Aqueous buffer protection system for biosensors

Abstract

To extend the usable life of a biosensor life while keeping a sensing system enclosed and minimizing the introduction of flushing solutions into a measurement line (e.g., a blood vessel) of a fluid system, such as a human blood vessel, a nutritional fluid line in a tissue cultivation system, or a circulation system in an organ preservation system.SOLUTION: A catheter, tube, or other lumen contains an active biosensor. One end of the lumen is introduced to a target fluid, and the other end is connected to a supply of a buffer solution (e.g., heparinized saline solution). By advancing the buffer solution along the lumen, a biological fluid (e.g., blood) can be purged from an area around a sensor material to halt any reactions. When a measurement is desired, then the buffer solution is withdrawn (e.g., suctioned) back into the supply, so that the biological fluid enters and contacts the sensor material.SELECTED DRAWING: Figure 4

Description

[Technical Field]

[0001] The present invention relates generally to sensors (eg, biosensors) for monitoring biological fluids such as blood, and more particularly to a protection system for extending the useful life of such biosensors. [Background technology]

[0002] Biosensors can be used to measure chemicals, other substances, and various properties of target biological fluids, such as blood. Measurands can include gas concentrations, protein concentrations, pH, and other parameters of the biological fluid. Some types of biosensors may use enzymes or other reactants to contact the fluid when making measurements. During their exposure to biological fluids, the reactions can eventually degrade the sensor material, causing the sensor to become less effective over time. In addition to sensor material degradation, the buildup of a protein layer or clotted blood around the sensor material during exposure can also reduce the sensor's effectiveness over time.

[0003] Examples of biosensors include enzyme-based amperometric glucose measurement sensors or blood parameter monitoring sensors such as the CDI® Blood Parameter Monitoring System available from Terumo Cardiovascular Systems Corporation, Ann Arbor, Michigan. The CDI® sensor measures pH, pCO2, pO2, K in the blood during cardiopulmonary bypass. + Visible fluorescence, reflectance, and / or other sensing elements are used to measure blood parameters including saturation, SO2, hemoglobin, hematocrit, etc. While continuous measurements may be desired in some cases, many parameters change slowly and therefore do not require continuous measurements. Instead, measurements may be taken periodically (especially during long-term monitoring). Summary of the Invention [Problem to be solved by the invention]

[0004] The objective of the present invention is to extend sensor life while keeping the sensing system enclosed (e.g., free from external contamination) and minimizing the introduction of flushing solutions into the measurement lines (e.g., blood vessels) of fluid systems targeted for measurement, which may include human blood vessels, nutrient fluid lines in tissue culture systems, circulatory systems in organ preservation systems, etc. [Means for solving the problem]

[0005] The present invention utilizes a catheter, tube, or other lumen to house an active biosensor. One end of the lumen is introduced into the target fluid, and the other end is connected to a source of buffer solution (e.g., heparinized saline). By advancing the buffer solution along the lumen, the biological fluid (e.g., blood) can be displaced from the area around the sensor material, halting any reactions. When a measurement is desired, the buffer solution is drawn back (e.g., aspirated) into the source, causing the biological fluid to enter the lumen and contact the sensor material. [Brief explanation of the drawings]

[0006] [Figure 1] FIG. 1 is a cross-sectional view of a conventional stylus sensor. [Figure 2] 1 is a cross-sectional view of an improved stylus sensor according to one embodiment of the present invention. [Figure 3] FIG. 3 is a side view of an alternative sensor element useful in the stylus sensor of FIG. 2. [Figure 4] FIG. 2 is a schematic diagram of another embodiment of the present invention. [Figure 5] 1 is a graph showing a sensor output signal over a measurement period. [Figure 6] FIG. 10 is a diagram of another embodiment of the present invention including multiple sensors along a series of capillaries. [Figure 7] FIG. 1 is a diagram of the hollow fiber portion of the base tissue culture system. [Figure 8]FIG. 8 is a diagram of a sensor and protection system adapted to obtain measurements within the hollow fibers of the tissue culture system of FIG. 7. [Figure 9] FIG. 10 is a diagram of an embodiment having a series of tandem sensors along a fluid path that are operated in stages. [Figure 10] FIG. 10 is a diagram of another embodiment including a tandem sensor. [Figure 11] 1 is a flow chart illustrating one preferred method for operating a tandem sensor. [Figure 12] 1 is a graph showing measured sensor values ​​for a target parameter over time, where sensor degradation results in a decrease in sensitivity to the target parameter. [Figure 13] FIG. 10 is a block diagram illustrating compensation of sensor measurements based on the contamination of a known low concentration of a target parameter in a buffer solution. [Figure 14] 1 is a flow diagram illustrating a method for detecting end of life of an individual sensor and for initiating a switchover to a new sensor in a group of tandem sensors. DETAILED DESCRIPTION OF THE INVENTION

[0007] 1 shows a conventional stylus sensor system that includes a hollow injection needle 10 having a tip that penetrates a blood vessel 11 and enters a blood stream 12. A sensor 13 has a sensing tip 14 that penetrates the blood stream 12 and provides a sensor output signal to a measurement circuit via electrical wire 15. Once the system is implanted in a patient, the sensor 13 remains in place and is continuously exposed to the blood stream 12.

[0008] In a first embodiment of the invention shown in FIG. 2, a sensing system 20 includes an implantable catheter 21 including a central lumen 22. The catheter 20 penetrates a blood vessel 23 and enters a blood stream 24. The catheter 21 has an open distal end 25. A sensor element 26 has a head end 27, an elongated body 28, and a tip 30. The elongated body 28 passes in a sealed manner through a fitting 31, which encloses and seals the proximal end of the catheter 21 when the sensor element 26 is attached. The length of the body 28 and catheter 21 is configured so that the tip 30 remains within the internal lumen 22 and is spaced a distance D from the distal end 25. A signal line 33 carries a sensor output signal from the sensor head 27 to measurement circuitry.

[0009] The fixture 31 includes an inlet 35 for receiving a buffer solution 36 from a reservoir 37 via tubing 38. The buffer solution 36 may be comprised of water or saline (e.g., Ringer's solution) and may include an anticoagulant such as heparin. The reservoir 37 has a volume sufficient to provide the buffer solution to fill the lumen 22. A plunger 39 is mounted for reciprocating longitudinal motion inside the reservoir 37 to selectively pump the buffer solution into the lumen 22 (e.g., toward the distal tip 25) by advancing the plunger 39 or to selectively withdraw the buffer solution from the lumen 22 (e.g., into the reservoir 37) by retracting the plunger 39. When the buffer solution is withdrawn from the lumen 22, suction draws blood from the bloodstream 24 into the lumen 22 so that the sensor tip 30 can be immersed in blood to perform the desired measurement. The plunger 39 may be threaded or connected to a shaft or other component that is threaded complementarily to the threaded inner diameter 40 of the reservoir 37, for example, to obtain longitudinal movement by rotating the plunger 39.

[0010] The sensor element 26 may consist of a microsensor containing an enzyme-modified electrode. Alternatively, a fiber optic microsensor 45 may be used, as shown in Figure 3. Fluorescent dye tip The tip 46 produces light when stimulated by a light source via an optical fiber, which varies depending on the particular parameter of the target fluid being monitored. The tip 46 is in a position such that when the sensor 45 is installed in the sensing system of FIG. 2, the tip 46 will be protected within the catheter lumen.

[0011] FIG. 4 shows another embodiment of a sensor system 50 for measuring properties of a sample fluid 51 in a conduit 52 (e.g., a blood vessel such as an artery, or a tissue culture system nutrient line). An enzyme-based or other type of sensor 53 is mounted in thin tubing 54 between the conduit 52 and a buffer solution supply unit 55. The sensor 53 is positioned so as to be exposed to the fluid in the tubing 54 and provides an electrical output signal to a controller or other measurement circuit (not shown). The supply unit 55 has a reservoir chamber 56 that contains a buffer solution 57. The unit 55 preferably has a cylindrical shape with a plunger 58 that is longitudinally movable while maintaining a fluid seal around its periphery. A handle 60 can be manipulated to move back and forth to control the flow of the buffer solution 57 in either direction through the tubing 54.

[0012] Tubing 54 is sufficiently narrow to minimize mixing of buffer solution 57 and sample fluid 51 along interface 61. By advancing plunger 58 into reservoir chamber 56, interface 61 can be sequentially advanced along positions A, B, and C. At position A, sensor 53 is exposed to sample fluid 51 and a measurement can be taken. At position C, sensor 53 is immersed in buffer solution 57, thereby inhibiting degradation of the sensor material. Thus, by appropriately moving plunger 58 (e.g., using a servo mechanism or manually), measurements can be obtained at a desired frequency while minimizing exposure of the sensor material and extending the sensor's useful life.

[0013] FIG. 5 illustrates a preferred method for controlling the plunger according to a desired sampling time. At an initial time in the graph of FIG. 5, the plunger may be in an advanced position such that the interface between the buffer solution and the sample fluid is at position C (i.e., the sensor is contacted by the buffer solution). The plunger is gradually retracted through position B, resulting in an increase in the sensor's output as the sample fluid is exposed. After the interface passes the sensor toward position A, the sensor output eventually reaches a saturation point where the sensor output levels off. Once the saturation point is reached (e.g., at position A), the plunger is held stable for the desired measurement interval. Depending on the mixing of the fluid at the interface and other factors over time, the plateauing may not occur until after multiple measurement cycles and progressively greater retraction of the plunger. By waiting for the saturation point to be detected, the present invention ensures that an undiluted sample of the sample fluid has reached the sensor.

[0014] At the end of the sampling period, the plunger is advanced to push against the interface, through position B, and back to position C. The sensor output can be monitored during plunger advancement. If the sensor output disappears, plunger advancement can be stopped.

[0015] 6 shows another embodiment in which one or more sensors are associated with the sample fluid by one or more sections of tubing. A blood vessel 70, or other conduit for sample fluid 72, is penetrated by a catheter or needle 71, which can carry fluid 72 to sensor 73. Sensor 73 is an in-line sensor that further advances fluid 72 via tubing 75 to another in-line sensor 74. A tubing section 78 connects sensor 74 to a supply unit 76 filled with buffer solution 77. Tube section 78 is a long line to reduce contamination and / or mixing. Compressing (i.e., squeezing) unit 76 advances buffer solution 77 through sensors 73 and 74, while decompressing (i.e., releasing) unit 76 advances sample fluid 72 to sensors 73 and 74. and advances into 74. Unit 76 may be a resilient elastomeric sphere that naturally re-expands after squeezing.

[0016] FIG. 7 shows a hollow fiber unit 80 (e.g., a bioreactor) having multiple hollow fibers 81 within an extracapillary space 82. In some embodiments, cells to be cultured can be placed within space 82 while a nutrient supply is circulated through fibers 81. This type of tissue culture system is described in U.S. Patent Application Publication No. 2016 / 0024455 A1, which is incorporated herein by reference. Chemical monitoring may be desired for at least one of the cellular components or the nutrient supply. The nutrient fluid may also destroy material in various sensors that can be used to characterize the fluid's condition. FIG. 8 shows one embodiment of the present invention adapted for use in a bioreactor. A chamber 85 is formed between flexible sheets 86 and 87 that are sealed together around the periphery of chamber 85. Chamber 85 is filled with a buffer solution 88. Sheet 87 is pierced by a catheter or needle 90 adapted for installation within the hollow fibers or interior chamber of a tissue culture device. A sensor 91 is mounted within catheter 90 to provide a sensor output signal to measurement circuitry (not shown). Pusher 92 can be activated to depress a coil spring 93 located within chamber 85 such that chamber 85 is compressed and buffer solution 88 is advanced along catheter 90 .

[0017] In addition to extending the useful life of a single sensor or a combination of various sensors, some embodiments of the present invention can achieve even longer-term extensions of the useful life of a sensing system by incorporating redundantly connected tandem sensors (e.g., sensors of the same type) in a serial configuration, allowing the first and second sensors to be exposed until their performance deteriorates, and then utilizing the sensor signal of only the second sensor. Additional sensors in the series may be utilized in the same manner, such that the third sensor is not exposed to the target fluid until the second sensor deteriorates. As a result, sensing of target parameters can occur for longer periods of time without requiring interruption of treatment or replacement of any devices or fluid conduits. The extended effective sensing time allows for the use of higher sampling frequencies (i.e., shorter times between successive samples) to better characterize the extracted parameters and respond more quickly to anomalies.

[0018] FIG. 9 illustrates a biosensor system for measuring properties of a sample fluid 105 in a body (e.g., a blood vessel) or tissue culture system. A buffer solution supply unit 100 has a reservoir chamber 103 that contains a buffer solution 102. The unit 100 preferably has a cylindrical shape with a plunger 101 that is longitudinally movable while maintaining a fluid seal around its periphery. The plunger 101 may include a handle coupled to an actuator (e.g., a linear motor, not shown) that moves the plunger 101 back and forth to control the flow of the buffer solution 102 in both directions through a conduit or tube 104. The actuator may be controlled by a control device 110 (e.g., a microcontroller). Tandem sensors S1, S2, and S3 are substantially identical (e.g., enzyme-based) sensors coupled in series along the tube 104 for controlled exposure to the buffer solution 102 or sample fluid 105. Each section of tubing 104 is relatively thin (i.e., the cross-sectional diameter is much smaller than the tubing length) to minimize mixing of the sample fluid 105 and buffer solution 102 at the fluid interface, which is initially at position 106 when tubing 104 enters the body (e.g., a blood vessel). When sampling first begins (i.e., all sensors have maximum remaining life), sample fluid 105 is delivered to sensor S1 only (considered a Stage 1 operation) by retracting plunger 101 a distance that retracts the fluid interface to position 107. During Stage 1, controller 110 exchanges electrical signals with sensor S1 (e.g., a drive signal to S1 and a measurement signal returned from S1). At the end of sample acquisition, Instead, plunger 101 is returned to its forward position so that the fluid interface returns to position 106. Stage 1 operation lasts for the useful life of sensor S1. During Stage 1, sensors S2 and S3 are never exposed to sample fluid 105, only buffer solution 102, and controller 110 ignores sensors S2 and S3. At the end of life (EOL) of sensor S1, sampling enters Stage 2 operation, in which sample fluid 105 is delivered to sensors S1 and S2 by retracting plunger 101 a distance that retracts the fluid interface to position 108 within tube 104. In Stage 2, controller 110 exchanges signals with sensor S2 and ignores sensors S1 and S3. At the EOL of sensor S2, sampling enters Stage 3 operation, in which sample fluid 105 is delivered to sensors S1, S2, and S3 by retracting plunger 101 a distance that retracts the fluid interface to position 109 within tube 104. In Stage 3, controller 110 exchanges signals with sensor S3 and ignores sensors S1 and S2. Between measurements in Stages 2 and 3, the fluid interface is preferably returned to position 106, but alternatively may simply be returned to a position that returns the buffer solution to the sensors that are then used to obtain the measurement results.

[0019] 10 shows another tandem embodiment in which tube 120 has successive sensors passing through it at respective positions along its length. Tube 120 is sufficiently narrow to minimize mixing of the buffer solution and sample fluid as the fluid interface is moved to various positions 121, 122, and 123 between successive sensors as each sensor is used at a respective stage of operation.

[0020] A preferred method of the present invention is shown in FIG. 11 , where the plunger is operating in Stage 1 mode in step 130. In step 131, the controller utilizes signals from sensor S1. A check is made in step 132 to determine if sensor S1 has reached an end-of-life (EOL) condition. The check may be based on the number of measurement cycles performed (compared to a threshold count) and / or the cumulative measurement time that sensor S1 has been exposed to the sample fluid (compared to a predetermined time period). Alternatively, the check may be based on an analysis of the sensor signal performed by the controller to detect when measurement performance has degraded. If the EOL of sensor S1 has not been reached, use of Stage 1 continues, and the EOL condition of sensor 1 is continuously monitored in step 132.

[0021] Once the EOL for sensor S1 is reached, the plunger begins operating in Stage 2 mode in step 133. The controller switches to utilize the sensor signal from sensor S2 in step 134. EOL is verified for sensor S2 in step 135. Once the EOL for sensor S2 is reached, the plunger operates in Stage 3 mode in step 136 and the controller switches to utilize the signal from sensor S3 in step 137.

[0022] In a further aspect of the invention, the degradation state of the sensor can be monitored throughout the sensor's useful life, and using the degradation state of the sensor, continuous calibration of the measurement is used to compensate for measurement errors that would otherwise affect conventional devices.

[0023] Because there is minimal mixing between the buffer solution and the target fluid, the composition of the buffer solution is substantially stable during use. A small but measurable amount of the target chemical, measured by the sensor, can be added to the buffer solution (preferably at a precisely controlled concentration). The amount of target chemical can be small enough so that there is little degradation of the sensor even when in contact with the sensor for an extended period of time. Thus, a predetermined calibration concentration of the target substance is added, where the calibration concentration is below the range of expected concentrations of the target substance to be encountered in the target fluid. If degradation occurs as a result of exposure to the target fluid during the accumulation of concentration measurements in the target fluid, the measured concentration in the buffer solution will also decrease. Because the actual concentration of the buffer solution is known, the difference between the degraded measurement result for the buffer solution and the known concentration can be used to determine the degree of degradation and to compensate the measured concentration of the target fluid.

[0024] For example, a sensor for monitoring blood lactate (e.g., to detect oxygen deficiency and / or organ failure during a surgical procedure) may need to measure lactate concentrations ranging from 30 to 50 mmol / L. The sensor may be configured with the CDI® blood parameter monitoring system described above or other commercially available sensors. By adding lactate to a buffer solution at a concentration of only 5 mmol / L, the sensor chemistry (e.g., a photoreactive dye) does not significantly degrade. However, during cyclic exposure to high levels of lactate in the target fluid, the sensor degrades, resulting in lower measurements for lactate concentration. Thus, measurements taken for the buffer solution (during a measurement period for the target fluid) may decrease to 4 or 3 mmol / L, and this decrease can be used to detect and / or compensate for sensor degradation.

[0025] As shown in FIG. 12, measurements from the sensor can degrade over time. Initially, a baseline value 140 is measured during exposure to a buffer solution with a known, predetermined value of approximately 5.0 mmol / L. The buffer solution is withdrawn from the sensor so that the sensor is exposed to the target fluid. After a transition period, a measurement value 141 is obtained for the target. The buffer solution is then advanced over the sensor during a dwell period and withdrawn to expose the sensor to the target fluid during a measurement period. The sensor degrades during the measurement period due to exposure to high concentrations of the target substance. During the dwell period, sensor measurements are periodically obtained for comparison with the known value. Subsequently (when degradation is occurring), a measurement value 142 obtained during the dwell period has an erroneous value of approximately 3.0 mmol / L. The decrease in the measurement value quantifies the magnitude of degradation that has occurred. Subsequent measurements 143 obtained for the target fluid degrade by the same magnitude. The difference between values ​​140 and 142 identifies a correction that can be applied to measurement value 143 to compensate for sensor degradation.

[0026] As shown in Figure 13, the measured concentration values ​​145 obtained for the target fluid are input into a correction coefficient matrix 146. Matrix 146 may be comprised of empirically derived correction coefficients that compensate for changes in sensor output at various levels of degradation. Matrix 146 may alternatively be comprised of equations or formulas. For example, for a 10% decrease in measurement buffer concentration, the measured target fluid concentration may be multiplied by 1.1.

[0027] To identify the appropriate coefficients to be applied, the most recent measured concentration values ​​147 for the buffer solution are input into matrix 146. Matrix 146 outputs measured target concentrations with improved accuracy based on the selected coefficients.

[0028] The rest measurement can be used to detect an end-of-life condition for any particular sensor. When the drop in detected value for the target substance in the buffer solution falls below a threshold, the particular sensor can no longer be trusted. The next sensor in the tandem sensor is then used, or if no other sensor is available, an error message can be generated to notify the user. For example, in a sensor system that measures glucose and has glucose added to a buffer solution at a concentration of 5 mol / L, the sensor can be considered to have reached its end-of-life when the detected amount of glucose during the rest period falls below 3 mol / L.

[0029] FIG. 14 shows a corresponding method in which the concentration of a target substance in a buffer solution is measured in step 150. A check is made in step 151 to determine whether the measured concentration is below a threshold value. The threshold value is selected to indicate a level of degradation above which the sensor is no longer suitable for use. If the measured concentration is not below the threshold value, the process returns to step 150 for a subsequent repeat of the check. If the measured concentration is below the threshold value, a check is made in step 152 to determine whether there are any remaining sensors that have not yet been exposed to biological fluid (e.g., blood). If there are no remaining sensors (e.g., no tandem sensors or the last tandem sensor has been used up), an error message is generated in step 153. Otherwise, a switch is made to a remaining sensor that still has useful remaining life. The newly selected sensor can then be monitored for degradation by returning to step 150. The present invention includes the following aspects. 1. A biosensor system comprising: a conduit having an inner lumen including a first end for receiving a target biological fluid and a second end; a sensor coupled to the lumen remote from the source of the target fluid; a supply unit for a buffer solution coupled to the lumen; Equipped with A biosensor system in which the supply unit includes a mechanism for advancing a buffer solution along the lumen so that the target fluid can be expelled from the area around the sensor, and when measurement is desired, the buffer solution is drawn back into the supply unit, thereby allowing biological fluid to enter the lumen and contact the sensor. 2. The biosensor system of claim 1, wherein the conduit comprises an implanted catheter configured to penetrate a blood vessel and the target fluid comprises blood. 3. The biosensor system according to 1., wherein the buffer solution is composed of physiological saline. 4. The biosensor system described in 1., wherein the supply unit includes a reservoir for storing a buffer solution, and the mechanism comprises a plunger mounted for reciprocating longitudinal movement inside the reservoir to selectively pump the buffer solution into the lumen by advancing the plunger, or to selectively withdraw the buffer solution from the lumen by retracting the plunger. 5. A biosensor system comprising: a conduit having an inner lumen including a first end for receiving a target biological fluid and a second end; a plurality of sensors coupled to the lumen at a series of spaced apart locations between the first end and the second end; a supply unit for a buffer solution coupled to the lumen; Equipped with the supply unit includes a mechanism for advancing a buffer solution along the lumen so that the target fluid can be displaced from a respective region in each of the sensors, and when a measurement is desired, the buffer solution is drawn back into the supply unit, thereby allowing the biological fluid to enter the lumen and contact at least one of the sensors; A biosensor system in which a buffer solution is advanced and withdrawn in stages, in a first stage only a first sensor is exposed to the target fluid, the first stage lasts for a first period of time, and a second stage follows the first stage, in which only the first and second sensors are exposed to the target fluid. 6. The biosensor system described in 5., wherein the second stage lasts for a second period of time and the third stage follows the second stage, and in the third stage the first sensor, the second sensor, and the third sensor are exposed to the target fluid. 7. The biosensor system of claim 5, wherein the conduit comprises an implanted catheter configured to penetrate a blood vessel and the target fluid comprises blood. 8. The biosensor system according to claim 5, wherein the buffer solution is composed of physiological saline. 9. The biosensor system of claim 5, wherein the supply unit includes a reservoir for storing a buffer solution, and the mechanism comprises a plunger mounted for reciprocating longitudinal movement inside the reservoir to selectively pump buffer fluid into the lumen by advancing the plunger, or to selectively withdraw buffer solution from the lumen by retracting the plunger. 10. A biosensor system comprising: a conduit having an inner lumen including a first end for receiving a target biological fluid and a second end; a sensor coupled to the lumen remote from the source of target fluid for detecting the target substance; a supply unit for a buffer solution coupled to the lumen; Equipped with the supply unit includes a mechanism for advancing a buffer solution along the lumen so that the target fluid can be displaced from the area around the sensor, and when a measurement is desired, the buffer solution is drawn back into the supply unit, thereby allowing the biological fluid to enter the lumen and contact the sensor; the buffer solution includes a predetermined calibration concentration of the target substance, the calibration concentration being less than a predetermined concentration range of the target substance in the target fluid; A biosensor system in which the difference between a measurement result of a target substance in a buffer solution and a predetermined calibration concentration determines a correction to be applied to the measurement for the target fluid. 11. The biosensor system according to claim 10, wherein the measurement result of the target substance in the buffer solution identifies the end of life of the corresponding sensor when the measurement result is below a threshold value. 12. The biosensor system of claim 10, wherein the conduit comprises an implanted catheter configured to penetrate a blood vessel and the target fluid comprises blood. 13. The biosensor system according to claim 10, wherein the buffer solution is composed of physiological saline. 14. The biosensor system of claim 10, wherein the supply unit includes a reservoir for storing a buffer solution, and the mechanism comprises a plunger mounted for reciprocating longitudinal movement inside the reservoir to selectively pump the buffer solution into the lumen by advancing the plunger, or to selectively withdraw the buffer solution from the lumen by retracting the plunger.

Claims

1. 1. A biosensor system comprising: a conduit having a lumen including a first end for receiving the target biological fluid and a second end; a sensor coupled to the lumen remote from the source of the target biological fluid and configured to detect a target substance; a supply unit for a buffer solution containing the target substance at a predetermined concentration, connected to said lumen; Equipped with the supply unit includes a mechanism for advancing the buffer solution along the lumen so that the target fluid can be displaced from the area around the sensor, and when a measurement is desired, the buffer solution is drawn back into the supply unit, thereby allowing the biological fluid to enter the lumen and contact the sensor; The biosensor system is configured such that a measurement of the target substance in the buffer solution indicates end of life for the corresponding sensor when the measurement is below a threshold value.

2. 10. The biosensor system of claim 1, wherein the conduit comprises an implanted catheter configured to penetrate a blood vessel, and the target fluid comprises blood.

3. The biosensor system of claim 1 , wherein the buffer solution is comprised of saline.

4. 2. The biosensor system of claim 1, wherein the supply unit includes a reservoir for storing the buffer solution, and the mechanism is comprised of a plunger mounted for reciprocating longitudinal movement inside the reservoir to selectively pump the buffer solution into the lumen by advancing the plunger or to selectively withdraw the buffer solution from the lumen by retracting the plunger.

5. 1. A biosensor system comprising: a conduit having a lumen including a first end for receiving the target biological fluid and a second end; a sensor coupled to the lumen remote from the source of the target fluid for detecting a target substance; a supply unit for a buffer solution coupled to said lumen; Equipped with the supply unit includes a mechanism for advancing the buffer solution along the lumen so that the target fluid can be displaced from the area around the sensor, and when a measurement is desired, the buffer solution is drawn back into the supply unit, thereby allowing the biological fluid to enter the lumen and contact the sensor; the buffer solution includes a predetermined calibration concentration of the target substance, the predetermined calibration concentration being less than a predetermined concentration range of the target substance in the target fluid; the difference between the measurement result of the target substance in the buffer solution and the predetermined calibration concentration determines a correction to be applied to the measurement for the target fluid; The biosensor system, wherein the measurement of the target substance in the buffer solution identifies an end of life for the corresponding sensor when the measurement is below a threshold value.

6. The biosensor system of claim 5 , wherein the conduit comprises an implantable catheter configured to penetrate a blood vessel, and the target fluid comprises blood.

7. The biosensor system of claim 5 , wherein the buffer solution is comprised of saline.

8. 6. The biosensor system of claim 5, wherein the supply unit includes a reservoir for storing the buffer solution, and the mechanism is comprised of a plunger mounted for reciprocating longitudinal movement inside the reservoir to selectively pump the buffer solution into the lumen by advancing the plunger or to selectively withdraw the buffer solution from the lumen by retracting the plunger.

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