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Old 05-22-2019, 04:09 PM   #1
potomac
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Default Question about typical lifespan of Illumina machines

Hi all,

I was wondering if anyone could comment generally about the lifespan of a typical Illumina machine?

My hypothesis is that the typical lab can get 6-8 years of life out of a machine. I know that some fairly big genomics labs are still running HiSeq 2500s, which were first released in 2012.

There must be some servicing to maintain the mechanical and optical parts that wear out. Different from Nanopore, which is solid state. Does the typical lab buy an Illumina machine and have it serviced a few times to keep it in working condition?

For a few years there's been a question around whether the market is saturated with Illumina machines.

I made a cool chart below to visualize the install base by the way. The company thinks it will be able to convert 25% of the HiSeq's currently installed to Novaseq by the end of 2019. I'm kind of sceptical of this though, based on what I know about the lifespans. Not everyone needs the kind of throughput the Nova gives too at the high $1 million price tag. I guess the NovaSeq has the speed benefit too from the 2-channel SBS chemistry, but not sure if that matters much.



p.s. I've been working on a personal project to better understand financial modelling and I thought Illumina was a great example of a company I know a little bit about. Would be happy to share my end result with folks here.

Last edited by potomac; 05-22-2019 at 04:12 PM.
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Old 05-22-2019, 05:38 PM   #2
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I guess it is not the throughput nor the lifespan of the instruments that kills the older sequencers; it is mostly the comparatively high costs per base. The exception are the MiSeqs because Illumina has not bothered to develop a new longer read sequencer.
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Old 05-22-2019, 09:19 PM   #3
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Quote:
Originally Posted by luc View Post
I guess it is not the throughput nor the lifespan of the instruments that kills the older sequencers; it is mostly the comparatively high costs per base. The exception are the MiSeqs because Illumina has not bothered to develop a new longer read sequencer.
Is it correct to think of the cost per base savings as tied to the reductions in consumable costs due to the new 2 channel sequencing method?

It seems that at the beginning of 2017, the customers most suited to switching from HiSeq to Novaseq were core labs, industry/pharma labs and diagnostics that need a lot of throughput. They could benefit from the consumable cost reductions. The smaller customers, not so much.

James Hadfield talks about that in his 2017 post here. But that's two years old now. Has much changed? Are the small and medium labs phasing out their HiSeqs?

http://enseqlopedia.com/2017/01/shou...houldYouBuyOne

Quote:
According to Illumina there is a $2-4 per Gb difference ($16/18 vs $20) for NovaSeq S1/S2 flowcells versus HiSeq 4000. This is a reduction of 10-20% on current costs for consumables only. The price per million reads please is less clear as the costs of S1/S2 flowcell kits has not been released.

NovaSeq may be economical when service contracts are taken into consideration. A fleet of 2500ís could be replaced with 1 NovaSeq saving significant sums on those expensive HiSeq contracts. But this will reduce a pretty good revenue stream for Illumina as the numbers of NovaSeq in the field is unlikely to hit the highs of the 2500!

Overall costs are likely to drop for users as NovaSeq replaces HiSeq 2500 and 4000, and cannibalises HiSeq X Ten. But those costs apply primarily to consumables. As sequencing prices continue to plummet, library-prep costs get higher and higher (relatively speaking). Today library is at least 50% of the cost of doing RNA-Seq of ChIP-seq. In the future it might be as high as 75% of the cost. We desperately need library-prep innovation!
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Old 05-24-2019, 11:16 AM   #4
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Quote:
Is it correct to think of the cost per base savings as tied to the reductions in consumable costs due to the new 2 channel sequencing method?
That may be partly true but we have no real idea of what the manufacturing costs for Illumina are for any of these reagents. Since they are the sole suppliers they get to set the price. They can make the market move (e.g. by making HiSeq reagents more expensive) in direction they want. Ultimately everyone is sensitive to pricing since customers always want to pay the least they can get away with.

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Are the small and medium labs phasing out their HiSeqs?
I would say no. It gives them flexible platform to move things around as needed. Not all core labs get to make libraries for customers and putting an unknown mix of customer libraries on an expensive NovaSeq run is a big risk. With introduction of NovaSeq SPrime flowcell Illumina is making things more flexible and trying to get people to move to NovaSeq platform.
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Old 05-24-2019, 01:51 PM   #5
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Quote:
... Are the small and medium labs phasing out their HiSeqs? ...

Very likely yes, since Illumina is manipulating the prices to their liking. HS4K reagent costs did increase by 6% this year (everything else by 3%); the costs for the small NovaSeq flowcells OTOH dropped by 20%. One gets the idea Illumina really wants you to buy a NovaSeq (and the NovaSeq successor in another year as well).
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Old 05-24-2019, 02:16 PM   #6
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Thanks for the responses guys. Very helpful.

I guess between the HiSeq reagent price increases and the S Prime Novaseq flowcell release (and 20% price drop this year?), llumina is using carrots and sticks to get labs to upgrade. But it's hard to quantify how many actually will.

I had the privilege of visting DeCode Genetics in Iceland last year. They do a lot of WGS work. I found it interesting that they had at least 10 HiSeq 2500's in operation last year. (Positive that was the model because I have a pic). I think they also had a Novaseq or two. They also had some ONT Promethions and MinIONs, and PacBio Sequels for longer reads.

I was wondering what the reason they hadn't upgraded could be? This was before the SPrime was released, so maybe that creates a better use case. Would it be likely that they'd use the rapid run mode on the 2500?

DeCode seems like it would be a good canary in the coal mine for the switch scenario from HiSeq to Nova. They have plenty of funding yet held off in the first year of the Novaseq's launch (2017-2018). Maybe now that changes with the above carrots and sticks.

Last edited by potomac; 05-24-2019 at 02:27 PM.
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Old 05-24-2019, 06:25 PM   #7
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Illumina did upgrade the HS2500 sequencers of a few selected companies to V4 chemistry compatibility - overall very few such compatible machines did exist. With this chemistry however, the HS2500 is actually very competitive to the HS4000, while also offering PE250 reads.
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Old 05-24-2019, 09:41 PM   #8
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Were those upgrades offered beginning around 2014? (Link: https://support.illumina.com/downloa...ion-sheet.html)
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Old 05-25-2019, 06:51 AM   #9
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Our small core lab likes the flexibility of the 2500, especially Rapid mode for small numbers of samples/unusual run requests. Replacing that functionality would require two machines (although we are adding a NextSeq to accommodate the increased demand for single-cell sequencing). And, b/c the facility handles user-supplied libraries, @GenoMax is spot-on with concerns about sample pooling (e.g., duplicate adapters) on the Novaseq, even w/ the S Prime flow cells. Absent multi-user pooling, per-lane run cost becomes more relevant than $ per GB - I believe the HiSeqs are competitive by that criterion (although I haven't crunched the numbers recently).
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Old 05-25-2019, 05:48 PM   #10
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Update from Decode is that they actually upgraded to Novaseq's right after I visited. The reason they held off was availability of the S4 flowcell (which can do about 50 human genomes in a run and helps them).

The main type of HiSeq lab that wouldn't want to upgrade to Novaseq seems to be smaller labs without the cash to upgrade ($950,000 is not insignificant, especially at universities and government), or labs more generally that have customer-supplied libraries and want the flexibility of the HiSeq's. Does that sound right? Missing any other types?
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Old 05-26-2019, 05:01 AM   #11
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@potomac: While it is tempting to have bragging rights of having the latest and greatest in house it is difficult to keep the beast fed (when reagents for an S4 run cost upwards of $30K). Need for sample numbers and consumable cost needs to be carefully considered before making the jump.

Places like DeCode which have full control over the entire pipeline so for them it makes sense to go NovaSeq (we have done concordance testing with samples from HiSeq and values were almost perfect).

Not buying a hot technology in the first year makes practical sense. You allow someone else to do the debugging for you. Once things settle, you buy in.
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Old 05-26-2019, 10:24 PM   #12
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How rare is it that a lab has full control over its entire pipeline? Maybe 10%, 20%, 30% or 40% of all labs that have Illumina machines?

I would guess most SeqAnswers posters are from university/research institute/government labs? Not sure if that's correct. Most of them don't have control over library creation because they're serving individual lab customers?

Wouldn't most clinical labs (diagnostics company, hospitals) have complete control? And most biopharma/industrial labs would too.

Another cool chart I made shows the breakdown of Illumina shipments. Illumina has reported these numbers informally for awhile in their earnings calls (I dug through them all here: https://seekingalpha.com/symbol/ILMN...gs/transcripts).

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