Patent Publication Number: US-10330603-B1

Title: Mass produced, low cost, portable test kit for the detection and identification of chemical and biological agents

Description:
RELATED APPLICATION DATA 
     The present application is a continuation-in-part of commonly-owned U.S. application Ser. No. 15/094,825, entitled MASS PRODUCED, LOW COST, PORTABLE TEST KIT FOR THE DETECTION AND IDENTIFICATION OF NARCOTICS, filed on Apr. 8, 2016, now U.S. Pat. No. 9,759,733, which patent is related to commonly-owned U.S. application Ser. No. 14/856,671, entitled PORTABLE LIQUID ANALYZER, filed on Sep. 17, 2015, now U.S. Pat. No. 9,989,473. Both patents are incorporated herein by reference in their entireties. 
    
    
     TECHNICAL FIELD OF THE INVENTION 
     The present invention relates to a portable test kit capable of identifying the presence of chemical and biological agents, a process to inexpensively mass produce the portable test kit and achieve long term commercial shelf life in the range of 2 to 3 years, and a method to use the portable test kit. 
     BACKGROUND ART 
     Most commercially available presumptive chemical and biological agents test devices and available IP and literature, use and describe methods which contain hazardous materials and sophisticated packaging which are not suitable for extremely cheap mass production in simple factory settings. 
     These test kits suffer from a variety of manufacture and end use problems, including but not limited to: (i) kit construction requires liquid dropper bottles, breakable glass or plastic ampoules, blister packs and pressurized aerosol spray cans filled with hazardous liquid reagents; (ii) the presence of hazardous liquid reagents poses problems with manufacturing and exposure limitations, storage and handling, strict packaging requirements and significant shipping restrictions; (iii) the volume or quantity of liquid reagent consumed during one single test is excessive and wasteful adding to costly, bulky and often overly complicated device construction design and packaging; (iv) during use, operators may be exposed to sharps and hazardous liquid reagent splash or overspray; (v) most prior art devices require multi-step operations in order to complete a single test; and (vi) none of the prior art kits and devices achieve the bench mark of true low cost mass manufacturing, which would be considered in the range of tens of millions of individual units per annum, with a commercial shelf life span of 2 to 3 years. 
     Impregnation of bibulous carriers with reagent solutions is an incredibly inefficient and costly method of presumptive test kit manufacture. Ultimately, the solvents used to dissolve the powdered reagents must be removed by evaporation. Often the solvents will be aqueous based and acidic in nature, which makes removal from the bibulous carrier hazardous, very costly, and will require very sophisticated laboratory equipment to minimize exposure and corrosion of the surrounds. In the event that the bibulous carrier can be dried, it must still be cut and presented in a kit format for ease of use. Often, this will incorporate plastic injection molded housings, which are magnitudes of order more expensive than paper based supports. Additionally, the cost of the injection die is excessive. The alternative low cost paper based solid support carrier option for a presumptive kit is often not possible, as the loaded bibulous carrier strips resist sticking and adhering to common pressure sensitive adhesives because of interaction with the impregnated reagent(s) and/or the pressure sensitive adhesives react with the impregnated reagent(s), destroying the kits. 
     SUMMARY OF THE INVENTION 
     Embodiments of the present invention provide a presumptive spot test kit which will facilitate identification of chemical and biological agents within suspect residues. 
     Embodiments of the present invention provide a presumptive kit, constructed of paper with color change reagents applied to the surface as one or more test zones, and a pre-wetted swab with non-hazardous co-solvents to facilitate enhanced suspect residue collection. 
     Embodiments of the present invention provide an extremely portable presumptive test kit, which has true low cost and mass manufacture capability on the order of millions of units per annum, while achieving a commercial kit shelf life, on the order of several years, with a reduced false detection rate. 
     Embodiments of the present invention also provide a method of kit manufacture and use. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  illustrates an embodiment of a diagnostic test paper made in accordance with the present invention; 
         FIG. 2  illustrates an embodiment of a swab made in accordance with the present invention; and 
         FIG. 3  illustrates a package into which a test paper and swab may be hermetically sealed. 
     
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
     The described features, structures, or characteristics of the invention may be combined in any suitable manner in one or more embodiments. In the following description, numerous specific details are provided to provide a thorough understanding of embodiments of the invention. One skilled in the relevant art will recognize, however, that the invention can be practiced without one or more of the specific details, or with other methods, components and so forth. In other instances, well-known structures, materials, or operations are not shown or described in detail to avoid obscuring aspects of the invention. 
     Chemical and Biological Agents are divided into several categories based on their mode of action on an organism.
         Blister agents:
           sulfur mustard (H, HD);   nitrogen mustard (HN);   lewisite (L);   phosgene oxime (CX).   
           Blood agents:
           hydrogen cyanide (AC)—Liquid, BP 26 deg cel. Volatile;   cyanogen chloride (CK);   arsine (SA). Lewisite (L) Adamsite.   
           Nerve agents (nerve agents belong chemically to the group of organo-phosphorus compounds):
           Tabun, O-ethyl dimethylamidophosphorylcyanide (GA);   Sarin, isopropyl methylphosphonofluoridate (GB);   Soman, pinacolyl methylphosphonofluoridate (GD);   Cyclohexyl methylphosphonofluoridate (GF);   O-ethyl S-diisopropylaminomethyl methylphosphonothiolate (VX).   
           Psychotomimetic agents:
           3-quinuclidinylbenzilate (BZ);   LSD.   
           Toxins:
           Bacterial toxins;   Plant toxins.   
               

     Contrary to the prior approaches for the presumptive identification of chemical and biological agents, the inventor has discovered that presumptive polyvalent ion powdered salts, carbohydrates and polyols and color change reagents can be successfully mixed with and/or made into encapsulating polymer solutions and printed onto any solid support structure, to be shaped and packaged. In combination with a simple cotton swab, such as a Q-tip® swab, which has been pre-wetted with a non-hazardous solvent and packaged, Embodiments of the present invention provide a low cost, mass producible, portable test kit for the presumptive identification of chemical and biological agents. 
       FIG. 1  illustrates an embodiment of a diagnostic test paper  10  made in accordance with this invention. The test paper  10  comprises a solid support surface or article  1 ; one or more encapsulated colorimetric reagents (CR)  2 ,  4 , printed at one or more locations onto the support surface  1 ; a physical gap or void  3  between the individual encapsulated reagent deposition interstices  2 ,  4  on the solid support surface  1  to prevent chemical interaction. 
       FIG. 2  illustrates an embodiment of a swab  30 , such as a Q-tip® swab, made in accordance with the present invention. The swab  30  comprises a cotton tip matrix  7 , dry or pre-wetted with one or more non-hazardous solvents, attached to one end of a handle  8 . 
     Solid Support 
     Suitable solid support surfaces or substrates to which the encapsulated presumptive reagents can be applied, is dictated only by end use requirements. In accordance with the current invention and without limitation, in some embodiments the solid support substrate  1  is paper, such as 100-400 gsm white, acid free, card sheet. 
     Sample Swab 
     In order to maximize solubility of both the suspect residue of chemical and biological agents and the presumptive test reagents, a suitable non-hazardous solvent and/or solvent mix provided in combination with a swabbing device. Numerous swab and co-solvent devices can be prepared including, but not limited to, a pre-wetted cotton swab and/or co-solvent shaft filled pop or snap swabs. 
     In one embodiment a kit  10 , the sample swab  30  is a pre-wetted, co-solvent, cotton swab  30 . Numerous swab/solvent devices can be prepared including, but not limited to, dip impregnation, shaft-handle fill and pop or snap swabs. Pre-impregnation of swabs may be achieved in mass by fully automated dip or spray machinery. 
     The swab  30  may be a polypropylene handle  8  with a cotton filament matrix head  7 . The sample swab may be dry or pre-impregnated with solvent to improve solubility of both CWA/BA and CR, maximizing sensitivity and color indication reactions. By way of example only, a suitable co-solvent is Iso-Propyl Alcohol ad-mixed with Dimethyl Sulphoxide. This co-solvent mix offers broad spectrum solubility of target and dry reagent compounds, while intensifying presumptive color change reactions. The combination of IPA with DMSO prevents freezing of solvents during long term storage and use in low temperature environments. This solvent combination also offers intensifying presumptive color change reactions, is non-hazardous, and has an extremely low cost. The volume of solvent required for pre-impregnation is in the range of 0.05-0.15 mL per swab. 
     Colorimetric Reagents 
     Colorimetric reagents (CR) may be selected according to at least: (a) liquid CR affinity for pre-adsorption onto dry, inert binders and subsequent milling into micronized powders; (b) powder CR affinity for milling into micronized powders; (c) degree of hygro-scopicity; (d) interaction with inert liquid diluents required for print manufacture; (e) level of UV and ambient condition degradation; and (f) selectivity for and color reaction intensity with CWA and BA. 
     Chemical Warfare Agent Detection 
     Without limitation, suitable CR capable of detecting gas and liquid phase pH changes may be selected from a group comprising: cresol red, methyl violet, crystal violet, ethyl violet, malachite green, methyl green, 2-(p-dimethylaminophenylazo)pyridine, paramethyl red, metanil yellow, 4-phenylazodiphenylamine, metacresol purple, orange IV, 4-o-tolylazo-o-toluidine, quinaldine red, 4,4′-bis(4-amino-1-naphthylazo)-2,2′-stilbenedisulfonic acid, p-naphtholbenzein, phenolphthalein, o-cresolphthalein, ethyl bis(2,4-dimethylphenyl)ethanoate, Thymolphthalein, alizarin yellow R, alizarin, p-(2,4-dihydroxyphenylazo) benzenesulfonic acid-sodium salt, 5,5′-indigodisulfonic acid-disodium salt, 2,4,6-trinitrotoluene, 1,3,5-trinitrobenzene, and clayton yellow. 
     Without limitation, suitable CR capable of detecting gas and liquid phase changes may be selected from a group comprising: merocyanine dyes, 4-[2-N-substituted-1,4-hydropyridin-4-ylidine)ethylidene]cyclohexa-2,5-di-en-1-one, red pyrazolone dyes, azomethine dyes, indoaniline dyes, diazamerocyanine dyes, indigoid dyes 2,6-diphenyl-4-(2,4,6-triphenylpyridinium-1-yl)phenolate, 1-ethyl-4-(methoxycarbonyl)pyridinium iodide,5-(dimethylamino)-5′-nitro-2,2′-bisthiophene, (2,4,6-triphenyl-I-pyridinio)-2,6-diphenylphenolate, and alizarin red s. 
     Without limitation, suitable CR capable of detecting the presence of liquid and solids comprising reactive nitrogen is determined by chemical reagents selected from a group comprising: 6-amino-1-naphthol-3-sulphonic acid, zinc, diphenylbenzidine, phenylanthranilic acid, aniline sulfate, diphenylamine, ethylenediamine, N-1 naphthyl dihydrochloride, potassium iodide, bismuth nitrate, and sodium hydrogen sulphate, hexachloroplatinic(IV) acid hydrate. 
     Without limitation, suitable CR capable of detecting the presence of volatile CWA (solid, liquid, gas) may be selected from a group comprising: sodium iodoplatinate, Alkyl magnesium bromide (Grignard reagent), B-napthol, selenious acid, indophenol blue, silver nitrate, Grignard&#39;s sodium iodide, sodium nitroprusside, quinone dichlorimide, mercuric nitrate, sodium iodide, N-chloramide, zinc Sulfate-Molybdic Acid, argentic nitrate, mercuric chloride, cuprous iodide, diphenylthiocarbazone, di-p-biphenylthiocarbazone, di-o-phenoxyphenylthiocarbazone, dianisylpropylene, p,p′-dinitrostilbene-o,o′-disodium sulfonate, 5-(or 8-) nitroisoquinoline, sodium iodoplatinate, chloroplatinic acid, phosphomolybdic acid, Mayer&#39;s reagent (KHgI2), metanil-yellow, N-chloramide, diphenylthiocarbazone, potassium iodide and starch, acidified phloxine, p-dimethylaminobenzaldehyde and syn-trimethoxybenzene, p-nitrobenzyl bromide, 4-(4-nitrobenzyl)pyridine-tetraethylenepentamine, palladium chloride, bromophthalein, anisaldehyde, 4-aminopyridine, 2-methylthioacridone, trichlorobenzoquinoneimide, zinc hexacyanoferrate, cupric acetate, malachite green, and p,p′-tetramethyldiaminodiphenylmethane (tetrabase). 
     Biological Agent Detection 
     Without limitation, suitable CR capable of detecting BA may be selected from a group comprising: acid fuschin, alcian blue 8gx, alizarin red s, 9-amino-6-chloro-2-methoxyacridine, aniline blue, auramine o, azure b, N,N′-[1,2-ethanediylbis(oxy-2,1-phenylene)]bis[N-(carboxymethyl)-, benzothiazolium, 2,2′-[1,3 propanediylbis[(dimethyliminio)-3,1-propanediyl-1(4H)-pyridinyl-4-ylidenemethylidyne]]bis[3-methyl-, iodide (1:4), brilliant cresyl blue, calcein, congo red, crystal violet, di-8-anepps, dihydroethidium, dihydrorhodamine 123, eosin b, fast green fcf, bicinchoninic acid, sodium carbonate, sodium potassium tartrate, sodium hydroxide, copper sulphate, pyrogallol red, sodium molybdate, succinic acid, sodium benzoate sodium oxalate, methanol, coomassie blue G-250, ethanol, phosphoric acid, and phosphomolybdate, phosphotungstate. 
     Reagent and Encapsulating Polymer Mixing 
     In embodiments of the present invention, raw CR product may be individually micronized in suitable a agitation mill system such as a laboratory ball, crusher, shaker mill, or the like. The process produces a sub-micron size powder capable of undergoing laydown print applications. 
     The fine CR powder may be added to inert liquid diluents which double as solid support binding agents during the printing process. The two components may be combined in a high speed impeller mixer or shaker or similar system until an homogenized suspension is obtained. Without limitation, the liquid diluents may be selected from a list including but not limited to: acrylic acid, polyvinyl alcohol, amino cross-linking agents, polyvinyl pyrrolidone, glycol-ethers, styrene, polyester, vinyl chloride, polyethylene, natural gums, poly-ethers and polyamides. The viscosity of the homogenized CR suspension may be adjusted using inert bulking agents including but not limited to silica, diatomaceous earth and mixtures of liquid diluent and combinations thereof. 
     Reagent Deposition 
     Deposition of the powdered reagent(s) mixture onto the dry solid support may be achieved by any suitable large scale printing system using standard factory equipment. For example, letterpress, rotary gravure, screen printing, tampography, wax printing, contact dosing, ultrasonic sputter, and spray and drop on demand printing may be used. In one embodiment, the preferred printing system includes screen printing using fully automated roll to roll, 32-62 mesh, multi-layer, high durability, UV cured screens. The printing system further includes downstream drying, guillotining, vertical/horizontal form fill seal capability, with additional individual strip and pouch numbering. 
     Drying the CR coated solid support may be achieved by any large volume drying process including but not limited to: fan forced heated air, UV or IR cure. 
     During production, representative, live sample, in house, batch testing of printed sheet product. Quarterly, representative, live sample, in house, batch testing of printed strip product, through years 1, 2 and 3 post production. 
     As illustrated in  FIG. 1 , the individual dried encapsulated chemical reagents  2 ,  4  may be printed onto the solid support article  1  separated by a physical space  3  between the individual encapsulated reagent deposition interstices  2 ,  4 , thus preventing chemical interaction and contamination of the reagents  2 ,  4  and maintain selectivity and reactivity for target molecule(s) and ion(s). 
     Packaging 
     In one embodiment of the present invention, the test kit, comprising both the sample collection swab  30  and a printed dry reagent test strip  10 , may be packaged individually in separate, moisture and UV resistant packages  40  ( FIG. 3 ) prior to use. Preferably the package  40  is a tear-open, form, fill, and seal sachet. The sachet  40  may be constructed from commercially available Paper/PET12 um/AL7 um/PE50 product, which is an extremely cheap, mass produced material. Individual pre-wetted sample swabs  30  and individual printed dry reagent test strips  10  be automatically packaged into individual sachets  40  by vertical and/or horizontal form fill seal machines. 
     Each test kit may include a test strip  10  printed with several CR  2 ,  4 , thus achieving broad spectrum detection of CWA and BA. Kit manufacture may utilize various approaches, in order to prevent CR degradation and maintain long term (i.e. several years) CR viability. Without limitation, such approaches may include: direct printing of mixed CR suspension, where reaction between individual CR on a single test strip  10  does not occur; overlay printing of individual CR; individual CR suspensions printed with a physical separation or void  3   FIG. 1 ) between the boundary edge of one dried CR zone  2  and the next dried CR zone  4 . The void  3  between dry CR zones  2 ,  4  on the solid support surface  1  may be a minimum of 1 mm. In addition, the printing of the CR suspension  2 ,  4  to the solid support  1  drying step occurs immediately post print. Finally, the shaped article is packaged within atmospheric, UV and moisture resistant packaging pouches  40 . 
     Use of Kit 
     The kit (test strip  10  and swab  30 , in the sealed package  40 ) may be carried in a pocket, belt case, glove box, brief case, etc. When a suspect residue or object is observed, both the sampling swab  30  and presumptive reagent strip  10  are removed from the sachet packaging  40 . The swab  30  is rubbed into the suspect residue, liquid, gel, solid and/or across suitable surfaces for several seconds, to facilitate the collection of a representative sample of the suspect residue. The swab  30  with the collected sample is then rubbed through the colorimetric reagent test zones  2 ,  4  on the paper strip  1  for several seconds, facilitating a rapid yes/no positive/negative colorimetric indication on the test strip  1  or swab  30  for the presence of target chemical or biological agents. 
     BENEFITS 
     Embodiments of test kits the present invention provide numerous benefits over existing test methods. Among such benefits: 
     The test kits of the present invention replace the need for sample workup and preparation in a laboratory setting as required by TLC analysis and remove the hazardous liquified diazonium salt spray or other hazardous liquid reagents, with a miniature, highly portable, dry stabilized diazonium salt test strip. Sample preparation, laboratory equipment, and numerous sequential steps are not required to perform the test. 
     The test kits of the present invention replace all sophisticated laboratory procedures and equipment, with a single step diazonium salt encapsulation and paper strip laydown methodology. The test kits do not require breakable ampoule packaging, and prevent solvents like DMSO from freezing by the addition of non-hazardous, low cost co-solvent. Further, single test kits are designed for mass manufacture at low cost with a 2 to 3 year shelf life and have a greatly reduced false indication rate. 
     The description of the present invention has been presented for purposes of illustration and description, but is not intended to be exhaustive or limited to the invention in the form disclosed. Many modifications and variations will be apparent to those of ordinary skill in the art. The embodiment was chosen and described in order to best explain the principles of the invention, the practical application, and to enable others of ordinary skill in the art to understand the invention for various embodiments with various modifications as are suited to the particular use contemplated.