Classifications

• • 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
  • G01N33/0004—Gaseous mixtures, e.g. polluted air
  • G01N33/0009—General constructional details of gas analysers, e.g. portable test equipment
  • G01N33/0027—General constructional details of gas analysers, e.g. portable test equipment concerning the detector
  • G01N33/0031—General constructional details of gas analysers, e.g. portable test equipment concerning the detector comprising two or more sensors, e.g. a sensor array

Definitions

• This invention relates generally to sensors and sensor systems for detecting analytes in fluids and, more particularly, to sensor systems that incorporate sensors having electrical properties that vary according to the presence and concentration of analytes, and to methods of using such sensor systems.
• BACKGROUND [0004] There is considerable interest in developing sensors that act as analogs ofthe mammalian olfactory system (Lundstrom et al. (1991) Nature 352:47-50; Shurmer and Gardner
• Patent No. 4,907,441 describes general sensor arrays with particular electrical circuitry.
• U.S. Patent No. 4,674,320 describes a single chemoresistive sensor having a semi-conductive material selected from the group consisting of phthalocyanine, halogenated phthalocyanine and sulfonated phthalocyanine, which was used to detect a gas contaminant.
• Other gas sensors have been described by Dogan et al., Synth. Met. 60, 27-30 (1993) and Kukla, et al. Films. Sens. Act. B., Chemical 37, 135-140 (1996).
• the detectors in such an array are placed in nominally spatially equivalent positions relative to the analyte flow path.
• any spatiotemporal differences between detectors are minimized, and the array response pattern is determined by the differing physicochemical responses ofthe various detectors towards the analyte of interest.
• the variations in analyte sorption amongst various detectors thus determines the resolving power ofthe detector array and determines the other performance parameters of such systems.
• the form factor ofthe individual detectors in such arrays is typically constrained by factors related to the mode of signal transduction.
• QCM quartz-crystal microbalance
• SAW devices must have specified dimensions so that a resonant bulk acoustic wave can be maintained in the quartz crystal transducer element.
• the geometry of SAW devices is constrained by the need to sustain a Rayleigh wave ofthe appropriate resonant frequency at the surface ofthe transducer crystal.
• Each detector in a QCM or SAW array typically has an identical area and form factor; consequently, the array response is based solely on the different polymer/analyte sorption properties ofthe differing detector films.
• the invention provides apparatus, systems and methods for detecting the presence of analytes in fluids.
• Sensor arrays incorporate multiple sensors or detectors.
• sensor arrays can incorporate multiple holes, pores or channels, thus increasing analyte flux.
• the geometry and spatiotemporal location of individual detectors can be optimized based on analyte characteristics, such as polymer/gas partition coefficients. For analytes with moderate polymer/gas partition coefficients, detector signal-to-noise can optimized for detectors of very large area. For analytes with high polymer/gas partition coefficients, detectors of small area will exhibit optimum vapor detection sensitivity. Manipulation ofthe geometric form factor of detectors can provide a convenient method for optimizing the S/N performance for a particular detector/analyte combination of interest. An array of nominally identical sorption detectors arranged linearly relative to the analyte flow path can produce different spatiotemporal response patterns for analytes having different polymer/gas partition coefficients.
• Analytes with moderate polymer/gas partition coefficients can produce the same signals on all detectors over a range of flow rates, whereas analytes with very large polymer/gas partition coefficients can produce signals that are highly dependent on the analyte flow rate and the spatial position ofthe detector in the array.
• Such a configuration can produce useful information on the composition of binary analyte mixtures and adds classification information to an array of compositionally different vapor detectors.
• the invention features flow-through systems for detecting an analyte in a fluid flow.
• the systems include a sensor array having a first face and a second face, a fluid flow system for introducing a fluid flow containing an analyte to the sensor array, such that upon introduction of a fluid flow to the sensor array a pressure differential is created between the first and second faces ofthe sensor array, and a processor configured to receive the response generated by the one or more first sensors and to process the response to detect at least one analyte in a fluid flow.
• the sensor array includes one or more first sensors and one or more fluid channels extending from the first face to the second face. At least one ofthe first sensors is located at a first position in the sensor array in contact with the first face ofthe sensor array.
• the sensors are configured to generate a response upon exposure ofthe sensor array to at least one analyte in a fluid flow.
• the sensor array can include a substrate having a first surface and a second surface.
• the fluid channels can extend from the first surface to the second surface.
• the fluid channels can include a plurality of pores in a microporous substrate material, or a plurality of holes introduced into an impermeable substrate material.
• the fluid flow system can include a predetermined sampling volume, with the sensor array located within the sampling volume.
• the first sensor can have a sensor volume substantially optimized to cause the first sensor to generate a response having a maximum signal to noise ratio for at least one target analyte.
• the sensor volume can be substantially optimized as a function of a partition coefficient K of at least one target analyte.
• the predetermined sampling volume can include a headspace proximate to the first sensor, the headspace having a headspace volume V ⁇ .
• the sensors can include one, or multiple, vapor sensors for detecting an analyte in a gas.
• the first sensors can include one, or multiple, liquid sensors for detecting an analyte in a liquid.
• the sensor array can include at least one second sensor located at a second position in the sensor array. The second position can be different from the first position relative to the fluid flow.
• the first and second sensors can each generate a response upon exposure ofthe sensor array to at least one analyte in a fluid flow, such that the responses generated upon exposure ofthe sensor array to at least one analyte in a fluid flow include a spatio-temporal difference between the responses for the first and second sensors.
• the processor can be configured to resolve a plurality of analytes in a fluid flow upon exposure of the sensor array to a fluid flow containing the plurality of analytes.
• the sensor array can include a plurality of second sensors. Each ofthe first sensor and a plurality ofthe second sensors can be located at a different position in the sensor array relative to the fluid flow.
• the first and second sensors can each generate a response upon exposure ofthe sensor array to at least one analyte in a fluid flow, such that the responses generated upon exposure ofthe sensor array to at least one analyte in a fluid flow include a spatio-temporal difference between the responses for the first and second sensors.
• the sensor array can include a first substrate forming a plate having a length, a width, and a depth, such that the length and the width in combination define a pair of substrate faces and the width and the depth in combination define a pair of substrate edges.
• the first substrate can be oriented in the sampling volume such that the substrate faces extend in a direction parallel to a direction ofthe fluid flow and the substrate edges are situated normal to the fluid flow.
• the first sensors can be located on one ofthe pair of substrate edges.
• the sensor array can include one or more second sensors located on one ofthe pair of substrate faces.
• the processor can be configured to resolve a plurality of analytes in a fluid flow upon exposure ofthe sensor array to a fluid flow containing the plurality of analytes.
• the sensor array can include a plurality of second sensors located at different positions along one ofthe pair of substrate faces, such that the responses generated upon exposure ofthe sensor array to at least one analyte in a fluid flow include a spatio-temporal difference between responses generated by each ofthe first and the plurality ofthe second sensors.
• the sensor array can include a plurality of substrates, each substrate forming a plate having a length, a width, and a depth, such that for each ofthe substrates the length and the width in combination define a pair of substrate faces and the width and the depth in combination define a pair of substrate edges.
• the substrates can be oriented in the sampling volume such that the substrate faces extend in a direction parallel to a direction ofthe fluid flow and the substrate edges are situated normal to the fluid flow.
• the sensor array can include one or more first sensors located on one ofthe pair of substrate edges and one or more second sensors located on at least one ofthe pair of substrate faces.
• At least one ofthe first sensor or the second sensors can have a sensor volume substantially optimized to achieve a maximum signal to noise ratio for at least one target analyte.
• the sensor volume can be substantially optimized as a function of a partition coefficient K of at least one target analyte.
• the predetermined sampling volume can include a headspace proximate to the first sensor, the headspace having a headspace volume V ⁇ .
• the invention features methods for detecting an analyte in a fluid flow.
• the methods include providing a sensor array having a first face and a second face and including one or more first sensors, exposing the sensor array to a fluid flow including an analyte under conditions sufficient to create a pressure differential between the first and second faces ofthe sensor array, measuring a response for the first sensors, and detecting the presence ofthe analyte in the fluid based on the measured response.
• the sensor array includes one or more fluid channels extending from the first face to the second face. At least one ofthe first sensors is located at a first position in the sensor array in contact with the first face ofthe sensor array. The first sensors are configured to generate a response upon exposure ofthe sensor array to at least one analyte in a fluid flow.
• Particular implementations ofthe invention can include one or more ofthe following features.
• the sensor array can include a substrate having a first surface and a second surface.
• the fluid channels can extend from the first surface to the second surface.
• the fluid channels can include a plurality of pores in a microporous substrate material, or a plurality of holes introduced into an impermeable substrate material.
• the fluid flow system can include a predetermined sampling volume, with the sensor array located within the sampling volume.
• the first sensor can have a sensor volume substantially optimized to cause the first sensor to generate a response having a maximum signal to noise ratio for at least one target analyte.
• the sensor volume can be substantially optimized as a function of a partition coefficient K of at least one target analyte.
• the predetermined sampling volume can include a headspace proximate to the first sensor, the headspace having a headspace volume V ⁇ .
• the sensors can include one, or multiple, vapor sensors for detecting an analyte in a gas.
• the first sensors can include one, or multiple, liquid sensors for detecting an analyte in a liquid.
• the sensor array can include at least one second sensor located at a second position in the sensor array. The second position can be different from the first position relative to the fluid flow.
• the first and second sensors can each generate a response upon exposure ofthe sensor array to at least one analyte in a fluid flow, such that the responses generated upon exposure ofthe sensor array to at least one analyte in a fluid flow include a spatio-temporal difference between the responses for the first and second sensors.
• Detecting the presence ofthe analyte in the fluid can include resolving a plurality of analytes in the fluid based on the measured response.
• the sensor array can include a plurality of second sensors. Each ofthe first sensor and a plurality ofthe second sensors can be located at a different position in the sensor array relative to the fluid flow.
• the first and second sensors can each generate a response upon exposure ofthe sensor array to at least one analyte in a fluid flow, such that the responses generated upon exposure ofthe sensor array to at least one analyte in a fluid flow include a spatio-temporal difference between the responses for the first and second sensors.
• the sensor array can include a first substrate forming a plate having a length, a width, and a depth, such that the length and the width in combination define a pair of substrate faces and the width and the depth in combination define a pair of substrate edges.
• the first substrate can be oriented in the sampling volume such that the substrate faces extend in a direction parallel to a direction ofthe fluid flow and the substrate edges are situated normal to the fluid flow.
• the first sensors can be located on one ofthe pair of substrate edges.
• the sensor array can include one or more second sensors located on one ofthe pair of substrate faces. Detecting the presence ofthe analyte in the fluid includes resolving a plurality of analytes in the fluid based on the measured response.
• the sensor array can include a plurality of second sensors located at different positions along one ofthe pair of substrate faces, such that the responses generated upon exposure ofthe sensor array to at least one analyte in a fluid flow include a spatio-temporal difference between responses generated by each ofthe first and the plurality ofthe second sensors.
• the sensor array can include a plurality of substrates, each substrate forming a plate having a length, a width, and a depth, such that for each ofthe substrates the length and the width in combination define a pair of substrate faces and the width and the depth in combination define a pair of substrate edges.
• the substrates can be oriented in the sampling volume such that the substrate faces extend in a direction parallel to a direction ofthe fluid flow and the substrate edges are situated normal to the fluid flow.
• the sensor array can include one or more first sensors located on one ofthe pair of substrate edges and one or more second sensors located on at least one ofthe pair of substrate faces. At least one ofthe first sensor or the second sensors can have a sensor volume substantially optimized to achieve a maximum signal to noise ratio for at least one target analyte.
• the sensor volume can be substantially optimized as a function of a partition coefficient K of at least one target analyte.
• the predetermined sampling volume can include a headspace proximate to the first sensor, the headspace having a headspace volume V ⁇ .
• the sensor volume can be substantially
• the first sensors can include one, or multiple,
• the first sensors can include one, or multiple, liquid sensors for detecting an analyte in a liquid.
• the invention features sensor arrays for detecting an analyte in a fluid.
• the sensor arrays include one or more substrates and one or more sensors in contact with the substrates. Each substrate has a first surface.
• the sensors are configured to generate a response upon exposure ofthe sensor array to at least one analyte in a fluid.
• Each sensor has a sensor volume. The sensor volume for at least one ofthe sensors is substantially optimized to cause the first sensor to generate an optimized response upon exposure ofthe sensor array to at least one target analyte.
• the sensor volume can be substantially optimized as a function of a sampling headspace volume ⁇ and a partition coefficient K of at least one target analyte.
• the sensors can include two or more optimized sensors. Each ofthe optimized sensors can be substantially optimized to generate an optimized response upon exposure ofthe sensor array to a different target analyte.
• the optimized response can have a substantially maximized signal to noise ratio.
• the invention features sensor arrays for detecting an analyte in a fluid flow.
• the sensor arrays include a substrate having a first surface and a second surface, one or more sensors in contact with the first surface, and one or more fluid channels extending from the first surface to the second surface.
• the sensors are configured to generate a response upon exposure ofthe sensor array to at least one analyte in a fluid flow.
• Particular implementations ofthe invention feature one or more ofthe following features.
• the fluid channels can be configured such that upon introduction of a fluid flow to the sensor array a pressure differential is created between the first and second surfaces ofthe substrate.
• the substrate can include a microporous material or an impermeable material.
• the fluid channels can include a plurality of pores in the substrate, or a plurality of holes introduced into the substrate.
• the sensors can include one, or multiple, vapor sensors for detecting an analyte in a gas.
• the sensors can include one, or multiple, liquid sensors for detecting an analyte in a liquid.
• the invention features sensor arrays having a first face and a second face for detecting an analyte in a fluid flow.
• the sensor arrays include one or more substrates, each substrate forming a plate having a length, a width, and a depth, such that the length and the width in combination define a pair of substrate faces and the width and the depth in combination define a first substrate edge and a second substrate edge; a plurality of sensors configured to generate a response upon exposure ofthe sensor array to at least one analyte in a fluid flow; and one or more fluid channels extending along one or more ofthe substrate faces from the first face of the array to the second face ofthe array.
• the first substrate edge for each ofthe substrates is aligned with the first face ofthe array.
• the sensors include one or more first sensors sensors and one or more second sensors. Each ofthe first sensors is located along one ofthe first substrate edges. Each ofthe second sensors is located along one ofthe substrate faces
• the sensors include a plurality of second sensors located at different positions along at least one ofthe pair of substrate faces, such that the responses generated upon exposure ofthe sensor array to at least one analyte in a fluid flow include a spatio-temporal difference between responses generated by each ofthe first and the plurality ofthe second sensors.
• the sensors include one, or multiple, vapor sensors for detecting an analyte in a gas.
• the sensors include one, or multiple, liquid sensors for detecting an analyte in a liquid.
• the invention features methods of fabricating a sensor array for detecting an analyte in a fluid.
• the methods include providing a substrate having a surface and a sampling headspace proximate to the surface; identifying a sampling headspace volume ⁇ for at least a portion ofthe sampling headspace, and a partition coefficient K of at least one target analyte in a sensing material; calculating a sensor volume based on the sampling headspace volume and the partition coefficient; and fabricating a sensor on the surface proximate to the at least a portion ofthe sampling headspace, the sensor including an amount ofthe sensing material derived from the calculated sensor volume.
• the sensor volume can be calculated based on the function T v
• FIG. 1 illustrates one implementation of a system involving a linear sensor array for detecting an analyte in a fluid.
• FIG. 2 illustrates a two-dimensional implementation of a sensor array for detecting an analyte in a fluid.
• FIG. 3 illustrates one implementation of a perforated two-dimensional sensor array.
• FIGS. 4 A and 4B illustrate a flow-through sensor system incorporating the perforated array such as is shown in FIG. 3.
• FIGS. 5 A and 5B illustrate an implementation of a system for detecting an analyte in a fluid involving a stacked sensor array.
• FIG. 6 is a diagram illustrating the equilibration between a finite volume of sampled analyte and a finite volume of sorption-based vapor detection film in a sensor array according to the invention.
• FIG. 7 illustrates a plot ofthe power spectral density of noise versus frequency for seven polymer-carbon black composite detector films according to the invention.
• FIGS. 8 A and 8B illustrate plots of spectral density of noise times frequency and the square of noise values as a function of volume for two polymer-carbon black composite detector films.
• FIGS. 9A and 9B illustrate a plot of differential frequency changes of quartz crystal microbalances coated with two polymer films during exposure to hexane and methanol.
• FIG. 10 is a table showing responses, noise, and S/N for two types of polymer- carbon black composite detectors in the configuration of FIG. 5A.
• FIG. 11 illustrates a plot of normalized relative differential resistance responses of polymer-carbon black composite detectors exposed to a high vapor pressure analyte (hexane), a moderately low vapor pressure analyte (dodecane) and a low vapor pressure analyte (tridecane) at a constant activity and volumetric flow rate.
• FIGS. 12A and 12B illustrate plots of normalized relative differential resistance responses for two different polymer-carbon black composite detectors to hexane and dodecane at a constant activity in air.
• FIG. 13 illustrates a plot of resistance response as a function of time for a polymer-carbon black composite detector exposed to both hexane and a mixture of hexane and dodecane.
• FIGS. 14A and 14B illustrate the relative differential resistance responses to hexane and dodecane after 40 seconds and 200 seconds of polymer-carbon black composite detectors located on the edge and face portions of a stacked sensor array as shown in FIG.
• FIG. 15 illustrates one implementation ofthe stacked sensor array of FIG. 5 A, involving 18 different detectors constructed from nine different sensor materials.
• FIG. 16 illustrates the average differential resistance response computed as the baseline normalized differential resistance change ofthe detectors in the stacked sensor array of FIG. 15 after exposure to dinitrotoluene in the presence of two potentially interfering compounds.
• FIG. 17 illustrates the normalized array fingerprint patterns of pure dinitrotoluene and DNT in the presence of large concentrations of acetone or water for the sensor array of FIG. 15.
• FIGS. IA, IB and 1C illustrate one example of a system 100 for detecting an analyte in a fluid.
• System 100 includes a sensor array 110, including a plurality of sensors 120 arranged on a substrate 125 along a fluid channel 130.
• sensor array 110 may be configured to include one or more fluid channels in addition to fluid channel 130, such as fluid channel 140 including additional sensors arranged along the same or a different substrate.
• a fluid to be analyzed which may be in gaseous or liquid form, is introduced to sensor array 110 through fluid inlet 160, for example from fluid reservoir 170.
• Response signals from the sensors 120 in sensor array 110 resulting from exposure ofthe fluid to the sensor array are received and processed in detector 180, which may include, for example, signal-processing electronics, a general-purpose programmable digital computer system of conventional construction, or the like.
• Sensors 120 can include sensors of any of a variety of known types, including, for example, surface acoustic wave sensors, quartz crystal resonators, metal oxide sensors, dye- coated fiber optic sensors, dye-impregnated bead arrays, micromachined cantilever arrays, vapochromic metalloporphyrins, composites having regions of conducting material and regions of insulating organic material, composites having regions of conducting material and regions of conducting or semiconducting organic material, chemically-sensitive resistor or capacitor films, metal-oxide-semiconductor field effect transistors, bulk organic conducting polymeric sensors, and other l ⁇ iown sensor types.
• sensors of any of a variety of known types including, for example, surface acoustic wave sensors, quartz crystal resonators, metal oxide sensors, dye- coated fiber optic sensors, dye-impregnated bead arrays, micromachined cantilever arrays, vapochromic metalloporphyrins, composites having regions of conducting material and regions of insulating organic
• sensor array 110 incorporates multiple sensing modalities, for example comprising a spatial arrangement of cross-reactive sensors 120 selected from known sensor types, such as those listed above, such that a given analyte elicits a response from multiple sensors in the array and each sensor responds to many analytes.
• the sensors in the array 110 are broadly cross-reactive, meaning each sensor in the array responds to multiple analytes, and, in turn, each analyte elicits a response from multiple sensors.
• Sensor arrays allow expanded utility because the signal for an imperfect "key" in one channel can be recognized through information gathered on another, chemically or physically dissimilar channel in the array.
• a distinct pattern of responses produced over the collection of sensors in the array can provide a fingerprint that allows classification and identification ofthe analyte, whereas such information would not have been obtainable by relying on the signals arising solely from a single sensor or sensing material.
• By developing an empirical catalogue of information on chemically diverse sensors - made, for example, with varying ratios of semiconducting, conducting, and insulating components and by differing fabrication routes - 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 sensor arrays of system 100 incorporate spatio- temporal response information that is used by detector 180 to aid in analyte detection and identification.
• the incorporation of data derived from spatio-temporal properties of a sensor array can impart useful information on analyte detection and identification relative to arrays where no spatiotemporal information is available because all sensors are nominally in identical positions with respect to the fluid flow characteristics and are exposed to the analyte at nominally identical times during the fluid sampling experiment.
• Electronics can be implemented in detector 180 to record a time delay between sensor responses and to use this information to characterize the analyte of interest in the fluid.
• This mode can also be advantageous because it can allow automatic nulling of any sensor drift, environmental variations (such as temperature, humidity, etc.) and the like. Also, a complex analyte mixture can be better resolved into its components based on the spatiotemporal characteristics ofthe array response relative only to the differences in fingerprints on the various sensors types in the array. Additionally, the method can be used in conjunction with differential types of measurements to selectively detect only certain classes or types of analytes, because the detection can be gated to only focus on signals that exhibit a desired correlation time between their responses on the sensors that are in different exposure times relative to the sensor response on the first sensor that detects an analyte.
• sensor arrays 110 can be configured such that low vapor pressure analytes in the gas phase will have a high affinity towards the sensors and will sorb strongly to them. This strong sorption produces a strong response at the first downstream sensor that the analyte encounters, a weaker response at the second downstream sensor, and a still weaker response at other downstream sensors. Different analytes will produce a detectable and useful time delay between the response ofthe first sensor and the response ofthe other downstream sensors. As a result, detector 180 can use the differences in response time and amplitude to detect and characterize analytes in a carrier fluid, analogous to the use of gas chromatography retention times, which are well known in the gas chromatography literature and art.
• Spatio-temporal information can be obtained from an array of two or more sensors by varying the sensors' exposure to the fluid containing the analyte across the array (e.g., by generating a spatial and/or temporal gradient across the array), thereby allowing responses to be measured simultaneously at various different exposure levels and for various different sensor compositions.
• an array can be constructed in two dimensions with sensors arranged at the vertices of a grid or matrix. Such arrays can be configured to vary the composition of the sensors in the horizontal direction across the array, such that sensor composition in the vertical direction across the array remains constant.
• spatio-temporal variation can be introduced by systematically varying the flow rate at which the analyte- containing fluid is exposed to the sensors in the array.
• measuring the response of each ofthe sensors 120 at a variety of different flow rates allows the simultaneous analysis of analytes at different sensor compositions and different exposure levels.
• the sensors defining each fluid channel are nominally identical - that is, the sensors within a given fluid channel are identical - while the array incorporates a predetermined inter-sensor variation in the chemistry, structure or composition ofthe sensors between different fluid channels.
• the variation can be quantitative and or qualitative.
• different channels can be constructed to incorporate sensors of different types, such as incorporating a plurality of nominally identical metal oxide gas sensors in a first fluid channel, a plurality of conducting polymer sensors in an adjacent fluid channel, and so on across the array.
• compositional variation can be introduced by varying the concentration of a conductive or semiconductive organic material in a composite sensor across fluid channels.
• a variety of different organic materials may be used in sensors in different channels. Similar patterns of introducing compositional variation into sensor arrays will be readily apparent to those skilled in the art.
• FIG. 1 A depicts the fluid channels as linear channels extending in just one direction
• sensor arrays can be configured to provide similar fluid channels having different geometries - for example, arrays with sensors arranged in two or more directions relative to the fluid flow, such as a circular array having a radial arrangement of sensors around a fluid introduction point.
• FIG. 2 illustrates a simply sensor array of this type - an array 200 of eight sensors 210.
• a stream 220 of fluid containing an analyte or analytes of interest is directed at surface 230, such that the stream contacts surface 230 at point 240, and then flows radially in both directions across the array.
• sensor array 110 has been described as inco orating one or more fluid channels each comprising a plurality of nominally identical sensors, those skilled in the art will recognize that the techniques described herein can be used to generate useful spatio-temporal information from arrays including a plurality of sensors all of different chemistry, structure or composition, with the fluid path being defined by the introduction ofthe fluid onto the array.
• spatio-temporal response data can be generated by introducing the fluid onto the array at varying flow rates, for example, by using a flow controller of known construction to systematically vary the rate at which the fluid is introduced over time.
• flow rate variation can be introduced by simply exposing the array to a naturally varying fluid flow, such as a flow of air.
• system 100 provides that an analyte (e.g., a gas analyte) can be directed through or to substrate 125 by including gaps or pores into the substrate or by using a substrate that itself is porous and highly permeable to the analyte of interest.
• an analyte e.g., a gas analyte
• a pressure differential between the top and bottom ofthe substrate allows the gas to be effectively sampled by the detectors (e.g., a sensor film deposited on substrate 125), enhancing the detection sensitivity ofthe entire sensor device and system.
• sensors 300 are arranged on a surface 310 of porous substrate 320 such that a fluid containing the analyte or analytes of interest strikes surface 310, interacts with sensors 300, and flows through pores 330.
• Sensors 300 can be fabricated as a sensor film deposited on top of substrate 320.
• a pressure differential can be established between the two sides 410 and 420 of a perforated or porous substrate 400 in order to direct the analyte to flow through the sensor film, optimizing analyte sorption and detection performance, as opposed to merely flowing nearby or parallel to the surface of a solid substrate 430.
• FIG. 4B One example of a flow-through apparatus incorporating such a perforated substrate is illustrated in FIG. 4B.
• a variety of different substrates, with a variety of different porosities can be used.
• Substrate 320 can be fabricated from a material that is not highly permeable by the analyte gas of concern, such as printed circuit board, ceramic, or a silicon wafer.
• pores 330 can take the form of a series of holes introduced into the substrate at well-defined positions and spacings. Hole density, hole diameter and/or sensor size can be optimized for a given analyte flow rate, analyte gas/solid partition coefficient, and analyte permeability into the sensor film, in order to allow the maximum amount of analyte to be captured by the sensor film during its flow by the sensor and sensor substrate.
• a preferred a flow-through detector configuration incorporates roughly 2-25% open area (98%-75% solidity, with the exact value depending on the analyte' s partition coefficient into the polymer film) for analyte detection.
• substrate 320 can be fabricated from a material that is porous to analyte flow.
• the porosity can be introduced through physical or chemical processes. Two such examples are Anopore alumina membranes and Nucleopore polymer membranes. As described above, optimum pore structure and pore distribution can be computed for certain specific conditions of analyte flow velocity, gas/polymer sorption coefficient, and other sensor and sensor parameters.
• the porous substrate is a microporous, branched- pore Anopore membrane having 200 nm diameter pores extending from one face through most ofthe membrane thickness, branching to 20 nm diameter pores in a narrow layer (e.g., 500 nm in a 60 micron membrane) at the opposite face.
• Sensors are deposited as thin films on this face (on top of conductive contacts deposited on the surface) using techniques such as those described below.
• the branched-pore membrane structure ensures that the detector face presents pores of a sufficiently small diameter to limit seepage ofthe sensor media into the membrane (e.g., excluding carbon black particles in a polymer-carbon black composite film as described below having particle sizes ranging from about 20 nm to about 50 nm), while also providing for a high fluid flux to the sensor film.
• the holes/pores can be replaced by their one-dimensional analog - linear or non-linear channels or gaps 500 in spacing through plates 510 that contain sensors on their edges 520.
• the performance of this type of system can also be computed using well-known equations for specific sensor/substrate conditions, hi some instances, this type of structure can be easier to manufacture than one with holes in the substrate.
• this type of structure offers the opportunity to introduce additional sensors 530 on the faces 540 ofthe stacked substrates, offering an opportunity to make measurements on sensor films placed both on the edges ofthe substrates as well as at various positions and in various geometries on the faces ofthe substrates.
• Measurement ofthe response at various positions on the substrate in this type of geometry permits the parallel analysis of vapors that possess different optimal sorption and/or detection regions on the sensor material in the presence ofthe flow onto and around the stacked substrates.
• the incorporation of different form factors of a given detector film in conjunction with specific types of analyte flow paths can provide very different detection performance for different types of analyte vapors. Accordingly, as will be described in more detail below, the use of an array of detectors that are nominally identical chemically, but which have different form factors relative to the analyte flow path, can provide useful information on the composition and identity of an analyte vapor.
• the form factor ofthe sensors in the array can be manipulated to optimize the signal to noise output ofthe system, yielding one or more sensors having optimal, or near-optimal, sensor volumes for one or more target analytes.
• resistors exhibit voltage fluctuations - known as Johnson noise - whose power spectrum is constant as the frequency is varied.
• the root mean squared (rms) noise voltage density ofthe Johnson noise, J N is related to the resistance, R, of a resistive detector as follows:
• the dependence ofthe signal produced by sorption of an analyte on the volume ofthe detector film can be determined as follows. Consider introducing a fixed quantity of an analyte into a sample chamber of total volume to produce an initial analyte
• the analyte can either be introduced as a pulse of concentrated analyte into the volume ⁇ or by introducing a sampled
• an analyte concentration C v is present in a total headspace volume > ⁇ .
• C v is the concentration ofthe analyte in the vapor phase, and both concentrations refer to the situation after equilibrium has been reached.
• N X 2 ⁇ p "1/2 (7)
• X 2 is a constant that is independent ofthe film volume.
• S/N X 1 C p / X 2 ⁇ p - 1/2 (8)
• Equation 10 Equation 10
• the maximal S/N ratio is obtained when the detector volume equals the headspace volume divided by the polymer/gas
• Equations 9 and 12 imply that there is an optimum detector film area for a given headspace volume and a given initial headspace analyte concentration. Smaller detector areas than this optimum value fail to exhibit optimally low noise, while larger detector areas result in the sorption ofthe fixed number of moles of analyte into too large of a polymer volume and therefore produce a reduced magnitude of signal after equilibrium has been reached.
• Another consequence of this analysis is that the different response properties of a set of detectors having a common polymer sorbent layer, but having different form factors, can provide information on the value of K, if ⁇ is known and/or is held constant
• differential resistance change ( ⁇ R/Rb) is linearly dependent on analyte concentration over a range of analyte/detector combinations and analyte concentrations (Severin, et al., Anal. Chem. 2000, 72, 658-668). Detection limits for such sensors can be estimated based on noise
• Table 1 also reports representative values taken from the literature for selected polymer- coated SAW vapor detectors for 158-MHz SAW oscillators at 298 K (Patrash, et al., Anal. Chem. 1993, 65, 2055-2066). For the given area, the detection limits are comparable for both types of signal transduction, although the carbon black composites exhibit somewhat higher sensitivity than the SAW devices for the analyte/polymer combinations chosen for comparison. Table 1 reports only limits of detection as opposed to limits of classification; the former quantity depends only on the properties ofthe analyte/detector combination, while the latter quantity also depends on the test set of analytes presented to the array as well as on the algorithms used to perform the classification.
• the limit of classification of an analyte has been shown to be within a factor of three ofthe limit of detection of that same analyte, indicating that the limit of classification is likely to be on the same order of magnitude as the limit of detection, at least for some tasks.
• the ⁇ R/R b signal ofthe detector is proportional to the swelling change ofthe detector film (Severin, et al., Anal. Chem. 2000, 72, 2008-2015), so increasing the detector area will reduce the signal (by diluting the fixed amount of sorbed analyte into a correspondingly larger volume of polymer). As long as the swelling is linearly dependent on the concentration of analyte sorbed into the polymer, this
• the S/N under such conditions scales as A "1/2 and small detector areas are favored.
• the design goal under such conditions is to insure that the most analyte is sorbed into the least area of detector film, and signals should only be acquired from the limited, highly analyte-swollen, portion ofthe detector. This principle is exemplified in the detector arrangement of FIGS. 5 A and 5B. [0076] This relationship also has implications for sample chamber design of vapor detector arrays.
• increasing the thickness ofthe headspace provides more analyte than is needed to attain the optimal S/N ratio for the detector response and requires introduction of more sample into the headspace chamber.
• the computed 3 ⁇ detection limit of a PCL-carbon black composite is 1.5 ng cm "2 . This value can only be reached in practice if an efficient sampling and delivery system is available, such that the full amount ofthe sampled analyte can be delivered effectively to the 1 cm 2 area ofthe detector film.
• the detection limit scales inversely with the film area and linearly with the efficiency of delivering analyte to the sampled film area.
• analytes with a high polymer/gas partition coefficient (generally analytes with low vapor pressures) would be sorbed into the smallest detector area possible, producing the largest signal and therefore the largest S/N ratio for that particular analyte/polymer/sampler combination.
• Higher vapor pressure analytes are, in turn, detected with higher S/N performance at detectors having larger film areas.
• an array of contacts spaced exponentially along a polymer film can be used advantageously to gain information on the sorption coefficients of analytes into polymers, and therefore can provide additional classification information on analytes and analyte mixtures relative only to equilibrium ⁇ R/Rb values on a detector film having a single, fixed form factor for all analytes. Additional
• analyte flow rate is also varied over the detector array. Variation in the geometric form factor of detectors can also provide practical advantages in the implementation of instruments based on arrays of vapor detectors. Although information similar to that produced by a collection of spatiotemporally arrayed detectors could in principle be obtained from an analysis ofthe time response of a collection of detectors that are equivalent both geometrically and with respect to the point of analyte injection, the spatiotemporal implementation discussed above has the advantage that analytes are detected on films that have nearly optimal S/N for the analyte of interest.
• the sensors and sensor arrays disclosed herein can act as "electronic noses" to offer ease of use, speed, and identification of analytes and/or analyte regions all in a portable, relatively inexpensive implementation.
• a wide variety of analytes and fluids may be analyzed by the disclosed sensors, arrays and noses so long as the subject analyte is capable generating a differential response across a plurality of sensors ofthe array.
• Analyte applications include broad ranges of chemical classes such as organics including, for example, alkanes, alkenes, alkynes, dienes, alicyclic hydrocarbons, arenes, alcohols, ethers, ketones, aldehydes, carbonyls, carbanions, biogenic amines, tl iols, 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 including, for example, alkanes, alkenes, alkynes, dienes, alicyclic hydrocarbons, arenes, alcohols, ethers, ketones, aldehydes, carbonyls, carbanions, biogenic amines, tl iols, polynuclear aromatics and derivatives of such organics, e.g., halide derivatives, etc.,
• the sensors, arrays and noses include environmental toxicology and remediation, biomedicine, materials quality control, food and agricultural products monitoring, anaesthetic detection, automobile oil or radiator fluid monitoring, breath alcohol analyzers, hazardous spill identification, explosives detection, fugitive emission identification, medical diagnostics, fish freshness, detection and classification of bacteria and microorganisms both in vitro and in vivo for biomedical uses and medical diagnostic uses, monitoring heavy industrial manufacturing, ambient air monitoring, worker protection, emissions control, product quality testing, leak detection and identification, oil/gas petrochemical applications, combustible gas detection, H 2 S monitoring, hazardous leak detection and identification, emergency response and law enforcement applications, illegal substance detection and identification, arson investigation, enclosed space surveying, utility and power applications, emissions monitoring, transformer fault detection, food/beverage/agriculture applications, freshness detection, fruit ripening control, fermentation process monitoring and control applications, flavor composition and identification, product quality and identification, refrigerant and fumigant detection, cosmetic/perfume/fragrance formulation, product quality testing
• Another application for the sensor-based fluid detection device in engine fluids is an oil/antifreeze monitor, engine diagnostics for air/fuel optimization, diesel fuel quality, volatile organic carbon measurement (VOC), fugitive gases in refineries, food quality, halitosis, soil and water contaminants, air quality monitoring, leak detection, fire safety, chemical weapons identification, use by hazardous material teams, explosive detection, breathalyzers, ethylene oxide detectors and anaesthetics.
• VOC volatile organic carbon measurement
• Biogenic amines such as putrescine, cadaverine, and spermine are formed and degraded as a result of normal metabolic activity in plants, animals and microorganisms, and have been identified and quantified using analytical techniques such as gas chromatography- mass spectrometry (GC-MS), high performance liquid chromatography (HPLC) or array based vapor sensing in order to assess the freshness of foodstuffs such as meats (Veciananogues, 1997, J. Agr. Food Chem., 45:2036-2041), cheeses, alcoholic beverages, and other fermented foods. Additionally, aniline and o-toluidine have been reported to be biomarkers for subjects having lung cancer (Preti et al., 1988, J.
• biogenic amines and thiols are biomarkers of bacteria, disease states, food freshness, and other odor-based conditions.
• the electronic nose sensor elements and arrays discussed herein can be used to monitor the components in the headspace of urine, blood, sweat, and saliva of human patients, as well as breath, to diagnose various states of health and disease.
• ⁇ can be used for food quality monitoring, such as fish freshness (which involves volatile amine signatures), for environmental and industrial applications (oil quality, water quality, air quality and contamination and leak detection), for other biomedical applications, for law enforcement applications (breathalyzers), for confined space monitoring (indoor air quality, filter breakthrough, etc) and for other applications delineated above to add functionality and performance to sensor arrays through improvement in analyte detection by use in arrays that combine sensor modalities.
• fish freshness which involves volatile amine signatures
• environmental and industrial applications oil quality, water quality, air quality and contamination and leak detection
• biomedical applications for other biomedical applications
• law enforcement applications for law enforcement applications (breathalyzers)
• confined space monitoring indoor air quality, filter breakthrough, etc
• SAW surface acoustic wave
• quartz crystal microbalance arrays composites consisting of regions of conductors and regions of insulators, bulk semiconducting organic polymers, and other array types exhibit improved performance towards vapor discrimination and quantification when designed according to the invention by directing the analyte through, towards or increase contact ofthe analyte with a sensor (e.g., wherein the array of sensors comprises a member selected from the group consisting of a metal oxide gas sensor, a conducting polymer sensor, a dye-impregnated polymer film on fiber optic detector, a polymer-coated micromirror, an electrochemical gas detector, a chemically sensitive field-effect transistor, a carbon black-polymer composite, a micro-electro- mechanical system device and a micro-opto-electro-mechanical system device).
• a sensor e.g., wherein the array of sensors comprises a member selected from the group consisting of a metal oxide gas sensor, a conducting polymer sensor,
• Breath testing has long been recognized as a nonintrusive medical technique that might allow for the diagnosis of disease by linking specific volatile organic vapor metabolites in exhaled breath to medical conditions (see Table 2).
• breath analysis offers several other potential advantages in certain instances, such as 1) breath samples are easy to obtain, 2) breath is in general a much less complicated mixture of components than either serum or urine samples, 3) direct information can be obtained on the respiratory function that is not readily obtainable by other means, and 4) breath analysis offers the potential for direct real time monitoring ofthe decay of toxic volatile substances in the body.
• Table 2 lists some ofthe volatile organic compounds that have been identified as targets for specific diseases using gas chromatography/mass spectrometry (GC/MS) methods, with emphasis on amines.
• GC/MS gas chromatography/mass spectrometry
• Uremia Preti, dimethylamine, trimethyla ine breath, urine
• Trimethylaminuria trimethyla ine breath, urine, Preti, 1992; Al aiz, sweat, vaginal
• Cystinuria Manolis cadaverine, piperidine, breath
• the invention is described with reference to resistive sensors. Although the invention is described with reference to chemical resistive sensors other types of sensors are applicable to the invention including, for example, heated metal oxide thin film resistors, polymer sorption layers on the surfaces of acoustic wave resonators, arrays of electrochemical detectors, conductive polymers or composites that consist of regions of conductors and regions of insulating organic materials and quartz crystal microbalance arrays.
• the sensors and sensor arrays comprise a plurality of differently responding chemical sensors.
• the array has at least one sensor comprising at least a first and second conductive lead 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 maximize signal-to-noise strength.
• the array is composed of a material comprising regions of an organic electrical conductor with regions of a compositionally dissimilar material that is an electrical conductor.
• the conductive sensor forms a resistor comprising a plurality of alternating regions of differing compositions and therefore differing conductivity transverse to the electrical path between the conductive leads.
• at least one ofthe sensors is fabricated by blending a conductive material with a conductive organic material. For example, in a colloid, suspension or dispersion of particulate conductive material in a region of conductive organic material, the regions separating the particles provide changes in conductance relative to the conductance ofthe particles themselves.
• the gaps of different conductance arising from the organic conductive material range in path length from about 10 to 1,000 angstroms, usually on the order of 100 angstroms.
• the path length and resistance of a given gap is not constant but rather is believed to change as the material absorbs, adsorbs or imbibes an analyte.
• the dynamic aggregate resistance provided by these gaps in a given resistor is a function of analyte permeation ofthe conductive organic regions of the material.
• the conductive material may also contribute to the dynamic aggregate resistance as a function of analyte permeation (e.g., when the conductive material is a conductive organic polymer such as polypyrrole and is blended with another organic conducting material to form the composite).
• a wide variety of conductive materials and dissimilar conductive organic materials can be used.
• one such region is comprised of an inorganic (Au, Ag) or organic (carbon black) conductive material, while the other region is comprised of a compositionally dissimilar organic conducting polymer (polyaniline, polypyrrole, polythiophene, polyEDOT, and other conducting organic polymers such as those identified in the Handbook of Conducting Polymers (Handbook of Conducting Polymers, second ed., Marcel Dekker, New York 1997, vols. 1 & 2)).
• Other combinations of conductor/organic conductor/ composite materials are also useful.
• an electrically conductive organic material that is dopable or undopable by protons can be used as the organic material in a composite where the compositionally different conductor is carbon black
• the conductive form of polyaniline commonly referred to as the emeraldine salt (ES), has been reported to deprotonate to the emeraldine base and become insulating in alkaline environments.
• Conductive materials for use in sensor fabrication can include, for example: organic conductors, such as conducting polymers (e.g., poly(anilines), poly(thiophenes), poly(pyrroles), poly(aceylenes), etc.), carbonaceous material (e.g., carbon blacks, graphite, coke, C60, etc.), charge transfer complexes (tetramethylparaphenylenediamine-chloranile, alkali metal tetracyanoquinodimethane complexes, tetrathiofulvalene halide complexes, etc.), and the like; inorganic conductors, such as metals/metal alloys (e.g., Ag, Au, Cu, Pt, AuCu alloy, etc.), highly doped semiconductors (e.g., Si, GaAs, InP, MoS 2 , TiO 2 , etc.), conductive metal oxides (e.g., In 2 O 3 , SnO 2 , Na 2 Pt
• Blends such as of those listed, may also be used.
• conductors include, for example, those having a positive temperature coefficient of resistance.
• the sensors are comprised of a plurality of alternating regions of a conductor with regions of a compositionally dissimilar conducting organic material. 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 regions of the conductor and the regions ofthe organic material.
• 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 regions thereof.
• 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.
• Such nanoparticles are optionally stabilized with organic ligands. Examples of colloidal nanoparticles for use in accordance with the present invention are described in the literature.
• the electrically conductive organic region can optionally be a ligand that is attached to a central core making up the nanoparticle.
• These ligands i.e., caps, can be polyhomo- or polyhetero- functionalized, thereby being suitable for detecting a variety of chemical analytes.
• the nanoparticles are stabilized by the attached ligands.
• the conducting component ofthe resistors are nanoparticles comprising a central core conducting element and an attached ligand optionally in a polymer matrix.
• various conducting materials are suitable for the central core.
• the nanoparticles have a metal core.
• Typical metal cores include, but are not limited to, Au, Ag, Pt, Pd, Cu, Ni, AuCu and mixtures thereof.
• the conductive organic material can be either an organic semiconductor or organic conductor.
• “Semi-conductors” as used herein, include materials whose electrical conductivity increases as the temperature increases, whereas conductors are materials whose electrical conductivity decreases as the temperature increases.
• organic materials that are useful in some embodiments ofthe sensors ofthe present invention are either semiconductors or conductors.
• Such materials are collectively referred to herein as electrically conducting organic materials because they produce a readily-measured resistance between two conducting leads separated by about 10 micron or more using readily-purchased multimeters having resistance measurement limits of 100 Mohm or less, and thus allow the passage of electrical current through them when used as elements in an electronic circuit at room temperature.
• Semi-conductors and conductors can be differentiated from insulators by their different room temperature electrical conductivity values. Insulators show very low room temperature conductivity values, typically less than about 10 ' ohm ⁇ cm "1 . Poly(styrene), poly(ethylene), and other polymers provide examples of insulating organic materials. Metals have very high room temperature conductivities, typically greater than about 10 ohm " cm "1 .
• Semi-conductors have conductivities greater than those of insulators, and are distinguished from metals by their different temperature dependence of conductivity, as described above.
• the organic materials that are useful in an embodiment ofthe sensors ofthe invention are either electrical semiconductors or conductors, and have room temperature electrical conductivities of greater than about 10 "6 ohm "1 cm “1 , typically having a conductivity of greater than about 10 "3 ohm " cm “1 .
• the sensors ofthe invention can include sensors comprising regions of an electrical conductor and regions of a compositionally different organic material that is an electrical conductor or semiconductor.
• electrical conductors include, for example, Au, Ag, Pt and carbon black, other conductive materials having similar resistivity profiles are easily identified in the art (see, for example the latest edition of: The CRC Handbook of Chemistry and Physics, CRC Press, the disclosure of which is incorporated herein by reference).
• insulators can also be incorporated into the composite to further manipulate the analyte response properties ofthe composites.
• the insulating region (i.e., non- conductive 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 regions thereof.
• Insulating organic materials that can be used for such purposes can include, for example: main- chain carbon polymers, such as poly(dienes), poly(alkenes), poly(acrylics), poly(methacrylics), poly(vinyl ethers), poly(vinyl thioethers), poly(vinyl alcohols), poly(vinyl ketones), poly(vinyl halides), poly(vinyl nitrites), poly(vinyl esters), poly(styrenes), poly(aryines), and the like; main- chain acyclic heteroatom polymers, such as poly(oxides), poly(caronates), poly(esters), poly(anhydrides), poly(urethanes), poly(sulfonate), poly(siloxanes), poly(sulfides), poly(thioesters), poly(sulfones), poly(sulfonamindes), poly(amides), poly(ureas), poly(phosphazens), poly(silanes), poly(s
• Nonconductive organic polymer materials may also be used.
• Combinations, concentrations, blend stoichiometries, percolation thresholds, etc. are readily determined empirically by fabricating and screening prototype resistors (chemiresistors) as described below.
• the chemiresistors can be fabricated by many techniques such as, but not limited to, solution casting, suspension casting, and mechanical mixing.
• solution cast routes are advantageous because they provide homogeneous structures and ease of processing.
• sensor elements may be easily fabricated by spin, spray or dip coating.
• 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 ofthe resistor components, but device fabrication is more difficult since spin, spray and dip coating are no longer possible.
• the chemiresistors can be fabricated by solution casting.
• the oxidation of pyrrole by phosphomolybdic acid represents such a system.
• the phosphomolybdic acid and pyrrole are dissolved in tetrahydrofuran (THF) and polymerization occurs upon solvent evaporation.
• THF tetrahydrofuran
• Certain conducting organic polymers can also be synthesized via a soluble precursor polymer.
• blends between the precursor polymer and the compositionally different material ofthe composite can first be formed followed by chemical reaction to convert the precursor polymer into the desired conducting polymer.
• poly(p-phenylene vinylene) can be synthesized through a soluble sulfonium precursor.
• Blends between this sulfonium precursor and a non-conductive or 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 to the desired poly(p-phenylene vinylene).
• suspension casting one or more ofthe components ofthe sensor 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 conductive organic or conductive polymer is dissolved in an appropriate solvent (such as THF, acetonitrile, water, etc.). Carbon black is then suspended in this solution and the resulting region is used to dip coat or spray coat electrodes.
• the relative ratio of conductive to compositionally different organic conductive or semiconductive organic material, along with the composition of any other insulating organic or inorganic components, can determine the magnitude ofthe response since the resistance ofthe elements becomes more sensitive to sorbed molecules as the percolation threshold is approached and as the molecules interact chemically with the components ofthe composite that adsorb or absorb the analyte.
• the film morphology is also important in determining response characteristics. For instance, uniform thin films respond more quickly to analytes than do uniform thick ones. However, it may be advantageous to include sensors of varying thickness to determine various diffusion coefficients or other physical characteristics ofthe analyte being analyzed.
• 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, UN-radiation cross-linking of poly(olefins), sulfur cross-linking of rubbers, e-beam cross-liriking 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 melting temperature (T m ) polymers), the incorporation ofthe 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 which provides means for supporting the leads.
• these supporting matrices can be porous or permeable to certain analytes across which a pressure difference is created to effectuate analyte contact with the sensor.
• 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 analog 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.
• the sensor arrays have a predetermined inter-sensor variation in the structure or composition ofthe conductive or semiconductive or insulating organic materials as well as in the conductive components and any insulating or plasticizing components ofthe composites.
• the variation may be quantitative and/or qualitative.
• the concentration ofthe conductive or semiconductive or insulating organic material in the composite can be varied across sensors.
• a variety of different organic materials may be used in different sensors.
• the anions that accompany conducting or semiconducting organic polymers such as polyaniline in some doping states can be compositionally varied to add diversity to the array, as can the polymer composition itself, either structurally (through use of a different family of materials) or through modification of the backbone and/or side chains of the basic polymer structure. This ability to fabricate many chemically different materials allows ready incorporation of a wide range of chemical diversity mto the sensor elements, and also allows facile control over the electrical properties ofthe sensor elements through control over the composition of an individual sensor element in the array.
• Insulating organic materials can also be used and blended into the array in order to further increase the diversity in one embodiment ofthe invention.
• organic polymers can provide the basic sensor components that respond differently to different analytes, based on the differences in polarity, molecular size, and other properties ofthe analyte in order to achieve the chemical diversity amongst array elements in the electronic nose sensors.
• Such insulators would include main-chain carbon polymers, main chain acyclic heteroatom polymers, main-chain heterocyclic polymers, and other insulating organic materials.
• these properties can be obtained by modification in the composition ofthe electrically conductive or electrically semiconductive organic component of the sensor composition by use of capping agents on a colloidal metal part ofthe conductive phase, by use of different plasticizers added to otherwise compositionally identical sensor elements to manipulate their analyte sorption and response properties, by variation in the temperature or measurement frequency ofthe sensors in an array of sensors that are otherwise compositionally identical, or a combination thereof and with sensors that are compositionally different as well.
• the sensors in an array can readily be made by combinatorial methods in which a limited number of feedstocks is combined to produce a large number of chemically distinct sensor elements.
• One method of enhancing the diversity of polymer based conductor/conductor or conductor/semiconductor or conductor/insulator chemiresistors is through the use of polymer blends or copolymers (Doleman, et al. (1998) Anal. Chem. 70, 2560-2654). Immiscible polymer blends may also be of interest because carbon black or other conductors can be observed to preferentially segregate into one ofthe blend components. Such a distribution of carbon black conduction pathways may result in valuable effects upon analyte sorption, such as the observance of a double percolation threshold.
• Binary polymer blend sensors can be prepared from a variety of polymers at incrementally different blend stoichiometries.
• a spray gun with dual controlled-flow feedstocks could be used to deposit a graded-composition polymer film across a series of electrodes.
• Such automated procedures allow extension ofthe sensor compositions beyond simple binary blends, thereby providing the opportunity to fabricate chemiresistors with sorption properties incrementally varied over a wide range.
• a combinatorial approach aided by microjet fabrication technology is one approach that will be known to those skilled in the art. For instance, a continuous jet fed by five separate feedstocks can fabricate numerous polymer blends in a combinatorial fashion on substrates with appropriately patterned sets of electrodes.
• the resistors can include nanoparticles comprising a central core conducting element and an attached ligand, with these nanoparticles dispersed in a semiconducting or conducting organic matrix.
• the nanoparticles have a metal core.
• a modification ofthe protocol developed by House et al. (the teachings of which are incorporated herein by reference), can be used.
• alkanethiolate gold clusters as an illustrative example, and not in any way to be construed as limiting, the starting molar ratio of HAuCU to alkanethiol is selected to construct particles ofthe desired diameter.
• the organic phase reduction of HAuCU 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, but may also range in size from about 5 nm to about 20 nm.
• sensors are prepared as composites of "naked” nanoparticles and a semiconducting or conducting organic material is added.
• the tenn "naked nanoparticles” means that the core has no covalently attached ligands or caps.
• a wide variety of semiconducting or conducting organic materials can be used in this embodiment.
• Preferred semiconducting or conducting materials are organic polymers. Suitable organic polymers include, but are not limited to, polyaniline, polypyrrole, polyacetylene, polythiophene, polyEDOT and derivatives thereof. Varying the semiconducting or conducting material types, concentration, size, etc., provides the diversity necessary for an array of sensors.
• the conductor to semiconducting or conducting organic material ratio is about 50% to about 90% (wt/wt).
• the general method for using the disclosed sensors, arrays and electronic noses, for detecting the presence of an analyte in a fluid, where the fluid is a liquid or a gas involves sensing the presence of an analyte in a fluid with a chemical sensor.
• a preferred detector array produces a unique signature for every different analyte to which it is expected to be exposed.
• Such systems can be constructed to include detectors that probe important, but possibly subtle, molecular parameters such as chirality.
• the term "chiral" is used herein to refer to an optically active or enantiomerically pure compound, or to a compound containing one or more asymmetric centers in a well-defined optically active configuration.
• a chiral compound is not superimposable upon its mirror image. Harnessing enantiomer resolution gives rise to myriad applications. For instance, because the active sites of enzymes are chiral, only the correct enantiomer is recognized as a substrate. Thus, pharmaceuticals having near enantiomeric purity are often many more times active than their racemic mixtures. However, many pharmaceutical formulations marketed today are racemic mixtures ofthe desired compound and its "mirror image.” One optical form (or enantiomer) of a racemic mixture may be medicinally useful, while the other optical form may be inert or even harmful, as has been reported to be the case for thalidomide.
• Suitable chiral resolving agents include, but are not limited to, chiral molecules, such as chiral polymers; natural products, such as, tartaric, malic and mandelic acids; alkaloids, such as brucine, strychnine, morphine and quinine; lanthanide shift reagents; chelating agents; biomolecules, such as proteins, cellulose and enzymes; and chiral crown ethers together with cyclodextrins.
• Plasticizers can also be used to obtain improved mechanical, structural, and sorption properties ofthe sensing films.
• Suitable plasticizers for use in the present invention include, but are not limited to, phthalates and their esters, adipate and sebacate esters, polyols such as polyethylene glycol and their derivatives, tricresyl phosphate, castor oil, camphor etc. Those of skill in the art will be aware of other plasticizers suitable for use in the present invention.
• the plasticizer can also be added to an organic polymer forming an interpenetrating network (IPN) comprising a first organic polymer and a second organic polymer formed from an organic monomer polymerized in the presence ofthe first organic polymer.
• IPN interpenetrating network
• This technique works particularly well when dealing with polymers that are immiscible in one another, where the polymers are made from monomers that are volatile. Under these conditions, the preformed polymer is used to dictate the properties (e.g., viscosity) ofthe polymer-monomer region. Thus, the polymer holds the monomer in solution.
• Examples of such a system are (1) polyvinyl acetate with monomer methylmethacrylate to form an IPN of pVA and pMMA, (2) pVA with monomer styrene to form an IPN of pVA and polystyrene, and (3) pVA with acrylonitrile to form an IPN of pVA and polyacrylonitrile.
• Each ofthe example compositions would be modified by the addition of an appropriate plasticizer. More than one monomer can be used where it is desired to create an IPN having one or more copolymers.
• the senor for detecting the presence of a chemical analyte in a fluid comprises a chemically sensitive resistor electrically connected to an electrical measuring apparatus where the resistor is in thermal communication with a temperature confrol apparatus.
• the chemically sensitive resistor(s) may comprise regions of a conductive organic polymer and regions of a conductive material which is compositionally different than the conductive organic material.
• the chemically sensitive resistor provides an electrical path through which electrical current may flow and a resistance (R) at a temperature (T) when contacted with a fluid comprising a chemical analyte.
• chemically sensitive resistor(s) ofthe sensor for detecting the presence of a chemical analyte in a fluid provide an electrical resistance (R m ) when contacted with a fluid comprising a chemical analyte at a particular temperature (T m ).
• the electrical resistance observed may vary as the temperature varies, thereby allowing one to define a unique profile of electrical resistances at various different temperatures for any chemical analyte of interest.
• a chemically sensitive resistor when contacted with a fluid comprising a chemical analyte of interest, may provide an electrical resistance R m at temperature T m where m is an integer greater than 1, and may provide a different electrical resistance R n at a different temperature T n .
• the difference between R m and R n is readily detectable by an electrical measuring apparatus.
• the chemically sensitive resistor(s) ofthe sensor are in thermal communication with a temperature confrol apparatus, tiiereby allowing one to vary the temperature at which electrical resistances are measured.
• the sensor comprises an array of two or more chemically sensitive resistors each being in thermal communication with a temperature control apparatus, one may vary the temperature across the entire array (i.e., generate a temperature gradient across the array), thereby allowing electrical resistances to be measured simultaneously at various different temperatures and for various different resistor compositions.
• a temperature control apparatus i.e., generate a temperature gradient across the array
• Methods for placing chemically sensitive resistors in thermal communication with a temperature control apparatus include, for example, attaching a heating or cooling element to the sensor and passing electrical current through said heating or cooling element.
• the temperature range across which electrical resistance may be measured will be a function ofthe resistor composition, for example the melting temperature ofthe resistor components, the thermal stability ofthe analyte of interest or any other component ofthe system, and the like.
• the temperature range across which elecfrical resistance will be measured will be about 10°C. to 80°C, preferably from about 22°C. to about 70°C. and more preferably from about 20°C. to 65°C.
• the senor can be subjected to an alternating electrical current at different frequencies to measure impedance. Impedance is the apparent resistance in an alternating electrical current as compared to the true elecfrical resistance in a direct current.
• the present invention is also directed to a sensor for detecting the presence of a chemical analyte in a fluid, said sensor comprising a chemically sensitive resistor electrically connected to an electrical measuring apparatus, wherein said resistor provides (a) an electrical path through said region of nonconductive organic polymer and said conductive material, and (b) an electrical impedance Z m at frequency m when contacted with a fluid comprising said chemical analyte, where m is an integer greater than 1 and m does not equal 0.
• the frequencies employed will generally range from about 1 Hz to 5 GHz, usually from about 1 MHZ to 1 GHz, more usually from about 1 MHZ to 10 MHZ and preferably from about 1 MHZ to 5 MHZ.
• Chemical analytes of interest will exhibit unique impedance characteristics at varying alternating current frequencies, thereby allowing one to detect the presence of any chemical analyte of interest in a fluid by measuring Z m at alternating frequency m.
• a Schlumberger Model 1260 Impedance/Gain-Phase Analyzer (Schlumberger Technologies, Farmborough, Hampshire, England) with approximately 6 inch RG174 coaxial cables is employed.
• the resistor/sensor is held in an Al chassis box to shield it from external electronic noise.
• one may vary both the frequency m ofthe electrical current employed and the temperature T n and measure the electrical impedance Z m;n , thereby allowing for the detection ofthe presence of a chemical analyte of interest.
• the present invention is also directed to a sensor for detecting the presence of a chemical analyte in a fluid
• said sensor comprising a chemically sensitive resistor electrically connected to an elecfrical measuring apparatus and being in thermal communication with a temperature control apparatus, wherein said resistor provides an electrical impedance Z m,n at frequency m and temperature T Tin when contacted with a fluid comprising said chemical analyte, where m and/or n is an integer greater than 1.
• the frequencies employed will generally not be higher than 10 MHZ, preferably not higher than 5 MHZ.
• Chemical analytes of interest will exhibit unique impedance characteristics at varying alternating current frequencies and varying temperatures, thereby allowing one to detect the presence of any chemical analyte of interest in a fluid by measuring Z m; negligence at frequency m and temperature T n .
• one particular sensor composition can be used in an array and the response properties can be varied by maintaining each sensor at a different temperature from at least one ofthe other sensors, or by performing the electrical impedance measurement at a different frequency for each sensor, or a combination thereof.
• Electronic noses for detecting an analyte in a fluid can be fabricated by electrically coupling the sensor leads of an array of differently responding sensors to an electrical measuring device (e.g., detector 180).
• the device measures changes in signal at each sensor ofthe array, preferably simultaneously and preferably over time.
• the signal is an elecfrical resistance, although it could also be an impedance or other physical property ofthe material in response to the presence ofthe analyte in the fluid.
• 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.
• the array includes usually at least ten, often at least 100, and perhaps 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 one million 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 first chemical analyte, and a second electrical resistance between its conductive leads when the resistor is contacted with a second fluid comprising a second, different, chemical analyte.
• 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 confrol, etc.
• the sensor array necessarily comprises sensors which respond differently to a change in an analyte concentration or identity, i.e., the difference between the first and second electrical resistance of one sensor is different from the difference between the first 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 signal which produces a response pattern associated with the exposure ofthe analyte.
• analyte detection systems comprising sensor arrays, an elecfrical 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
• signals are readily stored in a computer that contains a resident algorithm for data analysis and archiving. Signals can also be preprocessed either in digital or analog form; the latter might adopt a resistive grid configuration, for example, to achieve local gain confrol.
• long time adaptation electronics can be added or the data can be processed digitally after it is collected from the sensors themselves. This processing could be on the same chip as the sensors but also could reside on a physically separate chip or computer.
• Data analysis can be performed using standard chemometric methods such as principal component analysis and SIMCA, which are available in commercial software packages that run on a PC or which are easily fransferred into a computer running a resident algorithm or onto a signal analysis chip either integrated onto, or working in conjunction with, the sensor measurement electronics.
• the Fisher linear discriminant is one preferred algorithm for analysis ofthe data, as described below, h addition, more sophisticated algorithms and supervised or unsupervised neural network based learning/training methods can be applied as well (Duda, R. O.; Hart, P. E. Pattern Classification and Scene Analysis; John Wiley & Sons: New York, 1973, pp 482).
• the signals can also be useful in forming a digitally transmittable representation of an analyte in a fluid.
• Such signals could be transmitted over the Internet in encrypted or in publicly available form and analyzed by a cenfral processing unit at a remote site, and/or archived for compilation of a data set that could be mined to determine, for example, changes with respect to historical mean "normal" values ofthe breathing air in confined spaces, of human breath profiles, and of a variety of other long term monitoring situations where detection of analytes in fluids is an important value-added component ofthe data.
• Arrays of 20 to 30 different sensors may be sufficient for many analyte classification tasks but larger array sizes can be implemented as well.
• Temperature and humidity can be controlled but because a preferred mode is to record changes relative to the ambient baseline condition, and because the patterns for a particular type and concentration of odorant are generally independent of such baseline conditions, it is not critical to actively confrol these variables in some implementations ofthe technology. Where desired, such control can be achieved either in open-loop or closed-loop configurations.
• the sensors and sensor arrays disclosed herein can be used with or without preconcenfration ofthe analyte depending on the power levels and other system constraints demanded by the user. Regardless ofthe sampling mode, the characteristic patterns (both from amplitude and temporal features, depending on the most robust classification algorithm for the purpose) associated with certain disease states and other volatile analyte signatures can be identified using the sensors disclosed herein. These patterns are then stored in a library, and matched against the signatures emanating from the sample to determine the likelihood of a particular odoi falling into the category of concern (disease or nondisease, toxic or nontoxic chemical, good or bad polymer samples, fresh or old fish, fresh or contaminated air, etc.).
• Analyte sampling will occur differently in the various application scenarios.
• direct headspace samples can be collected using either single breath and urine samples in the case of sampling a patient's breath for the purpose of disease or health state differentiation and classification.
• extended breath samples passed over a Tenax, Carbopack, Poropak, Carbosieve, or other sorbent preconcenfrator material, can be obtained when needed to obtain robust intensity signals.
• Suitable commercially available adsorbent materials include but are not limited to, Tenax TA, Tenax GR, Carbotrap, Carbopack B and C, Carbotrap C, Carboxen, Carbosieve SIII, Porapak, Spherocarb, and combinations thereof.
• Preferred adsorbent combinations include, but are not limited to, Tenax GR and Carbopack B; Carbopack B and Carbosieve SIII; and Carbopack C and Carbopack B and Carbosieve SIII or Carboxen 1000.
• the analyte can be concentrated from an initial sample volume of about 10 liters and then desorbed into a concentrated volume of about 10 milliliters or less, before being presented to the sensor array.
• the absorbent material ofthe fluid concentrator can be, but is not limited to, a nanoporous material, a microporous material, a chemically reactive material, a nonporous material and combinations thereof.
• the absorbent material can concentrate the analyte by a factor that exceeds a factor of about 10 5 , or by a factor of about 10 2 to about 10 4 .
• removal of background water vapor is conducted in conjunction, such as concomitantly, with the concentration ofthe analyte.
• the concentration ofthe analyte Once the analyte is concentrated, it can be desorbed using a variety of techniques, such as heating, purging, stripping, pressuring or a combination thereof.
• the sample concenfrator can be wrapped with a wire through which current can be applied to heat and thus, desorb the concentrated analyte. The analyte is thereafter fransferred to the sensor array.
• Breath samples can be collected through a straw or suitable tube in a patient's mouth that is connected to the sample chamber (or preconcenfrator chamber), with the analyte outlet available for capture to enable subsequent GC/MS or other selected laboratory analytical studies ofthe sample.
• headspace samples of odorous specimens can be analyzed and/or carrier gases can be used to transmit the analyte of concern to the sensors to produce the desired response.
• the analyte will be in a liquid phase and the liquid phase will be directly exposed to the sensors; in other cases the analyte will undergo some separation initially and in yet other cases only the headspace ofthe analyte will be exposed to the sensors.
• the array will not yield a distinct signature of each individual analyte in a region, unless one specific type of analyte dominates the chemical composition of a sample. Instead, a pattern that is a composite, with certain characteristic temporal features ofthe sensor responses that aid in formulating a unique relationship between the detected analyte contents and the resulting array response, will be obtained.
• the Fisher linear discriminant searches for the projection vector, w, in the detector space which maximizes the pairwise resolution factor, i.e., rf, for each set of analytes, and reports the value of rf along this optimal linear discriminant vector.
• the rf value is an inherent property ofthe data set and does not depend on whether principal component space or original detector space is used to analyze the response data.
• This resolution factor is basically a multi-dimensional analogue to the separation factors used to quantify the resolving power of a column in gas chromatography, and thus the rf value serves as a quantitative indication of how distinct two patterns are from each other, considering both the signals and the distribution of responses upon exposure to the analytes that comprise the solvent pair of concern. For example, assuming a Gaussian distribution relative to the mean value ofthe data points that are obtained from the responses ofthe array to any given analyte, the probabilities of correctly identifying an analyte as a or b from a single presentation when a and b are separated with resolution factors of 1.0, 2.0 or 3.0 are approximately 76%, 92% and 98% respectively.
• Polymers including poly (ethylene-co-vinyl acetate) with 25% acetate
• PEVA poly(caprolactone)
• PCL poly(caprolactone)
• Carbon black-polymer composite suspensions used to form the detector films were prepared by dissolving 160 mg of polymer in toluene, followed by addition of 40 mg of carbon black (Cabot Black Pearls 2000) (Lonergan, et al., Chem. Mat. 1996, 8, 2298-2312). The mixtures were sonicated for 10 min and were then sprayed in several lateral passes using an airbrush (lowata HP-BC) held at a distance of 10 to 14 cm from the subsfrate.
• an airbrush lowata HP-BC
• Vapor Flow Apparatus An automated flow system was used to deliver pulses of a diluted stream of solvent vapor to the detectors (Doleman, et al., Anal. Chem. 1998, 70, 2560-2564).
• the carrier gas was oil-free air obtained from the house compressed air source (1.10 ⁇ 0.15 parts per thousand (ppth) of water vapor) controlled with a 28 L min "1 or a 625 ml min "1 mass flow controller (UNIT).
• a stream of carrier gas controlled by a 625 ml min "1 or a 60 ml min " mass flow controller was passed though one of five bubblers.
• the analyte-containing vapor was generated at higher flow rates, and a constant 200 ml min "1 was subtracted with a flow-regulated pump, permitting the difference to flow into the detector chamber. This flow was then divided into the two equally sized openings of the two channels in the chamber.
• the volumetric flow rates quoted below reflect the volumetric flow rate in each separate gap between the detector subsfrate and the Teflon-lined Al block.
• the temperature during data collection was approximately 294 K, and the temperature was passively controlled by immersing the solvent bubblers into large tanks of water.
• vapor presentations were 300 s in duration, and analyte exposures were separated in time by at least 75 min to minimize any possible influence ofthe previous exposure.
• ⁇ R final is the baseline resistance averaged over approximately 20 s prior to vapor presentation, and ⁇ R fmal is the differential resistance change relative to R b . The value of ⁇ R final was evaluated
• ⁇ N ms The rms noise, ⁇ N ms , of a detector was measured as the standard deviation of the data points obtained from the multimeter in the period immediately prior to each vapor presentation, divided by the average resistance value ofthe multimeter data points produced over that same measurement period. The period used to measure this baseline noise was equal to the time elapsed between determination ofthe baseline resistance and the determination ofthe differential resistance change upon analyte exposure.
• the multimeter was used to determine both the signal and noise values for this calculation because it was desirable to measure the signal and noise ofthe detectors using the same instrumental apparatus (i.e., the N in S/N is N OT s )•
• the values ofthe S/N were calculated independently for each separate presentation of analyte to each detector.
• the same analysis was used, except the noise was calculated over an interval of only 20 s, and 5 of these values, separated in time by 100 s, were averaged to generate N rms .
• these noise values, Nrms were first squared to yield N 2 r m s prior to plotting them against film volume.
• Example 1 Spectral Noise Measurements.
• the 1 M ⁇ low-noise resistance was formed from ten 100 k ⁇ wire- wound
• a control experiment was performed to evaluate whether film-substrate contacts dominated the observed noise properties ofthe detectors.
• Two composite films of approximately the same thickness, film area, and resistance were fabricated, with one film deposited in five 0.38 mm gaps between ten parallel 5.0 mm wide Cr/Au electrical contact pads, and the other film deposited across only one 2.0 mm gap between two parallel 5.0 mm wide Cr/Au contact pads.
• the additional film/substrate contacts produced no change in the relative noise power ofthe films, suggesting that the measured noise resulted primarily from the properties ofthe bulk detector film as opposed to the properties ofthe film electrode contacts.
• the properties of commercial, low noise, wire-wound resistors that had resistances similar to those ofthe carbon black composite films were also measured.
• FIG. 7 displays the noise power spectral density, S n (V b ), between 1 Hz and 800
• Hz for a set of carbon black composite thin film detectors as a function ofthe area covered by the composite between the electrical contact pads.
• the dimensions ofthe rectangularly shaped regions bridged by polymeric composite between the electrical contact pads were (in mm): 0.10 x 0.80, 0.20 x 1.60, 0.38 x 3.05, 0.40 x 3.20, 0.79 x 6.3, 2.03 x 16.3, 4.06 x 32.5.
• the PEVA-carbon black composite films were ⁇ 230 nm in thickness as determined by profilometry.
• An additional advantage of maintaining a constant aspect ratio for the different volume films is to reduce the variation in the noise that has been observed in some thick-film resistors of different aspect ratios.
• FIGS. 8 A and 8B illustrates the value ofthe S n * f product (crosses) for carbon
• Example 2 Determination of Polymer/Gas Partition Coefficients.
• Quartz crystal microbalance (QCM) measurements were performed on pure films of both PEVA and PCL at 294 K using 10 MHz resonant frequency quartz crystals and a measurement apparatus as described in Severin, et al., Anal. Chem. 2000, 72, 2008-2015.
• the frequency change upon exposure toe analyte vapor, ⁇ f an aiyt e. was calculated as the difference in the resonant frequency ofthe film-coated crystal during exposure to the specific analyte vapor relative to the baseline resonant frequency ofthe film- coated crystal in background air.
• the baseline frequency was taken as the mean frequency value obtained for the film-coated crystal during a 30 s period immediately prior to exposure to the analyte, and the frequency during exposure to analyte vapor was taken to be the mean frequency value observed between 80 s and 110 s after the vapor exposure had been initiated.
• the detector volume that will produce optimum signal/noise performance for a specific polymer/analyte combination can be calculated from Equation 12 if the polymer/gas partition coefficient is known. Accordingly, data for the partition coefficients of hexane and methanol into PCL and PEVA were determined using QCM measurements.
• FIGS. 9 A and 9B illustrate differential frequency
• the frequency shifts due to coating the crystal with the polymer were -6835 Hz for PEVA and -4355 Hz for PCL. [0152]
• ⁇ in the ideal gas constant (L atm mol "1 K '1 ), p is the density (g ml "1 ) ofthe polymer, T is the temperature (K), m is the slope of ⁇ f ana i yte versus concentration (Hz/parts per thousand
• Mw is the molecular weight (g mol '1 ) ofthe analyte
• ⁇ f po iy mer (Hz) is the frequency
• the values for these analytes were estimated by multiplying the measured polymer/gas partition coefficients for hexane by the ratio ofthe vapor pressures of dodecane and hexadecane relative to that of hexane (see Doleman, et al., Proc. Natl. Acad. Sci. U. S. A. 1998, 95, 5442-5447). This is a good approximation provided that the activity coefficients do not vary significantly for sorption of these three alkanes into the polymers of interest. As shown in FIG. 10, the polymer/gas partition coefficients varied from measured values of 10 for hexane and methanol to values of over 10 estimated for the lowest vapor pressure analyte, hexadecane.
• a linear array of detectors having a defined headspace and analyte flow configuration was constructed similar to the design illustrated in FIGS. 1 A, IB and lC.
• a series of parallel Cr/Au contacts was formed on each side of 75 mm x 25 mm glass slides. These contact electrodes were 1.8 mm long and were separated by a gap of 0.4 mm. Each pair of electrodes, which defined the contacts for an individual detector, was spaced 5 mm apart, permitting formation of 15 individual detectors on each side ofthe glass slide.
• the area surrounding the electrodes was coated with a thin layer of Teflon.
• Both sides ofthe substrate were masked, with the exception of a 5 mm by 75 mm rectangular region on each side ofthe substrate that was centered on the row of elecfrical contacts used to form the detectors.
• carbon black-PEVA composites were sprayed onto one side ofthe glass microscope slide and carbon black-PCL composites were sprayed onto the other side ofthe glass slide.
• the carbon black-polymer films covered the entire length of these substrates (Scheme II). Two such substrates were prepared.
• the resulting detectors had resistance values that ranged from 60 to 160 k ⁇ on the side sprayed with a PCL-carbon black composite and from 140 to 180
• a low volume vapor sample chamber was custom fabricated for the vapor response experiments.
• the detector substrate was placed between two pieces of Al, each of which had a recess 3.5 mm wide and 400 ⁇ m in depth machined along its length.
• a thin piece of Teflon tape was smoothed over the surface ofthe Al pieces and into the channel, effectively lining the top and the sides ofthe channel with an ⁇ 60 ⁇ m thick layer of Teflon. This Teflon prevented contact between the analyte and the Al and also formed an airtight gasket between each Al piece and the substrate.
• each channel 340 ⁇ m deep (400 ⁇ m channel depth minus 60 ⁇ m thickness of Teflon insulation) and 3.4 mm wide (3.5 mm machined width minus 2 x 0.06 mm thickness of Teflon insulation).
• Each channel spanned the entire length ofthe row of 15 detectors on its corresponding side ofthe substrate.
• the 3.4 mm width ofthe channel bounded the gas flow into a region that was less than the width ofthe detector film that had been sprayed onto the substrate. Hence, for the entire length ofthe channel, the detector film completely coated the substrate in the region adjacent to the channel.
• this experimental apparatus is analogous to probing the spatiotemporal distribution of analyte in the sorbent phase after injection of a sample onto a gas chromatography column or to ascertaining spectroscopically the position of analyte in a thin layer chromatography experiment as a function of time.
• the data are the relative differential resistance values measured in a 20 s period after 240 s of continuous exposure to the various analytes of interest.
• the analyte exposures used to produce these data were randomized with respect to analyte identity and with respect to the 5 replicate exposures of each analyte at the concentration of interest.
• the data in this figure have been normalized relative to the mean response ofthe first detector that physically encountered the analyte.
• the solid lines indicate responses when the analyte flowed in the direction from the leftmost detector (corresponding to the detector with the lowest numbered position) to rightmost detector.
• the normalization constants are: 10.8, 16.7, and 32.1, for hexane, dodecane, and tridecane, respectively.
• detectors was less than 5% ofthe mean ⁇ R/R b response value for this detector/analyte
• FIGS. 12A and 12B display similar data, collected on a different substrate, as a function of analyte flow velocity. Data presented are for two analytes, one having a high vapor pressure (hexane) and the other having a low vapor pressure (dodecane), both exposed to either PEVA-carbon black (FIG. 12 A) or to PCL-carbon black (FIG. 12B) composite detector films. For each flow rate, hexane and dodecane were alternately presented to the detectors. This procedure was repeated for each of 5 flow rates, proceeding sequentially from the lowest volumetric flow rate to the highest volumetric flow rate. This 10 exposure protocol was then repeated in its entirety 4 times, producing 50 total exposures of analyte to the detectors. [0165] For high vapor pressure analytes (i.e., analytes with relatively small
• the concentration ofthe low vapor pressure analyte stream is depleted by sorption into the first region of polymer composite film that it encounters, and the analyte concentration in the boundary layer that is exposed to the film is decreased further as the gas flow progresses along the length ofthe polymer composite.
• all detectors produced essentially identical responses at high flow rates, whereas at sufficiently low flow rates different responses were observed for detectors located in different positions relative to the position of analyte injection into the chamber. In this transitional region of behavior, analysis ofthe relative signal strengths ofthe detectors in the array can provide information on the partition coefficient ofthe analyte into the polymer film of interest.
• FIG. 11 shows this effect for hexane, dodecane, and tridecane.
• the effect of sorption of low vapor pressure analytes into the composite vapor detector films is also evident in the temporal response ofthe detectors.
• Example 3 The results obtained in Example 3 indicate that the noise decreases approximately as the square root ofthe detector area. Thus, for sufficient headspace volumes and quantities of sampled analyte so that the concentration of analyte sorbed into the polymer
• FIGS. 5 A and 5B To investigate this trade-off between detector S/N and detector area, stacked sensor arrays were constructed according to FIGS. 5 A and 5B, using rectangular 20 mm by 23 mm substrates that were fabricated by a commercial vendor (Power Circuits, Santa Ana, CA) using standard printed circuit board technology. Each of these substrates had electrical contacts deposited in a pattern that created a total of six detectors. Three detectors were located on the face ofthe substrate and three on the edge of the substrate. The three leading edge detectors were formed on the 840 ⁇ m thick edge ofthe substrate between parallel contacts that were located on each face ofthe circuit board.
• Three of these substrates were prepared by spraying PEVA-carbon black films onto the edge and face detectors ofthe substrates, and three by spraying PCL-carbon black films onto the edge and face detectors of the substrates.
• the films ofthe all individual detectors were isolated from each other by masking during spraying to produce a narrow (1 mm wide) gap in the detector film between adjacent detectors.
• Each ofthe six substrates was sprayed from an independently prepared suspension of carbon black and polymer, but both faces and the leading edge of a given substrate were sprayed from the same suspension.
• the two faces of a substrate were coated with a film of approximately the same resistance, to create films of similar thickness on each side of a given substrate.
• One substrate sprayed with a PEVA-carbon black composite and one sprayed with a PCL-carbon black composite were then assembled into a stack that also contained 760 ⁇ m thick Al plates and 105 ⁇ m thick Teflon spacers.
• This assembly created a set of small channels, each of dimensions 0.105 mm x 12 mm x 23 mm, that permitted vapor to be drawn over each set of face detectors.
• the Teflon spacers served as the side walls for each channel.
• the assembled stack was 4.59 mm high (2 x 0.840 mm + 3 x 0.760 mm + 6 x 0.105 mm). Three separate stack assemblies of this type were built.
• the stack assemblies were fitted into an Al chamber that had an open front and a tube connector on the back (away from the leading edge detectors). This tube connector was piped to a vacuum pump through a combination airflow meter and regulator (Cole Parmer). Each ofthe three stack assemblies used in this experiment contained six total channels formed collectively between the two substrates, the three Al plates, and the two walls ofthe chamber. Hence the volumetric flow of sampled gas through each individual channel was 1/6 ofthe volumetric flow of sample gas through the entire stack assembly. [0175] These stacked detector arrays were exposed to various analytes of interest.
• the face detector serves in essence as one large collection of detectors arranged linearly as in Example 3, thereby inherently averaging the responses, and providing reduced noise, for analytes with small polymer/gas partition coefficients.
• the edge detector has a small area so that it can provide enhanced S/N performance for analytes with large polymer/gas partition coefficients. Two such substrates were then stacked such that the leading edge of each detector first encountered the analyte flow, with a component ofthe flow subsequently being directed along the faces ofthe substrate.
• One substrate had one polymer type forming its detectors and the other substrate had a separate, different carbon black/polymer composite material forming all of its detectors.
• the gaps between the substrates and the adjacent Al plates were sufficiently thin to insure that the flow would proceed in the desired direction.
• the entire experimental procedure and data collection were fully repeated 3 independent times, each time with 2 independently prepared substrates that were assembled into the stacked configuration of FIGS. 5A and 5B.
• the detector films on the leading edge ofthe substrate had 1/24 the area ofthe films on the face ofthe detectors, and therefore exhibited higher noise levels than the detectors on the face ofthe substrate.
• Noise values, N ms. in the dc resistance readings measured using the multimeter were on average eight times higher for the PCL edge detectors than for the PCL face detectors, and were on average four times higher for the PEVA edge detectors than the PEVA face detectors (FIG. 10).
• the high vapor pressure analytes
• the face detectors exhibited S/N ratios that reflected the decrease in noise produced by large volume detector films.
• S/N values were ⁇ 6 times higher for PCL face detectors and were ⁇ 4 times higher for PEVA face detectors than for the corresponding edge detectors.
• the S/N values were about twice as high on the leading edge detectors as on the face detectors.
• the temporal evolution ofthe detector response properties can also be used to differentiate between analytes.
• FIGS. 14A and 14B the responses ofthe face and edge detectors to hexane were similar after 40 s of vapor presentation, and remained similar after 200 s. These hexane responses are similar in magnitude to the signals for dodecane after 200 s (FIG. 14B), and the two analytes could not easily be distinguished based on these data alone. However, the responses for these two analytes are clearly separable at 40 s (FIG.
• Example 5 Response at Constant Flow Rate of a Detector Array in the
• the composites used in this experiment were sprayed onto three circuit board substrates as illustrated in FIG. 15. Each substrate had electrical contacts deposited in a pattern that created a total of six detectors. Three detectors were located on each face (top and bottom) ofthe subsfrate and three detectors (ofthe same detector material) were located on the edge ofthe substrate. The three leading edge detectors were formed on the 840 ⁇ m thick edge ofthe substrate between parallel contacts that were located on each face ofthe circuit board. These detectors were located in positions 1, 2 and 3 of FIG. 15. The 20 mm by 23 mm faces ofthe circuit board supported the three larger detectors, each of which had dimensions of 2.0 mm by 15 mm.
• each substrate The electrodes that formed face detectors in the same location on the top and bottom of each substrate were wired together in parallel (i.e. the leads to face detector 1 on the top face were connected in parallel to the leads that addressed face detector 1 on the bottom face ofthe substrate).
• this arrangement therefore produced three face detectors, each having a total film area of 60 mm 2 (2 x 2.0 mm x 15 mm).
• Three of these substrates were stacked so that their leading edges were normal to the flow, and the flow through the gaps was controlled with a pump at 100 ml min l ; consequently, the total flow ofthe diluted vapor stream between each chip was much lower than that directed at the edge detectors.
• Saturated DNT vapor at 21°C was obtained from a glass tube approximately one meter in length that held ⁇ 180 g of loosely packed, granulated DNT.
• the air flow through this tube was 200 ml min "1 , with the background gas being oil-free laboratory air (1.10 ⁇ 0.15 parts per thousand (ppth) of water vapor).
• An additional gas stream passed through a bubbler that contained either acetone or water.
• Two in-line union-T's were used to mix the DNT vapor stream, the stream that contained either ofthe "interfering" vapors, and a background laboratory air gas stream.
• Flows were controlled with Teflon solenoid valves and mass flow controllers, in a computer-controlled system as described in Severin, et al., Anal. Chem. 2000, 72, 658-668.
• a short Teflon tube was connected to the output ofthe union to direct the gas toward the bank of detectors.
• the total flow rate of the gas directed at the detectors was held constant at 2 L min "1 during all parts ofthe experiment.
• the DNT concentration after dilution was 10% of its vapor pressure. At this dilution, the upper limit of the DNT concentration is 14 parts per billion (ppb) because the vapor pressure of DNT at room temperature is approximately 140 ppb.
• the concentration ofthe acetone was 12.9 parts per thousand (ppth). Although the background air stream always contained some water vapor, the concentration was roughly doubled to ⁇ 2.3 ppth during exposures that contained water as an "interfering" vapor.
• the vapor stream contained either pure DNT, water, or acetone; mixtures of DNT and water vapor; or mixtures of DNT and acetone vapor. Analyte exposures were 10 min in duration, and were separated in time by a 40 min exposure to the background air stream.
• the extrapolated response pattern ofthe detectors is similar to that of pure DNT even though the DNT was in the presence of much higher concentrations of acetone or water.
• the pre-equilibrium (time dependent) response pattern ofthe detectors to DNT or to any other analyte with a very high partition coefficient is expected to depend more closely on the film thickness ofthe individual detectors than on the specific interactions between the analyte and polymers ofthe individual detectors, the response pattern ofthe detectors to DNT is expected to be characteristic and is therefore useful in elucidating the existence of such a compound in the presence of high concentrations of interfering low partition coefficient compounds.

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