Method and apparatus for measurement of blood substitutes

• US 7,198,955 B1
• Filed: 10/16/1997
• Issued: 04/03/2007
• Est. Priority Date: 03/03/1997
• Status: Expired due to Fees

• Current Assignee: Covidien LP (Medtronic Plc)
• Original Assignee: NIR Diagnostics Incorporated
• Inventors: MacIntyre, Duncan, Samsoondar, James
• Primary Examiner(s): Soderquist; Arlen
• Application Number:
  US09/367,859
• Time in Patent Office: 3,456 Days
• Field of Search: 436/66, 436/71, 436/73, 436/79, 436 86-100, 436/164, 436/171, 436/175, 436/183, 436/125, 356/39, 435/15, 435/17, 435/21, 435/26
• US Class Current: 436/66
• CPC Class Codes: G01N 2496/15 containing dyes to mimic optical absorption of, e.g. hemoglobin
• CPC Class Codes: G01N 33/721 Haemoglobin
• CPC Class Codes: G01N 33/84 involving inorganic compounds or pH
• CPC Class Codes: G01N 33/96 involving blood or serum control standard
• CPC Class Codes: Y10T 436/14 Heterocyclic carbon compound [i.e. , O, S, N, Se, Te, as only ring hetero atom]
• CPC Class Codes: Y10T 436/141111 Diverse hetero atoms in same or different rings [e.g., alkaloids, opiates, etc.]
• CPC Class Codes: Y10T 436/142222 Hetero-O [e.g., ascorbic acid, etc.]
• CPC Class Codes: Y10T 436/143333 Saccharide [e.g., DNA, etc.]
• CPC Class Codes: Y10T 436/144444 Glucose
• CPC Class Codes: Y10T 436/145555 Hetero-N
• CPC Class Codes: Y10T 436/146666 Bile pigment
• CPC Class Codes: Y10T 436/147777 Plural nitrogen in the same ring [e.g., barbituates, creatinine, etc.]
• CPC Class Codes: Y10T 436/148888 Uric acid
• CPC Class Codes: Y10T 436/15 Inorganic acid or base [e.g. , hcl, sulfuric acid, etc. ]
• CPC Class Codes: Y10T 436/193333 In aqueous solution
• CPC Class Codes: Y10T 436/25125 Digestion or removing interfering materials

Abstract

A method is disclosed whereby the concentration of a blood substitute, such as cross-linked hemoglobin, in a serum or plasma specimen is rapidly and accurately identified and quantified. The method further takes the measured concentration of the blood substitute and uses it to correct for its effect, if any, on a measured analyte concentration, e.g., serum/plasma total protein. Further, the method allows for the determination of the concentration of true hemoglobin in the presence of blood substitutes. The method is carried out in respect of samples contained in a primary or secondary labelled tube, or a pipette tip used to dispense serum or plasma in a blood analyzer.

Claims

1. A method of determining a corrected concentration of an analyte contained in a specimen comprising a blood substitute interferent and a non-blood substitute interferent, said method comprising the steps of:

i) providing a first calibration algorithm for said blood substitute interferent, a second calibration algorithm for said non-blood substitute interferent, a first linear equation defining a relationship between a measured concentration of said analyte and a concentration of said blood substitute interferent, and a second linear equation defining a relationship between a measured concentration of said analyte and a concentration of said non-blood substitute interferent, said first and second calibration algorithms developed using a calibration set comprising variable amounts of said blood substitute interferent and said non-blood substitute interferent;

ii) measuring an absorbance or reflectance of radiation of said specimen in a tube or a pipette tip, wherein said measuring is performed in the absence of any reaction step that generates a chromophore within said specimen;

iii) using said first and second calibration algorithms and said absorbance or reflectance measured in step (ii) to calculate a concentration of said blood substitute interferent and a concentration of said non-blood substitute interferent in said specimen;

followed by

iv) determining an initial concentration of said analyte in said specimen disposed within an analysis slide with a slide analyzer, and

v) using said first and second linear equations from step (i), said concentrations from step (iii), and said initial concentration from step (iv), to determine said corrected concentration of said analyte.

2. The method of claim 1, wherein said analyte is selected from the group consisting of Na, K, Cl, HCO₃, Ca, Mg, creatinine, urea, total protein, gamma glutamyl transferase (GGT), aspartate amino transferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK), alkaline phosphatase (ALP) and total bilirubin (Tbili).

3. The method of claim 1 wherein reflectance is used in step (ii).

4. The method of claim 1 wherein the radiation is in the range of 474–

910 nm.

5. The method of claim 1 wherein absorbance is used in step (ii).

6. The method of claim 1, wherein said non-blood substitute interferent is selected from the group consisting of haemoglobin (Hb), bilirubin (BR), biliverdin (BV), turbidity and a mixture thereof.

7. The method of claim 1, wherein said blood substitute interferent is cross-linked hemoglobin.

8. A method of determining a corrected concentration of an analyte contained in a specimen comprising a blood substitute interferent, said method comprising the steps of:

i) providing a calibration algorithm for said blood substitute interferent and a linear equation defining a relationship between a measured concentration of said analyte and a concentration of said blood substitute interferent, said calibration algorithm developed using a calibration set comprising variable amounts of said blood substitute interferent;

ii) measuring an absorbance or reflectance of radiation of said specimen in a tube or a pipette tip, wherein said measuring is performed in the absence of any reaction step that generates a chromophore within said specimen;

iii) using said calibration algorithm and said absorbance or reflectance measured in step (ii) to calculate a concentration of said blood substitute interferent;

followed by

iv) determining an initial concentration of said analyte in said specimen disposed within an analysis slide with a slide analyzer, and

v) using said linear equation from step (i), said concentration from step (iii), and said initial concentration from step (iv), to determine said corrected concentration of said analyte.

9. The method of claim 8, wherein said analyte is selected from the group consisting of Na, K, Cl, HCO₃, Ca, Mg, creatinine, urea, total protein, gamma glutamyl transferase (GGT), aspartate amino transferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK), alkaline phosphatase (ALP) and total bilirubin (Tbili).

10. The method of claim 8, wherein reflectance is used in step (ii).

11. The method of claim 8, wherein the radiation is in the range of 474–

910 nm.

12. The method of claim 8, wherein absorbance is used in step (ii).

13. The method of claim 8, wherein said blood substitute interferent is cross-linked hemoglobin.