Towards enabling the decentralized collection of blood specimens
A serendipitous discovery led to the first FDA-cleared, microneedle-based, push-button blood-collection device.
The paper in Nature Biomedical Engineering is here: http://go.nature.com/2FrQ3Z0
Seventh Sense Biosystems was founded in 2008 by Drs. Robert Langer, R. Rox Anderson, Doug Levinson, Joerg Lahann and Samir Mitragotri, with the goal of bringing diagnostics closer to the patient. I joined Seventh Sense immediately after completing my graduate research in Dr. David Walt’s laboratory at Tufts University. The original product concept that Seventh Sense focused on developing was a wearable diagnostic technology consisting of a temporary tattoo made of biphasic biodegradable microparticle ‘ink’1. Conceptually, the particles would be inserted into a superficial layer of skin where interstitial fluid (ISF) resides. In response to changes in circulating biomarker levels in the ISF, the particles would preferentially bind in a way to make the tattoo change color. The resulting color change could potentially inform a person about an issue with his or her health in conjunction with any concurrent symptoms he or she might be exhibiting. Over time, the particles would biodegrade and be absorbed in the skin.
As part of this effort, my colleagues were working on a way to obtain ISF for our biomarker research and devised a method to extract fluid from the skin using microneedles and applied vacuum. The method involved inserting microneedles into the skin to access the shallow compartment where the ISF resides and then applying gentle suction to withdraw it. The result was that sampling sufficient volumes of ISF with this method was difficult without obtaining a significant amount of blood. In fact, we discovered that we could collect substantial volumes of blood easily and with little sensation using this method. This serendipitous result led the company to shift its focus toward developing this technology into an easy-to-use, integrated device for blood-sample collection (commercialized as 'TAP').
Greatly simplifying the blood-collection process was a logical objective, as blood-specimen collection is the first step of the traditional clinical diagnostic workflow and is often considered the most important. Developing an easy to use and virtually pain-free blood collection device resonated with everyone, because we were aware of the difficulties with current blood-collection methods as well as of trends in the diagnostic industry to reduce blood volumes required for diagnostic testing. Venipuncture can produce a high-quality sample when performed by a skilled individual; however, collecting milliliters of blood is becoming excessive for many point-of-care and central lab diagnostic technologies that require less sample to work with. Venipuncture also lends itself to a centralized sample-collection workflow; patients need to go to where the phlebotomists or other trained professionals are located to have a sample collected. Therefore, the diagnostic workflow is tied to these centralized locations for obtaining blood samples. In contrast, fingerstick can be performed in a more decentralized fashion without the aid of a phlebotomist; however, it can only reliably collect several microliters of blood unless one uses a large (and most likely painful) lancet. Even then, there have been concerns about sample variability and the ability to obtain a reproducible sample volume for analysis2.
We believed that creating a device that could be self-administered and used with minimal training to consistently and reproducibly collect 100-250 µL of blood would find itself at the intersecting trends of decentralized sample collection and of reduced blood-volume requirements for diagnostic testing. Our view is that TAP can eliminate the existing barriers to blood-sample collection, by enabling blood samples to be collected in places where it is difficult to do so today. Our ultimate vision for the device is one in which blood specimens can be collected in almost any venue (for example, in a physician’s office setting, at a pharmacy, on the sideline at a sporting event, at home, or in more remote or resource-limited settings) and then transported to a central location for testing. Alternatively, one could envision a scenario where samples are collected with TAP and then analyzed at the point-of-care for more immediate sample-to-answer results.
The final form of TAP that is presented in our paper evolved through several years of various design iterations and ideas presented by many different talented people. As my colleagues can attest, developing a new blood-collection methodology is not as easy as it sounds. However, we believe we have gained important insights into the microcirculatory system of the skin and into how capillary blood is collected . Through our years of research, we have learned how to control the factors that produce a high-quality blood sample. Additional work on the TAP platform continues, and we are encouraged by the progress we have made for future iterations of the device. Our ongoing work includes optimizing the blood-collection process for additional applications such as hematology and molecular diagnostics, in addition to developing plasma-separation technology.
Our paper: Blicharz, T. M. et al. Microneedle-based device for the one-step painless collection of capillary blood samples. Nat. Biomed. Eng. (2018) doi:10.1038/s41551-018-0194-1.
1. Roh, K.-H., Martin, D. C. & Lahann, J. Biphasic Janus particles with nanoscale anisotropy. Nat. Mater. 4, 759–763 (2005).
2. Bond, M. M. & Richards-Kortum, R. R. Drop-to-Drop Variation in the Cellular Components of Fingerprick Blood. Am. J. Clin. Pathol. 144, 885–894 (2015).