NMR detection of coagulation time
The invention relates to detecting coagulation and coagulation-related activities including agglutination and fibrinolysis of samples. More particularly the invention relates to methods and apparatus for monitoring coagulation and/or obtaining a coagulation time of a sample using NMR-based detectors.
1. A method of determining the coagulation time of a blood sample obtained from a subject, comprising:
(a) providing a blood sample from a subject;
(b) placing the blood sample in a carrier;
(c) mixing a coagulation reagent with said blood sample to initiate coagulation;
(d) measuring a T 2 relaxation time of the blood sample in the carrier within a detection volume of an NMR detector of an NMR device using a CPMG sequence until the blood sample is substantially fully coagulated, wherein in a coagulation-time-curve (i) an uncoagulated state is characterized by a first plateau in the coagulation-time-curve, the first plateau having a first average T 2 value, and (ii) a coagulated state is characterized by a second plateau in the coagulation-time-curve, the second plateau having a second average T 2 value, and wherein the CPMG sequence is characterized by parameters that permit detection of at least two values of the T 2 of the sample within about 10 seconds of performing step (c); and
(e) based upon the coagulation-time-curve determining the coagulation time of the sample.
2. The method of claim 1 , wherein the difference between the first average T 2 value and the second average T 2 value is at least 3%.
3. The method of claim 1 , wherein step (e) further comprises assessing the extent of coagulation in the sample based upon the decline in T 2 measured once the blood sample is substantially fully coagulated.
4. The method of claim 1 , wherein the coagulation reagent is a prothrombin time coagulation reagent.
5. The method of claim 1 , wherein the coagulation reagent is an activated partial thromboplastin time coagulation reagent.
6. The method of claim 1 , wherein the coagulation reagent is a partial thromboplastin time coagulation reagent.
7. The method of claim 1 , wherein the coagulation reagent is a thrombin clotting time coagulation reagent.
8. The method of claim 1 , wherein the coagulation reagent is a fibrinogen reagent.
9. The method of claim 1 , wherein the carrier is incubated to maintain the blood sample at a preferred temperature prior to step (c).
10. The method of claim 1 , wherein the carrier is placed in a heating block prior to step (c).
11. The method of claim 1 , wherein the volume of the blood sample is from 10 to 300 microliters.
12. The method of claim 1 , wherein the carrier comprises a surface fabricated from plastic.
13. The method of claim 1 , wherein the blood sample is a whole blood sample.
14. The method of claim 1 , wherein the blood sample is a plasma sample.
15. The method of claim 1 , wherein the CPMG sequence is characterized by an inter-echo delay of between 0.2 milliseconds and 2 milliseconds and a dwell time of between about 1 second and about 6 seconds.
16. The method of claim 15 , wherein the CPMG sequence is characterized by a recycle delay of about 1 second.
17. The method of claim 15 , wherein the CPMG sequence is characterized by a number of acquired echoes of between 500 and 2,000.
18. The method of claim 15 , wherein the CPMG sequence is characterized by an inter-echo delay of about 0.5 milliseconds.
19. The method of claim 15 , wherein the CPMG sequence is characterized by a dwell time of about 4.5 or about 5.5 seconds.