WO1991005508A1

WO1991005508A1 - MINIATURE pCO2 PROBE FOR IN VIVO BIOMEDICAL APPLICATIONS

Info

Publication number: WO1991005508A1
Application number: PCT/EP1990/001795
Authority: WO
Inventors: Emilio Sacristan; Albert Shahnarian; Robert A. Peura
Original assignee: Mountpelier Investments S.A.; Tonometrics, Inc.
Priority date: 1989-10-23
Filing date: 1990-10-23
Publication date: 1991-05-02
Also published as: AU6754790A; ZA908487B; US5158083A

Abstract

The pCO2 probe (10) has a miniaturized glass bulb pH sensor (14) concentrically arranged in a flexible, noncollapsible hollow tube (12). A silicone end cap (48) is expanded in a freon solvent and placed over the end of the tube while the freon evaporates, returning the end cap to its normal contracted size where it forms a tight elastic fit. The pH sensor (14) includes an internal electrode (26) and an outer electrode (30) which is concentrically wrapped about a glass bulb (20) so that the electrodes (26 and 30) are in close proximity. The glass bulb (20) and the chamber (18) defined by the tube walls (58) and silicone membrane (48) are both filled with suitable electrolytes of sufficient volume to minimize air bubbles. Without air bubbles, the electrodes (26 and 30) remain immersed in the respective electrolytes regardless of the physical orientation of the probe (10).

Description

MINIATURE pC0₂ PROBE FOR IN VIVO BIOMEDICAL APPLICATIONS

Background and summary of the invention

This invention relates to medical diagnostic equipment and methods and is particularly concerned with measurement of carbon dioxide in the body. The invention more particularly relates to an electrochemical pC0₂ sensor for making in vivo measurements.

A fall in the intramucosal pH may precede the development of intestinal ischemia and stress ulcera ion. The fall in pH in intestinal mucosa can be reliably calculated from a pC0₂ (partial pressure of C0₂) measurement using the Henderson-Hasselbalch equation. This is described in commonly assigned U.S. Patent No. 4,643,192, entitled "Hollow Viscous Tonometry" and continuation applications Serial Nos. 120,720 and 233,888 and in commonly assigned patent applications Serial Nos. 237,287 and 380,706 entitled "Remote Sensing Tonometric Catheter Apparatus and Method," and in Serial No. 237,286 entitled "Tonometric Catheter Combination," which are herein incorporated by reference.

In the above body of commonly assigned patent and applications certain techniques for sensing pC0₂ in vivo are described. Although semiconductor CHEMFET sensors and optical sensors are used, it would also be desirable to use electrochemical sensors for pC0₂ measurement. We have attempted to use conventional, commercially available electrochemical ρC0₂ sensors and have found them to be generally inadequate. Conventional electrochemical pC0₂ sensors, based on the Severinghaus technology, are not sufficiently miniaturized or constructed for use in vivo and

SUBSTITUTESHEET do not give accurate readings unless properly oriented. For example, many electrochemical pC0₂ sensors work properly only when physically oriented upright. They do not work properly when oriented on the side or upside down.

Addressing the needs of the biomedical community, the present invention overcomes the shortcomings of the prior art electrochemical pC0₂ sensor technology. The present invention provides a miniaturized pC0₂ sensor of the electrochemical type. The sensor is well adapted for actual insertion through an appropriate orifice into a hollow organ for in vivo pC0₂ measurement. The probe comprises a selectively permeable first membrane which defines a closed reference chamber. A first electrode is disposed in the reference chamber. The first membrane is preferably a bulb-like glass membrane which is permeable to H⁺ ions. A hollow flexible tube has a fluid tight plug inserted fully into one end leaving a test chamber space between the plug and the open end. An end cap comprising a selectively permeable second membrane is fitted over the open end to define a closed test chamber between end cap and plug. Preferably the second membrane comprises a silicone rubber which is permeable to C0₂ molecules. The first membrane, with first electrode enclosed, is disposed within the test chamber. A second electrode is disposed in the test chamber in proximity to the first membrane. Preferably the second electrode is wrapped about the bulb-like first membrane structure adjacent the first electrode. The reference chamber is filled with a first electrolyte of known H⁺ ion concentration. HC1 may be used for this purpose. The test chamber is filled with a second electrolyte preferably including bicarbonate ions. The test chamber and reference chamber are both of such a size, and the respective electrolytes are of such a volume, that the respective electrolytes remains in contact with the

SUBSTITUTESHEET corresponding electrodes over all spatial orientations of the probe. In other words, even when inserted through a body orifice, as in the case of a naso-gastric measurement, both electrodes remain in proper contact with their respective electrolytes, regardless of probe orientation. Accurate results are achieved whether the probe is right side up, upside down, or somewhere between.

The probe construction of the invention is well adapted to miniaturization and the probe can be in the form of an elongated tube of sufficient length and diameter to permit the tube to be slidably inserted through the channel of a naso-gastric tube, an endoscope, or the like. Also, if desired, a thermistor temperature sensor can be incorporated in the probe to give a reading of core temperature at the pC0₂ probe site, and allow the pC0₂ reading to be corrected for temperature.

Further according to the invention, the pC0₂ probe comprises a flexible and noncollapsible hollow tube which has an open end that defines inner and outer sidewalls.

A containment structure for defining a closed reference chamber is coaxially disposed within the hollow tube. The containment structure comprises a selectively permeable glass membrane portion which is adjacent to the open end of the hollow tube, and a carrier portion extending axially within the hollow tube. A supporting and sealing means is disposed in the hollow tube, in sealing contact with the inner sidewall to support the carrier portion of the containment structure. The first electrode has a portion disposed in the reference chamber and a portion which extends through and is supported by the carrier means. The reference chamber is substantially filled with a first electrolyte of known K⁺ ion concentration. A second electrode has a portion disposed concentrically around the glass membrane portion. The second electrode further has -a portion extending through

SUBSTITUTE SHEET the supporting and sealing means. An end cap, comprising a second membrane selectively permeable to C0_2/ is carried by the outer sidewall of the tube, in sealing contact therewith. The end cap thereby defines a fluid tight electrolyte chamber within the tube. The fluid tight chamber so defined thereby also contains the glass membrane portion.

The end cap has a radially extending planar or curved end face with a longitudinally extending cylindrical sidewall. The cylindrical sidewall is orthogonal to the end face. The end cap is elastically held in place by tensile forces of the end face which urge the cylindrical sidewall into contact with the outer sidewall of the hollow tube. The electrolyte chamber is substantially filled with a second electrolyte capable of changing pH in response to changes in C0₂ concentration.

For a more complete understanding of the invention and its objects and advantages, reference may be had to the following specification and to the accompanying drawings.

Brief Description of Drawings

Figure 1 is a fragmentary cross-sectional view of a presently preferred pC0₂ sensor in accordance with the invention; Figure 2 is a diagram exemplifying one use of the pC0₂ sensor of the invention;

Figure 3 is an enlarged fragmentary cross- sectional view of the pH sensor with helically wound second electrode also illustrated in Figure 1; Figure 4 is a similar enlarged fragmentary view of an alternate embodiment employing a cylindrical tube¬ like second electrode;

Figure 5 is a fragmentary cross-sectional view of an alternate preferred pC0₂ sensor with side port; Figures 6 and 7 illustrate-exemplary naso-gastric

SUBSTITUTESHEET tubes in cross section, each with channel for receiving the pC0₂ sensor of the invention;

Figures 8 and 9 illustrate an exemplary naso- gastric tube in combination with a probe such as the pC02 sensor of the invention, showing one apparatus and method for probe calibration.

Description of the Presently Preferred Embodiments

Referring to Figure 1, the pC0 probe is shown generally at 10. The probe comprises a flexible, noncollapsible hollow tube 12. Preferably constructed of polyethylene tubing. A suitable tubing of 2.92 mm inner diameter and 3.73 mm outer diameter is available from Clay Adams, a division of Becton Dickinson & Company, Parsippany, New Jersey 07054, under the Intramedic brand name. A pH probe 14, such as an esophageal probe Model MI-405-E available from Microelectrodes, Londonderry, New Hampshire, is coaxially arranged within tube 12 and held in place by silicone plug 16 approximately 1/2 inch in length. Silicone surgical tubing available from Dow Corning, Midland, Michigan, 48640, may be used for plug 16. Plug 16 is inserted into the end of tube 12, leaving a space which defines an electrolyte test chamber 18. Also see Figure 3.

The pH probe 14 may comprise a selectively permeable glass membrane 20 which is fashioned to include an enlarged bulb-like structure 22 and an elongated carrier portion 24. Disposed within glass membrane 20 is a first electrode 26 which includes a lead 28 that extends through and is supported by the carrier portion. A second electrode 30 is helically wound concentrically about glass membrane 20 and includes a lead 32. Second electrode 30 may be fabricated from a 3 inch length of silver wire, available from croelectrodes, Londonderry, New Hampshire. Electrode 30 is electroplated in HCl to add a coating of AgCl.

Leads 28 and 32 are connected respectively to the

SUBSTITUTE SHEET center conductor 34 and shield conductor 36 of a coaxial cable 40. The plastic jacket 42 may extend beneath a portion of second electrode 30 to contact the bulb-like structure 22, offering it more structural support. Coaxial cable 40 extends the entire length of tube 12 to provide conductors 34 and 36 for connection to measuring instruments. The pH probe depicted has a 1.6 mm diameter glass bulb and includes a 3 long coaxial cable of 1.4 mm outer diameter. Other pH probe sizes may also be used to practice the invention.

The glass membrane 20 is fully sealed about lead 28 to define a hollow interior which is filled with a first electrolyte of known H⁺ ion concentration. The glass from which membrane 20 is fabricated is permeable to H⁺ ions.

The details of one embodiment of electrode configuration are illustrated in Figure 3. In this embodiment, the second electrode comprises a silver wire helically wrapped around the bulb-like structure 22. In the alternative, the helically wound wire electrode may be replaced with a cylindrical silver tube. This is illustrated in Figure 4. The silver tube defines a second electrode 31. The tube may be crimped onto the end of the coaxial cable 40, with electrical connection made between the tube and the shield conductor 36. In both embodiments the silver second electrode is electroplated in hydrochloric acid to form a coating of AgCl. The electroplating may be done by filling the electrolyte test chamber 18 with hydrochloric acid and by temporarily inserting an electroplating electrode into the hydrochloric acid and applying an appropriate electroplating voltage between the electroplating electrode' and the silver second electrode. In the presently preferred embodiment, this electroplating technique is accomplished using pure, undiluted HCl and a voltage source of about 2 volts in series with a IK ohm resistor to limit current. The cathode is connected to

SUBSTITUTESHEET the second electrode and the anode is placed in the HCl for approximately 5 minutes. During this time the current is initially about 500 mA, falling to about 100 microamperes at completion. A nylon mesh spacer 46, available from Dow

Coming's blood gas analyzer electrode maintenance kit, is positioned over the open end of tube 12, in contact with the extreme end of bulb-like structure 22. An end cap 48 of silicone rubber or other suitable C0₂ permeable material is frictionally fit onto the end of tube 12 to seal the electrolyte test chamber 18. The silicone rubber end cap may be constructed from the tip end portion of a clinical tonometer balloon, available from Speciality Manufacturing Company, Saginaw, Michigan 48603. Other suitable materials include Teflon and Tefzel, both available from DuPont. Chamber 18 is filled with a second electrolyte containing bicarbonate ions. The preferred second electrolyte formulation comprises a mixture of 0.06 M KHC0₃; 3 M KC1; saturated with AgCl and a mold inhibitor, such as available from Dow Corning for use with the Dow Corning blood gas analyzer. End cap 48 forms a membrane which is permeable to C0₂. The end cap includes a radially extending planar or curved en face 52 and longitudinally extending cylindrical sidewall 54. The sidewall is generally orthogonal to the end face and the end cap is elastically held in place by tensile forces of the end face urging the cylindrical sidewall into contact with the outer sidewall 56 o tube 12. In manufacturing the pC0₂ probe of Figure 1, th pH probe is positioned inside tube 12 by first pullin the pH probe through plug 16 and then pulling the plu and probe assembly through the open end of tube 12 int frictional sealing contact with inner sidewall 58. I the alternative, the pH probe may be temporarily held i position with plug 16 being poured in a molten state an then hardened. Chamber 18, formed by leaving space a

SUBSTITUTE SHEET the end of plug 16, is then filled with the second electrolyte by orienting the tube with open end facing up and filling with a syringe. Next the nylon mesh spacer 46 is placed onto the rim of the open end of tube 12 where it adheres by cohesion. The spacer is used to ensure that the entire bulb-like structure 22 is at all times covered with electrolyte after assembled for use. The spacer prevents the end face 52 of the end cap from contacting the bulb-like structure 22. Next, the end cap is held open side up and filled to the brim with the second electrolyte. In order to ensure a tight fit, the end cap may be placed in a freon- based solvent prior to filling with electrolyte. The solvent causes the silicone end cap to expand, making it easy to slide onto the tube 12. With end cap held open side up, the tube 12 with pH probe and spacer installed is pressed into the end cap. Electrolyte spills over the rim of the end cap as the pH probe displaces the electrolyte. In this way no air bubble is trapped in the test chamber. With end cap installed, the freon is then permitted to evaporate from the silicone end cap material, whereupon the end cap shrinks to its original size and forms a tight, elastic fit.

If desired, a thermistor 60 may be positioned in the test chamber 18, with leads 62 and 64 extending through tube 12 for connection to suitable measurement equipment. A suitable thermistor is the Alpha NTC Micro- Thermistor (10 K ohms at 25_#C) available from Alpha Thermistor, Inc., San Diego, California, 92121. The leads 62 and 64 may be 0.028 inch outer diameter microminiature medical grade cable, available from Cooner Wire Co., Chatsworth, California, 91311.

Figure 2 illustrates one example of the pC0₂ probe in use as a naso-gastric measurement instrument. As illustrated, the operative end 66 of probe 10 is positioned in the hollow organ (in this case the stomach) where measurement is desired. The spatial orientation of

SUBSTITUTE SHEET the operative end is not of concern to the physician, since the probe will operate at all spatial orientations. This is attributed to the fact that both the glass membrane 20 and the electrolyte test chamber 18 are filled with a sufficient volume of the respective electrolytes so that the first and second electrodes remain in contact with the electrolyte at all orientations.

In constructing the probe to work at all spatial orientations, care is taken to prevent air bubbles from remaining in the test chamber 18 and in the glass membrane 20 over the anticipated operating temperature and pressure ranges. The pC0₂ probe can be made at any desired length to match the intended use. The non- inserted end can be provided with a fitting such as fitting 68, which electrically couples to conductors 34, 36, 62 and 64. Connecting cables 70 are then used to connect the pC0₂ probe and temperature sensor to the pC0₂ and temperature measurement equipment 72 and 74. An alternate embodiment of PC0₂ probe is illustrated in Figure 5. The embodiment of Figure 5 differs from the embodiment of Figure 1 in that the end of tube 12 is heat and/or solvent sealed and may include a silicone rubber tip 76. A side port 78 is cut in the sidewall of tube 12 and the pH probe is configured as illustrated generally at 80 to have a side-looking characteristic. End cap 48 extends over the plastic filler 76 and also over the side port 78, as illustrated. If desired, a thermistor 60 may be included. The side-looking pH probe 80 may be provided with a perforated silver tubular second electrode 82. The pH probe assembly may be held in place on the side of the jacket 42 of coaxial cable 40 with suitable glue as at 84 and 86. Like the probe of Figure 1, the alternate, side port construction of Figure 5 is also made so that both electrodes remain properly covered with electrolyte at all spatial orientations. Care is taken to prevent air

SUBSTITUTE SHEET bubbles from being trapped in the electrolyte chambers.

Probe Calibration Before use, and periodically during use the probe should be calibrated using a calibration solution of known C0₂ concentration. This may be done using ex-vivo automated calibration equipment of the type used to calibrate blood gas analyzers. Once the probe has been positioned in the body it may need to be retracted in order to calibrate. Although the probe is flexible enough to permit it to be retracted for calibration and then reinserted, retraction can be facilitated by fashioning the tonometric catheter with a suitable channel or conduit to slidably receive and guide the probe during insertion and retraction. Figures 6 and 7 are examples of two different naso-gastric tubes, shown in cross section, which have been adapted to include a sensor channel 100 in addition to the usual suction 102 and vent 104 channels or lumen. As illustrated in Figures 8 and 9, the tube tip 106 (in this case a naso-gastric tube) is provided with an appropriate window 108 covered by a silicone rubber or other permeable membrane 110. To insure that the operative end 112 of the probe is properly positioned in the window, a rubber stopper 114 is placed over the probe at the connector end 116. The stopper is positioned prior to insertion of the naso-gastric tube, with care being taken that the probe is properly positioned in the window 108 when the stopper is pressed into the non- working end of the tube. The stopper fits snugly abou the probe body and thereafter acts as a stop or guide to aid in registration of probe tip and window, even while the naso-gastric tube remains in place within the body.

As an alternative to retraction and full calibration of the probe, it is possible to readjust the probe calibration to compensate for drift without removing it. This is done by using the tube (in this example a naso-gastric tube) to extract a fluid sample from the body and thereafter to measure the sample's pC0₂. Using the measured sample reading and making the assumption that the pC0₂ at the probe site matches that of the extracted sample, the probe calibration setting may be adjusted.

From the foregoing it is seen that the pC0₂ probe of the invention is well adapted for biomedical applications where in vivo measurements are indicated. While the invention has been described in connection with the presently preferred embodiments, certain modifications can be made to the structure and certain changes can be made to the selection of materials used, without departing from the spirit of the invention as set forth in the appended claims.

SUBSTITUTE SHEET

Claims

IN THE CLAIMS;

1. A pC0₂ probe comprising: a selectively permeable first membrane defining a closed reference chamber; a first electrode disposed in said reference chamber; a hollow flexible tube having a fluid tight plug means and end cap means for defining a closed test chamber, said end cap means comprising a selectively permeable second membrane; said first membrane being disposed within said test chamber; a second electrode disposed in said test chamber and in proximity to said first membrane; a first electrolyte of predetermined ion concentration contained in said reference chamber and in contact with said first electrode; a second electrolyte contained in said test chamber; said test chamber being of such a size and said second electrolyte being of such a volume that said second electrolyte remains in contact with said second electrode over all spatial orientations of said probe.

2. The probe of Claim 1 wherein said first membrane defines a bulb-like structure.

3. The probe of Claim 1 wherein said first membrane is glass.

4. The probe of Claim 1 wherein said first membrane is a glass bulb.

5. The probe of Claim 1 wherein said first membrane is permeable to H⁺ ions.

SUBSTITUTESHEET

6. The probe of Claim 1 wherein said end cap means is of silicone rubber.

7. The probe of Claim 1 wherein said end cap means is elastically held on said tube.

8. The probe of Claim 1 wherein said second membrane is of silicone rubber.

9. The probe of Claim 1 wherein said second membrane is permeable to C0₂ molecules.

10. The probe of Claim 1 wherein said first electrolyte, said reference chamber and said first electrode comprise a pH electrode.

11. The probe of Claim 1 wherein said first electrolyte has a known concentration of H⁺ ions.

12. The probe of Claim 1 wherein said second electrolyte includes HC0₃.

13. The probe of Claim 1 wherein said first electrode includes a conductor extending out through said first membrane for electrically coupling a measurement device to said first electrode.

14. The probe of Claim 1 wherein said tube is elongated and flexible and wherein said first electrode includes a conductor extending out through said first membrane and along the interior of said tube for electrically coupling a measurement device to said first electrode.

15. The probe of Claim 1 wherein said tube is of a diameter to permit said tube to be slidably inserted through the channel of an endoscope.

SUBSTITUTESHEET

16. The probe of Claim 1 wherein said reference chamber is of such a size and said first electrolyte being of such a volume that said first electrolyte remains in contact with said first electrode over all physical orientations of said probe.

17. The probe of Claim 1 further comprising temperature sensing means disposed in said test chamber for measuring the temperature of said second electrolyte.

18. The probe of Claim 1 further comprising thermistor sensor disposed in said test chamber for electrically measuring the temperature of said second electrolyte.

19. A pC0₂ probe comprising: a flexible and noncollapsible hollow tube having an open end and defining inner and outer sidewalls; a containment means for defining a closed reference chamber coaxially disposed within said hollow tube, said containment means comprising a selectively permeable glass membrane portion adjacent said open end of said hollow tube and a carrier portion extending axially within said hollow tube; supporting and sealing means disposed in said hollow tube in sealing contact with said inner sidewall and supporting said carrier portion; a first electrode having a portion disposed in said reference chamber and a portion extending through and being supported by said carrier portion; said reference chamber being substantially filled with a first electrolyte of known H⁺ ion concentration; a second electrode having a portion disposed concentrically around said glass membrane portion and having a portion extending through said supporting and sealing means; end cap means comprising a second membrane selectively permeable to C0₂ carried by and in sealing

SUBSTITUTE SHEET contact with the outer sidewall of said tube to define fluid tight electrolyte chamber within said tube an containing said glass membrane portion; said end cap having a radially extending end fac with longitudinally extending cylindrical sidewal orthogonal to said end face, said end cap bein elastically held in place by tensile forces of said en face urging said cylindrical sidewall into contact wit said outer sidewall of said tube; said electrolyte chamber being substantiall filled with a second electrolyte capable of changing p in response to changes in C0₂ concentration.

SUBSTITUTESHEET

20. A method of manufacturing biomedical sensors comprising: placing at least one electrode structure in a noncollapsible hollow tube having an open end which defines an aperture and having a cylindrical outer wall of predetermined circumference; preforming an end cap of elastic material to have an end face portion and a cylindrical sidewall portion extending axially orthogonally to said end face portion, said end face portion being preformed to define a circumference which when unstressed and in ambient atmosphere is smaller than the predetermined circumference of said tube, and said end face portion being preformed to include a selectively permeable membrane; placing said preformed end cap in an environment which causes said elastic material to expand and allowing said end cap to expand to an expanded state in which the circumference of said end face portion is larger than the circumference of said tube; while in said expanded state, placing said end cap over the open end of said tube so that said membrane overlies said aperture; removing said end cap from said environment and allowing said end cap to shrink to a state in which the cylindrical sidewall portion contacts and conforms to the cylindrical outer wall of said tube thereby tending to hold said membrane in place over said aperture.

SUBSTITUTESHEET

21. A medical diagnostic instrument comprising: a tube adapted for insertion into a hollow organ having at least one lumen for extraction of fluids from the body; said tube having a channel extending generally parallel to said lumen and having a window communicating with said channel; a probe for sensing a condition of the hollow organ adapted for slidable insertion into and removal from said channel, said probe providing an electromagnetic signal indicative of the sensed condition of the hollow organ; whereby said probe is readily removable from said tube to facilitate probe calibration.

22. The instrument of claim 21 wherein said widow is provided with a permeable membrane covering.

23. The instrument of claim 22 wherein said covering is selectively permeable.

24. The instrument of claim 22 wherein said covering is selectively permeable to C0₂.

25. The instrument of claim 20 wherein said probe is adapted for sensing pC0₂.

26. The instrument of claim 20 wherein said tube and probe are elongated and said probe is provided with a stop means to restrict the extent to which said probe slides into said channel.

SUBSTITUTE SHEET