WO2001004624A1

WO2001004624A1 - Carbon dioxide sensor

Info

Publication number: WO2001004624A1
Application number: PCT/GB2000/002431
Authority: WO
Inventors: Jafar Albadran; Neil Hamilton Mcmurray
Original assignee: Sensormetrix International Limited
Priority date: 1999-07-10
Filing date: 2000-07-06
Publication date: 2001-01-18
Also published as: AU5692100A; GB9916236D0

Abstract

There is described a colorimetric device which contains an organic solvent soluble, substantially non-curable, hydrophobic silicone oligomer or polymer. There is especially described a colorimetric device, which is a CO2 detector and which comprises at least one pH sensitive dye, at least one phase transport enhancer and a hydrophobic silicone oligomer or polymer selected.

Description

CARBON DIOXIDE SENSOR

The present invention is concerned with devices which provide a detectable indication that a volume of gas has an increased proportion of carbon dioxide compared to that present in normal ambient air.

Methods of detecting or measuring the concentration of gaseous, carbon dioxide in a mixture of gases utilising chemical absoφtion are well known.

Indicating devices for the detection of carbon dioxide in a gas are disclosed in German Patents Nos. 919510 and 1007525. Both Patents disclose selective absoφtion of carbon dioxide on a substance which contains a pH sensitive dye. The change in the pH value caused by the carbon dioxide bound to the substance becomes apparent as a change in the colour of the dye which is present in the substance.

The disadvantage of this system is the need for the sensors to be kept in hermetically sealed glass tubes; once the surface of the sensor has come into contact with the carbon dioxide gas flow an irreversible reaction occurs.

US Patent No. 4,728,499 discloses a reversible carbon dioxide indicator which comprises a system consisting of a pH sensitive indicator dye, a basic substance and a viscous hygroscopic liquid. This indicator is capable of rapidly absorbing and desorbing carbon dioxide, so that the indicator can be used in hospitals to monitor the carbon dioxide content during inhalation. However, this system is disadvantageous because it is strongly hygroscopic and hence the indicator will absorb water vapour from the gas under investigation, which will ultimately result in the system no longer responding to carbon dioxide. This carbon dioxide sensor system also has the disadvantage that the indicator needs to be stored in a hermetically closed, absolutely dry environment free from carbon dioxide prior to use. European Patent No. 0 509 998 discloses a reversible colorimetric device, which is based on pH-sensitive indicator dye, water-insoluble organic quaternary hydroxide as a basic substance and additional substances in order to facilitate the absoφtion/desoφtion of carbon dioxide.

US Patent No. 5,005,572 discloses a CO₂ detector comprising a pH sensitive dye, a solid phase support and a phase transport enhancer. These systems are known to function reversibly for several days and are capable of satisfactory indication both in humid and dry environments. However, the major disadvantage is the strong base decomposes with time so that the indicator slowly becomes permanently acid, and thus exhibiting the acid colour all the time as if it were exposed permanently to high levels of carbon dioxide.

International Patent application No. WO96/24054 discloses a colorimetric device for indicating carbon dioxide, which contains:

(a) at least one pH sensitive dye;

(b) at least one basic substance (a phase transport enhancer) selected from quaternary ammonium salts, phosphonium salts and sulphonium salts; and (c) a water-insoluble organic substance of low volatility, which is not susceptible to alkaline hydrolysis and is liquid at room temperature or moderately elevated temperatures (such as below 100°C).

Such a device is reversible and does not need to be stored in a hermetically sealed, moisture-free environment.

However, the organic substances disclosed as component (c) in WO96/24504 are poor film-formers (that is, they have low cohesive and adhesive strength). They are also polar and are therefore hygroscopic and frequently water-soluble, which would be disadvantageous in a device for monitoring carbon dioxide in breath; furthermore they have disadvantageously low permeability to carbon dioxide. It is an object of the invention to alleviate the above mentioned disadvantages.

According to the invention we especially provide a colorimetric device which includes a silicone oligomer or polymer.

Thus according to the invention we provide a colorimetric device which includes an organic solvent soluble, substantially non-curable, hydrophobic silicone oligomer or polymer.

Thus we especially provide a colorimetric device comprising at least one pH sensitive dye and an organic solvent soluble, substantially non-curable, hydrophobic silicone oligomer or polymer.

Silicone oligomers or polymers have the advantage that they are highly permeable to carbon dioxide. For example, a typical silicone polymer for use according to the invention has a permeability (that is, the gas transmission rate of a film of the polymer of thickness 0.001 inch, expressed as cubic centimetres of gas transmitted though 1 mil of film per 24 hours pr square inch of film with one atmosphere differential across the film) which is typically of about 100,000 for oxygen and about 500,000 for carbon dioxide. This compares with figures of respectively about 1 ,000 and 5,000 for PTFE; 500 and 2,000 for low density polyethylene; 100 and 500 for cellulose acetate; and 1 and 1 for polyvinylidene chloride.

Thus, according to a further feature of the invention we provide a colorimetric device wherein the silicone oligomer or polymer has an oxygen permeability of up to 150,000 cm³ per 24 hrs, for example, 50,000 to 150,000 cm³ per 24 hrs, such as, 150,000 cm³ per 24 hrs.

According to a yet further feature of the invention we provide a colorimetric device wherein the silicone oligomer or polymer has a carbon dioxide permeability of up to 750,000 cm³ per 24 hrs, for example, 250,000 to 750,000 cm³ per 24 hrs, such as, 500,000 cm³ per 24 hrs.

The silicone oligomers and polymers used in the device according to the invention are, furthermore, easy to handle and to apply to a suitable substrate using an organic solvent such as a hydrocarbon type solvent (such as hexane), a chlorinated solvent (for example, chloroform or dichloromethane), an ether solvent (such as tetrahydrofuran), or a low molecular weight oligomeric silicone (such as a cyclic dimethyl silicone).

Because the silicone oligomers or polymers are substantially non-curable, the device has good storage stability and can be stored indefinitely in the solvent.

The silicone oligomers or polymers are also readily compatible with the pH sensitive dye and the basic substance, and can be applied in the form of a film on a preformed substrate (such as a plastics, paper or glass substrate). Alternatively (and preferably), the silicone may be applied as an impregnation throughout a porous carrier medium, for example, of glass fibre, paper, plastics, textile fabric or the like. It is particularly preferred to use such materials which have been provided with a hydrophobic surface treatment, for example, by silanisation.

The silicone oligomers or polymers are preferably substantially linear and substantially free of hydrophilic groups; preferred substituents for the silicone chain are methyl groups (although other low molecular weight hydrophobic groups may be employed, such as ethyl or trifiuoromethyl groups).

It is particularly preferred that the silicone oligomer or polymer is a linear polydimethylsiloxane. The silicone preferably has a molecular weight in the range of 200 to 200000, and is preferably optically transparent. When higher molecular weight silicone polymers are used they are very good binders and have a low glass transition temperature such that they maintain their physical properties over a wide range of temperatures. They are furthermore non-toxic and non- volatile, and hydrolytically stable.

The silicone oligomer or polymer is furthermore compatible with the indicator ingredients (the dye and the basic substrate), and can be free of migratable low molecular weight materials such as plasticisers or the like.

The substrate should be such that it is free of mobile components capable of migrating into the medium containing the dye and basic substance; equally it should resist migration of components from the dye and/or basic substance. If the film is used in a non-transmissive mode then the substrate may be reflective with a high albedo.

The pH-sensitive dye is preferably one which undergo a well defined colour change upon exposure to carbon dioxide (for example, it may undergo a blue to yellow colour change). Such dyes may be anionic or cationic, although anionic dyes are preferred. Examples of suitable indicator anions are azo dyes (including alpha naphthol orange), nitrophenol dyes (including m-nitrophenol and p-nitrophenol), phthalein dyes (including alphanaphtholphthalein and o-cresolphthalein), sulphonephthalein dyes (including m-creson puφle, cresol red, thymol blue and alphanapntholsulphonephthalein), triphenylmethane dyes (including rosolic acid) and indophenol dyes (including indophenol and l-naphthol-2-sulphonic acid indophenol).

The colorimetric device preferably includes, as phase transport enhancer. The phase transport enhancer may comprise a basic substance and may be any such phase transport enhancers conventionally used in the art. Thus, for example, phase transport enhancers described in the prior art of WO 96/24054 may be used. Therefore, preferred phase transport enhancers are ammonium salts, quaternary ammonium salts, phosphonium salts and sulphonium salts. Thus the phase transport enhancers may have the general formula (I): R¹

R^j

wherein X is N - R⁴, P - R⁴, or S;

R¹ to R are each Cl to 18 alkyl or aralkyl, or two of R¹ to R³ together complete an optionally substituted heterocyclic group containing up to 20 carbon atoms; R⁴ is C 13 to 17 alkyl; and

Y is an anion selected from halide, e.g. fluoride, chloride, bromide, iodide; carbonate and fluoroborate, e.g. tetra fluoroborate.

Such phase transport enhancers are generally applied to a support, in solution, together with the pH sensitive dye and the silicon oligomer or polymer. The phase transport enhancers enhance phase transport within the device, and thereby enhance response of the colour and visibility of the indicator dye.

The phase transport enhancers may be, for example, symmetrical C13 to 17 tetra- alkyl ammonium or asymmetric C18 ammonium salts (such as tripentyl-octadecyl ammonium) or a benzalkonium salt. Such salts are advantageous over known transport enhancers as they are less prone to migration, or extraction, presumably because of their relatively high molecular weight.

Alternatively, a conventional (lower molecular weight) phase transport enhancer, such as one of the compounds as one of the compounds described in US Patent No. 5,005,572 may be used.

The following example illustrates the preparation of an exemplary carbon dioxide sensor according to the invention. Example 1

Polydimethyl silicone films

Two samples of high molecular weight, straight chain polydimethylsilicones were obtained form Dow Corning. Both dissolved readily in dichloromethane from which thin, reasonably transparent films could be cast.

When the tetrabutyl ammonium salt of the dye m-cresol puφle was incoφorated in the solution of the polymer, a film which was highly sensitive to C0₂ was cast from the solution.

The solution was also used to impregnate glass microfibre filters (Whatman GF/C ex

Merck Ltd) of the type currently used in the "easy cap" (Nellcor Puritan Bennett) breath analyser (for detection of correct intubation during anaesthesia). The resultant disks had rapid response to CO₂, which was fast enough for breath by breath analysis.

The slight loss of sensitivity of these disks with increasing humidity (induced by continued breathing over the film) was alleviated by using a hydrophobic phase separation filter, based on silanised paper (Whatman IPS from Merck Ltd.) and using the more hydrophobic base Tetraoctylammonium hydroxide (TOAOH). A typical formulation for impregnating such a filter was as follows:

• 10ml 10% wt/vol polydimethylsilicone in dichloromethane

• 20ml dichloromethane • lOmg m-Cresol Puφle in 0.5ml 0.5M methanolic TOAOH.

When cast to form a film, the above gave a final film composition of:

• m-Cresol Puφle 1 (per hundred parts resin or polymer (phi)

• TOAOH 12 phr.

Claims

1. A colorimetric device which includes a silicone oligomer or polymer.

2. A colorimetric device according to claim 1 characterised in that the silicon oligomer or polymer is an organic solvent soluble, substantially non-curable, hydrophobic silicone oligomer or polymer.

3. A colorimetric device according to claim 1 characterised in that the colorimetric device comprises a pH sensitive dye.

4. A colorimetric device according to claim 1 characterised in that the silicone oligomer or polymer has an oxygen permeability of up to 150,000 cm³ per 24 hrs.

5. A colorimetric device according to claim 1 characterised in that the silicone oligomer or polymer has a carbon dioxide permeability of up to 750,000 cm per 24 hrs.

6. A colorimetric device according to Claim 1 characterised in that the silicone oligomers or polymers are substantially linear.

7. A colorimetric device according to Claim 1 characterised in that the silicone oligomers or polymers are substantially free of hydrophilic groups.

8. A colorimetric device according to Claim 1 characterised in that the silicone oligomers or polymers have methyl substituents.

9. A colorimetric device according to Claim 8 characterised in that the silicone oligomers or polymers have ethyl or trifluoromethyl substituents.

10. A colorimetric device according to Claim 1 characterised in that the silicone oligomers or polymers a polydimethylsiloxane.

11. A colorimetric device according to Claim 10 characterised in that the polydimethylsiloxane is linear.

12. A colorimetric device according to Claim 1 characterised in that the silicone has a molecular weight in the range of 200 to 200,000.

13. A colorimetric device according to Claim 1 characterised in that the silicone is optically transparent.

14. A colorimetric device according to Claim 1 characterised in that the silicone is substantially free of migratable low molecular weight materials.

15. A colorimetric device according to Claim 1 characterised in that it includes a phase transport enhancer of the general formula (I):

R^J

wherein X is N-R⁴, P-R⁴ or S;

R¹, R² and R³, which may be the same or different, are each Cl to 18 alkyl or aralkyl, or two of R¹, R² and R³ together complete an optionally substituted heterocyclic group containing up to 20 carbon atoms;

R⁴ is C13 to 17 alkyl; and Y is an anion selected from halide, carbonate and tetra fluoroborate.

16. A colorimetric device according to Claim 15 characterised in that the phase transport enhancer is a symmetrical C13 to 17 ammonium salt.

17. A colorimetric device according to Claim 15 characterised in that the phase transport enhancer is an asymmetric Cl 8 ammonium salt.

18. A colorimetric device according to Claim 17 characterised in that the asymmetric C18 ammonium salt is tripentyl-octadecyl ammonium.

19. A colorimetric device according to Claim 11 characterised in that the phase transport enhancer is a benzalkonium salt.

20. A colorimetric device according to Claim 15 characterised in that the device is a CO₂ detector.

21. A method of CO₂ detection which comprises placing a colorimetric detector according to claim 20 in situ and observing colour change.

22. A medical device including a CO₂ detector according to claim 20.

23. A medical device according to claim 22 characterised in that the device is an endotracheal intubation apparatus.

24. A method of determining the proper placement of an endotracheal tube which comprises inserting an endotracheal tube according to claim 19 into the trachea of a patient and observing a colour change.

25. The use of an organic solvent soluble, substantially non-curable, hydrophobic silicone oligomer or polymer in the manufacture of a colorimetric device according to claim 1.

26. A film formulation comprising at least on pH sensitive dye and an organic solvent soluble, substantially non-curable, hydrophobic silicone oligomer or polymer.

27. A film formulation according to claim 26 characterised in that the formulation also comprises a phase transport enhancer.

28. A colorimetric device substantially as described with reference to the accompanying examples.