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crispyambulance 20 minutes ago [-]
When practitioners say "PCR" they don't (usually) just mean amplifying DNA for use as part of the input to another process.
What they usually mean is PCR with chemistry that selectively amplifies some specific sequence of DNA. This chemistry has dyes in it which fluoresce when illuminated at some specific wavelength. The point of all this is to answer a "yes/no" question for the presence of some DNA sequence in the sample. This is done at scale with multiple chemistries looking for different DNA sequences. This is also known as "real-time PCR".
It's sort of like the biological-assay version of the kid's game "20-questions". If you do it right, it's an enormously powerful detection technique for medical purposes. It gives you your "answer" in a reasonable amount of time on your desk while you wait.
That said, there are biological assays that don't need the thermo cycling anymore. These newer assays use more sophisticated chemistry that amplifies at a constant heating temperature. In the simplest terms, they're just heaters combined with a fluorometer. It's potentially MUCH faster than realtime-PCR.
In any case, the only real serious money-making business for these instruments is in-vitro diagnostics. That requires FDA approval, and that means a ~10K minimum for the instrument and tens of dollars for the consumables containing the assays, and definitely a pricey service agreement for the instrument (eg Bio-Rad instruments).
A distant second money-making business would be research-use-only instruments, but these are not going to be inexpensive little devices.
fabian2k 4 hours ago [-]
This is about modern PCR, which is already optimized a lot compared to early PCR. And if you're in a "normal" lab, everything around the PCR, all the handling and preparation will be such a large chunk of time that improving the PCR time alone doesn't really matter that much.
In a very automated, high-throughput setting I'd imagine that parallelizing the PCR would be the best way to increase throughput. There probably isn't that much potential in speeding up the time compared to just multiplying the number of reactions. Which is part of the point of the article.
Regarding the cheaper lab instruments, I'm not quite convinced by these ultra cheap examples. Many lab instruments need quite a bit of precision and reliability, and I would be suspicious that the cheap examples here could compete in that regard. Even PCR needs pretty exact temperature control across many individual reaction vessels. Of course the margins on lab instruments are likely enormous, and there should be plenty of potential for cheaper ones. But I don't think the ultra-cheap DIY stuff will convince people, and it'll likely also fail at the purchasing process anyway for larger institutions.
otherme123 4 hours ago [-]
The way to sell new cheap stuff is to give it away for a period of time, with the obligation to buy the reactives from you (you just buy them and re-tag, as if they where specific for your machine). This way the lab can test the reliability of the machine without any risk.
Also, don't dismiss the user end here: people using the thermo are used to other interface(s), and they will complain endlessly about how bad it is if they fail to, for example, program the machine even if it is their fault. They don't want to think or struggle. If they do, they will tell their supervisor that the machine is crap, and you won't sell it even for 10$.
ezconnect 2 hours ago [-]
This is how the consumer Glucose meter market works. The machine is free and it only accept their rebranded sticks.
ajb 4 hours ago [-]
Although his details are likely correct, this is not an analysis from physical laws (and other hard requirements, eg usability requirements) which is what you need to show optimality, it's an exploration of the known options.
He makes the point that labs wouldn't adopt a cheaper machine - yes, much cheaper processes are often adopted first by outsiders, who couldn't afford the current ones. Not clear if there's a huge market for home PCR or similar (many DNA-active chemicals need to be used under controlled conditions because mucking with your DNA causes cancer -not sure about PCR specifically)
From a physical point of view, I wonder if energy- transfer thermal cyclers could be replaced by adiabatic compression, which is likely much faster. Depends how well these enzymes work at high pressure. Could be problematic at a process level though.
bahador 3 hours ago [-]
one of the coolest parts about the original inception was the application of taq polymerase. veritasium did a video of about it not too long ago. a friend of mine and a man whom i very much respect was mullis's lab manager at the time.
What they usually mean is PCR with chemistry that selectively amplifies some specific sequence of DNA. This chemistry has dyes in it which fluoresce when illuminated at some specific wavelength. The point of all this is to answer a "yes/no" question for the presence of some DNA sequence in the sample. This is done at scale with multiple chemistries looking for different DNA sequences. This is also known as "real-time PCR".
It's sort of like the biological-assay version of the kid's game "20-questions". If you do it right, it's an enormously powerful detection technique for medical purposes. It gives you your "answer" in a reasonable amount of time on your desk while you wait.
That said, there are biological assays that don't need the thermo cycling anymore. These newer assays use more sophisticated chemistry that amplifies at a constant heating temperature. In the simplest terms, they're just heaters combined with a fluorometer. It's potentially MUCH faster than realtime-PCR.
In any case, the only real serious money-making business for these instruments is in-vitro diagnostics. That requires FDA approval, and that means a ~10K minimum for the instrument and tens of dollars for the consumables containing the assays, and definitely a pricey service agreement for the instrument (eg Bio-Rad instruments).
A distant second money-making business would be research-use-only instruments, but these are not going to be inexpensive little devices.
In a very automated, high-throughput setting I'd imagine that parallelizing the PCR would be the best way to increase throughput. There probably isn't that much potential in speeding up the time compared to just multiplying the number of reactions. Which is part of the point of the article.
Regarding the cheaper lab instruments, I'm not quite convinced by these ultra cheap examples. Many lab instruments need quite a bit of precision and reliability, and I would be suspicious that the cheap examples here could compete in that regard. Even PCR needs pretty exact temperature control across many individual reaction vessels. Of course the margins on lab instruments are likely enormous, and there should be plenty of potential for cheaper ones. But I don't think the ultra-cheap DIY stuff will convince people, and it'll likely also fail at the purchasing process anyway for larger institutions.
Also, don't dismiss the user end here: people using the thermo are used to other interface(s), and they will complain endlessly about how bad it is if they fail to, for example, program the machine even if it is their fault. They don't want to think or struggle. If they do, they will tell their supervisor that the machine is crap, and you won't sell it even for 10$.
He makes the point that labs wouldn't adopt a cheaper machine - yes, much cheaper processes are often adopted first by outsiders, who couldn't afford the current ones. Not clear if there's a huge market for home PCR or similar (many DNA-active chemicals need to be used under controlled conditions because mucking with your DNA causes cancer -not sure about PCR specifically)
From a physical point of view, I wonder if energy- transfer thermal cyclers could be replaced by adiabatic compression, which is likely much faster. Depends how well these enzymes work at high pressure. Could be problematic at a process level though.
https://youtu.be/zaXKQ70q4KQ