U.S. patent application number 11/929145 was filed with the patent office on 2008-02-28 for automated inhalation toxicology exposure system and method.
This patent application is currently assigned to The Government of the United States, As Represented By The Secretary of the Army. Invention is credited to Justin M. Hartings, Chad J. Roy.
Application Number | 20080047554 11/929145 |
Document ID | / |
Family ID | 29710620 |
Filed Date | 2008-02-28 |
United States Patent
Application |
20080047554 |
Kind Code |
A1 |
Roy; Chad J. ; et
al. |
February 28, 2008 |
Automated Inhalation Toxicology Exposure System and Method
Abstract
In one embodiment, a method includes but is not limited to:
conditioning an inhalent environment; exposing a first organism to
the inhalent environment for a first-organism duration of time; and
exposing a second organism to the inhalent environment for a
second-organism duration of time. In addition to the foregoing,
other method embodiments are described in the claims, drawings, and
text forming a part of the present application. In one or more
various embodiments, related systems include but are not limited to
circuitry and/or programming for effecting the foregoing-referenced
method embodiments; the circuitry and/or programming can be
virtually any combination of hardware, software, and/or firmware
configured to effect the foregoing-referenced method embodiments
depending upon the design choices of the system designer. In one
embodiment, a system includes but is not limited to: an inhalent
manifold; a first independently-controllable exposure unit coupled
to said inhalent manifold; a second independently-controllable
exposure unit coupled to said inhalent manifold; and an exposure
control system operably coupled to either or both said first
independently-controllable exposure unit and said second
independently-controllable exposure unit.
Inventors: |
Roy; Chad J.; (New Orleans,
LA) ; Hartings; Justin M.; (Clarksburg, MD) |
Correspondence
Address: |
OFFICE OF THE STAFF JUDGE ADVOCATE;U.S. ARMY MEDICAL RESEARCH AND MATERIEL
COMMAND
ATTN: MCMR-JA (MS. ELIZABETH ARWINE)
504 SCOTT STREET
FORT DETRICK
MD
21702-5012
US
|
Assignee: |
The Government of the United
States, As Represented By The Secretary of the Army
Fort Detrick
MD
21702
|
Family ID: |
29710620 |
Appl. No.: |
11/929145 |
Filed: |
October 30, 2007 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
10166228 |
May 29, 2002 |
|
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|
11929145 |
Oct 30, 2007 |
|
|
|
09919741 |
Jul 31, 2001 |
6904912 |
|
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10166228 |
May 29, 2002 |
|
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60267233 |
Jan 31, 2001 |
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Current U.S.
Class: |
128/203.15 ;
119/420 |
Current CPC
Class: |
A01K 1/031 20130101;
A61B 5/4845 20130101; A61D 7/04 20130101; A61B 2503/42 20130101;
A61B 5/0806 20130101; A61B 2503/40 20130101; A61B 5/08
20130101 |
Class at
Publication: |
128/203.15 ;
119/420 |
International
Class: |
A61M 16/10 20060101
A61M016/10; A61D 7/00 20060101 A61D007/00 |
Goverment Interests
I. STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR
DEVELOPMENT
[0002] This invention was made with government support. The
government has certain rights in this invention.
Claims
1. A method comprising: automatically conditioning an inhalent
environment to achieve a predetermined environmental condition;
distributing to a first organism the conditioned inhalent
environment for a first-organism duration of time; and distributing
to a second organism the conditioned inhalent environment for a
second-organism duration of time; and wherein the first organism
and the second organism are exposed to the same conditioned
inhalant environment after the inhalent environment has been
completely conditioned.
2. The method of claim 1, wherein said automatically conditioning
an inhalent environment comprises: introducing an inhalent into an
inhalent manifold.
3. The method of claim 2, wherein said introducing an inhalent into
an inhalent manifold comprises: introducing the inhalent into an
inhalent intake plenum operably coupled with an inner manifold.
4. The method of claim 1, wherein said automatically conditioning
an inhalent environment comprises: monitoring at least one
environmental condition selected from an environmental-condition
group including temperature, relative humidity, pressure, and
inhalent concentration.
5. The method of claim 1, wherein said automatically conditioning
an inhalent environment comprises: adjusting at least one
environmental condition selected from an environmental-condition
group including temperature, relative humidity, pressure, and
inhalent concentration.
6. The method of claim 1, wherein said distributing to a second
organism comprises: coupling the inhalent environment to a second
apertured connector containing at least a part of the second
organism for the second-organism duration of time.
7. The method of claim 1, further comprising: performing an
inhalent or exposure study, wherein said performing the inhalent or
exposure study comprises said automatically conditioning, said
distributing to a first organism, and said distributing to a second
organism.
8. The method according to claim 1, further comprising distributing
clean air to at least one of the first organism and the second
organism during conditioning of the inhalent environment to a
predetermined environmental condition.
9. A system comprising: means for automatically conditioning an
inhalent environment to achieve a predetermined environmental
condition; means for automatically distributing to a first organism
the conditioned inhalent environment for a first-organism duration
of time; and means for automatically distributing to a second
organism the conditioned inhalent environment for a second-organism
duration of time; wherein both distributing means provide exposure
to the same conditioned inhalent environment after the
predetermined environmental condition is achieved.
10. The system of claim 9, wherein said means for automatically
conditioning an inhalent environment comprises: means for
introducing an inhalent into an inhalent manifold.
11. The system of claim 10, wherein said means for introducing an
inhalent into an inhalent manifold comprises: means for introducing
the inhalent into an inhalent intake plenum operably coupled with
an inner manifold.
12. The system of claim 9, wherein said means for automatically
conditioning an inhalent environment comprises: means for
monitoring at least one environmental condition selected from an
environmental-condition group including temperature, relative
humidity, pressure, and inhalent concentration.
13. The system of claim 9, wherein said means for automatically
conditioning an inhalent environment comprises: means for adjusting
at least one environmental condition selected from an
environmental-condition group including temperature, relative
humidity, pressure, and inhalent concentration.
14. The system of claim 9, wherein said means for automatically
distributing to a second organism comprises: means for coupling the
inhalent environment to a second apertured connector containing at
least a part of the second organism for the second-organism
duration of time.
15. The system of claim 9, further comprising: means for performing
an inhalent or exposure study, wherein said means for performing
the inhalent or exposure study comprises said means for
automatically conditioning, said means for distributing to a first
organism, and said means for distributing to a second organism.
16. The system according to claim 9, further comprising means for
distributing clean air to at least one of the first organism and
the second organism while the inhalent environment is being
conditioned to a predetermined environmental condition.
17. A method for performing an inhalation study using at least two
organisms, the method comprising: automatically conditioning an
inhalent environment to achieve a predetermined environmental
condition prior to distributing the inhalent environment to the
organisms; distributing the conditioned inhalent environment to a
first organism for a first-organism duration of time; distributing
the conditioned inhalent environment to a second organism for a
second-organism duration of time; and prior to distributing the
conditioned inhalent environment to the first organism and the
second organism, distributing clean air to the first organism and
the second organism; and wherein the first organism and the second
organism are exposed to the same conditioned inhalant environment
after the inhalent environment has been completely conditioned.
18. The method according to claim 17, wherein the inhalent
environment includes at least one material under testing.
Description
II. CROSS-REFERENCE TO RELATED APPLICATION
[0001] The present patent application is a continuation application
of U.S. patent application No. 10/166,228 filed May 29, 2002, which
is a continuation-in-part of U.S. patent application Ser. No.
09/919,741, now U.S. Pat. No. 6,904,912 B2, entitled Automated
Inhalation Toxicology Exposure System, filed Jul. 31, 2001, and
naming Chad J. Roy and Justin M. Hartings as inventors, which
claims the benefit of U.S. Provisional Patent Application No.
60/267,233, entitled Automated Inhalation Toxicology Exposure
System, filed Jan. 21, 2001, and naming Chad J. Roy and Justin M.
Hartings as inventors. These patent applications are hereby
incorporated by reference.
III. FIELD OF THE INVENTION
[0003] The present application relates, in general, to multi-animal
inhalation exposure systems.
IV. BACKGROUND OF THE INVENTION
[0004] Multi-animal inhalation exposure studies are generally
performed using multi-animal inhalant systems. In multi-animal
inhalation exposure studies, two or more animals are usually
exposed to an organic or inorganic inhalant within the confined
space of an inhalant chamber forming part of an inhalant
system.
[0005] In the related art, a multi-animal inhalant system is
typically one that provides mechanisms for exposing two or more
animals to an inhalant. The inventors named herein ("inventors")
have noticed several deficiencies and/or unmet needs associated
with related-art multi-animal inhalant systems, a few of which will
now be set forth (other related-art deficiencies and/or unmet needs
will become apparent in the detailed description below).
[0006] The inventors have discovered that it would be advantageous
for a multi-animal inhalent system to be able to condition an
inhalent environment prior to exposing animals to the inhalent
environment. The inventors have discovered that related-art
multi-animal inhalent systems do not tend to provide for the
conditioning of an inhalent environment prior to exposing the
animals to the inhalent environment. The inventors have thus
recognized that a need exists in the art for a multi-animal
inhalent system that provides the ability to condition an inhalent
environment prior to exposing the animals to the inhalent
environment.
[0007] The inventors have discovered that it would be advantageous
for a multi-animal inhalent system to be able to provide for
differing exposure durations during which animals are exposed to
the same inhalent environment. The inventors have discovered that
related-art multi-animal inhalent systems do not tend to provide
for differing exposure durations during which animals are exposed
to the same inhalent environment. The inventors have thus
recognized that a need exists in the art for a multi-animal
inhalent system that provides for differing exposure durations
during which animals are exposed to the same inhalent
environment.
[0008] The inventors have discovered that it would be advantageous
for a multi-animal inhalent system to be able to provide control
such that the exposure duration for each animal can be determined
based on respiratory volume measurements. The inventors have
discovered that related-art multi-animal inhalent systems do not
tend to provide control such that the exposure duration for each
animal can be determined based on respiratory volume measurements.
The inventors have thus recognized that a need exists in the art
for a multi-animal inhalent system that provides control such that
the exposure duration for each animal can be determined based on
respiratory volume measurements.
[0009] The inventors have discovered that it would be advantageous
for a multi-animal inhalent system to be able to automatically
control inhalent dose delivery and recording functions on an
identified-animal basis. The inventors have discovered that
related-art multi-animal inhalent systems do not automatically
control inhalent dose delivery and recording functions on an
identified-animal basis. The inventors have thus recognized that a
need exists in the art for a multi-animal inhalent system that
automatically controls inhalent dose delivery and recording
functions on an identified-animal basis.
[0010] The foregoing-described inventor discoveries constitute at
least a part of the inventive content herein.
V. BRIEF SUMMARY OF THE INVENTION
[0011] In one embodiment, a method includes but is not limited to:
conditioning an inhalent environment; exposing a first organism to
the inhalent environment for a first-organism duration of time; and
exposing a second organism to the inhalent environment for a
second-organism duration of time. In another method embodiment,
said conditioning an inhalent environment is characterized by:
introducing an inhalent into an inhalent manifold. In another
method embodiment, said introducing an inhalent into an inhalent
manifold is characterized by: introducing the inhalent into an
inhalent intake plenum operably coupled with an inner manifold. In
another method embodiment, said conditioning an inhalent
environment is characterized by: monitoring at least one
environmental condition selected from an environmental-condition
group including temperature, relative humidity, pressure, and
inhalent concentration. In another method embodiment, said
conditioning an inhalent environment is characterized by: adjusting
at least one environmental condition selected from an
environmental-condition group including temperature, relative
humidity, pressure, and inhalent concentration. In another method
embodiment, said exposing a first organism to the inhalent
environment for a first-organism duration of time is characterized
by: coupling the inhalent environment to a first apertured
connector, containing at least a part of the first organism, for
the first-organism duration of time. In another method embodiment,
said coupling the inhalent environment to a first apertured
connector, containing at least a part of the first organism, for
the first-organism duration of time is characterized by: starting
the first-organism duration of time upon an initial coupling of the
inhalent environment to the first apertured connector containing
the at least a part of the first organism; and terminating the
first-organism duration of time when a calculated first-organism
delivered dosage meets or exceeds a predefined first-organism
target dosage. In another method embodiment, said terminating the
first-organism duration of time when a calculated first-organism
delivered dosage meets or exceeds a predefined first-organism
target dosage is characterized by: detecting the first organism via
a first-organism biochip device implanted in the first organism;
and recalling the predefined first-organism target dosage in
response to the first-organism biochip device. In another method
embodiment, said terminating the first-organism duration of time
when a calculated first-organism delivered dosage meets or exceeds
a predefined first-organism target dosage is characterized by:
measuring a volume respirated by the first organism; calculating
the first-organism delivered dosage in response to the volume. In
another method embodiment, said measuring a volume respirated by
the first organism is characterized by: measuring a volume of an
animal restraint cartridge associated with a first-organism biochip
device. In another method embodiment, said measuring a volume of an
animal restraint cartridge associated with a first-organism biochip
device is characterized by: measuring a flow between an interior of
the animal restraint cartridge and an exterior of the animal
restraint cartridge. In another method embodiment, said coupling
the inhalent environment to a first apertured connector, containing
at least a part of the first organism, for the first-organism
duration of time is characterized by: opening a valve between the
inhalent environment and the first apertured connector at a
first-organism beginning time; and closing the valve between the
inhalent environment and the first apertured connector at a
first-organism ending time. In another method embodiment, said
coupling the inhalent environment to a first apertured connector,
containing at least a part of the first organism, for the
first-organism duration of time is characterized by: closing a
valve between a clean-air environment and the first apertured
connector at a first-organism beginning time; and opening a valve
between the clean-air environment and the first apertured connector
at a first-organism ending time. In another method embodiment, said
exposing a second organism to the inhalent environment for a
second-organism duration of time is characterized by: coupling the
inhalent environment to a second apertured connector containing at
least a part of the second organism for the second-organism
duration of time. In another method embodiment, said coupling the
inhalent environment to a second apertured connector containing at
least a part of the second organism for the second-organism
duration of time is characterized by: starting the second-organism
duration of time upon an initial coupling of the inhalent
environment to the second apertured connector containing the at
least a part of the second organism; and terminating the
second-organism duration of time when a calculated second-organism
delivered dosage meets or exceeds a predefined second-organism
target dosage. In another method embodiment, said terminating the
second-organism duration of time when a calculated second-organism
delivered dosage meets or exceeds a predefined second-organism
target dosage is characterized by: detecting the second organism
via a second-organism biochip device implanted in the second
organism; and recalling the predefined second-organism target
dosage in response to the second-organism biochip device. In
another method embodiment, said terminating the second-organism
duration of time when a calculated second-organism delivered dosage
meets or exceeds a predefined second-organism target dosage is
characterized by: measuring a volume respirated by the second
organism; and calculating the delivered dosage in response to the
volume. In another method embodiment, said measuring a volume
respirated by the second organism is characterized by: measuring a
volume of an animal restraint cartridge associated with a
second-organism biochip device. In another method embodiment, said
measuring a volume of an animal restraint cartridge associated with
a second-organism biochip device is characterized by: measuring a
flow between an interior of the animal restraint cartridge and an
exterior of the animal restraint cartridge. In another method
embodiment, said coupling the inhalent environment to a second
apertured connector containing at least a part of the second
organism for the second-organism duration of time is characterized
by: opening a valve between the inhalent environment and the second
apertured connector at a second-organism beginning time; and
closing the valve between the inhalent environment and the second
apertured connector at a second-organism ending time. In another
method embodiment, said coupling the inhalent environment to a
second apertured connector containing at least a part of the second
organism for the second-organism duration of time is characterized
by: closing a valve between a clean-air environment and the second
apertured connector at a second-organism beginning time; and
opening the valve between the clean-air environment and the second
apertured connector at a second-organism ending time. In another
method embodiment, the method is further characterized by
performing an inhalent or exposure study, wherein said performing
the inhalent or exposure study is characterized by said
conditioning, said exposing a first organism, and said exposing a
second organism. In addition to the foregoing, other method
embodiments are described in the claims, drawings, and text forming
a part of the present application.
[0012] In one or more various embodiments, related systems include
but are not limited to circuitry and/or programming for effecting
the foregoing-referenced method embodiments; the circuitry and/or
programming can be virtually any combination of hardware, software,
and/or firmware configured to effect the foregoing-referenced
method embodiments depending upon the design choices of the system
designer.
[0013] In one embodiment, a method includes but is not limited to:
conditioning an inhalent environment; exposing a first organism to
the inhalent environment until a calculated first-organism
delivered dosage meets or exceeds a predefined first-organism
target dosage; and exposing a second organism to the inhalent
environment until a calculated second-organism delivered dosage
meets or exceeds a predefined second-organism target dosage. In
another method embodiment, said conditioning an inhalent
environment is characterized by: introducing an inhalent into an
inhalent manifold. In another method embodiment, said introducing
an inhalent into an inhalent manifold is characterized by:
introducing the inhalent into an inhalent intake plenum operably
coupled with an inner manifold. In another method embodiment, said
conditioning an inhalent environment is characterized by:
monitoring at least one environmental condition selected from an
environmental-condition group including temperature, relative
humidity, pressure, and inhalent concentration. In another method
embodiment, said conditioning an inhalent environment is
characterized by: adjusting at least one environmental condition
selected from an environmental-condition group including
temperature, relative humidity, pressure, and inhalent
concentration. In another method embodiment, said exposing a first
organism to the inhalent environment until a calculated
first-organism delivered dosage meets or exceeds a predefined
first-organism target dosage is characterized by: detecting the
first organism via a first-organism biochip device implanted in the
first organism; and recalling the predefined first-organism target
dosage in response to the first-organism biochip device. In another
method embodiment, said exposing a first organism to the inhalent
environment until a calculated first-organism delivered dosage
meets or exceeds a predefined first-organism target dosage is
characterized by: measuring a volume respirated by the first
organism; calculating the first-organism delivered dosage in
response to the volume. In another method embodiment, said
measuring a volume respirated by the first organism is
characterized by: measuring a volume of an animal restraint
cartridge associated with a first-organism biochip device. In
another method embodiment, said measuring a volume of an animal
restraint cartridge associated with a first-organism biochip device
is characterized by: measuring a flow between an interior of the
animal restraint cartridge and an exterior of the animal restraint
cartridge. In another method embodiment, said exposing a second
organism to the inhalent environment until a calculated
second-organism delivered dosage meets or exceeds a predefined
second-organism target dosage is characterized by: detecting the
second organism via a second-organism biochip device implanted in
the second organism; and recalling the predefined second-organism
target dosage in response to the second-organism biochip device. In
another method embodiment, said exposing a second organism to the
inhalent environment until a calculated second-organism delivered
dosage meets or exceeds a predefined second-organism target dosage
is characterized by: measuring a volume respirated by the second
organism; and calculating the delivered dosage in response to the
volume. In another method embodiment, said measuring a volume
respirated by the second organism is characterized by: measuring a
volume of an animal restraint cartridge associated with a
second-organism biochip device. In another method embodiment, said
measuring a volume of an animal restraint cartridge associated with
a second-organism biochip device is characterized by: measuring a
flow between an interior of the animal restraint cartridge and an
exterior of the animal restraint cartridge. In another method
embodiment, said exposing a first organism to the inhalent
environment until a calculated first-organism delivered dosage
meets or exceeds a predefined first-organism target dosage is
characterized by: coupling the inhalent environment to a first
apertured connector containing at least a part of the first
organism. In another method embodiment, said coupling the inhalent
environment to a first apertured connector containing at least a
part of the first organism is characterized by: starting a
first-organism duration of time upon an initial coupling of the
inhalent environment to the first apertured connector containing
the at least a part of the first organism; and terminating the
first-organism duration of time when the calculated first-organism
delivered dosage meets or exceeds the predefined first-organism
target dosage. In another method embodiment, said coupling the
inhalent environment to a first apertured connector containing at
least a part of the first organism is characterized by: opening a
valve between the inhalent environment and the first apertured
connector at a first-organism beginning time; and closing the valve
between the inhalent environment and the first apertured connector
at a first-organism ending time. In another method embodiment, said
coupling the inhalent environment to a first apertured connector
containing at least a part of the first organism is characterized
by: closing a valve between a clean-air environment and the first
apertured connector at a first-organism beginning time; and opening
the valve between the clean-air environment and the first apertured
connector at a first-organism ending time. In another method
embodiment, said exposing a second organism to the inhalent
environment until a calculated second-organism delivered dosage
meets or exceeds a predefined second-organism target dosage is
characterized by: coupling the inhalent environment to a second
apertured connector containing at least a part of the second
organism. In another method embodiment, said coupling the inhalent
environment to a second apertured connector containing at least a
part of the second organism is characterized by: starting a
second-organism duration of time upon an initial coupling of the
inhalent environment to the second apertured connector containing
the at least a part of the second organism; and terminating the
second-organism duration of time when the calculated
second-organism delivered dosage meets or exceeds a predefined
second-organism target dosage. In another method embodiment, said
coupling the inhalent environment to a second apertured connector
containing at least a part of the second organism is characterized
by: opening a valve between the inhalent environment and the second
apertured connector at a second-organism beginning time; and
closing a valve between the inhalent environment and the second
apertured connector at a second-organism ending time. In another
method embodiment, said coupling the inhalent environment to a
second apertured connector containing at least a part of the second
organism is characterized by: closing a valve between a clean-air
environment and the second apertured connector at a second-organism
beginning time; and opening the valve between the clean-air
environment and the second apertured connector at a second-organism
ending time. In another method embodiment, the method is further
characterized by performing an inhalent or exposure study, wherein
said performing the inhalent or exposure study is characterized by
said conditioning, said exposing a first organism, and said
exposing a second organism. In addition to the foregoing, other
method embodiments are described in the claims, drawings, and text
forming a part of the present application.
[0014] In one or more various embodiments, related systems include
but are not limited to circuitry and/or programming for effecting
the foregoing-referenced method embodiments; the circuitry and/or
programming can be virtually any combination of hardware, software,
and/or firmware configured to effect the foregoing-referenced
method embodiments depending upon the design choices of the system
designer.
[0015] In one embodiment, a system includes but is not limited to:
an inhalent manifold; a first independently-controllable exposure
unit coupled to said inhalent manifold; a second
independently-controllable exposure unit coupled to said inhalent
manifold; and an exposure control system operably coupled to either
or both said first independently-controllable exposure unit and
said second independently-controllable exposure unit. In another
system embodiment, said inhalent manifold is characterized by: an
inhalent intake plenum operably coupled with an inner manifold. In
another system embodiment, said inhalent manifold is characterized
by: at least one environmental-condition sensor integral with said
inhalent manifold, said at least one environmental condition sensor
selected from an environmental-condition-sensor group including a
temperature sensor, a relative humidity sensor, a pressure sensor,
and an inhalent concentration sensor; and said exposure control
system operably coupled to said at least one
environmental-condition sensor. In another system embodiment, said
inhalent manifold is characterized by: at least one
environmental-condition controller integral with said inhalent
manifold, said at least one environmental-condition controller
selected from an environmental-condition-controller group including
a temperature controller, a relative humidity controller, a
pressure controller, and an inhalent concentration controller; and
said exposure control system operably coupled to said at least one
environmental-condition controller. In another system embodiment,
said first independently-controllable exposure unit coupled to said
inhalent manifold is characterized by: an
independently-controllable valve interposed between the inhalent
manifold and a first apertured connector; and said exposure control
system operably coupled to said independently-controllable valve
interposed between the inhalent manifold and a first apertured
connector. In another system embodiment, said first
independently-controllable exposure unit coupled to said inhalent
manifold is characterized by: an independently-controllable valve
interposed between the inhalent manifold and an exhaust manifold;
and said exposure control system operably coupled to said
independently-controllable valve interposed between the inhalent
manifold and the exhaust manifold. In another system embodiment,
said first independently-controllable exposure unit coupled to said
inhalent manifold is characterized by: an animal restraint
cartridge; a biochip device receiver integral with said animal
restraint cartridge; and said exposure control system operably
coupled to said a biochip device receiver. In another system
embodiment, said first independently-controllable exposure unit
coupled to said inhalent manifold is characterized by: an animal
restraint cartridge; a differential volume sensor operably coupled
to said animal restraint cartridge; and said exposure control
system operably coupled to said differential volume sensor. In
another system embodiment, said differential volume sensor operably
coupled to said animal restraint cartridge is characterized by: a
pneumotachograph operably coupled to said animal restraint
cartridge; and a differential pressure transducer operably coupled
to said pneumotachograph. In another system embodiment, said second
independently-controllable exposure unit coupled to said inhalent
manifold is characterized by: an independently-controllable valve
interposed between the inhalent manifold and a second apertured
connector; and said exposure control system operably coupled to
said independently-controllable valve interposed between the
inhalent manifold and the second apertured connector. In another
system embodiment, said second independently-controllable exposure
unit coupled to said inhalent manifold is characterized by: an
independently-controllable valve interposed between the inhalent
manifold and an exhaust manifold; and said exposure control system
operably coupled to said independently-controllable valve
interposed between the inhalent manifold and the exhaust manifold.
In another system embodiment, wherein said second
independently-controllable exposure unit coupled to said inhalent
manifold is characterized by: an animal restraint cartridge; a
biochip device receiver integral with said animal restraint
cartridge; and said exposure control system operably coupled to
said a biochip device receiver. In another system embodiment, said
second independently-controllable exposure unit coupled to said
inhalent manifold is characterized by: an animal restraint
cartridge; a differential volume sensor operably coupled to said
animal restraint cartridge; and said exposure control system
operably coupled to said differential volume sensor. In another
system embodiment, wherein said differential volume sensor operably
coupled to said animal restraint cartridge is characterized by: a
pneumotachograph operably coupled to said animal restraint
cartridge; and a differential pressure transducer operably coupled
to said pneumotachograph. In another system embodiment, wherein
said exposure control system is characterized by: circuitry for (a)
conditioning an inhalent environment in said inhalent manifold, (b)
controlling said first independently-controllable exposure unit
coupled to said inhalent manifold to expose at least a first
organism to the inhalent environment for at least a first-organism
duration of time, and (c) controlling said second
independently-controllable exposure unit coupled to said inhalent
manifold to expose at least a second organism to the inhalent
environment for at least a second-organism duration of time; and
said circuitry selected from an electrical-circuitry group
including electrical circuitry having at least one discrete
electrical circuit, electrical circuitry having at least one
integrated circuit, electrical circuitry having at least one
application specific integrated circuit, electrical circuitry
having a general purpose computing device configured by a computer
program, electrical circuitry having a memory device, and
electrical circuitry having a communications device. In another
system embodiment, said circuitry is characterized by: a data
processing system running a control program.
[0016] In one embodiment, a method includes but is not limited to:
detecting a first organism via a first-organism biochip device
implanted in the first organism; and controlling a first-organism
dosage in response to the first-organism biochip device. In another
method embodiment, said detecting a first organism via a
first-organism biochip device implanted in the first organism is
characterized by: detecting transmission from the first-organism
biochip device via a receiver paired with a predefined animal
restraint cartridge. In another method embodiment, said controlling
a first-organism dosage in response to the first-organism biochip
device is characterized by: recalling the predefined first-organism
target dosage in response to the first-organism biochip device; and
exposing the first organism to an inhalent environment until a
calculated first-organism delivered dosage meets or exceeds a
predefined first-organism target dosage. In another method
embodiment, said exposing a first organism to the inhalent
environment until a calculated first-organism delivered dosage
meets or exceeds a predefined first-organism target dosage is
characterized by: measuring a volume respirated by the first
organism; and calculating the first-organism delivered dosage in
response to the volume. In another method embodiment, the method is
further characterized by: detecting a second organism via a
second-organism biochip device implanted in the second organism;
and controlling a second-organism dosage in response to the
second-organism biochip device. In another method embodiment, said
detecting a second organism via a second-organism biochip device
implanted in the second organism is characterized by: detecting
transmission from the second-organism biochip device via a receiver
paired with a predefined animal restraint cartridge. In another
method embodiment, said controlling a second-organism dosage in
response to the second-organism biochip device is characterized by:
recalling the predefined second-organism target dosage in response
to the second-organism biochip device; and exposing the second
organism to an inhalent environment until a calculated
second-organism delivered dosage meets or exceeds a predefined
second-organism target dosage. In another method embodiment, said
exposing a second organism to the inhalent environment until a
calculated second-organism delivered dosage meets or exceeds a
predefined second-organism target dosage is characterized by:
measuring a volume respirated by the second organism; and
calculating the second-organism delivered dosage in response to the
volume. In addition to the foregoing, other method embodiments are
described in the claims, drawings, and text forming a part of the
present application.
[0017] In one or more various embodiments, related systems include
but are not limited to circuitry and/or programming for effecting
the foregoing-referenced method embodiments; the circuitry and/or
programming can be virtually any combination of hardware, software,
and/or firmware configured to effect the foregoing-referenced
method embodiments depending upon the design choices of the system
designer.
[0018] The foregoing is a summary and thus contains, by necessity,
simplifications, generalizations and omissions of detail;
consequently, those skilled in the art will appreciate that the
summary is illustrative only and is NOT intended to be in any way
limiting. Other aspects, inventive features, and advantages of the
devices and/or processes described herein, as defined solely by the
claims, will become apparent in the non-limiting detailed
description set forth herein.
VI. BRIEF DESCRIPTION OF THE SEVERAL VIEW OF THE DRAWINGS
[0019] FIG. 1 shows a high level pictographic representation of an
exposure system and associated hardware.
[0020] FIG. 2 depicts a pictographic representation of exposure
tower 100.
[0021] FIG. 3 illustrates a top view drawing of exposure module
104.
[0022] FIG. 4 shows a drawing of animal restraint cartridge 210 and
associated hardware. FIG. 4 also shows a biochip identification
device 412, implanted in animal 402 and preprogrammed with an
electronic identifier unique to animal 402.
[0023] The use of the same symbols in different drawings typically
indicates similar or identical items
VII. DETAILED DESCRIPTION OF THE INVENTION
a. Devices
[0024] A high level pictographic representation of an exposure
system and associated hardware is included as FIG. 1. Depicted is
exposure tower 100 composed of three distinct sections: input
module 102, exposure modules 104, and exhaust module 106. Shown
connected to the input module are inhalent air input hose 108 and
clean air input hose 110. Integral with inhalent air input hose 108
is inhalent dissemination device 112. Inhalent dissemination device
112 is meant to be indicative of a variety of different devices for
dispersing organic or inorganic substances in an aerosol, gas,
fume, dry powder, or other suitable form. Connected to exhaust
module 106 is output air hose 114. Shown coupled to exposure tower
100 is also wire bundle 116, meant to be indicative of a plurality
of wires connecting a variety of electronic devices housed in
exposure tower 100 to interface box 118. Operably coupled to
interface box 118 are also inhalent input air hose 108, clean air
input hose 110, and output air hose 114. Interface box 118 houses
the necessary power supplies, input airflow drivers, output airflow
drivers, data acquisition hardware, and other associated
electronics for the electronic devices in exposure tower 100.
Further illustrated is interface box 118 operably coupled to data
processing system 122. Residing in and running on data processing
system 122 is specially developed control program 124 where such
control program controls the various drivers, sensors, and other
electronic devices in interface box 118 and exposure tower 100.
[0025] With reference now to FIG. 2, depicted is a pictographic
representation of exposure tower 100. Shown are cutaway drawings of
input module 102, exposure module 104, and exhaust module 106.
Exposure module 104 is composed of three concentric manifolds all
composed of nonporous, autoclavable, non-reactive materials: inner
manifold 202, middle manifold 204, and outer manifold 206. A
plurality of annular shaped apertured connectors 208 are housed in
outer manifold 206. Each apertured connector is designed to support
and mate with animal restraint cartridge 210 inserted from outside
the outer manifold. A plurality of identical exposure modules 104
can be stacked between input module 102 and exhaust module 106 as
necessary to accommodate the number of animals to be included in
any particular study.
[0026] Input module 102 includes coupler fitting 212 which mates
with inhalent air input hose 108 (not shown in FIG. 2) and provides
the mechanism for introducing the inhalent into inhalent intake
plenum 214 and, hence, into inner manifold 202 of exposure module
104. Also provided with input module 102 is coupler fitting 216,
designed to be operably coupled with clean input air hose 110 (not
shown in FIG. 2) and providing the mechanism for introducing clean,
filtered air into clean air intake plenum 218 and, hence, into
middle manifold 204 of exposure module 104.
[0027] Further with respect to FIG. 2 is depicted a cutaway drawing
of exhaust module 106. Exhaust module 106 is provided with coupler
fitting 220 which mates with output air hose 114 (not shown in FIG.
2) and provides the mechanism for exhausting air from exhaust
module 106 and, hence, outer manifold 206 of exposure module
104.
[0028] Depicted in FIG. 3 is a top view drawing of exposure module
104. Shown in FIG. 3 is that housed in middle manifold 204 are
electronically controlled three-way valves 300a and 300b, each
associated with an apertured connector 208. Valve 300a is oriented
such that outlet 302a is plumbed to apertured connector 208, inlet
304a is plumbed to inner manifold 202, and inlet 306a is open to
middle manifold 204. Valve 300b is oriented such that outlet 302b
is plumbed to outer manifold 206, but not into apertured connector
208, inlet 304b is plumbed to inner manifold 202, and inlet 306b is
open to middle manifold 204. Valves 300a and 300b are coupled to
interface box 118 via wire bundle 116 and controlled by means of
control program 124 running on data processing system 122 (not
shown in FIG. 3).
[0029] This assembly of valves 300a and 300b allows each pair to be
electronically switched via control program 124 into either a
"bypass" condition or an "expose" condition. In the bypass
condition, valve 300a is set so that clean air from middle manifold
204 flows into inlet 306a, out of outlet 302a, through apertured
connector 208, and into outer manifold 206. In the bypass condition
valve 300b is set so that the inhalent atmosphere in inner manifold
202 flows into inlet 304b, out of outlet 302b, and directly into
outer manifold 206. In the expose condition valve 300a is set such
that the inhalent atmosphere in inner manifold 202 flows into inlet
304a, out of outlet 302a, through apertured connector 208, and into
outer manifold 206. In the expose condition valve 300b is set so
that clean air from middle manifold 204 flows into inlet 306b, out
of outlet 302b, and directly into outer manifold 206. Those having
ordinary skill in the art will appreciate that the herein described
dual-valve design allows the throughput of the inhalent to remain
substantially constant, in that when an animal's exposure to an
inhalent from the inhalent manifold (e.g., the inhalent intake
plenum 214 operably coupled with the inner manifold 202) is
terminated, the part of the inhalent throughput that was being
routed past the animal is instead routed to the exhaust, and in
that when an animal's exposure to an inhalent from the inhalent
manifold (e.g., the inhalent intake plenum 214 operably coupled
with the inner manifold 202) is began, the part of the inhalent
throughput that was being routed to the exhaust is instead routed
past the animal.
[0030] With reference now to FIG. 4, depicted is a drawing of
animal restraint cartridge 210 and associated hardware. Shown is
opening 400 through which the nose of animal 402 extends into the
chamber formed in apertured connector 208. Further demonstrated is
end cap 404 which is sealed after animal 402 is positioned in
restraint cartridge 210 with its nose extending through opening
400. Integral with end cap 404 is pneumotachograph 406 extending
into restraint cartridge 210. Pneumotachograph 406 is operably
coupled to pressure transducer 408 by tubes 410. Pressure
transducer 408 is coupled to interface box 118 via wire bundle 116
and monitored by control program 124 running on data processing
system 122 (not shown in FIG. 4). When animal 402 is positioned in
restraint cartridge 210 with its nose through opening 400 and end
cap 404 is sealed, an airtight chamber is formed. The
pneumotachograph/pressure transducer combination measures the flow
of air to and from restraint cartridge 210 in real-time as animal
402's thoracic cage expands and contracts with respiratory
function. These flow measurements are processed by control program
124 to calculate respiratory tidal volume, respiratory rate,
respiratory minute volume, and cumulative tidal volume in near-real
time for each animal simultaneously and independently.
[0031] An example calculation, using the foregoing-described
mechanisms, would be as follows. A rodent inside restraint
cartridge 210 inhales 120 .mu.l of air, thus expanding its thoracic
cage. This thoracic cage expansion results in 120 .mu.L of air
passing from restraint cartridge 210, through pneumotachograph 406
to the outside environment in the approximately 0.1 sec inhalation
time for the rodent. For a pneumotachograph with an approximately 2
mm.sup.2 cross-section, this 1.2 mL/sec flow generates a pressure
differential of approximately 0.03 WC'' (water column inches). In
response to this differential, pressure transducer 408 generates an
electrical current of 1.1 mA measured by the computer hardware in
interface box 118 and processed by control program 124 running on
data processing system 122.
[0032] Upon receiving the 1.1 mA signal, control program 124 calls
a calibration look up table, stored on data processing system 122
and scales the current to the 120 .mu.L tidal volume (TV) that the
rodent originally inhaled. In one implementation, the calibration
table is created and stored during initial system development and
is generated via use of an appropriate rodent ventilator.
[0033] In one implementation, in order to generate the calibration
table a ventilator is connected to the nose port of restraint
cartridge 210, and a rodent-sized phantom is placed inside. The
ventilator is then run at various respiratory rates and tidal
volumes characteristic of the rodent pulmonary function. For each
respiratory rate and tidal volume setting, the current generated by
differential pressure transducer 408 is measured. The scaling
factor needed to convert the current reading to the original tidal
volume is then assigned to that particular set of respiratory
parameters. Applying this process to the full range of relevant
tidal volumes and respiratory rates generates a matrix of
calibration scaling values. These values are stored in a
spreadsheet file. Based on the current generated and the
respiratory rate for each successive breath, control program 124
references the spreadsheet file to scale the current reading from
pressure transducer 408 appropriately. Alternatively, a
mathematical fit can be applied to the calibration data matrix
described, thus generating a formula that applies a scaling factor
appropriate to a particular tidal volume and respiratory rate
measured.
[0034] Successive tidal volume measurements are added by control
program 124 to generate a running cumulative tidal volume (CTV)
total. The time between successive breaths is also measured via a
timer feature inherent to control program 124, and used by control
program 124 to calculate respiratory rate (RR) and minute volume
(MV). Respiratory rate is calculated by dividing 60 by the time
between successive breaths in seconds. Minute volume is calculated
by multiplying tidal volume by the respiratory rate. The following
is an example of how successive tidal volume measurements, made
using the methodology described, are used to calculate these
parameters: TABLE-US-00001 Time (sec) TV (mL) CTV (ml) RR (b/min)
MV (mL/min) 0.00 0.120 0.120 -- -- 0.25 0.180 0.300 240 43.2 0.48
0.160 0.460 260 41.6 0.68 0.172 0.612 300 51.6 0.90 0.148 0.760 272
40.2 1.15 0.140 0.900 240 33.6
Note that RR and TV cannot be calculated for the first breath.
Since these parameters depend on the rate of breathing, at least
two measurements are required for their calculation.
[0035] Further with respect to FIG. 4 is biochip identification
device 412, shown implanted in animal 402 and preprogrammed with an
electronic identifier unique to animal 402. Also shown integrated
into restraint cartridge 210 is electronic receiver device 414.
Receiver device 414 reads the electronic signal from biochip device
412 and identifies animal 402. Receiver device 414 is coupled to
interface box 118 via wire bundle 116 (not shown in FIG. 4),
providing the means for control program 124 running on data
processing system 122 to identify animal 402 in restraint cartridge
210.
b. Description of System Operation:
[0036] When utilizing the system the operator first loads animals
implanted with biochip identification device 412 into restraint
cartridges 210. When restraint cartridges 210 are inserted into
apertured connectors 208, receiver devices 414 read the signals
emitted from biochip devices 412 and automatically identifies the
animal in each individual restraint. These identifications are
transmitted through wire bundle 116 into interface box 118 and to
data processing system 122. Control program 124 recalls a dose
schedule from a data base stored in data processing system 122 or
entered by the user and, based on the identity of the animal in
each restraint, identifies the inhalent dose that each animal is to
receive.
[0037] After all animals are loaded into apertured connectors 208
and identified, the user initiates the exposure sequence via the
graphical user interface of data processing system 122. Control
program 124 switches all valve pairs 300a and 300b to the bypass
condition, activates aerosol dissemination device 114, and
initiates the flows through inhalent air input tube 108, clean air
input tube 106, and output air tube 110.
[0038] Additionally, control program 124 initiates monitoring of
the environmental conditions (temperature, relative humidity,
pressure, inhalent concentration, etc.) in inner manifold 202 via a
plurality of sensors housed in interface box 118 and in inner
manifold 202. Control program 124 also electronically manages a
variety of devices (a humidification device, a heating/cooling
device, an inhalent dissemination device, flow controlling devices,
etc.) as necessary to achieve and maintain said environmental
conditions at levels defined by the user. Since all valve pairs
300a and 300b are in the bypass condition, all animals are supplied
with clean filtered air from middle manifold 204 and not exposed to
the inhalent while control program 124 achieves the user defined
environmental conditions in inner manifold 202.
[0039] Once all of the environmental conditions entered by the user
are achieved in inner manifold 202, control program 124 initiates
the animal exposure by electronically switching all valve pairs
300a and 300b to the expose condition. Additionally, control
program 124 initiates the comprehensive respiratory monitoring
algorithm for each animal utilizing the electronic signals
generated by pressure transducers 408. The algorithm simultaneously
monitors the cumulative tidal volume for every animal being exposed
in near real-time. Control program 124 uses this cumulative tidal
volume measurement in conjunction with the inhalent concentration
measurement acquired by environmental monitoring devices to
calculate the actual inhaled dose of the inhalent for each animal
in near real-time.
[0040] When an individual animal's inhaled dose as measured by the
respiratory monitoring algorithm of control program 124 equals that
called for by the dose schedule recalled via the animal
identification system, control program 124 switches valve pair 300a
and 300b corresponding to that animal from the expose to the bypass
condition. Meanwhile, valve pairs 300a and 300b corresponding to
other animals remain in the expose condition. Other animals
continue to be exposed until the respiratory monitoring algorithm
of control program 124 indicates that they have inhaled the dose
required by the dose schedule/identification algorithm. Control
program 124 switches each valve pair 300a and 300b to the bypass
condition when its corresponding animal has received the scheduled
dose. When the required doses are achieved for all animals and all
valve pairs 300a and 300b are in the bypass condition, control
program 124 deactivates aerosol dissemination device 114, and
terminates the flows through inhalent air input tube 108, clean air
input tube 106, and output air tube 110. Control program 124
notifies the user via an audible signal and a visible indication on
the graphical user interface of data processing system 122 that the
exposures for all animals are complete.
[0041] In addition to controlling all aspects of the exposure
described above, control program 124 writes, at a frequency defined
by the user, all environmental, flow, respiratory, and
identification data to a file for subsequent analysis.
Additionally, all operator keystrokes and actions initiated and
terminated by control program 124 are logged in a second file for
record keeping and quality control purposes.
[0042] Those having ordinary skill in the art will appreciate that
while there are many fields of application wherein the processes
and devices described herein will prove advantageous. One
particularly advantageous field of application is that of inhalant
and/or exposure studies. Various examples of how the processes and
devices described herein may be used in inhalant and/or exposure
studies are described in the following Addendum A.
[0043] Those having ordinary skill in the art will recognize that
the state of the art has progressed to the point where there is
little distinction left between hardware and software
implementations of aspects of systems; the use of hardware or
software is generally (but not always, in that in certain contexts
the choice between hardware and software can become significant) a
design choice representing cost vs. efficiency tradeoffs. Those
having ordinary skill in the art will appreciate that there are
various vehicles by which aspects of processes and/or systems
described herein can be effected (e.g., hardware, software, and/or
firmware), and that the preferred vehicle will vary with the
context in which the processes and/or systems are deployed. For
example, if an implementer determines that speed and accuracy are
paramount, the implementer may opt for a hardware and/or firmware
vehicle; alternatively, if flexibility is paramount, the
implementer may opt for a solely software implementation; or, yet
again alternatively, the implementer may opt for some combination
of hardware, software, and/or firmware. Hence, there are several
possible vehicles by which aspects of the processes described
herein may be effected, none of which is inherently superior to the
other in that any vehicle to be utilized is a choice dependent upon
the context in which the vehicle will be deployed and the specific
concerns (e.g., speed, flexibility, or predictability) of the
implementer, any of which may vary.
[0044] The foregoing detailed description has set forth various
embodiments of the devices and/or processes via the use of block
diagrams, flowcharts, and examples. Insofar as such block diagrams,
flowcharts, and examples contain one or more functions and/or
operations, it will be understood as notorious by those within the
art that each function and/or operation within such block diagrams,
flowcharts, or examples can be implemented, individually and/or
collectively, by a wide range of hardware, software, firmware, or
virtually any combination thereof. In one embodiment, the present
invention may be implemented via Application Specific Integrated
Circuits (ASICs). However, those skilled in the art will recognize
that the embodiments disclosed herein, in whole or in part, can be
equivalently implemented in standard Integrated Circuits, as one or
more computer programs running on one or more computers (e.g., as
one or more programs running on one or more computer systems), as
one or more programs running on one or more controllers (e.g.,
microcontrollers) as one or more programs running on one or more
processors (e.g., microprocessors), as firmware, or as virtually
any combination thereof, and that designing the circuitry and/or
writing the code for the software and or firmware would be well
within the skill of one of ordinary skill in the art in light of
this disclosure. In addition, those skilled in the art will
appreciate that the mechanisms of the present invention are capable
of being distributed as a program product in a variety of forms,
and that an illustrative embodiment of the present invention
applies equally regardless of the particular type of signal bearing
media used to actually carry out the distribution. Examples of
signal bearing media include, but are not limited to, the
following: recordable type media such as floppy disks, hard disk
drives, CD ROMs, digital tape, and computer memory; and
transmission type media such as digital and analogue communication
links using TDM or IP based communication links (e.g., packet
links).
[0045] In a general sense, those skilled in the art will recognize
that the various embodiments described herein which can be
implemented, individually and/or collectively, by a wide range of
hardware, software, firmware, or any combination thereof can be
viewed as being composed of various types of "electrical
circuitry." Consequently, as used herein "electrical circuitry"
includes, but is not limited to, electrical circuitry having at
least one discrete electrical circuit, electrical circuitry having
at least one integrated circuit, electrical circuitry having at
least one application specific integrated circuit, electrical
circuitry forming a general purpose computing device configured by
a computer program (e.g., a general purpose computer configured by
a computer program which at least partially carries out processes
and/or devices described herein, or a microprocessor configured by
a computer program which at least partially carries out processes
and/or devices described herein), electrical circuitry forming a
memory device (e.g., forms of random access memory), and electrical
circuitry forming a communications device (e.g., a modem,
communications switch, or optical-electrical equipment).
[0046] Those skilled in the art will recognize that it is common
within the art to describe devices and/or processes in the fashion
set forth herein, and thereafter use standard engineering practices
to integrate such described devices and/or processes into data
processing systems. That is, the devices and/or processes described
herein can be integrated into a data processing system via a
reasonable amount of experimentation.
[0047] The foregoing described embodiments depict different
components contained within, or connected with, different other
components. It is to be understood that such depicted architectures
are merely exemplary, and that in fact many other architectures can
be implemented which achieve the same functionality. In a
conceptual sense, any arrangement of components to achieve the same
functionality is effectively "associated" such that the desired
functionality is achieved. Hence, any two components herein
combined to achieve a particular functionality can be seen as
"associated with" each other such that the desired functionality is
achieved, irrespective of architectures or intermedial components.
Likewise, any two components so associated can also be viewed as
being "operably connected", or "operably coupled", to each other to
achieve the desired functionality.
[0048] While particular embodiments of the present invention have
been shown and described, it will be obvious to those skilled in
the art that, based upon the teachings herein, changes and
modifications may be made without departing from this invention and
its broader aspects and, therefore, the appended claims are to
encompass within their scope all such changes and modifications as
are within the true spirit and scope of this invention.
Furthermore, it is to be understood that the invention is solely
defined by the appended claims. It will be understood by those
within the art that, in general, terms used herein, and especially
in the appended claims (e.g., bodies of the appended claims) are
generally intended as "open" terms (e.g., the term "including"
should be interpreted as "including but not limited to," the term
"having" should be interpreted as "having at least," the term
"includes" should be interpreted as "includes but is not limited
to," etc.). It will be further understood by those within the art
that if a specific number of an introduced claim recitation is
intended, such an intent will be explicitly recited in the claim,
and in the absence of such recitation no such intent is present.
For example, as an aid to understanding, the following appended
claims may contain usage of the introductory phrases "at least one"
and "one or more" to introduce claim recitations. However, the use
of such phrases should not be construed to imply that the
introduction of a claim recitation by the indefinite articles "a"
or "an" limits any particular claim containing such introduced
claim recitation to inventions containing only one such recitation,
even when the same claim includes the introductory phrases "one or
more" or "at least one" and indefinite articles such as "a" or "an"
(e.g., "a" and/or "an" should typically be interpreted to mean "at
least one" or "one or more"); the same holds true for the use of
definite articles used to introduce claim recitations. In addition,
even if a specific number of an introduced claim recitation is
explicitly recited, those skilled in the art will recognize that
such recitation should typically be interpreted to mean at least
the recited number (e.g., the bare recitation of "two recitations,"
without other modifiers, typically means at least two recitations,
or two or more recitations).
[0049] From the foregoing it will be appreciated that, although
specific embodiments of the invention have been described herein
for purposes of illustration, various modifications may be made
without deviating from the spirit and scope of the invention.
Accordingly, the invention is not limited except as by the appended
claims.
Addendum A
Applications of Processes and Devices Described Herein
[0050] Those skilled in the art will recognize that the following
example applications are intended to be exemplary and non-limiting.
Those skilled in the art will recognize that many other
applications are possible based on the teachings herein. [0051] I.
Those skilled in the art will appreciate that, in the context of
preclinical animal studies involving various materials under
testing (MUT), which may include, but are not limited to, new
chemical entities (NCEs), biologically-derived products
(biologics), and miscellaneous MUTs such as environmental
contaminants, various implementations of the processes and devices
described herein can be utilized to significantly reduce the inputs
to such preclinical animal studies.
[0052] Those skilled in the art will appreciate that such inputs
may include but are not limited to time, cost, dose uncertainty,
and physical space requirements to accomplish said procedure(s)
associated with absorption, distribution, metabolism, and excretion
(ADME), toxicology, pharmacology and other miscellaneous studies
that require MUTs to be administered by inhalation. [0053] a.
Preclinical safety and efficacy studies for MUTs including NCEs and
biologics. In general, a series of animal studies must be performed
to satisfy regulatory requirements of various codified regulations
promulgated by national and international organizations (e.g.,
USFDA, EUCOM) whereas a MUT must be administered to selected animal
species in specified lengths of time, which may include acute (one
time administration), subchronic (repeated administration up to 90
days), and chronic administration (up to two years), usually in at
least two different species of animal, which may include rodents
(e.g., mice, rats, guinea pigs), dogs, rabbits, and nonhuman
primates to ensure safety and efficacy of the MUT as one of the
requisite experimental steps for the MUT to be administered in the
human population to inhibit the effects of or cure disease.
Preclinical studies (experimental studies with animals) are
performed prior to clinical studies, that is experimental studies
with selected human populations, to assess safety and efficacy of a
MUT. Generally, these procedures are performed in rodents at least
preliminarily, mainly because of cost and acquisition
considerations. In the case of MUTs whose indication, that is the
administration route, is inhalation, an exposure `system` must be
employed to accomplish dosing (e.g., administering the MUT
internally into the selected animal that is provided in a
volumetric concentration into the organism and expressed as a
proportional to the body weight of the said organism) of animals,
which is usually performed at multiple dosages to establish a
variety of predicted biological outcome such as organ toxicity,
enzymatic changes, lethality, therapeutic index,
pharmacodynamics/kinetics, and dose-response curves. Each dosage
group of a particular species or animal usually consists of a
statistically-derived number of animal based on the predicted
biological outcome, a typical number being 10 animals per dosage
group. If multiple doses are performed, for example three plus a
control group, with a control group being defined as a group of
animals experiencing the administration method of cohort dosage
groups but not actually receiving the MUT per se and rather
receiving the inert vehicle in which the MUT is combined with for
the purposes of dosing procedures (i.e., clean air), receiving and
the study is performed in two species of animals, for example, rats
and mice, then a typical number of animals included on a study for
one biological outcome is 80. [0054] i. Performance of inhalation
preclinical studies utilizing `traditional` dosing systems.
Continuing on the assumed number of rodents needed to accomplish a
study, for example a 90-day repeated dosing study containing three
dosage groups plus a control group, each per species, each group
consisting of 10 animals, to determine the resulting toxicological
effects, if any, of an MUT that culminates in sacrifice of all
animals +91 `days` after completion of the study. In general, most
exposure systems used to accomplish repeated dosing consist of a
dynamic chamber, that is an exposure chamber that introduces a flow
of air into the chamber housing the animal (or parts thereof) and
exhausts the contaminated air at a rate congruent to the
introduction, usually, allowing for a residence time that will
allow inhalation of the aerosolized MUT by the animals at a
particular rate congruent to a predetermined dose. In general, one
skilled in the art will generally acknowledge that each `daily`
dosing regime of a particular dosage group of animals exposed to a
particular concentration of MUT to achieve a particular dose will
usually consume at least 0.5 of a standard workday (four hours)
from set-up to returning the animals to their cages until the next
dosing. In general, each dosing experiment for the eight dosage
groups (three dosages plus control per species using two species)
would be accomplished separately (or at least in separate exposure
systems requiring equivalent personnel and MUT). In addition, if
one were to use either a singular or a battery of aerosol
generation devices to provide the necessary MUT entrained into the
experimental atmosphere for a singular or battery of inhalation
exposure systems, separate measurements of said atmospheres, which
may include characterization of the aerosol delivered to the
animals in the dosing group(s) which includes relative (single or
multiple) concentration determination of the MUT in the
experimental atmosphere provided to the animal to be internalized
via respiration which would equate to development of an `inhaled`
dose delivered daily during the 90 day repeated dosing study of the
hypothetical study, would be necessitated because of the nature of
the dosing procedures associated with experimentally similar, but
uniquely separate generation of aerosols into a single or battery
of inhalation exposure systems. In addition, the use of a single or
battery of exposure systems would require different laboratory
physical space requirements. One skilled in the art would tend to
acknowledge that of the commercially-available or custom-built
rodent inhalation systems, a physical footprint of a single system
(assuming an infinite vertical plane), including all ancillary
equipment associated with the hypothesized single inhalation
system, would tend to measure a minimum of 25 cubic feet (cu. ft).
[0055] 1. Estimation of time, cost, dosing uncertainty, and space
requirements using traditional inhalation systems. The time
required to accomplish a single daily dose to all groups (two
species, each consisting of three dosage groups plus a
species-specific control group) would equate to four (4.0) standard
workdays per dosage `day` as prescribed from the assumed 90 day
study design, which exceeds the intended `90` days for the `90` day
repeated dosage study. Utilizing the assumptions in the example, a
total of 360 standard workdays would be required to accomplish the
90 day repeated dosing regime portion prescribed by study design,
acknowledging that one using a battery of exposure systems, say
eight, to accomplish the daily dose could simultaneously accomplish
all the prescribed dosage groups at the same time in the same
actual workday, the personnel and associated support to perform
this task will be equivalent to the assumed 0.5 standard workday,
although time on the temporal scale for the aforementioned
experimental scenario would not be congruent to one using a single
exposure inhalation system attempting to accomplish the study.
Building on the presented example, if one skilled in the art were
to endeavor upon performing such a study, and had and singular or
battery of inhalation exposure system(s) at disposal to accomplish
the experiment, this would necessitate eight separate inhalation
administrations per dosing `day` for a prescribed 90 day repeated
dosing study for a total minimum of 720 dosing experimental
procedures, assuming no errors of personnel or experimental flaws
in the dosing administration, as defined by a single dose
administered to an animal dosage group on one of the 90 days in the
repeated dosing experimental design. If one were to assign an
arbitrary all-inclusive cost per hour that comprises a hypothetical
eight-hour workday of $1000 ($8,000 per day), the cost of
accomplishing a 90 day dosing study using an exposure system or a
battery thereof would be estimated at $2,800,000 ($2.8M). If one
were to assign the measurements associated with determining the
aerosol concentration in the experimental atmosphere(s) generated
during the 720 dosing administrations associated with the
prescribed study design, which one skilled in the art would
acknowledge is usually performed at least three times per exposure,
generally to determine an average and inherent width of the
confidence interval associated with said measurements, usually,
expressed in some format of a standard deviation of said
measurements, usually defined as the positive square root of the
total variance of all of the uncertainty.sup.1 components combined,
over the time associated with administering the prescribed dosage,
would total 2,160 individual measurements. .sup.1 Uncertainty of
measurement dose not imply doubt about the validity of a
measurement; on the contrary, knowledge of the uncertainty implies
increased confidence in the validity of the measurement result.
From: EURACHEM/CITAC Guide. Quantifying Uncertainty in Analytical
Measurement, Second Edition, Ed. Ellison, SLR, 2000.
[0056] Introduction of uncertainty of the measurements is inherent
due to the sheer number of the measurements taken during the daily
dosings, generally defined by the tenets of method validation,
comprising parameters among others such as bias, linearity,
detection limits, and robustness of measurements, most importantly
in this context being precision, being generally defined as the
reproducibility of a result either within a laboratory or operator,
equipment (i.e., inhalation exposure system(s)) and accuracy, being
generally defined as the closeness of the result that was
originally intended at the initiation of a particular inhalation
procedure, in this case the dosing of each animal group. Finally
the space requirements associated with accomplishing the said
dosing of the prescribed study would be, assuming a single or
battery of, for example eight, exposure system(s) would require 25
or 200 sq. ft. of laboratory space, respectively. [0057] ii.
Performance of preclinical study with the described processes and
device. As described by the processes and devices herein, the
processes and devices allow simultaneous daily dosing of all groups
and species (assuming that the other species is on the equivalent
phylogenetic scale) based on the electronic monitoring of the
individual animals' respiration all within the same exposure system
and aerosol stream. The processes and devices, as described herein,
assuming an infinite vertical plane, would significantly reduce the
four aforementioned conditions of time, cost, dosing uncertainty,
and space requirements over using traditional inhalation systems.
[0058] 1. Usage of the said processes and devices, as described
herein, to accomplish the equivalent dosing regime prescribed in
the hypothetical example would allow dosing of all eight dosage
groups (80 animals total) all within the typical 0.5 standard
workday, which is an obvious improvement of one attempting to
accomplish daily dosing with a single traditional inhalation
system, but the time savings over one using the alternative
scenario (a battery of inhalation systems) cannot be measured on
the temporal scale to realize inherent time savings based on
characteristics inherent to performing simultaneous dosing
procedures using multiple inhalation exposure systems, all
intrinsically requiring some form of simultaneous attention from
user resources (i.e., laboratory personnel) to successfully perform
daily dosing, which assuming that each system requires equivalent
resources for the various functioning components including, but not
limited to loading of the animals into separate systems, aerosol
generation, aerosol characterization, monitoring of animals, one
skilled in the art would acknowledge that this equates to
individual, say eight, separate exposures being performed, albeit
at the same time, resulting in an estimate of 360 standard workdays
using traditional inhalation system(s). The processes and devices,
as described herein, in one implementation relies on one physical
unit, which each animal's individual dose is controlled, and all of
the experimental atmosphere containing the MUT is being provided to
the animals at the same time from the same aerosol generation
source. Assuming the hypothetical experimental design, the `90` day
repeated dosing study would theoretically be reduced to 45 standard
workdays which is based on all exposure groups loaded into the same
exposure system at the same time and the dosing, assuming the
highest dosage group will be achieved within the assumed 0.5
standard workday. Building upon the demonstrated time savings using
the processes and devices as described herein, and assuming the
assigned arbitrary $1000 per hour/workday rate to accomplish this
study, the total cost for the study would be $360,000 based upon 45
standard workdays, comprised of a hypothetical eight hour workday
for performance of dosing of all groups for a `90` day repeated
study. The uncertainty, defined by precision and accuracy,
associated with the daily dosing in the context of the 90 day
repeated dosing regime, would be inherently minimized based on both
the exquisite control exhibited over each individual animal's
dosing and the reduction of the necessity of separate aerosol
generation using traditional inhalation system(s). The total number
of aerosol generation procedures associated with daily dosing, that
would consequently be characterized, would be 90. The space
associated with the processes and devices described herein, one
implementation, would occupy 25 sq. ft. and be equivalent to a
single traditional inhalation system. No further ancillary space is
needed, as the processes and devices as described herein, assuming
an infinite vertical plane, would emulate a traditional single
inhalation system in outward appearance. [0059] iii. Summary of
direct comparison between traditional inhalation systems and one
implementation of the processes and devices, as described herein,
with respect to time, cost, uncertainty of dose, and space
requirements. The time savings that would be realized via the usage
of one implementation of the processes and devices, as described
herein, would be advantageous over traditional systems currently
being utilized for animal studies similar to the example.
Performance of the study with of one implementation of the
processes and devices would require 45 standard workdays, or 360
hours, to accomplish the study; a total of 360 workdays, or 2,880
hours, would be required using either a single or a battery of
traditional inhalation systems. Using of one implementation of the
processes and devices over traditional inhalation system(s) would
result in a time savings to the user of 315 standard workdays, or
2,520 hours to accomplish the 90 day study, assuming equivalency
(two species of animals, each consisting of three dosage groups
plus a species control (8 groups total)). Building upon the time
savings demonstrated, assuming the hypothetical $1000 per hour
($8,000 per standard workday), performing the study using of one
implementation of the processes and devices would cost $360,000;
using traditional inhalation systems would theoretically cost
$2.8M. Using of one implementation of the processes and devices
results in a cost savings to the user of $2.44M. In other terms,
performing the 90 day study using of one implementation of the
processes and devices only costs approximately 12% of the
theoretical cost of performing the study with a traditional
exposure system or battery of systems. Uncertainty of dosing would
be vastly minimized utilizing of one implementation of the
processes and devices over traditional systems, primarily due to
monitoring each individual animal's dose, which is an aspect of
traditional systems that is not available within the state of the
art (at least in a simultaneous dosing scenario). Uncertainty of
dosing would be inherently reduced due to the reduction of number
of samples that are taken from the generated aerosol for daily
dosing of the animals. Measurements of the experimental atmospheric
concentration during the 90 separate aerosol generation procedures,
using one implementation of the processes and devices, assuming a
minimum of three measurements per generation to determine an
average and variance of experimental atmospheric concentration,
would total 180; traditional inhalation systems would require 720
independent aerosol generation procedures, either single or a
battery, assuming equivalency with respect to minimum sampling
number per aerosol generation procedure, would require 2,160
measurements. The number of samples needed to characterize the
concentration of the aerosol generated for purposes of dosing the
animals using one implementation of the processes and devices, as
described herein, is reduced by 1,980 samples, or approximately 9%
of the number of samples needed to characterize traditional
systems. Although the advantages of one implementation of the
processes and devices, as described herein, with respect to
precision and accuracy demand empirical determination, one skilled
in the art would acknowledge that a minimization of the separate
aerosol generation procedures and subsequent number of samples
needed to characterize the experimental atmosphere designed to
deliver a dose will inherently increase precision and accuracy of
the dosing of animal groups in the study. The physical space
requirements in the laboratory to utilize one implementation of the
processes and devices, as described herein, is estimated at 25 sq.
ft., this is equivalent to a single traditional inhalation system,
although to attain the capacity of dosing of animal groups that is
congruent and subsequently comparable with one implementation of
the processes and devices, as described herein, would require eight
traditional inhalation systems, which would require 200 sq. ft. of
physical space. The space requirements using one implementation of
the processes and devices, as described herein, is reduced by 175
sq. ft., or approximately 12% of the space requirements of the
battery of traditional inhalation systems needed to attain the
simultaneous capacity of one implementation of the processes and
devices, as described herein.
* * * * *