Indicator of hemolysis

• US 6,689,612 B2
• Filed: 05/03/2002
• Issued: 02/10/2004
• Est. Priority Date: 06/12/1996
• Status: Expired due to Fees

• Current Assignee: Nellcor Puritan Bennett LLC (Medtronic Plc)
• Original Assignee: Spectromedical Inc.
• Inventors: Samsoondar, James
• Primary Examiner(s): WALLENHORST, MAUREEN
• Application Number:
  US10/137,379
• Publication Number:
  US 20030027341A1
• Time in Patent Office: 648 Days
• Field of Search: 436/8, 436/11, 436/12, 436/16, 436/19, 436/66, 436/69, 702/19
• US Class Current: 436/8
• CPC Class Codes: G01N 2496/15 containing dyes to mimic optical absorption of, e.g. hemoglobin
• CPC Class Codes: G01N 33/72 involving blood pigments, e.g. haemoglobin, bilirubin or other porphyrins; involving occult blood
• CPC Class Codes: G01N 33/96 involving blood or serum control standard
• CPC Class Codes: Y10T 436/10 Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing
• CPC Class Codes: Y10T 436/102499 Blood gas standard or control
• CPC Class Codes: Y10T 436/103332 Bilirubin or uric acid standard or control
• CPC Class Codes: Y10T 436/105831 Protein or peptide standard or control [e.g., hemoglobin, etc.]
• CPC Class Codes: Y10T 436/106664 Blood serum or blood plasma standard or control

Abstract

The invention provides a method of monitoring calibration of a spectrophotometric apparatus including one or more calibration algorithms for one or more analytes. This method includes measuring absorbance of a quality control material with the apparatus to obtain a measurement, where the quality control material exhibits an absorbance spectra having a negative slope for a continuous spectral segment from about 5 nm to about 200 nm in length, and where the spectral segment includes a principal calibration wavelength for the one or more analytes. The method then involves calculating one or more concentration values from the measurement using the one or more calibration algorithms, followed by comparing the one or more concentration values with an assigned value given to the quality control material for each of the one or more analytes, and determining if there is a violation of a pre-established quality control rule. In this way one or more calibration algorithms of the apparatus may be monitored.

Claims

1. A method for producing a corrected predicted value for an indicator of hemolysis in a sample, in the presence of methemoglobin (metHb), said method comprising the steps of:

i) developing a first primary calibration algorithm for one of a total hemoglobin (Hb), an oxy-hemoglobin (oxy-Hb), or a total hemoglobin-methemoglobin (Hb-methb), for predicting a first value for one of said total Hb, said oxy-Hb, or said total Hb-metHb, in said sample wherein said total Hb, said oxy-Hb, or said total Hb-metHb serves as an indicator of hemolysis and said example;

ii) deriving a second primary calibration algorithm for said met-Hb, for predicting a second value for said met-Hb in said sample; and

iii) adding said predicted second value for said met-Hb to one said predicted first value for total Hb, said predicted first value for oxy-Hb, or said predicted first value for total Hb-metHb, to produce said corrected predicted value for an indicator or hemolysis.

2. The method of claim 1, wherein said step of developing (step i)) and said step of deriving (step ii)), each comprises the steps of:

a) collecting an absorbance measurement for each calibration sample in a primary calibration set, said calibration samples having known reference values for total Hb, oxy-Hb, metHb and total Hb-metHb;

b) calculating an order derivative of absorbance for each of said calibration samples; and

c) creating a primary calibration algorithm for each of said indicator of hemolysis and said met-Hb using said derivatives of absorbance, said known reference values, and a statistical technique.

3. The method of claim 2, wherein in said step of collecting (step a)), said reference values for either said total Hb or said oxy-Hb, are obtained from the measured amounts of said total Hb or said oxy-Hb, in the presence of one or more of oxy-Hb, deoxy-Hb, carboxy-Hb and met-Hb in said calibration samples.

4. The method of claim 3, wherein said oxy-Hb accounts for about 95% of total Hb in said sample, or wherein said total-Hb in said sample comprises about 95% oxy-Hb.

5. The method of claim 2, wherein in said step of creating (step c)), said statistical technique is selected from the group consisting of simple linear regression, multiple linear regression, partial least squares, and principal component analysis.

6. The method of claim 1, wherein said sample is one of serum, plasma, urine, synovial fluid or cerebrospinal fluid.

7. A method for flagging a predicted value for an indicator of hemolysis in a sample, in the presence of methemoglobin (metHb), said method comprising the steps of:

i) developing a first primary calibration algorithm for one of a total hemoglobin (Hb), an oxy-hemoglobin (oxy-Hb), or a total hemoglobin methemoglobin (Hb-metHb), for predicting a value for one of said total Hb, said oxy-Hb, or said total Hb-metHb, in said sample, wherein said total Hb, said oxy-Hb, or said total Hb-metHb serves as an indicator of hemolysis in said sample;

ii) deriving a second primary calibration algorithm for said met-Hb, for predicting a second value for said met-Hb in said sample;

iii) determining if said predicted met-Hb value exceeds a pre-determined value; and

iv) flagging said predicted value for said total Hb, said oxy-Hb or said total Hb-metHb, when said predicted met-Hb value exceeds said pre-determined value.

8. The method of claim 7, wherein said step of developing (step i)) and said step of deriving (step ii)), each comprises the steps of:

a) collecting an absorbance measurement for each calibration sample in a primary calibration set, said calibration samples having known reference values for total Hb, oxy-Hb, metHb and total Hb-metHb,

b) calculating an order derivative of absorbance for each of said calibration samples; and

c) creating a primary calibration algorithm for each of said indicator of hemolysis and said met-Hb using said derivatives of absorbance, said known reference values, and a statistical technique.

9. The method of claim 8, wherein in said step of collecting (step a)), said reference values for each of said total Hb or said oxy-Hb are obtained from the measured amounts of said total Hb or said oxy-Hb, in the presence of one or more of oxy-Hb, deoxy-Hb, carboxy-Hb and met-Hb in said calibration samples.

10. The method of claim 9 wherein said oxy-Hb accounts for about 95% of total Hb in said sample, or wherein said total-Hb in said sample comprises about 95% oxy-Hb.

11. The method of claim 8, wherein in said step of creating (step c)), said statistical technique is selected from the group consisting of simple linear regression, multiple linear regression, partial least squares, and principal component analysis.

12. The method of claim 7, wherein said sample is one of serum, plasma, urine, synovial fluid or cerebrospinal fluid.