DEVICES, SYSTEMS AND METHODS FOR EVALUATION OF HEMOSTASIS

• US 20180275150A1
• Filed: 05/29/2018
• Published: 09/27/2018
• Est. Priority Date: 02/15/2011
• Status: Active Grant

• Current Assignee: Hemosonics LLC (Stago International SAS)
• Original Assignee: Hemosonics LLC (Stago International SAS)
• Inventors: Viola, Francesco, Walker, William F., Browne, Gregory V., Magyar, Robert S., Hansen, Bjarne, Denny, Christopher G.
• Granted Patent: US 10,161,944 B2
• Time in Patent Office: Days
• CPC Class Codes: B01L 2200/04 Exchange or ejection of cartridges, containers or reservoirs
• CPC Class Codes: B01L 2200/0647 Handling flowable solids, e.g. microscopic beads, cells, particles
• CPC Class Codes: B01L 2300/02 Identification, exchange or storage of information
• CPC Class Codes: B01L 2300/024 Storing results with means integrated into the container
• CPC Class Codes: B01L 2300/027 Digital display, e.g. LCD, LED
• CPC Class Codes: B01L 2300/0627 Sensor or part of a sensor is integrated
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/123 Flexible; Elastomeric
• CPC Class Codes: B01L 2300/14 Means for pressure control
• CPC Class Codes: B01L 2300/16 Surface properties and coatings
• CPC Class Codes: B01L 2300/1805 Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
• CPC Class Codes: B01L 2400/0436 acoustic forces, e.g. surface acoustic waves [SAW]
• CPC Class Codes: B01L 2400/0439 ultrasonic vibrations, vibrating piezo elements
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/049 : vacuum
• CPC Class Codes: B01L 2400/0666 : Solenoid valves
• CPC Class Codes: B01L 3/5027 : by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/502761 : specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: B01L 3/527 : for a plurality of reagents
• CPC Class Codes: G01N 2800/224 : Haemostasis or coagulation
• CPC Class Codes: G01N 29/024 : by measuring propagation velocity or propagation time of acoustic waves
• CPC Class Codes: G01N 29/222 : Constructional or flow details for analysing fluids optoacoustic fluid cells G01N29/2425
• CPC Class Codes: G01N 33/86 : involving blood coagulating time or factors, or their receptors
• CPC Class Codes: G01N 35/00 : Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor

Abstract

Provided are devices, systems and methods for evaluation of hemostasis. In some embodiments, an apparatus is disclosed comprising a housing; a plurality of test chambers located in the housing, the plurality of test chambers including chambers configured for measurements via a system that interrogates one or more viscoelastic properties of test samples in the test chambers, wherein the one or more viscoelastic properties is used to characterize dynamics of coagulation and/or fibrinolysis.

Claims

1-73. -73. (canceled)

74. A method for evaluating hemostasis, comprising:

providing a disposable cartridge including a fluid pathway comprising an inlet for receiving a blood sample, wherein the inlet communicates with an inlet channel in the cartridge, the inlet channel communicating with at least a first channel and a second channel, wherein the first channel is in fluid communication with a first test chamber and the second channel is in fluid communication with a second test chamber, and wherein the disposable cartridge includes a thermally conductive portion;

introducing a blood sample into the inlet and then the inlet channel of the cartridge, wherein a first portion of the blood sample is received in the first channel and the first test chamber and a second portion of the blood sample is received in the second channel and the second test chamber;

adjusting the temperature of the blood sample, or a portion thereof, along the thermally conductive portion;

allowing the first portion of the blood sample to mix with a first reagent or combination of reagents to produce a first test sample;

allowing the second portion of the blood sample to mix with a second reagent or combination of reagents to form a second test sample;

interrogating the first test sample in the first test chamber to determine at least one parameter including a first parameter selected from the group consisting of clot time, clot stiffness, clot formation rate, and lysis time; and

interrogating the second test sample in the second test chamber to determine at least one parameter including a second parameter selected from the group consisting of clot time, clot stiffness, clot formation rate, and lysis time;

wherein the interrogation to determine the first parameter, the second parameter, or a combination thereof is based on a viscoelastic measurement of the blood sample.

75. The method of claim 74, wherein interrogating the first test sample to determine the first parameter includes assessing a change in mechanical properties of the first test sample.

76. The method of claim 75, wherein the first parameter is determined based on a stiffness measurement of the first test sample.

77. The method of claim 76, further comprising assessing platelet function by determining a differential between the first parameter and the second parameter, wherein the second parameter is determined based on a stiffness measurement of the second test sample.

78. The method of claim 77, wherein the second reagent or combination of reagents further includes an antagonist of platelet aggregation.

79. The method of claim 75, wherein at least one of the first parameter and the second parameter is associated with the stiffness of a fibrin network formed in the sample.

80. The method of claim 75, wherein the first reagent or combination of reagents includes an activator of coagulation that activates the first test sample via an intrinsic pathway of coagulation, an extrinsic pathway of coagulation, or a combination thereof.

81. The method of claim 80, wherein the first reagent or combination of reagents includes an activator of coagulation that activates the first test sample via an intrinsic pathway of coagulation and the second reagent or combination of reagents includes an activator of coagulation that activates the second test sample via an extrinsic pathway of coagulation.

82. The method of claim 81, wherein the first parameter and the second parameter both include clot time.

83. The method of claim 80, further comprising:

allowing a third portion of blood sample to mix with a third reagent or combination of reagents to produce a third test sample; and

interrogating the third test sample in the third test chamber to determine at least one parameter including a third parameter selected from the group consisting of clot time, clot stiffness, clot formation rate, and lysis time

84. The method of claim 83, wherein the third reagent or combination of reagents includes an activator of coagulation that activates the third test sample via an intrinsic pathway of coagulation, an extrinsic pathway of coagulation, or a combination thereof.

85. The method of claim 83, wherein the third reagent or combination of reagents further includes an antagonist of fibrinolysis.

86. The method of claim 74, further comprising:

determining, by a processor, a curve associated with the stiffness of each test sample as a function of time.

87. The method of claim 86, further comprising:

evaluating, by the processor, a derivative of the curve to determine at least one parameter of the test samples.

88. The method of claim 87, further comprising:

determining, by the processor, a clot time for a test sample based on a comparison of the derivative of the curve to a threshold value.

89. The method of claim 74, wherein the at least one of the first parameter and the second parameter is determined based on an application of the viscoelastic measurement to a viscoelastic model.

90. The method of claim 74, further comprising:

determining an intrinsic pathway coagulation factors index, an extrinsic pathway coagulation factors index, a platelets index, a fibrinogen index, a fibrinolysis index, or a combination thereof.

91. The method of claim 74, wherein the thermally conductive portion is located along the fluid pathway.

92. The method of claim 91, wherein the temperature of the blood sample, or a portion thereof, is adjusted to a temperature at or near normal body temperature.

93. The method of claim 74, further comprising:

allowing the first portion to mix with the first reagent or combination of reagents prior to entering the first test chamber and allowing the second portion to mix with the second reagent or combination of reagents prior to entering the second test chamber.

94. The method of claim 93, wherein allowing the first portion of the blood sample to mix with a first reagent or combination of reagents to produce a first test sample includes providing a magnetic component in the disposable cartridge and applying a magnetic field to facilitate mixing of the first portion of the blood sample and the first reagent or combination of reagents to produce the first test sample.

95. The method of claim 74, further comprising:

applying a pressure differential from a source external to the disposable cartridge to draw at least a portion of the blood sample to at least one of the first test chamber and the second test chamber.

96. The method of claim 95, wherein applying a pressure differential from a source external to the disposable cartridge includes applying a vacuum to the disposable cartridge.

97. The method of claim 95, further comprising:

preventing the blood sample from flowing out of the disposable cartridge.

98. The method of claim 74, wherein at least one of the first parameter and the second parameter is determined based on an elastic component derived from the viscoelastic measurement of the blood sample.

99. The method of claim 74, further comprising:

optically monitoring the fluid level in at least a portion of the disposable cartridge.

100. The method of claim 74, further comprising:

transmitting a first energy into the first test chamber or onto a transducer associated therewith; and

receiving a reflected second energy therefrom, wherein the received reflected second energy is used to determine the first parameter.

101. The method of claim 100, wherein the first and second energies are of the same form, and the form is acoustic energy.

102. A method for evaluating hemostasis, comprising:

feeding a blood sample to a disposable cartridge through an inlet in the cartridge, wherein the blood sample is directed through the inlet into an inlet channel in the cartridge, wherein a first portion of the blood sample flows from the inlet channel into the first channel and the first test chamber and a second portion of the blood sample flows into the second channel and the second test chamber, and wherein the disposable cartridge includes a thermally conductive portion therein;

adjusting the temperature of the blood sample, or a portion thereof, along the thermally conductive portion;

mixing the first portion of the blood sample with a first reagent or combination of reagents to produce a first test sample;

mixing the second portion of the blood sample with a second reagent or combination of reagents to form a second test sample;

interrogating the first test sample in the first test chamber to determine at least one parameter including a first parameter selected from the group consisting of clot time, clot stiffness, clot formation rate, and lysis time; and

interrogating the second test sample in the second test chamber to determine at least one parameter including a second parameter selected from the group consisting of clot time, clot stiffness, clot formation rate, and lysis time;

wherein the interrogation to determine the first parameter and/or the second parameter is based on a viscoelastic measurement of the blood sample.

103. The method of claim 102, wherein the step of feeding the blood sample to the disposable cartridge comprises:

inserting the blood sample into the disposable cartridge through the inlet from a sample container;

or

drawing the blood sample into the disposable cartridge through the inlet from a sample container.