Transdermal glucose measurement

| Comments (2) | Pharma
Coming from a background in spectroscopy, it's always bugged me that diabetics have to take physical samples to measure their blood glucose levels. If we can remotely measure the composition of the sun, 8 light minutes away, we should be able to measure the composition of some blood vessel 1 millimeter away. But no... You need to first take a sample (ouch!) and then do some chemical testing (that's what the test strips are for) [wikipedia background]. The meter is just a mechanical way of reading the result of the blood/strip reaction. We're talking pretty old-school analytical chemistry here. It looks like the situation is improving, though: some scientists in Hong Kong have developed a remote technique based on transdermal infrared spectroscopy.

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A friend of mine quite some time ago did some research on the use of Raman spectroscopy to measure the sugar level of the vitreous humor of the eye, which tracks blood sugar surprisingly well. This would be an instrument you just look into in order to take a blood sugar measurement.

I'm not sure what the current status of this is, but early on there seemed to be little interest from makers of blood sugar measurement devices, who make most of their money from selling test strips, not from the device itself.

I'm really surprised it is possible to pick out a glucose absorption peak transdermally well enough to determine concentration. (Ditto for doing Raman of the vitreous humor -- I'd also be surprised if the equipment to do Raman spectra of the vitreous humor were compact, but that's another story...)


Determining the composition of distant objects in the gas phase is pretty staightforward -- the lines are all nice and clean because the molecules are isolated from each other. Hell, in the gas phase, even UV/Vis electron absorption spectra are clean -- you can actually pick out different fine structure for vibrational transitions and such in the lab (which I've done and is really neat).


In liquid phase, though, your IR spectra are going to be less sharp, and you have vast numbers of other molecules around so you are going to have trouble picking up the vibrational absorption lines for glucose. I don't think any of the stretches in glucose are particularly unusual.


For those educated in such things, have a look:


http://www.aist.go.jp/RIODB/SDBS/cgi-bin/IMG.cgi?imgdir=ir&fname=NIDA70131&sdbsno=11521


The stuff over 1500 wavenumbers is pretty much what you would expect, including the big blob that says "lots of hydroxys", and the stuff down in the low wavenumbers all looks like the usual mess -- if you overlaid 20 other similar sized organics there I'm not sure you'd find much in the way of unmistakable peaks.


For laughs, here is fructose:


http://www.aist.go.jp/RIODB/SDBS/cgi-bin/IMG.cgi?imgdir=ir&fname=NIDA70116&sdbsno=1139


You'll notice, very similar (as you would expect) -- too similar to distinguish in the upfield region. Here is Tyrosine:


http://www.aist.go.jp/RIODB/SDBS/cgi-bin/IMG.cgi?imgdir=ir&fname=NIDA63698&sdbsno=1166


I picked it for the OH group, I fully admit, but look at the downfield mess -- you have 20 amino acids filling that region with cruft alone, not to mention thousands of other small molecules, and as you can see, you couldn't distinguish glucose from fructose or a bunch of other hexoses or even pentoses based on the stuff near the OH blob upfield.


You can always do a little linear algebra if you have enough spectral samples and you know the detailed spectra for all the components, but that's not the situation you are in here.


Second, and almost worse, figuring out concentration from the Beer-Lambert law depends on knowing your "path length" accurately. Given that you want blood glucose levels, and that you're traveling through all sorts of tissue (not just blood), and that measuring the thickness of the tissue you're going through is iffy in any case. You might be able to get ballpark, but you want accurate, because otherwise you're not going to take the right amount of insulin.


To be clear here, I'm not saying that this is impossible by any means. I'm mostly saying there has to be some trickery they are using here. What is it? Clearly this is not the same job as shining a beam through a cuvette or gas cell filled with pure material. So, how do they figure out the concentration in situ? I'm quite interested...

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