Chemistry: analytical and immunological testing – Composition for standardization – calibration – simulation,...
Reexamination Certificate
1998-12-11
2002-04-16
Wallenhorst, Maureen M. (Department: 1743)
Chemistry: analytical and immunological testing
Composition for standardization, calibration, simulation,...
C436S011000, C436S012000, C436S016000, C436S066000, C702S019000
Reexamination Certificate
active
06372503
ABSTRACT:
TECHNICAL FIELD
This invention is in the field of spectrophotometric determinations of concentrations of substances in solution and relates to a quality control (QC) material for monitoring instrument precision on a daily basis In particular the QC material is used to monitor instruments which are used to screen for serum or plasma specimen quantities of various interferents, by measurement of the near infrared (NIR) radiation and the adjacent visible radiation transmitted through a sample in a labelled tube, a pipette tip, or any similar material through which radiation can pass. The material can also serve as calibrators.
BACKGROUND OF INVENTION
Clinical laboratory tests are routinely performed on the 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 instrument 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 monitor calibration performance daily.
Internal quality control is a process used by all clinical laboratories for monitoring instrument calibration performance, particularly precision or reproducibility. It involves testing a stable material for the analyte(s) in question on a daily basis, and establishing target values for each analyte(s). Any stable material with similar spectral characteristics at selected wavelengths as the interferents under consideration, may be used as QC material, as long as a target value for the particular analyte can be assigned to it. Also, deviation from the target values resulting in violation of some pre-established rules, e.g., Westgard's multi-rules, should indicate a need for calibration adjustment or recalibration. Usually QC materials are tested daily, and at low, medium and high levels, in order to cover the dynamic range of a given assay. For any analyte, as long as the pre-established rules are not violated, the calibration algorithm for that analyte may be considered valid.
Accuracy or agreement with the true value or actual concentration of a particular analyte is usually not the primary concern with internal QC, therefore an accurate amount of the analyte does not have to be present in the QC material. However, concentrations of the interferents can be assigned to the QC material, and their predicted and assigned values can be used to adjust the initial calibration algorithms.
When recalibration is indicated, a series of 3 to 5 QC samples with assigned analyte concentrations (may be regarded as calibrators), can be used to make calibration adjustments; recalibration is not a simple process, and adjustment of the initial calibration for biases may be preferred.
DISCLOSURE OF INVENTION
The present invention provides a material which is able to allow for monitoring the calibration of spectrophotometric instruments which are used to measure concentrations of interferents using near infrared radiation and the adjacent visible radiation, and at the same time is stable at room temperature for a considerable period of time. The material can also be used to make calibration adjustments for biases, when necessary. This is also regarded as recalibration.
In its broad aspect the invention provides a quality control material for monitoring the calibration of instruments used to screen for interferents in serum or plasma specimens. In another aspect, the invention provides a quality control material to monitor the instrument calibrations for hemolysis, turbidity, bilirubinemia and biliverdinemia, either separately, or any two, or any three, or all four simultaneously, depending on the make-up of the quality control material. The material does not contain any blood products such as plasma lipids, bile pigments, or hemoglobin, is stable at room temperature, and is ready for use with up to four constituents.
In a further aspect, the invention provides a material and a method for monitoring the calibration of instruments used to screen for interferents in serum or plasma specimens using the quality control material of this invention.
In yet a further aspect, the invention provides a material and a method for adjusting the calibrations for biases, by using the slope and intercept of the linear regression equation obtained by plotting the assigned values of the respective interferents on the x-axis, and the predicted values, based on the original calibration algorithms, on the y-axis. This procedure is regarded herein as recalibration.
In a further aspect, the invention provides a substance with an absorbance spectrum which mimics the combined presence of hemoglobin, turbidity, bilirubin, and biliverdin at selected wavelengths in the 490 to 1085 nm region, and which combination of up to four substances provides a consistent stable composition.
In a particular embodiment, the invention relates to a composition containing amaranth, titanium dioxide, and methyl orange and biliverdin dihydrochloride. This composition is preferably prepared in a phosphate buffered saline and pH adjusted to about 7.4. In an alternative embodiment of this invention a lipid emulsion of any source commercially available, e.g., Intralipid™ (IL), can be used in place of titanium dioxide, methylene blue can be used in place of biliverdin dihydrochloride, and 10 millimoles per liter sodium bicarbonate must be used instead of the phosphate buffered saline. For stability, the latter can be sterilized by autoclaving. The amaranth is used to mimic hemoglobin, the titanium dioxide or IL is used to mimic turbidity, methyl orange is used to mimic bilirubin, and the methylene blue is used to mimic biliverdin. Other dyes may be used, for example, phenol red or basic fuchsin may be used to mimic hemoglobin; phenol red at acidic pH's or amaranth at slightly higher pH may be used to mimic bilirubin; azure, thionine, or toluidine blue O may be used in combination with amaranth, to mimic biliverdin. Also, in respect of alternatives to mimic turbidity, any substance which produces an absorbance pattern similar to the “apparent” absorbance in the region used by a calibration algorithm, may be used. One such example is copper sulfate. Turbidity causes an increase in the “apparent” absorbance. Apparent absorbance is based on the fact that transmitted light is measured and converted to absorbance units, therefore an instrument cannot distinguish true absorbance from loss of light due to scattering. In some cases, turbidity produces absorbance which is inversely proportional to wavelength. Turbidity is monitored by the slope of the absorbance curve at a single wavelength, namely, in the region greater than 800 nm.
In a preferred embodiment, the invention consists of amaranth, phenol red, copper sulfate, and toluidine blue O, in 100 millimoles per liter acetate buffer, pH 3 to 4. For low levels of BR, the amaranth can mimic both Hb and BR, making it possible to leave out phenol red. Within a given batch of QC material it is desirable to maintain a constant pH because spectral absorbance is affected by pH. Consequently, in a further aspect of the present invention, the pH of a given batch of QC material is maintained at a constant pH.
REFERENCES:
patent: 4001142 (1977-01-0
Wallenhorst Maureen M.
Zavis Katten Muchin
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