WO2004059286A2

WO2004059286A2 - Miniature electrode for detecting interstitial tissue ph

Info

Publication number: WO2004059286A2
Application number: PCT/US2003/040774
Authority: WO
Inventors: Thomas Hacker; Mark Takagi; Bill Miller; Michael Ross; Percy Jerry Cox; Jack Morris
Original assignee: Terumo Cardiovascular Systems Corporation
Priority date: 2002-12-20
Filing date: 2003-12-19
Publication date: 2004-07-15
Also published as: AU2003302258A8; WO2004059286A3; AU2003302258A1

Abstract

Miniature pH electrodes are provided that simultaneously measure pH and temperature to a high degree of sensitivity, demonstrate low pH drift, are quickly and easily equilibrated, and can be stored and sterilized in a hydrated state. The electrodes function even when fully immersed in an electrically conductive fluid such as blood without loss of accuracy or sensitivity. The electrodes can be inserted in the wall of the heart to a predetermined depth to monitor interstitial tissue pH during surgery.

Description

Miniature Electrode for Detecting Interstitial Tissue pH

Background

[0001] In the early 1900's, the principle of glass membranes for electrical-chemical determination of hydrogen ion concentration was recognized. The first commercially available glass membrane pH (pundus Hydrogenii) electrodes were developed in the 1920's. But not until the 1950's were pH measurements recognized as important diagnostic information in the medical arena.

[0002] The principle that two different pH solutions separated by a glass membrane exhibits a potential difference, or measured voltage, across that glass was the basis of all early electrical chemical pH sensors. This relationship between the pH of the known (half-cell) and unknown (to be measured) solutions can be described by the modified Nernst Equation, where the pH of the known and unknown values are the same when the potential is zero and a pH potential of 61.5 mV (millivolts) will be developed for every pH difference between the solutions at 37°C.

[0003] Based on these theories many manufacturers over the years have created pH electrodes of many shapes and sizes, based on different electro-chemical materials, buffer types, and methods depending on the required product needs. Some had internal combination reference cells and others, separate reference cells. Most applications were for chemical analysis of fluids.

[0004] Over the course of the past 20 years there has developed within the medical community interest in measuring pH within tissue. Shukri F. Khuri, MD demonstrated the importance of monitoring and controlling the pH of the myocardium during bypass surgery. See Shukri F. Khuri, MD "Myocardial Preservation During Coronary Artery Bypass Surgery" Cardiac Surgery: State of the Art reviews -Vol. 1 , No. 1 , October 1986. Watson and colleagues showed in a regional ischemic model that during coronary occlusion, a greater reduction in tissue pH occurred in the subendocardial layer than in the subepicardial layer. See WATSON et al. "Transmural pH gradient in canine myocardial ischemia," Am J Physiol 1984; 246: H232-/H238. However, the measurement of pH within tissue, particularly tissue within a living organism, presents many challenges that do not adapt well to conventional equipment and technology for the measurement of pH.

[0005] Physical size and shape of the electrode is of greatest concern. The pH-sensing probe must have a pointed, non-fracturing glass tip capable of piercing and passing into tissue. The electrode tip must be small to minimize trauma to the tissue. The electrode must also be constructed to have a specific length for proper penetration, yet not so long as to puncture through the opposite side of the layer of tissue being monitored. The electrode must remain where positioned, and the electrical connection must conveniently route away from the operating area yet still be able to function, totally immersed in blood or saline. Being a medical device for use on humans it must be capable of being sterilized, and ready from immediate use after removal from the packaging and still perform to strict standards of precision and accuracy.

[0006] Miniature or micro pH sensing probes are commercially available. For example, Microelectrodes, Inc. (Bedford, NH; www.microelectrodes.com) produces a series of small glass pH electrodes, some stand-alone half-cells (requires a separate reference electrode), and even miniature combination probes (a reference electrode is housed in the same probe body). Although the sensing glass tips of the sensors are very small and require minimal amount of contact area to function, some of which are actually embedded into needle tips for protection, they are unable to meet many of the tissue use requirements. The body portion of the probes, where the cable to sensor wire are terminated, is large in diameter and long; the cable and body exits the probe tip on the same vertical axis. Thus, if used as a tissue probe, these devices would be an obstacle for a surgeon to work around and he/she would be unable to suture it into a stationary position.

[0007] These probes are also designed such that only the tip of the probe, not the body or cable, touches the medium to be measured. Variations in temperature will affect the accuracy of pH measurements with glass electrodes and must be compensated for by either controlling the medium to be measured or measuring the medium and compensating for temperature gradients, deviations, or fluctuations through mathematical algorithms. The above devices have no temperature sensor and therefore must rely on a separate temperature-measuring device to obtain the required accuracy. Moreover, these electrodes are incapable of withstanding the effects of sterilization. [0008] Thermo Orion (Beverly, MA, formerly Orion Research, Inc; www.thermo.com) also makes pH sensors, including miniature or micro sensing probes. These are in-line probes, and despite their small size, they retain several significant shortcomings. For example, only the tips of the probes can be immersed; they have no means for temperature measurement; they are obtrusive for the surgeon; and are not suitable for sterilization.

[0009] Orion had also created miniature sensors purportedly for the measurement of pH within muscle tissue. As with the foregoing products, this sensor was linear in construction, and had no apparent means for monitoring or correcting for temperature. The sensor was supplied with a separate calibration buffer solution indicating that it was stored dry and required sterilization by the manufacturer or perhaps the user. It was necessary for the end user to hydrate the sensor, which resulted in a substantial delay (i.e., up to 17 hours) before the sensor could be employed to monitor pH.

[0010] Kent Scientific Corporation (Torrington, CT; www.kentscientific.com) also manufactures and sells miniature and sub-miniature pH electrodes. Some with internal reference schemes, some protected with needle tips, and one purportedly suitable for measuring muscle tissue pH (myocardial). Those sensors are promoted for use in animal research, and do not appear to be capable of withstanding the rigors of sterilization. As with the products discussed above, these sensors are in-line construction where only the tips are to be immersed, and they have no means for temperature measurement. Moreover, the construction of these sensors render them difficult, if not impossible to suture into place.

[0011] In the 1980's, Vascular Technologies Inc. (VTI, North Chelmsford, MA) promoted a pH electrode (the Khuri Regional Tissue pH Monitor) intended for measuring myocardial tissue in humans during open-heart surgery. These pH probes were constructed such that the tip and body/wire termination sections were divided by a flexible bend. This had the effect of controlling the insertion depth, and enabled the surgeon to suture the probe in place; however, the flexibility of the device made insertion and manipulation somewhat awkward. The flexible bend also directed the cable away from the area in which the surgeon was working.

[0012] The VTI sensor had a temperature-sensing device inside the internal buffer chamber in the glass to measure tissue temperature for compensation calculations. The probe used a separate external reference electrode to be embedded elsewhere on the body. The probe was unsterilized, and pouch packaged dry, accompanied by packaged bottled calibration buffers. With this probe, the end user is left to sterilize the pH probes (with ethylene oxide), and the reference electrode and calibration buffers (likely with steam) prior to use; and then hydrate the probes in the sterile calibration solution in a sterile arena prior to calibration; and then calibrate the sensor using the two sterilized calibration buffers.

[0013] The VTI probe had many shortcomings. The probe was packaged and shipped dry, thus requiring hydration by the end-user. One of skill in the art would have appreciated that dry probes would require a 12 to 24 hour hydration time to achieve drift-free readings.

[0014] Tissue pH sensors must also be capable of withstanding complete submersion in blood, saline, or other fluids. Sensors incapable of withstanding those conditions are unreliable, and therefore unsuitable for use during cardiac operations. The VTI probes were incapable of withstanding those conditions, often suffering aberrant readings or complete failure.

[0015] The defective design and construction of the VTI probes caused at least two problems. For one, embedding the temperature element in the corrosive internal buffer jeopardized electrical isolation. Secondly, the material selected and the construction of the wire termination section do not tolerate the harsh environment, nor do they achieve or maintain electrical isolation.

[0016] When properly hydrated, the VTI probes would occasionally function properly, but then fail shortly after immersion in a fluid. Still others would be non-functional right from the package. Often those units had lost internal buffer from inside the pH sensitive glass chamber. This is further evidence of improper adhesive selection or placement, and/or otherwise poor design or construction. Furthermore, the probes were stored dry, sterilized dry, and hydrated immediately before use. Thus, those probes were not constructed to withstand the rigors of sterilization and long-term storage in buffer.

[0017] The use of glass membranes in pH detection systems is a mature technology. Nonetheless, glass membrane technology has certain inherent limitations. Others working in the field have attempted to overcome those limitations by resort to alternative materials or methods to eliminate or ameliorate those limitations. [0018] U.S. Patent No. 4,816,131 to Bomsztyk uses the electrochemical principle and glass stems in the form of either dual or triple tubes, but replaces the glass membrane for ion transfer at the end of the tube with a polymeric membrane(s) plug. Although it permits a smaller sensor requiring less contact, it fails to address the tissue puncture, sterilization, and use functionality.

[0019] U.S. Patent No. 4,908,115 to Morita et al., describes a bonded bundle of carbon fiber potted together, an etching process at the distal end of the probe to create micro-holes, then adding an internal buffer gel into the micro-holes and capping the gel with an ion permeable membrane. This addresses only the functionality at the tip.

[0020] U.S. Patent No. 5,158,083 to Sacristan does not replace the glass technology but attempts to downsize it and create a flexible probe or delivery system. This results in a probe much like the above-mentioned "Microelectrodes, Inc" probe in a flexible tube for delivery. Although this reference fails to describe sterilization, the apparent intended application would require doing so. Furthermore, this approach does not address problems associated with tissue puncture. The use of a flexible shaft in this probe suggests that it does not resolve that problem.

[0021] Workers in the field have also turned to optical fiber technology to address some of the limitations described above. See U.S. Patent Nos. 4,200,110 to Peterson et al; 4,798,738 to Yafuso et al; 5,118,405 to Kaneko et al; 5,656.241 to Seifert; 5,813,403 to Soller et al; and 5,900,215 to Seifert. Fiber optics are small and do not require a separate reference sensor. However, this technology fails to resolve the difficulties presented by the requirements of tissue pH monitoring, particularly as implemented during surgery, i.e., tissue puncture, sterilization, cable management, sensor capture, etc.

[0022] There remains a need in the art for miniature electrochemical probes for measuring interstitial pH within mammalian tissue in vivo. Ideally, such probes will be sufficiently durable as to undergo a sterilization process, and are constructed such that they can be manufactured, sterilized, shipped, and stored in a hydrated state. The probes will thus avoid the need for the end user to both sterilize and hydrate the product immediately prior to use. Further, such probes will be capable of simultaneously measuring both pH and temperature, and will be constructed such that the probe is hermetically sealed and suitable for use in environments likely to result in immersion of the probe in fluid. The probe must also be constructed of suitable materials that it will not structurally fail, yet the materials and components will nonetheless operate reliably and accurately consistent with their intended purpose.

Summary of the Invention

[0023] The present invention provides a miniature electrochemical sensor or probe capable of measuring and monitoring interstitial pH and temperature of mammalian tissue in vivo. The probe is of the type comprising a sensing area of ion permeable glass. The probe is constructed such that it can be easily and efficiently inserted into the tissue of the myocardium without fracture, and without protruding from the opposite side of the myocardium. Thus, the probe can be easily and rapidly inserted into the myocardium by the end user with a high degree of confidence that the probe is intact and properly positioned within the myocardium to take the desired readings. Further the probe is constructed such that is readily secured in the appropriate position by one or more sutures.

[0024] While the present invention is described in terms of measurement of myocardial pH, it will understood by those skilled in the art that the probes of the present invention can readily be modified for the measurement of pH (and temperature) in other tissues in a living organism.

[0025] The probe is efficiently and thoroughly sealed from the environment by various hermetic seals, and is electrically shielded such that the probe can be used in the presence of fluids, including conductive fluids, such as water, saline, and blood.

[0026] The probe has an internal temperature sensor, so that fluctuations in temperature within the tissue being monitored can be assessed, and pH measurements can be adjusted accordingly.

[0027] The probe is also constructed such that the probe can be securely sutured into place, and the requisite electrical cables are conveniently diverted away from the surgical field and otherwise confined in a manageable bundle as by resort to a zip cord or the like. The body overmold of the probe (Fig 6) is configured such that it has one or more means for anchoring the probe in place in or on the tissue being monitored. In a preferred embodiment, the anchoring means comprise notches or recessed areas in the body overmold to accept a suture or other anchoring device. The recessed areas are preferably concentric with the body overmold. The probe might comprise alternative anchoring means such as wings, arms, cleats, or other extensions protruding from the body overmold; or it might comprise eyelets through which the suture can be passed.

[0028] The probe of the instant invention is further constructed such that it can be sterilized, as by gamma sterilization, and subsequently stored without requiring significant time for hydration and equilibration, and without impairing the performance of the probe. Preferably, the probes are stored such that the pH glass of the electrochemical half-cell subassembly is immersed in a gamma sterilizable buffer. In one embodiment, the probe is plugged into a cuvette containing the buffer such that the half-cell subassembly is immersed in the buffer. In this manner, the probe requires no hydration time; and the probe, cuvette, and buffer can all be sterilized, as by gamma radiation, and subsequently packaged, shipped, and stored in a sterile state. Buffers suitable for gamma sterilization are disclosed in contemporaneously filed U.S. Application No. , entitled "Gamma Sterilizable Buffer Solutions", which is incorporated herein by reference.

[0029] Similarly, a system for monitoring and calculating an integrated, or time averaged, pH value within tissue is described in contemporaneously filed U.S. Application No. , entitled " System For Monitoring And Calculating Integrated Tissue pH", which is incorporated herein by reference.

[0030] One embodiment of the probe of the instant invention comprises an electrochemical half-cell subassembly within a hollow tubular casing of ion permeable pH glass, said casing having at least one conical tip terminating with a beaded or ball radius tip. The ball radius tip imparts a fracture-resistance to the subassembly that permits the probe to puncture the tissue without structural failure.

[0031] The ball radius tip is flame formed on the sharp glass drawn down tip to prevent vertical axis stress cracks. The ball varies from about 0.006" R to about 0.013" R. Anything less might mean that the radius was not created at all; and any ball tip greater than about 0.013" makes insertion into tissue difficult.

[0032] The probe is of particularly small size and thus presents a small surface area for sensing pH. The pH glass is of a particularly low impedence, i.e., less than one giga-ohm, and preferably less than about 300 mega-ohms. [0033] Interior to the subassembly is a sensor wire and internal buffer. Appropriate sensor wires for detecting and monitoring pH are known in the art. Preferred sensor wire is a silver/silver chloride wire. Likewise, suitable internal buffers for pH sensing probes are known in the art. A preferred internal buffer is 3.0 Molar potassium chloride.

[0034] The pH glass casing is bonded or welded to a stem glass casing. The stem glass of the casing has a similar coefficient of expansion relative to the ion permeable glass such that the two can be welded without cracking during the cooling process. The stem glass casing forms a mating body for the half-cell subassembly that is of a similar shape and size. In preferred embodiments, the mating body is slightly larger in diameter than the half-cell subassembly. Preferably, there is a sloped or rounded transition from the pH glass to the stem glass casing. The sloped or rounded transition eliminates a sharp or angular step between the pH glass and the stem glass that can impede insertion of the probe into the tissue. In contrast, the smooth rounded contours of the probe of the instant invention facilitate insertion of the probe into the tissue, and further reduce the likelihood of a fracture developing in the glass probe.

[0035] The stem glass mating body houses an electrochemical junction (ec-junction) assembly, which in turn houses a temperature sensor, and affords electrical isolation from the environment. Within the mating body, the temperature-sensing device is isolated from the internal buffer solution.

[0036] Preferred embodiments further comprise highly electrical insulating adhesive bonding the temperature sensor in place, and such that the temperature sensor is electrically isolated from the internal buffer solution and the environment. By highly electrical insulating adhesive (also referred to herein as a non-conducting adhesive) is meant an adhesive having a volume resistance of at least about 10¹³ ohm-cm. Preferably, the adhesive possesses resistance of at least about 210 giga-ohms (210 x 10⁹ Ω) after 100% humidity storage for 1 week at 40°C. Alternatively, the highly insulating adhesive can be characterized in terms of dielectric strength. Preferably, the dielectric strength of the adhesive is at least about 400volts/mil in the fully cured state even after exposure to moisture.

[0037] The half-cell subassembly/ec-junction are electrically connected to a processing unit or monitor that converts the data from the probes into meaningful pH readings, and displays and/or records that information for the user. The processing unit is capable of calculating pH corrected for fluctuations in temperature within the tissue being monitored.

[0038] The probe is constructed such that there is a rigid right angle (90°) bend between the glass probe portion and the electrical connections leading to the processing unit to further facilitate insertion of the probe into the tissue of interest.

Brief Description of the Drawings

[0039] Figure 1 is a side view of the electrochemical half-cell subassembly.

[0040] Figure 2 is a cross sectional view of the miniature electrode for measuring tissue pH showing the half cell subassembly, the EC junction, the temperature sensor, the sensor wire, and adhesive.

[0041] Figure 3 illustrates the cable pod sensor, revealing the sensor wire, insulation triple coating inner shield, outer shield, temperature wire(s), and insulation.

[0042] Figure 4 illustrates a three-way zip cord with leads for the reference pod, the sensor number 1 pod, and the sensor number 2 pod.

[0043] Figure 5 includes a side view and a top view of the probe prior to application of the body overmold.

[0044] Figure 6 is a side view of a finished probe including a body overmold.

Detailed Description of the Invention

[0045] The probes of the present invention afford means for simultaneously measuring interstitial pH and temperature in tissue of a living organism. The probes are particularly useful for monitoring and measuring integrated pH during surgery, particularly cardiac surgery, although the dimensions of the probe can be modified to measure temperature/pH in virtually any type of tissue. By integrated pH is meant the average pH over time. The measurement of temperature is meant primarily to afford a means for correcting pH measurements as a result of variation in temperature.

[0046] The probes of the present invention are small with a radius puncture tip formed in pH membrane glass. The puncture tip comprises a small bead of the pH membrane glass. The puncture tip is constructed during the fabrication of the pH membrane onto the stem. In a preferred method, the end of the pH membrane is pulled off to a thin glass thread and broken off. If left unattended, this fracture surface is likely to propagate into a crack in the pH membrane as stress is applied during insertion into the tissue. To minimize this tendency to fracture, the thin threaded end of the pH glass is heated (fire polished) causing the glass thread to roll into a small ball (about 0.010 to about 0.030 inches diameter, preferably about 0.020 to about 0.024 inches in diameter, and still more preferably about 0.022 inches in diameter) at the tip of the pH membrane. This process produces residual stress annealing to further strengthen the puncture tip of the pH probe.

[0047] The membrane sensing probe tip is 1.5 mm and bonded into a plastic shank of 2.4 mm. The wires are terminated and sealed inside a molded body section. The molded body section is configured such that it is at about a right angle to the probe tip. Preferably, the molded body section is at about a 95° angle.

[0048] The probes (2) are preferably stored in one of two calibration buffers as part of a calibration cuvette along with a capped reference electrode. The two probes and reference electrode are connected to a single connector via a 3-pod zip cord. The whole assembly, i.e., sensors, cuvette cord, and connector are in a double pouch and radiation sterilized.

[0049] The precise size and shape of the sensor probe is dictated by the functional requirements of the particular application. Generally, the product must be small; have a durable, fracture proof tip; and enable the user to insert the probe to a depth of about 10 mm to 15.5 mm.

[0050] The insertion diameter should be under about 2.5 mm, and the wire termination body should be a minimum size so as to be not obtrusive. Specifically, the wire termination body should be less than 0.2" (5.1mm) in diameter and 0.75" (20mm) in length.

[0051] Preferably, the electrical wires for conveying data from the probe to a central processing unit and data readout device are directed off at an angle such that the wires are directed away from the surgical field during use. The cable end and sensors are constructed such that they can be fully submerged in fluid, such as saline or blood, yet retain all functional characteristics. [0052] The sensor assembly contains two sensing probes and a common reference sensor that must remain intact and functional when customary forces are applied to the cable and sensor sections, and the glass must not break under normal insertion and removal of the product from the calibration cuvette and tissue. The cable must be long enough, a minimum of 1.5 meters, to remove the sensor cable connector out of the sterile area into the non- sterile area.

[0053] In a preferred embodiment, the probe of the present invention is a sterile, single-use device. As such, the present invention affords a means whereby the user can remove a probe from the pouch, set it up for calibration, and calibrate it in less than 10 minutes. Preferably, the system will require a steady state for optimum calibration accuracy. Thus, for calibration purposes, the system might require a stability reading such that there is a change of less than about 0.01 pH units in 25 seconds; preferably less than about 0.005 pH units in 25 seconds; and most preferably about 0.0022 pH units or less in 25 seconds.

There is no need for hydrating the probe. The probes of the present invention can be packaged, sterilized, stored, and shipped all while the ion permeable pH glass of the electrode is immersed in a gamma sterilizable buffer as disclosed in contemporaneously filed U.S. Application No. , entitled "Gamma Sterilized Buffer Solutions For pH

Measurement."

[0054] The probes of the present invention are capable of meeting at least the following performance specifications:

Normal Operating Range 5.5 to 8.0 pH units

pH Accuracy ± 0.05 @25°C

95% pH Response Time 30 seconds @25°C

Operating Temperature Range 10° to 40°C

95% Temperature Accuracy ± 1.0°C

95% Temperature Response Time Less than 30 seconds

9 hr. Drift ± .10 @25°C Displayed values corrected to 37°C

HALF- CELL ELECTRODE SUBASSEMBLY

[0055] The half-cell electrode subassembly is a glass pH electrode composed of a thin, H⁺- ion responsive glass membrane sealed to a stem of high-resistance, non-responsive glass; and an internal reference electrode.

[0056] A preferred embodiment of the glass electrode of the present invention is schematically illustrated in FIGURE 1. The glass electrode is constructed of two glasses, a stem glass tube and a pH membrane glass. The stem glass tube is primarily to provide a structure to attach the pH sensitive glass, and secondly provides a surface in which to attach the half-cell electrode subassembly to the final sensor assembly. In a preferred embodiment, the stem glass is a sodium glass tube with an outside diameter of approximately 0.030 to about 0.070 inches, and preferably about 0.055 inches.

[0057] Due to the conditions under which the probes of the instant invention are used, and in view of the very small sensing area, the pH glass is a very low impedence material. The low impedance material of the present invention affords a very fast response time, and allows the use of the probe at very low temperatures.

[0058] In a preferred embodiment, the pH membrane glass is a lithium glass with oxide additives to reduce the impedance of the pH membrane to 30-300 megohm. The pH glass is blown out to a sensing area of between about 0.240 (6.1 mm) and about 0.160 inches (4.0 mm).

[0059] Typically, the internal electrode of a glass electrode is chosen from Ag/AgCI or Hg/Hg₂CI₂. In a preferred embodiment, a Ag/AgCI sensing wire is placed inside the glass tube assembly, the glass tube is filled with 3.0 M KCI internal buffer, sealed with a silicone bung, and backfilled with a non-conducting adhesive to provide the first of many hermetic seals. Preferred examples of non-conducting adhesives are bisphenol-A type epoxies, described more fully below.

[0060] The internal fill solution of the pH half-cell is matched with the internal fill solution of the reference electrode. The result of this combination yields accurate pH measurements regardless of the temperature of the reference electrode. Typical pH measurements are made with both reference electrode and pH electrode at the same temperature. If the two electrodes are not at the same temperature inaccuracies result. The probes of the present invention are thus configured and constructed such that the accuracy of the pH measurements is enhanced.

ELECTROCHEMICAL JUNCTION

[0061] The probe of the instant invention includes a novel electrochemical junction (ec- junction) component that affords numerous advantages, FIGURE 2. It captures and holds the temperature sensor in place, it creates a mating body in which to attach the glass half-cell assembly, it provides a link to the wire termination body, it provides electrical isolation from the environment, and it contributes to the structural shape and integrity of the assembly.

[0062] The temperature sensor is bonded in place with highly electrical insulating adhesive into a molded pocket in the ec-junction at a location directly above the top of the glass sensor sub assembly and below the right angle bend. The ec-junction is designed to route the temperature wires (2) away from the sensor wire for additional internal electrical isolation. The bonding provides a thermal link to the ec-junction that is in direct contact with the tissue. This is important to provide temperature compensation data to the monitor so that the pH accuracy values can be maintained over a range of temperatures. Other devices positioned the temperature sensor inside the corrosive glass internal buffer chamber. The probe of this invention, however, is constructed such that the temperature sensor is above and isolated from the buffer thereby placing it in a better thermoconducting and environmental resistant location. A temperature gradient model and testing indicates that this configuration provides fast, accurate measured values within the required specifications.

[0063] The Half-cell electrode subassembly stem glass is bonded into the ec-junction with highly electrical insulating moisture-resistant adhesive. A fillet of adhesive is provided at the transition area between the glass and plastic to provide to minimize puncture resistance during insertion. The sensor wire is also potted into the ec-junction with only the attachment point exiting the part for further assembly. In a preferred embodiment the non-conducting adhesive is an epoxy. A preferred epoxy is a modified bisphenol-A epoxy resin with a polyamide curing agent. Preferably, the non-conducting adhesive has a volume resistance greater than 10¹³ ohm-cm. [0064] Preferred embodiments incorporate two separate epoxies in the construction of the probe. The construction methodologies dictated the application of each. Bonding the glass cells to the ec-junction can be performed in batches and allowed to cure over time at room temperature.

[0065] The wire sealing required application and set after each part. The epoxy that contacts the patient and bonds the glass to the ec-junction was Loctite® M31CL, a two- part non-conducting medical-grade room temperature cure epoxy. The epoxy that seals and coats the wire terminations is Permabond® Lite-Lok 4001, a single part non-conducting UV activated medical grade epoxy.

[0066] Both epoxies are Class VI medical grade materials, both must provide electrical resistance over 210 giga-ohms (210 x 10⁹ Ω), even after extended exposure to moisture and have a high yield strength/and or elongation percent to bend no crack under load, but remain solid and can be cured at low temperature so as to not harm the sensor cell.

[0067] Companies such as 3M, Bacon, Bondline, Devcon, Dymax, Emerson & Cumings, Electrolite, Epoxy Technology, Loctite, Lord, Masterbond, and Permabond make an assortment of adhesives based on acrylics, urethanes, silicones, cyanoacrylics, and epoxies. Epoxies are preferred, particularly those that are resistant to the absorption of moisture and the concomitant loss of insulating properties.

[0068] Epoxy Technology, Loctite, Masterbond, and Permabond make medical grade epoxies. Epoxy Technologies' 301 and 302 series, Masterbond's EP21LV and EP42HT, and Permabond's 4E90 and 4E93 are room temperature-cure epoxies that are possible alternatives for Loctite M31CL. Permabond's Light-Lok 4001 is a medical grade UV curable epoxy suitable for use in the probes of the present invention.

SENSOR CABLE

[0069] In one embodiment, the system has cable(s) that connect the single common reference and the two sensor probes to the monitor. Preferably, the cables are coaxial cables bundled into a convenient, small, flexible cluster that can be separated as necessary. Each sensor (FIGURE 3) cable pod contains a triaxial cable signal wire, a triboelectric coating, insulation, internal shield, isolation wrap, two temperature wires each having their own insulation, an outer ground shield, and a soft, flexible medical-grade plastic jacket of a biocompatible material.

[0070] In a preferred embodiment, the system incorporates a 3 pod zip type cable (FIGURE 4) to enable the user to insert each of the three legs into its respective destination. As such, the assembly behaves as only one cable, but the cable can be unzipped to any appropriate length such that the individual cables are separated and directed to different destinations as required.

[0071] The cable is small and flexible so that it is easily manipulated and oriented by the user without the need for additional anchoring means. Thus, for example, the cable will not inadvertently invade the sterile field during surgery. The diameter of the cable is less than about 0.1 inches, and preferably less than 0.08 inches. Because the cables must be flexible, preferred cables connecting to each of the pH probes have a triboelectric coating to reduce any electronic noise that might be caused by movement of the cable.

[0072] The cables also possess an electronic shield layer over the pH probe connection that will completely enclose the inner connection and protect it from outside electronic interference. This shield will be an active, driven shield that will reduce the electronic load on the center pH connection. Outside of this inner shield are electrical connectors for the temperature monitoring device, e.g., two wires for connecting to a thermistor. Those connectors are preferably small gauge wires (about 30-38 AWG), and very flexible. The outermost layer comprises another electronic shield. That shield is the main layer of protection from electronic interference. The shield is connected to the system ground.

[0073] The full cable assembly preferably comprises at least three cables reversibly bundled together. Preferably, the cables are bundled or connected by a thin rib element. The thin rib element might comprise the same polymeric coating used on the exterior of the individual cables. The thin rib element is fabricated such that the individual cables can be readily separated as by tearing the rib element to any desired length. Thus, the end-user will be able to easily separate the two pH probes and the reference electrode to an appropriate distance to facilitate surgery.

[0074] The full cable assembly comprises at least two of the triboelectric coated, shielded cables described above attached together by a thin rib element between them. A third cable is similarly attached to the assembly. The third cable comprises a single flexible wire that can be attached to the reference electrode. This wire need not be shielded. Preferably, the individual cables within the assembly are distinguished in some visually apparent manner. For example, the center cable for the pH probe connection might be visibly distinguished with a dark stripe on a white background for identification purposes.

[0075] In preferred embodiments, the finished wire assembly is very flexible, does not hold a shape, and is fabricated from approved biocompatible materials. Still more preferred embodiments are constructed such that the wire assembly can be subjected to sterilizing doses of gamma radiation (i.e., about 15-40 kGy) without any substantial loss of performance or malfunction.

PROBE SUBASSEMBLY AND OVERMOLD

[0076] Connecting the ec-junction/half-cell subassembly to the cable is done in the body portion of the device, which is set off at about a right angle from the insertion shank. The wires within the cable pod are stripped to very specific lengths as are the sensor wire and temperature wires exiting the ec-junction subassembly. This staggering of wires and very short wire stripped ends assures that the solder points of the three terminations are not side by side to guarantee isolation. An "L" shaped leg molded as a part of the ec-junction aids in wire termination location and separation of signal wire from temperature wires. The inner shield is terminated very close to the signal wire, which is the longest of the three wires. This forces shielding to the very farthest possible point in the product.

[0077] The termination area is coated with a sealing, highly electrical insulating adhesive FIGURE 5. At this point the probe is electrically sealed.

[0078] To provide mechanical support, and secondary isolation, a plastic over-molded body is applied to the probe assembly, (FIGURE 6) Included in the molded body are means for anchoring the probe on or about the tissue of interest. These anchoring means can include wings, arms, cleats, eyelets, recessed areas, and the like. Preferably, the body overmold comprises recessed areas that accommodate sutures as the anchoring means. In one embodiment, the recessed areas are rings formed around the exterior of the body overmold and concentric with the cable pod. (FIGURE 6)

Claims

What is claimed is:

1. A pH electrode comprising: a. a membrane comprising a tubular section having a closed distal end and an open proximal end, and a body overmold capping the proximal end; b. said tubular section having a maximal outer diameter of about 0.030 inches to about 0.070 inches, an ion sensitive glass portion of about 0.240 to about 0.160 inches, and a high-resistance non-responsive glass portion; c. interior to said tubular section is a half-cell subassembly with an internal buffer solution, and a temperature sensor isolated from said buffer solution; and d. said electrode configured to penetrate mammalian tissue to a predetermined depth.

2. The electrode of claim 1 , wherein the ion sensitive glass has an impedance of about 30-300 megohms.

3. The electrode of claim 1 , wherein the pH accuracy is ± 0.05 or less at 25°C within an operating range of 5.5 to 8.0 pH units.

4. The electrode of claim 1 , wherein the electrode has a 9 hour drift of ± 0.10 or less at 25°C within an operating range of 5.5 to 8.0 pH units.

5. The electrode of claim 1 , wherein the half-cell subassembly and temperature sensor are in electrical communication with an insulated cable through the body overmold, and said body overmold is set off from the tubular section at about a right angle such that it impairs penetration of the electrode beyond a predetermined depth.

6. A pH electrode comprising: a. a membrane comprising a tubular section having a closed distal end and an open proximal end, and a body overmold capping the proximal end; b. said tubular section having a maximum outer diameter of about 0.030 inches to about 0.070 inches, an ion sensitive glass portion of about 0.240 to about 0.160 inches in length drawn down to a beaded tip, said bead having a radius of about 0.006 inches to about 0.013 inches, and a high-resistance non- responsive glass portion; c. interior to said ion sensitive glass portion of said tubular section is a half-cell subassembly with an internal buffer solution, and a temperature sensor isolated from said buffer solution; and d. said electrode configured to penetrate mammalian tissue to a maximum depth of about 10 mm to 15.5 mm.

7. The half-cell electrode of claim 6, having a pH accuracy of ± 0.05 or less at 25°C within an operating range of 5.5 to 8.0 pH units while immersed in a conductive fluid.

8. A pH electrode comprising: a. a membrane comprising a tubular section having a closed distal end and an open proximal end, and a body overmold capping the proximal end; b. said tubular section having a maximum outer diameter of about 0.030 inches to about 0.070 inches, an ion sensitive glass portion of about 0.240 to about 0.160 inches in length drawn down to a beaded tip, said bead having a radius of about 0.006 inches to about 0.013 inches, and a high-resistance non- responsive glass portion; c. interior to said ion sensitive glass portion of said tubular section is a half-cell subassembly with an internal buffer solution, and a temperature sensor isolated from said buffer solution; and d. said ion sensitive glass portion having an impedance of about 30-300 megaohms.

9. The electrode of claim 8, further comprising an electro-chemical junction configured to maintain the temperature sensor in chemical and electrical isolation from the half cell, and comprising an adhesive having a volume resistance greater than 10¹³ ohm-cm.

10. The electrode of claim 8, wherein the adhesive is a modified bisphenol A epoxy resin with a polyamide curing agent.

11. The electrode of claim 9, wherein the body overmold hermetically seals a point of electrical communication between the electro-chemical junction and an external device.

12. A pH electrode comprising: a. a membrane comprising a tubular section having a closed distal end and an open proximal end, and an electrochemical junction and a body overmold capping and hermetically sealing the proximal end; b. said tubular section having a maximum outer diameter of about 0.030 inches to about 0.070 inches, an ion sensitive glass portion of about 0.240 to about 0.160 inches in length drawn down to a beaded tip, said bead having a radius of about 0.006 inches to about 0.013 inches, and a high-resistance non- responsive glass portion; c. interior to said ion sensitive glass portion of said tubular section is a half-cell subassembly with an internal buffer solution, and a temperature sensor isolated from said buffer solution; and d. said electrochemical junction maintaining electrical isolation of the half cell subassembly and the temperature sensor and maintaining the temperature sensor within a molded pocket in the tubular section.

13. The electrode of claim 12, wherein the electrochemical junction comprises a sleeve covering a portion of the proximal end of the tubular section and wherein said sleeve and said tubular section are irreversibly bonded together with an adhesive having electrical resistance of at least 210 giga-ohms.

14. The electrode of claim 12, wherein the pH accuracy is ± 0.05 or less at 25°C within an operating range of 5.5 to 8.0 pH units.

15. The electrode of claim 12, wherein the ion sensitive glass has an impedance of about 30-300 megohms.