Apparatus and method for assaying coagulation in fluid samples
First Claim
Patent Images
1. A cartridge for delivering a fluid sample to an analysis location comprising:
- a housing having a closable sample entry port for receiving a fluid sample;
a holding chamber having a first end in communication with the entry port, the holding chamber having a second end with a capillary stop;
wherein the analysis location is in communication with the capillary stop; and
wherein the capillary stop selectively allows passage of the sample from the holding/chamber to the analysis location;
an overflow chamber in communication with the holding chamber, separated by a holding chamber wall which has an orifice for said communication, for handling overflow of incoming sample; and
a pump for providing a force to the fluid sample in the holding chamber, thereby allowing passage of the sample through the capillary stop.
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Accused Products
Abstract
This invention is a disposable cartridge for use at the patient side to perform traditional coagulation assays on fresh whole blood or blood derivative samples. The cartridge, in use with an electronic analyzer allows a fluid sample to be metered and quantitatively mixed with reagents which activate the coagulation cascade. An artificial substrate for thrombin, the enzyme whose action results in clot formation is also provided. Clot formation is subsequently detected using a microfabricated sensor also housed within the cartridge which detects electrochemically the product of the thrombin reaction upon the synthetic substrate.
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Citations
107 Claims
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1. A cartridge for delivering a fluid sample to an analysis location comprising:
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a housing having a closable sample entry port for receiving a fluid sample;
a holding chamber having a first end in communication with the entry port, the holding chamber having a second end with a capillary stop;
wherein the analysis location is in communication with the capillary stop; and
wherein the capillary stop selectively allows passage of the sample from the holding/chamber to the analysis location;
an overflow chamber in communication with the holding chamber, separated by a holding chamber wall which has an orifice for said communication, for handling overflow of incoming sample; and
a pump for providing a force to the fluid sample in the holding chamber, thereby allowing passage of the sample through the capillary stop. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37)
introducing the sample into a cartridge of claim 1 which includes an analysis location, metering a portion of the sample, moving the metered sample to the analysis location, mixing the metered sample with reagent at the analysis location, allowing the enzyme to react with the reagent, positioning the reacted sample at a sensor, and detecting the product of the enzyme reaction using the sensor.
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38. A cartridge adapted for use with an analyzer for assaying an enzyme in a fluid sample comprising:
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a housing having a sample entry port, overflow chamber, holding chamber, and an analysis location containing a hydrophobic area in part, an airtight entry port closure, a pump actuated by the analyzer for moving the sample within the cartridge, one or more reagent deposits in the analysis location comprising at least one substrate capable of reaction with an enzyme in the fluid sample, the reaction of the enzyme forming a detectable reaction product, a first sensor for detecting the location of the fluid sample, and a second sensor for detecting the detectable reaction product. - View Dependent Claims (39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83)
obtaining a sample of blood or blood derivative, placing the sample into the entry port of a cartridge of claim 38, closing the entry port, activating the pump, thereby forcing a sample from the sample chamber into the analysis chamber, oscillating the sample back and forth in the analysis chamber, and determining the concentration of the reaction product using the second sensor.
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75. The method of claim 74 wherein the pump oscillates the sample in the analysis chamber with the trailing edge of the sample positioned in the region of a selected sensor in order to dissolve the substrate in that portion of the sample near the trailing edge.
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76. The method of claim 74 wherein the oscillation is at a frequency in the range of 0.2 to 10 Hertz for a period in the range of 1 to 100 seconds.
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77. The method of claims 74 wherein the oscillation is at a frequency in the range of about 1.5 Hertz for a period of about 20 seconds.
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78. The method of claim 74 wherein the oscillation is at a frequency of about 0.3 Hertz and the second sensor generates a signal at each oscillation.
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79. The method of claim 74 wherein the oscillation is at a frequency sufficient to prevent settling of erythrocytes on a sensor.
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80. The method of claim 74 further comprising the step of:
storing an amperometric first sensor signal after a reagent is dissolved.
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81. The method of claim 80 further comprising the step of:
analyzing subsequent amperometric sensor signals to determine the maximum rate of change in sensor signal.
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82. The method of claim 81 further comprising the step of:
determining a fixed fraction of the maximum rate of change in the sensor signal.
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83. The method of claim 81 further comprising the step of:
determining the coagulation parameter from the first sensor signal and the fixed fraction.
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84. A single-use cartridge used in combination with an analyzer for determining a coagulation parameter of a sample of blood or blood derivative, comprising;
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a cartridge which includes an entry port for receiving a sample, an entry port closure, a holding chamber in communication at a first end with the entry port, and a capillary stop in communication with the holding chamber at a second end, the capillary stop also in communication with an analysis chamber, the holding chamber in communication with an overflow chamber for receiving and retaining excess sample, the overflow chamber in communication with a pneumatic pump actuated by the analyzer, the analyzer actuating the pneumatic pump to displace sample in the holding chamber through the capillary stop into the analysis chamber to deliver a metered portion of the sample into the analysis chamber, the analysis chamber containing a substrate for the enzyme thrombin capable of dissolving in the metered sample, an amperometric sensor for detecting the product of the reaction between thrombin and the substrate, and a conductimetric sensor for detecting the position of the sample in the analysis chamber, the amperometric sensor and the conductimetric sensor connected to the analyzer for providing output signals to the analyzer, the analyzer capable of using the output signal of the conductimetric sensor to actuate the pneumatic pump to control the position of the sample in the analysis chamber, the analyzer capable of determining the coagulation parameter from the output signal of the amperometric sensor, and the cartridge containing a hydrophobic area between the capillary stop and the analysis chamber to prevent sample in the analysis chamber from being drawn back into the holding chamber.
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85. A cartridge for delivering a fluid sample to an analysis location comprising:
- a housing having a closable sample entry port for receiving a fluid sample;
a holding chamber having a first end in communication with the entry port, the holding chamber having a second end with a capillary stop;wherein the analysis location is in communication with the capillary stop and comprising a pre-sensor chamber between the capillary stop and the analysis location, further comprising a hydrophobic area between the analysis location and the pre-sensor chamber; and
wherein the capillary stop selectively allows passage of the sample from the holding chamber to the analysis location;
an overflow chamber, in communication with the holding chamber for handling overflow of incoming sample; and
a pump for providing a force to the fluid sample in the holding chamber, thereby allowing passage of the sample through the capillary stop.
- a housing having a closable sample entry port for receiving a fluid sample;
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86. A cartridge for delivering a fluid sample to an analysis location comprising:
- a housing having a closable sample entry port for receiving a fluid sample;
a holding chamber having a first end in communication with the entry port, the holding chamber having a second end with a capillary stop;
wherein the analysis location is in communication with the capillary stop; and
wherein the capillary stop selectively allows passage of the sample from the holding chamber to the analysis location;an overflow chamber in communication with the holding chamber, for handling overflow of incoming sample; and
a pump in fluidic connection with the overflow chamber for providing a force to the fluid sample in the holding chamber, thereby allowing passage of the sample through the capillary stop. - View Dependent Claims (87, 88, 89, 90, 91, 92, 93, 94, 95, 96)
- a housing having a closable sample entry port for receiving a fluid sample;
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97. A cartridge for delivering a fluid sample to an analysis location comprising:
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a housing having a closable sample entry port for receiving a fluid sample;
a holding chamber having a first end in communication with the entry port, the holding chamber having a second end with a capillary stop;
wherein the analysis location is in communication with the capillary stop; and
wherein the capillary stop selectively allows passage of the sample from the holding chamber to the analysis location;
an overflow chamber in communication with the holding chamber which is above and in fluid communication with the holding chamber and separated by a holding chamber wall, for handling overflow of incoming sample; and
a pump for providing a force to the fluid sample in the holding chamber, thereby allowing passage of the sample through the capillary stop. - View Dependent Claims (98, 99, 100, 101, 102, 103, 104, 105, 106, 107)
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Specification