US20030166298A1 - Colorimetric artificial nose having an array of dyes and method for artificial olfaction - Google Patents

Colorimetric artificial nose having an array of dyes and method for artificial olfaction Download PDF

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US20030166298A1
US20030166298A1 US10/279,701 US27970102A US2003166298A1 US 20030166298 A1 US20030166298 A1 US 20030166298A1 US 27970102 A US27970102 A US 27970102A US 2003166298 A1 US2003166298 A1 US 2003166298A1
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Kenneth Suslick
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University of Illinois
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N31/00Investigating or analysing non-biological materials by the use of the chemical methods specified in the subgroup; Apparatus specially adapted for such methods
    • G01N31/22Investigating or analysing non-biological materials by the use of the chemical methods specified in the subgroup; Apparatus specially adapted for such methods using chemical indicators
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/27Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands using photo-electric detection ; circuits for computing concentration
    • G01N21/272Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands using photo-electric detection ; circuits for computing concentration for following a reaction, e.g. for determining photometrically a reaction rate (photometric cinetic analysis)
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/75Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/77Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
    • G01N21/78Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator producing a change of colour

Definitions

  • the present invention relates to methods and apparatus for artificial olfaction, e.g., artificial noses, for the detection of odorants by a visual display.
  • artificial olfaction e.g., artificial noses
  • artificial noses olfactory or vapor-selective detectors
  • Artificial noses that can detect many different chemicals are desirable for personal dosimeters in order to detect the type and amount of odorants exposed to a human, the presence of chemical poisons or toxins, the spoilage in foods, the presence of flavorings, or the presence of vapor emitting items, such as plant materials, fruits and vegetables, e.g., at customs portals.
  • Vapor-selective detectors or “artificial noses” are typically based upon the production of an interpretable signal or display upon exposure to a vapor emitting substance or odorant (hereinafter sometimes referred to as an “analyte”). More specifically, typical artificial noses are based upon selective chemical binding or an interface between a detecting compound of the artificial nose and an analyte or odorant, and then transforming that chemical binding into a signal or display, i.e., signal transduction.
  • Polymer arrays having a single dye have been used for artificial noses. That is, a series of chemically-diverse polymers or polymer blends are chosen so that their composite response distinguishes a given odorant or analyte from others.
  • Examples of polymer array vapor detectors including conductive polymer and conductive polymer/carbon black composites, are discussed in: M. S. Freund, N. S. Lewis, Proc. Natl. Acad. Sci. U.S. Pat. No. 92,2652-2656 (1995); B. J. Doleman, R. D. Sanner, E. J. Severin, R. H. Grubbs, N. S. Lewis, Anal. Chem. 70, 2560-2564 (1998); T.
  • interface materials include functionalized self-assembled monolayers (SAM), metal oxides, and dendrimers.
  • SAM functionalized self-assembled monolayers
  • SAW surface acoustic wave
  • Optical transducers (based on absorbance or luminescence) have also been examined. Examples of metal oxide, SAM, and dendrimer-based detectors are discussed in J. W. Gardner, H. V. Shurmer, P. Corcoran, Sensors and Actuators B 4, 117-121 (1991); J. W. Gardner, H. V. Shurmer, T. T. Tan, Sensors and Actuators B 6, 71-75 (1992); and R. M. Crooks, A. J. Ricco, Acc. Chem. Res. 31, 219-227 (1998). These devices also use a single dye.
  • the present invention comprises an array of dyes including at least a first dye and a second dye which in combination provide a spectral response distinct to an analyte or odorant.
  • the dyes of the present invention produce a response in the spectrum range of about 200 nanometers to 2,000 nanometers, which includes the visible spectrum of light. It has now been discovered that an array of two or more dyes responds to a given ligating species with a unique color pattern spectrally and in a time dependent manner. Thus, dyes in the array of the present invention are capable of changing color in a distinct manner when exposed to any one analyte or odorant.
  • the pattern of colors manifested by the multiple dyes is indicative of a specific or given analyte. In other words, the pattern of dye colors observed is indicative of a particular vapor or liquid species.
  • the dyes of the array are porphyrins.
  • the porphyrin dyes are metalloporphyrins.
  • the array will comprise ten to fifteen distinct metalloporphyrins in combination.
  • Metalloporphyrins are preferable dyes in the present invention because they can coordinate metal-ligating vapors through open axial coordination sites, and they produce large spectral shifts upon binding of or interaction with metal-ligating vapors.
  • porphyrins, metalloporphyrins, and many dyes show significant color changes upon changes in the polarity of their environment; this so-called solvatochromic effect will give net color changes even in the absence of direct bonding between the vapor molecules and the metal ions.
  • metalloporphyrins produce intense and distinctive changes in coloration upon ligand binding with metal ligating vapors.
  • the present invention provides a means for the detection or differentiation and quantitative measurement of a wide range of ligand vapors, such as amines, alcohols, and thiols. Further, the color data obtained using the arrays of the present innovation may be used to give a qualitative fingerprint of an analyte, or may be quantitatively analyzed to allow for automated pattern recognition and/or determination of analyte concentration. Because porphyrins also exhibit wavelength and intensity changes in their absorption bands with varying solvent polarity, weakly ligating vapors (e.g., arenes, halocarbons, or ketones) are also differentiable.
  • weakly ligating vapors e.g., arenes, halocarbons, or ketones
  • the parent porphyrin is also referred to as a free base (“FB”) porphyrin, which has two central nitrogen atoms protonated (i.e., hydrogen cations bonded to two of the central pyrrole nitrogen atoms).
  • FB free base
  • a preferred parent porphyrin is depicted in FIG. 2A, with the substitution of a two hydrogen ion for the metal ion (depicted as “M”) in the center of the porphyrin.
  • TTP stands for 5,10,1 5,20-tetraphenylporphyrinate(-2).
  • colorimetric difference maps can be generated by subtracting unexposed and exposed metalloporphyrin array images (obtained, for example, with a common flatbed scanner or inexpensive video or charge coupled device (“CCD”) detector) with image analysis software.
  • CCD charge coupled device
  • the present invention provides unique color change signatures for the analytes, for both qualitative recognition and quantitative analysis.
  • Sensor plates which incorporate vapor sensitive combinations of dyes comprise an embodiment of the present invention which is economical, disposable, and can be utilized to provide qualitative and/or quantitative identification of an analyte.
  • a catalog of arrays and the resultant visual pattern for each analyte can be coded and placed in a look-up table or book for future reference.
  • the present invention includes a method of detecting an analyte comprising the steps of forming an array of at least a first dye and a second dye, subjecting the array to an analyte, inspecting the first and second dyes for a spectral response, and comparing the spectral response with a catalog of analyte spectral responses to identify the analyte.
  • sensing is based upon either covalent interaction (i.e., ligation) or non-covalent solvation interactions between the analyte and the porphyrin array, a broad spectrum of chemical species is differentiable. While long response times (e.g., about 45 minutes) are observed at low analyte concentrations of about 1 ppm with reverse phase silica gel plates, use of impermeable solid supports (such as polymer- or glass-based micro-array plates) substantially increases the low-level response to less than 5 minutes.
  • an object of the present invention to provide methods and devices for artificial olfaction, vapor-selective detectors or artificial noses for a wide variety of applications. It is another object of the present invention to provide methods of detection and artificial noses that can detect low levels of odorants and/or where odorants may be harmful to living human, animal or plant cells. It is also an object of the present invention to provide methods of olfactory detection and artificial noses that can detect and quantify many different chemicals for dosimeters that can detect chemical poisons or toxins, that can detect spoilage in foods, that can detect flavorings and additives, and that can detect plant materials, e.g., fruits and vegetables.
  • Another object of the present invention is to provide for the detection of analytes using data analysis/pattern recognition techniques, including automated techniques.
  • Another object of the invention is to provide an artificial nose comprising an array, the array comprising at least a first dye and a second dye deposited directly onto a single support in a predetermined pattern combination, the combination of the dyes in the array having a distinct and direct spectral absorbance or reflectance response to an analyte wherein the first dye and the second are selected from the group of dyes consisting of chemoresponsive dyes, and the second dye is distinct from the first dye.
  • the first dye is selected from the group consisting of porphyrin, chlorin, chlorophyll, phtahlocyanine, and salen and their metal complexes.
  • the second dye is selected from the group consisting of acid-base indicator dyes and solvatochromic dyes.
  • Another object of the invention is to provide a method of detecting an analyte comprising the steps of: (a) forming an array of at least a first dye and a second dye deposited directly onto a single support in a predetermined pattern combination, the combination of the dyes in the array having a distinct and direct spectral absorbance or reflectance response to an analyte wherein the first dye and the second dye are selected from the group consisting of chemoresponsive dyes, and the second dye is distinct from the first dye, (b) subjecting the array to an analyte, (c) inspecting the array for a distinct and direct spectral absorbance or reflectance response, and (d) correlating the distinct and direct spectral response to the presence of the analyte.
  • the first dye is selected from the group consisting of porphyrin, chlorin, chlorophyll, phtahlocyanine, and salen and their metal complexes.
  • the second dye is selected from the group consisting of acid-base indicator dyes and solvatochromic dyes.
  • Another object of the invention is to provide an artificial tongue comprising an array, the array comprising at least a first dye and a second dye deposited directly onto a single support in a predetermined pattern combination, the combination of the dyes in the array having a distinct and direct spectral absorbance or reflectance response to an analyte wherein the first dye and the second are selected from the group of dyes consisting of chemoresponsive dyes, and the second dye is distinct from the first dye.
  • the first dye is selected from the group consisting of porphyrin, chlorin, chlorophyll, phtahlocyanine, and salen and their metal complexes.
  • the second dye is selected from the group consisting of acid-base indicator dyes and solvatochromic dyes.
  • Another object of the invention is to provide an artificial nose comprising an array, the array comprising at least a first dye and a second dye deposited directly onto a single support in a predetermined pattern combination, the combination of dyes in the array having a distinct and direct spectral absorbance or reflectance response to distinct analytes comprising one or more parent analytes or their derivatives, and an oxidizing source to partially oxidize at lest one distinct parent analyte to at least one corresponding derivative analyte of said parent analyte, the array at least in part having a stronger distinct and direct absorbance or reflectance response to the derivative analyte than to the corresponding parent analyte
  • FIG. 1 illustrates an embodiment of the optical sensing plate of the present invention using a first elution in the y axis and a second elution in the x axis of the plate.
  • the first elution R-OH/hexane and the second elution is R-SH/hexane.
  • FIG. 2A illustrates an embodiment of the invention using metalloporphyrins as the sensing dyes.
  • FIG. 2B illustrates an embodiment of the invention using metalloporphyrins as the sensing dyes.
  • FIG. 3A illustrates a vapor exposure apparatus for demonstration of the present invention.
  • FIG. 3B illustrates a vapor exposure apparatus for demonstration of the present invention.
  • FIG. 4 illustrates the color change profile in a metalloporphyrin array of FIG. 2 when used in the vapor exposure apparatus of FIG. 3A to detect n-butylamine. Metalloporphyrins were immobilized on reverse phase silica gel plates.
  • FIG. 5 illustrates a comparison of color changes at saturation for a wide range of analytes.
  • Each analyte was delivered to the array as a nitrogen stream saturated with the analyte vapor at 20° C.
  • DMF stands for dimethylformamide
  • THF stands for tetrahydrofuran.
  • FIG. 6 illustrates two component saturation responses of mixtures of 2-methylpyridine and trimethylphosphite. Vapor mixtures were obtained by mixing two analyte-saturated N 2 streams at variable flow ratios.
  • FIG. 7 illustrates a comparison of Zn(TPP) spectral shifts upon exposure to ethanol and pyridine (py) in methylene chloride solution (A) and on the reverse phase support (B).
  • FIG. 8 illustrates another embodiment of the present invention, and more particularly, an small array comprising microwells built into a wearable detector which also contains a portable light source and a light detector, such as a charge-coupled device (CCD) or photodiode array.
  • a wearable detector which also contains a portable light source and a light detector, such as a charge-coupled device (CCD) or photodiode array.
  • CCD charge-coupled device
  • FIG. 9 illustrates another embodiment of the present invention, and more particularly, a microwell porphyrin array wellplate constructed from polydimethylsiloxane (PDMS).
  • PDMS polydimethylsiloxane
  • FIG. 10 illustrates another embodiment of the present invention, and more particularly, a microplate containing machined teflon posts, upon which the porphyrin array is immobilized in a polymer matrix (polystyrene/dibutylphthalate).
  • a polymer matrix polystyrene/dibutylphthalate
  • FIG. 11 illustrates another embodiment of the present invention, showing a microplate of the type shown in FIG. 10, consisting of a minimized array of four metalloporphyrins, showing the color profile changes for n-octylamine, dodecanethiol, and tri-n-butylphosphine, each at 1.8 ppm.
  • FIG. 12 illustrates the immunity of the present invention to interference from water vapor.
  • FIG. 13 illustrates the synthesis of siloxyl-substituted bis-pocket porphyrins in accordance with the present invention.
  • FIGS. 14 a , 14 b , and 14 c illustrate differences in K eq for various porphyrins.
  • FIG. 15 illustrates molecular models of Zn(Si 6 PP) (left column) and Zn(Si 8 PP) (right column).
  • FIG. 16 illustrates an array containing illustrative examples of porphyrin, metalloporphyrin, acid-base indicator, and solvatochromatic dyes.
  • FIG. 17 illustrates the response of the array described in FIG. 16 to acid vapors, specifically formic acid, acetic acid, iso-valeric acid, and 3-methyl-2-hexenoic acid.
  • FIG. 18 illustrates a preferred array containing illustrative examples of porphyrin, metalloporphyrin, acid-base indicator, and solvatochromatic dyes.
  • FIG. 19 illustrates the response of the array described in FIG. 18 to acetone.
  • FIG. 20 illustrates a vapor exposure apparatus shown in FIG. 3B, further having a partial oxidation cartridge to provide increased sensitivity to analytes.
  • FIG. 1 A sensor plate 10 fabricated in accordance with the present invention is shown in FIG. 1.
  • Sensor plate 10 comprises a two-dimensionally spatially resolved array 12 of various sensing elements or dyes 14 capable of changing color upon interaction (e.g., binding, pi-pi complexation, or polarity induced shifts in color).
  • a library of such dyes 14 can be given spatial resolution by two-dimensional chromatography or by direct deposition, including, but not limited to, ink-jet printing, micropipette spotting, screen printing, or stamping.
  • metalloporphyrin mixture 6 is placed at origin 7 .
  • Sensor plate 10 can be made from any suitable material or materials, including but not limited to, chromatography plates, paper, filter papers, porous membranes, or properly machined polymers, glasses, or metals.
  • FIG. 1 also illustrates an embodiment of the optical sensing plate of the present invention using a first elution 8 in the y axis and a second elution 9 in the x axis of sensor plate 10 .
  • the first elution 8 is R—OH/hexane
  • the second elution 9 is R—SH/hexane.
  • the order of the first and second elutions can be reversed.
  • the first and second elutions are used to spatially resolve the metalloporphyrin mixture 6 in silica gel 5 . As shown in FIG.
  • the upper left hand quadrant 3 is characterized by metalloporphyrins that are “hard” selective, i.e., having a metal center having a high chemical hardness, i.e., a high charge density.
  • the lower right hand quadrant 2 is characterized by metalloporphyrins that are “soft” selective, i.e., having a metal center having a low chemical hardness, i.e., a low charge density.
  • the array can be a spatially resolved collection of dyes, and more particularly a spatially resolved combinatorial family of dyes.
  • a porphyrin-metalloporphyrin sensor plate was prepared and then used to detect various odorants. More specifically, solutions of various metalated tetraphenylporphyrins in either methylene chloride or chlorobenzene were spotted in 1 ⁇ L aliquots onto two carbon (“C2”, i.e, ethyl-capped) reverse phase silica thin layer chromatography plates (Product No. 4809-800, by Whatman, Inc., Clifton, N.J.) to yield the sensor array 16 seen in FIG. 2B. As shown in FIG. 2B and summarized in Table 1 below, the dyes have the following colors (the exact colors depend, among other things, upon scanner settings).
  • FIG. 2A A metalloporphyrin 15 , sometimes referred to as M(TPP), of the present invention is depicted in FIG. 2A.
  • FIG. 2A also depicts various metals of the metalloporphyrins 15 of the present invention, and corresponding metal ion charge to radius ratio (i.e., Z/r Ratio) in reciprocal angstroms.
  • the Z/r Ratio should preferably span a wide range in order to target a wide range of metal ligating analytes.
  • These metalloporphyrins have excellent chemical stability on the solid support and most have well-studied solution ligation chemistry.
  • Reverse phase silica was chosen as a non-interacting dispersion medium for the metalloporphyrin array 16 depicted in FIG.
  • FIG. 3A illustrates a vapor exposure apparatus 19 of the present invention.
  • FIG. 3B illustrates top and side views of bottom piece 21 and a top view of top piece 21 ′ of a vapor exposure flow cell 20 of the present invention.
  • each sensor plate 18 was placed inside of a stainless steel flow cell 20 equipped with a quartz window 22 as shown in FIGS. 3A and 3B. Scanning of the sensor plate 18 was done on a commercially available flatbed scanner 24 (Hewlett Packard Scanjet 3c) at 200 dpi resolution, in full color mode. Following an initial scan, a control run with a first pure nitrogen flow stream 26 was performed.
  • Hewlett Packard Scanjet 3c Hewlett Packard Scanjet 3c
  • the array 16 of plate 18 was then exposed to a second nitrogen flow stream 28 saturated with a liquid analyte 30 of interest.
  • the nitrogen flow stream 28 saturated with liquid analyte 30 results in a saturated vapor 32 .
  • Saturated vapor 32 , containing the analyte 30 of interest were generated by flowing nitrogen flow stream 28 at 0.47 L/min. through the neat liquid analyte 30 in a water-jacketed, glass fritted bubbler 34 . Vapor pressures were controlled by regulating the bubbler 34 temperature.
  • vapor channels 23 permit vapor flow to sensor plate 18 .
  • RGB red, green and blue
  • the system has parallels the mammalian olfactory system.
  • the dyes have the following colors in scans 42 , 44 , and 46 .
  • TABLE 2 (Summarizing Colors of Dyes in FIG. 4, Scans 42, 44, and 46) Sn 4+ - No Change Co 3+ - Green Cr 3+ - Green Mn 3+ - No Change Fe 3+ - Red Co 2+ - Faint Green Cu 2+ - No Change Ru 2+ - No Change Zn 2+ - Light Green Ag 2+ - No Change 2H + (Free Base “FB”) — Light Blue
  • porphyrins have been shown to exhibit wavelength and intensity changes in their absorption bands with varying solvent polarity, it is contemplated that the methods and apparatus of the present invention can be used to calorimetrically distinguish among a series of weakly ligating solvent vapors (e.g., arenes, halocarbons, or ketones), as shown for example in FIG. 5.
  • weakly ligating solvent vapors e.g., arenes, halocarbons, or ketones
  • FIG. 5 A comparison of color changes at saturation for a wide range of analytes is shown in FIG. 5. Each analyte is identified under the colored array 16 that identifies each analyte. ). DMF stands for the analyte dimethylformamide, and THF stands for the analyte tetrahydrofuran. As shown in FIG. 5 and summarized in Table 4 below, the colors of each dye in response to a particular analyte are as follows.
  • the degree of ligand softness increases from left to right, top to bottom as shown in FIG. 1.
  • Each analyte is easily distinguished from the others, and there are family resemblances among chemically similar species (e.g., pyridine and n-hexylamine). Analyte distinction originates both in the metal-specific ligation affinities and in their specific, unique color changes upon ligation.
  • Each analyte was delivered to the array as a nitrogen stream saturated with the analyte vapor at 20° C. (to ensure complete saturation, 30 min. exposures to vapor were used. Although these fingerprints were obtained by exposure to saturated vapors (thousands of ppm), unique patterns can be identified at much lower concentrations.
  • the metalloporphyrin array 16 has been used to quantify single analytes and to identify vapor mixtures. Because the images' color channel data (i.e., RGB values) vary linearly with porphyrin concentration, we were able to quantify single porphyrin responses to different analytes. Color channel data were collected for individual spots and plotted, for example, as the quantity (R plt ⁇ R spt )/(R plt ), where R plt was the red channel value for the initial silica surface and R spt the average value for the spot. For example, Fe(TFPP)(Cl) responded linearly to octylamine between 0 and 1.5 ppm. Other porphyrins showed linear response ranges that varied with ligand affinity (i.e., equilibrium constant).
  • the array of the present invention has demonstrated interpretable and reversible responses even to analyte mixtures of strong ligands, such as pyridines and phosphites, as is shown in FIG. 6. Color change patterns for the mixtures are distinct from either of the neat vapors. Good reversibility was demonstrated for this analyte pair as the vapor mixtures were cycled between the neat analyte extremes, as shown in FIG. 6, which shows the two component saturation responses to mixtures of 2-methylpyridine (“2MEPY”) and trimethylphosphite (“TMP”). Vapor mixtures were obtained by mixing the analyte-saturated N 2 streams at variable flow ratios.
  • strong ligands such as pyridines and phosphites
  • a single plate was first exposed to pure trimethylphosphite vapor in N 2 (Scan A), followed by increasing mole fractions of 2-methylpyridine up to pure 2-methylpyridine vapor (Scan C), followed by decreasing mole fractions of 2-methylpyridine back to pure trimethylphosphite vapor.
  • Response curves for the individual porphyrins allow for quantification of the mixture composition.
  • FIG. 7 shows a comparison of Zn(TPP) spectral shifts upon exposure to ethanol and pyridine (py) in methylene chloride solution (A) and on the reverse phase support (B).
  • the bands correspond, from left to right, to Zn(TPP), Zn(TPP)(C 2 H 5 OH), and Zn(TPP)(py), respectively.
  • Solution spectra (A) were collected using a Hitachi U-3300 spectrophotometer; Zn(TPP), C 2 H 5 OH, and py concentrations were approximately 2 ⁇ M, 170 mM, and 200 ⁇ M, respectively.
  • Diffuse reflectance spectra (B) were obtained with an integrating sphere attachment before exposure to analytes, after exposure to ethanol vapor in N 2 , and after exposure to pyridine vapor in N 2 for 30 min. each using the flow cell.
  • the present invention contemplates miniaturization of the array using small wells 60 ( ⁇ 1 mm), for example in glass, quartz, or polymers, to hold metalloporphyrin or other dyes as thin films, which are deposited as a solution, by liquid droplet dispersion (e.g., airbrush or inkjet), or deposited as a solution of polymer with metalloporphyrin.
  • small wells 60 ⁇ 1 mm
  • liquid droplet dispersion e.g., airbrush or inkjet
  • FIGS. 8, 9, and 10 These embodiments are depicted in FIGS. 8, 9, and 10 .
  • FIG. 8 illustrates the interfacing of a microplate 60 into an assembly consisting of a CCD 70 , a microplate 72 and a light source 74 .
  • FIG. 9 illustrates another embodiment of the present invention, and more particularly, a microwell porphyrin array weliplate 80 constructed from polydimethylsiloxane (PDMS).
  • PDMS polydimethylsiloxane
  • FIG. 10 demonstrates deposition of metalloporphyrin/polymer (polystyrene/dibutylphthalate) solutions upon a plate, which includes a series of micro-machined Teflon® posts 100 having the same basic position relative to each other as shown in FIG. 2A and FIG. 2B.
  • the colors for the dyes in the middle of FIG. 10 are summarized in Table 7 below. TABLE 7 Sn 4+ - Yellow Co 3+ - Orange Cr 3+ - Yellow Mn 3+ - Yellow Fe 3+ - Orange Co 2+ - Orange Cu 2+ - Orange Ru 2+ - Dark Yellow Zn 2+ - Orange Ag 2+ - Orange 2H + (Free Base “FB”) — Red
  • FIG. 11 shows the color profile changes from a microplate of the type shown in FIG. 10.
  • the microplate consisting of a minimized array of four metalloporphyrins, i.e., Sn(TPP)(CL 2 ), Co(TPP)(Cl), Zn(TPP), Fe(TFPP)(Cl), clockwise from the upper left (where TFPP stands for 5,10,15,20-tetrakis(pentafluorophenyl)porphyrinate).
  • TFPP stands for 5,10,15,20-tetrakis(pentafluorophenyl)porphyrinate.
  • FIG. 12 illustrates the immunity of the present invention to interference from water vapor.
  • the hydrophobicity of the reverse phase support greatly any possible effects from varying water vapor in the atmosphere to be tested.
  • a color fingerprint generated from exposure of the array to n-hexylamine (0.86% in N 2 ) was identical to that for n-hexylamine spiked heavily with water vapor (1.2% H 2 O, 0.48% hexylamine in N 2 ). See scans 120 , 122 and 124 .
  • the ability to easily detect species in the presence of a large water background represents a substantial advantage over mass-sensitive sensing techniques or methodologies that employ polar polymers as part of the sensor array.
  • analytes e.g., n-hexylamine vs. cyclohexylamine.
  • Functionalized metalloporphyrins that limit steric access to the metal ion are candidates for such differentiation. For instance, we have been able to control ligation of various nitrogenous ligands to dendrimer-metalloporphyrins and induce selectivities over a range of more than 10 4 .
  • TTMPP slightly-hindered tetrakis(2,4,6-trimethoxyphenyl)porphyrins
  • porphyrins include those whose periphery is decorated with dendrimer, siloxyl, phenyl, t-butyl and other bulky substituents, providing sterically constrained pockets on at least one face (and preferably both) of the porphyrin.
  • the sensor plates of the present invention can be used for the detection of analytes in liquids or solutions, or solids.
  • a device that detects an analyte in a liquid or solution or solid can be referred to as an artificial tongue.
  • the metal complexes and the solid support must preclude their dissolution into the solution to be analyzed. It is preferred that the surface support repel any carrier solvent to promote the detection of trace analytes in solution; for example, for analysis of aqueous solutions, reverse phase silica has advantages as a support since it will not be wetted directly by water.
  • Alternative sensors in accordance with the present invention may include any other dyes or metal complexes with intense absorbance in the ultraviolet, visible, or near infrared spectra that show a color change upon exposure to analytes.
  • These alternative sensors include, but are not limited to, a variety of macrocycles and non-macrocycles such as chlorins and chlorophylls, phthalocyanines and metallophthalocyanines, salen-type compounds and their metal complexes, or other metal-containing dyes.
  • the present invention can be used to detect a wide variety of analytes regardless of physical form of the analytes. That is, the present invention can be used to detect any vapor emitting substance, including liquid, solid, or gaseous forms, and even when mixed with other vapor emitting substances, such solution mixtures of substances.
  • the present invention can be used in combinatorial libraries of metalloporphyrins for shape selective detection of substrates where the substituents on the periphery of the macrocycle or the metal bound by the porphyrin are created and then physically dispersed in two dimensions by (partial) chromatographic or electrophoretic separation.
  • the present invention can be used with chiral substituents on the periphery of the macrocycle for identification of chiral substrates, including but not limited to drugs, natural products, blood or bodily fluid components.
  • the present invention can be used for analysis of biological entities based on the surface proteins, oligosacharides, antigens, etc., that interact with the metalloporphyrin array sensors of the present invention. Further, the sensors of the present invention can be used for specific recognition of individual species of bacteria or viruses.
  • the present invention can be used for analysis of nucleic acid sequences based on sequence specific the surface interactions with the metalloporphyrin array sensors.
  • the sensors of the present invention can be used for specific recognition of individual sequences of nucleic acids.
  • Substituents on the porphyrins that would be particularly useful in this regard are known DNA intercalating molecules and nucleic acid oligomers.
  • the present invention can be used with ordinary flat bed scanners, as well as portable miniaturized detectors, such as CCD detectors with microarrays of dyes such as metalloporphyrins.
  • the present invention can be used for improved sensitivity, automation of pattern recognition of liquids and solutions, and analysis of biological and biochemical samples.
  • the present invention includes modified porphyrins that have a super structure bonded to the periphery of the porphyrin.
  • a super structure bonded to the periphery of the porphyrin in accordance with the present invention includes any additional structural element or chemical structure built at the edge of the porphyrin and bonded thereto.
  • the super structures can include any structural element or chemical structure characterized in having a certain selectivity.
  • the super structures of the present invention include structures that are shape selective, polarity selective, inantio selective, regio selective, hydrogen bonding selective, and acid-base selective.
  • This structures can include siloxyl-substituted substituents, nonsiloxyl-substituted substituents and nonsiloxyl-substituted substituents, including but not limited to aryl substituents, alkyl substituents, and organic, organometallic, and inorganic functional group substituents.
  • a number of modified porphyrins have been synthesized to mimic various aspects of the enzymatic functions of heme proteins, especially oxygen binding (myoglobin and hemoglobin) and substrate oxidation (cytochrome P-450). See Suslick, K. S.; Reinert, T. J. J. Chem. Ed. 1985, 62, 974; Collman, J. P.; Zhang, X.; Lee, V. J.; Uffelman, E. S.; Brauman, J. I. Science 1993, 261, 1404; Collman, J. P.; Zhang, X. in Comprehensive Supramolecular Chemistry; Atwood, J. L.; Davies, J. E. D.; MacNicol, D.
  • the present invention includes the synthesis, characterization and remarkable shape-selective ligation of silylether-metalloporphyrin scaffolds derived from the reaction of 5,10,15,20-tetrakis(2′,6′-dihydroxyphenyl)porphyrinatozinc(II) with t-butyldimethylsilyl chloride, whereby the two faces of the Zn(II) porphyrin were protected with six, seven, or eight siloxyl groups.
  • Ligation to Zn by classes of different sized ligands reveal shape selectivities as large as 10 7 .
  • a family of siloxyl-substituted bis-pocket porphyrins were prepared according to the scheme of FIG. 13.
  • the abbreviations of the porhyrins that can be made in accordance with the scheme shown in FIG. 13 are as follows:
  • the synthesis of Zn[(OH) 6 PP], Zn(Si 6 PP), and Zn(Si8PP) is detailed below.
  • Zn[(OH) 6 PP] and Zn[(OH) 8 PP] were obtained (see Bhyrappa, P.; Vaijarnahimala, G.; Suslick, K. S. J. Am. Chem. Soc. 1999, 121, 262) from demethylation (see Momenteau, M.; Mispelter, J.; Loock, B.; Bisagni, E.
  • t-butyldimethylsilyl groups were incorporated into the metalloporphyrin by stirring a DMF solution of hydroxyporphyrin complex with TBDMSiCl (i.e., t-butyldimethylsilyl chloride) in presence of imidazole. See Corey, E. J; Venkateswarlu, A. J. Am. Chem. Soc. 1972, 94, 6190.
  • the octa (Zn(Si 8 PP)), hepta (Zn(Si 7 OHPP)), and hexa (Zn(Si 6 PP)) silylether porphyrins were obtained from Zn[(OH)gPP] and Zn[(OH) 6 PP], respectively.
  • the compounds were purified by silica gel column chromatography and fully characterized by UV-Visible, 1 H-NMR, HPLC, and MALDI-TOF MS.
  • the binding constants of silylether porphyrins are remarkably sensitive to the shape and size of the substrates relative to Zn(TPP). See FIGS. 14 a , 14 b , and 14 c .
  • the binding constants of different amines could be controlled over a range of 10 1 to 10 7 relative to Zn(TPP). It is believed that these selectivities originate from strong steric repulsions created by the methyl groups of the t-butyldimethylsiloxyl substituents. The steric congestion caused by these bulky silylether groups is pronounced even for linear amines and small cyclic amines (e.g., azetidine and pyrrolidine).
  • K eq linear /K eq cyclic ranges from 1 to 23 to 115 to >200 for Zn(TPP), Zn(Si 6 PP), Zn(Si 7 OHPP), and Zn(SigPP), respectively.
  • the ability to discriminate between linear and cyclic compounds is thus established.
  • FIG. 14 b A series of cyclic 2° amines (FIG. 14 b ) demonstrate the remarkable size and shape selectivities of this family of bis-pocket porphyrins. Whereas the binding constants to Zn(TPP) with those amines are virtually similar. In contrast, the K eq values for silylether porphyrins strongly depend on the ring size and its peripheral substituents. The effect of these shape-selective binding sites is clear, even for compact aromatic ligands with non-ortho methyl substituents (FIG. 14 c ).
  • FIG. 15 illustrates molecular models of Zn(Si 6 PP) (left column) and Zn(Si 8 PP) (right column).
  • the pairs of images from top to bottom are cylinder side-views, side-views, and top-views, respectively; space filling shown at 70% van der Waals radii; with the porphyrin carbon atoms shown in purple, oxygen atoms shown in red, silicon atoms in green, and Zn in dark red.
  • the x-ray single crystal structure of Zn(Si8PP) is shown; for Zn(Si 6 PP), an energy-minimized structure was obtained using Cerius 2 from MSI.
  • the Zn derivative was obtain by stirring methanol solution of H 2 [(OH) 6 PP] with excess Zn(O 2 CCH 3 ) 2 2H 2 O for 1 hour. Methanol was evaporated to dryness and the residue was dissolved in ethylacetate, washed with water, and the organic layer passed through anhyd. Na 2 SO 4 . The concentrated ethylacetate solution was passed through a silica gel column and the first band was collected as the desired product. The yield of the product was nearly quantitative.
  • the hexasilylether porphyrin was synthesized by stirring a DMF solution of 5-phenyl-10,15,20-tris(2/,6/-dihydroxyphenyl)-porphyrinatozinc(II) (100 mg, 0.13 mmol) with t-butyldimethyl silylchloride (1.18 g, 7.8 mmol) in presence of imidazole (1.2 g, 17.9 mmol) at 60° C. for 24 h under nitrogen. After this period the reaction mixture was washed with water and extracted in CHCl 3 . The organic layer was dried over anhyd. Na 2 SO 4 .
  • the crude reaction mixture was loaded on a short silica gel column and eluted with mixture of CHCl 3 /petether (1:1, v/v) to get rid of unreacted starting material and lower silylated products.
  • the desired compound was further purified by running another silica gel column chromatography using mixture of CHCl 3 /petether (1:3, v/v) as eluant.
  • the yield of the product was 60% based on starting hydroxyporphyrin.
  • the hepta- and octa-silylether porphyrins were synthesized by stirring DMF solution of 5,10,15,20-tetrakis(2/,6/-dihydroxyphenyl)porphyrinatozinc(II) (100 mg, 0.12 mmol) with t-butyldimethyl silylchloride (1.45 g, 9.6 mmol) in presence of imidazole (1.50 g, 22.1 mmol) at 60° C. for 24 h under nitrogen. After usual work-up the mixture of crude products were loaded on a silica gel column and eluted with mixture of CHCl 3 /pet.
  • ether (1: 1, v/v) to remove unreacted starting material and lower silylated products.
  • the major product isolated from this column is a mixture of hepta- and octa-silylated porphyrins.
  • the mixture thus obtained was further purified by another silica gel column chromatography using mixture of CHCl 3 /pet. ether (1:3, v/v) as eluant.
  • the first two bands were isolated as octa- and hepta-silylether porphyrin at 45% and 30% yield, respectively. Both the compounds were characterized by UV-Visible, 1 H NMR and MALDI-TOF spectroscopic techniques. The homogeneity of the sample was verified by HPLC.
  • an important further goal is the differentiation of analytes that do not bind or bind only weakly to metal ions.
  • Such analytes include acidic compounds, such as carboxylic acids, and certain organic compounds lacking ligatable functionality, such as simple alkanes, arenes, some alkenes and alkynes (especially if sterically hindered), and molecules sterically hindered as to preclude effective ligation.
  • One approach that has been developed to achieve this goal in accordance with the present invention is to include in the sensor array other chemoresponsive dyes, including pH sensitive dyes (i.e., pH indicator or acid-base indicator dyes that change color upon exposure to acids or bases), and/or solvatochromic dyes (i.e., dyes that change color depending upon the local polarity of their micro-environment).
  • pH sensitive dyes i.e., pH indicator or acid-base indicator dyes that change color upon exposure to acids or bases
  • solvatochromic dyes i.e., dyes that change color depending upon the local polarity of their micro-environment.
  • the present invention includes an artificial nose comprising an array, the array comprising at least a first dye and a second dye deposited directly onto a single support in a predetermined pattern combination, the combination of the dyes in the array having a distinct and direct spectral absorbance or reflectance response to an analyte wherein the first dye and the second dye are selected from the group consisting of chemoresponsive dyes, and the second dye is distinct from the first dye.
  • the first dye is selected from the group consisting of porphyrin, chlorin, chlorophyll, phtahlocyanine, and salen and their metal complexes.
  • the second dye is selected from the group of dyes consisting of acid-base indicator dyes and solvatochromic dyes.
  • the present invention includes a method of detecting an analyte comprising the steps of: (a) forming an array of at least a first dye and a second dye deposited directly onto a single support in a predetermined pattern combination, the combination of the dyes in the array having a distinct and direct spectral absorbance or reflectance response to an analyte wherein the first dye and the second dye are selected from the group consisting of chemoresponsive dyes, and the second dye is distinct from the first dye; (b) subjecting the array to an analyte; (c) inspecting the array for a distinct and direct spectral absorbance or reflectance response; and (d) correlating the distinct and direct spectral response to the presence of the analyte.
  • the first dye is selected from the group consisting of porphyrin, chlorin, chlorophyll, phtahlocyanine, and salen and their metal complexes.
  • the second dye is selected from the group of acid-base indicator dyes and solvatochromic dyes.
  • the present invention includes an artificial tongue comprising an array, the array comprising at least a first dye and a second dye deposited directly onto a single support in a predetermined pattern combination, the combination of the dyes in the array having a distinct and direct spectral absorbance or reflectance response to an analyte wherein the first dye and the second dye are selected from the group consisting of chemoresponsive dyes, and the second dye is distinct from the first dye.
  • the first dye is selected from the group consisting of porphyrin, chlorin, chlorophyll, phtahlocyanine, and salen and their metal complexes.
  • the second dye is selected from the group of dyes consisting of acid-base indicator dyes and solvatochromic dyes.
  • Chemoresponsive dyes are those dyes that change color, in either reflected or absorbed light, upon changes in their chemical environment.
  • Three general classes of chemoresponsive dyes are (1) Lewis acid/base dyes, (2) pH indicator dyes, and (3) solvatochromic dyes.
  • Lewis acid/base dyes are those dyes that contain a Lewis acidic or basic center (where a Lewis acid is an electron pair acceptor and a Lewis base is an electron pair donor) and change color in response to changes in the Lewis acidity or basicity of their environment.
  • a specific set of Lewis acid/base dyes includes dyes such as porphyrin, chlorin, chlorophyll, phtahlocyanine, and salen and their metal complexes.
  • pH indicator or acid-base indicator dyes are those that change color in response to changes in the proton acidity or basicity (also called Bronsted acidity or basicity) of their environment.
  • a specific set of pH indicator dyes include Chlorphenol Red, Bromocresol Green, Bromocresol Purple, Bromothymol Blue, Phenol Red, Thymol Blue, Cresol Red, Alizarin, Mordant Orange, Methyl Orange, Methyl Red, Congo Red, Victoria Blue B, Eosin Blue, Fat Brown B, Benzopurpurin 4B, Phloxine B, Orange G, Metanil Yellow, Naphthol Green B, Methylene Blue, Safranine O, Methylene Violet 3RAX, Sudan Orange G, Morin Hydrate, Neutral Red, Disperse Orange 25, Rosolic Acid, Fat Brown RR, Cyanidin chloride, 3,6-Acridineamine, 6′-Butoxy-2,6-diamino-3,3′-azodipyridine, para-Rosani
  • Solvatochromic dyes are those that change color in response to changes in the general polarity of their environment, primarily through strong dipole-dipole interactions. To some extent, all dyes inherently are solvatochromic, although some are much more responsive than others. A specific set of highly responsive solvatochromic dyes include Reichardt's Dye and Nile Red.
  • pH indicator i.e., acid-base indicator
  • solvatochromic dyes are useful to expand the range of analytes to which the arrays containing metalloporphyrins are sensitive, improve sensitivities to some analytes, and increase the ability to discriminate between analytes.
  • auxiliary dyes may be made in addition to those described and illustrated herein without departing from the spirit and scope of the present invention. Accordingly, the choice of dyes described and illustrated herein should be understood to be illustrative only and not limiting upon the scope of the present invention.
  • pH 1.8 (orange) to pH 2.0 (yellow); Transition interval (alkaline): pH 7.0 (yellow) to pH 8.8 (violet)
  • pH range violet 1.2-3.8 yellow
  • a low volatility liquid e.g., a plasticizer
  • a plasticizer is used in an array of the present invention to keep the dyes in the array from crystallizing and to enhance then response of the array to an analyte.
  • suitable low volatility liquids include, but are not limited to DOW CORNING 704 silicone diffusion pump fluid (Molecular Weight: 484.82, Density: 1.070, CAS Number: 3982-82-9), and diundecyl phthalate (Molecular Weight: 474.73, Density: 0.950, CAS Number: 3648-20-2, Formula: C 30 H 50 O 4 , Boiling Point (° C.): 523 at 760 torr), dibutyl phthalate (Molecular Weight: 278.4, Density: 1.048, CAS Number: 84-74-2, Formula: C 16 H 22 O 4 , Boiling Point (° C.): 340 at 760 torr), diisopropyl phthalate (Molecular Weight: 250.3, Density: 1.063, CAS Number: 605-45-8, Formula: C 14 H 18 O 4 ), squalane (Molecular Weight: 422.83, Density: 0.810, CAS Number: 111-01-3, Formula: C 30 H 62 , Boil
  • FIG. 16 illustrates an array containing illustrative examples of porphyrin, metalloporphyrin, acid-base indicator, and solvatochromatic dyes. Typical sizes can range from 0.5 mm to 2 cm on a side. Linear, hexagonal, or rectangular arrays are also easily used. From left to right and top to bottom the identities and colors of the dyes used in the illustrative example of FIG. 16 are listed in Table 11 as follows (the exact colors depend, among other things, upon scanner settings). TABLE 11 (Summarizing the Dyes and Colors in FIG.
  • FIG. 17 illustrates the response of the array described in FIG. 16 to acid vapors, specifically formic acid, acetic acid, iso-valeric acid, and 3-methyl-2-hexenoic acid.
  • the color changes of each dye in response to a particular analyte are shown as color difference maps, as follows (the exact colors depend, among others things, upon scanner settings). The color changes are derived simply by comparing the before exposure and after exposure colors and subtracting the two images (i.e., the absolute value of the difference of the red values becomes the new red value in the color difference map; etc. for green values and blue values).
  • “Dye - Difference Map Color”) (Analyte: Formic Acid 140 ppb) SnTPPCl 2 - CoTPP - CrTPPCl MnTPPCl FeTPPCl - CuTPP - Black Black (no Black Black Faint Blue Black (no (no change) (no (no Periphery change) change) change) change) AgTPP - NiTPP - InTPPCL - IrTPPCl - ZnTPP - FeTFPPCl - Black (no Black (no Black (no Black (no change) change) (no change) change) change) change) ZnSi 6 PP - ZnSi 7 OHPP - ZnSi 8 PP - H 2 TPP - H 2 FPP - Alizarin basic - Black (no Black (no Black (no Black (no Dark Blue change) change) change) change) change) change) Me Red - BCP -
  • FIG. 18 illustrates a preferred array containing illustrative examples of porphyrin, metalloporphyrin, acid-base indicator, and solvatochromatic dyes. Typical sizes of the array can range from 0.5 mm to 2 cm on a side. Linear, hexagonal or rectangular arrays are also easily used. From left to right and top to bottom the identities and colors of the dyes used in the illustrative example of FIG. 18 are listed in Table 13 as follows (the exact colors depend, among other things, upon scanner setting). TABLE 13 (Summarizing the Dyes and Colors in FIG.
  • SnTPPCl 2 is 5,10,15,20-Tetraphenyl-21H,23H-porphine tin(IV) dichloride
  • CoTPP is 5,10,15,20-Tetraphenyl-21H,23H-porphine cobalt(II)
  • CrTPPCl is 5,10,15,20-Tetraphenyl-21H,23H-porphine chromium(III) chloride
  • MnTPPCl is 5,10,15,20-Tetraphenyl-21H,23H-porphine manganese(III) chloride
  • FeTPPCl is 5,10,15,20-Tetraphenyl-21H,23H-porphine iron(III) chloride
  • CuTPP is 5,10,15,20-Tetraphenyl-21H,23H-porphine copper(II)
  • Zn(C 3 F 7 ) 4 P is meso tetra(heptafluoropropyl)porphine zinc(II)
  • ZnF 2 PP is 5,10,15,20-Tetrakis(2,6-difluorophenyl)-21H,23H-porphine zinc(II)
  • InTPPCl is 5,10,15,20-Tetraphenyl-21H,23H-porphine indium(III) chloride
  • ZnTMP is 5,10,15,20-Tetrakis(2,4,6-trimethylphenyl)-21H,23H-porphine zinc(II)
  • ZnTPP is 5,10,15,20-Tetraphenyl-21H,23H-porphine zinc(II)
  • FeTFPPCl is 5,10,15,20-Tetrakis(pentafluorophenyl)-21H,23H-porphine iron(III) chloride
  • ZnSi 6 PP is 5(phenyl)-10,15,20-trikis(2 ,6-disilyloxyphenyl)porphyrinatozinc(II)
  • ZnSi 7 OHPP is 5,10,15-trikis(2′,6′-disilyloxyphenyl)-20-(2/-hydroxy-6/-silyloxyphenyl)porphyrinatozinc(II)
  • ZnSi 8 PP is 5,10,15,20-tetrakis(2/,6/-disilyloxyphenyl)porphyrinatozinc(II)
  • H 2 TPP is 5,10,15,20-Tetraphenyl-21H,23H-porphine
  • H 2 FPP is 5,10,15,20-Tetrakis(pentafluorophenyl)-21H,23H-porphine
  • Azodipyridine is 6′-Butoxy-2,6-diamino-3,3′-azodipyridine
  • Rosaniline is Para-Rosaniline Base
  • FIG. 19 illustrates the response of the array described in FIG. 18 to acetone.
  • analytes that bind to metal ions in metallodyes and of acidic or basic analytes that effect other chemoresponsive dyes (e.g., pH sensitive dyes and solvatochromic dyes)
  • chemoresponsive dyes e.g., pH sensitive dyes and solvatochromic dyes
  • Such analytes include certain organic compounds lacking ligatable functionality, such as simple alkanes, arenes, alkenes and alkynes (especially if sterically hindered), and molecules sterically hindered as to preclude effective ligation.
  • the derivative analyte(s) may have stronger ligation, acid-base (including Lewis and/or Br?nsted acids and bases), hydrogen bonding, and/or dipolar interactions with an array of the present invention than does the parent analyte.
  • acid-base including Lewis and/or Br?nsted acids and bases
  • hydrogen bonding and/or dipolar interactions with an array of the present invention than does the parent analyte.
  • hexane can be partially oxidized to derivative analytes such as hexanoic acid, hexanol, hexanal, and C 6 -ketones.
  • a table or database of fingerprints of analytes can be made in accordance with the present invention by subjecting known analytes to partial oxidation pursuant to a certain protocol, and then observing and recording the absorbance or reflectance response an the above-described array to the partially oxidized known analytes. Later, an unknown analyte can be subjected to the same protocol of partial oxidation, and the resulting absorbance or reflectance response or the array to the partially oxidized unknown analyte can be matched with the corresponding fingerprint in the table or database of fingerprints.
  • a known source of hexane can be partially oxidized pursuant to a certain protocol, and the fingerprint of the resulting analyte can be observed and recorded.
  • An unknown analyte can then be partially oxidized pursuant to the same protocol, and if the fingerprint of the resulting analyte matches that of hexane, then the unknown analyte will have been identified as hexane.
  • an above-described array is first subjected to an unknown analyte that has not been partially oxidized. Should the array have no response or a weak response to the unknown analyte such that the unknown analyte cannot be determined, then the unknown analyte can be subjected to a particular partial oxidation protocol to form at least one derivative analyte corresponding to the unknown analyte. The array can then be subjected to the at least one derivative analyte and inspected for a direct and distinct spectral absorbance or reflectance response corresponding to the derivative analyte. The response or fingerprint can then be matched with the corresponding response or fingerprint of a known analyte that had been subjected to the same particular partial oxidation protocol, and thus the unknown analyte can be identified.
  • an oxidizing source For partial oxidation of the parent analyte to occur, an oxidizing source must react with the parent analyte.
  • the oxidizing source can be any suitable source of oxygen gas (e.g., as a component of air), or other oxidant or oxidizing agent (e.g., hydrogen peroxide, hypochlorite, chlorine dioxide, chlorine or other bleaching agents).
  • the oxidizing source must be present in a range of concentration or amount sufficient to result in forming a derivative analyte that has a stronger response with at least part of the array of the present invention than the parent analyte, but below that needed to fully oxidize the parent analyte completely to carbon dioxide.
  • the incoming gas to be analyzed is brought into contact with an oxidizing source.
  • the incoming gas having a parent analyte can be passed through a column or cartridge comprising a heterogeneous oxidation catalyst.
  • the outgoing gas coming out of the column or cartridge will comprise at least one derivative analyte that is then exposed to a dye array previously described above.
  • the time of transit (so-called “residence time” of the analyte gas) over or through the bed of oxidation catalyst can be adjusted by the flow rate or the physical length of the catalyst bed so as to optimize the partial oxidation of the parent analyte(s).
  • the extent of oxidation can also be adjusted by the concentration of the oxidant in the analyte gas or liquid (e.g., by adding O 2 or hydrogen peroxide).
  • Suitable oxidation catalysts are of many potential types, including but not limited to noble metals (e.g., Pt or Pd) or their oxides, early transition metal oxides (e.g., V 2 O 5 ), and metal-containing microporous zeolites.
  • noble metals e.g., Pt or Pd
  • Such oxidation catalysts can be used either in substantially pure form or supported on various high surface area supports, such as silica, alumina, charcoal, or diamtomaceous earth among others.
  • an oxidation catalyst is used, the extent of oxidation can also be adjusted by the temperature at which the catalyst is kept, such as a range that includes 100 K to 1000 K.
  • An embodiment may often utilize a catalyst of sufficient activity and concentration to permit its effective use at room temperature.
  • FIG. 20 illustrates an embodiment of a vapor exposure apparatus of the present invention.
  • the basic difference between the embodiment shown in FIG. 3B is that the embodiment shown in FIG. 20 further includes a partial oxidation cartridge 200 having a suitable oxidation catalyst 202 . Partial oxidation of the incoming gas or parent analyte 204 using oxidation catalyst 202 can be used to provide increased sensitivities to analytes.
  • the oxidation catalyst 202 of partial oxidation cartridge 200 can used in accordance with the present invention to provide increased sensitivities to analytes that do not have significant acidic or basic functionality, including alkanes, arenes, alkenes and alkynes (especially if sterically hindered), and molecules sterically hindered as to preclude effective ligation.
  • FIG. 20 illustrates top and side views of bottom piece 21 and a top view of top piece 21 ′ of a vapor exposure flow cell 20 of the present invention.
  • a sensor plate 18 having array 16 is placed inside of a flow cell 20 equipped with a quartz window 22 .
  • flow cell 20 is made from stainless steel.
  • Inlet 23 for the analyte vapor includes partial oxidation cartridge 200 .
  • cartridge 200 is packed with a solid or solid-supported oxidation catalyst 202 optimized for partial oxidation of the incoming analyte.
  • Cartridge 200 can be thermostated above or below room temperature as needed to optimize the partial oxidation of incoming analyte.
  • Outlet 23 ′ permits vapor flow out from sensor plate 18 .
  • incoming gas or parent analyte 204 is partially oxidized as it is passed through cartridge 200 , and the partially oxidized gas 206 , which now contains at least one derivative analyte, flows into contact array 16 of sensor plate 18 , and then exits from outlet 23 .′
  • a table of responses of the array(s) described herein to a plurality of distinct known analytes can be prepared and used identify an unknown analytes at a later time.
  • a method (I) of detecting at least one parent analyte comprises the steps of (a) forming an array by depositing at least a first dye and a second dye directly onto a single support in a predetermined patter combination, the combination of dyes in the array having a distinct and direct spectral or reflectance response to distinct analytes comprising one or more parent analytes or their derivatives, (b) partially oxidizing at least one parent analyte to form at least one derivative analyte corresponding to said parent analyte, (c) subjecting the array to the at least one derivative analyte, and (d) inspecting the first dye and the second dye for a direct and distinct spectral response corresponding to the derivative analyte.
  • a method (II) of detecting at least one unknown parent analyte comprises the steps of
  • step (e) forming an array identical to the array formed in step (a) by repeating step (a) or returning the array in step (a) to its condition prior to step (c),
  • step (e) subjecting the array formed in step (e) to the at least one derivative analyte corresponding to said unknown parent analyte
  • step (h) inspecting the array after step (g) for a direct and distinct spectral response to the derivative analyte corresponding to said unknown parent analyte
  • step (i) determining after step (h) whether the direct and distinct spectral response of the array to the derivative analyte corresponding to the unknown parent analyte matches the direct and distinct spectral response of the array to the derivative analyte corresponding to the known parent analyte in step (d).
  • the method (II) of the above paragraph can further comprise the step of subjecting the array formed in step (e) to the at least one unknown parent analyte prior to step (f) and determining whether the array formed in step (e) has a response insufficient to detect the unknown parent analyte prior to proceeding to step (f).
  • the method (II) can further comprise the step of subjecting the array formed in step (a) to the at least one known parent analyte prior to step (b) and determining whether the array formed in step (a) has a response insufficient to detect the unknown parent analyte prior to proceeding to step (b).
  • the present invention provides a method (III) of making a table of responses of an array to a plurality of distinct analytes comprising the steps of
  • step (g) forming an array identical to the array formed in step (a) by repeating step (a) or returning the array in step (a) to its condition prior to step (b),
  • step (h) subjecting the array formed in step (g) to at least one unknown parent analyte to determine whether the array has a response sufficient to detect the unknown parent analyte
  • step (i) if after step (h) the array has a response sufficient to detect the unknown parent analyte, then determining whether the response matches the response of a known patent analyte in step (c),
  • step (j) if after step (h) the array does not have a response sufficient to detect the unknown parent analyte, then partially oxidizing the at least one unknown parent analyte pursuant to the certain protocol to form at least one derivative analyte corresponding to said unknown parent analyte,
  • step (k) subjecting the array after step (j) to the at least one derivative analyte corresponding to said unknown parent analyte
  • step (l) inspecting the array after step (k) for a direct and distinct spectral response corresponding to the derivative analyte corresponding to said unknown parent analyte
  • step (m) determining after step (l) whether the direct and distinct spectral response of the array to the derivative analyte corresponding to the unknown parent analyte matches the direct and distinct spectral response of the array to the derivative analyte corresponding to the known parent analyte in step (f).

Abstract

The present invention involves an artificial nose comprising an array, the array comprising at least a first dye and a second dye deposited directly onto a single support in a predetermined pattern combination, the combination of dyes in the array having a distinct and direct spectral absorbance or reflectance response to distinct analytes comprising one or more parent analytes or their derivatives. In one embodiment, the invention further comprises an oxidizing source to partially oxidize at least one distinct parent analyte to at least one corresponding derivative analyte of said parent analyte, the array at least in part having a stronger distinct and direct absorbance or reflectance response to the derivative analyte than to the corresponding parent analyte.

Description

    CONTINUING APPLICATION DATA
  • This application is a Continuation-in-Part of U.S. application Ser. No. 09/705,329, filed on Nov. 3, 2000, which is a Continuation-in-Part of U.S. application Ser. No. 09/532,125, filed on Mar. 21, 2000, now U.S. Pat. No. 6,368,558.[0001]
  • [0002] This invention was made with Government support under Contract Nos. HL25934 awarded by the National Institutes of Health & Contract No. DAAG55-97-1-2211 awarded by the Department of the Army. The Government has certain rights in the invention.
  • FIELD OF THE INVENTION
  • The present invention relates to methods and apparatus for artificial olfaction, e.g., artificial noses, for the detection of odorants by a visual display. [0003]
  • BACKGROUND OF THE INVENTION
  • There is a great need for olfactory or vapor-selective detectors (i.e., “artificial noses”) in a wide variety of applications. For example, there is a need for artificial noses that can detect low levels of odorants and/or where odorants may be harmful to humans, animals or plants. Artificial noses that can detect many different chemicals are desirable for personal dosimeters in order to detect the type and amount of odorants exposed to a human, the presence of chemical poisons or toxins, the spoilage in foods, the presence of flavorings, or the presence of vapor emitting items, such as plant materials, fruits and vegetables, e.g., at customs portals. [0004]
  • Conventional artificial noses have severe limitations and disadvantages and are not considered generally useful for such purposes. Limitations and disadvantages of conventional artificial noses include their need for extensive signal transduction hardware, and their inability to selectively target metal-coordinating vapors and toxins. In addition, artificial noses which incorporate mass sensitive signal transduction or polar polymers as sensor elements are susceptible to interference by water vapor. This limitation is significant in that it can cause variable response of the detector with changes ambient humidity. See F. L. Dickert, O. Hayden, Zenkel, M. E. Anal. Chem. 71, 1338 (1999). [0005]
  • Initial work in the field of artificial noses was conducted by Wilkens and Hatman in 1964, though the bulk of research done in this area has been carried out since the early 1980's. See, e.g., W. F. Wilkens, A. D. Hatman. [0006] Ann. NY Acad. Sci., 116, 608 (1964); K. Pursaud, G. H. Dodd. Nature, 299, 352-355 (1982); and J. W. Gardner, P. N. Bartlett. Sensors and Actuators B, 18-19, 211-220 (1994).
  • Vapor-selective detectors or “artificial noses” are typically based upon the production of an interpretable signal or display upon exposure to a vapor emitting substance or odorant (hereinafter sometimes referred to as an “analyte”). More specifically, typical artificial noses are based upon selective chemical binding or an interface between a detecting compound of the artificial nose and an analyte or odorant, and then transforming that chemical binding into a signal or display, i.e., signal transduction. [0007]
  • Polymer arrays having a single dye have been used for artificial noses. That is, a series of chemically-diverse polymers or polymer blends are chosen so that their composite response distinguishes a given odorant or analyte from others. Examples of polymer array vapor detectors, including conductive polymer and conductive polymer/carbon black composites, are discussed in: M. S. Freund, N. S. Lewis, Proc. Natl. Acad. Sci. U.S. Pat. No. 92,2652-2656 (1995); B. J. Doleman, R. D. Sanner, E. J. Severin, R. H. Grubbs, N. S. Lewis, [0008] Anal. Chem. 70, 2560-2564 (1998); T. A. Dickinson, J. White, J. S. Kauer, D. R. Walt, Nature 382, 697-700 (1996) (polymer array with optical detection); A. E. Hoyt, A. J. Ricco, H. C. Yang, R. M. Crooks, J. Am. Chem. Soc. 117, 8672 (1995); and J. W. Grate, M. H. Abraham, Sensors and Actuators B 3, 85-111 (1991).
  • Other interface materials include functionalized self-assembled monolayers (SAM), metal oxides, and dendrimers. Signal transduction is commonly achieved with mass sensitive piezoelectric substrates, surface acoustic wave (SAW) transducers, or conductive materials. Optical transducers (based on absorbance or luminescence) have also been examined. Examples of metal oxide, SAM, and dendrimer-based detectors are discussed in J. W. Gardner, H. V. Shurmer, P. Corcoran, [0009] Sensors and Actuators B 4, 117-121 (1991); J. W. Gardner, H. V. Shurmer, T. T. Tan, Sensors and Actuators B 6, 71-75 (1992); and R. M. Crooks, A. J. Ricco, Acc. Chem. Res. 31, 219-227 (1998). These devices also use a single dye.
  • Techniques have also been developed using a metalloporphyrin for optical detection of a specific, single gas such as oxygen or ammonia, and for vapor detection by chemically interactive layers on quartz crystal microbalances. See A. E. Baron, J. D. S. Danielson, M. Gouterman, J. R. Wan, J. B. Callis, [0010] Rev. Sci. Instrum. 64, 3394-3402 (1993); J. Kavandi, et al., Rev. Sci. Instrum. 61, 3340-3347 (1990); W. Lee, et al., J. Mater. Chem. 3, 1031-1035 (1993); A. A. Vaughan, M. G. Baron, R. Narayanaswamy, Anal Comm. 33, 393-396 (1996); J. A. J. Brunink, et al., Anal. Chim. Acta 325, 53-64 (1996); C. Di Natale, et al., Sensors and Actuators B 44, 521-526 (1997); and C. Di Natale, et al., Mat. Sci. Eng. C 5, 209-215 (1998). However, these techniques either require extensive signal transduction hardware, or, as noted above, are limited to the detection of a specific, single gas. They are also subject to water vapor interference problems, as discussed previously.
  • While typical systems to date have demonstrated some success in chemical vapor detection and differentiation, these systems have focused on the detection of non-metal binding or non-metal ligating solvent vapors, such as arenes, halocarbons and ketones. Detection of metal-ligating vapors (such as amines, thiols, and phosphines) has been much less explored. Further, while some single porphyrin based sensors have been used for detection of a single strong acid, there is a need for sensor devices that will detect a wide variety of vapors. [0011]
  • To summarize, there are a number of limitations and drawbacks to typical artificial noses and single porphyrin based sensors. As noted above typical artificial noses are not designed for metal binding and metal ligating vapors, such as amines, thiols, and phosphines. Further, typical artificial noses require extensive signal transduction hardware, and are subject to interference from water vapor. As noted above, single porphyrin based sensors have been used for detection of a single strong acid, but cannot detect a wide variety of vapors. Thus, there is a need for new artificial noses and methods that overcome these and other limitations of prior artificial noses and single porphyrin based sensors and methods. [0012]
  • SUMMARY OF THE INVENTION
  • The present invention comprises an array of dyes including at least a first dye and a second dye which in combination provide a spectral response distinct to an analyte or odorant. The dyes of the present invention produce a response in the spectrum range of about 200 nanometers to 2,000 nanometers, which includes the visible spectrum of light. It has now been discovered that an array of two or more dyes responds to a given ligating species with a unique color pattern spectrally and in a time dependent manner. Thus, dyes in the array of the present invention are capable of changing color in a distinct manner when exposed to any one analyte or odorant. The pattern of colors manifested by the multiple dyes is indicative of a specific or given analyte. In other words, the pattern of dye colors observed is indicative of a particular vapor or liquid species. [0013]
  • In a preferred embodiment, the dyes of the array are porphyrins. In another preferred embodiment, the porphyrin dyes are metalloporphyrins. In a further preferred embodiment, the array will comprise ten to fifteen distinct metalloporphyrins in combination. Metalloporphyrins are preferable dyes in the present invention because they can coordinate metal-ligating vapors through open axial coordination sites, and they produce large spectral shifts upon binding of or interaction with metal-ligating vapors. In addition, porphyrins, metalloporphyrins, and many dyes show significant color changes upon changes in the polarity of their environment; this so-called solvatochromic effect will give net color changes even in the absence of direct bonding between the vapor molecules and the metal ions. Thus, metalloporphyrins produce intense and distinctive changes in coloration upon ligand binding with metal ligating vapors. [0014]
  • The present invention provides a means for the detection or differentiation and quantitative measurement of a wide range of ligand vapors, such as amines, alcohols, and thiols. Further, the color data obtained using the arrays of the present innovation may be used to give a qualitative fingerprint of an analyte, or may be quantitatively analyzed to allow for automated pattern recognition and/or determination of analyte concentration. Because porphyrins also exhibit wavelength and intensity changes in their absorption bands with varying solvent polarity, weakly ligating vapors (e.g., arenes, halocarbons, or ketones) are also differentiable. [0015]
  • Diversity within the metalloporphyrin array may be obtained by variation of the parent porphyrin, the porphyrin metal center, or the peripheral porphyrin substituents. The parent porphyrin is also referred to as a free base (“FB”) porphyrin, which has two central nitrogen atoms protonated (i.e., hydrogen cations bonded to two of the central pyrrole nitrogen atoms). A preferred parent porphyrin is depicted in FIG. 2A, with the substitution of a two hydrogen ion for the metal ion (depicted as “M”) in the center of the porphyrin. In FIG. 2A, TTP stands for 5,10,1 5,20-tetraphenylporphyrinate(-2). [0016]
  • In accordance with the present invention, colorimetric difference maps can be generated by subtracting unexposed and exposed metalloporphyrin array images (obtained, for example, with a common flatbed scanner or inexpensive video or charge coupled device (“CCD”) detector) with image analysis software. This eliminates the need for extensive and expensive signal transduction hardware associated with previous techniques (e.g., piezoelectric or semiconductor sensors). By simply differencing images of the array before and after exposure to analytes, the present invention provides unique color change signatures for the analytes, for both qualitative recognition and quantitative analysis. [0017]
  • Sensor plates which incorporate vapor sensitive combinations of dyes comprise an embodiment of the present invention which is economical, disposable, and can be utilized to provide qualitative and/or quantitative identification of an analyte. In accordance with the present invention, a catalog of arrays and the resultant visual pattern for each analyte can be coded and placed in a look-up table or book for future reference. Thus, the present invention includes a method of detecting an analyte comprising the steps of forming an array of at least a first dye and a second dye, subjecting the array to an analyte, inspecting the first and second dyes for a spectral response, and comparing the spectral response with a catalog of analyte spectral responses to identify the analyte. [0018]
  • Because sensing is based upon either covalent interaction (i.e., ligation) or non-covalent solvation interactions between the analyte and the porphyrin array, a broad spectrum of chemical species is differentiable. While long response times (e.g., about 45 minutes) are observed at low analyte concentrations of about 1 ppm with reverse phase silica gel plates, use of impermeable solid supports (such as polymer- or glass-based micro-array plates) substantially increases the low-level response to less than 5 minutes. [0019]
  • Thus, it is an object of the present invention to provide methods and devices for artificial olfaction, vapor-selective detectors or artificial noses for a wide variety of applications. It is another object of the present invention to provide methods of detection and artificial noses that can detect low levels of odorants and/or where odorants may be harmful to living human, animal or plant cells. It is also an object of the present invention to provide methods of olfactory detection and artificial noses that can detect and quantify many different chemicals for dosimeters that can detect chemical poisons or toxins, that can detect spoilage in foods, that can detect flavorings and additives, and that can detect plant materials, e.g., fruits and vegetables. [0020]
  • Another object of the present invention is to provide for the detection of analytes using data analysis/pattern recognition techniques, including automated techniques. [0021]
  • Another object of the invention is to provide an artificial nose comprising an array, the array comprising at least a first dye and a second dye deposited directly onto a single support in a predetermined pattern combination, the combination of the dyes in the array having a distinct and direct spectral absorbance or reflectance response to an analyte wherein the first dye and the second are selected from the group of dyes consisting of chemoresponsive dyes, and the second dye is distinct from the first dye. In one embodiment, the first dye is selected from the group consisting of porphyrin, chlorin, chlorophyll, phtahlocyanine, and salen and their metal complexes. In another embodiment, the second dye is selected from the group consisting of acid-base indicator dyes and solvatochromic dyes. [0022]
  • Another object of the invention is to provide a method of detecting an analyte comprising the steps of: (a) forming an array of at least a first dye and a second dye deposited directly onto a single support in a predetermined pattern combination, the combination of the dyes in the array having a distinct and direct spectral absorbance or reflectance response to an analyte wherein the first dye and the second dye are selected from the group consisting of chemoresponsive dyes, and the second dye is distinct from the first dye, (b) subjecting the array to an analyte, (c) inspecting the array for a distinct and direct spectral absorbance or reflectance response, and (d) correlating the distinct and direct spectral response to the presence of the analyte. In one embodiment, the first dye is selected from the group consisting of porphyrin, chlorin, chlorophyll, phtahlocyanine, and salen and their metal complexes. In another embodiment, the second dye is selected from the group consisting of acid-base indicator dyes and solvatochromic dyes. [0023]
  • Another object of the invention is to provide an artificial tongue comprising an array, the array comprising at least a first dye and a second dye deposited directly onto a single support in a predetermined pattern combination, the combination of the dyes in the array having a distinct and direct spectral absorbance or reflectance response to an analyte wherein the first dye and the second are selected from the group of dyes consisting of chemoresponsive dyes, and the second dye is distinct from the first dye. In one embodiment, the first dye is selected from the group consisting of porphyrin, chlorin, chlorophyll, phtahlocyanine, and salen and their metal complexes. In another embodiment, the second dye is selected from the group consisting of acid-base indicator dyes and solvatochromic dyes. [0024]
  • Another object of the invention is to provide an artificial nose comprising an array, the array comprising at least a first dye and a second dye deposited directly onto a single support in a predetermined pattern combination, the combination of dyes in the array having a distinct and direct spectral absorbance or reflectance response to distinct analytes comprising one or more parent analytes or their derivatives, and an oxidizing source to partially oxidize at lest one distinct parent analyte to at least one corresponding derivative analyte of said parent analyte, the array at least in part having a stronger distinct and direct absorbance or reflectance response to the derivative analyte than to the corresponding parent analyte [0025]
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • The file of this patent contains at least one drawing executed in color. Copies of this patent with color drawing(s) will be provided by the Patent and Trademark Office upon request and payment of the necessary fee. [0026]
  • FIG. 1 illustrates an embodiment of the optical sensing plate of the present invention using a first elution in the y axis and a second elution in the x axis of the plate. In this embodiment the first elution R-OH/hexane and the second elution is R-SH/hexane. [0027]
  • FIG. 2A illustrates an embodiment of the invention using metalloporphyrins as the sensing dyes. [0028]
  • FIG. 2B illustrates an embodiment of the invention using metalloporphyrins as the sensing dyes. [0029]
  • FIG. 3A illustrates a vapor exposure apparatus for demonstration of the present invention. [0030]
  • FIG. 3B illustrates a vapor exposure apparatus for demonstration of the present invention. [0031]
  • FIG. 4 illustrates the color change profile in a metalloporphyrin array of FIG. 2 when used in the vapor exposure apparatus of FIG. 3A to detect n-butylamine. Metalloporphyrins were immobilized on reverse phase silica gel plates. [0032]
  • FIG. 5 illustrates a comparison of color changes at saturation for a wide range of analytes. Each analyte was delivered to the array as a nitrogen stream saturated with the analyte vapor at 20° C. DMF stands for dimethylformamide; THF stands for tetrahydrofuran. [0033]
  • FIG. 6 illustrates two component saturation responses of mixtures of 2-methylpyridine and trimethylphosphite. Vapor mixtures were obtained by mixing two analyte-saturated N[0034] 2 streams at variable flow ratios.
  • FIG. 7 illustrates a comparison of Zn(TPP) spectral shifts upon exposure to ethanol and pyridine (py) in methylene chloride solution (A) and on the reverse phase support (B). [0035]
  • FIG. 8 illustrates another embodiment of the present invention, and more particularly, an small array comprising microwells built into a wearable detector which also contains a portable light source and a light detector, such as a charge-coupled device (CCD) or photodiode array. [0036]
  • FIG. 9 illustrates another embodiment of the present invention, and more particularly, a microwell porphyrin array wellplate constructed from polydimethylsiloxane (PDMS). [0037]
  • FIG. 10 illustrates another embodiment of the present invention, and more particularly, a microplate containing machined teflon posts, upon which the porphyrin array is immobilized in a polymer matrix (polystyrene/dibutylphthalate). [0038]
  • FIG. 11 illustrates another embodiment of the present invention, showing a microplate of the type shown in FIG. 10, consisting of a minimized array of four metalloporphyrins, showing the color profile changes for n-octylamine, dodecanethiol, and tri-n-butylphosphine, each at 1.8 ppm. [0039]
  • FIG. 12 illustrates the immunity of the present invention to interference from water vapor. [0040]
  • FIG. 13 illustrates the synthesis of siloxyl-substituted bis-pocket porphyrins in accordance with the present invention. [0041]
  • FIGS. 14[0042] a, 14 b, and 14 c illustrate differences in Keq for various porphyrins.
  • FIG. 15 illustrates molecular models of Zn(Si[0043] 6PP) (left column) and Zn(Si8PP) (right column).
  • FIG. 16 illustrates an array containing illustrative examples of porphyrin, metalloporphyrin, acid-base indicator, and solvatochromatic dyes. [0044]
  • FIG. 17 illustrates the response of the array described in FIG. 16 to acid vapors, specifically formic acid, acetic acid, iso-valeric acid, and 3-methyl-2-hexenoic acid. [0045]
  • FIG. 18 illustrates a preferred array containing illustrative examples of porphyrin, metalloporphyrin, acid-base indicator, and solvatochromatic dyes. [0046]
  • FIG. 19 illustrates the response of the array described in FIG. 18 to acetone. [0047]
  • FIG. 20 illustrates a vapor exposure apparatus shown in FIG. 3B, further having a partial oxidation cartridge to provide increased sensitivity to analytes.[0048]
  • DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
  • Production of the Sensor Plate of the Present Invention [0049]
  • A [0050] sensor plate 10 fabricated in accordance with the present invention is shown in FIG. 1. Sensor plate 10 comprises a two-dimensionally spatially resolved array 12 of various sensing elements or dyes 14 capable of changing color upon interaction (e.g., binding, pi-pi complexation, or polarity induced shifts in color). As shown in FIG. 1, a library of such dyes 14 can be given spatial resolution by two-dimensional chromatography or by direct deposition, including, but not limited to, ink-jet printing, micropipette spotting, screen printing, or stamping. In FIG. 1, metalloporphyrin mixture 6 is placed at origin 7. Next, the metalloporphyrin mixture 6 is eluted through a silica gel or reversed-phase silica gel 5 in sensor plate 10, and the metalloporphyrins are spatially resolved from each other and immobilized in silica gel 5 as depicted by the oval and circular shapes 4 as shown in FIG. 1. Sensor plate 10 can be made from any suitable material or materials, including but not limited to, chromatography plates, paper, filter papers, porous membranes, or properly machined polymers, glasses, or metals.
  • FIG. 1 also illustrates an embodiment of the optical sensing plate of the present invention using a [0051] first elution 8 in the y axis and a second elution 9 in the x axis of sensor plate 10. In this embodiment, the first elution 8 is R—OH/hexane and the second elution 9 is R—SH/hexane. The order of the first and second elutions can be reversed. The first and second elutions are used to spatially resolve the metalloporphyrin mixture 6 in silica gel 5. As shown in FIG. 1, the upper left hand quadrant 3 is characterized by metalloporphyrins that are “hard” selective, i.e., having a metal center having a high chemical hardness, i.e., a high charge density. As shown in FIG. 1, the lower right hand quadrant 2 is characterized by metalloporphyrins that are “soft” selective, i.e., having a metal center having a low chemical hardness, i.e., a low charge density. In accordance with the present invention, the array can be a spatially resolved collection of dyes, and more particularly a spatially resolved combinatorial family of dyes.
  • In accordance with the present invention, a porphyrin-metalloporphyrin sensor plate was prepared and then used to detect various odorants. More specifically, solutions of various metalated tetraphenylporphyrins in either methylene chloride or chlorobenzene were spotted in 1 μL aliquots onto two carbon (“C2”, i.e, ethyl-capped) reverse phase silica thin layer chromatography plates (Product No. 4809-800, by Whatman, Inc., Clifton, N.J.) to yield the [0052] sensor array 16 seen in FIG. 2B. As shown in FIG. 2B and summarized in Table 1 below, the dyes have the following colors (the exact colors depend, among other things, upon scanner settings).
    TABLE 1
    (Summarizing Colors of Dyes in FIG. 2B)
    Sn4+ - Green Co3+ - Red Cr3+ - Deep Green
    Mn3+ - Green Fe3+ - Dark Red Co2+ - Red
    Cu2+ - Red Ru2+ - Light Yellow Zn2+ - Greenish Red
    Ag2+ - Red 2H+ (Free Base “FB”) — Red
  • A [0053] metalloporphyrin 15, sometimes referred to as M(TPP), of the present invention is depicted in FIG. 2A. FIG. 2A also depicts various metals of the metalloporphyrins 15 of the present invention, and corresponding metal ion charge to radius ratio (i.e., Z/r Ratio) in reciprocal angstroms. The Z/r Ratio should preferably span a wide range in order to target a wide range of metal ligating analytes. These metalloporphyrins have excellent chemical stability on the solid support and most have well-studied solution ligation chemistry. Reverse phase silica was chosen as a non-interacting dispersion medium for the metalloporphyrin array 16 depicted in FIG. 2B, as well as a suitable surface for diffuse reflectance spectral measurements. More importantly, the reverse phase silica presents a hydrophobic interface, which virtually eliminates interference from ambient water vapor. After spotting, sensor plates 18 like the one depicted in FIG. 2B were dried under vacuum at 50° C. for 1 hour prior to use. Thus, immobilization of the metalloporphyrins on a reverse phase silica support is obtained. While ten (10) different metalloporphyrins are shown in FIG. 2A, those of skill in the art will recognize that many other metalloporphyrins are useful in accordance with the present invention. Those of skill in the art will further recognize that in accordance with the broad teachings of the present invention, any dyes capable of changing color upon interacting with an analyte, both containing and not containing metal ions, are useful in the array of the present invention.
  • Colorimetric Analysis Using the Sensor Plate [0054]
  • For the detection and analysis of odorants in accordance with the present invention, one needs to monitor the absorbance of the sensor plate at one or more wavelengths in a spatially resolved fashion. This can be accomplished with an imaging spectrophotometer, a simple flatbed scanner (e.g. a [0055] Hewlett Packard Scanjet 3c), or an inexpensive video or CCD camera.
  • FIG. 3A illustrates a [0056] vapor exposure apparatus 19 of the present invention. FIG. 3B illustrates top and side views of bottom piece 21 and a top view of top piece 21′ of a vapor exposure flow cell 20 of the present invention. In an embodiment of the present invention for purposes of demonstration, each sensor plate 18 was placed inside of a stainless steel flow cell 20 equipped with a quartz window 22 as shown in FIGS. 3A and 3B. Scanning of the sensor plate 18 was done on a commercially available flatbed scanner 24 (Hewlett Packard Scanjet 3c) at 200 dpi resolution, in full color mode. Following an initial scan, a control run with a first pure nitrogen flow stream 26 was performed. The array 16 of plate 18 was then exposed to a second nitrogen flow stream 28 saturated with a liquid analyte 30 of interest. As shown in FIG. 3A, the nitrogen flow stream 28 saturated with liquid analyte 30 results in a saturated vapor 32. Saturated vapor 32, containing the analyte 30 of interest were generated by flowing nitrogen flow stream 28 at 0.47 L/min. through the neat liquid analyte 30 in a water-jacketed, glass fritted bubbler 34. Vapor pressures were controlled by regulating the bubbler 34 temperature. As shown in FIG. 3B, vapor channels 23 permit vapor flow to sensor plate 18.
  • EXAMPLE 1
  • Scanning at different time intervals and subtracting the red, green and blue (“RGB”) values of the new images from those of the original scan yields a color change profile. This is shown for n-butylamine in FIG. 4, in which color change profiles of the [0057] metalloporphyrin sensor array 16 as a function of exposure time to n-butylamine vapor. Subtraction of the initial scan from a scan after 5 min. of N2 exposure was used as a control, giving a black response, as shown. 9.3% n-butylamine in N2 was then passed over the array and scans made after exposure for 30 s, 5 min., and 15 min. The red, green and blue (“RGB”) mode images were subtracted (absolute value) to produce the color change profiles illustrated. Virtually all porphyrins are saturated after 30 seconds of exposure, yielding a color fingerprint unique for each class of analytes, which is illustrated in FIG. 4.
  • More specifically, subtraction of the [0058] initial scan 40 from a scan after 5 min. of N2 exposure was used as a control, giving a black response, as shown in FIG. 4. A nitrogen flow stream containing 0.093% n-butylamine was then passed over the array 16 and scans 42, 44, and 46 were made after exposure for 30 seconds, 5 minutes, and 15 minutes, respectively. The RGB mode images were subtracted (absolute value) using Adobe Photoshop™ (which comprises standard image analyzing software), with contrast enhancement by expanding the pixel range (a 32 value range was expanded to 256 each for the R, G, and B values). Subtraction of exposed and unexposed images gives color change patterns that vary in hue and intensity. Because differentiation is provided by an array of detectors, the system has parallels the mammalian olfactory system. As shown in FIG. 4 and summarized in Table 2 below, the dyes have the following colors in scans 42, 44, and 46.
    TABLE 2
    (Summarizing Colors of Dyes in FIG. 4, Scans 42, 44, and 46)
    Sn4+ - No Change Co3+ - Green Cr3+ - Green
    Mn3+ - No Change Fe3+ - Red Co2+ - Faint Green
    Cu2+ - No Change Ru2+ - No Change Zn2+ - Light Green
    Ag2+ - No Change 2H+ (Free Base “FB”) —
    Light Blue
  • As summarized in Table 3 below, for the [0059] TTP array 16 depicted on the left-hand side of FIG. 4, the dyes have the following colors.
    TABLE 3
    Sn4+ - Greenish Yellow Co3+ - Red Cr3+ - Yellow with Dark Red
    Center
    Mn3+ - Greenish Yellow Fe3+ - Dark Red Co2+ - Red
    Cu2+ - Red Ru2+ - Light Yellow Zn2+ - Red
    Ag2+ - Red 2H+ (Free Base “FB”) — Red
  • EXAMPLE 2
  • Visible spectral shifts and absorption intensity differences occur upon ligation of the metal center, leading to readily observable color changes. As is well known to those with skill in the art, the magnitude of spectral shift correlates with the polarizability of the ligand; hence, there exists an electronic basis for analyte distinction. Using metal centers that span a range of chemical hardness and ligand binding affinity, a wide range of volatile analytes (including soft ligands, such as thiols, and harder ligands, such as amines) are differentiable. Because porphyrins have been shown to exhibit wavelength and intensity changes in their absorption bands with varying solvent polarity, it is contemplated that the methods and apparatus of the present invention can be used to calorimetrically distinguish among a series of weakly ligating solvent vapors (e.g., arenes, halocarbons, or ketones), as shown for example in FIG. 5. [0060]
  • A comparison of color changes at saturation for a wide range of analytes is shown in FIG. 5. Each analyte is identified under the [0061] colored array 16 that identifies each analyte. ). DMF stands for the analyte dimethylformamide, and THF stands for the analyte tetrahydrofuran. As shown in FIG. 5 and summarized in Table 4 below, the colors of each dye in response to a particular analyte are as follows.
    TABLE 4
    Analyte: DMF
    Sn4+ - No Change Co3+ - Green Cr3+ - No Change
    Mn3+ - No Change Fe3+ - No Change Co2+ - No Change
    Cu2+ - Blue Ru2+ - No Change Zn2+ - No Change
    Ag2+ - No Change 2H+ (Free Base “FB”) — Blue
    Analyte: Ethanol
    Sn4+ - Dark Blue Co3+ - No Change Cr3+ - Red
    Mn3+ - No Change Fe3+ - No Change Co2+ - No Change
    Cu2+ - No Change Ru2+ - No Change Zn2+ - Blue
    Ag2+ - No Change 2H+ (Free Base “FB”) - No
    Change
    Analyte: Pyridine
    Sn4+ - No Change Co3+ - Green Cr3+ - Dark Green
    Mn3+ - No Change Fe3+ - No Change Co2+ - No Change
    Cu2+ - No Change Ru2+ - No Change Zn2+ - Green
    Ag2+ - No Change 2H+ (Free Base “FB”) — Blue
    Analyte: Hexylamine
    Sn4+ - No Change Co3+ - Dark Green Cr3+ - Green
    Mn3+ - No Change Fe3+ - Red Co2+ - No Change
    Cu2+ - Blue Ru2+ - No Change Zn2+ - Green
    Ag2+ - Dark Blue 2H+ (Free Base “FB”) — Blue
    Analyte: Acetonitrile
    Sn4+ - Blue Co3+ - Dark Green Cr3+ - No Change
    Mn3+ - Yellow Fe3+ - Dark Green Co2+ - No Change
    Cu2+ - Blue Ru2+ - Blue (faint dot) Zn2+ - Blue
    Ag2+ - No Change 2H+ (Free Base “FB”) — Blue
    Analyte: Acetone
    Sn4+ - No Change Co3+ - No Change Cr3+ - Red (small dot)
    Mn3+ - No Change Fe3+ - No Change Co2+ - No Change
    Cu2+ - Dark Blue Ru2+ - No Change Zn2+ - Dark Blue
    Ag2+ - No Change 2H+ (Free Base “FB”) — Blue
    Analyte: THF
    Sn4+ - Dark Blue Co3+ - Green Cr3+ - Red
    Mn3+ - Blue (small dot) Fe3+ - Dark Green Co2+ - No Change
    Cu2+ - Blue Ru2+ - No Change Zn2+ - Blue
    Ag2+ - No Change 2H+ (Free Base “FB”) — Blue
    Analyte: CH2Cl2
    Sn4+ - Dark Blue Co3+ - No Change Cr3+ - No Change
    Mn3+ - Yellow and Red (small Fe3+ - No Change Co2+ - No Change
    dot)
    Cu2+ - Dark Blue Ru2+ - No Change Zn2+ - No Change
    Ag2+ - No Change 2H+ (Free Base “FB”) — Blue
    Analyte: CHCl3
    Sn4+ - Dark Blue Co3+ - Dark Green Cr3+ - Yellow (circle)
    Mn3+ - Yellow Fe3+ - Dark Green (very faint) Co2+ - No Change
    Cu2+ - Dark Blue (very faint) Ru2+ - No Change Zn2+ - Blue
    Ag2+ - Blue (very faint) 2H+ (Free Base “FB”) — Blue
    Analyte: P(OC2H5)3
    Sn4+ - No Change Co3+ - Yellow Cr3+ - Dark Green
    Mn3+ - No Change Fe3+ - Dark Green (very faint) Co2+ - Greenish Yellow
    Cu2+ - Dark Blue (faint) Ru2+ - No Change Zn2+ - Greenish Blue
    Ag2+ - Blue (very faint) 2H+ (Free Base “FB”) — Blue
    Analyte: P(C4H9)3
    Sn4+ - No Change Co3+ - Yellow and Red Cr3+ - Deep Red
    Mn3+ - No Change Fe3+ - Dark Green (faint) Co2+ - Red (with some yellow)
    Cu2+ - No Change Ru2+ - Dark Blue Zn2+ - Yellow
    Ag2+ - No Change 2H+ (Free Base “FB”) — No
    Change
    Analyte: C6H13SH
    Sn4+ - Green Co3+ - No Change Cr3+ - Yellow circle
    surrounded by greenish blue
    circle
    Mn3+ - Yellow Fe3+ - Dark Green Co2+ - No Change
    Cu2+ - Dark Blue (faint) Ru2+ - No Change Zn2+ - Green
    Ag2+ - Blue (very faint) 2H+ (Free Base “FB”) — Blue
    Analyte: (C3H7)2S
    Sn4+ - Dark Blue (faint) Co3+ - Deep Green Cr3+ - Green
    Mn3+ - No Change Fe3+ - Dark Green Co2+ - Dark Green (very faint)
    Cu2+ - Dark Blue (faint) Ru2+ - Green Zn2+ - Green
    Ag2+ - Blue (very faint) 2H+ (Free Base “FB”) — Blue
    Analyte: Benzene
    Sn4+ - No Change Co3+ - Green Cr3+ - Yellow (very faint)
    Mn3+ - Yellow (some green) Fe3+ - Dark Green Co2+ - No Change
    Cu2+ - No Change Ru2+ - No Change Zn2+ - Dark Green
    Ag2+ - No Change 2H+ (Free Base “FB”) — Blue
  • The degree of ligand softness (roughly their polarizability) increases from left to right, top to bottom as shown in FIG. 1. Each analyte is easily distinguished from the others, and there are family resemblances among chemically similar species (e.g., pyridine and n-hexylamine). Analyte distinction originates both in the metal-specific ligation affinities and in their specific, unique color changes upon ligation. Each analyte was delivered to the array as a nitrogen stream saturated with the analyte vapor at 20° C. (to ensure complete saturation, 30 min. exposures to vapor were used. Although these fingerprints were obtained by exposure to saturated vapors (thousands of ppm), unique patterns can be identified at much lower concentrations. [0062]
  • The [0063] metalloporphyrin array 16 has been used to quantify single analytes and to identify vapor mixtures. Because the images' color channel data (i.e., RGB values) vary linearly with porphyrin concentration, we were able to quantify single porphyrin responses to different analytes. Color channel data were collected for individual spots and plotted, for example, as the quantity (Rplt−Rspt)/(Rplt), where Rplt was the red channel value for the initial silica surface and Rspt the average value for the spot. For example, Fe(TFPP)(Cl) responded linearly to octylamine between 0 and 1.5 ppm. Other porphyrins showed linear response ranges that varied with ligand affinity (i.e., equilibrium constant).
  • EXAMPLE 3
  • The array of the present invention has demonstrated interpretable and reversible responses even to analyte mixtures of strong ligands, such as pyridines and phosphites, as is shown in FIG. 6. Color change patterns for the mixtures are distinct from either of the neat vapors. Good reversibility was demonstrated for this analyte pair as the vapor mixtures were cycled between the neat analyte extremes, as shown in FIG. 6, which shows the two component saturation responses to mixtures of 2-methylpyridine (“2MEPY”) and trimethylphosphite (“TMP”). Vapor mixtures were obtained by mixing the analyte-saturated N[0064] 2 streams at variable flow ratios. A single plate was first exposed to pure trimethylphosphite vapor in N2 (Scan A), followed by increasing mole fractions of 2-methylpyridine up to pure 2-methylpyridine vapor (Scan C), followed by decreasing mole fractions of 2-methylpyridine back to pure trimethylphosphite vapor. In both directions, scans were taken at the same mole fraction trimethylphosphite and showed excellent reversibility; scans at mole fractions at 67% trimethylphosphite (χtmp=0.67, Scans B and D) and of their difference map are shown (Scan E). Response curves for the individual porphyrins allow for quantification of the mixture composition. The colors of each dye upon exposure to the analytes TMP and 2MEPY are shown in FIG. 6 and are summarized in Table 5 below.
    TABLE 5
    Scan A, Analyte: Neat TMP
    Sn4+ - Dark Blue Co3+ - Yellow Cr3+ - No Change
    Mn3+ - Yellow with red center Fe3+ - Dark Green Co2+ - Greenish Yellow
    Cu2+ - Dark Blue Ru2+ - No Change Zn2+ - Blue
    Ag2+ - Green (very faint) 2H+ (Free Base “FB”) —
    Reddish Blue
    Scan B, Analyte: TMP,xTMP = 0.67
    Sn4+ - Blue Co3+ - Green Cr3+ - Green (small dot)
    Mn3+ - Yellow and Green Fe3+ - Green and Yellow Co2+ - Green with red center
    Cu2+ - Dark Blue Ru2+ - Purple (very faint) Zn2+ - Blue
    Ag2+ - Greenish Blue 2H+ (Free Base “FB”) —
    Reddish Blue
    Scan C, Analyte: Neat 2MEPY
    Sn4+ - Blue Co3+ - Green Cr3+ - No Change
    Mn3+ - Yellow and Green with Fe3+ - Red with some Yellow Co2+ - Green
    Red center
    Cu2+ - Dark Blue Ru2+ - Deep Blue Zn2+ - Green with some Blue
    Ag2+ - Green with some Blue 2H+ (Free Base “FB”) —
    Reddish Blue
    Scan D, Analyte: TMP,xTMP = 0.67
    Sn4+ - Blue Co3+ - Green Cr3+ - No Change
    Mn3+ - Yellow and Green Fe3+ - Green and Yellow Co2+ - Green
    Cu2+ - Dark Blue Ru2+ - Purple (very faint) Zn2+ - Blue
    Ag2+ - Greenish Blue (very 2H+ (Free Base “FB”) —
    faint) Reddish Blue
    Scan E
    Sn4+ - No Change Co3+ - No Change Cr3+ - No Change
    Mn3+ - No Change Fe3+ - No Change Co2+ - No Change
    Cu2+ - Blue (very faint) Ru2+ - Blue (small dot) Zn2+ - No Change
    Ag2+ - Blue (very faint) 2H+ (Free Base “FB”) — Green
  • EXAMPLE 4
  • In an effort to understand the origin of the color changes upon vapor exposure, diffuse reflectance spectra were obtained for single porphyrin spots before and after exposure to analyte vapors. Porphyrin solutions were spotted in 50 L aliquots onto a plate and allowed to dry under vacuum at 50° C. Diffuse reflectance spectra of the plate were then taken using a UV-visible spectrophotometer equipped with an integrating sphere. Unique spectral shifts were observed upon analyte exposure, which correlated well with those seen from solution ligation. For example, Zn(TPP) exposure to ethanol and pyridine gave unique shifts which were very similar to those resulting from ligand exposure in solution. FIG. 7 shows a comparison of Zn(TPP) spectral shifts upon exposure to ethanol and pyridine (py) in methylene chloride solution (A) and on the reverse phase support (B). In both A and B, the bands correspond, from left to right, to Zn(TPP), Zn(TPP)(C[0065] 2H5OH), and Zn(TPP)(py), respectively. Solution spectra (A) were collected using a Hitachi U-3300 spectrophotometer; Zn(TPP), C2H5OH, and py concentrations were approximately 2 μM, 170 mM, and 200 μM, respectively. Diffuse reflectance spectra (B) were obtained with an integrating sphere attachment before exposure to analytes, after exposure to ethanol vapor in N2, and after exposure to pyridine vapor in N2 for 30 min. each using the flow cell.
  • Improvement to Low Concentration Response [0066]
  • Color changes at levels as low as 460 ppb have been observed for octylamine vapor, albeit with slow response times due to the high surface area of the silica on the [0067] plate 18. The surface area of C2 plates is ≈350 m2/gram. Removal of excess silica gel surrounding the porphyrin spots from the plate 18 led to substantial improvements in response time for exposures to trace levels of octylamine. Because the high surface area of the reverse phase silica surface is primarily responsible for the increased response time, other means of solid support or film formation can be used to improve low concentration response.
  • Further, the present invention contemplates miniaturization of the array using small wells 60 (<1 mm), for example in glass, quartz, or polymers, to hold metalloporphyrin or other dyes as thin films, which are deposited as a solution, by liquid droplet dispersion (e.g., airbrush or inkjet), or deposited as a solution of polymer with metalloporphyrin. [0068]
  • These embodiments are depicted in FIGS. 8, 9, and [0069] 10. FIG. 8 illustrates the interfacing of a microplate 60 into an assembly consisting of a CCD 70, a microplate 72 and a light source 74. FIG. 9 illustrates another embodiment of the present invention, and more particularly, a microwell porphyrin array weliplate 80 constructed from polydimethylsiloxane (PDMS). The colors of the dyes shown in FIG. 9 are summarized below in Table 6.
    TABLE 6
    Sn4+ - Dark Red Co3+ - Dark Red Cr3+ - Dark Green
    Mn3+ - Green Fe3+ - Dark Red Co2+ - Yellowish Green
    Cu2+ - Deep Red Ru2+ - Dark Red Zn2+ - Red with some
    Yellow
    Ag2+ - Red 2H+ (Free Base “FB”) —
    Red
  • FIG. 10 demonstrates deposition of metalloporphyrin/polymer (polystyrene/dibutylphthalate) solutions upon a plate, which includes a series of micro-machined Teflon® posts [0070] 100 having the same basic position relative to each other as shown in FIG. 2A and FIG. 2B. The colors for the dyes in the middle of FIG. 10 are summarized in Table 7 below.
    TABLE 7
    Sn4+ - Yellow Co3+ - Orange Cr3+ - Yellow
    Mn3+ - Yellow Fe3+ - Orange Co2+ - Orange
    Cu2+ - Orange Ru2+ - Dark Yellow Zn2+ - Orange
    Ag2+ - Orange 2H+ (Free Base “FB”) — Red
  • The colors for the dyes on the right hand side of FIG. 10 are summarized in Table 8 below. [0071]
    TABLE 8
    Sn4+ - No Change Co3+ - Green Cr3+ - Red
    Mn3+ - Blue Fe3+ - Red Co2+ - Red, Green, Blue, and
    Yellow
    Cu2+ - Green with some Blue Ru2+ - Blue (very faint) Zn2+ - Yellow with some Red
    Ag2+ - Green with some Blue 2H+ (Free Base “FB”) — Green
    with some Blue
  • EXAMPLE 5
  • FIG. 11 shows the color profile changes from a microplate of the type shown in FIG. 10. The microplate, consisting of a minimized array of four metalloporphyrins, i.e., Sn(TPP)(CL[0072] 2), Co(TPP)(Cl), Zn(TPP), Fe(TFPP)(Cl), clockwise from the upper left (where TFPP stands for 5,10,15,20-tetrakis(pentafluorophenyl)porphyrinate). The color profile changes are shown in FIG. 11 after exposure to low levels of n-octylamine, dodecanethiol (C12H25 SH), and tri-n-butylphosphine (P(C4H9)3), each at 1.8 ppm, which is summarized in Table 9 below.
    TABLE 9
    Dyes on Teflon ®
    Sn — Dark Yellow Co — Red
    Zn — Red Fe — Orange with Red outline
    Dyes exposed to n-octylamine
    Sn — No Change Co — Green (very faint)
    Zn — Red Fe — Green
    Dyes exposed to C12H25SH
    Sn — Red Co — Green with some red, yellow and blue
    (faint)
    Zn — Red with some green and yellow Fe — Blue (very faint)
    Dyes exposed to P(C4H9)3
    Sn — No Change Co — Yellow with red center and some red periphery
    Zn — Green Fe — Yellow with some Green and Blue
  • The low ppm levels of octylamine, an analyte of interest, were generated from temperature-regulated octylamine/dodecane solutions with the assumption of solution ideality. The dodecane acts as a diluent to lower the level of octylamine vapor pressure for the purposes of this demonstration of the invention. [0073]
  • EXAMPLE 6
  • FIG. 12 illustrates the immunity of the present invention to interference from water vapor. The hydrophobicity of the reverse phase support greatly any possible effects from varying water vapor in the atmosphere to be tested. For instance, as shown in FIG. 12, a color fingerprint generated from exposure of the array to n-hexylamine (0.86% in N[0074] 2) was identical to that for n-hexylamine spiked heavily with water vapor (1.2% H2O, 0.48% hexylamine in N2). See scans 120, 122 and 124. The ability to easily detect species in the presence of a large water background represents a substantial advantage over mass-sensitive sensing techniques or methodologies that employ polar polymers as part of the sensor array. The color patterns shown in FIG. 12 are summarized in Table 10 below.
    TABLE 10
    Scan 120
    Sn4+ - No Change Co3+ - Green Cr3+ - Green
    Mn3+ - No Change Fe3+ - Red Co2+ - No Change
    Cu2+ - No Change Ru2+ - No Change Zn2+ - Green
    Ag2+ - No Change 2H+ (Free Base “FB”) — Dark
    Blue
    Scan
    122
    Sn4+ - No Change Co3+ - Green Cr3+ - Green
    Mn3+ - No Change Fe3+ - Red Co2+ - No Change
    Cu2+ - No Change Ru2+ - Green (small dot) Zn2+ - Green
    Ag2+ - No Change 2H+ (Free Base “FB”) — Dark
    Blue
    Scan
    124
    Sn4+ - Bluish Circle Co3+ - Bluish Circle Cr3+ - Bluish Circle
  • [0075]
    Sn4+ - Bluish Circle Co3+ - Bluish Circle Cr3+ - Bluish Circle
    Mn3+ - Bluish Circle Fe3+ - Bluish Circle Co2+ - Bluish Circle
    Cu2+ - Bluish Circle Ru2+ - Bluish Circle Zn2+ - Bluish Circle
    Ag2+ - Bluish Circle 2H+ (Free Base “FB”) — Bluish Circle
  • Additional Features of the Preferred Embodiments of the Invention [0076]
  • Having demonstrated electronic differentiation, an important further goal is the shape-selective distinction of analytes (e.g., n-hexylamine vs. cyclohexylamine). Functionalized metalloporphyrins that limit steric access to the metal ion are candidates for such differentiation. For instance, we have been able to control ligation of various nitrogenous ligands to dendrimer-metalloporphyrins and induce selectivities over a range of more than 10[0077] 4. As an initial attempt toward shape-selective detection, we employed the slightly-hindered tetrakis(2,4,6-trimethoxyphenyl)porphyrins (TTMPP) in our sensing array. With these porphyrins, fingerprints for t-butylamine and n-butylamine showed subtle distinctions, as did those for cyclohexylamine and n-hexylamine. Using more hindered metalloporphyrins, it is contemplated that the present invention can provide greater visual differentiation. Such porphyrins include those whose periphery is decorated with dendrimer, siloxyl, phenyl, t-butyl and other bulky substituents, providing sterically constrained pockets on at least one face (and preferably both) of the porphyrin.
  • In a similar fashion, it is contemplated that the sensor plates of the present invention can be used for the detection of analytes in liquids or solutions, or solids. A device that detects an analyte in a liquid or solution or solid can be referred to as an artificial tongue. Proper choice of the metal complexes and the solid support must preclude their dissolution into the solution to be analyzed. It is preferred that the surface support repel any carrier solvent to promote the detection of trace analytes in solution; for example, for analysis of aqueous solutions, reverse phase silica has advantages as a support since it will not be wetted directly by water. [0078]
  • Alternative sensors in accordance with the present invention may include any other dyes or metal complexes with intense absorbance in the ultraviolet, visible, or near infrared spectra that show a color change upon exposure to analytes. These alternative sensors include, but are not limited to, a variety of macrocycles and non-macrocycles such as chlorins and chlorophylls, phthalocyanines and metallophthalocyanines, salen-type compounds and their metal complexes, or other metal-containing dyes. [0079]
  • The present invention can be used to detect a wide variety of analytes regardless of physical form of the analytes. That is, the present invention can be used to detect any vapor emitting substance, including liquid, solid, or gaseous forms, and even when mixed with other vapor emitting substances, such solution mixtures of substances. [0080]
  • The present invention can be used in combinatorial libraries of metalloporphyrins for shape selective detection of substrates where the substituents on the periphery of the macrocycle or the metal bound by the porphyrin are created and then physically dispersed in two dimensions by (partial) chromatographic or electrophoretic separation. [0081]
  • The present invention can be used with chiral substituents on the periphery of the macrocycle for identification of chiral substrates, including but not limited to drugs, natural products, blood or bodily fluid components. [0082]
  • The present invention can be used for analysis of biological entities based on the surface proteins, oligosacharides, antigens, etc., that interact with the metalloporphyrin array sensors of the present invention. Further, the sensors of the present invention can be used for specific recognition of individual species of bacteria or viruses. [0083]
  • The present invention can be used for analysis of nucleic acid sequences based on sequence specific the surface interactions with the metalloporphyrin array sensors. The sensors of the present invention can be used for specific recognition of individual sequences of nucleic acids. Substituents on the porphyrins that would be particularly useful in this regard are known DNA intercalating molecules and nucleic acid oligomers. [0084]
  • The present invention can be used with ordinary flat bed scanners, as well as portable miniaturized detectors, such as CCD detectors with microarrays of dyes such as metalloporphyrins. [0085]
  • The present invention can be used for improved sensitivity, automation of pattern recognition of liquids and solutions, and analysis of biological and biochemical samples. [0086]
  • Superstructure Bonded to the Periphery of the Porphyrin [0087]
  • The present invention includes modified porphyrins that have a super structure bonded to the periphery of the porphyrin. A super structure bonded to the periphery of the porphyrin in accordance with the present invention includes any additional structural element or chemical structure built at the edge of the porphyrin and bonded thereto. [0088]
  • The super structures can include any structural element or chemical structure characterized in having a certain selectivity. Those of skill in the art will recognize that the super structures of the present invention include structures that are shape selective, polarity selective, inantio selective, regio selective, hydrogen bonding selective, and acid-base selective. This structures can include siloxyl-substituted substituents, nonsiloxyl-substituted substituents and nonsiloxyl-substituted substituents, including but not limited to aryl substituents, alkyl substituents, and organic, organometallic, and inorganic functional group substituents. [0089]
  • Superstructure Bis-Pocket Porphyrins [0090]
  • A number of modified porphyrins have been synthesized to mimic various aspects of the enzymatic functions of heme proteins, especially oxygen binding (myoglobin and hemoglobin) and substrate oxidation (cytochrome P-450). See Suslick, K. S.; Reinert, T. J. J. Chem. Ed. 1985, 62, 974; Collman, J. P.; Zhang, X.; Lee, V. J.; Uffelman, E. S.; Brauman, J. I. Science 1993, 261, 1404; Collman, J. P.; Zhang, X. in Comprehensive Supramolecular Chemistry; Atwood, J. L.; Davies, J. E. D.; MacNicol, D. D.; Vogtel, F. Eds.; Pergamon: New York, 1996; vol. 5, pp. 1-32; Suslick, K. S.; van Deusen-Jeffries, S. in Comprehensive Supramolecular Chemistry; Atwood, J. L.; Davies, J. E. D.; MacNicol, D. D.; Vogtel, F. Eds.; Pergamon: New York, 1996; vol.5, pp. 141-170; Suslick, K. S. in Activation and Functionalization of Alkanes; Hill, C. L., ed.; Wiley & Sons: New York, 1989; pp. 219-241. The notable property of many heme proteins is their remarkable substrate selectivity; the development of highly regioselective synthetic catalysts, however, is still at an early stage. Discrimination of one site on a molecule from another and distinguishing among many similar molecules presents a difficult and important challenge to both industrial and biological chemistry. See Metalloporphyrins in Catalytic Oxidations; Sheldon, R. A. Ed. Marcel Dekker: New York, 1994). Although the axial ligation properties of simple synthetic metalloporphyrins are well documented in literature, see Bampos, N.; Marvaud, V.; Sanders, J. K. M. Chem. Eur. J. 1998, 4, 325; Stibrany, R. T.; Vasudevan, J.; Knapp, S.; Potenza, J. A.; Emge, T.; Schugar, H. J. J. Am. Chem. Soc. 1996, 118, 3980, size and shape control of ligation to peripherally modified metalloporphyrins has been largely unexplored, with few notable exceptions, where only limited selectivities have been observed. See Bhyrappa, P.; Vaijayanthimala, G.; Suslick, K. S. J. Am. Chem. Soc. 1999, 121, 262; Imai, H.; Nakagawa, S.; Kyuno, E. J. Am. Chem. Soc. 1992, 114, 6719. [0091]
  • The present invention includes the synthesis, characterization and remarkable shape-selective ligation of silylether-metalloporphyrin scaffolds derived from the reaction of 5,10,15,20-tetrakis(2′,6′-dihydroxyphenyl)porphyrinatozinc(II) with t-butyldimethylsilyl chloride, whereby the two faces of the Zn(II) porphyrin were protected with six, seven, or eight siloxyl groups. This results in a set of three porphyrins of nearly similar electronics but with different steric encumbrance around central metal atom present in the porphyrin. Ligation to Zn by classes of different sized ligands reveal shape selectivities as large as 10[0092] 7.
  • A family of siloxyl-substituted bis-pocket porphyrins were prepared according to the scheme of FIG. 13. The abbreviations of the porhyrins that can be made in accordance with the scheme shown in FIG. 13 are as follows: [0093]
  • Zn(TPP), 5,10,15,20-tetraphenylporphyrinatozinc(II); [0094]
  • Zn[(OH)[0095] 6PP], 5-phenyl-10,15,20-tris(2/,6/-dihydroxyphenyl)porphyrinatozinc(II);
  • Zn[(OH)[0096] 8PP], 5,10,15,20-tetrakis(2/,6/-dihydroxyphenyl)porphyrinatozinc(II);
  • Zn(Si[0097] 6PP), 5(phenyl)-10,15,20-trikis(2/,6/-disilyloxyphenyl)porphyrinatozinc(II);
  • Zn(Si[0098] 7OHPP), 5,10,15-trikis(2/,6/-disilyloxyphenyl)-20-(2/-hydroxy-6/-silyloxyphenyl)porphyrinatozinc(II);
  • Zn(Si8PP), 5,10,15,20-tetrakis(2/,6/-disilyloxyphenyl)porphyrinatozinc(II). The synthesis of Zn[(OH)[0099] 6PP], Zn(Si6PP), and Zn(Si8PP) is detailed below. Zn[(OH)6PP] and Zn[(OH)8PP] were obtained (see Bhyrappa, P.; Vaijayanthimala, G.; Suslick, K. S. J. Am. Chem. Soc. 1999, 121, 262) from demethylation (see Momenteau, M.; Mispelter, J.; Loock, B.; Bisagni, E. J. Chem. Soc. Perkin Trans. 1, 1983, 189) of corresponding free base methoxy compounds followed by zinc(II) insertion. The methoxy porphyrins were synthesized by acid catalysed condensation of pyrrole with respective benzaldehydes following Lindsey procedures. See Lindsey, J. S.; Wagner, R. W. J. Org. Chem. 1989, 54, 828. Metalation was done in methanol with Zn(O2CCH3)2. The t-butyldimethylsilyl groups were incorporated into the metalloporphyrin by stirring a DMF solution of hydroxyporphyrin complex with TBDMSiCl (i.e., t-butyldimethylsilyl chloride) in presence of imidazole. See Corey, E. J; Venkateswarlu, A. J. Am. Chem. Soc. 1972, 94, 6190. The octa (Zn(Si8PP)), hepta (Zn(Si7OHPP)), and hexa (Zn(Si6PP)) silylether porphyrins were obtained from Zn[(OH)gPP] and Zn[(OH)6PP], respectively. The compounds were purified by silica gel column chromatography and fully characterized by UV-Visible, 1H-NMR, HPLC, and MALDI-TOF MS.
  • The size and shape selectivities of the binding sites of these bis-pocket Zn silylether porphyrins were probed using the axial ligation of various nitrogenous bases of different shapes and sizes in toluene at 25° C. Zn(II) porphyrins were chosen because, in solution, they generally bind only a single axial ligand. Successive addition of ligand to the porphyrin solutions caused a red-shift of the Soret band typical of coordination to zinc porphyrin complexes. There is no evidence from the electronic spectra of these porphyrins for significant distortions of the electronic structure of the porphyrin. The binding constants (K[0100] eq) and binding composition (always 1:1) were evaluated using standard procedures. See Collman, J. P.; Brauman, J. I.; Doxsee, K. M.; Halbert, T. R.; Hayes, S. E.; Suslick, K. S. J. Am. Chem. Soc. 1978, 100,2761; Suslick, K. S.; Fox, M. M.; Reinert, T. J. Am. Chem. Soc. 1984, 106, 4522. The Kq values of the silylether porphyrins with nitrogenous bases of different classes are compared with the sterically undemanding Zn(TPP) in FIGS. 14a, 14 b, and 14 c. It is worth noting the parallel between shape selectivity in these equilibrium measurements and prior kinetically-controlled epoxidation and hydroxylation. See Collman, J. P.; Zhang, X. in Comprehensive Supramolecular Chemistry; Atwood, J. L.; Davies, J. E. D.; MacNicol, D. D.; Vogtel, F. Eds.; Pergamon: New York, 1996; vol. 5, pp. 1-32; Suslick, K. S.; van Deusen-Jeffries, S. in Comprehensive Supramolecular Chemistry; Atwood, J. L.; Davies, J. E. D.; MacNicol, D. D.; Vogtel, F. Eds.; Pergamon: New York, 1996; vol. 5, pp. 141-170; Suslick, K. S. in Activation and FunctionalizationofAlkanes; Hill, C. L., ed.; Wiley& Sons: New York, 1989; pp.219-241; Bhyrappa, P.; Young, J.K.; Moore, J.S.; Suslick, K. S. J. Am. Chem. Soc., 1996,118,5708-5711. Suslick, K. S.; Cook, B. R. J. Chem. Soc., Chem. Comm. 1987, 200-202; Cook, B. R.; Reinert, T. J.; Suslick, K. S. J. Am. Chem. Soc. 1986, 108, 7281-7286; Suslick, K. S.; Cook, B. R.; Fox, M. M. J. Chem. Soc., Chem. Commun. 1985, 580-582. The selectivity for equilibrated ligation appears to be substantially larger than for irreversible oxidations of similarly shaped substrates.
  • The binding constants of silylether porphyrins are remarkably sensitive to the shape and size of the substrates relative to Zn(TPP). See FIGS. 14[0101] a, 14 b, and 14 c. The binding constants of different amines could be controlled over a range of 101 to 107 relative to Zn(TPP). It is believed that these selectivities originate from strong steric repulsions created by the methyl groups of the t-butyldimethylsiloxyl substituents. The steric congestion caused by these bulky silylether groups is pronounced even for linear amines and small cyclic amines (e.g., azetidine and pyrrolidine).
  • There are very large differences in K[0102] eq for porphyrins having three versus four silylether groups on each face (e.g., hexa- vs. octa-silylether porphyrins), as expected based on obvious steric arguments (see FIGS. 14a, 14 b, and 14 c). Even between the hexa-over hepta-silylether porphyrins, however, there are still substantial differences in binding behavior. It is believed that this is probably due to doming of the macrocycle in the hexa- and hepta-silylether porphyrins, which lessens the steric constraint relative to the octasilylether porphyrin. Such doming will be especially important in porphyrins whose two faces are not identical. The free hydroxy functionality of the hepta-silylether may play a role in binding of bi-functionalized ligands (e.g., free amino acids); for the simple amines presented here, however, we have no evidence of any special effects.
  • These silylether porphyrins showed remarkable selectivities for normal, linear amines over their cyclic analogues. For a series of linear amines (n-propylamine through n-decylamine), K[0103] eq were very similar for each of the silylether porphyrins. In comparison, the relative Keq for linear versus cyclic primary amines (FIG. 14a, n-butylamine vs. cyclohexylamine) were significantly different: Keq linear/Keq cyclic ranges from 1 to 23 to 115 to >200 for Zn(TPP), Zn(Si6PP), Zn(Si7OHPP), and Zn(SigPP), respectively. The ability to discriminate between linear and cyclic compounds is thus established.
  • A series of cyclic 2° amines (FIG. 14[0104] b) demonstrate the remarkable size and shape selectivities of this family of bis-pocket porphyrins. Whereas the binding constants to Zn(TPP) with those amines are virtually similar. In contrast, the Keq values for silylether porphyrins strongly depend on the ring size and its peripheral substituents. The effect of these shape-selective binding sites is clear, even for compact aromatic ligands with non-ortho methyl substituents (FIG. 14c).
  • The molecular structures of these silylether porphyrins explains their ligation selectivity. The x-ray single crystal structure of Zn(Si[0105] 8PP) has been solved in the triclinic P lbar space group. See Single crystal x-ray structure of Zn(Si8PP) shown in FIG. 15. As shown in FIG. 15, Zn(Si6PP) (energy minimized molecular model) and Zn(Si8PP) (single crystal x-ray structure) have dramatically different binding pockets. In the octasilylether porphyrin, the top access on both faces of the porphyrin is very tightly controlled by the siloxyl pocket. In contrast, the metal center of the hexasilylether porphyrin is considerably more exposed for ligation.
  • FIG. 15 illustrates molecular models of Zn(Si[0106] 6PP) (left column) and Zn(Si8PP) (right column). The pairs of images from top to bottom are cylinder side-views, side-views, and top-views, respectively; space filling shown at 70% van der Waals radii; with the porphyrin carbon atoms shown in purple, oxygen atoms shown in red, silicon atoms in green, and Zn in dark red. The x-ray single crystal structure of Zn(Si8PP) is shown; for Zn(Si6PP), an energy-minimized structure was obtained using Cerius 2 from MSI.
  • In summary, a series of bis-pocket siloxyl metalloporphyrin complexes were prepared with sterically restrictive binding pockets on both faces of the macrocycle. Ligation to Zn by various nitrogenous bases of different sizes and shapes were investigated. Shape selectivities as large as 10[0107] 7 were found, compared to unhindered metalloporphyrins. Fine-tuning of ligation properties of these porphyrins was also possible using pockets of varying steric demands. The shape selectivities shown here rival or surpass those of any biological system.
  • Examples of Synthesis of Super Structures [0108]
  • Synthesis of 5-phenyl-10,15,20-tris(2/,6/-dihydroxy-phenyl)-porphyrinatozinc(II), Zn[(OH)[0109] 6PP]:
  • The free base 5-phenyl-10,1 5,20-tris(2/,6/-dimethoxyphenyl)-porphyrin was synthesized by Lewis acid catalyzed condensation of 2,6-dimethoxybezaldehyde and benzaldehyde with pyrrole (3:1:4 mole ratio) following the Lindsey procedure. See Lindsey, J. S.; Wagner, R. W. J. Org. Chem. 1989, 54, 828. The mixture of products thus formed was purified by silica gel column chromatography (if necessary, using CH[0110] 2Cl2 as eluant). The isolated yield of the desired product was found to be 7% (wrt pyrrole used). The corresponding hydroxyporphyrins were obtained by demethylation with pyridine hydrochloride. See Momenteau, M.; Mispelter, J.; Loock, B.; Bisagni, E. J. Chem. Soc. Perkin Trans. 1, 1983, 189. After typical work-up known to those skilled in the art, the crude compound was purified by silica gel column chromatography using ethylacetate as eluant. The first fraction was Zn[(OH)6PP], which was collected and the solvent was removed. The yield of the product was 90% (based on starting hydroxyporphryin). 1H NMR of H2[(OH)6PP] in acetone-d6 (pPm): 8.96-8.79 (m, 8H, b-pyrrole H), 8.24 (m, 2H, o-H 5-Phenyl), 8.07 and 8.02 (2s, 6H, —OH), 7.83 (m, 3H, m,p-H 5-Phenyl), 7.50 (t, 3H, p-H hydroxyphenyl), 6.90 (d, 6H, m-H hydroxyphenyl), −2.69 (s, 2H, imino-H). Elemental analysis, calcd. for C44H30O6N4.H2O: C=72.5, H=4.4 and N=7.7%. Found C=72.7, H=4.4 and N=7.4%. The compound showed molecular ion peak at 711 (m/z calcd. for C44H30O6N4=710) in FAB-MS.
  • The Zn derivative was obtain by stirring methanol solution of H[0111] 2[(OH)6PP] with excess Zn(O2CCH3)22H2O for 1 hour. Methanol was evaporated to dryness and the residue was dissolved in ethylacetate, washed with water, and the organic layer passed through anhyd. Na2SO4. The concentrated ethylacetate solution was passed through a silica gel column and the first band was collected as the desired product. The yield of the product was nearly quantitative. 1H NMR of Zn(OH)6PP in acetone-d6 (ppm): 8.95-8.79 (m, 8H, b-pyrrole H), 8.22 (m, 2H, o-H 5-Phenyl), 7.79 (m, 3H, m,p-H 5-Phenyl), 7.75 and 7.65 (2s, 6H, —OH), 7.48 (t, 3H, p-H hydroxyphenyl), 6.88 (d, 6H, m-H hydroxyphenyl). Elemental analysis, calcd. for ZnC44H28O6N4.H2O: C=66.7, H=3.8, N=7.1 and Zn=8.3%. Found C=66.4, H=3.8, N=6.7 and Zn=8.2%. The compound showed molecular ion peak at 774 (m/z calcd. for ZnC44H28O6N4=773) in FAB-MS.
  • Synthesis of 5-phenyl-10,15,20-tris(2/,[0112] 6/-disilyloxyphenyl)-porphyrinatozinc(II), Zn(Si6PP):
  • The hexasilylether porphyrin was synthesized by stirring a DMF solution of 5-phenyl-10,15,20-tris(2/,6/-dihydroxyphenyl)-porphyrinatozinc(II) (100 mg, 0.13 mmol) with t-butyldimethyl silylchloride (1.18 g, 7.8 mmol) in presence of imidazole (1.2 g, 17.9 mmol) at 60° C. for 24 h under nitrogen. After this period the reaction mixture was washed with water and extracted in CHCl[0113] 3. The organic layer was dried over anhyd. Na2SO4. The crude reaction mixture was loaded on a short silica gel column and eluted with mixture of CHCl3/petether (1:1, v/v) to get rid of unreacted starting material and lower silylated products. The desired compound was further purified by running another silica gel column chromatography using mixture of CHCl3/petether (1:3, v/v) as eluant. The yield of the product was 60% based on starting hydroxyporphyrin.
  • [0114] 1H NMR in chloroform-d (ppm): 8.94-8.82 (m, 8H, b-pyrrole H), 8.20 (m, 2H, o-H 5-Phenyl), 7.74 (m, 3H, m,p-H 5-Phenyl), 7.49 (t, 3H, p-H hydroxyphenyl), 6.91 (t, 6H, m-H hydroxyphenyl), −0.02 and −0.34 (2s, 54H, t-butyl H), −0.43, −0.78 and −1.01 (3s, 36H, methyl H).
  • Elemental analysis, calcd. for ZnC[0115] 80H112O6N4Si6: C=65.8, H=7.7, N=3.8, Si=11.5 and Zn=4.5%. Found C=65.5, H=7.7, N=3.8, Si=11.2 and Zn=4.4%. The low resolution MALDI-TOF mass spectrum showed molecular ion peak at 1457 (m/z calcd. for ZnC80H112O6N4Si6=1458).
  • Synthesis of 5,10,15-tris(2/,6/-disilyoxyphenyl)-20-(2/-hydr-oxy-6/-silyloxyphenyl)porphyrinatozinc(II), [Zn(Si[0116] 7OHPP)], and 5,10,15,20-tetrakis(2/,6/-disilyloxyphenyl)porphy-rinato-zinc(II), [Zn(Si8PP)]:
  • The synthesis of [0117] precursor porphyrin 5,10,15,20-tetrakis-(2/,6/-dihydroxyphenyl)porphyrin and its Zn derivative was accomplished as reported earlier. See Bhyrappa, P.; Vaijayanthimala, G.; Suslick, K. S. J. Am. Chem. Soc. 1999,121,262. The hepta- and octa-silylether porphyrins were synthesized by stirring DMF solution of 5,10,15,20-tetrakis(2/,6/-dihydroxyphenyl)porphyrinatozinc(II) (100 mg, 0.12 mmol) with t-butyldimethyl silylchloride (1.45 g, 9.6 mmol) in presence of imidazole (1.50 g, 22.1 mmol) at 60° C. for 24 h under nitrogen. After usual work-up the mixture of crude products were loaded on a silica gel column and eluted with mixture of CHCl3/pet. ether (1: 1, v/v) to remove unreacted starting material and lower silylated products. The major product isolated from this column is a mixture of hepta- and octa-silylated porphyrins. The mixture thus obtained was further purified by another silica gel column chromatography using mixture of CHCl3/pet. ether (1:3, v/v) as eluant. The first two bands were isolated as octa- and hepta-silylether porphyrin at 45% and 30% yield, respectively. Both the compounds were characterized by UV-Visible, 1H NMR and MALDI-TOF spectroscopic techniques. The homogeneity of the sample was verified by HPLC.
  • For Zn(Si[0118] 7OHPP), 1HNMR in chloroform-d (ppm): 8.91 (m, 8H, b-pyrrole H), 7.50 (m, 4H, p-H), 7.01-6.81 (m, 8H, m-H), 0.11 to −0.03 (12s, 105H, t-butyl and methyl H). Elemental analysis, caled. for ZnC86H126O8N4Si7: C=64.3, H=7.8, N=3.5, Si=12.3 and Zn=4.1%. Found C=63.6, H=8.1, N=3.5, Si=12.1 and Zn=3.9%. The low resolution MALDI-TOF mass spectrum showed molecular ion peak at 1604 (m/z calcd. for ZnC86H126O8N4Si7=1604).
  • For Zn(Si[0119] 8PP), 1H NMR in chloroform-d (ppm): 8.89 (s, 8H, b-pyrrole H), 7.49 (t, 4H, p-H), 6.92 (d, 8H, m-H), 0.09 (s, 72H, t-butyl H), −1.01 (s, 48H, methyl H). Elemental analysis, calcd. for ZnC92H140O8N4Si8: C=64.2, H=8.1, N=3.3, Si=13.1 and Zn=3.8%. Found C=63.5, H=8.4, N=3.3, Si=12.8 and Zn=4.0%. The low resolution MALDI-TOF mass spectrum showed molecular ion peak at 1719 (m/z calcd. for ZnC92H140O8N4Si8=1718).
  • Additional Features of the Preferred Embodiments of the Invention [0120]
  • Having demonstrated electronic differentiation and shape-selective distinction of analytes that bind to metal ions in metallodyes, an important further goal is the differentiation of analytes that do not bind or bind only weakly to metal ions. Such analytes include acidic compounds, such as carboxylic acids, and certain organic compounds lacking ligatable functionality, such as simple alkanes, arenes, some alkenes and alkynes (especially if sterically hindered), and molecules sterically hindered as to preclude effective ligation. One approach that has been developed to achieve this goal in accordance with the present invention is to include in the sensor array other chemoresponsive dyes, including pH sensitive dyes (i.e., pH indicator or acid-base indicator dyes that change color upon exposure to acids or bases), and/or solvatochromic dyes (i.e., dyes that change color depending upon the local polarity of their micro-environment). [0121]
  • It has been discovered that the addition of pH sensitive dyes and solvatochromic dyes to other arrays containing metalloporphyrins as described above expands the range of analytes to which the arrays are sensitive, improves sensitivities to some analytes, and increases the ability to discriminate between analytes. [0122]
  • The present invention includes an artificial nose comprising an array, the array comprising at least a first dye and a second dye deposited directly onto a single support in a predetermined pattern combination, the combination of the dyes in the array having a distinct and direct spectral absorbance or reflectance response to an analyte wherein the first dye and the second dye are selected from the group consisting of chemoresponsive dyes, and the second dye is distinct from the first dye. In a preferred embodiment, the first dye is selected from the group consisting of porphyrin, chlorin, chlorophyll, phtahlocyanine, and salen and their metal complexes. In another preferred embodiment, the second dye is selected from the group of dyes consisting of acid-base indicator dyes and solvatochromic dyes. [0123]
  • The present invention includes a method of detecting an analyte comprising the steps of: (a) forming an array of at least a first dye and a second dye deposited directly onto a single support in a predetermined pattern combination, the combination of the dyes in the array having a distinct and direct spectral absorbance or reflectance response to an analyte wherein the first dye and the second dye are selected from the group consisting of chemoresponsive dyes, and the second dye is distinct from the first dye; (b) subjecting the array to an analyte; (c) inspecting the array for a distinct and direct spectral absorbance or reflectance response; and (d) correlating the distinct and direct spectral response to the presence of the analyte. In a preferred method, the first dye is selected from the group consisting of porphyrin, chlorin, chlorophyll, phtahlocyanine, and salen and their metal complexes. In another preferred method, the second dye is selected from the group of acid-base indicator dyes and solvatochromic dyes. [0124]
  • The present invention includes an artificial tongue comprising an array, the array comprising at least a first dye and a second dye deposited directly onto a single support in a predetermined pattern combination, the combination of the dyes in the array having a distinct and direct spectral absorbance or reflectance response to an analyte wherein the first dye and the second dye are selected from the group consisting of chemoresponsive dyes, and the second dye is distinct from the first dye. In a preferred embodiment, the first dye is selected from the group consisting of porphyrin, chlorin, chlorophyll, phtahlocyanine, and salen and their metal complexes. In another preferred embodiment, the second dye is selected from the group of dyes consisting of acid-base indicator dyes and solvatochromic dyes. [0125]
  • Chemoresponsive dyes are those dyes that change color, in either reflected or absorbed light, upon changes in their chemical environment. Three general classes of chemoresponsive dyes are (1) Lewis acid/base dyes, (2) pH indicator dyes, and (3) solvatochromic dyes. [0126]
  • Lewis acid/base dyes are those dyes that contain a Lewis acidic or basic center (where a Lewis acid is an electron pair acceptor and a Lewis base is an electron pair donor) and change color in response to changes in the Lewis acidity or basicity of their environment. A specific set of Lewis acid/base dyes includes dyes such as porphyrin, chlorin, chlorophyll, phtahlocyanine, and salen and their metal complexes. [0127]
  • pH indicator or acid-base indicator dyes are those that change color in response to changes in the proton acidity or basicity (also called Bronsted acidity or basicity) of their environment. A specific set of pH indicator dyes include Chlorphenol Red, Bromocresol Green, Bromocresol Purple, Bromothymol Blue, Phenol Red, Thymol Blue, Cresol Red, Alizarin, Mordant Orange, Methyl Orange, Methyl Red, Congo Red, Victoria Blue B, Eosin Blue, Fat Brown B, Benzopurpurin 4B, Phloxine B, Orange G, Metanil Yellow, Naphthol Green B, Methylene Blue, Safranine O, Methylene Violet 3RAX, Sudan Orange G, Morin Hydrate, Neutral Red, Disperse Orange 25, Rosolic Acid, Fat Brown RR, Cyanidin chloride, 3,6-Acridineamine, 6′-Butoxy-2,6-diamino-3,3′-azodipyridine, para-Rosaniline Base, Acridine Orange Base, Crystal Violet, and Malachite Green Carbinol Base. [0128]
  • Solvatochromic dyes are those that change color in response to changes in the general polarity of their environment, primarily through strong dipole-dipole interactions. To some extent, all dyes inherently are solvatochromic, although some are much more responsive than others. A specific set of highly responsive solvatochromic dyes include Reichardt's Dye and Nile Red. [0129]
  • It has been discovered that the following pH indicator (i.e., acid-base indicator) dyes and solvatochromic dyes are useful to expand the range of analytes to which the arrays containing metalloporphyrins are sensitive, improve sensitivities to some analytes, and increase the ability to discriminate between analytes. Those skilled in the art will recognize that other modifications and variations in the choice of such auxiliary dyes may be made in addition to those described and illustrated herein without departing from the spirit and scope of the present invention. Accordingly, the choice of dyes described and illustrated herein should be understood to be illustrative only and not limiting upon the scope of the present invention. [0130]
  • Chlorphenol Red [0131]
  • Molecular Formula: Cl[0132] 9H12Cl2O5S
  • Molecular Weight: 423.28 [0133]
  • CAS: 4430-20-0 [0134]
  • Transition interval: pH 4.8 (yellow) to pH 6.7 (violet) [0135]
  • Bromocresol Green [0136]
  • Synonyms: 3′,3″,5′,5″Tetrabromo-m-cresolsulfonphthalein; Bromcresol Green [0137]
  • Molecular Formula: C[0138] 21H14Br4O5S
  • Molecular Weight: 698.04 [0139]
  • CAS: 76-60-8 [0140]
  • pH=3.8 yellow [0141]
  • =5.4 blue [0142]
  • Bromocresol Purple [0143]
  • Synonyms: 5′,5″ dibromo-m-cresolsulfonphthalein; Bromcresol Purple [0144]
  • Molecular Formula: C[0145] 21H16Br2O5S
  • Molecular Weight: 698.04 [0146]
  • CAS:1 15-40-2 [0147]
  • pH=5.2 yellow [0148]
  • =6.8 blue [0149]
  • Bromothymol Blue [0150]
  • Synonyms: 3′,3″-Dibromothymolsulfonphthalein; Bromthymol Blue [0151]
  • Molecular Formula: C[0152] 27H28Br2O5S
  • Molecular Weight: 624.41 [0153]
  • CAS: 76-59-5 [0154]
  • pH=6.0 yellow [0155]
  • =7.6 blue [0156]
  • Phenol Red [0157]
  • Synonyms: Phenolsulfonphthalein [0158]
  • Molecular Formula: C[0159] 19H14O5S
  • Molecular Weight: 354.38 [0160]
  • CAS: 143-74-8 [0161]
  • pH=6.8 yellow [0162]
  • =8.2 red [0163]
  • Thymol Blue [0164]
  • Synonyms: Thymolsulfonphthalein [0165]
  • Molecular Formula: C[0166] 27H30O5S
  • Molecular Weight: 466.60 [0167]
  • CAS: 76-61-9 [0168]
  • pH=1.2 red [0169]
  • =2.8 yellow [0170]
  • =8 yellow [0171]
  • =9.2 blue [0172]
  • Cresol Red [0173]
  • Synonyms: Phenol, 4,4′-(1,1-dioxido-3H-2,1-benzoxathiol-3-ylidene)bis[2-methyl-(9CI)][0174]
  • Molecular Formula: C[0175] 21H18O5S
  • Molecular Weight: 382.43 [0176]
  • CAS: 1733-12-6 [0177]
  • pH 1.8 (orange) to pH 2.0 (yellow); Transition interval (alkaline): pH 7.0 (yellow) to pH 8.8 (violet) [0178]
  • Alizarin [0179]
  • Synonyms: 1,2-Dihydroxyanthraquinone, 9,10-Anthracenedione, 1,2-dihydroxy-(9CI) [0180]
  • Molecular Formula: C[0181] 14H8O4
  • Molecular Weight: 240.22 [0182]
  • CAS: 72-48-0 [0183]
  • pH=5.5 yellow [0184]
  • =6.8 red [0185]
  • =10.1 red [0186]
  • =12.1 violet [0187]
  • [0188] Mordant Orange 1
  • Synonyms: Alizarin Yellow R, C.I. 14030, 5-(4-nitrophenylazo)salicylic acid [0189]
  • Molecular Formula: C[0190] 13H9N3O5
  • Molecular Weight: 287.23 [0191]
  • CAS: 2243-76-7 [0192]
  • Methyl Orange [0193]
  • Synonyms: 4-(p-[Dimethylamino]phenylazo)benzenesulfonic acid, sodium salt [0194]
  • Acid Orange 52 [0195]
  • Molecular Formula: C[0196] 14Hl4N3O3SNa
  • Molecular Weight: 327.3 [0197]
  • pH 3.0 (pink)-pH 4.4 (yellow) [0198]
  • Methyl Red [0199]
  • Synonyms: 4-Dimethylaminoazobenzene-2′carboxylicacid; 2-(4-Dimethylaminophenylazo)-benzoic acid [0200]
  • Molecular Formula: C[0201] 15H15N3O2
  • Molecular Weight: 269.31 [0202]
  • CAS: 493-52-7 [0203]
  • pH=4.2 pink [0204]
  • =6.2 yellow [0205]
  • Reichardt's Dye [0206]
  • Synonyms: [2,6-diphenyl-4-(2,4,6-triphenylpyridinio)phenolate][0207]
  • Molecular Formula: C[0208] 41H29NO
  • Molecular Weight: 551.69 [0209]
  • CAS: 10081-39-7 [0210]
  • Nile Red [0211]
  • Synonyms: 5H-Benzo[a]phenoxazin-5-one, 9-(diethylamino)-(7CI, 8CI, 9CI), 9-(Diethylamino)-5H-benzo[a]phenoxazin-5-one; Nile Blue A oxazone [0212]
  • Molecular Formula: C[0213] 20H18N2O2
  • Molecular Weight: 318.38 [0214]
  • CAS: 7385-67-3 [0215]
  • Congo Red [0216]
  • Molecular Formula: C[0217] 32H24N6O6S2 Na2
  • Molecular Weight: 696.67 [0218]
  • CAS: 573-58-0 [0219]
  • pH range: blue 3.1-4.9 red [0220]
  • Victoria Blue B [0221]
  • Synonyms: [0222] Basic Blue 26, C.I. 44045
  • Molecular Formula: C[0223] 33H32ClN3
  • Molecular Weight: 506.10 [0224]
  • CAS: 2580-56-5 [0225]
  • Eosin Blue [0226]
  • Synonyms: (Acid Red 91, C.I. 45400, 4′,5′-dibromo-2′,7′-dinitrofluorescein, disodium salt) [0227]
  • Molecular Formula: C[0228] 20H8Br2N2O9
  • Molecular Weight: 624.08 [0229]
  • CAS: 548-24-3 [0230]
  • Fat Brown B [0231]
  • Synonyms: Solvent red 3 [0232]
  • Molecular Formula: C[0233] 18H16N2O2
  • Molecular Weight: 292.3 [0234]
  • CAS: 6535-42-8 [0235]
  • Benzopurpurin 4B [0236]
  • Synonyms: (C.I. 23500, Direct Red 2) [0237]
  • Molecular Formula: C[0238] 34H28N6O6S2
  • Molecular Weight: 724.73 [0239]
  • CAS: 992-59-6 [0240]
  • pH range: violet 1.2-3.8 yellow [0241]
  • Phloxine B [0242]
  • Molecular Formula: C[0243] 20H4Br4Cl4O5
  • CAS: 18472-87-2 [0244]
  • pH range: colorless 2.1-4.1 pink [0245]
  • Orange G [0246]
  • Synonyms: 1-Phenylazo-2-naphthol-6,8-disulfonic acid disodium salt [0247]
  • Molecular Formula: C[0248] 16H10N2Na2O7S2
  • Molecular Weight: 452. [0249]
  • pH range: yellow 11.5-14.0 pink [0250]
  • Metanil Yellow [0251]
  • Synonyms: (Acid Yellow 36, C.I. 13065) [0252]
  • Molecular Formula: C[0253] 18H15N3O3S Na
  • Molecular Weight: 375.38 [0254]
  • CAS: 587-98-4 [0255]
  • pH 1.5 (red) to pH 2.7 (yellow) [0256]
  • Naphthol Green B [0257]
  • Synonyms: ([0258] Acid Green 1, C.I. 10020)
  • Molecular Formula: C[0259] 10H7NO5S
  • Molecular Weight: 878.47 [0260]
  • CAS: 19381-50-1 [0261]
  • Methylene Blue [0262]
  • Synonyms: ([0263] Basic Blue 9, C.I. 52015)
  • Molecular Formula: C[0264] 16H18ClN3S
  • Molecular Weight: 373.90 [0265]
  • CAS: 7220-79-3 [0266]
  • Safranine O [0267]
  • Synonyms: (C.I. 50240, 3,7-diamino-2,8-dimethyl-5-phenylphenazinium chloride) [0268]
  • Molecular Formula: C[0269] 20H19ClN4
  • Molecular Weight: 350.85 [0270]
  • CAS: 477-73-6 [0271]
  • Methylene Violet 3RAX [0272]
  • Synonyms: [3-amino-7-(diethylamino)-5-phenylphenazinium chloride, C.I. 50206, N,N-diethylphenosafranine][0273]
  • Molecular Formula: C[0274] 22H23ClN4
  • Molecular Weight: 378.91 [0275]
  • CAS: 4569-86-2 [0276]
  • Sudan Orange G [0277]
  • Synonyms: [C.I. 11920, 4-(phenylazo)resorcinol, Solvent Orange 1][0278]
  • Molecular Formula: C[0279] 6H5N═NC6H3-1,3-(OH)2
  • Molecular Weight: 214.22 [0280]
  • CAS: 2051-85-6 [0281]
  • Morin Hydrate [0282]
  • Synonyms: (2′,3,4′,5,7-pentahydroxyflavone) [0283]
  • Molecular Formula: C[0284] 15H10O7
  • Molecular Weight: 302.24 [0285]
  • Neutral Red [0286]
  • Molecular Formula: C[0287] 15H16 N4.HCl
  • Molecular Weight: 288.78 [0288]
  • CAS: 553-24-2 [0289]
  • pH=6.8 red [0290]
  • =8.0 yellow [0291]
  • Disperse Orange 25 [0292]
  • Molecular Formula: C[0293] 17H17 N5O2
  • Molecular Weight: 323.36 [0294]
  • CAS: 31482-56-1 [0295]
  • Rosolic Acid [0296]
  • Molecular Formula: C[0297] 20H16O3
  • Molecular Weight: 290.32 [0298]
  • CAS: 603-45-2 [0299]
  • pH=5.0 yellow [0300]
  • =6.8 pink [0301]
  • Fat Brown RR [0302]
  • Molecular Formula: C[0303] 16H14N4
  • Molecular Weight: 262.32 [0304]
  • CAS: 6416-57-5 [0305]
  • Cyanidin Chloride [0306]
  • Molecular Formula: C15H11O6.Cl [0307]
  • Molecular Weight: 322.7 [0308]
  • CAS: 528-58-5 [0309]
  • 3,6-Acridineamine [0310]
  • Molecular Formula: C[0311] 13H11N3
  • Molecular Weight: 209.25 [0312]
  • CAS Number: 92-62-6 [0313]
  • 6′-Butoxy-2,6-diamino-3,3′-azodipyridine [0314]
  • Synonym: Azodipyridine [0315]
  • Molecular Formula: C[0316] 14H18N6O
  • Molecular Weight: 286.34 [0317]
  • CAS: 617-19-6 [0318]
  • para-Rosaniline Base [0319]
  • Synonym: Rosaniline [0320]
  • Molecular Formula: C[0321] 19H19N3O
  • Molecular Weight: 305.4 [0322]
  • CAS: 25620-78-4 [0323]
  • Acridine Orange Base [0324]
  • Molecular Formula: C[0325] 17H19N3
  • Molecular Weight: 265.36 [0326]
  • CAS: 494-38-2 [0327]
  • Crystal Violet [0328]
  • Molecular Formula: C[0329] 25H30N3Cl
  • Molecular Weight: 407.99 [0330]
  • CAS: 548-62-9 [0331]
  • pH=0 yellow [0332]
  • =1.8 blue [0333]
  • Malachite Green Carbinol Base [0334]
  • Molecular Formula: C[0335] 23H26N2O
  • Molecular Weight: 346.48 [0336]
  • CAS: 510-13-4 [0337]
  • pH=0.2 yellow [0338]
  • =1.8 blue-green [0339]
  • In a preferred embodiment, a low volatility liquid, e.g., a plasticizer, is used in an array of the present invention to keep the dyes in the array from crystallizing and to enhance then response of the array to an analyte. Examples of suitable low volatility liquids include, but are not limited to DOW CORNING 704 silicone diffusion pump fluid (Molecular Weight: 484.82, Density: 1.070, CAS Number: 3982-82-9), and diundecyl phthalate (Molecular Weight: 474.73, Density: 0.950, CAS Number: 3648-20-2, Formula: C[0340] 30H50O4, Boiling Point (° C.): 523 at 760 torr), dibutyl phthalate (Molecular Weight: 278.4, Density: 1.048, CAS Number: 84-74-2, Formula: C16H22O4, Boiling Point (° C.): 340 at 760 torr), diisopropyl phthalate (Molecular Weight: 250.3, Density: 1.063, CAS Number: 605-45-8, Formula: C14H18O4), squalane (Molecular Weight: 422.83, Density: 0.810, CAS Number: 111-01-3, Formula: C30H62, Boiling Point (° C.): 176 at 0.05 torr), triethylene glycol dimethyl ether (synonym: Trigluyme, Molecular Weight: 178.23, Density: 0.986, CAS Number: 112-49-2, Formula: C8H18O4, Boiling Point (° C.): 216 at 760 torr), and tetraethlyene glycol dimethyl ether (synonym: Tetraglyme, (Molecular Weight: 222.28, Density: 1.009, CAS Number: 143-24-8, Formula: C10H22O5, Boiling Point (° C.): 275-276at 760 torr).
  • FIG. 16 illustrates an array containing illustrative examples of porphyrin, metalloporphyrin, acid-base indicator, and solvatochromatic dyes. Typical sizes can range from 0.5 mm to 2 cm on a side. Linear, hexagonal, or rectangular arrays are also easily used. From left to right and top to bottom the identities and colors of the dyes used in the illustrative example of FIG. 16 are listed in Table 11 as follows (the exact colors depend, among other things, upon scanner settings). [0341]
    TABLE 11
    (Summarizing the Dyes and Colors in FIG. 16, i.e., “Dye - Color”)
    SnTPPCl2 - CoTPP - CrTPPCl - MnTPPCl - FeTPPCl - Light CuTPP -
    Light Green Peach Green Green Brownish Green Salmon
    AgTPP - NiTPP - InTPPCL - IrTPPCl - ZnTPP - Salmon FeTFPPCl -
    Salmon Pink Tan Pink Olive
    ZnSi6PP - ZnSi7OHPP - ZnSi8PP - H2TPP - H2FPP - Light Alizarin basic -
    Pink Deep Pink Pink Carmel Brown Violet
    Me Red - BCP - Dark BCPbasic - BTB - Dark BTB basic - Blue Ph Red basic -
    Orange Green Blue Yellow Lavender
    Nile Red - BCG - Blue BCG basic - CresRed - CresRed basic - CP Red -
    Violet Blue Brownish Purple Purple
    Purple
    R Dye - TB - Yellow TB basic - MeOr - MeOr basic - CP Red basic -
    Light Blue Greenish Yellow Orangish Brown Bluish
    Gray Purple
  • FIG. 17 illustrates the response of the array described in FIG. 16 to acid vapors, specifically formic acid, acetic acid, iso-valeric acid, and 3-methyl-2-hexenoic acid. As shown in FIG. 17 and summarized in Table 12 below, the color changes of each dye in response to a particular analyte are shown as color difference maps, as follows (the exact colors depend, among others things, upon scanner settings). The color changes are derived simply by comparing the before exposure and after exposure colors and subtracting the two images (i.e., the absolute value of the difference of the red values becomes the new red value in the color difference map; etc. for green values and blue values). If there is no change in the red, green, and blue color values of a dye in the after-exposure image, then the color difference map will show black (i.e., red value =green value =blue value =0). [0342]
    TABLE 12
    (Summarizing the Dyes and Color Changes in FIG. 17, i.e. “Dye - Difference
    Map Color”)
    (Analyte: Formic Acid 140 ppb)
    SnTPPCl2 - CoTPP - CrTPPCl MnTPPCl FeTPPCl - CuTPP -
    Black Black (no Black Black Faint Blue Black (no
    (no change) (no (no Periphery change)
    change) change) change)
    AgTPP - NiTPP - InTPPCL - IrTPPCl - ZnTPP - FeTFPPCl -
    Black (no Black (no Black Black (no Black (no Black (no
    change) change) (no change) change) change)
    change)
    ZnSi6PP - ZnSi7OHPP - ZnSi8PP - H2TPP - H2FPP - Alizarin basic -
    Black (no Black (no Black (no Black (no Black (no Dark Blue
    change) change) change) change) change)
    Me Red - BCP - BCP basic - BTB - BTB basic - Ph Red basic -
    Black (no Yellow White Black (no Red Green
    change) change) Periphery
    w/Yellow
    Center
    Nile Red - BCG - BCG CresRed - CresRed CP Red -
    Black (no Black (no basic - Black (no basic - Light Black (no
    change) change) Dark change) Green change)
    Purple
    R Dye - TB - Black TB basic - MeOr - MeOr basic - CP Red basic -
    Black (no (no change) Black (no Green and Dark Yellow
    change) change) Purple Purple Periphery and
    Purple center
    (Analyte: Formic Acid 210 ppb)
    SnTPPCl2 - CoTPP - CrTPPCl - MnTPPCl FeTPPCl - CuTPP - Black
    Black Black (no Black (no Black (no Black (no (no change)
    (no change) change) change) change)
    change)
    AgTPP - NiTPP - InTPPCL - IrTPPCl - ZnTPP - Black FeTFPPCl -
    Black (no Black (no Black (no Black (no (no change) Black (no
    change) change) change) change) change)
    ZnSi6PP - ZnSi7OH ZnSi8PP - H2TPP - H2FPP - Black Alizarin basic -
    Black (no PP - Black (no Black (no (no change) Black (no
    change) Black (no change) change) change)
    change)
    Me Red - BCP - BCP basic - BTB - BTB basic - Ph Red basic -
    Black (no Red Yellow Black (no Red Green
    change) Periphery and change)
    Red Center
    Nile Red - BCG - BCG basic - CresRed - CresRed basic - CP Red - Black
    Black (no Black (no Red periphery Black (no Green (no change)
    change) change) change)
    R Dye - TB - TB basic - MeOr - MeOr basic - CP Red basic -
    Black (no Black (no Black (no Black (no Black (no Yellow
    change) change) change) change) change) Periphery and
    Purple Center
    (Analyte: Formic Acid 340 ppb)
    SnTPPCl2 - CoTPP - CrTPPCl - MnTPPCl - FeTPPCl - CuTPP - Black
    Black Black (no Black (no Black (no Black (no (no change)
    (no change) change) change) change)
    change)
    AgTPP - NiTPP - InTPPCL - IrTPPCl - ZnTPP - FeTFPPCl - Black
    Black (no Black (no Black (no Black (no Black (no (no change)
    change) change) change) change) change)
    ZnSi6PP - ZnSi7OHPP ZnSi8PP - H2TPP - H2FPP - Alizarin basic -
    Black (no Black (no Black (no Black (no Black (no Green and Purple
    change) change) change) change) change)
    Me Red - BCP - BCP basic - BTB - BTB basic - Ph Red basic -
    Black (no Yellow White Black (no Yellow Green
    change) change)
    Nile Red - BCG - Red BCG basic - CresRed - CresRed CP Red - Green
    Black (no Red and Black (no basic - Light
    change) Purple change) Green
    R Dye - TB - Black TB basic - MeOr - MeOr basic - CP Red basic -
    Black (no (no change) Black (no Blue Purple White
    change) change)
    (Analyte: Formic Acid 680 ppb)
    SnTPPCl2 - CoTPP - CrTPPCl - MnTPPCl FeTPPCl - CuTPP - Black (no
    Black Black (no Black (no Black (no Black (no change)
    (no change) change) change) change)
    change)
    AgTPP - NiTPP - InTPPCL - IrTPPCl - ZnTPP - FeTFPPCl - Black
    Black (no Black (no Black (no Black (no Black (no (no change)
    change) change) change) change) change)
    ZnSi6PP - ZnSi7OHPP ZnSi8PP - H2TPP - H2FPP - Alizarin basic -
    Black (no Black (no Black (no Black (no Black (no Green and Purple
    change) change) change) change) change)
    Me Red - BCP - BCP basic - BTB - BTB basic - Ph Red basic -
    Black (no Yellow White Black (no Red Green
    change) change) Periphery
    and Yellow
    Center
    Nile Red - BCG Red BCG CresRed - CresRed CP Red - Black
    Black and Purple basic - Red Black (no basic - Green (no change)
    (no and Purple change)
    change)
    R Dye - TB - Black TB basic - MeOr - MeOr basic - CP Red basic -
    Black (no (no change) Black (no Light blue Purple White
    change) change)
    (Analyte: Acetic Acid 170 ppb)
    SnTPPCl2 - CoTPP - Black CrTPPCl - MnTPPCl FeTPPCl - CuTPP -
    Black (no change) Black (no Black (no Black (no Black (no
    (no change) change) change) change)
    change)
    AgTPP - NiTPP - Black InTPPCL - IrTPPCl - ZnTPP - Black FeTFPPCl -
    Black (no (no change) Black (no Black (no (no change) Black (no
    change) change) change) change)
    ZnSi6PP - ZnSi7OHPP - ZnSi8PP - H2TPP - H2FPP - Black Alizarin basic -
    Black (no Black (no Black (no Black (no (no change) Black (no
    change) change) change) change) change)
    Me Red - BCP - Red BCP basic - BTB - BTB basic - Ph Red basic -
    Black (no Orange Black (no Red Black (no
    change) change) change)
    Nile Red - BCG - Purple BCG basic - CresRed - CresRed basic - CP Red. -
    Black (no and Orange Purple Black (no Black (no Black (no
    change) Orange change) change) change)
    R Dye - TB - Black (no TB basic - MeOr - MeOr basic - CP Red
    Black (no change) Black (no Black (no Black (no basic - Black
    change) change) change) change) (no change)
    (Analyte: Acetic Acid 250 ppb)
    SnTPPCl2 - CoTPP - CrTPPCl - MnTPPCl - FeTPPCl - CuTPP - Black (no
    Black Black (no Black (no Black (no Black (no change)
    (no change) change) change) change)
    change)
    AgTPP - NiTPP - InTPPCL - IrTPPCl - ZnTPP - FeTFPPCl - Black
    Black (no Black (no Black (no Black (no Black (no (no change)
    change) change) change) change) change)
    ZnSi6PP - ZnSi7OHPP ZnSi8PP - H2TPP - H2FPP - Alizarin basic -
    Black (no Black (no Black (no Black (no Black (no Black (no change)
    change) change) change) change) change)
    Me Red - BCP - BCP basic - BTB - BTB basic - Ph Red basic -
    Black (no Yellow with Red Black (no Red Green
    change) Red Center change)
    Nile Red - BCG - BCG basic - CresRed - CresRed CP Red - Black
    Black (no Orange Red and Black (no basic - (no change)
    change) Purple change) Black (no
    change)
    R Dye - TB - Black TB basic - MeOr - MeOr basic - CP Red basic -
    Black (no (no change) Black (no Black (no Black (no White
    change) change) change) change)
    (Analyte: Acetic Acid 340 ppb)
    SnTPPCl2 - CoTPP - CrTPPCl - MnTPPCl - FeTPPCl - CuTPP - Black (no
    Black Black (no Black (no Black (no Black (no change)
    (no change) change) change) change)
    change)
    AgTPP - NiTPP - InTPPCL - IrTPPCl - ZnTPP - FeTFPPCl - Black
    Black (no Black (no Black (no Black (no Black (no (no change)
    change) change) change) change) change)
    ZnSi6PP - ZnSi7OHPP ZnSi8PP - H2TPP - H2FPP - Alizarin basic -
    Black (no Black (no Black (no Black (no Black (no Black (no change)
    change) change) change) change) change)
    Me Red - BCP - BCP basic - BTB - BTB basic - Ph Red basic -
    Black (no Yellow Yellow Black (no Ornage Green
    change) change)
    Nile Red - BCG - BCG basic - CresRed - CresRed CP Red - Black
    Black (no Faint Purple Black (no basic - (no change)
    change) Orange and change) Green
    Purple
    R Dye - TB - Black TB basic - MeOr - MeOr basic - CP Red basic -
    Black (no (no change) Black (no Black (no Black (no White
    change) change) change) change)
    (Analyte: Acetic Acid 650 ppb)
    SnTPPCl 2 - CoTPP - CrTPPCl - MnTPPCl - n FeTPPCl - CuTPP - Black (no
    Black Black (no Black (no Black (no Black (no change)
    (no change) change) change) change)
    change)
    AgTPP - NiTPP - InTPPCL - IrTPPCl - ZnTPP - FeTFPPCl - Black
    Black (no Black (no Black (no Black (no Black (no (no change)
    change) change) change) change) change)
    ZnSi6PP - ZnSi7OHPP ZnSi8PP - H2TPP - H2FPP - Alizarin basic -
    Black (no Black (no Black (no Black (no Black (no Faint Green
    change) change) change) change) change)
    Me Red - BCP - BCP basic - BTB - BTB basic - Ph Red basic -
    Black (no Yellow and Faint Orange Yellow Green
    change) Orange) Yellow
    Nile Red - BCG - BCG basic - CresRed - CresRed CP Red - Faint
    Black (no Black (no Purple Black (no basic - Green
    change) change) change) White
    R Dye - TB - Black TB basic - MeOr - MeOr basic - CP Red basic -
    Black (no (no change) Black (no Black (no Green White
    change) change) change)
    (Analyte: Iso-Valeric Acid 280 ppb)
    SnTPPCl2 - CoTPP - CrTPPCl - MnTPPCl - FeTPPCl - CuTPP - Black (no
    Black Black (no Black (no Black (no Black (no change)
    (no change) change) change) change)
    change)
    AgTPP - NiTPP - InTPPCL - IrTPPCl - ZnTPP - FeTFPPC - Black
    Black (no Black (no Black (no Black (no Black (no (no change)
    change) change) change) change) change)
    ZnSi6PP - ZnSi7OHPP ZnSi8PP - H2TPP - H2FPP - Alizarin basic -
    Black (no Black (no Black (no Black (no Black (no Black (no change)
    change) change) change) change) change)
    Me Red - BCP - Red BCP basic - BTB - BTB basic - Ph Red basic -
    Black (no Black (no Faint Red Black (no Orange Orange
    change) change) change)
    Nile Red - BCG - BCG basic - CresRed - CresRed CP Red - Black
    Black (no Faint Purple Red Black (no basic - Dark (no change)
    change) Periphery Periphery change) Green
    R Dye - TB - Red TB basic - MeOr - MeOr basic - CP Red basic -
    Black (no and Purple Red Green Green Green Periphery
    change) Periphery Periphery Center Periphery
    (Analyte: Iso-Valeric 420 ppb)
    SnTPPCl2 - CoTPP - CrTPPCl - MnTPPCl - FeTPPCl - CuTPP - Black (no
    Black Black (no Black (no Black (no Black (no change)
    (no change) change) change) change)
    change)
    AgTPP - NiTPP - InTPPCL - IrTPPCl - ZnTPP - FeTFPPCl - Black
    Black (no Black (no Black (no Black (no Black (no (no change)
    change) change) change) change) change)
    ZnSi6PP - ZnSi7OHPP ZnSi8PP - H2TPP - H2FPP - Alizarin basic -
    Black (no Black (no Black (no Black (no Black (no Black (no change)
    change) change) change) change) change)
    Me Red - BCP - Red BCP basic - BTB - BTB basic - Ph Red basic -
    Black (no Faint Black (no Orange and Faint Orange and
    change) Green and change) Yellow Green
    orange
    Nile Red - BCG - BCG basic - CresRed - CresRed CP Red - Black
    Black (no Orange Orange Black (no basic - (no change)
    change) Periphery change Green
    R Dye - TB - Black TB basic - MeOr - MeOr basic - CP Red basic -
    Black (no (no change) Black (no Green Green Green
    change) change)
    (Analyte: Iso-Valeric Acid 850 ppb)
    SnTPPCl2 - CoTPP - CrTPPCl - MnTPPCl - FeTPPCl - CuTPP - Black
    Faint Faint Purple Faint Faint Purple Faint Purple (no change)
    blue Purple
    AgTPP - NiTPP - InTPPCL - IrTPPC1 - ZnTPP - FeTFPPCl - Black
    Faint Blue Black (no Faint Pink Black (no Black (no (no change)
    change) change) change)
    ZnSi6PP - ZnSi7OHPP ZnSi8PP - H2TPP - H2FPP - Alizarin basic -
    Faint Blue Faint Blue Black (no Faint Blue Black (no Black (no change)
    change) change)
    Me Red - BCP - White BCP basic - BTB - Blue BTB basic - Ph Red basic -
    Black (no and Red Yellow and Red Red and Yellow and Red
    change) and Red Yellow
    Nile Red - BCG - White, BCG basic - CresRed - CresRed CP Red - Faint
    Black (no Red and Blue White Purple basic - Orange
    change) and Red Periphery Light Green
    R Dye - TB - Light TB basic - MeOr - MeOr basic - CP Red basic -
    Faint Red Blue Purple Green and Light Light Green
    Periphery Periphery Blue Green
    and Red
    Center
    (Analyte: Iso-Valeric Acid 1700 ppb)
    SnTPPCl2 - CoTPP - CrTPPCl - MnTPPCl - FeTPPCl - CuTPP - Black (no
    Black Black (no Black (no Black (no Black (no change)
    (no change) change) change) change)
    change)
    AgTPP - NiTPP - InTPPCL - IrTPPCl - ZnTPP - FeTFPPCl - Black
    Black (no Black (no Black (no Black (no Black (no (no change)
    change) change) change) change) change)
    ZnSi6PP - ZnSi7OHPP ZnSi8PP - H2TPP - H2FPP - Alizarin basic -
    Black (no Black (no Black (no Black (no Black (no Faint Purple
    change) change) change) change) change)
    Me Red - BCP - Red BCP basic - BTB - BTB basic - Ph Red basic -
    Black (no White Black (no White White and Purple
    change) change)
    Nile Red - BCG - Red BCG basic - CresRed - CresRed CP Red - Black
    Black and Purple White, Black (no basic - (no change)
    (no Red, and change) White
    change) Purple
    R Dye - TB - Black TB basic - MeOr - MeOr basic - CP Red basic -
    Black (no (no change) Faint Red Black (no Faint Green
    change) change) Green
    (Analyte: 3-Methyl-2-hexenoic Acid 12 ppb)
    SnTPPCl2 - CoTPP - CrTPPCl - MnTPPCl - FeTPPCl - CuTPP - Black (no
    Black Black (no Black (no Black (no Black (no change)
    (no change) change) change) change)
    change)
    AgTPP - NiTPP - InTPPCL - IrTPPCl - ZnTPP - FeTFPPCl - Black
    Black (no Black (no Black (no Black (no Black (no (no change)
    change) change) change) change) change)
    ZnSi6PP - ZnSi7OHPP ZnSi8PP - H2TPP - H2FPP - Alizarin basic -
    Black (no Black (no Black (no Black (no Black (no Black (no change)
    change) change) change) change) change)
    Me Red - BCP - Faint BCP basic - BTB - BTB basic - Ph Red basic -
    Black (no Purple White Black (no Red Purple and Green
    change) and Purple change)
    Nile Red - BCG - BCG basic - CresRed - CresRed CP Red - Black
    Black (no Faint Red Faint Black (no basic - Light (no change)
    change) and Purple White and change) Blue and
    Purple Green
    R Dye - TB - Black TB basic - MeOr - MeOr basic - CP Red basic -
    Black (no (no change) Black (no Black (no Blue and Green
    change) change) change) Green
  • FIG. 18 illustrates a preferred array containing illustrative examples of porphyrin, metalloporphyrin, acid-base indicator, and solvatochromatic dyes. Typical sizes of the array can range from 0.5 mm to 2 cm on a side. Linear, hexagonal or rectangular arrays are also easily used. From left to right and top to bottom the identities and colors of the dyes used in the illustrative example of FIG. 18 are listed in Table 13 as follows (the exact colors depend, among other things, upon scanner setting). [0343]
    TABLE 13
    (Summarizing the Dyes and Colors in FIG. 18, i.e., “Dye - Color”)
    SnTPPCl2- CoTPP - Tan CrTPPCl - Green MnTPPCl - FeTPPCl - Light CuTPP -
    Light Green with Dark Green Green Green Light Pink
    Center
    Zn(C3F7)4P - ZnF2PP - InTPPCl - ZnTMP - ZnTPP - FeTFPPCl -
    Gray Light Pink Reddish Beige Pink Salmon Beige
    ZnSi6PP - ZnSi7OHPP - ZnSi8PP - Light H2TPP - H2FPP - Neutral Red
    Pink Pink Pink Light Greenish Yellow Pink with
    Reddish Brown
    Beige Center
    Methyl Red - Disperse Rosolic Acid - Fat Brown Cyanidin Metanil
    Orange Orange 25 - Red RR - Dark Chloride - Yellow -
    Pinkish Reddish Brown Light
    Orange Yellow
    Nile Red - Mordant 3,6-Acridineamine Bromocresol Azodipyridine - Rosaniline -
    Yellow
    Light Purple Orange 1 - Yellow Green - Pink
    Light Yellow Dark Yellow
    Reichardt's Acridine Crystal Violet - Thymol Blue Congo Red - Malachite
    Dye - Teal Orange Dark Blue Purple Dark Red Green
    Base - Carbinol
    Yellow base - Light
    Blue
  • where [0344]
  • SnTPPCl[0345] 2 is 5,10,15,20-Tetraphenyl-21H,23H-porphine tin(IV) dichloride
  • Molecular Formula: C[0346] 44H28SnCl2N4
  • Molecular Weight: 802 [0347]
  • CAS: 26334-85-0; [0348]
  • CoTPP is 5,10,15,20-Tetraphenyl-21H,23H-porphine cobalt(II) [0349]
  • Molecular Formula: C[0350] 44H28CoN4
  • Molecular Weight: 671 [0351]
  • CAS: 14172-90-8; [0352]
  • CrTPPCl is 5,10,15,20-Tetraphenyl-21H,23H-porphine chromium(III) chloride [0353]
  • Molecular Formula: C[0354] 44H28CrClN4
  • Molecular Weight: 700 [0355]
  • CAS: 28110-70-5; [0356]
  • MnTPPCl is 5,10,15,20-Tetraphenyl-21H,23H-porphine manganese(III) chloride [0357]
  • Molecular Formula: C[0358] 44H28ClMnN4
  • Molecular Weight: 703 [0359]
  • CAS: 32195-55-4; [0360]
  • FeTPPCl is 5,10,15,20-Tetraphenyl-21H,23H-porphine iron(III) chloride [0361]
  • Molecular Formula: C[0362] 44H28ClFeN4
  • Molecular Weight: 704 [0363]
  • CAS: 16456-81-8; [0364]
  • CuTPP is 5,10,15,20-Tetraphenyl-21H,23H-porphine copper(II) [0365]
  • Molecular Formula: C[0366] 44H28CuN4
  • Molecular Weight: 676 [0367]
  • CAS: 14172-91-9; [0368]
  • Zn(C[0369] 3F7)4P is meso tetra(heptafluoropropyl)porphine zinc(II)
  • Molecular Formula: C[0370] 32H8ZnF28N4
  • Molecular Weight: 1044; [0371]
  • ZnF[0372] 2PP is 5,10,15,20-Tetrakis(2,6-difluorophenyl)-21H,23H-porphine zinc(II)
  • Molecular Formula: C44H[0373] 20F8N4Zn
  • Molecular Weight: 820; [0374]
  • InTPPCl is 5,10,15,20-Tetraphenyl-21H,23H-porphine indium(III) chloride [0375]
  • Molecular Formula: C[0376] 44H28ClInN4
  • Molecular Weight: 763; [0377]
  • ZnTMP is 5,10,15,20-Tetrakis(2,4,6-trimethylphenyl)-21H,23H-porphine zinc(II) [0378]
  • Molecular Formula: C[0379] 56H52N4Zn
  • Molecular Weight: 846 [0380]
  • CAS: 104025-54-9; [0381]
  • ZnTPP is 5,10,15,20-Tetraphenyl-21H,23H-porphine zinc(II) [0382]
  • Molecular Formula: C[0383] 44H28N4Zn
  • Molecular Weight: 678 [0384]
  • CAS: 14074-80-7; [0385]
  • FeTFPPCl is 5,10,15,20-Tetrakis(pentafluorophenyl)-21H,23H-porphine iron(III) chloride [0386]
  • Molecular Formula: C[0387] 44H8CIF20FeN4
  • Molecular Weight: 1063.85 [0388]
  • CAS: 36965-71-6; [0389]
  • ZnSi[0390] 6PP is 5(phenyl)-10,15,20-trikis(2 ,6-disilyloxyphenyl)porphyrinatozinc(II)
  • Molecular Formula: ZnC[0391] 80H112O6N4Si6
  • Molecular Weight: 1458; [0392]
  • ZnSi[0393] 7OHPP is 5,10,15-trikis(2′,6′-disilyloxyphenyl)-20-(2/-hydroxy-6/-silyloxyphenyl)porphyrinatozinc(II)
  • Molecular Formula: ZnC[0394] 86H126O8N4Si7
  • Molecular Weight: 1604; [0395]
  • ZnSi[0396] 8PP is 5,10,15,20-tetrakis(2/,6/-disilyloxyphenyl)porphyrinatozinc(II)
  • Molecular Formula: ZnC[0397] 92H140O8N4Si8
  • Molecular Weight: 1718; [0398]
  • H[0399] 2TPP is 5,10,15,20-Tetraphenyl-21H,23H-porphine
  • Molecular Formula: C[0400] 44H30N4
  • Molecular Weight: 614.75 [0401]
  • CAS: 917-23-7; [0402]
  • H[0403] 2FPP is 5,10,15,20-Tetrakis(pentafluorophenyl)-21H,23H-porphine
  • Molecular Formula: C[0404] 44H10F2ON4
  • Molecular Weight: 974.57 [0405]
  • CAS: 25440-14-6; [0406]
  • Azodipyridine is 6′-Butoxy-2,6-diamino-3,3′-azodipyridine [0407]
  • Molecular Formula: C[0408] 14H18N6O
  • Molecular Weight: 286.34 [0409]
  • CAS: 617-19-6; [0410]
  • Rosaniline is Para-Rosaniline Base [0411]
  • Molecular Formula: C[0412] 19H19N3O
  • Molecular Weight: 305.4 [0413]
  • CAS: 25620-78-4 [0414]
  • FIG. 19 illustrates the response of the array described in FIG. 18 to acetone. As shown in FIG. 18 and summarized in Table 14 below, the color changes of each dye in response to aceteone are as follows (the exact colors depend, among other things, upon scanner settings). The color changes are derived simply by comparing the before exposure and after exposure colors and subtracting the two images (i.e., the absolute value of the difference of the red values becomes the new red value in the color difference map; etc. for green values and blue values). If there is no change in the red, green, and blue color values of a dye in the after-exposure image, then the color difference map will show black (i.e., red value =green value =blue value =0). [0415]
    TABLE 14
    (Summarizing the Dyes and Colors in FIG. 19, i.e., “Dye - Color”)
    SnTPPCl2 - CoTPP - CrTPPCl - MnTPPCl FeTPPCl - CuTPP - Black
    Reddish Lavender Gray Pink Black (no (no change)
    Brown change)
    AgTPP - NiTPP - InTPPCL - IrTPPCl - ZnTPP - FeTFPPCl - Dark
    White Light Teal Blue Light Black (no Dark Cobalt
    Green change)
    ZnSi6PP - ZnSi7OHPP ZnSi8PP - H2TPP - H2FPP - Alizarin basic -
    Black (no Aqua Dark Teal Green White Dark Purple
    change) Periphery
    and Blue
    Center
    Me Red - BCP - BCP basic - BTB - BTB basic - Ph Red basic -
    Dark Blue Green Light Light Dark Blue Royal Blue
    Green Green
    Nile Red - BCG - Tan BCG basic - CresRed - CresRed CP Red - Gold
    Olive Black (no Dark Pink basic - Blue
    change)
    R Dye - TB - Brown TB basic - MeOr - MeOr basic - CP Red basic -
    Light Green Light Dark Blue Black (no change)
    Pink Green
  • Partial Oxidation [0416]
  • Having demonstrated electronic differentiation and shape-selective distinction of analytes that bind to metal ions in metallodyes and of acidic or basic analytes that effect other chemoresponsive dyes (e.g., pH sensitive dyes and solvatochromic dyes), there are further embodiments of the present invention that provide for the differentiation of analytes that do not bind or bind only weakly to metal ions. Such analytes include certain organic compounds lacking ligatable functionality, such as simple alkanes, arenes, alkenes and alkynes (especially if sterically hindered), and molecules sterically hindered as to preclude effective ligation. [0417]
  • By partially oxidizing (partial meaning oxidation that does not convert all of the carbon atoms of the analytes completely to carbon dioxide) such parent analytes, new mixtures of derivative analytes are formed that provide a unique analytical fingerprint for the presence of the parent analytes. The partial oxidation of such parent analytes to mixtures of alcohols, aldehydes, ketones, carboxylic acids, including small carboxylic acids (e.g., formic, acetic, propionic), carbon monoxide, and carbon dioxide can be easily accomplished, thus effecting the chemical conversion of weakly-responsive organic compounds to more volatile organic compounds. These more volatile organic compounds have a stronger interaction(s) with the array of the present invention, and thus provide stronger responses, than do the parent analytes with the array of the present invention. Preferably, for example, after partial oxidation of a parent analyte, the derivative analyte(s) may have stronger ligation, acid-base (including Lewis and/or Br?nsted acids and bases), hydrogen bonding, and/or dipolar interactions with an array of the present invention than does the parent analyte. For example, hexane can be partially oxidized to derivative analytes such as hexanoic acid, hexanol, hexanal, and C[0418] 6-ketones.
  • Thus, a table or database of fingerprints of analytes can be made in accordance with the present invention by subjecting known analytes to partial oxidation pursuant to a certain protocol, and then observing and recording the absorbance or reflectance response an the above-described array to the partially oxidized known analytes. Later, an unknown analyte can be subjected to the same protocol of partial oxidation, and the resulting absorbance or reflectance response or the array to the partially oxidized unknown analyte can be matched with the corresponding fingerprint in the table or database of fingerprints. For example, a known source of hexane can be partially oxidized pursuant to a certain protocol, and the fingerprint of the resulting analyte can be observed and recorded. An unknown analyte can then be partially oxidized pursuant to the same protocol, and if the fingerprint of the resulting analyte matches that of hexane, then the unknown analyte will have been identified as hexane. [0419]
  • In one embodiment, an above-described array is first subjected to an unknown analyte that has not been partially oxidized. Should the array have no response or a weak response to the unknown analyte such that the unknown analyte cannot be determined, then the unknown analyte can be subjected to a particular partial oxidation protocol to form at least one derivative analyte corresponding to the unknown analyte. The array can then be subjected to the at least one derivative analyte and inspected for a direct and distinct spectral absorbance or reflectance response corresponding to the derivative analyte. The response or fingerprint can then be matched with the corresponding response or fingerprint of a known analyte that had been subjected to the same particular partial oxidation protocol, and thus the unknown analyte can be identified. [0420]
  • For partial oxidation of the parent analyte to occur, an oxidizing source must react with the parent analyte. The oxidizing source can be any suitable source of oxygen gas (e.g., as a component of air), or other oxidant or oxidizing agent (e.g., hydrogen peroxide, hypochlorite, chlorine dioxide, chlorine or other bleaching agents). To achieve partial oxidation of the parent analyte, the oxidizing source must be present in a range of concentration or amount sufficient to result in forming a derivative analyte that has a stronger response with at least part of the array of the present invention than the parent analyte, but below that needed to fully oxidize the parent analyte completely to carbon dioxide. [0421]
  • In one embodiment, the incoming gas to be analyzed is brought into contact with an oxidizing source. For example, the incoming gas having a parent analyte can be passed through a column or cartridge comprising a heterogeneous oxidation catalyst. The outgoing gas coming out of the column or cartridge will comprise at least one derivative analyte that is then exposed to a dye array previously described above. The time of transit (so-called “residence time” of the analyte gas) over or through the bed of oxidation catalyst can be adjusted by the flow rate or the physical length of the catalyst bed so as to optimize the partial oxidation of the parent analyte(s). [0422]
  • The extent of oxidation can also be adjusted by the concentration of the oxidant in the analyte gas or liquid (e.g., by adding O[0423] 2 or hydrogen peroxide). Suitable oxidation catalysts are of many potential types, including but not limited to noble metals (e.g., Pt or Pd) or their oxides, early transition metal oxides (e.g., V2O5), and metal-containing microporous zeolites. Such oxidation catalysts can be used either in substantially pure form or supported on various high surface area supports, such as silica, alumina, charcoal, or diamtomaceous earth among others.
  • If an oxidation catalyst is used, the extent of oxidation can also be adjusted by the temperature at which the catalyst is kept, such as a range that includes 100 K to 1000 K. An embodiment may often utilize a catalyst of sufficient activity and concentration to permit its effective use at room temperature. [0424]
  • FIG. 20 illustrates an embodiment of a vapor exposure apparatus of the present invention. The basic difference between the embodiment shown in FIG. 3B is that the embodiment shown in FIG. 20 further includes a [0425] partial oxidation cartridge 200 having a suitable oxidation catalyst 202. Partial oxidation of the incoming gas or parent analyte 204 using oxidation catalyst 202 can be used to provide increased sensitivities to analytes. More specifically, the oxidation catalyst 202 of partial oxidation cartridge 200 can used in accordance with the present invention to provide increased sensitivities to analytes that do not have significant acidic or basic functionality, including alkanes, arenes, alkenes and alkynes (especially if sterically hindered), and molecules sterically hindered as to preclude effective ligation.
  • FIG. 20 illustrates top and side views of [0426] bottom piece 21 and a top view of top piece 21′ of a vapor exposure flow cell 20 of the present invention. In the embodiment shown in FIG. 20, for purposes of demonstration, a sensor plate 18 having array 16 is placed inside of a flow cell 20 equipped with a quartz window 22. In a preferred embodiment, flow cell 20 is made from stainless steel. Inlet 23 for the analyte vapor includes partial oxidation cartridge 200. Preferably, cartridge 200 is packed with a solid or solid-supported oxidation catalyst 202 optimized for partial oxidation of the incoming analyte. Cartridge 200 can be thermostated above or below room temperature as needed to optimize the partial oxidation of incoming analyte. Outlet 23′ permits vapor flow out from sensor plate 18. In accordance with this embodiment, incoming gas or parent analyte 204 is partially oxidized as it is passed through cartridge 200, and the partially oxidized gas 206, which now contains at least one derivative analyte, flows into contact array 16 of sensor plate 18, and then exits from outlet 23.′
  • In accordance with the present invention, a table of responses of the array(s) described herein to a plurality of distinct known analytes can be prepared and used identify an unknown analytes at a later time. [0427]
  • The present invention provides methods for detection. In one embodiment, a method (I) of detecting at least one parent analyte comprises the steps of (a) forming an array by depositing at least a first dye and a second dye directly onto a single support in a predetermined patter combination, the combination of dyes in the array having a distinct and direct spectral or reflectance response to distinct analytes comprising one or more parent analytes or their derivatives, (b) partially oxidizing at least one parent analyte to form at least one derivative analyte corresponding to said parent analyte, (c) subjecting the array to the at least one derivative analyte, and (d) inspecting the first dye and the second dye for a direct and distinct spectral response corresponding to the derivative analyte. [0428]
  • In another embodiment, a method (II) of detecting at least one unknown parent analyte comprises the steps of [0429]
  • (a) forming an array by depositing at least a first dye and a second dye directly onto a single support in a predetermined pattern combination, the combination of dyes in the array having a distinct and direct spectral absorbance or reflectance response to distinct analytes comprising one or more parent analytes or their derivatives, [0430]
  • (b) partially oxidizing at least one known parent analyte pursuant to a certain protocol to form at least one derivative analyte corresponding to said known parent analyte, [0431]
  • (c) subjecting the array to the at least one derivative analyte corresponding to said known parent analyte, [0432]
  • (d) inspecting the array for a direct and distinct spectral response to the derivative analyte corresponding to said known analyte, [0433]
  • (e) forming an array identical to the array formed in step (a) by repeating step (a) or returning the array in step (a) to its condition prior to step (c), [0434]
  • (f) partially oxidizing at least one unknown parent analyte pursuant to the certain protocol to form at least one derivative analyte corresponding to said unknown parent analyte, [0435]
  • (g) subjecting the array formed in step (e) to the at least one derivative analyte corresponding to said unknown parent analyte, [0436]
  • (h) inspecting the array after step (g) for a direct and distinct spectral response to the derivative analyte corresponding to said unknown parent analyte, and [0437]
  • (i) determining after step (h) whether the direct and distinct spectral response of the array to the derivative analyte corresponding to the unknown parent analyte matches the direct and distinct spectral response of the array to the derivative analyte corresponding to the known parent analyte in step (d). [0438]
  • The method (II) of the above paragraph can further comprise the step of subjecting the array formed in step (e) to the at least one unknown parent analyte prior to step (f) and determining whether the array formed in step (e) has a response insufficient to detect the unknown parent analyte prior to proceeding to step (f). The method (II) can further comprise the step of subjecting the array formed in step (a) to the at least one known parent analyte prior to step (b) and determining whether the array formed in step (a) has a response insufficient to detect the unknown parent analyte prior to proceeding to step (b). [0439]
  • The present invention provides a method (III) of making a table of responses of an array to a plurality of distinct analytes comprising the steps of [0440]
  • (a) forming an array by depositing at least a first die and a second dye directly onto a single support in a predetermined pattern combination, the combination of dyes in the array having a distinct and direct spectral absorbance or reflectance response to distinct analytes comprising one or more parent analytes or their derivatives, [0441]
  • (b) subjecting the array to at least one known parent analyte, [0442]
  • (c) inspecting the distinct and direct absorbance or reflectance response that exists of the array to the at least one known parent analyte, [0443]
  • (d) if no distinct and direct absorbance or reflectance response exists of the array to the at least one known parent analyte, then partially oxidizing the at least one known parent analyte pursuant to a certain protocol to form at least one derivative analyte corresponding to said known parent analyte, [0444]
  • (e) subjecting the array to the at least one derivative analyte corresponding to said known parent analyte, [0445]
  • (f) inspecting the array for a direct and distinct spectral response to the derivative analyte corresponding to said known analyte, [0446]
  • (g) forming an array identical to the array formed in step (a) by repeating step (a) or returning the array in step (a) to its condition prior to step (b), [0447]
  • (h) subjecting the array formed in step (g) to at least one unknown parent analyte to determine whether the array has a response sufficient to detect the unknown parent analyte, [0448]
  • (i) if after step (h) the array has a response sufficient to detect the unknown parent analyte, then determining whether the response matches the response of a known patent analyte in step (c), [0449]
  • (j) if after step (h) the array does not have a response sufficient to detect the unknown parent analyte, then partially oxidizing the at least one unknown parent analyte pursuant to the certain protocol to form at least one derivative analyte corresponding to said unknown parent analyte, [0450]
  • (k) subjecting the array after step (j) to the at least one derivative analyte corresponding to said unknown parent analyte, [0451]
  • (l) inspecting the array after step (k) for a direct and distinct spectral response corresponding to the derivative analyte corresponding to said unknown parent analyte, and [0452]
  • (m) determining after step (l) whether the direct and distinct spectral response of the array to the derivative analyte corresponding to the unknown parent analyte matches the direct and distinct spectral response of the array to the derivative analyte corresponding to the known parent analyte in step (f). [0453]
  • Many modifications and variations may be made in the techniques and structures described and illustrated herein without departing from the spirit and scope of the present invention. Accordingly, the techniques and structures described and illustrated herein should be understood to be illustrative only and not limiting upon the scope of the present invention. [0454]

Claims (30)

What is claimed is:
1. An artificial nose comprising an array, the array comprising at least a first dye and a second dye deposited directly onto a single support in a predetermined pattern combination, the combination of dyes in the array having a distinct and direct spectral absorbance or reflectance response to distinct analytes comprising one or more parent analytes or their derivatives, and an oxidizing source to partially oxidize at least one distinct parent analyte to at least one corresponding derivative analyte of said parent analyte, the array at least in part having a stronger distinct and direct absorbance or reflectance response to the derivative analyte than to the corresponding parent analyte.
2. The artificial nose of claim 1, wherein the at least one distinct parent analyte is from the group consisting of organic compounds lacking ligatable functionality and molecules sterically hindered as to preclude effective ligation, acid-base interaction functionality, hydrogen-base interaction functionality, and dipolar interaction functionality.
3. The artificial nose of claim 1, wherein the at least one corresponding derivative analyte has a stronger interaction with at least part of the array than its corresponding parent analyte.
4. The artificial nose of claim 3, wherein the stronger interaction is from the group consisting of ligation interaction, acid-base interaction, hydrogen-base interaction, and dipolar interaction.
5. The artificial nose of claim 1, wherein the oxidizing source comprises an oxidation catalyst.
6. The artificial nose of claim 5, wherein the oxidation catalyst from the group consisting of noble metals, noble metal oxides, early transition metals oxides and metal-containing microporous zeolites.
7. The artificial nose of claim 5, wherein the oxidation catalyst is contained in a cartridge.
8. The artificial nose of claim 1, wherein the oxidizing source is from the group consisting of substantially pure oxygen, air, hydrogen peroxide, hypochlorite, chlorine dioxide, chlorine or other bleaching agents.
9. The artificial nose of claim 5, wherein the oxidation catalyst is from the group consisting of platinum, palladium, and vanadium oxide.
10. The artificial nose of claim 5, wherein the partial oxidation of the at least one distinct analyte is conducted in a temperature range of between 100 K and 1000 K.
11. The artificial nose of claim 1, wherein the at least one derivative analyte is from the group consisting of alcohols, aldehydes, ketones, carboxylic acids, carbon monoxide, and carbon dioxide.
12. A method of detecting at least one parent analyte comprising the steps of (a) forming an array by depositing at least a first dye and a second dye directly onto a single support in a predetermined patter combination, the combination of dyes in the array having a distinct and direct spectral or reflectance response to distinct analytes comprising one or more parent analytes or their derivatives, (b) partially oxidizing the at least one parent analyte to form at least one derivative analyte corresponding to said parent analyte, (c) subjecting the array to the at least one derivative analyte, and (d) inspecting the first dye and the second dye for a direct and distinct spectral response corresponding to the derivative analyte.
13. A method of detecting at least one unknown parent analyte comprising the steps of
(a) forming an array by depositing at least a first dye and a second dye directly onto a single support in a predetermined pattern combination, the combination of dyes in the array having a distinct and direct spectral absorbance or reflectance response to distinct analytes comprising one or more parent analytes or their derivatives,
(b) partially oxidizing at least one known parent analyte pursuant to a certain protocol to form at least one derivative analyte corresponding to said known parent analyte,
(c) subjecting the array to the at least one derivative analyte corresponding to said known parent analyte,
(d) inspecting the array for a direct and distinct spectral response to the derivative analyte corresponding to said known analyte,
(e) forming an array identical to the array formed in step (a) by repeating step (a) or returning the array in step (a) to its condition prior to step (c),
(f) partially oxidizing at least one unknown parent analyte pursuant to the certain protocol to form at least one derivative analyte corresponding to said unknown parent analyte,
(g) subjecting the array formed in step (e) to the at least one derivative analyte corresponding to said unknown parent analyte,
(h) inspecting the array after step (g) for a direct and distinct spectral response to the derivative analyte corresponding to said unknown parent analyte, and
(i) determining after step (h) whether the direct and distinct spectral response of the array to the derivative analyte corresponding to the unknown parent analyte matches the direct and distinct spectral response of the array to the derivative analyte corresponding to the known parent analyte in step (d).
14. The method of claim 13 further comprising the step of subjecting the array formed in step (e) to the at least one unknown parent analyte prior to step (f) and determining whether the array formed in step (e) has a response insufficient to detect the unknown parent analyte prior to proceeding to step (f).
15. The method of claim 13 further comprising the step of subjecting the array formed in step (a) to the at least one known parent analyte prior to step (b) and determining whether the array formed in step (a) has a response insufficient to detect the unknown parent analyte prior to proceeding to step (b).
16. A table of responses of the array of the artificial nose of claim 1 to a plurality of distinct analytes.
17. A method of making a table of responses of an array to a plurality of distinct analytes comprising the steps of
(a) forming an array by depositing at least a first die and a second dye directly onto a single support in a predetermined pattern combination, the combination of dyes in the array having a distinct and direct spectral absorbance or reflectance response to distinct analytes comprising one or more parent analytes or their derivatives,
(b) subjecting the array to at least one known parent analyte,
(c) inspecting the distinct and direct absorbance or reflectance response that exists of the array to the known parent analyte,
(d) if no distinct and direct absorbance or reflectance response exists of the array to the at least one known parent analyte, then partially oxidizing the at least one known parent analyte pursuant to a certain protocol to form at least one derivative analyte corresponding to said known parent analyte,
(e) subjecting the array to the at least one derivative analyte corresponding to said known parent analyte,
(f) inspecting the array for a direct and distinct spectral response to the derivative analyte corresponding to said known analyte,
(g) forming an array identical to the array formed in step (a) by repeating step (a) or returning the array in step (a) to its condition prior to step (b),
(h) subjecting the array formed in step (g) to at least one unknown parent analyte to determine whether the array has a response sufficient to detect the unknown parent analyte,
(i) if after step (h) the array has a response sufficient to detect the unknown parent analyte, then determining whether the response matches the response of a known patent analyte in step (c),
(j) if after step (h) the array does not have a response sufficient to detect the unknown parent analyte, then partially oxidizing the at least one unknown parent analyte pursuant to the certain protocol to form at least one derivative analyte corresponding to said unknown parent analyte,
(k) subjecting the array after step 0) to the at least one derivative analyte corresponding to said unknown parent analyte,
(l) inspecting the array after step (k) for a direct and distinct spectral response corresponding to the derivative analyte corresponding to said unknown parent analyte, and
(m) determining after step (1) whether the direct and distinct spectral response of the array to the derivative analyte corresponding to the unknown parent analyte matches the direct and distinct spectral response of the array to the derivative analyte corresponding to the known parent analyte in step (f).
18. The method of claim 12 further comprising the step of forming a table of responses of the array to a plurality of distinct analytes.
19. An artificial tongue comprising an array, the array comprising at least a first dye and a second dye deposited directly onto a single support in a predetermined pattern combination, the combination of dyes in the array having a distinct and direct spectral absorbance or reflectance response to distinct analytes comprising one or more parent analytes or their derivatives, wherein the one or more parent analytes or their derivatives are in solution or liquid analytes, or analytes in a solid or solid analytes, and an oxidizing source to partially oxidize at least one distinct parent analyte to at least one corresponding derivative analyte of said parent analyte, the array at least in part having a stronger distinct and direct absorbance or reflectance response to the derivative analyte than to the corresponding parent analyte.
20. The artificial tongue of claim 19, wherein the at least one distinct parent analyte is from the group consisting of organic compounds lacking ligatable functionality and molecules sterically hindered as to preclude effective ligation, acid-base interaction functionality, hydrogen-base interaction functionality, and dipolar interaction functionality.
21. The artificial tongue of claim 19, wherein the at least one corresponding derivative analyte has a stronger interaction with at least part of the array than its corresponding parent analyte.
22. The artificial tongue of claim 21, wherein the stronger interaction is from the group consisting of ligation interaction, acid-base interaction, hydrogen-base interaction, and dipolar interaction.
23. The artificial tongue of claim 19, wherein the oxidizing source comprises an oxidation catalyst.
24. The artificial tongue of claim 23, wherein the oxidation catalyst from the group consisting of noble metals, noble metal oxides, early transition metals oxides and metal-containing microporous zeolites.
25. The artificial tongue of claim 23, wherein the oxidation catalyst is contained in a cartridge.
26. The artificial tongue of claim 19, wherein the oxidizing source is from the group consisting of substantially pure oxygen, air, hydrogen peroxide, hypochlorite, chlorine dioxide, chlorine or other bleaching agents.
27. The artificial tongue of claim 23, wherein the oxidation catalyst is from the group consisting of platinum, palladium, and vanadium oxide.
28. The artificial tongue of claim 23, wherein the partial oxidation of the at least one distinct analyte is conducted in a temperature range of between 100 K and 1000 K.
29. The artificial tongue of claim 19, wherein the at least one derivative analyte is from the group consisting of alcohols, aldehydes, ketones, carboxylic acids, carbon monoxide, and carbon dioxide.
30. A table of responses of the array of the artificial tongue of claim 19 to a plurality of distinct analytes.
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