Drawing from the technology used by diabetics to monitor their glucose levels, Dr. Shane Kasten at the U.S. Army Medical Research and Development Command’s U.S. Army Medical Research Institute of Chemical Defense developed an ultra-portable, easy-to-use device to provide early warning of suspected exposure to a chemical warfare nerve agent. The ChemDx Test System is designed to inform both medical and leadership decisions as to the timely use of medical countermeasures, thereby enhancing survivability with respect to medical treatment of chemical casualties on the battlefield and lowering the burden on the medical response. A utility patent for the device was issued on February 9.
Dermal exposures to some chemical warfare nerve agents can have a latent or pre-symptomatic period. However, even prior to the development of overt signs and symptoms, the enzymatic activity of blood cholinesterase enzymes (that is, acetylcholinesterase and butyrylcholinesterase) may become depressed following exposure. Specifically measuring the activity of acetylcholinesterase in the blood is an extremely sensitive method of determining whether an exposure to chemical nerve agents has occurred.
With the ChemDx Test System, the warfighter can, with minimal training, use a blood sample from a simple finger stick during the pre-symptomatic window to obtain a real-time assessment of acetylcholinesterase inhibition. As with a glucometer and glucose strips, the blood sample is applied to a specially configured test strip that has been inserted into the device for near real-time determination of the level of acetylcholinesterase activity in circulation. An indication of potential exposure is displayed in less than 40 seconds.
When Kasten began working at the USAMRICD in 2009, the need for a low-burden, low complexity test system to provide indication of exposure prior to overt symptoms had already been identified as a substantial technical need. A few years later, a U.S. Department of Defense program was initiated to develop wearable sensors. Kasten says he was “immediately intrigued with this wearable idea, but knew the technical hurdles would be great.”
He realized that a small hand-held device could offer much of the same convenience as a wearable sensor while providing near real-time assessment. Then, while having dinner with his family at a fast food restaurant, Kasten observed an elderly woman quickly and easily test her own glucose levels with a glucometer and test strips. This event also triggered memories of watching his sister use a glucometer daily to treat her diabetes.
“That's the moment I realized the glucometer/test strip was the most viable diagnostic platform for real-time, far-forward indication of exposure, potentially guiding treatment with a medical countermeasure therapy,” says Kasten.
“The next day I went to Walmart and Walgreens to buy several brands of glucose test strips to see if I could hack them by removing the proprietary chemistry and replacing it with acetylcholinesterase-based chemistry. Within about two weeks I found the test strip that gave me proof of concept."
Kasten received seed funding to begin developing the reagent formulation and prototypes of the test strips after showing his hacked test strips to a Defense Threat Reduction Agency science and technology manager visiting the USAMRICD. A full project from DTRA in 2017 resulted in the successful demonstration of the capabilities of the first prototype test strips and custom potentiostat to confirm exposure through an acetylcholinesterase assessment prior to the appearance of symptoms.
In 2018, the DOD made the decision to move the work to advanced development, which is being overseen by the Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense. An Other Transactional Authority contract was awarded to MRI Global for the development of prototypes, in partnership with the USAMRICD and Conductive Technologies Inc., and for sponsorship of the device’s approval through the U.S. Food and Drug Administration.
Over the past year, the USAMRICD provided analytical performance assessment of two successive prototypes of the ChemDx Test System. These studies included evaluating the accuracy, linearity, precision, and limits of detection/quantitation, and identifying potential interfering substances.
Additionally, Kasten along with co-worker Zachary Canter undertook feasibility efforts to determine whether the ChemDx Test System capabilities could be expanded to indicate exposure to a synthetic opioid by detecting an opioid metabolite in biological specimens. The project is exploring materials than can provide the sensitivity, specificity, and stability needed for a robust opioid sensor. Future work will continue to optimize the developed sensor, evaluate the sensor’s analytical performance and further integrate it into the ChemDx platform.