Macrophage hazardous material detection
Inventors
Assignees
Defense Threat Reduction Agency
Publication Number
US-9176117-B2
Publication Date
2015-11-03
Expiration Date
2032-06-14
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Abstract
Sentinel Cells, respond quickly and differentially to and among various high explosives (e.g., RDX, PETN, HMX, TNT, TNG), taggant (DMDNB), and bacteria, as well as volatiles of commercial C4, Semtex 1A, and military C4. These effects are observable within 5 minutes of exposure, indicate profound biological effects in exposed cells, and are distinctly different from responses to bacteria (e.g., E. coli, mycoplasma, lipopolysaccharide from E. coli, etc.). Quantitative and mechanistic analysis of the observations indicate that the mechanisms that give rise to these responses invoke different subsets of biochemical reactions. The mechanism within the exposed Sentinel Cells is also used in canine olfactory cells (e.g., bomb dogs). The nature of the explosives-induced biological effects provide for a cell based explosives detection system (i.e., a cellular dog nose), as well as a tool for the study of biological effects of energetic materials on humans.
Core Innovation
The invention provides compositions and processes for detection of energetic materials (EM) including explosives, chemical and/or biological weapons, and ionizing radiation using newly identified stationary macrophages termed Sentinel Cells (SC). These SC are isolated, culture stable, and uniquely responsive stationary macrophages derived illustratively from the vestibular labyrinth of a migratory poikilothermic teleost such as the Oyster Toadfish (Opsanus sp.). They provide a rapid, cell-based detector for EM with responses observable within minutes of exposure to various EM, displaying distinct biological effects different from responses to bacteria.
Sentinel Cells possess unexpectedly long life in culture (35+ months without media exchange), low metabolic and culturing requirements, and responsiveness specific to different energetic materials, allowing differentiation among explosives, taggants, bacteria, and toxins. Their mechanisms resemble those in canine olfactory cells, enabling a cellular explosives detection system akin to a 'cellular dog nose' and serving as tools to study biological effects of energetic materials on humans. The SC respond in complex, characteristic profiles to EM including high explosives (RDX, PETN, HMX, TNT, TNG), taggants like DMDNB, and volatiles from commercial and military explosives.
The Sentinel Cells are isolated from vestibular labyrinths, cultured on substrates such as biocleaned glass coverslips, and maintained under ambient temperatures without requiring serum, antibiotics, antifungals, or CO2 supplementation. Detection of EM involves exposing SC to the EM and detecting characteristic cellular responses including changes in nitric oxide synthase activity, DNA labeling, cell size, membrane morphology, apoptosis, and other cellular events, which vary distinctly by the EM type. These responses facilitate identification of the particular energetic material present.
Claims Coverage
The patent includes two independent claims covering the system comprising isolated stationary macrophages and their exposure to energetic materials for detection.
Use of sentinel cells isolated from vestibular labyrinth of Opsanus sp.
An isolated stationary macrophage cell isolated specifically from the vestibular labyrinth of a fish species, Opsanus sp., serving as the detector cell.
Use of substrate selected from glass
The cells contact a selectable substrate, notably glass, to maintain biological activity and responsiveness during detection.
Exposure to one or more specified energetic materials
The cells contact one or more energetic materials selected from a defined group including RDX, PETN, HMX, TNT, C4, Semtex A1, TNG, and DMDNB.
Characteristic and specific cellular responses for energetic material detection
The cells exhibit a defining set of cellular responses specific to each energetic material, including nitric oxide synthase activity, changes in DNA levels and structure, cell size, membrane alterations, nuclear morphology changes, apoptosis, and other detailed cellular events forming a fingerprint for the energetic material detected.
Together, the claims define a system using isolated stationary macrophages from a specific fish source cultured on a substrate, exposed to targeted energetic materials, and exhibiting a unique set of cellular responses that enable detection and identification of these materials.
Stated Advantages
Sentinel Cells provide rapid detection of energetic materials within minutes, often within one minute of exposure.
SC exhibit unexpectedly long viability in culture (over 35 months) without media exchange and have low metabolic and culturing requirements.
SC responses are specific and distinguishable among different energetic materials, bacteria, and toxins, enabling selective detection.
SC do not suffer distractions or fatigue like biological animals used for detection, such as bomb detection dogs.
The system offers a cell-based biological detection method that extends and integrates with existing detection technologies.
Documented Applications
Detection of various high explosives such as RDX, PETN, HMX, TNT, and TNG in solution, aerosol, or volatile forms.
Detection of taggants like 2,3-dimethyl-2,3-dinitrobutane (DMDNB).
Detection of commercial and military explosive formulations including C4 and Semtex A1.
Detection of bacterial agents such as Escherichia coli and mycoplasma as biological comparisons.
Use as a cellular 'dog nose' for near-range and standoff detection of energetic materials.
Study of biological effects of energetic materials on humans via in vitro Sentinel Cell responses.
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