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I will attempt a mRNA microfluidics effortpost (viral vector ones are there own things, and also completely separate from traditional mass-produced egg-grown vaccines, but those are being made by dozens of companies worldwide already because tissue culturing is more developed than microfluidics) Microfluidics in general Microfluidics is a big research area in the past few decades. It's about how fluid and particles behave in very small (~0.1-1000um wide) channels. This is interesting because a lot of fluid properties depend on forces that don't scale the same way with size. For example, if you took a big pipe and put both hot and cold water into one side of it, they will mix as they go down the pipe. If you do that in a microchannel, they'll stay on their sides without mixing. Microfluidics as a field is looking to describe behavior, and then use it to do stuff that's hard to do at macroscale Typical workflow for a research lab trying to see if an idea actually works is sending a design to a place with semiobsolete semiconductor fab equipment and getting it etched onto a silicon wafer for a few thousand dollars and a week or two of turnaround time. Then you use grad student labor to cast PDMS (a kind of rubber) off of the wafer mold, plasma treat the PDMS to mess with its surface chemistry, and attach it to a glass slide to make an enclosed channel. This has problems, but is workaround-able since you don't need high quality or high throughput. It's okay if some casts tear/don't fill the mold/clog/leak/etc because you're going to be looking at everything with a microscope anyway and you can mess with it till you get a good one. And you don't care if running for hours produces less than a drop of output since your papers are going to be presenting microscope pictures & video for things like 'this channel geometry makes oil-in-water droplets of consistent size', not using the output material for anything. (PDMS is also squishy and deforms when you pressurize it, which is annoying since dimensions change vs the mold) mRNA vaccine microfluidics The bottlenecking part of production is getting the mRNA inside a protective membrane of lipids. There's spare manufacturing capacity where you could get extra tanks of mRNA/lipid/buffer waiting to be packaged and spare manufacturing for getting assembled bubbles into vials, the limiting part is doing the bubble assembly. The assembly is done microfluidically. Each vaccine will have its own bespoke microfluidic chip design where you syringe pump in reagents at some particular flow rates+temperatures and the channel geometries make stuff fold into consistent assembled bubbles coming out the output. Unlike the research lab, you care about throughput and you care about quality. That means the chip design needs thousands of copies in parallel (just making it bigger would make it stop working) and you need a way to make it more reproducibly. This generally means photolithography etching glass to make the chips directly, similar to how semiconductor fab is photolithography for etching silicon (it has its own unique problems of course, since glass is not silicon and aspect ratios of the geometry being made are different). Immediate production None of this manufacturing looks anything like typical drug manufacturing or drug manufacturing equipment manufacturing and pharma companies don't have any relevant equipment or experience for it. They're outsourcing chipmaking to the few manufacturers that do do it. There aren't many of these, it's complicated and until recently hasn't had any mass manufacturing applications. If you were trying to set up a new vaccine factory, you'd hit a point in the process where you need to run stuff through a chip and be told "We get companies X, Y, Z to make these for us, we don't know of anyone else who can make them, and we're already buying the entire production". I don't think this is a developed vs developing world thing, it doesn't make sense to have a western pharma company set up a new factory either. If the entire world produces 1000 chips/day and the one existing vaccine factory can use all of that, it doesn't make sense to reduce the existing one to 900/day and try to set up a brand new factory elsewhere. Waiving the patent for the chip design doesn't get any more actual physical chips in existence. Long term production Since microfluidic mass production has an application now, factory capacity is going up and will continue going up. That takes time though. For comparison, a silicon semiconductor fab typically takes 2-3 years to go from start of construction to producing. ICs are a more complicated process because features are 10-100X smaller, but it's also a more well developed process that glass. There's also not really an IP barrier here. People know how to do lithography, machines just still have lead times to be made and it takes time to assemble and get everything working together so the endproduct is consistently good
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May 2, 2021 20:20
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Thank you for the post. It's really helpful to know that the process is somewhat similar to chip manufacturing as that's probably a much more familiar field to many. Can folks with experience in that can move over to this work? Are the same companies dominant in silicon etching also dominant in glass etching? Just not sure if the process you describe for research labs is the same process you describe for production mRNA work. Seems like it probably isn't (presumably cutting out a lot of steps + adding lots of quality control / process improvements).
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May 3, 2021 00:37
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Are there any more theories on when things might finally open back up? Looking at California's drop in cases and holding them low is some phenomenal progress. I think they are on track to hit the June 15th re-opening date. https://twitter.com/ashishkjha/status/1388900900886941697?s=20 https://twitter.com/SithyPoo/status/1388901929036750848?s=20
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May 3, 2021 00:47
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https://twitter.com/ashishkjha/status/1388900903768449025 This is some IHME‐level prognostication. The discrepancy in NPIs between these states is far larger than the discrepancy in vaccination uptake.
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May 3, 2021 00:54
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You also need to factor in acquired immunity, Oregon had rising cases and relatively high vaccination but still encountered rising cases.
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May 3, 2021 01:23
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Evil Robot posted:Thank you for the post. It's really helpful to know that the process is somewhat similar to chip manufacturing as that's probably a much more familiar field to many. Can folks with experience in that can move over to this work? Are the same companies dominant in silicon etching also dominant in glass etching? Just not sure if the process you describe for research labs is the same process you describe for production mRNA work. Seems like it probably isn't (presumably cutting out a lot of steps + adding lots of quality control / process improvements). Having been in the industry a decade ago and with friends still in it I would say that the best route for large scale manufacturing of glass plates with micrometer-level features and electrodes for flow control (iirc a lot of microfluidics uses static charges as valves) wouldn't be the wafer fabs but the LCD panel fabs.
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May 3, 2021 01:27
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Beyond the technology bottleneck for reactor manufacturer. It also take a ton of time to qualify a new installation. Trying to install all this new technology, and then prove it, and all the ancillary equipment needed to run it, works as expected every time is an immense undertaking. And, that's just to show the equipment works as expected. Once you've done that, you need to validate the process in that equipment to prove you can make the vaccine of acceptable quality every time you run. It be faster if you can retrofit an existing plant, but any new facility is years out from production.
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May 3, 2021 01:33
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Platystemon posted:https://twitter.com/ashishkjha/status/1388900903768449025 So... there's more to the story and we should not start to expect a significant drop in cases once we hit 50% vaccination?
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May 3, 2021 01:49
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sexpig by night posted:don't know if the literal number 1 but they're among the top for sure yea, the idea they're the international version of 'a homeless person' trying to make filet mignon is absolute insanity. India is a top producer but not for that type of vaccines. Their main output has been inactivated virus ones if I recall correctly, which is basically "jab eggs with an infected needle, wait, crack egg, purify and inactivate virus, send for bottling" For mRNA vaccines they would need new factories with complete technology transfer as everything up to bottling is completely different production lines. If they have had problems with their AZ scale up it might also be due to the general mess of global logistics and last year's crunch of large scale cełl culture supplies, something which have been hard to fix. As an example of hard to fix, one common polymer used in cell culture has large variances in effectiveness based on supplier and partly by batch. Thus you can't just source that easily from other suppliers and might simply have to wait for your favorite supplier to ramp up production or deliver your backlogged orders.
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May 3, 2021 02:35
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https://twitter.com/ryanstruyk/status/1388188124539465730?s=20 The new mason-dixon line
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May 3, 2021 03:32
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It's really interesting that experts itt are considering the technical arguments, while the patent lobbyists will probably make an economic one, probably either: 1. At this stage, the supply chain is one of the main limiting factors. If countries like India, China, Turkey (?) etc. could try to build up mRNA facilities, they will most likely start to secure supplies early on, either by contracts outbidding others or by hoarding. In any case, factor demand will increase. In fact, securing supplies allows resales if the mRNA project takes more time which would be profitable in a squeeze. This could increase cost of the vaccine (globally) and it is possible that this would also decrease global supply if the productivity is lower for new entrants. 2. mRNAs are meant to eventually defeat cancer. Decreasing input factor supply or (depending on whom you are lobbying) decreasing profit "incentives" by introducing competitors on the factor market, could delay the development of cancer vaccines. Both arguments are somewhat bullshit, economically speaking. However, these arguments will be brought up in court. And there, you could probably hire NERA, CRA or Analysis Group to produce a convincing assessment that both local and global supply would suffer by these actions. The other side would hire one of these companies to produce an assessment to the contrary. This is what would probably happen.
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May 3, 2021 07:03
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I think it's a moot point, overall, if out goal is to manufacture as many vaccine doses as possible. For that we need a vaccine that's way easier to produce without these moonshot nanolipid mixing technologies and without the potential quality control issues that vectored vaccines have. Inactivated virus vaccines come to mind but the problem with those is that this virus is incredibly dangerous, so you need a BSL-3 level biocontainment facility to produce them. If you're going to grow massive quantities of virus and then chemically deactivating them, the last thing you want is for that virus to escape and infect someone before it's deactivated. I'm honestly not sure how many of these type of facilities exist in low to medium income countries that could produce sufficient quantities of vaccine. Most of them are small research lab type places, not big production facilities. But I might be wrong. The other type of vaccine is a protein subunit vaccine. This is where you genetically modify an organism, like for example yeast to produce antigens of the pathogen you're targeting. In the case of SARS-CoV-2 the spike protein ofc. You grow these organisms in large bioreactors and once you have enough you break them open, filter out the proteins you want and combine them with an adjuvant to activate the immune system. So if you ask me, as far as building vaccine production capacity right now, we'd be far better off concentrating on those technologies that could be scaled up globally by many countries. However, I would like to reiterate my position that this technology should be shared with all of mankind. It's just not going to get us out of this current mess.
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May 3, 2021 08:10
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OddObserver posted:Lowlights:
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May 3, 2021 08:34
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Forgall posted:Cool cool, I've started coughing a bit after getting second dose and it still haven't cleared up 6 weeks later. Now wondering if I got lucky batch with live adenovirus bonus. It would be very difficult for the virus to make it from your deltoid to your lungs, so probably not.
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May 3, 2021 09:05
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spankmeister posted:It would be very difficult for the virus to make it from your deltoid to your lungs, so probably not.
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May 3, 2021 09:12
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Forgall posted:Is it only capable of replicating in the lungs? No, but it needs to get into the blood to make it out of the muscle into other organs, which doesn't happen very easily from what I understand.
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May 3, 2021 09:36
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spankmeister posted:No, but it needs to get into the blood to make it out of the muscle into other organs, which doesn't happen very easily from what I understand.
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May 3, 2021 09:42
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Forgall posted:I see. So it's more likely I just caught something (hopefully not covid) while getting my second shot. Given the time of year, it's more likely you have allergies.
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May 3, 2021 09:52
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spankmeister posted:I think it's a moot point, overall, if out goal is to manufacture as many vaccine doses as possible. It really sounds like it ought to be a two-pronged approach. Get construction started on as many mRNA moonshot factories (and factories to create the materials required to supply them) in as many countries as possible. Since they're going to take a long time to complete, also convert production in some more traditional facilities to a COVID vaccine that they can produce as-is in order to get as many people vaccinated now as possible. Then, as the moonshot factories start cranking out the good poo poo, start switching over to those. Assuming they end up testing as safe to use after having received a different type of vaccine, they could be used for boosters for the folks who got the other vaccines, and for full courses plus boosters for the folks who didn't get any at all.
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May 3, 2021 09:56
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Herstory Begins Now posted:Given the time of year, it's more likely you have allergies. I never had seasonal allergies in my life until last year!
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May 3, 2021 10:11
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https://www.nytimes.com/2021/05/02/us/miami-centner-academy-coronavirus-vaccine.html?action=click&module=Top%20Stories&pgtype=Homepage Florida being Florida folks. Fears of 'vaccine shedding' LMAO. I know it's really not funny, but it's irresistible to laugh.
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May 3, 2021 10:38
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spankmeister posted:No, but it needs to get into the blood to make it out of the muscle into other organs, which doesn't happen very easily from what I understand. I mean — not a doctor — but Dan Griffin was on TWIV two weeks ago talking about how actually we may have misunderstood the whole "inject into the deltoid to avoid the bloodstream" thing, because certain categories of people were more likely to have well-veined delts, and less-well trained people delivering jabs on an emergency basis would be even more likely to potentially inject into the bloodstream. This was one of the theories of action on why the adenovirus vaccines were causing clotting, although I don't know how that was considered in the final analysis.
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May 3, 2021 10:44
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Forgall posted:I see. So it's more likely I just caught something (hopefully not covid) while getting my second shot. If you want to be sure, why not get tested?
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May 3, 2021 10:48
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Petey posted:I mean — not a doctor — but Dan Griffin was on TWIV two weeks ago talking about how actually we may have misunderstood the whole "inject into the deltoid to avoid the bloodstream" thing, because certain categories of people were more likely to have well-veined delts, and less-well trained people delivering jabs on an emergency basis would be even more likely to potentially inject into the bloodstream. This was one of the theories of action on why the adenovirus vaccines were causing clotting, although I don't know how that was considered in the final analysis. Yeah I saw that. I do know they the EMA looked into this whole aspiration (pulling back) before injection thing in relation to the AZ blood clotting and there was no correlation. It was covered in either their Oxford/AZ or Janssen press conference. I'm also not a doctor, so perhaps OP should consult one if they're really worried. But I wouldn't be.
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May 3, 2021 10:54
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Petey posted:I mean — not a doctor — but Dan Griffin was on TWIV two weeks ago talking about how actually we may have misunderstood the whole "inject into the deltoid to avoid the bloodstream" thing, because certain categories of people were more likely to have well-veined delts, and less-well trained people delivering jabs on an emergency basis would be even more likely to potentially inject into the bloodstream. This was one of the theories of action on why the adenovirus vaccines were causing clotting, although I don't know how that was considered in the final analysis. BRB, buying stock in companies that make vein finders. https://www.youtube.com/watch?v=gR1Zve3tRpw
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May 3, 2021 11:40
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spankmeister posted:If you want to be sure, why not get tested? Agreed. Rather than passively worrying about your health for weeks, just go get tested. You're probably just fine, but testing is free and quite accessible now.
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May 3, 2021 12:04
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Haramstufe Rot posted:It's really interesting that experts itt are considering the technical arguments, while the patent lobbyists will probably make an economic one, People itt do care about sounding ghoulish though so they reach for technical reasons to explain to themselves why governments and corporations will let countless foreigners die if they can make a nickel off it. That can't be what's happening, it must be technically impossible to do anything else.
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May 3, 2021 13:29
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https://twitter.com/yashar/status/1389165593287225348 Well, gently caress.
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May 3, 2021 14:20
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IBroughttheFunk posted:https://twitter.com/yashar/status/1389165593287225348 This isn't anything different than what we've all been talking about in this thread forever. Covid won't go away, but it'll be largely manageable
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May 3, 2021 14:22
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IBroughttheFunk posted:https://twitter.com/yashar/status/1389165593287225348 Literally the only possible outcome without some sort of mandatory vaccination program.
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May 3, 2021 14:26
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Riptor posted:This isn't anything different than what we've all been talking about in this thread forever. Covid won't go away, but it'll be largely manageable unless you've had an organ transplant. then, rip. this is the best we could do without trying.
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May 3, 2021 14:30
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spankmeister posted:If you want to be sure, why not get tested? Do they even have readily available adenovirus tests? And even if they did, its an adenovirus, I'm not sure knowing gives you any additional options beyond waiting it out
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May 3, 2021 14:30
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And of course, the worst of the negative health impacts will be shouldered by poorer countries that lack the infrastructure to provide the regular boosters that'll be required. All because our gormless asses can't be bothered to care about anyone, or anything beyond our immediate comfort.
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May 3, 2021 14:30
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Insanite posted:unless you've had an organ transplant. Well that's why they said "largely". And honestly treating the huge amount of stuff thats been done as not trying is kinda insulting. This isnt a result of not trying so much as active sabotage against those who are.
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May 3, 2021 14:33
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Riptor posted:This isn't anything different than what we've all been talking about in this thread forever. Covid won't go away, but it'll be largely manageable Are boosters always going to be free? Has the govt said anything about this? I guess the best version of "normal" is mRNA tech getting better and better each year with free shots, so we can have two society tiers (and I'm in the one that doesn't have a lifespan of 65). smoobles fucked around with this message at 14:38 on May 3, 2021 |
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May 3, 2021 14:35
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GlyphGryph posted:Well that's why they said "largely". And honestly treating the huge amount of stuff thats been done as not trying is kinda insulting. This isnt a result of not trying so much as active sabotage against those who are. I'm perfectly comfortable insulting the United States' COVID19 response. Over half a million people have died, most of them needlessly, and now we're discontinuing NPI orders across the country without actually waiting for cases to be stamped out.
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May 3, 2021 14:36
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smoobles posted:Are boosters always going to be free? Has the govt said anything about this?
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May 3, 2021 15:03
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smoobles posted:Are boosters always going to be free? Has the govt said anything about this? Considering how hard it is already to get people vaccinated? Almost certainly. The pharma companies won't care, mRNA tech is a money-printing machine for a whole host of reasons. They can afford to let government subsidies cover a handful of COVID boosters on the cheap for the sake of PR.
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May 3, 2021 15:07
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Charles 2 of Spain posted:It'll be a subscription based model. They'll need a marketing name to sell it... I think "Ambrosia" sounds really nice. Evokes a nice green idea, like money.
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May 3, 2021 15:11
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NecroBob posted:They'll need a marketing name to sell it... I think "Ambrosia" sounds really nice. Evokes a nice green idea, like money. Old men, are the future.
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May 3, 2021 15:15
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