Compositions and methods for improved creatinine measurement accuracy and uses thereof

Patent metadata

Field	Value
Publication number	US-11327042-B2
Application number	US-201916429993-A
Country	US
Kind code	B2
Filing date	Jun 3, 2019
Priority date	Apr 5, 2019
Publication date	May 10, 2022
Grant date	May 10, 2022

Abstract

The disclosure relates to electrochemical sensors for measuring creatinine and creatine in a patient's blood. More particularly, the disclosure relates to compositions and methods for improving measurement accuracy of electrochemical sensors used for measuring creatinine and creatine.

First claim

We claim:

1. A method used with a calibrated creatine sensor and a calibrated creatinine sensor, the method comprising:
(a) measuring, with the calibrated creatine sensor, a measured creatine sensor current signal (MΔI2) of a first biological matrix correction solution (BMCS2) having a known concentration of creatine (CR_BMCS2), a known concentration of creatinine (CREA_BMCS2), and a predefined concentration of one or more biological matrix factors, where a predefined concentration of a biological matrix factor is an amount within a normal biological sample;
(b) determining a creatine sensor biological matrix correction factor (ΔCR) based on a measured concentration of creatine (MCR_BMCS2) in BMCS2 and CR_BMCS2, where MCR_BMCS2 is based on MΔI2;
(c) measuring, with the calibrated creatinine sensor, a measured creatinine sensor current signal (MΔI2′) of the BMCS2; and
(d) determining a creatinine sensor biological matrix correction factor (ΔCREA) based on a measured concentration of creatinine (MCREA_BMCS2) in the BMCS2 and CREA_BMCS2, where MCREA_BMCS2 is based on MΔI2′;
wherein CR_BMCS2 and CREA_BMCS2 have stable values based on a storage temperature of BMCS2 or based on a stable ratio of creatine to creatinine in BMCS2.

2. The method of claim 1 , wherein the one or more biological matrix factors in BMCS2 comprise one or more of Ca ++ , HCO 3− , pH, pCO 2 or pO 2 .

3. The method of claim 2 , wherein a concentration of Ca ++ is between about 0.4 and about 1.6 mg/dL and a concentration of HCO 3− is between about 10 and about 30 mmol/L.

4. The method of claim 1 , further comprising:
applying ΔCR to a creatine measurement obtained from a biological matrix sample.

5. The method of claim 1 , wherein ΔCREA is applied to a creatinine measurement obtained from a biological matrix sample.

6. The method of claim 1 , further comprising:
(e) measuring, with the calibrated creatine sensor, a second measured creatine sensor current signal (M2ΔI2) of a second biological matrix correction solution (BMCS3) having a known concentration of creatine (CR_BMCS3), a known concentration of creatinine (CREA_BMCS3), and the predefined concentration of one or more biological matrix factors;
(f) determining a second creatine sensor biological matrix correction factor (ΔCR′) based on a measured concentration of creatine (M2CR_BMCS3) in BMCS3 and CR_BMCS3, where M2CR_BMCS3 is based on M2ΔI2;
(g) measuring, with the calibrated creatinine sensor, a second measured creatinine sensor current signal (M2ΔI2′) of the BMCS3; and
(h) determining a second creatinine sensor biological matrix correction factor (ΔCREA′) based on a measured concentration of creatinine (M2CREA_BMCS3) in the BMCS3 and CREA_BMCS3, where M2CREA_BMCS3 is based on M2ΔI2′;
wherein CR_BMCS3 and CREA_BMCS3 have stable values based on a storage temperature of BMCS3 or based on a stable ratio of creatine to creatinine in BMCS3.

7. The method of claim 6 , wherein the one or more biological matrix factors in BMCS3 comprise one or more of Ca ++ , HCO 3− , pH, pCO 2 or pO 2 .

8. The method of claim 6 , wherein further comprising:
applying ΔCR′ to a Slope of a creatine measurement obtained from a biological matrix sample.

9. The method of claim 6 , wherein ΔCR, ΔCR′, ΔCREA and ΔCREA′ are applied to a Slope 1 and a Slope 2 of a creatinine measurement obtained from a biological matrix sample.

10. The method of claim 6 , wherein BMCS2 or BMCS3, respectively, comprises about 2-5 mg/dL of creatine and about 1-3 mg/dL of creatinine.

11. The method of claim 1 , wherein the stable ratio of creatine to creatinine is 1.5 to 2.

12. The method of claim 1 , wherein the stable values are stable for a minimum of 8 months.

13. A creatinine/creatine measuring system, comprising:
a calibrated creatine sensor;
a calibrated creatinine sensor;
one or more network interfaces to communicate in a computer network;
a processor coupled to the network interfaces and the creatine sensor and the creatinine sensor and adapted to execute one or more processes; and
a memory storing instructions for a process that is executable by the processor, the process comprising operations to:
(a) measure, with the calibrated creatine sensor, a measured creatine sensor current signal (MΔI2) of a first biological matrix correction solution (BMCS2) including a known concentration of creatine (CR_BMCS2), a known concentration of creatinine (CREA_BMCS2), and a predefined concentration of one or more biological matrix factors, where a predefined concentration of a biological matrix factor is an amount within a normal biological sample;
(b) determine a creatine sensor biological matrix correction factor (ΔCR) based on a measured concentration of creatine (MCR_BMCS2) in BMCS2 and CR_BMCS2, where MCR_BMCS2 is based on MΔI2;
(c) measure, with the calibrated creatinine sensor, a measured creatinine sensor current signal (MΔI2′) of BMCS2; and
(d) determine a creatinine sensor biological matrix correction factor (ΔCREA) based on a measured concentration of creatinine (MCREA_BMCS2) in the BMCS2 and CREA_BMCS2, where MCREA_BMCS2 is based on MΔI2′;
wherein CR_BMCS2 and CREA_BMCS2 have stable values based on a storage temperature of BMCS2 or based on a stable ratio of creatine to creatinine in BMCS2.

14. The creatinine/creatine measuring system of claim 13 , wherein the process further comprises operations to:
(e) measure, with the calibrated creatine sensor, a second measured creatine sensor current signal (M2ΔI2) of a second biological matrix correction solution (BMCS3) having a known concentration of creatine (CR_BMCS3), a known concentration of creatinine (CREA_BMCS3), and the predefined concentration of one or more biological matrix factors;
(f) determine a second creatine sensor biological matrix correction factor (ΔCR′) based on a measured concentration of creatine (M2CR_BMCS3) in BMCS3 and CR_BMCS3, where M2CR_BMCS3 is based on M2ΔI2;
(g) measure, with the calibrated creatinine sensor, a second measured creatinine sensor current signal (M2ΔI2′) of the BMCS3; and;
(h) determine a second creatinine sensor biological matrix correction factor (ΔCREA′) based on a measured concentration of creatinine (M2CREA_BMCS3) in the BMCS3 and CREA_BMCS3, where M2CREA_BMCS3 is based on M2ΔI2′;
wherein CR_BMCS3 and CREA_BMCS3 have stable values based on a storage temperature of BMCS3 or based on a stable ratio of creatine to creatinine in BMCS3.

15. The creatinine/creatine measuring system of claim 14 , wherein the operations comprise:
applying ΔCR, ΔCR′, ΔCREA and ΔCREA′ to a Slope 1 and a Slope 2 of a creatinine measurement obtained from a biological matrix sample.

16. The creatinine/creatine measuring system of claim 14 , wherein the stable values are based on a stable ratio of creatine to creatinine in BMCS3.

17. The creatinine/creatine measuring system of claim 14 , wherein the one or more biological matrix factors comprise one or more of Ca ++ , HCO 3− , pH, pCO 2 , or pO 2 .

18. The creatinine/creatine measuring system of claim 14 , wherein the operations comprise:
applying ΔCR′ to a Slope of a creatine measurement obtained from a biological matrix sample.

19. The creatinine/creatine measuring system of claim 13 , wherein the one or more biological matrix factors comprise one or more of Ca ++ , HCO 3− , pH, pCO 2 , or pO 2 .

20. The creatinine/creatine measuring system of claim 13 , wherein the operations comprise:
applying ΔCR to a creatine measurement obtained from a biological matrix sample.

Assignees

• Instr Laboratory Co

Inventors

• Xu Xiaoxian
• Pamidi Prasad
• Raimondi David
• Malhotra Ruchika
• Curley Matthew

Classifications

• C12Q1/002

  Electrode membranes · CPC title

• G01N33/70

  involving creatine or creatinine · CPC title

• C12Q1/005

  involving specific analytes or enzymes (including groups of enzymes, e.g. oxydases; C12Q1/004 takes precedence) · CPC title

• B01D69/12

  Composite membranes; Ultra-thin membranes · CPC title

• G01N27/333

  Ion-selective electrodes or membranes (glass electrodes G01N27/36) · CPC title