All the Chips on the Table

Courtesy Photo | The procedure from organ exposure to CB agents to liquid chromatography–mass spectrometry (LC/MS) analysis of biomarkers. (DEVCOM CCDC CBC image)  

FT. BELVOIR, VA, UNITED STATES

02.06.2023

Courtesy Story

Defense Threat Reduction Agency's Chemical and Biological Technologies Department

Current wearable-sensor capabilities have an ability to alert to potential COVID-19 exposure 48 hours prior to a positive diagnosis, but this capability has yet to be expanded to a broader spectrum of chemical and biological (CB) warfare agents of concern. Over the past several years, sensor algorithm research has shown promise in collecting human-exposure data from substitute CB agents such as natural infection of COVID-19, influenza, opioid administration during medical procedures, and vaccine trials.

To determine if these wearable-device algorithms can also alert warfighters to exposure of CB warfare agents, the Defense Threat Reduction Agency’s (DTRA) Chemical and Biological Technologies Department in its role as the Joint Science and Technology Office (JSTO) for the Chemical and Biological Defense Program (CBDP) is investing in research with the U.S. Army Combat Capabilities Development Command Chemical Biological Center (DEVCOM CCDC CBC).

DTRA JSTO procured custom multi-organ-on-a-chip technology through DEVCOM CBC to develop exposure studies specific to CBDP interests. Ongoing wearable sensor efforts have identified key physiological features for indicating exposure to CB agents including heart rate, heart rate variability, temperature, and respiratory rate, among others. As a result, the research team customized a multi-organ system that combined cardiac, lung, and skin tissues on a single chip. Researchers correspondingly selected CB agents with exposure routes that affect the lung, skin, and heart, including Bacillus anthracis, Staphylococcal enterotoxin B, Western Equine Encephalitis Virus, and carfentanil, which is a synthetic opioid approximately 10,000 times more potent than morphine and 100 times more potent than fentanyl.

The researchers conducted the first chip exposures on lung tissue exposed to carfentanil and subsequently collected samples such as metabolomics from all tissues (lung, skin, and heart) to determine the holistic effect from exposure. DTRA JSTO is using the data to inform predictive toxicology models as part of the Computational Rapid Identification and Scientific Analysis (CRISTAL) program and on a large scale will analyze multiomics—the scientific fields associated with measuring biological molecules in a high-throughput way—where the data sets from proteomics (proteins) and metabolomics (metabolites) will be analyzed to inform current work in biomarker-based detection of CB agents. DTRA JSTO also plans to conduct feasibility studies of correlating multiomics biomarkers with physiological response data and compare those to physiological data collected from wearable devices.

DTRA JSTO’s research aims to investigate the capability of determining physiological responses to true CB agents of concern from these studies and the capacity to develop vital sign correlations from multiomics data. The result would ultimately either validate current wearable-based early warning exposure algorithms or inform a need for early warning algorithms specific to each class of agent. This would lead to continued organ-on-a-chip work to conduct exposure studies on a full spectrum of CB agents of concern and at various dosages to develop early alerting algorithms catered to those agents.

This collaboration amongst multiple divisions in DTRA JSTO highlights not only the advancements and possibilities of organ-on-a-chip systems, but the streamlining of DTRA JSTO efforts to build a robust capability through a leaner and more holistic approach to benefit the Joint Force. The perspective from various areas of participation produces a more efficient trajectory of the project and the success of the joint effort to mitigate CB threat exposures more rapidly, with greater sensitivity, and with higher fidelity.

POCs: Chris Kiley, Ph.D., [e-mail]

• Date Taken: 02.06.2023
• Date Posted: 02.06.2023 15:44
• Story ID: 437952
• Location: FT. BELVOIR, VA, US