Implantable biosensor devices for monitoring cardiac marker molecules

• US 20050049472A1
• Filed: 08/29/2003
• Published: 03/03/2005
• Est. Priority Date: 08/29/2003
• Status: Active Grant

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Bennett, Tommy D., Yang, Zhongping, Manda, Ven
• Granted Patent: US 7,632,234 B2
• Time in Patent Office: Days
• US Class Current: 600/345
• CPC Class Codes: A61B 5/0031 Implanted circuitry
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
• CPC Class Codes: A61N 1/36514 controlled by a physiological quantity other than heart potential, e.g. blood pressure controlled by two or more physical parameters A61N1/36585

Abstract

An implantable biosensor system is disclosed for determining levels of cardiac markers in a patient to aid in the diagnosis, determination of the severity and management of cardiovascular diseases. The sensor includes nanowire sensor elements having a biological recognition element attached to a nanowire transducer that specifically binds to the cardiac marker being measured. Each of the sensor elements is associated with a protective member that prevents the sensor element from interacting with the surrounding environment. At a selected time, the protective member may be disabled, thereby allowing the sensor element to begin sensing signals within a living body.

Claims

1. An implantable sensor system for determining the presence or amount of an analyte in a patient, comprising:

a. a sensor element comprising a biological recognition element associated with a portion or portions of a transducer, the biological recognition element being capable of specifically binding to a substance in the patient in an amount related to the presence or amount of the analyte and wherein when the substance is bound a detectable signal is produced;

b. a controller associated with the sensor element to measure the detectable signal and relate the amount of the detectable signal measured with the presence or amount of analyte present in the patient; and

c. a protective member located adjacent the sensor element to shield the biological recognition member from a surrounding environment for a selectable time period.

2. The sensor system of claim 1, wherein the substance that specifically binds to the biological recognition element is the analyte being measured.

3. The sensor system of claim 1, wherein the transducer comprises a nanowire and a detector constructed and arranged to determine a property associated with the nanowire and the biological recognition element is positioned relative to the nanowire such that an interaction between the biological recognition element and the substance in the patient produces a detectable change in the property to produce the detectable signal.

4. The sensor system of claim 3, wherein the nanowire comprises a gated nanowire field effect transistor wherein an electrical property of the nanowire is sensitive to a change on a surface of the nanowire.

5. The sensor system of claim 1, wherein the sensor system is adapted to be implanted within the intra-cardiac circulatory system of the patient'"'"'s heart and the analyte is a cardiac marker.

6. The sensor system of claim 5, wherein the sensor system is adapted to be implanted within the coronary sinus.

7. The sensor system of claim 5, wherein the cardiac marker is BNP or a marker related to BNP levels.

8. The sensor system of claim 1, further including a control circuit coupled to the protective member to disable the protective member after the selectable time period.

9. The sensor system of claim 8, wherein the protective member is formed of biocompatible metal.

10. The sensor system of claim 8, wherein the protective member is formed of erodible polymer gel.

11. The sensor system of claim 8, wherein the protective member is formed of a material that substantially dissolves within a living body over the selectable time period.

12. The sensor system of claim 8, wherein the controller is associated with a cathode and an anode to cause a current to flow through the protective member.

13. The sensor system of claim 1, further including a plurality of sensor elements.

14. The sensor system of claim 13, wherein one or more sensor elements include a biological recognition element capable of specifically binding to a substance in the patient in an amount related to the presence or amount of a first analyte and one or more sensor elements include a biological recognition element capable of specifically binding to a substance in the patient in an amount related to the presence or amount of a second analyte.

15. The sensor system of claim 13, wherein each of the sensor elements is associated with a protective member.

16. The sensor system of claim 15, wherein the controller comprises a circuit capable of selectively disabling one or more of the protective members.

17. The sensor system of claim 1, wherein the biological recognition element is an antibody or portion of an antibody capable of binding to the analyte.

18. The sensor system of claim 1, wherein the biological recognition element is capable of reversibly binding to the substance.

19. A sensor system of claim 1, further including a therapy delivery system coupled to the controller to provide therapy to the patient, wherein the parameters of the therapy will vary based on the measurements of levels of the analyte in the patient.

20. A sensor system of claim 12, wherein a portion of the protective membrane is formed of a material that substantially dissolves within a living body over the selectable time period and wherein a portion of the protective membrane is formed of a material dissolves when current is caused to flow through the portion of the protective member.

21. The sensor system of claim 7, wherein the controller is adapted to compare measured BNP levels to preselected levels stored in the controller and the controller is connected to a cardiac resynchronization therapy device and includes a circuit to vary the AV interval of the cardiac resynchronization therapy device in response to measure BNP levels.

22. A method for determining the presence or amount of an analyte present in a patient, comprising:

a. implanting in the patient a sensor element comprising a biological recognition element associated with a portion or portions of a transducer, the biological recognition element being capable of specifically binding to a substance in the patient in an amount related to the presence or amount of the analyte and wherein when the substance is bound to the biological recognition element a detectable signal is produced; and

a controller connected to the sensor element adapted to measure detectable signal produced and that can relate the amount of detectable signal measured with the presence or amount of analyte present in the patient;

b. contacting the biological recognition element to tissue or fluid in the patient to allow the substance to bind to the biological recognition element;

c. measuring the amount of detectable signal produced when the substance binds to the biological recognition element; and

d. relating the amount of detectable signal produced to the amount or presence of analyte present in the patient.

23. The method of claim 22, wherein the substance that specifically binds to the biological recognition element is the analyte being measured.

24. The method of claim 22, further including providing a protective member is located adjacent the sensor element to shield the biological recognition member from a surrounding environment for a selectable time period and removing the protective member or a portion thereof so that the biological recognition element can contact tissue or fluid in the patient.

25. The method of claim 22, wherein the transducer comprises a nanowire and a detector constructed and arranged to determine a property associated with the nanowire and the biological recognition element is positioned relative to the nanowire such that an interaction between the biological recognition element and the substance in the patient produces a detectable change in the property to produce the detectable signal.

26. The method of claim 25, wherein the nanowire comprises a gated nanowire field effect transistor wherein an electrical property of the nanowire is sensitive to a change on a surface of the nanowire.

27. The method of claim 25, wherein the sensor element is implanted within the intra-cardiac circulatory system of the patient'"'"'s heart and the analyte is a cardiac marker.

28. The method of claim 27, wherein the sensor element is implanted within the coronary sinus.

29. The method of claim 27, wherein the sensor element is implanted within a cardiac vein.

30. The method of claim 27, wherein the cardiac marker is a marker selected from the group consisting of BNP, pre proBNP, NT pro BNP, C-type reactive protein, Troponin I, Troponin T, Myoglobin, D-Dimer and cytokines and the biological recognition element specifically binds the analyte.

31. The method of claim 27, wherein the cardiac marker is BNP or a marker related to BNP levels.

32. The method of claim 27, further comprising providing a plurality of sensor elements and a plurality of protective members coupled to a controller, and disabling at least one of the protective members to activate one or more of the sensor elements.

33. The method of claim 27, wherein one or more of a first set of sensor elements comprise a biological recognition element that specifically binds to a first substance in an amount related to the presence or amount of a first cardiac marker and one or more of a second set of sensor elements comprise a biological recognition element that specifically binds to a second substance in an amount related to the presence or amount of a second cardiac marker.

34. The method of claim 33, further including disabling one or more protective members shielding sensor elements of the first set to activate one or more of the sensor elements in that set and simultaneously or sequentially disabling one or more protective members shielding sensor elements of the second set to activate one or more of the sensor elements in that set.

35. The method of claim 34, wherein the first and second cardiac marker being measured is chosen because the level of one cardiac marker is a marker of cardiac cell injury and the other cardiac marker is a marker that indicates a pressure or volume change or stress of the patient'"'"'s heart.

36. The method of claim 32, wherein each of the sensor elements includes a known amount of biological recognition element attached to the nanowire, and wherein the biological recognition element in each sensor element is the same and each sensor element is shielded from the surrounding environment by one or more protective members, and further including adjusting the sensitivity of the measurement of cardiac marker being measured by disabling one or more protective members to activate a desired number of sensor elements for a selected period of time.

37. The method of claim 27, further including a therapy delivery system coupled to a controller and the sensor to provide therapy to the patient, wherein the parameters of the therapy will vary based on the measurements of levels of the cardiac marker in the patient.

38. The method of claim 32, including one or more protective members formed of a material that substantially dissolves within a living body over the selectable time period.

39. The method of claim 32, wherein one or more protective members are associated with a controller connected to a cathode and an anode capable of causing a current to flow through and disable one or more protective members, and further including disabling one or more protective members by flowing current therethrough at a desired time.

40. The method of claim 37, wherein the cardiac marker is BNP or a marker related to BNP levels.

41. The method of claim 40, including one or more protective members formed of a material that substantially dissolves within a living body over the selectable time period and further including measuring the level of BNP at a first desired time when one or more protective members is substantially dissolved after a selected time period and the sensor element activated, comparing the measured levels of BNP to preselected levels and varying the parameters of the therapy based on the comparison.

42. The method of claim 41, wherein the therapy delivery system is a cardiac resynchronization system and wherein the parameter of therapy varied is the AV interval of the system, comparing the measured levels of BNP to preselected levels and varying the parameters of the therapy based on the comparison.

43. A method of diagnosing, determining the severity of or managing cardiovascular disease in a patient comprising;

a. implanting into the patient a sensor comprising a plurality of sensor elements each sensor element comprising a biological recognition element associated with a portion or portions of a transducer, the biological recognition element being capable of specifically binding to a substance in the patient in an amount related to the level of a cardiac marker and wherein when the substance is bound a detectable signal is produced,

b. activating one or more of the sensor elements by disabling one or more protective members located adjacent the sensor to shield the biological recognition member from a surrounding environment;

c. measuring the amount of detectable signal produced;

d. relating the amount of detectable signal produced to the level of the cardiac marker present in the patient;

e. comparing the measured level of the cardiac marker to preselected levels of such cardiac marker to diagnosis, determine the severity of or manage cardiovascular disease.

44. The method of claim 43, wherein the cardiac marker is BNP.

45. The method of claim 43, further including a therapy delivery system connected to a controller that is associated with one or more sensor elements, wherein the therapy delivery system is providing therapy to the patient based on a set of preselected parameters as part of the management of the patient'"'"'s cardiovascular disease, and when the measured level of cardiac marker as compared to the preselected level of the cardiac marker indicate a worsening in symptoms of the patient'"'"'s cardiovascular disease, further including varying the parameters of the therapy.

46. The method of claim 45 wherein the therapy delivery system is a cardiac resynchronization therapy system.