Classifications

• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
  • G01N27/02—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance
  • G01N27/04—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance by investigating resistance
  • G01N27/12—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance by investigating resistance of a solid body in dependence upon absorption of a fluid; of a solid body in dependence upon reaction with a fluid, for detecting components in the fluid
  • G01N27/125—Composition of the body, e.g. the composition of its sensitive layer
  • G01N27/126—Composition of the body, e.g. the composition of its sensitive layer comprising organic polymers
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B82—NANOTECHNOLOGY
  • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
  • B82Y15/00—Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
  • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
  • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
  • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
  • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
  • G01N33/54366—Apparatus specially adapted for solid-phase testing
  • G01N33/54373—Apparatus specially adapted for solid-phase testing involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings

Definitions

• This invention relates generally to sensors for detecting analytes in fluids. More particularly, it relates to an array of sensors useful for constructing "electronic noses" for analyzing complex vapors and producing a sample output.
• the present invention relates to a device for detecting a chemical analyte in a fluid, which includes gases, vapors and liquids.
• the present invention relates to a device for detecting a chemical analyte, comprising: a sensor array connected to a measuring apparatus having at least one sensor comprising regions of nonconductive material and conductive material compositionally different than the nonconductive material, wherein the conductive material comprises a nanoparticle; and a response path through the regions of nonconductive material and the conductive material.
• the sensor array is based on a variety of "chemiresistor" elements. Such elements are simply prepared and are readily modified chemically to respond to a broad range of analytes.
• device includes a substrate having at least one surface and at least two sensors fabricated onto the surface, wherein each sensor has a first and second electrical lead which are electrically connected to a chemically sensitive resistor.
• the resistor comprises a plurality of alternating nonconductive regions (comprising a nonconductive organic material) and conductive regions (comprising a conductive material or particle).
• the electrical path between the first and second leads is transverse to (i.e., passes through) the plurality of alternating nonconductive and conductive regions.
• the resistor provides a difference in resistance between the conductive elements when 1) contacted with a fluid comprising a chemical analyte at a first concentration, than when contacted with a fluid comprising the chemical analyte at a second different concentration or 2) contacted with a fluid comprising a first chemical analyte at a concentration, than when contacted with a fluid comprising a second chemical analyte (different from the first) at the same concentration.
• the variability in chemical sensitivity from sensor to sensor is conveniently provided by qualitatively or quantitatively varying the composition of the conductive and/or nonconductive regions.
• the conductive material in each resistor is held constant (e.g., the same conductive material such as polypyrrole, or carbon black), while the nonconductive material varies between resistors (e.g., different polymers).
• the conductive material is a conductive particle, such as a nanoparticle.
• the alternating nonconductive regions can be a covalently attached ligand to a conductive core (the conductive region). These ligands can be polyhomo- or polyheterofunctionalized, thereby being suitable for the detection of various analytes.
• Arrays of such sensors are constructed with at least two sensors having different chemically sensitive resistors providing various differences in resistance.
• An electronic nose for detecting an analyte in a fluid can be constructed by using such arrays in conjunction with an electrical measuring device electrically connected to the conductive elements of each sensor.
• Such electronic noses can incorporate a variety of additional components, including means for monitoring the temporal response of each sensor, assembling and analyzing sensor data to determine analyte identity, analyte concentration, or quality control determinations. Methods of making and using the disclosed sensors, arrays and electronic noses are also provided. BRIEF DESCRIPTION OF THE DRAWINGS
• Fig 1(A) shows an overview of sensor design
• Fig 1(B) shows an overview of sensor operation
• Fig 1(C) shows an overview of system operation.
• Fig 2. shows a cyclic voltammogram of a poly(pyrrole)-coated platinum electrode.
• the electrolyte was 0.10 M [(C4H9) N] + [ClO 4 ] ⁇ in acetonitrile, with a scan rate of O. lO V s "1 .
• Fig 3(A) shows the optical spectrum of a spin coated poly(pyrrole) film that had been washed with methanol to remove excess pyrrole and reduced phosphomolybdic acid.
• Fig. 3(B) shows the optical spectrum of a spin-coated poly(pyrrole) film on indium-tin-oxide after 10 potential cycles between +0.70 and -1.00 V vs.
• SCE saturated Calomel Reference Electrode
• the spectra were obtained in 0.10 M KC1 - H 2 O.
• Fig. 4(A) shows a schematic of a sensor array showing an enlargement of one of the modified ceramic capacitors used as sensing elements.
• the response patterns to various analytes generated by the sensor array described in Table 5 are displayed for acetone Fig. 4(B); benzene Fig 4(C); and ethanol Fig 4(D).
• Figs. 5(A)-(D) shows the principle component analysis of autoscaled data from individual sensors containing different polymers.
• A poly(styrene);
• B poly- ⁇ -methyl styrene;
• C poly(styrene-acrylonitrile);
• D poly(styrene-allyl alcohol).
• Fig. 6(A) and 6(B) shows the principle component analysis of data obtained from all sensors described in Table 5. Conditions and symbols are identical to Figs. 5(A)-5(D).
• Fig 6A shows data represented in the first three principle components pel, pc2 and pc3, while
• Fig. 6B shows the data when represented in pel, pc2, and pc4.
• a higher degree of discrimination between some solvents could be obtained by considering the fourth principle component as illustrated by larger separations between chloroform, tetrahydrofuran, and isopropyl alcohol in Fig. 6B.
• Fig. 9 shows the first three principal components for the response of a carbon-black based sensor array with 10 elements.
• the non-conductive components of the composites used are listed in Table 5, and the resistors were 20 w/w% carbon black.
• Fig. 10 (A)-(B) shows a synthetic scheme of various nanoparticles of the present invention.
• Fig. 11 (A)-(B) shows response patterns of various sensors in an array to different analytes.
• the present invention provides sensor arrays for detecting an analyte in a fluid, which may be gaseous or liquid in nature in conjunction with an electrical measuring apparatus. These arrays comprise a plurality of compositionally different chemical sensors.
• the present invention relates to a device for detecting a chemical analyte comprising: a sensor array connected to a measuring apparatus having at least one sensor comprising regions of nonconductive material and conductive material compositionally different than the nonconductive material, wherein the conductive material comprises a nanoparticle; and a response path through the regions of nonconductive material and the conductive material.
• the sensor array is based on a variety of "chemiresistor" elements.
• Each sensor comprises at least first and second conductive leads electrically coupled to and separated by a chemically sensitive resistor.
• the leads may be any convenient conductive material, usually a metal, and may be interdigitized to manipulate the circuit resistance and maximize the signal to noise ratio.
• the resistor comprises a plurality of alternating nonconductive and conductive regions transverse to the electrical path between the conductive leads.
• the resistors are fabricated by blending a conductive material with a nonconductive material, e.g., an organic polymer, such that the electrically conductive path between the leads coupled to the resistor is interrupted by gaps of non-conductive organic polymer material.
• the matrix regions separating the particles provide the gaps.
• the colloid is a nanoparticle that is optionally stabilized.
• the nonconductive gaps range in path length from about 10 to 1,000 angstroms, usually on the order of 100 angstroms, providing individual resistance of about 10 to 1,000 m ⁇ , usually on the order of 100 m ⁇ , across each gap.
• the path length and resistance of a given gap is not constant, but rather is believed to change as the nonconductive organic polymer of the region absorbs, adsorbs or imbibes an analyte.
• the dynamic aggregate resistance provided by these gaps in a given resistor is a linear or non-linear function of analyte permeation of the nonconductive regions.
• the conductive material may also contribute to the dynamic aggregate resistance as a linear or nonlinear function of analyte permeation (e.g., when the conductive material is a conductive organic polymer, such as polypyrrole).
• the resistor comprises a plurality of alternating regions of a conductor with regions of an insulator. Without being bound to any particular theory, it is believed that the electrical pathway that an electrical charge traverses between the two contacting electrodes traverses both the region of a conductor and the region of an insulator.
• the conducting region can be anything that can carry electrons from atom to atom, including, but not limited to, a material, a particle, a metal, a polymer, a substrate, an ion, an alloy, an organic material, (e.g., carbon, graphite, etc.) an inorganic material, a biomaterial, a solid, a liquid, a gas or mixtures thereof.
• the insulating region can be anything that can impede electron flow from atom to atom, including, but not limited to, a material, a polymer, a plasticizer, an organic material, an organic polymer, a filler, a ligand, an inorganic material, a biomaterial, a solid, a liquid, a gas and mixtures thereof.
• a wide variety of conductive materials and nonconductive organic polymer materials can be used. Table 1 provides exemplary conductive materials for use in resistor fabrication; mixtures, such as those listed, can also be used.
• Table 2 provides exemplary nonconductive organic polymer materials; blends and copolymers, such as the polymers listed here, can also be used. Combinations, concentrations, blend stoichiometries, percolation thresholds
• the conductive material is a conductive particle, such as a colloidal nanoparticle.
• nanoparticle refers to a conductive cluster, such as a metal cluster, having a diameter on the nanometer scale. As described more fully below, such nanoparticles are optionally stabilized with organic ligands.
• the nonconductive region can optionally be a ligand that is attached to a central core making up the nanoparticle.
• ligands i.e., caps
• the nanoparticles, i.e., clusters, are stabilized by the attached ligands.
• concentration of the synthetic reagents the particle size can be manipulated and controlled.
• the resistors are nanoparticles comprising a central core conducting element and an insulating attached ligand optionally in a polymer matrix.
• various conducting materials are suitable for the central core.
• the nanoparticles have a metal core.
• Preferred metal cores include, but are not limited to, Au, Ag, Pt, Pd, Cu, Ni, AuCu and mixtures thereof. Gold (Au) is especially preferred.
• Au Au
• These metallic nanoparticles can be synthesized using a variety of methods. In a preferred method of synthesis, a modification of the protocol developed by House et al. (30) (the teachings of which are incorporated herein by reference), can be used.
• the starting molar ratio of HAuCl to alkanethiol is selected to construct particles of the desired diameter.
• the organic phase reduction of HAuCl 4 by an alkanethiol and sodium borohydride leads to stable, modestly polydisperse, alkanethiolate-protected gold clusters having a core dimension of about 1 nm to about 100 nm.
• the nanoparticles range in size from about 1 nm to about 50 nm. More preferably, the nanoparticles range in size from about 5 nm to about 20 nm.
• a molar ratio of HAuCl 4 to alkanethiol of greater than 1 : 1 leads to smaller particle sizes, whereas a molar ratio of HAuCl 4 to alkanethiol less than 1 : 1 yield clusters which are larger in size.
• a ratio of HAuCl 4 to alkanethiol it is possible to generate various sizes and dimensions of nanoparticles suitable for a variety of analytes.
• Ligands or caps of various chemical classes are suitable for use in the present invention.
• Ligands include, but are not limited to, alkanethiols having alkyl chain lengths of about C ⁇ -C 30 .
• the alkyl chain lengths of the alkanethiols are between about C 3 to about C ⁇ 2 .
• the nanoparticles' conductivity decreases as alkane length increases.
• Alkanethiols suitable for use can also be polyhomofunctionalized or polyheterofunctionalized (such as, at the ⁇ -position, or last position of the chain).
• polyhomofunctionalized means that the same chemical moiety has been used to modify the ligand at various positions within the ligand.
• Chemical moieties suitable for functional modification include, but are not limited to, bromo, chloro, iodo, fluoro, amino, hydroxyl, thio, phosphino, alkylthio, cyano, nitro, amido, carboxyl, aryl, heterocyclyl, ferrocenyl or heteroaryl.
• the ligands can be attached to the central core by various methods including, but not limited to, covalent attachment, and electrostatic attachment.
• polyheterofunctionalized means that different chemical moieties or functional groups are used to modify the ligands at various positions.
• This reaction can be a simultaneous exchange of a mixture of thiols onto the nanoparticle, or alternatively, a stepwise progressive exchange of different thiols, isolating the nanoparticle product after each step.
• the place exchange reaction replaces an existing alkanethiol with an alkanethiol comprising a functional group.
• Suitable ligands include, but are not limited to, polymers, such as polyethylene glycol; surfactants, detergents, biomolecules, such as polysaccharides: protein complexes, polypeptides, dendrimeric materials, oligonucleotides, fluorescent moieties and radioactive groups.
• the core acts as a scaffolding, which can support more complex organic ligands.
• These scaffolding can be used as a solid support for combinatorial synthesis.
• various functional groups can be attached to the core to achieve structural diversity.
• the combinatorial synthesis can be performed using a robotic armature system.
• these systems include automated workstations like the automated apparatus developed by Takeda Chemical Industries, LTD. (Osaka, Japan) and many robotic systems utilizing robotic arms (Zymate II, Zymark Corporation, Hopkinton, Mass.; Orca, Hewlett-Packard, Palo Alto, Calif.) which mimic the manual operations performed by a synthetic chemist.
• the nature and implementation of modifications to these methods (if any) so that they can operate will be apparent to persons skilled in the relevant art.
• steric crowding can accompany the introduction of numerous functional groups onto the surface of the nanoparticle core that is occupied by the ligand, such as an alkanethiolate ligand.
• the number of ligands and the amount of functionalization is directly proportional to the size of the central core.
• electrical conductivity becomes more difficult to measure when the ratio of metal to ligand decreases.
• the core can become too big to allow the ligands to solubilize the particle.
• those of skill in the art will select suitable ratios of core size to ligand amount for particular uses.
• sensors are prepared as composites of "naked” nanoparticles and an insulating material is added.
• the term “naked nanoparticles” means that the core has no covalently attached ligands or caps.
• insulating materials can be used in this embodiment.
• Preferred insulating materials are organic polymers. Suitable organic polymers include, but are not limited to, polycaprolactone, polystyrene, and poly(methyl methacrylate). Varying the insulating material types, concentration, size, etc., provides the diversity necessary for an array of sensors.
• the metal to insulating polymer ratio is about 50% to about 90%) (wt/wt).
• the metal to insulating polymer ratio is about 85% to about 90% (wt/wt).
• Sensors can also be prepared using the nanoparticle and an alkylthiol ligand as the sole insulating matrix.
• varying the ligand, ligand size and functionalization can provide sensor diversity.
• Sensor films can be cast on interdigitated electrode substrates.
• Sensors that are comprised either of naked nanoparticles or nanoparticles having ligands show a reversible increase in electrical resistance upon exposure to chemical vapors.
• Nanoparticles such as alkylthiol-capped gold colloids, are soluble or dispersible in a wide range of organic solvents having a large spectrum of polarity.
• the chemical analyte diffuses into and is dispersed within the nanoparticle ligands or insulating material and thereby changes the electrical properties of the sensors. These property changes which are then detected include, but are not limited to, resistance, capacitance, conductivity, magnetism, optical changes and impedance.
• the sensor arrays of the present invention comprise other sensor types.
• Various sensors suitable for detection of analytes include, but are not limited to: surface acoustic wave (SAW) sensors; quartz microbalance sensors; conductive composites; chemiresitors; metal oxide gas sensors, such as tin oxide gas sensors; organic gas sensors; metal oxide field effect transistor (MOSFET); piezoelectric devices; infrared sensors; sintered metal oxide sensors; Pd-gate MOSFET; metal FET structures; metal oxide sensors, such as a Tuguchi gas sensors; phthalocyanine sensors; electrochemical cells; conducting polymer sensors; catalytic gas sensors; organic semiconducting gas sensors; solid electrolyte gas sensors; piezoelectric quartz crystal sensors; dye-impregnated polymer films on fiber optic detectors; polymer-coated micromirrors; electrochemical gas detectors; chemically sensitive field-effect transistors; carbon black-polymer composite chemiresistors; micro-electro-mechanical system devices; and micro
• the chemiresistors of the present invention can be fabricated by many techniques including, but not limited to, solution casting, suspension casting and mechanical mixing.
• solution casting routes are advantageous because they provide homogeneous structures and are easy to process.
• resistor elements can be easily fabricated by spin, spray or dip coating. Since all elements of the resistor must be soluble, however, solution casting routes are somewhat limited in their applicability. Suspension casting still provides the possibility of spin, spray or dip coating, but more heterogeneous structures than with solution casting are expected.
• mechanical mixing there are no solubility restrictions since it involves only the physical mixing of the resistor components, but device fabrication is more difficult since spin, spray and dip coating are no longer possible. A more detailed discussion of each of these follows.
• the chemiresistors can be fabricated by solution casting.
• the oxidation of pyrrole by phosphomolybdic acid presented herein represents such a system.
• the phosphomolybdic acid and pyrrole are dissolved in tetrahydrofuran (THF) and polymerization occurs upon solvent evaporation.
• THF tetrahydrofuran
• the choice of non-conductive polymers in this route is, of course, limited to those that are soluble in the reaction media.
• the doping procedure exposure to I 2 vapor, for instance
• the doping procedure can be performed on the blend to render the substituted poly(cyclooctatetraene) conductive.
• the choice of non-conductive polymers is limited to those that are soluble in the solvents that the undoped conducting polymer is soluble in and to those stable to the doping reaction.
• Certain conducting polymers can also be synthesized via a soluble precursor polymer. In these cases, blends between the precursor polymer and the non-conducting polymer can first be formed followed by chemical reaction to convert the precursor polymer into the desired conducting polymer. For instance, poly(p-phenylene vinylene) can be synthesized through a soluble sulfonium precursor.
• Blends between this sulfonium precursor and the non-conductive polymer can be formed by solution casting. After which, the blend can be subjected to thermal treatment under vacuum to convert the sulfonium precursor into the desired poly(/?-phenylene vinylene).
• suspension casting one or more of the components of the resistor is suspended and the others dissolved in a common solvent.
• Suspension casting is a rather general technique applicable to a wide range of species, such as carbon blacks or colloidal metals, which can be suspended in solvents by vigorous mixing or sonication.
• the non-conductive polymer is dissolved in an appropriate solvent (such as THF, acetonitrile, water, etc.). Colloidal silver is then suspended in this solution and the resulting mixture is used to dip coat electrodes.
• Mechanical mixing is suitable for all of the conductive/non-conductive combinations possible.
• the materials are physically mixed in a ball-mill or other mixing device.
• carbon black / non-conductive polymer composites are readily made by ball-milling.
• mechanical mixing at elevated temperatures can improve the mixing process.
• composite fabrication can sometimes be improved by several sequential heat and mix steps.
• spray deposition can be used.
• the temperature can be elevated to promote a uniform film formation.
• the stable dispersions and homogenous films of these nanoparticles can also facilitate reproducible fabrication of the vapor sensors.
• the individual elements can be optimized for a particular application by varying their chemical make up and morphologies.
• the chemical nature of the resistors determines to which analytes they will respond and their ability to distinguish different analytes.
• the relative ratio of conductive to insulating components determines the magnitude of the response since the resistance of the elements becomes more sensitive to sorbed molecules as the percolation threshold is approached.
• the film morphology is also important in determining response characteristics.
• sensors can be chosen that are appropriate for the analytes expected in a particular application, their concentrations, and the desired response times. Further optimization can then be performed in an iterative fashion as feedback on the performance of an array under particular conditions becomes available.
• the resistor may itself form a substrate for attaching the lead or the resistor.
• the structural rigidity of the resistors may be enhanced through a variety of techniques: chemical or radiation cross-linking of polymer components (dicumyl peroxide radical cross-linking, UV-radiation cross-linking of poly(olef ⁇ ns), sulfur cross-linking of rubbers, e-beam cross-linking of Nylon, etc.), the incorporation of polymers or other materials into the resistors to enhance physical properties (for instance, the incorporation of a high molecular weight, high transition metal (Tm) polymers), the incorporation of the resistor elements into supporting matrices, such as clays or polymer networks (forming the resistor blends within poly(methylmethacrylate) networks or within the lamellae of montmorillonite, for instance), etc.
• the resistor is deposited as a surface layer on a solid matrix that provides means for supporting the leads.
• the solid matrix is a chemically inert, non-conductive substrate, such as a glass or ceramic.
• Sensor arrays particularly well-suited to scaled up production are fabricated using integrated circuit (IC) design technologies.
• the chemiresistors can easily be integrated onto the front end of a simple amplifier interfaced to an A/D converter to efficiently feed the data stream directly into a neural network software or hardware analysis section.
• Micro-fabrication techniques can integrate the chemiresistors directly onto a micro-chip which contains the circuitry for analogue signal conditioning/processing and then data analysis. This provides for the production of millions of incrementally different sensor elements in a single manufacturing step using ink-jet technology. Controlled compositional gradients in the chemiresistor elements of a sensor array can be induced in a method analogous to how a color ink-jet printer deposits and mixes multiple colors.
• a sensor array of a million distinct elements only requires a 1 cm x 1 cm sized chip employing lithography at the 10 ⁇ m feature level, which is within the capacity of conventional commercial processing and deposition methods. This technology permits the production of sensitive, small-sized, stand-alone chemical sensors.
• Preferred sensor arrays have a predetermined inter-sensor variation in the structure or composition of the nonconductive organic polymer regions.
• the variation may be quantitative and/or qualitative.
• the concentration of the nonconductive organic polymer in the blend can be varied across sensors.
• a variety of different organic polymers may be used in different sensors.
• a variety of capped colloids can be used as different sensors.
• a capped colloid system can be used in conjunction with a variety of polymer matrices as different sensors.
• An electronic nose for detecting an analyte in a fluid is fabricated by electrically coupling the sensor leads of an array of compositionally different sensors to an electrical measuring device. The device measures changes in resistivity at each sensor of the array, preferably simultaneously and preferably over time. Frequently, the device includes signal processing means and is used in conjunction with a computer and data structure for comparing a given response profile to a structure-response profile database for qualitative and quantitative analysis.
• such a nose comprises at least ten, usually at least 100, and often at least 1000 different sensors, though with mass deposition fabrication techniques described herein or otherwise known in the art, arrays of on the order of at least 10 6 sensors are readily produced.
• each resistor provides a first electrical resistance between its conductive leads when the resistor is contacted with a first fluid comprising a chemical analyte at a first concentration, and a second electrical resistance between its conductive leads when the resistor is contacted with a second fluid comprising the same chemical analyte at a second different concentration.
• the fluids may be liquid or gaseous in nature.
• the first and second fluids may reflect samples from two different environments, a change in the concentration of an analyte in a fluid sampled at two time points, a sample and a negative control, etc.
• the sensor array necessarily comprises sensors which respond differently to a change in an analyte concentration, i.e., the difference between the first and second electrical resistance of one sensor is different from the difference between the first and second electrical resistance of another sensor.
• the temporal response of each sensor is recorded.
• the temporal response of each sensor may be normalized to a maximum percent increase and percent decrease in resistance which produces a response pattern associated with the exposure of the analyte.
• a structure-function database correlating analytes and response profiles is generated. Unknown analyte may then be characterized or identified using response pattern comparison and recognition algorithms.
• analyte detection systems comprising sensor arrays, an electrical measuring device for detecting resistance across each chemiresistor, a computer, a data structure of sensor array response profiles, and a comparison algorithm are provided.
• the electrical measuring device is an integrated circuit comprising neural network-based hardware and a digital-analog converter (DAC) multiplexed to each sensor, or a plurality of DACs, each connected to different sensor(s).
• DAC digital-analog converter
• Analyte applications include broad ranges of chemical classes including, but not limited to organics such as alkanes, alkenes, alkynes, dienes, alicyclic hydrocarbons, arenes, alcohols, ethers, ketones, aldehydes, carbonyls, carbanions, polynuclear aromatics and derivatives of such organics, e.g., halide derivatives, etc., biomolecules such as sugars, isoprenes and isoprenoids, fatty acids and derivatives, etc.
• organics such as alkanes, alkenes, alkynes, dienes, alicyclic hydrocarbons, arenes, alcohols, ethers, ketones, aldehydes, carbonyls, carbanions, polynuclear aromatics and derivatives of such organics, e.g., halide derivatives, etc.
• biomolecules such as sugars, isoprenes and isoprenoids, fatty acids and derivatives, etc.
• the general method for using the disclosed sensors, arrays and electronic noses, for detecting the presence of an analyte in a fluid involves resistively sensing the presence of an analyte in a fluid with a chemical sensor comprising first and second conductive leads electrically coupled to and separated by a chemically sensitive resistor as described above by measuring a first resistance between the conductive leads when the resistor is contacted with a first fluid comprising an analyte at a first concentration and a second different resistance when the resistor is contacted with a second fluid comprising the analyte at a second different concentration.
• Example 1 This example illustrates the synthesis of colloidal gold nanoparticles with covalently attached alkylthiol ligands.
• the gold nanoparticles described herein were prepared using a procedure similar to the protocol developed by House et al. All solutions were prepared using volumetric procedures. Into a 100 ml flask, HAuC . (0.3047 mmol) and tetraoctyl- ammonium bromide (0.6764 mmol) were added. A yellow solution was formed which immediately turned brown. The mixture was shaken and, while stirring, 1-dodecanethiol (0.08684 mmol) was added followed by sodium borohydride (3.352 mmol). After about 12 hours, the organic layer was separated and left an interphase layer. The aqueous layer was extracted a second time with hexane, which again left an interphase layer.
• Example 2 This example illustrates conductivity measurements using the gold nanoparticles made in accordance with Example 1.
• Example 3 This example illustrates the use of gold nanoparticles as the conductive element in vapor sensors. Studies focused on the fabrication and application of nanoscale gold conductors in polymer composite sensors.
• the conductors were prepared with a modified procedure of Hostetler et al. (33). Briefly, short alkyl chain thiols were used as the passivating agent in conductor fabrication. Pentanethiol and hexanethiol capped particles, although soluble, generally have high electrical resistance. Propanethiol passivated gold nanoparticles formed highly conductive, but less soluble, aggregates during the purification procedure when a ratio of 6:1 gold:thiol was used. This passivated gold material was used as the conductor region. An array of 17 sensors was constructed using various organic polymers as the insulating region (see, Table 3), along with the propyl cap region.
• PEVA 25 is poly(ethylene-co-vinyl acetate 25% vinylacetate); PS is poly(styrene); PMMA is poly(methyl methacrylate); PVPyrolidone is polyvinylpyrolidone; PCL is polycaprolactone; and polyethylenimine is linear polyethylenimine.
• Example 4 i. Polymer Synthesis. Poly(pyrrole) films used for conductivity, electrochemical, and optical measurements were prepared by injecting equal volumes of N -purged solutions of pyrrole (1.50 mmoles in 4.0 ml dry tetrahydrofuran) and phosphomolybdic acid (0.75 mmoles in 4.0 ml tetrahydrofuran) into a N 2 -purged test tube. Once the two solutions were mixed, the yellow phosphomolybdic acid solution turned dark green, with no observable precipitation for several hours. This solution was used for film preparation within an hour of mixing. ii Sensor Fabrication.
• Poly(pyrrole) sensors were made by mixing two solutions, one of which contained 0.29 mmoles pyrrole in 5.0 ml tetrahydrofuran, with the other containing 0.25 mmoles phosphomolybdic acid and 30 mg of nonconducting organic material (e.g., a polymer) in 5.0 ml of tetrahydrofuran.
• the mixture of these two solutions resulted in a w:w ratio of pyrrole to polymer of 2:3.
• An inexpensive, quick method for creating the chemiresistor array elements was accomplished by effecting a cross-sectional cut through commercial 22 nF ceramic capacitors (Kemet Electronics Corporation).
• a data set obtained from a single exposure of the array to an odorant produced a set of descriptors (i.e., resistances), dj.
• the data obtained from multiple exposures thus produced a data matrix D where each row, designated by j, consisted of n descriptors describing a single member of the data set (i.e., a single exposure to an odor). Since the baseline resistance and the relative changes in resistance varied among sensors, the data matrix was autoscaled before further processing (19).
• Principle component analysis (19) was performed to determine linear combinations of the data such that the maximum variance [defined as the square of the standard deviation] between the members of the data set was obtained in n mutually orthogonal dimensions.
• the linear combinations of the data resulted in the largest variance [or separation] between the members of the data set in the first principle component (pel) and produced decreasing magnitudes of variance from the second to the n th principle component (pc2 - pen).
• the coefficients required to transform the autoscaled data into principle component space (by linear combination) were determined by multiplying the data matrix, D, by its transpose, D ⁇ (i.e., diagonalizing the matrix) (19)
• This operation produced the correlation matrix, R, whose diagonal elements were unity and whose off-diagonal elements were the correlation coefficients of the data.
• the total variance in the data was thus given by the sum of the diagonal elements in R.
• the n eigenvalues, and the corresponding n eigenvectors, were then determined for R.
• Each eigenvector contained a set of n coefficients which were used to transform the data by linear combination into one of its n principle components.
• the corresponding eigenvalue yielded the fraction of the total variance that was contained in that principle component.
• This operation produced a principle component matrix, P, which had the same dimensions as the original data matrix. Under these conditions, each row of the matrix P was still associated with a particular odor and each column was associated with a particular principle component.
• Fig. 2 shows the cyclic voltammetric behavior of a chemically polymerized poly(pyrrole) film following ten cycles from -1.00 V to +0.70 V vs. SCE.
• the cathodic wave at -0.40 V corresponded to the reduction of poly(pyrrole) to its neutral, nonconducting state
• the anodic wave at -0.20 V corresponded to the reoxidation of poly(pyrrole) to its conducting state (24).
• Fig 3 A shows the optical spectrum of a processed polypyrrole film that had been spin-coated on glass and then rinsed with methanol.
• the single absorption maximum was characteristic of a highly oxidized poly(pyrrole) (26), and the absorption band at 4.0 eV was characteristic of an interband transition between the conduction and valence bands.
• the lack of other bands in this energy range was evidence for the presence of bipolaron states (see, Fig. 3 A), as have been observed in highly oxidized poly(pyrrole) (26).
• Sensor arrays consisted of as many as 14 different elements, with each element synthesized to produce a distinct chemical composition and, thus, a distinct sensor response for its polymer film.
• the resistance, R, of each film-coated individual sensor was automatically recorded before, during, and after exposure to various odorants.
• a typical trial consisted of a 60 sec rest period in which the sensors were exposed to flowing air (3.0 liter-min "1 ), a 60 sec exposure to a mixture of air (3.0 liter-min "1 ) and air that had been saturated with solvent (0.5 - 3.5 liter-min "1 ), and then a 240 sec exposure to air (3.0 liter-min "1 ).
• the only information used was the maximum amplitude of the resistance change divided by the initial resistance, ⁇ R max /Ri, of each individual sensor element.
• Most of the sensors exhibited either increases or decreases in resistance upon exposure to different vapors, as expected from changes in the polymer properties upon exposure to different types chemicals (17-18).
• sensors displayed an initial decrease followed by an increase in resistance in response to a test odor. Since the resistance of each sensor could increase and/or decrease relative to its initial value, two values of ⁇ Rm ax /Ri were reported for each sensor.
• Figs. 4B-4D depict representative examples of sensor amplitude responses of a sensor array (see, Table 5).
• data were recorded for three separate exposures to vapors of acetone, benzene, and ethanol flowing in air.
• the response patterns generated by the sensor array described in Table 5 are displayed for: (B) acetone; (C) benzene; and (D) ethanol.
• the sensor response was defined as the maximum percent increase and decrease of the resistance divided by the initial resistance (gray bar and black bar, respectively) of each sensor upon exposure to solvent vapor. In many cases, sensors exhibited reproducible increases and decreases in resistance.
• An exposure consisted of: (i) a 60 sec rest period in which the sensors were exposed to flowing air (3.0 liter-min "1 ); (ii) a 60 sec exposure to a mixture of air (3.0 liter-min “1 ) and air that had been saturated with solvent (0.5 liter-min "1 ); and (iii) a 240 sec exposure to air (3.0 liter-min "1 ). It is readily apparent that these odorants each produced a distinctive response on the sensor array.
• Principle component analysis (19) was used to simplify presentation of the data and to quantify the distinguishing abilities of individual sensors and of the array as a whole.
• linear combinations of the ⁇ R ma ⁇ / i data for the elements in the array were constructed such that the maximum variance (defined as the square of the standard deviation) was contained in the fewest mutually orthogonal dimensions.
• the resulting clustering, or lack thereof, of like exposure data in the new dimensional space was used as a measure of the distinguishing ability, and of the reproducibility, of the sensor array.
• the black regions indicate clusters corresponding to a single solvent which could be distinguished from all others; gray regions highlight data of solvents whose signals overlapped with others around it. Exposure conditions were identical to those in Fig. 4. Since each individual sensor produced two data values, principle component analysis of these responses resulted in only two orthogonal principal components: pel and pc2.
• the selectivity exhibited by an individual sensor element the sensor designated as number 5 in Fig. 5 (which comprised poly(styrene)) confused acetone with chloroform, isopropyl alcohol, and tetrahydrofuran. It also confused benzene with ethyl acetate, while easily distinguishing ethanol and methanol from all other solvents.
• Fig. 6 shows the principle component analysis for all 14 sensors described in Table 5 and Figs. 4 and 5.
• Fig. 6A or 6B When the solvents were projected into a three dimensional odor space (Fig. 6A or 6B), all eight solvents were easily distinguished with the specific array discussed herein. Detection of an individual test odor, based only on the criterion of observing ⁇ 1% ⁇ Rm ax /Ri values for all elements in the array, was readily accomplished at the parts per thousand level with no control over the temperature or humidity of the flowing air. Further increases in sensitivity are likely after a thorough utilization of the temporal components of the ⁇ R m a x /Ri data as well as a more complete characterization of the noise in the array.
• the same sensor array was also able to resolve the components in various test methanol-ethanol mixtures (29). As shown in Fig. 7B, a linear relationship was observed between the first principle component and the mole fraction of methanol in the liquid phase, x m , in a CH 3 OH-C 2 H 5 OH mixture, demonstrating that superposition held for this mixture/sensor array combination. Furthermore, although the components in the mixture could be predicted fairly accurately from just the first principle component, an increase in the accuracy could be achieved using a multi-linear least square fit through the first three principle components. This relationship held for CH 3 OH/(CH 3 OH + C 2 H 5 OH) ratios of 0 to 1.0 in air-saturated solutions of this vapor mixture. The conducting polymer-based sensor arrays could therefore not only distinguish between pure test vapors, but also allowed analysis of concentrations of odorants as well as analysis of binary mixtures of vapors.
• This type of polymer-based array is chemically flexible, is simple to fabricate, modify, and analyze, and utilizes a low power dc resistance readout signal transduction path to convert chemical data into electrical signals. It provides a new approach to broadly-responsive odor sensors for fundamental and applied investigations of chemical mimics for the mammalian sense of smell. Such systems are useful for evaluating the generality of neural network algorithms developed to understand how the mammalian olfactory system identifies the directionality, concentration, and identity of various odors.
• Example 4 Fabrication and Testing of Carbon Black-based Sensor Arrays. i. Sensor Fabrication. Individual sensor elements were fabricated in the following manner. Each non-conductive polymer (80 mg, see Table 6) was dissolved in 6 ml of THF. Table 6.
• a sensor exposure consisted of (1) a 60 second exposure to flowing air (6 liter min-1), (2) a 60 second exposure to a mixture of air (6 liter min-1) and air that had been saturated with the analyte (0.5 liter min-1) and (3) a five minute recovery period during which the sensor array was exposed to flowing air (6 liter min-1).
• the resistance of the elements were monitored during exposure, and depending on the thickness and chemical make-up of the film, resistance changes as large as 250% could be observed in response to an analyte.
• Cited References 1. Lundstr ⁇ m et al. (1991) Nature 352:47-50; 2. Shurmer and Gardner (1992) Sens. Act. B 8: 1-11; 3. Reed (1992) Neuron 8:205-209; 4. Lancet and Ben-Airie (1993) Curr. Biol. 3:668-674; 5. Kauer (1991) 7 NS 14:79-85; 6. DeVries and Baylor (1993) Cell 10(S):139-149; 7. Gardner et al. (1991) Sens. Act. B 4:117-121; 8. Gardner et al. (1991) Sens. Act. B 6:71-75; 9. Corcoran et al. (1993) Sens. Act. B 15:32-37; 10.

Applications Claiming Priority (5)

Publications (2)

Family

ID=26778943

Family Applications (1)

Country Status (3)

Families Citing this family (32)

Citations (4)

Family Cites Families (13)

• 1999
  • 1999-06-08 WO PCT/US1999/012904 patent/WO2000000808A2/en active Application Filing
  • 1999-06-08 EP EP99931777A patent/EP1084390A4/de not_active Withdrawn
  • 1999-06-09 AU AU48210/99A patent/AU4821099A/en not_active Abandoned

Patent Citations (4)

Non-Patent Citations (5)

Also Published As

Similar Documents

Legal Events