Combined immunoassay and magnetic immunoassay systems and devices for extended range of sensitivity
Inventors
Hu, Jing Hua • Virtanen, Antti Leo Oskari • Miller, Cary James • Hardage, Kenneth Harold
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11680944-B2
Publication Date
2023-06-20
Expiration Date
Abstract
The present invention relates to systems that utilize a combination of immunoassay and magnetic immunoassay techniques to detect an analyte within an extended range of specified concentrations. In particular, a device is provided for detecting an analyte in a biological sample. The device includes a first electrochemical sensor positioned on a substrate. The first electrochemical sensor includes an immobilized layer of antibody configured to bind to the analyte. The device further includes a second electrochemical sensor positioned adjacent to the first electrochemical sensor on the substrate, and a magnetic material that generates a magnetic field aligned with respect to the second electrochemical sensor. The magnetic field captures magnetic beads that have an immobilized layer of antibody configured to bind to the analyte, and concentrates the magnetic beads on or near a surface of the second electrochemical sensor.
Core Innovation
The invention relates to combined non-magnetic and magnetic immunoassay point-of-care devices that use a planar substrate carrying first and second adjacent electrochemical sensors. The first electrochemical sensor includes an immobilized antibody layer configured to bind to an analyte, and the second electrochemical sensor is positioned adjacent to the first sensor. The device architecture includes a substrate opening extending to a region in the substrate below the second electrochemical sensor.
A composite material including a binder and a particulate magnetic material substantially fills the opening and generates a magnetic field aligned with respect to the second electrochemical sensor. Magnetic beads including immobilized antibodies are attracted onto or near the second electrochemical sensor. Dry reagent regions may be provided within the conduit, including antibody-enzyme conjugate, magnetic beads with capture antibodies, and signal antibodies configured to bind the analyte.
The device supports analyte detection over a wider concentration range by combining signals at the first electrochemical sensor and the second electrochemical sensor, including low-end and high-end sensitivity detection. The document describes high-sensitivity cardiac troponin I (cTnI) detection, using optional conductivity sensing for sample positioning and a crossover concentration zone with selection and combining of concentrations using weighted average concentration.
Claims Coverage
The document provides two independent device claims. The inventive features center on adjacent electrochemical sensors with immobilized antibody binding, a bottom-surface opening filled with a binder-containing particulate magnetic composite to align a magnetic field to a second sensor, and dry reagents that include magnetic beads with immobilized antibody plus signal antibodies.
Adjacent antibody-based electrochemical sensors on a planar substrate
A device including a first electrochemical sensor on a planar top surface of a substrate, the first electrochemical sensor including an immobilized layer of antibody configured to bind to an analyte, and a second electrochemical sensor on the planar top surface adjacent to the first electrochemical sensor.
Magnetic field alignment via a bottom opening filled with binder-particulate magnetic composite
An opening in a bottom surface of the substrate extending to a region in the substrate below an associated second electrochemical sensor, wherein a composite material including a binder and a particulate magnetic material substantially fills the opening and the particulate magnetic material generates a magnetic field aligned with respect to the second electrochemical sensor.
Dry magnetic beads with immobilized antibody and dry signal antibodies
First dry reagent comprising magnetic beads including an immobilized layer of antibody configured to bind to the analyte, and second dry reagent comprising signal antibodies configured to bind to the analyte.
Vertically aligned opening relative to second electrochemical sensor
A device wherein the opening extends from a bottom surface of the substrate to a region aligned vertically with respect to the second electrochemical sensor, and the particulate magnetic material generates a magnetic field vertically aligned with respect to the second electrochemical sensor.
Overall, claim coverage is directed to an immunoassay device that integrates adjacent electrochemical sensors with immobilized antibody layers, a bottom-surface opening filled by a binder-containing particulate magnetic composite to align a magnetic field relative to the second sensor, and dry reagents including magnetic beads with immobilized antibodies and signal antibodies that bind the analyte.
Stated Advantages
Extends analyte detection over a wider concentration range, including high-sensitivity cardiac troponin I, by combining detection at the first and second electrochemical sensors.
Documented Applications
Point-of-care electrochemical immunoassay detection of analytes, including high-sensitivity detection of cardiac troponin I (cTnI), in a conduit-based device.
Interested in licensing this patent?