{"id":6210,"date":"2021-05-23T10:38:00","date_gmt":"2021-05-23T10:38:00","guid":{"rendered":"https:\/\/41j.com\/blog\/?p=6210"},"modified":"2021-05-23T21:36:10","modified_gmt":"2021-05-23T21:36:10","slug":"miseq-cost-analysis","status":"publish","type":"post","link":"https:\/\/41j.com\/blog\/2021\/05\/miseq-cost-analysis\/","title":{"rendered":"MiSeq Cost Analysis"},"content":{"rendered":"\n<p>I&#8217;m curious to understand how cheap Illumina&#8217;s run cost (COGS) can get (as opposed to the cost per base). Illumina broadly have 4 classes of instrument. The iSeq, Miseq, NextSeq and NovaSeq. The NextSeq 550 seems like a Miseq++ and the NextSeq 1000\/2000 a NovaSeq&#8211; (as the former lacks patterned flowcells, and the later doesn&#8217;t have the throughput of the NovaSeq).<\/p>\n\n\n\n<p>The iSeq flowcells embed a CMOS image sensor. It&#8217;s likely difficult to get to a really low COGS here. The Novaseq uses patterned flowcells which they sell for &gt;$10000 and likely have associated costs. So that leaves the Miseq.<\/p>\n\n\n\n<p>The Miseq uses likely relatively inexpensive glass flowcell, and reagent cartridge. So I decided to take a look at that platform. The overall summary is that I&#8217;d guess at a lower bound a Miseq could be made for $5000, reagents likely cost at least $50.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">Instrument<\/h2>\n\n\n\n<p>I purchased an old MiSeq camera from eBay. I can&#8217;t find my notes but I remember it used a Sony image sensor from a DSLR camera. Likely a monochrome version of the IMX038. This is built into a custom camera module with a Xilinx FPGA and associated memory. This is the same sensor used in the Nikon D90, which retailed for $900. I think it&#8217;s unlikely that Illumina could get this sensor the relatively low volume and integrate it with an FPGA and memory for less than this.<\/p>\n\n\n\n<p><a href=\"https:\/\/fccid.io\/ZWF-MISEQ\/Block-Diagram\/MiSeq-Block-Diagram-1536935\">FCC reports provide a block diagram<\/a> of the instrument:<\/p>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"aligncenter size-large is-resized\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/41j.com\/blog\/wp-content\/uploads\/2021\/05\/image-6-1024x741.png\" alt=\"\" class=\"wp-image-6211\" width=\"502\" height=\"362\" srcset=\"https:\/\/41j.com\/blog\/wp-content\/uploads\/2021\/05\/image-6-1024x741.png 1024w, https:\/\/41j.com\/blog\/wp-content\/uploads\/2021\/05\/image-6-300x217.png 300w, https:\/\/41j.com\/blog\/wp-content\/uploads\/2021\/05\/image-6-150x109.png 150w, https:\/\/41j.com\/blog\/wp-content\/uploads\/2021\/05\/image-6-768x556.png 768w, https:\/\/41j.com\/blog\/wp-content\/uploads\/2021\/05\/image-6-1536x1112.png 1536w, https:\/\/41j.com\/blog\/wp-content\/uploads\/2021\/05\/image-6-2048x1482.png 2048w\" sizes=\"auto, (max-width: 502px) 100vw, 502px\" \/><\/figure><\/div>\n\n\n\n<p>You can get a rough idea of what&#8217;s in the platform from this. There&#8217;s a PI Z stage. A Y-stage. Illumination uses LEDs rather than lasers. A bunch of TECs for temperature control. And some embedded compute (I&#8217;d guess x86\/AMD64). Using this information my best guesses at the BOM cost for the most expensive components would be:<\/p>\n\n\n\n<ul class=\"wp-block-list\"><li>Cameras 2x Sony IMX038: Estimate $1800<\/li><li>Z-Stage (PI): $1000<\/li><li>Y-Stage: $100?<\/li><li>HDD: $50<\/li><li>Compute: $200<\/li><li>LEDs\/photodiodes: $50<\/li><li>TECs: $50<\/li><li>Nikon x20 Objective: $400<\/li><li>Fluidics System: $300<\/li><\/ul>\n\n\n\n<p>Which gives us a total of $3900, for an instrument that costs the region of 50 to 100K (if you have exact pricing let me know). $3900 is a lower bound in my view, putting the instrument together in low volume likely adds significant overhead. Still I don&#8217;t see any reason why you couldn&#8217;t put together a MiSeq like instrument for around $5000 in high volume.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">Flowcell and Reagent Cartridge<\/h2>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"aligncenter size-large is-resized\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/41j.com\/blog\/wp-content\/uploads\/2021\/05\/image-7-763x1024.png\" alt=\"\" class=\"wp-image-6212\" width=\"244\" height=\"327\" srcset=\"https:\/\/41j.com\/blog\/wp-content\/uploads\/2021\/05\/image-7-763x1024.png 763w, https:\/\/41j.com\/blog\/wp-content\/uploads\/2021\/05\/image-7-223x300.png 223w, https:\/\/41j.com\/blog\/wp-content\/uploads\/2021\/05\/image-7-112x150.png 112w, https:\/\/41j.com\/blog\/wp-content\/uploads\/2021\/05\/image-7-768x1031.png 768w, https:\/\/41j.com\/blog\/wp-content\/uploads\/2021\/05\/image-7-1144x1536.png 1144w, https:\/\/41j.com\/blog\/wp-content\/uploads\/2021\/05\/image-7.png 1152w\" sizes=\"auto, (max-width: 244px) 100vw, 244px\" \/><\/figure><\/div>\n\n\n\n<p>The Miseq flowcell seems to a simple glass substrate, with covalently bound oligonucleotides for capture. I&#8217;d be curious about accurate costings here, but I suspect it&#8217;s pretty cheap. Probably &lt;$10. There are various companies you can buy flowcells from in relatively small quantities for not much more than this.<\/p>\n\n\n\n<p>Which leaves us with the reagent cartridge:<\/p>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"aligncenter size-large is-resized\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/41j.com\/blog\/wp-content\/uploads\/2021\/05\/image-8-592x1024.png\" alt=\"\" class=\"wp-image-6213\" width=\"302\" height=\"522\" srcset=\"https:\/\/41j.com\/blog\/wp-content\/uploads\/2021\/05\/image-8-592x1024.png 592w, https:\/\/41j.com\/blog\/wp-content\/uploads\/2021\/05\/image-8-173x300.png 173w, https:\/\/41j.com\/blog\/wp-content\/uploads\/2021\/05\/image-8-87x150.png 87w, https:\/\/41j.com\/blog\/wp-content\/uploads\/2021\/05\/image-8-768x1329.png 768w, https:\/\/41j.com\/blog\/wp-content\/uploads\/2021\/05\/image-8-888x1536.png 888w, https:\/\/41j.com\/blog\/wp-content\/uploads\/2021\/05\/image-8.png 1146w\" sizes=\"auto, (max-width: 302px) 100vw, 302px\" \/><\/figure><\/div>\n\n\n\n<p>Digging through various bits of documentation it seems like we have 14 independent reagents in this cartridge:<\/p>\n\n\n\n<figure class=\"wp-block-table is-style-stripes\"><table><tbody><tr><td>1<\/td><td>IMT<\/td><td>Incorporation Mix<\/td><\/tr><tr><td>2<\/td><td>USM<\/td><td>Scan Mix<\/td><\/tr><tr><td>3<\/td><td>CMS<\/td><td>Cleavage Mix<\/td><\/tr><tr><td>4<\/td><td>AMS1<\/td><td>Amplification Mix, Read 1<\/td><\/tr><tr><td>5<\/td><td>AMS2<\/td><td>Amplification Mix, Read 2<\/td><\/tr><tr><td>6<\/td><td>LPM<\/td><td>Linearization Premix<\/td><\/tr><tr><td>7<\/td><td>LDR<\/td><td>Formamide<\/td><\/tr><tr><td>8<\/td><td>LMX1<\/td><td>Linearization Mix, Read 1<\/td><\/tr><tr><td>9<\/td><td>LMX2<\/td><td>Linearization Mix. Read 2<\/td><\/tr><tr><td>10<\/td><td>RMF<\/td><td>Resynthesis Mix<\/td><\/tr><tr><td>11<\/td><td>HP10<\/td><td>Primer Mix, Read 1<\/td><\/tr><tr><td>12<\/td><td>HP12<\/td><td>Index Primer Mix<\/td><\/tr><tr><td>13<\/td><td>HP11<\/td><td>Primer Mix, Read 2<\/td><\/tr><tr><td>14<\/td><td>PW1<\/td><td>Water<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<p>Most of these are either oligos (primers), polymerases, or nucleotides. None of which I imagine are particularly expensive. But it&#8217;s substantially more complex than the flowcell, and I imagine that QCing and putting this cartridge together along with the logistics around shipping it to customers is the dominating cost.<\/p>\n\n\n\n<p>It&#8217;s hard to get accurate volume pricing on these reagents. But I suspect that it costs &gt;$40. Which would put the cheapest MiSeq runs (~$500) within Illumina&#8217;s <a href=\"https:\/\/41j.com\/blog\/2018\/11\/illumina-consumables-are-90-profit\/\">overall 90% margins on consumables<\/a>.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>I&#8217;m curious to understand how cheap Illumina&#8217;s run cost (COGS) can get (as opposed to the cost per base). Illumina broadly have 4 classes of instrument. The iSeq, Miseq, NextSeq and NovaSeq. The NextSeq 550 seems like a Miseq++ and the NextSeq 1000\/2000 a NovaSeq&#8211; (as the former lacks patterned flowcells, and the later doesn&#8217;t [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[1],"tags":[],"class_list":["post-6210","post","type-post","status-publish","format-standard","hentry","category-uncategorized"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack_shortlink":"https:\/\/wp.me\/p1RRoU-1Ca","jetpack_sharing_enabled":true,"_links":{"self":[{"href":"https:\/\/41j.com\/blog\/wp-json\/wp\/v2\/posts\/6210","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/41j.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/41j.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/41j.com\/blog\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/41j.com\/blog\/wp-json\/wp\/v2\/comments?post=6210"}],"version-history":[{"count":6,"href":"https:\/\/41j.com\/blog\/wp-json\/wp\/v2\/posts\/6210\/revisions"}],"predecessor-version":[{"id":6220,"href":"https:\/\/41j.com\/blog\/wp-json\/wp\/v2\/posts\/6210\/revisions\/6220"}],"wp:attachment":[{"href":"https:\/\/41j.com\/blog\/wp-json\/wp\/v2\/media?parent=6210"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/41j.com\/blog\/wp-json\/wp\/v2\/categories?post=6210"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/41j.com\/blog\/wp-json\/wp\/v2\/tags?post=6210"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}