DEVICES AND METHODS FOR DETECTING THE PRESENCE OF

PHOSPHONYL FLUORIDES AND BIS-HALOALKYLENE SULFIDES

FIELD OF THE INVENTION

[0001] This invention relates to assays methods and devices which, in a preferred embodiment, permits the rapid and accurate detection of phosphonyl fluorides and bis- haloalkylene sulfides or alkylthioalkylene halides, or other acid releasing compounds.

BACKGROUND OF THE INVENTION

[0002 J The following discussion of the background of the invention is merely provided to aid the reader in understanding the invention and is not admitted to describe or constitute prior art. to the present invention.

[0003] Chemical toxic agents that interfere with cholinesterases are known to be lethal. Such toxic agents include compounds that contain halophosphonates, e.g., phosphonyl fluorides, which on reaction with water or alcohol release hydrofluoric acid as well as other toxic agents. These phosphonyl fluorides include nerve agents containing a P-F bond (e.g., sarin, cyciosarin, soman) which are intended to deactivate the cholinesterases thereby inducing death in the subject exposed to them, and the by-product is hydrofluoric acid,

[ΘΘ04] Sulfur mustards or mustard gas are a known class of toxic agents. For example, [bis (2-chloroethyl ethyl) sulfide], also known as sulfur mustard (H/HD) is one of the most common chemical warfare agents and has long been known to be a vesicant in humans and, when inhaled, causes extreme lung damaging reactions. Alkylthioalkylene halides such as 2-chloroethyl ethyl sulfide (CEES) or half sulfur mustard are also known for their toxicoiogical effect. Other known sulfur mustard agents include, without limitation, 1,2- bis-(2-chloroethylthio)-ethane (Q), bis-(2-chioroethylthioethyI)-ether (T), 2-chloroethyl chloromethyl sulfide, bis-(2-ciiloroethyithio)-metiiane (HK), bis-l,3-(2-chloroethylthio)-n- propane, bis-1 ,4-(2-chloroethyltbio)-n-butane, bis-1 ,5-(2-chloroethylthio)-n-pentane, and bis-(2-chloroethylthiomethyl)-ether.

[Θ005] The ability to detect toxic agents such as phosphonyl fluorides and bis-haloalkyi sulfides or alkylthioalkylene halides is based on their ability to release acids in detectable amounts. Accordingly, rapid and accurate detection of phosphonyl fluorides, bis- haloalkyl sulfides, alkylthioalkyiene halides and other toxic chemicals in chemical weapons is highly desirable.

[0006] Therefore, a need exists for methods and devices for the easy and rapid detection of phosphonyl fluoride, bis-haioalkyl sulfide, alkylthioaikylene halide or other toxic agents based weapons. The present invention provides devices and methods which provides a warning to the subject regarding the presence of phosphonyl fluoride, bis- haioalkyl sulfide or alkylthioaikylene halide based weapons or other toxic chemicals which release acids, e.g., hydrofluoric acid or hydrochloric acid.

SUMMARY OF THE INVENTION

[0007] This invention provides for a device capable of detecting the presence of phosphonyl fluorides, bis-haloalkyl sulfides or alkylthioaikylene halides, the device comprising a hydrogel, an indicator and a detection means,

[Θ008] In some embodiments, the indicator is selected from heptamethoxy red and hexamethoxy red or a combination thereof In one embodiment, the indicator generates an unequivocal color when contacted with a phosphonyl fluoride or other compounds which release acid. In some embodiments, the indicator changes from uncoiored to colored when contacted with a phosphonyl fluoride or other compounds which release acid. In some embodiments, the indicator is uncoiored at neutral pH.

[0009] In another aspect, a method of determining the presence of phosphonyl fluorides, bis-haloalkyl sulfides or alkylthioalkyiene halides is provided. The method comprises (i) selecting a hydrogel composition comprising an indicator which generates an unequivocal signal when the hydrogel composition is contacted with an acid; (ii) contacting said hydrogel composition with a substance suspected of containing phosphonyl fluorides, bis- haloalkyl sulfides or alkylthioaikylene halides (iii) determining the presence of phosphonyl fluorides, bis-haloalkyl sulfides or alkylthioaikylene halide s, by assessing the presence of said unequivocal signal.

[0010] in some embodiments, the indicator changes from uncoiored to colored when contacted with a phosphonyl fluoride, a bis-haioalkyl sulfide or an alkylthioaikylene halide. In some embodiments, the hvdrogel composition is uncolored prior to contacting with the phosphonyi fluoride, bis-haloalkyl sulfide, or alkylthioalkylene halide.

[0011 j in some embodiments, the detection means comprises instrumentation which allows for facile visual detection. In other embodiments, the detection means comprises instrumentation which allows for remote detection.

[0012 j in some embodiments, the device is in the form of a badge or a placard positioned on a soldier or a medic. In other embodiments, the device is placed in a drone or a robot.

DETAILED DESCRIPTION OF THE INVENTION

[0013] Before this invention is disclosed and described, it is to be understood that the aspects described below are not limited to specific compositions, methods, or uses as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular aspects only and is not intended to be limiting.

[0014] In this specification and in the claims that follow, reference will be made to a number of terms that shall be defined to have the following meanings:

[0015] St must be noted that, as used in the specification and the appended claims, the singular forms "a," "an" and "'the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a p indicator" includes mixtures of two or more such agents, and the like.

[0016] "Optional" or "optionally" means that the subsequently described event or circumstance can or cannot occur, and that the description includes instances where the event or circumstance occurs and instances where it does not.

[0017] Titles or subtitles may be used in the specification for the convenience of a reader, which are not intended to influence the scope of the present invention.

Additionally, some terms used in this specification are more specifically defined below. Defisiitiosis

[0018] "Alkyl" refers to monovalent saturated aliphatic hydrocarbyi groups having from 1 to 10 carbon atoms and, in some embodiments, from 1 to 6 carbon atoms. This term includes, by way of example, linear and branched hydrocarbyi groups such as methyl, ethyl, n-propyi, isopropyl, n-butyl, isobutyl, sec-butyS, t-butyl, n-pentyl, and neopentyl.

[0019J "C _x -C _y " with respect to a group refers to that group having from x to y carbon atoms.

[0020] "Alkylene" refers to divalent saturated aliphatic hydrocarbyi groups having from 1 to 25 carbon atoms and, in some embodiments, from 1 to 15 carbon atoms. The alkylene groups include branched and straight chain hydrocarbyi groups, such as methylene, ethylene, propylene, 2- methypropylene, pentylene, and the like.

[002i| Neutral pH has a value of about 7.0,

[0022] The term "acidic" as used herein refers to an acidic pH range produced by hydrogen fluoride (HF). As hydrogen fluoride is one of the strongest known acids, its formation leads to a rapid drop in pH from neutral pH to acidic pH.

[0023] A "transparent layer" includes both uncolored or colored layers provided that the viewer can see through the colored layer. For example, tinted eyeglasses are colored but transparent.

[0024] The term "colorless" refers to the lack of sufficient color so as to be deemed transparent and clear either visually or by instrumentation. When visually evaluated, the tenn "colorless" does not mean that there is no color but, rather, the color is either not visually detectable or minimally detectable such that the viewer sees a clear film.

[0025] The term "colorful" refers to sufficient color such that the color can be detected by visual observation.

[0026] The term "substance" refers to a material used to disseminate the compounds to be detected. The substance can be a gas or a carrier in the form of an aerosol, a spray, oil droplets, etc.

[0027] The term "signal" refers to any signal that can be detected directly or remotely which signal correlates to the presence of an acid generating substance. [ΘΘ28] The term "detecting" refers to the use of any device or means which can determine the presence of a signal, in an embodiment, the signal is monitored

continuously such that a machine-readable signal is detected and reported on an on-going basis, in an embodiment, the signal is detected and monitored intermittently, for example periodically every few hours or days. In an embodiment, the signal is detected at discrete times, for example when presence of toxic chemical agents is suspected or when the subject is in a war zone. In yet another embodiment, the signal is monitored visually.

[0029] The term "electromagnetic energy" refers to any wavelength of energy capable of being transmitted from the body as well as being monitored ex vivo. Examples of such energy include light in the ultraviolet (UV), visible and infrared (IR) portions of the light spectrum. Other examples include energy readable by magnetic resonance imaging (MR]), X-rays, and the like.

[0030] The term "produce or can be induced to produce a signal" means that the indicator directly or indirectly produces a signal. An example of indirect production of a signal is the use of energy directed to the indicator to induce fluorescence.

[0031 J The term "subject" or "patient" refers to any mammal and includes without limitation primates such as humans, monkeys, apes, and the like, and domesticated animals such as horses, dogs, cats, ovines, bovines, and the like.

[0032] As used herein, "nerve agent" refers to a chemical compound that disrupts the functioning of the nervous system of a subject, such as by inhibiting the actions of the enzyme acetylcholinesterase. A nerve agent can be any organophosphorus nerve agent, including, but not limited to G-type nerve agents and V-type nerve agents. Exemplary organophosphorus nerve agents include tabun (GA), sarin (GB), soman (GD), cyclosarin (GF), VX, Russian VX (VR), classified non-traditional nerve agents (NTAs) and diisopropylf luorophosphate (DFP) .

Devices

[0Θ33] In one aspect, provided herein are methods and devices capable of detecting the presence of chemical weapons and toxic chemical agents. Examples of these toxic chemical agents include nerve gas and sulfur mustard. In one aspect, methods and devices for detecting the presence of phosphonyl fluorides or other compounds which release hydrofluoric acid are provided. In another aspect, methods and devices for detecting the presence of bis-haloalkyl sulfides, or alkylthioalkylene halides are provided. In yet another aspect, methods and devices for detecting the presence of compounds which release an acid are provided.

[Θ034] In one embodiment, the device comprising a hydrogel, an indicator and a detection means. In one embodiment, the indicator is a pH indicator. In one embodiment, the indicator is transparent, in one embodiment, the indicating moiety is heptamethoxy red or hexamethoxy red. In one embodiment, the indicating moieties undergo a detectable colorimetric induction in response to a pH change resulting from the presence of an acid. In some embodiments, the acid is selected from the group consisting of carbonic acid, sulfuric acid, hydrochloric acid and hydrogen sulfide.

[0035] in one embodiment, the toxic chemical agents include halophosphonates. in one embodiment, the halophosphonate includes fluorophosplioiiates. In some embodiments, the fluorophosphonates can include nerve agents containing a P-F bond (e.g., sarin, cyclosariii, soman). In one embodiment, the fluorophosphonate include phosphoryl halide type nerve agents such as for example, sarin nerve gas (Isopropyl- ethyl-Phosphoryl Fluoride). In one embodiment, the fluorophosphonate include phosphonyl halide type nerve agents such as for example, methyl or ethyl phosphonyl diiluoride. Upon contact with moisture from the hydrogel, the phosphonyl fluorides release hydrofluoric acid which can be detected using the pH indicator.

[0036] In one embodiment, the toxic chemical agents include sulfur mustard agents. In one embodiment, the sulfur mustard agents include bis-haloalkyl sulfide and

alkylthioalkylene halide compounds. Examples of sulfur mustard agents include, without limitation, [bis (2-ch!oroethyI ethyl) sulfide] (H/HD or sulfur mustard), 2-Chloroethyl ethyl sulfide (CEES or half sulfur mustard), I ,2-Bis-(2-chloroethylthio)-ethane (Q), Bis- (2-chioroethylthioethyi)-ether (T), 2-Chloroethyl chloromethyi sulfide, Bis-(2- chloroethylmio)-methane (HK), Bis- 1 ,3-(2-chloroethylthio)-ii-propane, Bis- 1 ,4-(2- chloroethylthio)-n-butane, Bis- 1 ,5-(2-chioroethylthio)-n~pentane, and Bis-(2~

chloroethylthiomethyl )-emer. [ΘΘ37] In some embodiment, the sulfur mustard agents include compounds having the formula:

(C ₁ -C6)alky]-S-(C ₂ -C ₄ )a].kylene-X, wherein X is chloro, bromo or fl oro.

[0038] In some embodiment, the sulfur mustard agents include compounds having the formula:

X-(C]-C ₆ )alkyl-S-(C] -C6)alkyl-X, wherein X is chloro, bromo or fluoro.

[0039] In one embodiment, the toxic chemical agents include nitrogen mustard agents. In some embodiments, the nitrogen mustard agents include (bis-haloalkyl )alkyl amine or tris-haloalkyl amine compounds.

[0040] In some embodiments, the indicator generates an almost instantaneous color or color change when contacted with a phosphonyl fluoride or other compounds which release hydrofluoric acid. In other embodiments, the indicator generates an almost instantaneous color or color change when contacted with a bis-haloalkyl sulfide or a!kyfthioalkylene ha!ide compound. The almost instantaneous color change is due to the exceptional drop in pH of the water in the hydrogel due to the hydrolysis of the phosphony! fluorides, bis-haloalkyl sulfides, or a!kylthioalkylene halides. That hydrolysis releases an acid, e.g., hydrofluoric acid or hydrochloric acid, which immediately drops the pH.

[0041] The device can be in any suitable form to be positioned on the subject or at the site at which detection is sought. In some embodiments, the device can be a badge or a placard which is positioned on the body of a soldier or a medic, or it can be placed on mechanical equipments such as drones or robots.

Methods

[0042] In one aspect, a method of determining the presence of phosphonyl fluorides, bis- haloalkyl sulfides or alkylthioalkylene halides is provided. The method comprises (i) selecting a hydrogel composition comprising an indicator which generates an unequivocal signal when the hydrogel composition is contacted with an acid; (ii) contacting said hydrogel composition with a substance suspected of containing phosphonyl fluorides, bis- haloalkyl sulfides or aikyithioaikvlene halides (iii) determining the presence of

phosphonyi fluorides, bis-haloalkyl sulfides or aikyithioaikvlene halide s, by assessing the presence of said unequivocal signal.

[0Θ43] In some embodiments, the indicator generates an unequivocal color when contacted with a phosphonyi fluoride, a bis-haloalkyl sulfide or an alkylthioalkyiene halide or other compounds which release an acid. In some embodiments, the indicator changes from uncolored to colored when contacted with a phosphonyi fluoride, a bis- haloalkyl sulfide or an alkylthioalkyiene halide or other compounds which release an acid.

[0044] Upon exposure to a chemical weapon or toxic chemicals containing a phosphonyi fluoride, a bis-haloalkyl sulfide or an alkylthioalkyiene halide, the water in the hydrogel releases an acid, e.g., hydrofluoric or hydrochloric acid, which rapidly transforms the optically clear or uncolored indicator to a colored indicator.

[Θ045] In one embodiment, the device allows for facile visual detection of presence or absence of phosphonyi fluorides, bis-haloalkyl sulfides, alkylthioalkyiene halides or other compounds which release an acid. In other embodiments, the device allows for remote detection of presence or absence of phosphonyi fluorides, bis-haloalkyl sulfides, alkylthioalkyiene halides or other compounds which release an acid.

[Θ046] In one embodiment, the indicator comprises pH i dicating moieties selected from heptamethoxy red and hexamethoxy red or a combination thereof.

[0047] Toxic chemical compounds react with cholinesterases and form acidic byproducts such as e.g. phosphonyi fluorides, bis-haloalkyl sulfides, or alkylthioalkyiene halides. Mixtures of these by-products with moisture from the hydrogel result in the formation of acids such as e.g. hydrofluoric acid or hydrochloric acid. When a sufficient amount of acid is released, the pH indicator in the hydrogel composition produces a color change, e.g., from uncolored to colored that is readily discernible by even an untrained observer.

[ΘΘ48] Exemplary and non-limiting advantages of the devices and methods provided herein include the applicabili ty to any type of device used for detection of toxic chemical s. Further advantages include its ability to identify and report the presence of a phosphonyi fluoride based weapon. For example, the phosphonyl fluoride may be detected by a hydrogel, an indicator and detection means.

[0049] In some embodiments, the detection means comprises instrumentation which allows for facile visual detection. In other embodiments, the detection means comprises instrumentation which allows for remote detection.

[0050J in some embodiments, detection means may include a scanning technology can measure unique electromagnetic signatures due to the electronic change in the indicator. These electromagnetic signatures can provide self-reporting technology. Suitable electromagnetic scanning technologies are known in the art and include, but are not limited to, Fluorescence, Magnetic resonance imaging (MRI), Nuclear magnetic resonance (NMR), infrared Spectroscopy (IR), etc.

Hydrogels

[0051] In some embodiments, the indicator is included in a substance known in the art to be water permeable, hydronium ion permeable and biocompatible, such as, for example various polymeric material such as hydrogels. For example, water permeable, hydronium ion permeable and biocompatible materials include polymers of 2-hydroxyethyl methacrylate (HEMA), 2-hydroxyethyl acrylate, silicone hydrogels, and the like. In one embodiment, the hydrogel is optically uncolored as is the indicator. In another embodiment, the hydrogel contains from 15 percent to 80 percent by weight water as compared to the weight of the polymer.

[ΘΘ52] Suitable hydrogels are useful as matrices and as microspheres, nanospheres, and the like. See, for example, European Polymer Journal, 45 (6): 1689-97 and

Macromolecular Bioscience, 4 (0): 957 -62 (each of which is incorporated herein in its entirety by reference).

[0053] Certain exemplary and non-limiting acid degradable sugar based hydrogels are synthesized using a commercially available acid sensitive cross-linker, 3,9-divinyi- 2,4,8,10-tetraoxaspiro-[5,5]-undecane. The monomers used for polymerization are N- isopropylacryianiide (NIP AM) and d-gluconamidoethyl methacrylate (GAMA), which when polymerized in the presence of the acid degradable cross-linker yiel d hydrogels that can swell and degrade under acidic conditions, making them suitable for antibiotic and/or pH indicator delivery. The hydrogels are synthesized, using either a photo-initiator, Irgacure-2959 or a conventional initiator, potassium persulfate. The swelling capacity and antibiotic and/or pH indicator release from the hydrogels as a function of pH is tested by methods well known to the skilled artisan. The antibiotic and/or pH indicator release from the hydrogels can depend on the degree of cross-linking and the pH of the environment.

[0054] Other exemplary and non-limiting hydrogels include those based on di-acrylated Pluronic F-127 tri-block copolymer, prepared for example, by a photopoiymerization method.

[0055] In some embodiments, the indicator is entrapped within the polymeric film and typically within the hydrophihc, hydrcmium ion penetrating layer of the polymeric film. General methods for entrapment include those described in U.S. Patent 5,629,360. The indicator may also be entrapped within pores in the hydrophilic, hydronium ion penetrating layer. Suitable additives such as diatomaceous earth (DE), T1O ₂ , and Si0 ₂ or combinations thereof may be added to the layer to generate such pores. In some embodiments, the diatomaceous earth is in an amount of up to about 10 % w/w. In some embodiments, it is about 4 % w/w. In some embodiments, it is about 3 % w/w. Pores may also be generated by laser drilling. W eight percentages are based on the weight of the additive relative to the weight of the hydrophilic, hydronium ion penetrating layer.

Indicators

[0056] As used herein, the term "indicator" refers to a compound or device that produces a signal in presence of phosphonyl fluorides, bis-haloalkyl sulfides, alkylthioaikylene halides or other compounds which release an acid. The signal can be electromagnetic such as a change in absorption which can be observed by naked eye and/or by using an emission and/or absorption spectrophotometer. Such indicators include by way of example only, dyes including pH indicators, metals such as gadolinium, pH sensitive fluorescent indicators and the like.

[0057] In some embodiments, the indicator is pentamethoxy red, hexamethoxy red and/or heptamethoxy red, and combinations thereof. In one embodiment, the pH indicators are hexamethoxy red and/or heptamethoxy red or derivatives thereof. [ΘΘ58] Heptamethoxy red refers to the chemical 2,4,6,2',4 ^, ,2",4"-heptamethoxytri- phenyicarbinol having Formula (I) below and derivatives thereof which do not alter the ability of the compound to detect changes in pH. Hexamethoxy Red refers to the chemical 2,4,2\4 ^, ,2 ^, \4' ^! -hexamethoxytriphenylcarbmol having Formula (IX) below and derivatives thereof which do not alter the ability of the compound to detect changes in pH.

[0059] Heptamethoxy red exhibits a dynamic range between approximately pH 7 and pH 5, and hexamethoxy red exhibits a dynamic range between approximately pH 4.5 and pH 2.6. Both exhibit visually perceptible color change from colorless to colorful (reddish / violet red) when exposed to a sufficient amount of acid so as to lower the pH to a level necessary to effect color change. Derivatives of either hexamethoxy red or heptamethoxy red are contemplated to include substitution of one or more of the methoxy groups with a C2-C3 alkoxy group provided that such substitution does not alter the ability of the compound to detect changes in pH.

[0060J in some embodiments, the indicator or pH indicating moieties are in both gaseous and fluid communication with the substance that is being detected.

[Θ061] In some embodiments, indicators, can include, without limitation, one or more of pH sensitive, acid degradable, liposomes, micelles, microspheres, nanospheres, matrices, and the like. In some embodiments, the pH sensitive, preferably acid degradable, micelles, microspheres, nanospheres, matrices, and other acid degradable components, comprise one or more pH sensitive, preferably acid degradable, polymers. In some embodiments, the pH sensitive, preferably acid degradable, micelles, microspheres, nanospheres, matrices and other acid degradable components comprise acid degradable hydrogels and xerogels. In some embodiments, the acid degradable hydrogels, and xerogels comprise one or more pH sensitive, or preferably acid degradable, polymers.

[0062] Preferably, the hydro gel and the indicator are immobilized and are provided or enhanced by employing a membrane which is permeable to, for example, hydronium ions, gases, etc. In one embodiment, the hydrogel is immobilized by anchoring it to the device of this invention. The indicators can be immobilized by covalently attaching the indicator to a polymeric material that is pan of the device. Poiymerizable hexa- and heptamethoxy derivatives can be copoiymerized with other monomers to form immobilized indicators. Such poiymerizable indicators include those described in U.S. application publication no. 61/570,626, which is incorporated herein in its entirety by reference. The pH indicators can also be immobilized by incorporating it in a matrix, preferably an acid degradable matrix, from which the mdicator cannot leach out or cannot substantially leach out under normal physiological pH.

[0063] The indicator in the polymeric indicator film are employed in an amount effective for detecting a color change thereby evidencing a change in pH. As used herein, the term "detection" includes a color-change either visible by human eye having ordinary vision. Instrumentation may also be used. In some embodiments where the indicating moiety is embedded in the hydrophilic, hydronium ion penetrating Saver, the indicating moiety is employed in an amount of about 0.01 % w/w to about 10 % w w relative to the weight of that layer. In some embodiments the mdicator is employed in an amount of about 1 % w/w to about 3 % w/w.

[0064] in some embodiments, the indicator can be any mdicator compound, in some embodiments, the indicator can be a fluorescent indicator e.g., hexamethoxy red or derivatives thereof uch as those described in U.S. 8,425,996 which is incorporated herein by reference in its entirety. In some embodiments, the indicator can be any compound of Formula (I), ( IX), (HI) and (IV) described in U.S. Provisional Application No. 61/858077. In some embodiments, the indicator converts between a solid/gel and a liquid in a pH dependent manner.

[0065] In some embodiments, the indicator can be a polymeric mdicator film or a sandwich" type of polymeric indicator film as described in U.S. Patent Serial No.

12/693,375, which is incorporated herein by reference. [ΘΘ66] In some embodiments, the device has two or more different indicators or reporter compounds. For example, separate indicators can be used which one changes color in an acidic pH and another changes color in a basic pH. 0Θ67] The color change transition can be colored to imcolored or uncolored to colored or one color to another color or a first color to a second color to a third color to a fourth color and so on, depending upon the number of indicators used.

[0068] The color change transitions can be in acidic pH and in alkaline pH. The color change transitions can be in acidic pH and in acidic pH. The color change transitions can be in alkaline pH and in alkaline pH. The color change transitions can be in acidic pH, in acidic pH, in alkaline pH and in. alkaline pH (depending upon the number of indicators used).

[00691 it is contemplated that the pH sensitivity of some of the indicators used in the present methods is within ±0.5, preferably, within ±0.3, more preferably within ±0.2 of that of, for example, hexamethoxy red. It is also contemplated that pH sensitivity of the some of the indicators used in the present methods, is within ±0.5, preferably, within ±0.3, more preferably within ±0.2 of that of heptamethoxy red.

Additional Indicators and Reporters

[007 | in some embodiments, the device further comprises additional indicator or reporter compounds.

[0071] In some embodiments, the device further comprises one or more "additional indicators" described herein. Such additional indicators include a metal selected f om the group of a fluorescent moiety; a paramagnetic ion, such as gadolinium, europium, manganese, lanthanide, iron, and derivatives thereof; or a phase transition material. The indicator is capable of remote detection, for example by magnetic resonance imaging (MRI). Examples of these and other indicators are well-known in the art. For example, and without limiting the scope of the present invention, Amanlou, et al. describes several indicators that are commonly used in MRI, including small mononuclear or polynuclear paramagnetic chelates; metalloporphyrins; polymeric or macromolec lar carriers

(covaientiy or noncovalently labeled with paramagnetic chelates); particulate contrast agents (including fluorinated or non-fiuorinated paramagnetic micelles or liposomes) and paramagnetic or super paramagnetic particles (e.g., iron oxides, Gd3-Iabeled zeolites); dimagnetic CEST polymers; dimagnetic hyperpolarizatioii probes (gases and aerosols), and DC-labeled compounds or ions. Amanlou, et al., Current Radiopharmaceuticals 4, 31-43 (201 1).

[ΘΘ72] In some embodiments, the indicator is pH-sensitive or temperature-sensitive. In an embodiment, the indicator is a fluorescent moiety. Fluorescence is the light emitted when a molecule absorbs light at a higher energy wavelength and emits that light at a lower energy wavelength. In an embodiment, the fluorescent moiety is remotely detectable, for example by fluorescence spectroscopy.

[00731 hi some embodiments, the device comprises pH-sensitive indicators such as those described, for example, in U.S. Patent Pub. No. 201 1/0104261 Al and references therein, all of which are incorporated herein by reference in their entirety. Such p -sensitive indicators may include citraconyl-liiiked Gd chelates, Gd diethylenetriamine pentaacetic acid (DTP A) chelates, and Gd-DOTA chelates.

[0074J in some embodiments, the device, comprises a fluorescent pH indicators that can sense pH changes within physiological ranges. See, for example,

http://www.in viirogenxom/sit^

Handbook''pH-Indieators/Ό verview-o f-p H -Indi cators . html

UTILITY

[0075] The devices of this invention are useful as indicators for the detection of harmful chemical weapons and toxic chemicals, specifically phosphonyl fluoride based weapons. The ability to detect phosphonyl fluorides is based on the ability to release hydrofluoric acid in detectable amounts. The devices and m ethods allow for evaluation of presence or absence of a phosphonyl fluoride based weapon thereby preventing death and casualty of soldiers in a war zone. Likewise, the presence of dangerous mustard gases such as bis- haloalkyl sulfides and alkylthioalkylene halides is possible using the present technology. The devices and methods can also be used to detect the presence or absence of other toxic chemicals which release an acid. EXAMPLES

Exam le ^

[0076] Poly (2 -hydroxy ethyl methacrylate) (PHEMA) hydro gel is employed where the polymer has number average molecular weight of about 10,000 and a water content of about 40% based on the total weight of the composition. The composition contains about 1 % by we ght of hexamethoxy red, a commercially available pH indicator which is u colored at pH 7.

[0077] The molecular formula for PHEMA is:

wherein n is such that the average molecular weight is about 10,000.

[0078] The composition is placed into a badge or other device where the composition is exposed to ambient air. As shown in the reactions below, upon contact with water found in the hydrogel, both soman and sarin gases release hydrofluoric acid (HF), which rapidly reduces the pH such that the pH indicator turns to a brilliant reddish-purple, indicating the presence of such gas.

Sarin

[0079] It is to be understood that while the invention has been described in conjunction with the above embodiments, that the foregoing description and examples are intended to illustrate and not limit the scope of the invention. Other aspects, advantages and modifications within the scope of the invention will be apparent to those skilled in the art to which the invention pertains.