Electrochemical detection of ischemia

• US 20030132125A1
• Filed: 11/26/2002
• Published: 07/17/2003
• Est. Priority Date: 11/26/2001
• Status: Active Grant

• Current Assignee: Ischemia Technologies, Inc. (Abbott Laboratories Incorporated)
• Original Assignee: Ischemia Technologies, Inc. (Abbott Laboratories Incorporated)
• Inventors: Fagan, Gary, Wayment, Hollie, George, Shannon, Crosby, Peter A.
• Granted Patent: US 7,063,782 B2
• Time in Patent Office: Days
• US Class Current: 205/792
• CPC Class Codes: G01N 2333/765 Serum albumin, e.g. HSA
• CPC Class Codes: G01N 27/49 Systems involving the determination of the current at a single specific value, or small range of values, of applied voltage for producing selective measurement of one or more particular ionic species
• CPC Class Codes: G01N 33/5438 Electrodes
• CPC Class Codes: G01N 33/6887 from muscle, cartilage or connective tissue

Abstract

The subject invention comprises electrochemical methods and devices for in vitro detection of an ischemic event in a patient sample. Following addition of a known amount of a transition metal ion to the patient sample, electrodes are used to measure the current or potential difference of non-sequestered transition metal ion in the sample. The amount of non-sequestered transition metal ion in the sample reflects the degree of modification to albumin that is the result of an ischemic event.

Claims

1. A method for in vitro detection or measurement of albumin derivatives, which can be diagnostic of an ischemic event, said method comprising:

a) providing a patient sample comprising albumin and/or derivatives thereof in a vessel that is connected to an electrochemistry apparatus;

b) operating the electrochemistry apparatus to utilize an electrochemical technique;

c) optionally measuring a background characteristic electrochemical output signal of the sample;

d) adding a known amount of a transition metal ion to the sample, whereby at least some of the ion binds to said albumin metal sequestering sites and remaining ion is non-sequestered;

e) optionally adding an indicator or amplifier to the sample to bind to the non-sequestered ion;

f) measuring the characteristic electrochemical output signal associated with the non-sequestered ion;

g) optionally using a standard curve to convert the measured output signal to a converted value;

whereby the measured electrochemical output signal or the converted value, if it exceeds a predetermined value, can be diagnostic of an ischemic event.

2. The method of claim 1, wherein the known amount of metal ion is an excess amount.

3. The method of claim 1, wherein the characteristic electrochemical output signal is selected from the group consisting of current and voltage.

4. A method for in vitro detection or measurement of albumin derivatives, which can be diagnostic for an ischemic event, said method comprising:

a) providing a patient sample comprising albumin and/or derivatives thereof in a vessel having a reference electrode and a working electrode, said electrodes being operably connected to a potentiostat;

b) operating the potentiostat to apply a potential to the sample;

c) optionally offsetting a background current from redox reactions in the sample to zero;

d) adding a known amount of a transition metal ion to the sample, whereby at least some of the ion binds to said albumin metal sequestering sites and remaining ion is non-sequestered by albumin;

e) optionally providing an indicator or amplifier to the sample to bind to the non-sequestered metal ion;

f) permitting the reaction of ion and albumin to reach equilibrium or a predetermined processing time; and

g) measuring the current associated with the non-sequestered ion;

h) optionally using a standard curve to convert the measured current to a converted value;

whereby the measured current or converted value, if it exceeds a predetermined value, can be diagnostic of an ischemic event.

5. The method of claim 4, wherein the known amount of metal ion is an excess amount.

6. The method of claim 4 wherein said vessel further comprises an auxiliary electrode in said vessel that is operably connected to said potentiostat.

7. The method of claim 4 wherein said working electrode further comprises an indicator or amplifier to bind to non-sequestered metal ion.

9. The method of claim 6, wherein the known amount of metal ion is an excess amount.

10. The method of claim 4, wherein said diagnosed ischemic event is cardiac ischemia.

11. The method of claim 4, wherein said diagnosed ischemic event is silent ischemia.

12. The method of claim 4, wherein the diagnosed ischemic event is angina.

13. The method of claim 4, wherein the diagnosed ischemic event is myocardial infarction.

14. The method of claim 4, wherein the diagnosed ischemic event is temporally-limited ischemia.

15. The method of claim 4, wherein the diagnosed ischemic event is bowel ischemia.

16. The method of claim 4, wherein the diagnosed ischemic event is brain ischemia.

17. The method of claim 4, wherein the diagnosed ischemic event is placental insufficiency.

26. The method of claim 4, wherein said diagnosis of the ischemic event is used to evaluate efficacy of an in-situ coronary stent.

27. The method of claim 4, wherein said diagnosis of the ischemic event is used to evaluate efficacy of percutaneous cardiac intervention.

28. The method of claim 4, wherein said diagnosis of the ischemic event is used to evaluate efficacy of drug therapy.

32. A method of detecting or measuring exercise-induced ischemia by determining the level of ischemia in a patient during exercise, and before exercise, after exercise or both, and comparing said levels, wherein ischemic events are detected or measured using the method of claim 4.

8. A method for in vitro detection or measurement of albumin derivatives which may be diagnostic for an ischemic event, said method comprising:

a) providing a patient sample comprising albumin and/or derivatives thereof in a vessel having an ion selective electrode and a reference electrode, said electrodes being operably linked to an electrostat or a voltmeter, said ion selective electrode comprising a barrier that is selectively permeable to a transition metal ion;

b) operating the electrostat or voltmeter to measure the potential difference between the reference electrode and the ion selective electrode in contact with the sample;

c) optionally offsetting a background potential difference of the sample;

d) adding a known amount of said transition metal ion to the sample,

whereby at least some of the ion binds to said albumin metal sequestering sites and remaining ion is non-sequestered;

e) optionally providing an indicator or amplifier to the sample to bind with the non-sequestered metal ion;

f) permitting the non-sequestered metal ion to cross the membrane of the ion selective electrode; and

g) measuring the voltage associated with the ion activity difference across the ion selective electrode'"'"'s barrier;

h) optionally using a standard curve to convert the measured voltage to a converted value;

whereby the measured voltage or the converted value, if it exceeds a predetermined value, can be diagnostic of an ischemic event.

18. The method of claim 8, wherein the diagnosed ischemic event is cardiac ischemia.

19. The method of claim 8, wherein said diagnosed ischemic event is silent ischemia.

20. The method of claim 8, wherein the diagnosed ischemic event is angina.

21. The method of claim 8, wherein the diagnosed ischemic event is myocardial infarction.

22. The method of claim 8, wherein the diagnosed ischemic event is temporally-limited ischemia.

23. The method of claim 8, wherein the diagnosed ischemic event is bowel ischemia.

24. The method of claim 8, wherein the diagnosed ischemic event is brain ischemia.

25. The method of claim 8, wherein the diagnosed ischemic event is placental insufficiency.

29. The method of claim 8, wherein said diagnosis of the ischemic event is used to evaluate the efficacy of an in-situ coronary stent.

30. The method of claim 8, wherein said diagnosis of the ischemic event is used to evaluate the efficacy of a percutaneous cardiac intervention.

31. The method of claim 8, wherein said diagnosis of the ischemic event is used to evaluate the efficacy of drug therapy.

33. A method of detecting or measuring exercise-induced ischemia by determining the level of ischemia in a patient during exercise, and before exercise, after exercise or both, and comparing said levels, wherein ischemic events are detected or measured using the method of claim 8.

34. A device for in vitro electrochemical detection or measurement of albumin derivatives which can be diagnostic for an ischemic event, said device comprising:

an electronics module housing comprising a display means, a data entry and control means, an aperture, internal contacts in said aperture in electrical continuity with the display means, a power source and optionally a link to a laboratory information system; and

a sample analysis strip comprising a sample well, and a plurality of electrodes, each said electrode positioned in said sample well and connected via a corresponding trace to a corresponding contact on said strip;

wherein insertion of said strip into said module housing engages each said strip contact with said corresponding contact in the module aperture, which permits electrical continuity with said display means, whereby said albumin derivatives may be detected or measured.

35. The device of claim 34 wherein said link to a laboratory information system is selected from the group consisting of a direct electrical connection, an infrared link and/or a wireless link.

36. A device for in vitro electrochemical detection or measurement of albumin derivatives in a sample which may be diagnostic for an ischemic event, said method comprising:

a housing having an aperture formed therein for receiving a sample analysis strip, the sample analysis strip having a sample well, a plurality of electrodes positioned in the sample well and a like plurality of first contacts interconnected to the electrodes;

control means within said housing; and

a plurality of second contacts in said aperture electrically coupled with said control means for interconnecting with the plurality of first contacts when the sample analysis strip is inserted within the aperture;

wherein, upon insertion of the sample analysis strip into said aperture, each first contact engages a corresponding second contact whereby the albumin derivatives can be detected or measured by said control means.

37. The device of claim 36, further comprising a link to a laboratory information system.

38. The device of claim 37 wherein said link to a laboratory information system is selected from the group consisting of a direct electrical connection, an infrared link and a wireless link.

39. The device of claim 36, further comprising display means within said housing and electrically coupled with said control means, said display means operable to display information indicative of detected albumin derivatives.

40. The device of claim 36, further comprising data entry means electrically coupled to said control means.

41. The device of claim 36, said control means comprising:

means for measuring a characteristic electrochemical output signal associated with the sample in the sample analysis strip; and

means for determining whether the electrochemical output signal exceeds a predetermined value, whereby an ischemic event is indicated.

42. The device of claim 41, wherein the electrochemical output signal is a current associated with non-sequestered metal ion in the sample comprising albumin and/or derivatives thereof to which has been added a known amount of a transition metal ion.

43. The device of claim 41, wherein:

one of the electrodes comprises an ion selective electrode comprising a barrier that is selectively permeable to a transition metal ion;

the electrochemical output signal is a voltage associated with an ion activity difference across the barrier in the sample comprising albumin and/or derivatives thereof to which has been added a known amount of a transition metal ion.