Patent Application
20070291250
The present invention solves the problem of liquid calibrators and controls by providing a stable, inexpensive, non-hazardous solid substance(s) to provide a spectral reference used for the control and/or calibration of diagnostic analyzers. This solid substance is generally hereinafter generically referred to as a “solid control element.” It will be understood that even though “control” is used in describing the element in the description of preferred embodiments, the solid control element could be equally well used as a calibration element for a spectrophotometer. In those embodiments specifically describing calibration, the solid substance will be referred to as a “solid calibration element”.
The method of the present invention can be used in any analysis methodology and analyzer that includes detecting light from a sample to be assessed and is broadly referred to herein as spectrophotometry. This includes photometry which is sometimes defined as analysis of light radiation to correlate a response to only a particular wavelength.
Some examples include absorption photometry assays such as end-point reaction analysis and rate of reaction analysis, turbidimetric assays, nephelometric assays, radiative energy attenuation assays (such as those described in U.S. Pat. No. 4,743,561 and incorporated herein by reference), colorimetric assays, and fluorometry spectrophotometry assays, and immunoassays, all of which are well known in the art. A preferred analysis technique is absorption spectrophotometry, such as end-point reaction analysis, rate of reaction analysis and reagentless sample integrity assessments. Some or all of these techniques can be done with classic wet chemistries; thin film formatted “dry” chemistries such as Vitros® brand dry slides; bead and tube formats or microtiter plates; and the use of magnetic particles.
The preferred embodiments of the present invention are described with reference to absorption spectrophotometry although the broad aspect of the present invention is not so limited. Spectrophotometric techniques are described in, e.g., Modern Optical Methods of Analysis by Eugene D. Elson 1975, which is incorporated by reference in its entirety.
The solid control elements can be used in spectrophotometers on diagnostic analyzers, such as those described above. Spectrophotometers are known per se.
The solid control element is a colored solid, which provides reflection, transmission or scattering in a spectrum relevant to the method used to determine the presence or concentration of an analyte. In one embodiment, the solid control element will preferably be formed to be insertable into the vessel in which the measurement takes place. For example, in a cylindrical cuvette, the control element would take the shape of a cylindrical rod. In those instances where the vessel is a dry slide, such as those in Vitros® diagnostic analyzers, the control element would be a flat reflective surface. It is not necessary that the element occupy the entire volume of the vessel, only that part which is in the path of a beam of light incident on the spectrophotometer detector.
Another feature of the opaque region is described in connection with
The solid control element is made of any suitable material, such as an acrylic polymer or a polypropylene polymer, having an optical absorbance spectrum similar to the analyte to be controlled over wavelength ranges of interest. Dyes or texturing will be added to the material to give it similar spectral characteristics to the analyte of interest. The color provides spectral information that yields a specified analyte concentration via the instrument's method. The color and density of the element are chosen to provide an instrument prediction within the instrument operating range.
The skilled artisan would be capable of selecting the appropriate material for the analyte being calibrated or controlled. For example, in the case of sample quality assessment, a red transparent or translucent acrylic rod can be used which will give spectral characteristics similar to hemolysis, bilirubin (icterus) and turbidity (lipids). In another embodiment, a metering tip is formed from PD702 polypropylene with transparent red dye added and additional texture added to the molding tool. The texture scatters the light and simulates a turbid sample. Although red is referred to for sample quality, other colors may also be used depending on the analyte of interest.
In one embodiment, the solid control element may be inserted into a sample vessel or reaction vessel, providing a means to verify the overall process of transporting, positioning and reading the contents of the vessel. As described above, in another embodiment, the vessel itself will have the desired spectral characteristics to act as the control element. The vessel can be any suitable for spectrophotometric analysis. For example, a cuvette may be used, such as those described in U.S. Patent Application No. 2003/0003591, Des. 290,170 and U.S. Pat. No. 4,639,135 all of which are incorporated in their entireties. Other suitable vessels can include dry slides, such as Vitros® brand dry slides. For sample quality assessments a sealed metering tip, such as a Vitros® Versatip, sold by Ortho-Clinical Diagnostics can be used. Such tips are described in U.S. Pat. No. 6,797,518, incorporated herein by reference in its entirety. Useful translucent or transparent materials for the metering tips that allow desired spectral penetration are those commonly used to manufacture clinical analyzer disposable tips, including polypropylene and polyethylene. Since the solid control element does not deteriorate appreciably with time, the control element may be reused. Also in view of its stability, the solid control element could also be hard mounted on the diagnostic analyzer and be positioned as needed at the detector.
Advantages of the solid control element over liquid controls include:
The present invention also provides a method of calibrating a spectrophotometric process using the solid control element described above as a solid control element. The solid calibration element is inserted into the optical path of a spectrophotometer that includes a light source and a detector. The solid calibration element emits light corresponding to a specified concentration of one or more analytes to be measured when illuminated by the light source. At least one measurement is taken at one or more wavelengths by: directing a beam of light from the light source to the solid calibration element; transmitting the beam through the solid calibration element and optionally the vessel to be measured; and measuring the emitted light beam with the detector.
The detector output is correlated with the specified one or more analytes equivalent concentration of the solid calibration element to calibrate the spectrophotometric process using methods well known in the art. For example, determining the calibration can either be carried out by hand using a graph of absorbance versus concentration of analyte. More preferably, the correlation data can be loaded onto a computer and the computer determines the concentration of analyte based on input of absorbance. The calibration can also be carried out at different analyte concentrations by using additional calibration elements having transmittances corresponding to the different analyte concentrations. The present invention also provides a method for taking a control measurement in a spectrophotometric process. The process includes: providing a solid control element described above. The element is a translucent or transparent material which emits light corresponding to a specified concentration of one or more analytes to be measured. A light source, such as shown in
The present invention has been found to be particularly useful for sample quality assessments as described in U.S. Pat. No. 6,353,471, incorporated herein by reference.
Table 1 below compares the measured concentration (mg/dL) of hemoglobin, bilirubin (icterus) and lipids (turbidity) for both a red acrylic control element and a standard control fluid. As Table 1 indicates, the measured values for the solid control element were all within the operating range of the spectrophotometer.
It will be apparent to those skilled in the art that various modifications and variations can be made to the compounds, compositions and processes of this invention. Thus, it is intended that the present invention cover such modifications and variations, provided they come within the scope of the appended claims and their equivalents.
The disclosure of all publications cited above are expressly incorporated herein by reference in their entireties to the same extent as if each were incorporated by reference individually.
