Data processing: measuring – calibrating – or testing – Measurement system in a specific environment – Chemical analysis
Reexamination Certificate
1999-11-23
2002-10-22
Assouad, Patrick (Department: 2751)
Data processing: measuring, calibrating, or testing
Measurement system in a specific environment
Chemical analysis
C356S042000, C702S104000
Reexamination Certificate
active
06470279
ABSTRACT:
FIELD OF INVENTION
This invention is in the field of spectrophotometric determinations of concentrations of substances in solution and relates to methods of calibration of apparatus used to measure quantity of one or more analytes or interferents in a serum or plasma specimen, using synthetic fluids.
BACKGROUND OF INVENTION
Clinical laboratory tests are routinely performed on serum or plasma of whole blood. In a routine assay, red blood cells are separated from plasma by centrifugation, or red blood cells and various plasma proteins are separated from serum by clotting prior to centrifugation. Hemoglobin (Hb), light-scattering substances like lipid particles, and bile pigments bilirubin (BR) and biliverdin (BV) are typical substances which will interfere with and affect spectrophotometric and other blood analytical measurements. Such substances are referred to as interferents, and they can be measured spectrophotometrically. The presence of such interferents affects the ability to perform tests on the serum or plasma and as such can be said to compromise specimen integrity. An apparatus or instrument used for measuring interferents in serum and plasma i.e., assess specimen integrity, is a substitute for visual inspection. The interferents may be regarded as analytes, with respect to the apparatus used to measure the interferents. Because quantitative results from the determination of the concentration of such interferents are reported based on specific calibration algorithms, there is a need to calibrate and to monitor calibration performance daily.
Unlike many blood analytical apparatus, calibration of spectrophotometric apparatus used to measure quantity of one or more analytes or interferents in a serum or plasma specimen is a cumbersome time intensive exercise (Primary Calibration). Each apparatus used for the purposes of determining the concentration of interferents must be calibrated according to this process and over the lifetime of an apparatus can amount to a considerable amount of time and cost. Accordingly, a faster, more cost effective method of calibration is desirable. An example of a method developed to address such problems using synthetic fluids follows: calibrators or synthetic fluids are tested on first instrument that is shown to be in control by quality control fluids. The absorbance measurements are saved. Primary Calibration Algorithms are applied to absorbance measurements made on first instrument, and predict analyte concentration(s). Concentrations of the analyte(s) predicted for calibrators, are stored on a calibration diskette. Install Primary Calibration Algorithms on second instrument.
Test calibrators on second instrument during calibration procedures. Apply Primary Calibration Algorithms to absorbance measurements made on second instrument, and predict analyte concentration(s). For each analyte, plot concentrations from first instrument on the x-axis, against concentrations from second instrument on y-axis, and obtain linear regression equation.
The linear regression equation for a particular analyte would be in the form, y=mx+c, where m is the slope and c is the y-intercept. All subsequent predictions by second instrument for the same analyte would be adjusted by subtracting “c” and dividing the difference by “m.”
The major disadvantage with this method is that the calibrators need to be carefully designed to produce absorbance spectra that closely resemble the absorbance spectra of serum containing mixed or multiple interferents in the spectral section of the wavelengths used in the calibration algorithm. This can be accomplished through trial and error, but, the entire design and trial-and-error process must be repeated when new calibration algorithms use a different set of wavelengths. Also, such methods are only suitable when the calibration algorithms use a small number of wavelengths.
SUMMARY OF INVENTION
The present inventor has found that using synthetic fluids it is possible to rapidly and efficiently calibrate an apparatus and use the calibration algorithms of a First Apparatus which is conducted by the standard cumbersome time intensive exercise (“Primary Calibration”) and a method for calibrating an apparatus based on the calibration of a First Apparatus, and for recalibrating such apparatus, including recalibration of the First Apparatus. According to one embodiment, these apparatus use absorption of radiation to measure analytes in serum or plasma samples. Throughout this application reference is made to measurements through absorption of radiation.
Accordingly, the present invention provides a method for transferring a calibration algorithm from a First Apparatus to a Second Apparatus whereby the Second Instrument need not be calibrated in the same way in which the First Apparatus was calibrated, i.e, by conducting a Primary Calibration.
According to one embodiment the present invention provides a method for transferring a calibration algorithm from a First Apparatus to a Second Apparatus comprising:
(i) conducting a Primary Calibration of the First Apparatus to obtain at least one Primary Calibration Algorithm using a standard set of wavelengths;
(ii) obtaining measurements of absorbance of a set of calibrators on the First Apparatus at the standard set of wavelengths
(iii) obtaining calibration absorbance measurements of the set of calibrators on a Second Apparatus for at least one wavelength from the standard set of wavelengths;
(iv) establishing a First linear regression equation for each wavelength from the standard set of wavelengths using the calibration absorbance measurements from the First Apparatus and the Second Apparatus; and
(v) incorporating the at least one Primary Calibration Algorithm on the Second Apparatus.
According to a method of the invention there is further provided a method of determining the concentration of an analyte in a sample in a Second Apparatus comprising:
(i) transferring a calibration algorithm from a First Apparatus according to the method just outlined above;
(ii) in the Second Apparatus measuring the absorbance of the sample at the standard set of wavelengths;
(iii) adjusting the measurements of absorbance from the sample with the First linear regression equation to obtain a corrected absorbance; and
(iv) calculating a concentration for the analyte using the corrected absorbance. According to a preferred embodiment in the Primary Calibration Algorithms and the calibration absorbance measurements on the First Apparatus are electronically stored and installed on the Second Apparatus, more preferably on a floppy diskette or an EPROM.
According to another embodiment of the invention the samples used for the Primary Calibration are in a first type of vessel and the calibrators are in the same type of vessel, preferably a pipette tip, test tube (labelled or unlabelled), or blood bag tubing.
According to another embodiment of the method four calibrators are used, preferably all from the same batch, most preferably the calibrators mimic hemoglobin, bilirubin, turbidity or biliverdin.
According to another embodiment of the method the calibrators used in the Second Apparatus are exactly the same calibrators used to provide the absorbance measurement on the First Apparatus.
According to another embodiment of the method the standard wavelengths are measured in the near infrared and adjacent visible light spectrum, preferably ten absorbance measurements are taken at each wavelength of the standard wavelength set.
According to yet another embodiment, the method comprises conducting a Primary Calibration of a First Apparatus and using a quality control fluid to confirm the First Apparatus is functioning wherein the quality control fluid, or calibrator, is contained in a sample container. Next, two or more calibrators, called a “calibration set”, are submitted to the First Apparatus and the absorbance for each of the calibrators is measured on the First Apparatus. These absorbance measurements are stored and provide “calibration absorbance measurements” from the First Apparatus for a calibrati
Assouad Patrick
Katten Muchin Zavis & Rosenman
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