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US-12622608-B2 - Aqueous buffer protection system for biosensors

US12622608B2US 12622608 B2US12622608 B2US 12622608B2US-12622608-B2

Abstract

Usable life of a biosensor life is extended while keeping the 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. A catheter, tube, or other lumen contains the active biosensor. One end of the lumen is introduced to the 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, the biological fluid (e.g., blood) can be purged from the area around the 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 When a measurement is desired, then the buffer solution is withdrawn (e.g., suctioned) back into the supply so that the biological fluid enters and contacts the sensor material.

Inventors

  • Takeshi Tsubouchi

Assignees

  • TERUMO CARDIOVASCULAR SYSTEMS CORPORATION

Dates

Publication Date
20260512
Application Date
20220728

Claims (8)

  1. 1 . A biosensor system comprising: a conduit with an inner lumen with a first end for receiving a target biological fluid and a second end; a sensor coupled to the inner lumen remotely from a source of the target biological fluid, the sensor configured to detect a target substance; and a supply unit for a buffer solution coupled to the inner lumen, the buffer solution comprising a predetermined concentration of the target substance, wherein the supply unit includes a mechanism for advancing the buffer solution along the inner lumen so that the target biological fluid can be purged from an area around the sensor, wherein, when a measurement is desired, the buffer solution is withdrawn into the supply unit so that the target biological fluid enters the inner lumen and contacts the sensor, and wherein a measurement of the target substance in the buffer solution identifies an end-of-life of the sensor when the measurement is less than a threshold.
  2. 2 . The biosensor system of claim 1 wherein the conduit is comprised of an implantation catheter configured to penetrate a blood vessel, and wherein the target biological fluid is comprised of blood.
  3. 3 . The biosensor system of claim 1 wherein the buffer solution is comprised of a saline solution.
  4. 4 . The biosensor system of claim 1 wherein the supply unit includes a reservoir for storing the buffer solution, and wherein the mechanism is comprised of a plunger mounted for reciprocating longitudinal motion inside the reservoir in order to selectably pump the buffer solution into the inner lumen by advancing the plunger or to selectably withdraw the buffer solution from the inner lumen by retracting the plunger.
  5. 5 . A biosensor system comprising: a conduit with an inner lumen with a first end for receiving a target biological fluid and a second end; a sensor coupled to the inner lumen remotely from a source of the target biological fluid to detect a target substance; and a supply unit for a buffer solution coupled to the inner lumen, wherein the supply unit includes a mechanism for advancing the buffer solution along the inner lumen so that the target biological fluid can be purged from an area around the sensor, and wherein, when a measurement is desired, the buffer solution is withdrawn into the supply unit so that the target biological fluid enters the inner lumen and contacts the sensor, wherein the buffer solution includes a predetermined calibration concentration of the target substance, wherein the predetermined calibration concentration is less than a predetermined range of concentration of the target substance in the target biological fluid, wherein a difference between a measurement of the target substance in the buffer solution and the predetermined calibration concentration identifies a correction which is applied to the measurement for the target biological fluid, and wherein the measurement of the target substance in the buffer solution identifies an end-of-life of the sensor when the measurement is less than a threshold.
  6. 6 . The biosensor system of claim 5 wherein the conduit is comprised of an implantation catheter configured to penetrate a blood vessel, and wherein the target biological fluid is comprised of blood.
  7. 7 . The biosensor system of claim 5 wherein the buffer solution is comprised of a saline solution.
  8. 8 . The biosensor system of claim 5 wherein the supply unit includes a reservoir for storing the buffer solution, and wherein the mechanism is comprised of a plunger mounted for reciprocating longitudinal motion inside the reservoir in order to selectably pump the buffer solution into the inner lumen by advancing the plunger or to selectably withdraw the buffer solution from the inner lumen by retracting the plunger.

Description

CROSS REFERENCE TO RELATED APPLICATIONS This application is a continuation of PCT Application No. PCT/US2021/018148, filed Feb. 16, 2021, based on and claiming priority to U.S. Provisional Application No. 62/980,500, filed Feb. 24, 2020, and to U.S. Provisional Application No. 63/031,605, filed May 29, 2020, all of which are incorporated herein by reference in their entirety. BACKGROUND OF THE INVENTION The present invention relates in general to sensors (e.g., biosensors) for monitoring biological fluids such as blood, and, more specifically, to a protection system for prolonging a useful lifetime of such biosensors. Biosensors can be used for measuring chemicals, other substances, and various properties of a target biological fluid such as blood. The measured quantities can include concentration of gases, proteins, pH, and other parameters of biological fluids. Some types of biosensors may use enzymes or other reactive materials to contact the fluid when making a measurement. During the time they are exposed to the biological fluid, the reaction can eventually degrade the sensor materials such that the sensor becomes less effective over time. Besides degradation of sensor materials, a buildup of protein layers or clotted blood around the sensor material during exposure can also reduce effectiveness of the sensor over time. An example of a biosensor includes an enzyme-based amperometric glucose measurement sensor or a blood parameter monitoring sensor such as the CDI® blood parameter monitoring system which is available from Terumo Cardiovascular Systems Corporation of Ann Arbor, Michigan The CDI® sensor uses optical fluorescence, reflectance, and/or other sensing elements to measure blood parameters including pH, pCO2, pO2, K+, SO2, hemoglobin, hematocrit, and others in blood during cardiopulmonary bypass. Although continuous measurement may be desirable in some cases, many parameters change slowly such that continuous measurement is not required. Instead, measurements can be made periodically (especially during long duration monitoring). SUMMARY OF THE INVENTION An objective of the invention is to extend sensor life while keeping the sensing system enclosed (e.g., free from outside contamination) while minimizing the introduction of flushing solutions into a measurement line (e.g., a blood vessel) of a fluid system. The fluid system targeted for measurement can include a human vessel, a nutritional fluid line in a tissue cultivation system, a circulation system in an organ preservation system, and others. The invention utilizes a catheter, tube, or other lumen to contain the active biosensor. One end of the lumen is introduced to the 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, the biological fluid (e.g., blood) can be purged from the area around the 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 the lumen and contacts the sensor material. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a cross-sectional view of a conventional needle sensor. FIG. 2 is a cross-sectional view of a modified needle sensor according to one embodiment of the invention. FIG. 3 is a side view of an alternative sensor element useful in the needle sensor of FIG. 2. FIG. 4 is a schematic view of another embodiment of the invention. FIG. 5 is a graph illustrating a sensor output signal over a measurement cycle. FIG. 6 depicts another embodiment of the invention with multiple sensors along a series of tubing. FIG. 7 depicts a hollow fiber system portion of a base tissue cultivation system. FIG. 8 shows a sensor and protection system adapted to obtain measurements within the hollow fiber of the tissue cultivation system of FIG. 7. FIG. 9 shows an embodiment having tandem sensors in series along a fluid path to be operated in stages. FIG. 10 depicts another embodiment with tandem sensors. FIG. 11 is a flowchart showing one preferred method for operating tandem sensors. FIG. 12 is a graph showing measured sensor values for a target parameter over time, in which sensor degradation results in lowered sensitivity to the target parameter. FIG. 13 is a block diagram showing compensation of sensor measurements based on inclusion of a known low concentration of the target parameter in the buffer solution. FIG. 14 is a flowchart showing 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 PREFERRED EMBODIMENTS FIG. 1 shows a conventional needle sensor system with a hollow injection needle 10 having a tip penetrating a blood vessel 11 into a bloodstream 12. A sensor 13 has a sensing tip 14 penetrating bloodstream 12 and providing a sensor output signal over wires 15 to a measurement circuit.