Double logarithmic calibration method based on reagent for blood coagulation analyzer

Abstract

The invention discloses a double logarithmic calibration method based on a reagent for a blood coagulation analyzer, and relates to the technical field of in vitro diagnosis, and the method comprises the following steps: based on the deviation of temperature and turbidity, performing fractional normalization anti-interference correction on a detection signal through a detection signal correction function, obtaining a corrected detection signal, and generating a corrected detection signal curve; combining the corrected detection signal with an initial double logarithm calibration equation to generate a predicted concentration, comparing the predicted concentration with a reference concentration to obtain a concentration deviation, and generating an anti-interference correction response amount according to the solidification time in the corrected detection signal curve; on the basis of the anti-interference correction response quantity, calculating a double logarithmic residual error of the test sample, associating the double logarithmic residual error with the concentration deviation, and performing real-time step length adjustment on a coefficient in a detection signal correction function according to a residual error direction to generate an updated double logarithmic calibration equation. According to the invention, the accuracy and robustness of the double logarithmic calibration equation are improved.

Description

Technical Field

[0001] This invention relates to the field of in vitro diagnostic technology, and in particular to a double logarithmic calibration method based on reagents used in coagulation analyzers. Background Technology

[0002] In modern clinical testing, coagulation analyzers are commonly used to quantitatively assess blood coagulation function. Coagulation analyzers typically utilize optical measurement mechanisms such as turbidimetry and light scattering to monitor the reaction process in real time. By analyzing the main reaction light signal and the reference light signal, they quantify coagulation time and related concentration parameters. Standard calibration methods are usually based on a set of calibrated standard samples. They collect light intensity data, calculate the logarithmic optical response value, and use logarithmic transformation to establish a functional relationship between concentration and optical response. The routine procedure also simultaneously collects light intensity, temperature, and sample turbidity to improve measurement reliability and ensure the stability of calibration conditions.

[0003] In the conventional methods described above, although temperature and turbidity deviations can be recorded during real-time detection, they are often compensated only in a static manner. The compensation factor cannot be automatically adjusted with the dynamic shifts in the detection process, and optical drift in some reaction stages may still accumulate into the calibration relationship. In addition, the weighting mechanism of optical response values ​​in conventional methods is mostly based on fixed weights. However, the variability of repeated detections among standard samples is different, and using fixed weights may cause deviations in the proportion of influence of some concentration points on the final calibration. Summary of the Invention

[0004] In view of the aforementioned existing problems, the present invention is proposed.

[0005] Therefore, this invention provides a double logarithmic calibration method based on reagents for coagulation analyzers to solve the problems of calibration accuracy being easily affected by environmental interference and insufficient optical response stability.

[0006] To solve the above-mentioned technical problems, the present invention provides the following technical solution:

[0007] This invention provides a double logarithmic calibration method based on reagents for coagulation analyzers, comprising:

[0008] Standard samples based on reagents used in coagulation analyzers were tested, reference concentrations were recorded, and optical response values ​​were obtained. An initial double logarithmic calibration equation was established, and a standard baseline was established by recording reference values ​​of light intensity, temperature, and turbidity.

[0009] The test samples are tested, real-time monitoring data is collected and compared with a standard baseline to obtain the deviations in temperature and turbidity;

[0010] Based on the deviations in temperature and turbidity, the detection signal is subjected to fractional normalization anti-interference correction through the detection signal correction function, the corrected detection signal is obtained, and the corrected detection signal curve is generated.

[0011] By combining the corrected detection signal with the initial double logarithmic calibration equation, a predicted concentration is generated and compared with the reference concentration to obtain the concentration deviation. Based on the solidification time in the corrected detection signal curve, an anti-interference correction response is generated.

[0012] Based on the anti-interference correction response, the double logarithmic residual of the test sample is calculated, and the double logarithmic residual is correlated with the concentration deviation. The coefficients in the detection signal correction function are adjusted in real time according to the residual direction to generate the updated double logarithmic calibration equation.

[0013] As a preferred embodiment of the double logarithmic calibration method based on reagents for coagulation analyzers described in this invention, the steps of detecting standard samples based on reagents for coagulation analyzers, recording reference concentrations, and obtaining optical response values ​​are as follows:

[0014] Standard samples based on reagents used in a coagulation analyzer were tested, and multiple detection optical signals were obtained.

[0015] Based on multiple detections of optical signals, the reference concentration of the standard sample is recorded, and the detection results of the main reaction optical signal and the reference optical signal are extracted and the optical response value is calculated.

[0016] As a preferred embodiment of the double logarithmic calibration method based on reagents for coagulation analyzers described in this invention, the steps for establishing an initial double logarithmic calibration equation and establishing a standard baseline by recording reference values ​​of light intensity, temperature, and turbidity are as follows:

[0017] Logarithmic transformation is performed on the reference concentration and optical response value to obtain the logarithmic concentration and logarithmic optical response value, and the weighting coefficients of the initial double logarithmic calibration equation are fitted.

[0018] The initial double logarithmic calibration equation is established by performing a weighted linear regression on the logarithmic concentration, logarithmic optical response value, and the weighting coefficients of the initial double logarithmic calibration equation.

[0019] Based on the initial double logarithmic calibration equation, the light intensity, temperature, and turbidity collected under non-reactive conditions are time-averaged to obtain the reference values ​​of light intensity, temperature, and turbidity and generate a standard baseline.

[0020] As a preferred embodiment of the double logarithmic calibration method based on reagents for coagulation analyzers described in this invention, the real-time monitoring data includes the main reaction light signal, the reference light signal, the test sample temperature, and the test sample turbidity.

[0021] As a preferred embodiment of the double logarithmic calibration method based on reagents for coagulation analyzers described in this invention, the steps of detecting the test sample, collecting real-time monitoring data and comparing it with a standard baseline to obtain the deviations in temperature and turbidity are as follows.

[0022] The test samples were tested, real-time monitoring data was collected, and the temperature and turbidity sequences of the test samples were extracted.

[0023] The temperature sequence of the test sample is compared with the reference temperature value in the standard baseline to calculate the temperature deviation of the test sample;

[0024] The turbidity sequence of the test sample is compared with the baseline turbidity value in the standard baseline to calculate the turbidity deviation of the test sample.

[0025] As a preferred embodiment of the double logarithmic calibration method based on reagents for coagulation analyzers described in this invention, the steps of performing fractional normalization anti-interference correction on the detection signal based on temperature and turbidity deviations using a detection signal correction function, obtaining the corrected detection signal, and generating the corrected detection signal curve are as follows.

[0026] Based on the temperature and turbidity deviations of the test samples, temperature compensation factors and turbidity compensation factors are constructed.

[0027] Based on the temperature compensation factor and turbidity compensation factor, and combined with the difference between the main reaction optical signal and the reference optical signal, the detection signal is subjected to fractional normalization anti-interference correction through the detection signal correction function to obtain the corrected detection signal;

[0028] The corrected detection signals are plotted in chronological order as the corrected detection signal curve.

[0029] As a preferred embodiment of the double logarithmic calibration method based on reagents for coagulation analyzers described in this invention, the steps of combining the corrected detection signal with the initial double logarithmic calibration equation to generate a predicted concentration and comparing it with a reference concentration to obtain the concentration deviation are as follows.

[0030] Perform a logarithmic transformation on the corrected detection signal to obtain the logarithmic response.

[0031] The predicted concentration of the test sample is calculated based on the logarithmic response and the initial double logarithmic calibration equation.

[0032] Compare the predicted concentration with the reference concentration to obtain the concentration deviation.

[0033] As a preferred embodiment of the double logarithmic calibration method based on reagents for coagulation analyzers described in this invention, the step of generating an anti-interference correction response quantity based on the coagulation time in the corrected detection signal curve includes the following steps:

[0034] The solidification time is obtained by analyzing the slope change of the corrected detection signal curve.

[0035] Extract the corrected detection signal corresponding to the solidification time from the corrected detection signal curve;

[0036] Based on the solidification time and the corresponding corrected detection signal, an anti-interference correction response quantity is constructed.

[0037] As a preferred embodiment of the double logarithmic calibration method based on reagents for coagulation analyzers described in this invention, the steps for calculating the double logarithmic residuals of the test samples based on the anti-interference correction response are as follows:

[0038] Logarithmic transformation is performed on the anti-interference correction response and the predicted concentration to obtain the logarithmic anti-interference correction response and the logarithmic predicted concentration.

[0039] Substitute the logarithmic predicted concentration into the initial double logarithmic calibration equation to obtain the theoretical logarithmic response.

[0040] The difference between the logarithmic anti-interference correction response and the theoretical logarithmic response is calculated to obtain the double logarithmic residual of the test sample.

[0041] As a preferred embodiment of the double logarithmic calibration method based on reagents for coagulation analyzers described in this invention, the steps of correlating the double logarithmic residuals with the concentration deviation, adjusting the coefficients in the detection signal correction function in real time according to the residual direction, and outputting the updated double logarithmic calibration equation are as follows.

[0042] The sign of the double logarithmic residuals and the concentration deviation are determined, the residual direction is obtained, and combined with the step size parameter, a real-time step size adjustment is generated.

[0043] The real-time step size adjustment is linearly superimposed with the optical compensation coefficient, temperature compensation coefficient, and turbidity compensation coefficient in the detection signal correction function to obtain the updated optical compensation coefficient, temperature compensation coefficient, and turbidity compensation coefficient. These updated coefficients are then substituted into the initial double logarithmic calibration equation to generate the updated double logarithmic calibration equation.

[0044] The beneficial effects of this invention are as follows: By correcting for deviations based on temperature and turbidity, effective compensation is achieved for light intensity changes caused by environmental factors, ensuring that the corrected signal can more stably and accurately reflect the true concentration changes of the sample, thus improving the reliability and accuracy of the measurement; by dynamically updating the double logarithmic calibration equation through real-time step size adjustment, the accuracy and robustness of the double logarithmic calibration equation under long-term operation and different batches of reagents are improved. Attached Figure Description

[0045] To more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings used in the following description of the embodiments will be briefly introduced. 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.

[0046] Figure 1 This is a flowchart of a double logarithmic calibration method based on reagents used in coagulation analyzers.

[0047] Figure 2 A flowchart for standard sample calibration and standard baseline establishment.

[0048] Figure 3 This is a flowchart for anti-interference correction.

[0049] Figure 4 This is a flowchart for real-time step size adjustment. Detailed Implementation

[0050] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, the specific embodiments of the present invention will be described in detail below with reference to the accompanying drawings.

[0051] Many specific details are set forth in the following description in order to provide a full understanding of the invention. However, the invention may also be practiced in other ways different from those described herein, and those skilled in the art can make similar extensions without departing from the spirit of the invention. Therefore, the invention is not limited to the specific embodiments disclosed below.

[0052] Secondly, the term "one embodiment" or "embodiment" as used herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. The phrase "in one embodiment" appearing in different places in this specification does not necessarily refer to the same embodiment, nor is it a single or selective embodiment that is mutually exclusive with other embodiments.

[0053] Reference Figures 1-4 This is one embodiment of the present invention, which provides a double logarithmic calibration method based on reagents for coagulation analyzers, comprising the following steps:

[0054] S1. Detect standard samples based on reagents used in coagulation analyzers, record reference concentrations and obtain optical response values, establish an initial double logarithmic calibration equation, and establish a standard baseline by recording reference values ​​of light intensity, temperature and turbidity.

[0055] Standard samples based on reagents used in a coagulation analyzer were tested, and multiple detection optical signals were obtained.

[0056] Furthermore, standard samples with concentration gradients prepared according to logarithmic ratios are placed in the constant temperature reaction zone of the coagulation analyzer. The reagent cups, detection channels, and standard samples themselves are subjected to temperature leveling treatment, and each concentration of standard sample is subjected to no less than three repeated tests. During the detection process of the coagulation analyzer, the main reaction light signal and the reference light signal are synchronously acquired according to the preset scanning frequency (e.g., 100Hz) and stored in the form of time series.

[0057] It should be noted that the preset scanning frequency must meet the requirements of sufficient light intensity sampling density for double logarithmic calibration and no sampling omissions at solidification time detection points.

[0058] Based on multiple detections of optical signals, the reference concentration of the standard sample is recorded, and the detection results of the main reaction optical signal and the reference optical signal are extracted and the optical response value is calculated.

[0059] Furthermore, the reference concentration of each standard sample is recorded. The main response light signal and the reference light signal are differentially normalized using the response ratio function to obtain the initial value of the optical response. The initial values ​​of the optical response corresponding to the same reference concentration are averaged to generate the optical response value.

[0060] It should be noted that the response ratio function is expressed as:

[0061] ;

[0062] in, Indicates the first Initial values ​​for the optical response Indicates the first The peak value of the main reactive optical signal, Indicates the first The peak value of a reference optical signal, Represents a small constant that avoids division by zero (e.g. ).

[0063] Logarithmic transformations are performed on the reference concentration and optical response value to obtain the logarithmic concentration and logarithmic optical response value, and weighting coefficients are fitted to the initial double logarithmic calibration equation.

[0064] Furthermore, logarithmic transformations are performed on the reference concentration and optical response value of each standard sample to obtain the logarithmic concentration and logarithmic optical response value.

[0065] It should be noted that the reference concentration and optical response value are logarithmically transformed and expressed as follows:

[0066] ;

[0067] ;

[0068] in, Indicates the first Logarithmic concentration, Indicates the first The reference concentration for a standard sample, Indicates the first Logarithmic optical response values, Indicates the first The optical response values ​​of a standard sample.

[0069] Furthermore, for each reference concentration, the weighting coefficients of the initial double logarithmic calibration equation are obtained by calculating the relative standard deviation of the standard samples for multiple initial optical response values.

[0070] It should be noted that the weighting coefficients of the initial double logarithmic calibration equation are obtained by calculating the relative standard deviation of the standard samples, and are expressed as follows:

[0071] ;

[0072] ;

[0073] in, Indicates the first The relative standard deviation of a standard sample. Indicates the first The number of times a standard sample is repeatedly tested. Indicates the standard sample at the 1st Initial value of the optical response for the second detection. Indicates the first One optical response value represents the weighting coefficients of the initial double logarithmic scaling equation.

[0074] The initial double logarithmic calibration equation is established by performing a weighted linear regression on the logarithmic concentration, logarithmic optical response value, and the weighting coefficients of the initial double logarithmic calibration equation.

[0075] Furthermore, the weighting coefficients of the initial double logarithmic calibration equation are correlated with the corresponding logarithmic concentration and logarithmic optical response value, and a weighted linear regression is performed on all standard samples to establish the initial double logarithmic calibration equation.

[0076] It should be noted that the initial double logarithmic scaling equation is established as follows:

[0077] ;

[0078] ;

[0079] ;

[0080] in, This represents the slope of the initial double logarithmic scaling equation. This represents the intercept of the initial double logarithmic scaling equation.

[0081] Based on the initial double logarithmic calibration equation, the light intensity, temperature, and turbidity collected under non-reactive conditions are time-averaged to obtain the reference values ​​of light intensity, temperature, and turbidity and generate a standard baseline.

[0082] Furthermore, based on the initial double logarithmic calibration equation, the light intensity, temperature, and turbidity collected under the non-reactive state are continuously sampled at fixed time windows (e.g., 2 seconds), and the light intensity, temperature, and turbidity within the same time window are time-averaged to obtain light intensity reference values, temperature reference values, and turbidity reference values, respectively. By combining the light intensity, temperature, and turbidity reference values ​​in sequence, a standard baseline is generated.

[0083] S2. Test the sample, collect real-time monitoring data and compare it with the standard baseline to obtain the deviation of temperature and turbidity.

[0084] Real-time monitoring data includes the main reaction light signal, reference light signal, test sample temperature, and test sample turbidity.

[0085] The test samples are tested, real-time monitoring data is collected, and the temperature and turbidity sequences of the test samples are extracted.

[0086] Furthermore, the coagulation analyzer is used to test the test samples. It synchronously acquires the main reaction light signal, reference light signal, test sample temperature, and test sample turbidity at a preset scanning frequency (e.g., 100Hz). The acquired main reaction light signal, reference light signal, test sample temperature, and test sample turbidity are stored in the form of a time series. By reading the test sample temperature point by point in the time series, a test sample temperature sequence is generated. By reading the test sample turbidity point by point in the time series, a test sample turbidity sequence is generated.

[0087] The temperature sequence of the test sample is compared with the reference temperature value in the standard baseline to calculate the temperature deviation of the test sample.

[0088] Furthermore, by reading each temperature data point in the temperature sequence of the test sample point by point, the difference between each temperature data point and the temperature reference value in the standard baseline is calculated and all temperature differences are statistically analyzed to generate a temperature difference sequence; by performing time averaging on the temperature difference sequence, the temperature deviation of the test sample is generated.

[0089] The turbidity sequence of the test sample is compared with the baseline turbidity value in the standard baseline to calculate the turbidity deviation of the test sample.

[0090] Furthermore, by reading each turbidity data point in the turbidity sequence of the test sample point by point, the difference between each turbidity data point and the baseline turbidity value in the standard baseline is calculated and all turbidity differences are statistically analyzed to generate a turbidity difference sequence; by performing time averaging on the turbidity difference sequence, the turbidity deviation of the test sample is generated.

[0091] S3. Based on the deviation of temperature and turbidity, the detection signal is normalized by fractional anti-interference correction through the detection signal correction function to obtain the corrected detection signal and generate the corrected detection signal curve.

[0092] Based on the temperature and turbidity deviations of the test samples, temperature compensation factors and turbidity compensation factors are constructed.

[0093] Furthermore, based on the temperature and turbidity deviations of the test samples, the temperature deviation of the test samples is read, and the temperature compensation factor is calculated according to the linear relationship between temperature deviation and light intensity change; the turbidity deviation of the test samples is read, and the turbidity compensation factor is calculated according to the fractional change law between turbidity deviation and scattered light interference.

[0094] It should be noted that the temperature compensation factor is used to characterize the linear drift of the detection signal caused by the temperature deviation of the test sample; the turbidity compensation factor is used to characterize the scattering enhancement effect of the detection signal caused by the turbidity deviation of the test sample.

[0095] It should be noted that the temperature compensation factor is expressed as:

[0096] ;

[0097] in, Indicates the temperature compensation factor. This represents the temperature compensation sensitivity coefficient. This indicates the temperature deviation of the test sample.

[0098] It should be noted that the temperature compensation sensitivity coefficient is set by analyzing the optical response changes of standard samples under different temperature deviations. Specifically, the standard samples of a predetermined reference concentration are repeatedly tested under different temperature conditions, and the main response light signal and reference light signal are collected respectively. The corresponding optical response values ​​are calculated, and the change in optical response value is obtained. A temperature deviation is generated based on the reference temperature value in each test and the standard baseline. A one-to-one correspondence is established between each temperature deviation and the corresponding change in optical response value. By performing linear regression on the change in optical response value and temperature deviation, the sensitivity slope of the optical response value to the temperature deviation is obtained. The sensitivity slope obtained from the current linear regression is used as the value of the temperature compensation sensitivity coefficient. The value of the temperature compensation sensitivity coefficient satisfies the following condition: when the temperature deviation is zero, the temperature compensation factor is 1; when the temperature deviation is positive or negative, the temperature compensation factor is corrected for consistency with the change in optical response. For example, when the optical response value changes by 0.8% for every 1°C increase in temperature, the temperature compensation sensitivity coefficient is set to 0.008.

[0099] The sensitivity slope is used to characterize the degree to which the optical response value is affected by temperature deviation.

[0100] Turbidity compensation factor, expressed as:

[0101] ;

[0102] in, Indicates the turbidity compensation factor. This represents the turbidity compensation sensitivity coefficient. This indicates the turbidity deviation of the test sample.

[0103] It should be noted that the turbidity compensation sensitivity coefficient is set by analyzing the optical response variation of standard samples under different turbidity deviation conditions. Specifically, in the selected reference concentration standard samples, multiple different turbidity deviation conditions are constructed by controlling the light path and adding a verified turbidity interference medium. Under each turbidity deviation condition, repeated detection is performed multiple times to collect the main reaction light signal and the reference light signal, and the optical response value corresponding to each turbidity deviation condition is calculated. Each turbidity deviation condition forms a turbidity deviation with the reference value of turbidity in the standard baseline. For each turbidity deviation, the change in optical response under the current turbidity deviation condition is calculated compared to the optical response under the standard baseline condition. The turbidity deviation and the corresponding change in optical response are fitted with a linear regression to obtain the sensitivity slope of the change in optical response to the turbidity deviation. The sensitivity slope obtained from the current linear regression is used as the turbidity compensation sensitivity coefficient, and the turbidity compensation factor is 1 when the turbidity deviation is 0. When the turbidity deviation is not 0, the turbidity compensation factor cancels out the scattering interference caused by the turbidity deviation. For example, when the optical response value changes by 1% for every 0.01 unit increase in turbidity, the turbidity compensation sensitivity coefficient is set to 1.

[0104] Based on the temperature compensation factor and turbidity compensation factor, and combined with the difference between the main reaction optical signal and the reference optical signal, the detection signal is subjected to fractional normalization anti-interference correction through the detection signal correction function to obtain the corrected detection signal.

[0105] Furthermore, the main reaction light signal and the reference light signal are processed time-by-time, and temperature compensation factor and turbidity compensation factor are applied to the instantaneous amplitude of the main reaction light signal and the reference light signal, respectively; the intensity changes of the main reaction light signal and the reference light signal under temperature deviation and turbidity deviation conditions are corrected in real time; the main reaction light signal and the reference light signal after being corrected by temperature compensation factor and turbidity compensation factor are substituted into the detection signal correction function, and the instantaneous difference between the main reaction light signal and the reference light signal after temperature compensation factor and turbidity compensation factor correction is normalized by fractional operation to obtain the corrected detection signal, and all corrected detection signals are statistically analyzed to generate a corrected detection signal sequence.

[0106] It should be noted that the detection signal correction function is expressed as:

[0107] ;

[0108] ;

[0109] ;

[0110] in, This represents the corrected detection signal. This represents the main reaction light signal after temperature and turbidity compensation. Indicates the main reaction light signal, This represents the reference light signal after temperature and turbidity compensation. This represents the reference optical signal.

[0111] The corrected detection signals are plotted in chronological order as the corrected detection signal curve.

[0112] Furthermore, the corrected detection signals are arranged sequentially according to the sampling time order, and a unique time identifier is assigned to the corrected detection signal corresponding to each sampling time point to maintain the continuity of the corrected detection signals in the time dimension; the corrected detection signals at each sampling time point are connected by curves to form a corrected detection signal curve.

[0113] S4. Combine the corrected detection signal with the initial double logarithmic calibration equation to generate the predicted concentration and compare it with the reference concentration to obtain the concentration deviation. Based on the solidification time in the corrected detection signal curve, generate the anti-interference correction response quantity.

[0114] The corrected detection signal is logarithmically transformed to obtain the logarithmic response.

[0115] Furthermore, the corrected detection signal is processed point by point according to the sampling time point sequence. The corrected detection signal corresponding to each sampling time point is subjected to amplitude compression by logarithmic operation to obtain the logarithmic response.

[0116] It should be noted that the logarithmic response has monotonicity and linear fit characteristics in logarithmic space; by performing a logarithmic transformation on the corrected detection signal, the difference in light intensity magnitude is mapped to a smooth change on a logarithmic scale.

[0117] The predicted concentration of the test sample is calculated based on the logarithmic response and the initial double logarithmic calibration equation.

[0118] Furthermore, the logarithmic response is substituted point by point into the initial double-logarithmic calibration equation according to the sampling time points. The predicted logarithmic concentration for each sampling time point is calculated by using the slope and intercept of the initial double-logarithmic calibration equation. The logarithmic response is used as the input corresponding to the logarithmic optical response value. Based on the linear relationship between the logarithmic optical response value and the logarithmic concentration in the initial double-logarithmic calibration equation, the predicted logarithmic concentration for each sampling time point is obtained by performing an inverse variable solution operation on the initial double-logarithmic calibration equation. The predicted logarithmic concentration is then subjected to an inverse exponential transformation to obtain the predicted concentration of the test sample at each sampling time point.

[0119] Compare the predicted concentration with the reference concentration to obtain the concentration deviation.

[0120] Furthermore, each predicted concentration is compared point by point with the reference concentration of the test sample. By calculating the difference between the predicted concentration and the reference concentration, the average of all the differences between the predicted concentration and the reference concentration is calculated to generate the concentration deviation.

[0121] The solidification time is obtained by analyzing the slope change of the corrected detection signal curve.

[0122] Furthermore, the corrected detection signal curve is analyzed point-by-point according to time sequence to extract the instantaneous rate of change of the corrected detection signal curve at different time points; the slope within a continuous time window is obtained by calculating the corrected detection signal curve; after smoothing within the time window, a slope sequence of the corrected detection signal curve is generated; a slope transition threshold is set, and the slope sequence of the corrected detection signal curve is compared with the slope transition threshold. When the slope sequence of the corrected detection signal curve first exceeds the slope transition threshold at a time point, the current time point is taken as the solidification time.

[0123] It should be noted that setting the slope transition threshold specifically involves analyzing the corrected detection signal curve during the baseline phase to obtain the baseline slope sequence, and calculating the average and standard deviation of the absolute values ​​of the baseline slope sequence. The average of these two values ​​is taken as the slope transition threshold value. The range of the slope transition threshold value is... .

[0124] Extract the corrected detection signal corresponding to the solidification time from the corrected detection signal curve.

[0125] Furthermore, the corrected detection signal curve is analyzed point by point over time. The time point corresponding to the solidification time is located according to the time sequence. The time position that is consistent with the solidification time is retrieved on the corrected detection signal curve in the same time sequence. The corrected detection signal at the time position is read from the corrected detection signal curve, and the current corrected detection signal is taken as the corrected detection signal corresponding to the solidification time.

[0126] Based on the solidification time and the corresponding corrected detection signal, an anti-interference correction response quantity is constructed.

[0127] Furthermore, the solidification time is used as the time scale input, and the corrected detection signal corresponding to the solidification time is used as the signal amplitude input. The time scale input and the signal amplitude input are numerically verified respectively. The time scale input and the signal amplitude input are then jointly expressed in the order of time scale input first and signal amplitude input second to generate an anti-interference correction response.

[0128] It should be noted that after the time scale input and the signal amplitude input are numerically confirmed, the time scale input is used to characterize the reaction process of the test sample, and the signal amplitude input is used to characterize the optical amplitude of the test sample at the position of change in the reaction process.

[0129] S5. Based on the anti-interference correction response, calculate the double logarithmic residual of the test sample, correlate the double logarithmic residual with the concentration deviation, and adjust the coefficients in the detection signal correction function in real time according to the residual direction to generate the updated double logarithmic calibration equation.

[0130] Logarithmic transformations are performed on the anti-interference correction response and the predicted concentration to obtain the logarithmic anti-interference correction response and the logarithmic predicted concentration.

[0131] Furthermore, the anti-interference correction response is logarithmically transformed to generate a logarithmic anti-interference correction response, which is used to characterize the amplitude characteristics of the anti-interference correction response in logarithmic space; the predicted concentration is logarithmically transformed to generate a logarithmic predicted concentration, which is used to characterize the positional relationship of the predicted concentration in double logarithmic space.

[0132] Substitute the logarithmic predicted concentration into the initial double logarithmic calibration equation to obtain the theoretical logarithmic response.

[0133] Furthermore, the logarithmic predicted concentration is substituted into the initial double logarithmic calibration equation, and the logarithmic predicted concentration is calculated using the slope and intercept parameters in the initial double logarithmic calibration equation to obtain the theoretical logarithmic response.

[0134] The difference between the logarithmic anti-interference correction response and the theoretical logarithmic response is calculated to obtain the double logarithmic residual of the test sample.

[0135] Furthermore, the logarithmic anti-interference correction response and the theoretical logarithmic response are matched at the same time point. The deviation of the logarithmic anti-interference correction response relative to the theoretical logarithmic response is quantified. The deviation of the test sample in the double logarithmic space is obtained by calculating the measurable difference between the logarithmic anti-interference correction response and the theoretical logarithmic response in the double logarithmic space. The deviation of the test sample in the double logarithmic space is quantitatively described by a normalized scaling function (e.g., hyperbolic tangent function), generating the double logarithmic residual of the test sample.

[0136] It should be noted that the double logarithmic residuals of the test samples are used to characterize the degree of deviation between the detection response after anti-interference correction and the theoretical calibration relationship.

[0137] The sign of the double logarithmic residuals and concentration deviations is determined, the direction of the residuals is obtained, and combined with the step size parameter, a real-time step size adjustment is generated.

[0138] Furthermore, the double logarithmic residuals and concentration deviations are mapped point by point according to the same index order. For each corresponding double logarithmic residual and concentration deviation, the numerical signs of the double logarithmic residuals and concentration deviations are read and the signs are determined to obtain the residual direction quantity. The residual direction quantity is associated with the step size parameter, and the direction of action of the step size parameter is determined by the residual direction quantity. The numerical magnitude of the step size parameter and the directional attribute of the residual direction quantity are combined to form the real-time step size adjustment amount.

[0139] It should be noted that the sign determination is as follows: when the logarithmic residual is greater than 0 and the concentration deviation is greater than 0, the residual direction quantity is assigned a positive adjustment indicator; when the logarithmic residual is less than 0 and the concentration deviation is less than 0, the residual direction quantity is assigned a negative adjustment indicator; when the logarithmic residual is greater than 0 and the concentration deviation is less than 0, the residual direction quantity is assigned a reverse adjustment indicator; when the logarithmic residual is less than 0 and the concentration deviation is greater than 0, the residual direction quantity is assigned a reverse adjustment indicator; when the logarithmic residual is equal to 0 and the concentration deviation is not equal to 0, the residual direction quantity is assigned an adjustment indicator along the direction of the concentration deviation; when the concentration deviation is equal to 0 and the logarithmic residual is not equal to 0, the residual direction quantity is assigned an adjustment indicator along the direction of the logarithmic residual; when the logarithmic residual is equal to 0 and the concentration deviation is equal to 0, the residual direction quantity is assigned an indicator that no adjustment is needed.

[0140] The real-time step size adjustment is linearly superimposed with the optical compensation coefficient, temperature compensation coefficient, and turbidity compensation coefficient in the detection signal correction function to obtain the updated optical compensation coefficient, temperature compensation coefficient, and turbidity compensation coefficient. These updated coefficients are then substituted into the initial double logarithmic calibration equation to generate the updated double logarithmic calibration equation.

[0141] Furthermore, the real-time step size adjustment is allocated, applying it to the optical compensation coefficient, temperature compensation coefficient, and turbidity compensation coefficient respectively. An allocation factor is set, and the real-time step size adjustment is divided according to this factor, resulting in adjustments for the optical compensation coefficient, temperature compensation coefficient, and turbidity compensation coefficient. The optical compensation coefficient adjustment is linearly superimposed onto the optical compensation coefficient, the temperature compensation coefficient adjustment is linearly superimposed onto the temperature compensation coefficient, and the turbidity compensation coefficient adjustment is linearly superimposed onto the turbidity compensation coefficient, yielding updated optical compensation coefficients, temperature compensation coefficients, and turbidity compensation coefficients. The updated optical compensation coefficients are then... The optical compensation coefficient, temperature compensation coefficient, and turbidity compensation coefficient are applied to the instantaneous amplitudes of the main response optical signal and the reference optical signal, respectively. Under the updated compensation conditions, the main response optical signal and the reference optical signal regenerate the corrected detection signal sequence. Based on the updated detection signal sequence, the initial value of the optical response is recalculated and the updated optical response value is obtained through averaging. The updated logarithmic optical response value is obtained by performing a logarithmic transformation on the updated optical response value. The updated logarithmic optical response value, the corresponding logarithmic concentration, and the weighting coefficients of the initial double logarithmic calibration equation are substituted into the weighted linear regression calculation process to recalculate the slope parameter and intercept parameter, and generate the updated double logarithmic calibration equation.

[0142] It should be noted that the allocation factors include optical compensation coefficient allocation factors, temperature compensation coefficient allocation factors, and turbidity compensation coefficient allocation factors. The allocation factors are set according to the principle of prioritizing optical compensation and the principle of secondary priority for temperature and turbidity compensation, and the optical compensation coefficient allocation factors, temperature compensation coefficient allocation factors, and turbidity compensation coefficient allocation factors satisfy normalization constraints. The allocation factors are set based on the statistical characteristics of the detection data. Specifically, under conditions without significant abnormal interference, standard samples based on reagents used in coagulation analyzers are repeatedly tested, and optical response value sequences, temperature deviation sequences, and turbidity deviation sequences are collected. By statistically analyzing the fluctuation range of the optical response value sequences, the optical response value is calculated. The standard deviation of the sequence is used to obtain the optical perturbation intensity index. The temperature perturbation intensity index is obtained by jointly analyzing the temperature deviation sequence and the temperature compensation sensitivity coefficient, calculating the root mean square value of both the temperature compensation sensitivity coefficient and the temperature deviation sequence. Similarly, the turbidity perturbation intensity index is obtained by jointly analyzing the turbidity deviation sequence and the turbidity compensation sensitivity coefficient, calculating the root mean square value of both the turbidity compensation sensitivity coefficient and the turbidity perturbation sequence. The optical perturbation intensity index, temperature perturbation intensity index, and turbidity perturbation intensity index are normalized to obtain the optical compensation coefficient allocation factor, temperature compensation coefficient allocation factor, and turbidity compensation coefficient allocation factor, respectively. The value range of the optical compensation coefficient allocation factor is... The range of values ​​for the temperature compensation coefficient allocation factor is: The range of values ​​for the turbidity compensation coefficient allocation factor is: .

[0143] Among them, the optical response value sequence is used to reflect the fluctuation amplitude of optical noise; the temperature deviation sequence is used to reflect the degree of influence of temperature change on the detection signal; the turbidity deviation sequence is used to reflect the light scattering interference caused by turbidity change; the optical disturbance intensity index is used to characterize the strength of optical disturbance; the temperature disturbance intensity index is used to characterize the strength of temperature disturbance; the turbidity disturbance intensity index is used to characterize the strength of turbidity disturbance; the normalized optical compensation coefficient allocation factor is used to represent the proportion of optical disturbance in the overall disturbance; the normalized temperature compensation coefficient allocation factor is used to represent the proportion of temperature deviation in the overall disturbance; and the normalized turbidity compensation coefficient allocation factor is used to represent the proportion of turbidity deviation in the overall disturbance.

[0144] In summary, this invention achieves effective compensation for light intensity changes caused by environmental factors through temperature and turbidity-based deviation correction, ensuring that the corrected signal can more stably and accurately reflect the true concentration changes of the sample, thus improving the reliability and accuracy of the measurement; and improves the accuracy and robustness of the double logarithmic calibration equation under long-term operation and different batches of reagents by dynamically updating the double logarithmic calibration equation through real-time step size adjustment.

[0145] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, and all such modifications or substitutions should be covered within the scope of the claims of the present invention.

Claims

1. A double logarithmic calibration method based on reagents for coagulation analyzers, characterized in that: include, Standard samples based on reagents used in coagulation analyzers were tested, reference concentrations were recorded, and optical response values ​​were obtained. An initial double logarithmic calibration equation was established, and a standard baseline was established by recording reference values ​​of light intensity, temperature, and turbidity. The test samples are tested, real-time monitoring data is collected and compared with a standard baseline to obtain the deviations in temperature and turbidity; Based on the deviations in temperature and turbidity, the detection signal is subjected to fractional normalization anti-interference correction through the detection signal correction function, the corrected detection signal is obtained, and the corrected detection signal curve is generated. By combining the corrected detection signal with the initial double logarithmic calibration equation, a predicted concentration is generated and compared with the reference concentration to obtain the concentration deviation. Based on the solidification time in the corrected detection signal curve, an anti-interference correction response is generated. Based on the anti-interference correction response, the double logarithmic residual of the test sample is calculated, and the double logarithmic residual is correlated with the concentration deviation. The coefficients in the detection signal correction function are adjusted in real time according to the residual direction to generate the updated double logarithmic calibration equation.

2. The double logarithmic calibration method based on reagents for coagulation analyzers as described in claim 1, characterized in that: The steps for detecting standard samples based on reagents used in a coagulation analyzer, recording reference concentrations, and obtaining optical response values ​​are as follows. Standard samples based on reagents used in a coagulation analyzer were tested, and multiple detection optical signals were obtained. Based on multiple detections of optical signals, the reference concentration of the standard sample is recorded, and the detection results of the main reaction optical signal and the reference optical signal are extracted and the optical response value is calculated.

3. The double logarithmic calibration method based on reagents for coagulation analyzers as described in claim 2, characterized in that: The initial double logarithmic calibration equation is established by recording reference values ​​for light intensity, temperature, and turbidity to establish a standard baseline. The steps are as follows: Logarithmic transformation is performed on the reference concentration and optical response value to obtain the logarithmic concentration and logarithmic optical response value, and the weighting coefficients of the initial double logarithmic calibration equation are fitted. The initial double logarithmic calibration equation is established by performing a weighted linear regression on the logarithmic concentration, logarithmic optical response value, and the weighting coefficients of the initial double logarithmic calibration equation. Based on the initial double logarithmic calibration equation, the light intensity, temperature, and turbidity collected under non-reactive conditions are time-averaged to obtain the reference values ​​of light intensity, temperature, and turbidity and generate a standard baseline.

4. The double logarithmic calibration method based on reagents for coagulation analyzers as described in claim 3, characterized in that: The real-time monitoring data includes the main reaction light signal, the reference light signal, the temperature of the test sample, and the turbidity of the test sample.

5. The double logarithmic calibration method based on reagents for coagulation analyzers as described in claim 4, characterized in that: The steps for testing the sample, collecting real-time monitoring data, comparing it with a standard baseline, and obtaining the deviations in temperature and turbidity are as follows. The test samples were tested, real-time monitoring data was collected, and the temperature and turbidity sequences of the test samples were extracted. The temperature sequence of the test sample is compared with the reference temperature value in the standard baseline to calculate the temperature deviation of the test sample; The turbidity sequence of the test sample is compared with the baseline turbidity value in the standard baseline to calculate the turbidity deviation of the test sample.

6. The double logarithmic calibration method based on reagents for coagulation analyzers as described in claim 5, characterized in that: The deviation based on temperature and turbidity is corrected by performing fractional normalization anti-interference correction on the detection signal using a detection signal correction function. The corrected detection signal is then obtained and a corrected detection signal curve is generated. The steps are as follows. Based on the temperature and turbidity deviations of the test samples, temperature compensation factors and turbidity compensation factors are constructed. Based on the temperature compensation factor and turbidity compensation factor, and combined with the difference between the main reaction optical signal and the reference optical signal, the detection signal is subjected to fractional normalization anti-interference correction through the detection signal correction function to obtain the corrected detection signal; The corrected detection signals are plotted in chronological order as the corrected detection signal curve.

7. The double logarithmic calibration method based on reagents for coagulation analyzers as described in claim 6, characterized in that: The process involves combining the corrected detection signal with the initial double logarithmic calibration equation to generate a predicted concentration, which is then compared with a reference concentration to obtain the concentration deviation. The steps are as follows: Perform a logarithmic transformation on the corrected detection signal to obtain the logarithmic response. The predicted concentration of the test sample is calculated based on the logarithmic response and the initial double logarithmic calibration equation. Compare the predicted concentration with the reference concentration to obtain the concentration deviation.

8. The double logarithmic calibration method based on reagents for coagulation analyzers as described in claim 7, characterized in that: The steps for generating the anti-interference correction response based on the solidification time in the corrected detection signal curve are as follows: The solidification time is obtained by analyzing the slope change of the corrected detection signal curve. Extract the corrected detection signal corresponding to the solidification time from the corrected detection signal curve; Based on the solidification time and the corresponding corrected detection signal, an anti-interference correction response quantity is constructed.

9. The double logarithmic calibration method based on reagents for coagulation analyzers as described in claim 8, characterized in that: The steps for calculating the double logarithmic residuals of the test samples based on the anti-interference correction response are as follows: Logarithmic transformation is performed on the anti-interference correction response and the predicted concentration to obtain the logarithmic anti-interference correction response and the logarithmic predicted concentration. Substitute the logarithmic predicted concentration into the initial double logarithmic calibration equation to obtain the theoretical logarithmic response. The difference between the logarithmic anti-interference correction response and the theoretical logarithmic response is calculated to obtain the double logarithmic residual of the test sample.

10. The double logarithmic calibration method based on reagents for coagulation analyzers as described in claim 9, characterized in that: The steps for correlating the double logarithmic residuals with the concentration deviation, adjusting the coefficients in the detection signal correction function in real time according to the residual direction, and outputting the updated double logarithmic calibration equation are as follows. The sign of the double logarithmic residuals and the concentration deviation are determined, the residual direction is obtained, and combined with the step size parameter, a real-time step size adjustment is generated. The real-time step size adjustment is linearly superimposed with the optical compensation coefficient, temperature compensation coefficient, and turbidity compensation coefficient in the detection signal correction function to obtain the updated optical compensation coefficient, temperature compensation coefficient, and turbidity compensation coefficient. These updated coefficients are then substituted into the initial double logarithmic calibration equation to generate the updated double logarithmic calibration equation.

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