When asked what inspired him to develop fingerprick point-of-care tests (POCT), Eugene Chan, MD, recalled three experiences from his medical residency that impressed upon him the need for rapid, painless blood tests. The first was a time when it took more than an hour to obtain a blood sample from an HIV patient with collapsed veins. The second was an instance at a poorly staffed veterans’ hospital where the one person manning the lab struggled to get Chan a stat result at 3 a.m. 

“The third example was over at the Brigham and Women’s Hospital where there was a patient who had a surgical procedure and should have been monitored for her blood counts every two or three hours afterward,” said Chan, who is now CEO and head scientist of the DNA Medicine Institute (DMI) in Cambridge, Massachusetts. “But she was not monitored, because of the complexity and the fear of waking her up, so that patient actually died from post-surgical complications.”

Many reasons exist for why expanding the range of available fingerprick tests could benefit patients. Fingerprick POCT are ideal for limited-resource countries due to factors such as their low cost and simplicity. And as Chan’s experience from Brigham and Women’s shows, the appeal of fingerprick tests in the developed world is not only one of convenience. Patients can suffer serious consequences when certain tests can’t be done quickly and with small amounts of blood. George Whitesides, PhD, a professor of chemistry at Harvard University, also points out that even in the U.S., there are low- resource settings that need an alternative to centralized testing, such as inner cities, drug clinics, and Native American reservations.


Founded by Chan, DMI is home of the rHEALTH suite of instruments—three portable testing devices, two of which are handheld, that each run 16 different tests using only a few microliters of blood. The rHEALTH menu covers a wide range of assays, from hematology and basic blood chemistry tests to those for small molecules (e.g., vitamin D), large molecules (e.g., IgG), and biomarkers such as parathyroid hormone. DMI developed this varied offering of tests because when the company started out, Chan said, he and his colleagues wanted to demonstrate the broad capabilities of their platform. Now they are seeking Food and Drug Administration approval, one test at a time, and are focusing on the rHEALTH’s hematology assays first, as this is where they see the greatest need.

“We have looked at basically every single point-of-care device out there and where they fall down is doing things like cell counts, which are reasonably complicated and currently require large analyzers,” Chan said.

Notably, the rHEALTH is also one of the five remaining platforms in the Qualcomm Tricorder Xprize competition, in which teams are vying to create a mobile diagnostic device modeled after the fictional medical Tricorder from Star Trek.

A collection of innovations powers the rHEALTH. Nanoscale test strips, described by Chan as being “kind of like urinalysis test strips” that are each roughly the size of several blood cells, make it possible to perform multiple assays with a tiny sample. “Instead of putting a single drop of blood onto one test strip,” Chan said, “now imagine thousands of test strips and your single drop of blood.” Cytometry technology shrunk 1,000-fold reads the nanostrips to quantify the amount of each analyte detected. And at the heart of the instrument lies a sample prep unit that harnesses microfluidics technology to mix minute amounts of blood with reagents—no small feat, since blood is highly viscous and composed of large particles.

Chan takes issue with the rise of the term "microfluidics" as a clinical testing buzzword, pointing out that, as the rHEALTH shows, the ability to manipulate low volumes of liquid is only one of the many keys needed to unlock the full potential of fingerprick testing. “You need innovations in detection technologies, multiplexing, and sample preparation. And once you crack all those, it all needs to be put together in a pretty seamless manner,” he said.

Still, microfluidics is the common thread that ties together many of the recent advancements in fingerprick POCT. Whitesides’ research group has used microfluidics technology not only to shrink tests down to the size of a chess board square, but also to construct assays, including for liver function and cholesterol, out of paper. Samuel K. Sia, PhD, a professor of biomedical engineering at Columbia University in New York, has collaborated with Opko Diagnostics to develop a microfluidics-based smartphone accessory that can test for HIV, syphilis, and hemoglobin. Cepheid’s GeneXpert technology also employs microfluidics; the company’s CE-marked fingerprick Ebola test runs on this system, and Cepheid officials recently announced plans to develop a fingerprick HIV test for the forthcoming GeneXpert Omni, a handheld molecular POC instrument.

Putting It on Paper

Although microfluidic channels are typically either etched or molded into glass, silicone, or plastics, paper has certain qualities that can give it an edge over these traditional materials. In particular, paper’s ability to wick fluids makes it possible to distribute microliter volumes of samples without external pumps. Paper is also extremely inexpensive—the cost of materials for Whitesides’ liver function test only amounts to a few cents—and is biocompatible, making it a good matrix for stabilizing organic compounds such as proteins. 

Whitesides’ group has developed a variety of creative methods to construct microfluidic circuits with paper. Using a conventional office printer, patterns of wax ink can be printed on paper to form hydrophobic barriers that direct sample and reagent movement. Individual stamp-sized sheets can then be stacked with perforated, double-sided pieces of tape sandwiched between them; the holes punched in the tape form vertical channels, connecting the lateral channels traced on the different paper layers. The resulting three-dimensional paper devices are programmable, meaning that the end user can change the analytes they test for by choosing which channels and areas of the device to fill or not to fill with fluid.

With their remarkable versatility, paper-based diagnostics could one day be used to perform a wide range of fingerprick tests, from nucleic acid assays to immunoassays. An older and less fantastical use of paper—as a storage medium for the humble dried blood spot—might also play a role in the expansion of fingerprick testing, according to Sia. Though dried blood spot testing is primarily associated with newborn screening, Sia said that interest in dried blood spots has been growing for a long time as a quick and easy way to collect fingerprick samples from the general public.

As an example of where this could be useful, Sia cites the scenario of a traumatic brain injury. “It is important to look at the markers very soon after the injury. You can’t have a person go in a day or two later, because the blood at that point is not going to be the same as what it was right after the injury. And you may or may not have a point-of-care diagnostic device available, but if you can at least get the blood, you can preserve it to be analyzed later.”

The Limits of One Drop

While fingerprick testing comes with many advantages, this sample type is not without its drawbacks. Among them, a widely publicized study conducted at Rice University determined that hemoglobin measurements, as well as white blood cell and platelet counts, can vary significantly in different drops of blood collected from the same fingerprick (Am J Clin Pathol 2015;144:885–94). Meaghan Bond, PhD, a postdoctoral researcher in biomedical engineering at Rice and first author of the study, does not think fingerprick samples need to be banned for hematology or other tests, but does urge caution when using results from one drop of blood to affect patient care.   

“In some clinical scenarios, that level of variation doesn’t matter,” Bond said. “For example, if you’re just trying to get a basic assessment of whether a person is severely anemic or not. But if you are trying to get a more precise answer, now we know that we ought to look at other options for measuring that hemoglobin concentration, like collecting a larger volume of fingerprick blood or collecting venous blood.”

To deal with the shortcomings of fingerprick samples, Bond stressed the importance of educating clinicians and patients about the limits of POCT, as well as conducting further drop-to-drop studies to determine what other analytes are affected by this variability issue.

With the rHEALTH, meanwhile, Chan aims to offer a POC device that can provide the same analytical sensitivity and specificity as central laboratory instruments. “Third parties have demonstrated very, very high sensitivities of our rHEALTH technology,” he said, “which has been great because people always think they’re making a trade-off with the quality of data with point-of-care. But ideally, you should get the same types and quantities of values as the lab.”

Now in its final round, the Tricorder Xprize is currently testing just how close the rHEALTH comes to this ideal with real patients and doctors. The last lap of the competition kicked off in September and is expected to yield a winner by early 2017.