Highly sensitive system and methods for analysis of troponin

• US 7,838,250 B1
• Filed: 04/03/2008
• Issued: 11/23/2010
• Est. Priority Date: 04/04/2006
• Status: Active Grant

• Current Assignee: Singulex, Inc., Regents of the University of California (University of California)
• Original Assignee: Singulex, Inc., Regents of the University of California (University of California)
• Inventors: Todd, John, Livingston, Richard A., Held, Douglas, Puskas, Robert, Goix, Philippe J., Wu, Alan
• Primary Examiner(s): CHEU, CHANGHWA J
• Application Number:
  US12/062,412
• Publication Number:
  US 20080261242A1
• Time in Patent Office: 964 Days
• Field of Search: None
• US Class Current: 435/7.1
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/6486 Measuring fluorescence of biological material, e.g. DNA, RNA, cells G01N21/6428 takes precedence
• CPC Class Codes: G01N 2333/47 Assays involving proteins of known structure or function as defined in the subgroups
• CPC Class Codes: G01N 2800/32 Cardiovascular disorders
• CPC Class Codes: G01N 2800/324 Coronary artery diseases, e.g. angina pectoris, myocardial infarction
• CPC Class Codes: G01N 2800/325 Heart failure or cardiac arrest, e.g. cardiomyopathy, congestive heart failure
• CPC Class Codes: G01N 2800/50 Determining the risk of developing a disease
• CPC Class Codes: G01N 33/582 with fluorescent label
• CPC Class Codes: G01N 33/68 involving proteins, peptides or amino acids involving lipoproteins G01N33/92
• CPC Class Codes: G01N 33/6887 from muscle, cartilage or connective tissue
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere

Abstract

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.

Claims

1. A method for determining cardiovascular health of an individual comprising:

(i) measuring serum or plasma concentration of cardiac troponin I (cTnI) from a blood sample prior to conducting a stress test;

(ii) conducting a stress test on the individual;

(iii) measuring the stress induced concentration of cTnI from blood samples taken during or after the stress test;

(iv) comparing the cTnI concentrations before and during or after stress test to each other and to a concentration of cTnI in a normal population of about 7 pg/ml or less.

2. A method according to claim 1 wherein a blood sample is taken during the stress test.

3. The method according to claim 1 wherein a blood sample is taken after the stress test.

4. A method of determining cardiac damage in an individual comprising:

(i) obtaining a blood sample from the individual;

(ii) detecting a concentration of cTnI in the sample; and

(iii) comparing the detected cTnI concentration to a concentration of cTnI in a normal population of about 7 pg/ml or less, when the detected cTnI level is greater than the level of cTnI in a normal population of about 7 pg/ml, the individual is suspected of experiencing cardiac damage.

5. The method of claim 4 wherein the individual is a patient being evaluated for a at least one of possible cardiac event and cardiotoxicity.

6. A method of determining cardiac damage in an individual comprising:

(i) obtaining a series of blood samples from the individual at an interval of less than 8 hours;

(ii) detecting a level of cTnI in each sample;

(iii) comparing the detected level of cTnI in the series of samples to a level of cTnI in a normal population of about 7 pg/ml or less; and

(iv) determining cardiac damage in the individual when the level of cTnI in two or more samples in the series are greater than the level of cTnI in a normal population of about 7 pg/ml.

7. The method of claim 6 wherein the individual is a patient being evaluated for at least one of a possible cardiac event and cardiotoxicity.

8. A method of determining cardiac damage progression in an individual comprising:

(i) obtaining a series of blood samples from the individual at an interval of less than 8 hours;

(ii) detecting a level of cTnI in each sample;

(iii) comparing the detected level of cTnI in the series of samples to a level of cTnI in a normal population of about 7 pg/ml or less; and

(iv) determining that cardiac damage is resolving when the detected level of cTnI is above the level of cTnI in the normal population of about 7 pg/ml but decreases through the series of blood samples, and determining that cardiac damage is worsening when the detected level of cTnI is above the level of cTnI in the normal population of about 7 pg/ml and increasing through the series of blood samples.

9. The method of claim 8 wherein the individual is a patient being evaluated for at least one of a possible cardiac event and cardiotoxicity.