Nmr detection of coagulation time

Abstract

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 . (canceled) 
     
     
         2 . A method for determining the coagulation state and/or coagulation time of a sample using a nuclear magnetic resonance (NMR) device, comprising:
 a) performing NMR measurements on a sample within a detection volume of an NMR detector of the NMR device to determine at least two values of T 2  of the sample over time, the T 2  being responsive to coagulation in the sample; and   b) assessing the values determined in a) to obtain the coagulation state and/or coagulation time of the sample.   
     
     
         3 . (canceled) 
     
     
         4 . (canceled) 
     
     
         5 . A method for monitoring the coagulation of a sample from a test subject, the method comprising:
 (a) measuring a plurality of values of T 2  of the sample over time, wherein the T 2  is responsive to the coagulation state of the sample.   
     
     
         6 . The method of  claim 5 , further comprising (b) comparing the measured values of T 2  obtained in (a) with a standard coagulation-time-curve; and optionally further comprising (c) determining abnormal coagulation events from the comparison in (b). 
     
     
         7 . The method of  claim 4 , wherein the standard coagulation-time-curve is pre-determined or calculated. 
     
     
         8 . The method of  claim 4 , wherein the standard coagulation-time-curve is determined from a plurality of measured values of T 2  over time from one or more samples of one or a plurality of subjects. 
     
     
         9 . The method of  claim 8 , wherein the test subject is one of the subjects, and the standard coagulation-time-curve is prepared from measured values from one or more samples from the test subject. 
     
     
         10 . A method for diagnosing an abnormal clotting event in a sample of a test subject, comprising:
 a) measuring T 2  of the sample of the test subject over time, the T 2  being responsive to coagulation in the sample; and   b) comparing T 2  of the sample obtained in a) with those of a standard coagulation-time-curve of T 2  responsive to normal coagulation to thereby diagnose an abnormal clotting event in the subject.   
     
     
         11 . The method of  claim 10 , wherein the characteristics of the T 2  of the sample compared with those of the standard coagulation-time-curve are selected from the group consisting of overall change of T 2  over time, rate of T 2  change over time, clotting time determined from T 2  change, and fluctuation of T 2  change in the sample prior to coagulation. 
     
     
         12 . The method of  claim 11 , wherein a first test carrier containing a first sample from the subject, and a second test carrier containing a second sample from the subject are provided prior to the measuring, the first and second samples being collected from the subject at discrete times. 
     
     
         13 . The method of  claim 11 , further including comparing one or more characteristics of the T 2  of the first sample with those in the second sample to access difference(s) between the first and second samples in coagulation. 
     
     
         14 . The method of  claim 2 , wherein the T 2  is measured by using a CPMG sequence. 
     
     
         15 . The method of  claim 14 , wherein an uncoagulated sample is characterized by a first average T 2  value and a coagulated sample is characterized by a second average T 2  value, and parameters of the CPMG sequence have been optimized such that the difference between the first value and the second value is sufficient to determine whether a test sample is coagulated or uncoagulated based on measurement of T 2  using the CPMG sequence. 
     
     
         16 . (canceled) 
     
     
         17 . (canceled) 
     
     
         18 . The method of  claim 15 , wherein the sample is normal plasma, normal blood, or a fraction of normal blood. 
     
     
         19 . The method of  claim 15 , wherein the parameters are optimized to obtain a dwell time between any two measurements of T 2  sufficient to measure: at least two T 2  values while the sample is coagulating and before the sample is coagulated. 
     
     
         20 . The method of  claim 15 , wherein the CPMG sequence is characterized by parameters that have been optimized with respect to a normally coagulating sample, the normally coagulating sample in its uncoagulated state being characterized by a first T 2  value and in its coagulated state being characterized by a second T 2  value; the parameters having been optimized to yield:
 (a) a difference between the first value and the second value of at least 5% of the first value, and (b) a dwell time between any two measurements of T 2  sufficient to measure at least two T 2  values while the sample is coagulating and before the sample is coagulated,   
     
     
         21 . The method of  claim 14 , wherein pulse attenuation of the CPMG sequence has been optimized to reduce partly or completely heating of the sample due to measurement of T 2 . 
     
     
         22 . The method of  claim 14 , wherein the CPMG sequence is characterized by a recycle delay of between about 0.1 seconds and about 100 seconds, a number of acquired echoes of between 1 and about 10,000, an inter-echo delay of between about 0.01 milliseconds and about 10 milliseconds, and a dwell time between about 0.1 second and about 5,200 seconds. 
     
     
         23 - 24 . (canceled) 
     
     
         25 . The method of  claim 2 , wherein a coagulation reagent is mixed with the sample. 
     
     
         26 . (canceled) 
     
     
         27 . The method of  claim 25 , wherein the coagulation reagent is one or a combination of a prothrombin time (PT) reagent, a partial thromboplastin time (PTT) reagent, an activated partial thromboplastin time (APTT) reagent, thrombin clotting time (TCT) reagent, fibrinogen reagent, and/or activated clotting time (ACT) reagent. 
     
     
         28 . The method of  claim 25 , wherein the coagulation reagent is selected from the group consisting of a prothrombin time (PT) reagent, a partial thromboplastin time (PTT) reagent, an activated partial thromboplastin time (APTT) reagent, thrombin clotting time (TCT) reagent, fibrinogen reagent, and activated clotting time (ACT) reagent. 
     
     
         29 - 35 . (canceled)