Data processing: measuring – calibrating – or testing – Measurement system in a specific environment – Chemical analysis
Reexamination Certificate
1999-09-10
2002-08-20
Hilten, John S. (Department: 2863)
Data processing: measuring, calibrating, or testing
Measurement system in a specific environment
Chemical analysis
C702S030000
Reexamination Certificate
active
06438499
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to an analyzer which analyzes a chromatogram obtained by applying a sample containing plural analytes to liquid chromatography, gas chromatography or electrophoresis using a column, a slab or the like. In particular, it relates to a chromatogram analyzer preferably used for measurement of given analytes of interest, for example, in assays of catecholamines or amino acids in a blood sample or a urine sample and in assays for quality control.
2. Discussion of Background
For chromatographic measurement of the concentrations of analytes of interest, the analytes in a sample are separated by using a liquid chromatograph, a gas chromatograph or an electrophoresis instrument and detected to give a chromatogram. Subsequently, the chromatogram is analyzed for identification of the peaks in the chromatogram attributable to individual analytes (hereinafter sometimes referred to simply as peak identification). Finally, the heights or areas of the identified peaks are determined and compared with the heights or areas of peaks chromatographically obtained from a sample containing known amounts of identical analytes under the same conditions for quantification of the analytes.
For identification of the peak attributable to a particular analyte in chromatogram analyses, it has been conventional to detect a peak within a peak detection zone between a peak detection starting time and a peak detection ending time established before and after the time at which the particular analyte is expected to emerge as a peak (the reference peak emergence time; T
i
) by a change in the slope of the chromatogram from positive to negative or by an upturn with a slope changing from almost zero to positive and a subsequent downturn with a slope changing from negative back to almost zero in the chromatogram, or by the highest point of the chromatogram within the peak detection zone.
For identification of the peak attributable to a particular analyte, it has been conventional to fix a reference peak emergence time (T
i
) and a duration from the peak detection starting time and the peak detection ending time (&Dgr;T
i
) for the analyte and detect a peak within the peak detection zone defined by T
i
and &Dgr;T
i
(usually from T
i
−&Dgr;T
i
/2 to T
i
+&Dgr;T
i
/2).
In cases of identification of plural analyte peaks, each &Dgr;T
i
is usually smaller than the estimated intervals to neighboring peaks so that the peak detection zone determined for each peak does not overlap with the others.
In liquid chromatography, gas chromatography and electrophoresis, if the internal factors such as column or capillary, eluent or carrier gas composition and flow rate and the external factors such as temperature are constant, chromatograms can be obtained with good reproducibility, and the peak emergence time and the peak width for one analyte do not change a lot. Therefore, if these factors are constant, peak detection with narrow &Dgr;T
i
around T
i
leads to correct peak identification.
In practice, however, in chromatography, the same analyte can emerge as peaks with different shapes at different positions on chromatograms, and the actual peak emergence time can move forward or backward out of the peak detection zone for the analyte, because for example, in liquid chromatography, it is virtually impossible that the temperature, flow rate and eluent composition are always the same and because of difference in column performance among lots and change in column performance with time.
In such cases, conventional analysis methods can not identify peaks correctly, and reliable measurements are difficult. Even if a large &Dgr;T
i
(a wide peak detection zone) is fixed to allow peak detection despite a shift of the actual peak emergence time, there is a problem that correct peak identification is impossible when the actual peak emergence time for the analyte shifts by more than half of the estimated intervals to the emergence times of the neighboring peaks for some reason. Also a large &Dgr;T
i
increases the possibilities of misidentification of an interfering peak such as a ghost peak (a peak which emerges, for example, when the eluent is switched in liquid chromatography without attribution to any analyte) and a peak attributable to a contaminant as an analyte peak, and the possibilities of emergence of another analyte peak within the peak detection zone for the. analyte, and is, therefore, adverse to correct peak identification, after all.
SUMMARY OF THE INVENTION
Accordingly, the object of the present invention is to provide a chromatogram analyzer which identifies analyte peaks correctly without misidentifying ghost peaks or contaminant peaks as analyte peaks even if actual analyte peaks emerge at times different from T
i
to give a chromatogram different in shape and positions of peaks by various factors.
In order to achieve the above-mentioned object, according to claim
1
of the present application (hereinafter referred to as the first aspect of the present invention), the present invention provides a chromatogram analyzer which analyzes a chromatogram obtained by applying a sample containing n analytes (wherein n is a natural number of at least 2) to chromatography to detect peaks attributable to the n analytes, wherein the analyzer comprises a first storage means which stores m search sets each containing n non-overlapping peak detection zones which are defined by individual peak detection starting times and peak detection ending times (wherein m is a natural number of at least 2, and each peak detection zone for one analyte in an arbitrary search set overlaps with the peak detection zone for the same analyte in another search set); a second storage means which stores a chromatogram of the sample; a first arithmetic means which detects a peak, if any, within the peak detection zone for each of the n analytes in each search set and, if a peak is detected, matches the detected peak with the corresponding analyte, and if no peak is detected, matches no peak with the analyte to obtain identical or different peak identification results in the m search sets, and a second arithmetic means which selects one of the m peak identification results obtained by the first arithmetic means.
According to claim
4
of the present application (hereinafter referred to as the second aspect of the present invention), the present invention also provides a chromatogram analyzer which analyzes a chromatogram obtained by applying a sample containing n analytes (wherein n is a natural number of at least 3) to chromatography to detect peaks attributable to the n analytes, wherein the analyzer comprises a first storage means which stores m search sets each containing n non-overlapping peak detection zones which are defined by individual peak detection starting times and peak detection ending times (wherein m is a natural number of at least 2, and each peak detection zone for one analyte in an arbitrary search set overlaps with the peak detection zone for the same analyte in another search set); a second storage means which stores a chromatogram of the sample; a first arithmetic means which detects a peak, if any, within the peak detection zone for each of the n analytes in each search set and, if a peak is detected, matches the detected peak with the corresponding analyte, and if no peak is detected, matches no peak with the analyte to obtain identical or different peak identification results in the m search sets, and a second arithmetic means which selects one of the m peak identification results obtained by the first arithmetic means.
According to claim
21
of the present application (hereinafter referred to as the third aspect of the present invention), the present invention further provides a chromatogram analyzer which analyzes a chromatogram obtained by applying a sample containing at least three analytes, which comprises a second storage means which stores the chromatogram, a first arithmetric means which detects peaks in the chromatogram and identi
Hilten John S.
Tosoh Corporation
Washburn Douglas N
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