HK1113735B - Apparatus for ascertaining blood characteristics and probe for use therewith - Google Patents

Description

Device for detecting blood characteristics and probe for use therewith

Technical Field

The present invention relates to devices for measuring physiological parameters of individuals, and in particular to devices and methods for measuring blood gas parameters of patients.

Background

Determination of cardiac output, arterial blood gases, and other hemodynamic or cardiovascular parameters is critical in the treatment and care of patients, particularly those undergoing surgery or other complex medical procedures, as well as those under intensive care. Usually, pulmonary artery thermodilution catheters are used for cardiac output measurements, which have an error of 20% or more. The use of such thermodilution catheters has been found to increase hospital costs and subject patients to potential infections, arrhythmias, mechanical and medical accidents. Blood gas measurements have been made to date. Common blood gas measurement techniques require that a blood sample be drawn from a patient and transferred to a laboratory analyzer for analysis. The caregiver must then wait for the laboratory's results to report, with a delay of typically 20 minutes, and longer waiting times are not unusual.

Recent advances in the art have provided "point-of-care" blood testing systems in which the testing of blood samples is performed at the patient's bedside or in the area of the patient. Such systems include portable and hand-held units, as well as modular units that cooperate with bedside monitors. While most on-site treatment systems require blood to be drawn from the patient for clinical analysis, there are a few systems that do not. In such systems, intermittent blood gas measurements are made by flowing a sufficiently large blood sample into the arterial line to ensure that an undiluted blood sample is obtained on a sensor located in the line. After analysis, the blood is returned to the patient, the tubing is flushed, and the results are visualized on a clinical monitor.

One non-invasive technique, pulse oximetry, is used to estimate the percentage of hemoglobin in arterial blood that is saturated with oxygen. While pulse oximetry is able to estimate the oxygen content of arterial blood, they are not able to measure carbon dioxide, pH, or the oxygen content of veins. In addition, ex vivo pulse oximetry is typically performed at the fingertips and may even be skewed by peripheral vasoconstriction, even with nail polish.

Unfortunately, none of the available blood gas analysis systems or methods provide accurate, direct and continuous in vivo measurements of arterial and venous oxygen partial pressure, carbon dioxide partial pressure, pH and cardiac output while minimizing risk to the patient.

Disclosure of Invention

Coatings and the use of coatings in medical devices have been described previously herein. See, for example, U.S. Pat. nos. 3,443,869, 4,673,584, 5,997,517 and 5,662,960. The coating is used to maintain smoothness and minimize complications due to the use of in vivo and in vitro materials. A special coating needs to be reapplied to remain smooth and a special lubricious coating needs to incorporate a heparin salt solution to maximize immune tolerance. For these devices, such as catheters and probes, extraction from the physiological environment where the lubricant is reapplied increases the operating costs and risks the patient from mechanical and medical accidents. In addition, the coating is reapplied to reduce the gas permeability of the coated membrane.

Drawings

For a better understanding of the nature and details of the invention, reference should be made to the following drawings which are, in some instances, schematic illustrations in detail, and in which like reference numerals are used throughout.

FIG. 1 is an isometric view of an example device according to the present invention having a display module and a probe for monitoring a physiological parameter.

Figure 2 is an isometric view of the probe of figure 1.

FIG. 3 is an enlarged cross-sectional view of the probe of FIG. 1 adapted for multiple parameter measurement.

FIG. 4 is an enlarged cross-sectional view of the carbon dioxide sensor section of the probe of FIG. 1.

FIG. 5 is an enlarged cross-sectional view of the oxygen sensor section of the probe of FIG. 1.

Figure 6A is several views of a flex circuit assembly of another embodiment of the probe of figure 1.

Figure 6B is an isometric view of the probe of figure 1.

Fig. 7 is a flowchart of a surface treatment process of the probe in fig. 1.

Fig. 8 is a block diagram of a circuit included in the display module of fig. 1.

FIG. 9 is a flow chart of a processing algorithm for converting sensor input signals into displayable values executed by the display module of FIG. 1.

Fig. 10 is a plan view, partially cut away, of a kit of the invention.

Like reference numerals designate corresponding parts throughout the several views of the drawings.

Detailed Description

Referring to FIG. 1, an apparatus 10 for making intravascular measurements of physiological parameters or characteristics according to the present invention generally includes a display module 12 and one or more probes 18. As described in detail herein, display module 12 and probe 18 are particularly well suited for accurate and continuous in vivo measurements, as well as display of intravascular parameters, such as oxygen partial Pressure (PO)₂) Partial pressure of carbon dioxide (PCO)₂) And pH. Alternatively, two POs obtained from a pair of probes may be used₂The measurements are combined and the Cardiac Output (CO) is calculated, one of the probes of the pair being placed in an artery and the other in a vein. Alternatively, probe 18 may include sensors for other useful blood parameters, such as potassium, sodium, bilirubin, hemoglobin, glucose, blood pressure, and the like, in addition to the sensors previously described. Additional features of display module 12 and probe 18 are described in detail below and in co-pending U.S. patent application Ser. No. 09/956,064 at 9/18/2001 and in the present U.S. patent application Ser. No. 6,616,614, the entire contents of which are incorporated herein by reference.

As described herein, the probe 18 is removably connected to and communicates with the display module 12 via a first or module connector 15 and a mating second or probe connector 22 at a proximal end or distal end of the probe 18. As shown in FIG. 2, the probe 18 preferably comprises a resiliently elongate probe body or cannula 20 formed of a polymer or other suitable insulating material and having a diameter that is substantially the same throughout its length. The probe body 20 supports a plurality of electrical contacts, preferably at least two contacts, including a low-profile electrical connector 22, and includes a sensor section 24 and a blunt tip 26 near the distal end or tip of the probe 18. The electrical leads connected to the electrodes in the sensor section 24 of the probe 18 pass through the entire length of the cannula 20, preferably through a bore or lumen in the tubular cannula, and are connected to the electrical connector 22. The sensor section 24 of the probe 18 includes electrodes in a chamber filled with an electrolyte. The gas permeable window preferably comprises at least a portion of the chamber. All of the probe elements are sized to generally conform to the diameter range of the probe body 20, having a diameter ranging from 0.010 "to 0.035", but preferably 0.020 ", so that the entire probe 18, including the low profile electrical connector 22, can be passed through the internal bore of a suitable introducer, such as a hypodermic needle sized to access a blood vessel in the hand, wrist or forearm. Suitable hypodermic needle dimensions depending on the diameter of the probe body 20 can be as small as a 25 gauge needle having an inner diameter of at least 0.010 inch for this purpose, and can be as large as an 18 gauge needle having an inner diameter of at least 0.035 inch, with a preferred size being a 20 gauge needle having an inner diameter of at least 0.023 inch, which is suitable for use with a probe body having a nominal diameter of 0.020 inch. In the preferred embodiment, the probe 18 may have a suitable length, such as 25 centimeters, that allows insertion of the sensor section 24 near the distal end of the probe 18 into a blood vessel of the hand, wrist or forearm, while the low profile electrical connector 22 at the proximal or distal end of the probe 18 is connected to the display module 12, which may be tethered to the wrist of the patient.

The low profile electrical connector 22 is advantageous in this application because it allows the use of a conventional hypodermic needle or other suitable introducer to insert the probe 18 into a blood vessel with minimal trauma to the blood vessel. The probe 18 is inserted into a blood vessel by first inserting a hypodermic needle of appropriate size into the skin and then into the target blood vessel. The very sharp needle of the hypodermic syringe easily penetrates the skin, blood vessels beneath the skin, and blood vessel walls while causing minimal damage. Once the hypodermic needle is advanced into the target vessel, the probe 18 is inserted through the bore of the needle and into the vessel. The blunt tip 26 and the smooth surface treatment 38 on the probe 18 minimize the possibility of vessel damage as the probe 18 is advanced into the target vessel. Once the probe is properly positioned in the target vessel, the introducer needle is withdrawn from the artery and skin and the needle is completely removed from the probe 18 by sliding it off the proximal end of the probe 18 from the low profile electrical connector 22, leaving the probe 18 in place in the vessel. The small puncture wound left by the hypodermic needle heals rapidly around the body of the probe 18, thereby avoiding excessive bleeding. The puncture site was covered with bandages and tapes to prevent infection and anchor the probe. A moist paper pad or alcohol swab is used to wipe any blood residue from the low profile electrical connector 22 or the exposed portion of the probe 18 and then the probe connector 22 is connected to a mating receptacle 15 on the display module 12. In contrast to simple insertion methods that cause minimal trauma, facilitated by a low profile connector, conventional probes with standard electrical connectors require the use of a separate cannula sheath to insert the probe into the blood vessel. The split canula sheath is less sharp and more bulky than a hypodermic needle, and is more likely to cause stretching or rupture of the vessel wall, thereby increasing the risk of complications such as bleeding or prolonged healing time. Although the probe 18 is described as being used in a blood vessel, it should be understood that the probe may be inserted into other vessels, lumens or tissues within a patient by any suitable introducer within the scope of the invention.

In the preferred embodiment shown in fig. 3, the probe 18 is formed by a cannula, sleeve or body 20 of a suitable polymeric material that is used to form the structural element of the probe 18. All or a portion of the body 20 may also serve as a gas permeable membrane to enclose or at least surround the sensor chambers 41 and 51. The polymer sleeve material provides strength and elasticity and is thus used as a structural element of the probe 18. When the sleeve material is used as a gas permeable membrane, oxygen and carbon dioxide are also allowed to pass, while liquid water and ions dissolved in the water are not allowed to pass. The sleeve 20 defines the outer surface of the main body portion of the probe 18, and most of the sleeve 20 is preferably filled with a resilient polymer 33, such as an ultraviolet cured adhesive, to provide stability to the probe body 20, to anchor the electrical leads 34 and sensor electrode assembly, and to close the ends of the sensor chambers 41 and 51. The sleeve 20 provides a substantial part of the strength of the probe, especially in the sensor section 24, where both sensor chambers 41 and 51 are filled with liquid, and when all or part of the sleeve is made of a gas permeable material, the sleeve 20 may also form a circumferential window 31 for closing said sensor chambers.

The preferred material of construction for the sleeve 20 shown in fig. 3 is plastic, preferably a polymer, and more preferably polymethylpentene. The sidewall thickness of the sleeve 20 is in the range of 0.001 inch to 0.003 inch, and preferably 0.0015 inch. Of the commonly used polymers suitable for extrusion into thin-walled tubing, polymethylpentene has the highest permeability coefficients for oxygen and carbon dioxide available. In addition, it has maximum stiffness. Table 1 includes the gas permeability coefficient and stiffness-related elastic modulus of representative selected common polymeric materials, showing the advantage of polymethylpentene for this application.

Material	COPermeability coefficient (Barrer))	OPermeability coefficient (Barrer))	Tensile modulus (GPa)
				Polymethylpentene	80	27	1.5
Low density polyethylene	13	10	0.1-0.3
				Polytetrafluoroethylene	10	4.3	0.3-0.8
Polypropylene	8	2.3	0.9-1.5
				Polycarbonate resin	6.4	1.4	2.3-2.4
Polyimide, polyimide resin composition and polyimide resin composition	0.3	0.15	2-3
				Polyester	0.13	0.05	2-4
Nylon	0.09	0.04	2.6-3.0

1: barrer is the unit of gas permeability coefficient, equal to 10^-10(cm of gas passed per second at Standard temperature and pressure³) (film thickness cm)/(film area cm)²) V (gas pressure cmHg).

A cylindrical sleeve 20 of gas permeable membrane material is particularly advantageous as a sleeve for the blood gas sensor chamber 41 or 51, since it forms a complete circumferential window 31, thus maximizing the membrane area for a given sensor length. In addition to maximizing membrane area, the circumferential window 31 also inhibits "side wall effect" artifacts seen in prior blood gas sensor probes, where the gas permeable membrane on the tip or side of the blood gas sensor probe is fully or partially obstructed from exposure to blood when the probe inadvertently encounters a blood vessel wall. The circumferential window of the present invention eliminates the possibility of obstructing most of the membrane by the proximity of the probe to the vessel wall. For carbon dioxide sensors, the gas flow through the membrane primarily affects the response time of the sensor. The electrolyte or other solution in the carbon dioxide sensor chamber will eventually reach carbon dioxide equilibrium with the surrounding blood as long as there is a reasonable diffusion rate in the membrane. However, oxygen sensors rely on a continuous flow of oxygen across the membrane, which is consumed at the platinum sensing electrode, and therefore any significant blockage of oxygen flow to the sensing electrode affects the accuracy of the sensor. The sensitivity of the oxygen sensor to the "side wall effect" is minimized by having a membrane with a high permeability coefficient such that the reaction rate is limited primarily by the rate of oxygen consumption at the sensing electrode, which is determined by the exposed area of the platinum catalyst. In this case, the effect on the probe of local obstruction of the circumferential window 31 due to the proximity of the probe to the vessel wall can be minimized.

The probe body 20 supports electrical contacts 32 that make up the low-profile electrical connector 22 and contains electrical leads 34 and the sensor section 24 of the probe 18. The electrical contacts 32 are comprised of gold strips or the like, welded or soldered together with electrical leads 34, the electrical leads 34 being electrically coupled to one or more sensors in the sensor section 24 of the probe by any suitable lead for transmitting electrical signals from the multiple sensors, thus allowing electrical access to the probe from outside the patient's body. The multiple sensors may include a carbon dioxide sensor 40, an oxygen sensor 50, a thermocouple 47, and a pH sensitive electrode 58, or any combination of the above, or other sensors. At least a portion of the cannula 20 located within the blood vessel, including the sensor section 24, is preferably provided with a surface treatment 38 to inhibit the coagulation of thrombus, proteins or other blood components that would otherwise reduce blood flow in the blood vessel or impede the diffusion of oxygen or carbon dioxide into the sensing chambers 41 and 51. A preferred method of such surface treatment application will be described hereinafter.

FIG. 4 provides a detailed view of one embodiment of the carbon dioxide sensor 40 contained within the sensor section 24 of the probe 18. The carbon dioxide sensor 40 includes a chamber 41 containing an electrolyte solution, and first and second electrodes 43, 44. The sleeve 20 and the uv curable adhesive 33 used to close each end of the chamber 41 define the volume of the chamber. The chamber 41 is preferably filled with an electrolyte solution, such as NaHCO with 0.001 mole₃0.154 moles of NaCl (standard salt solution) (sodium bicarbonate). The pH of the solution changes with changes in the partial pressure of carbon dioxide and the electrodes 43 and 44 generate a potential in response to the pH. The reference electrode 43 for the carbon dioxide sensor may preferably be formed by a silver wire coated with silver chloride, by dipping the silver wire into molten silver chloride, or fabricated by known electrochemical processes. The sensing electrode 44 for the carbon dioxide sensor is a platinum wire coated with platinum dioxide, fabricated by sintering platinum dioxide powder on the surface of the platinum wire, or by an electrochemical or vapor deposition process. By welding or soldering, theElectrodes 43 and 44 are attached or otherwise connected to respective first and second electrical leads 45 or 46 (e.g., insulated copper wires).

Ideally, the carbon dioxide sensor 40 occupies a small axial length of the probe 18, in the range of 1 mm to 10 mm, but preferably 4 mm, so that the sensor section 24 of the probe 18 is short enough, for example less than 20 mm, but preferably less than 13 mm, to be easily advanced into a tortuous vessel. Although occupying a small axial length of the probe 18, the carbon dioxide sensor design provides a large electrode area and maintains a large physical separation between the electrodes. In addition, the carbon dioxide sensor provides an electrical lead path conduit to the multiple end electrodes of the multiple sensor probe, which are electrically isolated from the electrolyte solution within the carbon dioxide sensor chamber 41. In the embodiment shown in FIG. 4, both the reference electrode 43 and the sense electrode 44 are coiled around the tube 42, such as a polyimide tube with an outer diameter of 0.011 inches, an inner diameter of 0.009 inches, and a length of 8 millimeters. The coiled electrodes 43 and 44 provide a larger electrode area in a smaller volume, and the two electrodes 43 and 44 are physically separated from each other by coiling the reference electrode 43 around the proximal half of the tube 42 and the sensing electrode 44 around the distal half of the tube 42, with a larger axial spacing between the two coils, e.g., 1 mm. In addition, the lumen of the polyimide tube 42 provides a conduit for passage of the lead wires for more distal electrodes, electrically and physically isolated from the electrolyte solution in the sensor lumen 41 by multiple layers of insulation including insulating materials over the lead wires themselves, the polyimide tubing, and air or adhesive filling the lumen of the polyimide tube 42. The polyimide tube 42 is anchored in the adhesive 33 that closes the end of the sensor chamber 41, providing additional mechanical strength to the carbon dioxide sensor section of the probe 18 beyond that provided by the sleeve 20 alone. The electrolyte solution of the carbon dioxide sensor 40 is contained within the annular gap between the polyimide tube 42 and the sleeve or body 20 of the probe 18. The sleeve 20 may form a large surface area circumferential window 31 for the carbon dioxide sensor 40 that is less susceptible to occlusion caused by excessive proximity to the vessel sidewall.

Fig. 4 also shows a temperature sensing thermocouple 47 contained within the sensor section 24 of the probe 18. The thermocouple 47 may include a pair of lead wires 48 and 49 made of different materials, which are electrically connected to each other by welding or soldering. The wire is selected from a known pair of materials having a known temperature response, such as copper and constantan. The thermocouple junction is electrically isolated from the other sensor electrodes and is embedded within the sensor section 24 of the probe 18, in proximity to the other sensors, where the thermocouple junction will accurately reflect the temperature of the surrounding blood.

FIG. 5 provides a detailed view of one embodiment of the oxygen sensor 50 contained within the sensor section 24 of the probe 18. The oxygen sensor 50 may comprise a chamber 51 containing an electrolyte solution, and third and fourth electrodes 53, 54. The chamber 51 is defined by the sleeve 20 and the uv curable adhesive 33 closing each end of the chamber. The chamber is preferably filled with an electrolyte solution, for example 0.154 molar NaCl (standard salt solution), with 0.120 molar NaHCO₃(sodium bicarbonate) buffered. By biasing the electrodes with a suitable voltage, for example 0.70 volts, the platinum electrode 54 acts as a catalyst for a chemical reaction that consumes oxygen and generates an electrical current that is proportional to the rate of oxygen consumption at the platinum electrode, which in turn is dependent on the partial pressure of oxygen in the blood surrounding the sensor 50. The sodium bicarbonate buffer stabilizes the pH value of the electrolyte solution against changes that would otherwise be caused by chemical reactions that consume oxygen on the platinum electrode 54. When the buffer or electrolyte solution is depleted, or when the sensor chamber 51 is filled with excess silver chloride precipitate, the response of the oxygen sensor will change and the sensor will no longer be viable. Thus, the probe 18 advantageously provides a sufficiently large volume chamber filled with buffered electrolyte, thereby providing the desired lifetime of the oxygen sensor. The reference electrode 53 for the oxygen sensor 50 is preferably formed by a silver wire coated with silver chloride by dipping the silver wire into molten silver chlorideOr by known electrochemical machining. The sensing electrode 54 for the oxygen sensor 50 is a platinum wire. The electrodes are attached or coupled to respective third and fourth electrical leads 55 or 56 (e.g., insulated copper wires) by welding or soldering.

The oxygen sensor 50 preferably occupies a small axial length of the probe 18, in the range of 1 mm to 10 mm, but preferably 4 mm, so that the sensor section 24 of the probe 18 is short enough, for example less than 20 mm, but preferably less than 13 mm, to be easily advanced into a tortuous blood vessel. While the oxygen sensor occupies a small axial length of the probe 18, the sensor design provides a large electrode area, maintains a large physical separation between the electrodes, and provides a large volume of electrolyte solution. In addition, the sensing electrode 54 exposes only a small, well-defined surface area to the electrolyte solution. In addition, the oxygen sensor provides a conduit for passage of electrical leads to the multiple end electrodes of the multi-sensor probe, electrically isolated from the electrolyte solution within the oxygen sensor chamber 51. In the embodiment shown in FIG. 5, reference electrode 53 is coiled around tube 52, such as a polyimide tube having an outer diameter of 0.007 inches, an inner diameter of 0.005 inches, and a length of 5 millimeters. Coiled reference electrode 53 provides a larger electrode surface area in a smaller volume. The sensing electrode 54 is preferably formed by a platinum wire having a short exposed length and a small diameter, ranging from 0.001 inch to 0.008 inch, but preferably 0.002 inch.

The sensing electrode 54 is preferably formed by first oxidizing the surface of a platinum wire having a smaller diameter by heating in a furnace having an oxygen atmosphere, and then fusing a sealing glass bead 57 to the platinum wire. The sealing glass is selected to provide a range of 8.0 to 9.2X 10^-6Coefficient of thermal expansion in the range of/° K, but is preferably 8.6 × 10^-6Coefficient of thermal expansion of 9.0X 10 with platinum,/° K^-6The/° K approaches or matches. The glass forms a strong bond with the platinum oxide on the surface of the platinum wire and the matched coefficients of thermal expansion minimize thermal stress during cooling of the glass and platinum, thereby preventing glass breakage or separation of the glass from the electrodeThis phenomenon can lead to oxygen sensor drift when the exposed platinum electrode area changes. The glass beads 57 form a reliable enclosure for the platinum wire electrode 54, ensuring a stable platinum electrode area for non-offset operation of the device. The bond between the sealing glass and the platinum oxide wire is more cohesive and more resistant to flow than the bond formed by the adhesive used in prior oxygen sensor designs, making the present invention more stable and reliable than designs based on cohesive seals. Glass beads 57 are bonded to the end of tube 52 and the platinum wire distal end is trimmed flush, or inside the wire diameter at the tip of glass beads 57, completing the oxygen electrode assembly. The two electrodes 53 and 54 are physically isolated from each other because the reference electrode 53 is coiled around the tube 52, while the sensing electrode 54 is only exposed at the tip of the glass bead 57, at a large axial distance, for example 1 mm, from the reference electrode 53. In addition, the oxygen sensor 50 includes a conduit 59A, preferably formed by polyimide or other insulating tubing, which serves as a pathway for leads 59 to the plurality of distal pH sensing electrodes 58. The lead 59 is electrically and physically insulated from the electrolyte solution in the sensor chamber 51 by a plurality of insulating layers comprising an insulating material on the electrical lead 59, an insulating conduit 59A, and air or adhesive filling the lumen of the conduit 59A. The electrolyte solution of the oxygen sensor 50 is contained in the annular space between the polyimide tube 52 and the sleeve 20, and in the cylindrical space except for the tips of the glass beads 57 and the platinum sensing electrode 54. The cannula 20 preferably forms a circumferential window 31 of large surface area for the oxygen sensor 50 that is less prone to occlusion caused by excessive proximity to the vessel sidewall.

Fig. 5 also shows a detailed view of the pH sensor contained within the sensor section 24 of the probe 18. The pH sensor includes a noble metal electrode 58, such as a gold or platinum strip, and a reference electrode 43 or 53, wherein the noble metal electrode 58 is immobilized on the outer surface of the probe 18, directly exposed to blood. The reference electrode for the pH sensor preferably consists of a silver wire coated with silver chloride, made by dipping the silver wire into molten silver chloride, or by known electrochemical processes. The reference electrode 43 or 53 may be shared with the oxygen sensor 40 or the carbon dioxide sensor 50. The pH sensing electrode 58 is attached to an electrical lead 59 (e.g., an insulated copper wire) by welding or soldering.

As described above, the probe, which is typically constructed from various wires, tubes and electrodes, is inserted into the bore of the tubular sleeve 20, wherein the bore of the sleeve 20 is then filled with a binder and electrolyte solution to form the sensor. In an alternative embodiment, the flexible circuit replaces wires, tubes and electrodes. The flexible circuit can be mass produced in a low cost batch process, thereby minimizing the cost of the multiple sensor probe. FIG. 6A shows a flexible circuit 60 incorporating all of the electrical components of a multiple sensor blood gas sensor probe, including electrical contact pads 62 containing low profile electrical connectors 22, electrical leads 61, and different types of sensing electrodes 63-68, all fabricated on a flexible planar substrate having three layers of circuitry separated by two layers of a flexible insulating substrate, such as polyimide. Such flexible circuits may be fabricated using known batch processing in which successive layers of conductive material on an insulating substrate are deposited by electroplating, vapor deposition or other methods, and then patterned by photolithography, laser ablation or other methods. The patterned layers are bonded together with an insulating adhesive to complete the multilayer flexible circuit. Once the processing steps are complete, the individual circuits are cut into narrow strips of, for example, 0.015 inches in width so that the circuits can be inserted into the sleeve 20 and filled with adhesive 33 and electrolyte solution to form the sensor chambers 41 and 51 on the electrode segments of the flex circuit 60.

The flexible circuit 60 has a length of, for example, 25 centimeters, is suitable for a circuit longitudinally located within the lumen of the cannula, and may have a width ranging from 0.008 inches to 0.030 inches, and preferably 0.015 inches. The proximal end or portion of the flexible circuit 60 preferably has at least two pads 62, and more preferably seven pads 62, which serve as the electrical contacts 32 for the low-profile electrical connector 22. The connector pads 62 are gold plated thereon to provide reliable electrical contact with the mating connectors 15 of the display module 12. The connector pads are connected to traces or wires 61, are interposed or placed between the first and second insulating layers 161, 162 of the flexible circuit substrate, and more particularly form one or both of the inner surfaces 163 and 164 of the respective insulating layers 161 and 162. The traces 61 are in turn connected to a plurality of pads 63-66 and 68 near the distal end or portion of the flex circuit 60, which serve as electrodes for different sensors. The pads and traces of the flex circuit 60 are formed primarily of copper and the pads are plated with various metals, including silver, platinum, and gold, to form the electrodes of the various sensors. Pads 62, 63-66 and 68 on one or both exposed surfaces 166 and 167 of the flex circuit are connected to traces 61 by vias 69 or any other suitable means. The reference electrodes 63 and 65 of the oxygen, carbon dioxide, and pH sensors are preferably formed by subjecting a silver plated pad to a known electrochemical process in which silver reacts with chloride ions in solution to form a layer of silver chloride on the surface of the silver. The sensing electrode 64 of the carbon dioxide sensor is preferably formed by subjecting a platinized pad to a known electrochemical process in which platinum metal chemically reacts in a platinum chloride solution to form a platinum dioxide layer on the surface of the platinum. The sensing electrode 66 of the oxygen sensor is preferably formed by masking a platinum-plated pad electrode with an insulating material to define a small exposed area of platinum metal, where the area ranges from 0.001 inch to 0.008 inch in diameter, but is preferably 0.002 inch in diameter. The pH sensing electrode 68 is preferably a gold or platinum plated pad that is directly exposed to blood. The flexible circuit 60 may also house a temperature sensor in the form of a patterned thin film of known material, with a temperature sensing resistor 67 formed on the inner surface 163 of the first layer 161. Alternatively, the temperature sensor may be a diode, thermistor, or thermocouple bonded to one of the flexible circuit substrate layers 161 and 162.

Fig. 6B shows a flex circuit 60 comprising various electrodes inserted into the lumen or bore of the cannula 20, wherein the lumen or bore of the cannula 20 is preferably closed by the adhesive 33 and filled with an electrolyte solution to form the internal chambers 41 and 51 of the carbon dioxide and oxygen sensors. The proximal end or portion of the flexible circuit 60 includes embedded traces that serve as electrical leads 61 and gold plated pads that serve as electrical contacts 62 for the electrical connector 22. The embedded traces direct electrical signals from the sensor electrodes 63-68 to the electrical contact pads 62, the electrical contact pads 62 serving as the low-profile electrical connector 22 that may be coupled with the mating connector 15 of the display module 12.

As described hereinabove, at least a portion of the polymeric sleeve 20 forming the outer surface of the probe 18 is preferably provided with a durable surface treatment 38 to inhibit the coagulation of thrombus, proteins or other blood components that might otherwise impair blood flow in the artery or impede the transmission of oxygen or carbon dioxide through the circumferential window 31 into the sensing chamber 41 or 51 (see fig. 3). One preferred method of surface treatment of the cannula 20 is light-induced photopolymerization of N-vinylpyrrolidone to form a plurality of dense microscopic polymer strands of polyvinylpyrrolidone covalently bonded to the outer surface of the probe. The surface treatment 38 is durable because the chemical bonds anchoring the polymer strands to the underlying substrate are strong covalent bonds. The surface treatment 38 adds only a sub-micron thickness to the probe body 20, yet it provides the probe surface with hydrophilic properties that, when hydrated by contact with blood or water, make the probe surface highly smooth, thereby facilitating smooth passage of the probe 18 through the blood vessel. The hydrophilic surface treatment 38 also inhibits protein absorption on the underlying polymer substrate surface, thereby minimizing coagulation of thrombus, proteins, or other blood components on the probes 18. While the large dense polyvinylpyrrolidone micro-polymer strands provide shielding for the underlying outer wall of the cannula or cannula 20 from large protein molecules, it does not effectively prevent smaller molecules, such as oxygen or carbon dioxide molecules, from migrating through the side walls of the cannula. Thus, the surface treatment 38 of the polymethylpentene sleeve 20 allows for a robust, reliable passageway of blood gases, such as oxygen and carbon dioxide, through the circumferential window 31 to the oxygen and carbon dioxide sensor chambers 41 and 51 to be more easily formed, even after an extended residence time in the patient's bloodstream of up to three days.

One flow of the surface treatment of the polymer bushing material will be described hereinafter, and a flow chart of the flow is shown in fig. 7. As a preliminary work for the surface treatment process, two solutions, i.e., the sensitizing dilution solution 76 and the coating solution 79, are prepared. The sensitizing dilution 76 is prepared in two stages. In a first stage or step 74, which is carried out under room light illumination, a layer of nitrogen gas is applied to a volume of acetone, preferably 90 ml, after a period of purging of the acetone with nitrogen gas, for example five minutes. In a second stage or step 75, which is carried out under red light illumination, a mass of benzophenone, preferably 1.0 gram of benzophenone, is dissolved in acetone and additional acetone is added to the solution to form a total volume of 100 ml. The preparation of coating solution 79 is divided into two stages, both of which are performed under room light. In a first stage or step 77, a blanket of nitrogen is applied to a volume of distilled water, preferably 80 milliliters, in the flask after purging the distilled water with nitrogen for a period of time, for example five minutes. In a second stage or step 78, a mass of N-vinylpyrrolidone, preferably 11.4 grams of N-vinylpyrrolidone, is dissolved in distilled water while still applying nitrogen gas. The flask was capped and coating solution 79 was ready for storage and use.

The membrane tubing assembly is prepared for surface treatment in step 70 by placing a mandrel within a suitable length of polymethylpentene tubing and closing one end of the tubing. In a preliminary stage or step 71 of the surface treatment procedure conducted under indoor light illumination, the membrane tubing assembly was immersed in methanol and sonicated for five minutes to thoroughly clean the outer surface, then allowed to air dry for five minutes. In the second stage or step 72 of the surface treatment process, which is carried out under red light illumination, the membrane tubing assembly is immersed for 30 seconds in a sensitizing dilution 76 of benzophenone in acetone that is nitrogen purged. The sensitized membrane tubing assembly is then removed and placed in a desiccator, still under red light illumination, dried under a partial vacuum of, for example, 28mmHg for a period of time, for example, five minutes, then stored in an amber vial with a nitrogen blanket. In a third stage or step 73 of the surface treatment process carried out under room light illumination, the sensitized membrane tube assembly is immersed in a volume of N-vinylpyrrolidone coating solution 79, for example 30 ml, which has been heated to 60 ℃. The coating is cured by exposing the coating to ultraviolet curing light for a period of time, such as 90 seconds, during which the N-vinylpyrrolidone is polymerized to form a plurality of polyvinylpyrrolidone strands covalently bonded to the membrane tube substrate. The membrane tubing assembly is rinsed with a large volume of distilled water and then placed in a desiccator under a partial vacuum of, for example, 28mmHg for a period of time, for example, two hours, to complete the preparation of the surface treated membrane tubing.

The surface treated polymethylpentene tubing may be used as a sleeve 20 in the manufacture of a complete probe assembly which will retain the advantageous properties of the N-vinylpyrrolidone surface treatment. Alternatively, the probe assembly 18 may be fabricated by using untreated tubing, and then a surface treatment may be applied to the completed probe 18 by substantially the same method as previously described.

As shown in FIG. 1, display module 12 includes a housing 17 formed of a suitable material, such as plastic, that is sized so that it may be worn on a patient, such as a patient's wrist, arm or other limb, sometimes referred to herein as the subject, with a probe 18 inserted into a blood vessel of the hand, wrist or arm. The module 12 also includes a display 13, such as a Liquid Crystal Display (LCD), for displaying the measured parameters and other information, and adapted to make the measured parameters and other information more visible to an attending medical professional, sometimes referred to herein as a user. The display 13 may contain backlighting or other features that enhance the visibility of the display. Straps 14 connected to housing 17 are adapted to secure display module 12 to the subject's wrist. Alternatively, the module 12 may be connected to the subject's arm or a location near the subject. In the case where the subject is a young child (infant) at birth, the module 12 may optionally be strapped to the torso of the subject and the probe 18 inserted into the blood vessels of the umbilical cord. The belt 14 is composed of any suitable material, such as velcro, elastics, and the like. Buttons 16 or keys facilitate the entry of data and allow the user to act on display 13 and other components of module 12. Although three buttons are shown in fig. 1, any number or type of buttons, keypads, switches, etc. may be used to allow parameters or commands to be entered or otherwise connected to the device 10. The module 12 may also include wireless communication capabilities to facilitate display of physiological parameters on a remote monitor or computer system and/or to facilitate entry of patient parameters into the module 12 from a remote control panel or computer system. The module 12 also includes one or more connectors 15 that provide physical connection and communication with one or more probes 18. Each connector 15 preferably includes a receptacle adapted to receive, secure and engage a corresponding connector 22 on the proximal end of the probe 18.

In the preferred embodiment of the display module 12, the module is designed for low cost, so that the module can be packaged with the probe 18 and accessories as a usable kit 100, with all components of the kit packaged together in a sterile bag or other container 101, as shown in FIG. 10. In addition to the display module 12 and the stylet 18, the kit optionally includes a stylet holder 102 for protecting the stylet from damage or degradation, a wrist band 14 or other means for connecting the display module to a patient, needle or other introducer 103, an alcohol swab 104 for cleaning the skin surface prior to insertion of the catheter into a blood vessel and for cleaning blood or other debris from the stylet connector prior to connection of the stylet to the module, a bandage 105 for covering the puncture site and anchoring the stylet in place, and any other items that may be used to prepare and use the stylet 18 and display module 12. The display module 12 is also designed for low power requirements so that the module can be operated on battery power for the expected life of the device, for example 72 hours, without the need for battery replacement or connection to an external power source. The probe 18 is preferably adapted for single use, being a disposable device, because it has a limited lifetime and is intended to be in direct contact with the blood of a subject during use. The module 12 is sufficiently durable to be used many times, but the disposable module has the advantage of saving cost, eliminating the risk of infection associated with cleaning, replacing batteries, and reusing the disposable module for multiple patients. An additional advantage of the disposable module 12 packaged with the associated probe 18 is that calibration data can be stored in the module at the time of manufacture, greatly simplifying use of the device 10 by eliminating the need for the user to enter calibration data into the module prior to use of the probe 18. An additional advantage of the disposable module 12 packaged with the associated probe 18 is that the calibration data stored in the module at the time of manufacture can account for all monitor and probe errors and typical results in a single set of calibration coefficients, thereby avoiding the accumulation of errors caused by each individual calibration of the probe 18 and module 12. In a preferred embodiment of the module, no user input is required at all, eliminating the need for buttons, keypads, switches, etc. The display module 12 is automatically activated immediately upon connection of the probe 18 to the module 12 and all calibration data and other desired information is preprogrammed into the module at the time of manufacture.

Fig. 8 illustrates, in block diagram form, one embodiment of electronics 80 contained within display module 12. As shown, signals from one or more sensors provided on one or more probes 18 are passed through connector 15 to display module 12. The sensor signals are received by a plurality of analog signal conditioning circuits 82 corresponding to each sensor in the associated probe 18. The output of the analog signal conditioning circuit 82 leads directly to a microcontroller 81, such as a Texas instruments MSP430F435, which MSP430F435 includes many of the circuit elements required for the display module 12. Specifically, the microcontroller 81 includes analog multiplexers, and analog-to-digital converters that digitize analog signals from a plurality of analog signal conditioning circuits 82, as well as analog support circuits, including voltage references, temperature sensors, and power monitoring circuits. In a preferred embodiment, the algorithms for processing the signals, as well as the sensor and module calibration coefficients, are embodied in software stored in non-volatile memory contained in the microcontroller 81. The microcontroller 81 also contains a central processing unit for executing software algorithms, as well as other peripheral functions, including clock circuits, serial and parallel input/output interfaces, timers, and LCD driver circuits. The LCD driver circuit provides waveforms for the liquid crystal display 13 and the display module 12 may also establish communication with an external computer or module over a serial data link through an optional wireless interface circuit 83 or other suitable means. The combination of most of the required functions of the display module circuitry into a single, inexpensive, low power component, i.e., a microcontroller, allows the module to be made as a low cost, battery powered disposable unit.

Each analog signal conditioning circuit 82 is adapted for the particular type of sensor to which it is connected. For an oxygen sensor, the analog signal conditioning circuit may be a current-to-voltage converter with a full-range input current including the maximum full-range current expected for the oxygen sensor, e.g., 100 nanoamps, and a full-range output voltage matching the analog-to-digital converter input range. The input bias current of the oxygen sensing circuit is preferably substantially less than the normal sensor operating current, e.g., an input bias current of less than 100 pico amperes. For carbon dioxide or pH sensors, the analog signal conditioning circuit may be a voltage amplifier with very high input impedance, e.g., greater than 10¹²Ohms, and very low input bias and offset currents, e.g., less than 100 milliamperes. The circuit may include a fixed gain and compensation voltage that is selected to translate the full range of sensor voltages to match the analog-to-digital converter input range. The carbon dioxide or pH sensor circuit requirements can be met by an instrumentation amplifier or a simple operational amplifier circuit, the amplifier being selected to provide the required low input bias and offset current. For thermocouple temperature sensors, the analog signal conditioning circuit may be a high gain voltage amplifier with an input voltage range of 0 to 2 millivolts over the expected temperature range and an output voltage that matches the analog-to-digital converter input range. For the required heightThe gain thermocouple signal conditioning circuit, amplifier, preferably provides an input compensation voltage that is substantially less than the signal voltage, for example less than 10 microvolts.

Microcontroller 81 may execute a processing algorithm 90, shown in block diagram form in fig. 9, to convert the digitized sensor signals into displayable values. The processing algorithm includes digitizing the sampled sensor output in step 91, time filtering or averaging to reduce noise from external interference or other sources in step 92, correcting gain or compensation errors in the analog signal conditioning circuitry in step 93, combining gain, compensation, and linearity correction of the sensor calibration data in step 94, compensating for temperature dependence of gain, offset, and linearity of the sensor based on the measured probe temperature in step 95, and converting the values to desired units on the LCD for display in step 96. Indeed, if the module 12 and probe 18 are calibrated together as a disposable device, all of the gain, offset, non-linearity, temperature, and unit transformation coefficients of steps 93, 94, 95, and 96 may be combined into a single set of calibration functions that allow the filtered analog input to be directly converted to displayable values without the need to calculate any intermediate corrections and without the accumulation of errors caused by separate calibrations of the individual components of the device. The algorithm may optionally include step 97 of calculating other physiological parameters according to known formulas, possibly combining readings from multiple sensors, or combining multiple readings from a single sensor to provide additional useful information.

An example of a calculation based on a single reading from a single sensor is based on the corresponding oxygen (PaO)₂Or PvO₂) Partial pressure measurement to estimate arterial or venous oxygen saturation value (SaO)₂Or SvO₂). There is a known non-linear relationship between the oxygen saturation value in blood and the partial pressure of oxygen, but the saturation value is useful for calculation of cardiac output and other estimates of the patient's condition.

An example of a calculation based on multiple readings from a single sensor is the determination of the trend of the relevant blood gas parameter, i.e., whether the value is increasing, decreasing, or stable. Trends in blood gas parameters may be displayed symbolically on the display, making it easier for the user to quickly assess the condition of the patient.

An example of a calculation based on combined readings from multiple sensors is to use the carbon dioxide reading and the pH measurement to calculate bicarbonate levels. According to a known relationship, the logarithm of the bicarbonate concentration is equal to the pH plus CO₂The logarithm of the partial pressure, minus the constant 7.608. This equation applies to 37 ℃ blood, and can also compensate for temperature deviations from normal.

An example of a calculation based on combined readings from multiple sensors is to estimate cardiac output by a modified form of the Fick oxygen consumption method using arterial and venous oxygen readings. According to Fick oxygen consumption, cardiac output (liters per minute) is taken as the difference in oxygen concentration (O per liter of blood) in the passive veins₂Ml) was calculated. For the present invention, the oxygen consumption is estimated as 3 ml/kg times the subject's weight, which can be entered into the module by means of buttons or keys, or by wireless communication from an external computer or control panel. Assume the standard value of hemoglobin (12.5 g/dl), and the oxygen carrying capacity of hemoglobin (O per gram of hemoglobin)₂1.36 ml), and the arteriovenous oxygen concentration difference is calculated as an arterial oxygen saturation value and a venous oxygen saturation value (SaO)₂-SvO₂) The difference between the two is multiplied by O per liter of blood₂Standard value for ml 170 ml. In this calculation, the venous oxygen saturation value may be adjusted to compensate for the experimentally determined difference between the pulmonary arterial oxygen saturation value and the forearm venous oxygen saturation value.

The combination of the wireless interface circuit with the display module is advantageous in that it protects the electrical safety and freedom of movement of the patient borne by the autonomous, battery-powered display unit, while providing the advantages of an integrated system from a centralized data collection point of view. The compact display module of the present invention takes full advantage of wireless communication by freeing the subject from the tubes and cables that would normally tie the patient to the bed, and by eliminating the need for additional bulky equipment at the already crowded bedside.

From the foregoing, it can be seen that the device 10 and method of the present invention enable the measurement of blood gases, such as oxygen and carbon dioxide, and other blood parameters, including temperature and pH, of a subject. As described above, a probe may include more than one sensor, such as an oxygen sensor, a carbon dioxide sensor, a temperature sensor, and a pH sensor. The sensor is contained in a probe body having a smaller diameter than 0.023 "so that the probe can be easily inserted into a blood vessel of the hand, wrist or forearm through a 20-gauge needle. The probe includes at least one sensor having a window 31 with a large surface area and a high permeability to target gas molecules, which permeability makes it easier for blood gases to enter and exit the sensor chamber by rapid diffusion to ensure a rapid response to changes in blood gas concentration. The probe used is preferably blunt and atraumatic to the vessel wall, and is preferably provided with an anti-thrombogenic surface treatment to inhibit thrombus formation, or adhesion of proteins or other blood components, ensure consistent performance of the blood gas sensor, and minimize the need for continuous injection of heparin to maintain a blood clot-free environment. The probe carries the electronic signals from the sensor through electrical leads into a low profile electrical connector, or other electrical connector removably connected to a mating connector on the display module. The stealth of the preferred electrical connector allows for easier removal of the hypodermic needle or other introducer used to insert the probe into the lumen of a vein or artery in the simplest manner, thereby eliminating the need to use a separate cannula sheath or other more complex technique to insert the probe into the vessel. The display module is small and inexpensive and is particularly suitable for attachment to a patient's wrist. The devices and methods described herein may be adapted to the particular needs of a variety of different medical applications, several of which are outlined below.

For patients in the Intensive Care Unit (ICU) or cardiac intensive care unit (CCU), there is often a need to monitor arterial blood gases (oxygen and carbon dioxide) and pH. This monitoring is currently performed on an intermittent basis, typically three to twelve times a day, by drawing a blood sample from the arterial line of the patient's forearm and transferring the blood sample to a blood gas analyzer. The multiple sensor probe described herein, which provides continuous measurement of oxygen, carbon dioxide and pH, eliminates the need for locating and maintaining the arterial line and the repeated drawing of blood therefrom and the associated costs and risks. Furthermore, the continuous monitoring provided by the present invention gives a quick feedback on the effect of any intervention, such as adjustment of ventilation settings or medication intake. Timely feedback of the impact of medical intervention allows the subject to be more quickly detached from the ventilation device and freed from the ICU/CCU, which is advantageous for both the patient and the health care system.

In a subset of ICU/CCU patients, where there is a need to monitor cardiac output, a venous oxygen sensor probe is added to the aforementioned multi-sensor arterial probe, allowing the present invention to estimate cardiac output by using the modified arteriovenous oxygen concentration difference equation (fick's method) described above. Currently cardiac output is most frequently monitored using the thermodilution technique, which requires placement of a Swan-Ganz catheter in the jugular vein, through the right atrium and right ventricle, and into the bifurcation of the pulmonary artery. The thermodilution technique requires intermittent injections of ice salt pills whenever a reading of cardiac output is required. Replacing the right heart catheter with the present invention, through the elimination of the right heart catheterization procedure, greatly reduces the risk to the patient and provides greater utility in providing the required cardiac output readings immediately without the troublesome injection of ice salt.

In another subset of ICU/CCU patients, where there is a need for frequent monitoring of cardiac output rather than arterial blood gases, a simpler instrument is a venous oxygen probe for monitoring venous oxygen content. This value is combined with separate measurements of arterial oxygen saturation from a non-invasive pulse oximeter, hemoglobin density from daily blood samples, and oxygen consumption calculated from standard approximations based on weight and height, to calculate cardiac output according to the Fick method. The probe is positioned in the vein of the hand and an experimentally determined compensation factor is used to account for the difference between the oxygen saturation in the right atrium and the oxygen saturation in the vein of the hand. Alternatively, the oxygen probe may be inserted directly into the jugular vein in the neck, into the vena cava or right atrium of the heart, to provide a direct measurement of the oxygen saturation value of the mixed venous blood without the need for a compensation factor. In addition to the utility of estimating cardiac output, the level of oxygen in the veins is a particularly useful parameter for assessing the condition of a patient.

There is often a need for infants to monitor arterial and venous blood gases, as well as to measure cardiac output and other blood parameters. The invention is particularly suitable for infants, since it minimises, if not eliminates, the need to draw blood from an infant, i.e. requires a smaller volume of blood to be drawn. The addition of hemoglobin, bilirubin, electrolyte or glucose sensors to the blood gas and pH sensors increases the utility of the multisensor probe for this application. The probe is conveniently inserted into the arteries and veins of the umbilical cord, and the display module is sized to be worn around the abdomen of the infant.

In the diagnosis of congenital heart disease in infants and pediatric patients, there is often a need to sample oxygen saturation values at multiple locations throughout the heart chamber and in the aorta. This oxygen saturation value data is typically collected in conjunction with angiography of the heart and allows the activity of the malformed heart to be more accurately diagnosed and thus more appropriately treated for the patient. Currently, oxygen saturation value data is collected by drawing multiple blood samples from multiple locations throughout the heart and aorta with the aid of a smaller catheter. These blood samples were then transferred to a blood gas analyzer to obtain an oxygen saturation reading for each blood sample. By using the technique of the present invention, smaller oxygen sensors are fixed on a probe or a suitably sized guidewire, for example less than 0.023 "in diameter and between 50 cm and 150 cm in length, which can be advanced through a catheter to different locations within the heart and aorta to sample oxygen saturation levels in vivo, thereby reducing patient risk by eliminating the need to draw large blood samples from smaller subjects and by reducing procedure time.

In one aspect of the invention, a device is provided for use with a patient having a blood vessel carrying blood to ascertain characteristics of the blood. The device includes a display module and a probe having a distal end adapted to be inserted into a blood vessel of a patient and a proximal end coupled to the display module. The probe includes a gas sensor assembly secured at the distal end that provides an electrical signal to a display module when the probe is in blood. The probe has an anti-thrombogenic surface treatment for preventing blood components from adhering to the probe when the probe is in blood.

In another aspect of the invention, a probe for use with a patient having a blood vessel carrying blood to ascertain characteristics of the blood is provided. The probe includes a cannula adapted for insertion into a patient's blood vessel, and a gas sensor assembly mounted inside the cannula. The cannula has an anti-thrombogenic surface treatment for preventing blood components from adhering to the cannula when the cannula is in blood.

In another aspect of the invention, a probe for use with a patient having a blood vessel carrying blood to ascertain characteristics of the blood is provided. The probe includes a cannula having a proximal end and a distal end, the distal end being adapted to be inserted into a blood vessel of a patient. A gas sensor assembly is mounted inside the distal end of the cannula. The cannula has an annular window of gas permeable material extending around the gas sensor assembly.

In another aspect of the invention, a probe for use with a patient having a blood vessel carrying blood to ascertain characteristics of the blood is provided. The probe includes a cannula having a proximal end and a distal end, the distal end being adapted to be inserted into a blood vessel of a patient. An electrolyte solution is located in the cannula. A gas sensor assembly is mounted at the distal end of the cannula and includes an electrode in an electrolyte solution. The lead wire extends to the electrode, and the sealing glass extends around the lead wire. The lead wire has a thermal expansion coefficient, and the sealing glass has a thermal expansion coefficient approximately equal to that of the lead wire to prevent the lead wire from being separated from the sealing glass, thereby preventing an electrolyte solution from spreading between the lead wire and the sealing glass.

In another aspect of the invention, a device is provided for use with a patient having a blood vessel carrying blood to ascertain characteristics of the blood. The device includes a display module and a probe having a proximal end and a distal end. The distal end of the probe is adapted to be inserted into a blood vessel of a patient and has a gas sensor assembly for providing an electrical signal when the probe is located in the blood. The display module has a first connector and the proximal end of the probe has a second connector that mates with the first connector. The second connector has a cylindrical portion and an electrical contact extending around at least a portion of the cylindrical portion. A wire extends through the probe to electrically couple the gas sensor assembly to the electrical contact. The position of the electrical contacts is flush with the cylindrical portion so as to provide the second connector with a substantially smooth cylindrical surface. The first and second connectors allow connection and disconnection between the probe and the display module.

In another aspect of the invention, a probe for use with an introducer of a patient having a blood vessel carrying blood to ascertain characteristics of the blood is provided. The probe includes a cannula having a proximal end and a distal end. The distal end of the cannula is adapted to be inserted into a patient's blood vessel. A gas sensor assembly is located at the distal end of the cannula for providing an electrical signal when the cannula is in blood. A connector device is provided at the proximal end of the cannula. Whereby the distal end of the cannula is adapted to slide through the introducer when the cannula is inserted into the blood vessel. The cannula and the connector have dimensions that allow the introducer to slide off the proximal ends of the cannula and the connector after the distal end of the cannula is inserted into the blood vessel.

In one aspect, the invention also provides a device for use with a patient having a blood vessel carrying blood to ascertain characteristics of the blood. The device comprises a compact display module and a probe having a proximal end coupled to the display module and a distal end adapted for insertion into a patient's vessel. The distal end includes a sensor for providing an electrical signal to the display module when the probe is in blood. The probe has a calibration factor. The display module has a processor for processing the electrical signals to provide a reading, and a memory for storing the calibration coefficients. The processor is coupled to the memory to allow the processor to access calibration coefficients related to the processing of the electrical signals in order to enhance the accuracy of the readings.

In another aspect of the invention, a kit for use with a patient having a blood vessel carrying blood to ascertain characteristics of the blood is provided. The kit comprises a set of packages. Probes are contained within the package. The probe has a distal end adapted to be inserted into a patient's blood vessel and contains a sensor for providing an electrical signal. The probe has a calibration factor. A compact display module is contained within the package and has a processor and a non-volatile memory coupled to the processor. The calibration coefficients are stored in a memory of the display module. Whereby when the probe is coupled with the display module and the distal end inserted into the blood vessel and the electrical signal is received by the display module for providing a reading, the processor accesses the memory to utilize the calibration factor and thereby enhance the accuracy of the reading.

In another aspect of the invention, a probe for use with a patient having a blood vessel carrying blood to ascertain characteristics of the blood is provided. The probe includes a cannula adapted for insertion into a patient's blood vessel and having proximal and distal ends. An electrolyte solution is located at the distal end of the cannula. A gas sensor assembly is mounted at the distal end of the cannula and is located in the electrolyte solution. The gas sensor assembly includes a tube having a distal portion, and a first electrode coiled around the tube. The second electrode is carried by the distal portion of the tube. First and second leads extend from the proximal end of the cannula to the gas sensor assembly, the first lead being coupled to the first electrode, and the second lead extending through the tube and being coupled to the second electrode. The tube serves as a support for the first electrode and as a conduit for the second wire.

The invention also provides a probe for use with a patient having a blood vessel carrying blood to ascertain characteristics of the blood. The probe includes a cannula having a proximal end and a distal end. The distal end is adapted to be inserted into a blood vessel of a patient. The flexible circuit extends through at least a portion of the cannula. The flexible circuit has proximal and distal portions, and first and second electrodes formed on the distal portion, and first and second leads extending from the proximal portion to the first and second electrodes. An electrolyte solution is located at the distal end of the cannula adjacent the first and second electrodes.

Many of the probe and display modules according to the present invention have been fabricated and tested to demonstrate the feasibility and performance of the device. The following experimental data illustrate typical performance of the invention under experimental conditions.

Graph 1 shows the performance of representative examples of oxygen sensor probes over a range of dissolved oxygen concentrations at oxygen partial pressures of 0 to 150 mmHg. The response is linear over the range of interest making calibration to 5% accuracy a simple process.

Keimar’s O₂Response Curve of the probe at 37 ℃ (Probe # OX-090501-4)

Graph 1: oxygen sensor performance

In addition to exhibiting accuracy and linearity, oxygen sensors provide a rapid response to changes in dissolved oxygen concentration. Graph 2 shows the time response of a representative oxygen sensor probe to a series of step changes in oxygen partial pressure, confirming a settling time of less than 3 minutes within a 5% final value range.

Keimar O₂Response data of the probe at 37 ℃ (Probe # OX-090501-4)

Graph 2: oxygen sensor response

In addition to demonstrating accuracy, linearity, and rapid response, oxygen sensors also provide a lifetime of greater than 72 hours to meet the requirements of ICU/CCU monitoring applications. Graph 3 shows the stability of the oxygen sensor output over the course of a 90 hour long-term study. With constant temperature, room air, oxygen partial pressure of 150mmHg, the sensor output remains almost constant over a period of greater than 72 hours, except for minor expected changes in output due to temperature fluctuations and noise.

FIG. 3: oxygen sensor lifetime

Graph 4 shows the performance of representative examples of carbon dioxide sensor probes over a range of dissolved carbon dioxide concentrations at carbon dioxide partial pressures of 10 to 100 mmHg. The response shows the expected classical logarithmic performance of this type of pH-responsive sensor, making calibration to 5% accuracy a simple process.

Graph 4: carbon dioxide sensor performance

In addition to exhibiting accuracy and linearity, carbon dioxide sensors provide a fast response to changes in dissolved carbon dioxide concentration. Graph 5 shows the time response of a representative carbon dioxide sensor probe to a series of step changes in carbon dioxide partial pressure, confirming a set-up time of less than 3 minutes to the final value range of 5%.

FIG. 5: carbon dioxide sensor response

In addition to demonstrating accuracy, linearity, and fast response, carbon dioxide sensors also have an inherently longer lifetime because it does not consume electrode or electrolyte solution as does oxygen sensors.

Graph 6 shows the performance of a representative pH sensor output over a pH range of 4 to 10. The pH sensor is immobilized on a multi-sensor probe, wherein the multi-sensor probe further comprises an oxygen, carbon dioxide, and temperature sensor. The response shows a classical linear voltage response to a logarithmic pH parameter. The standard deviation of repeated measurements for one pH value is about 0.02pH, confirming that a calibration to the required 0.05pH accuracy is feasible over a physiological range of pH values of 7 to 8.

FIG. 6: pH sensor Performance

The response time of the pH sensor is fast, with a step change in pH occurring over a set-up time of about 10 seconds.

The sampled data shows that the accuracy, response time and lifetime provided by the oxygen, carbon dioxide and pH sensors according to the present invention meet the expected requirements of medical monitoring applications. All sampling probes have an outer diameter of 0.020 "as described in the preferred embodiment, and a single probe includes four sensors, namely oxygen, carbon dioxide, temperature and pH sensors.

In one aspect of the invention, a device is provided for use with a patient having a blood vessel carrying blood to ascertain characteristics of the blood. The apparatus comprises a display module and a probe having a distal end adapted to be inserted into a blood vessel of a patient and a proximal end coupled to the display module, the probe including a gas sensor assembly at the distal end for providing an electrical signal to the display module when the probe is in blood, the probe having an anti-thrombogenic surface treatment for preventing blood components from adhering to the probe when the probe is in blood.

The probe of such an apparatus may be gas permeable in the vicinity of the gas sensor assembly. The entire probe may be gas permeable and may be made of polymethylpentene. The surface treatment of such a device may be a hydrophilic surface treatment. The surface treatment of such a device may comprise a polyvinylpyrrolidone strand attached to the probe.

In another aspect of the invention, a probe for use with a patient having a blood vessel carrying blood to ascertain characteristics of the blood is provided. The probe includes a cannula adapted for insertion into a patient's blood vessel, the cannula having an anti-thrombogenic surface treatment for inhibiting blood components from adhering to the cannula when the cannula is in blood, and a gas sensor assembly mounted inside the cannula.

The cannula of such a probe may be gas permeable in the vicinity of the gas sensor assembly. The entire cannula may be made of a gas permeable material and such gas permeable material may be polymethylpentene. An electrolyte solution may be located within the cannula, and the gas sensor assembly may include first and second electrodes located in the electrolyte solution for providing an electrical output. The surface treatment of such a probe may be a coating. The surface treatment of such probes may be a hydrophilic surface treatment and may comprise a polyvinylpyrrolidone strand adhered to the probe.

In another aspect of the invention, a probe for use with a patient having a blood vessel carrying blood to ascertain characteristics of the blood. The probe may include a cannula having a proximal end and a distal end, the distal end adapted to be inserted into a blood vessel of a patient, the gas sensor assembly being mounted inside the distal end of the cannula, the cannula having an annular window of gas permeable material extending around the gas sensor assembly.

The entire cannula of such a probe may be made of a gas permeable material, and the gas permeable material may be polymethylpentene.

In another aspect of the invention, a probe for use with a patient having a blood vessel carrying blood to ascertain characteristics of the blood is provided. The probe may include a cannula having a proximal end and a distal end, the distal end adapted to be inserted into a blood vessel of a patient, an electrolyte solution located in the cannula, a gas sensor assembly mounted at the distal end of the cannula and including an electrode located in the electrolyte solution, a lead extending to the electrode, and a sealing glass extending around the lead, the lead having a coefficient of thermal expansion, and the sealing glass having a coefficient of thermal expansion approximately equal to the coefficient of thermal expansion of the lead to inhibit separation of the lead from the sealing glass, thereby inhibiting the electrolyte solution from extending between the lead and the sealing glass.

The wires of such probes have a cleaved end (cleaved extension) to form the active area of the electrode. The wire may be made of platinum. The gas sensor assembly of such a probe may include an additional electrode located in the electrolyte solution.

In another aspect, the invention provides a device for use with a patient having a blood vessel carrying blood to ascertain characteristics of the blood. The apparatus comprises a display module and a probe having a proximal end and a distal end, the distal end of the probe being adapted to be inserted into a blood vessel of a patient and having a gas sensor assembly for providing an electrical signal when the probe is positioned in blood, the display module having a first connector, the proximal end of the probe having a second connector that mates with the first connector, the second connector having a cylindrical portion and an electrical contact, wherein the electrical contact extends around at least a portion of the cylindrical portion, a wire extends through the probe electrically coupling the gas sensor assembly to the electrical contact, the electrical contact being positioned flush with the cylindrical portion so as to provide the second connector with a substantially smooth cylindrical surface, the first and second connectors allowing connection and disconnection between the probe and the display module.

The device may further comprise a strap connected to the display module for securing the control and display module to the wrist of the patient. Such a device may further comprise additional electrical contacts extending around at least a part of the cylindrical portion and being separate from the first-mentioned electrical contacts.

In another aspect of the invention, a probe for use with an introducer for a patient having a blood vessel carrying blood to ascertain characteristics of the blood. The probe may comprise a cannula having a proximal end and a distal end, the distal end of the cannula being adapted to be inserted into a blood vessel of a patient, the gas sensor assembly being located at the distal end of the cannula for providing an electrical signal when the cannula is located in blood, and the connector being provided at the proximal end of the cannula, whereby the distal end of the cannula is adapted to slide through the introducer when the cannula is inserted into the blood vessel, the cannula and the connector having dimensions that allow the introducer to slide off the proximal end of the cannula and the connector after the distal end of the cannula is inserted into the blood vessel.

Such a probe may be combined with an introducer. The introducer of such a probe may be a needle. The connector of such a probe may have a cylindrical portion and may have electrical contacts extending around at least a portion of the cylindrical portion and leads extending from the electrical contacts to the gas sensor assembly. The position of the electrical contacts of such a probe may be flush with the cylindrical portion in order to provide a connector with a substantially smooth cylindrical surface.

Another aspect of the invention is a device for use with a patient having a blood vessel carrying blood to ascertain characteristics of the blood. The device may comprise a compact display module and a probe having a proximal end coupled to the display module and a distal end adapted for insertion into a patient's vessel, the distal end including a sensor for providing an electrical signal to the display module when the probe is in blood, the probe having a calibration coefficient, the display module having a processor for processing the electrical signal to provide a reading, and a memory for storing the calibration coefficient, the processor being coupled to the memory to allow the processor to access the calibration coefficient in connection with the processing of the electrical signal so as to improve the accuracy of the reading.

The device may further comprise a strap connected to the display module for securing the display module to the wrist of the patient. The sensor of such a device may be selected from the group consisting of a gas sensor, an oxygen sensor, a carbon dioxide sensor, a pH sensor and a temperature sensor. Such a sensor may be a gas sensor assembly having first and second electrodes in an electrolyte solution. The display module of such devices may contain a wireless transmitter receiver circuit coupled to a processor to allow wireless reception of control signals from external sources, as well as wireless transmission of blood characteristics to external devices. The memory of such a device may be a non-volatile memory.

In another aspect of the invention, a kit for use with a patient having a blood vessel carrying blood to ascertain characteristics of the blood is provided. The kit may comprise a package within which the probe is contained and has a distal end adapted to be inserted into a patient's vessel, and a sensor for providing an electrical signal, the probe having a calibration factor, a compact display module contained within the package and having a processor and a non-volatile memory coupled to the processor, the calibration factor being stored in the memory of the display module, whereby when the probe is coupled to the display module and the distal end inserted into the vessel, and the electrical signal is received by the display module for providing a reading, the processor accesses the memory to utilize the calibration factor and thereby improve the accuracy of the reading.

The kit also includes a strap connected to the compact display module for securing the display module to the wrist of the patient. The sensors of the kit may be selected from the group consisting of gas sensors, oxygen sensors, carbon dioxide sensors, pH sensors and temperature sensors.

In another aspect of the invention, a probe for use with a patient having a blood vessel carrying blood to ascertain characteristics of the blood is provided. The probe may comprise a cannula adapted for insertion into a blood vessel of a patient and having a proximal end and a distal end, an electrolyte solution located at the distal end of the cannula, a gas sensor assembly mounted at the distal end of the cannula and located in the electrolyte solution, the gas sensor assembly having a tube with a distal portion, and a first electrode coiled around the tube, and a second electrode carried by the distal portion of the tube, first and second leads extending from the proximal end of the cannula to the gas sensor assembly, the first lead coupled to the first electrode, and the second lead extending through the tube and coupled to the second electrode, the tube thereby serving as a support for the first electrode, and as a conduit for the second lead.

The gas sensor assembly of such a probe may include a sealing glass that extends around the second lead of the distal portion of the tube to form the second electrode. The second wire may have a coefficient of thermal expansion, and the sealing glass has a coefficient of thermal expansion approximately equal to that of the second wire, so as to prevent the wire from separating from the sealing glass and thereby undesirably allow electrolyte solution to seep between the wire and the sealing glass. The second lead of the probe may have a platinum distal portion. The first electrode of the probe may be a reference electrode and the second electrode may be a carbon dioxide electrode. The first electrode of the probe may be a reference electrode and the second electrode may be an oxygen electrode.

In another aspect of the invention, a probe for use with a patient having a blood vessel carrying blood to ascertain characteristics of the blood is provided. The probe may include a cannula having a proximal end and a distal end, the distal end adapted to be inserted into a blood vessel of a patient, a flexible circuit extending through at least a portion of the cannula, the flexible circuit having proximal and distal portions, and first and second electrodes formed on the distal portion, and first and second leads extending from the proximal portion to the first and second electrodes, an electrolyte solution being located at the distal end of the cannula adjacent the first and second electrodes.

The cannula of the probe may be gas permeable adjacent the first and second electrodes. The entire cannula may be made of a gas permeable material. The gas permeable material of the probe may be polymethylpentene. The flexible circuit of the probe may include first and second layers of insulating material with first and second conductive lines extending along and between the first and second layers. Each of the first and second layers may have an exposed surface, and each of the first and second electrodes is a pad formed on one of the exposed surfaces of the first and second layers. The flexible circuit of the probe may include at least one layer of insulating material, first and second contact pads formed on the at least one layer of insulating material on a proximal portion of the flexible circuit and coupled to the first and second conductive lines, respectively, the first and second contact pads allowing electrical communication with the flexible circuit outside the patient's body. The cannula distal end may be adapted to slide through the introducer when the cannula is inserted into the blood vessel, the cannula and flexible circuit having dimensions that allow the introducer to slide off the proximal end of the cannula and flexible circuit after the distal end of the cannula is inserted into the blood vessel. The probe also includes an adhesive disposed inside the cannula for securing the flexible circuit within the cannula. The cannula of the probe may be provided with a sealed chamber in which the first and second electrodes are located and the electrolyte solution is located. The cannula of the probe may be equipped with an additional sealed chamber in which the third and fourth electrodes are located and an electrolyte solution is located.

While the invention is susceptible to various modifications and alternative forms, specific examples thereof are shown in the drawings and will herein be described in detail. It should be understood, however, that the invention is not to be limited to the particular forms or methods disclosed, but to the contrary, the invention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the appended claims.

Claims (16)

1. A small diameter probe for use with an introducer in a patient having a blood vessel carrying blood to ascertain characteristics of the blood, the probe comprising: a cannula having a proximal end and a distal end, the distal end of the cannula adapted to be inserted into a blood vessel of a patient; an oxygen and carbon dioxide sensor assembly located at the distal end of the cannula for providing an electrical signal when the cannula is located in blood; and a connector carried at a proximal end of the cannula, a distal end of the cannula being adapted to slide through the introducer when the cannula is inserted into the blood vessel, the cannula and the connector having dimensions such that: allowing the introducer to slide off the proximal end of the cannula and the connector after the distal end of the cannula is inserted into the blood vessel; the probe further comprises a flexible circuit extending through at least a portion of the cannula, the flexible circuit having proximal and distal portions, first and second electrodes formed on the distal portion of the flexible circuit, first and second leads extending from the proximal portion to the first and second electrodes, the first and second electrodes and the first and second leads forming at least a portion of the oxygen and carbon dioxide sensor assembly; the probe further comprises an electrolyte solution located at the distal end of the cannula adjacent the first and second electrodes, wherein the cannula is provided with a sealed chamber in which the first and second electrodes are located and the electrolyte solution is located within the sealed chamber.

2. The probe of claim 1 in combination with an introducer.

3. The probe of claim 2, wherein the introducer is a needle.

4. The probe of claim 1, wherein the connector has a cylindrical portion and has electrical contacts extending around at least a portion of the cylindrical portion and leads extending from the electrical contacts to the oxygen and carbon dioxide sensor assembly.

5. A probe according to claim 4, wherein the electrical contacts are located flush with the cylindrical portion so as to provide the connector with a substantially smooth cylindrical surface.

6. The probe of claim 1, wherein the cannula is provided with an additional sealed chamber in which the third and fourth electrodes are located, and an electrolyte solution is also located in the additional sealed chamber.

7. The probe of claim 1, wherein at least a portion of the proximal portion of the flexible circuit serves as the connector.

8. The probe of claim 1, wherein the flexible circuit has an exposed surface, each of the first and second electrodes being a pad formed on the exposed surface.

9. The probe of claim 1, further comprising an adhesive positioned inside the cannula to secure the flexible circuit within the cannula.

10. The probe of claim 1, wherein the cannula is gas permeable adjacent the oxygen and carbon dioxide sensor assembly.

11. The probe of claim 10, wherein the entire cannula is made of a gas permeable material.

12. The probe of claim 11, wherein the gas permeable material is polymethylpentene.

13. The probe of claim 1, wherein the connector has a cylindrical portion and electrical contacts extending around at least a portion of the cylindrical portion, wires extending through the probe electrically connecting the oxygen and carbon dioxide sensor assembly with the electrical contacts, the electrical contacts being positioned flush with the cylindrical portion to provide the connector with a substantially smooth cylindrical surface.

14. The probe of claim 13, further comprising an additional electrical contact extending around at least a portion of the cylindrical portion and separated from the first-mentioned electrical contact.

15. The probe of claim 1 in combination with a display module having a display connector to mate with a connector of the probe, the connector and the display connector allowing connection and disconnection between the probe and the display module.

16. The probe of claim 15, further comprising a strap coupled to the display module for securing the display module to a wrist of a patient.