The overall goal of this project is to advance our nation's ability to protect public health in the event of a large-scale, radiation/nuclear event by developing a single mobile point of care (POC) diagnostic device that will fill three identified gaps in our country's current radiation triage assessment capabilities. First, it will distinguish the worried-well from individuals exposed to radiation doses at a threshold of 2Gy; second, it will provide an assessment of hematopoietic acute radiation syndrome (H-ARS) severity risk, as well as a radiation dose estimate beyond 2Gy; and third, it will allow the detection and quantification of soluble (Specific Aim 1, SA1) and cell-surface associated (Specific Aim 2, SA2) blood- and organ-specific radiation damage biomarkers to provide critical information about major organ and physiological system damage/failure. The thrust of this proposal will be on developing and demonstrating the ability to detect radiation damage biomarkers on an innovative handheld device. The device is comprised of a well-vetted POC blood cell analyzer capable of performing a 5-part leukocyte differential analysis in field-settings using an innovative lensless microscopy technology. The device utilizes a fingerstick of whole blood and provides results in under 8 minutes. Here, we will further expand these capabilities to allow for the immunoassay-based analysis of blood/plasma radiation damage biomarkers. We initially will demonstrate the ability to detect and quantify three soluble biomarkers of radiation damage in human blood samples; serum amyloid-A, salivary ?-amylase, and Fms-related tyrosine kinase 3 ligand, representing markers of inflammation, salivary gland damage, and bone marrow progenitor cell distribution, respectively; thereby demonstrating the utility of the system for multiple systems damage assessment. Our immunoassay for soluble biomarkers will use a highly sensitive microsphere-complex formation format that also allows for multiplex capabilities. In addition, we will demonstrate the ability to detect a number of cell surface specific radiation damage biomarkers on our device. Lastly, we will integrate into the device two biodosimetry-specific algorithms to allow the conversion of blood cell enumeration data into indicators of radiation injury, dose exposure, and a prediction of the risk of development of H-ARS (Specific Aim 3, SA3). By providing a single portable diagnostic device capable of addressing many of the gaps that have been identified by NIAID in our country's ability to respond to severe radiation incidents we will significantly advance radiation triage public health responsiveness, as well as provide for the potential to revolutionize POC immunodiagnostics.
CellRADx is a handheld, rapid, easy-to-use biodosimetry device that will integrate cell-based biomarker assays and immunoassays of radiation injury biomarkers with novel algorithms to fill the unmet public health and medical needs to 1) distinguish individuals exposed to potentially lethal levels of radiation, 2) assess severity of radiation injuries in tissues and organs, and 3).predict early and late effects of acute radiation exposure during and after a public health radiation/nuclear emergency. The successful development and deployment of CellRADx will allow first responders and health authorities to 1) quickly screen (i.e., <2 Gy vs >2 Gy exposure) and triage individuals in a radiation mass casualty incident so that potentially limited medical countermeasures can be administered to those individuals most in need, and 2) predict acute- and late-effects of radiation tissue injuries so that medical treatments can be administered to decrease morbidity and mortality. The potential of CellRADx to help save many lives and enable timely medical treatment decisions will dramatically increase the Public Health emergency response capabilities for the United States.