Compositions and methods for improved creatinine measurement accuracy and uses thereof
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.
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.
21. The creatinine/creatine measuring system of claim 13 , wherein the operations comprise:
applying ΔCREA to a creatinine measurement obtained from a biological matrix sample.
22. The creatinine/creatine measuring system of claim 13 , wherein the stable ratio of creatine to creatinine is 1.5 to 2.