Patent Application
20080166792
The present invention relates to the use of capillaries as containers of media that react with ingredients that enter the capillaries by diffusion or by capillary action to form a measurable change such as a change in color, in which the color change is characteristic of a component of the fluid or of a group of materials with common characteristics. These devices, referred to as Capillary Detectors, (CD), can be used individually or as components of a system adapted for detecting one or more materials. Examples of the use of systems of CDs include detection of analytes in food, or contaminants or bacteria in water.
The need to determine quickly if a liquid contains specified materials is faced frequently in many fields. Examples include the detection of analytes or adulterants in drinking water and other fluids, the need to detect biological materials such as proteins or ketones in urine, the need to detect biohazards in water and other fluids, the need to determine if specific fluids contain materials that can affect their properties, such as detecting chromates or chlorides in industrial fluids, and even detecting hydrogen peroxide or acetone in fluids carried by passengers into aircraft. Although many analytical methods are available to address these problems, the available methods are expensive, lengthy, require complex instrumentation which cannot be easily handled by laymen or cannot be adopted to use in the field.
Adulteration of water by terrorists using hazardous biological materials or other analytes, has become a real threat and its implementation a realistic possibility. Threats have been made to poison unsuspecting random people around the world. As such, we can no longer take for granted that the food and/or water we consume are free of artificial poison(s).
Recent discoveries of liquid precursors to explosives in the hands of terrorists seeking to board aircraft has forced yet again another shift in the security procedures carried out in airports, and resulted in profound changes in search procedures used, as well as in the types of materials that passengers are allowed to bring on board.
A very large amount of money and other resources have been invested in developing methods for quick analysis of liquids, however, most of the available methods require very skilled labor, expensive instruments, access or proximity to well-equipped laboratory facilities, etc. Needless to say, the results of many of the available methods are not obtained in real time and thus cannot address contemporaneous needs where having an instantaneous result on site is critical to making a correct informed decision.
The objective of this invention is to describe a general, very low-cost and simple method for determining in real time if specific components are present in a liquid. The material to be detected, the analyte, may be inorganic, organic, biological or even a live microorganism. Examples will be described hereinafter where low cost CDs were constructed and used to determine such materials in solution using the CD.
A useful method for detecting an analyte in solution should be quick, reliable, easily applied, and the results unambiguously understood. In addition, it should be designed so that false negative and false positive errors are eliminated. From a practical point of view, the method and hardware should be relatively low cost, stable and compact, so that they can be widely disseminated to a wide range of users, both private and professional, and be readily available for use anywhere.
Towards that end, the present invention relates to a methodology and systems to rapidly and reliably determine if a fluid such as water contains acutely dangerous amounts of specific analytes, chemicals, biochemicals, biohazards etc., with no additional instrumentation besides the simple hardware supplied to the users.
It is therefore an object of the present invention to describe a generic apparatus for the detection of analytes in liquids.
A further object of the present invention is to describe a generic apparatus for the detection of analytes in liquids that is inexpensive and disposable.
In one implementation, the present invention relates to a calorimetric detection device for sensing the presence and/or the identity of at least one analyte in a liquid sample. Such detection device comprises:
Another implementation of the present invention relates to a method of sensing the presence and identity of at least one analyte in a liquid sample, said method comprising:
Another implementation of the present invention relates to a method of sensing the presence and identity of at least one analyte in a liquid sample, said method comprising:
In another implementation of the present invention relates to a method of sensing the presence and identity of at least one analyte in a liquid sample, wherein each layer of support material may consist of a mixture of several powders bearing different reagents to facilitate parallel or second order reactions to take place while maintaining the stability of the layer and the chemicals it supports.
Other aspects, features and embodiments of the invention will be more fully apparent from the ensuing disclosure and appended claims.
The present invention relates to an apparatus and method of using dry chemical techniques to detect analytes in fluids such as water, food extracts, fuels, industrial liquids and many other fluids. The presence of the desired analyte is indicated when the color of the support layer carrying the chromophore changes from one color to another. Other indicators, such as a change in fluorescence, may be used in special cases. As will be discussed herein, the present invention introduces several innovations to analyte detection including, but not limited to, the use of capillaries both as the sampling means for liquids as well as the containers for dry chemical in various forms to rapidly and simultaneously detect specific or classes of analytes, while eliminating interferences from secondary materials such as food ingredients or other components of the solution carrying matrix, reducing the sample preparation work needed, simplifying the result interpretation and qualitative and quantitative identification of the specific analyte detected.
The detection capillary of the present invention can be used to test for analyte contained in body fluids, e.g. for forensic purposes, environmental samples, industrial water, waster water, fluids from waste dumps, fluids from chemical processing facilities, etc.
It is noted that the porous entrance plug into the capillary may be made from different materials including porous oleophobic materials that deny droplets of oil entry into the capillary. This eliminates the need to use time consuming sample-preparation procedures to remove oils, particles, or in some cases to extract or concentrate the sample and thereby provide for a more rapid test.
As defined herein, “sample” is used generically and includes, without limitation, ingestible substances such as drinking water, ground water, all liquid and/or extractable solid foods, soil, biological samples, etc., process water, such as water from cooling tower, solutions of pharmaceuticals and solutions of intermediates used in making drugs, chemicals etc., bodily fluids such as urine and blood, substances used to cook e.g. oils, substances used to flavor liquid and/or solid foods (e.g., spices and other powders), and the materials in which the solid foods are cooked or washed. It is to be understood that these specific references are not meant to be limiting in any way, but rather to describe the broad scope of applications of this technique.
In most embodiments, the present invention utilizes no electronic instruments, sensors computers, power sources and other ancillary resources and it does not require calibration. In other words, the presence of analyte is detected calorimetrically using visual methods.
A quality assurance procedure (QA) may be built into the test procedure of all the embodiments as a method to reduce the number of false positive determinations and essentially eliminate the number of false negative determinations. This is done by using a second capillary along with the analytical one and using it to test a known liquid.
In another embodiment of the present invention, the use of calorimetric instruments is required to determine the analyte concentration based on the length of the color stain formed in the analyte detection.
In another embodiment of the present invention, a calorimetric instrument is used to trigger a secondary activity such as turning on a pump, opening a pneumatic valve, etc.
Although some of the elements of the chemistries described herein are known in the art, the methodology of their use, as well as the apparatuses in which they are incorporated, are new. The apparatus described herein eliminates or reduces interferences from various components of the carrying liquid matrix. Special verification tests were conducted to validate the applicability of the methodology and apparatus of the present invention to a wide range of various solutions including drinks, foods, cooking materials etc. The apparatus is a flexible system that can be used to detect one analyte or to determine systematically if any analyte, selected from a group of analytes, is present in the carrying solution. Furthermore, the results are unambiguously understood and as such, the methodology may be practiced by a wide range of users including lay people with only minimal training or knowledge of chemistry.
The methodology of the present invention, as described herein, is specifically directed to seven groups of analytes, but may be easily expanded to include other groups of analytes as well. The seven groups of analytes discussed herein are: anionic analytes, cationic analytes, analytes that can be induced to release a characteristic gas, water soluble organic analytes, water insoluble organic analytes in organic media or in suspension, liquid samples containing biological materials such as proteins, ketones, glycerides etc., and liquids containing live bacteria or viruses, etc.
The sensitivities of the methods of the present invention may be adjusted by changing the loadings of the reagents or the chromophores used in the various layers in the capillary detector.
The second technology described herein, i.e., screening tests, is used to detect or respond to multiple materials or analytes in a single test. Preferably, the apparatus of the present invention includes a chromophore, which changes to a unique color upon exposure to a unique analyte. It is also contemplated herein that the present methodology and process may include a screening reagent that changes to the same or to different colors upon contact with different materials or analytes.
For example, it is well known in the art that many metal cations react with the sulfide ion and form a colored compound. This is used in a generic test for the presence of metal cations. The color formed can sometimes provide presumptive identification of the specific metallic cation. These chemistries have been used in numerous qualitative analytical methodologies, however, heretofore have not been implemented in a dry chemical format for screening purposes.
The third technology described herein, i.e., validation of a positive result, is performed using dry chemical tabs including the screening reagent wherein the screening reagent responds specifically to the presence of a specific target analyte by changing colors. Embodiments of these chemistries have been described previously by Fiegl et. al. (“Spot Tests in Inorganic Analysis,” Elsevier Pub. Comp., Amsterdam, (1972)), Feigl F. (“Spot Tests in Organic Analysis,” Elsevier Pub. Comp., Amsterdam, (1956)), Junreis, E. (“Spot Tests Analysis,” John Wiley and Sons, New York, (1985)), and Badcock, N. R. (“Detection of analyteing by Substances other than Drugs: A Neglected Art”, Am. Clin. Biochem., 37, 146-157, (2000)) using spot test plates or impregnated papers. Such tests utilize liquid reagents and often require that the reagents be freshly prepared right before use and/or require special pretreatment conditions or heating. In contrast, the validation capillary detectors of the present invention eliminate the need for heating as well as the need to freshly prepare detection reagents.
Another novel technology is described herein, i.e., the option to include quality assurance (QA), to ensure that the detection capillary has operated properly, the chromophore is still effectively viable, and that no false negative or false positive occurred during the testing for analytes. The QA methodology has been designed to be fast and simple, so that the accurate testing of the samples for analytes can be completed in a relatively very short time. The QA process includes the addition of a second detection capillary and a known amount of analyte-containing pocket to the second capillary to validate the sensitivity of the screening reagent and thus effectively verify the validation process.
One embodiment of the present invention corresponds to a calorimetric detection capillary, in which the detection capillary includes a support layer having an amount of a chromophoric material in or on a porous support material. The chromophore may be dispersed on or in such support layer as micro- or nanoparticles, embedded or impregnated in a thin polymeric film deposited on the surface of the solid support. The chromophoric material is selected so that it reacts with the target analyte(s) to form a visible color change. The color change may be unique to the target analyte or to a group of analytes.
The chromophores of the present invention may include a species selected from the group consisting of molybdates, phosphomolybdates, tungstates, phosphotungstates, iron salts such as sulfates, metallic sulfides such as zinc, calcium, barium, aluminum or strontium sulfides, organic materials such as 8-hydroxy-quinoline and its derivatives, 1-(2-pyidylazo)-2-napthol (PAN) and related compounds that include azo derivatives of heterocyclic compounds, rubeanic acid, diethyldithiocarbamate, dithizone, zincon, diphenylcarbazone, diphenylcarbazide (DPC) rhodizonic acid and its salts, titan yellow, cadion, functionalized diazonium salts including arsenic and phosphonic diazonium salts, triphenylmethane and xanthenes and other materials used in the spectrometric, fluorometric or colorimetric determination of species. Preferably, the chromophore includes a mixture of iron (II) and iron (III) sulfate compounds. The chromophoric mixture optionally includes acids, bases, preservatives, reactants, oxidizing agents, reducing agents, chelating agents, buffers, stabilizers, etc. The chromophore used herein for illustration purposes is a mixture of iron sulfates to detect cyanides, azides and sulfides.
The support layer within the detection capillary may be as simple as paper pulp or shredded blotter paper or as sophisticated as microparticles of activated silica or alumina on a polymeric support wherein the chromophore is on or in the microparticulate material. Other support layers include, but are not limited to polymeric or glass beads, porous membranes, layered fibers and metallic films
The support layer may be chemically inert or it may be capable of assisting the reaction in some way. For example, the support layer may be acidic or basic. Other materials such as buffers, stabilizers or chelating agents may be incorporated within the chromophoric layer to facilitate the chromophoric reaction, prevent interferences, extend the shelf life of the chromophore, and increase its photostability. Importantly, the support layer must ensure maintenance of the chromophores on or in the support layer, must be physically and chemically capable of withstanding exposure to a variety of liquids, and must be non-reactive towards the chromophore and other ingredients in the chromophoric formulation. Optionally, the support layer may be liquid permeable.
Referring to
Written information identifying and/or quantifying the analyte and any other useful information may be printed on a paper onto which the capillary is glued, to assist in interpreting the results and comparing colors.
In another embodiment of the present invention is shown in
In yet another embodiment of the present invention, the chromophore is deposited on or in one solid support and a second reagent is deposited on a second solid support and the two solid supports are mixed together at a controlled ratio to form a single layer that can react with the analyte to form color. The reagent in the second support layer can help filter out solids and other interfering materials, to host conditioning materials such as pH buffers, materials that remove selectively interfering materials, etc.
Referring to
As previously introduced, the detection capillary may include written information instructing the user if and/or how much analyte is present, when necessary. Referring to
As previously introduced, the detection capillary may include written information instructing the user if and/or how much analyte is present, when necessary. In cases where various analytes form different colors with the same chromophore, the specific identity of the analyte may presumably be deduced by comparing the color to a color chart placed behind the capillary near the location where the color is expected to be formed. Examples of such capillaries include detection capillary for cyanides, azides and sulfides. The iron-based chromophore used in some of our examples forms blue, red and black colors with cyanides, azides and sulfides, respectively.
In yet another embodiment, the capillaries of the present invention may be sealed following manufacture. The end of the capillary may be notched to facilitate breaking it right before use by a simple bending operation.
The detection capillary is preferably sealed in an envelope that can be readily opened by the user with no tools. For example, the envelope may comprise metallic foil and/or polymeric film (e.g., polyethylene, polypropylene, polyester, etc.), said envelope including marks and/or labels instructing the user on how to open said envelope.
Another embodiment of the present invention is a kit comprising of many detection capillaries for various analytes which may be present in the same sample. The capillaries may be used individually in a sequence or placed in a single holder and dipped simultaneously in the liquid.
Another embodiment of the present invention is a kit comprising the detection capillary apparatus and instructions on how to use said apparatus to identify and/or quantify the analyte in a liquid sample. Optional components of said kit may include any or all of the following components as well as other components designed to facilitate the preparation of the sample or the analytical test. These components are a hand-held or small-sized instrumental calorimetric detector, a color chart for identification and/or quantification of the analyte(s), at least one known sample for the quality assurance process, and extraction reagents and instructions relating to the extraction of analyte(s) from some solid samples.
The features and advantages of the present invention are more fully shown by the following non-limiting examples.
Chromophore Formulation.
Dissolve 0.25 grams NH4Fe(SO4)2.12H2O in 5 ml water and add to it 3 grams of silica gel with particle size 63-200μ, nominal BET surface area 300 m2/gm. Dry the powder at 150° C. for 30 minutes.
Assembly of Azide Capillary.
1. Take a capillary 100 mm long and 1 mm ID, 1.5 mm OD.
2. Push a small piece of cotton approximately ½ inch into a capillary tube.
3. Fill the capillary to the top with the chromophore.
4. Compact the particles by tapping the capillary 5 times.
5. Plug the inlet of the capillary with another small piece of cotton.
Testing for Azide/Sulfide in Water.
Submerge the opening of the capillary in the water sample for 1-2 seconds and look on the color. Red color indicates the presence of azides and black color indicates the presence of sulfide. The colors form practically instantly.
Chromophore Formulation.
This detection capillary uses two porous support layers, one carrying an activation agent, denoted Mixture A, and the other a chromophore, denoted Mixture B.
Mixture A.
Dissolve 0.1 grams CuSO4 in 5 ml water and add to it 3 grams of silica gel with particle size 63-200μ, nominal BET surface area 300 m2/gm. Dry the powder at 150° C. for 30 minutes.
Mixture B.
Dissolve 5 milligrams tetra methyl benzidine, (TMB), in 5 ml 91% IPA and add to it 3 grams of silica gel with particle size 63-200μ, nominal BET surface area 300 m2/gm. Dry the powder at 150° C. for 5 minutes.
Assembly of Cyanide/Chromate Capillary.
1. Take a capillary 100 mm long and 1 mm ID, 1.5 mm OD.
2. Push a cotton plug approximately ½ inch into a capillary tube.
3. Pack ¼ of an inch of the open volume with Mixture B.
4. Insert a second cotton plug on top of the silica gel
5. Fill the capillary to the top with Mixture A.
6. Compact the particles by tapping the capillary 5 times.
7. Plug the top of the capillary with a small piece of cotton.
Testing for Cyanide/Chromates in Water.
Dip the opening of the capillary in the water sample for 1-3 seconds and look on the color. Blue color indicates the presence of cyanide and blue-violet color indicates the presence of chromates. The colors form practically instantly.
Chromophore Formulation.
This detection capillary uses two porous support layers, one carrying an activation agent, denoted Mixture A, and the other a chromophore, denoted Mixture B.
Mixture A.
Dissolve 1 gram Na2CO3 in 5 ml water and add to it 3 grams of silica gel with particle size 63-200μ, nominal BET surface area 300 m2/gm. Dry the powder at 150° C. for 30 minutes.
Mixture B.
Dissolve 0.2 grams manganese sulfate in 5 ml water and add to it 3 grams of silica gel with particle size 63-200μ, nominal BET surface area 300 m2/gm. Dry the powder at 150° C. for 30 minutes.
Assembly of the Peroxides Detection Capillary.
1. Take a capillary 100 mm long and 1 mm ID, 1.5 mm OD.
2. Push a cotton plug approximately ½ inch into a capillary tube.
8. Pack ¼ of an inch of the open volume with Mixture B.
9. Insert a second cotton plug on top of the silica gel
10. Fill the capillary to the top with Mixture A.
11. Compact the particles by tapping the capillary 5 times.
12. Plug the top of the capillary with a small piece of cotton.
Testing for Peroxides in Water.
Dip the opening of the capillary in the water sample for 1-3 seconds and look on the color. Black-Brown color indicates the presence of peroxides. The colors form practically instantly.
Chromophore Formulation.
This detection capillary uses two porous support layers, one carrying an activation agent, denoted Mixture A, and the other a chromophore, denoted Mixture B.
Mixture A.
Dissolve 10 milligram 1-(2-pyrdylazo)-2-naphthol in 5 ml acetone and add to it 3 grams of silica gel with particle size 63-200μ, nominal BET surface area 300 m2/gm. Dry the powder at 150° C. for 5 minutes.
Mixture B.
Dissolve 0.5 grams zinc chloride in 5 ml water and add to it 3 grams of silica gel with particle size 63-200μ, nominal BET surface area 300 m2/gm. Dry the powder at 150° C. for 30 minutes.
Assembly of the Flammables Detection Capillary.
1. Take a capillary 100 mm long and 1 mm ID, 1.5 mm OD.
2. Push a cotton plug approximately ½ inch into a capillary tube.
3. Pack ¼ of an inch of the open volume with Mixture B.
4. Insert a second cotton plug on top of the silica gel
5. Fill the capillary to the top with Mixture A.
6. Compact the particles by tapping the capillary 5 times.
7. Plug the top of the capillary with a small piece of cotton.
Testing for Peroxides in Water.
Dip the opening of the capillary in the water sample for 1-3 seconds and look on the color. Red color indicates the presence of peroxides. The colors form practically instantly. Typically, materials like acetone or iso-propanol will form a large diffused zone of color while hydrocarbons such as hexane or octane will form an intense red line.
Chromophore Formulation.
This detection capillary uses three porous support layers, one carrying an activation agent, denoted Mixture A, a reactive layer, denoted Mixture B, and a chromophore, denoted Mixture C.
Mixture A.
Dissolve 2 gram citric acid in 5 ml water and add to it 3 grams of silica gel with particle size 63-200μ, nominal BET surface area 300 m2/gm. Dry the powder at 150° C. for 30 minutes.
Mixture B.
Mix 1 grams of zinc dust <10 microns with 3 grams of silica gel with particle size 63-200μ, nominal BET surface area 300 m2/gm.
Mixture C.
Dissolve 0.2 grams sodium bromide and 0.2 grams mercuric bromide in 5 ml water and add to it 3 grams of silica gel with particle size 63-200μ, nominal BET surface area 300 m2/gm. Dry the powder at 150° C. for 30 minutes.
Assembly of the Arsenic/Antimony/Germanium Detection Capillary.
1. Take a capillary 100 mm long and 1 mm ID, 1.5 mm OD.
2. Push a cotton plug approximately ¾ inch into a capillary tube.
3. Pack ¼ of an inch of the open volume with Mixture C.
4. Insert a second cotton plug on top of the silica gel.
5. Pack ¼ of an inch of the remaining volume with Mixture B.
6. Insert a third cotton plug on top of the silica gel
7. Pack the remaining volume with Mixture A.
8. Compact the particles by tapping the capillary 5 times.
9. Plug the top of the capillary with a small piece of cotton.
Testing for Arsenic/Antimony/Germanium in Water.
Dip the opening of the capillary in the water sample for no more than 1-3 seconds and look on the color. Yellow, brown or black color in the end of the capillary indicates the presence of arsenic, antimony or germanium. The colors form in 12 to 30 seconds.
The chemicals and assembly of this detector is the same as that described in Example 5 but a strip of paper is attached to the capillary with gradations which show the length of the brown stain formed. The length of this stain is related to the amounts of Arsenic, Antimony or Germanium Compounds in the sample.
While the invention has been described herein in reference to specific aspects, features and illustrative embodiments of the invention, it will be appreciated that the utility of the invention is not thus limited, but rather extends to and encompasses numerous other variations, modifications and alternative embodiments, as will suggest themselves to those of ordinary skill in the field of the present invention, based on the disclosure herein. Correspondingly, the invention as hereinafter claimed is intended to be broadly construed and interpreted, as including all such variations, modifications and alternative embodiments, within its spirit and scope.
