U.S. patent application number 11/605727 was filed with the patent office on 2007-03-29 for device and method for collection of exhaled alveolar breath condensate.
This patent application is currently assigned to The Charlotte-Mecklenburg Hospital Authority. Invention is credited to Jeffrey A. Kline.
Application Number | 20070073183 11/605727 |
Document ID | / |
Family ID | 32908465 |
Filed Date | 2007-03-29 |
United States Patent
Application |
20070073183 |
Kind Code |
A1 |
Kline; Jeffrey A. |
March 29, 2007 |
Device and method for collection of exhaled alveolar breath
condensate
Abstract
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 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.
Inventors: |
Kline; Jeffrey A.;
(Charlotte, NC) |
Correspondence
Address: |
KENNEDY COVINGTON LOBDELL & HICKMAN, LLP
214 N. TRYON STREET
HEARST TOWER, 47TH FLOOR
CHARLOTTE
NC
28202
US
|
Assignee: |
The Charlotte-Mecklenburg Hospital
Authority
Charlotte
NC
|
Family ID: |
32908465 |
Appl. No.: |
11/605727 |
Filed: |
November 29, 2006 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10778477 |
Feb 13, 2004 |
|
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11605727 |
Nov 29, 2006 |
|
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60447581 |
Feb 14, 2003 |
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Current U.S.
Class: |
600/532 |
Current CPC
Class: |
A61B 5/412 20130101;
A61B 2010/0087 20130101; A61B 5/097 20130101; A61B 10/0045
20130101 |
Class at
Publication: |
600/532 |
International
Class: |
A61B 5/08 20060101
A61B005/08 |
Claims
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58. A breath condensate collection apparatus comprising: (a) a
housing; (b) a condensing chamber, carried by the housing, having
an inlet that receives exhaled breaths from a mammalian subject and
an outlet that permits a gaseous, non-condensed portion of the
exhaled breaths to escape from the condensing chamber; and (c) a
built-in refrigeration system, carried by the housing, including: a
compressor, an expansion valve, an evaporator pipe arranged to cool
the condensing chamber, and a condenser pipe arranged to dissipate
heat away from the condensing chamber.
59. The breath condensate collection apparatus of claim 58, wherein
the housing includes a cavity correspondingly shaped and sized to
carry the condensing chamber, and wherein the evaporator pipe is
disposed generally around the cavity.
60. The breath condensate collection apparatus of claim 59, wherein
when the condensing chamber is carried in the cavity, the
condensing chamber makes contact with a substantial portion of the
evaporator pipe.
61. The breath condensate collection apparatus of claim 59, wherein
the condensing chamber has walls constructed from a good heat
conducting material.
62. The breath condensate collection apparatus of claim 61, wherein
the walls of the condensing chamber are constructed from
aluminum.
63. The breath condensate collection apparatus of claim 59, further
comprising a ventilation system that dissipates heat generated by
the refrigeration system.
64. The breath condensate collection apparatus of claim 63, wherein
the ventilation system includes one or more vents in the
housing.
65. The breath condensate collection apparatus of claim 63, wherein
the ventilation system includes one or more fans.
66. The breath condensate collection apparatus of claim 59, further
comprising a temperature gauge arranged to provide an indication of
the temperature of the condensing chamber.
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Description
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application is entitled to the benefit of, and claims
priority to, provisional U.S. Patent Application Ser. No.
60/447,581 filed Feb. 14, 2003 and entitled "DEVICE AND METHOD FOR
COLLECTION OF EXHALED ALVEOLAR BREATH CONDENSATE," the entirety of
which is incorporated herein by reference.
BACKGROUND OF THE PRESENT INVENTION
[0002] 1. Field of the Present Invention
[0003] The present invention relates generally to breath condensate
collection, and more particularly, to full-featured breath
condensate collection apparatuses capable of separating the expired
airway phase of mammalian exhalation from the alveolar phase.
[0004] 2. Background
[0005] As is well known, exhaled breath condensate contains
water-soluble and water insoluble molecules, including dissolved
gases, organic solutes, ions and proteins. Analysis of the
molecular content of breath condensate can provide a method to
diagnose and prognose certain diseases. (S. A. Kharitonov and P. J.
Barnes, Exhaled markers of pulmonary disease, Am J Respir Crit Care
Med 163:1693-1722, 2001.) However, the measurement of substances in
exhaled condensate as a method to determine the presence of
pathophysiologic. processes in the lung alveoli is degraded by
contamination by substances arising from the mouth, nose, throat
and the tracheobronchial tree. Using two dimensional gel
electrophoresis, Griese and colleagues demonstrated distinctly
different proteins in breath condensate collected from oral
breathing, compared with nasal breathing (M. Griese, Proteomics
2:690-696, 2002.) This contamination can cause false positive
testing.
[0006] It is our hypothesis that a gating mechanism can be
triggered from the measurement of the partial pressure of carbon
dioxide in exhaled breath to open and close during the exhalation
cycle in a manner to separate out the contaminant breath volume,
generated during the expired airway phase of the exhalation cycle,
from the alveolar volume generated during the alveolar phase of the
cycle. The ability to selectively collect alveolar breath
condensate rapidly and easily with a point-of-care device would
improve the clinical utility of breath-based diagnosis for this
purpose, particularly in the emergency department or clinic
setting. The device described is designed to allow a patient to
breath into a handheld disposable chamber to facilitate the
collection of breath water vapor which can then be analyzed for
biochemicals to detect the presence of specific diseases, including
bacterial, chlamydial, mycoplasma, or fungal pulmonary infection,
pulmonary embolism, pulmonary ischemia, systemic gram negative
sepsis, fat embolism from sickle cell disease or after surgical
fixation of fractures, carcinoma of the lung, asthmatic
inflammation, and chronic obstructive pulmonary disease.
Experimental History and Observations Leading to Conception of
Invention
[0007] An experimental pulmonary vascular occlusion (PVO), induced
by venous infusion of polystyrene microspheres in rats, has been
used to determine three major findings related to the device of the
present invention. Using anesthetized, tracheostomized mechanically
ventilated rats, exhaled breath condensate was collected in a pilot
version of the present invention. The condensing chamber consisted
of a sterile pipette within dry ice. As compared with control rats,
increased concentrations of proteins, eicosinoid derivatives and
peptides associated with fibrinolysis were found in the condensate
of rats with PVO. (Nakos, Am J Resp Crit Care Med 1998, 158:1504.)
The magnitude of the concentration of these vasoconstrictive agents
correlated with the severity of hypoxemia and pulmonary
hypertension in the subject rats.
[0008] A variety of methods and apparatuses have been proposed for
use in breath analysis, but none accomplish the needs and benefits
of the present invention. Several of these, including U.S. Pat.
Nos. 6,033,368 and 6,419,634 to Gaston et al., U.S. Pat. No.
6,585,661 to Hunt et al., U.S. Publication No. 2003/0208132 A1 to
Baddour, Eur. Patent No. 0,759,169 B1 to Winsel et al., and PCT
Patent App. No. 02/082977 to Vaughan et al., disclose breath
condensate collection devices, but each has significant
shortcomings. First, no known apparatus includes the use of a
monitoring system in a breath condensate collection device as a
mechanism to trigger a valve open and shut during the exhalation
cycle for the purpose of collecting only one type of
condensate--i.e., alveolar condensate or expired airway condensate.
The former type of condensate is especially important in the use of
a breath collection device to diagnose lower tract pulmonary
infection, as it is necessary to eliminate contamination of the
breath sample from the nasopharyngeal flora. Similarly, the latter
type of condensate is especially important in diagnosing upper
tract infection.
[0009] Other devices or methods are known for separating the
expired airway phase from the alveolar phase for such purposes as
the detection of alcohol levels in a person's breath. For example,
U.S. Pat. No. 3,613,665 to Gorsuch, U.S. Pat. No. 3,830,630 to
Kiefer, U.S. Pat. No. 4,248,245 to Kempin, U.S. Pat. No. 5,327,901
to Delente, U.S. Pat. No. 5,376,555 to Forrester disclose methods
and apparatuses for achieving such separation. Some, but not all,
of these devices and methods use active mechanisms for providing
such separation, while others use passive means. Unfortunately, all
known devices and methods suffer drawbacks. For example, the
Gorsuch device measures temperature with a heated thermistor and
triggers a valve when the temperature differential indicates that
the alveolar phase has been reached, while the Kempin device
measures temperature differentials to determine when to divert
exhaled breath into a measuring chamber. Temperature-based valve
triggers may not be as reliable as desired. Neither the Kiefer
device nor the methodology disclosed by Forrester is used to
physically separate the alveolar phase breath from expired airway
phase breath. Instead, the filament used in Kiefer is used merely
to activate an alcohol-measuring section, while the Forrester
methodology uses automated analysis of infrared profiles of the
exhaled breath to identify the different phases thereof. Finally,
the Delente device is passive, relying on a simple technique to
retain in a collection chamber only the last portion of an exhaled
breath, which is assumed to be alveolar phase rather than expired
airway phase because it comes from the end of the exhaled breath.
None of these devices or methods are thus suitable for use in
breath condensate collection.
[0010] Moreover, none of the known devices or methods for
separating the expired airway phase from the alveolar phase have
been applied to breath condensate collection devices. In fact, some
of the devices, such as the Kempin device, takes steps or include
features specifically to avoid condensation because it interferes
with the measurement of the gases themselves. Finally, although the
Forrester methodology uses infrared analysis of exhaled breath,
none of the devices or methods use spectrometry methods to
determine when the alveolar phase of an exhaled breath has been
reached and to trigger a valve creating physical separation of the
alveolar phase from the expired airway phase.
[0011] A need exists for a specific condensation chamber designed
to allow delivery of a sample of condensate to an analysis system
that is separate from the machine in order to allow point-of-care
immunoassay for certain antigens. In particular, a need exists for
an immunoassay in the form of a small plastic cartridge, similar to
a conventional home pregnancy test kit except that the antibodies
in the matrix are directed against antigens that will help diagnose
pulmonary embolism and pulmonary infection. Antibodies that will
preferably be tested may include, but are not limited to,
fibrinopeptide A, d-dimer, thromboxane (and its metabolites),
leukotrienes, chemokines, interleukins, and bacterial, chlamydial,
viral and mycoplasma antigens. Although the general intent of
methodologies such as those disclosed in the Baddour and Vaughn
patents may be somewhat similar to some of the purposes of the
present invention, they fail to provide an apparatus for collecting
condensate and then injecting approximately 50-500 .mu.L of
condensate from a tip into the immunoassay kit. In addition, a need
exists for a device from which the condensate sample may be
delivered to an arterial blood gas machine for analysis of pH,
pCO.sub.2, pO.sub.2, lactate, urea, glucose and electrolytes.
[0012] The Baddour device is designed to collect exhaled breath
condensate from patients with asthma. The Baddour device does not
describe a plunger that extrudes the sample, but describes a
"duckbill" valve that appears to be an internal chamber for sample
collection. This must be removed and requires additional steps
before the sample can be analyzed. Baddour fails to disclose a tip
which can be used to dispense the condensate onto the immunoassay
filter, and fails to disclose a system of snaps to lock the handle
of the plunger in its "closed" position. All of these features are
very useful in facilitating simple breath condensate collection and
analysis. Neither the specific objective of injecting the sample
onto a port of an immunoassay, nor the objective of being able to
use the condenser as a delivery unit to perform point-of-care pH,
gas tension, lactate and urea measurements can be done with either
the Baddour or Vaughn device.
[0013] Although the Vaughn device appears to propose the use of an
endothermic reaction to cool a condensing chamber, it does not
disclose a means of packaging the reaction to make it easy to use
at the patient's bedside. The Vaughn device also requires a
complicated methodology for expressing collected condensate from a
side port of the condensing chamber. A need exists for a simpler
methodology.
[0014] No prior art device uses a flow transducer to indicate when
an adequate volume of breath has been collected, or provides visual
or aural feedback as to the rate and completion percentage. A
device having such features would be much more convenient to use
than prior art devices.
[0015] Further, no prior art device uses a high efficiency,
miniature refrigeration unit, disposed within the breath collection
device itself, to cool the breath condenser. Such a system would
allow a new condensing chamber to be cooled rapidly without storing
the chamber beforehand in a freezer and without resorting to means
such as an endothermic reaction to provide a cooling effect.
[0016] A need exists for a full-featured breath condensate
collection apparatus for separating alveolar phase exhaled breath
from expired airway phase exhaled breath, having improved cooling
features, a housing that substantially encloses the various
components in order to protect them, to protect the user from
uncomfortable heat or cold produced thereby, to avoid contamination
to or from the components, to provide greater convenience of use to
the user, and to provide built-in analysis of the condensate
collected therein.
SUMMARY OF THE PRESENT INVENTION
[0017] The device is designed to allow selective collection of
breath condensate contained within the alveolar volume of expired
breath. The device consists of port into which a patient breathes,
connected in fluid series to a chamber with a port to allow
transmission and measurement of percentage absorption of a light
beam in the exhaled sample. In a preferred embodiment, when the
concentration of CO.sub.2 increases above a specified threshold, or
increases at a specified rate, a rotary solenoid is actuated which
is connected to a valve. This action causes the valve to rotate
90.degree., causing the exhaled breath to be diverted into a
condensing chamber.
[0018] Other general features include a built-in refrigeration
system, a built-in analyzer, a flow transducer and microcontroller
for measuring total volume of exhaled breath and signaling the user
when a sufficient volume has been detected, and a housing in which
the various components may be carried, including some disposable
components and some reusable components.
[0019] Broadly defined, the present invention according to one
aspect is a method of diagnosing particular diseases based on
expired breath from a mammalian subject, including: providing a
breath condensate collection device having condensing chamber, a
fluid inlet and a fluid outlet; cooling the condensing chamber;
receiving, at the fluid inlet, at least one exhaled breath from a
mammalian subject; separating the exhaled breath into an expired
airway phase volume and an alveolar phase volume; condensing
portions of either the expired airway phase portion of the exhaled
breath or the alveolar phase volume of the exhaled breath, but not
both, in the condensing chamber to produce condensate on the inner
surfaces of the condensing chamber; removing the condensate from
the condensing chamber; analyzing the condensate for markers
indicative of respiratory disease; and rendering a diagnosis at
least partly on the basis of whether the condensate being analyzed
came from the expired airway phase portion of the exhaled breath or
the alveolar phase volume of the exhaled breath.
[0020] In features of this aspect, the separating takes place
between the fluid inlet and the condensing chamber; the markers
include biochemicals; the biochemicals include inorganic gases,
volatile organic molecules, proteins, nucleic acids, lipids, lipid
A, endotoxin and other impervious nonorganic exogenous materials;
the markers include microbes; the microbes include viruses, fungi,
mycoplasma, mycobacteria, bacteria, prions and protozoa; only the
alveolar phase volume of the exhaled breath reaches the condensing
chamber; alternatively, only the expired airway phase volume of the
exhaled breath reaches the condensing chamber; the receiving,
separating and condensing steps are repeated in order to increase
the amount of condensate produced in the condensing chamber; and
the method further includes expressing the condensate from the
condensing chamber using a piston assembly.
[0021] Broadly defined, the present invention according to another
aspect is a method of collecting breath condensate from a portion
of exhaled breath from a mammalian subject by separating the
expired airway phase of the breath from the alveolar phase,
including: providing a cartridge assembly and a condensing chamber,
the cartridge assembly having a breathing port and at least two
fluid outlets, at least one of which is in fluid communication with
the condensing chamber; cooling the condensing chamber; receiving,
at the breathing port in the cartridge assembly, at least one
exhaled breath from a mammalian subject; monitoring, in the
cartridge assembly, at least one characteristic of the exhaled
breath, the characteristic generally capable of distinguishing the
expired airway phase of the breath from the alveolar phase of the
breath; based on the state of the monitored characteristic,
diverting the flow of the exhaled breath through the cartridge
assembly from one fluid outlet to the other fluid outlet; and upon
receiving a diverted portion of the exhaled breath from the
cartridge assembly, condensing portions of the exhaled breath to
produce condensate on the inner surfaces of the condensing
chamber.
[0022] In features of this aspect, monitoring includes determining
when the exhaled breath has transitioned from the expired airway
phase to the alveolar phase, and diverting the flow of the exhaled
breath based on the state of the monitored characteristic includes
diverting the exhaled breath to the condensing chamber once it is
determined that the alveolar phase of the exhaled breath has begun;
cooling the condensing chamber includes cooling the condensing
chamber to a temperature of less than 0.degree. F.; the diverting
step includes adjusting the state of a valve assembly to prevent
the exhaled breath from passing into the condensing chamber until
the alveolar phase of the exhaled breath has begun and to force the
exhaled breath into the condensing chamber once the alveolar phase
of the exhaled breath has begun; cooling the condensing chamber
includes cooling the condensing chamber to a temperature of less
than 0.degree. C.; and the method further includes expressing the
condensate from the condensing chamber using a piston assembly.
[0023] In other features of this aspect, determining when the
exhaled breath has transitioned from the expired airway phase to
the alveolar phase includes determining when a predetermined level
of a particular predetermined gas is reached; the particular
predetermined gas is selected from the group consisting of
CO.sub.2, O.sub.2, N.sub.2, CO and NO; the monitoring, diverting
and condensing steps are repeated in order to increase the amount
of condensate produced in the condensing chamber; the monitoring,
diverting and condensing steps are repeated for a predetermined
period of time; the monitoring, diverting and condensing steps are
repeated until a predetermined volume of gas has passed into the
condensing chamber; the monitoring and diverting steps are carried
out automatically; and monitoring includes determining when the
exhaled breath has transitioned from the expired airway phase to
the alveolar phase, and diverting the flow of the exhaled breath
based on the state of the monitored characteristic includes
diverting the exhaled breath to the condensing chamber until it is
determined that the alveolar phase of the exhaled breath has
begun.
[0024] Broadly defined, the present invention according to another
aspect is breath condensate collection apparatus including: a
cartridge assembly having a breathing port adapted to permit a
mammalian subject to breathe in and out of the cartridge assembly,
at least a first fluid outlet and a second fluid outlet, a
monitoring system adapted to monitor at least one characteristic of
a generally gaseous fluid passing through the cartridge assembly,
the at least one characteristic generally capable of distinguishing
the expired airway phase of an exhaled breath from the mammalian
subject from the alveolar phase of the exhaled breath, and a valve
assembly operable to divert the flow of fluid, received via the
breathing port, to either the first fluid outlet or the second
fluid outlet on the basis of the state of the monitored
characteristic; and a condensing chamber having double side walls,
including an inner side wall and an outer side wall in spaced
relationship to one another, and first and second opposing ends,
the condensing chamber being in fluid communication with at least
one fluid outlet of the cartridge assembly.
[0025] In features of this aspect, the condensing chamber includes
an outlet and a one-way valve adapted to prevent gas from being
drawn into the condensing chamber during an inhalation by the
mammalian subject while permitting exhaled breath to be exhausted
therethrough during an exhalation by the mammalian subject; the
condensing chamber is cooled to a temperature of less than
0.degree. F.; the condensing chamber is cooled to a temperature of
less than 0.degree. C.; the apparatus further includes a plunger
assembly having a piston and a handle, the piston being slidably
disposed in the interior of the condensing chamber in snug contact
with the inner side wall and the handle extending from the first
end of the condensing chamber so as to permit the piston to be
moved within the central chamber; and in addition to the first
one-way valve, the cartridge assembly further includes an
inhalation port and a second one-way valve adapted to permit
breathing gas to be drawn into the cartridge assembly during an
inhalation by the mammalian subject, and the cartridge assembly
further includes a third one-way valve in at least one of the at
least two fluid outlets adapted to prevent gas from being drawn
into the cartridge assembly during an inhalation by the mammalian
subject while permitting exhaled breath to be exhausted
therethrough during an exhalation by the mammalian subject.
[0026] In other features of this aspect, the actuator device
operates the valve assembly to divert the flow of fluid, received
via the breathing port, to the second fluid outlet instead of to
the first fluid outlet when a predetermined level of a particular
predetermined gas is reached; the predetermined level is reached by
the level of the predetermined gas rising to the predetermined
level; the predetermined level is reached by the level of the
predetermined gas dropping to the predetermined level; the
particular predetermined gas is selected from the group consisting
of CO.sub.2, O.sub.2, N.sub.2, CO and NO; the breathing port, the
at least two fluid outlets and the valve assembly define a
cartridge, and the apparatus further includes a housing adapted to
carry the cartridge, the monitoring system and the condensing
chamber; and the cartridge is adapted to be removable from the
housing for disposal after a single use, while the monitoring
system is adapted for repeated reuse.
[0027] In still further features of this aspect, the actuator
device operates the valve assembly to divert the flow of fluid,
received via the breathing port, to the fluid outlet connected to
the condensing chamber when the predetermined level of the
particular predetermined gas is reached; the actuator device
operates the valve assembly to divert the flow of fluid, received
via the breathing port, away from the fluid outlet connected to the
condensing chamber when the predetermined level of the particular
predetermined gas is reached; the valve assembly includes a valve
adjustable between at least two positions, such that in the first
valve assembly state the valve is in a first position diverting
fluid received at the breathing port to the first fluid outlet and
away from the second fluid outlet, and in the second valve assembly
state the valve is in a second position diverting fluid received at
the breathing port to the second fluid outlet and away from the
first fluid outlet; the valve is a directional flap; the actuator
device is a rotary solenoid; and the valve assembly includes at
least two valves.
[0028] Broadly defined, the present invention according to another
aspect is an apparatus for separating the expired airway phase of
breath exhaled by a mammalian subject from the alveolar phase of
the exhaled breath, including: a fluid inlet; at least a first
fluid outlet and a second fluid outlet; a valve assembly adjustable
between at least two states: a first state wherein fluid received
at the fluid inlet is diverted to the first fluid outlet, and a
second state wherein fluid received at the fluid inlet is diverted
to the second fluid outlet; and a control system that adjusts the
state of the valve assembly, having a spectrometer arranged to
monitor at least one characteristic of a generally gaseous fluid
passing through the separation apparatus, the characteristic
generally capable of distinguishing the expired airway phase of an
exhaled breath from a mammalian subject from the alveolar phase of
the exhaled breath, and an actuator device, coupled to the
spectrometer and the valve assembly, that adjusts the state of the
valve assembly on the basis of the state of the monitored
characteristic.
[0029] In features of this aspect, the spectrometer is arranged to
measure the partial pressure of a particular predetermined gas in
the gaseous fluid passing through the separation apparatus; the
actuator device adjusts the state of the valve assembly from its
first state to its second state when the partial pressure of the
particular predetermined gas reaches a predetermined level; the
partial pressure reaches the predetermined level by rising to the
predetermined level; the partial pressure reaches the predetermined
level by dropping to the predetermined level; the particular
predetermined gas is selected from the group consisting of
CO.sub.2, O.sub.2, N.sub.2, CO and NO; the fluid inlet, the at
least two fluid outlets and the valve assembly define a cartridge
assembly, and the apparatus further includes a housing adapted to
carry the cartridge assembly and the control system; and the
cartridge assembly is adapted to be removable from the housing for
disposal after a single use, while the control system is adapted
for repeated reuse.
[0030] In other features of this aspect, the apparatus further
includes a chamber having an inlet connected in fluid communication
with one of the at least two fluid outlets and adapted to collect
at least a portion of the generally gaseous fluid passing through
the separation apparatus; the chamber is a condensing chamber
adapted to collect liquid condensed out of the generally gaseous
fluid; the chamber is connected to the second fluid outlet, and the
actuator device adjusts the valve assembly from the first state to
the second state when the partial pressure reaches the
predetermined level; the chamber is connected to the second fluid
outlet, and the actuator device adjusts the valve assembly from the
second state to the first state when the partial pressure reaches
the predetermined level; the valve assembly includes a valve
adjustable between at least two positions such that in the first
valve assembly state the valve is in a first position diverting
fluid received at the fluid inlet to the first fluid outlet and
away from the second fluid outlet, and in the second valve assembly
state the valve is in a second position diverting fluid received at
the fluid inlet to the second fluid outlet and away from the first
fluid outlet; the valve is a directional flap; the actuator device
is a rotary solenoid; and the valve assembly includes at least two
valves.
[0031] Broadly defined, the present invention according to another
aspect is a breath condensate collection apparatus including: a
housing; a condensing chamber, carried by the housing, having an
inlet that receives exhaled breaths from a mammalian subject and an
outlet that permits a gaseous, non-condensed portion of the exhaled
breaths to escape from the condensing chamber; and a built-in
refrigeration system, carried by the housing, having a compressor,
an expansion valve, an evaporator pipe arranged to cool the
condensing chamber, and a condenser pipe arranged to dissipate heat
away from the condensing chamber.
[0032] In features of this aspect, the housing includes a cavity
correspondingly shaped and sized to carry the condensing chamber,
and the evaporator pipe is disposed generally around the cavity;
when the condensing chamber is carried in the cavity, the
condensing chamber makes contact with a substantial portion of the
evaporator pipe; the condensing chamber has walls constructed from
a good heat conducting material; the walls of the condensing
chamber are constructed from aluminum; the apparatus further
includes a ventilation system that dissipates heat generated by the
refrigeration system; the ventilation system includes one or more
vents in the housing; the ventilation system includes one or more
fans; and the apparatus further includes a temperature gauge
arranged to provide an indication of the temperature of the
condensing chamber.
[0033] Broadly defined, the present invention according to another
aspect is a portable breath condensate collection apparatus
including: a housing having at least one compartment adapted to
receive and generally enclose a removable cartridge and a removable
condensing chamber in fluid communication with one another; a
removable, disposable cartridge, having at least one inlet, at
least one outlet and a mouthpiece in fluid communication with at
least one inlet, carried in the at least one compartment of the
housing such that at least a portion of the mouthpiece is carried
externally to the housing; and a removable condensing chamber,
having an inlet and an outlet, carried in the at least one
compartment of the housing such that the inlet is in fluid
communication with at least one outlet of the cartridge and the
outlet is open to the environment.
[0034] In features of this aspect, the at least one compartment
includes a compartment having a first section and a second section,
the cartridge is carried in the first compartment section and the
condensing chamber is carried in the second compartment section;
alternatively, the at least one compartment includes at least a
first compartment and a second compartment, the cartridge is
carried in the first compartment and the condensing chamber is
carried in the second compartment; the cartridge includes a valve
assembly for alternately permitting or preventing the flow of
fluids through the cartridge and into the condensing chamber; the
apparatus further includes a control system, carried by and
generally enclosed in the housing, for the valve assembly; and the
control system is adapted to remain in the housing for repeated
reuse while the cartridge and the condensing chamber are
removed.
[0035] In other features of this aspect, the apparatus further
includes an analyzer, carried by and generally enclosed in the
housing, adapted to provide information regarding the content of
breath condensate received therein, and a conduit disposed in
sealed fluid communication between the condensing chamber and the
analyzer, adapted to guide breathe condensate from the condensing
chamber to the analyzer; wherein the condensing chamber further
includes a piston and a handle, the piston is slidably disposed in
the interior of the condensing chamber in snug contact with the
inside of the condensing chamber and the handle extends from the
first end of the condensing chamber so as to permit the piston to
be moved within the central chamber; and the piston is operable to
force breath condensate collected in the condensing chamber to the
conduit leading to the analyzer.
[0036] Broadly defined, the present invention according to another
aspect is a breath condensate collection apparatus including: a
housing; a condensing chamber, carried by the housing; an inlet,
carried by the housing, that receives exhaled breath from a
mammalian subject; a conduit disposed in sealed fluid communication
between the inlet and the condensing chamber; a gas flow
measurement device, disposed in the conduit, that measures the flow
of gas through the conduit; and a control system, coupled to the
gas flow measurement device, that determines when a predetermined
volume of gas has passed through the conduit.
[0037] In features of this aspect, the conduit, the gas flow
measurement device and the control system are carried by the
housing; the apparatus further includes a signaling device that
generates a user-identifiable indication that the predetermined
volume of gas has passed through the conduit; the gas flow
measurement device is a gas flow transducer and the control system
includes a microcontroller that is electrically connected to the
gas flow transducer; the signaling device includes a speaker that
generates a user-audible signal; the user-audible signal changes,
as a mammalian subject breathes through the apparatus, to provide
an indication of progress toward reaching the predetermined volume
of gas; the signaling device includes at least one user-visible
light; and the at least one user-visible light includes a plurality
of user-visible lights that light sequentially, as a mammalian
subject breathes through the apparatus, to provide an indication of
progress toward reaching the predetermined volume of gas.
[0038] Broadly defined, the present invention according to another
aspect is a breath condensate collection apparatus for separating
the expired airway phase of breath exhaled by a mammalian subject
from the alveolar phase of the exhaled breath, including: a
housing; a cartridge assembly having a breathing port, at least two
fluid outlets, a valve assembly adjustable between at least two
states, including a first state wherein gas received at the
breathing port is diverted to a first of the at least two fluid
outlets, and a second state wherein gas received at the breathing
port is diverted to a second of the at least two fluid outlets, a
monitoring system arranged to monitor at least one characteristic
of gas passing through the separation apparatus, the characteristic
generally capable of distinguishing the expired airway phase of an
exhaled breath from a mammalian subject from the alveolar phase of
the exhaled breath, and an actuator device, coupled to the
monitoring system and the valve assembly, that adjusts the valve
assembly state on the basis of the state of the monitored
characteristic; a condensing chamber, having an inlet and an
outlet, carried by the housing such that the inlet is in fluid
communication with at least one outlet of the cartridge assembly
and the outlet is open to the environment; and a built-in
refrigeration system, carried by the housing.
[0039] In features of this aspect, the housing includes at least
one compartment adapted to receive and generally enclose the
cartridge assembly and the condensing chamber in fluid
communication with one another; the condensing chamber is adapted
to be removed from the housing after use and replaced by a
previously-unused condensing chamber; the cartridge assembly is
adapted to be removed from the housing after use and replaced by an
unused cartridge assembly; the condensing chamber has double side
walls and first and second opposing ends, and the double side walls
include an inner side wall and an outer side wall in spaced
relationship to one another; the built-in refrigeration system
includes a compressor, an expansion valve, an evaporator pipe
arranged to cool the condensing chamber, and a condenser pipe
arranged to dissipate heat away from the condensing chamber; and
the apparatus further includes a conduit disposed in sealed fluid
communication between the valve assembly and the condensing
chamber, a gas flow measurement device, disposed in the conduit,
that measures the flow of gas through the conduit, and a control
system, coupled to the gas flow measurement device, that determines
when a predetermined volume of gas has passed through the
conduit.
BRIEF DESCRIPTION OF THE DRAWINGS
[0040] Further features, embodiments, and advantages of the present
invention will become apparent from the following detailed
description with reference to the drawings, wherein:
[0041] FIG. 1 is a side view of a device for collection of exhaled
alveolar breath condensate in accordance with a preferred
embodiment of the present invention;
[0042] FIG. 2 is a front view of the device of FIG. 1;
[0043] FIG. 3 is a top view of the housing of FIG. 1 with the
cartridge lid removed to show the cartridge assembly;
[0044] FIG. 4 is a top view of the housing of FIG. 1 with the
cartridge assembly and the syringe removed;
[0045] FIG. 5 is a side cross-sectional view of the device of FIG.
2, taken along line 5-5;
[0046] FIG. 6 is a schematic view of the cartridge assembly of FIG.
3;
[0047] FIG. 7 is an enlarged perspective view of the cartridge of
FIG. 1;
[0048] FIG. 8 is a right side view of the cartridge of FIG. 7;
[0049] FIG. 9 is a top view of the cartridge of FIG. 7;
[0050] FIG. 10 is a rear view of the cartridge of FIG. 7;
[0051] FIG. 11 is a side view of the directional flap of FIG.
7;
[0052] FIG. 12 is a side perspective view of the directional flap
of FIG. 7;
[0053] FIG. 13 is a partially-schematic side cross-sectional view
of the cartridge of FIG. 10, taken along line 13-13, showing the
directional flap in a closed position;
[0054] FIG. 14 is a partially-schematic side cross-sectional view
of the cartridge of FIG. 10, taken along line 13-13, showing the
directional flap in an open position;
[0055] FIG. 15 is a left side view of the cartridge of FIG. 7
showing the attachment of a spring to the directional flap;
[0056] FIG. 16 is a rear view of the cartridge assembly of FIG. 3,
shown removed from the housing;
[0057] FIG. 17 is an enlarged perspective view of the rotary
solenoid of FIG. 16;
[0058] FIG. 18 is a side view of a first exemplary syringe for use
in the device of FIG. 1;
[0059] FIG. 19 is a front view of the syringe of FIG. 18;
[0060] FIG. 20 is a side cross-sectional view of the syringe of
FIG. 19, taken along line 20-20;
[0061] FIG. 21 is a side cross-sectional view of a device for
collection of exhaled alveolar breath condensate in accordance with
a second preferred embodiment of the present invention;
[0062] FIG. 22 is a side cross-sectional view of a device for
collection of exhaled alveolar breath condensate in accordance with
a third preferred embodiment of the present invention;
[0063] FIG. 23 is a side cross-sectional view of the device of FIG.
22 showing the plunger assembly in a fully inserted position;
and
[0064] FIG. 24 is a schematic view of an auxiliary control system
for use with the device of FIGS. 1, 21 and 22.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0065] Referring now to the drawings, in which like numerals
represent like components throughout the several views, the
preferred embodiments of the present invention are next described.
The following description of the preferred embodiment(s) is merely
exemplary in nature and is in no way intended to limit the
invention, its application, or uses.
[0066] FIG. 1 is a side view of a device 10 for collection of
exhaled alveolar breath condensate in accordance with a preferred
embodiment of the present invention. The device 10 includes a
housing 12, a disposable mouthpiece 14, a handle 16, an intake
cartridge assembly 20 and a syringe 80. The size and shape of the
housing 12 and the handle 16 are designed to permit the device 10
to be readily held by a patient, but the device 10 may also be
mounted on the side of a hospital bed or gurney, attached to a
rolling mobile stand, or the like, using suitable mounting hardware
(not shown).
[0067] FIG. 2 is a front view of the device 10 of FIG. 1. The
housing 12 is generally cylindrical and is designed to support the
intake cartridge assembly 20 and the syringe 80 therein. The
housing 12 includes a cartridge lid 13 secured to the remainder of
the housing 12 by a hinge 11. The cartridge lid 13 may thus be
opened to facilitate access to the cartridge assembly 20 disposed
inside the housing 12.
[0068] FIG. 3 is a top view of the housing 12 of FIG. 1 with the
cartridge lid 13 removed to show the cartridge assembly 20, FIG. 4
is a top view of the housing 12 of FIG. 1 with the cartridge
assembly 20 and the syringe 80 removed, and FIG. 5 is a side
cross-sectional view of the device 10 of FIG. 2, taken along line
5-5. As shown therein, the housing 12 may include a variety of
compartments, recesses, pockets or the like for receiving the
various components of the device 10. In particular, one end of the
housing 12 may be devoted to the components of the cartridge
assembly 20, while the other end houses the syringe 80. The housing
10 includes a cartridge compartment, a two spectrometer pockets, an
actuator pocket, and other pockets and recesses for various parts
and functions described below. In addition, the housing 12 includes
external openings through at each end as well as two openings in
its bottom and an opening penetrating the cartridge lid 13. The
purpose of each of these openings will become apparent
hereinbelow.
[0069] FIG. 6 is a schematic view of the cartridge assembly 20 of
FIG. 3. The cartridge assembly 20 includes a disposable cartridge
22 and a control system 60. The control system 60 is used to
control a directional flap 36 in the cartridge 22, which regulates
the path of exhaled breath through the cartridge 22. The operation
of the control system 60 and the cartridge 22 will be more fully
described hereinbelow.
[0070] FIGS. 7-10 are perspective, right side, top and rear views
of the cartridge 22 of FIGS. 5 and 6. The cartridge 22 may be
formed from polyethylene, polycarbonate, polyvinyl, plastic, glass
or the like and includes a breathing port 24, an inhalation port
26, an absorption chamber 28, a collection port 30, an exhaust vent
32, a pair of spectrometer windows 34 and a valve assembly that may
include the directional flap 36, a spring 50 and a pin or boss 52
protruding from an exterior surface of the cartridge 22. The
breathing port 24 is fluidly connected between the absorption
chamber 28 and the mouthpiece 14 to permit a user to breathe in and
out through the cartridge 22. The inhalation port 26 includes a
one-way valve 27 that permits ambient air to be drawn through the
cartridge 22 during the user's inhalation cycle. The collection
port 30 is in fluid communication with the syringe 80 and includes
a one-way valve 31 to prevent gases in the syringe 80 from
returning to the cartridge 22. The exhaust vent 32 permits unwanted
exhaled breath to be vented to the environment and includes a
one-way valve 33 to prevent air from entering the cartridge 22
therethrough. It should be noted that although FIGS. 7 and 10, and
some of the other illustrations, show the exhaust vent 32 as being
round, it may be preferable for the exhaust vent 32 to be
rectangular or some other shape. The emitter and sensor units 64,
66 of a spectrometer or other monitoring system 62 may be stationed
adjacent the spectrometer windows 34, as described below, in order
to measure the content of gas contained in the absorption chamber
28 of the cartridge 22.
[0071] FIGS. 11 & 12 are side and perspective views,
respectively, of the directional flap 36 of FIG. 7. The directional
flap 36 includes a central shaft 37, arranged around an axial pin
44, from which a deflector plate 38 is supported by a pair of arms
39, 41. As illustrated in FIG. 8, a pair of tabs 40, 42 extend
laterally from the ends of a flange 43, supported by the central
shaft 37, for purposes made clear hereinbelow. The directional flap
36 may be adjusted to force the exhaled breath in the interior of
the cartridge 22 to be exhausted either through the collection port
30 or the exhaust vent 32. As perhaps best shown in FIGS. 8 and 9,
the flap 36 is supported in the interior if the cartridge 22 by the
arms 39, 41, which extend through slots 45 in the sides of the
cartridge 22.
[0072] FIGS. 13 and 14 are partially-schematic side cross-sectional
views of the cartridge 22 of FIG. 10, taken along line 13-13,
showing the directional flap 36 in a closed position and an open
position, respectively. In the closed position shown in FIG. 13,
the deflector plate 38 blocks the air path to the collection port
30 that forms the portal between the cartridge 22 and the syringe
80. This forces all expelled breath to be exhausted through the
exhaust vent 32. On the other hand, in the open position shown in
FIG. 14, the deflector plate 38 covers the exhaust vent 32, forcing
all expelled breath through the collection port 30 and into the
syringe 80. Preferably, gaskets 46, 48 or other sealing devices and
methods may be used to seal the deflector plate 38 and any other
necessary surfaces of the directional flap 36 to the various
internal structures of the cartridge 22 in order to ensure that
gases of the wrong type are not passed through the wrong
opening.
[0073] FIG. 15 is a left side view of the cartridge 22 of FIG. 7
showing the attachment of the spring 50 to the directional flap 36.
The spring 50 or an equivalent device is preferably provided in
order to bias the directional flap 36 in a normally-closed
position. One purpose of this is to prevent gases and fluids
collected in the syringe 80 from escaping back through the
cartridge 22. In one embodiment, the spring 50 is a simple coil
spring that is interconnected between one of the tabs 42 on the
directional flap 36 and the boss 52 on the exterior surface of the
cartridge 22, as perhaps best shown in FIGS. 9 and 10. Other
biasing devices and methods will be apparent to one of ordinary
skill in the art.
[0074] Moreover, it will be apparent that the valve assembly may
take on any number of different constructions. For example, the
directional flap 36 and the biasing device may be internalized
within the cartridge 22 in order to provide better sealing, improve
operation, or the like. Further, the valve assembly may include two
flap-type valves operating in conjunction with each other instead
of the single flap 36 disclosed and described herein, or the
directional flap 36 may be replaced with a valve mechanism of any
suitable alternative type, including but not limited to one rotary
valve, a sliding door, a slip barrel, a plunger, or the like, with
corresponding changes to the cartridge, biasing device, and the
like being apparent to those of skill in the art.
[0075] Returning to FIG. 6, the control system 60 includes a
monitoring system 62, a control unit 67 and an actuator device 70.
The control unit 67 may include an amplifier/differentiator 68 and
a monitoring system controller 69. A variety of monitoring systems
may be employed using different physical phenomena as triggers for
the directional flap. One monitoring system 62 suitable for use in
the preferred embodiments of the present invention is a
spectrometer, which may be of any conventional type, including
infrared (IR), laser, and the like, and includes a radiation
source, or emitter unit 64, disposed on one side of the absorption
chamber 28 and a sensor unit 66 disposed on the opposite side,
adjacent the spectrometer windows 34. FIG. 16 is a rear view of the
cartridge assembly 20 of FIG. 3, shown removed from the housing 12.
In operation, radiation from the emitter unit 64 passes through the
spectrometer window on one side of the cartridge 22, through the
absorption chamber 28 and through the absorption window 34 to the
sensor unit 66, where the received radiation is analyzed.
[0076] IR spectrometers may use chopped IR light emission, where
the emission is chopped at a frequency appropriate to distinguish
absorbance of the gas of interest, such as CO.sub.2, from
background absorbance. Alternatively, laser diode spectrometry can
be used for detection of more than one gas for the purpose of
actuating the directional flap and for the purpose of determining
the presence of various pathophysiological processes that are
specific to certain disease states. Lasers using AlGaAs, AlGaInP or
a Vertical Cavity diodes operating in the near infrared or visible
light spectrum at room temperature and ambient pressure in the
1-100 mW power range will be sufficient. The physical length
between the emission and detection probe will be approximately 1-3
cm, but the apparent pathlength may be increased by light
reflection using dielectrim mirrors to increase sensitivity.
Detection wavelengths will be 1390 nm for CO.sub.2 and 760 nm for
O.sub.2, but other gases may be detected by the laser to assist in
diagnosis of specific diseases, including lung ischemia, by the
detection of the relative amounts of nitric oxide (NO) at 1800 nm
and carbon monoxide (CO) at 1570 nm. It is anticipated that further
research will reveal significance of laser-based quantification of
other inorganic gases and volatile organic compounds to serve as
adjuncts to the chemical analyses of the breath condensate in
arriving at a final diagnosis of certain disease processes.
[0077] Spectrometers are available from a variety of manufacturers,
and the selection and implementation of one suitable for use with
the present invention would be apparent to one of ordinary skill in
the art. As is well known, the sensor unit 66 measures the percent
transmission of the radiation to allow measurement of the partial
pressure of certain gases in the absorption chamber 28. Measured
gases may include carbon dioxide, oxygen, nitrogen, nitrogen
oxides, carbon monoxide, aliphatic and aromatic hydrocarbons,
isoprostenoid derivatives, or amino acids dissolved in exhaled
aerosolized droplets.
[0078] One type of actuator device 70 suitable for use in the
preferred embodiments of the present invention is a rotary
solenoid: The rotary solenoid 70 utilizes a clutch mechanism to
adjust or move the directional flap 36 back and forth between its
open and closed positions. FIG. 17 is an enlarged perspective view
of the rotary solenoid 70 of FIG. 16. As illustrated therein, an
actuator shaft 74 extends from the solenoid body 72. A slot 76 in
the end of the actuator shaft 74 may be firmly coupled to one of
the tabs 40 on the directional flap 36 in order to provide
rotational movement to the tab 40 and likewise rotating the
directional flap 36 between its open and closed positions. If
necessary, the directional flap tab 40 and the actuator shaft 74 of
the rotary solenoid 70 may be disposed coaxially with the pin 44 of
the directional flap in order to minimize wear on the components.
Rotary solenoids 70 are available from a variety of manufacturers,
and the selection and implementation of one suitable for use with
the present invention would be apparent to one of ordinary skill in
the art. It should also be apparent that other actuating devices
and methods may be employed without departing from the scope of the
present invention, including pulley mechanisms, magnetic actuation
of a metallic valve, and the like, triggered from expired volume
measured from a flow transducer rather than from light absorption
technique.
[0079] FIGS. 18 and 19 are side and front views, respectively, of a
first exemplary syringe 80 for use in the device 80 of FIG. 1. As
illustrated therein, the syringe 80 includes an insulated
condensing chamber 82 having a plunger assembly 84, an inlet 86 and
an exhaust port 88. The condensing chamber 82 may be constructed of
any suitable material, including, but not limited to, glass,
plastic, polyethylene, polycarbonate, or polyvinyl or other
synthetic polymer.
[0080] FIG. 20 is a side cross-sectional view of the syringe 80 of
FIG. 18, taken along line 20-20. As shown therein, the insulative
effect of the condensing chamber 82 may be provided by any of a
variety of materials either formed directly into the walls (not
illustrated) of the condensing chamber or sandwiched between an
inner wall 90 and an outer wall 92. Arranged peripherally between
the inner and outer walls 90, 92 is a layer of a material 94
suitable for creating an endothermic reaction, such as
NH.sub.4NO.sub.3, that has been vacuum-packed and sealed. The
condensing chamber 82 is preferably provided with a needle port 96
or some other means for permitting the sealed material 94 to be
hydrated or otherwise injected with a readily available catalyst in
order to trigger an endothermic reaction when the syringe 80 is
ready to be used. If NH.sub.4NO.sub.3 is to be used, then the
NH.sub.4NO.sub.3 may be hydrated with water in a 1:4 molar ratio.
Such a material is preferred because a user may trigger the
reaction by injecting the NH.sub.4NO.sub.3 material with a preset
volume of tap water or saline via the needle port 96, similar to
the way a nurse would "flush" an IV line. However, other materials
may likewise be used to create a suitable endothermic reaction.
[0081] The inner surfaces of the condensing chamber 82 define a
central cylinder in which is fitted the plunger assembly 84. The
plunger assembly 84 includes a piston 98, a rubber gasket 100, a
handle 102 extending from one end of the condensing chamber 82, and
a clip assembly 104 disposed at the handle end of the condensing
chamber 82. The inlet 86 is preferably disposed at the opposite end
of the condensing chamber 82 from the plunger assembly 84 and may
be arranged in the form of a nipple. The exhaust port 88 is
preferably disposed at the same end of the condensing chamber 82 as
the handle 102 and is equipped with a one-way valve 106 to permit
gases passing through the condensing chamber 82 to be exhausted
therethrough while preventing ambient gases from entering the
condensing chamber 82.
[0082] Although not shown herein, a second exemplary syringe
suitable for use (with minor modifications) in the device 10 of
FIG. 1 is a double-walled syringe of a type somewhat similar to one
disclosed in the commonly-assigned U.S. Provisional Patent
Application 60/434,916, filed Dec. 20, 2002. The construction of
this syringe is similar to that of the first, except that the space
between the inner and outer walls of the condensing chamber is
filled with water, polyethylene glycol ("PEG"), or another suitable
coolant material and the outer wall is then sealed to the inner
wall to prevent leakage. A syringe of this type may be cooled by
placing it in a standard freezer prior to use in order to lower the
temperature of the syringe to less than 0.degree. F., and
preferably to less than 0.degree. C. Details of this type of
syringe are provided in the aforementioned provisional patent
application.
[0083] In operation, the housing lid 13 is opened and the cartridge
assembly 20 is inserted into the housing 12 such that the various
components are snapped into place in their respective compartments
in the housing 12. Next, a syringe 80 of one of the types described
above is retrieved from storage and inserted into the open end of
the housing 12, nipple-shaped inlet 86 first, and pushed inward
until the inlet 86 is coupled to the collection port 30 of the
cartridge 22.
[0084] Depending on the syringe type, the syringe 80 may have been
stored in a refrigeration device, such as a conventional household
freezer, that is capable of lowering the temperature to less than
0.degree. F., and preferably less than 0.degree. C., in order to
freeze the jacket of coolant material 94 contained between the
inner and outer walls 90, 92 of the condensing chamber 82.
Alternatively, syringes of the endothermic reaction type may merely
be stored at an ambient temperature and then cooled to the desired
temperature by triggering an endothermic reaction therein when
ready for use. If the mouthpiece 14 is stored separately from the
rest of the device 10, then the mouthpiece 14 may be assembled to
the cartridge assembly 20. In some applications, such as when the
device 10 is to be attached to a bed or to a rolling stand, it may
be useful to connect the mouthpiece 14 to a longer tube (not shown)
in sealed fluid communication with the breathing port 24 of the
cartridge 22.
[0085] Once the device 10 is assembled, the patient positions the
mouthpiece 14 in sealed relationship to his mouth area and inhales
and exhales through the mouthpiece 14. When the patient inhales,
ambient air enters through the inhalation port 26 via the one-way
valve 27. The exhaled breath is guided into the absorption chamber
28 via the breathing port 24. Under the control of the monitoring
system controller 69, the spectrometer 62 measures the partial
pressure of certain gases in the absorption chamber 28 and delivers
an analog current to the amplifier/differentiator 68. For example,
the magnitude of the analog signal may be proportional to the
amount of CO.sub.2 present in the absorption chamber 28.
[0086] At the beginning of an expiration by the patient, the
patient's breath is dilute in carbon dioxide and rich in oxygen. In
one preferred embodiment, the rotary solenoid 70 and the
amplifier/differentiator 68 are calibrated such that the
directional flap 36 remains in its resting state, wherein the flap
36 is held in its closed position by the spring 50, and the airway
deadspace is shunted out the exhaust vent 32 to the environment. As
the patient's alveoli begin to empty during expiration, the partial
pressure of CO.sub.2 increases and the partial pressure of oxygen
decreases. The resulting signal generated by the
amplifier/differentiator 68 eventually activates the solenoid 70,
causing the directional flap 36 to open. At this point, the
alveolar gas and associated water content are directed selectively
to the syringe 80.
[0087] To maximize the efficiency of collection of breath
condensate, the deadspace volume of the cartridge 22 should
preferably be minimized to less than 20 mL. It will also be
preferable for patients to exhale deeply through the device 10 in
order to enhance the amount of condensation in the alveolar phase.
Thermodynamic and kinetic modeling has suggested that forced
exhalation will enhance the transfer of alveolar water into vapor
and droplet phase. Thus the device 10 is preferably designed to
impart a small resistance to exhaled flow. The outlet diameter and
length of the collection port 30, connected to the condensing
chamber 82, will be calibrated to provide a small amount of
resistance to exhalation, which the patient should be able to
detect, but which is not enough to cause exhalation to be
excessively laborious.
[0088] As portions of the expired breath pass into the syringe 80,
the moisture in the breath begins to condense on the inner surfaces
of the condensing chamber 82. Because of the depressed temperature
of the condensing chamber 82, condensate begins to collect and may
immediately freeze on the inner surfaces thereof. Once the
patient's breath has warmed the condensing chamber 82 sufficiently,
the condensate will melt and may be expressed from the condensing
chamber 82. The construction of the condensing chamber 82 is
preferably calibrated to provide a sufficient quantity of
condensate (approximately 250 microliters) after a predetermined
number of breaths. When sufficient condensate has been collected,
the syringe 80 may be removed from the housing 12 and the plunger
assembly 84 depressed to force the collected condensate from the
nipple 86 as described previously. Finally, once the condensate has
been collected and withdrawn, the mouthpiece 14, the cartridge 22
(but preferably not the control system 60, which is designed to
remain uncontaminated and would be relatively expensive to replace
after each use) and the syringe 80 may be disposed of according to
conventional waste disposition procedures, and the collected
condensate may be taken to a suitable analyzer for analysis.
[0089] Because of the relatively small quantities of liquid
condensate that may typically be collected using devices 10 of the
present invention, it may be useful to include specialized features
in the piston 98 and other components in order to maximize the
amount of condensate that may be collected. For example, although
not absolutely necessary, the piston 98 shown in the various
illustrations includes a tip or protrusion 99 of dimensions and
shape suitable for fitting snugly into the nipple-shaped inlet 86
when the plunger assembly 84 is fully depressed. This helps to
ensure that as much condensate as possible is forced out of the
inlet 86. In addition, however, the protrusion 99 may, for example,
include grooves, tunnels, or the like for guiding condensate from
the condensing chamber 82 to the inlet 86 and out. Specialized
pistons 98 such as these are more fully described in the
aforementioned U.S. Provisional Patent Application 60/434,916.
[0090] The analysis of the collected condensate may be carried out
using any conventional analysis technique or system. The analysis
may focus on identifying and quantifying the presence of a variety
of markers of various respiratory diseases. The markers may include
microbes such as viruses, fungi, mycoplasma, mycobacteria,
bacteria, prions and protozoa, and biochemicals such as inorganic
gases, volatile organic molecules, proteins, nucleic acids, lipids,
lipid A, endotoxin and other impervious nonorganic exogenous
materials such as inhaled particulate including asbestos,
silicates, coal dust and the like. These markers and the analysis
techniques and systems are well known to those of ordinary skill in
the art. Once the analysis is complete, however, a more accurate
diagnosis may be made by taking into account the exhalation cycle
phase or phases in which the markers were found.
[0091] FIG. 21 is a side cross-sectional view of a device 110 for
collection of exhaled alveolar breath condensate in accordance with
a second preferred embodiment of the present invention. In this
alternative embodiment preferred for its completely self-contained
nature, the device 110 includes a refrigeration system 120 built
into its housing 112. The refrigeration system 120 is generally of
conventional design and includes a compressor 122, an expansion
valve (not shown), a distribution system 126 and an exhaust system
140. However, it should be apparent that other types of cooling
systems may likewise be utilized without departing from the scope
of the present invention. For example, instead of a conventional
refrigeration system 120, the alternative device 110 may utilize a
cooling jacket comprised of a layer of a liquid having a very low
freezing point, such as PEG, in a bag made of rubber or the like,
or may use an electric cooler making use of the thermoelectric
effect, or other cooling methodologies.
[0092] The device 110 may utilize an alternative syringe 180 having
a single-walled condensing chamber 182 and a plunger assembly and
other features as described herein. The distribution system 126 is
a piping or tubing structure having a evaporator (cold) pipe or
coil 128 and a condenser (hot) coil 130. The evaporator coil 128
surrounds the recess into which the condensing chamber 182 is
inserted. Although not shown herein, the evaporator coil 128 may
even make direct contact with the wall of the condensing chamber
182. Preferably, the walls of the condensing chamber 182 are formed
of aluminum or another good heat conducting material, thus
permitting the refrigeration system 120 to rapidly cool the
condensing chamber 182, thus facilitating breath condensate
collection within seconds of inserting the syringe 180 therein.
[0093] The condenser coil 130 may be cooled using convection
cooling via the exhaust system 140, which may include fans 142 and
vents 144 such as those shown in the side and end, respectively, of
the housing 112 in FIG. 21. The exhausted heat should preferably be
directed away from the patient. The compressor 122 may operate
using standard 110 volt electrical power or using power supplied by
a suitable battery pack. A temperature gauge (not shown) may be
provided to indicate when the temperature of the condensing chamber
182 has been lowered sufficiently to allow breath condensation to
occur with adequate efficiency, which may be important if the
device 110 has not been used for an extended period of time.
[0094] FIG. 22 is a side cross-sectional view of a device 210 for
collection of exhaled alveolar breath condensate in accordance with
a third preferred embodiment of the present invention. In this
alternative embodiment preferred for its still greater
functionality and convenience, the device 210 includes a built-in
breath condensate analyzer 220. The built-in analyzer feature may
be combined with the built-in refrigeration system 120 described
above, or may be utilized separately. In order to deliver the
collected condensate to the analyzer 220, a syringe 280 having a
special condensing chamber 282 may be utilized. The condensing
chamber 282 differs from previously-described condensing chambers
82, 182 in that it includes a small side port 283 extending
radially from the entry end of the condensing chamber 282. This
permits collected condensate to be expressed directly into the
analyzer 220. In addition, it should be noted that the plunger
assembly 84 must include a tip or protrusion 99 of a type described
previously (or a similar structure) in order to completely plug the
nipple-shaped inlet 86 of the condensing chamber 282, thereby
preventing condensate from passing back into the cartridge 22 when
the plunger assembly 84 is depressed.
[0095] In use, a syringe 280 is first inserted into the housing 212
of the device 210. A groove or channel may be provided in the
recess of the housing 212 in order to guide the side port 283 into
fluid communication with an inlet 221 for the analyzer 220. If the
device 210 is equipped with a built-in refrigeration system 120 as
described previously, then the condensing chamber 282 may be cooled
once it is in place in the housing 112; otherwise, the condensing
chamber 282 should be cooled ahead of time. Condensate is then
collected in a similar manner to that described hereinabove. When
sufficient condensate has been collected, the plunger assembly 84
may be depressed until the plunger handle 102 snaps into place.
FIG. 23 is a side cross-sectional view of the device of FIG. 22
showing the plunger assembly 84 in a fully inserted position. This
forces the analyte out of the side port 283 and into the analyzer
220, which may include an analysis matrix, such as an immunoassay
screen, or permits it to be aspirated by vacuum into an analysis
chamber contained within the housing 212 of the device 210.
[0096] FIG. 24 is a schematic view of an auxiliary control system
54 for use with the devices 10, 110, 210 of FIGS. 1, 21 and 22. The
auxiliary control system 54 includes a flow transducer 55, a
microcontroller or other computer device or electronic logic module
56, and one or more signaling devices 57, 58. The flow transducer
55 may be installed anywhere along the flow path extending from the
directional flap 36 in the cartridge 22 to the exhaust port 88 of
the respective syringe 80, 180. 280 but is preferably installed at
the collection port 30 of the cartridge 22. The microcontroller 56
is interconnected between the flow transducer 55 and the signaling
devices 57, 58.
[0097] In operation, the flow transducer 55 measures the exhaled
alveolar volume passing through the collection port 30 of the
cartridge 22 and generates a corresponding analog signal that is
monitored by the microcontroller 56. The exhaled alveolar volume
that is required in order to produce the volume of condensate
needed for accurate chemical analyses can be preprogrammed, based
upon experimental analysis, into the microcontroller 56. When the
microcontroller 56 determines that that volume has been reached, it
transmits a suitable electronic signal to the signaling devices 57,
58, which may include a speaker, one or more LED's or other visual
signal devices, or the like. Thus, when the speaker 57 sounds or
the LED's 58 light, the operator of the respective device 10, 110,
210 is notified that the breath collection process has been
completed. Alternatively, the microcontroller 56 may utilize a more
complex signaling pattern, wherein the audible signal emitted by
the speaker 57 rises in pitch or in intensity as the process
progresses, or a series of LED's 58 are sequentially lit as the
process progresses. This approach allows the patient and operator
to know how much more breathing is required to complete
condensation collection, which may be particularly advantageous for
breath collection from children.
[0098] It should be apparent that the devices 10, 110, 210 of
various embodiments of the present invention may also be used to
capture expired breath from the expired airway phase, rather than
the alveolar phase, merely by reversing the triggering point for
the solenoid 70. This may be accomplished by calibrating the rotary
solenoid 70 and the amplifier/differentiator 68 such that the
directional flap 36 is initially held in its active state, wherein
the flap 36 is held in its open position by the solenoid 70.
Alternatively, the spring 50 or other biasing means may be adjusted
to bias the directional flap 36 in its open position, and the
control system 60 may be adjusted such that when the solenoid 70 is
activated, the flap 36 is closed.
[0099] The operation of this variation is as follows. As described
previously, at the beginning of an expiration by the patient, the
patient's breath is dilute in carbon dioxide and rich in oxygen.
Thus, when the flap 36 is open, the airway deadspace and associated
water content are directed selectively to the syringe 80. As the
patient's alveoli begin to empty during expiration, the partial
pressure of CO.sub.2 increases and the partial pressure of oxygen
decreases. The resulting signal generated by the
amplifier/differentiator 68 eventually deactivates the solenoid 70,
causing the directional flap 36 to close. At this point, the
alveolar gas is shunted out the exhaust vent 32 to the environment.
The threshold concentration value for CO.sub.2 is preferably set at
approximately 4 torr, so that once the concentration of CO.sub.2
exceeds that value, the actuator device 70 closes the flap 36, thus
preventing further exhaled breath from passing into the syringe
80.
[0100] Thus, this alternative arrangement may be used to provide
specific separation of the expired airway phase from the alveolar
phase. More specifically, this would allow selective
spectrophotometric measurement of expired concentrations of
inorganic gases and volatile organic compounds, as well as
collection of expired condensate derived only from the airway phase
of exhalation. Then, the condensing chamber 82 could be replaced
and the triggering mechanism could be reset to alveolar collection
mode, and the process repeated. Because the condensate collected
during alveolar collection mode would be from the same subject as
that collected during the expired airway mode, the cartridge 22
would not necessarily need to be replaced when changing modes;
however, the cartridge 22 may likewise be replaced, if desired, in
order to avoid contaminating the condensate collected in one mode
with any residual condensate or remaining fluids still present in
the cartridge 22 after operation in the first mode.
[0101] The advantage of this differential sample collection would
be the distinction of pathological processes affecting the lining
of the bronchial tree versus processes primarily affecting the
alveoli. The ability to distinguish lower airway disease (e.g., on
the basis of differential measurement of inflammatory markers) from
diseases affecting the conducting tract can have important
ramifications on treatment.
[0102] Based on the foregoing information, it is readily understood
by those persons skilled in the art that the present invention is
susceptible of broad utility and application. Many embodiments and
adaptations of the present invention other than those specifically
described herein, as well as many variations, modifications, and
equivalent arrangements, will be apparent from or reasonably
suggested by the present invention and the foregoing descriptions
thereof, without departing from the substance or scope of the
present invention. Accordingly, while the present invention has
been described herein in detail in relation to its preferred
embodiment, it is to be understood that this disclosure is only
illustrative and exemplary of the present invention and is made
merely for the purpose of providing a full and enabling disclosure
of the invention. The foregoing disclosure is not intended to be
construed to limit the present invention or otherwise exclude any
such other embodiments, adaptations, variations, modifications or
equivalent arrangements; the present invention being limited only
by the claims appended hereto and the equivalents thereof. Although
specific terms are employed herein, they are used in a generic and
descriptive sense only and not for the purpose of limitation.
* * * * *