Membrane seals for physiological sensors

Abstract

The invention relates to a physiological sensor for measuring carbon dioxide and a method for fixing a carbon dioxide permeable membrane of the physiological sensor. The physiological sensor comprises: a closed chamber containing a sensor liquid and at least partially bounded by a carbon dioxide permeable membrane (12); at least two electrodes (10) arranged in the chamber in contact with the sensor liquid; a support structure (23) for supporting the membrane (12); and at least one filament (28) wound around the support structure (23) and on top of the membrane (12) for fixing the gas permeable membrane (12) to the support structure (23).

Description

[0001] The present invention relates to techniques for sealing membranes on physiological sensors, and in particular wherein the physiological sensors are used for measuring the partial pressure of carbon dioxide (pCO2) in vivo or ex vivo.

[0002] Ischemia is the medical term for insufficient blood supply to an organ. If severe, it may lead to death of the affected tissue (infarction). A sensor may be provided to measure tissue pCO2, a parameter that increases significantly during the early and reversible stages of ischemia. Such a sensor preferably provides the ability to identify the onset of an ischemic event through real-time data.

[0003] Ischemia is the most common cause of death in the Western world. Thus, for example, myocardial infarction, cerebral infarction and other diseases characterized by insufficient perfusion to one or more organs are major factors in mortality.

[0004] If ischemia is detected in time, reperfusion (reversal of ischemia) is usually possible. Therefore, early detection of ischemia, followed by appropriate chemotherapy (e.g., with agents such as streptokinase, urokinase or t-PA for dissolving thrombi or emboli) or surgical intervention can save the affected organs as well as the patient's life.

[0005] Although the heart can be continuously monitored for ischemia using an electrocardiograph (ECG), other organs may become severely ischemic and cause irreversible damage before any symptoms are detected. In fact, many organs are "silent" when ischemia occurs. The phenomenon of silent myocardial infarction is now well recognized. In addition, the liver and kidneys may become severely ischemic without warning symptoms before organ damage is irreversible.

[0006] It is known that there is a clear correlation between pCO2 in or on the surface of an organ and the presence of ischemia in that organ. During tissue metabolic acidosis, such as during anaerobic metabolism that occurs when ischemia occurs in any organ or tissue, large amounts of carbon dioxide are formed. In fact, CO2 is freely permeable to cell membranes, and since blood flow to transport CO2 away in ischemia is absent or limited, CO2 accumulation in ischemic tissue will occur and pCO2 in or on ischemic tissue will increase.

[0007] Typically, in a healthy body, the maximum pCO2 in the blood (venous blood) is 6 kPa to 7 kPa, and the maximum pCO2 in healthy (aerobic) tissues is approximately 1 kPa to 3 kPa higher, although the maximum values ​​may vary from organ to organ, for example 8 kPa to 10 kPa for the kidney, 7 kPa to 10 kPa for the liver, and 8 kPa to 12 kPa for the intestine. When the oxygen supply is below the critical oxygen delivery level, the pCO2 values ​​measured in the tissues may rise 3-fold to 10-fold, and the elevated pCO2 levels give a clear indication of anaerobic metabolism and, if appropriate, therefore, of ischemia.

[0008] A sensor particularly suitable for pCO2 measurement is described in WO 2006 / 08505. The sensor comprises a substantially cylindrical plastic support surrounded by a membrane at least partially permeable to carbon dioxide. The support has a conical tip at its distal end and a main body extending from the tip to the proximal end. Two gold electrodes extending longitudinally along opposite sides of the main body are mounted on the main body. Two truncated conical protrusions are provided at the proximal and distal ends of the main body for fixing the membrane by friction fit, optionally supplemented by crimped connections. Thus, the sensor defines a closed chamber bounded by the membrane and comprising two electrodes. A membrane of a liquid substantially free of electrolytes, such as deionized water, is provided in the chamber in contact with the membrane and the two electrodes, so that the carbon dioxide passing through the membrane increases the concentration of bicarbonate ions in the liquid and thus increases the conductivity of the liquid.

[0009] It has been found that a friction fit does not secure the membrane well enough and that a crimp connection undesirably increases the diameter of the sensor.There is therefore a need for a new sensor that can be used to determine pCO2.

[0010] Viewed from a first aspect, the present invention provides a physiological sensor for measuring carbon dioxide, comprising: a closed chamber containing a sensor liquid and at least partially bounded by a carbon dioxide permeable membrane; at least two electrodes disposed within the chamber in contact with the sensor liquid; a support structure for supporting the membrane; and at least one filament wound around the support structure and on top of the membrane for securing the breathable membrane to the support structure.

[0011] The use of filaments to secure the gas-permeable membrane allows for gentle, even tension to be applied to the membrane at all points around the sensor while still allowing for small imperfections in the support structure or membrane.

[0012] Preferably, at least one filament is wound at least twice around the support structure. The filament applies a radial force at each point where it contacts the membrane, but each winding can be decoupled from the previous winding, meaning that the force is distributed along the length of the winding, but accumulates as a resultant force on the membrane with successive windings. Thus, the filament can create an airtight seal between the membrane and the support.

[0013] The at least one filament is preferably made of a biocompatible and medically approved material. In various exemplary embodiments, the at least one filament may be formed of any one or more of low density polyethylene (LDPE), high density polyethylene (HDPE), ultra high molecular weight polyethylene (UHMWPE), polytetrafluoroethylene (PTFE), ethylene tetrafluoroethylene (ETFE), fluorinated ethylene propylene (FEP), nylon, aramid or stainless steel.

[0014] The filament may be a single filament or a plurality of filaments.

[0015] At least one filament can be fixed to one or more of the following: itself, a support structure and a carbon dioxide permeable membrane. The at least one filament can be fixed by a fixing medium or by welding of the at least one filament. The fixing medium can include one or more of an adhesive, a glue and an epoxy such as a UV curable epoxy. Welding can be achieved by melting or fusing the end of the at least one filament, for example, via heat, via light or via a chemical reaction.

[0016] At least one filament can include a first filament wound around a supporting structure on a first side of a closed chamber, and the first side of the closed chamber can be the proximal side of the closed chamber. Optionally, at least one filament can include a second filament wound around a supporting structure on a second side of a closed chamber, and the second side of the closed chamber can be the distal side of the closed chamber. In this context, the tip of the sensor can be located at the distal end of the sensor. The tip can be configured to be placed in the tissue of an organ in use.

[0017] Two electrodes may optionally extend between the support structure and the membrane beneath one of the filaments.

[0018] In one embodiment, the sensor liquid may comprise a liquid substantially free of electrolytes, such as deionized or distilled water. By substantially free of electrolytes, it is meant that the ion osmolality of the liquid is no greater than that of a 5 mM aqueous sodium chloride solution at 37°C, preferably no greater than that of a 500 μM sodium chloride solution, more particularly no greater than that of a 10-5 M to 10-6 M HCl solution.

[0019] The mechanism by which the sensor is used to determine pCO2 is simple. In a purely protic solvent (such as water), the electrical resistance is high due to the lack of ionic species. The addition of CO2 causes H + Ions and HCO3 - The formation of ions (together with the water) and thus causes a decrease in resistance. Since the only factor causing the decrease in resistance in the sensor is the CO2 passing through the membrane, the change in resistance enables the measurement of pCO2.

[0020] According to H2O+CO2 to H + +HCO3 - The equilibrium constant of the equilibrium, CO2 concentration is equal to αpCO2 (where α is 0.310 at 25°C). The conductivity of the proton is G H+ =349.8S.cm 2 / mol, the conductivity of hydroxide is G OH- =198.3S.cm 2 / mol, and the conductivity of bicarbonate is G HCO3- =44.5S.cm 2 / mol.H + and OH - The concentration of H changes inversely, and + and HCO3 - The concentration of OH- is proportional to pCO2. Since the contribution of OH- is extremely small, the total conductivity of the solution is effectively proportional to pCO2. Therefore, the conductivity of the solution G 溶液 is given by:

[0021] G 溶液 =θ H+[ H + ]G H+ +θ OH- [OH - ]G OH- +θ HCO3- [HCO3 - ]G HCO3-

[0022] where θ H+、 θ OH- and θ HCO3- are the activity coefficients of the three ionic species.

[0023] The following table shows by way of example the measured pCO2 and pH values ​​and the + OH - and HCO3 - The corresponding calculated values ​​of H + and HCO3 - Increases with increasing pCO2.

[0024]

[0025] (pCO2 and pH measured at 37°C using a standard blood gas analyzer AB L(R) System 625).

[0026] The sensor liquid may also contain at least one metal or metal ion or metalloid ion, ie the sensor liquid may be an electrolyte solution. It has been found that adding at least one metal or metalloid ion to the sensor liquid leads to a significant increase in sensitivity to CO2.

[0027] The concentration of metal and / or metalloid ions in the liquid can be 0.01mmolL -1 To 20mmolL -1 , preferably 0.5mmolL -1 To 18mmolL -1 , more preferably 0.1mmolL -1 To 15mmolL -1 , even more preferably 0.25mmolL -1 To 12mmolL -1 , for example 0.5mmolL -1 To 10mmolL -1 within the range.

[0028] Typical metal ions include any transition metal or metal from Group 1, Group 2, Group 13 or Group 14 of the Periodic Table. It should be understood that the term "metalloid" as used herein refers to a chemical element having properties between those of typical metals and non-metals. Example metalloids include boron, silicon and germanium.

[0029] In a preferred embodiment, the metal and metalloid ions are selected from the group consisting of transition metals, Li, Na, Be, Mg, B, Al, Ga, In, Tl, Nh, Si, Ge, Sn, Pb and Fl. A particularly preferred group of metal and metalloid ions is Cr, Mn, Fe, Co, Ni, Cu, Zn, Pd, Ag, Cd, Al, Ga, In and Tl, in particular Al, Ni, Ag, Cu, Co and Pd.

[0030] Preferably, the metal ions include Cu ions. When there is a mixture of metal and / or metalloid ions, a preferred embodiment is a mixture of Cu ions and Al ions. Another preferred mixture is Cu ions, Al ions and Ni ions.

[0031] The metal or metalloid ions can be generated in situ by adding appropriate hydroxides, salts or complexes of the desired metal or metalloid ions. In an alternative embodiment, the metal and / or metalloid ions can be provided as isolated ions (usually in solution) added directly to the liquid. In yet another embodiment, the metal and / or metalloid ions are generated in situ from the metal surface or interface present in the sensor, for example by a chemical reaction or electrochemical reaction involving one or more metals.

[0032] In one embodiment, the sensor liquid may include a nonionic excipient. In this way, the osmolality of the sensor liquid in the chamber can be increased to prevent the sensor liquid from flowing out across the membrane without affecting the electrical properties of the sensor liquid. The excipient should have at least isotonicity, that is, it should be as osmotic as a 0.9% w / v NaCl aqueous solution. Therefore, the osmolality of the excipient in the chamber can be greater than the osmolality of a 0.9% w / v NaCl aqueous solution, preferably greater than the osmolality of a 1.8% w / v NaCl aqueous solution (twice isotonicity). An osmolality greater than the osmolality of a 4.5% w / v NaCl aqueous solution (five times isotonicity) or even greater than the osmolality of a 9% w / v NaCl aqueous solution (ten times isotonicity) can be used.

[0033] Any suitable non-ionic excipient that is inert to the proton and bicarbonate reactions in the chamber may be used. The excipient should also be soluble in the sensor liquid, such as water. The excipient is also ideally a recognized pharmaceutical excipient for intravenous use and has a low viscosity for simple filling of the chamber. The excipient should preferably be sterilizable and storage stable. Ideally, the excipient should inhibit microbial growth.

[0034] A suitable excipient is polyethylene glycol (PEG) and a presently preferred excipient is propylene glycol.

[0035] Preferably, the sensor liquid is aqueous and particularly preferably it comprises water, substantially free of electrolytes as defined above. Other solvents that react with CO2 to increase or decrease its conductivity (e.g. by the production or neutralization of ions) may likewise be used. In practice, however, it has been found that deionized or distilled water works particularly well, with or without the addition of a strong acid (e.g. HCl) to a concentration of 0.1 μM to 100 μM, preferably 0.5 μM to 50 μM, more particularly about 1 μM. The effect of such small additions of acid is generally to keep the pH of the liquid at or below 6, to avoid a significant contribution of hydroxide ions to the conductivity and to maintain the linearity of the pCO2 measurement.

[0036] The pCO2 sensor can function by applying an alternating potential to the electrodes, thereby inducing an alternating current in the sensor liquid. The sensor liquid should react with the carbon dioxide to change its conductivity. The frequency of the potential can be from 20 Hz to 10,000 Hz, preferably from 100 Hz to 4,000 Hz.

[0037] The pCO2 sensor may be provided with or may be connected to a power supply arranged to apply an alternating potential across the electrodes at a frequency of 100 Hz to 10,000 Hz. The frequency is preferably greater than 1 kHz. The frequency is preferably less than 5 kHz, more preferably less than 2 kHz. At frequencies below 100 Hz, the sensitivity of the pCO2 determination is reduced due to the electrical polarization and, in addition, the instrument response time becomes too slow, while at frequencies above 10 kHz, the sensitivity is reduced again due to the low impedance of the capacitors in the sensor. The power supply may be an AC power supply, or alternatively a DC power supply combined with an oscillator, i.e. a combination that together constitutes an AC power supply. The power supply is preferably such that the maximum current density through the liquid at the electrodes is not greater than 50 A / m 2 , preferably not more than 30A / m 2 , more preferably not more than 20A / m 2 , especially not more than 10A / m 2 , and most preferably about 1A / m 2 Or less. 20A / m 2 Higher current density values ​​of 100A or more should only be used at higher frequencies, such as 1 kHz to 10 kHz.

[0038] The minimum maximum current density is determined by the detection limit, but is reduced to 10 -8 A / m 2 Values ​​of 0.1 μA / m are available. However, the minimum maximum current density will usually be at least 0.1 μA / m 2 .

[0039] By operating at such current densities and voltage frequencies, and by appropriate construction, the sensor can determine the conductivity / resistance of the liquid into which the CO2 has migrated without any significant loss of accuracy as a result of the electrical polarization of the electrodes.

[0040] For particularly high accuracy, a lock-in amplifier set to the same frequency as the voltage generator or power supply can be used to determine the potential or current across the electrodes (and therefore the resistance or conductance of the fluid between the electrodes).

[0041] In addition, it is preferred to incorporate a high pass filter in the detection to screen out currents with a frequency of less than 100 Hz, preferably less than 150 Hz. The filter is preferably a passive filter, such as a capacitor and a resistor. If necessary, the power supply and detector circuitry may be included in the sensor, in which case, if it is desired that the sensor is wireless, it will also be preferred to be provided with means to enable remote detection of the signal, such as a transmitter, such as an RF transmitter. In this way, the sensor can be implanted, for example, in a patient at risk. Additional electrodes may be provided that are electrically connected to the patient, for example, to the patient's skin. In order to compensate for electromagnetic noise from the patient, the signal from the additional electrode may be processed together with the signal from the sensor.

[0042] The effects of electrical polarization are significantly reduced by increasing the surface area of ​​the electrode in contact with the liquid, for example by arranging the electrode in a hole arranged away from the plane of the membrane or by using a non-planar electrode surface (e.g. a rough or textured surface). Therefore, it is generally desirable that the ratio of the surface area of ​​the electrode in contact with the liquid is as large as possible, and that the depth of the liquid is as shallow as possible over as much of its area in contact with the membrane as possible. In this way, response time is reduced, electrical polarization is reduced, lower frequencies can be used and stray capacitance effects are significantly reduced.

[0043] Increased resistance relative to the resistance at the electrodes can be achieved by limiting the cross-sectional area of ​​the electrical path through the liquid between the electrodes at the area where the liquid contacts the membrane, for example by reducing the liquid depth for a portion of the path between the electrodes, and / or by ensuring a relatively large contact area between each electrode and the liquid.

[0044] The resistance of the sensor liquid at the membrane and between the electrodes can be increased by using structural elements to define a transmembrane liquid channel between the electrodes, for example by arranging the membrane across or in close proximity to an insulating chamber wall portion in which such a channel is formed, for example by etching. Likewise, a porous spacer can be arranged between the membrane and the chamber wall to define the depth of the liquid.

[0045] In practice, the use of such a spacer is important if the membrane is sufficiently flexible and the depth of liquid behind the membrane is sufficiently small for the measured conductance to vary with pressure under the pressure conditions experienced in use.

[0046] The support structure may include one or more sealing surfaces. Each filament may be wound around a sealing surface. Each sealing surface may have a smooth circumferential shape, and is preferably substantially cylindrical.

[0047] Optionally, the support structure may include stops on the distal and / or proximal sides of each sealing surface. The circumference of the stop may be greater than the circumference of the sealing surface. Thus, the stop may prevent the wound filament from moving along the length of the sensor.

[0048] In a preferred arrangement, the support structure may include a sensor body having a longitudinal axis. At least two electrodes may be spaced apart in a direction transverse to the longitudinal axis of the sensor body. The sensor body may include a plurality of support members extending outwardly from the longitudinal axis of the sensor body and defining at least one liquid channel between adjacent support members. The at least one liquid channel may provide a liquid path between the electrodes. The membrane may be supported by the support member and may provide an outer wall of the liquid channel.

[0049] This arrangement provides a compact construction of a sensor having a longitudinal geometry suitable for insertion into an organ. Furthermore, the support member can provide physical support for the membrane, as well as define a liquid channel of small cross-sectional area allowing accurate measurements.

[0050] In order to reduce the above-mentioned electric polarization effects, the electrodes can be located in recesses in the sensor body having a larger cross-sectional area than the liquid channel. In this way, the current density around the electrodes is reduced by the larger liquid volume.

[0051] The electrodes of the sensor may extend longitudinally, for example parallel to the longitudinal axis of the sensor body. Similarly, the liquid channel may be transverse (for example perpendicular) to the longitudinal axis of the sensor body. In a preferred arrangement, the sensor includes a plurality of liquid channels. For example, the sensor may include at least three liquid channels.

[0052] The support member may be transverse to the longitudinal axis of the sensor body. For example, the support member may be perpendicular to the longitudinal axis of the sensor body in a circumferential direction. In a preferred arrangement, the support member is in the form of a ring formed around the longitudinal axis of the sensor body. The cross-section of the support member may be of any suitable shape. For example, the support member may have a circular, in particular a substantially semicircular, cross-section, or alternatively, may have a substantially triangular, in particular a sawtooth-shaped cross-section, or further alternatively, may have a substantially rectangular cross-section.

[0053] The support member may be integrally formed with the sensor body, for example by injection moulding. The sensor preferably comprises at least four support members. The sensor body and / or the sensor may be generally cylindrical. The membrane may be arranged around the sensor body.

[0054] The described geometry may be applicable to any suitable sensor.In a preferred arrangement, the sensor is a pCO2 sensor.

[0055] In the case of constructing the sensor with the sensor liquid film in place, the electrodes are preferably inert materials or plated with inert materials so that the resistivity of the sensor liquid does not change significantly with storage. Suitable materials include platinum (especially black platinum), gold, silver, aluminum and carbon. Gold is particularly preferred. Generally, inert electrodes that do not produce solvated ions are preferred.

[0056] The membrane may be any material that is permeable to CO2 and substantially impermeable to the solvent of the sensor liquid, any electrolyte and water. For example, polytetrafluoroethylene such as Teflon(R), silicone rubber, polysiloxane, polyolefin or other insulating polymer membranes with a thickness of 0.5 μm to 250 μm may be used. The thicker the membrane, the slower the response time of the sensor will generally be. However, the thinner the membrane, the greater the risk of unevenness or perforation or other damage. However, conveniently, the membrane will be 1 μm to 100 μm thick, preferably 50 μm to 100 μm thick.

[0057] The support of the sensor may be of any suitable material, such as plastic. Preferably, the material should be able to withstand the conditions typically used in sterilization, such as radiation sterilization (e.g. using gamma radiation) or heat sterilization (e.g. using temperatures of about 121°C as used in autoclave sterilization). In the case of heat sterilization, the liquid is typically aseptically filled into the sensor after sterilization. The walls and membrane of the chamber may be the same material machined to have self-supporting walls and a thinner, gas-permeable membrane, such as The sensor may generally be relatively inexpensive and therefore, unlike prior art sensors, may be a disposable device. Furthermore, the electrode chamber may be made very small without difficulty (unlike prior art sensors containing glass electrodes, for which miniaturization presents insurmountable impedance problems). The arrangement provides a sensor, in particular a pCO2 sensor, which may be easily inserted into the tissue of an animal (including a human), which may remain in the tissue during monitoring and which may be easily removed when monitoring is complete.

[0058] The device is preferably small enough not to cause undue disturbance to the tissue to be monitored. Thus, the maximum diameter of the device may be 2 mm, preferably 1 mm. Sensors of such size and configuration may be readily produced: the size and configuration are particularly suitable for measuring pCO2 on or in the surface of an organ, duct or tissue such as the brain, heart, liver, kidney, pancreas, intestine, muscle or subcutaneous tissue. This is particularly interesting because it allows, for example, monitoring the function of an organ, duct or tissue during and after transplantation, in intensive care, after injury, in postoperative procedures, etc., and thus allows early detection of ischemia.

[0059] The partial pressure determined by the sensor may be a quantified value or it may simply be an indication of pCO2 being above or below one or more thresholds (indicating ischemia or non-ischemia), which value may vary depending on the location of the pCO2 measurement site.

[0060] The sensor can be used for a single measurement of pCO2 or, more preferably, can be used for continuous or repeated monitoring of patients, particularly at risk, such as patients in intensive care, patients undergoing or recovering from organ or tissue transplant surgery, patients assessed to have unstable angina, patients recovering from coronary artery bypass surgery, patients suffering from trauma (e.g., trauma to skeletal muscle), or patients suffering from hypovolemia (e.g., shock).

[0061] The device may include a plurality of sensors for the respective physiological parameters. For example, the device may include a series of sensors. For example, such sensors may measure one or more of the partial pressure of carbon dioxide, the partial pressure of oxygen, the oxygen saturation of hemoglobin, temperature, pH, or glucose concentration. In a currently preferred embodiment, the device includes a temperature sensor and a pCO2 sensor.

[0062] From a second aspect, the present invention also provides a method for fixing a carbon dioxide permeable membrane of a physiological sensor for measuring carbon dioxide, the method comprising: applying the carbon dioxide permeable membrane to a support structure to define a closed chamber of the physiological sensor; and winding at least one filament around the support structure on top of the membrane to fix the membrane to the support structure.

[0063] The physiological sensor may include any of the features of the sensors described above, and may include any optional features thereof.

[0064] The at least one filament may be wrapped at least twice around the support structure.The at least one filament may create an airtight seal between the membrane and the support structure.

[0065] At least one filament is preferably made of a biocompatible and medically approved material. In various exemplary embodiments, at least one filament can be formed of any one or more of the following: low density polyethylene (LDPE), high density polyethylene (HDPE), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluoroethylene (PTFE), ethylene tetrafluoroethylene (ETFE), fluorinated ethylene propylene (FEP), nylon, aramid or stainless steel.

[0066] The filament may be a single filament or a plurality of filaments.

[0067] The method may include securing at least one filament, for example, to one or more of: itself, a support structure, and a carbon dioxide permeable membrane.

[0068] The at least one filament may be fixed by using a fixing medium. The fixing medium may include one or more of an adhesive, a glue, and an epoxy, such as a UV curable epoxy.

[0069] The at least one filament may be fixed by welding of the at least one filament. Welding may be achieved by melting or fusing the ends of the at least one filament, for example, via heat, via light or via a chemical reaction.

[0070] The winding may include winding the first filament around the support structure on a first side of the closed chamber, which may be the proximal side of the closed chamber. The winding may further include winding the second filament around the support structure on a second side of the closed chamber, which may be the distal side of the closed chamber.

[0071] In one embodiment, the winding may be performed while the support structure is immersed in the sensor liquid.

[0072] Certain preferred embodiments of the present invention will now be described, by way of example only, and with reference to the accompanying drawings, in which:

[0073] Figure 1 is a schematic diagram of a sensing system incorporating a pCO2 sensor;

[0074] Figure 2 It is shown Figure 1 Schematic diagram of the measuring principle of the pCO2 sensor in the system;

[0075] Figure 3 is a partial cross-sectional view of a first pCO2 sensor;

[0076] Figure 4 is along Figure 3 A cross-sectional view of line AA;

[0077] Figure 4a Is Figure 4 Magnified view of the detail indicated by the circle in ;

[0078] Figure 5 is a diagram of the first pCO2 sensor with the membrane removed;

[0079] Figure 6 A method of fixing the membrane to the first pCO2 sensor is shown;

[0080] Figure 7 is a diagram of a wound filament securing a membrane to a first pCO2 sensor; and

[0081] Figure 8 is a perspective view of a second pCO2 sensor.

[0082] The pCO2 sensing system comprises a disposable sensor unit 1, an electronic surface unit 2, and a monitor unit 3, such as Figure 1 As shown. The disposable sensor unit 1 is packaged and delivered sterilely. The disposable sensor unit 1 includes a membrane-protected conductive pCO2 sensor 4 with a diameter of less than 1 mm, and a temperature sensor 5 integrated in the disposable sensor unit 1. Wires 6 electrically connect the pCO2 sensor 4 and the temperature sensor 5 to the electronic surface unit 2 through connectors.

[0083] The electronic surface unit 2 sends signals to the sensor unit 1 and receives signals from the sensor unit 1. The electronic surface unit 2 performs signal processing and transmits the conditioned signals to the monitor unit 3.

[0084] The monitoring unit 3 is based on a medical grade PC 7 (available from National Instruments Corporation, Austin, Texas) with a USB interface 18 and Labview software.

[0085] according to Figure 2 The measuring principle shown, the pCO2 sensor 4 is used to measure the level (partial pressure) of CO2 in a fluid (pCO2). The measuring chamber comprises two small cavities 9, in each of which an electrode 10 is placed. The two cavities 9 are connected by one or more channels 11 surrounded by a semipermeable membrane 12 (i.e. a membrane that only allows CO2 to be transmitted in and out of the volume of the sensor 4). The entire volume is filled with the sensor liquid.

[0086] The sensor liquid comprises an electrolyte solution or a liquid substantially free of ions, such as deionized water. The sensing liquid may optionally comprise a non-ionic excipient to prevent the sensor liquid from flowing across the membrane 12 without affecting the electrical properties of the sensor liquid. The excipient may comprise, for example, 2% to 40% propylene glycol.

[0087] The conductivity in the sensor liquid depends on the pCO2 and by measuring the conductivity between the electrodes 10 in the volume, information about the pCO2 can be extracted.

[0088] Figures 3 to 7 A first embodiment of a pCO2 sensor 4 is shown. The pCO2 sensor 4 comprises an injection-molded plastic support 23 which is substantially cylindrical and is surrounded by a semipermeable membrane 12. The support 23 has a tip 24 at its distal end and a main body 25 extending proximally from the tip 24. Two gold electrodes 10 are mounted on the main body 25, for example by gluing. The electrodes 10 extend longitudinally along opposite sides of the main body 25 and are received in corresponding recesses in the main body 25.

[0089] Between the tip 24 and the main body 25, a sealing surface 26 for fixing the membrane 12 is provided, as will be discussed in more detail later. A corresponding sealing surface 26 is provided at the proximal end of the main body 25. A pair of stop ribs 29 are provided on the proximal side and the distal side of each sealing surface 26, respectively. In addition, in order to avoid the formation of a water film into which ions may penetrate, the sealing surface 26 of the support body 23 can be selectively made hydrophobic.

[0090] The main body 25 of the support 23 is provided with a plurality of ribs 27 formed into a circular profile. The ribs 27 provide mechanical support for the membrane 12 and also define the fluid channels 11 required for the effective functioning of the pCO2 sensor 4. A reservoir 9' formed by a recess in which the electrode 10 is located is provided between each electrode 10 and the fluid channels 11 formed between the ribs 27. In order to reduce the electric polarization effect, the reservoir 9' provides an area of ​​relatively low current density around the electrode 10.

[0091] like Figure 6 and 7 As shown, during manufacture, the membrane 12 is fixed to the support 23 while being immersed in the sensor liquid so that the chamber bounded by the membrane 12, the electrode 10 and the ribs 27 is completely filled with the sensor liquid. Figure 2 The pCO2 sensor 4 is schematically shown in FIG.

[0092] Optionally, the membrane 12 can be first fixed to the support 23 at one end (e.g., the proximal end) (while outside the sensor liquid). Then, the membrane 12 can be fixed to the support 23 at the other end (e.g., the distal end) (while immersing this end in the sensor liquid). Thus, the liquid filling occurs in a separate step between the two fixing steps.

[0093] The membrane 12 is fixed to the support 23 using a high-strength filament 28 made of a biocompatible and medically approved material (e.g., a material for non-absorbable sutures or ligatures). Exemplary materials may include low-density polyethylene (LDPE), high-density polyethylene (HDPE), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluoroethylene (PTFE), ethylene tetrafluoroethylene (ETFE), fluorinated ethylene propylene (FEP), nylon, aramid, etc. Additional materials may include organic or metallic materials, such as stainless steel. The filament 28 may be single or multiple strands.

[0094] The filament 28 is wound around each sealing surface 26 of the support 23 on top of the membrane 12 so that the filament 28 surrounds the central axis of the pCO2 sensor 4. This presses the membrane 12 against the respective sealing surface 26 and allows the airtight seal between the membrane 12 and the support 23 to be closed. The winding of the filament can be started and / or stopped on the support 23 or on the membrane 12. The stop ribs 29 on either side of the sealing surface 26 have a greater circumference than the sealing surface 26 and serve to prevent the membrane 12 from moving proximally or distally if the membrane 12 is compressed relative to the support 23 by the wound filament 28.

[0095] After winding is completed, the wound filament 28 can be covered in a suitable fixing medium, such as an adhesive, glue or epoxy, UV-curable epoxy, etc. Fixing can also be achieved by melting, fusing, etc. the ends of the filament 28 with itself or with the film 12 or support 23 through heat, light, chemical reaction, etc.

[0096] Fixing or fusing of the filaments 28 can also take place during winding by the same means (heat, light, chemicals), for example by friction.

[0097] Using a filament 28 on top of the membrane 12 wrapped around the pCO 2 sensor 4 allows a gentle, uniform tension to be applied to the membrane 12 at all points around the pCO 2 sensor 4 , while still allowing for small defects in the support 23 or the membrane 12 .

[0098] The filaments 28 exert a radial force at each point where they contact the membrane 12, but each winding is separate from the previous winding, meaning that the force is distributed along the length of the winding, but accumulates as a resultant force on the membrane 12 as the winding increases, creating an airtight seal between the membrane 12 and the support 23.

[0099] The use of high strength filaments to secure the membrane 12 allows a strong clamping force to be achieved with very low added thickness - allowing thicknesses in the micrometer range.

[0100] The pCO2 sensor 4 may include more than one sensing chamber. For example, two parallel electrodes 10 separated by a longitudinal wall member may be provided on each side of the support 23. Thus, a sensing chamber is formed between one electrode 10 on one side of the support 23 to one electrode 10 on the other side of the support 23 through the fluid channels 11 between the ribs 27 on the top of the support 23. Respective sensing chambers are provided between the remaining electrodes 10 and the fluid channels 11 on the bottom of the support 23. The electrodes 10 from each of these chambers may be electrically connected to the corresponding electrodes from the other chamber, so that the electrical signal from the pCO2 sensor 4 reflects the conductivity of the two chambers.

[0101] Temperature sensor 5( Figures 3 to 8The temperature sensor 5 (not shown) takes the form of a thermocouple and can be connected to the end of the support 23 or can be arranged in the cable 6. The temperature sensor 5 is used both for the pCO2 correction calculation and for the measured tissue temperature to be displayed on the monitor 3, which provides useful information for medical diagnosis. The temperature sensor 5 has a minimum measuring range of at least 33°C to 42°C and a minimum accuracy of + / -0.2°C.

[0102] The cable 6 is electrically and mechanically connected to the electrodes 10 of the temperature sensor 5 and the pCO2 sensor 4. The electrodes 10 may be formed as extensions of the conductors of the cable 6. In case the cable 6 and the connection to the support 23 are sufficiently strong, the sensor unit 1 may be pulled out of its position of use using the cable 6. Alternatively, a Kevlar thread may be provided, for example incorporated with the cable 6 to provide a strong external mechanical connection.

[0103] The membrane 12 may extend proximally from the support 23 with the cable 6 to form a conduit around the cable 6. Alternatively, a separate conduit may be provided for the cable 6. In this case, the separate conduit may be bonded to the support 23 at the proximal end of the electrode 10 and the membrane 12.

[0104] During surgical procedures, the catheter tip with an integrated pCO2 sensor 4 is placed 0.5 cm to 4 cm into organ tissue to monitor ischemia over a period of up to two weeks. The sensor unit 1 can be used in orthopedic and reconstructive surgery to measure pCO2 in muscle and subcutaneous tissue and in organs such as the liver, kidney, pancreas, myocardium, brain and intestine. An insertion tool (not shown) can be used to place the sensor unit 1, and there may be a fixation aid to keep the sensor tip 24 in place.

[0105] The maximum diameter of the sensor unit 1 is 1 mm, and the maximum distance from the catheter tip to the sensor element is 2 mm. The pCO2 sensor 4 has a minimum pCO2 measurement range of 2 kPa to 25 kPa, and a minimum detectable pCO2 difference of 0.2 kPa. The response of the pCO2 sensor 4 is less than 20 seconds. The maximum allowed measurement current in any area of ​​the fluid chamber is such that j < 1 mA / cm 2 , while measuring the input voltage not exceeding 50mV RMS.

[0106] The electrodes 10 are gold plated and have a total area of ​​about 3 mm 2 . Measurement frequency f 测量 Should be above 100 Hz. At lower frequencies, polarization effects in the measurement chamber dominate the measurement. At frequencies above 10 kHz, the low impedance of the capacitor becomes an important issue. The measuring resistor R -测量 In the range of 500kOhm to 7MOhm.

[0107] Figure 8 An alternative design of the sensor unit 1 is shown having a capsule membrane 12 ′ instead of the tubular membrane 12 .

[0108] Figure 8 The sensor unit 1 shown in FIG. Figures 3 to 7 1 . However, instead of the membrane 12 having a tubular shape with an open end, the membrane 12' has a tubular shape with a closed distal end. This design means that the membrane only needs to be fixed to the support body 23 at the proximal end of the support body 23. The membrane 12' can be fixed in the same manner as discussed above using a wound filament 28.

[0109] Although only two designs of sensor unit 1 are shown, it will be appreciated that many further minor variations in design are possible.

[0110] The sensor unit 1 is electrically connected to the electronic surface unit 2 located on the patient's skin by a cable 6, the length of which is 5 cm to 2 meters. The maximum diameter of the cable / conduit is 1 mm, and the preferred length of the cable / conduit is about 50 cm. The cable / conduit is soft and flexible so that it does not excessively interfere with adjacent tissues and organs. The cable / conduit and its connection are also strong enough to withstand the strong pulling forces that may be caused by both normal use and "abnormal" use.

[0111] During sterilization, storage and transport, the sensor unit 1 is covered with deionized, sterile and endotoxin-free water to ensure that there is substantially no net loss of water from the sensor reservoir.

[0112] like Figure 1 and 2As shown, the electronic surface unit 2 includes a sine generator 13, which provides a voltage of at least 5 volts and a current supply of 50mV and is powered by a USB interface 18 or by a battery 14. A filter 15 is provided for filtering or averaging the input of the lock-in amplifier 16. A passive filter that reduces current consumption can be used. The preamplifier 17 is combined with a servo mechanism to remove DC current from the signal to reduce electrolytic effects. According to the servo arrangement, the output of the preamplifier is fed back to its input through a low-pass filter. Therefore, only the DC component of the output is fed back and cancels any DC current drawn through the pCO2 sensor 4. In this way, it is ensured that no DC current passes through the pCO2 sensor 4, which can degrade the electrode 10. The operational amplifier used in this stage consumes the least current and has a large CMMR value. At the same time, the bias current is minimal. The lock-in amplifier 16 amplifies the AC signal from the pCO2 sensor 4. This can be constructed with an operational amplifier or using an IC package with at least 1% accuracy for signal detection at frequencies below 1kHz. A galvanic division 19 such as an optical coupler or a coil coupler is provided to prevent noise from being transmitted from the monitor unit 3 and the associated cable 18. An optical coupler is generally advantageous due to the noise-to-signal ratio. A temperature signal amplification and conditioning unit 20 is provided to amplify the signal from the temperature sensor 5. The electronic unit 2 is powered via the USB interface 18. However, optionally, a rechargeable and replaceable standard battery 14 can be used, wherein the battery capacity is sufficient for at least 14 days of continuous monitoring. The surface unit 2 is also provided with an on / off indicator LED 21 and a battery status indicator (if appropriate). Communication between the surface unit 2 and the monitor 3 is via the USB interface 18. The USB cable between the surface unit 2 and the monitor 2 is light and flexible and is at least 1 m long, preferably about 2 m long.

[0113] like Figure 1 and 2 As shown, an AC current is generated by a sine generator 13 and fed to one of the pCO2 sensor electrodes 10 and a lock-in amplifier 16. The high-pass signal from the other pCO2 electrode 10 is passed through a filter 15 to a low noise amplifier 17 and from there to a lock-in amplifier 16, where it is compared with a reference signal generated by the sine generator 13. The non-in-phase components of the signal, i.e., the undesired components, are removed and the remaining part of the signal is amplified. The amplified signal is proportional to pCO2 (or conductivity) and is passed to the monitor 3 for recording or further processing.

[0114] The surface unit 2 may also be electrically connected to a reference electrode (not shown) which is electrically connected to the patient's skin. The signal from the reference electrode may be used to compensate the signal from the sensor unit 1 for the effects of electromagnetic noise generated by the patient.

[0115] A single surface unit 2 may receive signals from several sensor units 1 and provide multiple outputs to a monitor unit 3 .

[0116] The monitoring unit 3 comprises a portable PC 7 or similar computing device which can simultaneously collect signals from a number of different surface units 2. The power supply 22 for the monitoring unit 3 is of a medically approved type operating at both 110V and 230V.

[0117] The software functions of the monitor unit 3 can be implemented in Labview, a software package obtained from National Instruments in Austin, Texas, and capable of processing up to 4 different surface units simultaneously. The software facilitates the calibration of the sensor with three calibration points and a second-order calibration function. The software can be modified to support any other number of calibration points and calibration function types. The software also has the function of smoothing the signal from the pCO2 sensor 4 within a defined time interval. There can be at least two alarm levels for the measured values ​​and two alarm levels for their gradients. The measured value gradients are calculated for individually defined time intervals. The alarms are both visual and audible. The alarm indication can be stopped while keeping other alarms active. The monitor 3 can record all measured values, parameter settings and alarms throughout the session. With a recording interval of 30 seconds, there should be storage capacity for at least 10 two-week sessions on the hard disk. The session log can be saved to a writable data storage medium in a format readable by Microsoft Excel.

[0118] In summary, a physiological sensing device for measuring pCO2 comprises a closed chamber bounded at least in part by a carbon dioxide permeable membrane. Two electrodes are present within the chamber. The chamber contains a sensor liquid in contact with the electrodes and the membrane. The carbon dioxide permeable membrane is fixed to the support structure of the physiological sensing device by a filament wound around the support structure and wound on top of the membrane.

Claims

1. A physiological sensor for measuring carbon dioxide, comprising: a closed chamber containing a sensor liquid and at least partially bounded by a carbon dioxide permeable membrane; at least two electrodes disposed within the chamber in contact with the sensor liquid; a support structure for supporting the membrane, wherein the support structure has a tip at a distal end thereof and a main body extending from the tip toward a proximal end, a sealing surface provided with a pair of ribs being provided at least at a proximal end of the main body; as well as at least one filament wound around the support structure and on top of the membrane for securing the breathable membrane to the support structure, The filament is wound around the sealing surface of the support structure on top of the membrane so that the filament surrounds the central axis of the physiological sensor, the membrane is pressed against the sealing surface and allows an airtight seal to be closed between the membrane and the support structure, and the stop rib has a larger circumference than the sealing surface and prevents the membrane from moving proximally or distally when the membrane is compressed by the wound filament relative to the support structure.

2. A physiological sensor according to claim 1, wherein the at least one filament is formed by one or more of the following: low-density polyethylene (LDPE), high-density polyethylene (HDPE), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluoroethylene (PTFE), ethylene tetrafluoroethylene (ETFE), fluorinated ethylene propylene (FEP), nylon, aramid or stainless steel.

3. The physiological sensor according to claim 1 or 2, wherein the at least one filament has been fixed to one or more of the following: itself, the support structure and the carbon dioxide permeable membrane by a fixing medium or by welding of the filament.

4. The physiological sensor according to claim 1 or 2, wherein the at least one filament comprises: a first filament wrapped around the support structure on a proximal side of the closed chamber; and a second filament wrapped around the support structure on a distal side of the closed chamber.

5. A method for fixing a carbon dioxide permeable membrane of a physiological sensor for measuring carbon dioxide, the method comprising: applying the carbon dioxide permeable membrane to a support structure to define a closed chamber of the physiological sensor; wherein the support structure has a tip at a distal end thereof and a main body portion extending from the tip toward a proximal end, and a sealing surface provided with a pair of ribs is provided at least at a proximal end of the main body portion; as well as wrapping at least one filament around the support structure on top of the membrane to secure the membrane to the support structure, The filament is wound around the sealing surface of the support structure on top of the membrane so that the filament surrounds the central axis of the physiological sensor, the membrane is pressed against the sealing surface and allows an airtight seal to be closed between the membrane and the support structure, and the stop rib has a larger circumference than the sealing surface and prevents the membrane from moving proximally or distally when the membrane is compressed by the wound filament relative to the support structure.

6. The method of claim 5, wherein the at least one filament is formed from one or more of: low density polyethylene (LDPE), high density polyethylene (HDPE), ultra high molecular weight polyethylene (UHMWPE), polytetrafluoroethylene (PTFE), ethylene tetrafluoroethylene (ETFE), fluorinated ethylene propylene (FEP), nylon, aramid, or stainless steel.

7. The method according to claim 5 or 6, further comprising: securing the at least one filament to one or more of: itself, the support structure, and the carbon dioxide permeable membrane using a securing medium; or The at least one filament is secured to one or more of: itself, the support structure, and the carbon dioxide permeable membrane by welding of the at least one filament.

8. The method according to claim 5 or 6, wherein the winding comprises: winding a first filament around the support structure on a proximal side of the closed chamber, and A second filament is wrapped around the support structure on the distal side of the closed chamber.

9. The method according to claim 5 or 6, wherein the winding is performed while the support structure is immersed in a sensor liquid.

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