Aqueous buffer protection system for biosensors

Abstract

The useful life of a biosensor is extended while keeping the sensing system enclosed and minimizing the introduction of flushing solutions into measurement lines (e.g., blood vessels) in fluid systems such as human blood vessels, nutrient fluid lines in tissue culture systems, or circulatory systems in organ preservation systems. A catheter, tube, or other lumen houses the 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, terminating any reactions. When a measurement is desired, the buffer solution is drawn back (e.g., aspirated) into the source, thereby allowing the biological fluid to enter and contact the sensor material.

Description

Technical Field

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

Background Art

[0002] Biosensors can be used to measure chemicals, other substances, and various properties of a target biological fluid such as blood. The measured quantities can include gas concentration, protein concentration, pH, and other parameters of the biological fluid. Some types of biosensors can use enzymes or other reactants to contact the fluid when making measurements. While they are exposed to the biological fluid, the reaction can ultimately degrade the sensor material, thereby causing the sensor to become less effective over time. In addition to the degradation of the sensor material, the accumulation of a protein layer or clotted blood around the sensor material during exposure can also reduce the effectiveness of the sensor 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 of Ann Arbor, Michigan. The CDI® sensor uses visible fluorescence, reflectance, and / or other detection elements to measure blood parameters including pH, pCO2, pO2, K + , SO2, hemoglobin, hematocrit, etc. Continuous measurements may be desired in some cases, but many parameters change slowly, so continuous measurements are not required. Instead, measurements can be made periodically (especially during long-term monitoring).

Summary of the Invention

Problems to be Solved by the Invention

[0004] The object of the present invention is to extend the sensor life while keeping the detection system in an enclosed state (e.g., not subject to external contamination) and minimizing the introduction of a flushing solution into the measurement line (e.g., blood vessel) of the fluid system. The fluid system to be measured may include human blood vessels, nutrient fluid lines in tissue culture systems, circulation systems in organ preservation systems, and the like.

Means for Solving the Problem

[0005] The present invention utilizes a catheter, a tube, or other lumen to accommodate an active biosensor. One end of the lumen is introduced into the target fluid, and the other end is connected to a source of a buffer solution (e.g., heparinized saline). By advancing the buffer solution along the lumen, biological fluid (e.g., blood) can be expelled from the region around the sensor material to stop any reaction. When measurement is desired, the buffer solution is drawn back (e.g., suctioned) into the source, thereby allowing the biological fluid to enter the lumen and contact the sensor material.

Brief Description of the Drawings

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[0007] FIG. 1 shows a conventional touch needle sensor system including a hollow injection needle 10 having a tip that penetrates blood vessel 11 and enters blood flow 12. Sensor 13 has a sensing tip 14 that penetrates blood flow 12 and provides a sensor output signal to a measurement circuit through wire 15. When the system is implanted in a patient, sensor 13 remains in a predetermined position and is continuously exposed to blood flow 12.

[0008] In the first embodiment of the present invention shown in FIG. 2, the detection system 20 has an implantable catheter 21 including a central lumen 22. The catheter 20 penetrates through a blood vessel 23 and enters the blood flow 24. The catheter 21 has an open distal end 25. The sensor element 26 has a head end 27, an elongated body 28, and a tip 30. The elongated body 28 passes through the fixture 31 in a sealed manner. The fixture 31 encloses and seals the proximal end of the catheter 21 when the sensor element 26 is attached. The lengths of the body 28 and the catheter 21 are configured such that the tip 30 remains within the inner lumen 22 and is spaced from the distal end 25 by a distance D. The signal line 33 conveys the sensor output signal from the sensor head 27 to the measurement circuit.

[0009] The fixture 31 includes an inlet 35 for receiving the buffer solution 36 from the reservoir 37 via the tube 38. The buffer solution 36 may be composed of water or physiological saline (e.g., Ringer's solution), and may also contain an anticoagulant such as heparin. The reservoir 37 has a volume sufficient to provide a buffer solution for filling the lumen 22. The plunger 39 is mounted inside the reservoir 37 to selectively pump the buffer solution into the lumen 22 (e.g., towards 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 for reciprocating longitudinal movement. To immerse the sensor tip 30 in the blood for performing a desired measurement, when the buffer solution is withdrawn from the lumen 22, the blood is drawn into the lumen 22 from the blood flow 24 by the suction force. The plunger 39 may be screwed or connected to a shaft or other component that is complementarily threaded 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 can be composed of a microsensor including an enzyme-modified electrode. Alternatively, as shown in FIG. 3, an optical fiber microsensor 45 may be used. The fluorescent dye tip 46 generates light when stimulated by a light source via the optical fiber, which varies according to specific parameters of the target fluid being monitored. The tip 46 is positioned such that when the sensor 45 is installed within the detection system of FIG. 2, the tip 46 is protected within the catheter lumen.

[0011] FIG. 4 shows another embodiment of a sensor system 50 for measuring the characteristics of a sample fluid 51 within a conduit 52 (such as a blood vessel like an artery or a nutrient line of a tissue culture system). An enzyme-based or other type of sensor 53 is mounted within a thin tube 54 between the conduit 52 and a buffer solution supply unit 55. The sensor 53 is arranged to be exposed to the fluid within the tube 54 and provides an electrical output signal to a control device or other measurement circuitry (not shown). The supply unit 55 has a reservoir chamber 56 that houses a buffer solution 57. The unit 55 preferably has a cylindrical shape together with a plunger 58, and the plunger 58 is movable longitudinally while maintaining a fluid seal around its periphery. A handle 60 can be operated to move back and forth in order to control the flow of the buffer solution 57 in both directions through the tube 54.

[0012] The tube 54 is sufficiently thin to minimize the mixing of the buffer solution 57 and the sample fluid 51 along their interface 61. By advancing the plunger 58 into the reservoir chamber 56, the interface 61 can be advanced sequentially along positions A, B, and C. At position A, the sensor 53 is exposed to the sample fluid 51 and measurements can be taken. At position C, the sensor 53 is immersed in the buffer solution 57, as a result of which deterioration of the sensor material is suppressed. Therefore, by appropriately moving the plunger 58 (for example, using a servo mechanism or manually), measurement results can be obtained at a desired frequency while minimizing the exposure of the sensor material and extending the useful life of the sensor.

[0013] Figure 5 shows a preferred method of controlling the plunger according to the desired sampling time. At the initial time in the graph of Figure 5, the plunger can be in the forward 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, and as a result, the sensor is exposed to the sample fluid and the sensor output increases. After the interface passes over the sensor towards position A, the sensor output eventually reaches a saturation point where the sensor output levels off. When the saturation point (e.g., at position A) is reached, the plunger is held steady during the desired measurement interval. Depending on the mixing of the fluids at the interface and other factors that occur over time, the leveling off may not occur until after a plurality of measurement cycles have been performed and a gradually increasing retraction of the plunger has been obtained. By waiting for the detection of the saturation point, the present invention ensures that an undiluted sample of the sample fluid reaches the sensor.

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

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

[0016] FIG. 7 shows a hollow fiber unit 80 (e.g., a bioreactor) having a plurality of hollow fibers 81 within an extra-capillary space 82. In some embodiments, cells to be cultured can be disposed within the space 82 while a nutrient supply is circulated through the fibers 81. This type of tissue culture system is described in U.S. Patent Application No. 2016 / 0024455A1, which is incorporated herein by reference. Chemical monitoring may be desired for at least one of the cell components or the nutrient supply. The nutrient fluid may also destroy the materials in various sensors used to characterize the state of the fluid. FIG. 8 shows an 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 the chamber 85. The chamber 85 is filled with a buffer solution 88. The sheet 87 is penetrated by a catheter or needle 90 adapted for placement into the hollow fibers or internal chamber of a tissue culture device. A sensor 91 is mounted within the catheter 90 to provide a sensor output signal to a measurement circuit (not shown). An extruder 92 can be actuated to depress a coil spring 93 installed within the chamber 85 so that the chamber 85 is compressed and the buffer solution 88 is advanced along the catheter 90.

[0017] In addition to extending the service life of a single sensor or a combination of various sensors, some embodiments of the present invention incorporate tandem sensors (e.g., sensors of the same type) redundantly connected in series, whereby a further long-term extension of the service life of the detection system can be obtained. This arrangement exposes only the first sensor until the performance of the first sensor degrades, and then allows the first sensor and the second sensor to be exposed while utilizing only the sensor signal of the second sensor. Additional sensors that are present in succession, such as the third sensor not being exposed to the target fluid until the second sensor degrades, may be utilized in the same manner. As a result, detection of the target parameter can be carried out over a longer period of time without interruption of treatment or the need for replacement of any device or fluid conduit. The extended effective detection time enables the use of a higher sampling frequency (i.e., the time between consecutive samples is short) to more characterize the extracted parameter and respond more quickly to anomalies.

[0018] Figure 9 shows a biosensor system for measuring the properties of a specimen fluid 105 within a body (e.g., a blood vessel) or a tissue culture system. A buffer solution supply unit 100 has a reservoir chamber 103 that contains a buffer solution 102. Unit 100 preferably has a cylindrical shape together with a plunger 101, and the plunger 101 is movable longitudinally 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 can be controlled by a control device 110 (e.g., a microcontroller). The tandem sensors S1, S2, and S3 are substantially identical (e.g., enzyme-based) sensors that are coupled in series along the tube 104 for controlled exposure to the buffer solution 102 or the specimen fluid 105. Each section of the tube 104 is relatively narrow (i.e., the cross-sectional diameter is much smaller than the tube length) to minimize mixing of the specimen fluid 105 and the buffer solution 102 at the fluid interface, and the fluid interface is initially at position 106 when the tube 104 enters the body (e.g., a blood vessel). When sampling first begins (i.e., all sensors have their maximum remaining life), the specimen fluid 105 is delivered only to sensor S1 (viewed as stage 1 operation) by retracting the plunger 101 by a distance that retreats the fluid interface to position 107. During stage 1, the control device 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, the plunger 101 is returned to its forward position so that the fluid interface returns to position 106. The stage 1 operation persists over the useful life of sensor S1. During stage 1, sensors S2 and S3 are never exposed to the specimen fluid 105 and are only exposed to the buffer solution 102, and the control device 110 ignores sensors S2 and S3.At the end of life (EOL) of sensor S1, sampling enters stage 2 operation, in which the sample fluid 105 is delivered to sensors S1 and S2 by retracting the plunger 101 by a distance that retracts the fluid interface to position 108 within the tube 104. In stage 2, the control device 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 the sample fluid 105 is delivered to sensors S1, S2, and S3 by retracting the plunger 101 by a distance that retracts the fluid interface to position 109 within the tube 104. In stage 3, the control device 110 exchanges signals with sensor S3 and ignores sensors S1 and S2. During measurements in stages 2 and 3, the fluid interface is preferably returned to position 106, or alternatively, may be returned only to a position that returns the buffer solution to the sensor that is then used to obtain the measurement result.

[0019] Figure 10 shows another tandem-type embodiment having a continuous sensor that penetrates the tube 120 at respective positions along the length of the tube 120. The tube 120 is thin enough to minimize mixing of the buffer solution and the sample fluid when the fluid interface is moved to various positions 121, 122, and 123 between the continuous sensors such that each sensor is used in 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 at step 130. At step 131, the control device utilizes the signal from sensor S1. At step 132, a check is made to determine whether sensor S1 has reached the end-of-life (EOL) state. The check can 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 can be based on an analysis of the sensor signal performed by the control device to detect when the measurement performance has deteriorated. If sensor S1 has not reached EOL, the use of stage 1 continues and the EOL state of sensor 1 is continuously monitored at step 132.

[0021] When sensor S1 reaches EOL, the plunger begins to operate in stage 2 mode at step 133. The control device switches at step 134 to utilize the sensor signal from sensor S2. At step 135, EOL is checked for sensor S2. When EOL is reached for sensor S2, the plunger operates in stage 3 mode at step 136 and the control device switches at step 137 to utilize the signal from sensor S3.

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

[0023] The mixing of the buffer solution and the target fluid is minimal, so the composition of the buffer solution remains substantially stable during use. A small but measurable amount of the target chemical substance, measured by the sensor, can be added to the buffer solution (preferably at a precisely controlled concentration). The amount of the target chemical substance can be made sufficiently small so that there is little degradation of the sensor even when in contact with the sensor over a long period. Thus, a target substance at a given calibration concentration is added, where the calibration concentration is less than the range of the expected concentration 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. Since 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 extent of degradation and to compensate for the measured concentration of the target fluid.

[0024] For example, a sensor for monitoring lactate in blood (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 can be composed of the above-described CDI® blood parameter monitoring system or other commercially available sensors. By adding lactate to the buffer solution at a concentration of only 5 mmol / L, the chemicals in the sensor (e.g., a photoreactive dye) do not significantly degrade. However, during periodic exposure to high levels of lactate in the target fluid, the sensor degrades, thereby causing the measured value for the lactate concentration to be lower. Thus, the measured value obtained for the buffer solution (during the measurement period for the target fluid) can 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, the measured value from the sensor can decrease over time. First, a base value 140 is measured during exposure to a buffer solution at a known predetermined value of about 5.0 mmol / L. The buffer solution is withdrawn from the sensor such that the sensor will be exposed to the target fluid. After a transition period, a measured value 141 is obtained for the target. Thereafter, the buffer solution is advanced over the sensor during a rest 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 a high concentration of the target substance. During the rest period, sensor measurement results are periodically obtained for comparison with known values. Thereafter (as degradation is occurring), the measured value 142 obtained during the rest period has an incorrect value of about 3.0 mmol / L. The decrease in the measured value quantifies the extent of the degradation that has occurred. Subsequent measured values 143 obtained for the target fluid decrease by the same extent. The difference between values 140 and 142 identifies a correction that can be applied to measured value 143 to compensate for sensor degradation.

[0026] As shown in FIG. 13, the measured concentration value 145 obtained for the target fluid is input into a correction factor matrix 146. The matrix 146 can be composed of empirically derived correction factors that compensate for changes in the sensor output at various levels of degradation. The matrix 146 may alternatively be composed of equations or formulas. For example, for a 10% decrease in the measured buffer concentration, the measured target fluid concentration can be multiplied by 1.1.

[0027] To identify the appropriate factor to be applied, the most recent measured concentration value 147 for the buffer solution is input into the matrix 146. The matrix 146 outputs a measured target concentration with improved accuracy based on the selected factor.

[0028] End-of-life conditions for any particular sensor can be detected using rest measurements. When the detected value for a target substance in a buffer solution drops below a threshold, the particular sensor can no longer be relied upon. Then, either the next sensor in the tandem sensors is used, or, if no other sensors are available, an error message can be generated to inform the user. For example, in a sensor system that measures glucose and has glucose added to the buffer solution at a concentration of 5 mol / L, if the detected amount of glucose during the rest period drops below 3 mol / L, the sensor can be considered to have reached the end of its life.

[0029] Figure 14 shows the corresponding method in which the concentration of the target substance in the buffer solution is measured at step 150. A check is made at step 151 to determine whether the measured concentration is below the threshold. The threshold is selected to indicate a level of degradation beyond which the sensor is no longer suitable for use. If the measured concentration is not below the threshold, return to step 150 to repeat the subsequent checks. If the measured concentration is below the threshold, a check is made at step 152 to determine whether there is another sensor that has not yet been exposed to biological fluid (e.g., blood). If there are no remaining sensors (e.g., there are no tandem sensors or the last tandem sensor has been used up), an error message is generated at step 153. Otherwise, a switch is made to the remaining sensor that still has an effective remaining life. Thereafter, the degradation of the newly selected sensor can be monitored 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 away from a source of the target fluid; a supply unit for a buffer solution coupled to the lumen; and the supply unit includes a mechanism for advancing the buffer solution along the lumen such that the target fluid can be displaced from the region around the sensor, and when a measurement is desired, the buffer solution is drawn back into the supply unit, whereby the biological fluid enters the lumen and contacts the sensor, the biosensor system. 2. The biosensor system according to 1., wherein the conduit is an implantable catheter configured to penetrate a blood vessel, and the target fluid is blood. 3. The biosensor system according to 1., wherein the buffer solution is physiological saline. 4. The biosensor system according to 1., wherein the supply unit includes a reservoir for storing the buffer solution, and the mechanism is constituted by a plunger, and the plunger is attached to move back and forth longitudinally 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 positions between the first end and the second end; a supply unit for a buffer solution coupled to the lumen; and the supply unit includes a mechanism for advancing the buffer solution along the lumen such that the target fluid can be displaced from each respective region at each of the sensors, and when a measurement is desired, the buffer solution is drawn back into the supply unit, whereby the biological fluid enters the lumen and contacts at least one of the sensors. A buffer solution is advanced and withdrawn according to stages. In the first stage, only the first sensor is exposed to the target fluid. The first stage is for a first period. The second stage follows the first stage. In the second stage, only the first sensor and the second sensor are exposed to the target fluid. A biosensor system. 6. The biosensor system according to 5., wherein the second stage is for a second period, 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 according to 5., wherein the conduit is composed of an implantable catheter configured to penetrate a blood vessel, and the target fluid is composed of blood. 8. The biosensor system according to 5., wherein the buffer solution is composed of physiological saline. 9. The supply unit includes a reservoir for storing the buffer solution. The mechanism is composed of a plunger. The plunger is attached to move back and forth longitudinally inside the reservoir to selectively pump the buffer fluid into the lumen by advancing the plunger or to selectively withdraw the buffer solution from the lumen by retracting the plunger. The biosensor system according to 5. 10. A biosensor system, 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 away from a source of the target fluid for detecting a target substance; a supply unit for a buffer solution coupled to the lumen; comprising the supply unit includes a mechanism for advancing the buffer solution along the lumen so that the target fluid can be expelled from the region around the sensor. When a measurement is desired, the buffer solution is drawn back into the supply unit, whereby the biological fluid enters the lumen and contacts the sensor. the buffer solution contains a target substance at a predetermined calibration concentration, and the calibration concentration is less than a predetermined concentration range of the target substance in the target fluid. A biosensor system, wherein the difference between the measurement result of the target substance in the buffer solution and the predetermined calibration concentration identifies a correction to be applied to the measurement of the target fluid. 11. The biosensor system according to 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 less than a threshold value. 12. The biosensor system according to 10., wherein the conduit is an implantable catheter configured to penetrate a blood vessel, and the target fluid is composed of blood. 13. The biosensor system according to 10., wherein the buffer solution is composed of physiological saline. 14. The biosensor system according to 10., wherein the supply unit includes a reservoir for storing the buffer solution, the mechanism is composed of a plunger, and the plunger is mounted to reciprocate longitudinally 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. A biosensor system, comprising: a conduit having a lumen including a first end for receiving a target biological fluid and a second end; a sensor coupled to the lumen away from a source of the target biological fluid and configured to detect a target substance; a supply unit coupled to the lumen for a buffer solution containing the target substance at a predetermined concentration; wherein: the supply unit includes a mechanism for advancing the buffer solution along the lumen such that the target fluid can be expelled from an area around the sensor, and when a measurement is desired, the buffer solution is drawn back into the supply unit, whereby the biological fluid enters the lumen and contacts the sensor; the biosensor system is configured such that a measurement result of the target substance in the buffer solution indicates an end-of-life of the corresponding sensor when the measurement result is less than a threshold value.

2. The biosensor system according to claim 1, wherein the conduit is an implantable catheter configured to penetrate a blood vessel, and the target fluid is blood.

3. The biosensor system according to claim 1, wherein the buffer solution is physiological saline.

4. The biosensor system according to claim 1, wherein the supply unit includes a reservoir for storing the buffer solution, the mechanism is constituted by a plunger, and the plunger is mounted to reciprocate longitudinally inside the reservoir for selectively pumping the buffer solution into the lumen by advancing the plunger or selectively withdrawing the buffer solution from the lumen by retracting the plunger.

5. A biosensor system, comprising: a conduit having a lumen including a first end for receiving a target biological fluid and a second end; a sensor coupled to the lumen away from a source of the target biological fluid for detecting a target substance; a supply unit coupled to the lumen for a buffer solution; wherein: the supply unit includes a mechanism for advancing the buffer solution along the lumen such that the target fluid can be expelled from an area around the sensor, and when a measurement is desired, the buffer solution is drawn back into the supply unit, whereby the biological fluid enters the lumen and contacts the sensor. The buffer solution contains the target substance at a predetermined calibration concentration, and the predetermined calibration concentration is 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 identifies the correction applied to the measurement for the target fluid. The biosensor system wherein the measurement result of the target substance in the buffer solution identifies the end-of-life of the sensor corresponding when the measurement result is less than a threshold value. **Claim 6** The biosensor system according to claim 5, wherein the conduit is an implantable catheter configured to penetrate a blood vessel, and the target fluid is blood. **Claim 7** The biosensor system according to claim 5, wherein the buffer solution is composed of physiological saline. **Claim 8** The biosensor system according to claim 5, wherein the supply unit includes a reservoir for storing the buffer solution, the mechanism is composed of a plunger, and the plunger is mounted to reciprocate longitudinally 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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