A nanoelectronics-blood-based diagnostic biomarker for ME/CFS (2019) Esfandyarpour, Davis et al

Still trying to understand.

So if we have a silicon wafer, then the layers are being deposited onto one of its sides, which means the needles must be formed laying parallel to the wafer surface - else the layers would be oriented incorrectly within the needles.

But if the needles are parallel to the wafer surface, how do you then get an array of needles formed alongside each other? With this it seems like they would be formed in rows across the wafer, with each row top-to-tail with adjacent rows. Whereas what the need and presumably must actually be achieving is an x-y matrix of them when viewed when looking down onto the tips.

I know I'm missing something but no idea what.

 

@Barry Figure 1A shows a drawing of the needle. Think of the green labelled oxide as one side of the silicon wafer with an oxide layer deposited on it, all over one side. A 100nm gold layer is deposited and etched to a pattern to form the circuit trace to the pad (pad not shown, pad is where you connect your measurement wires) and for the nanoneedle tip. Then another 30nm oxide layer is deposited and etched to a pattern as an insulating layer, followed by another 100nm gold electrode and finally the top 20nm oxide layer, both etched to a pattern.

Hope that helps and doesn't muddy the waters too much.

 

Thanks @wigglethemouse. Yes, that is what I had concluded. So presumably that layer stack is the only one that is deposited onto the wafer? Meaning many needles laid alongside each other ("laying down") in rows across the wafer, and end-to-end across the wafer in the other direction. Like microscopic fence panels, immensely long relative to height. But to build a matrix of these you would then need to assemble thousands of these panels next to each other, so that when looking down on the tips you would see a m x n array of them.

Or ... do they deposit the above layer stack repeatedly, so it ends up with many layers of panels assembled alongside each other? So that if you were to look edgewise at the wafer, if you choose the right point, then you would be looking onto the tips of the needle array.

I'm familiar with the idea of fabricating circuitry onto a silicon wafer to produce 'chips', but only to a point. I'm guessing this sort of fabrication is maybe a bit different? Is it that actually hundreds or thousands of layers can be deposited onto the wafer, and maybe that is the bit I'm missing?

 

@Barry It's not very clear. Fig 1D shows the wafer with what looks like 15 squarish areas that are likely 15 nanoneedle dies per wafer. I assume the 15 squarish areas are separate dies judging on news article pictures of the nanoneedle. Each "die" has 12 micro channels. The small area drawn in kind of an oval shape in Fig 1D is zoomed up to be Fig 1E. This is a section of the micro channel showing sensor tips connected in a parallel circuit. It's not clear how this expands to the full channel, but I assume they are all connected in parallel as there are only two "pads" for probing, one at either end of the channel.

I'm assuming one micro channel with many sensing tips in parallel is one nanoneedle sensor. It is not clear if the 12 micro channels on one die section are connected in parallel as well or are in fact separate sensors.

Fig 1F is a zoomed in end view of the nanoneedle tip, but the dimensions don't seem to be the same as described in the text. It does seems to be 3-5um wide, but height looks way too tall...... so I won't post that picture here.

 

Light dawns @wigglethemouse .

One the basis it is a 4" wafer, I'd very roughly guess each channel to be about 15mm long. Fig. 1F shows needles are 2.5µm apart, so at a rough guess there will be in the order of 6000 nanoneedles per channel, assuming the spacing is constant along the whole channel.

From the description it seems a single channel forms a single sensor.

 

Ron Davis talked about the Nanoneedle at the recent Buttonwood Books book reading & Q&A event for the book "The Puzzle Solver" ("Waiting for Superman" in the UK). About 60mins in.

https://www.youtube.com/watch?v=9lyJ_pt1lKU

The key takeaway is that they need fresh blood from people who come to the lab. They wanted to test other diseases but those people don't want to come in to the lab to be tested because it is a pain for them to do with no benefit. They can't freeze the blood as it needs to be processed straight away so they can't get from other sources.

I thought this was really important as many people have stated they need to test other diseases as if that was a simple thing to do. It seems that it is not.

 

Well, I don't know about everybody who has called for testing against other diseases but I've never claimed that it's an easy thing to do.

Did Ron explain what OMF are doing to solve this puzzle then, given the title of the book? To help him along, the nanoneedle paper had a total of 40 patients and healthy controls, so if OMF had to pay $100 per additonal participant, that would only be $4000 / £2887 / EUR 3321, which they can well afford. I'd suggest given the potential of the nanoneedle that would be an investment well worth making.

 

I'd think if they could pitch it as COVID research, they'd have loads of clinics at least offering to help, who could then recruit patients locally?

Of course, they'd have to see if the signal works for long COVID too.

 

I thought they had ditched that idea since they found the blood needed a lab to prepare the sample before it could be tested? This would make the cheap mass produced option a bit pointless since there are fewer labs than gp surgeries etc. It didn’t work on untreated blood last I looked ? Perhaps they have solved this since I last read anything on it?

 

I'm 'one of those people'.
They were also going to test CCI patients.
https://www.s4me.info/threads/the-s...fs-discussion-thread.9638/page-55#post-218889

I also asked about using the nanoneedle on GWI patients:
https://www.s4me.info/threads/ronal...tation-at-the-iimec13.5793/page-4#post-106159

 

At this point, four years into R&D of the nanoneedle, I find it extremely hard to believe that they can't find anyone to use as a comparison against ME patients. To piggyback off of what @Andy said, there is a VA (Veterans Hospital) literally a mile from his lab. I'm almost certain that he could very easily get approval from the hospital admins to put up a sign on the bulletin board saying "$25 (or more) cash for your blood, all you need is documentation from your doctor saying you have X disease.” A few years ago when my father had to go into the VA for a procedure, in the waiting room Columbia University had a flyer for a Parkinsons study they were conducting. The study was not veteran exclusive and they paid $200 for a day of your time, and because the flyer was posted three counties north of Columbia University they offered to compensate the train ticket or parking. Even if Dr. Davis has to pick them up personally and listen to them talk about how they killed a North Korean in The Battle Of Pork Chop Hill for 20 minutes, I feel its a minor sacrifice he can make to see if the nanoneedle is a valid diagnostic tool for ME.

 

Yeah, this makes no sense. Recruiting sick and healthy participants for studies which are of no direct benefit to them is hard but not impossible. I’ve done it as have millions of other scientists despite not being allowed to offer financial incentives where I am. I find it very hard to believe they couldn’t get a few dozen ppl to donate a bit of blood. It’s not rocket science.

 

100 perc agree with everyone else. There is no problem giving some small reward for getting tested, and there is never a complete lack of other patients like this.

There is something else going on here. When OMF receives so much financial support from patients, they should be transparent about what that is

 

Here's a panel discussion with Ron Davis, Ami Mac & Michael Snyder titled "The Crisis: Post Covid Symptoms with Stanford University" that speaks to the question above.

Ron explains that the nanoneedle is of value as it can be used to differentiate "healthy" and "unhealthy" people even if it isn't specific to ME/CFS.

Speaking about the nanoneedle he said :

"And it could be that it is positive for other diseases and that's okay. When you try to diagnose something you don't necessarily have one test that will tell you what the disease is. You basically group them - is one way to do this. And it's like identifying a tree. Your first question is do they have needles or leaves and that splits them into about two different classes and then you go from there. And pretty soon with a few tests you can get it down to exactly it indicates what tree it is or what disease it is."

The discussion on the nanoneedle including the above quote starts at 30.23 and ends at 33.46.

https://www.youtube.com/watch?v=2d_rR-3fyhk

Edited for grammar.

 

Hmm. I don't think that's quite true, as if the nanoneedle is positive for most similar disease it won't help narrow down the branches. A non-specific test, broadly positive, unrelated to a clear, biological mechanism will serve little use and may not even help patient justify their sickness for disability. It'll just be a novelity.

 

[Internal Screaming]

 

surely an incentive payment and screening questionnaire is not beyond the capabilities of OMF. (Commonplace for any cohort selection)?

this is just such a ridiculous excuse for not doing things properly. One could conclude that they know this is now not something worth pursuing. Why they are being so evasive about it and not drawing a line under it though is unclear

I’ll speculate that it is probably because they don’t want to waste time telling people outside OMF formally by writing and submitting papers. It would be good to be honest about it with the people who have made the donations though ...in the spirit of openness and all that.

 

I'm even more confused now. How does Ron know that it isn't specific to ME if he hasn't been able to test it in other illnesses?

 

I don't understand. He says folks are coming in saying they've got MS or Diabetes, but also says he can't get folks with other illnesses? Sure just take those folks blood and instead of putting them in the healthy category, put them in the other illness category...
And have they asked ME patients to ask their family and friends. I know if i lived near the experiment my family and serveral friends would gladly donate their blood to try and help me. And in Covid times, that's an exciting day out

(Edited to fix the quote)