Planar sensor

Abstract

A CO.sub.2-sensitive planar sensing device is disclosed, which has an electrode with an ion-selective layer, an electrolyte layer and an outer layer. The electrolyte layer has osmotically active species in an amount of 0.8-6.0 milliosmol per m.sup.2 of electrolyte layer area, and has a hydrophilic osmolarity increasing component which does not add bicarbonate ions or chloride ions to the electrolyte layer.

Claims

1. A planar CO.sub.2-sensing device comprising: an electrode with an ion-selective layer, an electrolyte layer comprising osmotically active species in an amount of 0.8 to 6.0 milliosmol per m.sup.2 of the electrolyte layer area, wherein the electrolyte layer comprises at least two hydrophilic osmolarity increasing components having a weight average molecular weight in the range of 80 to 5,000 g/mole, wherein at least one of the at least two osmolarity increasing components has a weight average molecular weight in the range of 800 to 3,000 g/mole, and wherein the at least two hydrophilic osmolarity increasing components do not add bicarbonate ions or chloride ions to the electrolyte layer and are present in the electrolyte layer in an amount ranging from 0.05 to 1.2 millimol per m.sup.2 of the electrolyte layer area; and an outer layer, wherein the electrolyte layer is arranged between the ion-selective layer and the outer layer.

2. The sensing device according to claim 1, wherein the electrolyte layer comprises bicarbonate ions in an amount in the range of 0.1 to 1.0 millimol per m.sup.2 of electrolyte layer area.

3. The sensing device according to claim 1, wherein the electrolyte layer comprises chloride ions in an amount in the range of 0.05 to 1.0 millimol per m.sup.2 of electrolyte layer area.

4. The sensing device according to claim 1, wherein the electrolyte layer comprises osmotically active species in an amount of 0.8 to 2.5 milliosmol per m.sup.2 of electrolyte layer area.

5. The sensing device according to claim 4, wherein the hydrophilic osmolarity increasing components are present in the electrolyte layer in an amount in the range of 0.05 to 0.5 millimol per m.sup.2 of electrolyte layer area.

6. The sensing device according to claim 4, wherein the electrolyte layer comprises bicarbonate ions in an amount of in the range of 0.1 to 0.5 millimol per m.sup.2 of electrolyte layer area.

7. The sensing device according to claim 4, wherein the electrolyte layer comprises chloride ions in an amount in the range of 0.05 to 0.5 millimol per m.sup.2 of electrolyte layer area.

8. The sensing device according to claim 1, wherein at least one of the at least two hydrophilic osmolarity increasing components is selected from the group consisting of oligo(ethylene glycols), poly(ethylene glycols), monosaccharides, disaccharides, oligosaccharides, polysaccharides, and cyclodextrins.

9. The sensing device according to claim 1, wherein the at least two hydrophilic osmolarity increasing components contribute by more than 8% to the total osmolarity of the electrolyte layer.

10. The sensing device according to claim 1, wherein the electrolyte layer has a thickness in the range of 3 to 20 m.

11. The sensing device according to claim 1, wherein the electrolyte layer has a thickness in the range of 3 to 8 m.

12. The sensing device according to claim 1, wherein the electrolyte layer has a thickness in the range of 3 to 20 m when in equilibrium with a standard human blood sample.

13. The sensing device according to claim 1, wherein the electrolyte layer has a thickness in the range of 3 to 8 m when in equilibrium with a standard human blood sample.

14. The sensing device according to claim 1, wherein the electrolyte layer comprises osmotically active species of an osmolarity of 300 to 350 mOsM.

15. The sensing device according to claim 8, wherein the at least one of the at least two hydrophilic osmolarity increasing components is poly(ethylene glycol) of a weight average molecular weight of 1500 g/mole.

16. The sensing device according to claim 1, wherein the electrolyte layer further comprises an additional hydrophilic osmolarity increasing component of a weight average molecular weight of more than 5,000 g/mole.

17. The sensing device according to claim 16, wherein the additional hydrophilic osmolarity increasing components is selected from the group consisting of poly(vinylpyrrolidone), methylcellulose, hydroxylpropyl methyl cellulose, cellulose and other cellulose derivatives, and agar.

18. The sensing device according to claim 1, wherein the electrolyte layer further comprises an additional hydrophilic osmolarity increasing component of a weight average molecular weight of more than 10,000 g/mole.

19. The sensing device according to claim 17, wherein the additional hydrophilic osmolarity increasing components is a hydroxypropyl methyl cellulose.

20. The sensing device according to claim 1, wherein: at least one of the at least two hydrophilic osmolarity increasing component is selected from the group consisting of oligo(ethylene glycols), poly(ethylene glycols), monosaccharides, disaccharides, oligosaccharides, polysaccharides, and cyclodextrins; and wherein the electrolyte layer further comprises at least one additional hydrophilic osmolarity increasing component selected from the group consisting of poly(vinylpyrrolidone), methylcellulose, hydroxylpropyl methyl cellulose, cellulose and other cellulose derivatives, and agar.

21. The sensing device according to claim 1, wherein: at least one of the at least two hydrophilic osmolarity increasing components is a poly(ethylene glycol) with a weight average molecular weight of 1,500 g/mole; and wherein the electrolyte layer further comprises an additional hydrophilic osmolarity increasing component chosen from a hydroxypropyl methyl cellulose.

22. The sensing device according to claim 1, wherein the at least two hydrophilic osmolarity components are a poly(ethylene glycol) and a glycerol.

23. The sensing device according to claim 8, wherein the at least one of the at least two hydrophilic osmolarity increasing components is an oligo(ethylene glycol) comprising a weight average molecular weight in the range of 800 to 3,000 g/mole.

24. The sensing device according to claim 8, wherein the at least one of the at least two hydrophilic osmolarity increasing components is a poly(ethylene glycol) comprising a weight average molecular weight in the range of 800 to 3,000 g/mole.

Description

(1) The accompanying drawing, which is incorporated in and constitutes a part of this specification, illustrate an embodiment of the invention and together with the description serve to explain the principles of the invention. In the drawings:

(2) FIG. 1 illustrates a sectional side view of a planar, miniaturised CO.sub.2-sensitive Severinghaus-type sensor according to an embodiment of the present invention.

(3) With the FIGURE is shown a ceramic substrate 1 which carries all other layers of the sensing device.

(4) 3 is a central through-hole in the ceramic substrate, which is filled with an electronically conducting material like platinum or gold, and which connects electronically the back-side contact pad 2 and the front-side contact pad 4, both of which are made up of platinum or gold as well.

(5) A layer of contact material layer 5 is formed on top of and beyond the front-side contact pad 4. The layer of contact material 5 is formed from a material which is both electronically and ionically conducting, such as the sodium vanadium oxide compound described in U.S. Pat. No. 6,805,781.

(6) A first annular structure 6a surrounds the layer of contact material 5, the first annular structure 6a having a height similar to the total height of the front-side contact pad 4 and the layer of contact material 5. The first annular structure 6a is made from an electronically insulating material and provided, e.g. as described in U.S. Pat. No. 5,858,452.

(7) An annular reference electrode structure 4a+7 surrounds the first annular structure 6a. In this way the annular reference electrode structure 4a+7 is isolated from the layer of contact material 5.

(8) The annular reference electrode structure 4a+7 is made up of a core of silver (Ag) 4a, covered by mixture of Ag and silver chloride (AgCl) 7.

(9) For interconnection, the annular reference electrode structure 4a+7 is provided over two peripheral through-holes 3a and 3b, each of which are filled with platinum (Pt) paste and each of which connect back-side contact pads 2a and 2b made from Pt-paste, and annular Ag-core 4a.

(10) A second annular structure 6b surrounds the annular reference electrode structure 4a+7. The second annular structure 6b are made from the same electronically insulating material as first annular structure 6a, and provided, e.g. as described in U.S. Pat. No. 5,858,452.

(11) A pH-sensitive polymeric layer 8 comprising an H.sup.+-selective ionophore in PVC covers the layer of contact material 5 and part of the first annular structure 6a.

(12) An electrolyte layer 9 covers the pH-sensitive layer 8, the remaining part of the first annular structure 6a and the annular reference electrode structure 4a+7. The electrolyte layer 9 comprises sodium and/or potassium bicarbonate, sodium and/or potassium chloride along with a hydrophilic osmolarity increasing component like poly(ethylene glycol), the osmotic concentrations of these compounds making up a total in the range 0.8-6.0 milliosmol per m.sup.2 of electrolyte layer area.

(13) An outer layer 10 of silicone covers the electrolyte layer 9 and interfaces the second annular structure 6b, such that the height of the second annular structure 6b is approximately similar to the total height of the front-side contact pad 4, the layer of contact material 5, the pH-sensitive polymeric layer 8, the electrolyte layer 9 and the outer layer 10.

(14) The planar sensing device according to the embodiment of the invention shown in FIG. 1 may be prepared in accordance with the procedure conventionally used for the preparation of planar sensing devices, as will be evident to the person skilled in the art. Moreover, the preparation of a sensing device of the Severinghaus-type according to the invention is also described in Example 1.

(15) During operation of the sensing device, the back-side contact pads 2, 2a, and 2b are connected to usual measuring equipment for metering of the sensing device potential difference.

(16) The above description relates to a particular embodiment of the sensing device according to the invention which has an annular geometry. This geometry, however, should be considered as a particularly preferred embodiment of the invention and should not be understood as a limitation of the scope of the invention.

EXAMPLE 1

(17) A planar CO.sub.2-sensitive sensing device according to the invention was prepared as follows:

(18) Referring to FIG. 1 an alumina substrate 1 of a thickness of 700 m is provided with three subminiature through-holes 3, 3a and 3b in line, of a diameter of 20 m and at a center-center distance of 1000 m. Each of the through-holes 3, 3a and 3b is filled with platinum paste (P2607, SIKEMA) and connected to circular discs from similar platinum paste 2, 2a and 2b (diameter 50 m) on the substrate back side. Through-hole 3 is further connected to circular contact pad 4 (diameter 50 m) on the substrate front side and facing the below described sensor construction. Contact pad 4 is made from the above platinum paste. Through-holes 3a and 3b are further connected to an Ag (QS175 Silver Conductor from DuPont) core 4a of an annular reference electrode structure 4a+7.

(19) Further on the alumina substrate 1 are two annular structures of encapsulant, 6a and 6b, which are made from an electronically insulating material as described in U.S. Pat. No. 5,858,452. The first annular structure 6a, centered around pad 4, has an inner diameter of 700 m, a width of 500 m and a height of 20 m. The second annular structure 6b, likewise centered around pad 4, has an inner diameter of 2400 m, a width of 600 m and a height of 110 m.

(20) Each of the annular structures 6a and 6b has an inner layer facing the alumina substrate 1 and which are made from ESL glass 4904 from ESL Europe of the United Kingdom and an outer layer of polymer encapsulant from SenDx Medical Inc. of California, USA as disclosed in U.S. Pat. No. 5,858,452 to SenDx Medical Inc. of California, USA, and which comprises 28.1% by weight of polyethylmethacrylate (Elvacite, part number 2041, from DuPont), 36.4% by weight of carbitol acetate, 34.3% by weight of silaninized kaolin (part number HF900 from Engelhard), 0.2% by weight of fumed silica and 1.0% by weight of trimethoxysilane.

(21) The circular layer of contact material 5 is applied above and beyond the pad 4. The circular layer 5 has a diameter of 700 m and a thickness of 20 m, and it is applied according to the disclosure of U.S. Pat. No. 6,805,781. Thus, sodium vanadium bronze is ground in a ball mill to a particle size of approximately 1 m. This powder is then mixed in a ball mill with the acrylate binder system #1112S from ESL in a ratio between bronze and binder of 70:30 by weight. Printing of the layer of contact material 5 is done with a thick film printing apparatus (TF-100, MPM Corp.).

(22) The annular reference electrode structure 4a+7 is printed on top of the through-holes 3a and 3b. The structure 4a+7 is an annular structure of an inner diameter of 1700 m and an outer diameter of 2400 m, and is made up of Ag core (QS175 Silver Conductor from DuPont), covered by a paste of silver and silver chloride (Degussa RDAGCL 50% by weight of Ag/50% by weight of AgCl), acrylate resin and carbitol acetate. It is printed so that the structure 4a+7 has a total height of 20 m.

(23) For the pH-sensitive layer 8 the following composition is prepared: 144 mg of H.sup.+-ionophore TDDA (#95292, Fluka) is weighed and transferred under Ar-atmosphere with a Hamilton syringe through the septum into a 50 mL bluecap bottle. 72 mg of K-tetrakis, 1.6 g of PVC (MW 80,000 g/mol) and 3.2 g of dioctylphthalate (#80030, Fluka) are weighed and transferred to the bottle. 16.40 g newly distilled, cooled THF and 5.47 g of cyclohexanone are weighed and transferred to the bottle as well. The bottle is carefully turned, so the fluid runs along the sides of the bottle, until all the components are mixed. The bottle is not shaken or turned upside down.

(24) Approximately 150 mL of the above composition is applied by dispensing onto the layer of contact material 5. After drying in an oven at 40 C. for at least 15 minutes, another approximately 150 mL of the composition is applied, and subsequently dried in an oven at 40 C. for 24 h. In this way a structure of the pH-sensitive layer 8 is obtained which has a diameter of 1200 m and thus covering half the width of the annular structure 6a, and which has a height at the centre of the layer 8 of 40 m.

(25) The electrolyte layer 9 according to the invention is applied on top of the pH-sensitive layer 8. The electrolyte layer 9 is applied from an electrolyte solution which is an aqueous solution of KCl and NaHCO.sub.3, the concentration of KCl being 6.7 mM and the concentration of NaHCO.sub.3 being 11.9 mM. Further the electrolyte solution contains, as an osmolarity increasing component, 3.4 mM of polyethylene glycol PEG1500 (Sigma-Aldrich, 202436). Finally, the electrolyte solution as a whole contains 2 percent by weight of hydroxypropyl methyl cellulose (HPMC, Sigma, H9262). All ingredients are mixed in a blue-cap bottle.

(26) In this context it should be understood that the contribution from the hydroxypropyl methyl cellulose to the overall osmolarity of the electrolyte layer is less than 1%. This compound is provided with the electrolyte layer 9 mainly for viscosity control purposes.

(27) The electrolyte solution for the electrolyte layer 9 is dispensed over the entirety of the surface of the pH-sensitive layer 8, the outer part of the first annular structure 6a and the annular reference electrode structure 4a+7 to cover these completely and provide electrolytic contact between the two electrodes when the sensing device is in its hydrated state.

(28) The electrolyte layer 9 has a diameter of 2400 m, and is obtained by dispensing an amount of 120 nL of the electrolyte solution as described above, corresponding to a thickness as-prepared of approx. 25 m and in turn 1 millimol per m.sup.2 of osmotically active species. After dispensing, the electrolyte layer 9 is left to dry. The dried layer has a thickness of approx. 1 m.

(29) In its operative and wetted state the thickness of the electrolyte layer 9 is approx. 3 m. Such thickness is obtained in response to the osmolarity external the sensing device of approx. 320 mOsM as provided by blood samples and rinse and cleaning solutions applied with the sensing device. Thus, it should be understood, that in its operative state, the electrolyte layer osmolarity is approx. 320 mOsM, i.e. the electrolyte is concentrated by a factor of 7-8 from its as-prepared state.

(30) Finally electrolyte layer 9 is covered by an outer layer 10 in terms of a 50 m thick silicone membrane, dispensed in its un-cured state. Upon exposure to the humidity of the ambient air the silicone cures to form a strong, pinhole-free outer membrane for the whole device. The silicone material, which is TSE GE 399C from Toshiba, is diluted with 20% by weight of hexane to obtain a suitable viscosity. This outer layer 10 has a diffusion constant to water of approx. 410.sup.9 m.sup.2/s.

EXAMPLE 2

(31) A planar sensing device was alternatively prepared following all steps mentioned in Example 1 above, except that instead of 3.4 mM of poly(ethylene glycol) 1500, glycerol in the concentration of 3.4 mM was used as osmolarity increasing component in the electrolyte solution for the electrolyte layer 9.

EXAMPLE 3

(32) Further, a planar sensing device was alternatively prepared following all steps mentioned in Example 1 above, except that instead of 3.4 mM of poly(ethylene glycol) PEG1500, a mixture of 3.1 mM of poly(ethylene) glycol PEG1500 and 0.3 mM of glycerol was used as osmolarity increasing components in the electrolyte solution for the electrolyte layer 9.

COMPARATIVE EXAMPLE 1

(33) A planar sensing device was alternatively prepared following all steps mentioned in Example 1 above, except that instead of 3.4 mM of poly(ethylene glycol) PEG1500, glycerol in the concentration of 5 M was applied with the dispensing solution for the electrolyte layer 9. Such concentration of glycerol corresponds to the concept of high concentrations of osmotically active species as e.g. disclosed in U.S. Pat. No. 6,805,781.

(34) The planar sensing devices prepared as described in Examples 1-3 and Comparative Example 1 were tested as follows:

EXAMPLE 4

(35) The planar sensing devices of Example 1-3 and of Comparative Example 1 were tested in a modified ABL700 blood gas analyzer from Radiometer Medical ApS, the ABL700 blood gas analyzer sensor chamber being modified to accommodate the planar sensing devices.

(36) For rinsing and calibration, a buffered rinse solution and two pressurized gasses containing CO.sub.2 and O.sub.2 (and balanced with N.sub.2) were used. CO.sub.2 partial pressures of 5% and 10% were applied. The analyzers performed regular calibrations using these gasses and the rinse solution, and the response time of the sensors was observed.

(37) The response time of the planar sensing devices during calibration were calculated based on the sensors signals at t.sub.1=4 s, t.sub.2=8 s and t.sub.3=12 s, compared to the time of the CO.sub.2 exposure at t.sub.0=0 s. The response time is calculated as t.sub.90% which represents the time of reaching 90% of the full signal.

(38) Three sensors of each of Examples 1, 2 and 3, a total of nine sensors, were tested. All of the nine sensors displayed t.sub.90% response times of 5.01.5 seconds.

(39) Three sensors of Comparative Example 1 were tested. These three sensors displayed t.sub.90% response times of 1510 seconds.

(40) All sensors were exposed to an extended test scheme, during which regular calibrations were performed 200 times during a period of 20 days.

(41) Following such extended test, the nine sensors of Examples 1, 2 and 3 displayed a substantially unchanged t.sub.90% response time of 5.11.8 seconds.

(42) At the end of the extended test, the three sensors of Comparative Example 1 displayed a significantly increased response time in that the t.sub.90% response time was 2515 seconds.

(43) Post-test SEM investigations were performed on each of the twelve sensors.

(44) None of the nine sensors of Examples 1, 2 and 3 showed any sign of delamination following the extended test scheme. With all of the three sensors of Comparative Example 1 signs of delamination were observed.

(45) It will be apparent to those skilled in the art that various modifications and variations can be made in the sensor system and the sampling cell of the present invention without departing from the spirit or scope of the invention. Thus, it is intended that the present invention cover the modifications and variations of this invention provided they come within the scope of the appended claims and their equivalents.