Note: Descriptions are shown in the official language in which they were submitted.
ALVEOLAR BREATH COLLECTION APPARATUS
PRIORITY APPLICATIONS
[0001] This application is a continuation-in-part application of U.S.
Application No.
14/720,456 filed on May 22, 2015, which claims the benefit of U.S. Provisional
Application No.
62/002,159 filed on May 22, 2014, the content of each being incorporated
herein by reference in
its entirety.
TECHNICAL FIELD
[0002] An improved apparatus for medical diagnostics is provided. More
specifically, an
improved apparatus for receiving and sampling volatile organic compounds
(VOCs) from at least
one gas sample is provided, some or all of the gas sample comprising human
alveolar breath.
BACKGROUND
[0003] The analysis of volatile organic compounds (VOCs) in exhaled human
breath is
rapidly emerging as a painless, non-invasive alternative to conventional
methods of disease
diagnosis and metabolite measurement. Breath VOC measurement is also commonly
used for
monitoring the effects of human exposure to environmental pollutants and
drugs.
[0004] Hundreds of VOCs have been found in exhaled human breath, many of
which
originate from blood-air exchange in the lower (i.e. alveolar) area of the
lungs. Because these
compounds are mostly present at very small concentrations (parts-per-billion
or less), their
measurement by instruments such as GC-MS (Gas Chromatography ¨ Mass
Spectrometer) or
infrared cavity-enhanced technologies often requires pre-concentration by
filtering out undesired
compounds such as nitrogen (N2) and oxygen (02). The relatively large
quantities of water
vapour and carbon dioxide (CO2) present in exhaled breath should also be
filtered out since they
can hinder measurement of remaining VOCs in instruments such as GC-MS and
IR spectrometers.
[0005] United States Patent No. 5,465,728 to Philips discloses an
apparatus which is used
to collect mammalian breath for chemical analysis and as a diagnostic tool for
the physician.
The apparatus comprises a fluid reservoir container having first and second
ends and a body
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extending between these ends so as to define an interior chamber; a breath
entry portal; a breath
exit portal; a sampling portal; a jacket to maintain the temperature of the
chamber; a sample
container for holding samples of exhaled breath; and pump means for moving
selected samples
of breath from the reservoir container into the sample container.
[0006] United States Patent No. 6,726,637 also to Philips discloses an
arrangement for
the collection, concentration, and optional analysis of volatile organic
components in alveolar
breath that includes a condensation unit which removes water vapor from the
alveolar breath.
The arrangement has two significant shortcomings. The first is that the
disclosed method for
alveolar sampling is based on assumptions of the subject's lung capacity and
expiration rate.
The method is therefore subject to inaccuracies in cases where a particular
subject's lung
capacity and/or expiration rate deviates strongly from the normal assumptions.
Furthermore,
there is no discussion about how cross-contamination of VOCs between subjects
is prevented or
otherwise dealt with.
[0007] United States Patent No. 6,582,376 to Baghdassarian discloses a
device for
collecting alveolar breath. Breath is expired into the inlet of a hollow body.
The hollow body
has two outlets, with a valve disposed in each outlet. The concentration of a
specific gaseous
component of expired breath is monitored by a gas concentration monitor as the
expired breath
passes through the hollow body to determine when alveolar breath is present in
the hollow body.
When alveolar breath is present in the hollow body, the valve in the second
outlet is actuated to
an open position to collect the alveolar breath in the collection reservoir
affixed to the hollow
body at the second outlet. While the Baghdassarian apparatus employs a CO2-
based method for
discriminating between alveolar and tidal breath, it is unable to concentrate
VOCs and is unable
to remove undesired CO2 and water from the breath sample.
[0008] United States Patent Application Publication No. 2004/0162500 to
Kline discloses
a diagnosis method for respiratory disease based on the separation of the
expired airway phase in
an exhaled breath from the alveolar phase, and a device to accomplish the
method. The device
includes a cartridge assembly and a disposable condensing chamber carried in a
substantially
enclosed housing. The cartridge assembly includes a disposable cartridge and a
reusable control
system that monitors a characteristic of gas passing through the cartridge to
determine when to
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divert the exhaled breath to an exhaust outlet and when to divert the exhaled
breath to the
condensing chamber. The characteristic is selected as being representative of
the transition from
the expired airway phase to the alveolar phase. Also included are a
refrigeration system, an
auxiliary monitoring system for determining when a sufficient volume of gas
has been produced,
and a built-in analyzer.
[0009] The Kline device contains a mechanism capable of diverting the non-
alveolar
component of breath from being collected and concentrated, based on the
measurement of some
characteristic of the exhaled breath passing through. However, the Kline
Apparatus is designed
to collect breath water vapour for subsequent analysis of the breath
condensates found therein,
and is not appropriate for applications where it is desirable to filter out
such water and to
concentrate remaining breath VOCs.
[0010] United States Patent Application Publication No. US 2015/0335267
to Cormier
discloses an apparatus for collecting breath VOCs having sorbent tubes to
filter out nitrogen,
oxygen, water, and carbon dioxide, a capnometer or other device for
discriminating between
alveolar and non-alveolar portions of exhaled breath, a flowmeter for
measuring volume of
exhaled breath, and a collection chamber, such as a piston, for collecting and
concentrating
exhaled breath. Cormier discloses the use of a pump to draw captured breath
from the collection
chamber through one or more of the sorbent tubes. While the apparatus taught
in Cormier is
capable of isolating and concentrating the alveolar portion of exhaled breath,
the use of a pump
to deliver collected breath to the sorbent tubes can be problematic, as using
a pump to draw
collected breath from the collection chamber lacks responsiveness and
precision, and can also be
unsafe to the user. The lack of precision results from an "all-or-nothing"
approach where the
collection chamber must be completely filled and completely emptied, with no
opportunity to fill
only a portion of the collection chamber, or draw a portion of the collected
breath as there is no
method of determining how much breath has been collected in, or drawn from,
the collection
chamber. Further, as not all of the alveolar breath flowing to the collection
chamber is collected,
and some flows out through the exhaust port connected to the piston, the
device in Cormier must
oversample breath in order to collect the requisite volume of alveolar breath.
Additionally, as the
capnometer and flowmeter in Cormier are positioned in-line with the collection
chamber, there is
a risk of accumulated particles in the capnometer/flowmeter from prior samples
contaminating
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new breath samples. The system in Cormier is also unable to pump room air
through the
capnometer and flowmeter during sampling procedures to remove condensation
from the
components and the line, which is desirable as condensation can accumulate
contaminants.
Similarly, arranging the flowmeter and capnometer in-line with the rest of the
system results in a
longer travel distance between the mouthpiece and the collection chamber,
which provides more
opportunities for contaminants to collect. Further, the Cormier system, which
is restricted to the
use of a 4-way valve design, only permits one flow path to be open at a time,
precluding the
possibility of cleaning or flushing procedures with room air. There is a need
for an improved,
more accurate apparatus for collecting and sampling volatile organic compounds
from some or
all of the collected gas sample.
Summary of the Invention
[0011]
According to embodiments herein, an apparatus for collecting a gas sample and
sampling volatile organic compounds from the collected gas sample is provided,
the apparatus
for the improved collection and storage of volatile organic compounds (VOCs)
from a gas
sample for future analysis, the gas sample comprising, for example, human
breath or/or ambient
air. More specifically, the apparatus is configured to receive a gas sample,
via a gas inlet, into an
exhaust portion via a gas exhaust line, into a gas collection and sampling
portion via a gas
collection line, or both simultaneously. The exhaust portion and the gas
collection and sampling
portions may be in fluid communication with the gas inlet and with one
another. In some
embodiments, the apparatus may further comprise at least one auxiliary gas
inlet port.
[0012] In
some embodiments, the exhaust portion may be configured to provide a gas
volume measuring device, positioned on the exhaust line, for measuring the
volume of the gas
sample. The exhaust portion may further be configured to provide a gas
monitoring device,
positioned on the exhaust line, for measuring and monitoring at least one
physical characteristic
of the gas sample. The gas volume measuring device may comprise a flowmeter,
and the gas
monitoring device may comprise a capnometer.
[0013] The
exhaust portion may further comprise at least a first gas outlet for venting
some or all of the gas sample from the apparatus. The exhaust portion may
further comprise at
least a second gas outlet for venting ambient air passing through the exhaust
line out of the
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apparatus (i.e. flushing the exhaust line). In some embodiments, the exhaust
portion may
comprise a pump for controllably passing the ambient air along the exhaust
line, flushing the
exhaust line.
[0014] In some embodiments, the gas collection and sampling portion may
be configured
to provide a first gas collection portion, positioned on a first branch of the
gas collection line, the
= gas collection portion forming a gas collection chamber for receiving the
portion of the gas
sample, and a second gas sampling portion, positioned on a second branch of
the gas collection
line, the gas sampling portion formed to provide at least one gas sampling
device for sampling
volatile organic compounds from the gas sample. In other embodiments, the gas
collection and
sampling portion may further be configured to provide an ambient air
component, positioned on
a third branch of the gas collection line, for collecting and sampling ambient
air from the
environment. In some embodiments, the gas sampling devices may comprise
thermal desorption
tubes designed to filter out undesired compounds such as, without limitation,
nitrogen, oxygen,
water, and/or carbon dioxide.
[0015] In some embodiments, the first gas collection portion may be
configured to
provide a gas collection chamber for receiving a portion of the gas sample.
The chamber may be
formed to receive a reciprocating piston therein. The piston may be operably
connected to a drive
mechanism for actuating the piston between a first compressed position and a
second
decompressed position, such actuation drawing at least a portion of the gas
sample into the
collection chamber or, in reverse, to expel at least a portion of the gas
sample collected and
stored within the chamber.
[0016] In other embodiments, a method for collecting a gas sample and
sampling volatile
organic compounds from the collected gas sample is provided, the method
comprising receiving
the gas sample within a gas collection and sampling apparatus, measuring the
flow of the gas
sample, and monitoring and detecting at least one physical characteristic of
the gas sample, and
venting at least one first portion of the gas sample until a threshold flow
rate and threshold level
of the at least one physical characteristic is detected, directing at least
one second portion of the
gas sample to at least one gas sampling device for sampling at least one
volatile organic
compound from the sample.
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[0017] In some embodiments, the the flow of the gas sample is measured by
a gas
volume measuring device, such as a flowmeter, and the at least one physical
characteristic is
monitored and detected by a gas monitoring device, such as a capnometer. The
at least one
physical characteristic may comprise the level of carbon dioxide in the
sample.
[0018] In some embodiments, the apparatus may further comprises a gas
collection
chamber having a reciprocating piston slidably received therein and the
directing of the at least
one second portion of the gas sample comprises controllably actuating the
piston from a first
compressed position to a second decompressed position. In other embodiments,
the apparatus
further comprise a gas collection chamber for receiving and collecting at
least a portion of the
gas sample, and at least a portion of the venting of the at least one first
portion of the gas sample
and the collection of at least a second portion of the gas sample may occur
simultaneously. The
gas sample may comprise a sample of human breath or ambient air. Where the
sample is human
breath, the sample may further comprise alveolar air.
Brief Description of the Drawings
[0019] Embodiments of the invention will now be described with reference
to the
appended drawings in which:
[0020] Figure 1 is a schematic diagram of the present apparatus according
to
embodiments herein, the apparatus comprising an exhaust portion and a
collection and sampling
portion;
[0021] Figure 2A is a schematic diagram of the exhaust portion of the
apparatus of Fig.
1, the exhaust portion configured to vent some or all of an undesired gas
sample from the
apparatus via first gas outlet;
[0022] Figure 2B is a schematic diagram of the exhaust portion of Fig.
2A, the exhaust
portion configured to flush a gas sample through the exhaust portion and out a
second gas outlet,
such flushing operably controlled via at least one pump;
[0023] Figure 3A is a schematic diagram of the collection and sampling
portion of the
breath collection apparatus of Fig. 1, the collection and sampling portion
comprising a collection
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component, and wherein at least a portion of the gas sample entering the
apparatus is shown
being directed towards a collection chamber within the collection component
(the chamber being
"closed");
[0024] Figure 3B is a schematic diagram showing the collection component
of the
collection and sampling portion of Fig. 3A in isolation (the chamber being
"open");
[0025] Figure 3C is a schematic diagram of the collection and sampling
portion of the
breath collection apparatus of Fig. 1, the collection and sampling portion
comprising a sampling
component, and wherein at least a portion of the gas sample collected and
stored within the
collection component is being directed from the collection chamber within the
collection
component to the sampling component;
[0026] Figure 4A is a schematic diagram of the collection and sampling
portion of the
breath collection apparatus of Fig. 1, the collection and sampling portion
comprising a purge
component providing a flow of ambient air into the apparatus and towards the
collection
chamber of the collection component;
[0027] Figure 4B is a schematic diagram of the collection and sampling
portion of the
breath collection apparatus of Fig. 1, the collection and sampling portion
comprising a purge
component providing a flow of ambient air into the apparatus and towards the
sampling
component; and
[0028] Figure 5 is a block diagram of components of the breath collection
apparatus of
Figure 1, in communication with a microprocessor.
Detailed Description
[0029] According to embodiments herein, an apparatus 100 is disclosed for
the improved
collection and storage of volatile organic compounds (VOCs) from a gas sample
for future
analysis, the gas sample comprising, for example, human breath or/or ambient
air. As would be
understood, the collected and stored VOCs may be subjected to further analysis
via, for example,
the Laser Infrared Sample Analysis (LISA) device disclosed in U.S. Patent No.
8,288,727, to
Cormier et al., the contents of which are incorporated herein by reference in
their entirety.
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[0030] Fig. 1 provides a schematic diagram of components of the improved
gas sampling
apparatus 100, according to embodiments herein. Generally, apparatus 100 may
comprise at least
an exhaust portion 10 and a gas collection and sampling portion 20. As will be
described in
greater detail, apparatus 100 may be configured to receive and collect a gas
sample into the
collection and sampling portion 20, wherein the gas is collected within a
first gas collection
portion 20a and delivered to a second gas sampling portion 20b. Herein, the
gas collection and
sampling portion may be referred to collectively as the "gas collection"
portion. Apparatus 100
may further comprise at least one ambient air component 20c, for receiving and
sampling
ambient air from the environment surrounding the apparatus 100.
[0031] Advantageously, apparatus 100 may be configured to provide an
improved gas
collection mechanism, said mechanism provided more accurate and precise intake
of some or all
of the gas sample (described in detail below). For example, apparatus 100 may
be configured
such that components of the apparatus 100 are arranged in a manner to enhance
safety and that
minimizes cross-contamination of samples within the apparatus 100, and in a
manner that allows
for fast and efficient flushing (i.e. clearing or cleaning) of lines within
the apparatus 100.
Apparatus 100 will now be described in greater detail having regard to Figs. 1
¨5.
[0032] Herein, reference to general terms such as "upstream" and
"downstream" are
relative terms used for explanatory purposes only. Gas samples referred to
herein may mean, for
example, a human breath sample, an ambient air sample, or a combination
thereof. Where the
gas sample may comprise a human gas sample, the gas sample may contain
alveolar air within
the sample.
[0033] Having regard to Fig. 1, apparatus 100 may comprise a first
exhaust portion 10
housed within apparatus 100 and operatively connected in parallel and in fluid
communication to
the second gas collection and sampling portion 20. Exhaust portion 10 may be
connected to the
collection portion 20 via any means known in the art such as, for example, a
two-way valve 2.
Two-way valve 2 may serve to reversibly isolate or connect the exhaust and
collection portions
10,20. Apparatus 100 may include a gas inlet 4 (e.g. gas intake component, or
mouthpiece),
fluidly connected to both exhaust and collection portions 10,20. Where the gas
sample comprises
a sample of human breath, gas inlet 4 may comprise any mouthpiece known in the
art into which
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the subject exhales. Gas inlet 4 may be fitted with a disposable microbial
filter (not shown) to
prevent infection and transfer of bacteria. As will be described in detail
below, apparatus 100
may be configured to concentrate a plurality of received gas samples until,
for example, a
sufficient sample is achieved for sampling. For example, where the gas sample
comprises human
breath, multiple breath exhalations may be received via gas inlet 4 if desired
or needed for
testing, the resulting gas sample being a concentrated combination of the
multiple breath
exhalations.
[0034] Having regard to FIGS. 2A and 2B, exhaust portion 10 may be
configured to
measure the volume and the quality of the gas sample received from the gas
inlet 4 and, where
applicable, to vent some or all of the gas sample. Exhaust portion 10 may be
fitted, along an
exhaust line Le, with at least one gas volume measurement device 6, such as a
flowmeter, for
measuring the volume of the gas sample being provided (e.g. a breath sample
provided by a
subject during exhalation in the gas inlet or mouthpiece). Exhaust portion 10
may be further
configured to measure and monitor at least one physical characteristic of the
gas sample received
from the gas inlet 4. Exhaust portion 10 may be fitted, along the exhaust line
Le, with a gas
monitoring device 8, such as a capnometer, in fluid communication with gas
inlet 4 for receiving
the gas sample and discriminating between alveolar and non-alveolar air within
the gas sample.
In some embodiments, gas monitoring device 8 may determine the concentration
of CO2 in the
gas sample as a means for distinguishing between alveolar and non-alveolar air
in the sample,
such determination being made in real-time. The CO2-based technique of
discriminating between
alveolar and non-alveolar breath described above has been shown to be accurate
and to allow for
a robust normalization of breath VOCs. More information about the CO2-based
method may be
found in Cope et al., Effects of ventilation on the collection of exhaled
breath in humans, J App 1
Physiol 96: 1371-1379, 2004.
[0035] Where the gas sample is detected as containing undesired gas (e.g.
non-alveolar
air), apparatus 100 may advantageously be configured to direct some or all of
the undesired gas
sample out of the exhaust portion 10, thereby expelling the sample from the
apparatus 100 (FIG.
2A,2B). Alternatively, where the gas sample is detected as containing desired
gas (e.g. alveolar
air), apparatus 100 may also be advantageously operative to direct some or all
of the desired gas
sample, via two-way valve 2, into the gas collection and sampling portion 20
(FIG. 1). In other
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words, the present exhaust line Le of the exhaust portion enables the "side-
sampling" of the
collected gas sample in order to ensure that the sample contains the desired
gas prior to the
collection thereof (into the gas collection portion).
[0036] More specifically, having regard to Fig. 2A, exhaust portion 10 may
comprise at
least one first gas outlet 3 for expelling gas from the apparatus 100. For
example, in some
embodiments, gas monitoring device 8 may be operatively in fluid communication
with gas
volume device 6, such that, in combination, the gas monitoring and volume
devices may serve to
detect and monitor the flow of the gas sample and, where determined, to
operatively vent at least
a portion of the gas sample from the apparatus 100. Accordingly, in some
circumstances, at least
a portion of the gas sample received at the gas inlet 4 may be expelled from
the apparatus 100
via at least one first gas outlet 3. It should be understood that the at least
one first gas outlet 3
may vent a portion of the gas sample from the apparatus 100 without permitting
an influx of
ambient from flowing back into the system (e.g. where a subject may
inadvertently inhale while
engaged with the mouthpiece 4). Moreover, the at least one first gas outlet 3
may be configured
in a manner to prevent air from upstream within the exhaust portion 10 from
interfering with the
measurements of the gas monitoring device 8.
[0037] Having regard to Fig. 2B, exhaust portion 10 may be configured in a
manner to
remove condensation from the exhaust portion 10 (i.e. from the exhaust line
Le). For example, in
some embodiments, the exhaust portion 10 may further comprise at least one
pump 7, located
adjacent at least one second gas outlet 3' and downstream at least one valve
9. Where desired,
pump 7 may be activated to draw gas (e.g. ambient room air) into the gas inlet
4, through gas
volume and gas monitoring devices 6,8, such gas to flush through the exhaust
line and exhausted
out exhausted out secondary gas outlet 3'. In this manner, the activation of
pump 7 may serve to
clear the exhaust portion 10 devices and fluid lines communicating there
between, preventing the
accumulation of condensation and contaminants in devices and the lines.
[0038] In other embodiments, optionally and as a safety measure, the
exhaust portion 10
of apparatus 100 may further include at least one auxiliary gas inlet port 5
in fluid
communication with the exhaust portion 10. Preferably, the at least one
auxiliary gas inlet port 5
is positioned in a manner to allow an inflow of ambient air into the apparatus
100 (e.g. when a
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subject inadvertently seals their mouth to the gas inlet 4 when the apparatus
is operating, causing
the apparatus 100 to create a negative pressure). Having regard to FIGS. 1, 2A
and 2B, the at
least one auxiliary gas inlet port 5 may be positioned upstream of devices
6,8, the inlet port 5
having a one-way valve operative to provide a flow restriction path for
ambient air to enter the
apparatus 100, mitigating or eliminating any potential negative pressure in
the system, and
alleviating any potential for injury to a subject.
[0039] According to further embodiments herein, apparatus 100 may further
comprise
gas collection and sampling portion 20 (referred to as the "collection
portion"), the collection
portion 20 configured to both collect the at least one gas sample (e.g. to
actively draw in, store,
and force out gas samples towards the sampling devices) and to extract or
sample VOCs
therefrom (e.g. utilizing absorbent or adsorbent materials). Collection
portion 20 may be housed
within apparatus 100 and operatively connected in parallel and in fluid
communication to the
exhaust portion 10. It should be understood that the present apparatus 100 is
advantageously
configured to enable two-flow paths (i.e. the exhaust line and the collection
line), such flow
paths operative to, where desired, be simultaneously opened and receiving at
least a portion of
the at least one gas sample. By way of example, during the receiving of the
gas sample into the
apparatus 100, a portion of the sample (e.g. ¨20%) may be directed to the
exhaust line for
detection and analysis of alveolar vs. non-alveolar breath, while at least
another portion of the
same sample (e.g. ¨80%) may be direct to the collection line for collection
(assuming that the
portion of the sample being analyzed contains a desired threshold amount of
alveolar breath and
collection is warranted, see Arrows depicting gas flow in FIG. 3A). Collection
portion 20 may be
connected to exhaust portion 10 via any means known in the art such as, for
example, two-way
valve 2. In some embodiments, collection portion 20 may be fitted, along a gas
collection line Lc,
with a plurality of distinct, yet operably coupled components, namely a
collection component
20a, a sampling component 20b, and an ambient air component 20c, each
described in more
detail below. In this regard, gas collection line Lc, may be divided, having a
plurality of distinct
gas lines branching therefrom, and optionally having at least three distinct
gas lines (as described
below).
[0040] Having regard to Figs. 1 and 3A-3C, at least a portion of the gas
samples received
via gas inlet 4 may be controllably drawn into and stored into collection
component 20a, via a
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first branch of the gas collection line Lc, and directed into at least one
collection chamber 22. Gas
collection chamber 22 may be in fluid communication with gas inlet 4, for
receiving at least a
portion of the gas sample directly therefrom. Gas samples may be continually
drawn into and
stored within collection chamber 22 until a sufficient volume and quality of
sample is achieved
(i.e. for sampling and/or analysis).
[0041] Having specific regard to FIG. 3B, in some embodiments, gas
collection chamber
22 may comprise a generally tubular housing having a first end 21 and a second
end 23. At least
a portion of the gas samples entering collection portion 20a may be received
within gas
collection chamber 22, via a first branch of the gas collection line Lc, and
stored therein. In some
embodiments, at least a portion of the gas samples received via inlet 4 may be
directed, via two-
way valve 2, along gas collection line Lc, into chamber 22, such process
continuing until a
sufficient volume of sample is received within chamber 22. It should be
understood that the
sufficient volume of gas sample received and stored within collection chamber
22 may depend
upon the particular gas sample being collected and upon the particular VOCs
being collected
therefrom (e.g. the volume of ambient air and/or alveolar breath required to
be collected for
certain VOCs to be tested). By way of example, where the apparatus 100 is
arranged to sample
VOC type "A", collection of at least a portion of a gas sample may require 20L
of collected gas
sample to obtained, whereas where the apparatus 100 is arranged to sample VOC
type "B",
collection of at least a portion of a gas sample may only require 10L of
collected gas sample to
be obtained.
[0042] Chamber 22 may form an inner diameter configured to receive at
least one
reciprocating piston 24 therein. Piston 24 may be configured to have a first
piston head portion
25 (i.e. piston head portion 25 may extend across the entire cross-section of
chamber 22), and a
second piston shaft portion, the piston slidably actuable within collection
chamber 22. In some
embodiments, piston 24 may be controllably coupled to a drive mechanism 26,
the drive
mechanism 26 operable to actuate piston 24 between a first compressed position
and a second
decompressed position, wherein in the first compressed positioned (i.e. where
the piston 24 is
extended away from the drive mechanism and the chamber 22 is "closed"), the
piston 26 may be
positioned in a manner that little to no gas sample may enter collection
chamber 22 (FIG. 3A). In
the second decompressed position (i.e. where the piston 24 is retracted and
the chamber 22 is
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"opened"), the piston may be positioned in a manner to draw gas samples into
collection
chamber 22 (FIG. 3C). In some embodiments, drive mechanism 26 may comprise a
motor, such
as a stepper motor, or any other such motor operative to actuate piston 44
with increased
accuracy.
[0043] Advantageously, drive mechanism 26 may serve to accurately actuate
piston 24
from the first extended position to the second retracted position as a means
of controllably
drawing some or all of a gas sample into chamber 22. Moreover, where chamber
22 contains a
sufficient volume of a gas sample, drive mechanism 26 may serve to actuate the
piston 24 in
reverse (reducing the volume of gas sample within chamber 22 and creating an
increase in
pressure therein), effectively forcing the volume of gas sample within the
chamber 22 out of the
chamber 22 and towards the sampling component 20b. Piston 24 may be operably
connected to
drive mechanism 26 at its second shaft end. Arrows in FIGS. 3A and 3C denote
translation of
piston 24 between the compressed and decompressed positions, while gas cloud
schematic
denotes at least a portion of the gas sample within chamber 22, increasing or
decreasing with the
compression/decompression of the piston 24. While reference shall be made
herein to a "piston",
it would be understood that any other suitable devices operable to compress
gas samples may be
used in place of the piston without substantially altering the apparatus 100.
[0044] As above, gas collection and sampling portion 20 of apparatus 100
may further
comprise a sampling component 20b. Having specific regard to FIG. 3C, sampling
component
20b may be in fluid communication with collection component 20a, such that
sampling
component 20b may receive some or all of the gas sample received and stored
within collection
component 20a. The transmission of some or all of the gas sample into sampling
component 20b
may be controlled via first sampling valve 27. In some embodiments, sampling
valve 27 may be
positioned along the gas collection line Lc, i.e. along a second branch of the
gas collection line
Lc, in a manner to effectively connect or isolate the sampling component 20b
from the other
components of apparatus 100. As would be understood, apparatus 100 may further
comprise a
manifold (not shown), for releasably receiving and securing the at least one
sampling devices 30.
In operation, when the at least one sampling device 30 is secured to manifold,
fluid
communication is established between the input and output connections 35,37 of
the sampling
tubes 30.
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[0045] Sampling component 20b may be operative to receive and collect some
or all of
the gas sample within apparatus 100 for further analysis. In some embodiments,
sampling
component 20b may be configured to perform analytical thermal desorption of
some or all of the
gas sample. In that regard, sampling component 20b may comprise at least one
sampling device
30 (30a, 30b, ...30n), such as a thermal desorption tube, or other suitable
device, having a
sorbent material for sampling the gas sample. Thermal desorption tubes may be
operative to
collect desired VOCs from the gas sample by diffusion of the VOCs onto the
tubes packed with
the sorbent, while filtering out any undesired compounds. For example, thermal
desorption tubes
may be operative to collect VOCs of interest within the sample while filtering
out compounds
such as such as nitrogen (N2), oxygen (02), water (H20), carbon dioxide (CO2),
etc. Thermal
desorption tubes may comprise, for example, adsorbent materials such as
Chromosorbg or
Tenax , which allow small molecules such as water (H20) and carbon dioxide
(CO2) to pass
through while adsorbing or collecting the remaining larger VOCs of interest.
As would be
understood, apparatus 100 may be configured to incorporate different sampling
devices 30
having different sorbent materials such that different VOCs can be sampled. As
would be
understood, the at least one sampling devices 30 may be removed and replaced
from apparatus
100. For example, upon sampling, the at least one sampling devices 30 may be
removed from
apparatus 100 for further gas analysis. By way of example, further analysis
may be performed by
any suitable device such as the apparatus disclosed in United States Patent
No. 8,288,727 to
Cormier et al., the contents of which are incorporated herein by reference in
their entirety.
[0046] Having further regard to FIG. 3C, in some embodiments, sampling
component
20b may be positioned on a second branch of the gas collection line Le, with
each sampling
device 30 having corresponding gas inlet ports 31 (31a, 31b, ...31n) and gas
outlet ports 33 (33a,
33b, ...33n). In some embodiments, some or all of the gas sample may be
directed to the at least
one sampling devices 30 via corresponding input control valves 35. Some or all
of the gas
sample may be directed out of the at least one sampling device 30 via output
control valves 37.
Following sampling, some or all of the gas sample exiting the at least one
sampling device 30
may be expelled from apparatus 100 via gas exhaust port 28, such expulsion
controlled via at
least one exhaust valve 29. As depicted in FIG. 3C, gas exhaust port and valve
28,29 may be
positioned along the second branch of the gas collection line, at a terminal
end thereof, and
downstream of the at least one sampling devices 30.
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[0047] Having further regard to FIG. 3C, sampling component 20b may
further comprise
an optional gas bypass line 34, said bypass line 34 also stemming from the
second branch of the
gas collection line L. For example, in some embodiments, bypass line 34, may
be primed with
some or all of the gas sample (e.g. with alveolar or ambient air), or flushed
with ambient air to
clean all of the gas lines within the sampling component 20b (e.g. when the at
least one sampling
devices 30 have been removed from the apparatus 100 and the valves 35,37 are
open, and bypass
valve 39 is open).
[0048] As above, having regard to FIGS. 4A and 4B, apparatus 100 may
further comprise
an optional ambient air component (e.g. ambient air intake component) 20c, the
ambient air
component 20c configured to draw a sample of ambient air from the environment
into apparatus
100, via ambient air intake 40. Ambient air component 20c may be housed within
apparatus 100
and operatively connected in parallel and in fluid communication to gas
collection and sampling
components 20a,20b. In some embodiments, ambient air component 20c may
comprise a third
branch of the gas collection line Lc, whereby some or all of the sample of
ambient air received
by apparatus 100 may be directed to gas collection component 20a (FIG. 4A)
and/or gas
sampling component 20b (via the gas collection component 20a; FIG. 4B). In
operation, ambient
air may be received by the apparatus 100 and collected in chamber 22 of the
gas collection
component 20a. Once collected, some or all of the ambient air may then be
conveyed from the
gas collection portion 20a to the gas sampling portion 20b (e.g. for sampling
of VOCs
therefrom), as described above. Advantageously, in this manner, one or more
VOCs contained
within the ambient air sample may be compared to the VOCs from one or more of
the gas
samples provided to apparatus 100, such comparison performed to determine, for
example,
whether the VOCs measured in the gas sample might be produced endogenously by
a subject
providing the gas sample, or as a result of the subject having inadvertently
inhaling ambient air
prior to providing the gas sample.
[0049] Having regard to FIG. 4B, in some embodiments, ambient air
component 20c may
comprise at least one filter 41, such as a dust filter, positioned on the
ambient air line, for
filtering contaminants and other unwanted particles from the ambient air
sample received via
intake 40. In some embodiments, at least one ambient air control valve 42 may
be positioned
along the ambient air line and downstream of the ambient air intake 40, for
controllably
CA 2997070 2018-03-02
connecting or isolating ambient air portion 20c from the other components of
apparatus 100 (e.g.
exhaust and collection components 10,20).
[0050] According to embodiments herein, apparatus 100 may be operated
manually,
automatically, or a combination thereof. Having regard to FIG. 5, at least one
microprocessor
200 may be provided, such microprocessor 200 operably connected to, at least,
some or all of the
actuable components within apparatus 100 (e.g. without limitation, the drive
mechanism,
flowmeter, capnometer, one- and two-way valves, and/or pump). Microprocessor
200 may
activate apparatus 100 via at least one relay array 202.
[0051] For example, in some embodiments, the at least one microprocessor
200 may be
of executing computer readable program code stored on a computer readable
medium 204
Computer readable medium may include a main memory 206, such as a random
access memory
(RAM) or other dynamic storage device (e.g., dynamic RAM (DRAM), static RAM
(SRAM),
and synchronous DRAM (SDRAM)), in communication with microprocessor 200 for
storing
information and instructions to be executed by microprocessor 200. The main
memory 206 may
be used for storing temporary variables or other intermediate information
during the execution of
instructions by the microprocessor 200. Microprocessor 200 may include memory
structures
such as registers for storing such temporary variables or other intermediate
information during
execution of instructions 208. Apparatus 100 further includes a read only
memory (ROM) or
other static storage device (e.g., programmable ROM (PROM), erasable PROM
(EPROM), and
electrically erasable PROM (EEPROM)) in communication with microprocessor 200
via a bus or
other communications structure for storing static information and instructions
for the
microprocessor.
[0052] The apparatus 100 can also have a user interface display 210
connected to
microprocessor 200 for displaying status information and having a touch-button
interface 212 for
control by an operator of apparatus 100.
EXAMPLES
[0053] By way of the following Example, the present apparatus 100 will now
be
described in operation.
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[0054] In preparation for gas sampling procedures, valves along the
collection line Lc
(e.g. valves 2, 27, 42), valves providing gas samples to and from the at least
one sampling
devices 30 (e.g. valves 35, 37, 29), are closed, and piston 24 is actuated
into the fully compressed
or extended position. One or more new at least one sampling devices 30 are
placed into the
apparatus 100 (i.e. the manifold therein), such that input/output valves 35,37
and corresponding
input/output line connections are in fluid communication.
[0055] To begin, the operator activates the instruction set stored in the
computer readable
medium 204 of apparatus 100 via the touch-button interface 212, such that
apparatus 100 in turn
displays instructions for a subject via user interface display 210. The
subject is prompted to draw
in a breath and to exhale the breath into the gas inlet 4. As depicted in FIG.
2A, during the first
part of the exhalation, which can commonly comprise non-alveolar breath, valve
2 remains
closed such that flow of the non-alveolar breath is directed to the exhaust
portion 10. As would
be understood, the gas sample is directed along the exhaust line Le to the gas
volume measuring
device 6 and the gas monitoring device 8. The gas sample may then be vented
from apparatus
100 via first gas outlet 3. The subject may then be prompted to provide one or
more gas samples
into inlet 4 and the foregoing is repeated. As more of the at least one sample
passes along the
exhaust line Lõ gas monitoring device 8 may detect that the CO2 levels in the
sample has
reached and stabilized at or above an appropriate threshold level to indicate
that the sample
primarily contains alveolar breath. At this time, microprocessor 200 may be
automatically
activated to respond by signalling relay array 202 to open valve 2, and to
trigger drive
mechanism 26 to begin actuating piston 24 towards the decompressed position,
opening
collection chamber 22, drawing the gas sample received by apparatus 100 into
the collection
chamber 22. As the piston 24 translates from the extended position to the
retracted position, at
least a portion of the alveolar breath may still be directed through the
exhaust portion 10 along
the exhaust line L. In this regard, gas volume measuring device 6 may continue
to measure the
volume of gas passing through the device (i.e. the flow rate of the gas
sample). The actual (total)
exhalation flow rate can be calculated by adding the flow rate measured by the
gas volume
measuring device 6 with the volumetric rate (e.g. the speed) at which the
piston 24 actuates. The
volumetric rate at which piston 24 is translated towards the retracted
position should be less than
the total exhalation flow rate, thereby avoiding the creation of a negative
pressure while
collecting the gas sample (i.e. the alveolar breath sample). Advantageously,
the translation rate
17
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of the piston 24 can be precisely controlled, and can further be adjusted
periodically to account
for changes in the gas sampling intake rate (i.e. the subject's exhalation
rate). In other words, the
rate of the piston 24 actuation can be regulated such that the gas volume
measuring device 6
continues to measure a positive flow rate through the exhaust portion 10.
Precise regulation and
control of the rate of expansion of piston 24 is enabled by drive mechanism
26, such that where
the total exhalation flow rate of the gas sample falls below a certain
threshold, indicating, for
example, that the subject is running out of breath, the expansion of piston 24
can be slowed or
stopped, and valve 2 closed in order to keep the portion of the gas sample
collected in chamber
22 within the chamber 22.
[00561 Where it is detected that the volume of gas received and collected
within chamber
22 is insufficient for sampling and testing, further gas samples may be
provided. For example,
the subject may be prompted to draw in and exhale a second breath sample into
gas inlet 4, as
described above. Subsequent gas samples will be monitored by the gas
monitoring device to
ensure that, for example, non-alveolar portions of the breath sample will
again be vented out of
the exhaust portion 10 until a predetermined threshold of alveolar breath (or
CO2) is detected.
Again, once the threshold is achieved, microprocessor 200 will signal relay
array 202 to open
valve 2, and to operate drive motor 26 to retract piston 24 further within
chamber 22 to again
being collecting gas sample therein (and adding to the sample previously
collected).
[0057] Once a sufficient volume of gas sample is collected within chamber
22, the
apparatus 10 is prompted to cease receiving gas samples. The microprocessor
200 signals the
relay array 202 to close valve 2 and to open intake valves of the sampling
component 20b (e.g.
valves 27,35,37,29), thereby establishing fluid communication between the gas
collection
component 20a and the sampling component 20b. Microprocessor 200 then operates
drive
mechanism 26 to compress piston 24, directing the collected gas sample within
chamber 22 of
the collection component 20a, along the collection line Lc, to the sampling
component 20b. The
gas sample passes through the at least one sampling devices 30 and out of the
apparatus 10 (e.g.
via exhaust port 28). It should be understood that the gas sample may be
passed through one or
more of the at least one sampling devices 30 simultaneously by opening or
closing the
appropriate control valves 35,37. If any collected gas sample remains within
chamber 22, the
above steps can be repeated to convey any residual gas to the sampling
devices.
18
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[0058] Once a sufficient volume of sampled breath has been delivered to
the at least one
sampling devices 30, or the piston 24 has reached its fully extended position,
the VOCs are
sampled and stored within the at least one sampling devices 30 and the
microprocessor 200
signals the relay array 202 to deactivate the drive mechanism 26 and to close
all valves.
[0059] At times, it may be desirable to remove condensation that might
have
accumulated within the components of the apparatus 100. As above, purging of
the exhaust line
Lõ may be performed by closing valve 2 and opening valve 9. Microprocessor may
then activate
pump 7 to draw ambient air through inlet 4 and through the exhaust portion 10
via exhaust line
Le. Purged ambient air may be vented from the exhaust line via the at least
one second outlet 3'.
It is an object of the present apparatus 100 that gas monitoring and measuring
devices may be
easily cleaned of condensation and/or other contaminants therein.
[0060] At other times, it may be desirable to sample a gas sample
primarily comprising
ambient air in order to compare the VOCs in the sample with the VOCs in the
ambient air (i.e.
baseline VOCs present in the ambient air). As above, sampling of ambient air
may be performed
by closing valves 2,27 and opening valve 42 of the ambient air component 20c.
Drive
mechanism 26 may then be activated to actuate piston 24 to draw ambient air
into the apparatus
100 via inlet 40, and via optional filter 41, and into chamber 22. Once the
desired amount of
ambient air has been accumulated within chamber 22, valve 42 may be closed,
and control
valves allowing the passage of air through the at least one sampling devices
30 can be opened
(e.g. valves 27,35,37,29). As above, drive mechanism 26 can then be activated
to translate the
piston within chamber 22 to direct the ambient air within the chamber out
through exhaust port
28. It is an object of the present apparatus 100 to provide a method of
sampling ambient air from
the environment as a means of detecting VOCs in the ambient air, thereby
providing a baseline
VOC value in order to determine whether the VOCs sampled from the gas sample
are a result of
the gas sample or as a result of the ambient air (e.g. whether the VOCs may be
a result of the
subject drawing in and exhausting ambient air).
[0061] At yet other times, advantageously, it may be desirable to flush
the lines within
the apparatus 100 with ambient air. This may be performed by first removing
the at least one
sampling devices 30 from the manifold, opening the appropriate valves, and
operating the drive
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mechanism 26 to circulate ambient air through the apparatus 100. Such a
flushing process may
be performed and/or repeated as needed in order to ensure enhanced circulation
of ambient air
throughout the apparatus 100.
[0062] At yet other times, advantageously, it may be desirable to prime
the at least one
sampling component 20b with alveolar breath prior to sampling. This may be
performed by first
collecting alveolar breath into chamber 22, as described above, and then
closing the input valves
to the at least one sampling devices 35, but opening valves 27,39,29, such
that all three valves
are opened along bypass line 34. Using the drive mechanism 26, the piston 24
may be partially
collapsed, and alveolar air may be circulated from chamber 22 through sampling
component 20b
(via bypass line 34). When sampling VOCs from ambient air, this process can
also be used to
prime the sampling component 20b with ambient air by drawing in air through
ambient air
component 20c instead of alveolar breath from the gas inlet 4.
[0063] It is contemplated that alternative embodiments of the present
apparatus 100 may
be provided. For example, without limitation, the present apparatus may
further comprise heaters
associated with the sampling devices. Alternatively, additional input and
output ports may be
introduced to allow for desorption of samples contained in sampling devices to
be introduced
directly from the apparatus 100 to a VOC measurement instrument. It would be
understood that
sampling devices could then be conditioned by heating and purging and prepared
for the next
sample collection, without having to remove the sampling devices from the
apparatus 100.
Heaters could also be used to heat the lines and components of the device 100,
reducing
condensation therein. For example, heaters may be used to heat the lines
within the apparatus
100 to about 40 C such that moisture in the exhaled breath, which typically
has a maximum
temperature of 37 C, is not cooled by the components of the device 100 (and
minimizing
condensation thereof).
[0064] According to embodiments herein, the present apparatus
advantageously provides
the use of a drive mechanism to controllably and precisely actuate a piston
(or other
compressible device), improving the accuracy of the collection and sampling of
gas. A more
efficient apparatus is disclosed, as only the required volume of gas that is
collected is provided
to the sampling devices, thereby, in some cases, allowing only a single breath
sample to be
CA 2997070 2018-03-02
delivered to multiple sampling devices, reducing time spent reacquiring breath
samples from the
subject. Further, the present use of a drive mechanism allows microprocessor
to automatically
adjust the rate of gas sample collection much more quickly relative to, for
example, known gas
sampling apparatuses that employ pumps to actuate a piston, allowing for
precise adjustments to
the collection of breath so as to collect as much alveolar breath as possible
without creating
negative pressure in the system. Additionally, the present use of a drive
mechanism, instead of a
pump, allows for gas volume measuring and gas monitoring devices to be
positioned along and
exhaust line running in parallel to the collection line (i.e. instead of being
in-line therewith).
Such a configuration advantageously allows for the volume of breath collected
to be determined
by how much the piston has been expanded by the drive mechanism, thus reducing
the risk of
cross-contamination between the devices and the collection components. Further
still, the present
use of the drive mechanism to actuate a piston advantageously allows for
collected air or breath
in the collection chamber to be directed to multiple parts of the system at
once, allowing all the
lines of the device to be flushed at once.
[0065]
Although embodiments have been described with reference to the drawings, those
of skill in the art will appreciate that variations and modifications may be
made without
departing from the spirit, scope and purpose of the invention as defined by
the appended claims.
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