Open Medicine Foundation (OMF)

bobbler said:
Am I right in assuming that to measure impendence they are using the nanoneedle to penetrate the cell itself?
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I think I worked out not. You would need a concentric electrode to do that - like a Jack plug with one electrode at the tip and the opposite on the hilt. The nano needle isn't a needle but a bar with two electrodes side by side. If cells are unhappy you expect their permeability to increase and impedance across the membrane to decrease. This appears to be some change along the surface of the cell - which is why it seems to me such a strange thing to measure.
 
Jonathan Edwards said:
I think I worked out not. You would need a concentric electrode to do that - like a Jack plug with one electrode at the tip and the opposite on the hilt. The nano needle isn't a needle but a bar with two electrodes side by side. If cells are unhappy you expect their permeability to increase and impedance across the membrane to decrease. This appears to be some change along the surface of the cell - which is why it seems to me such a strange thing to measure.
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Thank you.

It's pretty relevant stuff to define in the methodology it feels - I tried google and was surprised that I didn't just get the answer. I've seen an engineering-related paper that talks of nanoneedles that can go inside (but then that just throws various other questions in my mind).

I'd initially assumed the electrode either side std 'resistance/capacitor' element in circuit but then second guessed myself as I though if it's the outside then it would be the membrane they are measuring and is there any way they could be doing that 'clean' of the plasma and salt itself etc.

I like to picture things to work out the problem and find it frustrating that I can't mostly!
 
bobbler said:
Am I right in assuming that to measure impendence they are using the nanoneedle to penetrate the cell itself?

and how do they get salt into the cell without it going into the plasma, and would it matter if they did?
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[EDIT - hadn't read Jonathan's post when I wrote this!]
The cell is in a dilute saline solution [but more salty than the cell] so the cells is basically less "concentrated" than the surrounding salty solution - so the cell has to pump salt out -- stressor/work.

I think the cell is intact so basically this is nanotechnology - it's possible to connect nanoelectrodes to the outer cell membrane and measure impedance across the cell [based on Jonathan's post it seems they measure along a piece of (outer) cell membrane - not "across" the cell]. I think a lot of concerns are based on the fact that this is an artificial scenario.
 
While we're sharing our confused memories of the explanations of the nano needle, I remembered it differently again. I thought it was about the cell's ability to keep salt out, ie active transport to counteract diffusion. So what is being measured is whether the salt content of the solution decreases because the cells are taking up salt and unable to pump it out again.
I suspect I've misremembered.
 
FMMM1 said:
I think a lot of concerns are based on the fact that this is an artificial scenario.
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For me it is more that I do not know why this measurement should be of any interest.
It is a bit like having a person in shock. If you measure impedance on their skin it may be low because they are sweaty but it would be more useful to check their pulse and blood pressure.
 
Trish said:
I've just started re reading Simon M's explanation. Looks like I was sort of right in my oversimplistic way:
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I'm not sure that Simon's account is quite right though! Hypertonic solution should make cells shrink, not swell. If the impedance has anything to do with the cell it must be something to do with a change in the structure of the membrane I think.
 
bobbler said:
Am I right in assuming that to measure impendence they are using the nanoneedle to penetrate the cell itself?
Click to expand...

As I understand it, they basically just added a little salt into the sample (which is plasma plus PBMCs). The nano-needle is not really a needle in the injecting sense; it's more of a very thin tube with little sensors sticking out into it.

They say that the change in impedance is probably because of the presence of molecules at the sensor tip, but it's not really clear what exactly they are measuring. It's an average value from measurements taken five times per second.
 
Trish said:
So what is being measured is whether the salt content of the solution decreases because the cells are taking up salt and unable to pump it out again.
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But when they added in the salt initially, there was a small decrease in impedance, then it returned to baseline for controls and increased significantly over time for patients. The impedance wouldn't increase above the baseline if it was just a matter of the salt content decreasing over time as the cells take it up. If it was just the salt content of the plasma that was being measured, the impedance would never increase above the baseline because the salt concentration would never go below the baseline level.

So whatever they measured, it's something more complex. The theory is it is related to cells pumping out the salt, but it's something more than just the resulting salt concentration.
 
LarsSG said:
As I understand it, they basically just added a little salt into the sample (which is plasma plus PBMCs). The nano-needle is not really a needle in the injecting sense; it's more of a very thin tube with little sensors sticking out into it.

They say that the change in impedance is probably because of the presence of molecules at the sensor tip, but it's not really clear what exactly they are measuring. It's an average value from measurements taken five times per second.
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I'm going round in circles imagining the set-up because that was exactly what I assumed at first thought, but then thought it didn't sound 'clean enough' in relation to the conclusions/description. I also then start thinking what is the concentration of cells to plasma to salt and whether electrodes are inside the plasma solution and at the point where salt is getting dripped in etc.

It's fascinating and whilst I'm not saying it isn't interesting that they are finding differences, I am curious as to precisely what they are doing to see what it actually might be showing/doing etc.
 
LarsSG said:
But when they added in the salt initially, there was a small decrease in impedance, then it returned to baseline for controls and increased significantly over time for patients. The impedance wouldn't increase above the baseline if it was just a matter of the salt content decreasing over time as the cells take it up. If it was just the salt content of the plasma that was being measured, the impedance would never increase above the baseline because the salt concentration would never go below the baseline level.

So whatever they measured, it's something more complex. The theory is it is related to cells pumping out the salt, but it's something more than just the resulting salt concentration.
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I noticed that decrease in impedance for all conditions where it wasn't healthy cells in healthy plasma. Which is where it got me thinking what the nanoneedle is precisely measuring and whether it was the salt. e.g. wondering whether even for the me/cfs cells in healthy plasma did they 'wash' the cell, which perhaps becomes pertinent if there is a smaller 'dip' in impedance and it is the membrane that the electrodes are attached to and where the salt would be dropping (ie any reaction that might be happenning due to ME/CFS plasma might start there).

I hadn't noticed the timescale was in hours, which also interested me when you think how much of a pool of plasma vs salt and concentrations/Ph then ions (given we are talking current would be relevant with impedance and a circuit round the cell) etc

My brain is trying to piece the bits together and ends up with more questions as I imagine it all!?
 
Thank you @Trish, I had forgotten this part.

From Simon's Blog
The researchers admit that they don’t know what biological differences lie behind the dramatic difference that the nanoelectric device shows between patients and controls. They speculate that they could be changes in the outer membrane of patients’ cells, amongst other possibilities. But the researchers are planning experiments to try to uncover the biology. The new work could be critical in understanding ME/CFS.
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The part I have underlined is what NIH is asking them to do before giving more funding to this project. Those experiments are on hold with no time frame of being resumed.
 
Merged thread

STUDY AIM
The overarching goal of RASPBERRY-ME project is the characterization of the biomolecular signature of Myalgic Encephalomyelitis using Label-free Raman Spectroscopy (RS) and machine learning models.
LEAD INVESTIGATORS
  • Alain Moreau, PhD
  • Mathieu Dehaes, PhD
  • Frédéric Leblond, PhD
STUDY HYPOTHESIS AND DESCRIPTION

Raman spectroscopy is a non-destructive, rapid, and low-cost technique allows the study of the molecular composition of biological fluids like blood, or inside a cell when combined with confocal microscopy. This innovative approach could lead to the development of diagnostic tools to better stratify ME patients and find the underlying causes of different symptoms like post-exertional malaise as well as clinical tools to validate the therapeutic potential of pharmacological treatments to treat, stop or mitigate ME through precision medicine.

We hypothesize that our approach will allow the identification of a biomolecular signature of ME both at baseline and in response to the application of a post-exertional stress challenge. We expect to stratify patients by differentiating severe cases from mild forms of ME. Results from this study will be further combined to ongoing proteomic and metabolomic profiling approaches to better understand the pathophysiology of ME.

https://www.omf.ngo/raspberry-me/

updates and potential at link,
see also tag 'raman'.
 
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It would be fantastic if OMF systematically did small but really well designed trials of the drugs that are promoted as being helpful. Those could potentially save people with ME/CFS lots of money and effort, stop scarce research funds being wasted on poorly done studies and get rid of some of the scam merchants that buzz around ME/CFS.

The big question is, will they be capable of doing really good trials unbiased by anyone without the necessary equipoise? I don't think we've seen good sizeable well managed studies done by OMF yet? If they can manage to start a good series of treatment trials, that is something I would definitely donate to. The key will be who they get to run and oversee the trials. Is there any information about that?
 
Hutan said:
It would be fantastic if OMF systematically did small but really well designed trials of the drugs that are promoted as being helpful. Those could potentially save people with ME/CFS lots of money and effort, stop scarce research funds being wasted on poorly done studies and get rid of some of the scam merchants that buzz around ME/CFS.

The big question is, will they be capable of doing really good trials unbiased by anyone without the necessary equipoise? I don't think we've seen good sizeable well managed studies done by OMF yet? If they can manage to start a good series of treatment trials, that is something I would definitely donate to. The key will be who they get to run and oversee the trials. Is there any information about that?
Click to expand...

I wonder if they have Ron Davis' 37 Tryptophan trap drugs list. If they do this might be one of the ways we find out about one/some of them if the list isn't a who's who of debunking or rubber stamping drugs believed to work or doing small trials to validate Long Covid larger trial findings.
 
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