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It's basically a little custom microscope with a few illuminators and a Z stage for focusing (not even an XY stage). Not surprising, as sequencing has been mic

by dekhn 3y ago

It's basically a little custom microscope with a few illuminators and a Z stage for focusing (not even an XY stage). Not surprising, as sequencing has been microscopy for a while now. It uses TIRF optics.

epistasis 3y ago
I'm sure you know this already, but for the benefit of the HN crowd... Yeah it's been unfortunate that the electronic sensors have not been able to keep up with the optical readouts. Ion Torrent and Genapsys are barely used due to accuracy problems, but Oxford Nanopore's considerable logistical benefits of tolerating a wide range of input DNA concentration, quick time to data, low capital cost, and long reads has kept them alive. Maybe they will grow more with higher accuracy. Illumina's patents ending recently has prompted a few new startups beyond 454.bio, including Element and Singluar, but with the stiff headwinds of FDA regulatory uncertainty and the long capital life of existing sequencers, it's hard for them to make progress even when they are far cheaper than Illumina. And then we have Ultima and MGI. The me of 10 years ago would not believe both 1) how many strong entrants we have to DNA sequencers these days, and 2) how much Illumina continues to dominate in sequencing. At some point us biologists only have ourselves to blame for our purchasing decisions and their consequences.
- ak217 3y ago
  It's been a while since I caught up with the field, and this sounds exciting. I'd like to learn more about what exactly has expired (or will expire?). Is it just the reversible terminator patents, or is there more? Is this the main patent in question? https://patents.google.com/patent/US7541444B2/en https://patents.google.com/patent/US7541444B2/en or are there others?
  - epistasis 3y ago
    I'm not an expert in the IP, but this 2021 summary is better than my best understanding https://41j.com/blog/2021/05/the-next-few-years-in-dna-sequencing/ https://41j.com/blog/2021/05/the-next-few-years-in-dna-seque...
- koeng 3y ago
  Oxford Nanopore with the new R10 cells is good enough for most synthetic biology applications (ie, plasmid sequencing and strain validation), which I'm super excited about. Combine low-capital and long-reads and you can do some really interesting things in the DNA assembly realm. It's pretty recent they got there though > At some point us biologists only have ourselves to blame for our purchasing decisions and their consequences Yep...
  - greazy 3y ago
    At the consensus level the accuracy is high. At the read level there's a lot of room foe improvement. Currently running r10 routinely for surveillance purposes. Seeing per read quality score average of 15.
- ejstronge 3y ago
  > Ion Torrent and Genapsys are barely used due to accuracy problems, Accurancy didn't have very much to do with Ion Torrent's demise. As we're reminded in the OP, Illumina pushed the MiSeq platform, and there wasn't much reason to transition to Ion Torrent. Now, with 250 bp+ PE reads on Illumina, there really isn't much special about Ion Torrent besides its somewhat superior homopolymer performance. > but Oxford Nanopore's considerable logistical benefits of tolerating a wide range of input DNA concentration, quick time to data, low capital cost, and long reads has kept them alive. Maybe they will grow more with higher accuracy. This statement is reasonable in today's era, but ONT was nowhere close to being competitive with Ion Torrent and other platforms during the time where labs were considering the Ion Torrent devices vs continued spend on Illumina platforms. The accuracy, tolerance to unusual DNA samples, and read length with clinically-relevant base qualities were unusable until 2018/2019.

by dekhn 3y ago

epistasis 3y ago

I'm sure you know this already, but for the benefit of the HN crowd... Yeah it's been unfortunate that the electronic sensors have not been able to keep up with the optical readouts. Ion Torrent and Genapsys are barely used due to accuracy problems, but Oxford Nanopore's considerable logistical benefits of tolerating a wide range of input DNA concentration, quick time to data, low capital cost, and long reads has kept them alive. Maybe they will grow more with higher accuracy. Illumina's patents ending recently has prompted a few new startups beyond 454.bio, including Element and Singluar, but with the stiff headwinds of FDA regulatory uncertainty and the long capital life of existing sequencers, it's hard for them to make progress even when they are far cheaper than Illumina. And then we have Ultima and MGI. The me of 10 years ago would not believe both 1) how many strong entrants we have to DNA sequencers these days, and 2) how much Illumina continues to dominate in sequencing. At some point us biologists only have ourselves to blame for our purchasing decisions and their consequences.

ak217 3y ago
It's been a while since I caught up with the field, and this sounds exciting. I'd like to learn more about what exactly has expired (or will expire?). Is it just the reversible terminator patents, or is there more? Is this the main patent in question? https://patents.google.com/patent/US7541444B2/en https://patents.google.com/patent/US7541444B2/en or are there others?
- epistasis 3y ago
  I'm not an expert in the IP, but this 2021 summary is better than my best understanding https://41j.com/blog/2021/05/the-next-few-years-in-dna-sequencing/ https://41j.com/blog/2021/05/the-next-few-years-in-dna-seque...
koeng 3y ago
Oxford Nanopore with the new R10 cells is good enough for most synthetic biology applications (ie, plasmid sequencing and strain validation), which I'm super excited about. Combine low-capital and long-reads and you can do some really interesting things in the DNA assembly realm. It's pretty recent they got there though > At some point us biologists only have ourselves to blame for our purchasing decisions and their consequences Yep...
- greazy 3y ago
  At the consensus level the accuracy is high. At the read level there's a lot of room foe improvement. Currently running r10 routinely for surveillance purposes. Seeing per read quality score average of 15.
ejstronge 3y ago
> Ion Torrent and Genapsys are barely used due to accuracy problems, Accurancy didn't have very much to do with Ion Torrent's demise. As we're reminded in the OP, Illumina pushed the MiSeq platform, and there wasn't much reason to transition to Ion Torrent. Now, with 250 bp+ PE reads on Illumina, there really isn't much special about Ion Torrent besides its somewhat superior homopolymer performance. > but Oxford Nanopore's considerable logistical benefits of tolerating a wide range of input DNA concentration, quick time to data, low capital cost, and long reads has kept them alive. Maybe they will grow more with higher accuracy. This statement is reasonable in today's era, but ONT was nowhere close to being competitive with Ion Torrent and other platforms during the time where labs were considering the Ion Torrent devices vs continued spend on Illumina platforms. The accuracy, tolerance to unusual DNA samples, and read length with clinically-relevant base qualities were unusable until 2018/2019.