U.S. patent application number 10/083984 was filed with the patent office on 2002-10-17 for aligned particle based sensor elements.
Invention is credited to Munoz, Beth C., Sunshine, Steven A..
Application Number | 20020149466 10/083984 |
Document ID | / |
Family ID | 37018906 |
Filed Date | 2002-10-17 |
United States Patent
Application |
20020149466 |
Kind Code |
A1 |
Sunshine, Steven A. ; et
al. |
October 17, 2002 |
Aligned particle based sensor elements
Abstract
The present invention relates to a sensor array for detecting an
analyte in a fluid, comprising first and second sensors formed by
chemically sensitive resitors, wherein the first sensor comprises a
region of aligned conductive material; or where each of the sensors
comprises alternating regions of nonconductive regions and aligned
conductive regions with each resistor providing an electrical path
through both the nonconductive region and the aligned conductive
region, while each sensor manifests a different electrical
resistance during contact with sample fluids having different
analyte concentrations via the monitoring arrangement of having the
sensors electrically connected to an electrical measuring
apparatus. The aligned conductive particle material is aligned by
exposure to either of an electric, magnetic, optical,
photo-electric, electromagnetic or mechanical field, which serves
to improve signal to noise ratio of vapor sensors allowing Lower
Detection Limits for vapors being sensed. Such Lower Detection
Limits allow for identification of lower concentrations of
hazardous material and is advantageous in medical applications,
such as detection of disease states in a patient
Inventors: |
Sunshine, Steven A.;
(Pasadena, CA) ; Munoz, Beth C.; (Pasadena,
CA) |
Correspondence
Address: |
TOWNSEND AND TOWNSEND AND CREW, LLP
TWO EMBARCADERO CENTER
EIGHTH FLOOR
SAN FRANCISCO
CA
94111-3834
US
|
Family ID: |
37018906 |
Appl. No.: |
10/083984 |
Filed: |
February 27, 2002 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
10083984 |
Feb 27, 2002 |
|
|
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09600346 |
Nov 9, 2000 |
|
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Current U.S.
Class: |
338/34 |
Current CPC
Class: |
G01N 33/0031 20130101;
H01B 1/24 20130101; H01B 1/22 20130101; H01B 1/20 20130101; H01C
7/005 20130101; G01N 27/126 20130101; H01C 17/06506 20130101; H01C
17/0652 20130101 |
Class at
Publication: |
338/34 |
International
Class: |
H01C 007/00 |
Foreign Application Data
Date |
Code |
Application Number |
Nov 30, 1999 |
US |
PCT/US99/28282 |
Claims
What is claimed is:
1. A sensor array for detecting an analyte in a fluid, said sensor
array comprising: first and second sensors wherein said first
sensor comprises a region of aligned conductive material; and
wherein said sensor array is electrically connected to an
electrical measuring apparatus.
2. The sensor array for detecting an analyte in a fluid in
accordance with claim 1, wherein said first and said second sensors
are first and second chemically sensitive resistors, each of the
chemically sensitive resistors comprising: a plurality of
alternating regions comprising a nonconductive region and an
aligned conductive region that is compositionally different than
the nonconductive region, wherein each resistor provides an
electrical path through said nonconductive region and the aligned
conductive region; a first electrical resistance when contacted
with a first fluid comprising an analyte at a first concentration;
and a second electrical resistance when contacted with a second
fluid comprising said analyte at a second different
concentration.
3. The sensor array for detecting an analyte in a fluid in
accordance with claim 1, wherein said conductive region is aligned
by exposure to a member selected from the group consisting of an
electric field, a thermal field, a magnetic field, an
electromagnetic field, a photoelectric field, a light field, a
mechanical field, and combinations thereof.
4. The sensor array for detecting an analyte in a fluid in
accordance with claim 3, wherein said conductive region is
electrically aligned.
5. The sensor array for detecting an analyte in a fluid in
accordance with claim 3, wherein said conductive region is
magnetically aligned.
6. The sensor array for detecting an analyte in a fluid in
accordance with claim 3, wherein said conductive region is
photolytically aligned.
7. The sensor array for detecting an analyte in a fluid in
accordance with claim 1, wherein said aligned conductive material
is a member selected from the group consisting of metal, magnetic
alloys, ceramics, oxides, intermetallic compounds, carbon black,
nanoparticles and composite materials.
8. The sensor array for detecting an analyte in a fluid in
accordance with claim 7, wherein said conductive material comprises
carbon black.
9. The sensor array for detecting an analyte in a fluid in
accordance with claim 7, wherein said conductive material comprises
a nanoparticle.
10. The sensor array for detecting an analyte in a fluid in
accordance with claim 7, wherein said conductive material comprises
a metal.
11. The sensor array for detecting an analyte in a fluid in
accordance with claim 10, wherein said metal is a member selected
from the group consisting of nickel, cobalt, iron, a ferrite and
their magnetic alloys.
12. The sensor array for detecting an analyte in a fluid in
accordance with claim 10, wherein said metal is a coating of a
substrate, said substrate is a member selected from group
consisting of glass, silicon, quartz, ceramic or combination
thereof.
13. The sensor array for detecting an analyte in a fluid in
accordance with claim 10, wherein said metal is a member selected
from the group consisting of a precious metal coating and precious
metal alloys.
14. The sensor array for detecting an analyte in a fluid in
accordance with claim 13, wherein said precious metal coating is a
member selected from the group consisting of silver, gold and
platinum.
15. The sensor array for detecting an analyte in a fluid in
accordance with claim 7, wherein said conductive region is an
oxide.
16. The sensor array for detecting an analyte in a fluid in
accordance with claim 15, wherein said conductive region is a
member selected from the group consisting of In.sub.2O.sub.3,
SnO.sub.2, Na.sub.xPt.sub.3O.sub.4, TiO.sub.2 and BaTiO.sub.3.
17. The sensor array for detecting an analyte in a fluid in
accordance with claim 1, wherein said aligned region is a material
selected from the group consisting of copper phthalocyanine and
phenothiazine.
18. A system for detecting an analyte in a fluid, said system
comprising: a sensor array comprising first and second sensors
wherein said first sensor comprises a region of aligned conductive
material which provides a response in the presence of said analyte;
an electrical measuring device electrically connected to the sensor
array; and a computer comprising a resident algorithm; the
electrical measuring device detecting the response and the computer
assembling the response into a sensor array response profile.
19. The system for detecting an analyte in a fluid in accordance
with claim 18, wherein said first and said second sensors are first
and second chemically sensitive resistors, each chemically
sensitive resistor comprising a plurality of alternating regions
comprising a nonconductive region and an aligned conductive region
that is compositionally different than said nonconductive region
wherein, each resistor provides an electrical path through said
nonconductive region and said aligned conductive region, a first
electrical resistance when contacted with a first fluid comprising
an analyte at a first concentration and a second different
electrical resistance when contacted with a second fluid comprising
said analyte at a second different concentration wherein, the
difference between said first electrical resistance and said second
electrical resistance of said first chemically sensitive resistor
being different from the difference between said first electrical
resistance and said second electrical resistance of said second
chemically sensitive resistor under the same conditions; and the
electrical measuring device detecting the first and said second
electrical resistances in each of said chemically sensitive
resistors and the computer assembling the resistances into a sensor
array response profile.
20. The system for detecting an analyte in a fluid in accordance
with claim 18, wherein said conductive region is aligned by
exposure to a member selected from the group consisting of an
electric field, a thermal field, a magnetic field, an
electromagnetic field, a photoelectric field, a light field or
combinations thereof.
21. The system for detecting an analyte in a fluid in accordance
with claim 20, wherein said conductive region is electrically
aligned.
22. The system for detecting an analyte in a fluid in accordance
with claim 20, wherein said conductive region is magnetically
aligned.
23. The system array for detecting an analyte in a fluid in
accordance with claim 20, wherein said conductive region is
photolytically aligned.
24. A method for detecting the presence of an analyte in a fluid,
said method comprising: providing a sensor array comprising first
and second sensors, wherein said first sensor comprises a region of
aligned conductive material; and contacting said sensor array with
said analyte to produce a response thereby detecting the presence
of the analyte.
25. The method for detecting an analyte in a fluid in accordance
with claim 24, wherein said first and said second sensors are first
and second chemically sensitive resistors each comprising a
plurality of alternating regions comprising a nonconductive region,
and an aligned conductive region that is compositionally different
than the nonconductive material, and wherein each resistor provides
an electrical path through said nonconducting regions and aligned
conductive regions, a first electrical resistance when contacted
with a first fluid comprising an analyte at a first concentration
and a second different electrical resistance when contacted with a
second fluid comprising said analyte at a second different
concentration.
26. The method for detecting an analyte in a fluid in accordance
with claim 24, wherein said conductive region is electrically
aligned.
27. The method for detecting an analyte in a fluid in accordance
with claim 24, wherein said conductive region is magnetically
aligned.
28. The method for detecting an analyte in a fluid in accordance
with claim 24, wherein said conductive region is photolytically or
mechanically aligned.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to U.S. patent application
Ser. No. 09/201,999, filed Dec. 1, 1998, the disclosure of which is
hereby incorporated by reference in its entirety for all
purposes.
BACKGROUND OF THE INVENTION
[0002] Electronic noses are artificial sensory systems that are
able to mimic chemical sensing. In some instances, electronic noses
are arrays of sensors, which are able to generate electrical
signals in response to analytes or vapors. For instance, it is
possible to detect volatile materials by directly or indirectly
measuring a response, such as a resistance, across each of the
sensors in the array. Moreover, by providing different variables in
each sensor of the array, such as the polymeric make-up of the
sensors, it is possible to characterize various chemical materials
according to the response of the array to that volatile
material.
[0003] The potential applications of electronic noses are great.
Examples of applications include, but are not limited to,
environmental control, quality control, assessment of food and
beverage products. For example, in relation to fish freshness, long
chain carbonyl compounds, such as myristaldehyde, can be correlated
with fresh fish, whereas short chain alcohols, dimethylsulfide and
amines, which increase as a function of time, are characteristic of
foul smelling fish.
[0004] U.S. Pat. No. 5,571,401, which issued to Lewis et al.
(incorporated herein by reference), discloses sensor arrays useful
for the detection of analytes. Each of these sensors comprise a
resistor having a plurality of alternating nonconductive regions
and conductive regions. As explained therein, gaps exist between
the conductive regions and the nonconductive regions. In these
sensors, the electrical path length and resistance of a given gap
are not constant, but change as the nonconductive region absorbs,
adsorbs or imbibes an analyte. The dynamic aggregate resistance
provided by these gaps is, in part, a function of analyte
permeation of the nonconductive regions.
[0005] The foregoing sensor is based on a conductive network in a
nonconductive matrix. The swelling of the nonconductive matrix
causes the conductive region to move apart changing the resistance
of the sensor. The change in the resistance of the sensor can be
correlated to the concentration of the vapor to be detected. The
greater the resistance change for a given level of vapor, the lower
the detection limit of the vapor being identified. It is thus
advantageous to maximize the resistance change associated with the
sensor elements.
[0006] One of the major challenges in sensor technology today is to
enhance the signal-to-noise ratio (SIN) of a sensor element. By
increasing the S/N of a sensor element, a lower detection limit is
possible (i.e., the lower the concentration of analyte it is
possible to detect). This is particularly useful in applications
such as the detection of low concentrations of explosives, landmine
detection or in medical applications such as in the detection of
microorganism off-gases.
[0007] The response of the sensors upon exposure to vapor is
dependent on various factors. One such factor is the percentage of
connected paths that are broken. The number of connected paths
prior to exposure to a vapor is related to the percolation
threshold. The percolation threshold is defined as the particle
volume fraction at which the conductivity of the resistor increases
rapidly (i.e., an infinite number of conductive paths are formed
and the lattice essentially transforms from an insulator to a
conductor). At low volume loadings, there are few connected paths;
whereas at high volume loadings there are many connected paths.
However, at low volume loadings, there is greater sensor
resistance. Unfortunately, there is concomitantly a high degree of
noise at low volume loadings so that the signal to noise ratio is
unsatisfactorily low.
[0008] In view of the foregoing, there is a need in the art to
improve the signal to noise of vapor sensors while maintaining low
volume loading. Low volume loading sensors result in more
resistance and thereby a broader detection limit and greater
dynamic range. The current invention fulfills this and other
needs.
SUMMARY OF THE INVENTION
[0009] In certain aspects, the present invention provides a sensor
array for detecting an analyte in a fluid, comprising: first and
second sensors wherein the first sensor comprises a region of
aligned conductive material; and wherein the sensor array is
electrically connected to an electrical measuring apparatus.
Preferably, the first and second sensors are first and second
chemically sensitive resistors, each of the chemically sensitive
resistors comprising: a plurality of alternating regions comprising
a nonconductive region, such as an organic material, and an aligned
conductive region. The aligned conductive region comprises an
aligned conductive material compositionally different from the
nonconductive region. Moreover, each sensor, such as a resistor,
provides an electrical path through the nonconductive region and
the aligned conductive region; and a first response such as an
electrical resistance, when contacted with a first fluid comprising
an analyte at a first concentration, and a second response when
contacted with a second fluid comprising the analyte at a second
different concentration.
[0010] In certain embodiments, the conductive region can be aligned
using various processing techniques including, but are not limited
to, exposure to an electric field, a thermal field, a magnetic
field, an electromagnetic field, a photoelectric field, a light
field, a mechanical field or combinations thereof
[0011] Various materials can form the aligned conductive region of
the present invention. Such materials include, but are not limited
to, conductive materials, semi-conductive materials, magnetic
materials, photoresponsive materials and combinations thereof The
aligned conductive materials are preferably embedded in an organic
matrix, such as a polymeric matrix.
[0012] In another aspect, the present invention relates to a system
for detecting an analyte in a fluid, the system comprising: a
sensor array comprising first and second sensors wherein the first
sensor comprises a region of aligned conducting material.
Preferably, the first and second sensors are first and second
chemically sensitive resistors, each chemically sensitive resistor
comprising a plurality of alternating regions comprising a
nonconductive region and an aligned conductive region. Preferably,
the aligned conductive region comprises an aligned conductive
material compositionally different than the nonconductive region.
Each sensor, such as a resistor, provides an electrical path
through the nonconducting region and the aligned conductive region,
a first response such as an electrical resistance, when contacted
with a first fluid comprising an analyte at a first concentration
and a second different response when contacted with a second fluid
comprising the analyte at a second different concentration, wherein
the difference between the first response and the second response
of the first chemically sensitive resistor being different from the
difference between the first response and the second response of
the second chemically sensitive resistor under the same conditions;
an electrical measuring device electrically connected to the sensor
array; and a computer comprising a resident algorithm; wherein the
electrical measuring device detecting the first and the second
responses in each of the chemically sensitive resistors and the
computer assembling the responses into a sensor array response
profile.
[0013] In yet another aspect, the present invention relates to a
method for detecting the presence of an analyte in a fluid that can
be either a liquid or a gas. The method comprising: providing a
sensor array comprising first and second sensors, wherein the first
sensor comprises a region of aligned conductive material; and
contacting the sensor array with the analyte to produce a response
thereby detecting the presence of the analyte. Preferably, the
first and second sensors are first and second chemically sensitive
resistors, each comprising a plurality of alternating regions
comprising a nonconductive region, such as an organic material, and
an aligned conductive region. The aligned conductive region
comprises an aligned conductive material compositionally different
from the nonconductive region. In this method, each resistor
provides an electrical path through the nonconducting region and
the aligned conductive region, a first response such as an
electrical resistance, when contacted with a first fluid comprising
an analyte at a first concentration and a second different response
when contacted with a second fluid comprising the analyte at a
second different concentration.
[0014] These and other features and advantages of the invention
will be more readily apparent and understood when read with the
detailed description that follows.
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] FIG. 1 shows a graph of a typical resistance versus volume
loading for a non-aligned composite sensor.
[0016] FIG. 2 shows a graph of resistance versus volume loading for
a composite sensor where the particles have been aligned.
[0017] FIG. 3 shows optical micrographs of unaligned sensor (left)
and aligned sensor (right) Black Pearl 2000 (40 wt %) in
1,2-polybutadiene.
DETAILED DESCRIPTION OF THE INVENTION AND PREFERRED EMBODIMENTS
[0018] Improvement of the signal to noise ratio of vapor sensors
allows for lower detection limits by increasing the dynamic range.
Lower detection limits allow for the identification of lower
concentration of materials. This is particularly useful when
detecting hazardous materials or in various medical applications.
Surprisingly, it has now been discovered that by intentionally
aligning the conductive region, there is an increase in the
detection limit, i.e., the sensor is capable of detecting lower
concentrations of analyte. As such, the present invention provides
a sensor array for detecting an analyte in a fluid, comprising:
first and second sensors wherein the first sensor comprises a
region of aligned conducting material; and wherein the sensor array
is connected to an electrical measuring apparatus. Preferably, the
first and second sensors are first and second chemically sensitive
resistors, each of the chemically sensitive resistors comprising: a
plurality of alternating regions comprising a nonconductive region,
such as a nonconductive organic material, and aligned conductive
region, such as an aligned conductive material or particle. The
aligned conductive region is compositionally different from the
nonconductive region. The sensors such as resistors, provide an
electrical path through the alternating regions comprising a
nonconductive region, such as an organic material, and an aligned
conductive region, a first response when contacted with a first
fluid comprising an analyte at a first concentration, and a second
response when contacted with a second fluid comprising the analyte
at a second different concentration.
[0019] As explained previously, the response upon exposure to a
vapor is dependent on various factors. One such factor is the
percentage of connected paths in the alternating regions that are
broken. The number of connected paths prior to exposure to a vapor
is related to the percolation threshold. The percolation threshold
is defined as the volume fraction at which the conductivity of the
resistor increases rapidly. At low volume loadings, there are very
few connected paths. At high volume loadings, there are many
connected paths. Upon exposure to vapors, composite sensors will
exhibit a large change in resistance near their percolation
threshold. Before the advent of the present invention, the noise
level associated with such low volume loadings was prohibitively
high. However, by aligning the conductive region, lower volume
loadings can now be used. Moreover, by aligning the conductive
region, the percolation threshold is easier to obtain at low volume
loadings.
[0020] The sensors of the present invention have an aligned
conductive region that results in reduced percolation thresholds.
Reduced percolation thresholds mean that a slight swelling of the
composite sensor can result is a-very large change in resistance.
This is because the few conductive particles are all participating
in the connected paths, and any discontinuity in the connectivity
results in a large resistance change. Thus, the alignment of the
conductive region results in all of the particles participating in
the connected electrical paths. By aligning the conductive region,
these systems will produce a stable base resistance and thereby
enhance the signal-to-noise ratio. To achieve equivalent or near
equivalent noise levels, it is important to ensure that the
alternating regions are stable. This can be accomplished in the
present invention by, for example, cross-linking the polymer matrix
in the nonconducting region or by any other suitable means.
[0021] The alignment of the conductive region, e.g., material or
particles, is effected through the application of various
processing techniques. For instance, polarization techniques can be
used to align the conducting region. Suitable polarization
techniques include, but are not limited to, exposure to an electric
field, a thermal field, a magnetic field, an electromagnetic field,
a photoelectric field, a light field, a mechanical field or
combinations thereof The techniques employed to align the particles
depends in part on the particle composition.
[0022] Suitable particles for use in the present invention include
particles with a permanent magnetic dipole including, but not
limited to, iron, nickel or cobalt require the use of a magnetic
field for polarization to occur. Particles such as carbon black,
coke, C.sub.60, and the like, TiO.sub.2, BaTiO.sub.3,
In.sub.2O.sub.3, SnO.sub.2, Na.sub.xPt.sub.3O.sub.4, conducting
polymers, metals such as platinum, copper, gold, silver etc.,
polarize with application of an electric field. In some
embodiments, the conductive material is a conducting polymer, or an
insulating polymer with conductive fillers. Suitable conductive
polymers are disclosed in U.S. Pat. No. 5,571,401, which issued
Nov. 5, 1996, and WO 99/31494, which published on Jun. 24, 1999. As
disclosed in WO 99/31494, the sensors taught therein comprise
substituted polythiophenes. One polymer is poly
(3,3"-dihexyl-2-2":5',2"-- terthiophene). In a preferred
embodiment, the conductive particle is carbon black.
[0023] In an equally preferred embodiment, the conductive material
can be a particle, such as a gold nanoparticle, with a capping
ligand shell. A preferred nanoparticle is disclosed in WO 99/27357,
entitled "Materials, Method and Apparatus for Detection and
Monitoring Chemical Species," published Jun. 3, 1999. Examples of
colloidal nanoparticles for use in accordance with the present
invention are described in the literature (see, Templeton et al. J.
Am. Chem. Soc. (1 998) 120 :1906-1911; Lee et al., Isr. J Chem.
(1997) 37: 213-223 (1997); Hostetler et al. LANGMUIR (1998)
14:17-30; Ingram et al., J. Am. Chem. Soc., (1997) 119 :9175-9178;
Hostetler et al., J. Am Chem. Soc. (1996) 118 :4212-4213; Henglein
J Phys. Chem. (1993) 97 :5457-5471; Zeiri, J. Phys. Chem. (1992)
96:5908-5917; Leff et al., LANGMUIR (1996)4723-4730. Moreover,
particles such as copper phthalocyanine and phenothiazine polarize
when illuminated. All of these polarization techniques can be used
to generate sensors of the present invention.
[0024] Polarization processing, such as magnetic field processing,
involves exposure to various polarization mechanisms having
different directions and optionally, different strengths. For
example, during fabrication of the present sensors, exposure to a
magnetic field can optionally be in one direction, such as in the
x-, y- or z-direction; in two directions, such as x- and
y-directions, x-and z-directions or y- and z-directions; or in
three directions, such as x-, y- and z-directions. In a preferred
embodiment, the polarization processing is along the same axis as
the vapor measurement. For instance, if the vapor measurement is
along the z-direction, particle alignment will be along the
z-direction. In an equally preferred embodiment, the direction of
expansion of the alternating regions is along the same axis as the
vapor measurement. As used herein, the x-, y-, and z-axes have
their traditional meaning, i.e., the x and y axes are in the plane
of the sensor substrate and the z axis is perpendicular to the x
and y origins.
[0025] In addition to magnetic field processing, sensor fabrication
of the present invention can include other modes of polarization.
For example, photosensitive conductive material will be exposed to
optical radiation, such as visible, infrared or ultraviolet light.
Electrosensitive conductive material involves exposure to electric
fields having different directions and different strengths.
[0026] As previously discussed, enhancing the response of the
sensor can be accomplished by confining the direction of expansion
of the alternating regions to be along the axis of measurement or,
preferably, along the axis of the particle alignment For instance,
a polymer can have a 2% volume expansion on exposure to a certain
vapor concentration. If this swelling can be isolated to one
dimension, then the linear expansion can be as high as 8% causing a
much larger change in resistance than would occur without
confinement.
[0027] Aligning the conductive region e.g., material or particles,
in a nonconducting matrix during deposition causes an increase in
the number of conductive paths which in turn, results in a very low
base resistance. As discussed earlier, the formation of a
conductive path is related to the percolation threshold of the
material. The percolation threshold varies from material to
material depending on factors, such as particle size, shape and
composition. Alignment of the conductive region will cause
percolation to occur at a much lower volume loading. Thus, sensors
containing aligned conductive regions will give a larger signal
when exposed to a vapor compared to a sensor without aligned
regions. As the nonconductive region, such as an organic polymer,
swells, disruption of the particle chains occurs and a lowering in
the conductivity or an increase in the resistance occurs. As the
polymer desorbs, the particles return to their minimum energy state
that corresponds to particle alignment.
[0028] Non-sensor alignment of particles are known. For instance,
U.S. Pat. No. 4,177,228 issued to Prolss, entitled "Method of
Production of a Micro-Porous Membrane for Filtration Plants,"
discloses the alignment of particles by various techniques.
Likewise, U.S. Pat. No. 5,742,223, issued to Simenddinger, entitled
"Laminar Non-linear Device with Magnetically Aligned Particles,"
discloses composites with magnetically and electrically conductive
particles. In addition, U.S. Pat. No. 4,838,347, issued to Dentini,
entitled "Thermal Conductor Assembly," discloses a polymer field
with thermally conducting magnetically aligned particles.
Furthermore, U.S. Pat. No. 5,104,210, issued to Tokas, entitled
"Light Control Films and Method of Making," discloses composites of
magnetically alignable particles.
[0029] In certain aspects, the present invention relates to
conductive regions capable of alignment including, but not limited
to, conductive, semi-conductive, magnetic and photoresponsive
particles embedded in a nonconductive region, such as an organic
matrix, For instance, in one embodiment, particles suitable for
use, while preferably spherical, are not limited by their shape and
can even be in the form of flakes. Suitable particulate materials
that are magnetic include, but are not limited to, metals such as,
nickel, cobalt and iron and their magnetic alloys. Other suitable
magnetic particles include, but are not limited to, oxides and
intermetallic compounds as are known in the art. Composite
materials can also be used. These material include, but are not
limited to, nickel coated with copper, or magnetically thermally
conducting ceramics (see, U.S. Pat. No. 4,838,347, incorporated
herein by reference). Additional magnetic particles include, but
are not limited to, alloys containing nickel, iron, cobalt and
ferrites. Also conductive surface coatings can be used. Precious
metal coatings include, but are not limited to, silver, gold and
precious metal alloys (see, U.S. Pat. Nos. 4,923,739 and 4,737,112
incorporated herein by reference).
[0030] In certain embodiments, the conductive region can be a
substrate, such as a particle, coated with metal. Suitable
substrates include, but are not limited to, glass, silicon, quartz,
ceramic or combination thereof
[0031] The present invention has advantages over current sensor
technology. One advantage is the use of lower concentrations of
particles, which leads to ease of dispersion. To a first
approximation, the rate of particle sedimentation is proportional
to the number of particles in the dispersion. Another advantage is
the increased stability of the sensors of the present invention,
especially when the polymer matrix is crosslinked (i.e., the
polymer molecules are interconnected forming a 3-dimensional
network). A third advantage is an increase in the sensitivity of
the sensors leading to lower limits of detection (i.e., increased
dynamic range). The latter advantage is due to the much higher
signal-to-noise ratio given by the sensors having an aligned
conductive region.
[0032] More particularly, the major advantage of this invention
over the sensors of the prior art is that the signal-to-noise ratio
is much higher. Because of the increase in the signal-to-noise
ratio, the limit of detection increases (i.e., a smaller
concentration of analyte is capable of detection). In addition, the
response time is faster. A faster response time is critical in
applications such as quality control where the analyte may be on a
conveyor belt with a very short time for detection. In general,
sensors with greater response times are better than sensor with
lower response times. Various sensor responses of the present
invention include, but are not limited to, resistance, capacitance,
inductance, impedance, and combinations thereof.
[0033] In certain aspects, the nonconductive region of the sensors
comprise an organic material. In certain preferred aspects, the
organic material is an organic polymer. Organic polymers suitable
for use in the present invention include, but are not limited to,
those set forth in Table 1.
1TABLE 1 Major Class Examples Main-chain carbon polymers
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 nitriles),
poly(vinyl esters), poly(styrenes), poly(arylenes), etc. Main-chain
acyclic heteroatom polymers poly(oxides), poly(carbonates),
poly(esters), poly(anhydrides), poly(urethanes), poly(sulfonates),
poly(siloxanes), poly(sulfides), poly(thioesters), poly(sulfones),
poly(sulfonamides), poly(amides), poly(ureas), poly(phosphazenes),
poly(silanes), poly(silazanes), etc. Main-chain heterocyclic
polymers poly(furan tetracarboxylic acid diimides),
poly(benzoxazoles), poly(oxadiazoles),
poly(benzothiazinophenothiazines), poly(benzothiazoles),
poly(pyrazinoquinoxalines), poly(pyromellitimides),
poly(quinoxalines), poly(benzimidazoles), poly(oxindoles),
poly(oxoisoindolines), poly(dioxoisoindolines), poly(triazines),
poly(pyridazines), poly(piperazines), poly(pyridines),
poly(piperidines), poly(triazoles), poly(pyrazoles),
poly(pyrrolidines), poly(carboranes), poly(oxabicyclononanes),
poly(dibenzofurans), poly(phthalides), poly(acetals),
poly(anhydrides), carbohydrates, etc.
[0034] The sensors of the present invention can be fabricated by
many techniques including, but not limited to, solution casting,
suspension casting, matrix assisted pulsed laser evaporation
(MAPLE), MAPLE-Direct Write (MAPLE-DW) (see, R. Andrew McGill, et
al., IEEE Transactions on Ultrasonics, Ferroelectrics, and
Frequency Control 45:1370-1380 (1998), and mechanical mixing. In
general, solution casting routes are advantageous because they
provide homogeneous structures and are easy to process. With
solution casting routes, resistor elements can be easily fabricated
by spin, spray or dip coating. Since all elements of the resistor
must be soluble, solution casting routes can be somewhat limited in
their applicability. Suspension casting still provides the
possibility of spin, spray or dip coating, but more heterogeneous
structures than with solution casting are expected. With mechanical
mixing, there are no solubility restrictions since it involves only
the physical mixing of the resistor components, but device
fabrication is more difficult since spin, spray and dip coating are
no longer possible. In certain embodiments, the resistor is
deposited as a surface layer on a solid matrix that provides means
for supporting the leads. Typically, the solid matrix is a
chemically inert, nonconductive substrate, such as a glass or
ceramic.
[0035] Sensor arrays of the present invention are particularly
well-suited to scaled up production by being fabricated using
integrated circuit (IC) design technologies. For example, 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 that contains the
circuitry for analogue signal conditioning/processing and then data
analysis. This provides for the production of millions of
incrementally different sensor elements in a single manufacturing
step using ink-jet technology. Controlled compositional gradients
in the chemiresistor elements of a sensor array can be induced in a
method analogous to how a color ink-jet printer deposits and mixes
multiple colors. However, in this case, rather than multiple
colors, a plurality of different polymers in a solution which can
be deposited are used. A sensor array of a million distinct
elements only requires a 1 cm.times.1 cm sized chip employing
lithography at the 10 .mu.m feature level, which is within the
capacity of conventional commercial processing and deposition
methods. This technology permits the production of sensitive,
small-sized, stand-alone chemical sensors,
[0036] The fabrication of the sensors of the present invention
involves polarization processing of the conductive material.
Suitable polarization processing includes, but is not limited to,
magnetic field processing which involves exposure to magnetic
fields, photolytic field processing which involves exposure to
optical radiation, electric field processing which involves
exposure to electric fields, and combinations thereof In photolytic
field processing, light sensitive material can be exposed to
optical radiation, such as visible, infrared, or ultraviolet light
(see, U.S. Pat. No. 4,737,112). All of the foregoing polarization
processing techniques can have different axes direction and
different strengths.
[0037] Preferred sensor arrays have a predetermined inter-sensor
variation in the structure or composition of the nonconductive
regions (e.g. the nonconductive organic material). The variation
can be quantitative and/or qualitative. For example, the
concentration of the nonconductive organic material in the blend
can be varied across sensors. Alternatively, a variety of different
alignment techniques are possible within the sensor array. For
example, the polarization processing techniques (e.g., magnetic and
electric fields) can vary across the array of sensors.
[0038] An electronic nose for detecting an analyte in a fluid is
fabricated by electrically coupling the sensor leads of an array of
compositionally different sensors to an electrical measuring
device. The device measures changes in resistivity at each sensor
of the array, preferably simultaneously and preferably over time.
Frequently, the device includes signal processing means and is used
in conjunction with a computer and data structure for comparing a
given response profile to a structure-response profile database for
qualitative and quantitative analysis.
[0039] As such, in another embodiment, the present invention,
relates to a system for detecting an analyte in a fluid,
comprising: a sensor array comprising first and second sensors
wherein the first sensor comprises a region of aligned conducting
material. Preferably, the first and second sensors are first and
second chemically sensitive resistors, each chemically sensitive
resistor comprising a plurality of alternating regions comprising a
nonconductive region, such as a nonconductive organic material, and
an aligned conductive region, such as an aligned conductive
material compositionally different than the nonconductive region.
Each resistor provides an electrical path through the alternating
nonconducting region and the aligned conductive regions, a first
response such as an electrical resistance, when contacted with a
first fluid comprising an analyte at a first concentration and a
second different response when contacted with a second fluid
comprising the analyte at a second different concentration, the
difference between the first response and the second response of
the first sensor being different from the difference between the
first response and the second response of the second sensor under
the same conditions; an electrical measuring device electrically
connected to the sensor array; and a computer comprising a resident
algorithm; the electrical measuring device detecting the first and
said second responses in each of the sensors and the computer
assembling the responses into a sensor array response profile.
[0040] Typically, such sensor arrays and electronic noses of the
present invention comprise at least ten, usually at least 100, and
often at least 1000 different sensors, though with mass deposition
fabrication techniques described herein or otherwise known in the
art, arrays of on the order of at least 10.sup.6 sensors are
readily produced.
[0041] In operation, preferably each resistor provides a first
electrical resistance between its conductive leads when the
resistor is contacted with a first fluid comprising an analyte at a
first concentration, and a second electrical resistance between its
conductive leads when the resistor is contacted with a second fluid
comprising the same analyte at a second different concentration.
The fluids can be liquid or gaseous in nature. The first and second
fluids may reflect samples from two different environments, a
change in the concentration of an analyte in a fluid sampled at two
time points, a sample and a negative control, etc. The sensor array
necessarily comprises sensors that respond differently to a change
in an analyte concentration, i.e., the difference between the first
and second electrical resistance of one sensor is different from
the difference between the first and second electrical resistance
of another sensor. In addition, the sensor array can comprise
redundant sensors that can be advantageous for maximizing the
signal and thus reducing the noise in the signal.
[0042] In a preferred embodiment, the temporal response of each
sensor (resistance as a function of time) is recorded, The temporal
response of each sensor may be normalized to a maximum percent
increase and percent decrease in resistance which produces a
response pattern associated with the exposure of the analyte. By
iterative profiling of known analyses, a structure-function
database correlating analyses and response profiles is generated.
Unknown analyte can then be characterized or identified using
response pattern comparison and recognition algorithms.
Accordingly, analyte detection systems comprising sensor arrays, an
electrical measuring device for detecting resistance across each
chemiresistor, a computer, a data structure of sensor array
response profiles, and a comparison algorithm are provided. In
another embodiment, 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).
[0043] 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 of generating a differential response across a plurality
of sensors of the array. Analyte applications include broad ranges
of chemical classes including, but not limited to, organics such as
alkanes, alkenes, alkynes, dienes, alicyclic hydrocarbons, arenes,
heterocyclics, alcohols, ethers, ketones, aldehydes, carbonyls,
carbanions, polynuclear aromatics and derivatives of such organics,
e.g., halide derivatives, etc., microorganism off-gases, fungi,
bacteria, microbes, viruses, metabolites, biomolecules such as
sugars, isoprenes and isoprenoids, fatty acids and derivatives,
etc.
[0044] Accordingly, commercial applications of the sensors, arrays
and noses include environmental toxicology and remediation,
biomedicine, materials quality control, food and agricultural
products monitoring. Further applications include, but are not
limited to: heavy industrial manufacturing (automotive, aircraft,
etc.), such as ambient air monitoring, worker protection, emissions
control, and product quality-testing; oil/gas petrochemical
applications, such as combustible gas detection, H.sub.2S
monitoring, and hazardous leak detection and identification;
emergency response and law enforcement applications, such as
illegal substance detection and identification, arson
investigation, hazardous spill identification, enclosed space
surveying, and explosives detection; utility and power
applications, such as emissions monitoring and transformer fault
detection; food/beverage/agriculture applications, such as
freshness detection, fruit ripening control, fermentation process
monitoring and control, flavor composition and identification,
product quality and identification, and refrigerant and fumigant
detection; cosmetic/perfume applications, such as fragrance
formulation, product quality testing, and patent protection
fingerprinting; chemical/plastics/pharmaceuticals applications,
such as fugitive emission identification, leak detection, solvent
recovery effectiveness, perimeter monitoring, and product quality
testing; hazardous waste site applications, such as fugitive
emission detection and identification, leak detection and
identification, and perimeter monitoring; transportation
applications, such as hazardous spill monitoring, refueling
operations, shipping container inspection, and
diesel/gasoline/aviation fuel identification; building/residential
applications, such as natural gas detection, formaldehyde
detection, smoke detection, automatic ventilation control (cooking,
smoking, etc.), and air intake monitoring; hospital/medical
applications, such as anesthesia and sterilization gas detection,
infectious disease detection, breath, wound and body fluids
analysis, and telesurgey.
[0045] In yet another aspect, the present invention relates to a
method for detecting the presence of an analyte in a fluid
comprising: providing a sensor array comprising first and second
sensors, wherein the first sensor comprises a region of aligned
conductive material; and contacting the sensor array with the
analyte to produce a response thereby detecting the presence of the
analyte. Preferably, the first and second sensors are first and
second chemically sensitive resistors each comprising a plurality
of alternating nonconductive regions, such as nonconductive organic
material, and aligned conductive regions, such as an aligned
conductive material compositionally different than the
nonconductive region, each resistor providing an electrical path
through the nonconducting region and aligned conductive region, a
first response such as an electrical resistance, when contacted
with a first fluid comprising an analyte at a first concentration
and a second different response when contacted with a second fluid
comprising the analyte at a second different concentration.
[0046] The general method for using the disclosed sensor arrays and
electronic noses for detecting the presence of an analyte in a
fluid preferably involves resistively sensing the presence of an
analyte in a fluid with a chemical sensor comprising first and
second conductive leads electrically coupled to and separated by a
chemically sensitive resistor as described above by measuring a
first resistance between the conductive leads when the resistor is
contacted with a first fluid comprising an analyte at a first
concentration and a second different resistance when the resistor
is contacted with a second fluid comprising the analyte at a second
different concentration.
[0047] In certain embodiments, the methods and systems of the
present invention can be used for monitoring medical conditions and
disease processes. For instance, WO 98/29563, published Jul. 9,
1998, and incorporated herein by reference, discloses a method for
monitoring conditions in a patient wherein a sample is obtained
from a patient over a period of time. The samples are then flowed
over a gas sensor and a response is measured. Thereafter, the
response is correlated with known responses for known conditions.
The conditions include, but are not limited to, the progression and
or regression of a disease state, bacterial infections, viral,
fungal or parasitic infections, the effectiveness of a course of
treatment and the progress of a healing process.
[0048] In another embodiment, the methods and systems of the
present invention can be used for monitoring medical conditions in
a respiring subject. For instance, WO 98/39470, published Sep. 11,
1998, and incorporated herein by reference, discloses a method for
detecting the occurrence of a condition in a respiring subject. The
method comprises introducing emitted respiratory gases to a gas
sensing device, detecting certain species present in the gas and
correlating the presence of the species with certain conditions. A
wide variety of conditions can be ascertained using this aspect of
the present invention. These conditions include, but are not
limited to, halitosis, ketosis, yeast infections, gastrointestinal
infections, diabetes, alcohol, phenylketonuria, pneumonia, and lung
infections. Those of skill in the art will know of other conditions
and diseases amenable to the methods and systems of the present
invention.
[0049] In certain aspects, the sensor arrays, systems and methods
of the present invention comprise: first and second sensors wherein
the first sensor comprises a region of aligned conducting material.
The second sensor can also comprise a region of aligned conductive
material. However, in certain other embodiments, the second sensor
is a different sensor type. Suitable sensor types include, but are
not limited to, a surface acoustic wave (SAW) sensor; a quartz
microbalance sensor; a conductive composite; a metal oxide gas
sensor, an organic gas sensor; an infrared sensor; a sintered metal
oxide sensor; a phthalocyanine sensor; an electrochemical cell; a
conducting polymer sensor; a catalytic gas sensor; an organic
semiconducting gas sensor; a solid electrolyte gas sensor; a
temperature sensor; a humidity sensor; fiber optic micromirrors;
dye impregnated polymeric coatings on optical fibers and a
Langmuir-Blodgett film sensor. Those of skill in the art will know
of other sensors suitable for use in the present invention.
[0050] In certain aspects, the sensors of the present invention
comprise a chiral center. For instance, European Patent Application
No. 0 794 428, published Sep. 10, 1997, describes sensors capable
of distinguishing between enantiomers. The sensor comprise a pair
of spaced apart contacts and a conducting polymer material spanning
the gap. The polymer has chiral sites in the polymer material
formed by incorporating optically active counter ions such as
camphor sulfonic acid.
[0051] Moreover, WO 99/40423, published Aug. 12, 1999, discloses
sensor arrays of that are capable of distinguishing or
differentiating between chiral compounds. That publication relates
to a device for detecting the presence or absence of an analyte in
a fluid, the device comprises a sensor, the sensor comprising a
chiral region. The sensor comprises a conductive region and a
nonconductive region, wherein at least one of the conductive and
nonconductive regions is chiral, and wherein the analyte generates
a differential response across the sensor.
[0052] In certain other embodiments, the sensor arrays of the
present invention comprise sensors disclosed in WO 99/00663,
published Jan. 7, 1999. As taught therein, a combinatorial approach
for preparing arrays of chemically sensitive polymer-based sensors
are capable of detecting the presence of a chemical analyte in a
fluid contact therewith. The described methods and devices comprise
combining varying ratios of at least first and second organic
materials which, when combined, form a polymer or polymer blend
that is capable of absorbing a chemical analyte, thereby providing
a detectable response. The detectable response of the sensors
prepared by this method is not linearly related to the mole
fraction of at least one of the polymer-based components of the
sensor.
[0053] The following examples are offered by way of illustration
and not by way of limitation.
EXAMPLES
Example 1
[0054] This Example illustrates the difference in percolation
threshold in non-aligned sensors versus aligned sensors.
[0055] The percolation threshold is defined as the particle volume
fraction at which the conductivity of the resistor increases
rapidly i.e., an infinite number of conductive paths are formed and
the lattice essentially transforms from an insulator to a
conductor. FIG. 1 illustrates atypical resistance versus volume
loading for a non-aligned composite sensor, where the percolation
threshold occurs at about 20 volume percent filler. FIG. 2 shows a
graph of resistance versus volume loading for a composite sensor
where the particles have been aligned. The percolation threshold
occurs at about 5 volume percent filler.
Example 2
[0056] This Example illustrates a sensor array that was fabricated
by depositing Black Pearl 2000 (40 wt %) dispersed in
1,2-polybutadiene in the presence of an electric field.
[0057] The conductive particles respond to the field by migrating
to minimum energy states, which in this case corresponds to
chain-like structures aligned parallel to the electric field. As
the solvent evaporates the chains are locked in place. FIG. 3
illustrates the particle alignment after using 48 volts across the
sensor electrodes during the deposition process.
[0058] All publications, patents and patent applications mentioned
in this specification are herein incorporated by reference into the
specification in their entirety for all purposes. Although the
invention has been described with reference to preferred
embodiments and examples thereof, the scope of the present
invention is not limited only to those described embodiments. As
will be apparent to persons skilled in the art, modifications and
adaptations to the above-described invention can be made without
departing from the spirit and scope of the invention, which is
defined and circumscribed by the appended claims.
* * * * *