Highly sensitive system and method for analysis of troponin
The invention provides methods, compositions, kits, and systems for the sensitive detection of cardiac troponin. Such methods, compositions, kits, and systems are useful in diagnosis, prognosis, and determination of methods of treatment in conditions that involve release of cardiac troponin.
1. A method for determining cardiac damage in a human subject, comprising:
(a) determining concentration of cardiac troponin I (cTnI) in a blood, serum or plasma sample from the subject in an assay having a limit of detection for cTnI of less than 3 pg/mL by comparing a measured concentration of cTnI in the sample to a standard curve generated by running cTnI standards of known concentration in the assay;
(b) comparing the determined concentration of cTnI in the sample to a threshold concentration of cTnI in blood, serum or plasma in a healthy population, wherein the threshold concentration represents the 99th percentile of cTnI in the healthy population and is within the range of 1 pg/ml to 10 pg/ml, and wherein the threshold concentration determined by a method having a limit of detection for cTnI of less than 3 pg/mL;
(c) determining cardiac damage in the subject when the concentration of cTnI in the sample is greater than the threshold concentration.
2. The method of claim 1 , wherein the cardiac damage is a result of myocardial infarction, cardiac toxicity, acute coronary syndrome, myocarditis, or heart failure.
3. The method of claim 1 , wherein the assay has total imprecision (CV) of less than or equal to 10% at the threshold concentration.
4. The method of claim 1 , wherein the threshold is established at the 99th percentile with a corresponding total imprecision (CV) of less than or equal to 10%.
5. The method of claim 1 , wherein cardiac damage is determined when the threshold concentration of cTnI is about 7 pg/ml.
6. The method of claim 1 , wherein cardiac damage is determined when the threshold concentration of cTnI is about 8 pg/ml.
7. The method of claim 1 , wherein cardiac damage is determined when the threshold concentration of cTnI is about 9 pg/ml.
8. The method of claim 1 , wherein cardiac damage is determined when the threshold concentration of cTnI is about 10 pg/ml.
9. The method of claim 1 , wherein the sample is a whole blood sample.
10. The method of claim 1 , wherein the sample is a plasma sample.
11. The method of claim 1 , wherein the sample is a serum sample.
12. A method for determining cardiac damage in a human subject, comprising:
(a) determining a concentration of cardiac troponin I (cTnI) in a blood, serum or plasma sample from the subject in an assay having a limit of detection for cTnI of less than 3 pg/mL by interpolating the measured concentration of cTnI in the sample through a standard curve generated by running cTnI standards of known concentration in the assay;
(b) comparing the determined concentration of cTnI in the sample to a threshold concentration of cTnI in blood, serum or plasma in a healthy population, wherein the threshold concentration represents the 99th percentile of cTnI in the healthy population and is within the range of 1 pg/ml to 10 pg/ml, and wherein the threshold concentration determined by a method having a limit of detection for cTnI of less than 3 pg/mL;
(c) determining cardiac damage in the subject when the concentration of cTnI in the sample is greater than the threshold concentration.
13. The method of claim 12 , wherein the cardiac damage is a result of myocardial infarction, cardiac toxicity, acute coronary syndrome, myocarditis, or heart failure.
14. The method of claim 12 , wherein the assay has total imprecision (CV) of less than or equal to 10% at the threshold concentration.
15. The method of claim 12 , wherein the threshold is established at the 99th percentile with a corresponding total imprecision (CV) of less than or equal to 10%.
16. The method of claim 12 , wherein cardiac damage is determined when the threshold concentration of cTnI is about 7 pg/ml.
17. The method of claim 12 , wherein cardiac damage is determined when the threshold concentration of cTnl is about 8 pg/ml.
18. The method of claim 12 , wherein cardiac damage is determined when the threshold concentration of cTnI is about 9 pg/ml.
19. The method of claim 12 , wherein cardiac damage is determined when the threshold concentration of cTnI is about 10 pg/ml.
20. The method of claim 12 , wherein the sample is a whole blood sample.
21. The method of claim 12 , wherein the sample is a plasma sample.
22. The method of claim 12 , wherein the sample is a serum sample.