medical equipment for measuring blood coagulation time; electronic device including electrodes
Inventors
Harding, Ian • Iyengar, Sridhar G. • Nguyen, Ha • Williams, Richard
Assignees
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Publication Number
US-7837941-B2
Publication Date
2010-11-23
Expiration Date
Abstract
A device for measuring blood coagulation time is formed from a first substrate; a second substrate; a spacer layer disposed between the first and second substrates, said spacer layer having an opening formed therein defining a sample receiving chamber, a vented sink chamber, and an elongated reservoir forming a conduit for liquid movement between the sample receiving chamber and the sink chamber; a first electrode disposed on the first substrate, said first electrode being exposed in the reservoir portion through a first opening in the spacer layer; and a second electrode disposed on the second substrate, said second electrode being exposed in the reservoir portion through a second opening in the spacer layer. The device of the invention is used in combination with an apparatus that is connected to the first and second electrodes for measuring current flow between the first and second electrodes. Changes in observed current are indicative of flow through the device, and a cessation of flow indicates coagulation.
Core Innovation
A device is described for measuring blood coagulation time using first and second electrodes disposed on first and second substrates, respectively. A spacer layer disposed between the substrates defines an opening that includes a sample receiving chamber, a vented sink chamber, and an elongated reservoir forming a conduit for liquid movement between the sample receiving chamber and the sink chamber. The vented sink chamber is vented to the atmosphere.
The first and second electrodes are exposed through a reservoir portion of the opening in the spacer layer and are in electrically conductive contact with the elongated reservoir. An electrical signal can be detected between the first and second electrodes when a conductive liquid sample is disposed in the reservoir, while at least one electrode is electrically insulated from the sample receiving chamber and from the sink chamber. The relative sizes of the reservoir, the sink, and a region at the connection of the reservoir and the sink are such that the time required for emptying sample from the reservoir in the absence of coagulation is greater than the time required for coagulation to occur.
The device further includes first and second contact leads extending from the first and second electrodes for connection of the device to an apparatus for measuring an electrochemical signal between the first and second electrodes through the sample in the reservoir. The described current profiles relate coagulation-dependent changes including decay, transitions, and cessation to determine coagulation time, including approaches based on rate of current change and transitions to a plateau.
Embodiments described include refinement of reservoir/sink geometry and constraining relationships that define conduit behavior, including a reservoir cross-sectional area relationship relative to the sample receiving chamber and sink chamber. Additional embodiments describe particular electrode materials, insulating/adhesive layer construction, and venting features, as well as reagents for coagulation promotion and target-analyte driven changes in apparent clotting time using a second reagent and a target analyte material, including configurations in which the second reagent and the target analyte material are members of an antibody/antigen pair.
Claims Coverage
The document provides one independent claim that covers the overall device architecture and operating relationships for measuring blood coagulation time, and dependent claims that add specific electrode, geometric, wetting-agent, and analyte-dependent coagulation refinements. The independent claim includes four main inventive areas.
Two-substrate spacer layer defining sample receiving chamber, vented sink chamber, and elongated reservoir conduit
A spacer layer disposed between first and second substrates has an opening defining a sample receiving chamber, a vented sink chamber, and an elongated reservoir forming a conduit for liquid movement between the sample receiving chamber and the sink chamber, wherein the vented sink chamber is vented to the atmosphere.
Exposed first and second electrodes insulated from sample receiving and sink chambers
A first electrode on the first substrate and a second electrode on the second substrate are exposed through the reservoir portion of the opening and are in electrically conductive contact with the elongated reservoir such that an electrical signal can be detected between the first and second electrodes when a conductive liquid sample is disposed in the reservoir, with at least one electrode electrically insulated from the sample receiving chamber and from the sink chamber.
Reservoir and sink sizing so emptying without coagulation is slower than coagulation
The relative sizes of the reservoir, the sink, and a region at the connection of the reservoir and the sink are such that the time required for emptying sample from the reservoir in the absence of coagulation is greater than the time required for coagulation to occur.
Contact leads connecting the device to electrochemical signal measurement through the sample
First and second contact leads extending from the first and second electrodes are provided for connection of the device to an apparatus for measuring an electrochemical signal between the first and second electrodes through a sample in the reservoir.
Overall claim coverage centers on an electrochemical blood coagulation time device that combines a spacer-layer-defined geometry with an elongated reservoir conduit and a vented sink, two reservoir-exposed electrodes electrically insulated from the sample receiving and sink chambers, a size relationship ensuring reservoir emptying without coagulation takes longer than coagulation, and electrode contact leads for electrochemical signal measurement. Dependent refinements add specific material and geometric constraints, wetting agents, and analyte-dependent coagulation using a second reagent and a target analyte material, including an antibody/antigen pair configuration.
Stated Advantages
Enables determining blood coagulation time from electrochemical signal changes between first and second electrodes through a sample in the reservoir.
Uses reservoir/sink relative sizing such that emptying in the absence of coagulation is greater than the time required for coagulation, supporting electrochemical detection of coagulation timing.
Documented Applications
Pathogen identification based on agglutination-induced flow changes reflected as apparent clotting time, including pathogen detection using antibody/antigen interactions for Staphylococcus aureus/clumping factor.
Blood typing, including A/B/Rh typing, based on agglutination-induced flow changes reflected as apparent clotting time.
Hemagglutinin/viral assays, including influenza hemagglutinin, based on agglutination-induced flow changes reflected as apparent clotting time.
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