Cartridge device with segmented fluidics for assaying coagulation in fluid samples

Abstract

The present invention relates to analytical testing devices comprising segmented fluidics and methods for assaying coagulation in a fluid sample received within the segmented fluidics. For example, the present invention may be directed to sample analysis cartridge including an inlet chamber, a first conduit comprising a first junction configured to split a biological sample into at least first and second segments, a second conduit comprising a first reagent, a first sensor region, and a first fluidic lock valve, and a third conduit comprising a first flow restrictor region, a second reagent, and a second sensor region. The sample analysis cartridge further includes a pump configured to independently mix the first segment in the second conduit and the second segment in the third conduit, and independently position the first segment over the first sensor region and position the second segment over the second sensor region.

We claim: 
     
         1 . A method of separating and analyzing a fluid sample within a sample analysis cartridge, the method comprising:
 receiving a fluid sample in an inlet chamber of the sample analysis cartridge;   moving the fluid sample from the inlet chamber to a conduit using a pump;   separating the fluid sample into at least first and second segments using a first junction within the conduit;   moving the first segment of the fluid sample into a first conduit using a first flow restrictor and moving the second segment of the fluid sample into a second conduit, the first flow restrictor being within the second conduit,   independently, mixing the first segment of the fluid sample with a first reagent in the first conduit and mixing the second segment of the fluid sample with a second reagent in the second conduit, the independent mixing being performed using the pump; and   independently, positioning the first segment of the fluid sample comprising the first reagent over a first sensor region located within the first conduit and positioning the second segment of the fluid sample comprising the second reagent over a second sensor region located within the second conduit.   
     
     
         2 . The method of  claim 1 , wherein the second segment of the fluid sample moved into the second conduit is smaller in volume as compared to the first segment of the fluid sample moved into the first conduit. 
     
     
         3 . The method of  claim 2 , wherein the first flow restrictor is a capillary burst valve, a fluidic constriction, a fluidic resistance or any combination thereof. 
     
     
         4 . The method of  claim 2 , wherein the smaller volume of the second segment of the fluid sample allows for the first segment of the fluid sample to be mixed with the first reagent in the first conduit independently of the second segment of the fluid sample mixing with the second reagent or the second segment of the fluid sample vacating the second conduit. 
     
     
         5 . The method of  claim 4 , wherein the positioning the first segment of the fluid sample over the first sensor region comprises pushing the first segment of the fluid sample over the first sensor region to a first fluidic lock valve, such that the first segment of the fluid sample is locked within the first conduit. 
     
     
         6 . The method of  claim 5 , wherein the first fluidic lock valve provides a first pressure resistance, such that the second segment of the fluid sample pushes past the first flow restrictor and allows for the second segment of the fluid sample to be mixed in the second conduit independently of the first segment of the fluid sample in the first conduit. 
     
     
         7 . The method of  claim 6 , wherein a start time of the mixing of the second segment of the fluid sample with the second reagent is performed at a time subsequent to a start time of the mixing of the first segment of the fluid sample with the first reagent. 
     
     
         8 . The method of  claim 1 , wherein:
 the positioning the first segment of the fluid sample over the first sensor region comprises pushing the first segment of the fluid sample over the first sensor region to a first fluidic lock valve such that the first segment of the fluid sample is locked within the second conduit; and   the positioning of the second segment of the fluid sample over the second sensor region comprises pushing the second segment of the fluid sample over the second sensor region to a second fluidic lock valve, such that the second segment of the fluid sample is locked within the second conduit.   
     
     
         9 . The method of  claim 8 , wherein the first fluidic lock valve is a membrane sponge valve, a microchannel capillary, or a micro-array valve, and the second fluidic lock valve is a membrane sponge valve, a microchannel capillary, or a micro-array valve. 
     
     
         10 . The method of  claim 1 , wherein the first flow restrictor within the second conduit is configured to cause preferential movement of the fluid sample into the first conduit and to form the first segment of the fluid sample. 
     
     
         11 . The method of  claim 10 , further comprising diverting flow of the fluid sample to the first junction through a second junction using an overflow conduit comprising a second flow restrictor. 
     
     
         12 . The method of  claim 11 , wherein any residual pressure or movement of the fluid sample after the positioning of the first and second segments of the fluid sample over the first and second sensor regions, respectively, proceeds into the overflow conduit. 
     
     
         13 . The method of  claim 11 , wherein:
 the positioning of the first segment of the fluid sample over the first sensor region comprises pushing the first segment of the fluid sample over the first sensor region to a first fluidic lock valve, such that the first segment of the fluid sample is locked within the first conduit; and   the positioning of the second segment of the fluid sample over the second sensor region comprises pushing the second segment of the fluid sample over the second sensor region to a second fluidic lock valve, such that the second segment of the fluid sample is locked within the second conduit.   
     
     
         14 . The method of  claim 13 , wherein the first fluidic lock valve provides a first pressure resistance and the second fluidic lock valve provides a second pressure resistance. 
     
     
         15 . The method of  claim 14 , wherein any residual pressure or movement of the fluid sample after the locking the first and second segments of the fluid sample proceeds into the overflow conduit. 
     
     
         16 . The method of  claim 15 , wherein the second flow restrictor comprises a lower pressure resistance than that of the first and second pressure resistances. 
     
     
         17 . The method of  claim 1 , wherein the first sensor region comprises at least one prothrombin time sensor, and the second sensor region comprises at least one activated partial thromboplastin time sensor. 
     
     
         18 . The method of  claim 17 , further comprising analyzing an extrinsic pathway of coagulation in the first segment of the fluid sample using the at least one prothrombin time sensor, wherein the first reagent comprises a thrombin-cleavable peptide with a detectable moiety. 
     
     
         19 . The method of  claim 17 , further comprising analyzing an intrinsic pathway of coagulation in the second segment of the fluid sample using the at least one activated partial thromboplastin time sensor, wherein the second reagent comprises a thrombin-cleavable peptide with a detectable moiety. 
     
     
         20 . The method of  claim 1 , wherein the first sensor region comprises a first sensor, and the second sensor region comprises a second sensor. 
     
     
         21 . The method of  claim 1 , wherein the sample comprises a biological sample.