[2YwaZHXV]

Existing analysers already use very small samples.

See Siemens Advia 1800 specs under "Microvolume Technology" https://www.healthcare.siemens.com/clinical-chemistry/system...

It only uses 30ul of sample to run up to 15 assays.

How is that any different from what Theranos was doing?

Only difference is that you collect a bigger vial when using the Siemens machine. And then don't use most of it. So why not collect a smaller vial?

[exelius]

There’s no benefit to doing so; and smaller vials are harder to preserve. Measurements on blood draws are not exact, and pre-measured preservatives in the vials and the blood have to be in the right ratios.

This is easier to do consistently in larger vials, reducing the error in this part of the process to acceptable levels. It’s the same reason why a recipe will normally be more consistent when making a larger batch.

So you could collect less, but the way the modern lab industry operates (collecting samples, preserving them, and shipping them to an offsite lab for analysis) there is little business benefit to using smaller collection vials.

[2YwaZHXV]

Ok, so you're giving a business reason to not collect smaller samples. Which is fine and totally valid. Theranos was under the impression that there was an untapped opportunity for smaller samples.

But, the wording of the parent comment was saying that it was supposedly clearly technically impossible because of the small sample size. The OP said "I just never, ever understood how the sampling rate could ever work" and "and this should've been screamingly obvious to everyone since the beginning." That seems very different from "this is a very hard problem due to X, Y, and Z", especially since commercial machines that everyone here gets blood results from are already only taking small samples from the collected vials so the biggest challenge just seems to be in the collection and transport.

I agree that everything is easier with a bigger collection size, however "hard" is different from impossible.

[ethbro]

Out of curiousity, how tight are the preservative:blood ratios before Bad Things (i.e. things that would invalidate the test results) start to happen?

[2YwaZHXV]

That's a good question. Looking at this: http://apps.who.int/iris/bitstream/10665/65957/1/WHO_DIL_LAB... for EDTA (a very common anticoagulant "preservative") it is 1.2 to 2.0 mg/mL, so a decent range. But, this is one source and it will also depend on what the test is looking for.

[CptFribble]

There are a few reasons you collect a full vial instead of a tiny one:

1. Multiple tests. Most people aren't going to the doctor for a single test. A majority of the testing is Comprehensive Metabolic Panels, which covers 20-30 different things at least. Many patients get a CMP plus other stuff, so enough is drawn for all the tests at once.

2. Possible retesting. There are dozens of things that can go wrong between drawing the blood and sending a result to the doctor. Maybe a tech drops the tube and spills some blood out. Maybe the machine has a problem mid-test and you have to rerun the samples after it's fixed. Maybe the patient has a critically high/low range of something and you need to retest for confirmation. The worst possible scenario for a lab is to have to call the patient back in for more blood, because that causes patient pain and could make the doctor start using a different lab if they're perceived as unreliable. There's actually a legal requirement for labs to store blood for a week after testing, just in case.

3. Different test requirements. The CMPs usually test the serum only (i.e. your blood gets put through a centrifuge), but there are a variety of tests that run on whole blood. Because of the possible re-testing above, and because whole blood test samples need to have anticoagulant added, you'll usually have two separate tubes drawn for whole blood vs. serum tests.

[2YwaZHXV]

OK, so these are more business reasons for bigger samples than technical reasons.

1. Ok, so that can still be done with small samples, it's just a matter of collecting enough. The link I gave showed 15 tests in 30ul of sample. So, 60ul would be enough for your 30 tests. The amount used per test (for many many tests) is still very small compared to the amount drawn.

2. I imagine if a tube is dropped and some sample is lost they consider the whole sample lost. Since if sample got out that also means that stuff can get in, possibly contaminating it. The poor customer experience of having to go back in to be re-drawn is a poor business choice, but again, not a technical hurdle with being able to perform tests. Having enough sample for re-testing a week later is also just a matter of collecting sufficient sample. So, you would need 120+ul of sample (from previous example of 30 tests) to meet that requirement (plus some amount for loss in equipment, etc). But, it is still a far cry from the 2000+ul typically drawn.

3. You actually often have more than 2 drawn, since each tube has a different kind (if any) anticoagulant and if they get sent to different labs they may need duplicates of the same anti-coagulant. This also doesn't have anything to do with the size of the sample required for a test. So, you can collect a bunch of small samples instead of bigger samples. That's not a technical hurdle for being able to perform a test on a small volume of blood.

[semi-extrinsic]

Well, because you can get a sample that's a lot more representative of the actual bulk bloodstream by a) diluting out the contaminants always present in the first part of the sample, and b) drawing the sample from a large vein rather than tiny ones in the fingertip.