Electrochemical detection of magnetic particle mobility
Inventors
Newman, Peter Michael • Chatelier, Ronald Christopher
Assignees
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Publication Number
US-8974658-B2
Publication Date
2015-03-10
Expiration Date
Abstract
An exemplary embodiment of the invention may include a method for electrochemically monitoring the mobility of particles in a fluid in response to an external field, the method may include monitoring an electrical characteristic of the fluid in an electrochemical cell, the fluid comprising particles that can be moved under the influence of an externally applied field; observing changes in the electrical characteristic caused by particle movement induced by the external field; and inferring a change in the physical state of the fluid from a change in the magnitude of the electrical characteristic observed.
Core Innovation
An electrochemical method monitors the mobility of particles in a fluid in response to an external field by monitoring an electrical characteristic of the fluid in an electrochemical cell, where the fluid comprises magnetic particles that can be moved under the influence of the external field. The external field comprises a changing external magnetic field, and movement of the magnetic particles induced by the external field causes an electrical characteristic that includes a magnitude change due to a change in the mobility of the magnetic particles.
A change in the mobility of the magnetic particles is detected from a change in the magnitude of the electrical characteristic observed. In monitored coagulation contexts, mobility changes alter the magnitude and amplitude of electrical current peaks, enabling inference of a physical state change in the fluid.
The monitored electrical characteristic is described with electrochemical current measurements using an electrochemical cell and soluble electroactive species, including ferricyanide/ferrocyanide, where peak-based clot-time determination is performed by observing current peak behavior and using peak detection criteria such as local maxima, transformed current signals, and peak cessation criteria.
Clot time is further defined using algorithmic peak analysis rules including nth percentile and peak-height thresholding, and calibration is documented using plasmas with known INR. Sensor and meter concepts are described, including a two-electrode strip configuration and a magnetic-field-based monitoring scheme in a detection chamber, including use with coagulation reagents.
Claims Coverage
The document contains one independent claim directed to electrochemically monitoring magnetic particle mobility in response to a changing magnetic field, with dependent claims refining the electrochemical signal observation and mobility-to-detection mapping, including peak-based clot-time determination and threshold/percentile algorithmic rules. Overall, the inventive features center on a magnetic-particle mobility readout using an electrical characteristic in an electrochemical cell and detecting mobility changes from magnitude changes in that electrical characteristic.
Electrochemical monitoring of magnetic particle mobility under a changing magnetic field
Monitoring an electrical characteristic of a fluid in an electrochemical cell, the fluid comprising magnetic particles that can be moved under an external field that comprises a changing external magnetic field; observing an electrical characteristic caused by movement of the magnetic particles induced by the external field, wherein the magnitude of the electrical characteristic can change due to a change in mobility; and detecting a change in mobility from a change in the magnitude of the electrical characteristic observed.
Detecting clot-time from electrochemical current peak behavior
Observing electrochemical current caused by movement of magnetic particles induced by the changing external magnetic field, where magnitude changes are used to determine a clotting time based on current peak behavior.
Percentile-based clot time determination using nth percentile thresholding
Defining a clot time by determining when an nth percentile of data around each point drops below a predetermined threshold, where the nth percentile is between the 50th and 100th percentiles.
Peak-height threshold clot time determination
Determining clot time based on when the height of peaks in current falls below a predetermined threshold using an algorithm.
Two-electrode strip with parallel electrodes separated by 0.05 to 0.5 mm
Performing the method using two electrodes that are parallel to each other and separated by 0.05 to 0.5 mm.
Coagulation of whole blood or plasma on a clotting-factor-containing strip
Using a strip containing clotting factors to correct deficient clotting factors in whole blood or plasma where coagulation causes a change in the physical state of the blood or plasma.
The claim set is primarily covered by a method that electrochemically monitors magnetic particle mobility in a fluid under a changing external magnetic field by detecting mobility changes from magnitude changes in an electrical characteristic observed in an electrochemical cell. Dependent coverage further specifies clot-time determination using electrochemical current peaks and algorithmic clot-time rules including nth percentile thresholding and peak-height thresholding, and narrows implementation to a two-electrode strip geometry and coagulation contexts using clotting-factor-containing strips for correcting deficient clotting factors.
Stated Advantages
Enables detection of a change in mobility of magnetic particles from a change in magnitude of an electrical characteristic.
Enables inference of a physical state change in the fluid using changes in magnitude and amplitude of electrical current peaks.
Supports clot-time determination using peak-based analysis rules including percentile and peak-height thresholds.
Documented Applications
Blood/plasma coagulation monitoring, including prothrombin time (PT) and International Normalized Ratio (INR) monitoring for warfarin therapy.
Use of mediator chemistry including ferricyanide/ferrocyanide in the electrochemical monitoring approach.
Sensor and meter use in a detection chamber with an electrochemical cell concept including a two-electrode strip.
Clot-time determination using peak-based algorithms with peak detection and peak cessation criteria for monitored coagulation reactions.
Use with strips containing clotting factors to correct deficient clotting factors in whole blood or plasma.
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