Rapid detection method for specific biomarker of precocious puberty of central girls

Abstract

The invention relates to the technical field of biomedical detection, in particular to a rapid detection method for a specific biomarker of precocious puberty of central girls. When a blood sample is detected, an original light intensity sequence of the chromatographic test strip is obtained and adjusted into a standardized net signal sequence; the color band width is controlled by the chromatography flow velocity and can reflect the fluid diffusion level under the sample viscosity, so that the quality control line reference width and the waveform sharpness are determined, and the waveform distribution characteristics are grasped; if the blood viscosity is increased, the light intensity of quality control and interference capture intervals is distorted, and when the light intensity of the interference capture intervals meets preset conditions, saturation evaluation indexes are determined according to peak shape characteristics and quality control line related parameters of the interference capture intervals, and the saturation degree is evaluated; analyzing the light intensity in a membrane gap interval to obtain a background trailing ratio, and quantifying the leakage flux of free interferents; finally, the saturation evaluation index and the background trailing ratio are fused to obtain a blood sample effective value, the sample condition can be comprehensively and accurately reflected, and whether the sample is suitable for detection or not can be determined.

Description

Technical Field

[0001] This invention relates to the field of biomedical detection technology, specifically to a rapid detection method for specific biomarkers of precocious puberty in centrally affected girls. Background Technology

[0002] Central precocious puberty (CPP) in girls is an endocrine disorder that seriously affects children's growth, development, and mental and physical health. Accurate and rapid detection of CPP in girls is crucial for early diagnosis, timely intervention, and treatment, effectively preventing adverse consequences such as short stature and psychological problems. Early screening for CPP relies on detecting trace peptide markers such as Kisspeptin, an upstream regulator of gonadotropin-releasing hormone, in peripheral blood. Due to poor compliance with intravenous blood collection in children, rapid immunochromatographic detection using whole blood from the fingertip has significant clinical application value.

[0003] Chromatographic test strip technology is a rapid, gradual, and low-cost monitoring method that has been widely used in the biomedical field. When testing blood samples from girls, current technologies typically rely on light intensity thresholds or simple background subtraction to interpret the results. However, due to significant differences in blood viscosity among different children, and the presence of heterophilic antibodies or rheumatoid factor in some children, these interfering substances are prone to non-specific adsorption, leading to reduced effectiveness of the blood sample and severely affecting the final interpretation results. Summary of the Invention

[0004] To address the technical problem that the blood viscosity varies significantly among different children, and some children may have heterophile antibodies or rheumatoid factor, which can easily lead to non-specific adsorption of these interfering substances, reducing the effectiveness of blood samples and severely affecting the final interpretation results, the present invention aims to provide a rapid detection method for specific biomarkers of precocious puberty in centrally affected girls. The specific technical solution adopted is as follows: When testing blood samples, the original light intensity sequence on the chromatographic test strip is obtained, and the original light intensity sequence is adjusted to obtain a standardized net signal sequence. In the standardized net signal sequence, the reference width of the control line is determined based on the numerical characteristics of the light intensity; the sharpness of the control line waveform is determined according to the distribution characteristics of the light intensity in the standardized net signal sequence. When the light intensity in the interference capture region of the standardized net signal sequence meets the preset conditions, the saturation evaluation index of the interference capture region is determined based on the peak shape characteristics of the light intensity in the interference capture region, the reference width of the quality control line, and the sharpness of the quality control line waveform; within the membrane gap region, the overall level of light intensity is analyzed to obtain the background tailing ratio. The saturation evaluation index and background trailing ratio are fused using preset saturation term weights, leakage term weights, and coupling term weights to obtain the effective value of the blood sample; the effectiveness of the blood sample is judged based on the effective value of the blood sample.

[0005] Furthermore, the method for obtaining the standardized net signal sequence includes: Within the quality control interval, the index corresponding to the maximum light intensity value is marked as the center index of the quality control line; In the original light intensity sequence, the difference between the index of each sampling point and the center index of the quality control line is used as the index of each sampling point in the normalized net signal sequence; The mean value of all light intensities within the background noise interval is used as the membrane background baseline value. When the light intensity at a certain sampling point is less than or equal to the membrane background baseline value, the light intensity at that sampling point in the standardized net signal sequence is set to 0. Otherwise, the difference between the light intensity at that sampling point and the membrane background baseline value is used as the light intensity at that sampling point in the standardized net signal sequence.

[0006] Furthermore, the method for obtaining the reference width of the quality control line includes: In the standardized net signal sequence, the process will be traversed from the center index of the quality control line to both sides, and the index where the light intensity is first less than or equal to half of the peak value will be recorded as the boundary index. The absolute value of the difference between the two boundary indices is multiplied by the step size as the reference width of the quality control line.

[0007] Furthermore, the method for obtaining the sharpness of the control line waveform includes: In the standardized net signal sequence, the light intensity corresponding to the two boundary indices and the indices between them is taken as a subsequence; In the subsequence, the kurtosis of all light intensities is calculated as the sharpness of the control line waveform.

[0008] Furthermore, the method for obtaining the saturation evaluation index includes: The product of the quality control line reference width and the preset rheological position compensation coefficient is used as the width comparison value; The sequence of interference capture interval is extracted from the standard net signal sequence as the target sequence; In the target sequence, the full width at half maximum (FWHM) of the largest peak in the waveform is obtained. When the FWHM is less than the width comparison value, the physical width residual is set to 0; otherwise, the physical width residual is set to the difference between the FWHM and the width comparison value. In the target sequence, peak shape characteristics are analyzed and compared with the sharpness of the control line waveform to determine the collapse index; The product of the square of the collapse index and the preset morphological sensitivity coefficient is used as the distortion factor, and the sum of the distortion factor and the preset constant is used as the distortion penalty value. The normalized value of the sum of the distortion penalty value and the physical width residual is used as the saturation evaluation index of the interference capture interval.

[0009] Furthermore, the method for obtaining the collapse index includes: In the target sequence, the index corresponding to the maximum light intensity value is used as the center index of the interference line, the ratio of the full width at half maximum to the step size is rounded up as the index width comparison value, the difference between the interference line index and the index width comparison value is used as an index boundary value, and the sum of the interference center index and the index width comparison value is used as an index boundary value. The kurtosis of the light intensity corresponding to the two index boundary values ​​and the index between them is calculated as the measured sharpness of the interference line. When the sharpness of the control line waveform is less than the measured sharpness of the interference line, the collapse index is set to 0; otherwise, the difference between the sharpness of the control line waveform and the measured sharpness of the interference line is used as the collapse index.

[0010] Furthermore, the method for obtaining the background trailing ratio includes: Within the membrane gap, the mean light intensity at all sampling points in the standardized net signal sequence is obtained and normalized to serve as the background trailing ratio.

[0011] Furthermore, the method for obtaining the valid values ​​of the blood sample includes: The product of the saturation evaluation index and the background trailing ratio is used as a coupling factor; Multiply the preset saturation term weight by the saturation evaluation index, multiply the preset leakage term weight by the background tailing ratio, multiply the preset coupling term weight by the coupling factor, and then perform negative correlation mapping and normalization on the sum of the three products to obtain the effective value of the blood sample.

[0012] Furthermore, the determination of blood sample validity based on the valid values ​​of the blood sample includes: If the valid value of a blood sample is less than or equal to the preset system safety threshold, the blood sample is determined to be an invalid sample; otherwise, the blood sample is determined to be a valid sample.

[0013] Furthermore, the standard deviation of all light intensities within the background noise range is taken as the background noise background value, and the preset condition is: In the standardized net signal sequence, the maximum light intensity value located within the interference capture interval is greater than or equal to three times the background noise level. This invention has the following beneficial effects: When testing blood samples from girls, obtaining the original light intensity sequence from the chromatographic test strip and adjusting it to obtain a standardized net signal sequence can eliminate inherent light reflection or autofluorescence interference from the test strip material itself, providing a reliable data basis. The control line, pre-coated with sufficient secondary antibody, reacts with the gold-labeled complex in an antibody excess state. Therefore, its band width is mainly controlled by the current chromatographic flow rate, objectively reflecting the inherent fluid diffusion level at the current sample viscosity. Thus, in the standardized net signal sequence, the reference width and waveform sharpness of the control line are determined based on the numerical and distribution characteristics of the light intensity, thus capturing the waveform distribution characteristics of the control line. Furthermore, given that increased blood viscosity reduces the chromatographic flow rate, causing simultaneous distortion of light intensity in both the control and interference capture regions, and considering that a substantial detection risk only arises when uncaptured free interfering substances overflow and migrate downstream with the fluid, a saturation evaluation index for the interference capture region is determined based on the peak shape characteristics, control line reference width, and control line waveform sharpness of the light intensity within the interference capture region when the light intensity in the standardized net signal sequence meets preset conditions. This index is used to assess the saturation level of the interference capture region. The overall intensity level of the light intensity within the membrane gap is analyzed to obtain the background tailing ratio, quantifying the dynamic leakage flux of free interfering substances. Finally, the fusion of the saturation evaluation index and the background tailing ratio yields the effective value of the blood sample, which more comprehensively and accurately reflects the true condition of the sample. This helps to quickly and accurately determine whether the blood sample is suitable for the detection of specific biomarkers for central precocious puberty in girls, saving detection time and cost and improving detection efficiency. Attached Figure Description

[0014] To more clearly illustrate the technical solutions and advantages in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0015] Figure 1 A flowchart illustrating a rapid detection method for specific biomarkers of central precocious puberty in girls, provided as an embodiment of the present invention; Figure 2 The present invention provides a flowchart of a method for obtaining a saturation evaluation index according to an embodiment of the present invention. Detailed Implementation

[0016] To further illustrate the technical means and effects adopted by the present invention to achieve its intended purpose, the following, in conjunction with the accompanying drawings and preferred embodiments, details the specific implementation, structure, features, and effects of a rapid detection method for specific biomarkers of central precocious puberty in girls according to the present invention. In the following description, different "one embodiment" or "another embodiment" do not necessarily refer to the same embodiment. Furthermore, specific features, structures, or characteristics in one or more embodiments can be combined in any suitable form.

[0017] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0018] The following description, in conjunction with the accompanying drawings, details the specific scheme of a rapid detection method for specific biomarkers of central precocious puberty in girls provided by the present invention.

[0019] Please see Figure 1 The diagram illustrates a method flowchart for rapid detection of specific biomarkers for central precocious puberty in girls according to an embodiment of the present invention. The method includes the following steps: Step S1: When testing a blood sample, the original light intensity sequence on the chromatographic test strip is obtained, and the original light intensity sequence is adjusted to obtain a standardized net signal sequence.

[0020] When testing the girl's blood sample, the system drives the photoelectric scanning device to perform step scans along the length of the chromatographic test strip. The total physical length of the scan is set to cover the entire field of view from the sample application end to the absorbent pad end. The total number of scan steps is denoted as N, and the step size, or step accuracy, is set to... (In this embodiment of the invention, the value is 0.02 mm). During the scanning process, for each step position (sampling point) n (n=1, 2, 3..., N), the photoelectric response value, that is, the light intensity, is read synchronously. Thus, the original light intensity sequence of the chromatographic test strip can be generated. The original light intensity sequence completely records the optical distribution information of all lines and areas on the chromatographic test strip.

[0021] Here is a brief explanation of the lines and areas on a chromatography test strip: The basic structure of a chromatography test strip consists of: the sample pad, usually located at the very front of the strip and the area where the sample first contacts; the conjugate pad, immediately following the sample pad, which stores markers containing specific antibodies or antigens; the nitrocellulose membrane (NC membrane), located after the conjugate pad, which is the core functional area of ​​the strip, and contains the test line and control line; and the absorbent pad area, located at the very back of the strip. The functional areas include: the test line, fixed to the nitrocellulose membrane, its position depending on the strip design, generally near the absorbent pad; the control line, usually located near the conjugate pad of the test line; and the interference line, used to capture interfering substances in the sample, usually located before the test line.

[0022] In this embodiment of the invention, according to the flow direction of the liquid on the chromatographic test strip (from upstream to downstream, i.e., from the sample application end to the absorbent pad end), the distribution of each region is as follows: Background noise region, located at the upstream end and before the interference line, is a blank membrane used to measure background noise; Interference capture region, located after the background noise region and before the detection line, is coated with "vacuum cleaner" material (such as IgG) to intercept interfering substances; Membrane gap region, located in the blank area between the interference line and the detection line, physically corresponds to the blank area of ​​the nitrocellulose membrane without capture antibody coating, and is a leakage monitoring area; Target detection region, located after the membrane gap region, is coated with detection antibody to capture the target analyte; Quality control region, located at the downstream end, should show color regardless of whether there is a target analyte, to prove that the chromatography process is complete.

[0023] Because the viscosity differences in blood samples can cause fluctuations in the chromatographic flow rate, which in turn can cause slight shifts in the physical position of the color bands on the membrane, and because the chromatographic test strip material has an inherent autofluorescence background, directly using absolute coordinates and the original light intensity for analysis will introduce a large error. Therefore, the original light intensity sequence can be adjusted to obtain a standardized net signal sequence.

[0024] Preferably, in one embodiment of the present invention, the method for obtaining the standardized net signal sequence includes: Control lines play a crucial role in chromatographic test strip detection. On chromatographic test strips, control lines are usually associated with specific markers. When the sample flows through them, a significant change in light intensity occurs, forming a light intensity peak. Therefore, by finding the index (step position number n) corresponding to the maximum light intensity value within the control interval, the center position of the control line can be accurately located. That is, within the control interval, the index corresponding to the maximum light intensity value is marked as the center index of the control line, providing a benchmark for subsequent standardization of sampling positions.

[0025] It should be noted that if the maximum light intensity value here is less than the preset effective intensity threshold (set to 50 light intensity units in this embodiment of the invention), it is directly determined to be invalid and no further process is required. If it is greater than or equal to the preset effective intensity threshold, the subsequent process continues.

[0026] Then, in the original light intensity sequence, the difference between the index of each sampling point and the center index of the quality control line is used as the index of each sampling point in the standardized net signal sequence. At this time, the index of the maximum light intensity value is 0.

[0027] The mean of all light intensities within the background noise interval is calculated as the membrane background baseline value. When the light intensity at a certain sampling point is less than or equal to the membrane background baseline value, it indicates that the light intensity at that sampling point mainly comes from background noise. In this case, the light intensity at that sampling point in the standardized net signal sequence is set to 0. When the light intensity at a certain sampling point is greater than the membrane background baseline value, it is considered that the light intensity at that sampling point may be generated by the target substance. Therefore, the difference between the light intensity at that sampling point and the membrane background baseline value is taken as the light intensity at that sampling point in the standardized net signal sequence, which is used to more accurately reflect the content of the target substance in the blood sample.

[0028] Therefore, the index and light intensity at each sampling point can be adjusted to obtain a standardized net signal sequence.

[0029] It should be noted that the collection and acquisition of personal information data in the embodiments of the present invention are all authorized by the relevant users, and the process does not violate relevant laws and regulations, nor does it violate public order and good morals.

[0030] Step S2: In the standardized net signal sequence, determine the reference width of the control line based on the numerical characteristics of the light intensity; determine the sharpness of the control line waveform according to the distribution characteristics of the light intensity in the standardized net signal sequence.

[0031] Due to factors such as differences in physical condition, the differences in fingertip blood samples from different girls may be significant, so a fixed standard cannot be used for measurement. Therefore, in this embodiment of the invention, the performance of the blood sample in the quality control line and quality control interval on the chromatographic test strip can be used as the standard.

[0032] First, because the quality control zone is pre-coated with sufficient secondary antibody, its reaction with the gold-labeled complex is in an antibody excess state. Therefore, its band width is mainly controlled by the current chromatography flow rate, which can objectively reflect the inherent fluid diffusion level under the current blood sample viscosity. Thus, in the standardized net signal sequence, the reference width of the quality control line can be determined based on the numerical characteristics of light intensity, serving as a dynamic benchmark for subsequent judgment of whether other lines have undergone abnormal physical broadening.

[0033] Preferably, in one embodiment of the present invention, the method for obtaining the reference width of the quality control line includes: The control line typically represents a region of peak light intensity, reaching its maximum value at the center (the center index of the control line) and gradually decreasing towards both sides. When the light intensity drops to half of the peak value, it can be considered that it has exceeded the main influence range of the control line. Therefore, in the standardized net signal sequence, the control line is traversed from the center index to both sides. The index where the light intensity is first less than or equal to half of the peak value is recorded as the boundary index. The product of the absolute value of the difference between the two boundary indices and the step size is used as the reference width of the control line to characterize the physical diffusion benchmark.

[0034] Furthermore, the waveform of the control line under normal chromatography should exhibit a standard normal distribution (Gaussian distribution). However, chemical saturation caused by antigen overload can lead to a flattening of the waveform top. Therefore, in order to establish a waveform benchmark when chemical saturation has not occurred, this embodiment of the invention determines the sharpness of the control line waveform based on the distribution characteristics of light intensity in the standardized net signal sequence.

[0035] Preferably, in one embodiment of the present invention, the method for obtaining the sharpness of the control line waveform includes: First, in the standardized net signal sequence, the light intensity corresponding to the two boundary indices and the indices between them is taken as a subsequence. Since the fourth central moment is often used in statistics as an important indicator to describe the distribution of data, it can be used to reflect the distribution characteristics of the waveform and quantify its sharpness. Therefore, in the subsequence, the kurtosis of all light intensities is calculated (the fourth central moment divided by the fourth power of the standard deviation and then subtracted by 3) as the quality control line waveform sharpness, which can serve as a key internal standard to distinguish between physical diffusion and chemical interference.

[0036] Step S3: When the light intensity in the interference capture interval of the standardized net signal sequence meets the preset conditions, the saturation evaluation index of the interference capture interval is determined based on the peak shape characteristics of the light intensity in the interference capture interval, the reference width of the quality control line, and the sharpness of the quality control line waveform; within the membrane gap interval, the overall level of light intensity is analyzed to obtain the background tailing ratio.

[0037] This step aims to distinguish between "false broadening" (physicorheological factors) caused by high-viscosity blood and "true accumulation" (chemoimmunological factors) caused by heterophile antibody overload. First, it's necessary to determine whether substantial protein adsorption has occurred within the interference capture region. This is to avoid generating physically meaningless random values ​​by extracting morphological features from pure background noise. Therefore, the light intensity within the interference capture region of the standardized net signal sequence can be analyzed to determine if it meets preset conditions, i.e., whether subsequent calculations are necessary.

[0038] Standard deviation is an important statistic for measuring the dispersion of data. Within the background noise range, light intensity will exhibit certain random fluctuations, which reflect the instability of the background noise. Therefore, the standard deviation of all light intensities within the background noise range is first taken as the background noise background value. Then, preferably, in one embodiment of the present invention, the preset conditions are set as follows: In analytical chemistry and signal processing, a signal is generally considered to be real only if its intensity exceeds three times the noise level, which means that the subsequent calculation process is meaningful. Therefore, the preset condition is: in the standardized net signal sequence, the maximum light intensity value located in the interference capture interval is greater than or equal to three times the background noise level.

[0039] It should be noted that if the preset conditions are not met, the blood sample will be deemed invalid and will need to be resampled or diluted.

[0040] Increased blood viscosity reduces the chromatography flow rate, causing isotropic Gaussian diffusion of both the control line and the interference line (i.e., increased width but stable kurtosis). Conversely, interference concentrations exceeding the binding site capacity result in non-Gaussian distortion of the interference line, exhibiting a flat-topped or trapezoidal shape (i.e., significantly reduced kurtosis). Therefore, under the aforementioned preset conditions, the peak shape characteristics of light intensity in the interference capture interval can be analyzed and compared with the control line reference width and control line waveform sharpness obtained in step S2 to calculate the saturation evaluation index of the interference capture interval.

[0041] Preferably, in one embodiment of the present invention, the method for obtaining the saturation evaluation index includes: Please see Figure 2 The diagram illustrates a method flowchart for obtaining a saturation evaluation index according to an embodiment of the present invention. The method includes the following steps: Step S301: Extract the interference capture interval from the standard net signal sequence as the target sequence, analyze the peak shape characteristics of the light intensity in the target sequence and combine it with the reference width of the quality control line to determine the physical width residual.

[0042] The farther the liquid travels on the membrane, the slower the flow rate. Slower flow rates lead to longer diffusion times. Furthermore, since the detection line is upstream, the liquid arrives first, while the control line is downstream, the liquid arrives later. Therefore, the control line, which is inherently present on the chromatography strip, is used as a benchmark for the current fluid state. A preset rheological position compensation coefficient is introduced to establish a correlation between the theoretical physical width of the interference line and the measured width of the control line. This compensation coefficient comprehensively characterizes the difference in the physical design width between the interference line and the control line, as well as the compensation for fluid velocity attenuation caused by different chromatography distances. Therefore, the product of the control line reference width and the preset rheological position compensation coefficient is used as the width comparison value. This width comparison value characterizes the "theoretical physical width" of the interference line within the interference capture interval predicted based on the current flow rate and positional differences.

[0043] Then, in the target sequence, the full width at half maximum (FWHM) of the largest peak in the waveform is obtained. The FWHM characterizes the width of the measured waveform of the interference line within the interference capture interval. The difference between the FWHM and the width comparison value is calculated. This difference specifically characterizes the spatial expansion component caused by excessive antigen accumulation. When the FWHM is less than the width comparison value, the physical width residual is set to 0; otherwise, the physical width residual is set to the difference between the FWHM and the width comparison value. The smaller the physical width residual, the more it indicates that the widening of the interference line fully conforms to the fluid rheological law and is a normal physical phenomenon.

[0044] It should be noted that the preset rheological position compensation coefficient is a dimensionless engineering coefficient used to comprehensively characterize the difference in the physical design width between the interference capture line and the quality control line, as well as the fluid velocity attenuation effect caused by their different positions on the chromatography membrane. This coefficient is usually obtained through standard sample testing and calibration, and its typical value ranges from 0.8 to 1.3, for example, it is 1.15 in this embodiment of the present invention.

[0045] Step S302: In the target sequence, analyze the peak shape characteristics and compare them with the sharpness of the control line waveform to determine the collapse index.

[0046] When a high concentration of interfering substances is present in a blood sample, the optical response distribution of the band will exhibit statistical characteristics highly correlated with chemical saturation, i.e., the top of the waveform tends to be flat, resulting in a kurtosis value that is significantly lower than that of the standard Gaussian distribution. Therefore, in the target sequence, the index corresponding to the maximum light intensity value is used as the center index of the interference line, and the ratio of the full width at half maximum (FWHM) to the step size (set to 0.02 mm in step S1 in this embodiment) is rounded up as the index width comparison value. The difference between the interference line index and the index width comparison value is used as an index boundary value, and the sum of the interference center index and the index width comparison value is used as an index boundary value. Then, the kurtosis of the light intensity corresponding to these two index boundary values ​​and the index between them (the fourth central moment divided by the fourth power of the standard deviation and then subtracted by 3) is calculated as the measured sharpness of the interference line.

[0047] Next, the measured sharpness of the interference line within the interference capture interval is compared with the sharpness of the control line waveform. When the sharpness of the control line waveform is less than the measured sharpness of the interference line, it indicates that the signal has not collapsed within the interference capture interval, so the collapse index is set to 0. Otherwise, the difference between the sharpness of the control line waveform and the measured sharpness of the interference line is used as the collapse index.

[0048] Step S303: Combine the physical width residual with the collapse index to obtain the saturation evaluation index of the interference capture range.

[0049] To integrate the features of the two dimensions mentioned above (collapse index and physical width residual) into a saturation index, a preset shape sensitivity coefficient can be called. Its function is to adjust the penalty weight of the algorithm for non-Gaussian (flat-top) waveform distortion. The larger the coefficient, the more sensitive the system is to waveform distortion.

[0050] The product of the square of the collapse index and the preset morphological sensitivity coefficient is used as the distortion factor, and the sum of the distortion factor and the preset constant is used as the distortion penalty value. In other words, the square term is used to penalize and weight the morphological distortion.

[0051] Finally, the normalized sum of the distortion penalty value and the physical width residual is used as the saturation evaluation index of the interference acquisition range. The larger the saturation evaluation index, the more abnormal the interference line width has increased in the interference acquisition range, accompanied by a flat-top distortion of the waveform. The larger the value, the higher the risk of interception failure in the interference acquisition area.

[0052] Normalization is a well-known technique in the art. The normalization function can be linear normalization or standard normalization, etc. For example, maximum and minimum value normalization can be used (where the maximum and minimum values ​​can be obtained experimentally), or the Sigmoid function can be used for normalization. The specific normalization method is not limited here.

[0053] It should be noted that the recommended range for the preset morphological sensitivity coefficient is 1.5 to 3.0, and in this embodiment of the invention, it is set to 2.0; to prevent over-adjustment, the preset constant is set to 1.

[0054] While the saturation evaluation index of the interference capture interval reveals the risk of interception failure at the source, this is not directly equivalent to a false positive result. Only when uncaptured free interference spills out and migrates downstream with the fluid does it constitute a substantial detection risk. Therefore, it is necessary to further quantify the material residue in the membrane gap interval between the interference line and the detection line. Thus, this study analyzes the overall level of light intensity located in the membrane gap interval within the normalized signal sequence to obtain the background tailing ratio.

[0055] Preferably, in one embodiment of the present invention, the method for obtaining the background trailing ratio includes: Under normal circumstances, the membrane gap interval should be blank. However, if the interfering substance crosses the interference capture interval, it will leave a trace in the membrane gap interval. Therefore, the light intensity in the membrane gap interval can quantify this trace. Thus, within the membrane gap interval, the mean value of the light intensity at all sampling points in the standardized net signal sequence is obtained and normalized as the background tail ratio. The background tail ratio is used to objectively reflect the dynamic leakage flux of free interfering substances. The larger the value, the higher the leakage and the greater the risk.

[0056] It should be noted that normalization is a technique well-known to those skilled in the art, and the choice of normalization function can be linear normalization or standard normalization, etc. The specific normalization method is not limited here.

[0057] Step S4: Use the preset saturation term weight, leakage term weight, and coupling term weight to fuse the saturation evaluation index and background tailing ratio to obtain the effective value of the blood sample; judge the validity of the blood sample based on the effective value of the blood sample.

[0058] Simple interception failure (source risk) does not affect the reliability of the results if it does not cause significant leakage (path risk); a simple increase in background leakage risk may also stem from non-specific adsorption. Only when interception saturation failure and contaminant leakage logically occur simultaneously does it constitute a confirmed high-risk interference environment. Therefore, in this step, the aim is to generate a quantified effective value for the blood sample through multi-dimensional coupled calculations.

[0059] Preferably, in one embodiment of the present invention, the method for obtaining the effective value of a blood sample includes: A risk assessment weight set is set, which includes three weights: saturation weight, used to adjust the attention to the degree of saturation of the interference line, with a value of 1.5 in this embodiment; leakage weight, used to adjust the attention to the degree of tailing of the membrane gap interval, with a value of 1.2 in this embodiment; and coupling weight, used to adjust the nonlinear penalty when the above two factors occur concurrently, with a value of 3.0 in this embodiment.

[0060] Then, the product of the saturation evaluation index and the background tailing ratio is used as the coupling factor. The preset saturation term weight is multiplied by the saturation evaluation index; the larger this value, the higher the risk of interception failure in the interference capture area, and thus the greater the possibility of sample failure. The preset leakage term weight is multiplied by the background tailing ratio; the larger this value, the higher the dynamic leakage flux of the interfering substance, also indicating a greater possibility of sample failure. The preset coupling term weight is multiplied by the coupling factor; the larger this value, the higher both the saturation evaluation index and the background tailing ratio, meaning the current sample's detection environment has extremely low reliability and there is severe matrix interference. Therefore, the sum of the above three products is negatively correlated and normalized to correct the logical relationship, thus obtaining the effective value of the blood sample. Based on the above analysis, a larger effective value of the blood sample indicates a better detection environment, lower matrix interference, and higher reliability of the detection results. The negative correlation mapping and normalization here can be performed using the formula... ,in, Let x represent an exponential function with the natural constant e as the base, and let x represent the independent variable.

[0061] Once the valid value of the blood sample is obtained, the validity of the blood sample can be judged based on this indicator.

[0062] Preferably, in one embodiment of the present invention, the process for determining the validity of a blood sample includes: When the valid value of a blood sample is less than or equal to the preset system safety threshold, the blood sample is determined to be invalid, and the operator should be prompted to dilute or resample the blood sample; conversely, when the valid value of a blood sample is greater than the preset system safety threshold, the blood sample is determined to be valid.

[0063] It should be noted that in this embodiment of the present invention, the preset system safety threshold is 0.3, which can be determined based on a large number of clinical samples.

[0064] After obtaining a valid sample, the doctor can determine whether the blood sample is positive or negative based on existing judgment methods or experience.

[0065] To facilitate calculations, all index data involved in the calculations in this embodiment of the invention have undergone data preprocessing to eliminate the influence of dimensions. The specific methods for eliminating the influence of dimensions are well-known to those skilled in the art and are not limited here.

[0066] In summary, when testing blood samples from girls, obtaining the original light intensity sequence from the chromatographic test strip and adjusting it to obtain a standardized net signal sequence can eliminate inherent light reflection or autofluorescence interference from the test strip material itself, providing a reliable data basis. The control line, pre-coated with sufficient secondary antibody, reacts with the gold-labeled complex in an antibody excess state. Therefore, its band width is mainly controlled by the current chromatographic flow rate, objectively reflecting the inherent fluid diffusion level at the current sample viscosity. Thus, in the standardized net signal sequence, the reference width and waveform sharpness of the control line are determined based on the numerical and distribution characteristics of the light intensity, thus grasping the waveform distribution characteristics of the control line. Furthermore, given that increased blood viscosity reduces the chromatographic flow rate, causing simultaneous distortion of light intensity in both the control and interference capture regions, and considering that a substantial detection risk only arises when uncaptured free interfering substances overflow and migrate downstream with the fluid, a saturation evaluation index for the interference capture region is determined based on the peak shape characteristics, control line reference width, and control line waveform sharpness of the light intensity within the interference capture region when the light intensity in the standardized net signal sequence meets preset conditions. This index is used to assess the saturation level of the interference capture region. The overall intensity level of the light intensity within the membrane gap is analyzed to obtain the background tailing ratio, quantifying the dynamic leakage flux of free interfering substances. Finally, the fusion of the saturation evaluation index and the background tailing ratio yields the effective value of the blood sample, which more comprehensively and accurately reflects the true condition of the sample. This helps to quickly and accurately determine whether the blood sample is suitable for the detection of specific biomarkers for central precocious puberty in girls, saving detection time and cost and improving detection efficiency.

[0067] It should be noted that the order of the above embodiments of the present invention is merely for descriptive purposes and does not represent the superiority or inferiority of the embodiments. The processes depicted in the accompanying drawings do not necessarily require a specific or sequential order to achieve the desired result. In some embodiments, multitasking and parallel processing are also possible or may be advantageous.

[0068] The various embodiments in this specification are described in a progressive manner. The same or similar parts between the various embodiments can be referred to each other. Each embodiment focuses on describing the differences from other embodiments.

Claims

1. A rapid detection method for specific biomarkers of precocious puberty in centrally affected girls, characterized in that, The method includes: When testing blood samples, the original light intensity sequence on the chromatographic test strip is obtained, and the original light intensity sequence is adjusted to obtain a standardized net signal sequence. In the standardized net signal sequence, the reference width of the control line is determined based on the numerical characteristics of the light intensity; the sharpness of the control line waveform is determined according to the distribution characteristics of the light intensity in the standardized net signal sequence. When the light intensity in the interference capture region of the standardized net signal sequence meets the preset conditions, the saturation evaluation index of the interference capture region is determined based on the peak shape characteristics of the light intensity in the interference capture region, the reference width of the quality control line, and the sharpness of the quality control line waveform; within the membrane gap region, the overall level of light intensity is analyzed to obtain the background tailing ratio. The saturation evaluation index and background trailing ratio are fused using preset saturation term weights, leakage term weights, and coupling term weights to obtain the effective value of the blood sample; the effectiveness of the blood sample is judged based on the effective value of the blood sample.

2. The rapid detection method for specific biomarkers of central precocious puberty in girls according to claim 1, characterized in that, The method for obtaining the standardized net signal sequence includes: Within the quality control interval, the index corresponding to the maximum light intensity value is marked as the center index of the quality control line; In the original light intensity sequence, the difference between the index of each sampling point and the center index of the quality control line is used as the index of each sampling point in the normalized net signal sequence; The mean value of all light intensities within the background noise interval is used as the membrane background baseline value. When the light intensity at a certain sampling point is less than or equal to the membrane background baseline value, the light intensity at that sampling point in the standardized net signal sequence is set to 0. Otherwise, the difference between the light intensity at that sampling point and the membrane background baseline value is used as the light intensity at that sampling point in the standardized net signal sequence.

3. The rapid detection method for specific biomarkers of central precocious puberty in girls according to claim 2, characterized in that, The method for obtaining the reference width of the quality control line includes: In the standardized net signal sequence, the process will be traversed from the center index of the quality control line to both sides, and the index where the light intensity is first less than or equal to half of the peak value will be recorded as the boundary index. The absolute value of the difference between the two boundary indices is multiplied by the step size as the reference width of the quality control line.

4. The rapid detection method for specific biomarkers of central precocious puberty in girls according to claim 3, characterized in that, The method for obtaining the sharpness of the control line waveform includes: In the standardized net signal sequence, the light intensity corresponding to the two boundary indices and the indices between them is taken as a subsequence; In the subsequence, the kurtosis of all light intensities is calculated as the sharpness of the control line waveform.

5. The rapid detection method for specific biomarkers of central precocious puberty in girls according to claim 1, characterized in that, The method for obtaining the saturation evaluation index includes: The product of the quality control line reference width and the preset rheological position compensation coefficient is used as the width comparison value; The sequence of interference capture interval is extracted from the standard net signal sequence as the target sequence; In the target sequence, the full width at half maximum (FWHM) of the largest peak in the waveform is obtained. When the FWHM is less than the width comparison value, the physical width residual is set to 0; otherwise, the physical width residual is set to the difference between the FWHM and the width comparison value. In the target sequence, peak shape characteristics are analyzed and compared with the sharpness of the control line waveform to determine the collapse index; The product of the square of the collapse index and the preset morphological sensitivity coefficient is used as the distortion factor, and the sum of the distortion factor and the preset constant is used as the distortion penalty value. The normalized value of the sum of the distortion penalty value and the physical width residual is used as the saturation evaluation index of the interference capture interval.

6. The rapid detection method for specific biomarkers of central precocious puberty in girls according to claim 5, characterized in that, The method for obtaining the collapse index includes: In the target sequence, the index corresponding to the maximum light intensity value is used as the center index of the interference line, the ratio of the full width at half maximum to the step size is rounded up as the index width comparison value, the difference between the interference line index and the index width comparison value is used as an index boundary value, and the sum of the interference center index and the index width comparison value is used as an index boundary value. The kurtosis of the light intensity corresponding to the two index boundary values ​​and the index between them is calculated as the measured sharpness of the interference line. When the sharpness of the control line waveform is less than the measured sharpness of the interference line, the collapse index is set to 0; otherwise, the difference between the sharpness of the control line waveform and the measured sharpness of the interference line is used as the collapse index.

7. The rapid detection method for specific biomarkers of central precocious puberty in girls according to claim 1, characterized in that, The method for obtaining the background trailing ratio includes: Within the membrane gap, the mean light intensity at all sampling points in the standardized net signal sequence is obtained and normalized to serve as the background trailing ratio.

8. The rapid detection method for specific biomarkers of central precocious puberty in girls according to claim 1, characterized in that, The method for obtaining the valid values ​​of the blood sample includes: The product of the saturation evaluation index and the background trailing ratio is used as a coupling factor; Multiply the preset saturation term weight by the saturation evaluation index, multiply the preset leakage term weight by the background tailing ratio, multiply the preset coupling term weight by the coupling factor, and then perform negative correlation mapping and normalization on the sum of the three products to obtain the effective value of the blood sample.

9. A rapid detection method for specific biomarkers of central precocious puberty in girls according to claim 1, characterized in that, The determination of blood sample validity based on the valid values ​​of the blood sample includes: If the valid value of a blood sample is less than or equal to the preset system safety threshold, the blood sample is determined to be an invalid sample; otherwise, the blood sample is determined to be a valid sample.

10. A rapid detection method for specific biomarkers of central precocious puberty in girls according to claim 2, characterized in that, The standard deviation of all light intensities within the background noise range is taken as the background noise background value, and the preset condition is: The maximum light intensity value in the interference capture interval of the standardized net signal sequence is greater than or equal to 3 times the background noise level.

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