AU631854B2 - Breath sampler - Google Patents

Description

_1 I OPI DATE 05/09/90 APPLN. ID 50940 PCT AOJP DATE 11/10/90 PCT NUMBER PCT/US90/00584 INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (51) International Patent Classification 5 (11) G01N 1/00 Al (43) (21) International Application Number: (22) International Filing Date: 2 Priority data: 305,286 2 Februa 463,574 11 Janua PCT/US90/00584 February 1990 (02.02.90) ry 1989 (02.02.89) ry 1990(11.01.90) International Publication Number: WO 90/09572 International Publication Date: 23 August 1990 (23.08.90) (81) Designated States: AT (European patent), AU, BE (European patent), CA, CH (European patent), DE (European patent), DK (European patent), ES (European pa.

tent), FR (European patent), GB (European patent), 11 (European patent), JP, LU (European patent), NL (Eu ropean patent), NO, SE (European patent).

Published With international search report.

Before the expiration of the time limit for amending the claims and to be republished in the event of the r- eipi o/ amendments.

631354 (71) Applicant: THE UNITED STATES OF AMERICA, represented by THE SECRETARY, UNITED STATES DE- PARTMENT OF COMMERCE [US/US]; Washington, DC 20231 (US).

(72) Inventor: GLASER, Robert, A. 7501 Abbie Place, Apt. 3, Cincinnati, OH 45237 (US).

(74) Agents: OLIFF, James, A. et al.; Oliff Berridge, 277 S.

Washington Street, Alexandria, VA 22314 (US).

(54)Title: BREATH SAMPLER 2 3 0 (57) bstract An apparatus (200) for sampling volumetric quantities of human exhaled breath has three conduits and may be provided in a Y- or T-shaped configuration. The free end of conduits (262) is adapted to connect with the mouth of the subject being tested.

Another of the conduits (214) is adapted to pass air to the subject, this conduit being provided with a suitable filtering mechanism (230) such as a charcoal inhalation canister, and an inlet check valve (215). The third (218) of the three conduits supports an appropriate sampling canister (250) for receiving exhaled breath from the subject, and this conduit is also provided with a one way check valve (217).

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BREATH SAMPLER Field of the Invention The present invention relates to methods and devices for measuring and analyzing contents of gas samples, and more particularly to a method and apparatus for sampling volumetric quantities of human exhaled breath, and then either performing on-site analyses for measuring volatile compounds present in the sampled volume of breath, or storing the sampled volume so that appropriate analyses can be performed at a later time.

BACKGROUND OF THE INVENTION For nearly two decades, there has been a growing need for gas sampling devices capable of applications beyond the more typical uses, as for example achieving law enforcement objectives breathalyzers) and achieving medical objectives patient breathing assist). Indeed, since 1970 when OSHA was established, there has been an increased awareness of the need to continuously monitor conditions in the workplace to assure compliance with Federal and State regulations.

Since breath is the only biological fluid that may be obtained non-invasively and on demand, it is currently the matrix of choice for a number of applications as for example in law enforcement and medical evaluation such as breathalyzers and patient breathing assist. These uses generally rely on the fact that the concentration of the analyte of interest is in very high concentrations such as ethanol or carbon dioxide and can be analyzed with instrumentation that does not require separation of the analyte from other interferents.

Initial attempts at collecting exhaled breath samples for analyses of volatile substance content involved the use of two types of apparatus, namely the glass sample tube and the gas sampling bag. The glass sample tube permitted only a limited sample volume to be colJected, and its use was short-lived. On the other hand, the gas sampling bag enjoyed a far longer usefulness for this purpose. Nevertheless, this apparatus has WO 90/09572 PCT/US90/00584 -2its shortcomings as well, and for those reasons its use also is inherently limited. Most significant among the objections is that in most circumstances the bag becomes bulky after sample collection and must be almost immediately transferred to a laboratory in order that desired analyses can be performed.

Furthermore when using such gas collection containers, concentration of a gas component using an absorbent is generally not feasible and therefore measuring an analyte in large volumes of exhaled breath that are contributed over a long period of time is not practical.

For the purposes of this art, two different breath samples can be taken, namely a "mixed" and an "end" or alveolar breath sample. A solvent in the deep lung or alveolar region of the lung is in intimate contact with solvent in the bloodstream. If a sample of solvent in the deep lung air is obtained that sample will be referred to as an alveolar or end-expired sample. As the solvent is exhaled, the sample becomes diluted with air in the upper respiratory track and is known as a mixed -expired sample. Generally an alveolar sample is regarded as being indicative of bloodstream solvent concentrations since that sample is in intimate contact with solvent in the blood stream. The manual technique for end-expired sampling requires the subject to hold his breath for about 20 seconds then to exhale, discarding the first 30-50% of the sample; and finally collecting 3the end-expired portion of the sample with the sampling device. There are also automated techniques for sampling end-expired air.

The concentrations of solvents in an exhaled breath sample are normally very low. Therefore, it has been found necessary to have the analytes in the bag sufficiently concentrated on an appropriate sorbent prior to analysis. In addition, if the analytes are stored in the bag for extended periods, severe losses of analyte ~Ys r WO 90/09572 PCT/ US90/00584 3 may occur by absorption of the analyte iinto the bag wall or permeation of the analyte through the bag wall. In using the gas sampling bag, it has become apparent that concentrations of the analytes on solid sorbent material is generally not feasible in the field. The only technique for concentrating the contents of the bag is via indirect means. The sample must first be trapped in the bag. A solid sorbent sampler is then connected at one end to the bag and the other end to a pump. A known volume of air in the bag is then sampled. Thus, outside of the laboratory, neither the gas sampling bag nor the glass sample tube has been found to facilitate either direct concentration of volatile analytes in the samples taken or storage of the taken samples for extended periods of time.

Subsequently, other devices have been developed for sampling volumes of exhaled breath. For example, U.S. Patent No. 4,046,014 to Boehringer et al discloses a charcoal tube sample device for sampling respiratory gases in alveolar air. Another sampling device, which employs changes in pressure or flow rate in a main gas flow tube to initiate the sampling process as well as to terminate it, is disclosed in U.S. Patent No. 4,297,871.

Still another gas sampling device, disclosed in U.S.

Patent No. 3,858,593 to Ryan et al, incorporates a cylindrical alveolar gas trapping device having check valves at opposite ends which are openable upon application of exhalation pressure, and a side wall valved access tube for selective romoval of the trapped gas from within the cylinder to a gas analyzer. Each of these subsequently developed devices also suffer disadvantages which make them undesirable for use. In particular, there is no provision for continuous mixed-expired sampling or filtering of inhalation air, and no provision for storing the collected gas sample for analysis at a subsequent time.

II par WO 90/09572 PCT/US90/0058: 4 Objects of the Invention It is therefore an object of the invention to overcome deficiencies in the prior art, such as indicated above.

It is a further object of the present invention to provide improvements in analysis an" in gaseous sampling.

It is another object of the present invention to provide a breath sampling device capable of sampling trace amounts of compounds in large volumes of human breath for analysis by conventional gas analyzer apparatus or other analytical procedures to determine the presence of trace levels of volatile compounds.

It is still another object of the invention to sample trace analytes using a layered sorbent sampling scheme. For example, high molecular weight analytes are collected on the first layer of the sampling stack using a carbon-type sorbent. Low-molecular weight compounds pass through the first stage and are collected on the second or tertiary stage using a sorbent such as molecular sieves.

It is still another object of this invention that the sidestream port may be used for purposes other than sampling. For example, in order to count the number of breaths, the port may be connected to a pressure sensor that converts positive or negative pressure impulses into a signal that is registered by a counter.

It is still another object of the invention to provide a mainstream- or sidestream sample canister that can be desorbed by solvents or thermal desorption techniques or by supercritical fluid extraction.

Yet another object of the invention is to provide a breath sampling device capable of collecting mainstream samples or sidestream samples using sorbents.

Suitable activated charcoal-based sorbents include any activated natural charcoal as well as synthetic charcoals. An example of a natural charcoal is coconut-based I- I- LI ia PCT/ US90/00584 WO 90/09572 5 charcoal. Examples of synthetic charcoals include activated charcoal cloth, activated petroleum or coal based charcoals, and other activated carbons which are commercially available such as Carbotrap®, Carbosieve®, and Carbopack®. Suitable inorganic sorbents include the molecular sieves (synthetic or natural zeolites), silica gel and diatomaceous earth sorbents. Suitable synthetic resin sorbents include porous polymers such as Tenax®, XAD-2®, the Porapak® series polymers Porapak S), and the Chromosorb® series polymers Chromosorb 101).

Another possible collection technique for both mainstream and sidestream sampling is to use a reagentcoated sorbent where the reagent reacts with the exhaled analyte to form a stable derivative. For example lowmolecular weight aldehydes can be sorbed by contact with 2-(hydroxymethyl)piperidine-coated XAD-2. The unstable aldehydes are converted to oxazolidine derivatives which are stable and can be stored for later analysis.

Yet another object of the invention is to provide a breath sampling device capable of sidestream monitoring of the breath concentrations using suitable detection means such as a mass-spectrometer for breathby-breath measurements of the relevant analytes. No technique other than a face mask previously permitted such monitoring in a contaminated environment.

Yet another object of the invention is to obtain a multi-breath sample. In this case the exhaled breaths are all passed through the same adsorbent bed so that the analyte from all the breaths are sorbed. This permits the measurement of very dilute concentrations of analyte which are sorbed from large volumes of breath over extended sampling periods.

Still another object is to provide a breath sampling device having alternative configuratjins which permit the collection of sidestream or mainstream samples, which faciitate purification of inhaled air or I

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WO 90/09572 PCT/US90/00584 -6use a predetermined breathing gas source such as pressurized air, and which enable collection of the samples without use of a facemasko Yet a further object is to provide a breath sampling device having almost no plastic components, other than a mouthpiece and an inlet check valve diaphragm, with which the breath sample comes in contact.

However, the sampler could be made from PTFE (Teflon®) or any plastic which has minimal capacity to absorb solvents.

Still a further object of the invention is to provide a unified sampler which can be used for both mixed and alveolar breath sampling.

It is still another object of the present invention to provide a system whereby collected samples of breath analytes can be analyzed at any convenient time, for example immediately on-site or after shipment of sorbent canisters to a laboratory having sophisticated equipment.

Yet another object is to provide a breath scmpling device capable of being heated so that condensation of water vapor and analyte are prevented.

Yet another embodiment of the invention is to test a subject in the presence of contaminated air by not filtering the inhaled air. By measuring the amount exhaled, one can determine the amount or percent absorbed by the subject and thereby determine the dose received.

The invention is applicable to a number of situations where monitoring one's breath may be desirable in accordance with the invention. These include: a. Control of substance abuse by determination of the concentration of volatile solvents or other materials that are present in the breath such as alcohol or tol'ene from inhalation of paint thinner vapors or glue sniffing.

b. Measurement of volatile compounds such as oral antiseptics in support of advertising efficacy -I -~q WO 90/09572 PCT/US90/00584 7 claims by cosmetic manufacturers. Similarly, volatile compounds in the breath that are present from smoking, such as nicotine, may be measured for smoking-cessation or for other research purposes.

c. Measurement of trace levels of endogenous compounds in the breath that may be markers of a disease state such as breath acetone in diabetes.

d. Measurement of volatile endogenouslyproduced or used compounds such as carbon dioxide, oxygen or various other metabolites.

e. Monitoring workers or residents in the vicinity of hazardous areas, especially wastesites, for uptake of toxic chemicals.

f. Estimation of blood concentrations of absorbed organic solvents and of the volatile metabolites of these compounds that are excreted in the breath.

g. Measurement of natural air gasses which are not metabolically used or produced such as nitrogen to provide internal controls and comparisons.

h. Support of breath-based biological exposure indices (BEI,s) for control of worker exposure to hazardous compounds, especially solvents. The BEI's establish maximum concentrations for hazardous compounds in the various biological fluids. As such, this approach is superior to environmental monitoring of worker breathing zones to assure compliance with current State and Federally-mandated concentration standards. Breath based BEI's have been promulgated by the American Conference of Governmental Industrial Hygienists since 1981, and recognize that adsorption of hazardous chemicals by workers is quite variable due to dermal exposure and to ergonomic differences that affect individual ventilation rates.

The breath-based BEI's to be supported by this invention may rely on either or both mixed and alveolar sampling.

The Federal Republic of Germany currently has standards for maximal levels of chemicals in the breath of exposed workers.

WO 90/09572 PC/US90/00584 Generally, these situations demand that the sample be stored for later analysis by sophisticated separation technology and analytical techniques. In addition, the analyte concentration is expected to be very low because the sample may be collected hours after exposure or it may be present in only trace amounts. For example breath levels of such analytes are measured in the parts-per-billion to parts-per-million range. In order to accurately measure such levels and to establish standards to deal with such small amounts, a breath sampling technique shou'.d permit concentration of the analyte. In addition, the device should be compact enough to allow shipment to the laboratory for analysis if on-site analysis is not performed.

The above and other objects and the nature and advantages of the present invention will become apparent from the following detailed description of certain specific embodiments taken in conjunction with the drawing, wherein: BRIEF DESCRIPTION OF THE DRAWING Figure 1 is a detailed schematic illustration of a first configuration of the sampling device of the oresent invention; Figure 2 is a detailed schematic illustration of a second configuration of the sampling device of the present invention; Figure 3 is a detailed schematic illustration of a modification of the sampling device configuration shown in Figure 2; Figure 4 is an exploded view of the components of one embodiment of the sampling canister contemplated for use with any of the embodiments of the sampling devices shown in Figures 1, 2, or 3; Figure 5 is an exploded view of the components of a second embodiment of a sampling canister which can be used with any of the embodiments of the sampling devices shown in Figures 1, 2, or 3; WO 90/09572 PCT/US90/00584 -9- Figures 6 and 7 show a tool which can be used to load the check valves used with the sampling devices of the present invention; Figures 8 and 9 show another similar tool, Figure 9 being a schematic view showing use of such tool in use; Figure 10 is a schematic view of an improved sample canister for granular sorbents and/or combination of charcoal cloth and granular sorbents; Figure 11 is a schematic view of another improved sample canister for granular sorbents; and Figure 12 is a schematic view of another alveolar sampler using granular sorbents.

Figure 13 is a schematic view of a mainstreain sample canister that is primarily intended for permanently containing the charcoal cloth or granular sorbents.

Figure 14 is an "L"-shaped configuration of the sampler, which further minimizes void volume.

Figure 15 is a schematic view of a square mainstream sample canister.

Figure 16 shows the construction of a removable square container for granular sorbents.

Figure 17 shows the construction of a square container for use with removable charcoal cloth sorbents.

Figure 18 shows a dose receiving sampler designed for the subject to use while exposed to the analyte gas. However, in order for the dose to be extimated the inhalation canister is first removed.

Otherwise, this sampler may be used for mixed-expired sampling as the samplers described in Figures 1 and 2.

Figure 19 shows a sample canister with sorbent for alternate use in the system of Figure 4.

DETAILED DESCRIPTION OF THE INVENTION Referring now to the drawing, it will be understood that while the present invention may be embodied in a variety of configurations, for purposes of illustration WO 90/09572 PCT/US90/O0584 10 two configurations will be discussed below, namely a "Y" configuration and configuration, as well as a variation of the latter. All of these configurations can be used for different types of sampling, although a particular cc .figuration may provide advantages relative to a particular type of sampling. Thus, the configuration shown in Figure 1 minimizes the void volume as much as possible within manufacturing tolerances, thereby minimizing rebreathing of partially delivered samples from the void volume of the sampler device. The configuration shown in Figure 2 enables collection of both mixed-expired and end-expired samples using a single collection canister. The variation of Figure 3 is primarily intended for single breath end-expired sampling, although it can also be used for single breath mixed-expired sampling. For all these configurations, the present invention contemplates that, subsequent to collection of the breath sample, analysis for the analytes contained in the collection canister will be made with conventional analysis equipment, Looking first at Figure 1, the sampling device 100 involves a main body 110 having a tubular mouthpiece support portion 120 on which a bite wing mouthpiece, such as shown in Figure 2, may be mounted, an inhalation canister support portion 130 for attaching a charcoal inhalation canister 140, a sample canister attachment portion 150 for attachment of a sample canister 160, and a sidestream port 170 for collection of sidestream samples. The port 170 is disposed substantially centrally of the main body and opens into the main body from one side thereof. Sidestream samples may be collected on sorbents contained in stainless steel or glass tubes attached to the port 170 via appropriate ferrules and fittings, or other similar mechanical connection means.

The inhalation canister support portion 130 comprises a two part structure including a first tubular part 132 formed as an integral part of the main body and extending ~s~sP~i~P~_ WO 90/09572 PCT/ US90/00584 11 having a longitudinal axis extending) at an angle of about 1200 from the longitudinal axis of the tubular mouthpiece support portion 120. The first tubular part 132 includes an annular end disposed in a plane perpendicular to the longitudinal axis of the first tubular part 132.

The inhalation canister support portion 130 also includes a second tubular part 133 having at one end an annular face matching the surface area and configuration of the end face of the first tubular part. The first and second tubular parts are secured to one another, with their annular end faces disposed in opposition to one another, via a clamp means. In effecting this connection, an annular gland or seal 134 is disposed and maintained between and spaces the end faces from one another. Various materials are effective for use as the seal; however, the preferred material is polytetrafluorethylene-covered silicone rubber.

The second tubular part includes an annular edge positioned forwardly of the clamped, sealed end faces, and the forwardmost end 136 of the second tubular part is provided with a threaded inner or outer surface 142 for making threaded engagement with a complementarily threaded outer or inner surface 142 on the charcoal inhalation canister 140, thereby insuring that the canister 140 is securely attached to the second tabular part. An inlet check valve 180, having a twof.;.' function, is disposed on the annular ledge 135. The major functions of the inlet check valve 180 are: to open under negative pressure (inhalation) thus permitting the user to inhale from the ambient through the inhalation canister 140; to close under pressure and thereby prevent exhaled air from escaping from the main body of the sampler back through the inhalation canister 140; and to direct the exhaled sample through the sample bed in section 160 of the sampler.

The sample canister support portion 150

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WO 90/09572 PCT/US90/00584 12 includes a first canister housing part 151, a second canister retaining part 152 and a third housing part 153 for enga.gement of a volume measuring device (not shown, but to be discussed later). The first housing part 151 comprised a tubular member, formed integrally with the main body and having a longitudinal axis disposed at approximately 1200 from the longitudinal axis of both the inhalation canister support portion 132 and the mouth- 1iece support portion 120, and an annular sleeve 155 attached at the forward end of the tubular member.

Sleeve 155 is provided with a forward facing annular land 154 for retaining a first polytetrafluoroethylene (PTFE or "Teflon") gasket T1 and a forwardly extending annular cuff 156 bearing a, set of internal threads.

Housed within a sleeve 155 forwardly of the land 154 is a sample canister 160. Secured by threads within cuff 156 is the externally threaded, rearwardly facing, annular extension 157 of the canister retaining part 152. A second PTFE gasket T2 is supported on the forward facing land 150 of retaining part 152, and the sample canister is held securely between the PTFE gaskets Tl, T2 within sleeve 155 when the retaining part 152 is threaded tightly in a rearward direction and within the sleeve 155. The housing part 153, secured within the forward end of retaining part 152 by a welded connection, comprises an annular sleeve member having a forwardly facinj annular seat 159 at its rearward end. Disposed on, and secured to, the annular seat 159 is an outlet check valve 190 having a construction which is the same as that of inlet check valve 180.

The major functions of the outlet check valve 190 are as follows: to close under negative pressure (inhalation) and prevent environmental contaminants from entering the sampler body; to open under positive pressure (exhalation) _id thereby permit the sample stream to pass through the sample bed i section 150 of the sampler; and to direct the exhaled sample through 1 n WO 90/09572 PCT/US90/00584 1 13 the sample bed in section 160 of the sampler.

Each check valve 180, 190 comprises a one-way diaphragm-type valve with an integral cross-hatch support. Welded to the center rf the support is a retainer bud for the valve diaphragm. The cross-hatch support is of the type known as a "low flow resistance" cross-hatch, is made of stainless steel, and is silversoldered to a land at the respective inlet or outlet location. The purpose of the cross-hatch support is to provide a retention foundation for the respective diaphragm valve during inhalation or exhalation.

Figure 2 illustrates a second breath sampler device 200 exhibiting the configuration described above which facilitates obtaining mixed-expired breath samples. This second device includes a tubular main body 210 to which a stainless steel compression fitting 212 is secured (via welding) at an opening substantially centered in the tubular main body 210. The fitting 212 is provided to facilitate the collection of sidestream samples, and it is to be understood that the diameter of the fitting may be chosen as a function of the particular application or task to be accomplished. One side of the tubular main body 210 (hereinafter refrrred to as the "inlet" side) supports, via a first threaded connection means 214, an inhalation canister 230. An inlet check valve 215 is located downstream of the threaded connection means 214. Directly opposite the inlet side of the main body is the "outlet" side where the sampling caniscer 240 is located and supported on the main body via a second threaded connection 216. An outlet check valve 217 is positioned downstream of the second threaded connection. In Figure 2, the inlet canister, the mouthpiece support and the sample canister are shown attached to the sampler main body 210 by threaded connections. However, these connections could also be accomplishec' by use of alternative fittings e.g. tapered sleeve- or O-ring type slip fittings.

WO 90/09572 PCT/US90/00584 14 Typically, both the inlet and outlet check valve bodies are fabricated from stainless steel discs.

A plurality of openings (four equiangularly spaced openings in the preferred embodiment) are provided in the discs to form an array which facilitates air flow through the discs. Retainer buds are welded directly to the center of the discs to assist in securing the silicone rubber diaphragms against dislodgement. On the downstream side of outlet check valve 217 is a tapered connection 218 which connects directly to a respirometer 250 used to measure and record the volumes' of exhaled breath. This connection has been made to facilitate connection to the respirometer; but other volumetric devices may be used br connecting them with suitable fittings and connections to the tapered connection 218.

Through a third threaded connection 219, a tubular mouthpiece support portion 220 is coupled to the main body 210 of the sampler device. A bitewing mouthpiece 260 includes an elongated sleeve portion 262 adapted to be mounted over the tubular mouthpiece support portion 220, and a mouth engaging portion 264.

The mouthpiece support portion 220 may also be directly connected to the sampling canister 240, as seen in Figure 3. This modification of the Figure 2 ccnfiguration facilitates single-breath "end-expired" collection of sa-ples. It should therefore be clear that both the "mixed-expired" sampling device shown in Figure 2, and the "end-expired" sampling device shown in Figure 3, are designed so that either one will fit with the same mouthpiece support portion. The support acts as the mouthpiece for the configuration shown in Figure 3. In both of the Figure 2 and Figure 3 embodiments of the sampling device, the inlet and outlet check valves employed are substantially identical with those used in the sampling device of Figure 1. Moreover, the sampling canister 240 used in the embodiments of Figures 2 and 3 is preferably substantially the same as that described lp-l I WO 90/09572 PC/US90/0584 15 above for use with the embodiment of Figure 1.

The design may be L-shaped as shown in Figure 14. This embodiment minimizes sampler void volume and permits the sample canister to be directly in the path of the exhaled sample so that there are not angles which produce back pressure and turbulene which under certain circumstances may be undesirable.

Because of its construction, the Y-configured sampler shown in Figure 1 is particularly constructed for continuous mixed-expired breath sampling. This was the prototype sampler. It is the most expensive and least flexible of the illustrated embodiments. The inhalation canister 140 is attached to the main body of the sampler 110 via a Tri-clover clamp 134. This clamp permits the inhalation canister assembly to be removed from the main sampler body in order for the inlet check valve (180) to be replaced. Unless a single sampler is dedicated to each subject, the Y design, as configured in Figure 1, alsc requires that the sample canister (stack) be removed and stored immediately after sampling. This introduces the possibility of passive sampling of contaminants in the industrial environment by the charcoal cloth sorbent and may limit the reliability of the sample.

In order to avoid the use of the Tri-clover clamp, reduce fabrication costs and to make the sampler more flexible, the sampler shown in P'igure 2 was created. In that sampler, the threaded inhalation canister support (214 of Figure 2) is we'.ded to the main body of the T, eliminating the neei for a Tri-clover clamp and substantially reducing fabrication costs. A conventional stainless steel pipe may be used as the main body of the sampler. In addition, this construction places the removable sampling cup in a canister that may be removed from the main body of the sampler and shipped off for analysis. This canister may also be directly attached to the respirometer via the tapered fitting (218 of Figure As configured in Figure 2, the sampler ~lll-s~ scprp II~-91~B-1[3 FIIIPI~ IIII~IP~ICIF' 1 IIC (P]a I WO 90/09572 PCT/US90/00584 16 permits continuous mixed-expired breath sampling (mainstream or sidestream) just as does the sampler in Figure 1. However, when the sampler of Figure 2 is disassembled and re-configured to the sampler of Figure 3, single breath end-expired (or for that matter single-breath 'I mixed-expired) samples may be obtained.

In the sampler of Figure 2, the inhalation canister support 214 cannot be separated from the main sampler body to permit loading of the inlet check valve. The outlet check valve 217 is in a deep, inaccessible chamber of the sample canister. Therefore, a means of loading the inlet check valve into the sampler body and the outlet check valve into the sample canister iis desirable. That is the purpose of the loading tool shown in Figures 6 and 7. The use of this tool actually dictates the configuration of the sampler in Figure S2, or the L-shaped configuration in Figure 18, because of 1I the necessity to permit ready accessibility of the check ji valve loading tool to the inlet check valve support i 20 through the opening at 216 in Figure 2. However, a Universal Check Valve Loading Tool (see below) has been created to allow the inlet check valve to be loaded into a Y-shaped main body or an L-shaped main body that has no access port. Therefore, it is also possible to replace the T-shaped main body of the sampler in Figure 2 with a [i lower void volume L-shaped or Y-shaped main body, while still retaining the flexibility 'f the T-shaped design.

All that is required for this purpose is to machine the main sampler body from a Y-shaped pipe fitting or fabricate the body in an L-shape or to cast the body in a Y or L-shape.

In suimnary, the Y, the L and the T configurations permit mixed-expired sampling. The particular Y design as shown in Figure 1 permits only mixed-expired sampling because it is not shown with a removable sample canister and mouthpiece as is the T-shaped design of Figure 2. However, there is nothing intrinsic in the ~c Ir r -Lh IL. -I WO 90/09572 PCr/US90/00584 17 design of a Y-shaped sampler that would permit only mixed-expired sampling, e.g. the Y-shaped sampler of Figure 1 can be easily adapted as noted above for obtaining single breath end-expired or mixed-expired samples.

Figure 4 illustrates the structural elements contained within one embodiment of the samplii g canister used in the present invention. PTFE gaskets 402 and 402' are positioned at the top and bottom of the stack of elements. The gaskets provide a secure seal around the canister af .er it has been loaded into the sampler device. The sampling "stack" further includes a cylindrical torous weight or retainer 404, a first stainless steel retainer screen 406, charcoal cloth sorbent bed 408, and a second stainless steel retainer screen 410.

The weight or retainer 404 retains sorbent bed 408 in the canister by compressing the first retainer screen 406 against bed 408. To prevent inhalation of sorbent fines, a second retainer screen 410 having a fine mesh is placed atop the array of openings 413 in the canister 412. The openings 413 preferably are provided in symmetrical array to form a grating.

The sampler canister 412 into which the stack of elements fits is designed to accommodate a large plurality ul wafers of charcoal cloth of which the sorbent bed 408 is comprised (one embodiment contemplates element (11) wafers), including if necessary or desired, stainless steel screens for separating the adjacent scrbent waf'ers. An anti-rotation lug 414 is provided via spot welding) on the interior of the annular wall of the canister. The lug 414 engages with the cutout 405 provided in the exterior annular surface of the torous weight 404 for preventing the weight from rotating the retainer screen 406 as the canister is being loaded into the sampler housing. In this way, the sorbent bed is protected against being torn and the formation of fines during loading of the canister is prevented.

2118~ WO 90/09572 PCT/US90/00584 18 A second embodiment of the sampler canister, which is illustrated in Figure 5, is contemplated for use with the embodiments of sampling devices shown in Figures 1, 2 or 3. This embodiment shows the use of charcoal cloth sorbents, although granular sorbents, such as silica gels or porous polymers could also be used. The canister comprises an assembly of elements including a torous shaped weight or retainer 504, a first retainer screen 506, a first sorbent bed 508, a second retainer screen 510, a second sorbent bed 516 and a third retainer screen 518. This assembly of elements is disposed within a stainless steel canister cup 512 having a bottom perforated with an array 513 of openings. An antirotational lug 514 is provided on the annular surface of the cup for engagement in the anti-rotational cutout 505 provided on the annular outer surface of the torous retainer 504.

As with the first embodiment of sampler canister illustrated in Figure 4 and described above, two gaskets 502, 502' are positioned atop and below the sampler canister to provide a secure seal around the canister once it has been loaded into the sampler device. By using this second embodiment of sampler canister, granular rorbents may be held in the cup 512 by the first, second and third retainer screens (506, 510 and 518, respectively), or by the use of discs of very fine mesh stainless steel which are centered on, and soldered or welded to, a thin metal ring. Alternatively, the discs could be press-fit to and about the thin metal ring. Preferably, the outer diameter of the ring would be about equal to the inner diameter of the cup.

Sorbents may be separated into front and back sections, and may be retained in place using the discs or the screens.

In embodiments of the sampler device shown, the stainless steel canister cup may be eliminated from the canister housing or support member, and alternatively I c- L Ilt-_ WO 90/09572 PCT/ US90/00584 19 perforated discs of stainless steel may be welded to the inside of the canister housing or support member to form an equivalent cup base or bottom, and thereafter the sorbent beds and screens can be assembled to form the sampler canister.

In operation, the sampler devices shown in Figures 1 and 2 function in the same manner as a respirator mask. The subject (user), wearing a nose clamp and biting a bitewing mouthpiece, is instructed to breathe by mouth only. At the beginning of inhalation, negative pressure created inside the main body of the sampler closes the outlet or exhalation check valve and opens the inlet or inhalation check valve, thereby permitting fresh air to be drawn through the charcoal canister (140 in Figure 1 and 230 in Figure When the subject exhales, the positive pressure created in the sampler main body forces the inlet check valve to close and the outlet check valve to open. Volatile compounds in the subject's breath are adsorbed from the mainstream gas flow on the charcoal cloth sorbent medium or granular sorbent medium in the sample canister, or from the sidestream flow using other sorbents.

For collection of mainstream breath samples, exhaled volumes may be recorded using a Wright respirometer or other v---etric device. For sampling breath from the sidestreac., the sample volume is recorded by multiplying the duration of sampling by the sampling flowrate, and then by a correction factor that accounts for the percent of time the subject spends exhaling.

Laboratory studies have shown that such a correction factor is approximately 0.65. Other techniques to estimate sidestream sample concentration may also be used.

Tests with volunteers have shown 'hat sidestream carbon dioxide concentrations are approximately 71% of mainstream concentrations. Therefore, the sidestream sample concentration may be estimated by determining the mass sampled, dividing that mass by the volume sampled (i.e.

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WO 90/09572 PCT/US90/00584 20 actual sidestream flowrate x time), and then dividing that concentration by 0.71 to correct approximately to mainstream concentrations.

Either the mainstream, or the sidestream, mode of sampling permits large volumes of mixed-exhaled breath to be sampled without prior collection in and concentration from a gas-sample bag. In this way sufficient quantities of the absorbed compounds are permitted to be collected for analysis.

The check valves disclosed in each of the embodiments of the sampler device, the embodiments shown in Figures 1-3, can either be removable or nonremovable. Non-removable valves could be secured, as by a press-fit or by welding, to their respective supporting structures. Removable check valves might be desirable where frequent cleaning of the valves is required, or where the contemplated cleaning process for the valves would not be practically carried out with the valves secured within their respective sampling devices.

While the outlet check valve has been shown in each of the embodiments to be placed in a specific location, it is possible to have the outlet check valve disposed in still other locations. For example it may be useful to place the outlet check valve upstream of the sampler canister. Without the sample canister attached the subject may flush his lungs free of environmentallycontaminated air for a prescribed period, by inhaling fresh purified air through the inhalation canister or other air source and venting the exhaled air to th' atmosphere through the outlet check valve. Thereafter the sampler canister is attached to the sampler. The concentrations of the sdmples are then reflective only of bloodstream contamination levels and not of environmental contamination levels.

Figures 6 and 7 disclose a valve mounting tool, the use of which is for loading check valve diaphragms of the kind which can be removed from the sampler devices of WO 90/09572 PCr/US90/00584 21 the present invention. Figure 6 illustrates the tool in a position in which a check valve has been inserted in preparation for mounting in a sampler device, while Figure 7 illustrates the tool in a position in which the check valve has been mounted.

As shown in Figures 6 and 7, the tool 600 comprises an elongated guide tube 610 havin a first push rod insertion end 612 and a second check valve supporting end 614. The length of the guide tube 610 is significantly greater than its diameter, and supports in its interior an elongated push rod 640. An elongated cutout or slot 620 extends, from a location adjacent the second end 614 of the guide tube, along a short length of the guide tube in a direction towards the first end 612 thereof. A narrow strap of thin gauge 'etal 611 (preferably, stainless steel) is welded to one end of the push rod 640 which is inserted into and housed within the guide tube 610. Prior to insertion of the rod 640 into the guide tube 610, one free end of the strap is welded to the center of the circular peripheral edge surface of the one end of the push rod to lie adjacent to the longitudinal extent of the push rod. The other end of the strap further protrudes diametrically through the cutout and is welded to the inner annular surface of an outer sleeve member 650, which is disposed over and rides along the exterior of the guide tube 610.

In order to load the inlet or outlet check valves, the outer sleeve member 650 is moved rearwardly (to the right in Figures 6 and 7) over the guide tube 610 by the push rod 640. The check valve to be loaded is then pushed over the guide tube 610 and is retained in any suitable manner, e.g. the check valve can be made of a resilient or elastic material which deforms or makes a friction fit with the guide tube.

The second end 614 of guide tube 610 is inserted into the inlet or outlet check valve mounting structure (in each of the sampler embodiments disclosed Nvt) 90109572PC/UO004 PCT/US90/00-584 22 above) such that the guide tube is disposed over the retainer bud. The pushrod 640 is then pushed back through the guide tube 610 so that the outer sleeve member 650 engages the check valve and pushes it from the guide tube onto the retainer stem.

Removal of the check valve may be effected by using long term tweezers, or some equivalent tool.

In the sampler devices described hereinabove, the exhaled volume of the mainstream sample is determined using an accurate volume measurement device, as for example a Wright respirometer. Volume measurements made are independent of the use of an inaccurate and imprecise technique e.g. collection of exhaled water on a high pressure-drop adsorbent, such as molecular sieves, where the amount of exhaled water collected must be assumed to be directly proportional to the volume exhaled.

The foregoing sampler devices permit sidestream, as well as mainstream, sampling. Sidestream sampling is important, and a capability for conducting this mode of sampling has been designed into the sampler devices of the present invention, for several reasons: Although the pressure drop associated with a charcoal cloth sorbent bed is low, subjects with respiratory problems may not be able to exhale through a sorbent bed.

Sampling from the sidestream enables the user to employ sorbents that are selective to the collection and analysis of specific analytes. 2or example, research has indicated thit alcohols are only poorly recovered from charcoal cloth, and it may thus be necessary to use sidestream sampling for collection of such analytes.

The capacity of the charcoal cloth sorbent bed for high vapor pressure solvents such as methylene chloride may be limited. Sidestream samples can be collected at any desired flowrate on the sorbent of choice, such that problems with breakthrough are -7 WO 90/09572 PCT/US90/00584 23 minimized.

Multiple, and therefore replicate, samples may be obtained using the sidestream sampling option.

One or more sorbents may be used to trap selective analytes at a variety of flowrates.

The sidestream port enables the sampler to be connected to an appropriate continuous monitor for breath-by-breath measurements. In this manner, the sidestream port facilitates frequent and continuous analysis of breath samples which are uncontaminated by the analytes in the work environment.

Pressure- or flow-sensors may be connected to the sidestream port to measure the number of breaths and or the pressure/flow profile of each breath, In order to permit a low void volume Y-shaped design for the main sampler body that does not have a removable check valve assembly, it is necessary to employ a valve-loading tool as shown in Figure 8 similar in function to that shown in Figures 6 and 7.

Referring to Figure 8, two hollow cylinders (A) and are used as guide tubes and are connected at a hinged joint As configured, the two guide tubes (A) and may be rotated relative to one another by approximately 1200 in order to assure the proper angle of orientation of the tool relative to the retainer bud when the tool is inserted in the sampler body. However other angular orientations are also possible for example 900 !i for use with an L-shaped sampler that has no side access port. The hinge must be relatively "stiff" and a positive "stop" attached to the guide tube (see Figure in order to prevent the two guide tubes from being bent at an angle greater than 1200 or other preferred angle relative to one another. The stop is a small metal stud welded to the body of tube just above the hinge. The push rod is a cylinder housed in a long section of the guide tube. An outer sleeve slides over the other section guide tube and is 5 rasg WO 90/09572 PCT/US90/00584 24 welded to a short metal tang A slot has been cut into guide tube The tang slips through the slot inside of tube A relatively stiff cable (H) connects the pushrod to the tang At one end, the cable is welded or press-fit to the push rod At the other end, the cable is welded or pressfit to the tang The tool operates in the same way as the tool described in Figures 5 and 5. That is, the outer sleeve is pulled back over the guide tube by pulling the push rod back to the loading position. The check valve is then slipped onto tube Section of the tool is then inserted into the body of the sampler and forced up against the inner wall of the sampler body to bend the tool at the hinge to approximately 1200 or other preferred angle. The section guide tube is then forced over the retainer bud. The pushrod is pushed, forcing the cable through guide tubes and causing the outer sleeve to slide along outside of guide tube B, thus pushing the check valve onto the check valve support. To improve functioning, inner cable guides as shown in Figure 8 may also be used.

One embodiment of a sample canister for granular sorbents and for combinations of granular sorbents and charcoal cloth is shown in Figure 10. In this configuration, the sorbent beds are retained in separate canisters of the type 517 shown in Figure 5. Alternatively, this embodiment may also be used to retain several, e.g. primary, secondary and even tertiary, beds of charcoal cloth sorbent. However, in order to minimize presare drops caused by large amounts of granular sorbent, it is preferred that the retainer cup not be as deep as that ased for charcoal cloth sampling in previously discussed embodiments. The canisters are stacked atop one another as shown in Figure 10. This arrangement permits a more positive seal of granular sorbent beds into the canister than are provided by those in the I I WO 90/09572 PC'F/US90/00584 25 previous embodiments of Figures 4 and 5. There should be no possibility of granular sorbent from one sorbent section being accidentally mixed together with that of another sorbent section by spillage. Granular sorbent is retained in each of the cups by the fine-mesh stainless steel screens that are spot welded to the inside base of the cup (over the grating) and to the bottom of the heavy retainer grating.

These heavy retainer gratings serve to flatten the sorbent bed and thus prevent channeling during sampling. They essentially replace the torous weight of the previous embodiment. However, this construction does not include an anti-rotational lug in the sampler cup to engage a cut out on the heavy stainless steel grating as with the previous embodiment. Granular sorbents require a very tight seal to be held in place. The sorbent may be blown or fall out of the sampler past such an opening. Essentially, this is a cup-in-a-cup design. It may also be desirable to ensure that the individual sorbent beds be separated or sealed by Teflon gaskets as shown in Figure Alternatively, the granular sorbents may be used with a canister such as that shown in Figure 11, this canister has also been fabricated from two stainless steel cups, an upper and a lower The outside diameter of the upper cup is approximately equal in the inside diameter of the lower cup. Fine-mesh retainer screens (diameter internal diameter of the upper cup) have been spot-welded over the grating in the inside of both cups. In addition, a retainer ring has been press fit into the upper cup as shown. The entire upper assembly is then inverted and press- fit into the lower cup. Once press-fit together the two cups, A and B, are permanently affixed to oilC aiother. The granular sorbents may be added or rEmoved from the canister from a port that is drilled into the side of the assembled canister, the hole may be threaded. This port is plugged WO 00/09572 PCT/US9G.V'j584 26with a threaded metal plug or a small plug of silanized glass wool or a teflon plug once the canister has be=,c filled with sorbent. Dimensions are as shown on Figure 11.

Along these same lines, another embodiment is shown in Figure 12 for another alveolar sampler which also employs granular sorbents. This device is primarily intended for sampling extremely low concentrations of 'i solvents in alveolar brerth. Samples of alveolar air collected with the device are primarily intended to be.

analyzed by thermal desorption. Thermal desorbers are commercially available and used extensively in environmental monitoring. For sampling, stainless steel or glass tubes, generally ranging in diameter from 0.25" to 0.625" are loaded with a sorbent. The manual breath sampling technique is used with this device. The subject exhales the end portion of the breath sample into the sorbent bed. The contaminants present in the air are trapped on the sorbent. The tube is capped and returned to the lab ratory for analysis. During analysis, the tube is inserted into the thermal desorber where it is heated under a stream of inert gas such as nitrogen.

This flushes the trapped solvent(s) from the sorbent into a gas chromatograph where it is analyzed. The major advantage of thermal desorption is that all of the solvent is removed from the sorbent bed by the thermal desorption process, and injected into the chromatograph for analysis. This contrasts with solvent desorption where the sample is diluted with solvent and only a very small portion of the sample is injected into the analytical instrument. Thus, thermal desorption significantly enhances sensitivity relative to solvent desorption and permits the analysis of much lower quantities of analyte than would be possible for analysis by solvent desorption.

The sampler of Figure 12 described below is adapted for use with a 0.625" O.D. x 0.579" I.D. x C -C I~IIIPIY PIII~BI~B~ WO 90/09572 PCT/US90/00584 27 long stainless steel thermal desorption tube, i.e. the type that is used with a Tekmar® thermal desorber. The solvents present in the breath are sampled on beds of a porous polymer such as Tenax®; however, many other sorbents including charcoal cloth may be used for this purpose. This device is primarily intended to be used where the concentration of sample in alveolar breath is very low. Again, both front and back absorbing sections are used. The device is configured similarly to the granular sample canister shown in Figure 10. The 0.625" OD thermal desorber tube is welded as shown to a 0.866" (22mm) tapered adaptor to form the main body of the sampler. The tapered adaptor permits ready attachment of the sampler to a Wright respirometer. The sorbent is retained in primary and backup stainless steel cartridges (B and B' respectively) that are approximately 0.579" OD. The bottom of each cartridge is a grating to which fine mesh stainless steel screen has been spot welded on the inside. At the top of each cartridge are separate heavy stainless steel retainer grating (C and C' for the primary and backup sections respectively). Fine-mesh stainless steel screen is spot-welded to the bottom of each grating. These gratins slip inside the sample cartridges and retain the sorbent bed in place. Alternatively, plugs of silanized glass wool may be used in place of these gratings.

The sampler is loaded as follows: first, the backup cartridge is slipped into the sampler body.

The backup cartridge rests on a land at the bottom of the cylinder housing. A Teflon gasket is inserted above the backup cartridge. The primary sorbent cartridge is then inserted. Another Teflon gasket is placed behind the front cartridge. Once inserted, the cartridges are held in place in the sampler body by a retainer tube (approximately 0.579" OD) that compresses against the upper stainless steel retainer grating as shown. There are holes in the retainer tube (at I WO 90/09572 PCT/ US90/00584 28 ':i I 1 1 i i i i I) and in the main body of the sampler (at As the retainer tube is inserted into the main sampler body, the holes on the retainer tube and on the main sampler body are aligned and a small threaded retainer key is inserted through the hole in the outer sampler body and into the matching hole on the inner retainer tube. This arrangement locks the canisters into place and keeps the entire assembly tight.

Once sampling is completed, the sampler is returned to the laboratory for analysis. The sampler is disassembled by first removing the threaded retainer key. The entire assembly including the retainer cylinder, the primary 1:ickup sample cartridges and the Teflon gaskets are then removed by pushing the sample cartridges out of the sampler with a convenient tool a solid rod) from the open end of the sampler body welded to the adaptor Each of the cartridges are then separately inserted into a 0.579" ID thermal desorber tube to which a land such as D of Figure 11 has been welded. The cartridges would be inserted such that they rested atop the land. Each cartridge is then separately analyzed by placing the assembly inside a thermal desorber oven unit for analysis.

Although I have specified thermal desorption as the most desirable desorption procedure, other techniques for recovering the solvent from the sorbent, e.g. solvent desorption or extraction with supercritical fluids, may also be used as applicable.

Unlike some other sorbent containers, the container of Figure 13 can be made so it cannot be disassembled. It is primarily intended for use in an occupational health clinic where complaints regarding exposure may be substantiated, perhaps several days postexposure by sampling a large volume of breath using such a container. Since the sorbent cannot be readily removed from the container for solvent desorption, it is I WO 90/09572 PCT/US90/00584 29 preferred that the sample be desorbed by thermal means or using supercritical fluids.

The canister of Figure 15 can essentially replace canister 240 in Figure 2. It is preferred that this cannot be constructed of inert materials which do not sorb volatiles such as stainless steel, anodized aluminum, or PTFE (Teflon@). Here the body of the sample canister does not have to be divided into threaded male and female components as does the canister of Figures 1, 2 and 3. Rather than separating the two halves of the canister to insert the sorbent container(s) such as part 412 in Figure 4, the cover on the top of the sampling chamber is removed and individual sample containers inserted. A retainer shim has also been included in the sampler arrangement. For ease of viewing, this retainer shi is shown outside the body of the sampler. Alternatively, the shim may be permanently held in place at the outlet end of the body of the sampler using the retainer bolts shown. Its purpose is to seal the individual sample containers against one another during use. The sorbent containers are loosely inserted into the canister. The two retainer bolts on the backside of the canister body are then tightened against the shim forcing it against the sorbent containers. This arrangement should also facilitate the recovery of the sorbent container froni the canister, as the user would not need to forcibly remove tight fitting sample containers from the canister, but simply release the retainer shim and remove the sample containers. In addition, it allows ready use of oversized or multi-depth sample containers.

As shown in Figure 15, the cover is mounted to the sampler body with screws; a gasket is used to seal the cover with the body. Alternatively, the cover may be mounted to the sampler body by sliding it in a track mounted to the top of that body or sealed in place with a clamr!., A reason for this arrangement is to permit ready use of granular sorbents. The granular sorbent is

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WO 90/09572 PCT/US90/00584 30 compressed in place with the weights shown to prevent channeling through the sorbent bed during sampling.

However, the sorbent container may also be used with charcoal such as charcoal cloth in three-wafer sections. In addition, this permits the use of doublesize sorbent containers for granular sorbents weighted as necessary with oversize weights.

The arrangement has a further advantage of i reducing waste of the charcoal cloth sorbent and of the fine mesh retainer screen. Cutting circular wafers of charcoal cloth or fine mesh screen from a rectangular roll of sheet stock does not allow all of that stock to be used whereas the use of square or rectangular wafers will.

The container channel support of Figure 16 may be fabricated separately from stainless steel- or aluminum-channel stock. The front and back fine mesh stainless steel screens a. approximately 40-mm square, giving approximately the same exposed surface area as that of the currently proposed 45 mm diameter wafers of charcoal cloth. These screens are inserted into the protruding arms of the channel support. The inner shim assembly is then forced as shown into the channel support to retain the screen in place. In order to stabilize the j 25 assembly, the outer channel support may be spot-welded or ,i bolted to the inner retainer shim.

ji The container channel support of Figure 17 is fabricated as described above for granular sorbents; however, it may not be as deep as the channel support since the charcoal wafers are very thin. The front finemesh stainless steel screen is inserted into the channel support. Typically, three 40 mm square wafers of the charcoal cloth are laid over the front fine mesh screen in the channel support, followed by a large mesh backup screen. A thin square inner shim assembly is then inserted over the large-mesh back screen to retain the sorbent assembly in place. Alternatively, a two-leafed WO 90/09572 PCT/ US9 0/00584 31 spring-loaded thin inner shim assembly may be used for this purpose; the two legs are compressed then inserted and allowed to expand to seal the bed in place.

One possible sampling configuration would involve three sample containers of the type described by Figure 17 where the samplL canister would contain front, middle and back sorbent sections of charcoal cloth wafers or wafers of other sorbent material. This arrangement finds use for high-vapor pressure analytes that migrate from one sorbent section to the next during storage because it permits the individual sorbent sections to be separated from one another immediately after sampling.

Alternatively, it permits spacers such as thin 40 mm square sheets of stainless steel to be inserted between the three sorbent sections to minimize such migration.

Another obvious configuration is assembled as above except that the entire sorbent bed is placed in a tripledepth channel support. First, the front fine mesh retainer screen is inserted, followed by the front charcoal cloth sorbent bed, a large mesh spacer screen, the middle charcoal cloth bed, another large-mesh spacer screen, and finally the backup charcoal cloth bed followed by the back large mesh screen, followed by the retainer clip.

Another variation on the sampler configuration is one which permits estimation of the total amount of analyte received by the subject, This is shown by Figure 18 which lacks a filter to remove the analyte from the ambient air and is specifically designed to be used in an area of contaminated air. The contaminated air is inhaled through an inhalation check valve and exhaled through a canister of sorbent. To ensure that all the exhaled air and none of the inhaled or ambient air passes through the sorbent canister, at least one and preferably two check valves, one on each side of the canister are added. The conduit leading from the mouthpiece may also optionally have an access port for sampling the air or I r i- A WO 90/09572 PCr/ US90/00584 32 replacing the inlet check valve(s).

The dose a subject receiv.s can be calculated by measuring the total volume inhaled multiplied by the analyte concentration and the percent absorbed by the subject. The percentage absorbed can easily be calculated from the amount measured in the canister. From the does absorbed per breath one can then determine the total dose absorbed by the subject and act accordingly. Air concentrations of various analytes are fair measures of one's exposure to gasses and volatile chemicals but they do not indicate the actual amount received. In accordance with the invention one finally has an easy, unobtrusive, and readily repeatable technique on demand to determine the estimated amount the body actually absorbed.

Figure 19 shows a single sorbent retainer ring that may replace part 404. The retainer may fit into the sample canister 412. At the bottom, it engages the rear retainer screen 406 and at the top it engages the Teflon washer 402 in Figare 4. Along with the torous, the retainer ring may have a cutout to engage an antirotational lug in the sample canister. The system may use any particular sorbent or combination of sorbents.

The foregoing description of the specific embodiments will so fully reveal the general nature of the invention that others can, by applying current knowledge, readily modify and/or a'apt for various applications such specific embodiments without departing from the generic concept, and, therefore, such adaptations and modifications should and are intended to be comprehended within the meaning and range of equivalents of the disclosed embodiments. It is to be understood that the phraseology or terminology employed herein is for the purpose of description and not of limitation.

Claims (29)

1. Apparatus for collectingAbreath samples of a subject for subsequent determination of analyte content, comprising: a tubular body having a first and second ends; first conduit means for selectively loading the tubular body with the subject's breath, said first conduit means communicating with said tubular body at a to location intermediate4said first and second ends; second conduit means fluidly communicating with said first end of said tubular body, said second conduit means including air filtering means and selectively operable valve means for admitting ambient air through sa;3 filtering means and into said tubular body when =a subject inhales through conduit means; third conduit means fluidly communicating with said second end of said tubular body, said third conduit means including sample collection means for collecting breath samples of a subject for subsequent determination of analyte content and selectively operable valve means for admitting exhaled breath from said tubular body into said sample collection means when a=use-r exhales hthgrg-i a E>4zs egF i- means, said valve means in said second duit means being rendered inoperable when said val means in said third conduit means is rendered ope le, and said valve means in said third conduit me s being rendered inoperable when said valve means i said second conduit means is rendered operable.

2. The appara s of claim 1, wherein said tubular body has a sub antially "T-shaped" configuration.

3. Theapparatus of claim 1, wherein said first, secon and third conduit means each define a longitudi 1 axis, the longitudinal axis of said first condi means being disposed at an angle to said second and condui-t .an. oSf osaid tubular body. N, SUBSTITUTE SHEET 33 :j SUBSTITUTE SMET -oC w/tlk -33A through said first conduit means; and desorbing means for desorbing and measuring breath samples collected in said sample collection means; said valve means in said second conduit means being rendered inoperable when said valve means in said third conduit means is rendered operable, and said valve means in said third conduit means being rendered inoperable when said valve means in said second conduit means is rendered operable. 2. The apparatus of claim 1, wherein said tubular body has a substantially "T-shaped" configuration. 3. The apparatus of claim 1, wherein said first, second and third conduit means each define a longitudinal axis, the longitudinal axis of said first conduit means being e 15 disposed at an angle to said second and third conduit means of said tubular body. I o *g o• 2 I c WO 90/09572 PCT/US90/00584 34

4. The apparatus of claim 3, wherein said angle comprises at least 90 degrees.

The apparatus of claim 3, wherein said angle is 120 degrees.

6. The apparatus of claim 1, wherein said valves in each of said second and third conduit means comprises a check valve.

7. The apparatus of claim 6, wherein each of said check valves is removable from its respective con- ]0 duit means.

8. The apparatus of claim 1, wherein said sample collection means comprises a container including at least one bed of sorbents.

9. The apparatus of claim 8, wherein said at least one bed of sorbents comprises a bed of charcoal cloth.

The apparatus of claim 1, wherein said tubular body includes an opening and connection means at said opening for connecting means for carrying out side- stream sampling. =11. Aas, 1x- e-i_-re nguad-L= in a tubular conduit means, comprising: an elongated guide tube having first valve supporting end and a second open end, aid guide tube including a slot formed at one si thereof and extending along the longitudinal axis o said guide tube, an elongated push rod slidably su orted concentrically within said guide tube for m ement along the longi- tudinal axis of said guide ube, said push rod having means, attached to on end thereof, which extends radially outwardly fro the guide tube, and an o er sleeve member disposed concentri- cally about sa guide tube for movement along the longi- tudinal ax' of said guide tube, whereby, in order to mount a heck valve in a tubular conduit means, the push rod moved away from the first end of the guide tube so ~r~l ^j) CdS Ff Re iti. rrr _Traagtla s4 -34A-

11. Apparatus for inserting and mounting the selectively operable valves in the second jr third tubular conduit means in an apparatus of claim 1 or for inserting and mounting the valve means in the second or third openings of claim 23, comprising: an elongated guide tube having a first valve supporting end and a second open end, said guide tube including a slot formed at one side thereof and extending along the longitudinal axis of said guide tube, an elongated push rod slidably supported concentrically within said guide tube for movement along the longiLudinal axis of said guide tube, said push rod having means, attached to one end thereof, which extends radially outwardly from the guide tube, and 15 an outer sleeve member disposed concentrically about said guide tube for movement along the longitudinal axis of said guide tube, whereby, in order to mount a check valve in a tubular conduit means, the push rod is moved away from the first end of the guide tube so that the 20 outer sleeve member is moved in a corresponding 9748i PCT/US 9 /00 o 8 SPaEA/US 030or 1990 direction, the valve is disposed over and pushed onto said guide tube first end, and said push rod is moved back toward the guide tube first end so that 'he outer sleeve S member forces the valve off the first end of the guide tube and into its mounting in a respective conduit means.

12. The apparatus of claim 11 wherein the guide tube is hinged.

13. The apparatus of claim 1 wherein the sample collection means or air filtering means comprises a removable canister containing a sorbent.

14. The apparatus of claim 1 wherein the sample collection means or air filter means comprises a square or rectangular cross section.

15. The apparatus of claims 13 or 14 wherein the sorbent comprises charcoal cloth.

16. A method formeasuring volatile organic com- pound analytes in a sample of breath, comprising prefil- tering the gas inhaled by the subject with a sorbent capable of significantly removing either the analyte or the volatile organic compound to be measured or a compound which may interfere with either the concentration, sorp- tion, release, or measurement of the analyte; and passing a breath sample through a sorbent capable of retaining one or more of said analytes, desirbing at least one of the analytes from the sorbent, and measuring the volatile organic compound analytes released from the sorbent.

17. A method forimeasuring an analyte in a multi-breath sample, comprising passing multiple breaths through a sorbent capable of retaining one or more analytes, desorbing the analyte from the sorbent, and measuring the analyte released from the sorbent, said multiple breaths being passed directly from a subject to the sorbent.

18. The method of claim 17 further comprising prefiltering the gas inhaled by the subject with a sorbent capable of significantly removing either the analyte or the SUBSTITUTE SHEET 1, SUBST1TI Sit®E~ i/u^ I PCT/US 90/0058 IPEA/US 0 DEC1990 35/1 volatile organic compound to be measured or a compound which may interfere with either the concentration, sorption, release, or measurement of the analyte.

19. The method of claim 16 or 17, wherein a common exhaled gas is measured along with the analyte and 8~ j i, \J emm' VIM~~f~ Wt TVAOS 36 the two amot.nts compared.

The method of claim 16 wherein the breath sample contains air from more than one exhalation.

21. The method of claim 16 or 17 wherein the analyte desorbed by thermal desorption.

22. The method of claim 16 or 17 wherein the breath sample is an alveolar breath sample.

23. Apparatus for collecting and measuring exhaled breath samples of a subject breathing air containing an analyte and for subsequent determination of the analyte in exhaled breath, comprising a tubular conduit having one opening adapted to receive exhaled gas from the subject, a second opening connected tc sample collecting means, a third opening to permit inhalation of ambient air through air filtering means, and desorbing means for desorbing and 04;: measuring the analyte collected in the sample collection means wherein the second and third openings contain valve mean. to permit only exhaled gas to pass through the sample collection means. 20

24. The apparatus of claim 23 wherein the sample collection means contains a sorbent capable of retaining at least one analyte.

25. The apparatus of claim 23 wherein the valve means are check valves.

26. The apparatus of claim 25 wherein sample collection means has a check valve at least upstream or on both sides of it to minimize ambient air or inhaled air from being collected.

27. The method of claim 16 or 7' wherein the subject is inhaling gas containing the analyte

28. The method of claim 27 whereby one determines the amount or percentage of analyte absorbed by the subject. 9748i 37

29. The apparatus of claim 1, 11 or 23 substantially as hereinbefore described with reference to any one of the drawings. The method of claim 16 or 17 substantially as hereinbefore described with reference to any one of the examples. DATED: 4 June, 1992. PHILLIPS ORMONDE FITZPATRICK ATTORNEYS FOR:- THE UNITED STATES OF AMERICA, REPRESENTED BY THE SECRETARY, UNITED STATES DEPARTMENT OF COMMERCE 9000i ee