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

This application is a Continuation-in-Part of U.S. application Ser. No. 09/705,329, filed on Nov. 3, 2000, now U.S. Pat. No. 6,495,102, 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.

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.

The present invention relates to methods and apparatus for artificial olfaction, e.g., artificial noses, for the detection of odorants by a visual display.

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.

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).

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. 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.

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. USA 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. 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, 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, 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. DiNatale, 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.

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.

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.

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.

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.

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 5,10,15,20-tetraphenylporphyrinate(-2).

In accordance with the present invention, calorimetric 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.

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.

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.

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.

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. 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.

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.

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.

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.

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.

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.

FIG. 9 illustrates another embodiment of the present invention, and more particularly, a microwell porphyrin array wellplate constructed from polydimethylsiloxane (PDMS).

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).

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.

Production of the Sensor Plate of the Present Invention

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). 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 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 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).

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. 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

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 Hewlett Packard Scanjet 3c), or an inexpensive video or CCD camera.

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. 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 .

Synthesis of 5-phenyl-10,15,20-tris(2′,6′-dihydroxy-phenyl)-porphyrinatozinc(II), Zn[(OH) 6 PP]:

The free base 5-phenyl-10,15,20-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 2 Cl 2 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) 6 PP], which was collected and the solvent was removed. The yield of the product was 90% (based on starting hydroxyporphryin). 1 H NMR of H 2 [(OH) 6 PP] in acetone-d 6 (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 C 44 H 30 O 6 N 4 .H 2 O: 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 C 44 H 30 O 6 N 4 =710) in FAB-MS.

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. 1 H NMR of Zn(OH) 6 PP in acetone-d 6 (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 ZnC 44 H 28 O 6 N 4 .H 2 O: 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 ZnC 44 H 28 O 6 N 4 =773) in FAB-MS.

Synthesis of 5-phenyl-10,15,20-tris(2′,6′-disilyloxyphenyl)-porphyrinatozinc(II), Zn(Si 6 PP):

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.

1 H 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 80 H 112 O 6 N 4 Si 6 : 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 ZnC 80 H 112 O 6 N 4 Si 6 =1458).

Synthesis of 5,10,15-tris(2′,6′-disilyoxyphenyl)-20-(2′-hydr-oxy-6′-silyloxyphenyl)porphyrinatozinc(II), [Zn(Si 7 OHPP)], and 5,10,15,20-tetrakis(2′,6′-disilyloxyphenyl)porphy-rinato-zinc(II), [Zn(Si 8 PP)]:

The synthesis of 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 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.

For Zn(Si 7 OHPP), 1 H NMR 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, calcd. for ZnC 86 H 126 O 8 N 4 Si 7 : 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 ZnC 86 H 126 O 8 N 4 Si 7 =1604).

For Zn(Si 8 PP), 1 H 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 ZnC 92 H 140 O 8 N 4 Si 8 : 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 ZnC 92 H 140 O 8 N 4 Si 8 =1718).

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).

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.

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.

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.

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.

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-Rosaniline Base, Acridine Orange Base, Crystal Violet, and Malachite Green Carbinol Base.

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.

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.

Chlorphenol Red

Molecular Formula: C 19 H 12 Cl 2 O 5 S

Molecular Weight: 423.28

CAS: 4430-20-0

Transition interval: pH 4.8 (yellow) to pH 6.7 (violet)

Bromocresol Green

Synonyms: 3′,3″,5′,5″Tetrabromo-m-cresolsulfonphthalein; Bromcresol Green

Molecular Formula: C 21 H 14 Br 4 O 5 S

Molecular Weight: 698.04

CAS: 76-60-8

pH = 3.8 ⁢ ⁢ yellow = 5.4 ⁢ ⁢ blue

Bromocresol Purple

Synonyms: 5′,5″ dibromo-m-cresolsulfonphthalein; Bromcresol Purple Molecular Formula: C 21 H 16 Br 2 O 5 S Molecular Weight: 698.04 CAS: 115-40-2

pH = 5.2 ⁢ ⁢ yellow = 6.8 ⁢ ⁢ blue

Bromothymol Blue

Synonyms: 3′,3″-Dibromothymolsulfonphthalein; Bromthymol Blue Molecular Formula: C 27 H 28 Br 2 O 5 S Molecular Weight: 624.41 CAS: 76-59-5

pH = 6.0 ⁢ ⁢ yellow = 7.6 ⁢ ⁢ blue

Phenol Red

Synonyms: Phenolsulfonphthalein Molecular Formula: C 19 H 14 O 5 S Molecular Weight: 354.38 CAS: 143-74-8

pH = 6.8 ⁢ ⁢ yellow = 8.2 ⁢ ⁢ red

Thymol Blue

Synonyms: Thymolsulfonphthalein Molecular Formula: C 27 H 30 O 5 S Molecular Weight: 466.60 CAS: 76-61-9

pH = 1.2 ⁢ ⁢ red = 2.8 ⁢ ⁢ yellow = 8 ⁢ ⁢ yellow = 9.2 ⁢ ⁢ blue

Cresol Red

Synonyms: Phenol, 4,4′-(1,1-dioxido-3H-2,1-benzoxathiol-3-ylidene)bis[2-methyl-(9CI)] Molecular Formula: C 21 H 18 O 5 S Molecular Weight: 382.43 CAS: 1733-12-6

pH 1.8 (orange) to pH 2.0 (yellow); Transition interval (alkaline): pH 7.0 (yellow) to pH 8.8 (violet)

Alizarin

Synonyms: 1,2-Dihydroxyanthraquinone, 9,10-Anthracenedione, 1,2-dihydroxy-(9CI) Molecular Formula: C 14 H 8 O 4 Molecular Weight: 240.22

pH ⁢ = 5.5 ⁢ ⁢ yellow = 6.8 ⁢ ⁢ red = 10.1 ⁢ ⁢ red = 12.1 ⁢ ⁢ violet

Mordant Orange 1

Synonyms: Alizarin Yellow R, C.I. 14030, 5-(4-nitrophenylazo)salicylic acid Molecular Formula: C 13 H 9 N 3 O 5 Molecular Weight: 287.23 CAS: 2243-76-7

Methyl Orange

Synonyms: 4-(p-[Dimethylamino]phenylazo)benzenesulfonic acid, sodium salt Acid Orange 52 Molecular Formula: C 14 H 14 N 3 O 3 SNa Molecular Weight: 327.3 pH 3.0 (pink)—pH 4.4 (yellow)

Methyl Red

Synonyms: 4-Dimethylaminoazobenzene-2′carboxylicacid; 2-(4-Dimethylaminophenylazo)benzoic acid Molecular Formula: C 15 H 15 N 3 O 2 Molecular Weight: 269.31 CAS: 493-52-7

pH = 4.2 ⁢ ⁢ pink = 6.2 ⁢ ⁢ yellow

Reichardt's Dye

Synonyms: [2,6-diphenyl-4-(2,4,6-triphenylpyridinio)phenolate] Molecular Formula: C 41 H 29 NO Molecular Weight: 551.69 CAS: 10081-39-7

Nile Red

Synonyms: 5H-Benzo[a]phenoxazin-5-one, 9-(diethylamino)-(7CI, 8CI, 9CI), 9-(Diethylamino)-5H-benzo[a]phenoxazin-5-one; Nile Blue A oxazone Molecular Formula: C 20 H 18 N 2 O 2 Molecular Weight: 318.38 CAS: 7385-67-3

Congo Red

Molecular Formula: C 32 H 24 N 6 O 6 S 2 .Na 2 Molecular Weight: 696.67 CAS: 573-58-0

pH range: blue 3.1-4.9 red

Victoria Blue B

Synonyms: Basic Blue 26, C.I. 44045 Molecular Formula: C 33 H 32 ClN 3 Molecular Weight: 506.10 CAS: 2580-56-5

Eosin Blue

Synonyms: (Acid Red 91, C.I. 45400, 4′,5′-dibromo-2′,7′-dinitrofluorescein, disodium salt) Molecular Formula: C 20 H 8 Br 2 N 2 O 9 Molecular Weight: 624.08 CAS: 548-24-3

Fat Brown B

Synonyms: Solvent red 3 Molecular Formula: C 18 H 16 N 2 O 2 Molecular Weight: 292.3 CAS: 6535-42-8

Benzopurpurin 4B

Synonyms: (C.I. 23500, Direct Red 2) Molecular Formula: C 34 H 28 N 6 O 6 S 2 Molecular Weight: 724.73 CAS: 992-59-6

pH range: violet 1.2-3.8 yellow

Phloxine B

Molecular Formula: C 20 H 4 Br 4 Cl 4 O 5 CAS: 18472-87-2

pH range: colorless 2.1-4.1 pink

Orange G

Synonyms: 1-Phenylazo-2-naphthol-6,8-disulfonic acid disodium salt Molecular Formula: C 16 H 10 N 2 Na 2 O 7 S 2 Molecular Weight: 452. pH range: yellow 11.5-14.0 pink

Metanil Yellow

Synonyms: (Acid Yellow 36, C.I. 13065) Molecular Formula: C 18 H 15 N 3 O 3 S.Na Molecular Weight: 375.38 CAS: 587-98-4 pH 1.5 (red) to pH 2.7 (yellow)

Naphthol Green B

Synonyms: (Acid Green 1, C.I. 10020) Molecular Formula: C 10 H 7 NO 5 S Molecular Weight: 878.47 CAS: 19381-50-1

Methylene Blue

Synonyms: (Basic Blue 9, C.I. 52015) Molecular Formula: C 16 H 18 ClN 3 S Molecular Weight: 373.90 CAS: 7220-79-3

Safranine O

Synonyms: (C.I. 50240, 3,7-diamino-2,8-dimethyl-5-phenylphenazinium chloride) Molecular Formula: C 20 H 19 ClN 4 Molecular Weight: 350.85 CAS: 477-73-6

Methylene Violet 3RAX

Synonyms: [3-amino-7-(diethylamino)-5-phenylphenazinium chloride, C.I. 50206, N,N-diethylphenosafranine] Molecular Formula: C 22 H 23 ClN 4 Molecular Weight: 378.91 CAS: 4569-86-2

Sudan Orange G

Synonyms: [C.I. 11920, 4-(phenylazo)resorcinol, Solvent Orange 1] Molecular Formula: C 6 H 5 N═NC 6 H 3 -1,3-(OH) 2 Molecular Weight: 214.22 CAS: 2051-85-6

Morin Hydrate

Synonyms: (2′,3,4′,5,7-pentahydroxyflavone) Molecular Formula: C 15 H 10 O 7 Molecular Weight: 302.24 Neutral Red Molecular Formula: C 15 H 16 N 4 .HCl Molecular Weight: 288.78 CAS: 553-24-2

pH = 6.8 ⁢ ⁢ red = 8.0 ⁢ ⁢ yellow

Disperse Orange 25

Molecular Formula: C 17 H 17 N 5 02 Molecular Weight: 323.36 CAS: 31482-56-1

Rosolic Acid

Molecular Formula: C 20 H 16 O 3 Molecular Weight: 290.32 CAS: 603-45-2

pH = 5.0 ⁢ ⁢ yellow = 6.8 ⁢ ⁢ pink

Fat Brown RR

Molecular Formula: C 16 H 14 N 4 Molecular Weight: 262.32 CAS: 6416-57-5

Cyanidin chloride

Molecular Formula: C15H11O6.Cl Molecular Weight: 322.7 CAS: 528-58-5

3,6-Acridineamine

Molecular Formula: C 13 H 11 N 3 Molecular Weight: 209.25 CAS Number: 92-62-6

6′-Butoxy-2,6-diamino-3,3′-azodipyridine

Synonym: Azodipyridine Molecular Formula: C 14 H 18 N 6 O Molecular Weight: 286.34 CAS: 617-19-6

para-Rosaniline Base

Synonym: Rosaniline Molecular Formula: C 19 H 19 N 3 O Molecular Weight: 305.4 CAS: 25620-78-4

Acridine Orange Base

Molecular Formula: C 17 H 19 N 3 Molecular Weight: 265.36 CAS: 494-38-2

Crystal Violet

Molecular Formula: C 25 H 30 N 3 .Cl Molecular Weight: 407.99 CAS: 548-62-9

pH = 0 ⁢ ⁢ yellow = 1.8 ⁢ ⁢ blue

Malachite Green Carbinol Base

Molecular Formula: C 23 H 26 N 2 O Molecular Weight: 346.48 CAS: 510-13-4

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 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 , 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: C 8 H 18 O 4 , 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: C 10 H 22 O 5 , Boiling Point (° C.): 275-276 at 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).

where TPP=5,10,15,20-tetraphenylporphyrinate(-2);

Zn (Si 6 PP)=5(phenyl)-10,15,29-trikis(2′,6′-disilyloxyphenyl)porphyrinatozinc(II); Zn(Si 7 OHPP)=5,10,15trikis(2′,6′-disilyloxyphenyl)-20-(2′-hydroxy-6′-silyloxyphenyl)porphyrinatozinc(II); Zn(Si 8 PP)=5,10,15,20-tetrakis(2′,6′-disilyloxyphenyl)porphyrinatozinc(II); Me Red=Methyl Red; BCP=Bromocresol Purple; BTB=Bromothymol Blue; Ph Red=Phenol Red; BCG=Bromocresol Green; CresRed=Cresol Red; CP Red=Chlorophenol Red; R Dye=Reichardt's Dye; TB=Thymol Blue; MeOr=Methyl Orange; and basic indicates the addition of KOH until the color of the basic form of the indicator dye was observed.

Note: DOW CORNING 704 silicone diffusion pump fluid (Molecular Weight: 484.82, Density: 1.070, CAS Number: 3982-82-9) was added to all porphyrin solutions: 40 μl/ml.

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).

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).

where

SnTPPCl 2 is 5,10,15,20-Tetraphenyl-21H,23H-porphine Tin(W) Dichloride

Molecular Formula: C 44 H 28 SnCl 2 N 4 Molecular Weight: 802 CAS: 26334-85-0;

CoTPP is 5,10,15,20-Tetraphenyl-21H,23H-porphine Cobalt(II)

Molecular Formula: C 44 H 28 CoN 4 Molecular Weight: 671 CAS: 14172-90-8;

CrTPPCl is 5,10,15,20-Tetraphenyl-21H,23H-porphine Chromium(III) Chloride

Molecular Formula: C 44 H 28 CrClN 4 Molecular Weight: 700 CAS: 28110-70-5;

MnTPPCl is 5,10,15,20-Tetraphenyl-21H,23H-porphine Manganese(III) Chloride

Molecular Formula: C 44 H 28 ClMnN 4 Molecular Weight: 703 CAS: 32195-55-4;

FeTPPCl is 5,10,15,20-Tetraphenyl-21H,23H-porphine Iron(III) Chloride

Molecular Formula: C 44 H 28 ClFeN 4 Molecular Weight: 704 CAS: 16456-81-8;

CuTPP is 5,10,15,20-Tetraphenyl-21H,23H-porphine Copper(II)

Molecular Formula: C 44 H 28 CuN 4 Molecular Weight: 676 CAS: 14172-91-9;

Zn(C 3 F 7 ) 4 P is Meso tetra(heptafluoropropyl)porphine Zinc(II)

Molecular Formula: C 32 H 8 ZnF 28 N 4 Molecular Weight: 1044;

ZnF 2 PP is 5,10,15,20-Tetrakis(2,6-difluorophenyl)-21H,23H-porphine Zinc(II)

Molecular Formula: C 44 H 20 F 8 N 4 Zn Molecular Weight: 820;

InTPPCl is 5,10,15,20-Tetraphenyl-21H,23H-porphine Indium(III) Chloride

Molecular Formula: C 44 H 28 ClInN 4 Molecular Weight: 763;

ZnTMP is 5,10,15,20-Tetrakis(2,4,6-trimethylphenyl)-21H,23H-porphine Zinc(II)

Molecular Formula: C 56 H 52 N 4 Zn Molecular Weight: 846 CAS: 104025-54-9;

ZnTPP is 5,10,15,20-Tetraphenyl-21H,23H-porphine Zinc(II)

Molecular Formula: C 44 H 28 N 4 Zn Molecular Weight: 678 CAS: 14074-80-7;

FeTFPPCl is 5,10,15,20-Tetrakis(pentafluorophenyl)-21H,23H-porphine Iron(III) Chloride

Molecular Formula: C 44 H 8 ClF 20 FeN 4 Molecular Weight: 1063.85 CAS: 36965-71-6;

ZnSi 6 PP is 5(phenyl)-10,15,20-trikis(2′,6′-disilyloxyphenyl)porphyrinatozinc(II)

Molecular Formula: ZnC 80 H 112 O 6 N 4 Si 6 Molecular Weight: 1458;

ZnSi 7 OHPP is 5,10,15-trikis(2′,6′-disilyloxyphenyl)-20-(2′-hydroxy-6′-silyloxyphenyl)porphyrinatozinc(II)

Molecular Formula: ZnC 86 H 126 O 8 N 4 Si 7 Molecular Weight: 1604;

ZnSi 8 PP is 5,10,15,20-tetrakis(2′,6′-disilyloxyphenyl)porphyrinatozinc(II)

Molecular Formula: ZnC 92 H 140 O 8 N 4 Si 8 Molecular Weight: 1718;

H 2 TPP is 5,10,15,20-Tetraphenyl-21H,23H-porphine

Molecular Formula: C 44 H 30 N 4 Molecular Weight: 614.75 CAS: 917-23-7;

H 2 FPP is 5,10,15,20-Tetrakis(pentafluorophenyl)-21H,23H-porphine

Molecular Formula: C 44 H 10 F 20 N 4 Molecular Weight: 974.57 CAS: 25440-14-6;

Azodipyridine is 6′-Butoxy-2,6-diamino-3,3′-azodipyridine

Molecular Formula: C 14 H 18 N 6 O Molecular Weight: 286.34 CAS: 617-19-6;

Rosaniline is Para-Rosaniline Base

Molecular Formula: C 19 H 19 N 3 O Molecular Weight: 305.4 CAS: 25620-78-4

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).

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.