Roundtable Discussion; The Future of Mineral Sands. Watch the video here.
@Monkshood - as I said yesterday, I have no personal experience of LFD's but I am told that the viscosity of the solution is a critical factor as is the draw time. Even the pressure the plastic cassette components exerts in the strip can (I'm told) adversely influence the way the chromatography runs.
I'm with you in that it does seem very simplistic and should one would expect be highly adaptable. The long lead times however make me think there must be more complexity than it first appears.
Thanks for your contributions this evening - and PAH and CO - good discussion
Ophidian
I think it is a lot about preserving the characteristics of the chromatography change too much and it runs completely differently hence if there is a system that works use it as a basis for development - That is what I thought the advantage of going with Mologic was rather than trying to develop from scratch just with Affimers as both Cytiva and BBI seemingly failed to do.
Ophidian
@Monkshood - Mologic had their own IP which is what allowed for a better LoD - I can't remember the details but I assumed that was part of the reason for using an antibody. Also - I seem to recall that the detection line is a mouse antigen - will need to check my notes but to be honest can't really be that exercised about it.
Ophidian
@monkshood - I read it in the Mologic datasheet some time back. If you recall I had info that Mologic were involved to achieve a lower LoD and did a bit of sniffing about.
Since this thread has now moved on a ways from the simplistic model I described yesterday please note: whilst the Affimers are basically "stuck" on the detection line and because they are also bound to the antigen which is also bound to the antibody the colour comes out. The actual mechanics however have the affimers wicking through the membrane and they are captured on the detection line.
Whilst it has been questioned (and a bit more strongly than that in some places) - I still believe that the affimer is in fact a ****tail of at least two affimers which I also didn't confuse yesterdays very simple description with.
Ophidian
Hi Bella - the original Saliva system which is the one shown in the Avacta animation used affimers not antibodies whereas (as some only realised very recently), the Mologic developed version uses antibodies to lug around the gold.
Ophidian
wcotter17 - assume for arguments sake that there are 100 virus particles on the LFD. To be detected the virus particle needs to be both picked up by the antibody carrying the gold nonparticle that causes the colour change at the detection line and also by the Affimer which differentiates it from every other thing the antibody has picked up.
If the antibodies only pick up 80 virus particles then even if the affimer finds all 100, only the 80 with the gold will be picked up on the detection line and change colour.
Hope this helps
Ophidian
"So great wise Ophidian says AVA6K has had no adverse affects, like it's fact. And herin lies the bastard problem."
It is fact you bloody moron it's a regulated clinical trial - any adverse events need to be reported immediately - joker
@Monkshood - yes and it's a great question - one I certainly don't have the answer to. Perhaps a ****tail - ?
Longer term why not an affimer, but that potentially is a completely different device. I have heard rumours that Saliva could make a return, there is also the S & N combo talked about any of which could be in development and have a different chromatography including new or combinations of antibodies / affimers. Until we are given more info it is all guesswork
Ophidian
. It is however a commercially available antibody but more importantly it is one that has been developed in addition to the colloidal gold solution ad the nitrocellulose strip and the absorbent pads and all the rest of the stuff that goes into making the LFD. All the stuff that in combination defines the chromatographic characteristics of the device – characteristics that we don’t want to just abandon or risk playing around with too much.
If (I think it’s more likely when) an alternative antibody with comparable characteristics is identified it will be easily slotted into the design without creating too many ripples of change to be accommodated.
Why doesn’t the current Velcro stick the omicron – I honestly don’t know, but given the multitude of changes to the spike we know are in the omicron variant it’s probably something rather subtle.
Why don’t Avacta just design an affimer to do the job instead like with the Saliva version – well that is probably an option but everything else would need to be optimised and that really would require both time and a revalidation of the whole including clinical validation (in my view). As it is, I’d be very surprised if just a change on the transport antibody necessitated a full revalidation, more likely a comparability protocol – after all the affimer that is doing the actual detecting hasn’t changed.
Ophidian
I chose to stay off of LSE today but I have noted many narratives on here that are just plain evil, manipulative and nasty as well as (in my view) wrong. So here is a post to try and explain some of the things that have been topics today.
It has been a truly horrible day for investors, there is no getting away from that, but it can be made much worse by poor decision making based on inaccurate information. Given my usual treatment on here I won’t be engaging in debate I will however try to respond to what I think are genuine questions. Bear in mind please these are my opinions, I’ve never been involved personally with the development of either affimers nor with a Lateral Flow Device.
First off – lets look at just how the LFD works. There is a really good video on the Abingdon website here:
https://www.youtube.com/watch?v=z07CK-4JoFo
Now bear in mind that this is showing a device that detects TWO antigens so is a bit more complex, however the video is very useful.
We need to know that the line that comes out on the LFD for both detection and the control line is actually caused by Gold – we see the colour because it is a concentration of colloidal gold being captured in a small space so the concentration manifests as more intense colour.
The gold is carried by an antibody which also picks up the virus particle. When it reaches the detection line our Affimer grabs hold of the virus binding at the specific binding site for the affimer and so as well as the virus, the gold is captured and that is what we then see.
The second line also catches the gold but not necessarily with a bound virus particle but we see that line as proof that the chromatography (the wicking along the membrane) got that far as it has to have to get past the detection line which always comes first.
If you pause the animation at about 1 min 24 seconds you get little labels clearly showing WHERE the unique Antigen binding is and it is this that makes the affimer LFD so very good because of the affimers high selectivity.
Now – back in the days of Cytiva and Saliva LFD there certainly was a suggesting that the transporting mechanism could also be an affimer – indeed the Avacta video shows it as such but whilst that would certainly be an option (and even though Alastair Smith has told us that the Saliva version is still there and works and could be used again in the future) – switching to nasal swabbing gave an opportunity to standardise many of the component parts of the LFD to make it’s commercialisation more straight forward and cost effective (and presumably quicker).
So going back a bit again – the virus particles are picked up by an antibody – it’s a pretty poorly discriminating antibody not specific at all like the affimer is. It’s basically a cheap biological Velcro that picks up stuff to transport to the detection line to be assessed by the selectivity of the affimer as Sars-Cov2 (of any variant) or just a cold virus or whatever.
cont/
The Affimer selectively binds the sars-cov2 Spike protein on the detection line.
The Sars-Cov2 virus particle arrives at the detection line (along with anything else - not then detected by the affimer) by being transported by a colloidal gold/antibody system.
Ophidian (only post today)
It is the adjournment debate tomorrow so right at the end of the session. Neale Hanvey gets up to half an hour to make his points and get them on the record with the minister put up. Please email or Tweet your own MP to encourage them to attend the adjournment debate (the chamber is often basically empty by then). There simply has to be some effort to support the UK diagnostics industry going forward, to shine a light on the atrocious science at Porton Down that favours Chinese imports and to ensure we have a thriving sector to combat this and future pandemics.
Ophidian (don't vote this up - just Tweet your MP)