Combined immunoassay and magnetic immunoassay systems and devices for extended range of sensitivity
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.
1. A device for detecting an analyte in a biological sample comprising:
a substrate including a planar top and bottom surface;
a first electrochemical sensor positioned on the top surface of the substrate, the first electrochemical sensor including an immobilized layer of antibody configured to bind to the analyte;
a second electrochemical sensor positioned on the top surface of the substrate and adjacent to the first electrochemical sensor;
an opening in the bottom surface of the substrate extending to a region in the substrate below the second electrochemical sensor; and
a composite material including a binder and a particulate magnetic material, the composite material substantially filling the opening,
wherein a shape of the opening includes a substantially triangular cross-section, and a base of the substantially triangular cross-section is co-planar with the bottom surface of the substrate and an apex of the substantially triangular cross-section is below the second electrochemical sensor, and
wherein the particulate magnetic material generates a magnetic field that is aligned with respect to the second electrochemical sensor.
2. The device of claim 1 , further comprising a first reagent region coated with an antibody-enzyme conjugate for the analyte.
3. The device of claim 2 , further comprising a second reagent region coated with magnetic beads that include an antibody immobilized to a surface of the magnetic beads for the analyte.
4. The device of claim 3 , wherein the first reagent region and the second reagent region are located on the substrate, and the magnetic field is configured to focus and attract the magnetic beads onto a surface of the second electrochemical sensor once the magnetic beads are mixed with the biological sample.
5. The device of claim 1 , wherein the shape of the opening is selected from the group consisting of: a cone, a pyramid, a tetrahedron, a polygon of conical form, and a V-shaped trench.
6. The device of claim 1 , wherein the substantially triangular cross-section extends through at least 75 % of a distance from the bottom surface to the top surface of the substrate.
7. The device of claim 1 , wherein the binder is a thermal setting ink, a polyimide, or polyvinyl alcohol (PVA).
8. The device of claim 1 , wherein the particulate magnetic material is comprised of neodymium iron boron (NdFeB) alloy or aluminum nickel cobalt (AlNiCo) alloy.
9. The device of claim 1 , wherein the magnetic field is greater than about 0.1 Tesla and is orthogonal to a horizontal plane of the top surface of the substrate.
10. The device of claim 1 , wherein the magnetic field is greater than about 0.5 Tesla and is orthogonal to a horizontal plane of the top surface of the substrate.
11. The device of claim 1 , wherein the first electrochemical sensor and the second electrochemical sensor comprise a gold microarray electrode.
12. The device of claim 4 , wherein the analyte is cardiac troponin I (cTnl).
13. The device of claim 12 , wherein the immobilized layer of antibody of the first electrochemical sensor is configured to bind to cTnl.
14. The device of claim 12 , wherein the antibody immobilized to the surface of the magnetic beads is configured to bind to cTnl.