Stabilization of labile analytes in reference materials

Patent metadata

Field	Value
Publication number	US-9506939-B2
Application number	US-201414270701-A
Country	US
Kind code	B2
Filing date	May 6, 2014
Priority date	May 6, 2013
Publication date	Nov 29, 2016
Grant date	Nov 29, 2016

Abstract

Provided herein are assay control materials comprising stable analytes and lyophilized unstable analytes, and methods of making and using the same.

First claim

What is claimed is:

1. A multianalyte control kit comprising
a first container holding at least one unstable control analyte, wherein the at least one unstable control analyte is lyophilized in the form of beads; and
a second container holding at least one stable control analyte in a base matrix solution from a biological sample from which the unstable control analyte has been removed, wherein the biological sample is saliva, lymph, urine, milk, mucus, cerebrospinal fluid (CSF), cell lysate, or tissue culture supernatant, wherein the base matrix solution comprises a buffer selected from HEPES and Tris, wherein the buffer is in an amount to control the pH of the base matrix solution in a range from 6 to 8.

2. The multianalyte control kit of claim 1 , wherein the base matrix solution comprises at least one component selected from the group consisting of: a protease inhibitor, a chelating agent, a salt, a antioxidant, an antioxidant enzyme, a cryoprotectant, a surfactant, and an antibiotic agent.

3. The multianalyte control kit of claim 1 , further comprising at least one additional container holding the at least one lyophilized unstable control analyte in the form of beads at a different concentration than in the first container, and at least one further additional container holding the at least one stable control analyte in a base matrix solution at a different concentration than in the second container, wherein the base matrix solution comprises a buffer selected from HEPES and Tris, wherein the buffer is in an amount to control the pH of the base matrix solution in a range of 6 to 8.

4. The kit of claim 1 , wherein the base matrix solution is urine depleted for the unstable control analyte.

5. The kit of claim 1 , wherein the at least one unstable control analyte is bilirubin or creatinine or both bilirubin and creatinine, and wherein the biological sample is urine.

6. The kit of claim 5 , wherein the base matrix solution was generated in a method comprising treating urine with creatininase.

7. The kit of claim 5 , wherein the at least one stable control analyte is selected from the group consisting of amylase, calcium, chloride, cortisol, glucose, hCG, magnesium, microalbumin, phosphorus, potassium, sodium, urea nitrogen, and uric acid.

8. The kit of claim 7 , wherein the at least one stable analyte further comprises one or more of ketones, leukocyte esterase, nitrite, protein, and urobilinogen.

9. The kit of claim 1 , wherein the base matrix solution comprises PEG, HSA, BSA, human hemoglobin, a protease inhibitor, a chelating agent, an antioxidant, an antioxidant enzyme, a cryoprotectant, a surfactant, or an antibiotic agent.

10. The kit of claim 1 , wherein the unstable control analyte is selected from the group consisting of creatinine, bilirubin, salicylate, a triglyceride, alanine aminotransferase (ALT), alkaline phosphatase, high density lipoprotein, pseudocholinesterase, folate, and homocysteine.

11. The method of claim 1 , wherein the base matrix solution further comprises phosphate buffer saline (PBS).

12. A method for assembling the multianalyte control kit of claim 1 , the method comprising
lyophilizing at least one unstable analyte into the form of beads to generate the at least one unstable control analyte in the form of beads in the first container; and
adding at least one stable analyte to a base matrix solution that comprises a buffer selected from HEPES and Tris, wherein the buffer is in an amount to control the pH of the base matrix solution in a range of 6 to 8, to generate the at least one stable control analyte in the base matrix solution in the second container.

13. The method of claim 12 , wherein the at least one unstable control analyte is selected from the group consisting of creatinine, bilirubin, salicylate, a triglyceride, alanine aminotransferase (ALT), alkaline phosphatase, high density lipoprotein, pseudocholinesterase, folate, and homocysteine.

14. A method for preparing a control from the multianalyte control kit of claim 1 , the method comprising,
suspending the at least one unstable control analyte in a solution to form a suspended at least one unstable analyte, and
combining the suspended at least one control unstable analyte with the at least one stable control analyte.

15. The method of claim 14 , wherein the suspending and combining steps are separate.

16. The method of claim 14 , wherein the at least one unstable control analyte and at least one stable control analyte are added to a base matrix solution.

17. The method of claim 16 , wherein the base matrix solution is processed urine that was generated in a method comprising treating urine with creatininase.

18. The method of claim 14 , wherein the base matrix solution comprises at least one component selected from the group consisting of: a protease inhibitor, a chelating agent, buffer, a salt, an antioxidant, an antioxidant enzyme, a cryoprotectant, a surfactant, and an antibiotic agent.

19. The method of claim 14 , wherein the at least one unstable control analyte is selected from the group consisting of creatinine, bilirubin, salicylate, triglyceride, alanine aminotransferase (ALT), alkaline phosphatase, high density lipoprotein, pseudocholinesterase, folate, and homocysteine.

Assignees

• Bio Rad Laboratories Inc

Inventors

• Ebrahim Alireza
• De Vore Karl
• Spates Christopher

Classifications

• F26B5/06

  the process involving freezing · CPC title

• G01N33/96 Primary

  involving blood or serum control standard · CPC title

• G01N2496/80

  Multi-analyte reference solutions containing cholesterol, glucose and the like · CPC title