CN104394765A

CN104394765A - System for measuring breath analytes

Info

Publication number: CN104394765A
Application number: CN201380017939.2A
Authority: CN
Inventors: L·M·艾哈迈德; B·萨特菲尔德; R·L·马蒂诺; Z·B·史密斯
Original assignee: Invoy Technologies LLC
Current assignee: Invoy LLC
Priority date: 2012-02-01
Filing date: 2013-02-01
Publication date: 2015-03-04
Also published as: AU2013215601A1; WO2013115933A1; EP2809230A1; EP2809230A4

Abstract

In accordance with one aspect of the invention, a system is provided for sensing an analyte in breath of a user. The system comprises a base; a breath input operatively coupled to the base that receives the breath; a cartridge coupled to the base and in fluid communication with the breath input to receive the breath, wherein the cartridge comprises an interactant subsystem that is selected to undergo a reaction with the analyte when the analyte is present in the breath and to undergo an optical change corresponding to the reaction; and an optical subsystem coupled to the base and configured to sense the optical change, wherein the optical subsystem generates an output comprising information about the analyte in response to the optical detection. Methods are also provided.

Description

For measuring the system of breath analysis thing

Technical field

The present invention relates generally to the analysis thing for measuring in expiration, and the endogenous during preferred people exhales analyzes the system of thing, equipment and method.

Background technology

There is a lot of situation, wherein wish to analyze in sense gasses the existence of thing and/or amount or concentration." analysis thing " is widely used for meaning seeking using chemical constituent or the composition of equipment according to various aspects of the invention and method sensing as the term is employed herein.Analyze other material that thing can be or can comprise element, compound or other molecule, lewis' acid fragment or may contain in a fluid.In certain situation, embodiment and method, can exist and analyze thing and target more than one and be to sense multiple analytes." fluid " is widely used for comprising when by flowing during External Force Acting and the material that changes of its shape as the term is employed herein.It comprises liquids and gases, is not only respective pure form, and is also like this time under heterogeneous state, such as serosity, suspension, aqueous colloidal dispersion, aerosol etc.Newtonian fluid is the most applicable is applied to the present invention, but non-newtonian behaviour to a certain degree can be receptible, and this depends on specific application, and this is not intended to restriction." gas " also uses and widely according to its general sense as the term is employed herein, not only comprises pure gas phase but also comprises steam, on-liquid fluid-phase, gaseous colloid suspension, carries or be suspended in solid phase particle material in gas or steam or liquid phase microdroplet etc. secretly." sensing " and " sensing " is widely used for meaning detect one or more existence analyzing thing or measure one or more amount analyzing thing or concentration as the term is employed herein.

Under many circumstances, to need or the support equipment (equipment as available in hospital, laboratory or test facilities) of wishing to analyze or otherwise carry out this type of assessment to the analysis thing in field and not requiring costliness and heaviness.Usually wish in some cases to use well-equipped equipment haply, preferably portable and usual preferred wieldy equipment carries out this and analyzes.In some cases, also need or wish in real time or the analysis thing sensed in real time in fluid stream to be close to.In addition and in general, wish very much accurately and reliably to complete this type of sensing.

The background matrix of exhaling proposes multiple challenge to sensing system, and they need complicated treatment step and make system combination become to be applicable to become impossible by the shape factor of the portable use of amateur end user further.Such as, exhale and comprise high-caliber humidity and moisture, this may disturb sensor or cause condensation in portable set, and other problem.And, usually changing quite remarkable from the flow velocity of exhaling during user body adduction collection call gas or pressure.Known flow rate variable effect, affects the reaction of chemical sensor usually significantly.Exhaling, exactly when directly collecting from user, being generally core temperature or close to core temperature, this obviously may be different from environment temperature.In addition, body temperature may be different or even for used aloned person between different users, also different on the different dates.Therefore designing breath analysis device is not simple task, makes people attempt to design portable and that field is applicable equipment more difficult to a certain extent.

It should be noted that measuring the endogenous in exhaling analyzes the different challenge of thing existence and need the technology and equipment different from measuring exogenous analysis thing.Endogenous is analyzed thing for those generation by health (eliminating gastrointestinal lumen) and is analyzed things, and exogenous analysis thing be due to external action or due to user consumption be present in expiration those analyze things.But, very multiple analyte be produce endogenously and also can be outer seedbed introduce.Such as, by amino acid metabolism, Inner seedbed produces ammonia, but also can from environment as the seedbed, household cleaning articles for use China and foreign countries containing ammonia is introduced.Term " endogenous " uses according to its general sense in this area.Endogenous is analyzed thing and is produced by natural or non-natural mode in human body, its tissue or organ (usually getting rid of gastrointestinal lumen).

The endogenous measured in exhaling is analyzed thing and be there is multiple significant challenge.Endogenous is analyzed thing in expiration, is usually had significantly lower concentration, is usually about a few millionths (ppm), parts per billion (ppb) or less.In addition, endogenous analyzes measurement needs discrimination analysis thing in the composite interstitial substance of background gas of thing.Be not that typically atmospheric gas forms (such as, being mainly nitrogen), but expired gas have high humility content and larger gas concentration lwevel.This causes the unique challenges of chemosensitivity, selectivity and stability aspect.Such as, contribute to chemical substance that expiration ammonia measures preferably under 3% to 6% steam and 3% to 5% carbon dioxide exist sensitivity reach 50ppb.

Owing to even detecting the historical difficulty in endogenous breath analysis thing, do not studying other challenge widely.Example of this type of challenge comprises: (a) makes analysis thing with health or disease state is associated, (b) measures and provide exhale these of feature such as flow velocity and expiratory pressure of people and analyze thing, (c) sensitivity and optionally measure these and analyze thing and (d) and in portable, the cost that can implement in medical environment or home environment effectively encapsulate, carry out all these operate.

Colorimetric equipment is a kind of method for measuring the reaction relating to breath analysis thing.The colorimetric method of endogenous breath analysis is subject to the puzzlement of very long response time and expensive components in history.Usually, this alanysis must be carried out in the lab.Therefore, there are the needs to a kind of breath analysis device, described breath analysis device accurately and rapidly can measure the endogenous expiration component that exists with relatively low concentration as acetone, except cheap and except can being used by layman, also need not wait as long for result.If breath analysis device can measure multiple analytes, be then also preferred.

Summary of the invention

According to an aspect of the present invention, a kind of system for sensing the analysis thing in user expiration is provided.Described system comprises pedestal; The expiration input that the reception that may be operably coupled to pedestal is exhaled; Be connected to pedestal and be communicated with to receive the gas storehouse (cartridge) of exhaling with expiration input fluid, wherein said gas storehouse comprises the reaction that is selected to experience and analysis thing when analyzing thing and being present in expiration and experiences and the described interactant subsystem reacting corresponding optical change; And be connected to described pedestal and be configured to sense the optical subsystem of optical change, wherein said optical subsystem produces the output comprised about the information analyzing thing in response to optical detection.

Expiration input option comprises ozzle and the connector for being connected the inhuman expiration container wherein holding expiration.The preferred embodiment of inhuman expiration container can comprise bag, as Tedlar bag.Described gas storehouse is preferably removably connected to pedestal.Described gas storehouse also optionally but preferably include handle and preferably include light shield apparatus.Or rather, in some cases, Problems existing is the component in gas storehouse such as may be subject to surround lighting adverse effect as chemical constituent.Therefore, in preferred at present embodiment in some according to the present invention and method, the pedestal of system comprises and is formed inner and shield described inside and makes it from the outer surface of ambient light effects, and wherein said outer surface comprises hole; And described gas storehouse comprises when substantially coincideing to be connected to pedestal in gas storehouse with described hole and shields surround lighting and prevent it from entering the guard shield of described hole.

In certain embodiments, pedestal is configured to accept expiration from multiple expiration input.Pedestal can be configured to accept the expiration of variable-volume and/or remove the expiration of unwanted volume further.

In some cases, need or wish to adopt multistage response system.Therefore, in some at present preferred embodiments and method, interactant subsystem comprises and is selected to the experience when analyzing thing and being present in expiration and reacts with analyze thing first and produce the first interactant of the first intermediate; And be selected to experience and react with second of described first intermediate and to cause the second interactant of the optical change corresponding with described second reacting phase.Illustrative but at present in preferred example at one, the first interactant comprises and there is not the primary amine being connected to the first substrate under tertiary amine haply; And the second interactant comprises tertiary amine.

Optical subsystem can be configured in many ways and sense optical change according to multiple various criterion.It can be configured to the scheduled time sensing optical change such as after be input in input of exhaling by exhaling.In some preferred embodiments, system can be included in the flow sensor sensing expiration feature when expiration is moved in systems in which further; And optical subsystem is configured to sense the optical change in response to flow sensor.

Described system can also and preferably include the processor performing difference in functionality in systems in which.One of those functions can comprise use process information, as system is configured to the discriminating of one or more specific analyte sensed; The information relevant to analyzing thing, concentration range as expected, state, reactivity, temperature and/or pressure dependency, partial pressure and other vapor state information etc.; Flow performance, as fluid temperature (F.T.), pressure, humidity, quality or volume flow rate etc., measures within the scope of each comfortable certain hour statically or dynamically.Process information also can comprise the information relevant to gas storehouse, such as gas storehouse type, its be configured to sense one or more analyze things, its capacity, its permeability or flow performance, its Expected Time Of Response etc.Process information also can comprise to expiration input relevant information, such as, as expired gas temperature, pressure, humidity, expection composition etc.In this type of optimum decision system and method, optical subsystem is preferably configured to sense in response to processor with in response to one or more the optical change in this type of information about the information based on process.

In the embodiment and method of some optimum decision systems, also provide a kind of flow facilitator, it is preferably connected to pedestal.Described flow facilitator contributes to expiration and flow to flow in gas storehouse and with interactant subsystem and contact.

According to another aspect of the present invention, a kind of method for sensing the analysis thing in user expiration is provided.Described method comprises the gas storehouse providing and comprise a chamber, and described chamber comprises the reaction that is selected to experience and analysis thing when analyzing thing and being present in expiration and experiences and the described interactant subsystem reacting corresponding optical change.Described method also comprises providing the expiration flow path in the chamber comprising the gentle storehouse of input of exhaling and arranging optical sensor makes it be in the relation fixing relative to described chamber.In addition, described method comprise make described exhale mobile by flow path, exhale mobile by make optical sensor detecting optical change during flow path and in response to optical detection output packet containing about the output of information analyzing thing.

The method at present preferred embodiment in, the providing to be included in flow path of flow path provides ozzle; And mobile being comprised by flow path of exhaling makes user be exhaled to flow path by ozzle.In addition or alternatively, the providing also can be included in flow path inhuman expiration container be provided of flow path; And mobile can being comprised by flow path of exhaling makes expiration flow to flow path from inhuman expiration container.

Described method at present preferred embodiment in, gas storehouse is removably connected to pedestal.Described method is also optionally included in exhale to move and makes it from ambient light effects by shielding interactant during chamber.

Described method at present preferred embodiment in, wherein interactant comprises and is selected to the experience when analyzing thing and being present in expiration and reacts with analyze thing first and produce the first interactant of the first intermediate; And be selected to experience and react with second of described first intermediate and the second interactant causing the optical change of to react corresponding with described second.At one at present preferably but only in illustrative embodiment, the first interactant comprise haply tertiary amine not in the presence of be connected to the primary amine of the first substrate; And the second interactant comprises tertiary amine.

In current preferred method embodiment, cause optical sensor detecting optical to change and be included in expiration initial movable by the scheduled time sensing optical change after flow path.Alternatively or in addition, described method can be included in the feature that when moving in flow path, sensing is exhaled of exhaling; And cause optical sensor detecting optical to change can comprise in response to sensed characteristic to sense optical change.Cause optical sensor detecting optical to change and also can comprise in response to process information if the process information of general introduction more than is herein to sense optical change.

In the preferred implementation of described method, mobile being comprised by flow path of exhaling is promoted that expiration flow to intracavity and flows with interactant subsystem and contacts.

According to another aspect of the present invention, a kind of system for sensing the analysis thing in user expiration is provided.Such as at needs or when wishing to use one or more analysis things of multiple step process such as to promote to sense, this system can be used.This system comprises pedestal; The expiration input that the reception that may be operably coupled to pedestal is exhaled; And be connected to pedestal and be communicated with to receive the gas storehouse of exhaling with described expiration input fluid.Described gas storehouse comprises and is selected to the experience and first of described analysis thing when analyzing thing and being present in expiration and reacts the first interactant to produce the first intermediate.Described system comprises the distributing equipment of distribution second interactant being connected to pedestal further, and described second interactant is selected to experience and reacts with second of the first intermediate, wherein produces and reacts corresponding optical change with described.Described system comprises further and is connected to pedestal and is configured to sense the optical subsystem of optical change, and wherein said optical subsystem produces the output comprised about the information analyzing thing in response to optical detection.

Input of exhaling can comprise ozzle, for connect the connector of the inhuman expiration container (such as bag) of wherein holding expiration or the two.

Described gas storehouse is removably connected to pedestal.It preferably but optionally comprise handle.

Specifically, when built-in system component has heliosensitivity as interactant, pedestal can comprise forming inside and shielding described inside makes it from the outer surface of ambient light effects, and wherein said outer surface comprises hole; And described gas storehouse can comprise when substantially coincideing to be connected to pedestal in gas storehouse with described hole and shields surround lighting and prevent it from entering the guard shield of described hole.

Interactant subsystem preferably includes and to be selected to when analyzing thing and being present in expiration experience and to analyze first reacting and produce the first interactant of the first intermediate of thing; And be selected to experience and react with second of described first intermediate and the second interactant causing the optical change of to react corresponding with described second.Illustrative but the current preferred example as one, the first interactant can comprise haply tertiary amine not in the presence of be connected to the primary amine of the first substrate; And the second interactant can comprise tertiary amine.

In certain embodiments, interactant subsystem can comprise sodium nitroprusside, dinitrophenylhydrazine, sodium dichromate, pararosaniline, bromophenol blue, DCCA salt, sodium salicylate, sodium dichromate, crystal violet, benzyl mercaptan or its combination.

In preferred embodiments, interactant subsystem is configured to the Endogenous level measuring the analysis thing in exhaling, and wherein this type of level can be 5ppm or less.

With above-described embodiment is the same with option herein, the scheduled time that distributing equipment can be configured to after be input in input of exhaling by exhaling distributes the second interactant.Alternatively or in addition, described system can be included in the flow sensor sensing expiration feature when expiration is moved in systems in which; And distributing equipment can be configured to distribute the second interactant in response to flow sensor.

Also illustrated by reference this paper other embodiment above-described and method, described system can comprise processor further, and described processor comprises process information, such as, as this paper those information above-described; And distributing equipment can be configured to distribute the second interactant in response to processor based on process information.

Optical subsystem according to this aspect of the invention also can comprise parts as discussed herein above and feature and/or as the above flow facilitator more fully described herein.

According to another aspect of the present invention, provide a kind of system for sensing the analysis thing in user expiration, wherein said system comprises pedestal; The expiration input that the reception that may be operably coupled to described pedestal is exhaled; Removably be connected to pedestal and be communicated with to receive the gas storehouse of exhaling with expiration input fluid; And be connected to the sensing subsystem of pedestal, wherein said pedestal comprises forming inside and shielding described inside makes it from the outer surface of ambient light effects, and wherein said outer surface comprises hole, and of the present inventionly comprise the guard shield improving further and be connected to described gas storehouse in this respect, described guard shield and described hole substantially identical to be connected to pedestal in gas storehouse time shield surround lighting and prevent it from entering described hole.

According to a further aspect of the invention, a kind of system for sensing the multiple analytes in user expiration is provided.Described system can comprise pedestal; The expiration input that the reception that may be operably coupled to pedestal is exhaled; Be connected to pedestal and be communicated with to receive multiple gas storehouses of exhaling with expiration input fluid, wherein each gas storehouse comprises corresponding interactant subsystem, and it is unique relative to other gas storehouse interactant and is selected to the experience when correspondence analysis thing is present in expiration and analyzes the corresponding of analysis thing corresponding in thing with these and react to form corresponding product state; And be connected to pedestal and be configured to sense product state and the sensing subsystem producing the output of the information comprised about multiple analytes.

According to a further aspect of the invention, a kind of method for sensing the multiple analytes in user expiration is provided.Described method comprises providing and is connected to pedestal and is communicated with to receive multiple gas storehouses of exhaling with expiration input fluid, wherein each gas storehouse comprises corresponding interactant subsystem, and it is unique relative to other gas storehouse interactant and is selected to the experience when correspondence analysis thing is present in expiration and analyzes the corresponding of analysis thing corresponding in thing with these and react to form corresponding product state; And cause and be connected to pedestal and be configured to sense the sensing subsystem sensing product state of product state and produce the output of the information comprised about multiple analytes.

According to another aspect of the present invention, a kind of system for sensing the analysis thing in patient expiration is provided.Described system comprises gas storehouse, the reaction volume that described gas storehouse comprises the first container, fluid container and is communicated with described fluid container fluid with described first container, described first container comprises the first interactant and described fluid container comprises fluid, and wherein said fluid container has initial fluid level and the space above initial fluid level.Described system also comprises pedestal, and described pedestal comprises for the flow path flowed in described pedestal of exhaling; The expiration input sink be communicated with described flow path fluid, it receives exhales and the flow path that led; Gas storehouse is removably received in pedestal with the gas storehouse shell making reaction volume be communicated with flow path fluid; Distributing equipment, its initial fluid horizontal down in fluid container form hole and the pressure relaxed in the space above initial fluid level to make fluid trickle container and to flow into reaction volume, thus promote the optical change in reaction volume relative at least one analyzed in the existence of thing and concentration; And sensing optical change produce the optical subsystem of output comprised about the information analyzing thing in response to optical change.Allotter preferably includes elongated component, such as, as pin, pin, bar etc.It can comprise solid component or it can comprise fluid passage.

In different aspect of the present invention and their preferred embodiment, distributing equipment and correlation function relate to Liquid distribution in liquid container.For realizing this operation, below the initial liquid level of liquid container, forming hole, being preferably in this horizontal down completely and being more preferably in bottom of liquid container or other position to make to obtain from container the liquid of maximum.Distribution function also relates to the pressure when fluid shifts out liquid container in the horizontal superjacent air space of mitigation initial fluid, shifts out liquid container and move in reaction volume to make fluid.This realizes preferably by piercing through or otherwise formed opening in liquid superjacent air space, with make gas can enter described space with equalizing pressure, avoid being formed negative pressure or vacuum in space and thus allow liquid to flow out or otherwise shift out the hole below the initial liquid level of liquid container.Therefore, be preferably slender member and be positioned at deployed position outside liquid container, wherein said slender member forms hole and the pressure relaxed in the horizontal superjacent air space of initial fluid, to make fluid trickle container and to flow into reaction volume at the initial fluid horizontal down of fluid container.Slender member can comprise such as pin, pin, bar etc.

According to another aspect of the present invention, a kind of method for sensing the analysis thing in patient expiration is provided.Described method comprises provides gas storehouse, the reaction volume that described gas storehouse comprises the first container, fluid container and is communicated with described fluid container fluid with described first container.First container comprises the first interactant and fluid container comprises fluid.Fluid container has the space above initial fluid level and initial fluid level.Described method also comprises provides pedestal, and described pedestal comprises the flow path flowed in pedestal for exhaling, the expiration input sink be communicated with described flow path fluid, gas storehouse shell, distributing equipment and optical subsystem.Described method comprises in gas storehouse shell gas storehouse being inserted into pedestal further to make reaction volume to be communicated with flow path fluid and to cause to exhale to flow in flow path and to flow in reaction volume.After expiration flows through reaction volume, described method comprises and uses distributing equipment to form hole and the pressure relaxed in the horizontal superjacent air space of initial fluid to make fluid trickle container and to flow into reaction volume at the initial fluid horizontal down of fluid container, thus promotes the optical change in reaction volume relative at least one analyzed in the existence of thing and concentration.In addition, described method comprises sensing optical change and produces the output comprised about the information analyzing thing in response to optical change.

According to a further aspect of the invention, a kind of system for sensing the analysis thing in patient expiration is provided.Described system comprises the gas storehouse with reaction volume and to the opaque guard shield of surround lighting.It comprises pedestal further, and described pedestal comprises for the flow path flowed in described pedestal of exhaling; The expiration input sink be communicated with flow path fluid, it receives exhales and by described expirations guiding flow path and by reaction volume, wherein exhales by reaction volume mobile phase for the optical change of at least one promotion to reaction volume analyzed in the existence of thing and concentration; Removably be received in gas storehouse with the gas storehouse shell making reaction volume be communicated with flow path fluid in pedestal, wherein the guard shield in gas storehouse coordinates with the gas storehouse shell of pedestal and is mapped to reaction volume to block ambient lighting; And sensing optical change produce the optical subsystem of output comprised about the information analyzing thing in response to optical change.

Accompanying drawing explanation

To be incorporated in this description and the accompanying drawing forming the part of this description illustrates preferred embodiment and method at present of the present invention, and to be used from the detailed description one of general remark given above and the preferred embodiment hereafter provided and method and to explain principle of the present invention.In the accompanying drawings:

Fig. 1 illustrates the comprehensive diagram for detecting equipment and the disposable pneumo storehouse changed from the colorimetric of reacting with breath analysis thing.

Fig. 2 illustrates the example of the expiration collecting bag with integrated flow measurement capacity.

Fig. 3 shows the example that the indirect expiration undertaken by input of exhaling is collected.

Fig. 4 describes the general layout of optics sensing subsystem structure.

Fig. 5 describes the general layout of optics sensing subsystem structure from top view.

Fig. 6 describes the pneumatic handle being suitable for the measurement of high-quality breath.

Fig. 7 illustrates a kind of method using ball-valve dedicated to carry out parts minimizing.

Fig. 8 illustrates the breath analysis equipment according to another current preferred embodiment of the present invention.

Fig. 9 is the hardware block diagram of equipment shown in Fig. 8.

Figure 10 is the perspective view of the expiration sample sack for Collection and preservation expiration sample and for the breath analysis equipment that expiration sample inputted Fig. 8 to Fig. 9.

Figure 11 illustrates the exemplary reaction initiator based on pin.

Figure 12 illustrates and utilizes linear actuators to be inserted into gas storehouse in base unit.

Figure 13 illustrates the details of slide mechanism relative to an embodiment in sensor gas storehouse.

Figure 14 illustrates the example of the breath analyzer post based on Tenax TA.

Figure 15 display can be pressed into the example of the substrate slice of fixed disk.

Figure 16 illustrates the exemplary general synoptic diagram that gas storehouse is designed.

Figure 17 illustrates a replacement scheme of the keeper (130) of the Figure 16 for holding reactive particle.

Figure 18 illustrates three embodiments of the paper tinsel ampoule that can pierce through.

Figure 19 illustrates some embodiment of the ampoule that can pierce through.

Figure 20 illustrates the embodiment of the tank pierced through for receiving fluids.

Figure 21 illustrates the different dried reagents be encapsulated in single post.

Figure 22 illustrate be encapsulated in single post another organize stacking dried reagent.

Figure 23 illustrates the reagent using compressible porous media to remain on appropriate position.

Figure 24 illustrates that liquid reagent can be fixed to an example of the mode that the mode in gas storehouse can discharge when reacting with it.

Figure 25 shows that liquid reagent can be fixed to another embodiment of the mode that the mode in gas storehouse can discharge when reacting with it.

Figure 26 illustrates an example in many liquid gas storehouse.

Figure 27 illustrates another example in many liquid gas storehouse.

Figure 28 illustrates some the gas storehouses design that can repeatedly apply.

Figure 29 illustrates the embodiment that gas storehouse is designed.

Figure 30 illustrates the description of flow path after fluid-tight destroyed and fluid-tight are formed.

Figure 31 illustrates an embodiment in the gas storehouse with developer solution.

Figure 32 is according to various aspects of the invention for the schematic diagram of use in the breath analysis equipment of Fig. 8 to Fig. 9 one of gas storehouse preferred embodiment at present.

Figure 33 is an embodiment of ampoule puncturing mechanism.

Figure 34 is another embodiment of ampoule puncturing mechanism.

Figure 35 is an embodiment of ampoule breaking mechanism.

Figure 36 is another example of ampoule puncturing mechanism.

Figure 37 is another example of ampoule puncturing mechanism.

Figure 38 is another example of ampoule breaking mechanism.

Figure 39 is an embodiment of ampoule fixed policy.

Figure 40 is another embodiment of ampoule fixed policy.

Figure 41 is another embodiment of ampoule fixed policy.

Figure 42 is another example of ampoule breaking mechanism.

Figure 43 illustrates an embodiment based on the expiration of repeatedly the breathing sampling ring of breathing out in base unit.

There is in the disposable container that Figure 44 illustrates in base unit (instead of in disposable pneumo storehouse) embodiment of the expiratory measurements system of developer solution.

Detailed description of the invention

Now in detail with reference to as described herein below and preferred embodiment and method at present of the present invention as accompanying drawing illustrated by, wherein in whole accompanying drawing, similar reference character indicates similar or corresponding part.But, it should be noted that the present invention in it is more extensive, be not limited to specific detail, typical equipments and method and in this part in conjunction with shown in preferred embodiment and method and described illustrative example.In view of this description and suitable equivalent, the present invention points out and clearly requirement in the dependent claims particularly according to its different aspect.

Introduction

The present invention relates to the analysis thing for sensing in expiration and be preferred for sensing the equipment of analysis thing and method that Inner seedbed produces.Described equipment and method can and preferably include the gas storehouse comprised or containing expiration reactive chemical, described chemical substance namely with exhale in specific or required chemical species or the chemical constituent of component reaction.Preferably, these expiration reactive chemicals are specific, are also even specific under expiration background.

An interested especially field relates to breath analysis.What comprise at illustrative expiration composition is the analysis thing be associated with morbid state, described analysis thing comprise to list in following table 1 those.As mentioned above, there are about 300 kinds of VOCs identified in expiration, all these compounds are for using this type of embodiment and method to carry out the candidate molecule thing analyzed.In addition, in some cases, the combination of the composition (analysis thing) in expiration can be used as excellent disease marker relative to the existence of any single analysis thing.

Table 1

Other example analyzing thing can comprise bromobenzene, bromochloromethane, bromodichloromethane, bromofom, Celfume, 2-butanone, n-butyl benzene, the second month in a season-butyl benzene, tert-butyl benzene, Carbon bisulfide, carbon tetrachloride, chlorobenzene, ethyl chloride, chloroform, chloromethanes, 2-chlorotoluene, 4-chlorotoluene, two bromochloromethanes, the bromo-3-chloropropane of l, 2-bis-, glycol dibromide, methylene bromide, 1,2-dichloro-benzenes, 1,3-dichloro-benzenes, Isosorbide-5-Nitrae-dichloro-benzenes, dichlorodifluoromethane, 1,1-dichloroethanes, 1,2-dichloroethanes, vinylidene chloride, cis-l, 2-dichloroethylene, trans-1,2-dichloroethene, 1,2-dichloropropane, 1,3-dichloropropane, 2,2-dichloropropane, 1,1-dichloropropylene, cis-l, 3-dichloropropylene, trans-l, 3-dichloropropylene, ethylo benzene, hexachlorobutadiene, methyl-n-butyl ketone, cumene, P-Cymene, METHYLENE CHLORIDE, 4-methyl-2 pentanone, methyl t-butyl ether, naphthalene, n-propylbenzene, styrene, unsym.-tetraehloroethane, sym.-tetrachloroethane, tetrachloroethylene, toluene, 1，2，3-trichlorobenzene, 1,2,4-trichloro-benzenes, 1，1，1-trichloroethane, vinyl trichloride, trichloroethylene, Arcton 11, glyceryl trichloride, 1，2，4-trimethylbenzene, 1，3，5-trimethyl-benzene, vinyl acetate, vinyl chloride, dimethylbenzene, two Bromofluoromethanes, toluene-d8, 4-bromofluoro benzene.

For acetone measurement, interested scope is different in a physiologically.In the preferred embodiment of meals monitoring, preferred measuring range is 0.5ppm to 5ppm under 0.1ppm definition case.For monitoring ketogenic diet, preferred measuring range is 1ppm to 10ppm under 0.1ppm definition case.For monitoring diabetic ketoacidosis, preferred measuring range is 5ppm to 50ppm under 1ppm definition case.For the type ii diabetes that screening is possible, preferred measuring range is 1ppm to 10ppm under 0.1ppm definition case.Be in the prediabetic individuals under diabetic renal papillary necrosis danger for screening, preferred measuring range is 1ppm to 10ppm under 0.1ppm definition case.

For sensing or the measurement of ammonia, interested scope is different in a physiologically.In the preferred embodiment of monitoring protein metabolism, preferred measuring range is 0.05ppm to 2ppm under 0.01ppm definition case.For renal failure possible in monitoring prediabetes, preferred measuring range is 0.5ppm to 5ppm under 0.1ppm definition case.For before dialysis, period or monitor dialysis patient afterwards, preferred measuring range is 0.2ppm to 2ppm under 0.1ppm definition case.For monitoring liver failure or relevant disease as hepatic encephalopathy, preferred measuring range is 0.5ppm to 5ppm under 0.1ppm definition case.For screening Reye syndrome (Reyesyndrome), preferred measuring range is 0.5ppm to 5ppm under 0.1ppm definition case.In the immunoenzyme technics of screening urea cycle disorder, preferred measuring range is 0.5ppm to 5ppm under 0.1ppm definition case.Expose for measurement environment or work, preferred measuring range is 0.5ppm to 5ppm under 0.1ppm definition case.

According to an aspect of the present invention, as above listed, a kind of system for sensing the analysis thing in user expiration is provided herein.Described system comprises pedestal; The expiration input that the reception that may be operably coupled to pedestal is exhaled; Be connected to pedestal and be communicated with to receive the gas storehouse of exhaling with expiration input fluid, wherein said gas storehouse comprises the reaction that is selected to experience and analysis thing when analyzing thing and being present in expiration and experiences and the described interactant subsystem reacting corresponding optical change; And be connected to described pedestal and be configured to sense the optical subsystem of optical change, wherein said optical subsystem produces the output comprised about the information analyzing thing in response to optical detection.

According to another aspect of the present invention, as discussed herein above, a kind of method for sensing the analysis thing in user expiration is provided.Described method comprises the gas storehouse providing and comprise a chamber, and described chamber comprises the reaction that is selected to experience and analysis thing when analyzing thing and being present in expiration and experiences and the described interactant subsystem reacting corresponding optical change.Described method also comprises providing the expiration flow path in the chamber comprising the gentle storehouse of input of exhaling and arranging optical sensor makes it be in the relation fixing relative to described chamber.In addition, described method comprise make described exhale mobile by flow path, exhale mobile by cause optical sensor detecting optical to change during flow path and in response to optical detection output packet containing about the output of information analyzing thing.

In order to these aspects of the present invention are described, describe current preferred embodiment referring now to other figure in Fig. 1 and accompanying drawing and this embodiment of use illustrated preferred method embodiment at present.But, should understand and not necessarily be restricted to this type of specific and illustrative equipment and method according to the present invention of these aspects.

Equipment according to aspects of the present invention and method can comprise or comprise any or all with lower component: the insertion mechanism in pedestal, input of exhaling, gas storehouse, sensing subsystem, pneumatic handle, reaction initiator, power booster, expiration regulator, digital converter or gas storehouse.Each in these parts can also comprise subassembly.Any or all parts of the present invention can be comprised in pedestal or otherwise and be connected to pedestal.In one embodiment of the invention, pneumatic handle is comprised in pedestal.In another embodiment, expiration input is comprised in pedestal.In addition, described equipment can comprise tracking and/or monitoring software.

Described pedestal optionally forms shell or the junction point of other parts for forming breath analysis device equipment.

Fig. 1 is that a current preferred embodiment of the system of thing is analyzed at least one measured in expiration in some aspect according to the present invention.Described system comprise (2) form in base unit pedestal, this be the distributing equipment of insertion mechanism (8) form in gas storehouse, optics sensing subsystem (10), at this especially in pneumatic handle (12) fluxus formae promoters and digital converter (14).Base unit (2) receives expiration via expiration input (4) from user.The insertion mechanism in gas storehouse comprises the device for inserting gas storehouse, wherein said gas storehouse comprise can at least one analyze when thing is present in expiration with the concentration being less than about 5ppm and its reaction to produce the reactive chemical of optical change.Optics sensing subsystem measures optical change.Pneumatic handle is preferably included in base unit, although always not this situation.Pneumatic handle allows the reactive chemical of exhaling with in gas storehouse to interact.Digital converter quantizes to sense the optical change of subsystem measurement by optics and output packet contains the display analyzing the information of thing about the described at least one in expiration.

Base unit can be and receives any device of exhaling from user.In certain embodiments, base unit comprises pneumatic handle.In preferred embodiments, base unit is portable and can be used by individual patient.Temperature and humidity change that base unit can also can experience (measure and compensate) is to improve the accuracy of measuring process.

Input of exhaling can be and can receive any parts of expiration from user and optionally perform expiration function of measuring.Expiration input can optionally comprise expiration regulating step, but this also can be processed by base unit itself.Input of exhaling also can comprise sampling of exhaling, and it preferably utilizes the bin for holding expiration sample.

Usually, collection of exhaling relates to the collection of expiration sample.This type of collection of exhaling can be direct or indirect.Direct example of exhaling collection relates to user and directly exhales in equipment or base unit.This example shown in Figure 29.Indirect expiration collection relates to such as user and exhales in collection container (such as, collecting bag), and wherein said container is connected to evacuating equipment.Fig. 3 shows the example that the indirect expiration undertaken by input of exhaling is collected.What have an other outlet tap (32) non-ly relapses the part that three-way valve (30) can make repeatedly to exhale and deposits to successively in collecting bag (34).The ozzle that tool is with or without integrated antibacterium/virus filter (35) prevents user cross-contamination.

For the relatedness improving the measurement result obtained by breath analysis device, can refer to such as following details and carry out collection of exhaling: the cumulative volume of the expiration that (a) collects; The source (such as, upper respiratory tract gas contrast alveolar gas) of b expiration that () collects; The number of times of c expiration that () collects; (d) exhale collect before and during experimenter physiological status (such as, the resting state with eupnea relative to the active state of respiratory frequency contrast overventilation with increase, as an example); And the respiratory effort of (e) sample collection mechanism (such as, experimenter whether need to be breathed by high resistant gathering-device within the persistent period extended or whether described mechanism allows eupnea to exhale).

As mentioned, expiration inputs the expiration that the optionally First Astronautic Research Institute for Measurement and Test collects.The metering of exhaling means the volume measuring the expiration inputted.This can be realized in many ways by those skilled in the art, comprise the amount of the expiration of actual measurement sampling (such as, use Pneumotachometers and record the cumulative volume of the expiration in specified rate time range) or limited by sample volume, such as, by making user exhale in the container of fixed volume.

In one that the present invention relates to collection of indirectly exhaling, expiration input can have integrated metered capacity, as having the expiration collecting bag of integrated flow measurement capacity.

Fig. 2 illustrates the example of the expiration collecting bag with integrated flow measurement capacity.Expiration sampling bag (20) is by form the impervious wall material of interested analysis thing and their environmental disturbances thing also comprises the expiration entrance (24) being equipped with ozzle (22) in some cases.Assembly upper part holds the electronic equipment and/or the plant equipment that are applicable to analyze or regulate expiration sample, comprises visual detector (26) in some cases.Electronic equipment can be made from multiple components, and described parts comprise temperature probe, pressure converter, timing circuit, humidity sensor and depend on other parts of application.Plant equipment can comprise one-way breather valve, flow restrictor, scrubber or desiccant chamber, computer control valve or automatic valve, hand-operated valve and other device.In one embodiment, check valve (24) is designed to coordinate with the receptor port on base unit, and described base unit is equipped with finger piece or the prodger that check valve is opened in design.This system can be collected expiration sample from user and make it be included in sampling bag, and interacts without the need to user.Bag being connected to base unit allows finger piece or prodger to open check valve (such as, flapper valve), removes by the pneumatic handle of such as base unit to make the content of bag.User does not need manually to interact with valve.User's Interface button (28) is also shown in Fig. 2, illustrates user and the possible interaction of electronic equipment, such as, to start intervalometer.Bag the second end (25) can be equipped with similar devices.Such as, lower part (25) is equipped with the second check valve, to exhale in the first check valve (24) and breathes out by second (25), thus last air part of breathing out is trapped in bag to make user.This can be used for sampling such as dark alveolar air space, and when not having the second check valve, collected air is the Part I be blown in equipment.Described bag can be assemblied in other point equally, such as, in side or above/back side.

Although wish to obtain representative expiration sample, for whole sample volume to be analyzed differ be decided to be favourable or needs.On the contrary, in some embodiments, representative sample can be analyzed.The reason of expiration of the whole volume of Water demand may not be the gelation of desiccant material.As mentioned, expiration input optionally can comprise sampling of exhaling, and this preferably uses sample bomb.Such as, sample bomb can be the one milliliter of syringe extracting representative sample from such as exhaling bag.In this construction, user is exhaled in exhaling bag, and described exhaling bag contains a certain amount of expired gas sample.Exhaling bag can and preferably be contained in the metered capacity that user determines the sample volume of sample volume and/or time per unit when bag is inflated.The gas once bag is substituted the bad for the good, just triggers sampling mechanism, to extract the expired gas of some smaller size smaller and this expired gas to be stored in sample bomb.Sampling mechanism can be active efflux, but it also can be need user apply power to collect sample by power driven tools, as syringe.Then, bag is bled.Then, less expiration sample stays in sample bomb by user.This sample bomb can be used for expiration sample " injection " in base unit.

The instantiation regulated of exhaling comprises: (a) dry (such as, removing moisture); (b) washing (such as, removing carbon dioxide or VOC); And (c) heats or cooling blast (condensation prevents/promotes).As mentioned above, expiration regulatory function (if carrying out) is by input or the piece-rate system execution of exhaling.

In one embodiment of the invention, collection of exhaling is carried out dividually with breath analysis.Separately these steps form some advantage that can be applicable to very much some application.Such as, if be high (such as, packed bed reactor) by the respiratory resistance of chemical reaction element, then user experiences more comfortable expiration to the collection in container by with respiratory resistance that is few and even that do not have.Then equipment itself can by sample or its partial delivery in reactive chemical, for sensing object.

Carry out exhaling a kind of method of collecting dividually for using active gas sample with breath analysis.Exactly, in breath analysis equipment, expiration sample must be directed to reactivity or the analyte-sensitive region of sensor system.Passive or driving mechanism can be used for this object.Passive system relate to use various parts, as flow restrictor, flow distribution device and do not need input energy other machinery (except exhale during apply except pressure).With wherein user is firmly contrary to these passive systems of reactive regions by expiration incoming call, initiatively gas sample equipment can be used for user to exhale to separate to sending of reactive regions with gas.The high pressure degradation of the such as controlled gas delivery flow velocity of sensor restrictive condition, stable driving pressure, upper reaches, sensor region amount can be breathed with user and require to separate.Specifically, the requirement of being blown by the breathing of the prolongation of high pressure drop system or user steady pressure or flow velocity is got rid of.In addition, the gas delivery parameter exceeding user ability can be realized.Such as, health adult is only about 0.3psi by the producible maximum pressure of forced expiration, and initiatively gas treatment equipment does not have this restriction.This makes the sensor of broad range be constructed to possibility.As another example, use initiatively gas delivery device that the low flow velocity of 50ml per minute can be made to continue some minutes, and the burden that the expiration that can not continue in identical period increase exports.(when insignificant respiratory resistance, comfortable people's breathing rate is 6L about per minute).

Develop the detector for multiple application and can be applicable to breath analysis.The test format being suitable for given application depends on the character of the chemical reaction for detecting given analysis thing.

Optics sensing subsystem can be any detector or other sensor that can measure optical change.This can be the direct measurement of optical change.It also can be the indirect inspection (such as, being changed by other energy state) of optical change.Optical change can relate to any following every or its combination separately, and without restriction: reflectance, absorbance, fluorescence, chemiluminescence, bioluminescence, polarization change, phase transformation, divergence, scattering, evanescent wave and surface plasmon resonance or other optical change any well known by persons skilled in the art.

Optics sensing subsystem can be accommodated in base unit or it can be the separate modular be inserted in base unit.Optics sensing subsystem can single use or it can repeatedly use.Optics sensing subsystem also can comprise continuously for measuring a detector row of optical change.

In the preferred embodiment utilizing in reflectance, absorbance and fluorescence any one, exciting light is supplied to system and follows the trail of the change of this light relative to the change of the chemical state of sensor system.The amount of the unmodulated light entering sensing subsystem is preferably made to minimize and only measure the light changed by chemical system.Such as, the chemical system producing maximum absorbance change under 400nm is preferably implemented with the exciting light of 400nm, and this is as contrary in electric filament lamp with unfiltered wideband light source.But if base unit intention measures the number of chemical material with multiple spectrum characteristic, then broadband excitation source can be preferably.

Excitaton source includes but not limited to electric filament lamp, as tengsten lamp and Halogen light; Arc light, as xenon, sodium, hydrargyrum; Light emitting diode and laser.Exciting light can benefit from regulating effect, such as, filter, polarize or any other method well known by persons skilled in the art.Such as, the light of the wavelength of Wavelength matched chemical system peak response is only allowed to be applicable to increase the signal to noise ratio of optical system.

Each in these forms all can adopt on-the-spot inquiry or sweep mechanism.Scanning system is applicable to expiratory measurements equipment, especially when analyte concentration is changed to the instruction of the analyte concentration in expiration along axis change and this.

Fig. 4 and Fig. 5 describes the embodiment of the optical configuration being applicable to endogenous expiration sensing.Fig. 4 describes the general layout of the optics sensing subsystem structure comprising photographing unit (36) relative to light source (38) gentle storehouse (40).Fig. 5 describes like from top view, and the relative angle of excitaton source (42) and the plane of incidence in gas storehouse (44) and the focal plane with photographing unit (46) is shown.This embodiment reduces the dazzle from excitaton source and is suitable for the high quality image of catching sensor chemical substance.Described image can be processed to obtain or interpolation from the dependency of the color analyzing thing exhalation concentrations and colour developing.Photographing unit is especially well suited for base systems, wherein detects number of chemical material due to the other ability provided by wide spectral range, spectrum sensitivity (image is captured as redness, green and blue pixel) and high-space resolution degree.Specifically, spatial resolution allows very simple apparatus to arrange the application being used for broad range, the such as quality assurance.Other embodiment such as light detecter for semiconductor can provide low processor cost and compact size.

In different preferred embodiment at present of the present invention and method embodiment, equipment comprise promote to exhale or expiration sample by the flow facilitator of the flow path of device.Flow facilitator can comprise promotion gas and kinetically cause or allowing to exhale and the interactional any device of reactive chemical in gas storehouse.Such as, flow facilitator can comprise a series of dedicated pipelines not allowing the condensation of endogenous breath analysis thing.Flow facilitator also can comprise the Pneumotachometers for differential pressure measurement.In a presently preferred embodiment, the actuator that flows is connected to base unit and is preferably comprised in described base unit.Flow facilitator can be used for from different source sampling gas, and described source comprises expiration sample sack, mixture and surrounding air.

Fig. 6 describes pneumatic handle (12) the fluxus formae promoters in being applicable to the measurement of high-quality breath.Expiration sample is connected to the pump (48) being configured to extract sample out.Then expiration sample be forced through pulse damper (50) and be then pushed in flowing stratification element (flow lammarization element) (52).Then the pressure converter in fluid restrictor (54) is easily used to measure the stratification stream of no pulse.The pressure drop exceeding known restriction can be used for the amount of the gas quantizing to flow through limiter, especially accurately can estimate the viscosity of gas in described limiter.

Characterize viscosity fully to estimate and described program utilizes the temperature and pressure measurement result of gas componant estimation/knowledge and gas itself.This structure with the parts of appropriate algorithm can be used for the amount that Measurement accuracy flows through the gas of passage, with regard to the number of moles of gas of time per unit.When under downstream valve (58) is in figure 6 in the closed position, sample pump promotes expiration sample by post (62).According to selected parts, flow velocity and attainable driving pressure can be suitably selected to apply.The power that user is exhaled is separated with the exposure of sensor to gaseous sample, and this greatly increases can the scope of application of successful implementation.And gas delivery can be to persistent period of sensor element to be held manageable and can exceed comfort level or the energy of user expiration input system.Be configured to extract second pump (60) of exhaling out by closing upstream valve (56) and starting, reverse by the flowing in gas storehouse.

The compact pneumatic parts forming this scheme are obtainable.Other pump and valve configurations can be preferably, particularly based on reversible, arrhea with the system of the pump of metering.When need not switch the pump of entrance when allowing gas flow reversal, parts (58) and (60) can be removed and in one embodiment, pump (48) can be used to promote and pull gas by gas storehouse from schematic diagram.And the pump of stopping backflow can getting rid of the needs to valve (56) and (58) when being not activated.In addition, pulse damper (50) may be combined with into single parts with layered element (52), the same with the pressure converter (54) on assembled pulse antivibrator (50), layered element (52) and flow restrictor.There is the pump of the metered capacity of structure, such as, there is the piston pump of the stroke volume of setting, also can be used for getting rid of parts more described herein.The another kind of method reducing parts utilizes ball-valve dedicated, as shown in Figure 7.Special valve has two flow locations (64) and (66).In flow locations (64), pump (70) can be extracted out and exhales and promote air by sensor post (72) from exhaling bag (68).In flow locations (66), having same pump (70) that same pipeline connects can gas bleeding and be discharged in air and (guarantee that exhaling bag (68) is found time completely) from post.This is an example of system, and pneumatic handle can receive the expiration of variable-volume and remove unwanted volume in the system.

In order to further illustrate various aspects of the present invention, be used for the device 410 of the ammonia sensed in expiration sample by describing another current preferably embodiment according to the present invention now.The perspective view of described device is shown Fig. 8 and Fig. 9 provides its hardware block diagram.In this preferred embodiment, therefore device 410 is also not limited to the use in laboratory or medical environment for the portable set being applicable to onsite application or use in patient or experimenter family.

Device 410 comprises expiration sample collection subsystem 412 and expiration sample analysis subsystem 14.In this preferably but only illustrative embodiment, expiration sample collection subsystem 412 and expiration sample analysis subsystem 414 are that entity separates, attachable and dismountable parts, but this not necessarily need or restriction.Such as wherein expiration sample collection subsystem 412 and analyzing subsystem 414 alternative constructions be comprised in individual unit are in scope of the present invention.

Although expiration sample collection subsystem 412 can comprise the direct vent conduit leading to analyzing subsystem 414, it provides and keeps or store expiration sample until be ready for breath analysis and when requiring to analyze by the device of expiration Sample delivery to analyzing subsystem in this embodiment.Expiration sample collection subsystem 412 can comprise various ways, as long as it can carry out the function as described herein required for it.

In this embodiment, expiration sample subsystem 412 comprise for retain expiration sample and for by expiration Sample delivery to such as herein below the expiration sample sack assembly 416 of expiration sample analysis subsystem that further describes.According to this embodiment as Figure 10 dividually and the expiration sample sack assembly 416 illustrated enlargedly comprises dismountable expiration sample input block 416a and bag unit 416b, the latter comprises expiration sample sack 418.

Expiration sample input block 416a is provided in one way expiration sample being input to the device in bag unit 416b, makes in this way not allow pollutant or other unwanted extraneous gas or material (outside expiration sample itself) to penetrate in bag 418.Although multiple expiration sample is input as possible, in current preferred expiration sample subsystem 412, expiration sample input block 416a comprises ozzle 420.Substitute expiration sample input example can comprise tubulose or based on conduit input, expiration sample is assigned to the input etc. in parts or section.

Expiration sample sack 418 comprises and has small permeability to the expiration sample of the type that this system uses or do not have infiltrative elasticity airtight bag.To store or under reserve, interested one or more are analyzed things and left or in the retention time expected or wish, should be zero or as much as possible close to zero and certainly lower than the lower power of test scope of overall device, with the result making this type of seepage not affect sensing by the permeability of bag.Usually the example being applicable to the bag of this purposes comprises Tedlar bag and mylar foil bag.Expiration sample sack 416 according to this embodiment comprises mylar foil bag, and described mylar foil bag is generally preferred based on it to the relatively low permeability of ammonia.

Expiration sample subsystem and in this embodiment or rather for expiration sample input block 416a also comprise regulate original expiration sample to make the expiration conditioning equipment of its tool level likely or scope or moisture or relative humidity.In a presently preferred embodiment, expiration conditioning equipment comprises and is communicated with prefilter 422 with bag 418 fluid, and it enters the inside of bag 418 to make to be input to expiration sample in ozzle through prefilter 422 between bag itself and ozzle 420.

Prefilter 422 comprises particle dry agent 424.The granularity (comprising particle size distribution) of preferred selection desiccant 422 is that the effective danger still accidentally being sucked by patient or other user or absorbed is down to minimum to make it.This balance must consider a fact, namely usually reduces to can be used for aqueous phase mutual effect compared with coarsegrain and removes the total surface area of water.In some cases, such as this latter possible impact can be reduced by the porous or flexibility that increase granule itself.In view of these standards, particle dry agent 424 has the screen size of at least 1 and more preferably has about 1 and screen size about between 100.Consider relative importance level really and reliably removed to required level, required screen size is preferably the comparatively low side compared with broad range, and such as about 5 and about between 80, and be more preferably about 10 and about between 30-40.

Preferred selection desiccant material analyzes things or only Trace bio-element with one or more making it can not extract ammonia interested from expiration sample.This means that desiccant 424 can not extract any available analyses thing to be sensed or extract to a certain extent, but quantity is far below sensing or measure threshold value, can not be adversely affected to make one or more measurements analyzing thing of exhaling in its sensitivity and range of error in sample analysis equipment.Consider the particle properties of desiccant and the possibility of picked-up danger, sieve plate 426 is arranged at each flowing end of prefilter 422.

Unless expiration sample input block 416a and or rather ozzle 420 and patient directly contact and therefore sterilize up hill and dale, otherwise can not to reuse.In addition, prefilter 422 retains or limits some component of expiration sample, comprises water and the microorganism may carried by water or other pollutant and is not having can not reuse in thorough disinfection situation similarly.Therefore, in a presently preferred embodiment, the detachable expiration sample input block 417a comprising ozzle 420 and prefilter 422 is dismountable and disposable.

In this embodiment, bag unit 416b is configured to (to connect expiration sample input block 416a during this period) during " collection " pattern and receives and retain expiration sample, and for expiration sample analysis subsystem 414 provides expiration sample, unit 416b is dismantled from unit 416a simultaneously.Lasso 430 is fixedly connected to one end of bag 418, contiguous with prefilter 422.Use adapter 432 by bag unit 416b and or rather lasso 430 be removably connected to expiration sample input block 416a and be connected to prefilter 422 or rather.These parts connect in a gastight manner, and to make when patient is insufflated in ozzle 420, expiration sample is advanced through prefilter 422 and lasso 430 and to enter bag 418 inner and do not leak.In this embodiment, check valve 434 is simple flapper valve, it is arranged at the seam between the inside, top of lasso 430 and bag 418, to be blown in ozzle 420 to make expiration and to enter in bag 418 via prefilter 422, and lasso 430 to be trapped within bag inner and do not allow to depart from.

In order to reaffirm and clarify, expiration sample collection subsystem 412 comprises two main dismountable parts, i.e. expiration sample input block 416a and expiration sample sack unit 416b.Input block 416a comprises the ozzle 420 and prefilter 422 that are fixed to one another connection.Bag unit 416b comprises the bag 418 with the lasso 430 be fixedly connected with.These two parts 416a with 416b are detachably connected by adapter 432.After removal, bag unit 416b can be used for expiration sample analysis subsystem 414 as described herein below.The input block 416a directly contacted by patient is disposable and discardable.

With reference to breath analysis subsystem 414 and see Fig. 9, it comprises the base unit 440 (also illustrating in fig. 8) held as the following various parts more fully described.There is provided input port 442 for receiving the far-end of lasso 430 and therefore forming gas-tight seal and the flow path between bag 418 inside and the internal flow path 444 of base unit 440 at base unit 440 top.Roofbolt or pillar 442a are arranged to interact with the check valve 434 in bag unit 416b and to open described check valve 434 in port 442, to make to allow the expiration sample in bag 418 to flow in flow path 444.Flow path 444 starts at input port 442 place and extends through base unit 440, more fully describes, extend to exhaust port 446 and stretch out from described exhaust port 446 as following herein.For directed reference, from bag 418 and on the direction of exhaust port 446 along the flowing of flow path 444 or be mobilely called as " downstream " in this article and be called as " upstream " in this article flowing from exhaust port 446 towards the rightabout of input port 442.

Some flow performance of the expiration sample of the adjustment in quantitative measurement flow path 444 is useful and in most cases for important.The example of this type of flow performance comprises flow velocity, flow (quality or volume) etc.Therefore, in this embodiment, effusion meter 448 is positioned in flow path 444, in the downstream of input port 442.Effusion meter 448 measures flow velocity and the flow of the expiration sample in this position.

What expiration sample analysis subsystem 414 was included in effusion meter 438 downstream further is flow restrictor 450 fluxus formae actuator and the pump 442 in flow restrictor 448 downstream.Pump 452 has appropriate size and power, and to make when considering holonomic system as described herein structure, it is applicable to extract the expiration sample of adjustment from bag 418 and cause expiration sample flow by flow path 444 and flow out exhaust port 446.Flow restrictor 450 is for absorbing and eliminating the fluctuation formed by pump 452.

Expiration sample analysis unit 414 comprises the expiration sample analyzing and regulate further and detects sensor or the sensing cell of ammonia existence in the sample to which and (preferably) concentration.

Device 410 uses colorimetric principle to sense interested one or more and analyzes thing.Or rather, expiration sample analysis subsystem according to this aspect of the invention comprises the expiration sample that receives and regulate and causes it and the interactional interaction object area of interactant.One or more in the sample of interactant and adjustment are analyzed thing and are interacted and cause the optical signature in interaction object area analyze the amount of thing relative to one or more in expiration sample and change.In other words, when analyzing thing and interactant reacts, the content of reaction volume experiences the optical change relative to initial optical condition.Such as it exists and concentration is embodied in optical change to make about the information needed analyzing thing to design described system.

Can with the optical signature be combined in this respect of the present invention comprise relative to analyze thing exist under change or any optical measurements of changing relative to analyte concentration.Example comprise a kind of color of reaction vessel, multiple color or spectral composition, radiant intensity under characteristic frequency, frequency band, frequency range, reflectance, absorbance, fluorescence and other.

As device 410 embody, the sensing cell of expiration sample analysis subsystem 414 comprises the detachable gas storehouse 460 containing reaction volume, in the case, comprises the post 462 containing interactant 464.Such as, as shown in Figure 8, the front outer surface of base unit 440 has gas storehouse receiving portion or the gas storehouse shell of rectangular hole 466 form.Gas storehouse 460 be sized and be configured to the form of shading substantially or shading sealing therewith hole 466 coordinate.Post 460 comprises tubulose or cylindrical space, and described space comprises reaction volume or container 462, has entry pore 468 and exit aperture 470 in corresponding end.

Interactant 464 is configured to analyze thing with interested one or more in expiration sample and interacts to produce " product " (such as, product or resulting composition) and cause the optical signature between interactant and product to change relative to the amount with the interactional analysis thing of described interactant.Such as in packed bed structure, described interactant can comprise solids fraction, as having multiple beadlet or other substrate on selective active surface or surfactant.Interactant 464 also can comprise other form, such as, as liquid phase, serosity etc.Should note, term used herein " reaction " uses with its wide significance and can not only comprise the chemical reaction relating to covalent bond or ionic bond, but also comprise the interaction of other form, such as complexation, chelating, Physical interaction as Van der Waals bond etc.

In preferred embodiment at present of the present invention and method embodiment, it is desirable to use little disposable pneumo storehouse as gas storehouse 460, for (such as, the every day) use termly of individual in clinic or family.Large consumable goods (i.e. interactant) be inconvenient and relative costly.In order to reduce to analyze the size of consumable goods required for one or more analysis things interested and the size of overall device, the usually interactant of preferred smaller particle size.

In addition, according to this aspect of the invention, device comprises sensing optics changing features and exports the sensor of the representative signal of optical signature change.As device 410 embody and see Fig. 9, described sensor comprises optical detection subsystems, described subsystem comprises the photographing unit 490 with relative lighting device 492, digit preference photographing unit, and it can obtain optical signature and the optical signature change of reaction volume 462.Illumination apparatus 492 is provided to provide light or suitably electromagnetic radiation in one way at reaction vessel 464 place or by described reaction vessel 464, makes the content of described radiation and reaction vessel interact in this way and is then directed to photographing unit 490.Light or electromagnetic radiation can consist essentially of single-frequency (single, narrow-band), one group of these type of single-frequency, one or more frequency ranges etc.In current preferred device 410, illumination apparatus 492 provides white light or broadband light with constant intensity level.(see the arrow at illumination apparatus 492 place at Fig. 9.)

Digital camera 490 produces the signal embodied about the optical information of one or more optical signatures interested.Multiple known transformation technology settling signal can be used to produce.The digital camera of commercially available acquisition such as usual digital picture is provided when obtaining digital picture automatic download or transmit timing or frame-type video signal.

Device 410 comprises that to be arranged at base unit 440 inner and may be operably coupled to digital camera 490 with the processor 494 from its Received signal strength further.In this embodiment, processor 494 comprises general purpose microprocessor or the microcontroller of commercially available acquisition, it is properly configured and is programmed for and performs function as herein described, and standard internal affairs well known by persons skilled in the art process, test and other function.Power supply (not shown) to be arranged in base unit 440 and to may be operably coupled to processor 492 and sensor parts, thinks the energy that those equipment provide required.

The information that device 410 can use any one in output form or form or array output to collect from breath analysis.In this particular, device 410 comprises that to be arranged at base unit 440 outside and may be operably coupled to the touch-screen display 496 of processor 494.Processor 494 is configured and is programmed on touch-screen display 496, providing option, order, instruction etc. and reading and touch order that response receives on the display when receiving touch order from user.Processor 494 also to the information of user output sensing, such as, to analyze the form of the concentration of thing in expiration sample.But this is also nonrestrictive.Export also or in addition can comprise and have the wired of another equipment or (more preferably) wireless data link or communication subsystem 498, such as care-giver such as doctor, kinsfolk, monitoring personnel etc. therefrom can monitor the centralized data base of output.

There are a lot of reactions that much can be used for sensing the interested multiple analytes of possibility.In some in these reactions, can use relatively simple single step reaction, such as wherein expiration sample contacts with interactant, subsequently the change of display optical feature.But, in other cases, need to perform multiple treatment step.Illustrative but important example can be wherein expiration sample and must contact with the first interactant and the reaction then contacted as the second reactant, solvent, enzyme etc. with another kind of interactant subsequently.Equipment of the present invention such as also optionally can comprise reaction initiator or distributing equipment.Reaction initiator or distributing equipment can be any device allowing the haptoreaction chemical substances such as developer solution.(reaction initiator or distributing equipment comprise pin, and the tank of described needle-penetration developer solution, to make described solution passive exposure reactive chemical, more fully describes as following herein.) in some breath analysis application, need or wish that three kinds, four kinds or more planting independent material (interactant, solvent, developing agent etc.) introduces at different time (such as simultaneously, successively etc.), but described material needs to store dividually before the use.When material is liquid phase (including but not limited to liquid, liquid suspension etc.), this type of situation can be special needs.

Need and situation to solve this type of, the present invention according to different aspect comprise use independent liquid container or this type of liquid container multiple (further receptacle) and need application-specific on hand time and distribute the distributing equipment of those liquid as required.

In this respect of the present invention in order to illustrate, Figure 11 illustrate based on pin 80 exemplary allocations of communication resources equipment or reaction initiator 73.In this example, the linear actuators 75 with the pin of connection is housed inside in the top section (74) in gas storehouse locating clip gripping members (76).In order to discharge the liquid that can pierce through and comprise in container (78), then linear actuators 75 driving needle (80) first passes through sealed bottom by top seal.Once seal break-off, liquid just discharges to be pumped by external pneumatic handle as described elsewhere or to be passed through reaction bed with capillarity.

Another part of appliance optionally comprised of the present invention is power booster.In a preferred embodiment, power booster is comprised in base unit.Power booster improves the reactivity analyzed between thing and reactive chemical.An example is that jolting reaction vessel is to allow to increase mixing.Also can serviceability temperature control improve reactivity or improve sensor system performance in addition.Temperature can be completed in many ways control, comprise the conduction heating of IR heating and use resistance heater.Add at IR and hanker, IR emission lamp is targeted interested region and illumination causes non-contact thermal.The resistive element contacted with the heat conductor be building up in gas storehouse can be used, the sealing of such as, paper tinsel around developer solution, to increase reaction temperature and therefore augmenting response speed.

The temperature comprising cooling controls also to be applicable to and controls sorption and desorption from adsorptive resin such as Tenax TA or silica gel.Conduction cooled via amber ear note (Peltier) element can contribute to the absorbability increasing resin.

The insertion mechanism in gas storehouse can adopt various ways.The means inserted for gas storehouse comprise such as: (a) spring loads insertion, (b) linear activated insertion, the insertion of (c) annular gasket o ring, the cooperation of (d) conical compression and (e) snap fit.The insertion mechanism in gas storehouse can comprise the controlling organization of this type of parameter of such as humidity, temperature, pH and optical phenomena (as light).Such as, the insertion mechanism in gas storehouse can comprise light-shading apparatus.Preferably, inserting mechanism enables gas storehouse be inserted in base unit with an angle relative to ground.But this angle improves the comfort level of user can not tilt very much, to reduce the gravity contributing to liquid developer Solution Dispersion during the inserting step of gas storehouse.Described angle is preferably in the scope relative to the vertical line 15 degree to 45 degree perpendicular to bottom surface.

In spring-loaded insertion method, the slide head under spring force can be used to press against gas storehouse against the pad on base unit.Gas storehouse pedestal, for the pressure initiation close fluid face seal of pad, is enough pressure (such as high to 5psi) for driving sample by the response element that sensor gas storehouse holds in may being needed.In order to insert gas storehouse, gas storehouse to slide in slip carrier and promotes spring until gas storehouse abuts against pad location by user, this with cylindrical battery is inserted in common consumer device similar.Lever can be used provide the substituted device promoting spring.

The another kind of method that base unit is inserted in gas storehouse is utilized linear actuators.As shown in figure 12, in this example, gas storehouse (82) are compressed between top (84) and bottom (86) surface.In this example, the slide mechanism of above-described spring-loaded insertion embodiment is combined with linear actuators instead of spring.In preferred embodiments, top surface is by for moveable and lower surface is by for fixing, and No leakage connection and inlet duct will be connected to top fixed surface.

Figure 13 illustrates the details of an embodiment of the slide mechanism relating to sensor gas storehouse.In fig. 13, linear actuators (88) promotes sliding platform (90) up and down to engage with gas storehouse (92) and to depart from.Sliding platform can comprise other element, such as, be applicable to the independent linear actuators (94) piercing through operation.In this construction, be in the base section (96) of clamp system with the interactional pipeline in gas storehouse, described base section (96) keeps fixing to reduce the functional requirement of pipeline.In the case, before gas storehouse is inserted, actuator position is become retracted mode, described actuator raises chuck makes it away from top side, gas storehouse.Form enough distances to be unhinderedly inserted in the receptor of gas storehouse to allow gas storehouse.Once location, gas storehouse, user just presses the button the control electronic equipment indicating gas storehouse loosely to locate, and linear actuators extends until sense for stoping the power needed for further extension (estimating as used the power of concrete actuator/current curve) or until arriving the position of specifying after this.

Another embodiment that mechanism is inserted in gas storehouse is annular gasket or o ring.In this embodiment, the o ring be assemblied on the cylindrical base bar of gas storehouse can be used to provide the sealing of needs.In the case, when pedestal bar is inserted in circular reception device, o ring groove keeps o ring.Suitably determine that the size receiving wall is to seal for o ring.Alternatively, o ring can be bound by the reception wall of base unit.The power of spring, linear actuators or user can be used to provide insertion force.

Conical compression coordinates the insertion mechanism that also can be used as gas storehouse.In this embodiment, the taper pedestal bar in gas storehouse can be used for being formed does not have the No leakage fluid of o ring or pad to connect.In the case, taper pedestal compressed fit is in slightly different tapered receiver device.The power of user is used to insert and remove gas storehouse.Or, linear actuators and pin bonding scheme can be used to be pushed in gas storehouse in receptor and to be extracted after measurement terminates.

Another example inserted based on the gas storehouse of user power input is loop fastener scheme.In this design, hasp receptor is made into gas storehouse pedestal.When pressed against the cushion film in equipment base in gas storehouse, hasp receptor with coordinate snap-engagement in base apparatus.In order to discharge gas storehouse, the hasp of load on spring in base unit is retracted.

Untreated expiration may be not suitable for and sensing chemical substance direct interaction.When required chemical system is subject to the adverse effect of the existence of these chemicals, due to humidity, oxygen or carbon dioxide, produced problem is a problem especially.Expiration adjusting device and method optionally can be used by equipment of the present invention.Expiration adjustment can comprise potentially following any one or all: the washing of moisture removal, carbon dioxide, oxygen are removed, the removal of the interference VOC carried of exhaling, gaseous sample heating, gaseous sample cooling, make that gaseous sample and derivating agent react, the compression of gaseous sample or decompress(ion) and other method for the preparation of the expiration analyzed.

Utilizing in an embodiment of exhaling and regulating, desiccant can be used for removing moisture.Usually, given desiccant has different affinitys for number of chemical material.Such as, the water content of usual known anhydrous calcium chloride under acetone exists preferentially in conjunction with moisture and during the removing of appropriate calcium chloride therefore can be used to exhale keeps acetone concentration complete simultaneously.The example of other desiccant is what known, comprises CaSO ₄(calcium sulfate), molecular sieve 4A and active carbon.Each the removal moisture in these examples can be used, but carefully must guarantee that interested analysis thing can not be removed from gaseous sample.

May contribute to measuring successful aqueous chemical material for wherein different pH, may need to remove CO from expiration sample ₂.Soda lime is typically used as the CO from exhaling again in the expired gas in loop ₂detergent, but also can be very valuable as the component of breath analytical system.Other sorbent material multiple is known, such as Tenax TA, active carbon and ascarite.

A lot of adsorbent is applicable makes pre-concentration element.Silica gel can be used for catching acetone and is captured as microlitre volume to make large volume.Such as, acetone can be collected from 450mL exhales sample and can be encapsulated into and account for about 35 microlitre volumes, be greater than 10, in the silica gel particle of 000 times of concentration.Pre-concentration can be used for assembling enough analysis things increases response speed and the response time therefore reducing induction apparatus to cause detectable reaction and to be applicable to.In some cases, the reagent of absorption can react in position.In other cases, analysis thing being eluted adsorbent can be useful.In this, a kind of preferred reagent is Tenax TA.Compared with moisture, acetone is adsorbed onto in Tenax granule securely, makes moist expiration sample can be passed through Tenax grain bed like this, thus catches acetone third and retain few moisture.At 20 DEG C, the breakthrough volume of water is little of every gram of Tenax TA 65ml, and the gas meaning available small size removes moisture from Tenax post.At high temperature, breakthrough volume is even less.In contrast to this, the breakthrough volume of acetone is about 6 liters every gram.

Example based on the breath analyser of Tenax TA illustrates in fig. 14.In this figure, two-piece type gas storehouse is made up of snap fit top part together (98) and bottom parts (100).The container of developer solution (102) is positioned to have in the top part (98) of paper tinsel barrier, as discussed previously.Porous open celled foam plug or other porous material (104) are oriented to Tenax TA granule post (106) to be pressed onto against mesh grid barrier (108).Or, by porous and enough hard with compressed fit to the single component in pocket as porous polyethylene replaces component (104) and (108).Make moistening expiration sample from bottom side through reactive chemical, thus discharge by the non-hermetically sealed interface between gas storehouse top part (98) and bottom parts (100).Then, paper tinsel barrier is damaged and developer solution is pulled through and has on the Tenax granule of the acetone of catching.Reagent in developer solution and acetone interact to produce color products with other binding reagents.In this construction, special drying material may no longer need, even when the existence sensitivity of cycle chemistry material to water.

Tenax TA and other adsorbent resin are also applicable to catches and delivery system.In these methods, interested analysis thing is captured and is concentrated in resin, simultaneously interfering material specifically water freely flow through and do not retain.The analysis thing of catching is discharged by thermal desorption or eluting subsequently, with at other position response.This type of scheme controls chemical reaction in view of not being applicable to by the interfering material of alternate manner selective removal, or colorimetric detection is carried out in the position be applicable to being easier to optical read-out.

In figure 3, the non-three-way valve (30) that relapses with other outlet tap (32) can make the part of many expiration deposit to successively in collecting bag (34).The ozzle that tool is with or without overall antibacterium/virus filter (35) prevents user cross-contamination.User is air-breathing first, opens at non-the first check valve relapsed in valve, thus allows surrounding air to be full of pulmonary.When exhaling, open the second check valve (first closedown), thus allow the air of breathing out flow into collecting bag (34) and flow out other outlet tap (32).Ratio by the entry resistance of regulation bags and outlet tap regulates the gas and every part of ratio of exhaling of filling described bag.Fig. 3 also illustrates flow circuits example, wherein V _aand V _brepresent ambient pressure (a) and bag pressure (b); R _i, R _oand R _brepresent entry resistance (i), resistance to flow output (o) and bag entry resistance (b); D _i, D _band D _orepresent entrance (i), bag outlet (b) and environment Outlet check valves.The dead volume of valve housing should be made to minimize to reduce the amount of the surrounding air be blown in sample sack.In fact the sensing (such as use embedded pressure converter) of alternate embodiment based on expiration flow direction of the method and the ACTIVE CONTROL of check valve, to eliminate the dilution carried out expiration sample by the surrounding air spilt because dead volume intersects.

Be similar to circuit, voltage represents gas pressure and electric current represents air-flow.User controls to exhale (relative to V at the voltage at junction diode place simultaneously _afor just) and air-breathing (relative to V _bbe negative).Collect fraction expired gas and known resistance than time, the gas in the volume of gas of so being breathed out by user in setting-up time and bag is proportional.The total amount of known expired gas in setting-up time is for estimating that the analysis thing molal quantity of being exhaled within a certain period of time by individuality is valuable.This information is applicable to the physiological significance explaining breath analysis substrate concentration.Resitstance voltage divider is it should be noted that reliably to carry out and without the pressure (Vs) in measuring samples, as long as bag does not start substantive inflation to make to release bag wall for bag pressure.Can be used for recording time of exhaling and collecting and spending with timing unit similar described in Fig. 2 and optionally control check valve.The alternative use of the equipment in Fig. 3 allows to average to expiration.Replace with single expiration filling bag, user repeatedly can be exhaled and each part of exhaling and other in bag are exhaled and be mixed.This type of average sample can be used for increasing the repeatability between sample.

Gas storehouse comprises another aspect of the present invention.Gas storehouse comprises can with at least one breath analysis thing and the preferred reactive chemical that reacts of at least one endogenous breath analysis thing.There is multiple gas storehouse structure, it can be used from system one according to the present invention and measure at least one in exhaling and analyze thing, preferred endogenous analysis thing.

In one embodiment, gas storehouse comprises the enclosure with expiration flow path, and described flow path is connected to further and automatically reacts initiator, and described reaction initiator allows developer solution haptoreaction chemical substance.Gas storehouse preferably comprises the porous media with reactive chemical positioned adjacent.Gas storehouse can comprise single reaction chemical substance or multiple reactive chemical.

In another embodiment, gas storehouse comprises the pneumatic loader of conveying developer solution by gas storehouse.

Another embodiment of the invention and in, gas storehouse blocks surround lighting when inserting in base unit and preferably includes handle.As discussed herein above, when built-in system component as interactant, midbody product etc. be heliosensitivity, pedestal can comprise and formed inner and shield described inside and makes it from the outer surface of ambient light effects, and wherein said outer surface comprises hole; And described gas storehouse can comprise when substantially coincideing to be connected to pedestal in gas storehouse with described hole and shields surround lighting and prevent it from entering the guard shield of described hole.

Gas storehouse can be designed to various shape and size to promote different application.In one embodiment, gas storehouse is made up of following: the first Room containing the first developing agent of (a) reactive chemical, (b) and (c) second Room containing the second developing agent.First and second developing agents can be identical or different.In another embodiment, gas storehouse is made up of following: room containing developing agent of (a) reactive chemical, (b) and (c) are for being connected to the mechanism of pneumatic loader or remover or (d) for being connected to the mechanism of reaction initiator by gas storehouse.In a preferred embodiment, gas storehouse does not need the outside liquid flowing to gas storehouse.

The exemplary general synoptic diagram of gas storehouse design illustrates in figure 16.This gas storehouse is preferred for optical detection and preferably includes the reactive chemical that can be used for detecting the analysis thing that endogenous produces in people's expiration.At this, in gas storehouse shell (120) be made up of single-piece, comprise reactive chemical (128).Preferred but nonessential, described shell is made up of optically transparent material and forms.There is the film (122) reactive chemical and expiration regulator (124) separated.In this embodiment, expiration regulator (124) is desiccant, but this its also can be detergent or pre-concentration agent.Make expiration regulator by perforated membrane (126) compact package.In some embodiments, the peelable barrier material that maybe can the pierce through downside that can be fixed in gas storehouse is with the storage of increase reactivity chemical substance and expiration regulator.Be keeper (130) at the opposite side of reactive chemical.Keeper is for keeping reactive chemical compact package.This keeper can be the compressed fit part, gas storehouse pad, o ring etc. of molding.This keeper top is porous media (132).Porous media is designed to allow liquid development agent solution (133) to flow to reactive chemical.In an alternative embodiment, component (130) and (132) are replaced into the two all compressible one-component be coupled in encapsulation pocket and porous.Hydrophilic porous polyethylene pan is applicable to this object.Developer solution is contained in and easily breaks in ampoule (133), described ampoule is arranged in the receptor of gas storehouse shell (131) upper part, promotes the discharge of air when described gas storehouse shell is formed with vertical channel to flow into be filled with the passage of reactive chemical (128) at developer solution.With piercing through the receptor (131) of film (134) sealed packet containing ampoule.Once gas storehouse is inserted in base unit, is just pierced through by the reaction initiator of base unit and can pierce through film and container can be pierced through flow in reactive chemical to make liquid.Can not leak out from the gas storehouse after use in order to ensure residual liquid, there is the rubber septum (136) in blanket gas storehouse.Gas storehouse is preferably designed to make developer solution by reactive chemical and/or regulator (such as, desiccant) " absorption ", can not leak by bottom gas storehouse to make it.An optional interpolation is connected to pneumatic loader or remover (not shown).This pneumatic loader/remover is used as pump and pulls/promote developer solution by gas storehouse.Therefore, can be oriented to when liquid is interacted with reactive chemical due to gravity or capillarity in gas storehouse, it also can be designed to allow via pneumatic loader/remover interaction initiatively automatically.

Figure 17 illustrates the replacement scheme of the keeper (130) of the Figure 16 for holding reactive particle (128).The main shell of the packed bed of plastics gas storehouse (138) forming reactions material (142).Permeable keeper (140) be fixed on as other parts the bottom side of post of being discussed.Porous material, such as plastics, metal, pottery; Or fiber, as glass or metal wool, by compressed fit in passage.Abut against encapsulating material (142) and compress porous plug to prevent from moving during use or conveying.

In Figure 16, illustrational honeycomb seal (132) is preferably made up of the material with following characteristic: aperture (can retain granule, such as 75 micron particle), high hole area (low pressure drop, low flow resistance), be inertia to interested analysis thing, be easy to automatic clamping and placing, can be fully adhered on substrate.The material of sheet form is easy to a large amount of production usually.The thin slice of various substrate is easy to be pressed into laminate.First the thin slice of porous is easy to be processed to fixed disk.Figure 15 display can be pressed into the example of the substrate slice of fixed disk.There is the thin polyimides (0.001 "-0.003 ") of bonding backing thin slice is perforated into and there is one group of hole (110) (such as, having the Devinall SP200 polyimide that FastelFilm 15066 bonds backing).Thin woven nylon net thin slice (307x307 order, the 9318T48 from McMaster-Carr) is pressed into the laminate with perforation polyimides.Then bore a hole to be formed the lamination dish (118) with poriferous circular to laminate with larger diameter instrument.Perimeter comprises the top side ring of polyimides.These dishes, even navigate in dark groove to be easy to location easily through vacuum mode pickup.Dish uses hot-pressing tool to be adhered to and receives surface.Special adhesive melts under 66C, and this is far below the fusing point being suitable for the multiple plastics making gas wall material.Coil and use commercial rotary cutter and other conventional tool of production to be formed by this method.These dishes are specially adapted to retain reaction medium in deep hole, such as, (324) in Figure 29, as discussed below.

Paper tinsel and other plastics many also can be used for bonding backing.In some methods of attachment, polyimides top layer can be preferably layers of foil, because layers of foil can have the comparatively main trend be separated with its bonding backing during some hot pressing, particularly when contact surface area is larger.Polyimides can be preferred relative to other plastics due to its possible high heat trnasfer with to the opposing of pyrolytic damage, particularly when using hot classification polyimides.

Liquid can be comprised in gas Hatch Opening bag, uses gas storehouse material as having the sidewall of paper tinsel or being bonded to other envelope barrier on surface, gas storehouse.For Aggressive solvents, such as dimethyl sulfoxine or methanol, this type of solution can be attacked binding agent due to solvent and be temporary transient.One embodiment of the invention use unitary part receiving fluids reagent.This allows the complete control of material of liquid comes into contact (wall in gas storehouse does not need to be concerned about material, interacts unless related to solvent).Various " tank " of configurable liquid and these tanks can put into the opening bags of gas storehouse top part.Preferably, liquid tank or the liquid of ampoule to maintenance are complete inertia.Figure 18 illustrates three embodiments of the paper tinsel ampoule that can pierce through, as described in following paragraph.

Easily broken solvent ampoule manufactures by multiple method.Such as, in one case, flange taper paper tinsel pedestal (152) is soldered or be otherwise bonded to and can weld or on heat-sealable intermediate materials (150), to form the latter half of gas storehouse shell.Top foil layer (146) be connected to equally can weld or heat-sealable intermediate materials (148) to form the first half of gas storehouse shell.Then, the latter half is loaded with volatile liquid and the first half ultra-sonic welded or be heat-sealing to the latter half.Volatile liquid is comprised in four barriers: form the foil material of primary contact surface, can weld/salable intermediate materials (such as, lower thermal conductivity thermoplastic), welding point (binding agent) between paper tinsel with plastics, can weld welding point (lower thermal conductivity thermoplastic) between intermediate materials.This is configured to useful, because (a) its permission bonding time solidifies (before filling solvent, binding agent can solidify completely), therefore, it is possible to adopt the binding agent of broad range independent of the existence of solvent; B conduction heating that () is caused by ultra-sonic welded is shielded by lower thermal conductivity thermoplastic, thus eliminates or control the amount of filling solvent of evaporation loss during ultra-sonic welded.

Thermodynamic barrier material is another example easily breaking solvent ampoule.Second situation uses the latter half to insert material as thermodynamic barrier by two paper tinsel gas storehouse shells half part ultra-sonic welded each other.That is, top foil (154) is connected to bottom foil (156) by direct ultra-sonic welded metal forming.Solvent is filled for welding in advance, carries out Thermal protection by thermodynamic barrier (the wax cone (164) as hollow).The conduction heating impact that thermodynamic barrier causes during solvent must be protected to make it avoid being subject to ultra-sonic welded, but it also must be easy to pierce through.Other material such as thin plastics, rubber or silicone spray binding agent also can be applicable.

Being adjusted to of thermodynamic barrier method carries out ultra-sonic welded under existence of suitably dispelling the heat.Ultrasonic welding fixture comprises the annular holder be made up of high-conductivity metal.Described fixture from external position upcountry engagement top and the bottom metal foils of ultra-sonic welded, to make any heat conducting and radiating away from welding point in conductive fixture.The alternative method of heat radiation also can be applicable as blown bottom foil with cooling-air, and this depends on the solvent of use.

Third method for solvent encapsulating depends on the sealed between top foil (158) and bottom foil (162).The pad (160) comprising wax pad between the layers or be made up of solvent resistant material, to increase volatile liquid to the retention time in ampoule.The gasket material with suitable elasticity and the barrier characteristics to interested solvent must be selected.

Ampoule also can by the multiple material blow molding comprising glass and plastics.The heavy wall that these homogenous material ampoules are still enough to by the thin-walled that can carry out ampoule puncture the barrier characteristics obtaining needs is formed.

Metal is excellent as barrier material and can is undertaken sealing (such as, beverage can) by crimping in a gastight manner.Can be manufactured by aluminum and other metal micro-ampoules and be put into the head in disposable pneumo storehouse.

Figure 19 illustrates some embodiment of the ampoule that can pierce through.In this embodiment, cold forming paper tinsel (176) or other pierced through barrier material be shaped use bounding point to connect the head part of base plastic carrier (172).These points can contact with a series of concave station (188) and be intended to be connected to base plastic carrier by bottom ampoule in non-hermetically sealed mode.Ampoule (176) underfill has solution and temporary barrier (180) fixedly can carry out seal fluid.Temporary barrier is fixed by Pressuresensitive Adhesive, hot setting adhesive or other conventional method any.The binding agent of temporary barrier does not need to resist and retain described solution and has exceeded time required for seal process.Then bonding ball (182) is applied.This binding agent forms the fixing barrier retaining solution, but temporary barrier (180) allows fixing barrier material (182) to solidify independent of Solution Active.Liquid barrier material dish (184) covers.The independent material (186) of optional placement as rubber septum, with prevent liquid after barrier breakdown temporarily by.

The method can be used for granule to remain on encapsulation state.That is, by compressible porous material (190) is directly positioned under base plate (176), can immobilized particles.

Figure 20 illustrates the embodiment of the tank that can pierce through.In this example, tank of the thin end (192) casting mold that is thermoplastic.After by required liquid filling, can via proper method as ultra-sonic welded or heat seal connect barrier material (such as, having the layering paper tinsel of thermoplastic plastic layer).If desired, after with liquid filling tank, barrier material (196,198) widely can be fixed.Optionally, according to the material requirements of held liquid, barrier material (196,198) is connected directly to tank (note, described tank does not need to be made up of thermoplastic) by Pressuresensitive Adhesive, hot pressing type binding agent or other method.The modification of this design uses thick-walled plastic cylinder as ampoule body and seals two ends with piercing through barrier material.

Single analysis thing gas storehouse can be configured to promote that number of chemical is reacted in many ways.The dried reagent of series of columns can be packaged in piling post (wherein the movement of granule is not problem) or be encapsulated in the separation bag in equipment.Some examples illustrate in Figure 21 and Figure 22.

In figure 21, three kinds of different dried reagents (200,202,204) are packaged in single post.Perforated membrane (206) and (208) are in appropriate location to keep reagent.When film is in appropriate location, reagent can have different size.The reagent that the partial encapsulation of increase diameter is other can be used, to make to form flat ledge, can holding device be fixed thereon.

Reagent shown in Figure 22 is stacking.When different reagent (212 and 214) that need fixed class like size, they can be encapsulated in single post as shown in figure.Needs are separated and holding device (216) by larger particles (218).A kind of segregation method utilizes thin porous material dish, such as nylon wire as described in Figure 15, but aerated plastics or other porous media can be used in other embodiments.Can use and keep film (210) and (220) to seal outer end.It is generally desirable that the mode reagent that can not move freely to make reagent encapsulates packed column.In the case, compressible porous media can be used to fix material.Figure 23 illustrates this structure.In this figure, gas storehouse is by two-piece type, and namely top part (222) and frame piece (228) composition are formed.First dried reagent (232) is packaged in the lowermost pocket of pedestal, is kept by two perforated membranes (230 and 234).Second dried reagent (226) is packaged in the newel in gas storehouse.At the top of newel, wide aperture is molded to dried reagent (relax and fill tolerance) that accommodation fills a little and is conducive to compressing reagent with porous compressible material.This material, when being compressed by top (222), still allows fluid to be communicated with by top part and bottom parts, simultaneously compression drying reagent 226) to make them keep fixing.

Liquid reagent can be packaged in sensor gas storehouse to promote to be applicable to the number of chemical reaction of breath analysis.Figure 24 illustrates that liquid reagent can be fixed to the reality of the mode that the mode in gas storehouse can discharge with it within the response time.In the top part (240) in gas storehouse, provide the storing apparatus (238) of liquid reagent.This can be the different parts (238) of the pocket putting into top part (240) or it can form entirety with top part.Under any circumstance, this agent ampule (238) can pierce through between film (252) at two and comprise liquid reagent, and described film (252) is impermeable or be otherwise applicable to interested reagent.In the time needed, solid or hollow pin (236) is depressed by described film, thus cause liquid reagent flow through the taper interrupter (250) in gas storehouse and by down going channel (246), flow to reaction bed (244).In this construction, the sealing between top part (240) and frame piece (242) be not airtight (with allow gas from reaction bed (244) flow through top and flow to outside).Therefore, liquid reagent preferably has low viscosity and suitable surface tension, drops onto reaction bed top always and be drawn in reaction bed when starting suction pump (248) to make liquid.

Figure 25 provides another embodiment.In this alternative constructions, hole (260) are driven in top part to provide gas outlet when top part (254) is fixed with gas-tight seal with bottom parts (256).In the case, gas to flow on reaction bed and flows out outlet (260).Then, sell (262) be depressed by top barrier and then by bottom barrier, fill to allow gas the space vacated to discharge comprised liquid and to form hole.Liquid filling down going channel (264), closes and exports and form fluid-tight, liquid can be pulled by passage to make suction pump (268) and pass through reaction bed.

The extension of liquid containing/relieving mechanism as previously discussed allows plurality of liquid reagent to be incorporated in single gas storehouse.Figure 26 and Figure 27 illustrates the example in many liquid gas storehouse.In fig. 26, two reagent wells A and B comprise two kinds of reagent (or a kind of reagent, if needed) between destructible sealing as discussed above.Down going channel is merged into single pipeline.When the first seal break-off, from A liquid as before fill down going channel, wherein it is subsequently by connecting pump sucking-off.Then, destroy the sealing containing liquid B and carry out same program.Figure 27 illustrates the top part comprising four this liquid containers.The method permission reagent carries out very complicated fluid treatment, and described reagent is positioned on single disposable.

Although chemical reagent can be consumed by each reaction, gas storehouse of the present invention does not need to be restricted to single and uses.Repeatedly use equipment can be made up of the band of the equipment in single substrate or conveyer belt gear.This identical shape factor can be used for the multiple analytes allowing to be measured by sequential processing or parallel processing in single expiration sample.

Figure 28 illustrates some the gas storehouses design can carrying out these application.In band or the blister package of the left side of figure display reaction channel.Each available identical or different reagent filling in four passages (292,294,296,298) of description, this depends on whether repeat measure acetone, separately repetition twice measurement acetone and ammonia for four times or measure from 4 kinds of simple sample independent analysis things for (as an example).Each passage can with independent paper tinsel barrier (300) or the single foil strip sealing being placed in whole top.Reduction material volume and wall thickness can be made near packed column to realize optically transparent window.Base apparatus must comprise four stationary conduits or moving-member (with movement actuator or the workbench comprising multichannel gas storehouse).As shown in figure 28, multichannel can be merged in conveyor-type equipment (306), and its rotation makes each passage align with the seal break-off/fluid drives head of fixed position.

Figure 29 illustrates an embodiment of the gas storehouse design promoting or complete following task: flow direction that (a) sample drying, (b) sample concentration, (c) example reaction, (d) build controls (via an irreversible check valve, in diagram and three check valves similar), (e) two-phase reagent container (solid reaction chemical substance, liquid developer), reagent interface (holding device) that (f) is cheap, (g) be easy to insert in base apparatus and (h) low reagent volume.

Exemplary gas storehouse in Figure 29 is combined with suitable reagent, is applicable to measure the acetone in people's expiration.Gas storehouse is formed by such as forming with the snap fit two-piece type be mechanically anchored in together.Top part (312) is connected to frame piece (314).Top part and frame piece is made to form gas-tight seal by design.Liquid reagent is involved to be contained in the pocket (316) of top part.The developer solution that embodiment comprises between being sealed by two paper tinsels forms, described paper tinsel seal a top planes being positioned at pocket and second be positioned in base plane.In bottom foil sealing below, the bubble entrapment that taper pocket (318) is made into promote liquid reagent drippage and does not have interval.Reactive chemical is packaged in the post (322) extending past frame piece center.In order to reduce the tolerance of reactive chemical encapsulation, strengthen the width of the top of reaction column.Porous compressible medium leaves the roomy post part of top in, and to make when top part (312) abuts against frame piece (314) sealing, compact package is loaded into the reactive explosive in post (322).Usually, foam-in-place type is well suited for being used as the compressible maintenance barrier of porous, as long as chemical substance and system compatible with both open celled foams of molding in advance and cutting.The post of non-compact package stands material and moves, and this is the situation hindering repeatability and increase measurement error.Drying material is packaged in lower wider post (326).Honeycomb seal (324) is connected on the top board of (326), so that the maintaining body providing gas to allow for reaction material.In one embodiment, the nylon wire of braiding provides this device to cause insignificant resistance to air-flow simultaneously.Similar barrier (328) forms the bottom surface of post (326).Form the pedestal in gas storehouse, catch gasket compression, so that making to be communicated with the No leakage of gas delivery pipeline becomes possibility to promote to abut against in base apparatus.Pocket is made into gas bulkhead to strengthen colorimetric detection.Pocket depth is selected as making wall thickness to minimize the mechanical integrity in retained gas storehouse simultaneously, particularly relative to the wider hole required for the pocket comprising auxiliary reagent.Adjustment is can be passed through, to promote effective lighting and specifically to weaken the dazzling reflection of exciting light relative to the wall angle on four relative square limits in gas storehouse.

Gas storehouse and the how interactional preferred embodiment of base unit are in the following manner.First, user is opened the door by the wall of base apparatus and gas storehouse is placed in gas storehouse receptor.User does not need very large power when inserting and direction of insertion is limited by mechanical stopping piece.Side in (four sides) two sides in gas storehouse is towards Optical devices.Receive the gas storehouse receptor in gas storehouse (top in gas storehouse tilts away from user relative to bottom thus) during gas storehouse is inserted, increase accessibility and the comfortableness of user at a certain angle.Once gas storehouse is loosely positioned in described equipment, provide plant equipment, thus make top side, gas storehouse compress constraint pad in base apparatus.See Figure 12 and Figure 13.This is compressed in forming surface between the pad in gas storehouse and bottom and seals, thus provides and can stand mobile expiration sample and be connected with the No leakage fluid of developer solution by the driving pressure required for gas storehouse and different compartment thereof.Once gas storehouse is in appropriate location, just collect expiration sample by the sampling of multiple device such as expiration collecting bag or effluent.Once gaseous sample is ready for measurement, just start pneumatic handle, extracting breathing gas and be first pumped through desiccant bed out from gas collection vessel, then pumped by gas storehouse by reaction column.See Figure 30.Gas storehouse is designed to open wide air-flow at two ends.Open bottom side (desiccant side) by mesh grid barrier, open top side by top part (338) to the non-hermetic seals of pedestal (340).Therefore, when gas is pushed through column bottom, they can be discharged by top, although developer reservoir barrier does not destroy.When the expiration sample of applicable volume is forced through post with the flow velocity selected, developer storing apparatus breaks.See Figure 24.Point pin (236) is driven through the lid in gas storehouse, with the top barrier (252) making it first destroy storing apparatus, then destroys bottom barrier.Preferably slower pin actuating speed and suitably comprise the developing agent of volume, to prevent from overflowing at the period developing agent of breaking.Also preferably storing apparatus stands this type of ability of being out of shape when being out of shape and causing developer solution to overflow in period of breaking.Once released development agent, it just fills taper pocket (250).Taper pocket helps to form fluid-tight (251), to make, when liquid is pulled by post, to be drawn in continuously in post by developing agent.The amount being pulled through the developing agent of post controls by regulating pump persistent period pulled of circulating, or can adopt closed-loop device.Imaging system (see Fig. 4 and Fig. 5) is for recording and the ratio colour response caused by the analyte response of reaction bed and developer solution.Developer solution can major part be included in desiccant bed.When preventing to be exposed to the possible user under specific hazardous solvent, optional top and bottom partition can be building up in gas storehouse.

Figure 16 illustrates a kind of method for optimizing built for single analysis thing gas storehouse.The single-piece (120) of the transparent plastic (as acrylic acid) of molding forms gas storehouse shell.Granule as discussed previously retain barrier (122) be connected to flow channel bottom and preferably by having woven nylon center (198x 198 order, 0.0031 " opening; 49% hole) heat bonding backing (Fastel 15066; 3 mil thickness) polyimides (Devinall, 2 mil thickness) form.Desiccant material (30-60 order anhydrous calcium chloride) desiccant-filled room (124).The granule similar with (122) retains barrier (126) and is placed in bottom, to hold desiccant.Reaction material (100-140 order, ratio is the granule that the amination of 2:1 is connected with Nitroprusside) is placed in flowing post (128), and the top of passage is opened wide to promote that low tolerance is filled.Porous material (130) such as glass cotton, stainless (steel) wire or porous, hydrophilic vinyon (preferably) are placed on reaction particles.In some embodiments, reaction particles (128) and porous barrier (130) may need other device to pressed against granule.O ring, external teeth throw-out collar or deformable keeper ring are applicable to this object, but aerated plastics can make himself compressed fit and not need these devices.Preferably seal the pierced through liquid ampoule (133) that forms of tank and be placed in supporting outer by having the thermoplasticity that can pierce through barrier at top and bottom in the mode not closing air-flow.Top, gas storehouse, with piercing through paper tinsel (134) and liquid barrier spacer layer (136) sealing, can not be leaked by lid to make liquid after use gas storehouse.

Figure 31 illustrates a kind of method for optimizing in the gas storehouse for using Figure 16 to discuss.When piercing through pin (342) and being in position (A) that retract completely, top barrier (344) is not destroyed and makes air-flow be impossible by gas storehouse.When pin is in the first extended position (B), top barrier is destroyed to make gas can from the flows in gas storehouse by around multiple porous barrier, reaction bed, liquid ampoule and by the hole (348) of piercing through pin.At the second extended position (C), liquid discharges and by the suction force of pump or be pulled through reaction bed downwards by capillarity from ampoule (346).Pin in base unit (343) can be used for piercing through bottom barrier material and flow in gas storehouse to allow gas.The method allows gas storehouse sealed for storage and transport and automatic puncturing and do not have extra user step in use.And the partition at top and the extra barrier of bottom can be used for holding the liquid in gas storehouse after usage.Notice that the barrier holding desiccant or other adjustment material is in this figure not shown.

Gas storehouse 510 according to another current preferred embodiment of the present invention illustrates at Figure 32.This gas storehouse can be preferred in breath analysis equipment, such as, as shown in above composition graphs 8 to Fig. 9 herein with as described in.Gas storehouse 510 comprises body or shell 512, and it comprises solid plastic cylindrical parts in this embodiment.Shell 512 has entrance 514, and wherein expiration sample is input in gas storehouse 510.Expiration sample is upwards advanced through round the longitudinal axis in gas storehouse 510 substantial cylindrical flow channel placed in the middle.Note, the direction exporting () to it from the inlet face in gas storehouse 510 is called as " downstream direction " (supposing that gas (expiration sample) flows at this downstream direction) among Figure 32 upwards in this article, and contrary direction, is namely called as " upstream " direction towards the direction that entrance 514 is downward in the accompanying drawings in this article.

Gas storehouse 510 comprises porous polyethylene dish 516 in its input.The downstream of and then coiling 516 is the regulator 518 comprising desiccant.Fiber polyethylene pan 520 is arranged at the downstream of and then drying regulator 518 and contact drying regulator 518.Porous polyethylene dish 522 is arranged at the downstream of and then coiling 520.Dish 520 forms the container of one or more interactants 526 or the lower boundary in region 524 that are arranged in container 524.In this embodiment, one or more interactants 526 comprise solid phase material, such as, as those materials as herein described.Porous polyethylene dish 528 is arranged at the downstream in container or region 524 and forms its coboundary or downstream boundary.In this embodiment, container 524 comprises the neck portion 524a expanded a little, and described neck portion 524a comprises the solid phase material filled.The layers of foil tabletting 530 comprising the layers of foil be sandwiched between two thermoplastic material layers is arranged at the downstream of and then coiling 528.Gas storehouse shell 512 comprises via dish 528 in the hole 532 of its lower end (as shown in figure 32) to reaction volume 524 opening.Layers of foil tabletting 530 is arranged at the bottom in this hole.

Liquid container 534 is arranged in hole 532.The diameter of the diameter than hole 532 of liquid container 534 is less a little, to make to provide via dish 528 circular passage or air vent 536 that are communicated with reaction volume 524 fluid.Liquid container 534 comprises liquid 538, and described liquid 538 comprises interactant, developing agent, catalyst, solvent etc.In its original state, namely before the use, liquid 538 has initial liquid level 540 in container 534.The base section of liquid container 534 comprises layers of foil tabletting 530.Liquid container 534 also has top, and it comprises layers of foil tabletting 542 in this embodiment, and it is preferably similar or identical with layers of foil preform layer 530.But being and then material layer 544 on layers of foil preform layer 542, is fiber polyethylene layer in this embodiment, it provides elastic packing and absorbing fluid 538 for container 534.That each side of container 534 can comprise rigidity and relatively frangible material, as glass, Merlon and acrylic resin etc.In every side in gas storehouse 510, preferably layers of foil preform layer 548 is as previously discussed encapsulated and the content in blanket gas storehouse.They preferably seal each end to shell 512.The top of container 534, bottom and each side should be inertia relative to liquid 538 certainly, to avoid structural deterioration, liquid contamination or poisoning etc.

The layer comprising layers of foil tabletting 530 in this embodiment plays the effect of the bottom of sealed ampoule or tank to prevent leak of liquid.It is also used as the border of described expiration sample flow when the expiration sample sent from conversion zone 524 flows to downstream.Gas (expiration sample) in passage 536 by distributing equipment such as equipment 73 after wherein forming one or more hole by way of parenthesis aerofluxus by top layers 542 and 544.Distributing equipment can and be preferred in the case analyze starting stage because expiration sample is advanced through post 524 and flow out post 524, but this is before dispense liquid 538, to provide this discharge path of gas.The layers of foil tabletting top of liquid container 534 and bottom are also for having enough elastic, enough tough and tensile (non-brittle), to make distributor such as distributor 73 can form one or more hole in this type of layers of foil tabletting each of sufficient size, to realize required function and can not be broken.

As in this paper other embodiment above-described, gas storehouse 510 is configured to operate together together with distributing equipment such as extension device (such as, pin, pin, bar etc.).For purposes of illustration, distributing equipment 73 illustrates in Figure 32.

In a lot of preferred embodiment or application, wish liquid container or at least in the above-described container liquid more preferably can directly be adjacent to described reaction volume in reaction volume by close proximity by its one or more holes distributed.In this type of embodiment and application, preferably and in some cases even necessarily, there is provided medium at one or more tap places of liquid container, to be shifted out by capillarity or capillarity to promote liquid or flow out and flow to reaction volume away from liquid container.More preferably, bottom of liquid container and reaction volume top should be adjacent to each other, but by means of only this wicking material separately.Further preferably, between those two surfaces except wicking material, there is not air gap or other space.This is provided by porous polyethylene dish 528 in gas storehouse 510, and described dish 528 is adjacent with the layers of foil 530 bottom liquid container 534 and adjacent with reaction volume 524 and open wide it with interaction container.

When starting to exhale sample analysis, the input sealing 548 at input 514 place is pierced through assembly 550 by sealing and is pierced through.Assembly 550 comprises the block 552 being connected to movable actuator 554.Assembly 550 also comprises pin 556, and described pin 556 comprises the fluid passage 558 that fluid is connected to expiration sample, and described expiration sample is such as from the flow path 444 of the base unit 440 of Fig. 9.Under normal condition before it is analyzed, block 552 is spaced apart with gas storehouse 510.When expiration sample analysis starts, block 552 is moved to input 514 place in gas storehouse 510 with actuator 554 and pin 556 is inserted through layer 548, to make expiration sample flow by flow path 444 and to flow in gas storehouse input 514.

As found out in such as Figure 32, gas storehouse 510 has and extends through regulator 518 and container reaction volume 524 and the flow path extended to outside around ampoule 534 from its entrance 514.When gas storehouse 510 is in the gas storehouse shell 454 of pedestal 430 being inserted into Fig. 8 and Fig. 9, as 434 alignd and a part for flow path 434 as described in becoming with such as flowing through herein as described in above reference Fig. 9 about inserting this flow path of being configured to as described in mechanism make to bring about the desired sensation in storehouse 510 herein.

Figure 33 illustrates and pierces through previously described liquid container as pierced through the substituted device of tank (Figure 17).In this figure, the pin 601 tilted at a certain angle relative to tank illustrate pin do not need to pierce through tank from top by bottom in case pierce through the tank of below liquidus for twice and the pressure also controlled container to promote liquid flow.First pin 601 remains on the spare space as shown in figure A.In order to pierce through ampoule 602, pin is driven through two positions of ampoule, one above liquidus and one below liquidus, as shown in panelb.When a hole is positioned at below liquidus and another is positioned at above liquidus, liquid freely flows out from ampoule, flow in conversion zone 603, as shown in figure C.

Figure 34 to illustrate in single operation two pins be used in can pierce through ampoule liquidus below form a hole and above liquidus, form a hole to relax inner ampoule pressure and to promote the mode of liquid flow.In the case, be configured to the ampoule 608 that can pierce through tank (Figure 17) and be positioned over side in gas storehouse shell 609.Needle carrier 610 is oriented to be driven through side, gas storehouse to interact with ampoule.The bottom that ampoule 608 can or can can't help to be partially filled forms; As described herein, ampoule bottom angled (" filling ") is retained in ampoule to make few fluid after the rupture.Use this hardware to carry out expiratory measurements can comprise the following steps widely: first, as shown in figure A, make needle carrier 610 get out destruction and can pierce through barrier material 611.When barrier breakdown, as shown in panelb, gaseous sample upwards can flow, by conversion zone 613 from pump 612 or expiration sample source, barrier material 614 around ampoule 608 and by piercing through, thus be discharged to air or waste gas and may be intended to discharge Anywhere.Figure C illustrates that needle assembly 610 is advanced further left and causes ampoule 608 to pierce through at 2.One below liquidus and one above liquidus.Hole above liquidus regulates the pressure (vacuum) in ampoule to be formed, and the orifice allowing liq of below is drained in conversion zone 613 simultaneously.

Figure 35 illustrate can be formed below the liquidus of ampoule hole and without pin mode and pressure in ampoule to not be used in the mode forming hole above an ampoule liquidus example to promote liquid flow can be relaxed.In this example, wave welding head of ultrasonic wave, IR heater or contact heater head 620 for producing heat in ampoule 621, and described ampoule 621 is manufactured to and forms air relief valve 622 below liquidus.This can such as use blow-fill-Sealing Technology uses plastic containers materials to carry out, wherein seal nipple is designed to break when pressure in ampoule is enough high.In order to releasing liquid from ampoule, as shown in panelb, heat energy is connected to the layers of foil tabletting barrier material 621 on filled ampoule content or ampoule top side by wave welding head of ultrasonic wave, IR heater or contact heater head 620.High temperature increases the pressure in sealed ampoule, causes ampoule to break at air relief valve 622 place and then promotes that ampoule is emptied in conversion zone 623.

Figure 36 illustrate can from the ampoule of filling under higher than ambient the mode of releasing liquid.In this example, puncture member 626 is positioned in the reception bag in gas storehouse 627.Puncture member can with gas storehouse material integrally or can be the parts of insertion.Ampoule 627 can be pierced through be placed in puncture member, but enough not cause puncture member to carry out the weight pierced through.In order to releasing liquid from ampoule 628, applicator member 629 is reduced to above ampoule, as shown in panelb.Cause puncture member 626 to destroy can to pierce through the bottom of ampoule 628 with enough power ampoule of exerting pressure downwards, thus form hole at night below line.In the case, ampoule is made up of two inner spaces 630 and 631.Lower space 631 is equipped with liquid reagent.Upper space 630 is equipped with pressure medium.Separately two spaces are expandable membrane or material interface region 632, and it makes two inner spaces 630 and 631 (and they comprise medium) keep different and not mix.When prelum 629 causes puncture member 626 to pierce through bottom ampoule 628, the pressure increased in top interior space 630 causes film or material interface region 632 to extend and therefore the meeting of removing in bottom internal space 631 otherwise hinders any vacuum of flowing; Liquid is assigned in conversion zone 633.

Figure 37 illustrates that the pressure that can relax after ampoule fractures in ampoule not be used in the example that ampoule top forms the mode in hole to promote liquid to flow out ampoule.In this example, there is the ampoule 636 that can pierce through bottom and can be pushed in puncture member 637 as previously described, formed below liquid filling line to cause hole.Hinder the vacuum of ampoule emptying rate of liquid to relax the meeting that can be formed in ampoule after destroying, heat is connected to the dilatable balloon material 639 filled and be easy to the material shunk when heating by wave welding head of ultrasonic wave, IR heater or conductive contacts heater head 638.Therefore, after ampoule pierces through as shown in panelb, as shown in figure C, start heater head 638 to make the balloon material 639 of filling expand, thus cause the removal that otherwise can hinder the vacuum of Liquid distribution in ampoule.

Figure 38 illustrates that hole can be formed at below ampoule liquidus and the vacuum mode that the air of injection can be used to relax.In this example, the pin with internal flow path 640 is reduced to be had in the ampoule 641 of air relief valve 642, as shown in figure A and figure B.Ampoule 643, most preferably be the top can piercing through tank and can pierce through part (contrary with description) and be made up of rubber or separator material, to make to form the pin wall of air-tight fit by needle-penetration and ampoule top can pierce through part.The pressurized interior region of ampoule is formed as schemed the air Injection (such as passing through pump) shown in C, thus the reduction of vacuum causing the destruction of air relief valve 642 and can be formed in addition in ampoule in response to evacuation of fluids.

Figure 39 illustrates that the ampoule making to pierce through is fixed on a position to pierce through at ampoule the device that period promotes fluid flowing.Gas storehouse 650 is manufactured to has star pocket 651.Ampoule 652 can be pierced through by compressed fit in described pocket.Star configuration or other non-circular geometry are designed to provide contact point, thus the compressible steam vent 653 being coupled to the Liquid distribution of protection promotion simultaneously in pocket of ampoule.Compressed fit like this, the piercing through pin and upwards can not carry ampoule along with it of retraction, this can hinder fluid to flow in conversion zone, as described in other parts under many circumstances downwards.

Figure 40 illustrates and is fixed on a position with an example of the device making it and can not be raised when pin is retracted for making to pierce through ampoule.In this example, ampoule 656 can be pierced through to be placed in the pocket in gas storehouse 657.Compo (as fiber polyethylene) coils 658 and is placed in ampoule top.Compo is spongiform and as the spring that press against ampoule top.Barrier material 659 is placed in top, gas storehouse 657 as plastics/layers of foil tabletting and seals (or being adhesively fixed) to gas storehouse 657.Therefore, when upwards retracting after needle-penetration ampoule, as described in other parts, ampoule its retract with moving up and by fixed dwell a position, be tightly connected to wicking material 660 as porous polyethylene, to promote Liquid distribution.Figure A illustrates the isometric view of these parts and schemes the side view that B illustrates these parts.

Figure 41 illustrates and can pierce through the example that ampoule remains on the device of a position after by the needle-penetration as described in other parts.In this example, ampoule 663 is made into be similar to and has the pierced through tank (Figure 20) that film can be pierced through in top and bottom.But in this example, tank body is made up of star extrusion.In the compressible looping pit 664 be engaged in gas storehouse 665 of this ampoule, be fixed on a position to make ampoule and can not will be pulled up during pin is retracted.Gap between ampoule and annular hole wall forms the steam vent promoting that liquid distributes from ampoule.The extrusion profile of ampoule does not need for star; The contact point provided with the gas storehouse receiving pocket can be provided, make compressed fit become may but also keep enough gap with any profile of the promotion aerofluxus when ampoule discharge.

Figure 42 illustrates an example of the ampoule that can only pierce through with pressure.Ampoule 669 is manufactured to has two air relief valve 670 and 671.The drive nozzle 672 with gasket seal is lowered to contact ampoule, as shown in panelb.First flow nozzle causes the destruction of top air relief valve 670, causes the destruction of bottom pressure relief valve 671 subsequently.The destruction of bottom pressure relief valve 671 forms hole below ampoule liquid filling line; Air inlet (by having the drive nozzle 672 of gasket seal) regulates the vacuum that can form to hinder flowing in ampoule.Alternatively, after destruction air relief valve, regracting has the drive nozzle 672 of gasket seal, leaving pore in ampoule, to promote that liquid is found time from ampoule.

Expiration can use on-line equipment input equipment.Figure 43 illustrates the mode that can complete this operation.User is insufflated to flexible pipe one end, and described flexible pipe is equipped with the non-optional antibacterial/virus filter relapsing three-way valve and be connected to inner accommodation container (361).User exhale continuously inside hold in container time, air is pushed through expiratory gas flow measurement device (362), as pneumotachometer or turbine flowmeter.Other device of flow measurement is well known by persons skilled in the art and also can uses at this.Sensor sampling ring (360) use pump uses previously described method to be extracted out from inside accommodation container by gas with the speed controlled.Then, gas enters in gas storehouse for analyzing or sensing region.Use the method for expiratory gas flow measurement device to make it possible to collect the generation information analyzing thing speed, this can have the function larger than simple measurement of concetration.

To describe the method being used for the analysis thing measured in patient expiration according to a further aspect in the invention now, it uses the gentle storehouse 510 of preferred breath analysis system 410.But will be appreciated that, described method might not be limited to these preferred devices and other device and parts can be used for practice or implement described method.

According to the method, first the gas storehouse comprising the following is provided: the first container, fluid container and the reaction volume be communicated with described fluid container fluid with described first container, wherein said first container comprises the first interactant and described fluid container comprises fluid, and wherein said fluid container has initial fluid level and the space above initial fluid level.These aspects in this embodiment by providing gas storehouse 510 as discussed herein above to provide described method.

Described method also comprises provides pedestal, and described pedestal comprises the flow path flowed in pedestal for exhaling, the expiration input sink be communicated with described flow path fluid, gas storehouse shell, distributor and optical subsystem.This preferred embodiment in by providing the base unit 430 of Fig. 8 as discussed herein above to provide in these of described method, described base unit 430 comprises one of distributing equipment embodiment disclosed herein.

Described method comprises further and is inserted in gas storehouse in the gas storehouse shell of pedestal, is communicated with flow path fluid to make reaction volume.Herein preferred embodiment in, this comprises and being inserted in gas storehouse 510 in the gas storehouse shell 452 of base unit 430.

Then described method comprise cause exhale in flow path flowing and flow in reaction volume.

After expiration flows through reaction volume, pressure when described method comprises use distributor in the initial fluid horizontal down formation hole of fluid container and at fluid trickle container in the horizontal superjacent air space of mitigation initial fluid to make fluid trickle container and to flow into reaction volume, thus promotes the optical change relative at least one in the existence of analysis thing and concentration in reaction volume.

Described method also comprises sensing optical change and produces the output comprised about the information analyzing thing in response to optical change.This is preferably by use optical detection subsystems (comprising illumination apparatus 92 and photographing unit 90), and the processor 94 of system 410 and output (display 96 and/or communication export 98) are implemented.

" interactant " or " interactant subsystem " interacts by various ways and analysis thing, and described mode includes but not limited to chemical reaction, catalysis, absorption, absorption, combination, fit interaction, Physical entrapment, phase transformation or its any combination.Biochemical reaction such as DNA and RNA hybridization, protein interaction, antibody-antigene reaction also can be used as interactional mechanism in this system.The example of " interaction " scheme can comprise such as physics or chemical absorbing or absorption, physics or chemical reaction, Van der Waals interact, absorb or releasing heat conversion of energy, cause the transformation etc. of optical change." interactant " and " reactive chemical " is used interchangeably as used herein.

Reactive chemical is preferably interactional (such as, large moisture concentration, CO under the typical context of expired gas even ₂deng).Reactive chemical should analyze the level of thing in response to endogenous in expiration further.In embodiments of the invention spendable reactive chemical and they be found in table 2 for some examples of the analysis thing detected.

table 2

In one embodiment of the invention, reacting substance is connected to surface.Surface can have different geometry and have different composition.Such as, surface can be one group of beadlet be made up of Silicon stone.Or surface can be one group of nanotube be made up of quartz.In preferred embodiments, surface comprises one group of beadlet.Preferably, the diameter of described beadlet is between about 40 microns and about 100 microns.Different materials can be used for forming described surface.The type on surface comprises metal, pottery, polymer and a lot of other types.Some particular instances that can be used for the material of silane coupler include but not limited to Silicon stone, quartz, glass, aluminium oxide, aluminium silicate (such as, clay), silicon, copper, stannum oxide, Talcum, inorganic oxide and other material a lot of well known by persons skilled in the art.The example that can be used for the material of amino coupling agent comprises all types of polymer etc. with epoxide, aldehydes or ketones functional chemistries.The example that can form the material of coupling agent coupling with free radical comprises acrylates, methacrylate and has many polymer of aromatic series key, two carbon bond or single carbon bond and other material a lot of well known by persons skilled in the art.

In some embodiments, reactive chemical is coupled to surface by using coupling agent." coupling agent " is broadly defined as the chemicals, molecule or the material that required chemical functional group can be coupled to (definition see " reaction ") surface.Preferred coupling agent have branch chemical functional group or can with surperficial coupling during branching." branch chemical functional group " or " branching " refer to that each surface binding site has more than one chemical reaction part.Branching can be comprised in single coupling agent or can be reacted each other by some coupling agents and realize.Such as, during reaction tetraethyl orthosilicate can mix to increase branching with aminopropyl trimethyoxysilane.

There is multiple coupling agent well known by persons skilled in the art.In the classification of silane, there is thousands of functional chemical being connected to silane.Silane can be coupled to a lot of surface, preference silica surface and metal-oxide, and again can form surface.The example of common functional silane comprises TSL 8330, hydroxypropyltriethoxysilane, lignocaine propyl trimethoxy silicane and a lot of other silane.

The coupling agent with unhindered amina is easy to be coupled to the surface with epoxide, aldehyde and ketone and other chemical part.The coupling agent with epoxide, aldehyde and ketone also can be used for comprising medium to the surface of strong nucleopilic reagent as amine, mercaptan, hydroxyl and a lot of other affinity reagent.

Some coupling agents are connected to surface by radical reaction, as acrylates and methacrylate etc.

Some coupling agents not with breath analysis thing direct reaction.On the contrary, they are semi-commercial (semiworks) production.The coupling agent that " semi-commercial (semiworks) production " reacts for its chemical functional group and another kind of coupling agent.Such as, lignocaine propyl trimethoxy silicane with the reaction of acetone in be semi-commercial (semiworks) production.It not with acetone direct reaction, but to react with sodium nitroprusside, and then react with acetone.Another example of semi-commercial (semiworks) production can be and uses glycidoxypropyl group triethoxysilane, and its epoxy-functional can react to obtain required functional group with the main body of other molecule.Multiple semi-commercial (semiworks) production is well known by persons skilled in the art.

Embodiment 1

The reactive chemical being used for acetone is described.

By two groups of Silicon stone beadlet (130 order to 140 order) and DEAPMOS or aminopropyltriethoxywerene werene (APTES) coupling.3g Silicon stone beadlet is placed in the mixture of 8.1mL 2-propanol, 1.2mL 0.02N HCl and 2.7mL APTES, or alternatively, 1.5g beadlet is placed in the mixture of 4.05mL 2-propanol, 0.6mL 0.02N HCl and 1.35mLDEAPMOS.Then beadlet vortex effect a few second is allowed at room temperature jolting 10 minutes.Then beadlet is centrifugal to make beadlet at pipe bottom precipitation simply.Decant excess solution, leaves beadlet and is only enough to cover their DEAPMOS or APTES mixture.Then, beadlet is hatched 1 little of 2 hours at 90 DEG C, until their bone dries.DEAPMOS beadlet is coupled to further sodium nitroprusside (SNP).By 3.75mL SNP solution (10%SNP in deionized water, 4%MgSO ₄) add in the beadlet of 1.5g DEAPMOS coupling, then at room temperature by its jolting 5 minutes.Then, fluid is sloughed by vacuum filtration.Then, under vacuo at room temperature by beadlet drying 2 hours.

The beadlet that 1.5g SNP reacts is added in the beadlet of 3.0g APTES coupling and jolting until Homogeneous phase mixing.The beadlet that about 0.025g mixes is placed in capillary glass tube (0.25 in length ", internal diameter 2.7mm).450mL expiration sample in tedlar bag is pumped through CaCl with 150mL/min ₂pretreatment zone (long 0.35 ", internal diameter 0.25 ") and then through on beadlet.Developer solution (0.5% ethanolamine in 25% dimethyl sulfoxine methanol solution) is added in beadlet.After the period of 1 minute to 3 minutes, if acetone exists with the level being greater than 0.1ppm, then there is blue bar.The length of blue bar increases along with acetone concentration and increases.

Embodiment 2

The reactive chemical being used for acetone is described.

By continuing 20mg DNPH to be dissolved in 10 minutes the concentrated solution preparing DNPH in 40uL concentrated sulphuric acid in 5 minutes under 90C.This solution of 8uL is added in 200uL propanol.0.1g 130 order to 140 order Silicon stone beadlet to be added in described solution and at simple vortex, under 90C, to hatch 1 hour, until beadlet is dry and can free-flow.

The beadlet of preparation is placed in capillary glass tube (0.25 in length ", internal diameter 2.7mm).450mL expiration sample in tedlar bag is pumped into 150mL/min through CaCl ₂pretreatment zone (long 0.35 ", internal diameter 0.25 ") and then through on beadlet.Length has the existence of the buff stain instruction acetone of concentration dependent.

Embodiment 3

The reactive chemical being used for ammonia is described.

Concentrated bromophenol blue mixture is prepared by 0.1g bromophenol blue being added in 10mL propanol.After jolting 1 hour, described mixture is ready to use.And the bromophenol blue of not all is dissolved in solution.Stock solution prepares 1:10 diluent in propanol thus.200uL 0.1N HCl is added to 4mL 1:10 diluent and mixes.Add in mixture by 1.8g 35 order to the 60 order Silicon stone beadlet with 60 dust apertures, vortex also at room temperature hatches 10 minutes.Then, under 80C, beadlet is hatched 25 minutes.Liquid should evaporate, but beadlet must be bonded together.Now, beadlet is placed in vacuum lower 1 hour, to complete drying.The separatory such as preparation (about 0.05g/ equal portions) are also stored in household freezer or under vacuum.

The beadlet of preparation is placed in capillary glass tube (long by 0.25 " to 1 ", internal diameter 1.2mm).900mL expiration sample in tedlar bag is pumped through Ascarite II pretreatment zone (long by 0.7 ", internal diameter 0.25 ") with 225mL/min and then through on beadlet.Length and kinetics have the existence of the navy blue stain instruction ammonia of concentration dependent.Detectability is less than 50ppb.

Embodiment 4

The reactive chemical being used for oxygen is described.

Under drying nitrogen, 0.1g titanous chloride. is dissolved in 10mL acetone or acetonitrile.This solution of 200uL is added in 0.1g 130 order to 140 order Silicon stone beadlet.By mixture drying 1 hour under 90C.

Under drying nitrogen, long by 0.25 " the beadlet filling of the capillary glass tube preparation of internal diameter 2.7mm and gas-tight seal.During analyzing, removing or puncture through seal and by the 150mL expiration sample in tedlar bag with 150mL/min through beadlet 30 seconds.Based on the concentration of the oxygen existed, observe the color change of the length dependent from dark purple to colourless.The HCl catching release is applied at the silica gel bed of capillary tube one end.

Embodiment 5

The reactive chemical being used for carbon dioxide is described.

0.1g crystal violet is dissolved in 10mL propanol.1:10 diluent is prepared in propanol.10uL 1MNaOH is added in this solution of 200uL.Then, add 0.1g 130 order to 140 order Silicon stone beadlet and mix.By mixture drying 1 hour under 90C.

Long 0.25 " beadlet of the capillary glass tube preparation of internal diameter 2.7mm is filled and gas-tight seal.During analyzing, removing or puncture through seal and by the 150mL expiration sample in tedlar bag with 150mL/min through beadlet 30 seconds.Based on the concentration of the carbon dioxide existed, observe and change from colourless to the color of the length dependent of blueness.

Embodiment 6

The reactive chemical being used for aldehyde is described.

Can by one group of Silicon stone beadlet (100 order to 140 order) and DEAPMOS coupling.1.5g beadlet is placed in the mixture of 4.05mL2-propanol, 0.6mL 0.02N HCl and 1.35mL DEAPMOS.Acid during coupling in solution, except reaction described in catalysis, tertiary amine forms positive charge.By beadlet vortex effect a few second and then jolting 10 minutes are allowed.Then by beadlet simply centrifugal action to make beadlet at pipe bottom precipitation.Decant excess solution, leaves beadlet and is only enough to cover their DEAPMOS mixture.Then, beadlet is hatched 1 little of 2 hours at 90 DEG C, until their bone dries.DEAPMOS beadlet is coupled to magenta or pararosaniline further.3.75mL solution (in deionized water 0.2% pinkish red or pararosaniline) is added in the beadlet of 1.5g DEAPMOS coupling, then, by its jolting 5 minutes.Then, fluid is sloughed by vacuum filter.Then, under vacuo at room temperature by beadlet drying 2 hours.

About 0.1g beadlet is placed in capillary glass tube (1 in length ", internal diameter 2.7mm).450mL expiration sample in tedlar bag is pumped through beadlet with 150mL/min.Developer solution (0.2M sulphuric acid) is added in beadlet with catalytic reaction.After a few minutes, if there is aldehyde, then there is claret-red vitta.The length of color bar and intensity increase along with aldehyde concentration and increase.

Embodiment 7

An embodiment of equipment is applicable to analyze thing gas storehouse via difference and measures multiple analytes in conjunction with single base unit.Such as, if user object is to measure acetone, then by acetone gas storehouse insertion equipment.If object is carbon dioxide, so by carbon dioxide gas storehouse insertion equipment.When there is following situation, can measure any chemical substance described in the disclosure by this way: 1) in gas storehouse, comprise all reactive chemicals, described gas storehouse dimensionally tight fit suitably can sample reaction bed to make the optical system of pedestal reader; 2) base unit scalable sample volume; 3) base unit scalable sample flow rate; 3) base unit gas storehouse receptor height is adjustable with the gas storehouse holding variable height when needed; And 4) base unit can send and to be applicable to and may the exciting light of variable spectrum.

The system being designed by different gas storehouse and single base unit measurement acetone and ammonia is described in detail at this.Chemical property is described in the analysis of other breath analysis thing of other parts by similar with the description comprised at this.Base unit is made up of automatic sliding clamp mechanism, as discussed previously, carry out for terminating stroke to clamp the device in gas storehouse below using thus: a) use the visual cues in gas storehouse itself, use photographing unit or software as automatically identified or manually enter the knowledge that base unit software obtains the gas storehouse fixture height needed; B) chucking power is set to make to promote to terminate clamping stroke when it advances in needs certain force.Measuring by the electric current of linear actuators is a kind of means, and applied force can be determined and advance for terminating to impact thus.Base unit can regulate sample volume by using by the following volume flow measurement system formed: differential pressure conditioner, ambient temperature sensor, ambient pressure sensor and raw sensor data is changed into the appropriate algorithm of mass flow data.In base unit, the feedback to air pump can be provided by service property (quality) flow data, thus cause carrying out adjusted volume flow rate with different in flow rate stabilized delivery, although gas storehouse encapsulates and may change the gained resistance of air-flow.Base unit comprises the light installing LED based on the surface with white emission spectrum.Described LED or can not be in computer and control with under its variable intensity.Acetone gas storehouse is long by 0.25 by being of a size of " diameter 2.7mm, the reaction bed with SNP beadlet as described in Example 1 form.The gas pretreatment zone in gas storehouse be positioned at reaction bed upstream and by the length 0.35 in gas storehouse " × diameter 0.25 " anhydrous calcium chloride that comprises of region forms.With 150 standard cubic centimeters by gas delivery in post, continue about 3 minutes.Developer solution is comprised in destroyed cylinder above reaction bed, to make the destruction of cylinder cause developer solution capillarity to reaction bed, thus generation is easy to by the color comprising following optical system evaluation: White LED, miniature CMOS photographing unit and simple algorithm as discussed previously.Identical base unit can also evaluate the color produced in the ammonia post of the ammonia chemical substance described in detail in based on embodiment 3.Reaction bed length is 0.25 " to 1 ", diameter is 1.2mm.Gas pretreatment column is by growing 0.7 " and diameter 0.25 " Ascarite II form.Make the expiration sample of 900 standard cubic centimeters through reaction bed with 225 standard cubic centimeters per minute.Do not need developer solution and will be used for evaluating the color of generation in the foregoing optical system of this embodiment and this color is associated with the concentration of ammonia in expiration.

Embodiment 8

The multiple analyte gas storehouse in single flow path with reactive chemical is described at this.In this embodiment, single gas storehouse can be measured from both the ammonia of single source and acetone in single situation.In this embodiment, gas storehouse is configured to evaluate quantitatively the acetone concentration exhalation concentrations scope of 0.5ppm to 5ppm (such as, between) and only qualitative assessment ammonia density (whether such as, assessing expiration ammonia density more than 0.5ppm).Gas storehouse is made up of the reactive chemical from embodiment 1 and 3.In the column dimension described in embodiment 7, pretreatment zone is made up of anhydrous calcium chloride.First by 0.05 " to deposit to internal diameter 2.7mm long by 0.3625 for ammonia react granular layer " post in.By the beadlet of aerated plastics be separated plug (1/16 " thick, 50 microns to 90 micron openings, hydrophilic polyethylene) be placed on ammonia layer, and then then acetone beadlet is deposited into about 0.25 " thick.Alternatively, bead size can be coordinated to remove diffusion barrier.Developer solution is comprised in cylinder above post.The analysis of expiration sample is carried out: with 150 standard cubic centimeters per minute, the expiration sample of 450 standard cubic centimeters is pumped through analytical column as following.After Sample delivery, the optical system be made up of CMOS photographing unit and White LED assesses the color produced in ammonia beadlet.Then, released development agent solution is to react with acetone beadlet.After setting developing time, such as 3 minutes, use the color in identical optical system evaluation acetone reaction bed.Note, the addressable LED of different spectral emissions can be used for the sensitivity changing optical system.Such as using White LED as excitaton source assessment acetone concentration and using blue led (such as, having peak value at 470nm place to excite) to assess ammonia density can be favourable for some application.

Notional amendment of embodiment 8 uses the multiple reactive chemical in identical flow path, with the more interested single analyte of Measurement accuracy.In this embodiment, the chemical substance of carbon dioxide (and/or water) and ammonia is fixed on jointly grow up about 0.5 " in the post of internal diameter 1.2mm.By the concentration of carbon dioxide (and/or water) for compensating the apparent concentration of ammonia because ammonia react be easy to be found in people exhale in water and the pH reaction of gas concentration lwevel interference.

Embodiment 9

This embodiment describes a kind of device in detail, the chemical substance comprised in multiple flow path can be used to assess multiple analytes in single expiration sample by means of this device.Multiple flow path can be comprised, although this embodiment describes the situation with the single gas storehouse of multiple flow path in detail in single gas storehouse or in multiple gas storehouse.

Hardware (detecting based on while acetone and ammonia) required for this embodiment forms by unnecessary or a small amount of amendment of hardware system described in the early time.Gas storehouse is molded as two passages had for reactive chemical and preconditioning agent.When acetone passage needs developing agent, ammonia does not need, base unit comprises single ampoule and destroys pin, and it is oriented to the acetone Channel Interaction with gas storehouse.Sampling pump system is also redundancy, and wherein mass flowmenter and sampling pump are exclusively used in each analysis channel.Keep the ability changing flow velocity and delivery volume independently.Single pump and metering system is used to be distributed to by stream for not too wishing in two analysis channels, because flow velocity is not independent variable and increase the shortage to the control of delivery volume due to the variability problem of post encapsulation.But, for some application, drive the single gas delivery system of two analysis channels to can be useful.In order to the color detected in two passes produces, single camera must focus on and comprises interested whole region (across two passages), comprises removable optical element (mirror system by the suitable passage of photographing unit " sensing "), be self moveable (being arranged on slide rail), or multiple photographing unit must be used.

Embodiment 10

A kind of increasing changes the volume flowing through the gas of post to the method for the detection range of fixed column.Generally speaking, lower detectability is realized by increasing the gas volume flowing through post.Such as, can use the expired volume of 450 standard cubic centimeters that gas storehouse is adjusted to the sensitivity of 0.5ppm to 5ppm acetone.If expect that sample to be measured is in the lower scope of such as 0.1ppm to 0.5ppm acetone, then the gas of larger volume can flow through post, changes similar color change with the color produced with produce with the higher concentration gas of lower volume.Therefore, for given flow velocity, the analyte concentration in the calibration curve determination gas of applicable sample time can be used.But, the consumption being limited in preconditioning component of the method.Such as, the expired volume of sampling is made to double to need the desiccation making anhydrous calcium chloride to double.Fortunately, the excessive encapsulation of anhydrous calcium chloride does not have significant illeffects to acetone concentration, if therefore the method is used for the measuring range by regulating sample volume to carry out extension device, so application is suitable for the desiccant encapsulation gas storehouse of minimum required detectability.

Response time can be used for the concentration assessing sample.In this method, the rate of change that color produces is used for the analyte concentration determined in sample.The reason that this mode works is because generally speaking, and except the final color realized, the speed of chemical reaction is subject to reactant concentration impact.Therefore, optical system and appropriate algorithm will be passed through the repeatedly reading of acquisition and determine that color produces speed and carries out concentration evaluation.Color can be generated produce the calibration curve of RATES's analyte concentration (under prescribed conditions, such as, sample volume, flow velocity and reaction temperature) and can use it for and carry out analyte concentration assessment quickly.By the flow velocity of adjustments of gas by post, the method makes it possible to select different post sensitivity.

Embodiment 11

The all embodiments described in the disclosure are at present inferred, all liq reagent component to be contained in disposable pneumo storehouse and to use the release of reaction initiator for reaction.For some application, can preferred receiving fluids developer solution in base unit instead of in disposable pneumo storehouse.The scheme that can realize the mode of this operation is illustrated in Figure 44.In this scheme, use the emptying gaseous sample from bag of the first pump (1), described first pump (1) promotes the lower fixed claw (2) of sample by clamp mechanism, by having the reaction column (3) of suitable preconditioning component, by upper removable pawl (4) and release three-way valve (5) of clamp mechanism.When needs developer solution, switch three-way valve (5) position flows through feed hose (6) to allow solution from pressurized liquid reagent bottle (7).Second pump (8), for pressure being applied to the headroom of bottle, being drawn into feed hose (6) to cause bottle content and being drawn in the reaction bed (3) in gas storehouse.Substitute pump/valve constitution and cause different swept volumes and different liquids contact point, this developer solution required for given application can have some advantage.The advantage of this scheme is: a) never by developer solution humidify gas sampling path (that is, insert from analyze the second gas storehouse time, the gas of sampling does not need to blow over by the pipe of previous developing agent moistening, removeoutside reaction bed downstream); B) the second pump (8) can not contact developer solution and therefore not need the wettable material special to application; And c) make liquid path not be exposed in air (dry with fluid line) due to three-way valve (5).

embodiment 12

Embodiment is prepared in the gentle storehouse of acetone reagent.At this, a kind of method for measuring the acetone in people's expiration is described.The reagent in encapsulation gas storehouse is prepared as following.APTES beadlet is prepared by being added in 200ul APTES and 400ul propanol by 0.5g 140 order to 170 order silica gel.By thorough for beadlet vortex 10 second.Add 0.4ml 1N H2SO4 and vortex 10 second.Under 80C, beadlet hatched 10 minutes and then solidify 1 hour at 11 oc.

1.67% and 6.67%SNP solution is prepared by being dissolved in by SNP in 25%DMSO methanol solution.By solution storage in lighttight container.20 order to 30 order Ascarite II are available finished product and are used as detergent and desiccant.

Gas storehouse is prepared, for use: by 1/16 as following " thick porous polyethylene dish is placed in the pocket in plastics gas storehouse.Then insert also is 1/16 " thick but can be compressed to roughly 1/32 " thick porous polyethylene dish.Then 0.9mlAscarite II is added to 5/16 " in the pocket of diameter.Another porous polyethylene dish is pressed onto 5/16 " in the pocket of diameter, to keep Ascarite II.From the other end in gas storehouse, add 170 such as prepared above order APTES beadlet to conversion zone, described conversion zone comprises the region of the extruded cross section with roughly 2mm × 4.5mm, groove depth 4mm, and described beadlet overflows the about 1mm of fixed disk pocket.By 1/8 " thick porous polyethylene dish is firmly pressed onto in pocket, closely to keep APTES beadlet.Above fixed disk ampoule being reduced to pocket 1/8 " place.(by filling 5/16 with the 1.67%SNP of 75 microlitres in 25%DMSO methanol solution " diameter polyethylene hollow cylinder, prepare ampoule in the polyethylene/paper tinsel sealing of two ends lamination).By 1/16 " thick porous polyethylene dish to be placed on ampoule and with the polyethylene/paper tinsel barrier material of lamination in top and sealed bottom gas storehouse.Top barrier should press against porous polyethylene, ampoule be firmly fixed on a position and get rid of the probability of ampoule movement during operation, to form space bottom ampoule and between porous polyethylene top, APTES beadlet remains in conversion zone by described space.

embodiment 13

The gas storehouse with pedestal and expiration sample is used to measure the embodiment of acetone.Measure as following: user is exhaled in the exhaling bag of about 500ml volume.Bag to be positioned in bag receptor and gas storehouse bright is as noted earlier inserted in the pedestal of equipment.After beginning is clicked on base unit computer interface, when linear actuators engages bottom gas storehouse with base apparatus internal pipeline blanket gas storehouse.Bottom side, needle-penetration gas storehouse ES in sealed bottom piston.Reduce the pin from top, gas storehouse, to pierce through top side, gas storehouse ES.About 400ml exhales from bag, is delivered through bottom side, gas storehouse by pump and flow rate pump hardware, and wherein then first gas enter APTES beadlet bed through Ascarite II bed.When piercing through recently, gas flows through ampoule and discharges by the hole in top barrier.After send gas about 3 minutes with about 135 standard cubic centimeters (SCCM) per minute, with first then destroying ampoule through the front needle of bottom barrier through ampoule top barrier.When porous polyethylene abuts against compact package bottom ampoule, SNP developer solution is easy to capillarity and reacts beadlet by APTES.After approximately 3 minutes, obtain the image of conversion zone and color quantity of formation is used for estimating the acetone concentration in expiration sample.

Claims

1., for sensing a system for the analysis thing in patient expiration, described system comprises:

Gas storehouse, the reaction volume that described gas storehouse comprises the first container, fluid container and is communicated with described fluid container fluid with described first container, described first container comprises the first interactant and described fluid container comprises fluid, and wherein said fluid container has initial fluid level and the space above described initial fluid level; And

Pedestal, it comprises

For the flow path that described expiration is flowed in described pedestal;

The expiration input sink be communicated with described flow path fluid, it receives described expiration and leads in described expiration path by described expiration;

Gas storehouse shell, described gas storehouse is removably received in described pedestal by it, is communicated with described flow path fluid to make described reaction volume;

Distributing equipment, it forms hole and the pressure relaxed when described fluid flows out described liquid container in the described space above described initial fluid level at the described initial fluid horizontal down of described fluid container, flow out described liquid container to make described fluid and flow into described reaction volume, thus promoting the optical change relative at least one in the existence of described analysis thing and concentration in described reaction volume; And

Optical subsystem, it senses described optical change and produces the output of the information comprised about described analysis thing in response to described optical change.

2. the system as claimed in claim 1, wherein said first container and described fluid container adjacent one another are.

3. the system as claimed in claim 1, wherein said reaction volume is in described first container.

4. the system as claimed in claim 1, wherein said liquid container comprises the first sealing surfaces being arranged at above described liquid and above described space, and described first sealing surfaces comprises pressure-activated sealing, when the pressure in described sealing reaches predeterminated level, described sealing is opened.

5. the system as claimed in claim 1, wherein said liquid container comprises the second sealing surfaces be arranged at below described liquid, and described second sealing surfaces comprises pressure-activated sealing, when the pressure in described pressure-activated sealing reaches predeterminated level, described pressure-activated sealing is opened.

6. the system as claimed in claim 1, wherein said liquid container has outer surface at described hole place and described hole place on described outer surface is provided with wicking material.

7. system as claimed in claim 6, wherein:

Described first container comprises top surface; And

The described outer surface of described liquid container is adjacent with the described top surface of described first container, contacts the described outer surface of described liquid container and the described top surface of described first container of described wicking material contact to make described wicking material at described hole place.

8. system as claimed in claim 7, wherein said wicking material contacts the described outer surface of described liquid container and the described top surface of described first container of described wicking material contact and do not have space at described hole place.

9. the system as claimed in claim 1, wherein said liquid container is opaque to surround lighting.

10. the system as claimed in claim 1, wherein said liquid container is opaque to surround lighting.

11. the system as claimed in claim 1, wherein said reaction volume is opaque to surround lighting.

12. the system as claimed in claim 1, wherein said allotter comprises slender member and the actuator for moving to deployed position from initial position, described in described initial position, slender member is in described liquid container outside, form described hole at the described initial fluid horizontal down of slender member described in described deployed position in described fluid container and relax the described pressure in the described space above described initial fluid level, flow out described fluid container to make described fluid and flow into described reaction volume.

13. the system as claimed in claim 1, wherein said slender member comprises pin.

14. the system as claimed in claim 1, wherein said slender member comprises bar.

15. the system as claimed in claim 1, wherein said slender member comprises fluid passage.

16. systems as claimed in claim 12, wherein said liquid container comprises the first sealing surfaces being arranged at above described liquid and above described space, and described first sealing surfaces comprises a kind of material, when described slender member contacts described material with the power of predeterminated level, described material forms hole.

17. systems as claimed in claim 12, wherein:

Described liquid container comprises and is arranged at the first sealing surfaces above described liquid and the second sealing surfaces below described liquid; And

Described slender member extends through described first and second sealing surfaces.

18. systems as claimed in claim 12, the primary importance of wherein said slender member above described initial liquid level and the second position below described initial liquid level extend through described liquid container.

19. the system as claimed in claim 1, wherein said fluid container comprises multiple fluid further receptacle.

20. systems as claimed in claim 19, wherein said multiple fluid further receptacle is arranged adjacent to each other along pipeline.

21. systems as claimed in claim 19, wherein said multiple fluid further receptacle is arranged adjacent to each other in conveyer belt.

22. the system as claimed in claim 1, wherein said pedestal comprises the described expiration of promotion further and moves in the flow channel and the mobile pump by described reaction volume.

23. the system as claimed in claim 1, wherein said pedestal comprises the pump promoting that described liquid flows from liquid container.

24. the system as claimed in claim 1, wherein said pedestal comprises the pump of the pressure in the liquid superjacent air space of mitigation in liquid container.

25. the system as claimed in claim 1, wherein:

Described liquid container comprises the first sealing surfaces being arranged at above described liquid and above described space;

Described first sealing surfaces comprises pressure-activated sealing, and when the pressure in described sealing reaches predeterminated level, described sealing is opened; And

Described pedestal comprises the pump promoting that described pressure-activated sealing is opened.

26. the system as claimed in claim 1, wherein:

Described liquid container comprises the second sealing surfaces be arranged at below described liquid;

Described second sealing surfaces comprises pressure-activated sealing, and when the pressure in described pressure-activated sealing reaches predeterminated level, described pressure-activated sealing is opened; And

27. the system as claimed in claim 1, wherein said gas storehouse is included in when described gas storehouse is arranged in described pedestal and stops that surround lighting prevents it to be irradiated to the guard shield of described reaction volume.

28. the system as claimed in claim 1, wherein said liquid container comprises and stops that surround lighting prevents it to be irradiated to the outer surface of described liquid.

29. 1 kinds for sensing the method for the analysis thing in patient expiration, described method comprises:

Gas storehouse is provided, the reaction volume that described gas storehouse comprises the first container, fluid container and is communicated with described fluid container fluid with described first container, described first container comprises the first interactant and described fluid container comprises fluid, and wherein said fluid container has initial fluid level and the space above described initial fluid level;

There is provided pedestal, described pedestal comprises the flow path flowed in described pedestal for described expiration, the expiration input sink be communicated with described flow path fluid, gas storehouse shell, distributing equipment and optical subsystem;

Described gas storehouse is inserted in the described gas storehouse shell of described pedestal, is communicated with described flow path fluid to make described reaction volume;

Described expiration is made to flow in described flow path and flow into described reaction volume;

After described expiration flows through described reaction volume, described distributing equipment is used to form hole and the pressure relaxed when described fluid flows out described liquid container in the described space above described initial fluid level at the described initial fluid horizontal down of described fluid container, flow out described liquid container to make described fluid and flow into described reaction volume, thus promoting the optical change relative at least one in the existence of described analysis thing and concentration in described reaction volume; And

Sense described optical change and produce the output of the information comprised about described analysis thing in response to described optical change.

30. 1 kinds for sensing the system of the analysis thing in patient expiration, described system comprises:

Comprise reaction volume and the gas storehouse to the opaque guard shield of surround lighting; And

Pedestal, it comprises

For the flow path that described expiration is flowed in described pedestal;

The expiration input sink be communicated with described flow path fluid, it receives described expiration and by the described flow path of described expiration guiding and by described reaction volume, and wherein said expiration promotes the optical change at least one in the existence relative to described analysis thing of described reaction volume and concentration by the flowing of described reaction volume;

Gas storehouse shell, described gas storehouse is removably received in described pedestal by it, to make described reaction volume be communicated with described flow path fluid, the described guard shield in wherein said gas storehouse coordinates with the described gas storehouse shell of described pedestal, to stop that surround lighting prevents it to be irradiated to described reaction volume; And

31. 1 kinds for sensing the gas storehouse used in the analysis thing in patient expiration at use pedestal, wherein said pedestal comprises the flow path flowed in described pedestal for described expiration, the described expiration of reception be communicated with described flow path fluid and by the described expiration input sink led in described flow path of exhaling, described gas storehouse is removably received into the gas storehouse shell in described pedestal, and sense described optical change and produce the optical subsystem of the output of the information comprised about described analysis thing in response to described optical change, described gas storehouse comprises reaction volume and to the opaque guard shield of surround lighting, wherein said gas storehouse is configured to be removable installed in the shell of described gas storehouse, be communicated with to receive described expiration with described flow path fluid to make reaction volume, wherein said expiration promotes the optical change at least one in the existence relative to described analysis thing of described reaction volume and concentration by the flowing of described reaction volume, and the described guard shield in wherein said gas storehouse coordinates to stop that surround lighting prevents it to be irradiated to described reaction volume with the described gas storehouse shell of described pedestal.