by the time you do the 3 flow cell/person (minimum -- they claim 10-20GB/flow cell but that's bullshit -- so at least ~4K, probably closer to $8k of chemistry/person). You can get a used MiSeq and for ~$50k then its ~1500/person
- daemonk 9y agoIf you want to do absolutely everything yourself from DNA extraction to sequencing and data analysis, then yes, this is probably the cheapest way. But you also need to consider how you prepare your DNA to go into the Nanopore. It's a lot more investment than you might think. Extracting your DNA in a clean enough way for it to work with the Nanopore will require equipment/facilities that most people will not have access to (phenol/chloroform is the optimal way to extract DNA, which will require a fume hood and toxic chemical disposal). Depending on how you want to prep your DNA, you might need more specialized equipment/reagents (Ampure beads, ligation kits, end-prep/TA-tailing, etc).
- josephpmay 9y agoThere is a good reply to you that is currently dead for some reason, so I’m reposting it here for people who don’t have dead visible: > You're buying a service for the 500-800$. Here you're buying a flowcell for 1000$ (the "sequencer" is more or less free). The technology is pretty different and a lot more bleeding edge. If what you want is just a genome aligned to a known reference and you can wait a few days then this is not what you want. We use ONT's minION for strange niche stuff, where either the DNA prep method matters or the latency (the time from loading to the first data out of the machine) matters. Read quality is typically not as good as illumina, so for applications where we need quality we stick with the NextSeq. There's no reason to think nanopore technology won't get better though, but for now, if you've got the money illumina is still the way to go most of the time. >
- bayesian_horse 9y agoThe minion is a device you own. You don't need to ship the samples (which can be a problem, imagine ebola samples). You wait a maximum of 2 days for most of the results.
- bmcusick 9y agoSo what’s a whole human genome sequence cost? That’s the usual metric machines are listed by.
- callesgg 9y agoI looked in to it 4 months ago the cheepest service I could find was 2500 usd.
- bayesian_horse 9y agoI believe Nanopore Technologies is about to announce that a $1000 Human genome is possible with the PromethION, a big brother of the MinION.
- chrisamiller 9y agoIt's really comparing apples and oranges. If you want a 30x whole genome for genotyping, you'll use short read technologies and it'll be way less expensive. The enormous reads offer a different window into genomes, by spanning repetitive regions where short reads can't be accurately placed. For lots of applications, the sweet spot is to use long reads for "scaffolding", then build up coverage with short reads.
- drefanzor 9y agoI need one of these to identify the neighbor that lets their dog fertilize my lawn. At least .. I hope it's a dog.
- bayesian_horse 9y agoA $100 wildlife camera may solve that problem for you.
- ohazi 9y agoHow much are the flow cells?
- ohazi 9y agoAh. ~$500 - $1000 each. That seems like an expensive consumable, but I have no basis for comparison. Is this a lot? https://store.nanoporetech.com/flowcells.html https://store.nanoporetech.com/flowcells.html
- bobbyrepliesof 9y agoThe washing procedure is a simple 2-step process and the kit contains buffers to remove the previous library and equilibrate for reuse or storage. There are sufficient reagents supplied for 12 washes. https://store.nanoporetech.com/catalog/product/view/id/122/s/flow-cell-wash-kit-r9/category/28/ https://store.nanoporetech.com/catalog/product/view/id/122/s...
- daemonk 9y agoThe flowcell is a consumable. You can run it for ~2 days on average. You can wash it out and run other samples during the 2 days if you want, but it will stop working after ~2 days of running. And in my experience, the washing buffer doesn't do a great job. I read somewhere there is ~10% carryover.
- deleted 9y ago[deleted]
- bayesian_horse 9y agoIt's the major cost of sequencing with this system. Apparently, overall, the cost is a bit higher than with the current industry leader. Apparently the cost is competitive for what it does.
- deleted 9y ago[deleted]
- userbinator 9y agoFor an interesting contrast, here's a look inside two DNA sequencers from the last decade, costing two orders of magnitude more (and also roughly two orders of magnitude larger in volume and weight): https://www.youtube.com/watch?v=XaumUp4GpCw https://www.youtube.com/watch?v=XaumUp4GpCw https://www.youtube.com/watch?v=3K9whMm7vvc https://www.youtube.com/watch?v=3K9whMm7vvc It's almost like Moore's law.
- Odenwaelder 9y agoThey are orders of magnitude more precise, and this is the important part. A human genome has 3 billion basepairs, even if you have 99,99% accuracy, this is not enough.
- bayesian_horse 9y ago99,99% accuracy is enough, especially if you need 30X coverage. Also, the initial Human genome wasn't that good either...
- chrisamiller 9y agoIt far outstrips Moore's law :) https://www.researchgate.net/profile/Orit_Shaer/publication/316801394/figure/fig1/AS:494380326846464@1494880863561/Figure-11-A-graph-demonstrating-the-precipitous-decline-in-genome-sequencing-cost-since.png https://www.researchgate.net/profile/Orit_Shaer/publication/...
- daemonk 9y agoI just ran a couple of flowcells last week. I've ran 8 total so far now. My impression is that it can be very inconsistent depending on the quality of the flowcell that they send you and your DNA prep. Great for smallish genomes (bacteria), not enough throughput/quality for large eukaryotic genomes (1gb+) unless you got money to burn.
- oh_sigh 9y ago$1,000 for the starter pack - what kind of use can you get out of that, and how much are the ongoing costs for the flowcells and anything else that needs to be replenished? Are you using it for fun? professionally? academically?
- aFLH7U2daj 9y agoFlow cells are 1000$ each (unless you buy a lot of them), the sequencer is basically a USB dongle with a uC in it and all the important stuff is in the flow cell. Flow cells are basically disposable (but you mail them back). You get one-ish use out of a flow cell though they can be "washed" and realoaded. Reagent kits run a few hundred dollars depending on what your doing and you get several uses out of them. IIRC it's not certified for use as a medical diagnostics device so it's "research only". It's a nice system with great (none) upfront costs that has a lot of potential. But read quality and quanity per dollar aren't as good as what we get with our NextSeq (which by contrast costs something crazy like 300-400k)
- comstock 9y agoNextSeq is expensive, but there are cheaper options (from 30k) and you can just send your samples to a sequencing service. I’ve seen costs for a whole human genome at high coverage of between 1 and 3000USD.
- chrisamiller 9y agoBe careful about defining "high coverage" as 30x. Many applications (especially cancer) really require 100x or more to overcome purity and ploidy, or to identify subclonal populations.
- dooglius 9y agoI remember looking into this device before, but as I recall it was intended for small bacterial genomes. A quick Google turns up that a paper using the device to sequence a human genome has only just been published [0] hence the update to the website. I'm not at all familiar with the technology, but doesn't the fact that experts have only just now been able to sequence human DNA mean it would be pretty unlikely the device could be used as-is for "production" usage? [0] https://sci-hub.la/downloads/8a73/10.1038@nbt.4060.pdf https://sci-hub.la/downloads/8a73/10.1038@nbt.4060.pdf
- dnautics 9y agoHuman dna is not particularly special except there's so much of it relative to bacteria and also the sequencing method is stochastic.
- atg_gcg_aca_aca 9y agoA few years ago, the sequencing field was really excited for this platform as an alternative/competitor to Illumina. Unfortunately, the MinION platform has never been able to generate enough high-quality data for most eukaryotic sequencing use cases. The MinION still has it's niche... long read sequencing can resolve problematic regions of the genome, and the minION is the only option for rapid sequencing in the field. For production genome sequencing centers though, Illumina's still the dominant tech. Their HiSeq X platform can put out a human genome right about $1k.
- folli 9y agoWhere do you see PacBio?
- arca_vorago 9y agoWhile I've been out of the area for almost 3 years now (I sysadmin-supported GS FLX from Roche/454, MiSeq and HiSeq from Illumina, and PGM from IonTorrent), the thing to remember is that each sequencer has it's strengths and weaknesses depending on what you want. Do you want to focus on read length, run time, reads per run, reagent cost, equipment cost, accuracy, etc. As for pacbio, if I remeber correctly, their cost was low (high equipment cost though) and sequencing was relatively fast, but at a reduction of accuracy. Never dealt with them first hand though.
- gourneau 9y agoNASA took one of these up to the International Space Station, which I think is pretty neat. https://www.nasa.gov/mission_pages/station/research/news/dna_sequencing https://www.nasa.gov/mission_pages/station/research/news/dna...
- deleted 9y ago[deleted]
- GolDDranks 9y agoHow far away we are from a 100$ genome? I've heard that the cost/performance development rate is 'super-Moorean'.
- atg_gcg_aca_aca 9y agoHere's the Sequencing & Moore's Law plot that I'm tired of seeing in every genome sequencing presentation ever. https://wi-images.condecdn.net/image/W5YlBgPjX36/crop/1620 https://wi-images.condecdn.net/image/W5YlBgPjX36/crop/1620 Since 2013, Illumina's brought the price of a genome to about $1k with the HiSeq X, which essentially scales up their existing tech. No idea what the next few years hold, but I'm excited to see insurance companies beginning to cover genome sequencing as an affordable diagnostic tool.
- tintor 9y agoIs there an updated plot going up to 2017?
- martinpw 9y agohttps://www.nextbigfuture.com/2017/11/update-on-genome-sequencing-costs.html https://www.nextbigfuture.com/2017/11/update-on-genome-seque... Interestingly the cost had not dropped in the past two years. Also the graph references genome.gov but that site appears to be unavailable at the moment.
- bayesian_horse 9y agoThe question is also what exactly you get. Illumina's technology gives you very short pieces of DNA. I'd call it confetti sequencing. Pacbio and Nanopore both go for longer sequences. This is important when trying to assemble the pieces to a bigger picture.
- tjridesbikes 9y agoI think I could help answer this. The cost of computation has gone down so much that its just a fraction of the price for your whole genome sequencing. The cost comes from preparation, reagents, and storage. Illumina sells their own reagents, so the cost is really dependent on them. We've worked really hard to get the computation cost of genome sequencing as low as possible, and we just passed a major milestone last year. Source: Software Engineer for a well-known non-profit sequencing lab/center.
- aghillo 9y agoCan we ever imagine dna sequencing been done like a remoter sensor? E.g. automated sampling for e(environmental) dna,in-situ sequencing (single and multi species targeting), results transmitted back wirelessly. A biodiversity IoT system?
- bayesian_horse 9y agoAll the technology required already exists. You'd just need a compelling enough application.
- tlrobinson 9y ago> You'd just need a compelling enough application. Pshhh, easy: Gattaca kidding
- Iv 9y agoFast mapping of epidemics outbreaks?
- rmp_ 9y agohttps://vimeo.com/125796581 https://vimeo.com/125796581 is a grand vision ONT have in the works
- cgravill 9y agoThere's a Microsoft Research project that does something like this with mosquitoes for disease management: https://www.microsoft.com/en-us/research/project/project-premonition/ https://www.microsoft.com/en-us/research/project/project-pre... (note: I work at MSR, but on other projects)
- shrikant 9y agoI came across this at a MongoDB conference last year, and thought the demos / videos looked bloody cool. Here's some more detail on the tech works: https://www.mongodb.com/blog/post/oxford-nanopore-technologies-powers-real-time-genetic-analysis-using-docker-mongodb-and-aws https://www.mongodb.com/blog/post/oxford-nanopore-technologi...
- aghillo 9y agoThat’s extremely interesting, thank you for posting the link.
- yread 9y agoThere was a cool visualization from data produced on nanopore on /r/dataisbeautiful recently [1]. It really shows the strengths of the device - ~50kb region with 3kb imperfect repeats. This would be impossible to align properly with <1kb reads from illumina. The paper is worth a read if you're interested in sequencing. They basically did a de novo sequencing of a bacterial genome on the cheap. And in the assembly they had more than 1000 reads longer than 100kb. Using this in combination with an Illumina sequencer is probably the best though. [1] https://www.reddit.com/r/dataisbeautiful/comments/7rpdr0/weve_published_our_nippostrongylus_brasiliensis/ https://www.reddit.com/r/dataisbeautiful/comments/7rpdr0/wev...
- comstock 9y agoThat’s great, but for a company that has raised on a valuation of >2BUSD how are they going to compete with Illumina. The read lengths might be long, but the error rate is a couple of orders of magnitude higher. I can’t see a market large enough for highly error’d log reads to support their valuation.
- danieltillett 9y agoAs some that works in this industry the most amazing thing is the original sequencing technology (Sanger) is still going strong and about as much Sanger sequencing is being done now as back in the early 00s [0]. 0. https://en.m.wikipedia.org/wiki/Sanger_sequencing https://en.m.wikipedia.org/wiki/Sanger_sequencing
- jlebrech 9y agosequencing is only half the story, after this we'll have software to find out allergies or perfect diets, etc..
- cstross 9y agoI'm pretty sure we are now just a couple of marketing cycles away from a version of this being re-packaged and sold to police departments around the world as a tool for identifying suspects in a cloud database of DNA sequences belonging to People of Interest. (You don't need a complete sequence for that, just enough unique markers to ID somebody.) Goodbye "papers, please", hello "cheek swab, please".
- bayesian_horse 9y agoToo expensive with the current nanopore technology. And with any other technology, including a miniaturized PCR implementation, it would be too slow.
- jrm5100 9y agoThe forensic field moves very slowly in adopting new technology since they have to do a lot of re-validation every time anything changes. This idea already here, but with technology based on older/simpler methods. One example is Intigenx: https://integenx.com/rapidhit-system/ https://integenx.com/rapidhit-system/ The FBI has plans for implementing them: https://www.fbi.gov/news/testimony/fbis-plans-for-the-use-of-rapid-dna-technology-in-codis https://www.fbi.gov/news/testimony/fbis-plans-for-the-use-of.... The laws just need to catch up (or prevent it).
- oliwarner 9y agoIt's like Gillette, HP and Keurig got together to collaborate in the sequencing game.
- rubidium 9y agoConsumables consumables consumables. It's remarkable the perverse economic rules that make disposables with vendor lockin a feature. Opex vs capex.
- brohee 9y agoCould it be used with e.g., a drop of blood, to see which bacteria strain is making you sick?
- searine 9y agoYes, if you were willing to shell out 1000 bucks for the test, and if the bacteria was in your bloodstream (unlikely). If you swabbed, cultured, and sequenced, it'd be a better test. I've personally used the oxford nanopore to diagnose malaria subtypes from ~1ml blood draws. Though it took awhile to do so, well beyond clinically relevant time periods. Our best turn around was about 2 days for sequence, but analysis takes much longer.
- chrisamiller 9y agoCulturing is the problem, though, right? Many types of bacteria (including some pathogens) really do not like to grow on most media. There's no doubt that sequencing is the future of infection diagnosis. It's just a matter of how long it takes to get there (cost and complexity both have to drop).
- indescions_2018 9y agoA more interesting race for bio-entrepreneurs. Rather than $1K human sized whole exome. May be the race to develop a $1 plasmid, BAC or small microbial genome sequencer. At that cost, seed level investment in single purpose bio-factories becomes very attractive.
- sdcuevas 9y agoOxford Nanopore is burning through at least $1 million a week of their investors income with virtually no sales to support their market valuation. Will they be the next Theranos? https://www.jcapitalresearch.com/uploads/2/0/0/3/20032477/2017_12_13_ipo.pdf https://www.jcapitalresearch.com/uploads/2/0/0/3/20032477/20...
- bayesian_horse 9y agoMaybe it's just the company's spin, but apparently they are not keeping up with the orders. Also, the technology is working, and it is working competetively well for certain applications.
- comstock 9y agoI would guess they currently make a loss on every device shipped. Most current sales are about generating press coverage/traction, not revenue.
- eggie 9y agoThe technology really works and is generating results at a rapid pace. This will absolutely not be the next Theranos, although you may be right that there are issues of burnrate and maybe even mismanagement. To me the fact that they have a patent monopoly on "putting DNA through a protein pore with voltage sensing" is tragic. Who knows were we would be today if these patents had been granted to the public domain.
- sdcuevas 9y agoLet's assume the company statements are true, they are shipping on time; what is the break even point for shipping $1,000 starter kits, flow cells, and sample prep items? How many devices are they shipping? What's their revenue? https://www.investopedia.com/terms/b/breakevenanalysis.asp https://www.investopedia.com/terms/b/breakevenanalysis.asp Are they anywhere near break even or are they going to require another large infusion of venture capital and can Nanopore find these new investors?
- rotexo 9y agoOne thing I'm excited for here is targeted sequencing using read-until. In this method, you monitor the current trace coming off of individual pores, and if you determine that the DNA in that pore is not part of your sequence of interest, you can reverse the voltage to remove the DNA and start sequencing another molecule. I think this will open up a lot of applications for human genomics. If you're interested in Oxford Nanopore, you might also keep an eye out for Roswell Biotechnologies (https://www.genomeweb.com/sequencing/roswell-biotechnologies-harnesses-molecular-electronics-chip-based-dna-sequencing https://www.genomeweb.com/sequencing/roswell-biotechnologies...). TL;DR: their sequencer involves immobilizing polymerases in circuits so you can measure the current changes that occur as the polymerase adds bases to a strand. This might be a good approach, since it doesn't involve optics (like IonTorrent and minION, keeping costs down) and you get a current event per base (as opposed to per 5-6 bases as with minION), making basecalling easier and potentially more accurate. And it will be fast, since you're reading as fast as the polymerase can work. They want to get up to 10kb reads, and I imagine they could increase the consensus accuracy per read by looping around a single molecule of DNA several times, like with PacBio. Seems feasible too (after all, PacBio has successfully been able to integrate polymerases into very small features rather well, so I see no showstoppers there).
- daemonk 9y agoThere is a group in UK (Matt Loose's group) that I think is working a lot on read-until. I haven't really kept up with it. I think the key for read-until to work is ultimately probably going to be better hardware as you need to be able to analyze the trace signal and compare it against a database fast enough to tell the device to kick it out. There are plenty of software optimizations that can be done to compress the signal or extract relevant regions, but the comparison to a database will be difficult to do fast.
- rotexo 9y agoThe computational barriers are definitely an issue. I thought I had read rumors on twitter that ONT was trying to implement read-until on one of their larger-scale sequencers (one of the ones with compute integrated). Barring that, the Cas9-mediated targeting method looks somewhat promising (https://www.youtube.com/watch?v=DGDH-FdoARM https://www.youtube.com/watch?v=DGDH-FdoARM). No need for amplification! Though for applications with human DNA you might run into some issues with the copy number of a sequence of interest if you’re starting out with a normal amount of genomic DNA.
- JPLeRouzic 9y agoDo you think, dear HNers, that it would be possible to make a DIY version of the Minion and the capsules/flowcells? Many thanks