With just a wee prick and a few drips, researchers hope to one day test for a wide range of ailments. Such low-pain, low-drain blood diagnostics would mean doctors could ditch big needles and vein-hunting, making patient care more pleasant. And those mini blood tests could offer easy, non-invasive testing alternatives in resource-poor healthcare settings, such as clinics in developing countries.

But making that diagnostic dream into a clinical reality may be bloody challenging, new data suggests.

Tiny blood droplets that leak successively from a pricked finger can have widely variable contents, researchers reported in the American Journal of Clinical Pathology. In some cases, test results on such finger-bled droplets had nearly eight times more variation than vein-harvested blood samples—the gold standard. Only when the authors tested upwards of five drops combined (60 to 100 microliters) were they able to get accurate results. The study raises concerns that new diagnostic tests that rely on blood drops may yield inaccurate results.

“There’s a big push right now, especially for low-resources settings, to develop tests that can be done with very tiny sample volumes,” senior author Rebecca Richards-Kortum, a bioengineer at Rice University, told Ars. “The main message that I hope people take away,” she said, “is that you shouldn’t just assume that you can reduce that volume without looking first to see: does it vary from drop to drop?”

Among the many medical companies pushing for such low-volume technology, Theranos Inc. has arguably made the biggest splash. The now-beleaguered startup and its high-profile founder, Elizabeth Holmes, touted technology that could perform clinical tests with just a few drops of blood, offering a menu of more than 200 tests, ranging from cholesterol to anemia. But the company has been plagued by criticism after a Wall Street Journal article called into question the accuracy of those tests. The article cited former employees who said the company wasn’t relying on its own technology due to problems.

Whether drop-to-drop variation is part of those problems is unclear. The company has yet to publish data on the accuracy of its tests (though Holmes announced that it plans to).

Theranos declined to comment for this story.

The swing is the thing

The company has so far only received FDA approval on one of its prick-based blood tests. But that test may be a best-case scenario, William Clarke, a clinical chemist at Johns Hopkins University, told Ars. The test detects a herpes infection, which is a yes-or-no, present-or-absent kind of test—not a test with the possibility of big swings, Clarke said.

Swings were the problem in the study led by Richards-Kortum. She and her colleague Meaghan Bond drew blood from 11 healthy donors and used successive finger droplets for a handful of tests, including ones that measured hemoglobin and white blood cells. At first, the researchers thought maybe their equipment was off. But after testing the samples further, diluting them into larger volumes of liquid and comparing results with venous samples as controls, the researchers found that the droplets themselves varied.

The results are not shocking, Clarke said. The study only looked at relatively big, cell-based blood components, he noted, which may drain out differently depending on blood flow. And, he noted, some other tests using blood drops, such as glucose, have been worked out and are accurate. But, he added, the study offers a good reminder that diagnostic developers need to be careful.

Each blood component, from cholesterol to iron, might have its own drop-to-drop variation and minimum accurate volume, he said. And that variability could be different in each patient population. For instance, if Richards-Kortum’s study swapped healthy blood donors for people with poor blood flow, such as those with heart failure, the measured droplet variability might have been very different.

Still, variability might not make a diagnostic test useless, Clarke noted. Any test or sample method will have variability, it’s just a matter of how much and if a health professional can still use the results to make the right call.

The key here is to just be very aware of the quality and the limits of each test, he said.

American Journal of Clinical Pathology, 2015. DOI: 10.1309/AJCP1L7DKMPCHPEH (About DOIs).