Methods for detecting hook effect(s) associated with anaylte(s) of interest during or resulting from the conductance of diagnostic assay(s)

Patent metadata

Field	Value
Publication number	US-12313626-B2
Application number	US-201917279958-A
Country	US
Kind code	B2
Filing date	Sep 20, 2019
Priority date	Sep 28, 2018
Publication date	May 27, 2025
Grant date	May 27, 2025

Abstract

Devices and methods for the hook effect detection associated with analytes of interest in the conductance of one or more diagnostic assays, including, without limitation, immunoassays.

First claim

What is claimed is:

1. A method for determining the presence of a hook effect in a patient's liquid test sample to determine the accuracy of concentration measurements of at least one target analyte of interest present within the patient's liquid test sample, the method comprising the steps of:
conducting at least one diagnostic assay on a patient's liquid test sample within a diagnostic assay reaction vessel of a diagnostic assay system to determine the concentration of at least one target analyte of interest present in the patient's liquid test sample, wherein during the conductance of the at least one diagnostic assay, at least a first absorbance measurement (MR1) of the patient's liquid test sample, a second absorbance measurement (MR2) of the patient's liquid test sample, and a final absorbance measurement (MRC) of the patient's liquid test sample are recorded via optical interrogation of the patient's liquid test sample, wherein MR1, MR2, and MRC are taken under the same measurement conditions but at different times such that MR1 is taken at a first time (T 1 ), MR2 is taken at a second time (T 2 ), and MRC is taken at a conclusion of the diagnostic assay, and wherein T 1 and T 2 each occur after a time when the patient's liquid test sample is mixed with an assay reagent and before a time when the diagnostic assay reaches its final absorbance, whereby T 1 , T 2 , and MRC monitor reaction kinetics of the at least one diagnostic assay;
determining a final concentration result of the at least one target analyte associated with the MRC of the patient's liquid test sample;
establishing whether the final concentration result of the at least one target analyte exceeds a predetermined concentration value; and
if the final concentration result of the at least one target analyte exceeds a predetermined concentration value, determining the presence of a hook effect associated with the at least one target analyte of interest present in the patient's liquid test sample by utilizing the MR1, MR2, and MRC in a detection formula, the detection formula comprising the following:
IF (the at least one target analyte's concentration result is ≥ C) AND ((MCR-MR2)/(MR2-MR1) >R), THEN the at least one target analyte of interest present in the patient's liquid test sample is subject to the hook effect,
wherein C is the predetermined concentration value, and R is a predetermined limit for a ratio value to assess reaction kinetics of the at least one diagnostic assay,
further wherein at least one result of the detection formula is output to a user.

2. The method of claim 1 , wherein the patient's liquid test sample is urine.

3. The method of claim 1 , wherein the at least one target analyte of interest is selected from the group selected from a peptide, a protein, and combinations thereof.

4. The method of claim 3 , wherein the at least one target analyte of interest is microalbumin.

5. The method of claim 1 , wherein the optical interrogation is performed by an optical device selected from the group consisting of a spectrophotometer, a fluorometer, and a nephelometer.

6. The method of claim 1 , wherein the at least one diagnostic assay is an immunoassay.

7. The method of claim 1 , wherein the predetermined concentration value is a value selected from a range of from about 0 milligrams/liter to about 500 milligrams/liter.

8. The method of claim 1 , wherein the predetermined concentration value is a value selected from a range of from about 0 milligrams/liter to about 300 milligrams/liter.

9. The method of claim 1 , wherein the diagnostic assay reaction vessel comprises a reaction cassette for use within a diagnostic analyzer.

10. The method of claim 9 , wherein the reaction cassette comprises at least two compartments, wherein each of the at least two compartments comprise at least one diagnostic assay reagent.

11. The method of claim 10 , wherein the at least one diagnostic assay reagent comprises an antibody.

12. The method of claim 11 , wherein the at least one antibody is an antibody of microalbumin.

13. The method of claim 1 , wherein the reaction vessel comprises at least one optical read window, and further wherein the optical interrogation occurs within the at least one optical read window.

14. The method of claim 1 , wherein the user is at least one computer functionally connected to the diagnostic assay system, and further wherein the detection formula is stored in non-transient memory of the at least one computer.

15. The method of claim 1 , wherein the output to the user is a notice that the at least one result of the detection formula indicates that the at least one target analyte of interest is subject to the hook effect, thereby allowing the user to conduct subsequent analyses on the patient's liquid test sample to determine an accurate concentration of the at least one target analyte of interest present in the patient's liquid test sample.

16. A method for determining the presence of a hook effect in a patient's liquid test sample to determine the accuracy of concentration measurements of at least one target analyte of interest present within the patient's liquid test sample, the method comprising the steps of:
conducting at least one diagnostic assay on a patient's liquid test sample within a diagnostic assay reaction vessel of a diagnostic assay system to determine the concentration of at least one target analyte of interest present in the patient's liquid test sample, wherein during the conductance of the at least one diagnostic assay, at least a first absorbance measurement (MR1) of the patient's liquid test sample and a second absorbance measurement (MR2) of the patient's liquid test sample are recorded via optical interrogation of the patient's liquid test sample, wherein MR1 and MR2 are taken under the same measurement conditions but at different times such that MR1 is taken at a first time (T 1 ) and MR2 is taken at a second time (T 2 ), and wherein T 1 and T 2 each occur after a time when the patient's liquid test sample is mixed with an assay reagent and before a time when the diagnostic assay reaches its final absorbance, whereby T 1 and T 2 monitor reaction kinetics of the at least one diagnostic assay;
determining a concentration result of the at least one target analyte associated with the MR2 of the patient's liquid test sample;
establishing whether the concentration result of the at least one target analyte exceeds a predetermined concentration value; and
if the concentration result of the at least one target analyte exceeds a predetermined concentration value, determining the presence of a hook effect associated with the at least one target analyte of interest present in the patient's liquid test sample by utilizing the MR1 and MR2 in a detection formula, the detection formula comprising the following:
IF (Target Analyte Concentration is >C) AND (MR1/MR2)>R, THEN the at least one target analyte of interest present in the patient's liquid test sample is subject to the hook effect,
wherein C is the predetermined concentration value, and R is a predetermined limit for a ratio value to assess reaction kinetics of the at least one diagnostic assay,
further wherein at least one result of the detection formula is output to a user.

17. The method of claim 16 , wherein the patient's liquid test sample is urine.

18. The method of claim 16 , wherein the at least one target analyte of interest is selected from the group selected from a peptide, a protein, and combinations thereof.

19. The method of claim 18 , wherein the at least

Assignees

• Siemens Healthcare Diagnostics Inc

Inventors

• Chaney Julie
• Stradinger Jon
• Kauffmann Aaron
• Mayfield Jeffrey
• Zimmerle Chris

Classifications

• G01N2333/76

  Assays involving albumins other than in routine use for blocking surfaces or for anchoring haptens during immunisation · CPC title

• G01N2021/825

  Agglutination · CPC title

• G01N33/54393

  Improving reaction conditions or stability, e.g. by coating or irradiation of surface, by reduction of non-specific binding, by promotion of specific binding · CPC title

• G01N21/82

  producing a precipitate or turbidity · CPC title

• G01N21/78

  producing a change of colour · CPC title