Claims for Patent: 8,852,877

Summary for Patent: 8,852,877

Title:	Apparatus and method for identifying a hook effect and expanding the dynamic range in point of care immunoassays
Abstract:	The present invention relates to systems and methods for the rapid in situ determination of the existence of a hook effect and expansion of the dynamic range of a point of care immunoassay. For example, a system for identifying a hook effect and expanding the dynamic range of an immunoassay is provided that may include a primary sensor having first immobilized antibodies that may be configured to generate a first signal based on a presence or absence of a target analyte in a sample. The system may further include an attenuated sensor having second immobilized antibodies at a reduced concentration relative to a concentration of the first immobilized antibodies on the primary sensor and that may be configured to generate a second signal based on the presence or absence of the target analyte in the sample. The system may further include a processor configured to determine a presence of a hook effect in the immunoassay based on relative values of the first and second signals and optionally determine the target analyte concentration of the sample.
Inventor(s):	Campbell; John (Woodlawn, CA), Nguyen; Linda (Gloucester, CA), Smith; James (North Gower, CA), Weiss; Wenda (Munster, CA)
Assignee:	Abbott Point of Care Inc. (Princeton, NJ)
Application Number:	14/141,837
Patent Claims:	1. A system for identifying a hook effect in an immunoassay, the system comprising: a primary sensor comprising first immobilized antibodies and configured to generate a first signal based on a presence or absence of a target analyte in a sample; an attenuated sensor comprising second immobilized antibodies at a reduced concentration relative to a concentration of the first immobilized antibodies on the primary sensor and configured to generate a second signal based on the presence or absence of the target analyte in the sample; and a processor configured to determine a presence of a hook effect in the immunoassay based on relative values of the first and second signals. 2. The system of claim 1, wherein the first immobilized antibodies comprise a first affinity for the target analyte and the second immobilized antibodies comprise a second affinity for the target analyte, the first affinity being different from the second affinity. 3. The system of claim 1, wherein the first and second immobilized antibodies are the same antibodies. 4. The system of claim 1, wherein the first and second immobilized antibodies are immobilized on microparticles. 5. The system of claim 4, wherein the microparticles are adsorbed over the primary sensor and the attenuated sensor. 6. The system of claim 5, wherein the first and second immobilized antibodies comprise at least one antibody specific to the target analyte. 7. The system of claim 6, wherein the microparticles adsorbed over the attenuated sensor comprise the second immobilized antibodies and a co-absorbate. 8. The system of claim 7, wherein the microparticles adsorbed over the primary sensor do not comprise the co-absorbate. 9. The system of claim 7, wherein the co-absorbate dilutes surface activity of the second immobilized antibodies on the microparticles adsorbed over the attenuated sensor. 10. The system of claim 7, wherein the presence of the co-absorbate on the microparticles over the attenuated sensor provides the reduced concentration of the second immobilized antibodies relative to the concentration of first immobilized antibodies. 11. The system of claim 7, wherein the co-absorbate comprises non-specific antibodies and/or proteins. 12. The system of claim 11, wherein the non-specific antibodies comprise mouse IgG or goat IgG. 13. The system of claim 11, wherein the proteins comprise bovine serum albumin (BSA) or human serum albumin (HSA). 14. The system of claim 1, wherein the processor is further configured to determine a concentration of the target analyte based on the presence of the hook effect and the relative values of the first and second signals. 15. The system of claim 1, further comprising at least one additional sensor comprising third immobilized antibodies at a different concentration relative to the concentrations of the first and second immobilized antibodies and configured to generate a third signal based on the presence or absence of the target analyte in the sample, wherein the processor is further configured to determine a concentration of the target analyte based on the presence of the hook effect and relative values of the first, second, and third signals. 16. An immunosensor system for identifying a hook effect in an immunoassay, the immunosensor system comprising: a primary immunosensor comprising a first immobilized antibody and configured to generate a first signal based on a sandwich between the first immobilized antibody, a target analyte, and a labeled antibody; an attenuated immunosensor comprising a second immobilized antibody at a reduced concentration relative to a concentration of the first immobilized antibody and configured to generate a second signal based on a sandwich between the second immobilized antibody, the target analyte, and the labeled antibody; and a processor configured to determine a presence of a hook effect in the immunoassay based on relative values of the first and second signals. 17. The immunosensor system of claim 16, wherein the first immobilized antibodies comprise a first affinity for the target analyte and the second immobilized antibodies comprise a second affinity for the target analyte, the first affinity being different from the second affinity. 18. The immunosensor system of claim 16, wherein the first and second immobilized antibodies are the same antibodies. 19. The immunosensor system of claim 16, wherein the primary immunosensor and the attenuated immunosensor are electrochemical sensors. 20. The immunosensor system of claim 16, wherein the labeled antibody is labeled with alkaline phosphatase (ALP). 21. The immunosensor system of claim 16, wherein the labeled antibody is labeled with alkaline phosphatase (ALP) and the first and second signals are generated at the primary immunosensor and the attenuated immunosensor respectively from an electroactive species with a phosphate moiety that is cleaved by the ALP. 22. The immunosensor system of claim 16, wherein the primary immunosensor and the attenuated immunosensor are disposed in a disposable cartridge that is configured to perform the immunoassay to determine a presence of the target analyte in a sample. 23. The immunosensor system of claim 22, wherein the sample comprises a blood sample. 24. The immunosensor system of claim 16, wherein the target analyte is selected from the group consisting of: troponin I, troponin T, creatine kinase myocardial band (CKMB), procalcitonin, beta human chorionic gonadotropin (bHCG), human chorionic gonadotropin (HCG), N-terminal pro brain natriuretic peptide (NTproBNP), pro brain natriuretic peptide (proBNP), brain natriuretic peptide (BNP), myoglobin, parathyroid hormone, d-dimer, neutrophil gelatinase-associated lipocalin (NGAL), galectin-3, and prostate specific antigen (PSA). 25. The immunosensor system of claim 16, wherein the second immobilized antibody is provided at the attenuated immunosensor at less than about 5% of a binding capacity of the first immobilized antibody provided at the primary immunosensor. 26. The immunosensor system of claim 16, wherein the processor is configured to determine the lack of the hook effect when the second signal from the attenuated immunosensor is high and the first signal from the primary immunosensor is commensurately high. 27. The immunosensor system of claim 16, wherein the processor is configured to determine the presence of the hook effect when the second signal from the attenuated immunosensor is low and the first signal from the primary immunosensor is high. 28. The immunosensor system of claim 16, wherein the first and second immobilized antibodies have an affinity constant in a range of about 1.times.10.sup.-7 to 1.times.10.sup.-15. 29. The immunosensor system of claim 16, wherein the first and second immobilized antibodies are immobilized on microparticles having a diameter in a range of about 0.01-5.0 .mu.m. 30. The immunosensor of claim 16, wherein: the primary immunosensor further comprises a first electrode and a first polyvinyl alcohol layer (PVA), the first PVA layer being disposed between the first electrode and the first immobilized antibody; and the attenuated immunosensor further comprises a second electrode and a second PVA layer, the second PVA layer being disposed between the second electrode and the second immobilized antibody. 31. An immunosensor system comprising: a plurality of immunosensors, wherein each immunosensor of the plurality of immunosensors comprises a different concentration of an immobilized antibody specific to an analyte of interest, and each immunosensor is configured to generate a signal based on a sandwich between the immobilized antibody, the analyte of interest, and a labeled antibody; and a processor configured to determine a presence of a hook effect in an immunoassay based on relative values of each generated signal. 32. The immunosensor system of claim 31, wherein the processor is further configured to determine a concentration of the analyte of interest based on the presence of the hook effect and the relative values of each generated signal. 33. A method for identifying a hook effect in an immunoassay, the method comprising: providing a sample to a primary sensor comprising first immobilized antibodies; generating a first signal from the primary sensor based on a presence or absence of a target analyte in the sample; providing the sample to an attenuated sensor comprising second immobilized antibodies provided at a reduced concentration relative to a concentration of the first immobilized antibodies; generating a second signal from the attenuated sensor based on the presence or absence of the target analyte in the sample; determining a ratio of the first and the second signals based on relative values of the first and second signals; and determining a presence or absence of a hook effect in the immunoassay based on the determined ratio. 34. The method of claim 33, further comprising determining a concentration of the target analyte based on the presence or absence of the hook effect and the relative values of the first and second signals. 35. The method of claim 33, further comprising: providing the sample to at least one additional sensor comprising third immobilized antibodies at a different concentration relative to the concentrations of the first and second immobilized antibodies; generating a third signal based on the presence or absence of the target analyte in the sample; and determining a concentration of the target analyte based on the presence or absence of the hook effect and relative values of the first, second, and third signals. 36. A method of using an attenuated immunosensor for identifying a hook effect in an immunoassay for a target analyte, the method comprising: applying a sample to a primary immunosensor comprising a first immobilized antibody; generating a first signal from the primary immunosensor based on a sandwich between the first immobilized antibody, the target analyte, and a labeled antibody; applying the sample to the attenuated immunosensor comprising a second immobilized antibody provided at a reduced concentration relative to a concentration of the first immobilized antibody; generating a second signal from the attenuated immunosensor based on a sandwich between the second immobilized antibody, the target analyte, and the labeled antibody; computing relative values of the first and second signals; determining a ratio of the first and second signals based on the relative values of the first and second signals; and determining a presence or absence of a hook effect in the immunoassay based on the determined ratio.

Details for Patent 8,852,877

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	01/15/1974		2032-12-28
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	12/27/1984		2032-12-28
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	02/15/1985		2032-12-28
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	02/16/1990		2032-12-28