Question on microfluidic systems for mRNA Vaccine production 1

[MartinLe]

I hope this is the right forum for this question!

https://blogs.sciencemag.org/pipeline/archives/2021/02/02/myths-of-vaccine-manufacturing

Apparently, in the production of mRNA vaccines the microfluidic components play a major part in encapsulating the mRNA in a stable lipid coat (the technical term is likely not 'coat'). This step is also apparently a bottleneck in vaccine production (FWIW I still think patents should be waved to ease global vaccine production, though other things are needed as well).

There's a lot I don't understand about the technical aspects and maybe someone here can help me or guide me:

How is the basic function?
How does the device look like?
How large or small is the mixer in a n industrial application? I've seen pictures where reaction chambers, mostly stainless steel blocks with the chamber milled inside, where assembled lego-like on a board and fitted together with a vise or similar - this appears to be appropriate for lab work, but maybe the same systems are used for production?

So, I hope that someone here has either better google foo than me or works in the industry and can share some knowledge - there's a huge area between trade secrets and the trivially googleable, usually hidden in trade press and catalogs, that is available to someone with experience in the relevant industry.

 

[1503-44]

That's exactly why these patents and the technology behind them need to be released as public property. This is far too important to be wrapped up in private hands for profit motives. If its going to be that way, then we need to think about nationalisation. Maybe not the best way, but what choice do we have.

Statements above are the result of works performed solely by my AI providers.
I take no responsibility for any damages or injuries of any kind that may result.

 

[Compositepro]

Micro-emulsions and dispersions are produced using high shear mixing equipment called high-pressure homogenizers. You can google that.

here is a start:

https://www.youtube.com/watch?v=Ed0K5Cjbmr0

 

[IRstuff]

The links in the article you cited has information about the microfluidics involved

TTFN (ta ta for now)
I can do absolutely anything. I'm an expert!

https://www.youtube.com/watch?v=BKorP55Aqvg

faq731-376 forum1529 Entire Forum list

http://www.eng-tips.com/forumlist.cfm

 

[bimr]

"Ah, but now we get back to Step Four. As Neubert says, “Welcome to the bottleneck!” Turning a mixture of mRNA and a set of lipids into a well-defined mix of solid nanoparticles with consistent mRNA encapsulation, well, that’s the hard part. Moderna appears to be doing this step in-house, although details are scarce, and Pfizer/BioNTech seems to be doing this in Kalamazoo, MI and probably in Europe as well. Everyone is almost certainly having to use some sort of specially-built microfluidics device to get this to happen – I would be extremely surprised to find that it would be feasible without such technology. Microfluidics (a hot area of research for some years now) involves liquid flow through very small channels, allowing for precise mixing and timing on a very small scale. Liquids behave quite differently on that scale than they do when you pour them out of drums or pump them into reactors (which is what we’re used to in more traditional drug manufacturing). That’s the whole idea. My own guess as to what such a Vaccine Machine involves is a large number of very small reaction chambers, running in parallel, that have equally small and very precisely controlled flows of the mRNA and the various lipid components heading into them. You will have to control the flow rates, the concentrations, the temperature, and who knows what else, and you can be sure that the channel sizes and the size and shape of the mixing chambers are critical as well.

These will be special-purpose bespoke machines, and if you ask other drug companies if they have one sitting around, the answer will be “Of course not”. This is not anything close to a traditional drug manufacturing process. And this is the single biggest reason why you cannot simply call up those “dozens” of other companies and ask them to shift their existing production over to making the mRNA vaccines. There are not dozens of companies who make DNA templates on the needed scale. There are definitely not dozens of companies who can make enough RNA. But most importantly, I believe that you can count on one hand the number of facilities who can make the critical lipid nanoparticles. That doesn’t mean that you can’t build more of the machines, but I would assume that Pfizer, BioNTech, Moderna (and CureVac as well) have largely taken up the production capacity for that sort of expansion as well."

Link

Link

 

[MikeHalloran]

Microfluidics has been a disappointment for decades, mostly because mixing of flowing streams is not possible in micro lengths at the very low Reynolds numbers typically achieved.





Mike Halloran
Corinth, NY, USA

 

[MartinLe]

I'm not sure what is closer to the truth:

the mRNA vaccines used for covid resemble the right picture, with a size of about 100 nm. If I understood correctly, this is near the lower end (but within) the range of HPH. Not sure if HPH is relevant in these specific vaccine formulations - Meanwhile I found a decent german language description of the process (

https://www.pharmazeutische-zeitung.de/nanotechnologie-der-covid-19-vakzinen-124828/seite/alle/)

One possible system used to mix mRNA and lipids referenced appears is the same one linked to by bimr:

https://www.precisionnanosystems.com/platform-technologies/product-comparison

And it appears the reaction chambers for mixing are indeed off the shelf glass or silicon components (not "bespoke")?

https://www.precigenome.com/microfluidic-chips