CN112444589A - Chromatographic peak detection method, device, computer equipment and storage medium - Google Patents

Chromatographic peak detection method, device, computer equipment and storage medium Download PDF

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CN112444589A
CN112444589A CN202011398945.5A CN202011398945A CN112444589A CN 112444589 A CN112444589 A CN 112444589A CN 202011398945 A CN202011398945 A CN 202011398945A CN 112444589 A CN112444589 A CN 112444589A
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chromatographic
peak
signal
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hemoglobin
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CN112444589B (en
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徐岩
曾映
胡明龙
纪道锐
胡文雍
杨文创
伍方辉
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Lifotronic Technology Co ltd
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Abstract

The present application relates to a chromatographic peak detection method, apparatus, computer device and storage medium. The method comprises the following steps: acquiring a starting point coordinate, an end point coordinate and a peak point coordinate of a chromatographic peak in an original chromatographic signal; separating chromatographic signals of corresponding chromatographic peaks from the original chromatographic signals according to the starting point coordinates and the end point coordinates; fitting the corresponding chromatographic signals according to the fitting functions corresponding to the chromatographic peaks to obtain fitting signals corresponding to the chromatographic peaks; the fitting function is a function constructed based on the peak point coordinates; peak areas of chromatographic peaks were calculated based on the fitted signals. The method can ensure that the detection result of detecting the chromatographic peak has repeatability.

Description

Chromatographic peak detection method, device, computer equipment and storage medium
Technical Field
The present application relates to the field of computer technologies, and in particular, to a method and an apparatus for detecting a chromatographic peak, a computer device, and a storage medium.
Background
With the development of computer technology, chromatography is widely used in detecting the content of various compounds in a sample to be detected. When chromatography is used, it is necessary to calculate the peak area of each chromatographic peak from each chromatographic peak separated from the original chromatographic signal.
However, when adjacent chromatographic peaks in the original chromatographic signal are overlapped or a part of the chromatographic signal is incomplete, when the same sample to be detected is detected for multiple times, the results obtained by each detection of the chromatographic peaks corresponding to the same compound may have large differences, and the repeatability of the detection result is poor.
Disclosure of Invention
In view of the above, it is necessary to provide a chromatographic peak detection method, an apparatus, a computer device and a storage medium capable of providing a repetitive detection result.
A method of chromatographic peak detection, the method comprising:
acquiring a starting point coordinate, an end point coordinate and a peak point coordinate of a chromatographic peak in an original chromatographic signal;
separating chromatographic signals of corresponding chromatographic peaks from the original chromatographic signals according to the starting point coordinates and the end point coordinates;
fitting the corresponding chromatographic signals according to the fitting functions corresponding to the chromatographic peaks to obtain fitting signals corresponding to the chromatographic peaks; the fitting function is a function constructed based on the peak point coordinates;
calculating peak areas of the chromatographic peaks based on the fitted signals.
In one embodiment, the chromatographic peak comprises a glycated hemoglobin chromatographic peak; said calculating peak areas of said chromatographic peaks based on said fitted signals comprises:
and calculating the peak area of the glycosylated hemoglobin chromatographic peak based on the fitting signal corresponding to the glycosylated hemoglobin chromatographic peak.
In one embodiment, the chromatographic peaks further comprise a hemoglobin variant chromatographic peak; said calculating peak areas of said chromatographic peaks based on said fitted signals further comprises:
calculating the peak area of the hemoglobin variant chromatographic peak based on the fitting signal corresponding to the hemoglobin variant chromatographic peak;
the method further comprises the following steps:
and calculating the content of the glycosylated hemoglobin according to the peak area of the glycosylated hemoglobin chromatographic peak, the peak area of the hemoglobin variant chromatographic peak and the total peak area calculated based on the original chromatographic signal.
In one embodiment, the calculating the content of glycated hemoglobin from the peak area of the glycated hemoglobin chromatographic peak, the peak area of the hemoglobin variant chromatographic peak, and the total peak area calculated based on the raw chromatographic signal comprises:
inputting the peak area of the glycosylated hemoglobin chromatographic peak, the peak area of the hemoglobin variant chromatographic peak and the total peak area into a calculation function for calculation to obtain the content of the glycosylated hemoglobin;
wherein the calculation function is:
Figure BDA0002816379270000021
y is the content of the glycated hemoglobin, S1Is the peak area of the glycated hemoglobin chromatographic peak, S is the total peak area, S2Is the peak area of the chromatographic peak of the hemoglobin variant.
In one embodiment, the acquiring the start point coordinate, the end point coordinate and the peak point coordinate of the chromatographic peak in the raw chromatographic signal comprises:
starting from an initial chromatographic signal point in a chromatographic peak identification window, sequentially taking the chromatographic signal points in the chromatographic peak identification window as a current calculation node, and traversing and calculating a first signal mean value of a preset number of chromatographic signal points before the calculation node and a second signal mean value of the preset number of chromatographic signal points after the calculation node;
and determining the starting point coordinate, the end point coordinate and the peak point coordinate of the chromatographic peak according to the first signal mean value and the second signal mean value of the chromatographic signal point.
In one embodiment, the determining the start point coordinate, the end point coordinate and the peak point coordinate of the chromatographic peak according to the first signal mean value and the second signal mean value of the chromatographic signal point comprises:
aiming at the signal mean values corresponding to the chromatographic signal points in the chromatographic peak identification window, when the difference values between the first signal mean values and the second signal mean values corresponding to a plurality of continuous computing nodes are gradually increased and are all larger than a preset threshold value, selecting a first computing node from the plurality of computing nodes of which the corresponding difference values are larger than the preset threshold value, and determining the coordinate of the selected computing node as a starting point coordinate;
selecting a second calculation node corresponding to the difference value smaller than a difference threshold value from the difference value between the first signal mean value and the second signal mean value corresponding to the calculation node, and determining the coordinate of the second calculation node as the coordinate of the peak point;
when the difference values between the first signal mean value and the second signal mean value corresponding to the continuous multiple calculation nodes are gradually reduced and are all smaller than a preset threshold value, selecting a third calculation node from the multiple calculation nodes of which the corresponding difference values are smaller than the preset threshold value, and determining the coordinate of the third calculation node as the terminal point coordinate.
In one embodiment, said fitting the respective chromatographic signals according to the fitting function corresponding to the chromatographic peak comprises:
inputting the chromatographic signals into corresponding fitting functions for fitting;
wherein the fitting function is:
Figure BDA0002816379270000031
Kland KrIs constant, u is the time of appearance of the chromatographic peak, t is the time variable, y (t) is the chromatographic signalNumber (n).
In one embodiment, the chromatographic peak comprises a hemoglobin chromatographic peak; after the obtaining of the start point coordinate, the end point coordinate and the peak point coordinate of the chromatographic peak in the original chromatographic signal, the method further comprises:
acquiring the predicted peak value coordinate of the hemoglobin chromatographic peak;
acquiring the maximum peak value in a preset time period before and after the predicted peak value coordinate; the peak value is the peak value of the hemoglobin chromatographic peak;
calculating the peak area of a chromatographic peak appearing after the peak generation time;
and when the peak area and the peak appearance time of the target chromatographic peak appearing after the peak value generation moment meet preset conditions, determining the target chromatographic peak as the hemoglobin variant chromatographic peak.
In one embodiment, before the obtaining of the start point coordinate, the end point coordinate, and the peak point coordinate of the chromatographic peak in the original chromatographic signal, the method further includes a step of smoothing a chromatographic signal point to be smoothed in the original chromatographic signal: taking the average value of at least three continuous chromatographic signal points including the chromatographic signal point to be smoothed in the original chromatographic signal as the signal value of the chromatographic signal point to be smoothed to obtain a smoothed chromatographic signal;
the acquiring of the start point coordinate, the end point coordinate and the peak point coordinate of the chromatographic peak in the original chromatographic signal comprises:
and acquiring a starting point coordinate, an end point coordinate and a peak point coordinate of a chromatographic peak in the chromatographic signal after the smoothing treatment.
A chromatographic peak detection apparatus, the apparatus comprising:
the acquisition module is used for acquiring a starting point coordinate, an end point coordinate and a peak point coordinate of a chromatographic peak in an original chromatographic signal;
the separation module is used for separating chromatographic signals of corresponding chromatographic peaks from the original chromatographic signals according to the starting point coordinates and the end point coordinates;
the fitting module is used for fitting the corresponding chromatographic signals according to the fitting functions corresponding to the chromatographic peaks to obtain fitting signals corresponding to the chromatographic peaks; the fitting function is a function constructed based on the peak point coordinates;
and the calculation module is used for calculating the peak area of the chromatographic peak based on the fitting signal.
In one embodiment, the chromatographic peak comprises a glycated hemoglobin chromatographic peak; the computing module is further configured to:
and calculating the peak area of the glycosylated hemoglobin chromatographic peak based on the fitting signal corresponding to the glycosylated hemoglobin chromatographic peak.
In one embodiment, the chromatographic peaks further comprise a hemoglobin variant chromatographic peak; the computing module is further configured to:
calculating the peak area of the hemoglobin variant chromatographic peak based on the fitting signal corresponding to the hemoglobin variant chromatographic peak;
and calculating the content of the glycosylated hemoglobin according to the peak area of the glycosylated hemoglobin chromatographic peak, the peak area of the hemoglobin variant chromatographic peak and the total peak area calculated based on the original chromatographic signal.
In one embodiment, the calculation module is further configured to:
inputting the peak area of the glycosylated hemoglobin chromatographic peak, the peak area of the hemoglobin variant chromatographic peak and the total peak area into a calculation function for calculation to obtain the content of the glycosylated hemoglobin;
wherein the calculation function is:
Figure BDA0002816379270000051
y is the content of the glycated hemoglobin, S1Is the peak area of the glycated hemoglobin chromatographic peak, S is the total peak area, S2Is the peak area of the chromatographic peak of the hemoglobin variant.
In one embodiment, the obtaining module is further configured to:
starting from an initial chromatographic signal point in a chromatographic peak identification window, sequentially taking the chromatographic signal points in the chromatographic peak identification window as a current calculation node, and traversing and calculating a first signal mean value of a preset number of chromatographic signal points before the calculation node and a second signal mean value of the preset number of chromatographic signal points after the calculation node;
and determining the starting point coordinate, the end point coordinate and the peak point coordinate of the chromatographic peak according to the first signal mean value and the second signal mean value of the chromatographic signal point.
In one embodiment, the obtaining module is further configured to:
aiming at the signal mean values corresponding to the chromatographic signal points in the chromatographic peak identification window, when the difference values between the first signal mean values and the second signal mean values corresponding to a plurality of continuous computing nodes are gradually increased and are all larger than a preset threshold value, selecting a first computing node from the plurality of computing nodes of which the corresponding difference values are larger than the preset threshold value, and determining the coordinate of the selected computing node as a starting point coordinate;
selecting a second calculation node corresponding to the difference value smaller than a difference threshold value from the difference value between the first signal mean value and the second signal mean value corresponding to the calculation node, and determining the coordinate of the second calculation node as the coordinate of the peak point;
when the difference values between the first signal mean value and the second signal mean value corresponding to the continuous multiple calculation nodes are gradually reduced and are all smaller than a preset threshold value, selecting a third calculation node from the multiple calculation nodes of which the corresponding difference values are smaller than the preset threshold value, and determining the coordinate of the third calculation node as the terminal point coordinate.
In one embodiment, the fitting module is further configured to:
inputting the chromatographic signals into corresponding fitting functions for fitting;
wherein the fitting function is:
Figure BDA0002816379270000061
Kland KrIs constant, u is the appearance of the chromatographic peakPeak time, t is a time variable.
In one embodiment, the chromatographic peak comprises a hemoglobin chromatographic peak; the device further comprises:
the acquisition module is further used for acquiring the predicted peak value coordinates of the hemoglobin chromatographic peak;
the acquisition module is further used for acquiring the maximum peak value in a preset time period before and after the expected peak value coordinate; the peak value is the peak value of the hemoglobin chromatographic peak;
the calculation module is further used for calculating the peak area of a chromatographic peak appearing after the peak generation moment;
and the determining module is used for determining the target chromatographic peak as the hemoglobin variant chromatographic peak when the peak area and the peak-appearing time of the target chromatographic peak appearing after the peak generating moment meet preset conditions.
In one embodiment, the apparatus further comprises:
the smoothing module is used for taking the average value of at least three continuous chromatographic signal points including the chromatographic signal point to be smoothed in the original chromatographic signal as the signal value of the chromatographic signal point to be smoothed to obtain a smoothed chromatographic signal;
the obtaining module is further configured to:
and acquiring a starting point coordinate, an end point coordinate and a peak point coordinate of a chromatographic peak in the chromatographic signal after the smoothing treatment.
A computer device comprising a memory and a processor, the memory storing a computer program, characterized in that the processor realizes the steps of the chromatographic peak detection method when executing the computer program.
A computer-readable storage medium, on which a computer program is stored, which, when being executed by a processor, carries out the steps of the chromatographic peak detection method.
In the above embodiment, the computer device first obtains the start point coordinate, the end point coordinate, and the peak point coordinate of the chromatographic peak in the original chromatographic signal, and separates the chromatographic signal of the corresponding chromatographic peak from the original chromatographic signal according to the start point coordinate and the end point coordinate. And then, fitting the corresponding chromatographic signals according to the fitting functions corresponding to the chromatographic peaks to obtain fitting signals corresponding to the chromatographic peaks. The computer device calculates peak areas of chromatographic peaks based on the fitted signals. After fitting the chromatographic signal by the fitting function, the computer equipment can enable the fitting signal to approach the ideal chromatographic signal. Therefore, the peak area of the chromatographic peak calculated by the computer equipment according to the fitting signal has higher repeatability and accuracy.
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FIG. 1 is a schematic flow chart of a chromatographic peak detection method in one embodiment;
FIG. 2 is a schematic flow chart illustrating the determination of start point coordinates, end point coordinates, and peak point coordinates in one embodiment;
FIG. 3 is a schematic flow chart illustrating the process of determining the coordinates of the start point, the end point, and the peak point in another embodiment;
FIG. 4a is a schematic flow chart illustrating a method for determining hemoglobin variant chromatographic peaks in one embodiment;
FIG. 4b is a schematic representation of a raw chromatographic curve and a fitted signal curve in one embodiment;
FIG. 5 is a block diagram showing the structure of a chromatographic peak detecting device in one embodiment;
FIG. 6 is a block diagram showing the structure of a chromatographic peak detecting device in another embodiment;
FIG. 7 is a diagram illustrating an internal structure of a computer device according to an embodiment;
fig. 8 is an internal structural view of a computer device in another embodiment.
Detailed Description
In order to make the objects, technical solutions and advantages of the present application more apparent, the present application is described in further detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the present application and are not intended to limit the present application.
According to the chromatographic peak detection method provided by the application, computer equipment firstly obtains a starting point coordinate, an end point coordinate and a peak point coordinate of a chromatographic peak in an original chromatographic signal, and separates a chromatographic signal of a corresponding chromatographic peak from the original chromatographic signal according to the starting point coordinate and the end point coordinate. And then, fitting the corresponding chromatographic signals according to the fitting functions corresponding to the various chromatographic peaks to obtain the fitting signals corresponding to the various chromatographic peaks. The computer device calculates peak areas of the spectral peaks based on the fitted signals. The computer device may be a terminal or a server. The terminal can be, but is not limited to, various personal computers, notebook computers, smart phones, tablet computers and portable wearable devices, and the server can be implemented by an independent server or a server cluster formed by a plurality of servers.
In one embodiment, as shown in fig. 1, there is provided a chromatographic peak detection method comprising the steps of:
s102, the computer equipment acquires the coordinates of a starting point, an end point and a peak point of a chromatographic peak in the original chromatographic signal.
Wherein the raw chromatographic signal is an image signal generated by a computer device according to the input electric signal. The electric signal is generated according to the composition of the sample to be detected after the detection equipment detects the sample to be detected. When a compound sample passes through a detection material in the detection device, the detection device responds to various compound components in the sample to be detected, and generates an electric signal according to the response result.
The original chromatographic signal comprises chromatographic peaks corresponding to all components in a sample to be detected, namely each chromatographic peak corresponds to a compound, and the chromatographic signal value of each coordinate point in the chromatographic peak is in direct proportion to the concentration of the corresponding compound. Wherein, the chromatographic peak can be a liquid phase chromatographic peak or a gas phase chromatographic peak. The constituent components in the compound sample may include hemoglobin, glycated hemoglobin, hemoglobin variant, and the like, but are not limited to the above compounds, and may include other compounds.
And S104, separating the chromatographic signal of the corresponding chromatographic peak from the original chromatographic signal by the computer equipment according to the starting point coordinate and the end point coordinate.
The starting point coordinate is the coordinate of the starting point of the corresponding chromatographic peak, and is the time when the compound corresponding to the chromatographic peak begins to be separated from the sample to be detected.
Wherein, the end point coordinate is the coordinate of the end point of the corresponding chromatographic peak, and is the time when the compound corresponding to the chromatographic peak is separated from the compound sample.
After acquiring the start point coordinates and the end point coordinates, the computer device separates the chromatographic signal between the start point coordinates and the end point coordinates corresponding to each chromatographic peak from the original chromatographic signal to perform fitting processing on the separated chromatographic signal.
S106, fitting the corresponding chromatographic signals by the computer equipment according to the fitting functions corresponding to the chromatographic peaks to obtain fitting signals corresponding to the chromatographic peaks; the fitting function is a function constructed based on the coordinates of the peak points.
In this case, the fitting is performed by approximating the points in the coordinate system with a smooth curve, that is, a curve reasonably reflecting the distribution trend of the points. This curve can be represented by a fitting function. The fitting function may be selected from a plurality of options, and the fitting function that minimizes the sum of absolute values of deviations between the fitted curve and the curve before fitting, or the fitting function that minimizes the maximum absolute value of deviation between the fitted curve and the curve before fitting, or the fitting function that minimizes the sum of squares of the fitted curve and the curve before fitting may be selected. In one embodiment, the fitting function is a function constructed based on the peak point coordinates.
The fitting signal is a signal obtained by fitting the chromatographic signal with a fitting function, and the fitting process may be an operation of the chromatographic signal with the fitting function, for example, a multiplication of the fitting function and the chromatographic signal.
S108, the computer device calculates peak areas of chromatographic peaks based on the fitting signals.
After obtaining the fitting signals corresponding to the chromatographic peaks, the computer device respectively performs integral calculation on the fitting signals corresponding to the chromatographic peaks to obtain peak areas of the chromatographic peaks.
The chromatographic peak may include at least one of a glycated hemoglobin chromatographic peak, a hemoglobin chromatographic peak, and a hemoglobin variant chromatographic peak, but is not limited to the chromatographic peaks corresponding to these compounds, and may also include chromatographic peaks corresponding to other compounds separated from the sample to be detected. The computer device can obtain the peak area of the chromatographic peak of the compound by carrying out integral calculation on a fitting signal corresponding to the chromatographic peak of the compound, and further obtain the content of the compound by calculating the peak area of the chromatographic peak of the compound when necessary.
In the above embodiment, the computer device first obtains the start point coordinate, the end point coordinate, and the peak point coordinate of the chromatographic peak in the original chromatographic signal, and separates the chromatographic signal of the corresponding chromatographic peak from the original chromatographic signal according to the start point coordinate and the end point coordinate. And then, fitting the corresponding chromatographic signals according to the fitting functions corresponding to the chromatographic peaks to obtain fitting signals corresponding to the chromatographic peaks. The computer device calculates peak areas of chromatographic peaks based on the fitted signals. After fitting the chromatographic signal through the fitting function, the computer equipment can enable the fitting signal to approach an ideal chromatographic signal, so that the peak area of the chromatographic peak calculated by the computer equipment according to the fitting signal has higher repeatability and accuracy.
In one embodiment, the chromatographic peak comprises a glycated hemoglobin chromatographic peak; the computer device calculating peak areas of chromatographic peaks based on the fitted signal comprises: and calculating the peak area of the glycosylated hemoglobin chromatographic peak based on the fitting signal corresponding to the glycosylated hemoglobin chromatographic peak.
And after the fitting signal corresponding to the chromatographic peak is obtained, the computer equipment performs integral calculation based on the fitting signal corresponding to the glycosylated hemoglobin chromatographic peak to obtain the peak area of the glycosylated hemoglobin chromatographic peak.
In one embodiment, the chromatographic peaks further comprise a hemoglobin variant chromatographic peak; the computer device calculating peak areas of chromatographic peaks based on the fitted signal further comprises: calculating the peak area of the hemoglobin variant chromatographic peak based on the fitting signal corresponding to the hemoglobin variant chromatographic peak; the method further comprises the following steps: the content of glycated hemoglobin is calculated from the peak area of the glycated hemoglobin chromatographic peak, the peak area of the hemoglobin variant chromatographic peak, and the total peak area calculated based on the original chromatographic signal.
And after the computer equipment obtains the fitting signal corresponding to the hemoglobin variant chromatographic peak, performing integral calculation on the fitting signal corresponding to the hemoglobin variant chromatographic peak to obtain the peak area of the hemoglobin variant chromatographic peak.
Since the contents of glycated hemoglobin and hemoglobin variant separated at each time are proportional to the areas of the chromatographic signals of the respective chromatographic peaks in the signal section, the computer device can calculate the contents of glycated hemoglobin from the peak areas of the glycated hemoglobin chromatographic peaks, the peak areas of the hemoglobin variant chromatographic peaks, and the total peak area calculated based on the original chromatographic signals.
Wherein the total peak area is the area between the signal curve and the signal baseline of the original chromatographic signal. The computer equipment can perform integral calculation on the original chromatographic signal to obtain the total peak area.
In one embodiment, the computer device calculates the glycated hemoglobin content from a peak area of a glycated hemoglobin chromatographic peak, a peak area of a hemoglobin variant chromatographic peak, and a total peak area calculated based on the raw chromatographic signal, comprising: inputting the peak area of the glycosylated hemoglobin chromatographic peak, the peak area of the hemoglobin variant chromatographic peak and the total peak area into a calculation function for calculation; the calculation function is:
Figure BDA0002816379270000101
wherein y is the content of glycated hemoglobin, S1Is the peak area of the chromatographic peak of the glycosylated hemoglobin, S is the total peak area, S2Is the peak area of the chromatographic peak of the haemoglobin variant.
In one embodiment, the computer device inputs the chromatographic signals into corresponding fitting functions for fitting. Wherein the fitting function is:
Figure BDA0002816379270000102
Kland KrConstant, the time of appearance of the corresponding chromatographic peak, t is the time variable, and y (t) is the chromatographic signal. Where e is a natural constant in mathematics and has a value of about 2.71828. Wherein, the computer equipment can fit the chromatographic peak data according to the curve shape of each chromatographic peak to obtain KlAnd Kr. For example, the computer device will KlAnd KrSet to a constant between 1 and 5.
The process of fitting the chromatographic peak by the computer device may be to perform a mathematical operation on the chromatographic signal corresponding to the chromatographic peak by using a fitting function, for example, the computer device multiplies the chromatographic signal by the fitting function.
Wherein, the parameter u in the fitting function h (t) corresponding to the chromatographic signal is the peak emergence time of the corresponding chromatographic peak. For example, when the chromatographic signal is a chromatographic signal corresponding to glycated hemoglobin, u in the fitting function h (t) is the peak appearance time of the glycated hemoglobin chromatographic peak; when the chromatographic signal is the chromatographic signal corresponding to the hemoglobin variant, u in the fitting function h (t) is the peak emergence time of the chromatographic peak of the hemoglobin variant; when the chromatographic signal is that corresponding to other compounds, u in the fitting function h (t) is the corresponding peak time of the corresponding compound.
When the computer equipment performs fitting on the chromatographic signal, inputting the chromatographic signal y (t) into a fitting function h (t) for operation to obtain a fitting signal. Since the chromatographic signal is a finite signal, the resulting fitted signal is convergent. The signal value of the fitted signal at the peak point obtained according to the fitting function h (t) is equal to the signal value of the chromatographic signal at the peak point, whereas the signal value of the fitted signal approaches the value of the baseline of the original chromatographic signal when it is positive or negative infinite. Between the start point and the peak point and between the peak point and the end point, the signal value of the fitted signal approximates the signal value of the chromatographic signal. Since the signal value of the fitting signal approaches to 0 when t is positive and negative infinity, the computer device can integrate the fitting signal in the signal range from positive infinity to negative infinity, and the integrated result can accurately reflect the content of the compound corresponding to the chromatographic peak when the integrated result is the peak area of the corresponding chromatographic peak.
Because the Gaussian kernel function can provide continuity and smoothness in the fitting process, when the fitting function is used by computer equipment to fit chromatographic signals, the chromatographic signals are multiplied by the fitting function, even if the chromatographic peaks corresponding to the chromatographic signals are incomplete or small convex peaks or concave peaks are mixed in large chromatographic peaks, namely under the condition that the chromatographic signals are discontinuous or unsmooth, the fitting function can fit the chromatographic signals, and the fitting results obtained by multiple times of fitting are the same, so that the fitting result is accurate and high in stability.
The fitting function h (t) is constructed in a left-right segmentation mode by taking the peak emergence time of the corresponding chromatographic peak as a demarcation point, so that the mathematical expressions for fitting the left side and the right side of the peak emergence time of the chromatographic peak are different, the asymmetric peak can be fitted more accurately, the fitting stability of the asymmetric peak is improved, and under-fitting is prevented. Generally, a common type of asymmetric peak is a trailing peak.
In one embodiment, the computer device obtains the coordinates of the start point, the end point and the peak point of a chromatographic peak in the raw chromatographic signal, as shown in fig. 2, comprising the steps of:
and S202, the computer device starts from the initial chromatographic signal point in the chromatographic peak identification window, sequentially takes the chromatographic signal points in the chromatographic peak identification window as the current calculation node, and traverses the first signal mean value of the preset number of chromatographic signal points before the calculation node and the second signal mean value of the preset number of chromatographic signal points after the calculation node.
And S204, the computer equipment determines the coordinates of the starting point, the end point and the peak point of the chromatographic peak according to the first signal mean value and the second signal mean value of the chromatographic signal point.
Wherein the chromatographic peak identification window is determined by the computer device based on the time at which each constituent component in the compound sample is separated from the compound sample. And the chromatographic signal of the chromatographic peak corresponding to each component is contained in the chromatographic peak identification window.
Wherein the preset number is determined by the computer device according to the smoothness degree of the chromatographic peak. When the chromatographic peak is smoother, the computer device may set the preset number to a smaller value, for example, 3; when the chromatographic peak has more peaks and valleys, the computer device may set the predetermined number to a larger value, for example, 5.
Starting from the initial chromatographic signal point in the chromatographic peak identification window, if the computer device judges that the chromatographic peak is in the ascending trend according to the second signal mean value and the first signal mean value of a plurality of continuous chromatographic signal points, the computer device selects one of the plurality of chromatographic signal points in the ascending trend as the starting point of the chromatographic peak.
After determining the starting point of the chromatographic peak, the computer device continues to calculate the first signal mean value and the second signal mean value of each calculation node, and if the second signal mean value is larger than the first signal mean value, the computer device updates the chromatographic signal point of the current calculation node to the peak point. And after the computer equipment sequentially calculates the various chromatographic signal points in the complete chromatographic peak identification window in a traversing manner, the chromatographic signal point at the corner point where the second signal mean value is smaller than the first signal mean value is the peak value point updated finally.
The computer device continues to calculate the first signal mean value and the second signal mean value of each of the calculation nodes within the chromatographic peak identification window after the time of the peak point after determining the peak point of the chromatographic peak. And if the computer equipment judges that the signal value of the chromatographic signal does not continuously decrease according to the second signal mean value and the first signal mean value of the continuous chromatographic signal points, the computer equipment selects one of the chromatographic signal points of which the decreasing trend is close to the end as the end point of the chromatographic peak.
In one embodiment, as shown in fig. 3, the computer device determines the start point coordinate, the end point coordinate and the peak point coordinate of each chromatographic peak according to the first signal mean value and the second signal mean value of each chromatographic signal point, including the following steps:
s302, aiming at the signal mean values corresponding to the chromatographic signal points in the chromatographic peak identification window, the computer equipment selects a first computing node from a plurality of computing nodes of which the corresponding difference values are greater than a preset threshold value when the difference values between the first signal mean values and the second signal mean values corresponding to a plurality of continuous computing nodes are gradually increased and are all greater than the preset threshold value, and determines the coordinate of the selected computing node as the starting point coordinate.
S304, in the difference value between the first signal mean value and the second signal mean value corresponding to the calculation node, the computer equipment selects the corresponding second calculation node when the difference value is smaller than the difference value threshold value, and determines the coordinate of the second calculation node as the peak point coordinate.
S306, when the difference values between the first signal mean value and the second signal mean value corresponding to the continuous multiple computing nodes are gradually reduced and are all smaller than a preset threshold value, the computer equipment selects a third computing node from the multiple computing nodes of which the corresponding difference values are smaller than the preset threshold value, and determines the coordinate of the third computing node as the terminal coordinate.
When the difference value between the first signal mean value and the second signal mean value corresponding to a plurality of continuous computing nodes is gradually increased and is larger than a preset threshold value from the initial chromatographic signal point in the chromatographic peak identification window, the chromatographic signal is indicated to be in an ascending trend. Therefore, the computer device selects one of the corresponding calculation nodes with the difference value between the first signal mean value and the second signal mean value larger than the preset threshold value as the starting point coordinate.
And when the computer equipment determines that the difference values between the first signal mean value and the second signal mean value corresponding to the continuous multiple computing nodes are gradually reduced and are all smaller than a preset threshold value, the descending trend of the chromatographic signals tends to end. Therefore, the computer device selects one of the corresponding calculation nodes with the difference value between the first signal mean value and the second signal mean value smaller than the preset threshold value as the endpoint coordinate.
The computer equipment determines the starting point coordinate, the end point coordinate and the peak point coordinate of each chromatographic peak according to the first signal mean value and the second signal mean value of each chromatographic signal point, even if burrs exist in chromatographic signals, the computer equipment judges according to the mean values of a plurality of continuous chromatographic signal points before and after each chromatographic signal point, so that the determination of the starting point coordinate, the end point coordinate and the peak point coordinate is not influenced by the burrs, and the accuracy of determining the starting point coordinate, the end point coordinate and the peak point coordinate of each chromatographic peak is improved.
In one embodiment, the chromatographic peak comprises a hemoglobin chromatographic peak; as shown in fig. 4a, after the computer device obtains the coordinates of the starting point, the end point and the peak point of the chromatographic peak in the original chromatographic signal, the method for determining the chromatographic peak of the hemoglobin variant further comprises the following steps:
s402, the computer device obtains the predicted peak value coordinates of the hemoglobin chromatographic peak.
S404, the computer equipment obtains the maximum peak value in a preset time interval before and after the coordinate of the expected peak value, wherein the peak value is the peak value of the hemoglobin chromatographic peak.
S406, the computer device calculates a peak area of a chromatographic peak appearing after the peak generation timing.
And S408, when the peak area and the peak-appearing time of the target chromatographic peak appearing after the peak generation moment meet preset conditions, the computer equipment determines the target chromatographic peak as the hemoglobin variant chromatographic peak.
Wherein the predicted peak coordinate of the hemoglobin chromatographic peak is the time coordinate of the predicted peak of the hemoglobin chromatographic peak.
The predicted peak coordinates are determined by the computer device based on the reagents used to separate the constituent components of the compound sample, the instrument used to separate the compounds of the compound sample, and the temperature at which the compounds are separated.
And the computer equipment counts the time of the peak point of the hemoglobin chromatographic peak when different chromatographic elution reagents, different elution equipment and chromatographic columns are used for detecting the sample to be detected at different temperatures. The statistical result shows that the peak appearance time (namely the retention time) of the hemoglobin chromatographic peak in different samples to be tested is stable when the temperature, the chromatographic elution reagent and the elution equipment are determined. Therefore, the computer device calibrates the elution device and determines the expected peak coordinates based on temperature, elution reagent, chromatography column, etc. prior to testing the sample to be tested.
Wherein the computer device may set a preset time period before and after the predicted peak coordinates. For example, the computer device sets the pre-set period before and after to within 5 seconds before and after the expected peak coordinates.
Wherein the peak-out time of the target chromatographic peak is the time at which the peak of the target chromatographic peak appears.
Wherein the preset condition is a condition determined by the computer device according to a property that a hemoglobin variant chromatographic peak generally has. For example, the computer device determines the preset condition based on a relationship between a peak area of a chromatographic peak of the hemoglobin variant and a total peak area. For example, the computer device determines the preset condition as a ratio of the third peak area to the total peak area being greater than a ratio threshold, e.g., the ratio threshold is 1%. For example, the peak of the hemoglobin variant chromatogram usually comes out later than the hemoglobin chromatogram peak.
Since the peak point of the hemoglobin chromatographic peak appears in the preset time period before and after the expected peak coordinate, the computer device obtains the maximum peak value in the preset time period before and after the expected peak coordinate, and the peak value is the peak value of the hemoglobin chromatographic peak. The computer equipment can determine the peak point coordinates of the hemoglobin chromatographic peak according to the peak value of the hemoglobin chromatographic peak.
Depending on the nature of the hemoglobin variant in the compound sample, the chromatographic peak to which the hemoglobin variant corresponds generally occurs after the time of generation of the hemoglobin chromatographic peak. Therefore, the computer device calculates peak areas of the respective chromatographic peaks appearing after the peak generation time, and when the peak areas satisfy a preset condition, determines a chromatographic peak corresponding to the peak area satisfying the preset condition as a hemoglobin variant chromatographic peak.
The computer device first determines an expected peak coordinate of the hemoglobin chromatographic peak and then determines the hemoglobin chromatographic peak within a predetermined time period before and after the expected peak coordinate. Since the computer device has limited the range over which the maximum peak occurs, i.e., the peak of the hemoglobin chromatographic peak, and not the peak of the hemoglobin variant chromatographic peak. Therefore, the computer device does not recognize the hemoglobin variant chromatographic peak as a hemoglobin chromatographic peak, thereby causing an inability to correctly recognize the hemoglobin variant chromatographic peak. That is, the computer device is not caused to identify the hemoglobin variant in the compound sample as the hemoglobin variant, so that the wrong content of the glycated hemoglobin is calculated, and the accuracy of the content of the glycated hemoglobin calculated by the computer device is improved.
In one embodiment, before the computer device obtains the start point coordinate, the end point coordinate, and the peak point coordinate of the chromatographic peak in the raw chromatographic signal, the method further comprises: when the chromatographic signal points to be smoothed in the original chromatographic signal are smoothed, taking the average value of at least three continuous chromatographic signal points including the chromatographic signal points to be smoothed in the original chromatographic signal as the signal value of the chromatographic signal points to be smoothed to obtain the smoothed chromatographic signal; the obtaining of the starting point coordinate, the end point coordinate and the peak point coordinate of the chromatographic peak in the original chromatographic signal comprises: and acquiring the coordinates of the starting point, the end point and the peak point of each chromatographic peak in the smoothed chromatographic signal.
Because of the possible presence of glitches or anomalous outlier signal points in the original chromatographic signal, the computer device is affected in determining the starting point coordinates, the end point coordinates and the peak point coordinates of the chromatographic peak. Therefore, the computer device firstly smoothes the original chromatographic signal and then obtains the coordinates of the starting point, the end point and the peak point of the chromatographic peak in the original chromatographic signal.
In one embodiment, the computer device calculates an average value for the signal values of every 3 consecutive signal points, starting from the signal point of the original chromatographic signal at 0 seconds, and assigns the calculated average value to the second signal point.
In one embodiment, after acquiring the raw chromatographic signal, the computer device calculates an average of the signal values of the raw chromatographic signal over an initial preset period of time and over a preset period of time at the end of the period of time based on the signal values of the raw chromatographic signal over the initial preset period of time and determines a baseline of the raw chromatographic signal based on the calculated average. The computer device re-determines the baseline of the original chromatographic signal to prevent the computed peak area corresponding to the chromatographic peak from being inaccurate due to the unstable baseline.
In one embodiment, the detection device detects a blood sample using cation exchange chromatography, obtains a raw chromatographic signal, and the computer device plots the raw chromatographic curve as shown in FIG. 4 b. Where the abscissa in fig. 4b is a time variable in x 0.1s and the ordinate represents the chromatographic signal in x 0.033 mOD. Where s is second and mOD is absorbance.
The specific process of obtaining the peak area of the glycosylated hemoglobin chromatographic peak by the computer equipment according to the original chromatographic signal is as follows: the computer device averages the original chromatographic signal over three consecutive signal values over a glycated hemoglobin peak identification window (in this example, the abscissa is between 400 × 0.1s and 700 × 0.1 s); within the glycated hemoglobin peak identification window, the time corresponding to the highest point of the mean (in this example, t ═ 525 × 0.1s) is the peak appearance time of the glycated hemoglobin chromatographic peak. The computer device uses the fitting function h (t) to fit the chromatographic signal corresponding to the chromatographic peak of glycated hemoglobin in the original chromatographic curve to obtain a fitted signal curve as shown in fig. 4 b. And for the fitted signal curve, the computer equipment sums the signal values of the fitted signal curve in a signal interval from 0 to plus infinity to obtain the peak area of the chromatographic peak of the glycated hemoglobin of 5015.62. Wherein the fitting function
Figure BDA0002816379270000161
KlAnd KrA constant of 0-5, u is the peak appearance time of the chromatographic peak of the glycosylated hemoglobin, t is a time variable, and y (t) is a chromatographic signal corresponding to the chromatographic peak of the glycosylated hemoglobin.
It should be understood that although the various steps in the flow charts of fig. 1-4a are shown in order as indicated by the arrows, the steps are not necessarily performed in order as indicated by the arrows. The steps are not performed in the exact order shown and described, and may be performed in other orders, unless explicitly stated otherwise. Moreover, at least some of the steps in fig. 1-4a may include multiple steps or multiple stages, which are not necessarily performed at the same time, but may be performed at different times, which are not necessarily performed in sequence, but may be performed in turn or alternately with other steps or at least some of the other steps or stages.
In one embodiment, as shown in fig. 5, there is provided a chromatographic peak detecting device comprising: an acquisition module 502, a separation module 504, a fitting module 506, and a calculation module 508, wherein:
an obtaining module 502, configured to obtain a start point coordinate, an end point coordinate, and a peak point coordinate of a chromatographic peak in an original chromatographic signal;
a separation module 504, configured to separate a chromatographic signal of a corresponding chromatographic peak from an original chromatographic signal according to the start point coordinate and the end point coordinate;
a fitting module 506, configured to fit the corresponding chromatographic signal according to the fitting function corresponding to the chromatographic peak to obtain a fitting signal corresponding to the chromatographic peak; the fitting function is a function constructed based on the peak point coordinates;
a calculating module 508 for calculating peak areas of the chromatographic peaks based on the fitted signal.
In the above embodiment, the computer device first obtains the start point coordinate, the end point coordinate, and the peak point coordinate of the chromatographic peak in the original chromatographic signal, and separates the chromatographic signal of the corresponding chromatographic peak from the original chromatographic signal according to the start point coordinate and the end point coordinate. And then, fitting the corresponding chromatographic signals according to the fitting functions corresponding to the chromatographic peaks to obtain fitting signals corresponding to the chromatographic peaks. The computer device calculates peak areas of chromatographic peaks based on the fitted signals. After fitting the chromatographic signal by the fitting function, the computer equipment can enable the fitting signal to approach the ideal chromatographic signal. Therefore, the peak area of the chromatographic peak calculated by the computer equipment according to the fitting signal has higher repeatability and accuracy.
In one embodiment, the chromatographic peak comprises a glycated hemoglobin chromatographic peak; the calculation module 508 is configured to:
and calculating the peak area of the glycosylated hemoglobin chromatographic peak based on the fitting signal corresponding to the glycosylated hemoglobin chromatographic peak.
In one embodiment, the chromatographic peaks further comprise a hemoglobin variant chromatographic peak; the calculation module 508 is further configured to:
calculating the peak area of the hemoglobin variant chromatographic peak based on the fitting signal corresponding to the hemoglobin variant chromatographic peak;
the content of glycated hemoglobin is calculated from the peak area of the glycated hemoglobin chromatographic peak, the peak area of the hemoglobin variant chromatographic peak, and the total peak area calculated based on the original chromatographic signal.
In one embodiment, the calculation module 508 is further configured to:
inputting the peak area of the glycosylated hemoglobin chromatographic peak, the peak area of the hemoglobin variant chromatographic peak and the total peak area into a calculation function for calculation to obtain the content of the glycosylated hemoglobin;
wherein the calculation function is:
Figure BDA0002816379270000181
y is the content of glycated hemoglobin, S1Is the peak area of the chromatographic peak of the glycosylated hemoglobin, S is the total peak area, S2Is the peak area of the chromatographic peak of the haemoglobin variant.
In one embodiment, the obtaining module 502 is further configured to:
starting from the initial chromatographic signal point in the chromatographic peak identification window, sequentially taking the chromatographic signal points in the chromatographic peak identification window as the current calculation node, and traversing the first signal mean value of the preset number of chromatographic signal points before the calculation node and the second signal mean value of the preset number of chromatographic signal points after the calculation node;
and determining the coordinates of the starting point, the ending point and the peak point of the chromatographic peak according to the first signal mean value and the second signal mean value of the chromatographic signal point.
In one embodiment, the obtaining module 502 is further configured to:
aiming at signal mean values corresponding to chromatographic signal points in a chromatographic peak identification window, when difference values between first signal mean values and second signal mean values corresponding to a plurality of continuous computing nodes are gradually increased and are all larger than a preset threshold value, selecting a first computing node from the plurality of computing nodes of which the corresponding difference values are larger than the preset threshold value, and determining the coordinate of the selected computing node as a starting point coordinate;
selecting a second computing node corresponding to the difference value smaller than the difference threshold value from the difference value between the first signal mean value and the second signal mean value corresponding to the computing node, and determining the coordinate of the second computing node as the coordinate of the peak point;
and when the difference values between the first signal mean value and the second signal mean value corresponding to the continuous plurality of calculation nodes are gradually reduced and are all smaller than a preset threshold value, selecting a third calculation node from the plurality of calculation nodes of which the corresponding difference values are smaller than the preset threshold value, and determining the coordinate of the third calculation node as the terminal point coordinate.
In one embodiment, the fitting module 506 is further configured to:
inputting the chromatographic signals into corresponding fitting functions for fitting;
wherein the fitting function is:
Figure BDA0002816379270000191
Kland KrConstant, u is the time of peak appearance of the chromatographic peak, t is the time variable, and y (t) is the chromatographic signal. Wherein, KlAnd KrConstant, can be obtained by fitting the chromatographic peak data. Where e is a natural constant in mathematics and has a value of about 2.71828.
In one embodiment, the chromatographic peak comprises a hemoglobin chromatographic peak; as shown in fig. 6, the apparatus further comprises:
an obtaining module 502, further configured to obtain an estimated peak coordinate of a hemoglobin chromatographic peak;
the obtaining module 502 is further configured to obtain a maximum peak value within a preset time period before and after the expected peak value coordinate; the peak value is the peak value of a hemoglobin chromatographic peak;
the calculating module 508 is further configured to calculate a peak area of a chromatographic peak appearing after the peak generation time;
the determining module 510 is configured to determine the target chromatographic peak as the hemoglobin variant chromatographic peak when a peak area and a peak appearance time of the target chromatographic peak occurring after the peak generation time meet preset conditions.
In one embodiment, the apparatus further comprises:
the smoothing module 512 is configured to, when performing smoothing on a to-be-smoothed chromatographic signal point in an original chromatographic signal, use an average value of at least three consecutive chromatographic signal points including the to-be-smoothed chromatographic signal point in the original chromatographic signal as a signal value of the to-be-smoothed chromatographic signal point, so as to obtain a smoothed chromatographic signal;
the obtaining module 502 is further configured to:
and acquiring the coordinates of the starting point, the end point and the peak point of each chromatographic peak in the smoothed chromatographic signal.
In one embodiment, the chromatographic peak detecting device can be, for example, a liquid chromatograph or a gas chromatograph. More specifically, the chromatographic peak detecting device is a hemoglobin analyzer.
For specific limitations of the chromatographic peak detecting device, reference may be made to the above limitations of the chromatographic peak detecting method, which are not described herein again. The various modules in the chromatographic peak detection device can be realized in whole or in part by software, hardware and a combination thereof. The modules can be embedded in a hardware form or independent from a processor in the computer device, and can also be stored in a memory in the computer device in a software form, so that the processor can call and execute operations corresponding to the modules.
In one embodiment, a computer device is provided, which may be a server, the internal structure of which may be as shown in fig. 7. The computer device includes a processor, a memory, and a network interface connected by a system bus. Wherein the processor of the computer device is configured to provide computing and control capabilities. The memory of the computer device comprises a nonvolatile storage medium and an internal memory. The non-volatile storage medium stores an operating system, a computer program, and a database. The internal memory provides an environment for the operation of an operating system and computer programs in the non-volatile storage medium. The database of the computer device is used for storing chromatographic peak detection data. The network interface of the computer device is used for communicating with an external terminal through a network connection. The computer program is executed by a processor to implement a chromatographic peak detection method.
In one embodiment, a computer device is provided, which may be a terminal, and its internal structure diagram may be as shown in fig. 8. The computer device includes a processor, a memory, a communication interface, a display screen, and an input device connected by a system bus. Wherein the processor of the computer device is configured to provide computing and control capabilities. The memory of the computer device comprises a nonvolatile storage medium and an internal memory. The non-volatile storage medium stores an operating system and a computer program. The internal memory provides an environment for the operation of an operating system and computer programs in the non-volatile storage medium. The communication interface of the computer device is used for carrying out wired or wireless communication with an external terminal, and the wireless communication can be realized through WIFI, an operator network, NFC (near field communication) or other technologies. The computer program is executed by a processor to implement a chromatographic peak detection method. The display screen of the computer equipment can be a liquid crystal display screen or an electronic ink display screen, and the input device of the computer equipment can be a touch layer covered on the display screen, a key, a track ball or a touch pad arranged on the shell of the computer equipment, an external keyboard, a touch pad or a mouse and the like.
It will be appreciated by those skilled in the art that the configurations shown in fig. 7 and 8 are only block diagrams of some configurations relevant to the present disclosure, and do not constitute a limitation on the computer device to which the present disclosure may be applied, and a particular computer device may include more or less components than those shown in the figures, or may combine certain components, or have a different arrangement of components.
In one embodiment, a computer device is provided, comprising a memory and a processor, the memory having a computer program stored therein, the processor implementing the following steps when executing the computer program: acquiring a starting point coordinate, an end point coordinate and a peak point coordinate of a chromatographic peak in an original chromatographic signal; separating chromatographic signals of corresponding chromatographic peaks from the original chromatographic signals according to the starting point coordinates and the end point coordinates; fitting the corresponding chromatographic signals according to the fitting functions corresponding to the chromatographic peaks to obtain fitting signals corresponding to the chromatographic peaks; the fitting function is a function constructed based on the peak point coordinates; peak areas of chromatographic peaks were calculated based on the fitted signals.
In one embodiment, the chromatographic peak comprises a glycated hemoglobin chromatographic peak; the processor, when executing the computer program, further performs the steps of: and calculating the peak area of the glycosylated hemoglobin chromatographic peak based on the fitting signal corresponding to the glycosylated hemoglobin chromatographic peak.
In one embodiment, the chromatographic peaks further comprise a hemoglobin variant chromatographic peak; the processor, when executing the computer program, further performs the steps of: calculating the peak area of the hemoglobin variant chromatographic peak based on the fitting signal corresponding to the hemoglobin variant chromatographic peak; the content of glycated hemoglobin is calculated from the peak area of the glycated hemoglobin chromatographic peak, the peak area of the hemoglobin variant chromatographic peak, and the total peak area calculated based on the original chromatographic signal.
In one embodiment, the processor, when executing the computer program, further performs the steps of: inputting the peak area of the glycosylated hemoglobin chromatographic peak, the peak area of the hemoglobin variant chromatographic peak and the total peak area into a calculation function for calculation to obtain the content of the glycosylated hemoglobin; wherein the calculation function is:
Figure BDA0002816379270000211
y is the content of glycated hemoglobin, S1Is the peak area of the chromatographic peak of the glycosylated hemoglobin, S is the total peak area, S2Is the peak area of the chromatographic peak of the haemoglobin variant.
In one embodiment, the processor, when executing the computer program, further performs the steps of: starting from the initial chromatographic signal point in the chromatographic peak identification window, sequentially taking the chromatographic signal points in the chromatographic peak identification window as the current calculation node, and traversing the first signal mean value of the preset number of chromatographic signal points before the calculation node and the second signal mean value of the preset number of chromatographic signal points after the calculation node; and determining the coordinates of the starting point, the ending point and the peak point of the chromatographic peak according to the first signal mean value and the second signal mean value of the chromatographic signal point.
In one embodiment, the processor, when executing the computer program, further performs the steps of: aiming at signal mean values corresponding to chromatographic signal points in a chromatographic peak identification window, when difference values between first signal mean values and second signal mean values corresponding to a plurality of continuous computing nodes are gradually increased and are all larger than a preset threshold value, selecting a first computing node from the plurality of computing nodes of which the corresponding difference values are larger than the preset threshold value, and determining the coordinate of the selected computing node as a starting point coordinate; selecting a second computing node corresponding to the difference value smaller than the difference threshold value from the difference value between the first signal mean value and the second signal mean value corresponding to the computing node, and determining the coordinate of the second computing node as the coordinate of the peak point; and when the difference values between the first signal mean value and the second signal mean value corresponding to the continuous plurality of calculation nodes are gradually reduced and are all smaller than a preset threshold value, selecting a third calculation node from the plurality of calculation nodes of which the corresponding difference values are smaller than the preset threshold value, and determining the coordinate of the third calculation node as the terminal point coordinate.
In one embodiment, the processor, when executing the computer program, further performs the steps of: inputting the chromatographic signals into corresponding fitting functions for fitting; wherein the fitting function is:
Figure BDA0002816379270000221
Kland KrConstant, u is the time of peak appearance of the chromatographic peak, t is the time variable, and y (t) is the chromatographic signal. Wherein, KlAnd KrConstant, can be obtained by fitting the chromatographic peak data. Wherein e is self in mathematicsHowever, the value is about 2.71828.
In one embodiment, the processor, when executing the computer program, further performs the steps of: acquiring an estimated peak value coordinate of a hemoglobin chromatographic peak; acquiring maximum peak values in preset time periods before and after the predicted peak value coordinate; the peak value is the peak value of a hemoglobin chromatographic peak; calculating the peak area of a chromatographic peak appearing after the peak generation moment; and when the peak area and the peak-appearing time of the target chromatographic peak appearing after the peak value generation moment meet preset conditions, determining the target chromatographic peak as the hemoglobin variant chromatographic peak.
In one embodiment, the processor, when executing the computer program, further performs the steps of: taking the average value of at least three continuous chromatographic signal points including the chromatographic signal point to be smoothed in the original chromatographic signal as the signal value of the chromatographic signal point to be smoothed to obtain the smoothed chromatographic signal; the obtaining of the starting point coordinate, the end point coordinate and the peak point coordinate of the chromatographic peak in the original chromatographic signal comprises: and acquiring the coordinates of the starting point, the end point and the peak point of the chromatographic peak in the chromatographic signal after the smoothing treatment.
In one embodiment, a computer-readable storage medium is provided, having a computer program stored thereon, which when executed by a processor, performs the steps of: acquiring a starting point coordinate, an end point coordinate and a peak point coordinate of a chromatographic peak in an original chromatographic signal; separating chromatographic signals of corresponding chromatographic peaks from the original chromatographic signals according to the starting point coordinates and the end point coordinates; fitting the corresponding chromatographic signals according to the fitting functions corresponding to the chromatographic peaks to obtain fitting signals corresponding to the chromatographic peaks; the fitting function is a function constructed based on the peak point coordinates; peak areas of chromatographic peaks were calculated based on the fitted signals.
In one embodiment, the chromatographic peak comprises a glycated hemoglobin chromatographic peak; the computer program when executed by the processor further realizes the steps of: and calculating the peak area of the glycosylated hemoglobin chromatographic peak based on the fitting signal corresponding to the glycosylated hemoglobin chromatographic peak.
In one embodiment, the chromatographic peaks further comprise a hemoglobin variant chromatographic peak; the computer program when executed by the processor further realizes the steps of: calculating the peak area of the hemoglobin variant chromatographic peak based on the fitting signal corresponding to the hemoglobin variant chromatographic peak; the content of glycated hemoglobin is calculated from the peak area of the glycated hemoglobin chromatographic peak, the peak area of the hemoglobin variant chromatographic peak, and the total peak area calculated based on the original chromatographic signal.
In one embodiment, the computer program when executed by the processor further performs the steps of: inputting the peak area of the glycosylated hemoglobin chromatographic peak, the peak area of the hemoglobin variant chromatographic peak and the total peak area into a calculation function for calculation to obtain the content of the glycosylated hemoglobin; wherein the calculation function is:
Figure BDA0002816379270000231
y is the content of glycated hemoglobin, S1Is the peak area of the chromatographic peak of the glycosylated hemoglobin, S is the total peak area, S2Is the peak area of the chromatographic peak of the haemoglobin variant.
In one embodiment, the computer program when executed by the processor further performs the steps of: starting from the initial chromatographic signal point in the chromatographic peak identification window, sequentially taking the chromatographic signal points in the chromatographic peak identification window as the current calculation node, and traversing the first signal mean value of the preset number of chromatographic signal points before the calculation node and the second signal mean value of the preset number of chromatographic signal points after the calculation node; and determining the coordinates of the starting point, the ending point and the peak point of the chromatographic peak according to the first signal mean value and the second signal mean value of the chromatographic signal point.
In one embodiment, the computer program when executed by the processor further performs the steps of: aiming at signal mean values corresponding to chromatographic signal points in a chromatographic peak identification window, when difference values between first signal mean values and second signal mean values corresponding to a plurality of continuous computing nodes are gradually increased and are all larger than a preset threshold value, selecting a first computing node from the plurality of computing nodes of which the corresponding difference values are larger than the preset threshold value, and determining the coordinate of the selected computing node as a starting point coordinate; selecting a second computing node corresponding to the difference value smaller than the difference threshold value from the difference value between the first signal mean value and the second signal mean value corresponding to the computing node, and determining the coordinate of the second computing node as the coordinate of the peak point; and when the difference values between the first signal mean value and the second signal mean value corresponding to the continuous plurality of calculation nodes are gradually reduced and are all smaller than a preset threshold value, selecting a third calculation node from the plurality of calculation nodes of which the corresponding difference values are smaller than the preset threshold value, and determining the coordinate of the third calculation node as the terminal point coordinate.
In one embodiment, the computer program when executed by the processor further performs the steps of: inputting the chromatographic signals into corresponding fitting functions for fitting; wherein the fitting function is:
Figure BDA0002816379270000241
Kland KrIs constant, u is the peak-off interval of chromatographic peaks, t is the time variable, and y (t) is the chromatographic signal. Wherein, KlAnd KrConstant, can be obtained by fitting the chromatographic peak data. Where e is a natural constant in mathematics and has a value of about 2.71828.
In one embodiment, the computer program when executed by the processor further performs the steps of: acquiring an estimated peak value coordinate of a hemoglobin chromatographic peak; acquiring maximum peak values in preset time periods before and after the predicted peak value coordinate; the peak value is the peak value of a hemoglobin chromatographic peak; calculating the peak area of a chromatographic peak appearing after the peak generation moment; and when the peak area and the peak-appearing time of the target chromatographic peak appearing after the peak value generation moment meet preset conditions, determining the target chromatographic peak as the hemoglobin variant chromatographic peak.
In one embodiment, the computer program when executed by the processor further performs the steps of: taking the average value of at least three continuous chromatographic signal points including the chromatographic signal point to be smoothed in the original chromatographic signal as the signal value of the chromatographic signal point to be smoothed to obtain the smoothed chromatographic signal; the obtaining of the starting point coordinate, the end point coordinate and the peak point coordinate of the chromatographic peak in the original chromatographic signal comprises: and acquiring the coordinates of the starting point, the end point and the peak point of the chromatographic peak in the chromatographic signal after the smoothing treatment.
It will be understood by those skilled in the art that all or part of the processes of the methods of the embodiments described above can be implemented by hardware instructions of a computer program, which can be stored in a non-volatile computer-readable storage medium, and when executed, can include the processes of the embodiments of the methods described above. Any reference to memory, storage, database or other medium used in the embodiments provided herein can include at least one of non-volatile and volatile memory. Non-volatile Memory may include Read-Only Memory (ROM), magnetic tape, floppy disk, flash Memory, optical storage, or the like. Volatile Memory can include Random Access Memory (RAM) or external cache Memory. By way of illustration and not limitation, RAM can take many forms, such as Static Random Access Memory (SRAM) or Dynamic Random Access Memory (DRAM), among others.
The technical features of the above embodiments can be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the above embodiments are not described, but should be considered as the scope of the present specification as long as there is no contradiction between the combinations of the technical features.
The above-mentioned embodiments only express several embodiments of the present application, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the concept of the present application, which falls within the scope of protection of the present application. Therefore, the protection scope of the present patent shall be subject to the appended claims.

Claims (12)

1. A chromatographic peak detection method, characterized in that the method comprises:
acquiring a starting point coordinate, an end point coordinate and a peak point coordinate of a chromatographic peak in an original chromatographic signal;
separating chromatographic signals of corresponding chromatographic peaks from the original chromatographic signals according to the starting point coordinates and the end point coordinates;
fitting the corresponding chromatographic signals according to the fitting functions corresponding to the chromatographic peaks to obtain fitting signals corresponding to the chromatographic peaks; the fitting function is a function constructed based on the peak point coordinates;
calculating peak areas of the chromatographic peaks based on the fitted signals.
2. The method of claim 1, wherein the chromatographic peak comprises a glycated hemoglobin chromatographic peak; said calculating peak areas of said chromatographic peaks based on said fitted signals comprises:
and calculating the peak area of the glycosylated hemoglobin chromatographic peak based on the fitting signal corresponding to the glycosylated hemoglobin chromatographic peak.
3. The method of claim 2, wherein the chromatographic peaks further comprise a hemoglobin variant chromatographic peak; said calculating peak areas of said chromatographic peaks based on said fitted signals further comprises:
calculating the peak area of the hemoglobin variant chromatographic peak based on the fitting signal corresponding to the hemoglobin variant chromatographic peak;
the method further comprises the following steps:
and calculating the content of the glycosylated hemoglobin according to the peak area of the glycosylated hemoglobin chromatographic peak, the peak area of the hemoglobin variant chromatographic peak and the total peak area calculated based on the original chromatographic signal.
4. The method of claim 3, wherein said calculating glycated hemoglobin content from peak areas of said glycated hemoglobin chromatographic peak, peak areas of said hemoglobin variant chromatographic peak, and a total peak area calculated based on said raw chromatographic signal comprises:
inputting the peak area of the glycosylated hemoglobin chromatographic peak, the peak area of the hemoglobin variant chromatographic peak and the total peak area into a calculation function for calculation to obtain the content of the glycosylated hemoglobin;
wherein the calculation function is:
Figure FDA0002816379260000011
y is the content of the glycated hemoglobin, S1Is the peak area of the glycated hemoglobin chromatographic peak, S is the total peak area, S2Is the peak area of the chromatographic peak of the hemoglobin variant.
5. The method of claim 1, wherein said obtaining the start point coordinates, end point coordinates and peak point coordinates of a chromatographic peak in the raw chromatographic signal comprises:
starting from an initial chromatographic signal point in a chromatographic peak identification window, sequentially taking the chromatographic signal points in the chromatographic peak identification window as a current calculation node, and traversing and calculating a first signal mean value of a preset number of chromatographic signal points before the calculation node and a second signal mean value of the preset number of chromatographic signal points after the calculation node;
and determining the starting point coordinate, the end point coordinate and the peak point coordinate of the chromatographic peak according to the first signal mean value and the second signal mean value of the chromatographic signal point.
6. The method of claim 5, wherein determining the start point coordinate, the end point coordinate, and the peak point coordinate of a chromatographic peak from the first signal mean and the second signal mean of the chromatographic signal points comprises:
aiming at the signal mean values corresponding to the chromatographic signal points in the chromatographic peak identification window, when the difference values between the first signal mean values and the second signal mean values corresponding to a plurality of continuous computing nodes are gradually increased and are all larger than a preset threshold value, selecting a first computing node from the plurality of computing nodes of which the corresponding difference values are larger than the preset threshold value, and determining the coordinate of the selected computing node as a starting point coordinate;
selecting a second calculation node corresponding to the difference value smaller than a difference threshold value from the difference value between the first signal mean value and the second signal mean value corresponding to the calculation node, and determining the coordinate of the second calculation node as the coordinate of the peak point;
and when the difference values between the first signal mean value and the second signal mean value corresponding to the continuous multiple calculation nodes are gradually reduced and are all smaller than the preset threshold value, selecting a third calculation node from the multiple calculation nodes of which the corresponding difference values are smaller than the preset threshold value, and determining the coordinate of the third calculation node as the terminal point coordinate.
7. The method of claim 1, wherein fitting the respective chromatographic signals according to the fitting function corresponding to the chromatographic peak comprises:
inputting the chromatographic signals into corresponding fitting functions for fitting;
wherein the fitting function is:
Figure FDA0002816379260000021
Kland KrIs constant, u is the time of peak appearance of the chromatographic peak, t is the time variable, and y (t) is the chromatographic signal.
8. The method of claim 1, wherein the chromatographic peak comprises a hemoglobin chromatographic peak; after the obtaining of the start point coordinate, the end point coordinate and the peak point coordinate of the chromatographic peak in the original chromatographic signal, the method further comprises:
acquiring the predicted peak value coordinate of the hemoglobin chromatographic peak;
acquiring the maximum peak value in a preset time period before and after the predicted peak value coordinate; the peak value is the peak value of the hemoglobin chromatographic peak;
calculating the peak area of a chromatographic peak appearing after the peak generation time;
and when the peak area and the peak appearance time of the target chromatographic peak appearing after the peak value generation moment meet preset conditions, determining the target chromatographic peak as the hemoglobin variant chromatographic peak.
9. The method of claim 1, wherein before obtaining the coordinates of the start point, the end point and the peak point of the chromatographic peak in the original chromatographic signal, the method further comprises the step of smoothing the chromatographic signal point to be smoothed in the original chromatographic signal:
taking the average value of at least three continuous chromatographic signal points including the chromatographic signal point to be smoothed in the original chromatographic signal as the signal value of the chromatographic signal point to be smoothed to obtain a smoothed chromatographic signal;
the acquiring of the start point coordinate, the end point coordinate and the peak point coordinate of the chromatographic peak in the original chromatographic signal comprises:
and acquiring a starting point coordinate, an end point coordinate and a peak point coordinate of a chromatographic peak in the chromatographic signal after the smoothing treatment.
10. A chromatographic peak detection device, characterized in that the device comprises:
the acquisition module is used for acquiring a starting point coordinate, an end point coordinate and a peak point coordinate of a chromatographic peak in an original chromatographic signal;
the separation module is used for separating chromatographic signals of corresponding chromatographic peaks from the original chromatographic signals according to the starting point coordinates and the end point coordinates;
the fitting module is used for fitting the corresponding chromatographic signals according to the fitting functions corresponding to the chromatographic peaks to obtain fitting signals corresponding to the chromatographic peaks; the fitting function is a function constructed based on the peak point coordinates;
and the calculation module is used for calculating the peak area of the chromatographic peak based on the fitting signal.
11. A computer device comprising a memory and a processor, the memory storing a computer program, characterized in that the processor realizes the steps of the method of any one of claims 1 to 9 when executing the computer program.
12. A computer-readable storage medium, on which a computer program is stored, which, when being executed by a processor, carries out the steps of the method of any one of claims 1 to 9.
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