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Want to build a sequencer? 454.bio opens up their plans

145 点作者 mfld超过 1 年前

18 条评论

epistasis超过 1 年前
The most interesting thing here is the open-source bio startup aspect. This is a bold step, and I hope it prompts more startups to go this direction.<p>They are clearly at the early stage of tech dev. And the reward of $200k for the polymerase to allow longer reads seems pretty low to me... unless you&#x27;re a grad student and the university doenst take your IP...<p>Honestly it&#x27;s pretty hard to get lab access without somebody also getting rights to your IP, and labs are a bit more expensive than setting up an H100, so it might be tough going.<p>Even if no external party solves their polymerase problem I have a good feeling about this direction though. Godspeed.
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codetrotter超过 1 年前
Not the kind of sequencer I was first expecting[0], but I&#x27;ll take it.<p>[0]: <a href="https:&#x2F;&#x2F;www.sweetwater.com&#x2F;insync&#x2F;step-sequencer&#x2F;" rel="nofollow">https:&#x2F;&#x2F;www.sweetwater.com&#x2F;insync&#x2F;step-sequencer&#x2F;</a>
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ak217超过 1 年前
This is super interesting and a promising development for those of us dreaming of running a lab out of a garage. I&#x27;ve never worked with Rothberg directly, but I&#x27;ve read great stories of him cultivating entrepreneural talent in molecular biology.<p>When PacBio was scaling their technology, they had lots of problems with photobleaching. It turns out shining intense laser light at a polymerase-nucleotide-fluorophore complex and inducing lots of electron flux in the fluorophore eventually causes an electron to get overexcited, jump around, and damage the machinery. PacBio eventually invested a lot in builidng elaborate shields into the nucleotide-fluorophore link, able to absorb the stray electrons and save the polymerase.<p>Given that experience, I&#x27;d expect shining intense UV light into a TIRF volume to break the reversible terminator link will cause lots of photobleaching. It will be interesting to see if 454.bio can overcome this.
lbotos超过 1 年前
Straight to the &quot;Build&quot; page: <a href="http:&#x2F;&#x2F;454.bio&#x2F;docs&#x2F;build&#x2F;" rel="nofollow">http:&#x2F;&#x2F;454.bio&#x2F;docs&#x2F;build&#x2F;</a>
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daemonk超过 1 年前
The problem of non-selective cleavage of all terminators, whether they have been incorporated or not seems to be the most significant one. Is engineering a selective polymerase really the best solution here? If you don&#x27;t top-up the reaction with un-cleaved terminators, won&#x27;t the reaction become slower and slower as you go? The ideal solution is somehow have terminators that will only get cleaved after incorporation (maybe due to conformational changes); but I can see how that&#x27;s probably even harder to engineer than a selective polymerase.<p>I can see that the complex microfluidics and reagent cycling can be a big added complexity&#x2F;cost. The continuous process is definitely more elegant, but also seems really difficult to get right for longer read lengths and I wonder if it is really worth it.<p>What would be the potential benefits of the continuous process? I guess cheaper reagents since it is a one-pot process and faster sequencing speed since you don&#x27;t need to cycle reagents?
Jun8超过 1 年前
This really gets my blood flowing, it really is the future! The question is: can we get experimentation in biology, say, for high schoolers and undergrads, as easy&#x2F;cheap&#x2F;interesting as computing? On the order of buying a good laptop, i.e. - $1,500. What can be done on the order of buying a rapid and a few sensors and a breadboard, $50-$100?<p>Unfortunately pretty much biological equipment is so expensive and relatively hard to use. Case in point: my son is looking to measure amylase activity in the presence of various inhibitors for diabetes research. The cheapest spectrophotometer devices are $1k-$2k. Surely there must be a way to lose some accuracy but bring the price to $100-$200.
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inciampati超过 1 年前
I got my start in genomics working on an open source DNA sequencer. In the end, we built a powerful scanning fluorescent microscopy platform that saw a few beautiful experiments done on it. I always wondered when this might happen in a truly open way. With the right tech and a focused corporate backing it really could happen. Maybe this is the beginning of something very interesting.
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AtomicOrbital超过 1 年前
A real catalyst would be to couple a sequencer to digitize the DNA together with a matter compiler to output real DNA from the digital DNA representation<p>Why? craft software to grow the organism in a biologically plausible manner in simulation from the digital DNA... then expose evolutionary pressure to this growth to evolve the DNA in simulation into a more value added organism<p>real organism --&gt; sequence it&#x27;s DNA into digital DNA --&gt; evolve the DNA in simulation software --&gt; output real DNA from digital DNA --&gt; insert this evolved real DNA into a real cell to clone an organism now with enhanced attributes
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dekhn超过 1 年前
It&#x27;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.
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userbinator超过 1 年前
I was curious about the reappearance of that number in a biology context (to me, it evokes a famous car engine), and remembered this interesting video on the old and once-very-expensive Roche 454 GS (also a very automotive-sounding name) sequencer:<p><a href="https:&#x2F;&#x2F;www.youtube.com&#x2F;watch?v=XaumUp4GpCw" rel="nofollow">https:&#x2F;&#x2F;www.youtube.com&#x2F;watch?v=XaumUp4GpCw</a>
lynx23超过 1 年前
I need coffee. It took me almost two paragraphs to understand the topic is DNA Sequencing and not sequencing a synthesizer (music).
jesprenj超过 1 年前
I&#x27;m not educated in molecular biology. Will this device enable DIY enthusiasts to sequence their entire DNA, the whole 700 MB of it, at home? Or is the device only able to sequence small chunks of the DNA?<p>Is the device able to sequence DNA with minimal errors?
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CyberDildonics超过 1 年前
Someone really should have put &quot;DNA sequencer&quot; in the title.
w10-1超过 1 年前
Sorry, I just don&#x27;t see how to extend the limited read length of ~5 without more microfluidics, and the reagent story is unclear.
Palomides超过 1 年前
single digit read lengths is pretty rough, I don&#x27;t have the chemistry knowledge to tell if this approach is scalable
potsandpans超过 1 年前
Kinda cool, I&#x27;m out of my depth here. What would be some interesting things to do with this once it was built?
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wslh超过 1 年前
ELI5: could you have your full DNA? I thought that a device retrieving your full DNA is in the USD 100k range.
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pixl97超过 1 年前
How long before I can build my own, hook it to ChatGPT, make the national news and all the AI safety people go ballistic?