Disposable system for analysis of hemostatic function
Inventors
Viola, Francesco • Higgins, Timothy • Homyk, Andrew • Corey, F. Scott • Regan, Franklin F. • Walker, William F. • Bryant, David • Givens, Thomas • Lloyd, Cynthia Ann
Assignees
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Publication Number
US-11366093-B2
Publication Date
2022-06-21
Expiration Date
Abstract
A disposable system, in some embodiments, includes a multi-channel or multi-chamber test cartridge device configured to operate with a testing system for evaluation of hemostasis in a subject by in vitro evaluation of a test sample from the subject. The disposable system, in some embodiments, is configured to interrogate the test sample to evaluate clot stiffness, strength, or other mechanical properties of the test sample to assess the function of various physiological processes occur during coagulation and/or dissolution of the resulting clot.
Core Innovation
A method receives in a cartridge a sample from a sample holding tube and meters the sample in a plurality of metering chambers to form a plurality of metered samples. Each metered sample is mixed with a respective set of one or more reagents, or combinations of reagents, to form a respective mixed sample. Mixing includes repeatedly flowing the first metered sample along a mixing path that includes a first metering chamber, a first set of one or more reagent pockets containing the first set of reagents, and a first serpentine pathway in communication with the metering chamber and reagent pockets.
The first metered sample is repeatedly flowed in a first direction and in a second direction reversed from the first direction from a first detection zone located in, or after, the first serpentine pathway through at least a portion of the serpentine pathway toward the first metering chamber. The first metering chamber is connected to a first testing chamber through the first serpentine pathway and the first set of one or more reagent pockets. The repeated flow is carried out by applying a varying pressure from a measurement system at a first port in communication with the first serpentine pathway.
After mixing, the method drives the first mixed sample into the first testing chamber and interrogates the first testing chamber by the measurement system to determine one or more viscoelastic properties of the first mixed sample. The determined one or more viscoelastic properties are provided for an assessment of hemostasis of the sample. The cartridge supports multi-channel hemostasis testing by metering, reagent mixing via serpentine pathways over reagent pockets, driving mixed samples to dedicated testing chambers, and measurement interrogation to assess viscoelastic behavior.
The described approach supports reagent sets used to modulate hemostasis, including coagulation activators, platelet modulators, and fibrinolysis-related agents. Example reagents described include lyophilized reagent beads in reagent pockets and reagents that include kaolin, heparinase I, thromboplastin, polybrene, abciximab and cytochalasin D, tranexamic acid, and agents associated with calcium for citrated whole blood. The method also includes determining viscoelastic properties such as shear modulus and using those determinations for hemostasis assessment, including clot time and stiffness change, with fibrinolysis-related metrics using measurements with and without fibrinolysis inhibitors.
Claims Coverage
The independent claim is claim 1, and it covers a cartridge-based method in which metered sample portions are mixed with reagent sets via repeated bidirectional flow through a serpentine mixing pathway over reagent pockets, then driven to a testing chamber where the measurement system interrogates viscoelastic properties to assess hemostasis. Across dependent claim refinements, inventive features are further specified by reagent storage format, pressure-driven bidirectional flow at a port, and the viscoelastic property and outputs determined by the measurement system.
Repeated serpentine mixing with bidirectional flow over reagent pockets
Mixing each metered sample with a respective set of one or more reagents or combinations of reagents by repeatedly flowing the first metered sample in a first direction along a mixing path that includes the first metering chamber, the first set of one or more reagent pockets, and the first serpentine pathway to a first detection zone, and in a second direction reversed to the first direction from the first detection zone back through the serpentine pathway toward the first metering chamber.
Varying pressure-driven, port-based mixing cycles
Repeatedly flowing the first metered sample in the first and second directions over the mixing path from an application of a varying pressure from a measurement system at a first port in communication with the first serpentine pathway.
Driven transfer to testing chamber followed by viscoelastic interrogation
Driving the first mixed sample into the first testing chamber and interrogating the first testing chamber by the measurement system to determine one or more viscoelastic properties of the first mixed sample, wherein the determined one or more viscoelastic properties is provided for an assessment of hemostasis of the sample.
Reagent pockets containing lyophilized beads
The first set of one or more reagent pockets contains the first set of one or more reagents or a combination of reagents provided as one or more lyophilized beads.
Shear modulus as a determined viscoelastic property
The measurement system determines the shear modulus of the first mixed sample as one or more viscoelastic properties of the sample.
Pressure-defined bidirectional movement through the serpentine pathway
Flowing the first metered sample by applying first and then opposite positive or negative pressure from a measurement system at a first port to move the sample through a first serpentine pathway in first and second directions.
Overall claim coverage centers on a cartridge method combining metering, repeatedly cycled bidirectional serpentine mixing over reagent pockets under varying port-based pressure, and interrogation of viscoelastic properties in a testing chamber to assess hemostasis, with refinements specifying lyophilized reagent storage, shear modulus determination, and pressure-defined bidirectional flow.
Stated Advantages
Provides an assessment of hemostasis of the sample using determined viscoelastic properties of the mixed sample.
Documented Applications
Point-of-care hemostasis testing by preparing and analyzing blood or plasma samples in a disposable multi-channel cartridge integrated with a measurement system to assess viscoelastic properties related to clot time, clot stiffness, and hemostatic indices, including fibrinolysis-related metrics.
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