U.S. patent application number 10/754018 was filed with the patent office on 2004-08-19 for referencing and rapid sampling in artificial olfactometry.
This patent application is currently assigned to Cyrano Sciences, Inc.. Invention is credited to Hermann, Bruce, Munoz, Beth C., Sunshine, Steven A..
Application Number | 20040161370 10/754018 |
Document ID | / |
Family ID | 31890846 |
Filed Date | 2004-08-19 |
United States Patent
Application |
20040161370 |
Kind Code |
A1 |
Sunshine, Steven A. ; et
al. |
August 19, 2004 |
Referencing and rapid sampling in artificial olfactometry
Abstract
Devices and methods are disclosed that are effective to produce
reliable vapor measurements in the presence of drift. In certain
instances the sensor module is mounted externally on a housing. In
other instances, the sensor module contains a first sensor element
incorporating a first array of sensors and a second sensor element
incorporating a second array of sensors wherein both sensor
elements are mounted externally on the housing. In other
embodiments, the present invention relates to mapping an x-y
surface for detection of an analyte, the method includes moving in
tandem at least two sensor arrays separated by a distance "d"
across an x-y surface to produce a plurality of responses and
analyzing the responses to map the x-y surface for detection of an
analyte. Moreover, the present invention provides a sensor module,
such as in a handheld device, comprising at least two pneumatic
vapor paths and at least two sensor arrays. The dual pneumatic
train allows rapid sensing as it increases the duty cycle
frequency.
Inventors: |
Sunshine, Steven A.;
(Pasadena, CA) ; Hermann, Bruce; (Winston Salem,
NC) ; Munoz, Beth C.; (Pasadena, CA) |
Correspondence
Address: |
Foley & Lardner
Suite 500
3000 K Street, N.W.
Washington
DC
20007
US
|
Assignee: |
Cyrano Sciences, Inc.
Pasadena
CA
|
Family ID: |
31890846 |
Appl. No.: |
10/754018 |
Filed: |
January 7, 2004 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10754018 |
Jan 7, 2004 |
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09713756 |
Nov 14, 2000 |
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6703241 |
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60165437 |
Nov 15, 1999 |
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Current U.S.
Class: |
422/83 ;
422/98 |
Current CPC
Class: |
Y10T 436/10 20150115;
G01N 33/0006 20130101; G01N 33/0031 20130101 |
Class at
Publication: |
422/083 ;
422/098 |
International
Class: |
G01N 027/00; G01N
021/00; G01N 033/00; G01N 031/00 |
Claims
What is claimed is:
1. A method for reducing drift in an artificial olfaction device
having an array of sensors, said method comprising: contacting said
array of sensor with an analyte at a first temperature to produce a
first response; contacting said array of sensor with said analyte
at a second temperature to produce a second response; and
subtracting the first response from the second response thereby
reducing drift in said sensor array.
2. The method of claim 1, wherein at least one sensor in said array
of sensors in selected from the group consisting of a conducting
and nonconducting regions sensor, a SAW sensor, a quartz
microbalance sensor, a conductive composite sensor, a chemiresitor,
a metal oxide gas sensor, an organic gas sensor, a MOSFET, a
piezoelectric device, an infrared sensor, a sintered metal oxide
sensor, a Pd-gate MOSFET, a metal FET structure, a electrochemical
cell, a conducting polymer sensor, a catalytic gas sensor, an
organic semiconducting gas sensor, a fiber optical chemical sensor,
a solid electrolyte gas sensors, and a piezoelectric quartz crystal
sensor.
3. The method of claim 2, wherein at least one sensor is a
conducting and nonconducting regions sensor.
4. The method of claim 2, wherein at least one sensor is a SAW
sensor.
5. The method of claim 1, wherein said analyte and said sensor
array are equilibrated at said first temperature.
6. The method of claim 1, wherein said analyte and said sensor
array are equilibrated at said second temperature.
7. The method of claim 1, wherein the difference between said first
temperature and said second temperature is between about 5.degree.
C. and about 150.degree. C.
8. The method of claim 7, wherein the difference between said first
temperature and said second temperature is between about 2.degree.
C. to about 70.degree. C.
9. The method of claim 1, wherein said artificial olfaction device
comprises two arrays of sensors.
10. The method of claim 1, wherein said artificial olfaction device
is a handheld device.
11. A sensor module configured for external mounting on a sensing
apparatus for detecting an analyte in a fluid, said sensor module
comprising: a casing sized and configured to be received in a
receptacle of the sensing apparatus; at least two sensor to provide
a distinct response when exposed to one or more analytes; and an
electrical connector configured to be releasably engageable with a
mating electrical connector of the sensing apparatus when the
sensor module is received in the receptacle, said electrical
connector transmitting the characteristic signals from the at least
two sensors to the sensing apparatus.
12. The sensor module of claim 11, wherein said sensor module
comprises a memory device.
13. The sensor module of claim 11, wherein at least one sensor in
said array of sensors in selected from the group consisting of a
conducting and nonconducting regions sensor, a SAW sensor, a quartz
microbalance sensor, a conductive composite sensor, a chemiresitor,
a metal oxide gas sensor, an organic gas sensor, a MOSFET, a
piezoelectric device, an infrared sensor, a sintered metal oxide
sensor, a Pd-gate MOSFET, a metal FET structure, a electrochemical
cell, a conducting polymer sensor, a catalytic gas sensor, an
organic semiconducting gas sensor, fiber optical chemical sensor, a
solid electrolyte gas sensors, and a piezoelectric quartz crystal
sensor.
14. The sensor module of claim 13, wherein at least one sensor is a
conducting and nonconducting regions sensor.
15. The sensor module of claim 13, wherein at least one sensor is a
SAW sensor.
16. The sensor module of claim 11, wherein said sensing apparatus
is a handheld device.
17. A sensing device for detecting an analyte, said device
comprising: a housing; a sensor module mounted externally on said
housing and incorporating an array of sensors, each of said sensors
providing a different response in the presence of said analyte; a
monitoring device mounted on said housing and configured to monitor
said responses of the array of sensors incorporated in the sensor
module, and further configured to produce a plurality of sensor
signals; and an analyzer mounted on said housing and configured to
analyze said plurality of sensor signals to identify said
analyte.
18. The sensor device according to claim 17, wherein said sensor
module is capable of automatic physical movement.
19. The sensor device according to claim 17, wherein said sensor
module comprises at least two pneumatic vapor paths and at least
two sensor arrays.
20. The sensor device according to claim 17, wherein said response
is a member selected from the groups consisting of resistance,
impedance, mechanical capacitance, inductance, frequency, magnetic
and optical.
21. The sensor device according to claim 17, wherein at least one
sensor is selected from the group consisting of inorganic metal
oxide semiconductors, intrinsically conducting polymers, mass
sensitive piezoelectric sensors, surface acoustic wave sensors and
nonconducting and conducting regions sensors.
22. The sensor device according to claim 17, wherein said analyzer
comprises a comparison algorithm wherein said comparison is
performed using a pattern recognition algorithm which is a member
selected from the group consisting of principal component analysis,
Fisher linear discriminant analysis, soft independent modeling of
class analogy, K-nearest neighbors, and canonical discriminant
analysis.
23. A sensing device for detecting an analyte in a fluid, said
device comprising: a first sensor element having a first sensor
array for producing a response in the presence of said analyte; a
second sensing element having a second sensor array for referencing
said system; a computer coupled to said first and said second
sensing elements having a resident algorithm.
24. The sensing device according to claim 23, wherein said first
sensing element is physically located distinctly from said second
sensing element.
25. The sensing device according to claim 24, wherein said second
sensing element has attached thereto a pasivation layer.
26. The sensing device according to claim 25, wherein said
pasivation layer comprises a material that is a member selected
from the group consisting of SiO.sub.2 and SiO.sub.2 based
films.
27. The sensing device according to claim 26, wherein said
SiO.sub.2 based film is a member selected from the group consisting
of thermal oxides, silane, SiH.sub.4, testraethoxysilane,
Si(OC.sub.2H.sub.5).sub.4, silicate glasses, and spin on glass.
28. The sensing device according to claim 24, wherein said first
sensing element is in a first sample chamber and said second
sensing element is in a second sample chamber.
29. The sensing device according to claim 24, wherein said second
sensing element has attached thereto a porous membrane layer.
30. The sensing device according to claim 29, wherein said porous
membrane layer limits diffusion of said analyte.
31. The sensing device according to claim 24, wherein said second
sensing element is a reference element and sensing element is
temperature controlled.
32. A method for mapping an x-y surface for detection of an
analyte, said method comprising: moving in tandem at least two
sensor arrays separated by a distance "d" across an x-y surface to
produce a plurality of responses; and analyzing said responses and
thereby mapping the x-y surface for detection of said analyte.
33. A parallel independent sensor array device for detecting a
plurality of test samples independently and simultaneously, said
parallel independent sensor array device comprising: a parallel
matrix of sensors to produce a plurality of responses each of said
plurality of responses generated from a corresponding plurality of
test samples; and an electrical measuring apparatus to
simultaneously detect each of said plurality of responses.
34. The device of claim 33, further comprising a computer coupled
to each of said sensors having a resident algorithm.
35. The device of claim 33, wherein each of said plurality of
responses is generated from a member selected from the group
consisting of antibiotics, catalysts, drugs, biomolecule binding
efficiencies, nucleic acid hybridizations, ligand-ligand
interactions, biomolecule interactions, and drug candidates.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to U.S. Provisional Patent
Application No. 60/165,437, filed Nov. 15, 1999, the teaching of
which incorporated herein by reference in its entirety for all
purposes.
FIELD OF THE INVENTION
[0002] In general, this invention relates to chemical sensing, and
in particular, to referencing, rapid sampling and methods of
reducing or eliminating drift in artificial olfactometry.
BACKGROUND OF THE INVENTION
[0003] An electronic nose is an array of chemical sensors coupled
with computerized multivariate statistical processing tools. These
sensors respond to a wide variety of analytes giving rise to a
unique signature or pattern for a given analyte. The pattern is
interpreted using pattern recognition algorithms to identify or
quantify the analyte of interest.
[0004] In general, the chemical sensors are based on physical or
chemical absorption, chemical desorption or optical properties that
take place on the sensors. Suitable sensor types include metal
oxide semiconductors, metal oxide semiconducting field effect
transistors, conducting organic polymers, quartz microbalance,
surface acoustic wave devices and conducting and nonconducting
regions sensors.
[0005] For the analysis of organic solvent vapors, certain devices,
such as surface acoustic wave devices, respond to the extent of
vapor sorption. This sorption is typically rapid, reversible and is
proportional to vapor concentration. However, various drawbacks
exist. For example, certain sensors are susceptible to humidity,
have low confidence limits, are susceptible to drift and are
unstable. In certain instances, instability can be corrected using
background subtraction techniques. Humidity in the vapor can be
eliminated by using a preconcentrator with water vapor absorbents.
Confidence limits can be enhanced by using a limit of recognition
that is defined as the concentration below which a vapor can no
longer be reliably recognized from its response pattern (see,
Zellers et al., Analytical Chemistry, 70, 4191-4201 (1998)).
[0006] Drift is one of the most serious drawbacks of sensor
technology. Drift is defined as the temporal shift of sensor
response under constant or static conditions. The reason for
certain types of drift is not well understood, but it is believed
to result from unknown dynamic processes. Temperature or pressure
fluctuations, or changes in the sensing environment can also cause
drift. When the reasons for drift are known, it is sometimes
possible to develop mathematical models that can compensate for its
effects (see, Semin et al., Meas. Techn. 38, 30-32 (1995)). Work
has been done on ways to improve the stability of sensors; however,
it is not yet possible to fabricate sensors with no drift at
all.
[0007] One possible solution to the effects of drift is to use a
reference gas (see, Fryder et al. Transducers '95 and Eurosensors
IX, Stockholm Sweden, pp. 683-686 (1995)). This technique is
difficult or impractical in some situations, such as a handheld
sensing device. Another technique is the use of a theory of hidden
variable dynamics for the rejection of common mode drift. Moreover,
the hidden variable approach can be couple with adaptive estimation
methods to compensate for drift (see, Holmberg et al., Sensors and
Actuators B 42, 285-294 (1997).
[0008] In view of the inherent instability of certain sensor
arrays, there remains a need to have effective referencing and
calibration in spite of the presence of drift. Devices and methods
are needed which effectively produce reliable vapor measurements in
the presence of drift. The present invention fulfills these and
other needs.
SUMMARY OF THE INVENTION
[0009] Temporal shift of sensor response under constant conditions
is one of the most serious drawbacks of sensor technology. Devices
and methods are needed which are effective to produce reliable
vapor measurements in the presence of temporal shift.
[0010] As such, in certain aspects, the present invention provides
a method for reducing drift in an artificial olfaction device
having an array of sensors, the method comprising: contacting the
array of sensor with an analyte at a first temperature to produce a
first response; contacting the array of sensor with the analyte at
a second temperature to produce a second response; and subtracting
the first response from the second response thereby reducing drift
in the sensor array. In certain instances, the artificial olfaction
device is a handheld device.
[0011] In another embodiment, the present invention provides a
sensor module configured for external mounting on a sensing
apparatus for detecting an analyte in a fluid, the sensor module
comprising: a casing sized and configured to be received in a
receptacle of the sensing apparatus; at least two sensor to provide
a distinct response when exposed to one or more analytes located
within the sample chamber; and an electrical connector configured
to be releasably engageable with a mating electrical connector of
the sensing apparatus when the sensor module is received in the
receptacle, the electrical connector transmitting the
characteristic signals from the at least two sensor to the sensing
apparatus.
[0012] In yet another embodiment, the present invention provides a
sensing device for detecting an analyte, comprising: a housing; a
first sensor element incorporating a first array of sensors and a
second sensor element incorporating a second array of sensors
wherein both sensor elements are mounted externally on the housing.
In certain embodiments, the first sensing element is designed to
sense a vapor, and is referred to as the sensing element. The
second sensor element is designed as a reference for the device and
is referred to as the referencing element. In certain aspects, a
physical barrier exists between the reference sensor element and
the analyte to be identified. Preferably, the reference element is
pasivated with a material to prevent the analyte from contacting
the surface of the reference element.
[0013] In still yet another embodiment, the present invention
provides a sensing device for detecting an analyte, comprising: a
housing; a sensor module mounted externally on the housing and
incorporating an array of sensors, each of the sensors providing a
different response in the presence of the analyte; a monitoring
device mounted on the housing and configured to monitor the
responses of the array of sensors incorporated in the sensor
module, and further configured to produce a corresponding plurality
of sensor signals; and an analyzer mounted on the housing and
configured to analyze the plurality of sensor signals to identify
the analyte.
[0014] In still other embodiments, the present invention relates to
mapping an x-y surface for detection of an analyte, the method
comprising: moving in tandem at least two sensor arrays separated
by a distance "d" across an x-y surface to produce a plurality of
responses; analyzing the responses and thereby mapping the x-y
surface for detection of an analyte. In certain preferred
embodiments, the tandem sensor system resides on a x-y
translational stage.
[0015] In yet another embodiment, the present invention provides a
sensor module, such as in a handheld device, comprising at least
two pneumatic vapor paths and at least two sensors arrays. The dual
pneumatic train allows rapid sensing as it increases the duty cycle
frequency.
[0016] These and other aspects of the present invention will become
more apparent when read with the detailed description and figures
that follow.
BRIEF DESCRIPTION OF THE DRAWINGS
[0017] FIG. 1 illustrates a top perspective view of an embodiment
of an electronic nose device of the present invention.
[0018] FIG. 2 illustrates a sensor response using a device of the
present invention.
[0019] FIG. 3 illustrates a top perspective view of an embodiment
of an electronic nose device of the present invention.
[0020] FIG. 4 illustrates differential flow pneumatics of the
present invention.
[0021] FIG. 5 illustrates a top sectional view of an embodiment of
the present invention.
[0022] FIGS. 6A-B illustrate Panel 6A a top sectional view of an
embodiment of the present invention and Panel 6B a module cover
embodiment.
[0023] FIG. 7 illustrates drift in sensor arrays.
[0024] FIG. 8 illustrates a sensor response using a device of the
present invention.
DETAILED DESCRIPTION OF THE INVENTION AND PREFERRED EMBODIMENTS
[0025] I. Devices
[0026] A. Externally Mounted Sensor Module
[0027] In certain aspects, the present invention provides a sensing
device for detecting an analyte, comprising: a housing; a sensor
module mounted externally on the housing comprising an array of
sensors, each of the sensors providing a response in the presence
of the analyte; a monitoring device mounted on the housing and
configured to monitor the responses of the array of sensors
incorporated in the sensor module, further configured to produce a
corresponding plurality of sensor signals; and an analyzer mounted
on the housing and configured to analyze the plurality of sensor
signals to identify the analyte.
[0028] Preferably, the sensor module is capable of automatic
physical movement. The physical movement is controlled by a
controller that is configured to control the sensor module. This
automatic physical movement of the sample module allows referencing
of the sensor arrays. For instance, the sensor module is placed in
a first position to be calibrated. The first position does not
expose the sensor array to the test area or sample containing the
analyte. Thus, the first position is a calibration position wherein
the sensor response is set to a null value. After the sensor array
is calibrated or nulled, the sensor module is automatically moved
closer to the test sample or area containing the vapor or analyte
to be measured. Sampling of the vapor is quick and reliable, and
because the sensor module is externally mounted, the response of
the sensor array is not impeded by sensor array pneumatics. As will
be apparent to those of skill in the art, although the sensor array
is set to a null value, it is possible that some background signal
exists.
[0029] In an especially preferred embodiment, the externally
mounted sensor is on a handheld electronic nose. As shown in FIG.
1, the sensor module is externally mounted. FIG. 1 shows a top
perspective view of an embodiment of a handheld device. The
handheld device includes an elongated housing having a lower end
sized to be conveniently grasped and supported by the hand of an
operator. A display 12 and several push-button control switches 12a
through 12c are located on the housing's topside, for convenient
viewing and access by the operator. Push-buttons 12a-c can be used
to control the device during its various operating modes. Display
12 displays information about such operating modes and the results
of the device's sensing and fluid detection. As use herein, a fluid
is a unit of a vapor, liquid, solution, gas, or other forms, and
mixtures thereof, of a substance being analyzed. Thus, a fluid
sample can include chemical analytes, odors, vapors, and others.
The sample can comprise a single analyte or a plurality of
analytes.
[0030] A tubular wand 13 having an externally mounted sensor 14 and
an exhaust port 15 are provided to respectively receive and
discharge samples to be analyzed. In certain embodiments, the
externally mounted sensor is a plug-in sensor module. The operation
of electronic circuitry of sensor modules, similar to the
externally mounted sensor module of the present invention, is
described in detail in U.S. Pat. No. 6,085,576, issued Jul. 11,
2000, to Sunshine et al. and incorporated herein by reference.
[0031] In one embodiment, the externally mounted sensor module of
the present invention incorporates "swap and sniff" technology.
Advantageously, the externally mounted modules can be easily
swapped to compensate for various analytes or for specific
environmental conditions. In certain aspects, a sensor module is
configured to be releasable engageable into an external portion of
a handheld device.
[0032] The sensor module includes a casing having at least two
sensors and an electrical connector. The casing is sized and
configured to be received in an external receptacle of the sensing
apparatus. The electrical connector is configured to be releasably
engageable with a mating electrical connector of the sensing
apparatus when the sensor module is received in the receptacle. The
electrical connector transmits the characteristic signals from the
sensors to the sensing apparatus. In certain embodiments, the
characteristic sensor parameters and data are stored in a memory
devices such as an electrically programmable ROM (EPROM), an
electrically erasable and programmable PROM (EEPROM), and other
memory technologies, integrated in the sensor module. As will be
apparent to those of skill in the art, the externally mounted
sensors does not preclude the presence of an internally mounted
sensor.
[0033] In certain aspects, the sensor module contains a heating
element. An on-board processor can be used to provide temperature
control for each individual sensor array device in the sensor
module. In one implementation, each sensor array device can include
a backside heater. Further, the processor can control the
temperature of the sample chambers either by heating or cooling
using a suitable thermoelectric device. Moreover, the analyte vapor
can be heated and cooled within strict temperature limits.
[0034] As illustrated in FIG. 2 the response of a sensor array
using the foregoing movable or retractable sensor module embodiment
is shown. At point "A", the sensor module is away from the sample
in a first position. The sensor module is then placed in a second
position, wherein the sample module is over the sample or area to
be tested and the sensor responds (point "B"). Thereafter, the
sensor is moved back to the first position. Using this
configuration for a sensing device, it is possible to take
advantage of the decrease in concentration as a function of
distance to calibrate or reference the sensing device. With
reference to FIG. 1 for example, the tubular wand 13 having an
externally mounted sensor 14 can be telescopically retracted to
provide the first position. In the fully retracted position the
sensor module is in the first position. In the fully extended
position the sensor module is in the second position.
[0035] B. Externally Mounted Sensor Module Having Two Sensor
Elements
[0036] In another aspect, the present invention provides a sensing
device for detecting an analyte, comprising: a housing; a first
sensor element incorporating a first array of sensors and a second
sensor element incorporating a second array of sensors wherein both
sensor elements are mounted externally on a housing. In certain
embodiments, the first sensing element is designed to sense a
vapor, and is referred to herein as the sensing element. In certain
aspects, the second sensor element is designed as a reference, and
is referred to herein as the referencing element. In a preferred
aspect, the first sensor element is a first array of sensors and
the second sensor element is a second sensor array, wherein the
first and second sensor arrays comprise sensors that are
compositionally similar or the same. As will be apparent to those
of skill in the art, the externally mounted sensors does not
preclude the presence of an internally mounted sensor.
[0037] As shown in FIG. 3, the artificial olfaction device 20 has a
tubular wand 23 that has an externally mounted first sensor module
24 and an externally mounted second sensor module 25. Preferably,
the first sensor module comprises a sensor array and the second
sensor module comprises a sensor array having similar or the same
sensor type. For example, if sensor element in 24 comprises surface
acoustic wave sensors, the referencing sensor element in 25 will
also comprise surface acoustic wave sensors. In this manner, both
the first sensor element and the second sensor element have similar
or the same sensor type.
[0038] In other aspects, the device comprises two sensor elements
that are externally mounted, wherein the second sensor element is
positionally located differently (e.g., further away from the
object to be measured) than the first sensor element. In this
aspect, a vapor concentration gradient exists to provide a
"reference" and a real measurement. The first sensor element
closest to the sample provides the real measurement. The second
sensor element, i.e., the reference sensor element, is located
further away from the object to be measured and thus provides a
reference.
[0039] In a further aspect, the present invention provides a device
having two sensor elements wherein the location of the two sensors
and differential vapor detection can be used for analyte
determination. For instance, two sensors i.e., sensor element 1 and
sensor element 2, can be separated by some distance, "d," and if
the vapor at point 1 is different than at point 2 (point 1 and
point 2 are separated by distance "d") there will be a differential
response between sensor element 1 and sensor element 2. This
differential response can be used to reference the two sensors with
respect to drift.
[0040] In addition to referencing, the sensors can be used to
advantageously map a surface, such as a planar surface. For
example, if the two sensors are separated by 1 inch i.e., "d"=1
inch, and one sensor is placed over the test sample and the other
sensor is not over the test sample, this will create a differential
signal. However, if both sensor elements are over a test sample or
not over a test sample, the differential reading will be close to
zero. This differential response is useful for mapping a surface.
If the objective is to locate contamination on a surface, for
example, a countertop, dirty floorboards, hazardous leaks, fecal
matter, anywhere there is a point source having a chemical profile,
the edge of the contamination will signal a positive response. This
is advantageous because any deviation indicates a response. In
general, a deviation from a zero response is typically more
sensitive than trying to see a small change on a large
baseline.
[0041] As such, in certain embodiments, the present invention
relates to mapping an x-y surface for detection of an analyte, the
method comprising: moving in tandem at least two sensor arrays
separated by a distance "d" across an x-y surface to produce a
plurality of responses; analyzing the responses and thereby mapping
the x-y surface for detection of an analyte. In this embodiment,
the two sensor arrays are separated by a distance "d". If one
sensor array is placed over an analyte, the analyte being on the
x-y surface, and the other sensor is not over the analyte, this
will create a differential signal between the sensor arrays.
However, if both sensor arrays are over the analyte or,
alternatively, not over the analyte, the differential reading will
be small or close to zero. The resolution of the analyte on the x-y
surface is inversely proportional to the distance "d". The greater
the resolution required, the smaller the distance separating the
tandem sensor array.
[0042] Using the methods of the present invention, it is also
possible to increase the dynamic range of the sensor arrays. The
dynamic range is characterized by the lowest detectable amount of
analyte, which is given by the noise of the sensor response, and
the maximum detectable amount of analyte that is given by the
saturation effects of the sensor. Using the devices of the present
invention, it is possible to reduce the noise level of the sensor
system thereby increasing the dynamic range of the sensor
arrays.
[0043] C. Pneumatics
[0044] As shown in FIG. 4, in certain embodiments, the present
invention relates to an increased duty-cycle pneumatic sensing
train 30. In a preferred embodiment, the sensor module comprises at
least two pneumatic vapor paths 33, 35 and at least two sensor
arrays 36, 37. In a preferred differential flow pneumatic train 30
of the present invention, sensors 36, 37 can be independently
externally mounted, internally mounted, or alternatively, one
sensor can be externally mounted and one sensor can be internally
mounted.
[0045] In operation, sensor 36 is used to detect an analyte. While
sensor 36 is being purged, sensor 37 can be used for detection or
vise versa. Using the differential flow pneumatics of the present
invention, it is possible to increase the frequency of analyte
detection. In certain other embodiments, the pneumatics permits
switching between a calibration source and an analyte source. Where
sensor calibrations are frequent, the module of the present
invention provides the ability to switch gases on a schedule
consistent with desired pre-programmed calibration cycles.
[0046] In a further aspect, the present invention relates to sensor
pneumatics comprising a pump having a reverse flow feature. The
pump functions in alternative modes wherein in the first mode,
sample air is taken in, and in a reverse mode, background air
purges the system. In this manner, the duty cycle can be increased
over conventional pumps.
[0047] D. Pasivasion Layer
[0048] In other embodiments, the present invention provides a
sensing device comprising a first sensor element and a second
sensor element that are physically located in spatially similar or
identical positions with regard to the analyte; however, the
analyte is prevented or blocked from contacting the second sensor
element (i.e., the reference sensor). In this embodiment, a
physical barrier exists between the reference sensor element and
the analyte to be identified. Preferably, the sensing element is
pasivated with a material to prevent the analyte from contacting
the surface of the sensing element. Suitable pasivation materials
include, but are not limited to, SiO.sub.2 and SiO.sub.2 based
films, thermal oxides, silane, SiH.sub.4, Si.sub.3N.sub.4,
tetraethoxysilane, Si(OC.sub.2H.sub.5).sub.4, boro silicate
glasses, and spin on glass.
[0049] FIG. 5 shows a top sectional view of an embodiment of a
sensor module that includes four plug-in sensor devices 41A and 41B
within a single cavity or sample chamber 42. Disposed atop sensor
array 41A is a pasivation layer 43 (hatched lines) to prevent or
block the analyte from contacting sensor array 41A.
[0050] In another embodiment, the sensing device is configured so
vapors do not contact the surface of the second sensor element i.e.
the reference element. This can be accomplished by the use of a
second sensor module. The reference-sensing module completely
encloses the reference sensors, thereby preventing vapors to
contact the surface of the sensors. With regard to FIG. 6, a top
sectional view of an embodiment having two modules 51 and 54
wherein the first module is a sensing module 51 that includes 2
plug-in sensor devices 52 and 52A. The second sensing element 54 is
a referencing element and also includes 2-plug-in sensor devices 53
and 53A. Sample chamber 54 is defined, in part, by a cover 55 (FIG.
6B) that is secured over module 54.
[0051] In another aspect, the reference element has a porous
membrane associated therewith. In this way, the analyte's contact
with the sensor array is slowed. The porous membrane limits
diffusion to the reference sensor. This process of limited
diffusion of the analyte allows sampling of the sensors at
different points of time and thus, referencing and calibration can
be done simultaneously. The sensors are identical and thus the
responses are identical. The pasivation material only slows
diffusion and is not analyte selective. Suitable porous pasivation
layers include, but are not limited to, porous plastics, Teflon,
and dialysis materials.
[0052] Moreover, the pasivation layer can reduce or eliminate
humidity. Using an absorption or adsorption material especially
designed for water vapor, the pasivation layer can reduce or
eliminate humidity in the test sample.
[0053] E. Methods to Reduce Drift
[0054] Instabilities and drift are serious problems in chemical
sensors and could effect the identification of analytes.
Noncumulative drift denotes statistical variations of the sensor
signal or response. Cumulative drift leads to irreversible changes
of calibration and can result from sensor deterioration. FIG. 7 is
an xy plot 70 of sensor signal versus time. Short-term drift can
occur after switching on the sensor array device 71. These
short-term drifts are caused by the time required to establish
steady-state conditions, such as a constant operational temperature
of the sensor array. In certain instances, thermal drift is related
to changes of the sensor signal upon variations of ambient
temperature. Sensor signals 74 and 75 show actual analyte sensing.
Thermal drift can be reduced or eliminated by maintaining the
sensor module at a uniform temperature. It is possible to reduce,
compensate or eliminate drift using differential temperature
measurements.
[0055] As such, the present invention provides a method for
reducing drift by using differential thermal measurements. Thus, in
another embodiment, the present invention provides a method for
reducing drift in an array of sensors, comprising: contacting the
array of sensor with an analyte at a first temperature to produce a
first response; contacting the array of sensor with the analyte at
a second temperature to produce a second response; and subtracting
the first response from the second response thereby reducing
drift.
[0056] In this embodiment, the need to take a background response
requirement for a baseline has been alleviated. Prior to the
present invention, analyte detection required the background or
ambient response to be taken as a reference. This background or
reference sample is then subtracted from the test response. This
method can be inefficient because the background has to be purged
before an analyte can be measure. To increase the sensor array duty
cycle, it has been discovered that the array of sensors can measure
the analyte at two temperatures, and thereby alleviate the purge
cycle. This dramatically increases sensor sampling and duty cycle.
In certain aspects, the sampling is performed at two temperature
values, wherein the temperature values differ between about
5.degree. C. and about 150.degree. C. More preferably, the
temperatures differ between about 2.degree. C. to about 70.degree.
C. In certain aspects, the analyte and the sensor array are
equilibrated at the first temperature. In addition, the analyte and
the sensor array are optionally equilibrated at the second
temperature. In certain embodiments, the artificial olfaction
device comprises two arrays of sensors.
[0057] In another aspect of differential measurements, the present
invention relates to a method for reducing drift by using
differential sensor measurements. Similar to thermal differences,
the use of sensor arrays having various sensor thickness results in
eliminating drift. Thus, in yet another embodiment, the present
invention provides a method for reducing drift in an array of
sensors, comprising: contacting a first sensor having a first
sensor thickness with an analyte to produce a first response;
contacting a second sensor having a second sensor having a second
sensor thickness with the analyte at a second temperature to
produce a second response; and subtracting the first response from
the second response thereby reducing drift.
[0058] F. Methods to Calibrate
[0059] In general, for unequivocal characterization of their
dynamic and static properties, sensors have to be calibrated and
tested. In the simplest case, the calibration curve for sensor
arrays is linear. The devices of the present invention provide
internal diagnostics and built-in self-calibration features, which
allow for improved performance. Moreover, the sensors of the
present invention have the ability to perform internal diagnostics
and self-calibration, thereby validating that the sensor is
operating within acceptable tolerances. In certain embodiments, the
devices and methods of the present invention provide the means to
automatically calibrate in-situ sensor arrays, for many different
analyte mixtures. The sensor calibration is routinely scheduled
over an extended period at the user's discretion. In certain
aspects, the devices of the present invention provide an interface
to record, display and analyze sensor data in real time against an
analyte standard.
[0060] II. Sensor Arrays
[0061] The devices and methods of the present invention include an
array of sensors and, in certain instances, the sensors as
described in U.S. Pat. No. 5,571,401 are used. Sensors suitable for
detection of analytes associated with agricultural products
include, but are not limited to, surface acoustic wave (SAW)
sensors; quartz microbalance sensors; conductive composites;
chemiresitors; metal oxide gas sensors, such as tin oxide gas
sensors; organic gas sensors; metal oxide field effect transistor
(MOSFET); piezoelectric devices; optical sensors; sintered metal
oxide sensors; Pd-gate MOSFET; metal FET structures; conducting-and
nonconducting regions-disposed on metal FET structures; metal oxide
sensors, such as a Tuguchi gas sensors; phthalocyanine sensors;
electrochemical cells; conducting polymer sensors; catalytic gas
sensors; organic semiconducting gas sensors; solid electrolyte gas
sensors; temperature sensors, humidity sensors, piezoelectric
quartz crystal sensors; and Langmuir-Blodgett film sensors.
[0062] In a preferred embodiment, the sensors of the present
invention are disclosed in U.S. Pat. No. 5,571,401, incorporated
herein by reference. Briefly, the sensors described therein are
conducting materials and nonconducting materials arranged in a
matrix of conducting and nonconducting regions. The nonconductive
material can be a nonconducting polymer such as polystyrene. The
conductive material can be a conducting polymer, carbon black, an
inorganic conductor and the like. The sensor arrays comprise at
least two sensors, typically about 32 sensors and in certain
instances 1000 or more sensors. The array of sensors can be formed
on an integrated circuit using semiconductor technology methods, an
example of which is disclosed in PCT Publication WO 99/08105,
entitled "Techniques and Systems for Analyte Detection," published
Feb. 19, 1999, and incorporate herein by reference. Another
preferred sensor is disclosed in WO 99/27357 entitled "Materials,
Method and Apparatus for Detection and Monitoring Chemical
Species," published Jun. 3, 1999, and incorporated herein by
reference.
[0063] In one embodiment, the sensor arrays are formed from
composites of
poly(3,4-ethylenedioxy)thiophene-poly(styrenesulfonate) as a
conductive component with an insulating polymer (see, Solzing et
al., Anal. Chem., 72, 3181-3190 (2000) incorporated herein by
reference). The insulating polymers can be for example,
poly(vinylacetate), poly(epichlorohydrin), poly(ethylene oxide),
etc.
[0064] In other instances, the sensors are disclosed in WO
00/00808, published on Jan. 6, 2000, to Lewis et al. and
incorporated herein by reference. Chemical sensors are disclosed
comprising a plurality of alternating nonconductive regions
(comprising a nonconductive material) and conductive regions
(comprising a conductive material), wherein the conducting region
comprises a nanoparticle.
[0065] Preferably, the sensor arrays of the present invention
comprise at least one sensor selected from the following group of
sensors, inorganic metal oxide semiconductors such as tin-oxide
based sensors, intrinsically conducting polymers such as polymers
of pyrrole, thiophene and aniline, mass sensitive piezoelectric
sensors such as bulk acoustic wave and surface acoustic wave
sensors, polymer compositions on metal FET, and
nonconducting/conducting regions sensors.
[0066] As will be apparent to those of skill in the art, the
sensors making up the array of the present invention can be made up
of various sensor types as set forth above. For instance, the
sensor array can comprise a conducting and nonconducting regions
sensor, a SAW sensor, a metal oxide gas sensor, a conducting
polymer sensor, a Langmuir-Blodgett film sensors, polymer
composites on metal FET, and combinations thereof.
[0067] In certain embodiments, the temporal response of each sensor
(response as a function of time) is recorded and can be displayed.
Various responses include, but are not limited to, resistance,
impedance, capacitance, inductance, magnetic, work function,
optical, etc. The temporal response of each sensor can be
normalized to a maximum percent increase and percent decrease that
produces a response pattern associated with the exposure of the
analyte. By iterative profiling of known analytes, a
structure-function database correlating analytes and response
profiles is generated. Unknown analytes can then be characterized
or identified using response pattern comparison and recognition
algorithms. Accordingly, analyte detection systems comprising
sensor arrays, a measuring device for detecting responses across
each sensor, a computer, a display, a data structure of sensor
array response profiles, and a comparison algorithm(s) or
comparison tables are provided. In another embodiment, the
electrical measuring device or detector 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).
[0068] In certain embodiments, the present invention provides an
array of an array of sensors. As used herein, an array of an array
of sensor is termed a massively parallel independent array (MPIA).
This device is a matrix of sensors that can sense multiple bottles
or vessels simultaneously. The device is especially useful for
assaying or for diagnostic purposes for multiple vessels. For
example, in a combinatorial library of catalysts, a MPIA can be
used to simultaneously determine catalysts having unique signature
patterns of interest. Using the MPIA systems of the present
invention it is possible to monitor the efficiency of antibiotics,
catalysts, drugs, biomolecule binding efficiencies, nucleic acid
hybridizations, ligand-ligand interactions, biomolecule
interactions, potential drug candidates, etc. See, WO 99/53300,
published Apr. 13, 1999, to Lewis et al. incorporated herein by
reference. WO 99/53300 discloses chemical sensors for detecting the
activity of a molecule or analyte of interest. The chemical sensors
comprise an array or plurality of chemically sensitive resistors
that are capable of interacting with the molecule of interest,
wherein the interaction provides a resistance fingerprint. The
fingerprint can be associated with a library of similar molecules
of interest to determine the molecule's activity.
[0069] In one embodiment, the MPIAs of the present invention are
fabricated using combinatorial techniques. Devices for the
preparation of combinatorial libraries are commercially available
(see, e.g., 357 MPS, 390 MPS, Advanced Chem Tech, Louisville Ky.,
Symphony, Rainin, Woburn, Mass., 433A Applied Biosystems, Foster
City, Calif., 9050 Plus, Millipore, Bedford, Mass.). A number of
well known robotic systems have also been developed for solution
phase chemistries. These systems include automated workstations
like the automated synthesis apparatus developed by Takeda Chemical
Industries, LTD. (Osaka, Japan) and many robotic systems utilizing
robotic arms (Zymate II, Zymark Corporation, Hopkinton, Mass.;
Orca, Hewlett-Packard, Palo Alto, Calif.) which mimic the manual
synthetic operations performed by a person of skill in the art. The
nature and implementation of modifications to these devices (if
any) so that they can operate as discussed herein will be apparent
to skilled artisans. Moreover, combinatorial methods of making
sensors are disclosed in WO 99/00663, published Jan. 7, 1999, to
Lewis et al. and incorporated herein by reference. The methods
disclosed therein combine various ratios of at least first and
second organic materials to fabricate sensors.
[0070] The MPIA can utilize sensors as disclosed in WO 99/40423,
published Aug. 12, 1999, to Lewis et al. and incorporated herein by
reference. Arrays of sensors useful for analyzing chiral analytes
and producing a sample output are disclosed. The array comprises
compositionally different sensors, wherein a sensor comprises a
chiral region. The analyte generates a differential electrical
response across the sensor thereby being detected.
[0071] In certain instances, the sensor arrays comprise sensors
having aligned particle based sensor elements as disclosed in WO
00/33062, published Jun. 8, 2000, to Sunshine et al. and
incorporated herein by reference. The sensor arrays disclosed
therein comprise first and second sensors wherein the first sensor
comprises a region of aligned conductive material; electrically
connected to an electrical measuring apparatus. The aligned
conductive material improves the signal to noise of vapor sensors
allowing lower detection limits. Such lower detection limits allow
for the identification of lower concentrations of hazardous
material and is advantageous in medical applications, such as the
detection of disease states.
[0072] In certain other embodiments, the sensor arrays are
chemically sensitive resistors wherein the resistors are composed
of a conductor (e.g. carbon black) and a conducting polymer, such
as polyaniline. The polyaniline composites can be used to detect
biogenic amine odorants such as putrescine, cadaverine and spermine
(see, Sotzing et al., Chem. Mater. 12, 593-595 (2000) incorporated
herein by reference.).
[0073] III. Preconcentrator
[0074] In certain aspects, the present invention optionally
comprises a preconcentrator. In this aspect, a volume of the gas to
be sampled is introduced into a sample chamber where it is
transported by means of convention, such as convection, into the
vicinity of the sorbent material. Suitable transporting means
include, but are not limited to, a fan, an air pump, or it can be
means for heating the cylindrical container to create a convective
air flow between the inlet and the outlet. The sorbent material is
chosen from known materials designed for the purpose of sorbing
gases, vapors, and the like. In certain embodiments, the sorbent
material includes, but is not limited to, a nanoporous material, a
microporous material, a chemically reactive material, a nonporous
material and combinations thereof. Such absorbents include, for
example, activated. carbon, silica gel, activated alumina,
molecular sieve carbon, molecular sieve zeolites, silicalite,
AlPO.sub.4, a polymer, a co-polymer, polymer blends, alumina and
mixtures thereof. In certain embodiments, the absorbent has a pore
size from about 1 nm to about 100 nm and, preferably, from about 1
nm to about 50 nm.
[0075] Suitable commercially available adsorbent materials are
disclosed in U.S. Pat. No. 6,085,576 and 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. Those skilled in the art will know of other
suitable absorbent materials.
[0076] After sometime period that is chosen to be adequate for
sorbing the desired analytes from the vapor phase onto the
material, the circulation is stopped and then the material is
desorbed from the sorbent phase and released into the sensor
chamber. The desorbing of the concentrated analyte from the sorbent
can be accomplished by thermal means, mechanical means or a
combination thereof. Desorption methods include, but are not
limited to, heating, purging, stripping, pressuring or a
combination thereof.
[0077] In certain embodiments, the sample concentrator is wrapped
with a wire through which current can be applied to heat and thus,
desorb the concentrated analyte. The analyte is thereafter
transferred to the sensor array.
[0078] The process of sorbing the material onto the sorbent phase
not only can be used to concentrate the material, but also can be
advantageously used to remove water vapor. The water vapor is
preferably removed prior to concentrating the analyte; however, in
various embodiments, the vapor can be removed concomitantly or
after the analyte is concentrated. In a preferred embodiment, the
water vapor is removed prior to presenting the desired analyte gas
mixture to the sensor array. Thus, in certain embodiments, the
fluid concentrator contains additional absorbent material to not
only concentrate the analyte, but to remove unwanted materials such
gas contaminates and moisture.
[0079] IV. Algorithms
[0080] The device and methods of the present invention optionally
comprise pattern recognition algorithms. Many of the algorithms are
neural network based algorithms. A neural network has an input
layer, processing layers and an output layer. The information in a
neural network is distributed throughout the processing layers. The
processing layers are made up of nodes that simulate the neurons by
its interconnection to their nodes.
[0081] In operation, when a ANN is combined with a sensor array,
the sensor data is propagated through the networks. In this way, a
series of vector matrix multiplications are performed and unknown
analytes can be readily identified and determined. The neural
network is trained by correcting the false or undesired outputs
from a given input. Similar to statistical analysis revealing
underlying patterns in a collection of data, neural networks locate
consistent patterns in a collection of data, based on predetermined
criteria.
[0082] Suitable pattern recognition algorithms include, but are not
limited to, principal component analysis (PCA), Fisher linear
discriminant analysis (FLDA), soft independent modeling of class
analogy (SIMCA), K-nearest neighbors (KNN), neural networks,
genetic algorithms, fuzzy logic, and other pattern recognition
algorithms. In a preferred embodiment, the Fisher linear
discriminant analysis (FLDA) and canonical discriminant analysis
(CDA) and combinations thereof are used to assess patterns in
responses from the electronic noses of the present invention.
Operating principles of various algorithms suitable for use in the
present invention have been disclosed (see, Shaffer et al.,
Analytica Chimica Acta, 384, 305-317 (1999)). The Fisher linear
discriminant analysis as it pertains to artificial olfaction is
disclosed in WO 99/61902, published Dec. 2, 1999, to Lewis et al.,
and incorporated herein by reference.
[0083] V. Networked Systems
[0084] In certain instances, the devices, methods and apparatus of
the present invention can be used in a networked environment. For
instance, the networked systems of the present invention allow the
methods to be carried out in one location such as with a handheld
device and subsequently transmit digital signals over a computer
network, such as the Internet, for analysis at a remote location.
Suitable methods and systems for detecting and transmitting sensory
data over a computer networked are disclosed in WO 00/52444,
published Sep. 8, 2000, to Sunshine et al. and incorporated herein
by reference.
[0085] As disclosed therein, communication between the on-board
processor of an artificial olfaction device and the host computer
is available to configure the device and to download data from or
to the outside world, in real time or at a later time via a number
of communication interfaces including, but not limited to, an
RS-232 interface, a parallel port, an universal serial bus (USB),
an infrared data link, an optical interface and an RF interface.
Serial communications to the outside world are provided by the
on-board low power RS-232 serial driver. Communication to the
outside world includes, but is not limited to, a network, such as a
computer network e.g. the Internet accessible via Ethernet, a
wireless Ethernet, a token ring, a modem, etc. A transfer rate of
9600 bits/second can transmit approximately 400 data points/second,
and higher transfer rates can be used.
[0086] The computer network can be one of a variety of networks
including a worldwide computer network, an Internet, the Internet,
a WAN, a wireless network, a LAN or an intranet. It should be
understood that conventional access to the computer network is
conducted through a gateway. A gateway is a machine, for example, a
computer that has a communication address recognizable by the
computer network.
VI. EXAMPLES
[0087] The following examples are offered to illustrate, but not to
limit the claimed invention.
Example 1
[0088] This Example illustrates an e-nose device having two sensor
arrays wherein sensor element 2 has a porous membrane associated
therewith.
[0089] In this Example, the detection and identification of
analytes will be accomplished by using an electronic nose having
two 32-sensor arrays. Sensor element 1 (having 32-sensors) is a
sensing array and sensor element 2 (having 32-sensors) is a
referencing array. Sensor element 2 has a porous membrane
associated therewith. The analyte's contact with the reference
sensor array will thus be slowed. The porous membrane limits
diffusion to the 2nd sensor. This process of limited diffusion of
the analyte allows sampling of the sensors at different points of
time and thus, referencing and calibration can be done
simultaneously.
[0090] A Keithley electrometer and scanner will be used to scan the
resistances of two 32-sensor arrays during the experiment. In
certain instances, the temperature of the substrates will not be
controlled and the measurements will be done at room temperature.
For each sample test, there will be 60 seconds of background
recording (purged with air), 120 seconds of exposure time, 120
seconds of recovery time (purged with air with RH level of about
3%), 180 seconds of recovery without recording the data (purged
with air), and 30 seconds of final recording time (purged with
air).
[0091] The response patterns from the two 32-sensor array will have
good reproducibility. The response (the normalized resistance
change, (R.sub.max-R.sub.0)/R.sub.0), where R.sub.max and R.sub.0
are the maximum and base (initial) resistance, respectively) of
each of the sensor arrays to each sample tested will be employed to
form a covariance matrix, which is used to do principal component
analysis. PCA of the analytes plus control will be clearly
discriminated by the sensor array. SIMCA is also used to evaluate
the data.
[0092] As shown in FIG. 8, the sensor response 81 at time t.sub.1
where the first sensor is just beginning to respond 82 will give a
.DELTA.R/R value and the second sensor array will give a second
response 83. The two individual .DELTA.R/R values (for the first
and second trace) can be used to calibrate the system. The sensor
arrays are identical and therefore, the two responses are
identical. The pasivation material on the second sensor only slows
diffusion and is not selective.
Example 2
[0093] This Example illustrates differential temperature
measurement of sensor arrays.
[0094] In this method an analyte is detected at two temperatures.
The first sampling is conducted at ambient temperature and the
second temperature is at 60.degree. C. In this experiment, the
drift of the sensor array can be reduced using differential thermal
measurements. Thus, by contacting the array of sensor with an
analyte at a first temperature to produce a first response and
subsequently contacting the array of sensors with the analyte at a
second temperature to produce a second response and thereafter,
subtracting the first response from the second response the drift
can be reduced. Thus, the need to take a background response has
been alleviated. Using this method, dramatic increases in sensor
sampling and duty cycle are achieved.
Example 3
[0095] This Example illustrates the use of a massively parallel
independent array (MPIA) to monitor a reaction such as the
conversion of one reactant to another using a combinatorial library
of catalysts. The method is a way of evaluating catalyst
activity.
[0096] A different catalyst is loaded into small wells of a
microtiter plate (e.g., 96-well or 384-well microtiter plates)
together with the target reactants. In certain aspects, the
catalysts are prepared using combinatorial techniques. Such
catalysts include for instance, palladium on carbon (having various
weight percents of palladium e.g., 1%, 2%, 3%, etc.), Raney nickel,
Raney copper, etc. The MPIA is mounted on the headspace of the
microtiter plate for real time monitoring of the conversion process
related to catalytic activity. In a preferred embodiment, above
each well in the microtiter plate, is a sensor array (i.e., at
least two sensors). Thus, in certain aspects, such as in a 96 well
format, there are at least 192 total sensors in the MPIA. In a 384
format, there are in certain aspects, at least 768 sensors in the
MPIA.
[0097] Specific examples of catalytic activity include, but are not
limited to, the hydrogenation of 1-hexyne to 1-hexene or to hexane
(i.e. the fully saturated hydrocarbon) using a variety of oxides as
the catalysts. The decrease in 1-hexyne concentration and the
increase in concentration of the saturated hydrocarbons can be
monitored using the sensor array(s) and analyzed with a computer in
real time. Complete conversion of the 1-hexyne can also be
determined.
[0098] Another specific example includes the dehydrogenation of
cyclohexane to benzene using a library of solid-state catalysts.
The decrease in cyclohexane concentration and the increase in
benzene concentration can be monitored using a sensor array(s) and
the conversion monitored real time.
[0099] Advantageously, independent response patterns for each
sensor array are simultaneously monitored and compared. Thus, using
the MPIA in a 96-well format of the present invention, sensor array
above well 1-96 is compared with sensor array 33-96 and so forth.
Thus, each sensor array within the MPIA (1-96, 2-96, 3-96, 4-96,
etc.) is simultaneously and independently monitored. In operation,
a matrix of response patterns is generated and compared using
pattern recognition algorithms. In certain aspects, the efficiency
of the reactions is monitored in real time. Preferably, the MPIA
system resides in a networked environment. Using the MPIA systems
of the present invention it is possible to monitor the efficiency
of antibiotics, catalysts, drugs, biomolecule binding efficiencies,
nucleic acid hybridizations, ligand-ligand interactions,
biomolecule interactions, drug candidates, etc.
[0100] It is understood that the examples and embodiments described
herein are for illustrative purposes only and that various
modifications or changes in light thereof will be suggested to
persons skilled in the art and are to be included within the spirit
and purview of this application and scope of the appended claims.
All publications, patents, and patent applications cited herein are
hereby incorporated by reference in their entirety for all
purposes.
* * * * *